Review Article Cardiomyopathy

7/18/2019 Review Article Cardiomyopathy

http://slidepdf.com/reader/full/review-article-cardiomyopathy 1/9

Review Article

Cardiomyopathy in Young Adults

Introduction

Cardiomyopathy are commonly divided into three types: dilated, hypertrophic and restrictive

forms. The estimated prevalence of dilated cardiomyopathy is 920 cases per 100,000 persons, 50

to 200 cases per 100,000 persons of hypertrophic cardiomyopathy while restrictive

cardiomyopathy is the rarest encountered form1. In young adults, peripartum cardiomyopathy

constitutes a rare but potentially life-threatening condition when left untreated. In this review

article, we will present an overview of peripartum cardiomyopathy, its management, prognosisand prevention.

Case illustration

A 33 year old female was brought to the hospital because of her generalized edema and

shortness of breath. The patient history reveals that the symptoms originated 5 months earlier. At

5 months postpartum, an ulcer appeared on the anterior medial left leg. The ulcer was red, tender

and oozing clear liquid. She was taken to the nearest health clinic where she was diagnosed with

diabetes mellitus and discharged with ‗sugar pills‘, the names of which the patient could not

recall. However, the ulcer remained unchanged. Financial difficulties had hindered the patient

from seeking medical care and by the fourth month of illness, the edema had spread to both of

her upper and lower extremities along with a new onset of dyspnea. At this point, she was taken

to a hospital in order to receive treatment.

Medical history reveals that the patient was diagnosed with gestational hypertension at

the second trimester of pregnancy. Tetanus vaccination status has never been administered. The

patient and family denied a history of seizure or hemorrhage during labor. She gave birth at 36

weeks of gestation to a viable 3,3kg male infant who is healthy and thriving presently. On the

eleventh month postpartum, patient was taken to the hospital and a full investigation was

performed. On physical examination, she was conscious but in moderate pain. Vital signs were

at normal range. Generalized edema was observed throughout the body with pitting edema on

both of her lower extremities. Massive ascites with abdominal circumference of 106cm was also

observed. Laboratory result showed normocytic normochromic anemia (Hb 11, 50 g/dL, Ht

36,84%). Urine analysis revealed cloudy appearance with the presence of high leukocyte

esterase, 16 leukocytes (N: 0-10) and 1+ bacteria. Erythrocyte sedimentation rate was elevated at



20mm/hr along with total bilirubin of 1.4g/dL (N: 0.20-1.0g/dL). Albumin value was 3.01

(N:3.50-5.00g/dL) and potassium levels were 2.8g/dL (N: 3.6-5.0g/dL). Abdominal ultrasound

revealed massive ascites and other abdominal organs are within normal size range. Chest

roentgenogram revealed a CTR ratio of greater than 50% and increased bronchopulmonary

vasculature. Lung bases are cloudy and filled with fluid. A twelve-lead standard

electrocardiogram (ECG) showed tachycardia and right axis deviation. Echocardiography

revealed severe left ventricular systolic dysfunction with ejection fraction of 30% and dilated left

ventricle.

Disease Classification

Cardiomyopathy is classified into two forms2:

1). Primary form – disease are caused by damage to the heart muscle asa result of idiopathic or genetic mutations. Examples includehypertrophic cardiomyopathy, arrhythmogenic right ventricularcardiomyopathy, isolated ventricular non-compaction, mitochondrial

myopathy, eosinophilic endomyocardial disease and endomyocardialfibrosis.

2). Secondary form – disease are caused by damage to the heart muscle

as a result of insult from other factors such as drugs, autoimmunecondition, infections, granulomatous infiltrations, metabolic problems,

connective tissue disorders and neuromuscular disorders .

In many cases, cardiomyopathy is classified into three morphologic

types: dilated, restrictive and hypertrophic due to the differences in their

pathophysiology and anatomic features.

Case Definition

Peripartum cardiomyopathy is defined as cardiac failure that occurs (all most be present)3:

1) In the last month of pregnancy or within five months of delivery

2) No identifiable cause of cardiac failure3) No recognizable heart disease before the last month of pregnancy

4) An ejection fraction of less than 45% or the combination of an M-mode fractional

shortening of less than 30% and an end-diastolic dimension greater than 2.7cm/m2.

Figure 1



Clinical Presentation

The early stages of cardiomyopathy are commonly asymptomatic. As the disease progresses

which may take months to years after the initial insult, patients commonly classic symptoms of

congestive heart failure some of which may be alone or in combination of 4:

I. Dyspnea with or without exertion

II. Palpitations and Diaphoresis

III. Angina

IV. Ascites

V. Peripheral Edema

VI. Pulmonary Edema

VII. Unexplained Fatigue

VIII. Syncope

IX. In some cases, sudden death

Laboratory evaluation may also be beneficial in differentiating between the three forms of

cardiomyopathy5:

Table 1.

