THE - Tehran University of Medical Sciencesthc.tums.ac.ir/UserFiles/shahraky/files/V7 - N_02 - 2012.pdf · Seifollah Abdi, MD Tehran University of Medical Sciences Alireza Amirzadegan,

THE JOURNAL OF TEHRAN UNIVERSITY HEART

CENTEREditor-in-Chief

Associate & Managing Editor

International Editors

ABBASALI KARIMI, MDPROFESSOR OF CARDIAC SURGERY

TEHRAN UNIVERSITY OF MEDICAL SCIENCES

SEYED HESAMEDDIN ABBASI, MDTEHRAN HEART CENTER

TEHRAN UNIVERSITY OF MEDICAL SCIENCES

Editorial BoardHossien Ahmadi, MDTehran University of Medical SciencesShahin Akhondzadeh, PhDTehran University of Medical Sciences Mohammad Alidoosti, MDTehran University of Medical Sciences Mohammad Ali Boroumand, MDTehran University of Medical Sciences Gholamreza Davoodi, MDTehran University of Medical SciencesAhmad Reza Dehpour, PhDTehran University of Medical SciencesAbbasali Karimi, MDTehran University of Medical SciencesSeyed Ebrahim Kassaian, MDTehran University of Medical SciencesDavood Kazemi Saleh, MD Baghiatallah University of Medical SciencesMajid Maleki, MDTehran University of Medical SciencesMehrab Marzban, MDShahid Beheshti University of Medical SciencesMansor Moghadam, MDTehran University of Medical Sciences Sina Moradmand Badie, MDTehran University of Medical SciencesSeyed Mahmood Mirhoseini, MD, DSc, FACC, FAES Tehran University of Medical Sciences

Zohair Yousef Al-halees, MD , FRCSC, FACS King Faisal Heart Institute, Saudi Arabia Yadolah Dodge, PhD University of Neuchâtel, SwitzerlandAli Dodge–Khatami, MD, PhDUniversity of Hamburg- Eppendorf School of Medicne, Germany Iradj Gandjbakhch, MDHopital Pitie, FranceOmer Isik, MDYeditepe University, School of Medicine, Turkey Sami S. Kabbani, MDDamascus University Cardiovascular Surgical Center, SyriaKayvan Kamalvand, MD, FRCP, FACC William Harvey Hospital, United Kingdom Jean Marco, MD, FESCCentre Cardio- Thoracique de Monaco, FranceAli Massumi, MDTexas Heart Institute, U. S. ACarlos-A. Mestres, MDUniversity of Barcelona, Spain

Fred Morady, MD University of Michigan, U. S. AMohammed T. Numan, MDUniversity of Texas, U. S. AAhmand S. Omran, MD, FACC, FASE King Abdulaziz Cardiac Center, Saudi Arabia Fausto J. Pinto, MD, PhD, FESC, FACC, FASA, FSCAI, FASELisbon University, Portugal Mehrdad Rezaee, MD, PhDStanford University, School of Medicine, U. S. AGregory S. Thomas, MD, MPH, FACC, FACP, FASNCUniversity of California, U. S. ALee Samuel Wann, MDWisconsin Heart Hospital, U. S. AHein J. Wellens, MD Cardiovascular Research Institute, Maastricht, The Netherlands Douglas P. Zipes, MD Indiana University, School of medicine, U. S. A

Seyed Rasoul Mirsharifi, MDTehran University of Medical SciencesAhmad Mohebi, MD Tehran University of Medical Sciences Mohammad-Hasan NamaziShaheed beheshti University of Medical SciencesEbrahim Nematipour, MDTehran University of Medical SciencesRezayat Parvizi, MDTabriz University of Medical SciencesMasoud PezeshkianTabriz University of Medical SciencesHassan Radmehr, MD Tehran University of Medical SciencesSaeed Sadeghian, MDTehran University of Medical SciencesMojtaba Salarifar, MDTehran University of Medical SciencesNizal Sarraf –Zadegan, MDIsfahan University of Medical SciencesAhmad Yaminisharif, MDTehran University of Medical SciencesMohammad Reza Zafarghandi, MDTehran University of Medical SciencesAliakbar Zeinaloo, MDTehran University of Medical Sciences

Advisory BoardKiyomars Abbasi, MDTehran University of Medical SciencesSeifollah Abdi, MD Tehran University of Medical SciencesAlireza Amirzadegan, MDTehran University of Medical SciencesNaser Aslanabadi, MDTabriz University of Medical SciencesCarlo Briguori, MDClinica Mediterranea Hospital, Naples, ItalyAlaide Chieffo, MDSan Raffaele Scientific Institute, Milano, ItalySirous Darabian, MDSt. John Cardiovascular Reserach Center, USASaeed Davoodi, MDTehran University of Medical SciencesIraj Firoozi, MDTehran University of Medical SciencesSeyed Khalil Foroozannia, MDShaheed Sadoghi University of Medical SciencesAlfredo R. Galassi MD, FACC, FESC, FSCAICannizzaro Hospital, Catania, ItalyArmen Gasparyan MD, PhDArmeniaAli Ghaemian, MDMazandaran University of Medical SciencesNamvar Ghasemi Movahedi, MDTehran University of Medical SciencesAbbas Ghiasi, MDTehran University of Medical SciencesAli Kazemi Saeed, MDTehran University of Medical SciencesAli Mohammad Haji Zeinali, MDTehran University of Medical Sciences

Mohammad Jafar Hashemi, MD Tehran University of Medical SciencesSeyed Kianoosh HoseiniTehran University of Medical Sciences Elise Langdon- NeunerEuropean Medical Writers Association, AustriaJalil Majd Ardekani, MDTehran University of Medical SciencesFardin Mirbolook, MDGilan University of Medical Sciences Mehdi Najafi, MDTehran University of Medical Sciences Younes Nozari, MDTehran University of Medical SciencesHamid Reza Pour Hosseini, MDTehran University of Medical Sciences Hakimeh Sadeghian, MD Tehran University of Medical SciencesMohammad Saheb Jam, MD & PT Tehran University of Medical SciencesAbbas Salehi Omran, MD Tehran University of Medical SciencesMahmood Shabestari, MDMashhad University of Medical Sciences Shapour Shirani, MD Tehran University of Medical SciencesAbbas Soleimani, MDTehran University of Medical SciencesSeyed Abdolhosein Tabatabaei, MDTehran University of Medical SciencesMurat Ugurlucan, MDDuzce Ataturk State Hospital, TurkeyArezou Zoroufian, MD Tehran University of Medical Sciences

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Farshad Amouzadeh

The Journal of Tehran University Heart Center

ContentVolume: 7 Number: 2 Spring 2012


TEHRAN HEART CENTER

Review Article The Potential Role of Clinical Pharmacy Services in Patients with Cardiovascular DiseasesAzita Hajhossein Talasaz …………….....…………………………………………..…....................................................................................................

Original Articles Effectiveness of Two-Year versus One-Year Use of Dual Antiplatelet Therapy in Reducing the Risk of Very Late Stent Thrombosis after Drug-Eluting Stent Implantation Hamid Reza Poorhosseini, Seyed Kianoosh Hosseini, Tahereh Davarpasand, Masoumeh Lotfi Tokaldany, Mojtaba Salarifar, Seyed Ebrahim Kassaian, Mohammad Alidoosti, Younes Nozari, Ebrahim Nematipour, Ali Mohammad Haji Zeinali, Hasan Aghajani, Ali Reza Amirzadegan ………............…....

A Comparison of Selenium Concentrations between Congestive Heart Failure Patients and Healthy Volunteers Ali Ghaemian, Ebrahim Salehifar, Hanieh Shiraj, Zeinolabedin Babaee ..........................................................................................................................

Frequency and Predictors of Renal Artery Stenosis in Patients Undergoing Simultaneous Coronary and Renal CatheterizationNavid Rokni, Mojtaba Salarifar, Elham Hakki Kazazi, Hamidreza Goodarzynejad …………….....................................................................................

Factors Associated with Delay in Thrombolytic Therapy in Patients with ST-Elevation Myocardial InfarctionAmir Alishahi Tabriz, Mohammad-Reza Sohrabi, Nazanin Kiapour, Shahrooz Yazdani ………..................……............................................................

Discharge against Medical Advice among Inpatients with Heart Disease in IranJila Manouchehri, Hamidreza Goodarzynejad, Zohreh Khoshgoftar, Mahmood Sheikh Fathollahi, Maryam Aghamohammadi Abyaneh .....................

Case ReportsRole of IVUS in Assessing Spontaneous Coronary Dissection: a Case Report Amin Daoulah, Awad Al Qahtani, Majed Mazen Malak, Saud Al Ghamdi ….............………………………………….....….........................................

Supravalvar Mitral Ring: a Case ReportBahador Baharestani, Reza Sadat Afjehi, Nader Givtaj, Mehrzad Sharifi .…………….................................................……...........................................

Prinzmetal’s Angina in a Pregnant Woman: A Case Report Fariba Almassinokiani, Mahmood Reza Alebouyeh, Farshad Entesari, Seyed Hashem Sezavar Seyedi, Alireza Almasi, Hossein Akbari, Hossein Saidi, Homa Homam ...……………………..…………………….………………………..................................................…..…....................................

Letter to the EditorPrediction of Primary Slow-Pathway Ablation Success Rate according to the Characteristics of Junctional Rhythm Developed during the Radiofrequency Catheter Ablation of Atrioventricular Nodal Reentrant Tachy-cardia Gholamreza Davoodi ...……………………………………...…....……………….…………………........................………..…....................................

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REVIEW ARTICLE

41 The Potential Role of Clinical Pharmacy Services in Patients with Cardiovascular Diseases

Azita Hajhossein Talasaz, Pharm D, BCPS*

Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

*Azita Hajhossein Talasaz, Assistant Professor of Clinical Pharmacy, Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 1417614411. Tel: +98 9123778707. Fax: +98 21 66954709. E-mail: [email protected].

Clinical pharmacy is deemed an integral component of a health care system. The presence

of clinical pharmacists in medical rounds could assist physicians in optimizing patients' pharmacotherapy. Moreover, clinical pharmacists may reduce adverse effects and medication errors insofar as they contribute significantly to the detection and management of drug-related problems, not least in patients with cardiovascular diseases, who have the highest rank in the frequency of medication errors. Clinical pharmacists can also collaborate with physicians in the management of cardiovascular risk factors as well as anticoagulation therapy based on patients’ specific situations.

In summary, the practice of clinical pharmacy is considered a crucial part of a health care team to improve the level of patients' care by increasing the quality of therapy with the least expense for a health care system.

ORIGINAL ARTICLES

47 Effectiveness of Two-Year versus One-

Year Use of Dual Antiplatelet Therapy in Reducing the Risk of Very Late Stent Thrombosis after Drug-Eluting Stent Implantation

Hamid Reza Poorhosseini, MD, Seyed Kianoosh Hosseini, MD, Tahereh Davarpasand, MD*, Masoumeh Lotfi Tokaldany, MD, MPH, Mojtaba Salarifar, MD, Seyed Ebrahim Kassaian, MD, Mohammad Alidoosti, MD, Younes Nozari, MD, Ebrahim Nematipour, MD, Ali Mohammad Haji Zeinali, MD, Hasan Aghajani, MD, Ali Reza Amirzadegan, MD

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

*Tahereh Davarpasand, Cardiology Department, Tehran Heart Center, North Kargar Street, Tehran, Iran. 1411713138. Tex: +98 21 88029256. Fax: +98 21 88029256. E-mail: [email protected].

Background: Impact of 12 months’ versus 24 months’ use of dual antiplatelet therapy on the

prevalence of stent thrombosis in patients undergoing percutaneous coronary intervention (PCI) with the drug-eluting stent (DES) is not clear. As a result, duration of dual antiplatelet therapy is still under debate among interventionists.

Conclusion: In our study, the extended use of dual antiplatelet therapy (for more than 12 months) was not significantly more effective than Aspirin monotherapy in reducing the risk of myocardial infarction or stent thrombosis, death from cardiac cause, and stroke.

Our study did not have sufficient statistical power to allow for a firm conclusion regarding the safety of Clopidogrel discontinuation after 12 months. Larger clinical trials will, therefore, be necessary to resolve this issue.

53 A Comparison of Selenium Concentrations

Spring 2012

Summary of Contents

What you will find in this IssueVolume: 7 Number: 2

TEHRAN HEART CENTER

between Congestive Heart Failure Patients and Healthy Volunteers

Ali Ghaemian, MD1, Ebrahim Salehifar, PharmD2*, Hanieh Shiraj, MD3, Zeinolabedin Babaee, MD4

1Mazandaran Heart Center, Mazandaran University of Medical Sciences, Sari, Iran.2Mazandaran University of Medical Sciences, Thalassemia Research Center, Sari, Iran.3Shafa General Hospital, Sari, Iran.4Mazandaran University of Medical Sciences, Sari, Iran.

*Ebrahim Salehifar, Associate Professor of Clinical Pharmacy, Department of Clinical Pharmacy, Thalassemia Research Center, Mazandaran University of Medical Sciences, Faculty of Pharmacy, Km 18 Khazarabad Road, Khazar Sq., Sari, Iran. 4818893716. Tel: +98 15 13543081. Cell Phone: +98 911 1544526. Fax: +98 15 13543084. E-mail: [email protected].

Background: Selenium (Se) is an essential trace element mainly obtained from seafood, meat, and

cereals. Se deficiency has been identified as a major contributing factor in the pathogenesis of certain congestive heart failure (CHF) syndromes. Since there is controversy over the prevalence of Se deficiency among patient with CHF, the aim of this study was to assess the serum Se concentrations in patients with CHF and compared them with the Se status of healthy controls.

Conclusion: In conclusion, although we did not find a causal relationship between Se and CHF in the northern part of Iran, we recommend that monitoring dietary determinants can be helpful in the treatment and management of CHF patients in all areas.

58 Frequency and Predictors of Renal Artery Stenosis in Patients Undergoing Simultaneous Coronary and Renal Catheterization

Navid Rokni, MD, Mojtaba Salarifar, MD*, Elham Hakki Kazazi, MD, Hamidreza Goodarzynejad, MD


*Mojtaba Salarifar, Associate Professor of Interventional

Cardiology, Cardiology Department, Tehran Heart Center, North Kargar Street, Tehran Heart Center, Tehran, Iran. 1411713138. Tel: +98 21 88029257. Fax: +98 21 88029256. E-mail: [email protected].

Background: Atherosclerotic renal artery stenosis (ARAS) remains underdiagnosed due to its

nonspecific demonstrations. We aimed to both estimate the frequency of ARAS in high-risk non-selected patients undergoing simultaneous coronary and renal catheterization and possibly identify a predictive model for ARAS using baseline clinical, laboratory, and coronary angiographic variables.

Conclusion: ARAS is prevalent in patients undergoing coronary angiography for suspected CAD. Three-vessel CAD or two-vessel CAD (LAD + LCX) is a powerful predictor of ARAS along with female sex, older age, hypertension, and history of renal failure. The advantage of revascularization over medical therapy for ARAS is still unclear. Although risk versus benefit was not tested in this study, given the progressive nature of ARAS and the need for early detection and intervention, it appears that clinicians could consider renal catheterization in combination with coronary angiography particularly in female patients with advanced age and with significant CAD stenoses in the LAD and LCX.

65 Factors Associated with Delay in Thrombolytic Therapy in Patients with ST-Elevation Myocardial Infarction

Amir Alishahi Tabriz, MD, Mohammad-Reza Sohrabi, MD, MPH*, Nazanin Kiapour, MD, Shahrooz Yazdani, MD

Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

*Mohammad-Reza Sohrabi, Associate Professor of Community Medicine, Department of Community Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, P.O.Box: 193954719, Evin, Tehran, Iran. 1985717443. Tel: + 98 21 23872567. Fax: + 98 21 98 22439936. E-mail: [email protected].

Background: Treatment delay in the management of ST-elevation myocardial infarction conversely

correlates with prognosis and survival of the patients. This study aimed to investigate factors associated with delay in the thrombolytic therapy of these patients in Tehran.

TEHRAN HEART CENTER

Conclusion: We observed that the total time between the onset of symptoms in the patients with STEMI and the initiation of thrombolytic therapy was longer than treatment golden time. Shifting the place of diagnosis and treatment from the emergency department of hospitals to where the patient is located can reduce this gap time.

72 Discharge against Medical Advice among Inpatients with Heart Disease in Iran

Jila Manouchehri, PhD, Hamidreza Goodarzynejad, MD*, Zohreh Khoshgoftar, MSc, Mahmood Sheikh Fathollahi, PhD, Maryam Aghamohammadi Abyaneh, BS


*Hamidreza Goodarzynejad, Research Department, University of Medical Sciences, Tehran Heart Center, North Kargar Street, Tehran, Iran. 1411713138. Tel: +98 21 88029245. Fax: +98 21 88029731. E-mail: [email protected].

Background: Discharge against medical advice (DAMA) is a relatively common problem

worldwide. We sought to determine the prevalence of and reasons for DAMA among inpatients of our cardiac center.

Conclusion: The most frequent self-reported reasons for DAMA in a sample of Iranian cardiac patients included lack of consent to surgery or invasive procedures, personal or family issues, and feeling well, respectively. Providing strategies for decreasing the rate of DAMA by analyzing the current circumstances and developing effective interventions may benefit both patients (improving their health) and health care systems (decreasing unnecessary readmissions). We believe that qualitative research (e.g. semi-structured interviews with patients and perhaps physicians and hospital staff) is likely to be beneficial.

CASE REPORTS

78 Role of IVUS in Assessing Spontaneous Coronary Dissection: a Case Report

Amin Daoulah, MD1*, Awad Al Qahtani, MD2, Majed Mazen Malak, MD3, Saud Al Ghamdi, CVT1

1King Faisal Specialist Hospital & Research Center-Jeddah, Jeddah, Saudi Arabia.2Hamad Medical Corporation, Doha, Qatar.3King Abdulaziz University Hospital, Jeddah, Saudi Arabia.

*Amin Daoulah, Consultant, Cardiovascular Department, King Faisal Specialist Hospital & Research Center-Jeddah, P.O. Box: 40047. Jeddah 21499, Saudi Arabia. Tel: +96 62 667 7777. Fax: +96 62 667 7777. E-mail: [email protected].

Spontaneous coronary artery dissection (SCAD) is a rare condition that can result in unstable angina,

acute myocardial infarction, and sudden death. This condition may occur particularly in women during late pregnancy and in the postpartum period. We present the case of a 33-year-old African American woman, who had spontaneous left anterior descending coronary artery (LAD) dissection two weeks postpartum, resulting in acute ST-segment elevation myocardial infarction with severe left ventricular dysfunction. The use of the intravascular ultrasound (IVUS) in our case confirmed the diagnosis and helped with stent sizing and implantation. On subsequent follow-up, there was marked left ventricular function recovery and clinical improvement.

82 Supravalvar Mitral Ring: a Case Report

Bahador Baharestani, MD*, Reza Sadat Afjehi, MD, Nader Givtaj, MD, Mehrzad Sharifi, MD

Department of Cardiac Surgery, Rajaie Cardiovascular, Medical and Research Center, Tehran University of Medical Sciences, Tehran, Iran.

*Bahador Baharestani, Assistant Professor of Cardiac Surgery, Departement of Cardiac Surgery, Tehran University of Medical Sciences, Rajaie Cardiovascular, Medical and Research Center, Vali-Asr Street, Tehran, Iran. 1996911151. Tel: +98 21 23922156. Fax: + 98 21 22042026. E-mail: [email protected].

Supravalvar mitral ring is a rare congenital heart defect of surgical importance. The condition is

characterized by an abnormal ridge of the connective tissue on the atrial side of the mitral valve. It often substantially obstructs the mitral valve inflow. We herein introduce a case of a supravalvar mitral ring in a 17-year-old male, who was admitted to our hospital with cardiac syncope. He had undergone a cardiac operation for ventricular septal defect (VSD) closure

TEHRAN HEART CENTER


and mitral valve repair 15 years before. Transthoracic echocardiography, transesophageal echocardiography, and finally cardiac catheterization revealed a neglected supravalvular mitral ring. The ring was resected in a second operation, and the patient was discharged from the hospital symptom free.

85 Prinzmetal’s Angina in a Pregnant Woman: A Case Report

Fariba Almassinokiani, MD1, Mahmood Reza Alebouyeh, MD1, Farshad Entesari, MD1, Seyed Hashem Sezavar Seyedi, MD1, Alireza Almasi, MD2, Hossein Akbari, MD3, Hossein Saidi, MD1*, Homa Homam, MD4

1Rasool Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran.2Firoozgar Hospital, Tehran University of Medical Sciences, Tehran, Iran.3Hazrat Fatemeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.4Akbarabadi Hospital, Tehran University of Medical Sciences, Tehran, Iran.

*Hossein Saidi, Assistant Professor of Emergency Medicine, Tehran University of Medical Sciences, Rasool Akram Hospital, Sattarkhan Street, Niayesh Street, Tehran, Iran. Tel: + 98 21 3100639. Fax: + 98 21 66509283. E-Mail: [email protected].

Acute myocardial infarction (MI) during pregnancy is rare and MI due to Prinzmetal's angina is much

rarer. We present a 35-year-old, obese, multigravida, and pre-eclamptic woman, who developed acute anterior wall MI at the 30th week of gestation. On coronary angiography, the second obtuse marginal branch was totally occluded and the right coronary artery (RCA) was normal. Three days later, she had chest pain and ST elevation in the inferior leads. On second angiography, there was narrowing in the RCA, while the obtuse marginal branch was patent. We presume that this discrepancy between the first and second electrocardiograms and angiographic findings was due to Prinzmetal’s angina.

LETTER TO THE EDITOR

90 Prediction of Primary Slow-Pathway Ablation Success Rate according to the Characteristics of Junctional Rhythm

Developed during the Radiofrequency Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia

Gholamreza Davoodi, MD*


*Gholamreza Davoodi, Associate Professor of Cardiology, Department of Cardiac Electrophysiology, Tehran Heart Center, Tehran University of Medical Sciences, North Kargar Street, Tehran, Iran. 1411713138. Tex: +98 21 88029256. Fax: +98 21 88029256. E-mail: [email protected].

The Journal of Tehran University Heart Center41

TEHRAN HEART CENTER

Review Article

The Potential Role of Clinical Pharmacy Services in Patients with Cardiovascular Diseases

*Corresponding Author: Azita Hajhossein Talasaz, Assistant Professor of Clinical Pharmacy, Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 1417614411. Tel: +98 9123778707. Fax: +98 21 66954709. E-mail: [email protected].

Azita Hajhossein Talasaz, Pharm D, BCPS*

Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Clinical pharmacy is deemed an integral component of a health care system. The presence of clinical pharmacists in medical rounds could assist physicians in optimizing patients' pharmacotherapy. Moreover, clinical pharmacists may reduce adverse effects and medication errors insofar as they contribute significantly to the detection and management of drug-related problems, not least in patients with cardiovascular diseases, who have the highest rank in the frequency of medication errors. Clinical pharmacists can also collaborate with physicians in the management of cardiovascular risk factors as well as anticoagulation therapy based on patients’ specific situations.

In summary, the practice of clinical pharmacy is considered a crucial part of a health care team to improve the level of patients' care by increasing the quality of therapy with the least expense for a health care system.

Introduction

The practice of clinical pharmacy is regarded as an imperative part of a health care team to provide the best quality use of medicines. This goal can be achieved by participation in the management of individual patients, incorporation of the best available evidence, and transfer of this knowledge to health care professionals in all practice settings to guarantee the utmost possible quality of patient care.1

The main objective of this review is to summarize the role of clinical pharmacy services in all facets of cardiovascular diseases (CVD) in hospitalized patients.

For the purposes of the present review, databases including

MEDLINE/PUBMED and Scopus as well as trial registries were systematically searched from inception through March 2nd, 2012. Keywords were: clinical pharmacy/pharmacist and cardiology, cardiovascular, cardiac, heart failure, hypertension, diabetes, dyslipidemia, and anticoagulant. Attempts were made to include all studies reporting the impact of clinical pharmacy services with a focus on an inpatient setting. European studies that involved hospital pharmacists were also included since the number of clinical pharmacists was limited in these countries. The primary outcome measure assessed was the difference between the levels of care in patients receiving pharmaceutical services versus those receiving standard treatment. The results of this search were classified into prevention of drug-related

Keywords: Pharmacy • Cardiovascular diseases • Professional role • Patient care team

J Teh Univ Heart Ctr 2012;7(2):41-46

This paper should be cited as: Talasaz AH. The Potential Role of Clinical Pharmacy Services in Patients with Cardiovascular Diseases. J Teh Univ Heart Ctr 2012;7(2):41-46.

Received 08 January 2012; Accepted 10 February 2012

42


problems, management of cardiovascular risk factors, pharmaceutical care provided for heart failure patients, and anticoagulant management service.

Prevention and Reduction of Episodes of Drug-Related Problems

A known drawback of medications is the untoward events that can occur in the wake of their use.2-6 These detrimental effects can happen as a result of the inevitable pharmacological properties of medicines or their improper use, which is referred to as medication errors. Medication errors mostly occur in the prescribing process7 but they are not unavoidable: the fewer medication errors, the less morbidity, mortality, hospital stay, and cost.8-10 The presence of clinical pharmacists in rounds in tandem with other health care professionals is an effective strategy for reducing the number of preventable adverse events.11-14 On account of the fact that cardiovascular medications are the class with the most severe untoward events,15 it is even more important to have clinical pharmacists participate in cardiology wards.

The predominance of errors in cardiovascular medications can be attributed to the fact that the number and complexity of options in this therapeutic class continue to rise.1 Cooperation between clinical pharmacists and physicians at the time of ordering can both prevent adverse events and help in identifying errors.12 Clinical pharmacists can help physicians upon prescribing by providing them with detailed information on the pharmacokinetic and pharmacodynamic characteristics of medications such as dosing, interactions, indications, and alternatives based on the patient’s situation.12

To sum up, clinical pharmacists’ contribution in cardiac unit rounds or visits is considered to be one of the major fields in which their presence has been proved to be very helpful.

Management of Cardiovascular Risk Factors

Clinical pharmacists play an essential role in the management of patients with chronic diseases. Their mission in optimizing treatment outcomes by increasing the rate of achieving therapeutic goals and decreasing the cost of therapy for both patients and health care settings is believed to be crucial.16-21

Hyperglycemia

Hyperglycemia is associated with poor clinical outcomes in patients with any kind of concomitant diseases.22

Increased mortality is observed in hyperglycemic patients hospitalized in an intensive care unit.23 Complications of cardiac surgery, including wound infections, is more

frequently seen in patients with hyperglycemia.24, 25 Acute or stress-induced hyperglycemia rather than chronic diabetes is a better predictor of surgery-associated complications and mortality.26, 27 Irrespective of the reason behind high blood glucose level, hyperglycemic patients with CVD, including those with acute myocardial infarction, arrhythmia, unstable angina, and pulmonary embolism, tend to show increased mortality. The fact that half of patients in cardiac care units may have diabetes28, 29 adds to the significance of blood glucose level control in those with CVD. Furthermore, some of the medications used in the pharmacotherapy of CVD may induce new onset diabetes.30 Diuretics, beta blockers, and calcium channel blockers are believed to increase the risk of new onset diabetes.31-37

Clinical pharmacists’ role is even further highlighted in the elaboration and implementation of the protocols for glycemic control, calculation of required insulin dose, monitoring of patients’ blood glucose level, and reconciliation of discharge medication.38 The active presence of clinical pharmacists in the insulin regimen management of hospitalized patients was reported to have reduced length of hospital stay, rate of hyperglycemia, and also hypoglycemic events.39 Moreover, the inappropriate use of sliding scale insulin regimen without using basal insulin reduced significantly (p value < 0.0001).39

Clinical pharmacists should, therefore, be present as a team member in the management of hyperglycemia in an inpatient setting in order to furnish the necessary information regarding blood glucose monitoring with a view to bettering patients’ clinical outcome. It is deserving of note that fear of hypoglycemia is one of the barriers to adequate blood glucose control; clinical pharmacists’ input could help in overcoming this problem.38

Hypertension

Proper management of hypertension is of great importance in patients with CVD. Controlling blood pressure can decrease the incidence of myocardial infarction (20-25%) and heart failure (more than 50%).40 The British Heart Foundation Statistics Database estimated that only 40% of treated hypertensive patients were controlled.41 The number was the same for the United States, where 37% of hypertensive patients were at their blood pressure goal.42 Although it seems that limited access to care might be a common reason for poor blood pressure control,40 Hyman and Pavlik reported that most cases of uncontrolled hypertension occurred in elderly patients who had frequent physician visits.43 Regular physician visits did not lead to improved control of blood pressure in other studies, as well.44, 45

The presence of pharmacists to monitor hypertensive patients’ use of medications, provide information about potential adverse effects, and avoid drug interactions is encouraged by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood

Azita Hajhossein Talasaz.

TEHRAN HEART CENTER


Pressure.46 Several studies have demonstrated that the incorporation of clinical pharmacists in the management of hypertensive patients yields promising outcomes.47-51 This involvement could have a superior consequence if made in the hospital setting rather than the community (49-53% vs. 96-98%).52, 53 The discrepancy may be explained by the fact that in community pharmacies, close communication between pharmacists and physicians may not be feasible. A meaningfully positive impact on physicians’ prescription of medicines requires face-to-face academic visits between pharmacists and physicians in the practice setting.54 In a randomized, controlled trial on 95 hypertensive patients having been randomly distributed between a control arm of standard medical care and an intervention arm in which a physician and pharmacist collaborated with each other as a team, the systolic and diastolic blood pressures declined significantly in the intervention arm as compared to those in the control arm (23 vs. 11 mmHg and 14 vs. 3 mmHg),48

which led to a higher achievement rate of blood pressure goal in the intervention arm. In conclusion, the attendance of clinical pharmacists as an integral member of a health care team could enhance the rate of blood pressure control and lessen drug interactions and costs for both patients and health care systems.

The involvement of clinical pharmacists in the treatment decision-making process at the time of the prescription of medications is advantageous to the management of patients, especially those with chronic diseases. In several hospital settings, physicians’ responsibility is to diagnose the disease; whereas in situations where pharmacotherapy is required, clinical pharmacists should select the best choice and monitor patients for clinical response.47

Hyperlipidemia

A systematic review of 21 randomized clinical trials, conducted on studies that evaluated the impact of clinical pharmacy services on the screening and treatment of patients with dyslipidemia, revealed that collaborative care involving clinical pharmacists had led to improved outcomes in patients with dyslipidemia.55 This improved level of care was manifested by better control of total cholesterol, low-density lipoprotein (LDL), and triglyceride.56 Such success can be explained by the fact that clinical pharmacists play a significant role in making effective drug-therapy selection as well as educating patients regarding dyslipidemia and prescribed medications; this can enhance control and adherence in the long term.57

In a prospective study, conducted by Bozovich et al., the proportion of patients at their LDL goal at 6 months’ follow-up was higher in those enrolled in clinical pharmacist-managed lipid disorders clinic than in the ones having received standard care provided by cardiologists (69% vs. 50%, p value = 0.016).58 Geber et al. evaluated the level of

care provided by clinical pharmacists as opposed to that furnished via standard care by physicians in patients with high baseline LDL59 and reported a significantly high number of patients who attained their LDL goal among those receiving pharmacotherapy care compared to the ones receiving standard care (p value < 0.001).

In brief, collaboration between clinical pharmacists and physicians for the management of patients with dyslipidemia can increase the number of individuals who succeed in achieving their target lipid levels. Therefore, the establishment of such clinical pharmacy clinics should be supported particularly in communities where patients are generally unaware of the role of clinical pharmacists.

Management of Patients with Heart Failure

Patients with heart failure experience frequent hospital admissions due to the progressive and chronic nature of their disease.60 These frequent hospital admissions may beget changes in patients’ drug regimens. Prescription errors or alterations to patients’ medications without the provision of sufficient education can result in readmissions.61, 62 Pharmacotherapy management is the main treatment in patients with heart failure; optimizing the pharmacological therapy and encouraging patients’ adherence are essential for improving disease management and reducing the rate of hospitalization.63

Pharmaceutical care provided by clinical pharmacists as members of a multidisciplinary team responsible for patients with heart failure can decrease the risk of hospitalization.64,

65 Not only can pharmacists’ interventions improve patients’ adherence but also they can offer them economic assistance by reducing health care-associated costs.66 Such targets can be achieved by counseling clinical pharmacists before patient discharge.67 Clinical pharmacists can avoid prescription errors and provide patients with education regarding the medications ordered.63, 67 Moreover, in the care of patients with heart failure after the implantation of left ventricular assist devices, clinical pharmacists are known to have improved drug-therapy issues significantly.68 These services rendered by clinical pharmacists can bring about a decrease in patients’ readmissions and an increase in their quality of life.69-71

One of the other approaches that clinical pharmacists can apply to help patients with heart failure is to reduce the rate of discrepancies between prescribed medications in each of admissions and those used previously by reviewing patients’ preadmission medication lists.63 This can be achieved by taking a past medical history of patients upon admission and providing physicians with this information at the time of ordering.72

In a nutshell, because heart failure is associated with high


44


rates of hospital admissions73 and clinical pharmacists’ interventions can reduce this rate by one third,64 the presence of clinical pharmacists in the heart failure team is highly recommended.64

Anticoagulants Clinic

A clinical pharmacist-managed anticoagulation service is believed to boost the control of patients with respect to therapeutic goals and reduce the rate of adverse effects of anticoagulants as well as the occurrence of thromboembolic events as was attested to by studies that involved trained clinical pharmacists in the management of patients on anticoagulants due to a wide variety of indications and durations using a specialized approach.74-77 In the Witt et al. study, the level of care provided by clinical pharmacists was compared to that furnished by experienced physicians: patients in the former group showed a statistically significant decrease in anticoagulation therapy and thromboembolic complications.78 This improved outcome in those enrolled in the pharmacotherapy clinic is due to the greater percentage of time that the patients spent on their therapeutic goals.

Clinical pharmacists devise protocols for every single anticoagulant utilized in a hospital setting and define parameters with which they can initiate, monitor, and adjust anticoagulation therapy in every written protocol. Drawing upon these protocols, clinical pharmacists review and manage each patient’s therapy and also evaluate the response on a daily basis.79

Other services that clinical pharmacists can provide for patients on anticoagulant therapy include management of anticoagulants adverse effects, management of anticoagulant therapy in patients before any kind of surgery, and change in the anticoagulant management where necessary. All of these services can be valuable in lessening the complications of anticoagulant management and by extension, health care expenditure.75, 76

Consequently, the superior outcome of anticoagulation management along with a reduction in costs supports the recommendation for a widespread implementation of clinical pharmacists’ anticoagulation management.

Other Activities

Clinical pharmacy services are not limited to the above-mentioned activities. Among the ever-expanding roles that clinical pharmacists implement in the health care system, therapeutic drug monitoring and managing of patients’ pharmacotherapy are of great importance inasmuch as they can significantly improve patient care. Any changes in patients’ situations can create alterations to the pharmacokinetic and pharmacodynamic of medications. The presence of clinical

pharmacists can be helpful in such circumstances, for these changes normally necessitate modification in drug dosing.

Perioperative and postoperative management of patients undergoing cardiac surgery is another area where clinical pharmacists can come to the aid of physicians, not least in determining the optimal time for the cessation and re-initiation of the medications that patients receive before surgery and thus reducing drug-related complications.

Conclusion

Cumulative evidence in the existing literature supports the benefits of the presence of clinical pharmacists in a hospital setting, and in particular, in cardiology wards. Clinical pharmacists’ participation in medical rounds can be helpful in the prevention of medication errors and their expertise in pharmacotherapy can assist in managing drug therapy based on patient-specific factors. Improvements in patients’ safety, level of care, and anticoagulant management in addition to better control of cardiovascular risk factors and reduction in health care costs justify the need for active collaboration between clinical pharmacists and physicians in the management of patients with cardiovascular diseases.

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48. Neto PR, Marusic S, de Lyra Júnior DP, Pilger D, Cruciol-Souza JM, Gaeti WP, Cuman RK. Effect of a 36-month pharmaceutical care program on the coronary heart disease risk in elderly diabetic and hypertensive patients. J Pharm Pharm Sci 2011;14:249-263.

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56. Machado M, Nassor N, Bajcar JM, Guzzo GC, Einarson TR. Sensitivity of patient outcomes to pharmacist interventions. Part III: systematic review and meta-analysis in hyperlipidemia management. Ann Pharmacother 2008;42:1195-1207.

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58. Bozovich M, Rubino CM, Edmunds J. Effect of a clinical pharmacist-managed lipid clinic on achieving National Cholesterol Education Program low-density lipoprotein goals. Pharmacotherapy 2000;20:1375-1383.

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60. Jaarsma T, Haaijer-Ruskamp FM, Sturm H, Van Veldhuisen DJ. Management of heart failure in The Netherlands. Eur J Heart Fail 2005;7:371-375.

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63. Eggink RN, Lenderink AW, Widdershoven JW, van den Bemt PM. The effect of a clinical pharmacist discharge service on medication discrepancies in patients with heart failure. Pharm World Sci 2010;32:759-766.

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TEHRAN HEART CENTER

Effectiveness of Two-Year versus One-Year Use of Dual Antiplatelet Therapy in Reducing the Risk of Very Late Stent Thrombosis after Drug-Eluting Stent Implantation

*Corresponding Author: Tahereh Davarpasand, Cardiology Department, Tehran Heart Center, North Kargar Street, Tehran, Iran. 1411713138. Tex: +98 21 88029256. Fax: +98 21 88029256. E-mail: [email protected].

Hamid Reza Poorhosseini, MD, Seyed Kianoosh Hosseini, MD, Tahereh Davarpasand, MD*, Masoumeh Lotfi Tokaldany, MD, MPH, Mojtaba Salarifar, MD, Seyed Ebrahim Kassaian, MD, Mohammad Alidoosti, MD, Younes Nozari, MD, Ebrahim Nematipour, MD, Ali Mohammad Haji Zeinali, MD, Hasan Aghajani, MD, Ali Reza Amirzadegan, MD

Original Article


Received 20 September 2011; Accepted 05 February 2012

Abstract

Background: Impact of 12 months’ versus 24 months’ use of dual antiplatelet therapy on the prevalence of stent thrombosis in patients undergoing percutaneous coronary intervention (PCI) with the drug-eluting stent (DES) is not clear. As a result, duration of dual antiplatelet therapy is still under debate among interventionists.

Methods: From March 2007 until August 2008, all consecutive patients with successful PCI who received at least one DES and were treated with dual antiplatelet therapy (Clopidogrel + Aspirin) were included. All the patients were followed up for more than 24 months (mean = 35.27 ± 6.91 months) and surveyed for very late stent thrombosis and major cardiovascular events.

Results: From 961 patients eligible for the study, 399 (42%) discontinued Clopidogrel after 12 months and 562 (58%) continued Clopidogrel for 24 months. The clinical and procedural variables were compared between the two groups. In the 12 months’ use group, two cases of definite thrombosis occurred at 18 and 13 months post PCI. In the 24 months’ use group, 2 cases of definite thrombosis occurred at 14 and 28 months post PCI, one of them with stenting in a bifurcation lesion. Five cases of probable stent thrombosis were detected at 21, 28, 32, 33, and 34 months after the procedure. It is of note that amongst the 10 cases of stent thrombosis, only 1(10%) thrombosis occurred when the patient was on Clopidogrel and Aspirin and all the other 9 (90%) cases of thrombosis appeared after the discontinuation of the dual antiplatelet therapy.

Conclusion: Extended use of dual antiplatelet therapy (for more than 12 months) was not significantly more effective than Aspirin monotherapy in reducing the risk of myocardial infarction or stent thrombosis, death from cardiac cause, and stroke.


This paper should be cited as: Poorhosseini HR, Hosseini SK, Davarpasand T, Lotfi Tokaldany M, Salarifar M, Kassaian SE, Alidoosti M, Nozari Y, Nematipour E, Haji Zeinali AM, Aghajani H, Amirzadegan AR. Effectiveness of Two-Year versus One-Year Use of Dual Antiplatelet Therapy in Reducing the Risk of Very Late Stent Thrombosis after Drug-Eluting Stent Implantation. J Teh Univ Heart Ctr 2012;7(2):47-52.

Keywords: Drug-eluting stents • Clopidogrel • Angioplasty • Thrombosis

48

The Journal of Tehran University Heart Center Hamid Reza Poorhosseini et al.

IntroductionIt has been demonstrated that the implantation of the

drug-eluting stent (DES) reduces the angiographic restenosis and the need for repeat revascularization compared with the bare metal stent.1-6 However, the use of the DES results in a prothrombothic environment, predisposing the patient to late stent thrombosis.7, 8 Clopidogrel and Aspirin are the major antiplatelet drugs for the prevention of stent thrombosis. The risk of early thrombosis events amongst patients with the DES is remarkably reduced by dual antiplatelet therapy.9,

10 According to the current guidelines, antiplatelet therapy is needed for at least 9 to 12 months after the implantation of the DES;11 still, reports of late and very late stent thrombotic events have raised doubts about whether this regimen is sufficient.12, 13 One recent report suggested that although a two-year dual antiplatelet regimen with Aspirin and Clopidogrel could prevent the occurrence of very late stent thrombosis after percutaneous coronary intervention (PCI) with the DES,14 the role of a longer use of Clopidogrel in preventing very late stent thrombosis (one year after angioplasty) needs to be proved. In a recent study, the use of dual antiplatelet therapy for more than 12 months in patients with the DES was not more effective than Aspirin monotherapy in reducing the rate of myocardial infarction or cardiac death.15

The aim of this study was to compare the impact of 12 months’ versus 24 months’ use of dual antiplatelet therapy on the prevalence of stent thrombosis in patients undergoing PCI with DES implantation.

Methods

From March 2007 until August 2008, all consecutive patients who underwent successful PCI in Tehran Heart Center, received at least one DES, were treated with dual antiplatelet therapy (Clopidogrel + Aspirin), and were free of major adverse cardiac or cerebrovascular events for a 12-month period after angioplasty were included in this study. Patients were excluded if there was an occurrence of a cardiogenic shock before the procedure, a major complication in the laboratory (death, Q wave myocardial infarction, emergency open cardiac surgery, and cerebrovascular accident), and contraindications to the use of antiplatelet drugs. This study was approved by our institutional review board for the human research. Pre-procedural and procedural information was drawn from the PCI registry of Tehran Heart Center.

The procedural description and detailed definition of the pre- and post-procedural variables in our data registry can be found in our previous studies.16, 17 In summary, all the PCIs were performed using an arterial access via the standard techniques. The patients received 325 mg of Aspirin before

the procedure, and coronary stenting was performed via the routine methods. Following stent placement, the patients received dual antiplatelet therapy with Aspirin (100 mg/day) and Clopidogrel (75 mg/day) for at least 12 months after the implantation of DES.

Given the controversy in recent years over the time course of the dual antiplatelet therapy use, from 2008 our patients were advised to receive Clopidogrel for either 24 months or 12 months at the interventionists’ discretion. Thus, the patients were divided into two groups: those receiving Aspirin and Clopidogrel for 24 months and those receiving Aspirin and Clopidogrel for 12 months.

The patients were visited in the outpatient clinic 1, 6, and 12 months after PCI regularly and annually thereafter. At these visits, clinical status, all interventions, outcome events, and adverse events were recorded. Those who did not come to the clinic were followed up by telephone and were questioned about the discontinuation time of Clopidogrel and any event. In the case of hospitalization due to myocardial infarction in centers other than our institution, the patients were asked to refer to our outpatient clinic together with all their records of detailed clinical and procedural information during that hospitalization. Patients who interrupted the antiplatelet therapy before the completion of the above-mentioned duration were excluded. Withdrawal of antiplatelet therapy was defined as the interruption of antiplatelet therapy for 7 days regardless of the cause.

The follow-up data were evaluated in detail for death, myocardial infarction, repeated revascularization either via PCI or coronary artery bypass grafting, and cerebrovascular accident during the follow-up period. The end goal of our study was the occurrence of stent thrombosis, defined in accordance with the previously published criteria.18 The primary endpoint was the first occurrence of myocardial infarction or death from a cardiac cause. The principal secondary endpoints were death from any cause, stroke, and stent thrombosis.

All deaths were considered to be from a cardiac cause unless an unequivocal non-cardiac cause could be established. Definite stent thrombosis was defined as in-stent thrombosis, with or without vessel occlusion, confirmed by angiography or by pathological examination.

Probable stent thrombosis, defined as myocardial infarction or death in the first 30 days after the procedure, was not included because the focus of our study was on later events (after a one-year follow-up). Possible stent thrombosis was defined as myocardial infarction in the distribution of the targeted vessel, where stent thrombosis was not angiographically confirmed and in the absence of any other obvious cause.

The continuous variables are presented as mean ± standard deviation. The groups were compared using the Student t-test. The categorical variables are presented by frequencies, and the proportions were compared using the Chi-square test

TEHRAN HEART CENTER


Effectiveness of Two-Year versus One-Year Use of Dual Antiplatelet Therapy ...

patients in group 2 underwent primary PCI. The baseline clinical and procedural characteristics of the two study groups are summarized in Table 1. In each group, more than half of the patients had multi-vessel coronary artery disease, and one quarter underwent multi-vessel PCI. No significant difference was observed in terms of the clinical and procedural variables between the two groups. Table 2 demonstrates the distribution of the different DESs in each group. The paclitaxel-eluting stent was the most common type of the DES utilized.

The mean follow-up time was 35.27 ± 6.91 months for all the patients: 35.55 ± 6.63 months for the 12 months’ use group and 35.07 ± 7.10 months for the 24 months’ use group. During the follow-up period, 11 (1.1%) patients died, 6 (0.6%) of them from cardiac causes. Twelve (1.2%) patients had an acute myocardial infarction and 4 (0.4%) had a stroke. Three patients underwent primary PCI and none of them developed complications. The rate of thrombosis was 10/961 (1%): 4 (0.4%) were definite and 6 (0.6%) were possible cases of stent thrombosis. Repeat revascularization was performed in 22 (2.3%) patients.

After the two-year follow-up period, there was no significant difference with respect to the survival and treatment effects between the two groups (Table 3).

and Fisher exact test when the expected frequency was less than 5. Event-free survival analysis was performed using the Kaplan-Meier method with log-rank test group comparison. The statistical analyses were carried out with SPSS 15.0 (SPSS, Inc., Chicago, Illinois), and p values < 0.05 (two tailed) were considered statistically significant.

Results

A total of 961 (83.27%) of the 1154 patients, who underwent angioplasty in our center between March 1st, 2007 and August 31st, 2008, were eligible to be enrolled in this study. The patients were categorized into two groups according to the duration of their dual antiplatelet therapy.

The mean age was 57 years, and 31% of the patients were women. Group 1 included 399 (42%) patients who stopped Clopidogrel after 12 months and group 2 consisted of 562 (58%) patients who received Clopidogrel for 24 months (100% of the patients were on Clopidogrel and Aspirin at the defined time for each group). From these, 852 (88.7%) patients received one and 109 (11.3%) more than one DES and 69 (7.2%) patients received bare metal stents in addition to the DES. One (3%) patient in group 1 and two (4%)

Table 1. Demographic, clinical and procedural characteristics of study population*

12 months 24 months P valueClinical characteristics

Mean age (y) 57.54±10.06 57.66±9.10 0.854Female 124 (31.1) 178 (31.7) 0.845Previous myocardial infarction 179 (45.1) 232 (41.5) 0.270Diabetes mellitus 132 (33.2) 167 (29.8) 0.260Hypertension 185 (46.6) 267 (47.7) 0.742Hypercholesterolemia 288 (72.5) 375 (67) 0.065Renal failure 6 (1.5) 3 (0.5) 0.123

Angiographic and procedural characteristicsMulti-vessel coronary disease 217 (54.4) 333 (59.3) 0.140Left ventricular ejection fraction 52.16±9.02 51.66±9.57 0.431Treated vessel

Left anterior descending 276 (62.3) 404 (63.1) 0.783Circumflex 60 (13.5) 84 (13.1) 0.842Right coronary 97 (21.9) 137 (21.4) 0.847Left main 1 (0.2) 2 (0.3) 0.999Saphenous vein graft 9 (2.0) 12 (1.9) 0.825

More than one DES implanted 41 (10.3) 68 (12.1) 0.380Concomitant BMS implanted 24 (6.0) 45 (8.0) 0.239Ostial lesion 21 (4.7) 47 (7.3) 0.082Bifurcation lesion 49 (11.1) 54 (8.4) 0.148At least one lesion type B2/C 351 (88.2) 507 (90.2) 0.316Total occlusion 33 (7.4) 51 (8.0) 0.753Multi-vessel PCI 92 (23.1) 125 (22.2) 0.766Mean RVD 3.12±0.37 3.15±0.36 0.205Mean stent length 31.85±13.47 31.96±13.37 0.901Mean Lesion length 26.24±8.64 26.19±8.35 0.928

*Data are presented as mean±SD or n (%) DES, Drug-eluting stent; BMS, Bare metal stent; PCI, Percutaneous coronary intervention; RVD, Reference vessel diameter

50


Table 2. Comparison of different types of drug-eluting stents between patients receiving 12 months’ and 24 months’ dual antiplatelet therapy*

12 months 24 months P valuePaclitaxel 234 (51.7) 302 (46.5) 0.094Sirolimus 76 (16.8) 104 (16.0) 0.740Zotarolimus 72 (15.9) 119 (18.3) 0.292Everolimus 62 (13.7) 105 (16.2) 0.256Others 9 (2.0) 19 (2.9) 0.329

*Data are presented as n (%)

Table 3. Comparison of major cardiac events between patients receiving 12 months' and 24 months' dual antiplatelet therapy*

12 months 24 months P valueCardiac death 1 (0.3) 5 (0.9) 0.378Myocardial Infarction 3 (0.8) 9 (1.6) 0.378Revascularization (CABG or PCI) 11 (2.8) 11 (2..0) 0.414Definite stent thrombosis 2 (0.5) 2 (0.4) 0.999Total stent thrombosis 3 (0.8) 7 (1.2) 0.536Cerebrovascular accident 0 4 (0.7) 0.146

*Data are presented as n (%)CABG, Coronary artery bypass grafting; PCI, Percutaneous coronary intervention

In the 12 months’ use group, two cases of definite thrombosis occurred at 18 and 13 months post PCI. One possible case of stent thrombosis was observed in this group after 30 months; this patient had stenting in a bifurcation lesion. In the 24 months’ use group, two definite cases of stent thrombosis occurred at 14 and 28 months post PCI; one had stenting in a bifurcation lesion. Overall, five cases of possible stent thrombosis were detected at 21, 28, 32, 33, and 34 months after the procedure. It is deserving of note that amongst the 10 cases of stent thrombosis, only 1 (10%) thrombosis occurred when the patient was on Clopidogrel and Aspirin and all the other 9 (90%) cases of stent thrombosis appeared after the discontinuation of the dual antiplatelet therapy. All of the 10 patients received DES implantation.

The Kaplan-Meier estimates of freedom from total and definite stent thrombosis and major cardiac adverse events are depicted in Figures 1 and 2.

There was no significant difference between the two treatment groups as regards the risk of primary and secondary endpoints. However, amongst the patients assigned to receive dual antiplatelet therapy, as compared with those receiving Aspirin alone, there was a non-significant increase in the risk of myocardial infarction, stoke, thrombosis, and death.

Discussion

In this study, we found no significant benefit associated with Clopidogrel continuation (use of Clopidogrel plus

Hamid Reza Poorhosseini et al.

Aspirin) as compared with Clopidogrel discontinuation (use of Aspirin alone) after 12 months in reducing the incidence of stent thrombosis, myocardial infarction, stroke, death, and repeat revascularization. The occurrence of the endpoints was higher with Clopidogrel plus Aspirin than that with Aspirin alone, but this difference was not significant.

A

BFigure 1. The Kaplan-Meier estimates of total thrombosis free (A) and definite thrombosis free (B) survival

TEHRAN HEART CENTER


Effectiveness of Two-Year versus One-Year Use of Dual Antiplatelet Therapy ...

A

BFigure 2. The Kaplan-Meier estimates of primary end point free (cardiac death and myocardial infarction [MI]) (A) and secondary end point free (cerebrovascular [CVA], thrombosis and total death) (B) survival

Our findings showed that the rate of stent thrombosis in patients who underwent successful DES implantation was 1%. Moreover, 90% of the cases of stent thrombosis occurred after the discontinuation of the dual antiplatelet therapy either after 12 months’ or after 24 months’ use.

The rate of stent thrombosis was between 0% and 2% in previous reports.19 Total stent thrombosis after 6 months’ follow-up in patients undergoing DES implantation who received dual antiplatelet therapy for at least 6 months was 1% in the Ong et al. study.20 In line with their findings, in the present study the overall rate of stent thrombosis in patients receiving the DES and at least 2 years of dual antiplatelet therapy was 1% during a mean follow-up time of 35 months.

Park et al.21 reported that Clopidogrel continuation for more than one year did not decrease stent thrombosis and clinical events after DES implantation, and findings by Roy et al.16 showed that the discontinuation of Clopidogrel during a 12-month period after PCI was not predictive of stent thrombosis. In the present study, 90% of the stent thrombosis events occurred after the discontinuation of Clopidogrel either after 12 months’ or after 24 months’ use of this drug, which bears out the findings of a study by Eisenstein et al.,17 who concluded that in patients receiving PCI, the long-term risk for death and major cardiac events was significantly increased amongst patients in the DES group who had discontinued Clopidogrel therapy at 6 or 12 months. Both results are in favor of the idea that the DES may require protracted and possibly indefinite Clopidogrel therapy, although larger studies17 have suggested that all patients with the DES may benefit from receiving Clopidogrel for up to 24 months after PCI. These results have led to uncertainty about the minimal necessary duration of dual antiplatelet therapy after the implantation of the DES. Our study suggests that the discontinuation of Clopidogrel therapy after approximately one year might have a favorable risk-benefit ratio. Be that as it may, our study is limited by a lack of randomization and by selection bias (longer dual antiplatelet therapy in high-risk patients for stent thrombosis) as well as a small number of patients and a relatively short follow-up period. Because of the small number of the primary and secondary end points, these findings should be interpreted with caution and the interpretation must be speculative, although a similar result was reported in the Park et al. study.15 Some other limitations of our study should also be taken into consideration: due to the small size of the study population and the small number of the cardiac event rates, our study was underpowered and thus unable to detect a clinically significant difference in the outcomes. Our findings should be confirmed or refuted through larger randomized, clinical trials with long-term follow-up periods.

Conclusion

In our study, the extended use of dual antiplatelet therapy (for more than 12 months) was not significantly more effective than Aspirin monotherapy in reducing the risk of myocardial infarction or stent thrombosis, death from cardiac cause, and stroke.

52

The Journal of Tehran University Heart Center Hamid Reza Poorhosseini et al.

Our study did not have sufficient statistical power to allow for a firm conclusion regarding the safety of Clopidogrel discontinuation after 12 months. Larger clinical trials will, therefore, be necessary to resolve this issue.

Acknowledgements

We would like to thank Miss Fatemeh Esfahani and Mina Pashang for their kind assistance in data gathering and Dr. Mahmood Sheikh Fathollahi for his assistance in data analysis.