Dilated Restrictive Hypertrophic

ChestRoentgenogram

1). Moderate to marked

cardiac silhouetteenlargement2).Pulmonary venoushypertension

Mild cardiac silhouetteenlargement

Mild to moderate cardiacsilhouette enlargement

ElectrocardiogramST-segment and T-wave

abnormalitiesLow voltage,

conduction defectsST-segment and T-wave

abnormalities

EchocardiogramLeft ventriculardilatation and

dysfunction

1). Increased left

ventricular wallthickness2). Normal or mildlyreduced systolicfunction

1). Asymmetric septal

hypertrophy2). Systolic anterior

motion (SAM) of themitral valve



Dilated Cardiomyopathy

Alcohol 1)Consuming >90g/day

2)Polymorphism ofgene ALDH2 encodingalcohol metabolizing

enzyme

Peripartum 1)Develop at the last

trimester to within fivemonths postpartum

2)Inflammatorymyocarditis, immune

activation and gestationalhypertension

NeuromuscularDisease

Duchenne MuscularDystrophy associatedwith myocyte death.

Drugs1)Antineoplastic

Agents2)Anthracyclin

derivative3)Damage to inner

mitochondrialmembrane

Tako-TsuboDCM/Stress

1)Ballooning of coronaryepicardial coronary

vessels2)Associated withsudden stress or

adrenergic surge oncardiac muscle

Arrythmogenicdysplasia Right

VentricularCardiomyopathy/

Dysplasia 1)Autosomal dominant

mutationof Plakophilin-2(PKP-2) gene

2)Abnormalities indesmosomes causing

detachment and myocyteapoptosis and fibrofatty

replacement

Left Ventricularnoncompaction1)Result from arrest ofnormal embryogenesis2)Presence of multipledeep trabeculations orsinusoids that form in

the myocardium

Cardiac

catheterization

1). Left ventricular

dilatation anddysfunction2). Elevated left and

open right sided filling pressures

3).Diminished cardiacoutput

1). Normal or mildlyreduced systolicfunction

2). Elevated left- andright-sided filling

pressures

1). Vigorous systolic

function2). Dynamic leftventricular outflow

obstruction3). Elevated left- and

right-sided filling pressures

Etiology and Pathogenesis

The major cause of dilated cardiomyopathy is myocardial damage due to prolonged or

continuous unknown infection, metabolic problems or exposure to toxic agents. On the otherhand, about one third of these patients have familial forms of dilated cardiomyopathy most

commonly caused by mutations in genes encoding for sarcomeric proteins of the heart5. As a

result, these abnormal proteins cause contractile dysfunction by impairing the production and/ortransmission of force of heart pump. Multiple etiologies are related to the development of dilated

cardiomyopathy and they can be seen as listed below:

Figure 2



Hypertrophic Cardiomyopathy

Cardiac DanonDisease

1)Mutation is an X-linkedlysosome-associatedmembrane (LAMP2)

2)Enlarged ventricularmyocytes with Periodic Acid

Schiff positive inclusions

3)LV hypertrophy andventricular pre-excitation

Friedrich's Ataxia1)Autosomal recessive

spinocerebellardegenerative

2)Inadequate levels offrataxin (protein involved in

iron metabolism)

3)Lacking in cellular disarray

in histopathologyexamination.

Fabry Disease

1)An X-linked lysosomalstorage disease caused by

deficiency of lysosomalalpha-galactoside A.

2) Accumulation ofglycosphingolipids

3)Associated with AVconduction abnormalities

and ventriculartacharrythmias

Glycogen Storagecardiomyopathy

1)Mutation in the regulatorygamma-2 subunit (PRKAG2) of

adenosine monophospate-activated protein kinase (AMPK)

2)Characterized by myocytes with

vacuoles in the myocyes thatstain for gylcogen in

histopathology examination

Hypertrophic cardiomyopathy is found in about 1 out of 500 of the general population5. The

most striking abnormality seen in this disease is diastolic dysfunction which may be detected

Doppler tissue imaging and results in elevated LV end-diastolic pressure. The pattern ofhypertrophy differs from those caused by aortic stenosis and hypertension as there are a

disproportionate and disorganized arrangement of myocytes with disorganization of myofibrillar

architecture, along with a variable degree of myocardial fibrosis and thickening of the smallintramural coronary arteries6.

Figure 3



The hallmark of restrictive cardiomyopathy is abnormal diastolic function due to rigid

ventricular walls. At the later stage the disease may impair systolic function as progressive injury

occurs to the myocytes. Partial obliteration of the ventricular cavity by fibrous tissue andthrombus are major contributors to the increased resistance in ventricular filling in restrictive

cardiomyopathy5.