References1. Babapulle MN, Eisenberg MJ. Coated stents for the prevention of

restenosis: part II. Circulation 2002;106:2859-2866.2. Colombo A, Drzewiecki J, Banning A, Grube E, Hauptmann K,

Silber S, Dudek D, Fort S, Schiele F, Zmudka K, Guagliumi G, Russell ME. Randomized study to assess the effectiveness of slow- and moderaterelease polymer-based paclitaxel-eluting stents for coronary artery lesions. Circulation 2003;108:788-794.

3. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315-1323.

4. Stone GW, Ellis SG, O’Shaughnessy CD, Martin SL, Satler L, McGarry T, Turco MA, Kereiakes DJ, Kelley L, Popma JJ, Russell ME. Paclitaxeleluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial. JAMA 2006;295:1253-1263.

5. Babapulle MN, Joseph L, Belisle P, Brophy JM, Eisenberg MJ. A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents. Lancet 2004;364:583-591.

6. Alidoosti M, Salarifar M, Haji-Zeinali AM, Kassaian SE, Dehkordi MR, Fathollahi MS. Clinical outcomes of drug-eluting stents compared with bare metal stents in our routine clinical practice. Hellenic J Cardiol 2008;49:132-138.

7. Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, Gold HK, Virmani R. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 2007;115:2435-2441.

8. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006;48:193-202.

9. Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, Rumsfeld JS, Messenger JC, Khanal S, Peterson ED, Bach RG, Krumholz HM, Cohen DJ. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug eluting stent placement: results from the PREMIER registry. Circulation 2006;113:2803-2809.

10. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126-2130.

11. King SB, III, Smith SC, Jr, Hirshfeld JW, Jr, Jacobs AK, Morrison DA, Williams DO, Feldman TE, Kern MJ, O’Neill WW, Schaff HV, Whitlow PL; ACC/AHA/SCAI, Adams CD, Anderson JL, Buller CE, Ceager MA, Ettanger SM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Page RL,

Riegel B, Tarkington LG, Yancy CW. 2007 Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol 2008;51:172-209.

12. Butler MJ, Eccleston D, Clark DJ, Butler MJ, Eccleston D, Clark DJ, Ajani AE, Andrianopoulos N, Brennan A, New G, Black A, Szto G, Reid CM, Yan BP, Shaw JA, Dart AM, Duffy SJ; Melbourne Interventional Group. The effect of intended duration of clopidogrel use on early and late mortality and major adverse cardiac events in patients with drug-eluting stents. Am Heart J 2009;157:899-907.

13. Weideman RA, Little BB, Kelly KC, Rao SV, Reilly RF, Brilakis ES. Comparison of the impact of short (<1 year) and long term (> or =1year) clopidogrel use following percutaneous coronary intervention on mortality. Am J Cardiol 2008;102:1159-1162.

14. Tanzilli G, Greco C, Pelliccia F, Pasceri V, Barillà F, Paravati V, Pannitteri G, Gaudio C, Mangieri E. Effectiveness of two-year clopidogrel + aspirin in abolishing the risk of very late thrombosis after drug-eluting stent implantation (from the TYCOON [two-year ClOpidOgrel need] study). Am J Cardiol 2009;104:1357-1361.

15. Park SJ, Park DW, Kim YH, Kang SJ, Lee SW, Lee CW, Han KH, Park SW, Yun SC, Lee SG, Rha SW, Seong IW, Jeong MH, Hur SH, Lee NH, Yoon J, Yang JY, Lee BK, Choi YJ, Chung WS, Lim DS, Cheong SS, Kim KS, Chae JK, Nah DY, Jeon DS, Seung KB, Jang JS, Park HS, Lee K. Duratin of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 2010;362:1374-1382.

16. Roy P, Bonello L, Torguson R, Okabe T, Pinto Slottow TL, Steinberg DH, Kaneshige K, Xue Z, Satler LF, Kent KM, Suddath WO, Pichard AD, Lindsay J, Waksman R. Temporal relation between clopidogrel cessation and stent thrombosis after drug-eluting stent implantation. Am J Cardiol 2009;103:801-805.

17. Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, Mark DB, Kramer JM, arrington RA, Matchar DB, Kandzari DE, Peterson ED, Schulman KA, Califf RM. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA 2007;297:159-168.

18. Mauri L, Hsieh WH, Massaro JM, Ho KK, D’Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007;356:1020-1029.

19. Moreno R, Fernandez C, Hernandez R, Alfonso F, Angiolillo DJ, Sabate M, Escaned J, Banuelos C, Fernandez-Ortiz A, Macaya C. Drug-eluting stent thrombosis: results from a pooled analysis including 10 randomized studies. J Am Coll Cardiol 2005;45:954-959.

20. Ong AT, Hoye A, Aoki J, van Mieghem CA, Rodriguez Granillo GA, Sonnenschein, Regar E, McFadden EP, Sianos G, van der Giessen WJ, de Jaegere PP, de Feyter P, van Domburg RT, Serruys PW. Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus, or paclitaxel stent implantation. J Am Coll Cardiol 2005;45:947-953.

21. Park DW, Yun SC, Lee SW, Kim YH, Lee CW, Hong MK, Cheong SS, Kim JJ, Park SW, Park SJ. Stent thrombosis, clinical events, and influence of prolonged clopidogrel use after placement of drug-eluting stent: data from an observational cohort study of drug-eluting versus bare-metal stents. J Am Coll Cardiol Intv 2008;1:494-503.


TEHRAN HEART CENTER

Original Article

A Comparison of Selenium Concentrations between Con-gestive Heart Failure Patients and Healthy Volunteers

*Corresponding Author: Ebrahim Salehifar, Associate Professor of Clinical Pharmacy, Department of Clinical Pharmacy, Thalassemia Research Center, Mazandaran University of Medical Sciences, Faculty of Pharmacy, Km 18 Khazarabad Road, Khazar Sq., Sari, Iran. 4818893716. Tel: +98 15 13543081. Cell Phone: +98 911 1544526. Fax: +98 15 13543084. E-mail: [email protected].

Ali Ghaemian, MD1, Ebrahim Salehifar, PharmD2*, Hanieh Shiraj, MD3, Zeinolabedin Babaee, MD4

1Mazandaran Heart Center, Mazandaran University of Medical Sciences, Sari, Iran.2Mazandaran University of Medical Sciences, Thalassemia Research Center, Sari, Iran.3Shafa General Hospital, Sari, Iran.4Mazandaran University of Medical Sciences, Sari, Iran.

Received 21 September 2011; Accepted 10 February 2012

Abstract

Background: Selenium (Se) is an essential trace element mainly obtained from seafood, meat, and cereals. Se deficiency has been identified as a major contributing factor in the pathogenesis of certain congestive heart failure (CHF) syndromes. Since there is controversy over the prevalence of Se deficiency among patient with CHF, the aim of this study was to assess the serum Se concentrations in patients with CHF and compared them with the Se status of healthy controls.

Methods: The study included 77 patients (age, 68.4 ± 10.4 years old; 40.3% female) and 73 healthy volunteers (64.9 ± 4.7 years old; 35.6% female). A complete medical/drug history and physical examination were performed for all patients and healthy volunteers. All patients had symptoms and signs of CHF and had a left ventricular ejection fraction (EF) of < 40% obtained by echocardiography. The Se concentration was assessed by atomic absorption spectrometer with the Graphite Tube Atomizer. The limit of measurement was 5 μg/L.

Results: The Se concentrations in CHF patients did not show a significant difference from those of healthy controls (185.9 ± 781.2 μg/L vs. 123.3 ± 115.5 μg/L, respectively; p value = 0.499). There was no correlation between serum Se concentrations and EF in both the normal group and the patients with heart failure (p value = 0.96 and 0.99; r = 0.006 and 0.002 for patients and healthy volunteers, respectively).

Conclusion: In this study, serum Se levels in CHF patients were similar to those of controls and the Se concentrations did not correlate with the degree of left ventricular dysfunction.


This paper should be cited as: Ghaemian A, Salehifar E, Shiraj H, Babaee Z. A Comparison of Selenium Concentrations between Congestive Heart Failure Patients and Healthy Volunteers. J Teh Univ Heart Ctr 2012;7(2):53-57.

Keywords: Selenium • Heart failure • Atrial fibrillation

Introduction

Chronic heart failure (CHF) is the common end-result of many cardiovascular diseases. Despite the improvements

in the methods of prevention and the new strategies in the treatment of patients, the incidence of CHF is increasing in many countries.1, 2 In recent years, the focus of research for the treatment of CHF patients has been on drug therapies

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The Journal of Tehran University Heart Center Ali Ghaemian et al.

and devices, while other factors may affect the rise in the number of CHF patients. For example, oxidative stress may contribute to the pathogenesis of CHF;3, 4 and some clinical and experimental studies have shown that in CHF patients, free radical formation is increased and antioxidant defenses are reduced.3, 5, 6 Also, dietary trials that assessed the impact of high intakes of natural antioxidants showed that the incidence of CHF was reduced.7, 8

Selenium (Se), an essential trace mineral, is mainly obtained from seafood, meat, and cereals. Se deficiency has been identified as a major contributing factor in the pathogenesis of certain CHF syndromes. For instance, in areas with low soil Se contents such as eastern China and western Africa, Se deficiency is associated with cardiomyopathy.9, 10 Moreover, there are cases of cardiomyopathy associated with low Se levels in malnourished HIV-infected patients in western countries11 and in patients on chronic parenteral nutrition.12 It has also been reported that serum levels of Se were lower in idiopathic dilated and also ischemic cardiomyopathy patients compared with levels in healthy controls.13 On the other hand, in another report, the mean serum Se levels in 30 patients with idiopathic cardiomyopathy did not show any difference from those of healthy individuals.14 It has been suggested that Se may be involved in the deconditioning of skeletal and cardiac muscles and in CHF symptoms such as fatigue and low exercise tolerance, rather than in ventricular dysfunction.15, 16

Regarding the controversy over the prevalence of Se deficiency among CHF patients, the present study aimed at assessing serum Se levels in a relatively large population of advanced CHF patients and comparing them with those of healthy controls.

Methods

This study was performed at Mazandaran Heart Center, Sari, Iran, during an 11-month period beginning in March 2010. We enrolled 77 patients and 73 healthy volunteers as the control group. The patients were selected from those who were followed at the hospital clinic. All the patients had CHF symptoms and a left ventricular ejection fraction (LVEF) of < 0.40. In the CHF group, 39 patients had chronic atrial fibrillation (AF) and 38 patients were in sinus rhythm.

The patients were on medications, including angiotensin converting enzyme (ACE) inhibitors, diuretics, digitalis, beta blockers, and angiotensin receptor blockers (ARBs). The calculation of the LVEF was according to Simpson's rule.17

The healthy controls were recruited from the family members of the patients at the hospital or those undergoing cardiovascular screening at the clinic. For the control group, in addition to echocardiography, we took a complete medical and drug history and performed a complete physical

examination. None of the control group members had chronic diseases such as diabetes mellitus, hypertension, and hyperlipidemia. Nearly all the patients and controls were permanent residents in the northern part of Iran at the time of study. Electrocardiograms (ECG) and echocardiography were performed for all the subjects. All the volunteers had normal ECG and echocardiographic findings. The volunteers did not have a history of consuming ACE inhibitors, ARBs, digitalis, and diuretics and did not receive any Se-containing supplements within the prior three weeks.

A 10 ml blood sample was taken from the patients and the control group, which was then heated in special tubes of water bath (37 °C) for 1 h. The samples were centrifuged (1500 rpm) and frozen at -20 °C after serum isolation. Varian AA240FS atomic absorption spectrometer with the Graphite Tube Atomizer (Mulgrave Victoria, Australia) was used to determine Se concentrations. Five hundred micro liters of the sample were diluted with 2 ml of the Trinon-ascorbic acid reagent. A 50 ppb standard was prepared by diluting the 1000 ppm standard, with distilled water. The sample concentrations were calculated on the basis of computer-determined calibration graphs. The limit of measurement was 5 μg/L.18

Statistical analysis was performed using the SPSS 16 software. An independent samples t-test was used for the comparison of the quantitative variables between the patient and control groups. The chi-Square test was utilized for the nominal variables. The relationship between Se concentration and LVEF was assessed using Pearson’s Correlation test. A p value < 0.05 was considered significant, and the power of study was 10% (Z1-β = - 1.28).

Results

The demographic, echocardiographic data, and Se levels of “heart failure” and “control” groups are shown in Table 1. The CHF patients were more frequently diabetic. The average age of the control group was near that of the patients. The mean values of left atrial areas (LAA) and left ventricular systolic and diastolic diameters were higher in patients than in the controls, which was statistically significant.

Also, the average heart rate and systolic and diastolic blood pressures of the patients were higher than the values in the control group and it was statistically significant.

As is presented in Figure 1, the median Se concentrations in the CHF patients were not significantly different from those of the control group. Also, we did not find any statistically significant difference between the Se concentrations in the CHF patients with atrial fibrillation and those who had sinus rhythm (p value = 0.39). We also made separate comparisons between the Se concentrations in patients with and without AF and those of the control group, with the Se concentrations showing no statistically significant difference between the

TEHRAN HEART CENTER


A Comparison of Selenium Concentrations between Congestive Heart Failure ...

groups (Figure 2). There was no correlation between serum Se concentrations

and EF in both the normal group and CHF patients (p value = 0.96 and 0.99; r = 0.006 and 0.002 for patients and healthy volunteers, respectively).

Table 1. Basic demographic, clinical, and echocardiographic data as well as selenium levels of heart failure and control groups*

Heart Failure(n=77)

Control(n=73) P value**

Age (y) 68.4±10.4 64.9±4.7 0.02Female 31 (40.3) 26 (35.6) 0.55Weight 67.1±13.6 66.5±5.0 0.77Height 165.2±9.2 166.7±7.5 0.32BMI 24.4±3.7 24.0±2.2 0.46HLP 18 (25.4) - < 0.01DM 15 (18.3) - < 0.01SBP 136.4±29.1 129.2±7.5 0.04DBP 81.3±15.4 72.4±6.6 < 0.01HR 92.0±21.4 72.1±4.7 < 0.01LAA 28.5±8.2 19.5±1.1 < 0.01LVDD 61.9±8.9 49.8±1.5 < 0.01LVSD 52.4±8.7 31.4±2.3 < 0.01LVEF 25.2±6.3 54.3±2.6 < 0.01Selenium 185.9±781.2 123.3±115.5 0.49

*Data are presented as mean±SD or n (%)**P value (independent samples t-test, and Chi-Square for quantitative and qualitative variables, respectively)BMI, Body mass index; HLP, Hyperlipidemia; DM, Diabetes mellitus; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; HR, Heart rate; LAA, Left atrium area; LVDD, Left ventricle diastolic diameter; LVSD, Left ventricle systolic diameter; LVEF, Left ventricle ejection fraction

Figure1. Selenium concentrations in congestive heart failure patients versus control (P value: independent samples t-test; patients versus control)

Figure 2. Comparison between selenium concentrations in congestive heart failure (HF) patients with/without atrial fibrillation (AF) and those of the control (P value, independent samples t-test; patients of each group versus control)

Discussion

This is the first study in the northern part of Iran to compare Se concentrations in a relatively large number of CHF patients with those of a control group. Nonetheless, we did not find any significant difference between the two groups. It had previously been shown that in both CHF and healthy groups there was a similar relationship between dietary and blood Se levels.14 The northern part of Iran has a Mediterranean climate and diet. The Mediterranean diet is a Se-rich diet including seafood and vegetables, and it is considered a cardioprotective diet.8 The relatively wider dispersion of Se concentrations in CHF patients may partially be related to the consumption of a wider range of Se-containing food. However, we do not have any definite explanation as to the cause.

It is now widely accepted that diet-derived antioxidants may play a role in the development, progress, and prevention of CHF. For instance, some clinical studies have suggested that CHF may be associated with increased free radical formation and reduced antioxidant defenses.15, 19, 20 Still, it is important to know whether any specific micronutrient deficiency might have a causal relationship with CHF and/or whether it can aggravate CHF symptoms. For example, hypozincemia in CHF patients may be an effect of diuretic drugs, but there are no definite data on the clinical effect of zinc supplementation in these patients. Nevertheless, there are some CHF syndromes in which Se deficiency has been identified as a contributing factor in the etiology. For example, in China an endemic cardiomyopathy called Keshan disease has been illustrated to be the result of Se deficiency.10, 21

56


But, in Keshan disease Se levels correlate with the clinical severity of CHF, rather than the degree of left ventricular dysfunction. Interestingly though, Se supplementation resulted in a reduced mortality rate.12, 21, 22 In endemic areas, however, after raising Se levels in residents, clinically latent cases were still found. Thus, although Se deficiency can also influence the clinical severity of Keshan disease, it is not the specific etiologic factor for the occurrence of it. Also, in Western countries, cases of congestive cardiomyopathy associated with low serum vitamins and trace elements have been reported in malnourished HIV-infected patients and in subjects on chronic parenteral nutrition.15

In a relatively small number of CHF patients, de Lorgeril et al. found lower dietary intake and blood levels of Se compared with those of healthy controls.15 Also, blood levels of Se were lower in CHF patients. There was a positive correlation between Se intake and blood levels, and the low dietary intake accounted for the low blood Se levels. In our study, we did not find any statistically significant difference regarding the blood Se levels between the CHF and healthy controls. Also, the blood Se levels in both CHF and healthy controls in our study were higher than those in the study by Lorgeril et al. Thus, we think that the Mediterranean diet in the northern part of Iran, which includes seafood and vegetables, has resulted in normal, rather than deficient, blood Se levels in this area. This confirms the finding by de Lorgeril et al., who did not find a causative relationship between Se deficiency and CHF. In addition, in our study, Se concentrations did not show any association with the severity of ventricular dysfunction assessed by echocardiography. On the other hand, blood Se was strongly related to maximum oxygen consumption and exercise tolerance in CHF patients,15 and also in Keshan disease even a mild deficiency in Se could influence the severity of the disease. Be that as it may, the mechanism by which Se deficiency results in some CHF symptoms is not well defined and it has been suggested that Se may be involved in skeletal and cardiac muscle deconditioning rather than in left ventricular dysfunction.16, 21

Se is an essential trace element. Its primary role is that of an antioxidant in the enzyme glutathione peroxidase (GP), the main intracellular antioxidant. Depletion of Se leads to a decrease in GP activity. Selenoprotein P is another selenoprotein and its primary role is as an extracellular antioxidant.23 Also the Se-dependent thioredoxin reductase system may be involved in ascorbate regeneration.24 Consequently, in addition to their role in vascular endothelial function,25 selenoproteins act as antioxidants. Considering the fact that CHF is associated with peripheral vasoconstriction and impaired skeletal muscle metabolism,26 Se-dependent systems are very important defense mechanisms in humans.

However, there are some limitations to the present study. For example, the relationship between dietary and blood Se levels in CHF and healthy groups has previously been shown. In our study, we did not have a definite dietary

comparison between patients and controls; CHF patients may have been advised to take more vegetables and seafood after developing the disease.

The power of the present study is 10%. We do realize that this amount of the power is really low; it is worthy of note, however, that choosing the number of cases was based on the previous similar studies (study of Sahin et al.,13 Heart failure: n = 54, Healthy Volunteers: n = 30; study of de Lorgeril et al.,15 Heart failure: n = 21, Healthy Volunteers: n = 18). The number of cases included in our study was 77 patients and 73 healthy volunteers, which was higher than those in the aforementioned studies. The low power of our study can be explained by the great SD of the Se levels, especially in heart failure patients.

Conclusion

In conclusion, although we did not find a causal relationship between Se and CHF in the northern part of Iran, we recommend that monitoring dietary determinants can be helpful in the treatment and management of CHF patients in all areas.

Acknowledgment

This study was approved and supported by a grant from the Research and Technology Deputy of Mazandaran University of Medical Sciences.

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Sutton GC, Grobbee DE. The epidemiology of heart failure. Eur Heart J 1997;18:208-225.

2. Gheorghiade M, Bonow RO. Chronic heart failure in the United States: a manifestation of coronary artery disease. Circulation 1998;97:282-289.

3. Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A, Omran AS, Jeejeebhoy KN. Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol 1998;31:1352-1356.

4. Givertz MM, Colucci WS. New targets for heart failure therapy: endothelin, inflammatory cytokines and oxidative stress. Lancet 1998;352:34-38.

5. Bauersachs J, Bouloumi´e A, Fraccarollo D, Hu K, Busse R, Ertl G. Endothelial dysfunction in chronic myocardial infarction despite increased vascular endothelial nitric oxide synthase and soluble guanylate cyclase expression: role of enhanced vascular superoxide production. Circulation1999;100:292-298.

6. Dhalla AK, Hill M, Singal PK. Role of oxidative stress in transition of hypertrophy to heart failure. J Am Coll Cardiol 1996;28:506-514.

7. Singh RB, Rastogi SS, Verma R, Laxmi B, Singh R, Ghosh S, Niaz MA. Randomized controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow-up. Br Med J 1992;304:1015-1019.

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8. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors and the rate of cardiovascular complications after myocardial infarction. Final report of the Lyon Diet Heart Study. Circulation 1999;99:779-785.

9. Neve J. Selenium as a risk factor for cardiovascular diseases. J Cardiovasc Risk 1996;3:42-47.

10. Ge K, Yang G. The epidemiology of Se deficiency in the etiological study of endemic diseases in China. Am J Clin Nutr 1993;57:259S-263S.

11. Chariot P, Perchet H, Monnet I. Dilated cardiomyopathy in HIV-infected patients. N Engl J Med 1999;340:732-735.

12. Huttunen JK. Selenium and cardiovascular diseases. An update. Biomed Environ Sci 1997;10:220-226.

13. Sahin I, Taşkapan C. Trace element status (Se, Zn, Cu) in heart failure. Anadolu Kardiyol Derg 2006;6:216-220.

14. da Cunha S, Albanesi Filho FM, da Cunha Bastos VL, Antelo DS, Souza MM. Thiamin, Se, and copper levels in patients with idiopathic dilated cardiomyopathy taking diuretics. Arq Bras Cardiol 2002;79:454-465.

15. de Lorgeril M, Salen P, Accominotti M ,Cadau M, Steghens JP, Boucher F, de Leiris J. Dietary and blood antioxidants in patients with chronic heart failure. Insights into the potential importance of Se in heart failure. Eur J Heart Fail 2001;3:661-669.

16. de Lorgeril M, Salen P. Selenium and antioxidant defenses as major mediators in the development of chronic heart failure. Heart Fail Rev 2006;11:13-17.

17. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358-367.

18. Navarro M, Lopez H, Ruiz ML, Gonzalez S, Perez V, Lopez MC. Determination of selenium in serum by hydride generation atomic absorption spectrometry for calculation of daily dietary intake. Sci Total Environ 1995;175:245-252.

19. Shokrzadeh M, Ghaemian A, Salehifar E, Aliakbari S, Saravi SS, Ebrahimi P. Serum zinc and copper levels in ischemic cardiomyopathy. Biol Trace Elem Res 2009;127:116-123.

20. Salehifar E, Shokrzadeh M, Ghaemian A, Aliakbari S, Saeedi Saravi SS. The study of Cu and Zn serum levels in idiopathic dilated cardiomyopathy (IDCMP) patients and its comparison with healthy volunteers. Biol Trace Elem Res 2008;125:97-108.

21. de Lorgeril M, Salen P, Defaye P. Importance of nutrition in chronic heart failure patients. Eur Heart J 2005;26:2215-2217.

22. Xu GL, Wang SC, Gu BQ, Yang YX, Song HB, Xue WL, Liang WS, Zhang PY. Further investigation on the role of Se deficiency in the etiology and pathogenesis of Keshan disease. Biomed Environ Sci 1997;10:316-326.

23. Burk RF, Hill KE. Selenoprotein P. A selenium-rich extracellular glycoprotein. J Nutr 1994;124:1891-1897.

24. May JM, Mendiratta S, Hill KE, Burk RF. Reduction of dehydroascorbate to ascorbate by the selenoenzyme thioredoxin reductase. J Biol Chem 1997;272:22607-22610.

25. Drexler H. Endothelium as a therapeutic target in heart failure. Circulation 1998;98:2652-2655.

26. Okita K, Yonezawa K, Nishijima H, Hanada A, Ohtsubo M, Kohya T, Murakami T, Kitabatake A. Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure. Circulation 1998;98:1886-1891.

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Frequency and Predictors of Renal Artery Stenosis in Patients Undergoing Simultaneous Coronary and Renal Catheterization

*Corresponding Author: Mojtaba Salarifar, Mojtaba Salarifar, Associate Professor of Interventional Cardiology, Cardiology Department, Tehran Heart Center, North Kargar Street, Tehran Heart Center, Tehran, Iran. 1411713138. Tel: +98 21 88029257. Fax: +98 21 88029256. E-mail: [email protected].

Original Article


Received 29 November 2011; Accepted 27 February 2012

Abstract

Background: Atherosclerotic renal artery stenosis (ARAS) remains underdiagnosed due to its nonspecific demonstrations. We aimed to both estimate the frequency of ARAS in high-risk non-selected patients undergoing simultaneous coronary and renal catheterization and possibly identify a predictive model for ARAS using baseline clinical, laboratory, and coronary angiographic variables.

Methods: The records of 866 patients aged ≥ 21 years undergoing simultaneous coronary and renal angiography were retrieved for analysis from our computerized database. The degree of ARAS was estimated visually by experienced attending interventional cardiologists. Lesions with an estimated stenosis of ≥ 50% were considered significant. Multivariable stepwise logistic regression models were used to identify the risk factors predicting the presence and extent of ARAS.

Results: Of a total of 866 consecutive patients undergoing renal angiography in conjunction with coronary angiography (mean age ± SD: 63.06 ± 10.32, ranging from 24 to 89 years), 454 (57%) were men. A total of 345 (39.8%) cases had significant ARAS, 77 (22.3%) of which were bilateral. Using significant ARAS as the dependent variable, six variables were identified as the independent predictors significantly associated with the presence of ARAS, namely age, female sex (male sex was found to be a protector), hypertension, history of renal failure, left anterior descending artery (LAD) stenosis > 50%, and left circumflex artery (LCX) stenosis > 50%. The Gensini score was not found to be a predictor of the presence of ARAS, but it was more likely associated with a trend towards a more extensive ARAS (adjusted OR = 1.00, 95% CI = 1.00-1.01; p value = 0.039). Other independent determinants of the ARAS extent were the same as the predictors of the ARAS presence.

Conclusion: Although risk versus benefit was not tested in this study, it seems that clinicians could consider renal catheterization in combination with coronary angiography particularly in female patients with advanced age and with significant coronary artery stenoses in the LAD and LCX.


This paper should be cited as: Rokni N, Salarifar M, Hakki Kazazi E, Goodarzynejad HR. Frequency and Predictors of Renal Artery Stenosis in Patients Undergoing Simultaneous Coronary and Renal Catheterization. J Teh Univ Heart Ctr 2012;7(2):58-64.

Keywords: Renal artery obstruction • Coronary angiography • Renal insufficiency

Navid Rokni, MD, Mojtaba Salarifar, MD*, Elham Hakki Kazazi, MD, Hamidreza Goodarzynejad, MD

TEHRAN HEART CENTER


IntroductionRenal artery stenosis is a potential cause of secondary

hypertension, ischemic nephropathy, and end-stage renal disease. Atherosclerosis is by far the most common etiology of renal artery stenosis in the elderly.1, 2 Although as the narrowing of the renal artery lumen progresses, renal perfusion declines and eventually renal function and structure are compromised,3, 4 patients with atherosclerotic renal artery stenosis (ARAS) are often asymptomatic with no characteristic laboratory findings, making its early diagnosis a major clinical problem. Paradoxically, diagnosis of ARAS at an early stage is of paramount importance because despite the uncertainty that exists about the benefit of revascularization over medical therapy for ARAS,5 it has been demonstrated that timely intervention using revascularization technique, surgery, or percutaneous transluminal angioplasty (PTA) may modify the natural history and outcomes.6

ARAS and coronary artery disease (CAD) originate from similar multiple risk factors for the development of atherosclerosis so that not surprisingly patients with ARAS more commonly have CAD and vice versa.7-10 Presence of ARAS worsens the course of CAD, leading to increased risk of adverse coronary events, more frequent episodes of coronary revascularization, and higher mortality.11-13 Because of the high coexistence of CAD and ARAS in patients with angiographically documented CAD,9, 10 it has been recommended that renal angiography be performed consecutively in the same setting.14 However, operators are reluctant to perform renal angiography in combination with coronary angiography for several reasons: renal angiography is an invasive method; it can result in the dislodgment of the atheromatous debris; and it has severe complications, including contrast-associated nephropathy.

Therefore, identifying patients at high risk for ARAS in patients referred for coronary angiography is of great clinical importance and may influence treatment decisions in this population. We sought to find the independent determinants of the presence of significant stenosis in one or both renal arteries with a view to estimating the frequency of ARAS in high-risk non-selected patients undergoing simultaneous coronary and renal catheterization and possibly identifying a predictive model for ARAS using baseline clinical, laboratory, and coronary angiographic variables.

Methods

Between October 2009 and July 2011, a total of 18419 cardiac catheterizations were performed at our center. Clinical and procedural data were prospectively collected and entered into a computerized database on all patients undergoing cardiac catheterization at Tehran Heart Center. The records of 866 (4.7%) patients aged ≥ 21 years

undergoing simultaneous coronary and renal angiography, representing our study population, were retrieved for analysis. The indication for renal angiography was at the discretion of the attending interventionist, but the procedure was mostly performed in patients with severe or resistant hypertension and renal dysfunction or in those suffering from pulmonary edema with preserved systolic function. Due to the retrospective nature of the study, requirement for written informed consent was waived by the institutional Ethics Committee.

Definition of CAD risk factors has been described previously.15 In brief; analyzed risk factors of CAD included age, male sex, cigarette smoking, hyperlipidemia, diabetes, hypertension, and family history of CAD. Patients having angiographic evidence of atherosclerosis (≥ 50% luminal stenosis in at least one coronary artery or major branch segment in their epicardial coronary tree) were considered to have CAD, and patients with no luminal stenosis or patients with < 50% luminal stenosis at coronary angiography were considered to have normal coronary.

Renal function was evaluated by serum Cr and CrCl, calculated using the Cockcraft-Gault equation. In all the patients, serum Cr level in mg/dl was determined before the procedure. The following equation was used: CrCl = (140 - age [y]) × weight (kg) × 0.85 (if female) / (serum Cr [mg/dL] × 72)

The calculated value of CrCl was multiplied by the factor of 0.85 in the female patients because the proportion of muscle mass to body weight is relatively lower in women than in men. The Cockroft-Gault equation was adjusted for the body surface area (BSA) by multiplying it by (1.73/BSA) and expressed compared to the average sized man as mL/min/1.73 m2. The BSA itself was calculated using the following DuBois formula: BSA (m2) = (weight [kg]) 0.425 × (height [cm]) 0.725 × 0.007184.16

Using standard angiographic techniques, coronary angiographies were performed via the percutaneous femoral approach. The presence and severity of CAD was determined using the clinical vessel score. The angiograms were categorized as revealing < 50% luminal stenosis (minimal CAD) or as having one (mild), two (moderate), or three (severe) major epicardial coronary arteries with more than 50% luminal obstructions. The left main stem (LMS) stenosis was regarded as one vessel. If the LMS and the left anterior descending (LAD) and/or left circumflex (LCX) arteries were affected, this was counted as 2 points. The visually determined greatest reduction percentage of the luminal diameter in any view compared with the nearest normal segment was defined as the degree of stenosis.

After the completion of their cardiac catheterization procedure, the patients underwent either selective or non-selective renal angiography. Abdominal aortography was performed using a pigtail catheter and an injection of 30 to 35 ml of nonionic contrast agent (Ultravist-370, Shering AG,

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60


factors predicting the presence of ARAS were expressed as odds ratios (OR) with 95% CIs as well. Using multivariable stepwise analysis, the variables were entered into the logistic regression model based on their statistical significance in the univariable analyses (entering criterion: p value ≤ 0.15). Amongst the Cumulative Logit Models for Ordinal Responses, the Proportional Odds Model was applied for the factors associated with the extension of ARAS (the ordinal response), which is the most commonly used model as the multivariable analysis.17 In the final model, the associations between the independent predictors and the extension of ARAS were also expressed as odds ratios (OR) with 95% CIs.

For the statistical analyses, the statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL) and SAS version 9.1 for Windows (SAS Institute Inc., Cary, NC, USA) were utilized. All the p values were two-tailed, with statistical significance defined by a p value ≤ 0.05.

Results

Of a total of 866 consecutive patients undergoing renal

Germany; or Visipaque-320, GE Healthcare, Ireland) with a pump injector at a rate of 20 ml/sec. Selective angiography was encouraged in patients with renal dysfunction, hypertension, and severe CAD, and generally 5 or 6 Fr catheters - renal double curve (RDC), right Judkins coronary, or left internal mammary artery (LIMA) catheters - with hand injections of 7 to 10 ml of nonionic contrast agent (Ultravist-370, Shering AG, Germany; or Visipaque-320, GE Healthcare, Ireland) were employed in each main and accessory renal artery. The degree of ARAS was estimated visually by experienced attending interventional cardiologists. Lesions with an estimated stenosis of ≥ 50% were considered significant.

The results are reported as mean ± standard deviation (SD) for the quantitative variables, and the categorical variables are summarized by absolute frequencies and percentages. The continuous variables were compared using the one-way analysis of variance (ANOVA) or Kruskal-Wallis test, whenever the data were ordinally scaled or when equal variances assumption was violated, while the categorical variables were compared using the chi-square test or Mantel-Haenszel chi-square test for trend.

Multivariable stepwise logistic regression models for risk

Navid Rokni et al.

Table .1 Baseline clinical characteristics of the study population*

No RAS** (n=521)

Unilateral RAS (n=268)

Bilateral RAS (n=77) P value

Age (y) 61.60±10.31 64.51±10.01 67.92±9.36 <0.001

Male sex 311 (59.7) 146 (54.5) 37 (48.1) 0.093

Body mass index (kg/m2) 28.14±4.94 28.14±4.92 26.37±4.49 0.017

Waist circumference (cm) 102.18±11.38 102.26±10.48 97.42±10.99 0.009

Hypertension 393 (75.4) 228 (85.1) 66 (85.7) 0.002

Diabetes 189 (36.3) 111(41.4) 28 (36.4) 0.355

Hyperlipidemia 359 (68.9) 218 (68.8) 58 (75.3) 0.477

Current smoker 120 (23.0) 46 (17.2) 12 (15.6) 0.082

Family history of CAD 88 (16.9) 40 (14.9) 6 (7.8) 0.114

History of MI 177 (34.0) 102 (38.1) 30 (39.0) 0.431

History of renal failure 63 (12.1) 52 (19.4) 22 (28.6) <0.001

History of hemodialysis 6 (1.2) 3 (1.1) 4 (5.2) 0.042

History of PVD 29 (5.6) 19 (1.1) 9 (11.7) 0.119

History of CVA 3 (5.8) 10 (3.7) 11 (14.3) 0.002

History of heart failure 24 (4.6) 13 (4.9) 2 (2.6) 0.691

Drug history

ACE-inhibitors 213 (40.9) 123 (45.9) 36 (46.8) 0.315

Beta-blockers 398 (76.4) 204 (76.1) 56 (72.7) 0.780

Statins 319 (61.2) 173 (64.6) 43 (55.8) 0.352

Insulin 38 (7.3) 37 (13.8) 10 (13.0) 0.009

Prior PCI 32 (6.1) 18 (6.7) 3 (3.9) 0.661

Prior CABG 25 (4.8) 14 (5.2) 5 (6.5) 0.812

*Data are presented as mean ± SD or n (%)**Renal artery stenosis < 50%RAS, Renal artery stenosis; CAD, Coronary artery disease; MI, Myocardial infarction; PVD, Peripheral vascular disease; CVA, Cerebrovascular accident; ACE, Angiotensin-converting enzyme; PCI, Percutaneous coronary intervention; CABG, Coronary artery bypass graft

TEHRAN HEART CENTER



Table .2 Laboratory and coronary angiographic characteristics of the studied patients*

No RAS** (n=521)

Unilateral RAS(n= 268)

Bilateral RAS(n=77) P value

Fasting blood glucose (mg/dl) 121.52±51.55 130.26±60.79 121.14±30.39 0.132

Triglyceride (mg/dl) 159.47±92.83 173.99±151.20 160.94±82.31 0.764

HDL-cholesterol (mg/dl) 42.14±11.48 42.98±12.81 41.11±11.47 0.649

LDL-cholesterol (mg/dl) 110.55±37.96 109.80±40.11 121.19±41.07 0.153

Total cholesterol (mg/dl) 177.92±45.16 179.99±50.95 188.92±47.22 0.212

Creatinine (mg/dl) 1.27±0.81 1.49±1.29 1.66±1.49 0.001

CrCl-c ( mL/min/1.73m2 ) 69.19±27.70 60.90±29.78 49.27±21.13 <0.001

CAD vessel score <0.001

< 50% 142 (27.3) 33 (12.3) 6 (7.8)

Single-vessel disease 103 (12.8) 37 (13.8) 13 (16.9)

Two-vessel disease 94 (18.0) 56 (20.9) 15 (19.5)

Three-vessel disease 182 (34.9) 142 (53.0) 43 (55.8)

Left main 18 (3.5) 14 (5.2) 6 (7.8) 0.161

LAD 329 (63.1) 213 (79.5) 64 (83.1) <0.001

LCX 246 (47.2) 188 (80.1) 53 (68.8) <0.001

RCA 262 (50.3) 174 (64.9) 55 (71.4) <0.001

Gensini score 52.37±52.29 72.24±58.35 83.79±66.33 <0.001

LVEF (%) 50.05±11.63 49.46±11.34 48.40±11.74 0.312

HbA1c (%) 8.09±1.75 7.91±1.54 7.96±1.77 0.870*Data are presented as mean ± SD or n (%)**Renal artery stenosis < 50%RAS, Renal artery stenosis; HDL, High-density lipoprotein; LDL, Low-density lipoprotein; CrCl-c; Creatinine clearance corrected for body surface area; CAD, Coronary artery disease; LAD, Left anterior descending; LCX, Left circumflex artery; RCA, Right coronary artery; LVEF, Left ventricular ejection fraction; HbA1c; Hemoglobin A1c

Table 3. Multivariable-adjusted predictors for renal atherosclerosis presence and extent separately

PredictorsPresence of RAS Extent of RAS

OR (95% CI) P value OR (95% CI) P value

Age (y) 1.03 (1.02-1.05) <0.0001 1.04 (1.02-1.05) <0.0001

Male sex 0.60 (0.44-0.82) 0.0039 0.58 (0.43-0.78) 0.0004

Hypertension 1.67 (1.13-2.47) 0.0005 1.62 (1.11-2.38) 0.0129

History of RF 1.82 (1.22-2.70) 0.0064 1.82 (1.26-2.64) 0.0015

LAD vessel disease 1.67 (1.14-2.45) 0.0081 1.52 (1.03-2.26) 0.0345

LCX vessel disease 2.04 (1.45-2.88) <0.0001 1.61 (1.11-2.32) 0.0113

Gensini score - - 1.00 (1.00-1.01) 0.0392RAS, Renal artery stenosis; OR, Odds ratio; CI, Confidence interval; RF, Renal failure; LAD, Left anterior descending; LCX, Left circumflex

angiography in conjunction with coronary angiography (mean age ± SD: 63.06 ± 10.32, ranging from 24 to 89 years), 454 (57%) were men. A total of 345 (39.8%) cases had significant ARAS, 77 (22.3%) of which were bilateral. On coronary angiography, 9.1% had normal coronary arteries and 11.8% had minimal coronary artery disease. One-vessel, two-vessel, and three-vessel disease were detected in 17.7%, 19.1%, and 42.4% of the patients, respectively. The baseline clinical characteristics of the studied patients according to the presence and extent of ARAS are presented in Table 1. Patients with ARAS were older, more hypertensive, and more likely to have a previous history of myocardial infarction, cerebrovascular accident,

renal failure, and hemodialysis. They also more commonly received insulin therapy. Patients without ARAS (n = 521) as compared to patients with uni- or bilateral RAS (n = 345) had statistically similar BMI (28.14 ± 4.94 vs. 27.74 ± 4.88, p value = 0.204) (not shown in Table 1).

Table 2 shows that unsurprisingly, the serum level of creatinine was significantly greater in the ARAS group than that in the No ARAS group, while the opposite was true for creatinine clearance. Although the involvement of the left main did not differ between the groups, significant ARAS was more frequently seen in the patients with three-vessel disease or in those with the involvement of each main coronary artery. Severity of CAD, reflected by the Gensini

62


score, was also higher in the ARAS group than in those without significant renal stenosis. Moreover, there was a strongly significant linear trend of higher Gensini score with increasing ARAS extent - from No ARAS to unilateral and from unilateral to bilateral RAS - (p value < 0.001 for the Mantel-Hanzel Test of Linear Trend).

In the multivariable logistic regression model, using significant ARAS as the dependent variable, six variables were identified as the independent predictors significantly associated with the presence of ARAS, namely age, female sex (male sex was found to be a protector), hypertension, history of renal failure, LAD stenosis > 50%, and LCX stenosis > 50% (Table 3). The predictive performance of the risk model assessed by using the area under the ROC curve (AUC) was good (c = 0.7). Because Hosmer-Lemeshow p value was 0.52 (p value < 0.05 indicates a poor fit), the model was also found to fit the data well. As can be seen in Table 3, according to the Proportional Odds model, the Gensini score was more likely to be associated with a trend towards more extensive ARAS (adjusted OR = 1.00, 95% CI = 1.00-1.01; p value = 0.039). The other independent determinants of the ARAS extent were the same as the predictors of the ARAS presence.

Discussion

In the present study, we investigated patients undergoing simultaneous coronary and renal angiography and found that angiographically evident ARAS (defined as lumen occlusion ≥ 50%) was common (near 40%) in this group of patients. Moreover, we included clinical and coronary angiographic variables in a multivariable regression model to predict ARAS in the studied patients. Six variables, i.e. age, female sex, hypertension, history of renal failure, LAD stenosis ≥ 50%, and LCX stenosis ≥ 50% were found to be the independent predictors of the ARAS presence. The Gensini sore in addition to the six aforementioned variables constituted the seven independent predictors of the ARAS extent in our study population.

The prevalence of significant ARAS in patients undergoing coronary angiography for suspected CAD has been estimated to range from 3% to near 20%.18 The high prevalence of ARAS in our study can de explained by the fact that we performed renal angiography mostly in patients with severe or resistant hypertension and renal dysfunction or in those suffering from pulmonary edema with preserved systolic function. This finding is in accordance with that of a previous study examining a contemporary coronary angiography population by using protocol-based patient selection and catheterization.19

Several previous investigators have suggested that a strong association exists between ARAS and CAD.4, 9, 12,

18-24 In a most recent study on 492 consecutive patients

referred for cardiac catheterization, significant two-vessel and three-vessel CAD were found to be strong predictors of the presence of ARAS.18 We found that the LAD and LCX stenoses were the independent predictors of ARAS, indicating that patients with a combination of the LAD and LCX two-vessel disease as well as patients with three-vessel disease are at higher risk for the presence of ARAS. Weber-Mzell et al.9 also found the LAD, LCX, and RCA stenoses to be more frequent in patients with significant ARAS in the uni- but not multivariable analysis. However, they showed that having more extensive coronary lesions was an independent predictor of ARAS. In another study, the LAD disease was univariately more frequent in patients with significant ARAS (defined as stenosis > 75%) but only three-vessel disease remained as independent predictor in the multivariable model.12 The severity of CAD as assessed by the Gensini score was not a predictor of significant ARAS, but it independently predicted the extent of ARAS in our study population.

In line with most of the studies that found older age as an independent predictor of ARAS,10, 18, 25, 26 age was strongly and independently associated with ARAS in our study population. In this study, female sex was also significantly associated with ARAS. Wang et al. explained this association by the more advanced age of their female as compared to male patients. It is intriguing that after adjusting for age, CAD severity (by using the Gensini score), and other factors, our multivariable model revealed a strong association between ARAS and female gender, which is of particular interest insofar as CAD burden was greater amongst the male patients. Several previous studies have also shown such a relationship between female gender and the presence of ARAS in multivariable-adjusted models;7, 18, 19, 25, 27 this finding remains to be explained.

A significant association was found between hypertension with the presence of ARAS in our study, which is in agreement with numerous prior studies.4, 20, 21, 24, 25, 27, 28 However, others have not identified hypertension as a predictor of ARAS.7, 12,

18, 29-31 Hypertension has been observed to be both a risk factor and possibly a sign for the activation of renin-angiotensin system secondary to ARAS.27

Although diabetes and hyperlipidemia play an essential role in the pathogenesis of atherosclerosis, in our study, there were no relationships between ARAS and diabetes and hyperlipidemia as well as smoking or family history of CAD. This is in concordance with the results from other similar studies.7, 18, 21, 29 Moreover, our univariable analyses showed that insulin use was significantly associated with ARAS but this was not confirmed in the multivariable analysis.

Our data demonstrated that history of renal failure was unsurprisingly independently associated with ARAS. Serum creatinine has been considered a prominent predictor of ARAS in patients undergoing cardiac catheterization in most but not all studies.7, 24, 32, 33 Also, two studies have

Navid Rokni et al.

TEHRAN HEART CENTER


suggested that the severity of renal failure is more related to parenchymal injury than the severity of stenosis.34, 35

The main limitation of the current study was its retrospective cross-sectional design. Another drawback was that the study was conducted in a single center, which may have rendered it biased with respect to patient enrolment. Be that as it may, it is worthy of note that ours is a tertiary referral center admitting patients from across the country. The study was also limited by the absence of protocol-based patient selection. Finally, we did not use quantitative analyses for the severity of CAD or ARAS.

Conclusion

ARAS is prevalent in patients undergoing coronary angiography for suspected CAD. Three-vessel CAD or two-vessel CAD (LAD + LCX) is a powerful predictor of ARAS along with female sex, older age, hypertension, and history of renal failure. The advantage of revascularization over medical therapy for ARAS is still unclear. Although risk versus benefit was not tested in this study, given the progressive nature of ARAS and the need for early detection and intervention, it appears that clinicians could consider renal catheterization in combination with coronary angiography particularly in female patients with advanced age and with significant CAD stenoses in the LAD and LCX.

Acknowledgment

This study was supported by Tehran Heart Center, University of Medical Sciences. We thank Dr. Arash Jalali for the statistical analyses.

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13. Edwards MS, Craven TE, Burke GL, Dean RH, Hansen KJ. Renovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study. Arch Intern Med 2005;165:207-213.

14. Cardoso de Carvalho F, Bregagnollo E, Santos Silva V, Brunie A, da Silva Franco RJ, Martin LC, Gavras I, Gavras H. Frequency of coronary artery disease in patients with renal artery stenosis without clinical manifestations of coronary insufficiency. Am J Hypertens 2006;19:1125-1128.

15. Sadeghian S, Karimi A, Salarifar M, Lotfi M, Tokaldany MD, Kazzazi EH, Fathollahi MS. Using workload to predict left main coronary artery stenosis in candidates for coronary angiography. J Teh Univ Heart Ctr 2007;3:145-150.

16. Lin J, Knight EL, Hogan ML, Singh AK. A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease. J Am Soc Nephrol 2003;14:2573-2580.

17. Agresti A. Logit model for multinominal responses. In: Agrestic A, ed. Categorical Data Analysis. 2nd ed. Boston: John Wiley & Sons; 2002. p. 267-313.

18. Bageacu S, Cerisier A, Isaaz K, Nourissat A, Barral X, Favre JP. Incidental visceral and renal artery stenosis in patients undergoing coronary angiography. Eur J Vasc Endovasc Surg 2011;41:385-390.

19. Buller CE, Nogareda JG, Ramanathan K, Ricci DR, Djurdjev O, Tinckam KJ, Penn IM, Fox RS, Stevens LA, Duncan JA, Levin A. The profile of cardiac patients with renal artery stenosis. J Am Coll Cardiol 2004;43:1606-1613.

20. Yamashita T, Ito F, Iwakiri N, Mitsuyama H, Fujii S, Kitabatake A. Prevalence and predictors of renal artery stenosis in patients undergoing cardiac catheterization. Hypertens Res 2002;25:553-557.

21. Wang Y, Ho DS, Chen WH, Wang YQ, Lam WF, Shen ZJ, Lu CZ, Chui M. Prevalence and predictors of renal artery stenosis in Chinese patients with coronary artery disease. Intern Med J 2003;33:280-285.

22. Khosla S, Kunjummen B, Manda R, Khaleel R, Kular R, Gladson M, Razminia M, Guerrero M, Trivedi A, Vidyarthi V, Elbzour M, Ahmed A. Prevalence of renal artery stenosis requiring revascularization in patients initially referred for coronary angiography. Catheter Cardiovasc Interv 2003;58:400-403.

23. Liu BC, Tang RN, Feng Y, Wang YL, Yin LF, Ma GS. A single Chinese center investigation of renal artery stenosis in 141 consecutive cases with coronary angiography. Am J Nephrol 2004;24:630-634.

24. Park S, Jung JH, Seo HS, Ko YG, Choi D, Jang Y, Chung N, Cho SY,


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Shim WH. The prevalence and clinical predictors of atherosclerotic renal artery stenosis in patients undergoing coronary angiography. Heart Vessels 2004;19:275-279.

25. Crowley JJ, Santos RM, Peter RH, Puma JA, Schwab SJ, Phillips HR, Stack RS, Conlon PJ. Progression of renal artery stenosis in patients undergoing cardiac catheterization. Am Heart J 1998;136:913-918.

26. Zhang Y, Ge JB, Qian JY, Ye ZB. Prevalence and risk factors of atherosclerotic renal artery stenosis in 1,200 Chinese patients undergoing coronary angiography. Nephron Clin Pract 2006;104:c185-192.

27. Tumelero RT, Duda NT, Tognon AP, Thiesen M. Prevalence of renal artery stenosis in 1,656 patients who have undergone cardiac catheterization. Arq Bras Cardiol 2006;87:248-253.

28. Song HY, Hwang JH, Noh H, Shin SK, Choi DH, Shim WH, Lee HY, Cho SY, Han DS, Choi KH. The prevalence and associated risk factors of renal artery stenosis in patients undergoing cardiac catheterization. Yonsei Med J 2000;41:219-225.

29. Jean WJ, al-Bitar I, Zwicke DL, Port SC, Schmidt DH, Bajwa TK. High incidence of renal artery stenosis in patients with coronary artery disease. Cathet Cardiovasc Diagn 1994;32:8-10.

30. Siogas C, Goudevenos J, Pappas S, Foussas S, Graekas G, Siamopoulos K, Sideris D. Usefulness of renal arteriography following coronary angiography. J Invasive Cardiol 1996;8:223-227.

31. Leandri M, Lipiecki J, Lipiecka E, Hamzaoui A, Amonchot A, Mansour M, Albuisson E, Citron B, Ponsonnaille J, Boyer L. Prevalence of renal artery stenosis in patients undergoing cardiac catheterization: when should abdominal aortography be performed? Results in 467 patients. J Radiol 2004;85:627-633.

32. Rath PC, Agarwala MK, Dhar PK, Ahsan SA, Das NK, Patil N. Renal artery involvement in patients of coronary artery disease undergoing coronary angiography--a prospective study. J Assoc Physicians India 2002;50:523-526.

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35. Wright JR, Duggal A, Thomas R, Reeve R, Roberts IS, Kalra PA. Clinicopathological correlation in biopsy-proven atherosclerotic nephropathy: implications for renal functional outcome in atherosclerotic renovascular disease. Nephrol Dial Transplant 2001;16:765-770.

Navid Rokni et al.


TEHRAN HEART CENTER

Factors Associated with Delay in Thrombolytic Therapy in Patients with ST-Elevation Myocardial Infarction

*Corresponding Author: Mohammad-Reza Sohrabi, Associate Professor of Community Medicine, Department of Community Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, P.O.Box: 193954719, Evin, Tehran, Iran. 1985717443. Tel: + 98 21 23872567. Fax: + 98 21 98 22439936. E-mail: [email protected].

Original Article

Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Received 03 October 2011; Accepted 29 January 2012

Abstract

Background: Treatment delay in the management of ST-elevation myocardial infarction conversely correlates with prognosis and survival of the patients. This study aimed to investigate factors associated with delay in the thrombolytic therapy of these patients in Tehran.

Methods: Between 2007 and 2010, the interval between the self-reported time of the onset of symptoms and initiation of the thrombolytic agent in 513 patients with a diagnosis of acute ST-elevation myocardial infarction was recorded. Medical history and socio-demographic characteristics of the patients treated within two hours after the onset of symptoms and patients treated after two hours from the onset of symptoms were compared, and the odds ratios were calculated using logistic regression.

Results: The mean age of the patients was 61.2 (SD = 11.1) years, and 76% of the patients were male. The median time between the onset of symptoms and treatment was 158 (SD = 30.4) minutes. Mean for decision time was 61 (SD = 19), which was responsible for 83% of the entire treatment delay. The mean transportation time was 34 (SD = 12) minutes, and the median door-to-needle time was 44 minutes. Odds ratio for history of diabetes mellitus was 1.90 (95% CI: 1.26-2.87), for hypertension was 1.55 (95% CI: 1.08-2.23), and for prior coronary heart disease was 1.47 (95% CI: 1.17-1.84).

Conclusion: The most important factor associated with delay in treatment was decision time. Improving emergency medical services dispatch time, obtaining pre-hospital electrocardiograms for early diagnosis, and pre-hospital initiation of thrombolytic therapy may reduce the delay time.


This paper should be cited as: Alishahi Tabriz A, Sohrabi MR, Kiapour N, Yazdani S. Factors Associated with Delay in Thrombolytic Therapy in Patient with ST-Elevation Myocardial Infarction. J TehUniv Heart Ctr 2012;7(2):65-71.

Keywords: Myocardial infarction • Thrombolytic therapy • Emergency medical services • Iran

Amir Alishahi Tabriz, MD, Mohammad-Reza Sohrabi, MD, MPH*, Nazanin Kiapour, MD, Shahrooz Yazdani, MD

Introduction

ST-elevation myocardial infarction (STEMI) is a major cardiovascular event, which may result in great mortality and morbidity. Myocardial damage caused by acute STEMI is a time-dependent process. Reperfusion therapy can alter

the course of infarction, limit extent of damage, and improve subsequent prognosis.1-3 Thrombolysis is still the most common reperfusion method used in myocardial infarction, and the greatest benefit is obtained when thrombolytic agents are administered within the first hour after myocardial infarction (MI).4 The efficacy of reperfusion therapies is

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The Journal of Tehran University Heart Center Amir Alishahi Tabriz et al.

decreased with the prolongation of the time interval between the onset of symptoms and treatment.5-7 It is estimated that the benefit is a reduction of 1% in death, for every hour saved when administering the drug within the first six hours after MI.8 In addition, it has been demonstrated that 25% of patients treated with thrombolytic agents within the first hour leave the hospital with no evidence of myocardial necrosis, a concept termed aborted MI.9 Treatment delays with either thrombolytic therapy or primary percutaneous coronary intervention (PPCI) are associated with higher six-month mortality in patients with STEMI receiving reperfusion therapy.10 However, it has been observed that in many situations, thrombolytic therapy is carried out after a longer period than the recommended time period.11 A number of factors determine the delay in starting thrombolytic therapy such as contacting emergency medical services (EMS), transporting the patient, admitting the patient in the emergency department, initial assessment of the patient including obtaining and interpreting the electrocardiogram (ECG), decision making, and delay in preparing the drug.12

Because the prevalence of MI has increased substantially in recent years, it is important that all avenues of treatment of the MI patient such as treatment delay factors be explored. Although timely initiation of reperfusion therapy in patients with STEMI is of great importance, in real practice still there are many factors leading to treatment delay. The International Registry Data shows that only 41% of patients who receive in-hospital thrombolytic agents present to hospital within two hours of symptom onset and only one third receive treatment within two hours.13 Treatment delay variables differ in different countries according to cultural, economic, educational, and social backgrounds.14, 15 In the scientific literature, there is very little evidence about the different components of treatment delay and their duration in the clinical setting of developing countries such as Iran.