Complications4

A. Atrial FibrillationB. Mitral regurgitationC. Conduction abnormalities

D. Congestive Heart FailureE. Stroke or ThromboembolismF. Hepatomegaly as a result of persistent elevated systemic venous pressure

restrictiveCardiomyopathy

Eosinophilicendomyocardial disease

1)Loeffler's endocarditis orfibroplastic endocarditis

2)Heart cells that are damaged dueto toxic efects of eosinophilic

proteins

3)Hepatosplenomegaly andlocalized eosinophilic infiltration of

other organs commonly present

Iron-overload

cardiomyopathy1)Associated with

frequent bloodtransfusions

2)Hemoglobinopathy -Thalassemia

Cardiac Amyloidosis

1)Deposition of amyloid incardiac interstitium

2)Heart cells is non-compliantand has a waxy appearance

3) Four common symptoms(alone or in combination):

diastolic dysfunction, systolicdysfunction, arrythmias and/or

orthostatic hypotensionCarcinoid

syndrome1) Endocardial fibrosis,

stenosis andregurgitation oftricuspid and/orpulmonary valve

Deficiency 1)Thiamine (B1)

2)Electrolytes3)Selenium

Figure 4



Management

In general, all patients suffering from congestive heart failure should be treated promptly. It is importantto treat the fluid retention with diuretics before initiating an ACE inhibitor or ARB (if patient is intolerant

of ACE-inhibitor)6. Beta-blockers should then be started after the ACE inhibitor has been uptitrated. If

the patient remains asymptomatic, an aldosterone antagonist, ARB or digoxin may be added as ―tripletherapy‖. Anticoagulation and antiplatelet therapy may be considered in patients with depressed left

ventricular function because these patients are at an increased risk of thromboembolism or stroke6.

Preferably, warfarin is prescribed in cases of heart failure, chronic or paroxysmal atrial fibrillation, or in patients who have a history of pulmonary emboli, including stroke and transient ischemic attack. Lowdose aspirin (75-81mg) is used for the prevention of myocardial infarction and death.

Heart Failure treatment during pregnancy

In peripartum cardiomyopathy, treatment are focused on halting the sequel of heart failure. Pregnant

patients are prescribed medications such as hydralazine and nitrates which can reduce afterload along

with digoxin, beta-blockers and loop diuretics6. The use of angiotensin-converting enzyme and

angiotensin receptor blocker are contraindicated in pregnancy because they have been associated withfetopathy such as fetal hypotension, oligohydramnios-anuria and renal tubular dysplasia 7,8. Pregnant

women should also receive anticoagulation therapy as the risk of thromboembolic complications increases

due to higher concentrations of factors II, VII, VIII, X and plasma fibrinogen. The therapy are given and

should be continued up to 6 weeks postpartum or until a normal left ventricular function is confirmed 3.

Warfarin is not used in pregnancy as they can cause spontaneous cerebral hemorrhage when used in the

second and third trimester of pregnancy9,10, however unfractionated or low-molecular-weight heparin can

safe to use in pregnancy.

Heart Failure treatment postpartum

Treatment for postpartum cardiomyopathy is identical to those who are nonpregnant and includes the use

of ACE inhibitors and ARB. Dosage is one-hald the maximum antihypertensive dose. Selective and non-selective beta-blockers are recommended for peripartum cardiomyopathy6 as they have been proven toimprove symptoms, ejection fraction and survival rates. Dosage goal for non-selective beta-blockers such

as carvedilol is 25mg twice a day up to 50mg twice a day for larger patients. Selective beta-blockers suchas metaprolol succinate 100mg can also be given once a day. Diuretics may be used for symptomatic

relief of edema and the use of sprinolactone or digoxin are used in patients who have New York HeartAssociation class III or IV symptoms.

Other proposed therapies include calcium channel antagonists11

, statins12

, monoclonal antibodies13

,

interferon beta14,immunoadsorption15, therapeutic apheresis16, and cardiomyoplasty17.

Prognosis

Prognosis of patients with peripartum cardiomyopathy are based on T-Troponin levels, ORS duration and

ejection fraction. A troponin-T concentration of more than 0.04ng/mL are predictive of persistent left

ventricular dysfunction, a QRS duration of 120ms or more is a risk factor for death and sudden death 18,



while ejection fractions of less than 30% are more indicative of poor left ventricle recovery. Other factors

associated with the lack or recovery include an initial left ventricular end-diastolic dimension of greater

than 5.6cm, left ventricular thrombus and African American race6.

A study on peripartum cardiomyopathy by Elkayam et al19 reported a two year follow-up that out of 100

patients who had the disease, 54 of them had recovered normal left ventricular fucntion at the end of 2

years, nine people that died and four of them which recieved a heart transplant.