This cross-sectional study was conducted to investigate factors associated with thrombolytic therapy delay in STEMI patients in Tehran (the Capital of Iran) with the ultimate goal of effecting a reduction in STEMI burden.

Methods

This cross-sectional study was performed in three random samples of Tehran’s general teaching hospitals, namely Loghman Hakim Medical Center, Imam Hussein Hospital, and Taleghani Hospital, between October 2007 and January 2010. At the time of patient arrival in the emergency department, patients with acute coronary syndrome were screened via the ECG, physical examination, serum biochemical markers of necrosis, and history by well-trained physicians and nurses. Diagnosis of STEMI was based on typical symptoms, typical rise and gradual fall or a more rapid rise and fall of biochemical markers of myocardial

necrosis, and concurrent ST-T changes. ST-T changes compatible with STEMI were defined as ST elevation of at least one millimeter in at least two contiguous or related ECG leads or new left bundle branch block according to the American Heart Association’s guidelines. After the selection of patients with acute STEMI, contraindications of thrombolytic therapy in each patient were reviewed. Patients with a diagnosis of STEMI who were eligible for thrombolytic therapy were included in our study. The initial sample of this study consisted of 585 patients, and the following patients were excluded sequentially: patients who had been transferred from another medical center (n = 5), patients who developed symptoms for acute MI after hospital admission date and time (n = 3), uncooperative patients (n = 8), patients who did not use EMS (self transportation) (n = 28), patients who had an unknown time of symptom onset (n = 10), patients who did not have new or presumed new ST-segment elevation in two or more leads or left bundle branch block on the first ECG (n = 3), and patients who were visited by a physician before hospital arrival (n = 15). Finally, 513 patients (389 men and 124 women) with a diagnosis of acute STEMI fulfilled our inclusion criteria.

The physician completed case record forms at the time of admission. In all the patients, a detailed medical history of previous hospitalization for cardiovascular disease, presence or management of hypertension (blood pressure greater than or equal to 140/90 mmHg or use of antihypertensive drugs), hypercholesterolemia (total serum cholesterol greater than 200 mg/dl or use of lipid-lowering agents), renal failure (serum creatinine greater than 1.7 mg/dl), and diabetes mellitus (use of anti-diabetic medication or fasting blood glucose greater than 126 mg/dl) was recorded. Socio-demographic characteristics (e.g. age and sex) and current smoking status were also recorded.

Because occlusion may occur intermittently, myocardial demands may vary, and the presence and function of collateral circulation may play an important role, the timing of the onset of ischemic symptoms is only a crude measure for determining when the infarct-related artery occluded and myocyte necrosis began, thus self-reported time of the onset of symptoms as time of acute MI was recorded as accurately as possible. The time of contact with EMS was obtained from forms completed by the emergency medical technicians, the time when the patient arrived at the hospital was recorded from the admission form, the precise time of the initiation of the thrombolytic agent was obtained from the hospital records, and the interval between the self-reported time of the onset of symptoms and initiation of the thrombolytic agent was defined as treatment delay time. Based on treatment delay time, the patients were divided initially into two categories: patients treated within two hours after the onset of symptoms (early treatment) and patients treated after two hours from the onset of symptoms (late treatment). This two-hour time point was chosen because it has been shown that

TEHRAN HEART CENTER


Factors Associated with Delay in Thrombolytic Therapy in Patients with ST-Elevation ...

the beneficial effect of thrombolytic therapy is substantially higher in patients presenting within two hours after symptom onset compared to those presenting later.16

The study was approved by the Medical Research Ethics Committee of Shahid Beheshti University of Medical Sciences and was carried out in accordance with the Declaration of Helsinki (1989) of the World Medical Association.

Continuous variables are presented as mean values and standard deviation. The categorical variables are presented as absolute and relative frequencies. Differences in the distribution of characteristics in the patients, classified according to the extent of pre-hospital delay, were examined using the chi-square test for the discrete variables, while the t-test was employed to examine differences between the different delay groups for the continuous variables. Logistic regression analysis was utilized to determine which of the socio-demographic, clinical, and behavioral characteristics best distinguished between the two groups. The logistic regression analysis initially included the patients’ age, sex, smoking habits, and medical history in conjunction with the use of lipid-lowering agents and anti-hypertensive and anti-diabetic drugs. Final models were constructed by using the stepwise regression procedure. All the statistical calculations were performed using SPSS software, version 19.0 (SPSS Inc, Chicago, Il, USA). The logistic regression analysis results are presented as calculated odds ratios with 95% confidence intervals. Significance level for analysis was defined as p value < 0.05.

Results

During the 3 years of the study period, 513 patients with

STEMI were treated with thrombolytic agents. Of this total, 76% were male, 42% were smokers, 17% were known cases of diabetes mellitus, 35% had a history of hypertension, 46% were known cases of hypercholesterolemia, 5% were known cases of renal failure, and 43% had a history of prior coronary heart disease (CHD). The mean age of the patients was 61.2 (SD = 11.1) years, with 33% of them being older than 70 years. The baseline characteristics of the patients treated with thrombolytic agents with the extent of treatment delay are presented in Table 1. Amongst the patients with STEMI, those treated with thrombolytic agents after two hours of symptom onset were more likely not only to be male (p value = 0.033), elderly (p value < 0.001), and current smokers (p value < 0.001) but also to have a history of hypertension (p value < 0.001), diabetes mellitus (p value = 0.093), hypercholesterolemia (p value = 0.003), and renal failure (p value < 0.001) (Table1).

Logistic regression was performed to identify which socio-demographic, clinical, or lifestyle characteristics of the patients contributed significantly to the prediction of late (> 2 hours) versus early (≤ 2 hours) treatment. The results of this analysis showed that the patients with a history of diabetes mellitus (OR: 1.90, 95% CI: 1.26-2.87), hypertension (OR: 1.55, 95% CI: 1.08-2.23), and prior CHD (OR: 1.47, 95% CI: 1.17-1.84) were significantly more likely to receive treatment late (p value < 0.001) (Table 2).

The overall median (25th and 75th percentiles) time between the onset of symptoms and treatment was 158 (30 and 420) minutes. Moreover, 46 (9%) patients sought medical care at least 6 hours after the onset of symptoms, while only 97 (19%) patients presented at the hospital within two hours from the onset of symptoms. The mean time from the onset of symptoms to calling EMS was 61 ± 19 minutes. The mean time from the onset of symptoms of acute MI to admission to

Table 1. Baseline characteristics of patients treated with thrombolytic agents with the extent of treatment delay (n=513)*

≤ 2-hour delay(n=82)

> 2-hour delay(n=431) P value

Men 63 (77) 366 (85) 0.033Age(y) 61.17±11.07 65.17±11.07 <0.001Diabetes Mellitus 21 (25) 134 (31) 0.093

Hypertension 31 (38) 237 (55) <0.001

Hypercholesterolemia 39 (47) 211 (49) 0.003

Renal Failure 3 (4) 26 (6) <0.001

Prior CHD 34 (42) 203 (47) 0.745

Current Smoking 27 (33) 198 (46) <0.001Prior Medication

ACE Inhibitor 6.56 (8) 60.34 (14) 0.021

Beta Blocker 4.92 (6) 38.79 (9) 0.065Diuretic 4.10 (5) 51.72 (12) 0.034Calcium Antagonist 5.74 (7) 56.03 (13) <0.001Statin 9.84 (12) 64.64 (15) 0.013

*Data are presented as mean±SD or n(%) CHD, Coronary heart disease

68


hospital was 146 ± 20 minutes. The mean transportation time from the patient place to the hospital was 34 ± 12 minutes, and the interval between symptom onset and initiation of thrombolytic therapy was162 ± 42 minutes.

After controlling the confounding factors, we found no significant difference in time of symptom to ambulance arrival and ambulance arrival to treatment with respect to age (p value = 0.23), sex (p value = 0.061), history of hypertension (p value = 0.063), diabetes mellitus (p value = 0.071), hypercholesterolemia (p value = 0.059), renal failure (p value = 0.079), prior CHD (p value = 0.053), and current smoking (p value = 0.064) (Table 3).

Table 2. Factors significantly associated with treatment delay of more than 2 hours

Characteristics Adjusted OR (95% CI)

Diabetes Mellitus 1.90 (1.26-2.87)

Hypertension 1.55 (1.08-2.23)

Prior CHD 1.47 (1.17-1.84)

CHD, Coronary heart disease

Discussion

The result from this study showed that thrombolytic therapy delay contains two different components: pre-hospital and intra-hospital delay. Pre-hospital delay includes the two major components of decision and transportation periods, and decision time represents the interval between the onset of symptoms until the patient notices the gravity of the problem and seeks medical attention. Decision delay was more pronounced than were the other elements of the patients’ treatment (transfer and intra-hospital delays).

As treatment efficacy is reduced by the passage of time, we conducted this study to investigate reasons for thrombolytic therapy delay in Tehran. Recognition of factors contributing to thrombolytic therapy delay could enlighten our vision to change our country-based guidelines of chest pain management. By recognition of treatment delay factors,

healthcare policy makers can perform interventions in different levels of treatment delay and finally reduce the enormous mortality and morbidity burden caused by STEMI.

The mean age of the patients in this study was similar to that in the Behjati et al. study (61.20 ± 12.38).17 Our result indicates that 83% of the entire pre-hospital delay was related to the time from symptom onset to the first medical contact and only 19% of the subjects made a call for help within two hours of the onset of coronary symptoms; and in 9%, the delay was greater than six hours, which is compatible with other studies.18 Symptoms were not recognized as coronary in origin in most cases. In all the cases where delay was more than one hour, the main reason for the delay was thinking that symptoms would go away or that they were not serious. Disinclination to call the EMS reflected the belief that the symptoms were not grave enough to warrant an ambulance.

Our results also show that the older patients are more likely to receive treatment late, which is consistent with prior studies of in-hospital fibrinolysis.19 This could be due to the frail general health condition of the elderly at large and the fact that most of the time they suffer from different kinds of pains, most of them impermanent. Consequently, old patients are more prone to assume that the symptoms are temporary and will sooner or later go away.

The female patients in our study had called for help earlier than the male patients, which is not consistent with prior studies. Previous research showed that female patients with STEMI were more likely to present to hospital by ambulance but conversely had delayed time from symptom onset to in-hospital fibrinolysis.18 This could be a reflection of different cultural views over health and life, between Iranian men and women. Iranian women constitute the bulk of the audience of most radio and television health programs, and they are in general more concerned about their health. On the other hand, the delay between admission to hospital and initiation of fibrinolysis in the women in the present study could be in consequence of lower rates of STEMI in women and high prevalence of psychosomatic syndrome among them.

Our study demonstrates that transportation time in Tehran is about 34 minutes, which is not longer than that reported

Amir Alishahi Tabriz et al.

Table 3. Mean time of components of treatment delay in patients with STEMI*

Symptom onset to ambulance call/min Symptom onset to hospital admission/min Symptom onset to treatment/minSex

Male 70.1±20.4 148.6±21.4 169.3±49.8Female 65.4±19.5 143.1±19.8 159.6±39.6

Diabetes mellitus 89.3±25.1 169.9±25.7 188.4±47.5Hypertension 83.6±23.3 165.4±24.3 184.5±46.6

Hypercholesterolemia 85.5±23.2 169.4±23.2 189.1±47.7

Renal failure 79.8±22.2 162.7±23.3 181.4±45.5Prior CHD 75.7±21.4 159.3±22.6 178.3±46.7Current smoking 71.4±19.2 152.4±19.7 173.3±44.9

*Data are presented as mean±SDSTEMI, ST elevation myocardial infarction; CHD, Coronary heart disease

TEHRAN HEART CENTER


in other countries.20 Needless to say, the existence of high urban traffic in large cities such as Tehran may contribute to delayed treatment.

Although it would be ideal that the time between patient arrival and thrombolytic infusion was no more than 30 minutes (door-to-needle time), in our study, the median door-to-needle time was 44 minutes, which is compatible with a prior study.20 One of the probable delay factors is the time required to transfer patients to the coronary care unit (CCU), where the thrombolytic is administered. There is reduction in the thrombolytic therapy administration time when it is administered in the emergency department. A previous study showed a reduction of 58 minutes when these procedures started in the emergency department rather than exclusively in the CCU.21 By contrast, another study22 found an increase from 3.4% to 12% in the death rate when the therapy was administered in the emergency department. Another factor reported as a reducing factor in door-to-needle time is night shift care. This factor can be considered a time reducer, considering that during the night shift there is a reduction in the number of patients, thus care is provided faster.

In conclusion, major efforts are needed to understand and modify behavior of patients with chest pain to further reduce delays in treatment. It is important to inform the general population and especially high-risk persons about manifestations of myocardial ischemia and a need to prompt hospital referral by means of ambulance in case of STEMI symptoms. While chest pain is the most important symptom of heart attack, results from the National Registry of Myocardial Infarction, USA suggested that 33% of the patients admitted to the hospital with MI did not have chest pain on admission to the hospital. Less knowledge of common symptoms is also important for prompt health seeking. In the REACT study, 67% of the participants identified arm pain or numbness, 51% identified shortness of breath, and 10% classified jaw, neck, or back pain as heart attack symptoms. There may be an urgent need for the public to recognize multiple symptoms of heart attack. Strategies to reduce patient delay times must focus on educating the public on the recognition and diversity of coronary symptoms and the benefits of prompt presentation to the hospital by the emergency ambulance service. Health care professionals should review and consult with patients and their families the need to seek urgent medical attention for a pattern of symptoms, including chest discomfort, extreme fatigue, and dyspnea, especially if accompanied by diaphoresis, lightheadedness, palpitations, or a sense of impending doom.23, 24

A meta-analysis of studies comparing pre-hospital and in-hospital thrombolysis has shown a relative reduction in short-term mortality of about 7%with pre-hospital thrombolysis.25 Pre-hospital fibrinolysis also has been associated with much shorter ischemic times and a 30% mortality reduction compared with in-hospitalfibrinolysis.26 Public campaigners

and medical care providers have a substantial role in this regard. Precise data registration and monitoring of the duration of pre-hospital delays are crucial for planning strategies and protocols to abolish referral delays of patients with acute MI and establish early reperfusion, which can subsequently decrease mortality.27 In the meantime, efforts should be made to lift the early management of patients with STEMI from the emergency department to the ambulance because this saves at least 30 to 60 minutes in time to proper treatment. An organized network of assessment, treatment, and transfer should be established and adapted to the local situation to manage STEMI patients optimally, with continuous monitoring of the clinical results achieved. Similarly, building the necessary systems of care to coordinate EMS and hospitals so that catheterization laboratories can be activated before the patient arrives at the hospital may require capital equipment, training of emergency medical personnel, and collaboration across service providers not under the control of the hospital. An organized network of assessment, treatment, and transfer should be established and adapted to the local situation to manage STEMI patients optimally, with continuous monitoring of the clinical results achieved.

It is fundamental for the health care delivery team to make an effort to develop health care protocols so as to improve the quality of emergency services. This would help to provide quicker service to patients with heart disease, which would significantly reduce the time spent between the onset of the event and myocardial reperfusion. From the moment a patient with chest pain arrives at the hospital, there is a race against time. Chest pain guidelines recommend that every patient with suspected acute coronary syndrome (ACS) in the emergency room get an ECG immediately, in the first 5 to 10 minutes after reaching the hospital. One of the reasons for door-to-ECG delay is that the examination is performed only upon medical order, after assessment. Since the nursing team is responsible for the first part of the assessment, it is important for one specific nurse to screen the cases and determine emergency care procedures through initial assessment and requesting an ECG. This would provide agility, quickness, and effectiveness in the care process. Thrombolytic therapy must be initiated in emergency departments, and it should be instituted by the first physician capable of making the diagnosis and of determining the patient’s eligibility for this treatment. The use of thrombolytic therapy can be increased by raising public awareness of acute MI symptoms, not least amongst those at higher risk, i.e. the elderly, smokers, diabetics, and hypertensives, as well as by providing necessary equipment and transportation facilities for the timely transfer of patients to emergency departments with adequately trained medical staff. The issue of documenting organizational practices is complex; however, our approach was designed to reflect the combined views of key staff involved with treating patients


70


with STEMI.The findings of this study are meant to stimulate

discussion about the main factors associated with treatment delay in patients with STEMI in Tehran. The present study, however, has some limitations, first and foremost amongst which is that because its sample was limited to adults from three major hospitals of Tehran, the results may not be generalizable to broad populations of Iran. It is worthy of note, however, that in order to decrease the effect of this selection bias, we selected the hospitals in different socio-economic classes of Tehran. Another weakness in the current study is that although the data were produced using a rigorous methodology, they came from cross-sectional, self-report assessments and did not include history of chronic medical problems of the patients and medication use for heart disease: this may reflect certain biases. Much work also remains to be done to evaluate the opportunities and pitfalls of electronic communication between patients and health professionals and to integrate these tools into clinical practice if they prove to be effective, without disadvantaging those who have different preferences or those who benefit from more traditional modes of communication.

Conclusion

We observed that the total time between the onset of symptoms in the patients with STEMI and the initiation of thrombolytic therapy was longer than treatment golden time. Shifting the place of diagnosis and treatment from the emergency department of hospitals to where the patient is located can reduce this gap time.

Acknowledgements

It is a pleasure to acknowledge the many talented collaborators, including the physicians, nurses, paramedics, patients, and others, who contributed to this field and our work.

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9. Taher T, Fu Y, Wagner GS, Goodman SG, Fresco C, Granger CB, Wallentin L, van de Werf F, Verheugt F, Armstrong PW. Aborted myocardial infarction in patients with ST-segment elevation: insights from the assessment of the safety and efficacy of a new thrombolytic regimen-3 trial electrocardiographic substudy. J Am Coll Cardiol2004;44:38-43.

10. Nallamothu B, Fox KA, Kennelly BM, Van de Werf F, Gore JM, Steg PG, Granger CB, Dabbous OH, Kline-Rogers E, Eagle KA; GRACEInvestigators. Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention. The Global Registry of Acute Coronary Events. Heart 2007;93:1552-1555.

11. Ting HH, Bradley EH, Wang Y, Nallamothu BK, Gersh BJ, Roger VL, Lichtman JH, Curtis JP, Krumholz HM. Delay in presentation and reperfusion therapy in ST-elevation myocardial infarction: Am J Med 2008;121:316-323.

12. Pitsavos C, Kourlaba G, Panagiotakos DB, Stefanadis C; GREECS Study Investigators. Factors associated with delay in seeking health care for hospitalized patients with acute coronary syndromes: the GREECS study. Hellenic J Cardiol 2006:47:329-336.

13. Widimský P, Budesínský T, Vorác D, Groch L, Zelízko M, Aschermann M, Branny M, St’ásek J, Formánek P; ‘PRAGUE’ Study Group Investigators.Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction: final results of the randomized national multicentre trial–PRAGUE-2. Eur Heart J 2003;24:94-104.

14. Ottesen MM, Dixen U, Torp-Pedersen C, Køber L.Prehospital delay in acute coronary syndrome - an analysis of the components of delay. Int J Cardiol 2004;96:97-103.

15. Goldberg RJ, Steg PG, Sadiq I, Granger CB, Jackson EA, Budaj A, Brieger D, Avezum A, Goodman S. Extent of, and factors associated with delay to hospital presentation in patients with acute coronary disease (the GRACE registry). Am J Cardiol 2002;89:791-796.

16. Kennedy JW, Martin GV, Davis KB, Maynard C, Stadius M, Sheehan FH, Ritchie JL. The western Washington intravenous streptokinase in acute myocardial infarction randomized trial. Circulation 1988;77:345-352.

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17. Sadeghian H, Sheikhvatan M, Mahmoodian M, Sheikhfathollahi M, Hakki E, Sadeghian A,Behnam B,Haji Zeinali AM, Semnani V. Comparison of short-term clinical outcome of non-ST elevation versus ST elevation myocardial infarction. J Teh Univ Heart Ctr 2009;4:97-102.

18. Leslie WS, Urie A, Hooper J, Morrison CE. Delay in calling for help during myocardial infarction: reasons for the delay and subsequent pattern of accessing care. Heart 2000;84:137-141.

19. Leizorovicz A, Haugh MC, Mercier C, Boissel JP. Pre-hospital and hospital time delays in thrombolytic treatment in patients with suspected acute myocardial infarction: analysis of data from the EMIP study. European myocardial infarction project. Eur Heart J 1997;18:248-253.

20. Ortolani P, Marzocchi A, Marrozzini C, Palmerini T, Saia F, Serantoni C, Aquilina M, Silenzi S, Baldazzi F, Grosseto D, Taglieri N, Cooke RM, Bacchi-Reggiani ML, Branzi A. Clinical impact of direct referral to primary percutaneous coronary intervention following pre-hospital diagnosis of ST-elevation myocardial infarction. Eur Heart J 2006;27:1550-1557.

21. McLean S, O’Reilly M, Doyle M, O Rathaille M. Improving door-to-drug time and ST segment resolution in AMI by moving thrombolysis administration to the emergency department. Accid Emerg Nurs 2004;12:2-9.

22. Hourigan CT, Mountain D, Langton PE, Jacobs IG, Rogers IR, Jelinek GA, Thompson PL. Changing the site of delivery of thrombolytic treatment for acute myocardial infarction from the coronary care unit to the emergency department greatly reduces door to needle time. Heart 2000;84:157-163.

23. Robertson RM, Taubert KA. Warning signs for heart attack and stroke: what more can we do? J Cardiopulm Rehabil 2005;25:40-42.

24. Moser DK, Kimble LP, Alberts MJ, Alonzo A, Croft JB, Dracup K, Evenson KR, Go AS, Hand MM, Kothari RU, Mensah GA, Morris DL, Pancioli AM, Riegel B, Zerwic JJ. Reducing delay in seeking treatment by patients with acute coronary syndrome and stroke: a scientific statement from the American Heart Association Council on Cardiovascular Nursing and Stroke Council. Circulation 2006;114:168-182.

25. Morrison LJ, Verbeek PR, McDonald AC, Sawadsky BV, Cook DJ. Mortality and prehospital thrombolysis for acute myocardial infarction: a meta-analysis. JAMA 2000;283:2686-2692.

26. Björklund E, Stenestrand U, Lindbäck J, Svensson L, Wallentin L, Lindahl B. Pre-hospital thrombolysis delivered by paramedics is associated with reduced time delay and mortality in ambulance-transported real-life patients with ST-elevation myocardial infarction.Eur Heart J 2006;27:1146-1152.

27. Dieker HJ, Liem SS, El Aidi H, van Grunsven P, Aengevaeren WR, Brouwer MA, Verheugt FW. Pre-hospital triage for primary angioplasty directreferral to the intervention center versus interhospital transport. J Am Coll Cardiol Intv 2010;3:705-711.


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Discharge against Medical Advice among Inpatients with Heart Disease in Iran

*Corresponding Author: Hamidreza Goodarzynejad, Research Department, University of Medical Sciences, Tehran Heart Center, North Kargar Street, Tehran, Iran. 1411713138. Tel: +98 21 88029245. Fax: +98 21 88029731. E-mail: [email protected].

Original Article


Received 30 October 2011; Accepted 27 February 2012

Abstract

Background: Discharge against medical advice (DAMA) is a relatively common problem worldwide. We sought to determine the prevalence of and reasons for DAMA among inpatients of our cardiac center.

Methods: From a total of 20289 discharges from our cardiac teaching hospital, 992 (4.9%) patients at a minimum age of 18 years were cases of DAMA. After excluding 49 cases due to missing data, we retrospectively analyzed our prospectively collected data from 943 patients, who were DAMA cases. Patients' characteristics, including demographic details, reason for discharge, insurance status, and length of stay before discharge, were examined.

Results: The mean age of the study patients was 60.7 ± 13.0 (range, 18-94 years) with a male-to-female ratio of 2.1/1. Lack of consent to surgery or other invasive procedures was the reason cited for DAMA in 31% of the patients, followed by personal or family issues (17%). No reason for DAMA was reported in 26 (2.8%) of the patients. Women compared to men were more likely to cite "lack of consent to surgery or invasive procedures" as the reason for DAMA (p value = 0.005), whereas men more prevalently stated "personal or family issues" as the reason for DAMA (18.7% vs. 12.7%, p value = 0.022).

Conclusion: The most frequent self-reported reason for DAMA in our cardiac patients was lack of consent to surgery or invasive procedures. This may be because of fear of undergoing invasive procedures such as revascularization. Explaining the stages of a given invasive procedure to patients and comparing its risks versus benefits may lessen impulsive decision-making and DAMA.

J Teh Univ Heart Ctr 2012;7(2):72-77.

This paper should be cited as: Manouchehri J, Goodarzynejad H, Khoshgoftar Z, Sheikh Fathollahi M, Aghamohammadi Abyaneh M. Discharge against Medical Advice among Inpatients with Heart Disease in Iran. J Teh Univ Heart Ctr 2012;7(2):72-77.

Keywords: Patient discharge • Heath care surveys • Heart diseases • Iran

Jila Manouchehri, PhD, Hamidreza Goodarzynejad, MD*, Zohreh Khoshgoftar, MSc, Mahmood Sheikh Fathollahi, PhD, Maryam Aghamohammadi Abyaneh, BS

Introduction

The instance of a patient already in hospital wishing to leave against clinicians’ advice is referred to as self-discharge or discharge against medical advice (DAMA). DAMA is a relatively common problem of health care systems, accounting for as many as 2% of all hospital discharges.1,

2 Because lengths of stay (LOS) are commonly several days, these patients often remain acutely ill at the time of self-discharge, and they may remain exposed to the risk of inappropriately treated medical problem, resulting in the need for readmission.3-5 It is not surprising that DAMA poses a major problem for many clinicians who treat inpatients,6,

7 particularly those with heart trouble because incomplete

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therapy in conditions such as ischemic heart disease may exert a negative impact on health outcome. Additionally, consequent care will be probably associated with more challenges and higher overall costs over time.8, 9 Avoiding DAMA is, thus, likely to be beneficial for both patients and health systems.

DAMA occurs for a variety of reasons.10, 11 Green et al. found that the majority of the their DAMA cases were in consequence of personal reasons, financial problems, and legal issues such as a court date.11 A good understanding of patients’ reasons for DAMA may assist health care providers in averting some of these premature discharges.

Patients’ consideration of DAMA may be influenced by race/ethnicity and cultural factors or other contextual factors, including differences in the health care system, relationship between primary care physicians and hospital-based physicians, insurance coverage, and styles of communication between physicians and patients.7 While there are several studies available from dominantly western countries regarding the prevalence of DAMA,7 to the best of our knowledge, there is only one study on DAMA among emergency-admitted patients in Iran,12 and no such published data exist in hospitalized patients. We, therefore, sought to determine the prevalence of and also the reasons for DAMA in an Iranian sample of cardiac patients.

Methods

Between September 2008 and November 2009, this study was conducted over a 14-month period at Tehran Heart Center, a major referral and educational hospital dedicated to cardiac patients and affiliated to Tehran University of Medical Sciences. Tehran Heart Center comprises 4 intensive care units (ICUs) (74 beds), 5 cardiac care units (CCUs) (72 beds), 7 post-CCUs) (178 beds), and 5 surgical wards (120 beds) and boasts full-time accomplished specialists, well-trained nurses, and state-of-the-art diagnostic and therapeutic equipment. The center provides diagnostic and treatment services at much lower costs than do hospitals in the private sector. The hospital has considerable patient loads from Tehran (capital city) and other large and small cities and towns. On average, 8500 coronary angiographic procedures, 3500 surgical operations, and 1500 percutaneous coronary intervention (PCI) procedures are performed in this hospital per annum.

We identified 20289 discharges of consecutive hospitalized patients at a minimum age of 18 years after excluding the patients who had expired in the hospital (n = 342). Of these, 992 patients were cases of DAMA. After the exclusion of those with missing data (n = 49), the remaining 943 patients formed the study population.

According to the policies of Tehran Heart Center, a request for DAMA is considered only when a related form

is completed and signed by the patient or his/her legal custodian. The “DAMA form” was designed on the basis of the reasons cited by patients in the past for self-discharge and the potential reasons reported in prior studies. A list of reasons are provided in this form including lack of consent to surgery or invasive procedures, personal or family issues, feeling well, financial problems, transfer to another hospital, no noticeable improvements, requesting temporary leave from hospital stay during public or extended holidays, dissatisfaction with hospital services/facilities, seeking consultation elsewhere, delay in the delivery of health care services, dissatisfaction with the staff’s behavior, and other reasons. Patients should then list, in order of importance, the reason(s) for DAMA. In case patients cite more than one reason for DAMA, the principal reason is considered the one appearing first on the list. Other data are filled out by the nursing staff.

In the present study, data on the discharge dates, reason(s) provided for DAMA by the patients, hospitalization ward, and the patients’ file numbers were obtained from these forms. These data were thereafter merged with the hospital registration database using the patients’ file number to obtain the other variables of the patients, including insurance status, demographic characteristics, and LOS before DAMA. Demographic information was comprised of such biological characteristics as age, gender, and race/ethnicity. Insurance status was categorized as uninsured, Social Security Organization (SSO), Medical Service Insurance Organization (MSIO), complementary insurance, and others. Finally, the prospectively collected data were analyzed.

The data are presented as mean ± SD (standard deviation) for the quantitative variables and are summarized by absolute frequencies and percentages for the categorical variables. The categorical variables were compared using the two-sided Pearson chi-square test or the Fisher exact test (as appropriate). The continuous variables were compared using the student t-test or nonparametric Mann-Whitney U test when the presumption of normality was disrupted by the Kolmogorov-Smirnov test.

For the statistical analyses, the statistical software SPSS version 16.0 for Windows (SPSS Inc., Chicago, IL) was employed. All the p values were two-tailed, with statistical significance defined by a p value ≤ 0.05.

Results

Over the 14-month study period, there were 20289 discharges, of which 992 (4.9%) were cases of DAMA. Analysis was conducted in 943 patients after the exclusion of 49 patients due to missing data. Modes of admission were the emergency department in 380 (40.3%) patients, hospital transfer in 13 (1.4%), and routine or elective in 550 (58.3%). The most prevalent type of procedure cited by the study


74


population as the principal reason for DAMA was cardiac surgery (54%), followed by PCI (15.4%), and coronary angiography (11.5%). Medical therapy was recommended in the remaining 180 patients with DAMA (19.1%).

The baseline characteristics of the DAMA cases, for men and women separately, are depicted in Table 1. The mean age of the study patients was 60.7 ± 12.0 (range = 18-94 years) with a male-to-female ratio of 643/300. Nearly one third of the study patients were in the age group of 61-70 years. The most common age group was 51-60 years in the men and 61-70 years in the women. In our DAMA cases, the male patients were younger and more educated than were the female patients. As is shown in Table 1, the mean LOS in hospital was 5.5 ± 5.3 days for the whole population (range = 1-55 days), and over 60% of the patients had stayed for 5 days or less prior to DAMA. This variable was significantly different between the men and women (5.1 ± 4.7 vs. 6.3 ± 6.4, p value = 0.002). There was no statistically significant difference between the men and women with regard to the other baseline variables. Figure 1 demonstrates the frequency distribution of LOS in hospital before DAMA.

Figure 1. Frequency distribution of length of stay in hospital before self-discharge

Reasons given for DAMA as stated by the patients or their companions are listed in Table 2. The most frequently cited reason was lack of consent to surgery or other invasive procedures (31%), followed by personal or family issues (17%). The next three most commonly reasons stated for DAMA were feeling well (13%), financial problems (11%), and desire to be transferred to another hospital (10%). No reason for DAMA was reported in 26 (2.8%) of the patients. The women compared to the men were more likely to cite “lack of consent to surgery or invasive procedures” as the reason for self-discharge (p value = 0.005), whereas the men more prevalently stated “personal or family issues” as the reason for DAMA (18.7% vs. 12.7%, p value = 0.022).

Eighty-three (8.8%) patients cited more than one reason for opting for DAMA. The most common second reasons for DAMA were personal or family issues (29%), financial problems (18%), feeling well (15%), and desire to be transferred to another hospital (15%).

Among the 943 DAMA cases in the analysis, 183 (19.4%) were readmitted within the study period: 95 (51.9%) of them returned to the hospital within 15 days, 73 (39.9%) within 16-90 days, and the remaining 15 (8.2%) more than 90 days following DAMA. The mean time interval to readmission was 32.8 days in this subgroup; the interval to readmission was 18.0 days longer for the women than that for the men (45.8 vs. 27.8 days, p value = 0.028).

Discussion

DAMA creates a challenge for physicians and other health care providers, in part due to the association of premature self-discharge with multiple readmissions. As is reported in the literature, DAMA has been a universal problem for more than half a century troubling both general medicine and psychiatric hospitals. However, most of the early studies were performed on the psychiatric patients in the USA.13, 14

The present study found a DAMA rate of 4.9%. This rate is similar to that reported among hospitalized patients with asthma4 but higher than that for medical admissions (typically less than 4%).15 Yet, it is lower than the rate among patients hospitalized for human immunodeficiency virus (HIV) infections (13%),16 substance abuse (23%),17 and psychiatric problems (typically more than 20%).18 Based on the patient population and the type of therapy, the rate of DAMA differs widely, and as was previously suggested by Baptist et al.,4 patients with chronic medical conditions may be at a higher risk for DAMA.

In line with earlier studies,10, 19, 20 our DAMA cases were more frequently men. Higher involvement of the 61-70-year-old age group in this study could be explained by the nature of cardiac diseases, which are more common in the elderly.

Exploring the reasons for DAMA, we observed a reasonable number of forms (2.8%) that had no reason documented. Contrary to a previous report from a general hospital,21 our analysis of the reasons stated by our DAMA cases revealed that a medical factor (reluctance to undergo an invasive therapeutic procedure), rather than social factors (e.g., personal or family issues), was the most common reason for DAMA among the study population. One reason for that could be the different study groups with different cultures and backgrounds. The fact that reluctance to undergo an invasive therapeutic procedure was the most frequent reason for DAMA may be due to the patients’ fear of undergoing such invasive procedures as revascularization. Explaining the stages of a given invasive procedure and its risks and benefits to patients may reduce impulsive decision-making and DAMA by such patients.

Chiming in with some previously conducted research,10, 20,

22 we found that financial problems were among the major reasons for DAMA. There are also some reports that hospital stays may be longer than it is necessary regardless of the

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Table 1. Baseline characteristics of the study population stratified by gender*

All(n=943)

Men(n=643)

Women(n=300) P value**

Age (y) 60.68±13.00 59.56±13.08 63.08 ±12.51 <0.001Age category (y) <0.001 18-40 57 (6.0) 41 (6.4) 16 (5.3) 41-50 157 (16.6) 121 (18.8) 36 (12.0) 51-60 222 (23.5) 172 (26.7) 50 (16.7) 61-70 275 (29.2) 162 (25.2) 113 (37.7) 71-80 192 (20.4) 119 (18.5) 73 (24.3) > 80 40 (4.2) 28 (4.4) 12 (4.0)Education (y) 7.46±5.70 8.75±5.50 4.66±5.09 <0.001LOS before self-discharge (d) 5.49±5.31 5.13±4.69 6.27±6.39 0.002Marital status 0.772 Single 109 (11.6) 73 (11.4) 36 (12.0) Married 834 (88.4) 570 (88.6) 264 (88.0)Domicile 0.205 Tehran city 662 (70.2) 438 (68.1) 224 (74.7) Tehran province 115 (12.2) 86 (13.4) 29 (9.7) Neighboring provinces 88 (9.3) 64 (10.0) 24 (8.0) Other provinces 78 (8.3) 55 (8.6) 23 (7.7)Ethnicity 0.234 Fars 598 (63.4) 418 (65.0) 180 (60.0) Tork 155 (16.4) 95 (14.8) 60 (20.0) Shomali 118 (12.5) 80 (12.4) 38 (12.7) Other 72 (7.6) 50 (7.8) 22 (7.3)Health insurance 907 (96.2) 615 (95.6) 297 (97.3) 0.207 SSO 438 (48.3) 301 (48.9) 137 (46.9) MSIO 392 (43.2) 262 (42.6) 130 (44.5) Others 77 (8.5) 52 (8.5) 25 (8.6)Complementary health insurance 155 (16.4) 96 (14.9) 59 (19.7) 0.068Hospital ward 0.065 CCU 197 (20.9) 122 (19.0) 75 (25.0) Post-CCU 616 (65.3) 435 (67.7) 181 (60.3) Surgery 130 (13.8) 86 (13.4) 44 (14.7)

*Data are presented as mean±SD or n (%) **P values for men vs. womenLOS, Length of stay; SSO, Social security organization; MSIO, Medical service insurance organization; CCU, Cardiac care unit

Table 2. Self-reported reasons by the 943 hospitalized cardiac patients for leaving the hospital against medical advice*

All(n=943)

Men(n=643)

Women(n=300) P value**

Lack of consent to surgery or invasive procedures 290 (30.8) 179 (27.8) 111 (37.0) 0.005Personal or family issues 158 (16.8) 120 (18.7) 38 (12.7) 0.022Feeling well 122 (12.9) 86 (13.4) 36 (12.0) 0.558Financial problems 105 (11.1) 75 (11.7) 30 (10.0) 0.449Desire to be transferred to another hospital 95 (10.1) 69 (10.7) 26 (8.7) 0.327No noticeable improvements 56 (5.9) 34 (5.3) 22 (7.3) 0.216Requesting temporary leave from hospital stay during public or extended holidays 27 (2.9) 18 (2.8) 9 (3.0) 0.863No reason mentioned 26 (2.8) 20 (3.1) 6 (2.0) 0.322Dissatisfaction with hospital services/facilities 22 (2.3) 12 (1.9) 10 (3.3) 0.165Seeking consultation elsewhere 13 (1.4) 9 (1.4) 4 (1.3) 0.999Delay in delivery of health care services 8 (0.8) 7 (1.1) 1 (0.3) 0.447Dissatisfaction with the staff’s behavior 7 (0.7) 3 (0.5) 4 (1.3) 0.218Other reasons 14 (1.5) 11 (1.7) 3 (1.0) 0.566

*Data are presented n (%) **P values for men vs. women


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severity of illness and without necessarily influencing the patient’s outcome.23, 24 Therefore, longer LOS may be a contributing factor for increasing the rate of DAMA in the patients with a desire to do so.25 We, however, observed a mean LOS of 5.5 days and more than 60% of our cases requested DAMA within 5 days. This may be due to the fact that such patients are much less likely to be transferred or to undergo cardiac procedures such as revascularization.

Another reason for DAMA on the part of patients is disagreement with the physician’s judgment of their health status. In our study, 12.9% of the patients cited feeling well as the reason to leave the hospital, which is far less than that reported by another Iranian study on patients admitted to the emergency department.12

Reducing the rates of DAMA requires, first and foremost, an awareness of patients’ rationales for taking this particular route. In this study, five factors that contributed to our patients’ opting for DAMA were lack of consent to surgery or other invasive procedures, personal or family issues, feeling well, financial problems, and desire to be transferred to another hospital. We found that many of our patients had decided on DAMA in order to refuse invasive procedures.

The concept of respect is of great importance in the Iranian culture. Iranian physicians are liable to deem it disrespectful if patients ask too many questions or doubt their professional opinions. On the other hand, many patients feel that a second professional opinion will enable them to make a better informed decision about their course of treatment. In our experience, Iranian heart specialists and surgeons are less likely to take the time to explain the reason for procedures to their patients. This ineffective physician-patient communication more often than not, leaves the patient with insufficient information about his or her illness and its treatment modalities; hence the fear of the medical procedures on the part of the patient. This may in part explain why so many patients refuse to be subjected to invasive procedures.

The main limitation of this study is the lack of a control group to compare DAMA patients with those who are discharged normally. The comparisons between men and women are also undercut by the absence of multivariable adjustment and a denominator: without knowing the denominator, it is not possible to know whether sex-related differences in DAMA reflect true differences by sex or simply the characteristics of the patients admitted. Still, similar to the USA, the mean age of Iranian cardiac patients is higher among women than among men, which reflects the earlier age of heart disease onset in men.26 This may explain why the female DAMA cases were older than their male counterparts in our study population. The current study has three other limitations of note as well. First, using self-report forms is often biased due to a tendency among people to give socially desirable answers. To address this inherent shortcoming, we asked the patients or their companions to complete the form

only minutes before they left the hospital so that a patient dissatisfied with the care provided by the hospital would not worry about the possibility of the staff regarding him or her as ungrateful. Second, we were unable to follow up all the patients to determine the outcome of DAMA, i.e. whether they were re-admitted to our hospital or other hospitals or whether they died. And finally, some of the reasons cited for DAMA by our patient population, e.g. transfer to another hospital or seeking consultation elsewhere, seem to overlap with the others.

It is deserving of note that although all the patients were from a single center, the conclusions of the present study may be generalizable to other hospitals in Iran because ours is a tertiary referral centre receiving patients from all over the country.

Conclusion The most frequent self-reported reasons for DAMA in a

sample of Iranian cardiac patients included lack of consent to surgery or invasive procedures, personal or family issues, and feeling well, respectively. Providing strategies for decreasing the rate of DAMA by analyzing the current circumstances and developing effective interventions may benefit both patients (improving their health) and health care systems (decreasing unnecessary readmissions). We believe that qualitative research (e.g. semi-structured interviews with patients and perhaps physicians and hospital staff) is likely to be beneficial.

Acknowledgment

This study was supported by Tehran Heart Center, affiliated to Tehran University of Medical Sciences. We wish to thank the surgery data base group at Tehran Heart Center for its support.

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Case Report

Role of IVUS in Assessing Spontaneous Coronary Dissec-tion: a Case Report

*Corresponding Author: Amin Daoulah, Consultant, Cardiovascular Department, King Faisal Specialist Hospital & Research Center-Jeddah, P.O. Box: 40047. Jeddah 21499, Saudi Arabia. Tel: +96 62 667 7777. Fax: +96 62 667 7777. E-mail: [email protected].

Amin Daoulah, MD1*, Awad Al Qahtani, MD2, Majed Mazen Malak, MD3, Saud Al Ghamdi, CVT1

1King Faisal Specialist Hospital & Research Center-Jeddah, Jeddah, Saudi Arabia.2Hamad Medical Corporation, Doha, Qatar.3King Abdulaziz University Hospital, Jeddah, Saudi Arabia.

Received 05 July 2010; Accepted 11 June 2011

Abstract

Spontaneous coronary artery dissection (SCAD) is a rare condition that can result in unstable angina, acute myocardial infarction, and sudden death. This condition may occur particularly in women during late pregnancy and in the postpartum period. We present the case of a 33-year-old African American woman, who had spontaneous left anterior descending coronary artery (LAD) dissection two weeks postpartum, resulting in acute ST-segment elevation myocardial infarction with severe left ventricular dysfunction. The use of the intravascular ultrasound (IVUS) in our case confirmed the diagnosis and helped with stent sizing and implantation. On subsequent follow-up, there was marked left ventricular function recovery and clinical improvement.


This paper should be cited as: Daoulah A, Al Qahtani A, Mazen Malak M, Al Ghamdi S. Role of IVUS in Assessing Spontaneous Coronary Dissection. J Teh Univ Heart Ctr 2012;7(2):78-81.

Keywords: Ultrasonography, intreventional • Coronary vessels • Dissection • Coronary angiography • Myocardial infarction

Introduction

Primary spontaneous coronary artery dissection (SCAD) as a cause of acute coronary syndrome or sudden death is a rare entity with complex pathophysiology. It appears mostly in young women without traditional risk factors for coronary artery disease and a significant proportion of them present during the peripartum period. Early recognition of SCAD is important for initiation appropriate management.1

Case report

A 33-year-old African-American woman (Para = 2, Gravida = 0) was discharged home after an uneventful full-term vaginal delivery of a healthy baby. Two weeks postpartum, she presented to a regional hospital with severe chest pain of 24-hours’ duration radiating to both arms. She did not have a history of hypertension, hypercholesterolemia, or diabetes mellitus or connective tissue disorder. She denied any history of medication that could have caused vasoconstriction or recreational drugs use, and she had had no intense physical activity prior to the onset of chest pain. There was no past history of spontaneous abortion. On physical examination, she had a pulse rate of 52 beats per min and a blood pressure of 150/85 mmHg. There was

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Role of IVUS in Assessing Spontaneous Coronary Dissection: a Case Report

no clinical evidence of the Marfanoid feature or connective tissue disease, and her cardiovascular examination was essentially normal. The pelvic examination was significant for heavy vaginal bleeding. Her initial electrocardiogram (ECG) showed ST segment elevation throughout the antero-lateral leads (Figure 1). A bedside echocardiogram revealed severe hypokinesia of the antero-apical walls and lateral walls with left ventricular ejection fraction < 40%. Cardiac enzymes were elevated with peak total creatine kinase (CK) 500 IU/L (normal < 145 Iu/L), peak CK-MB 235 IU/L (normal < 16 Iu/L), and troponin 6 g/L (normal < 0.4 g/L).

Figure 1. 12-lead electrocardiogram showing ST segment elevation through the anterolateral leads

Electrolytes and complete blood count test were normal. Erythrocyte sedimentation rate (ESR) was 3 and C-reactive protein (CRP) < 1. Thrombolytic therapy was contraindicated in her case; therefore, within one hour, the patient was transferred to the cardiac center for urgent coronary angiography and revascularization. The invasive coronary angiography showed mild ectasia with abnormal flow and ‘hang-up’ of contrast in the proximal part of the left anterior descending artery (LAD), which suggested a dissection flap. Also, there was a significant caliber reduction with thrombolysis in myocardial infarction (TIMI) Grade 2 flow in the distal part, and the rest of the study was unremarkable (Figure 2). An intravascular ultrasound (IVUS) was preformed to assess the size of the vessel and confirm the diagnosis (Figure 3). Thereafter, the patient underwent coronary artery angioplasty to the area of dissection, whereby two bare metal stents (4.0 x 16 mm, and 4.0 x 12 mm) were deployed at 16 atmospheres across the lesion in the proximal and mid –LAD. Post-stent IVUS showed good result with no further residual dissection detected and good stent wall opposition and expansion (Figure 4).

After revascularization, an intra-aortic balloon pump (IABP) was placed for hemodynamic support, and the patient was started on intravenous heparin. In addition, after consultation with her obstetrics/gynecologist, we initiated an eptifibatide infusion in order to reduce the risk of thrombosis and then she was transferred to the coronary care unit. The following day, the patient was asymptomatic, with stable vital signs and improved myocardial ischemia blood works,

so the intravenous medication and IABP were discontinued and she was started on oral medications which included Aspirin, Clopidogrel, Ramipril, Metoprolol, and Simvastatin. Her hospital course was uneventful. On day six, she was discharged home. Her two dimensional echocardiography before discharge revealed ejection fraction (EF) > 50%. She remained symptom free during her follow-ups.

Figure 2. Right anterior oblique projection of the left anterior descending artery (LAD) demonstrating proximal ectasia and an intimal flap. There is significant caliber reduction distally with reduced flow

Figure 3. Cross-section of the mid-left anterior descending artery showing an intramural dissection between the media and adventitia, spanning from 5 to 9 o’clock (arrows)

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The Journal of Tehran University Heart Center Amin Daoulah et al.

Figure 4. Post-stent intravascular ultrasound showing a good stent wall opposition with no further residual dissection detected

Discussion

Spontaneous coronary artery dissection (SCAD) is a rare well recognized cause of acute coronary syndrome. Seventy-five percent of cases occur in females with a mean age of 40 years and 33% are in the peripartum period.1 It leads to sudden cardiac death in 50% of cases and a further 20% die within hours of symptom onset. Clearly, the mortality rate depends upon the extent and location of the dissection. SCAD is a result of a hematoma formation within the outer third of the tunica media, with subsequent expansion leading to compression of the true lumen and resultant myocardial ischemia.2 A combination of hemodynamic factors and changes in the integrity of the coronary vessel lead to SCAD, which is often seen in the absence of atherosclerotic disease. SCAD is difficult to identify by conventional cardiac catheterization and may be an under recognized phenomenon. Dissection may be missed in the absence of an intimal tear or if the true lumen is severely narrowed. The classic angiographic appearance includes contrast media seen in two lumens separated by a radiolucent intimal flap, with persistence of contrast in the false lumen after washout from the remainder of the vessel. Also, hematoma filling the false lumen may simulate intracoronary thrombus. Consequently, the diagnosis of SCAD increasingly relies on IVUS, which can identify the presence and extent of medial hematoma.

The rarity and poor survival of SCAD limits data on the best available treatment options. Medical therapy of SCAD is appropriate for patients with resolution of symptoms and limited disease. Nitrates, beta blockers, and calcium channel blockers are thought to reduce coronary spasm and extent dissection.3 Aspirin, Clopidogrel, and low-molecular weight

heparin may limit hematoma formation and subsequent luminal compression.4 The role of glycoprotein IIb/IIIa inhibitors is unclear.5 Thrombolytic therapy may lyse the compressing hematoma and allow the native vessel to re-open. However, there have been several deaths following thrombolytic therapy in middle-aged females presenting with acute coronary syndrome (ACS) in the absence of atherosclerotic risk factors.6 Clearly, lysis might allow expansion of the intramural hematoma and further myocardial ischemia from the native lumen compression. Surgical revascularization is best reserved for the left main, multi-vessel disease, or refractory ischemia despite aggressive medial therapy.7 In the case of a well-localized symptomatic single coronary dissection not involving the left main, percutaneous coronary intervention with stenting is possible.8

Patients who have experienced peripartum dissection should be counseled against future pregnancies as the risk of dissection increases with multiparity and increasing age.9

Patients should be followed clinically for symptoms of recurrent ischemia. Routine angiographic follow-up is not recommended. Stress testing with nuclear perfusion imaging is reasonable for surveillance, especially in patients with dissections of large vessels with large areas of myocardium at risk.

Conclusion

We conclude that the diagnosis of SCAD should be considered in the differential diagnosis of chest pain, especially in younger patients, peripartum women, and patients with underlying connective tissue disease. If the diagnosis of SCAD is suspected, then patients should be referred for primary percutaneous coronary intervention, where the diagnosis of coronary dissection can be made by coronary angiography and an IVUS may help in stent sizing and implant.

References1. Bac DJ, Lotgering FK, Verkaaik AP, Deckers JW. Spontaneous

coronary artery dissection during pregnancy and postpartum. Eur Heart J 1995;16:136-138.

2. Nalbandian RM, Chason JL. Intramural (intramedial) dissecting hematomas in normal or otherwise unremarkable coronary arteries: a “rare” cause of death. Am J Clin Pathol 1965;43:348-356.

3. Choi JW, Davidson CJ. Spontaneous multivessel coronary artery dissection in a long-distance runner successfully treated with oral antiplatelet therapy. J Invasive Cardiol 2002;14:674-678.

4. Sarmiento-Leite R, Machado PR, Garcia SL. Spontaneous coronary artery dissection: sent it or wait for healing? Heart 2003;89:164-166.

5. Cheung S, Mithani V, Watson RM. Healing of spontaneous coronary artery dissection in the context of glycoprotein IIb/IIIa inhibitor therapy: a case report. Catheter Cardiovasc Interv

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2000;51:95-100.6. Behnam R, Tillinghast S. Thrombolytic therapy in spontaneous

coronary artery dissection. Clin Cardiol 1991;14:611-614.7. DeMaio SJ, Jr, Kinsella SH, Silverman ME. Clinical course and

long-term prognosis of spontaneous coronary artery dissection. Am J Cardiol 1989;64:471-474.

8. Klutsein MW, Tzivoni D, Bitran D, Mendzelevski B, Ilan M, Almagor Y. Treatment of spontaneous coronary artery dissection: report of three cases. Cathet Cardiovasc Diagn 1997;40:372-376.

9. Koul AK, Hollander G, Moskovits N, Frankel R, Herrera L, Shani J. Coronary artery dissection during pregnancy and the postpartum period: two case reports and review of literature. Catheter Cardiovasc Interv 2001;52:88-94.

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Case Report

Supravalvar Mitral Ring: a Case Report

*Corresponding Author: Bahador Baharestani, Assistant Professor of Cardiac Surgery, Departement of Cardiac Surgery, Tehran University of Medical Sciences, Rajaie Cardiovascular, Medical and Research Center, Vali-Asr Street, Tehran, Iran. 1996911151. Tel: +98 21 23922156. Fax: + 98 21 22042026. E-mail: [email protected].

Bahador Baharestani, MD*, Reza Sadat Afjehi, MD, Nader Givtaj, MD, Mehrzad Sharifi, MD

Department of Cardiac Surgery, Rajaie Cardiovascular, Medical and Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Received 22 January 2011; Accepted 25 May 2011

Abstract

Supravalvar mitral ring is a rare congenital heart defect of surgical importance. The condition is characterized by an abnormal ridge of the connective tissue on the atrial side of the mitral valve. It often substantially obstructs the mitral valve inflow. We herein introduce a case of a supravalvar mitral ring in a 17-year-old male, who was admitted to our hospital with cardiac syncope. He had undergone a cardiac operation for ventricular septal defect (VSD) closure and mitral valve repair 15 years before. Transthoracic echocardiography, transesophageal echocardiography, and finally cardiac catheterization revealed a neglected supravalvular mitral ring. The ring was resected in a second operation, and the patient was discharged from the hospital symptom free.


This paper should be cited as: Baharestani B, Sadat Afjehi R, Givtaj N, Sharifi M. Supravalvar Mitral Ring: a Case Report. J Teh Univ Heart Ctr 2012;7(2):82-84.

Keywords: Mitral valve • Heart defects congenital • Syncope

Introduction

Supravalvar mitral ring is a circumferential ridge or membrane arising from the left atrial wall overlying the mitral valve and frequently attached to the mitral valve.1 Variable in thickness and extent, the ring ranges from a thin membrane to a thick discrete fibrous ridge.2 The membranous variety may be difficult to detect because the membrane often adheres to the anterior mitral valve leaflet while remaining just proximal to the posterior mitral leaflet. Adhesion to the valve may impair the opening of the leaflets, and this impairment may be the main mechanism of mitral valve inflow obstruction in some patients. In other patients, the ring may be large enough to protrude into the mitral valve inflow and cause obstruction. The supramitral ring may initially be incomplete and eccentric, allowing for an unobstructed flow through the

mitral valve. However, turbulence can cause a progressive increase in the supravalvar membrane or ridge thickness, worsening mitral inflow obstruction.3 The same mechanism is responsible for the acquired variety of supravalvar mitral stenosis, which occurs after mitral annuloplasty for the repair of mitral regurgitation.

We herein present a case of a supraventricular ring in a 17-year-old male, who presented with syncope.

Case Report

A 17-year-old male with cardiac syncope was admitted by our hospital. About 15 years ago, he had undergone a cardiac operation for ventricular septal defect (VSD) closure and mitral valve repair.

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In chest X-ray both lungs were clear, and the electrocardiogram result showed normal sinus rhythm, had undergone right bundle branch block, and right ventricular hypertrophy.