Prevention

Since peripartum cardiomyopathy is a rare form of idiopathic primary myocardial disease with a yet

indefinite etiologic cause, prevention are mainly targeted at halting more damage to the dilated heart and

these includes medications such as diuretics, beta-blockers ARB and ACE inhibitors. In patients whose

left ventricular function has fully recovered, subsequent pregnancy still carries a low risk for developing

another sequel of cardiomyopathy20

. On the other hand, if left ventricular function has not recovered, the

risk of worsening heart failure and long-term systolic dysfunction are high and subsequent pregnancy

should be avoided.

References

1. Epidemiology of cardiomyopathy. Clinical Key Elsevier 2012. Retrieved 17 January 2013

2. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies:a positionstatement from the European Society Of Cardiology Working Group on Myocardial andPericardial Diseases. European Heart Journal 2008; 29:270 – 276

3. Ramaraj R, Sorell VL. Peripartum cardiomyopathy: disease causes, diagnosis and treatment.Cleveland Clinic Journal of Medicine 2009;76 (5)

4. Baughman KL et al: Braunwald‘s Heart Disease. Elsevier, Philadelphia, Pennsylvania, 2005

5. Wynne J, Braunwald E: Cardiomyopathy and Myocarditis. Harrison‘s Cardiovascular Medicine.McGraw-Hill, 2010.

6. Amos AM, Jaber WA, Russell SD. Improved outcomes in peripartum cardiomyopathy withcontemporary. American Heart Journal 2006; 152:509 – 513.

7. Pearson GD, Veille JC, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung,and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop

recommendations and review. JAMA 2000; 283:1183 – 1188.

8. Andrade SE, Raebel MA, Brown J, et al. Outpatient use of cardiovascular drugs during pregnancy. Pharmacologic Epidemiology Drug Safety 2008; 17:240 – 247.

9. Ray JG, Vermeulen MJ, Koren G. Taking ACE inhibitors during early pregnancy: is it safe?Canadian Family Physician 2007; 53:1439 – 1440.



10. Clark NP, Delate T, Witt DM, Parker S, McDuffie R. A descriptive evaluation of unfractionated

heparin use during pregnancy. Journal of Thrombolysis 2008

11. Narin C, Reyhanoglu H, Tulek B, et al. Comparison of different dose regimens of enoxaparin indeep vein thrombosis therapy in pregnancy. Advanced Therapy 2008; 25:585 – 594.

12. Yuan Z, Kishimoto C, Shioji K. Beneficial effects of low-dose benidipine in acute autoimmunemyocarditis: suppressive effects on inflammatory cytokines and inducible nitric oxide synthase.Circulation Journal 2003; 67:545 – 550.

13. Li WM, Liu W, Gao C, Zhou BG. Immunoregulatory effects of atorvastatin on experimental

autoimmune myocarditis in Lewis rats. Immunology Cell Biology 2006; 84:274 – 280.

14. Yuan HT, Liao YH, Wang Z, et al. Prevention of myosin-induced autoimmune myocarditis inmice by anti-L3T4 monoclonal antibody. Canadian Journal of Physiology and Pharmacology

2003; 81:84 – 88.

15. Kuhl U, Pauschinger M, Schwimmbeck PL, et al. Interferon-beta treatment eliminatescardiotropic viruses and improves left ventricular function in patients with myocardial persistenceof viral genomes and left ventricular dysfunction. Circulation 2003; 107:2793 – 2798.

16. Felix SB, Staudt A. Non-specific immunoadsorption in patients with dilated cardiomyopathy:mechanisms and clinical effects. International Journal of Cardiology 2006; 112:30 – 33.

17. Bosch T. Therapeutic apheresis — state of the art in the year 2005. Therapeutic Apheresis and

Dialysis 2005; 9:459 – 468.

18. Liu Z, Yuan J, Yanagawa B, Qiu D, McManus BM, Yang D. Coxsackie virus induced

myocarditis: new trends in treatment. Expert Review of Anti Infective Therapy 2005; 3:641 – 650.

19. Elkayam U, Akhter MW, Singh H, et al. Pregnancy-associated cardiomyopathy:clinicalcharacteristics and a comparison between early and late presentation. Circulation 2005;111:2050 – 2055.

20. Fett JD, Christie LG, Murphy JG. Brief communication: Outcomes of subsequent pregnancy after peripartum cardiomyopathy: a case series from Haiti. Annals of Internal Medicine 2006; 145:30 – 34.

Figures:

1. Figure 1. Revised by Malcolm J. ―Types of Cardiomyopathies". The Merck Manual Home HealthHandbook 2008

http://www.eymj.org/DOIx.php?id=10.3349/ymj.2006.47.6.759

http://en.wikipedia.org/wiki/Yonsei_Medical_Journal

http://en.wikipedia.org/wiki/Yonsei_Medical_Journal

http://www.eymj.org/DOIx.php?id=10.3349/ymj.2006.47.6.759

Documents

Review Article Cardiomyopathy