Transthoracic echocardiography, transesophageal echocardiography, and finally cardiac catheterization revealed ejection fraction of 50-55%, pulmonary hypertension with pulmonary artery pressure (PAP) of 80/40 mm Hg, pulmonary capillary wedge pressure of 23 mm Hg, gradient in the mitral valve plane of 40 mm Hg, no residual VSD, no patent ductus arteriosus (PDA), bicuspid aortic valve, no aortic insufficiency, no aortic stenosis, no sub-aortic web, normal coronary arteries, mild mitral regurgitation, moderate to severe mitral stenosis, supra mitral valve ring, normal left ventricle size, moderate right ventricle enlargement, and moderate systolic dysfunction.

There was a free floating high redundant obstructive membrane in the left atrium that was attached to the mid portion of the anterior mitral valve leaflet and also in the medial and base of the posterior mitral valve leaflet and large papillary muscles in the left ventricle (Figure 1).

Figure 1. Transesophageal echocardiography (TEE): in the apical four-chamber view, an annular structure is attached like a membrane to the atrial wall and the anterior mitral leaflet, and in close proximity of the posterior leaflet (arrow)

It also extended just adjacent to the lower limb of the left atrium appendage mouth with a small orifice (6 mm) in the lateral side and also multiple small fenestrations (by 2 dimensional echocardiography), resulting in a severely restricted diastolic flow (mean peak gradient = 9.3 mm Hg).

This web was not found in MRI cine turbo-flash images acquired on a 1.5 T scanner (Magnetom Vision-Siemens) in the four-chamber view (3A) and the transverse plane, short-axis view (Figure 2).

The patient’s ascending aorta, descending aorta, and aortic arch were tortuous with moderate narrowing of

the descending aorta distal to the subclavian artery with a systolic gradient of about 30 mm Hg, which was suggestive of insignificant coarctation of the aorta.

Doppler of the carotids and sonography of the abdomen and pelvis were both normal. The patient underwent surgery under endotracheal general anesthesia and in supine position. After heparinization, extracorporeal circulation was established between the venae cava and the ascending aorta. Following a median sternotomy, a cross clamp was placed on the aorta. Via antegrade intermittent hypothermic blood cardioplegia from the aortic root, cardiac arrest was established. Hypothermia was mild (30° C). A vent was placed through the right superior pulmonary vein. Standard left atriotomy was made. There was a long supravalvar muscular band, which was resected (Figure 3). Incision of the left atriotomy was closed. The saline test of the mitral valve was almost normal. The postoperative course was uneventful with successful anatomical correction. Postoperative echocardiographic data confirmed complete correction. The patient was underweight and acyanotic after the operation.

Discussion

Supravalvar mitral ring rarely occurs as an isolated defect; other congenital heart defects coexist in 90% of patients. The mitral valve itself is often abnormal and stenotic at the valvar or subvalvar level; fusion of leaflets, a small valve orifice, and abnormal papillary muscles are common abnormalities. Shone’s complex is a combination of four congenital heart defects: supravalvar mitral ring, parachute mitral valve, subvalvar aortic stenosis, and aortic coarctation. Other common associated lesions in patients with supravalvar mitral ring are ventricular septal defect (VSD), PDA, atrioventricular (AV) canal defect, and tetralogy of Fallout.4

Uncommonly associated defects include atrial septal defect, cor triatriatum, left superior vena cava, unroofed coronary sinus, partial anomalous pulmonary venous drainage, pulmonary venous obstruction, double-orifice mitral valve, and Wolff-Parkinson-White syndrome.5

Lesions such as transposition of the great arteries, atrioventricular discordance, and double-outlet right ventricle are occasionally complicated by a supravalvar left atrioventricular valvular ring.

Obstruction to the mitral inflow results from the reduced area of the mitral valve orifice. When clinically significant, a diastolic pressure difference occurs between the left atrium and the left ventricle. Left atrial and pulmonary venous pressures increase, leading to exudation of fluid into the pulmonary interstitial, which increases lung stiffness. Breathlessness and tachypnea are secondary to the interstitial edema and diminished pulmonary compliance.6 In severe cases, frank pulmonary edema can occur.7 An associated atrial septal defect may decompress the left atrium, reducing

Supravalvar Mitral Ring: a Case Report

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or masking the severity of the mitral valve obstruction. Associated lesions such as VSD or PDA, which increase the left ventricle output, exacerbate the manifestations of mitral inflow obstruction.8 Conversely, a supravalvar mitral ring may be difficult to detect in conditions with a diminished pulmonary blood flow such as Tetralogy of Fallot.9 Persistently elevated pulmonary venous hypertension leads to pulmonary arterial hypertension, rise in pulmonary vascular resistance, and eventual failure of the right ventricle and tricuspid regurgitation. There are no data available on the incidence of supravalvar mitral ring. It also deserves of note that predilection for race, age, and sex has not been found yet.

Treatment is the surgical resection of the web, but balloon dilatation is reported to have been successfully performed under fluoroscopic and transesophageal echocardiographic guidance by some authors.10

Figure 2. MRI cine turbo-flash images acquired on a 1.5 T scanner (Magnetom Vision-Siemens) in the four-chamber (3A) and transverse plane, short-axis view. These images do not show congenital heart disease.

Figure 3. The supra mitral valvular ring, which was resected from the atrial aspect of the mitral valve

ConclusionPreoperative identification of a supravalvular mitral ring

is the target for obtaining good surgical results. For the

identification of this congenital heart disease, TEE is not only feasible but also easy.

References1. Srinivasan V, Lewin AN, Pieroni D, Levinsky L, Alicea JR,

Subramanian S.Supravalvular stenosing ring of the left atrium: case report and review of the literature. Cardiovasc Dis 1980;7:149-158.

2. Shone JD, Sellers RD, Anderson RC, Adams P, Jr, Lillehei CW, Edwards JE. The developmental complex of “parachute mitral valve”, supravalvular ring of the left atrium, sub aortic stenosis, and coarctation of the aorta. Am J Cardiol 1963;11:714-725.

3. Oglietti J, Reul GJ, Jr, Leachman RD, Cooley DA. Supravalvular stenosing ring of the left atrium. Ann Thorac Surg 1976;21:421-424.

4. Sullivan ID, Robinson PJ, de Leval M, Graham TP. Membranous supravalvular mitral stenosis: a treatable form of congenital heart disease. J Am Coll Cardiol1986;8:159-164.

5. Anabtawi IN, Ellison RG. Congenital stenosing ring of the left atrio ventricular canal (supra valvular mitral stenosis). J Thorac Cardiovasc Surg 1965;45:994-1005.

6. Narvencar KP, Jaques e Costa AK, Patil VR. Shone’s complex. J AssocPhysicians India 2009;57:415-416.

7. McCartney FJ, Scott O, Ionesco MI, Deverall PB. Diagnosis and management of parachute mitral valve and supra valvar mitral ring. Br Heart J 1974;36:641-652.

8. Chung KJ, Manning JA, Lipchik EO, Gramiak R, Mahoney EB. Isolatedsupravalvular stenosing ring of the left atrium: diagnosis before operation and successful surgical treatment. Chest 1974;65:25-28.

9. Snider AR, Roge CL, Schiller NB, Silverman NH. Congenital left ventricular inflow obstruction evaluated by two-dimensional echocardiography. Circulation 1980;61:848-855.

10. Abdul Aziz B, Alwi M. Balloon dilatation of congenital mitral stenosis in a critically ill infant. Catheter Cardiovasc Interv 1999;48:191-193.

Bahador Baharestani et al.


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Prinzmetal’s Angina in a Pregnant Woman: a Case Report

*Corresponding Author: Hossein Saidi, Assistant Professor of Emergency Medicine, Tehran University of Medical Sciences, Rasool Akram Hospital, Sattarkhan Street, Niayesh Street, Tehran, Iran. Tel: + 98 21 3100639. Fax: + 98 21 66509283. E-Mail: [email protected].

Case Report

Fariba Almassinokiani, MD1, Mahmood Reza Alebouyeh, MD1, Farshad Entesari, MD1, Seyed Hashem Sezavar Seyedi, MD1, Alireza Almasi, MD2, Hossein Akbari, MD3, Hossein Saidi, MD1*, Homa Homam, MD4

1Rasool Akram Hospital, Tehran University of Medical Sciences, Tehran, Iran.2Firoozgar Hospital, Tehran University of Medical Sciences, Tehran, Iran.3Hazrat Fatemeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.4Akbarabadi Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Acute myocardial infarction (MI) during pregnancy is rare and MI due to Prinzmetal's angina is much rarer. We present a 35-year-old, obese, multigravida, and pre-eclamptic woman, who developed acute anterior wall MI at the 30th week of gestation. On coronary angiography, the second obtuse marginal branch was totally occluded and the right coronary artery (RCA) was normal. Three days later, she had chest pain and ST elevation in the inferior leads. On second angiography, there was narrowing in the RCA, while the obtuse marginal branch was patent. We presume that this discrepancy between the first and second electrocardiograms and angiographic findings was due to Prinzmetal’s angina.

Abstract

Keywords: Prinzmetal’s variant angina • Myocardial infarction • Pregnancy

Introduction

Ischemic heart disease is rare during pregnancy, occurring in approximately one in 10,000 live births. The risk of myocardial infarction (MI) in pregnancy is reported from one per 37,500 to 6.2 per 100,000 deliveries.1-3 The diagnosis is by clinical findings, electrocardiogram (ECG), and measurement of the serum level of the cardiac specific contractile protein, Troponin 1.4, 5 The most common forms of angina are stable and unstable angina, which are usually due to atherosclerosis. But coronary spasm, coronary dissection, and thrombus have been reported as other causes.6, 7 Prinzmetal’s angina (variant angina) is rare and it accounts for only 2 out of every 100 cases of angina.

We report a pregnant woman who presented with signs and symptoms of acute MI and whose ECG findings and Troponin 1 level were compatible with MI, leading to the final diagnosis of Prinzmetal’s angina.

Case Report

A 35-year-old woman, gravid 3 (with a history of two cesarean section operations), developed acute MI at the 30th week of gestation. She was a non-smoker and had no history of drug abuse or systemic disease. She referred to the emergency ward due to a sudden, severe pain in the neck and between the two scapulas that had started during sleep at 5 am,


This paper should be cited as: Almassinokiani F, Alebouyeh MR, Entesari F, Sezavar Seyedi SH, Almasi A, Akbari H, Saidi H, Homam H. Prinzmetal’s Angina in a Pregnant Woman: Case Report. J Teh Univ Heart Ctr 2012;7(2):85-89.

Received 04 February 2011; Accepted 09 July 2011

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with cold sweat and nausea. Her blood pressure was 200/150 mm Hg; she had a history of increased blood pressure of two weeks’ duration. The patient also had tachycardia, rales in the bases of the lungs, signs of anteroseptal MI in the ECG (Figure 1), and increased Troponin 1 blood level.

We performed a cesarean section operation because of severe preeclampsia, repeat cesarean section, and transverse lie. Four days after delivery, the patient’s blood pressure was 140/80 mmHg and coronary angiography showed total occlusion of the second obtuse marginal artery (OM2) in addition to diffuse spasm of the left circumflex coronary artery (LCx) (Figure 2). The right coronary artery (RCA) was normal. At the seventh day after delivery in the ward, the patient had chest pain and ST-segment elevation in the inferior leads (Figure 3) as well as signs of pulmonary edema. The ECG changes reversed after intravenous Trinitroglycerin (Figure 4). Based on the ECG, the diagnosis was inferior wall ischemia. We performed angiography for a second time and surprisingly the LCx and OM2 coronary arteries were normal and there was narrowing in the RCA (Figure 5).

Figure 1. Signs of acute anteroseptal myocardial infarction on admission electrocardiogram

A

B

CFigure 2. Coronary catheterization in the fourth day of hospitalization. A and B are the right anterior oblique (RAO) caudal and the left anterior oblique (LAO) caudal views of the left coronary, respectively. Diffuse left circumflex artery spasm is visible (arrows) in addition to the absence of the second obtuse marginal artery. C is the left anterior oblique cranial view of the right coronary injection, showing that the right coronary artery and its branches were normal

Fariba Almassinokiani et al.

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Prinzmetal’s Angina in a Pregnant Woman: A Case Report

Figure 3. Seventh day after delivery, at 6:00 am, signs of previous anteroseptal myocardial infarction are visible in addition to signs of acute inferior wall ischemia because of Prinzmetal’s angina

Figure 4. Electrocardiogram on the fourth day after delivery at 8:00am, after intravenous Trinitroglycerin (IV TNG) administration, indicated that inferior wall ischemia (due to obtuse marginal artery spasm) had disappeared

A

B

CFigure 5. Coronary catheterization in the seventh day of hospitalization. A and B are the right anterior oblique (RAO) caudal and the left anterior oblique (LAO) caudal views of the left coronary, respectively. They show relief of the left circumflex artery spasm and visibility of the second obtuse marginal artery (arrows), which was not visible in the previous angiography. C is the left anterior oblique cranial view of the right coronary injection, which shows obvious narrowing of the distal segment of the RCA and its branches (arrows), which were normal in the previous angiogram

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Figure 6. Electrocardiogram at the time of discharge showed that the inferior wall ischemia had disappeared, but signs of anteroseptal MI due to previous probable left anterior descending artery spasm at the time of admission still persisted

Figure 7. Electrocardiogram about three months after discharge demonstrated signs of anteroseptal myocardial infarction with no visible

inferior wall ischemia

We conclude that this discrepancy between the first and second ECGs and angiographic findings were due to Prinzmetal’s angina. A few days later, the patient was discharged (blood pressure = 130/80 mmHg) on Diltiazem, Atorvastatin, Captopril, Nitrocontin, Furosemide, and Clopidogrel while the ECG showed previous anteroseptal MI (Figure 6). An ECG three months after discharge showed the same findings too (Figure 7).

Discussion

MI in pregnancy is rare but can produce significant maternal and neonatal morbidity. Prompt diagnosis and immediate therapy are necessary to lower the high likelihood of the mortality of mother and fetus. The highest incidence of MI seems to occur in the third trimester and in multigravidas older than 33 years old. Acute MI in pregnancy is commonly located in the anterior wall, and acute maternal death rate is reported to be 19-30%.1-3, 8 Complications of pregnancy that are significantly associated with acute MI are preeclampsia, postpartum hemorrhage, postpartum infection, and fluid and electrolyte imbalance.1, 9 Shock from postpartum hemorrhage,10 ergonovine,11 and prostaglandin E1 (PGE1)12 is reported as a risk factors for MI in pregnancy.

Our patient was a 35-year-old, obese, multiparous, pregnant woman with preeclampsia, and her symptoms of MI appeared at rest in the early hours of morning.

Angina pectoris in pregnancy is rare and Prinzmetal’s angina is much rarer. It accounts for 2% of all cases of angina. Prinzmetal’s angina usually occurs at rest and happens between the midnight and early morning. People with Prinzmetal’s angina are often younger than those with the other forms of angina. It is caused by vasospasm but the mechanism of spasm is unknown yet. The gold standard for diagnosis is coronary angiography with injection of provocative agents (like Ergonovine) into the coronary arteries. Exaggerated spasm is diagnostic of Prinzmetal’s angina. Also administration of intracoronary nitroglycerin in cases of vasospasm can cause marked diffuse vasodilatation.13 Treatment with calcium-channel blockers or nitrates eliminates spasm in most of these patients.

Conclusion

In our patient, the discrepancy between the first and second angiographic findings was the confirmatory evidence that she had Prinzmetal’s angina. This conclusion was derived from the fact that the first angiographic examination showed that the LAD coronary artery was normal despite the definite occurrence of an MI in its territory, thus suggesting

Fariba Almassinokiani et al.

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Prinzmetal’s Angina in a Pregnant Woman: A Case Report

transient spasm. Furthermore, a subsequent bout of inferior wall ischemia with confirmation of transient spasm by angiography was another piece of confirmatory evidence. Last but not least, asymptomatic RCA spasm, detected in the last angiography, was another clue to the propensity of the coronary arteries to vasospasm, which is the sine qua non of Prinzmetal’s angina.

References1. James AH, Jamison MG, Biswas MS, Brancazio LR, Swamy GK,

Myers ER. Acute myocardial infarction in pregnancy: a United States population-based study. Circulation 2006;113:1564-1571.

2. Ladner HE, Danielsen B, Gilbert WM. Acute myocardial infarction in pregnancy and the puerperium: a population-based study. Obstet Gynecol 2005;105:480-484.

3. Macarthur A, Cook L, Pollard JK, Brant R. Peripartum myocardial ischemia: a review of Canadian deliveries from 1970 to 1998. Am J Obstet Gynecol 2006;194:1027-1033.

4. Nabatian S, Quinn P, Brookfield L, Lakier J. Acute coronary syndrome and preeclampsia. Obstet Gynecol 2005;106:1204-1206.

5. Shade GH, Jr, Ross G, Bever FN, Uddin Z, Devireddy L, Gardin JM. Troponin 1 in the diagnosis of acute myocardial infarction in pregnancy, labor and postpartum. Am J Obstet Gynecol 2002;187:1719-2170.

6. Kealey A. Coronary artery disease and myocardial infarction in pregnancy: a review of epidemiology, diagnosis, and medical and surgical management. Can J Cardiol 2010;26:185-189.

7. Iadanza A, Del Pasqua A, Barbati R, Carrera A, Gentilini R, Favilli R, Pierli C. Acute ST elevation myocardial infarction in pregnancy due to coronary vasospasm: a case report and review of literature. Int J Cardiol 2007;115:81-85.

8. Roth A, Elkayam U. Acute myocardial infarction associated with pregnancy. Ann Intern Med 1996;125:751-762.

9. Poh CL, Lee CH. Acute myocardial infarction in pregnant women. Ann Acad Med Singapore 2010;39:247-253.

10. Karpati PC, Rossignol M, Pirot M, Cholley B, Vicaut E, Henry P, Kévorkian JP, Schurando P, Peynet J, Jacob D, Payen D, Mebazaa A. High incidence of myocardial ischemia during postpartum hemorrhage. Anesthesiology 2004;100:30-36.

11. Sutaria N, O’Toole L, Northridge D. Postpartum acute MI following routine ergometrine administration treated successfully by primary PTCA. Heart 2000;83:97-98.

12. Schulte-Sasse U. Life threatening myocardial ischaemia associated with the use of prostaglandin E1 to induce abortion. BJOG 2000;107:700-702.

13. Ornek E, Ornek D, Murat SN, Turfan M. Angiographic documentation of coronary artery spasm induced by anesthesia. J Anesth 2010;24:452-455.

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Letter to the Editor

I was interested in the study published by Dr. Bagherzadeh et al.1 and congratulate them on their publication. There are some points in the aim of their study, method, and results, however, which I believe require further clarification.

1. The Introduction states that “Thus far, the most conventional marker and end point for successful radiofrequency (RF) ablation has been considered the loss of the inducibility of atrioventricular nodal reentrant tachycardia (AVNRT); be that as it may, it has been reported to be not inducible in up to 10% of patients. This disadvantage has prompted scientists to focus on identifying an accurate alternative end point for predicting the success rate of the slow-pathway RF ablation of AVNRT.” Also, the Discussion somehow repeats that: “Loss of the inducibility of AVNRT has been considered the end point for successful slow-pathway RF ablation; however, AVNRT is not inducible in up to 10% of patients during ablation. Nowadays, JR developed during the slow-pathway RF ablation of AVNRT has been identified as a sensitive surrogate end point for successful AVNRT ablation”. I take from these statements that given the unfeasibility of AVNRT induction in 10 % of cases during the electrophysiology (EP) study in conjunction with the clinical presence of arrhythmia (and probably other factors that convince the operator that the patient’s clinical arrhythmia is most probably AVNRT), when the operator decides to ablate the slow pathway, the presence of JR during ablation can be a surrogate for non inducibility. Nevertheless, in this article this is not the case. As the esteemed authors have mentioned in all their cases, arrhythmia was inducible and non inducibility was their gold standard for successful ablation. It is known that the 12-lead surface electrocardiogram (ECG) can only be suggestive of AVNRT, and after the completion of EP study and appropriate maneuvers can the diagnosis be confirmed.2 All the authors’ patients, therefore, must have had inducible arrhythmia

and the above-mentioned sentences in the Introduction and Discussion seem unrelated to this study and its stated aims. Investigation into the said issues would require another study design whereby- for example- in a group of patients with documented supraventricular tachycardia (SVT) compatible with AVNRT but non-inducible in the EP laboratory, the effect of ablation and presence of JR during ablation could be studied in other surrogates such as evidence of dual physiology or even the clinical outcome.

2. In their ablation technique, the esteemed authors report that after each RF application, inducibility was checked after Isoproterenol infusion. I think this is not a common practice,3 and most operators perform pacing maneuvers first and only if the arrhythmia is not inducible, do they tend to resort to Isuprel infusion. Furthermore, not only should the Isoproterenol dose and infusion duration be mentioned but also there should be a mention of the number of cases in which arrhythmia became inducible only after Isuprel infusion.

My other question is concerned with the RF power utilized in the study. Let us consider this scenario: If the investigators obtained JR but the highest temperature amounted to- for example- 47, did they stop the ablation or did they continue with higher powers? In my opinion, the power settings and policy on the minimum acceptable temperature rise in the study need elucidation.

3. I am none the wiser as to why the patients who needed more than 5 RF applications were excluded. Surely, this must have significantly influenced the average lesion number.

4. In the Results, the following points should be further elaborated upon:

A. The authors report that “Initial successful RF ablation with the loss of AVNRT inducibility was achieved in 43 (57.3%) patients using a total of 119 (73.5%) RF energy applications.” What is missing here is a clear definition of the phrase: “initial success”. If it means that these were the cases in which the first RF application was successful, why is the mean number of the RF applications in this group 1.77 rather than 1?

B. It is also confusing that in Table- 1, in the successful RF application group (43 patients), the mean number of the RF applications is 1.77 and the total number of the RF applications is 119 (which is expected to be: 43 × 1.77 = 76) and in the group with at least one unsuccessful RF application which contains a total number of 32 patients with a mean RF application of 2.69, again the total number of the RF application is 43, which is not equal to 32 × 2.69 = 86.

Needless to say, these figures should be corrected or clarified.

Prediction of Primary Slow-Pathway Ablation Success Rate according to the Characteristics of Junctional Rhythm Developed during the Radiofrequency Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia

TEHRAN HEART CENTER


References1. Bagherzadeh A, Rezaee ME, Moshkani Farahani M. Prediction

of primary slow-pathway ablation suc¬cess rate according to the characteristics of junctional rhythm developed during the radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia. J Teh Univ Heart Ctr 2011;6:14-18.

2. Josephson MD. Supraventricular tachycardias. In: Josephson ME, ed. Clinical Cardiac Electrophysiology, Techniques and Interpretations. 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2008. p. 175-284.

3. Jackman WM, Beckman KJ, McClelland JH, Wang X, Friday KJ, Roman CA, Moulton KP, Twidale N, Hazlitt HA, Prior MI. Treatment of supraventricular tachycardia due to atrioventricular nodal reenty by radiofrequency catheter ablation of slow- pathway conduction. N Engl J Med 1992;327:313-318.

Gholamreza Davoodi, MDAssociate Professor of Cardiology,Department of Cardiac Electrophysiology,Tehran Heart Center, Tehran University of Medical Sciences,North Kargar Street, Tehran, Iran. 1411713138. Tex: +98 21 88029256. Fax: +98 21 88029256. E-mail: [email protected].

Prediction of Primary Slow-Pathway Ablation Success Rate according ...


Note of Thanks

“The Journal of Tehran University Heart Center” wishes to extend its heartfelt thanks to the following reviewers, who for all their hectic scientific schedules, voluntarily offered their invaluably incisive and impartial evaluation of the received manuscripts in 2010-2011.

1. Kyomars Abbasi

2. Parviz Abdolmaleki

3. Hasan Aghajani

4. Farzane Ahmadi

5. Seyed Hossein Ahmadi

6. Ali Akbari Sari

7. Shahram Akhlaghpoor

8. Mohammad Alasti

9. Zohair Al-halees

10. Mohammad Alidoosti

11. Simin Almasi

12. Fariba Almassi Nokiani

13. Alireza Amirzadegan

14. Edmo Atique Gabriel

15. Shahdad Azmoon

16. Kamran Babazadeh

17. Jamshid Bagheri

18. Ata Allah Bagherzadeh

19. Bahadour Baharestani

20. Khosro Barkhordari

21. Mehrdad Behmanesh

22. Mohammad Ali Boroumand

23. Mohammad Borzoee

24. Ali Bozorgi

25. Carlo Briguori

26. Alaide Chieffo

27. Majid Chinikar

28. Alexandru Cozma

29. Seyed Mohammad Dalili

30. Morteza Daliri Joupari

31. Sirous Darabian

32. Gholamreza Davoodi

33. Saeed Davoodi

34. Ali Dodge-Khatami

35. Mahmoud Eftekharzadeh

36. Masod Eslami

37. Maryam Esmaeilzadeh

38. Leila Ettefagh

39. Homa Falsoleiman

40. Mohammad Farahbakhsh

41. Saeedeh Forghani

42. Reza Forough

43. Mohammad Fotuhi

44. Alfredo Galassi

45. Armen Gasparyan

46. Samad Ghaffari

47. Hossein Ghanaati

48. Abbas Ghiasi

49. Kheirollah Gholami

50. Ali Mohammad Haji Zeinali

TEHRAN HEART CENTER


51. Laleh Hakemi

52. Mehdy Hasanzadeh Delui

53. Seyed Ahmad Hassantash

54. Seyed Kianoosh Hoseini

55. Arash Jalali

56. Yaser Jenab

57. Keyvan Kamalvand

58. Shahrokh Karbalai

59. Seyed Ebrahim Kassaian

60. Ali Kazemisaeed

61. Zahra Keirandish

62. Maryam Keshtkar

63. Abbas Keshtkar

64. Mohammad Reza Khajavi

65. Mohammadreza Khatami

66. Javad Kojuri

67. Amit Kumar

68. Mehrab Marzban

69. Asghar Mazarei

70. Carlos - A. Mestres

71. Seyed Rasoul Mirsharifi

72. Farzaneh Mirzaaghaee

73. Mohammad Reza Mohajeri

74. Zeinab Moinfar

75. Mojtaba Mojtahedzadeh

76. Hassan Moladoust

77. Shahram Momtahan

78. Ali Montazeri

79. Maryam Moradian

80. Sina Moradmand

81. Randa Mostafa

82. Randa Mostafa

83. Namvar g. Movahedi

84. Mahdi Najafi

85. Paridokht Nakhostin Davary

86. Mohamad Hasan Namazi

87. Mehrdad Namdari

88. Seyed Mahdi Nassiri

89. Afshin Niakan

90. Younes Nozari

91. Saeed Oraii

92. Mohamad Ali Ostovan

93. Rezayat Parvizi

94. Farah Peiravian

95. Fausto Pinto

96. Reza Pour Bahador

97. Hamidreza Pour hosseini

98. Shahram Rabbani

99. Amir Reza Radmard

100. Hassan Radmehr

101. Fakher Rahim

102. Seyed Mansour Rayegani

103. Soheil Saadat

104. Siamak Sabour

105. Feridoun Sabzi

106. Saeed Sadeghian

107. Hakimeh Sadeghian

108. Mohammad Sahebjam

109. Mojtaba Salarifar

110. Mohammad Salasel


111. Rezvanieh Salehi

112. Abbas Salehi Omran

113. Javad Salimi

114. Reza Shahsiah

115. Farshad Shakerian

116. Alireza Shakibafard

117. Mahmood Sheikh Fathollahi

118. Shapour Shirani

119. Mahmoode Shirzad

120. Hatef Shojaei

121. Abbas Soleimani

122. Alireza Soltani

123. Akbar Soltanzadeh

124. Maryam Sotoudeh Anvari

125. Gregory Thomas

126. Farzaneh Torkan

127. Mehrnoush Toufan Tabrizi

128. Samuel Wann

129. Ahmad Yamini Sharif

130. Saeed Yazdankhah

131. Fardin Yousefshahi

132. Mohammad Reza Zafarghandi

133. Hamid Zahedi

134. Amir Farhang Zand Parsa

135. Aliakbar Zeinaloo

136. Arezou Zoroufian

TEHRAN HEART CENTER


INTERNATIONAL CARDIOVASCULAR SURGERY MEETINGS CALENDER (2012-2013)

Congress Time - Location Address

Intermediate Cardiac Surgery

APACVS 30th Annual Winter Educational Meeting

47th Annual Meeting of The Society of The Thoracic Surgeon

2011 SCMR/Euro CMR Scientific Sessions

11th Annual International Symposium on Congenital Heart Disease

40th Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery

Annual Meeting of Indian Association of Cardiovascular Thoracic Surgeon (57th)

EACTS Robotic Course (Part II)

The 3rd Joint meeting 29th Cardiovascular Surgical Symposium 6th Cardiac Surgery Update & Progress

5-6 January 2011London

UK

28-30 January 2011 San Diego, CAUnited States

31 January-02 February 2011San Diego, CAUnited States

03-06 February 2011Nice

France

10-13 February 2011FL

United States

13-16 February 2011StuttgartGermany

16-20 February 2011Mahabalipuram

India

23-26 February 2011 Strasbourg

France

26 February-05 March 2011Zürs

Austria

http://www.rcseng.ac.uk/education/courses/intermediate-cardiac-surgery

http://www.apacvs.org/documents/PDF/APACVS_Program_San_Diego_2010-.pdf

http://www.sts.org/sections/annualmeeting/

http://www.scmr.org/

http://www.allkids.org/conferences

http://www.gstcvs.org/sections/meetings/index.html

http://www.ctcon2011.com/conference.htm

http://www.eacts.org/content/eacts-meetings-courses

http://www.surgery-zurs.at/



Re-evolution Summit II: Minimal Access & Hybrid Cardiac Surgery With the Cardiovascular Simulation Stampede

The Society of Cardiovascular Anesthesiologists (SCA) 16th Annual Update on Cardiopulmonary Bypass

EACTS Right ventricular outflow tract mangement from neonates to adults: an interdisciplinary view

Marbella Aortic Symposium - Disasters In Open and Endovascular Aortic Procedures, Learning from Complications

31st Annual 2011 CREF Perfusion Meeting cardiothoracic surgery symposium

EACTS Course “Open and endovascular aortic therapy”

Society for Cardiothoracic Surgery in Great Britain and Ireland (SCTS) Annual meeting and cardiothoracic forum 2011

Asia Pacific Heart Valve Forum - Beyond the Basics

31st Annual Meeting for The International Society for Heart and Lung Transplantation (ISHLT)

AmSECT 49th International Conference

50 Years of Cardiac Surgery University Hospital Zurich

18th Annual Conference of the Egyptian Society of Cardiothoracic Surgery

Arteriosclerosis, Thrombosis and Vascular Biology 2011 Scientific Sessions in collaboration with the Council on Peripheral Vascular Disease

Advanced Cardiac Techniques in Surgery (ACTS) 2011

Mitral 2011 Conclave

7th International Conference of the Pediatric Mechanical Circulatory Support Systems & Cardiopulmonary Perfusion

03-05 March 2011Houston, TXUnited States

06-11 March 2011Whistler, BC

Canada

11-12 March 2011Palma de Majorca

Spain

11-12 March 2011Marbella

Spain

09-13 March 2011Newport beach, CA

United States

16-18 March 2011Windsor

UK

20-22 March 2011London

UK

31 March-01 April 2011Brisbane, Queensland

Australia

13-16 April 2011San Diego, California

United States

13-16 April 2011New Orleans, LA

United States

15-16 April 2011Zurich

Switzerland

27-29 April 201Alexandria

Egypt

28-30 April 2011Chicago, IL

United States

04-05 May 2011New York, NYUnited States

05-06 2011 MayNew York, NYUnited States

05-07 May 2011PhiladelphiaUnited States

[email protected]

http://www.scahq.org/sca3/events/2011/cbp/abstracts/

http://www.eacts.org/content/eacts-meetings-courses

http://www.MAS2011.COM

http://www.amainc.com/cref_cardiothoracic.html

http://www.eacts.org

http://meeting.scts.org/

http://www.tayloredimages.com.au

http://www.ishlt.org

http://www.amsect.org

http://www.50yearscardiacsurgery.ch/

http://escts2011.com

http://www.americanheart.org/presenter.jhtml?identifier=3057022

http://www.promedicacme.com

http://www.aats.org/mitral/index.html

http://www.hmc.psu.edu/childrens/pedscpb

TEHRAN HEART CENTER


AmSECT Perfusion Safety & Best Practicesin Perfusion


07-11 May 2011PhiladelphiaUnited States

11-13 May 2011AthensGreece

12-13 May 2011New York, NYUnited States

20-22 May 2011MoscowRussian

24-26 Mar 2011Houston, TXUnited States

26-29 May 2011Phuket

Thailand

08-11 June 2011Washington, DC

United States

09-10 June 2011Liverpool

United Kingdom

09-11 June 2011Crete

GREECE

13-15 June 2011Berlin

Germany

14-18 June 2011New Orleans, LA

United States

23-26 June 2011IstanbulTurkey

25-28 June 2011Barcelona

Spain

24-26 July 2011Queensland

Australia

17-18 September 2011Singapore

01-05 October 2011Lisbon

Portugal

American Association for Thoracic Surgery's 91st Annual Meeting

MIRA (Minimally Invasive Robotic Association) 6th International Congress

Innovations and Practical Applications in Vascular Surgery Special Sessions: Management of Non-Healing Wounds

The 60th International Congress of the European Society for Cardiovascular and Endovascular Surgery (ESCVS)

Houston Aortic Symposium: Frontiers in Cardiovascular Diseases, The Fourth in the Series

ASCVTS-ATCSA 2011 Joint Meeting of 19th

ASCVTS and 21st ATCSA

The international society for minimally invasive cardiothoracic surgery (ISMICS) 2011 Annual Meeting

Liverpool Aortic Symposium IV New Frontiers - Bi-annual event

European Society for Surgical Research (ESSR) Annual Scientific Congress 2011

21st Congress of the World Society of Cardio-Thoracic Surgeons

5th Annual The New Orleans Conference: Practices in Cardiac Surgery and Extracorporeal Technologies

3rd Scientific Meeting of The World Society for Pediatric and Congenital Heart Surgery

6th Biennial Meeting - Joint meeting of the Society for heart valve Disease & Heart Valve Society Of America

2011 ISCVID - 11th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections

Inaugural Meeting Of The Federation Of Asian Perfusion Societies - “New Frontiers In Cardiovascular Perfusion”

25th European Association for Cardio-thoracic Surgery (EACTS) Annual Meeting

http://www.aats.org/

http://www.mirasurgery.org/abstracts/index.php

http://www.columbiasurgery.org/cme/event_20110512.html

http://escvs2011.org/escvs/

http://www.promedicacme.com/meeting/Houston-Aortic-Symposium-Frontiers-

in-66.html

http://www.ascvts-atcsa2011.org/

http://www.ismics.org/annualMeeting.html

http://[email protected]

http://www.essr.org/cms/website.php?id=/en/essr_home.htm

http://www.wscts2011.com/

http://www.TheNewOrleansConference.com

http://www.wspchs2011.org/en/

http://[email protected]

http://www.iscvid2011.com

http://www.secretariat@ssect.

http://www.eacts.org/


INTERNATIONAL CARDIOVASCULAR MEETING AND CONGRESSES CALENDER (2012-2013)

Title Location Start Date End Date

Miami Beach, FLUnited States

Reno, NevadaUnited States

Kohala CoastHawaii

Coral Gables, Florida United States

Truckee, caUnited States

Snowbird, UtahUnited States

BrusselsBeIgium

LondonUK

St. Petersburg, FloridaUnited States

Bahrain

Scottsdale, AZUnited States

LondonUK

16 January 2011

27 January 2011

31 January 2011

3 February 2011

6 February 2011

9 February 2011

10 February 2011

10 February 2011

10 February 2011

11 February 2011

13 February 2011

17 February 2011

20 January 2011

30 January 2011

3 February 2011

5 February 2011

9 February 2011

12 February 2011

11 February 2011

11 February 2011

13 February 2011

13 February 2011

17 February 2011

18 February 2011

3rd Asia PCR/ SingLive 2012

32nd Annual Seminar of The American Academy of Cardiovascular Perfusion

Arrhythmias & the Heart

Cardiovascular Disease Prevention 2011: Ninth Annual Comprehensive Symposium

Vascular Care 2011

36th Annual Cardiovascular Conference at Snowbird

30th Annual Scientific Meeting of the Belgian Society of Cardiology

3rd National Conference Chronic Heart Failure and Hypertension 2011

11th Annual International Symposium on Congenital Heart Disease

Bahrain 2011 Pan Arab and European HTN Conference

iCON 2011 – International Congress for Endovascular Interventions

Diagnostic and Interventional Radiology 2011 2nd national conference

TEHRAN HEART CENTER



Scottsdale, AZUnited States

KishIran

GenoaItaly

Hong Kong

Washington, DC United State

CancúnMexico

San Diego, CAUnited States

Snowmass Village, COUnited States

YokohamaJapan

CairoEgypt

BudapestHungary

Houston, TXUnited States

GenoaItaly

BrusselsBelgium

New OrleansUnited States

MarmarisTurkey

CannesFrance

LondonUK

GenevaSwitzerland

SeoulKorea

Houston, TXUnited States

Baltimore, MDUnited States

17 February 2011

23 February 2011

24 February 2011

25 February 2011

27 February 2011

28 February 2011

3 March 2011

13 March 2011

18 March 2011

23 March 2011

24 March 2011

24 March 2011

31 March 2011

1 April 2011

2 April 2011

6 April 2011

8 April 2011

9 April 2011

14 April 2011

27 April 2011

28 April 2011

4 May 2011

19 February 2011

25 February 2011

26 February 2011

27 February 2011

1 March 2011

4 March 2011

4 March 2011

18 March 2011

20 March 2011

25 March 2011

26 March 2011

26 March 2011

02 April 2011

2 April 2011

2 April 2011

10 April 2011

10 April 2011

12 April 2011

16 April 2011

29 April 2011

30 April 2011

7 May 2011

Scottsdale Interventional Forum 2011

5th Annual Cardiovascular Congress (MECC 2011)

10th Genoa Meeting on Hypertension, Diabetes and Renal Diseases

CardioRhythm 2011

CRT 2011: Cardiovascular Research Technologies

16th Annual 2011 Cardiology at Cancún-Focus on Clinical Cardiology and Prevention

The Future of Genomic Medicine IV

Interventional Cardiology 2011: 26th Annual International Symposium

75th Annual Scientific Meeting of the Japanese Circulation Society (JCS2011)

Heart Attack 2011 /5th Acute Cardiac Care Course

XII International Forum for the Evaluation of Cardiovascular Care

The Houston Aortic Symposium: Frontiers in Cardiovascular Diseases, the Fourth in the Series

IX National Congress of the Italian Society for Cardiovascular Prevention - (SIPREC)

11th Annual Spring Meeting on Cardiovascular Nursing

60th Annual Scientific Session & Expo, ACC i2 Summit

8th Mediterranean Meeting on Hypertension and Atherosclerosis

6th Clinical Update on Cardiac MRI & CT

33rd Chairing Cross International Symposium: Vascular & Endovascular Consensus Update

EuroPRevent 2011

Angioplasty Summit: Transcatheter Cardiovascular Therapeutics Asia Pacific 2011

Concepts in Contemporary Cardiovascular Medicine 2011

SCAI 2011 Scientific Sessions



Kuala Lumpur Malaysia

Baltimore, MDUnited States

San JuanPuerto Rico

Miami Beach, FLUnited States

TehranIran

FlorenceItaly

AmsterdamNetherlands

ParisFrance

GothenburgSweden

MarseilleFrance

New Orleans, LAUnited States

MarrakeshMorocco

Hammam SousseTunisia

New York, NYUnited States

MilanItaly

FrankfurtGermany

FrankfurtGermany

South CarolinaUnited States

BarcelonaSpain

MadridSpain

GothenburgSweden

Orlando, FLUnited States

5 May 2011

6 May 2011

6 May 2011

8 May 2011

10 May 2011

11 May 2011

15 May 2011

17 May 2011

21 May 2011

27 May 2011

1 June 2011

1 June 2011

9 June 2011

15 June 2011

17 June 2011

23 June 2011

23 June 2011

23 June 2011

24 June 2011

26 June 2011

26 June 2011

26 June 2011

8 May 2011

6 May 2011

7 May 2011

11 May 2011

13 May 2011

14 May 2011

18 May 2011

20 May 2011

24 May 2011

28 May 2011

4 June 2011

5 June 2011

11 June 2011

18 June 2011

20 June 2011

25 June 2011

25 June 2011

26 June 2011

28 June 2011

29 June 2011

29 June 2011

30 June 2011

18th Asian Pacific Congress of Cardiology (APSC 2011)

Complex Coronary Complications (C3) Summit, in Conjunction with the SCAI 2011 Scientific Sessions

New Advances in Cardiovascular and Endovascular Technologies

17th Annual Interventional Cardiology Fellows Course

17th Congress of Iranian Heart Association

42 ND Congress of ANMCO Italian Association of Hospital Cardiologists

ICNC10 - Nuclear Cardiology and Cardiac CT

EuroPCR

Heart Failure Congress 2011

RHYTHM 2011

12th Annual New Cardiovascular Horizons

8th Metabolic Syndrome, Type II Diabetes and Atherosclerosis Congress

The 8 th Tunisian and European days of Cardiology Practice

Live Symposium of Complex Coronary & Vascular Cases 2011

21st Annual Scientific Meeting of the European Society of Hypertension (ESH)

iCi 2011 - Imaging in Cardiovascular Interventions

CSI 2011-Congenital & Structural Interventions

14th Annual Cardiothoracic Update and TEE Board Review

3rd Annual Joint Scientific Meeting of the Heart Valve Society of America & Society for Heart Valve Disease

EUROPACE, the Meeting of the European Heart Rhythm Association (EHRA) 2011

79th European Atherosclerosis Society Congress (EAS 2011)

Complex Cardiovascular Catheter Therapeutics (C3)

TEHRAN HEART CENTER



Basic Cardiovascular Sciences 2011 Scientific Sessions

59th Annual Scientific Meeting of the Cardiac Society of Australia and New Zealand (CSANZ2011) in conjunction with the 35th Annual Scientific Meeting of the International Society for Heart Research

ESC Congress 2011

20th EuroChap 2011 European Congress of the International Union of Angiology

CIRSE 2011

27th Annual Echocardiography in Pediatric and Adult Congenital Heart Disease

9th International Congress on Coronary Artery Disease

14th British Society for Heart Failure (BSH) Annual Autumn Meeting 2011

Heart, Vessels & Diabetes European Conference

Multidisciplinary European Endovascular Therapy (MEET 2011)

EUROECHO 2010

New Orleans, LAUnited States

New ZealandAustralia

ParisFrance

PortoroseSlovenia

MunichGermany

Rochester, MN,United States

Venice Italy

LondonUK

Athens

RomeItaly

CopenhagenDenmark

18 July 2011

11 August 2011

27 August 2011

7 September 2011

10 September 2011

9 October 2011

23 October 2011

24 November 2011

3 November 2011

1 December 2011

8 December 2010

21 July 2011

15 August 2011

31 August 2011

9 September 2011

14 September 2011

12 October 2011

26 October 2011

25 November 2011

5 November 2011

3 December 2011

11 December 2010


Information for Authors

The first three consecutive issues of "The Journal of Tehran University Heart Center" were published under the title of "The Journal of Tehran Heart Center" with ISSN: 1735-5370. From the fourth issue onward, however, the journal has been entitled ‘’The Journal of Tehran University Heart Center" with ISSN:1735-8620.

"The Journal of Tehran University Heart Center" aims to publish the highest quality material, both clinical and scientific, on all aspects of Cardiovascular Medicine. It includes articles related to research findings, technical evaluations, and reviews. In addition, it provides a forum for the exchange of information on all aspects of Cardiovascular Medicine, including educational issues. "The journal of Tehran University Heart Center" is an international, English language, peer reviewed journal concerned with Cardiovascular Medicine. It is an official journal of the Cardiovascular Research Center of the Tehran University of Medical Sciences (in collaboration with the Iranian Society of Cardiac Surgeons) and is published quarterly. Papers submitted to this journal which do not adhere to the Instructions for Authors will be returned for appropriate revision to be in line with the Instructions for Authors. They may then be resubmitted. Submission of an article implies that the work described has not been published previously (except in the form of an abstract or as part of a published lecture or academic thesis), that it is not under consideration for publication elsewhere, that its publication is approved by all Authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, without the written consent of the publisher.

Four double spaced copies on 8 1/2 × 11 in. paper should be sent to: Dr. A. Karimi, Editor in Chief, "The Journal of Tehran University Heart Center", Tehran Heart Center, North Kargar Street,

The Journal of Tehran University Heart Center” accepts the following categories of articles:”Guest Editorial Original Article Clinical and pre-clinical papers based on either normal subjects or patients and the result of cardiovascular pre-clinical

research will be Considered for publication provided they have an obvious clinical relevance. Brief communication Case reportReview Article "The Journal of Tehran University Heart Center" publishes a limited number of scholarly, comprehensive reviews whose

aims are to summarize and critically evaluate research in the field addressed and identify future implications. Reviews should not exceed 5000 words.

Letter to editor Letters to the editor must not exceed 500 words and should focus on a specific article published in "The Journal of Tehran

University Heart Center" within the preceding 12 weeks. No original data may be included. Authors will receive pre-publi-cation proofs, and the authors of the article cited invited to reply.

Scope of the journal

Article Categories

Submission of manuscripts

TEHRAN HEART CENTER


Authors whose first language is not English are requested to have their manuscripts checked carefully before submission. This will help expedite the review process and avoid confusion. Abbreviations of standard SI units of measurement only should be used.

The Authors should state that their study complies with the Declaration of Helsinki that the locally appointed ethics committee has approved the research protocol and that informed consent has been obtained from the subjects (or their guardians).

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Declaration of Helsinki

All manuscripts correctly submitted to will first be reviewed by the Editors. Some manuscripts will be returned to authors at this stage if the paper is deemed inappropriate for publication in “The Journal of Tehran University Heart Center”, if the paper does not meet submission requirements, or if the paper is not deemed to have a sufficiently high priority. All papers considered suitable by the Editors to progress further in the review process will undergo appropriate peer review and all pa-pers provisionally accepted for publication will undergo a detailed statistical review.

All submitted manuscripts must not exceed 5000 words, including References, Figure Legends and Tables. The number of Tables, Figures and References should be appropriate to the manuscript content and should not be excessive. Authors should comply with the manuscript formatting and the ethical conventions of the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” issued by the International Committee of Medical Journal Editors ( http://www.icmje.org ).

Review of manuscripts

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Tehran, Iran. 1411713138. Photocopies or good reproductions of illustrations are acceptable only on the spare copies. Included also should be a set

of the electronic files of the manuscript on floppy - disk or CD-ROM. For preparation of electronic files, see the instructions herein below.

Also, manuscripts can be submitted electronically via the journal’s website: http://jthc.tums.ac.ir. On-line submission al-lows the manuscript to be handled in electronic forms throughout the review process.

Authors should comply with the clinical trial registration statement from the ICMJE. More information can be found at www.icmje.org. Clinical trial reports should also comply with the Consolidated Standards of Reporting Trials (CONSORT) and include a flow diagram presenting the enrollment, intervention allocation, follow-up, and data analysis with number of subjects for each (www.consort-statement.org). Please also refer specifically to the CONSORT Checklist of items to include when reporting a randomized clinical trial.

Original articles should be divided into the following sections: (1) Title page, (2) Abstract and Keywords, (3) Introduc-tion, (4) Methods, (5) Results, (6) Discussion, (7) Conclusion, (8) Acknowledgements, (9) References, (10) Figure legends, (11) Tables, (12) Figures.

Clinical trials

Section of the manuscripts

General format

Prepare your manuscript text using a word processing package. Submissions of text in the form of PDF files are not


The title page should include the following: (1) the title, (2) the name (s) of authors and their highest degree ( no more than 12 authors are acceptable), (3) the institution (s) where work was performed, (4) institution, and location of all authors, (5) the address, telephone number, fax number and e-mail address of the corresponding author.

Title page

All abstracts may not contain more than 250 words and should also be submitted as a separate file. The abstract should be formatted with the following heading: (1) Background, (2) Methods, (3) Results, (4) Conclusion.

A maximum of six Keywords may be submitted.

The review process will not begin until all figures are received. Figures should be limited to the number necessary for clarity and must not duplicate data given in tables or in the text. They must be suitable for high quality reproduction and should be submitted in the desired final printed size so that reduction can be avoided. Figures should be no larger than 125 (height)×180 (width) mm (5×7 inches) and should be submitted in a separate file from that of the manuscript.

Abstract

Figures

permitted. Manuscripts should be double-spaced, including text, tables, legends and references. Number each page. Please avoid footnotes; use instead, and as sparingly as possible, parenthesis within brackets. Enter text in the style and order of the Journal. Type references in the correct order and style of the journal. Type unjustified, without hyphenation, except for compound words. Type headings in the style of the journal. Use the TAB key once for paragraph indents. Where possible use Times New Roman for the text font and Symbol for the Greek and special characters. Use the word processing formatting features to indicate Bold, Italic, Greek, Maths, Superscript and subscript characters. Clearly identify unusual symbols and Greek letters. Differentiate between the letter o and zero, and the letters I and i and the number 1. Mark the approximate position of each figure and table. Check the final copy of your paper carefully, as any spelling mistakes and errors may be translated into the typeset version.

Figures should be saved in TIFF format at a resolution of at least 300 pixels per inch at the final printed size for colour figures and photographs, and 1200 pixels per inch for black and white line drawings. Although some other formats can be translated into TIFF format by the publisher, the conversion may alter the tones, resolution and contrast of the image. Digital colour art should be submitted in CMYK rather than RGB format, as the printing process requires colours to be separated into CMYK and this conversion can alter the intensity and brightness of colours. Therefore authors should be satisfied with the colours in CMYK (both on screen and when printed) before submission. Please also keep in mind that colours can appear differently on different screens and printers. Failure to follow these guides could result in complications and delays.

Photographs: Photographs should be of sufficiently high quality with respect to detail, contrast and fineness of grain to withstand the inevitable loss of contrast and detail inherent in the printing process. Please indicate the magnification by a rule on the photograph. Colour figures: There is a special charge for the inclusion of colour figures. Figure legends: These should be on a separate, numbered manuscript sheet grouped under the heading “Legends” on a separate sheet of the manuscript after the References. Define all symbols and abbreviations used in the figure. All abbreviations and should be redefined in the legend.

Electronic submission of figures

Tables should be typed with double spacing, but minimizing redundant space and each should be placed on a separate sheet. Tables should be submitted, wherever possible, in portraits, as opposed to landscape, layout. Each Table should be numbered in sequence using Arabic numerals. Tables should also have a title above and an explanatory footnote below. All abbreviations and should be redefined in the Footnote.

Tables

TEHRAN HEART CENTER


All manuscripts selected for publication will be reviewed for the appropriateness and accuracy of the statistical methods used and the interpretation of statistical results. All papers submitted should provide in their Methods section a subsection detailing the statistical methods, including the specific method used to summarize the data, the methods used to test their hypothesis testing and (if any) the level of significance used for hypothesis testing.

At submission, the editors require authors to disclose any financial association that might pose a conflict of interest in connection with the submitted article. All sources of funding for the work should be acknowledged in a footnote on the title page and in the Acknowledgements within the manuscript, as should all the institutional affiliations of the authors (includ-ing corporate appointments). Other kinds of associations, such as consultancies, stock ownership or other equity interest or patent-licensing arrangements should be disclosed to the editors in the cover letter at the time of the of submission. If no conflict of interest exists, please state this in the cover letter.

Page proofs will be sent to the corresponding author. Please provide an e-mail address to enable page proofs to be sent as PDF files via e-mail. These should be checked thoroughly for any possible changes or typographic errors. Significant alterations instigated at this stage by the author will be charged to the author. It is the intention of the Editor to review, correct and publish your article as quickly as possible. To achieve this it is important that all of your corrections are returned to us in one all- inclusive mail or fax. Subsequent additional corrections will not be possible, so please ensure that your first communication is complete.

Statistics

Conflict of interest

Proofs

Number references sequentially and use Arabic number in superscript to cite the reference in the text. All references should be compiled at the end of the article in the Vancouver style. Complete information should be given for each reference including the title of the article, abbreviated journal title and page numbers. All authors should be listed. Personal communi-cations; manuscripts in preparation and other unpublished data should not be cited in the reference list but may be mentioned in parentheses in the text. Authors should get permission from the source to cite unpublished data.

Titles of journals should be abbreviated in accordance with Index Medicus (see list printed annually in the January issue of Index Medicus). If a journal is not listed in Index Medicus then its name should be written out in full.

Article citation example:Journal citation example: 1. Schroeder S, Baumbach A, Mahrholdt H. The impact of untreated coronary dissections on the

acute and long-term outcome after intravascular ultrasound guided PTCA. Eur Heart J 2000;21:137-145.Chapter citation example: 2. Nichols WW, O’Rourke MF. Aging, high blood pressure and disease in humans. In: Arnold

E, ed. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. 3rd ed. London/Melbourne/Auckland: Lea and Febiger; 1990. p. 398-420.

Webpage citation example: 3. Panteghini M. Recommendations on use of biochemical markers in acute coronary syn-drome: IFCC proposals. eJIFCC 14. http://www.ifcc.org/ejifcc/vol14no2/1402062003014n.htm (28 May 2004). Where the date in parenthesis refers to the access date.

Reference format

All sources of funding and support, and substantive contributions of individuals, should be noted in the Acknowledge-ments, positioned before the list of references.

Acknowledgements


TEHRAN HEART CENTER

Subscription Form

The Journal of Tehran University Heart CenterNew Subscription: Continuation of Subscription:

Subscription Form

The Journal of Tehran University Heart CenterNew Subscription: Continuation of Subscription:

Surname:First Name:Hospital or Organization: Date of subscription: Full mail address:

P.O.BOX: Tell: Fax:E-mail: The annual Subscription and postage rate: 100/000 Rials for Iran and US $ 100 including postage for other countries.

Please liquidate the total amount of Subscription and postal charges into: Bank: Refah Branch Code: 1232 Account: Tehran Heart Center Account Number: 200001.28

and send the original Bank slip along with Duly completed form of Subscription to the following address:

Tehran Heart Center,North Karegar Street,Tehran, Iran: 1411713138Tel: +98 21 88029720Fax: +98 21 88029702E-mail: [email protected]

Surname:First Name:Hospital or Organization: Date of subscription: Full mail address:

P.O.BOX: Tell: Fax:E-mail: The annual Subscription and postage rate: 100/000 Rials for Iran and US $ 100 including postage for other countries.

Please liquidate the total amount of Subscription and postal charges into: Bank: Refah Branch Code: 1232 Account: Tehran Heart Center Account Number: 200001.28

and send the original Bank slip along with Duly completed form of Subscription to the following address:

Tehran Heart Center,North Karegar Street,Tehran, Iran: 1411713138Tel: +98 21 88029720Fax: +98 21 88029702E-mail: [email protected]

TEHRAN HEART CENTER

Documents

THE - Tehran University of Medical Sciencesthc.tums.ac.ir/UserFiles/shahraky/files/V7 - N_02 - 2012.pdf · Seifollah Abdi, MD Tehran University of Medical Sciences Alireza Amirzadegan,