Arrhythmias in Chronic Kidney Arrhythmias in Chronic Kidney DiseaseDisease

Prof. Samir Morcos Rafla

FACC, FESC

Alexandria Univ.

Arrhythmias in chronic kidney diseaseArrhythmias in chronic kidney disease

Heart Heart 2011;2011;9797:766-773:766-773

Chronic kidney disease (CKD) is defined Chronic kidney disease (CKD) is defined as evidence of kidney damage or a as evidence of kidney damage or a glomerular filtration rate (GFR) ≤60 glomerular filtration rate (GFR) ≤60 ml/min/1.73 mml/min/1.73 m22 (table 1) (table 1) . .

The most common causes of CKD are The most common causes of CKD are hypertension and diabetes mellitus. The hypertension and diabetes mellitus. The many causes of CKD are associated with many causes of CKD are associated with different varying prognosesdifferent varying prognoses . .

The life expectancy of a 25-year-old The life expectancy of a 25-year-old dialysis patient is 12 years, compared with dialysis patient is 12 years, compared with 32 years for an age equivalent transplant 32 years for an age equivalent transplant recipient and 52 years for a 25-year-old in recipient and 52 years for a 25-year-old in the general population.the general population.

  Even patients with CKD stage 5 will only Even patients with CKD stage 5 will only have a 20–25% chance of surviving long have a 20–25% chance of surviving long enough to require dialysis. enough to require dialysis. The greatest The greatest cause of death in CKD is premature cause of death in CKD is premature cardiovascular diseasecardiovascular disease..

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Both cardiac and renal systems appear to Both cardiac and renal systems appear to

be completely interdependent, further be completely interdependent, further

emphasizing the concept of the emphasizing the concept of the

‘‘cardiorenal syndromecardiorenal syndrome’. ’. This is highlighted This is highlighted

when considering arrhythmias in patients when considering arrhythmias in patients

with impaired renal function.with impaired renal function.

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The arrhythmia burden of the patient with The arrhythmia burden of the patient with CKD is high, with the single greatest CKD is high, with the single greatest contributor to mortality in end stage renal contributor to mortality in end stage renal disease (ESRD) being sudden cardiac disease (ESRD) being sudden cardiac death (SCD).death (SCD).

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Ventricular arrhythmias and sudden death in Ventricular arrhythmias and sudden death in patients with chronic kidney disease.patients with chronic kidney disease.

J Ren Care. 2010 May;36 Suppl 1:54-60 2010 May;36 Suppl 1:54-60..

One in four dialysis patients will die suddenly. Most do One in four dialysis patients will die suddenly. Most do not fall into the high-risk categories that are associated not fall into the high-risk categories that are associated with sudden death in the general population. The cause with sudden death in the general population. The cause of sudden death in the dialysis population is unknown. It of sudden death in the dialysis population is unknown. It may be related to factors associated with chronic kidney may be related to factors associated with chronic kidney disease (CKD) itself, for exampledisease (CKD) itself, for example, inflammation, vascular , inflammation, vascular stiffness, left ventricular hypertrophy, coronary artery stiffness, left ventricular hypertrophy, coronary artery disease, electrolyte/fluid abnormalities or autonomic disease, electrolyte/fluid abnormalities or autonomic dysfunction. dysfunction.

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Studies of patients with implantable cardioverter Studies of patients with implantable cardioverter defibrillators have shown that patients with CKD defibrillators have shown that patients with CKD are more likely to use their devices for ventricular are more likely to use their devices for ventricular arrhythmias but in spite of this still have a high arrhythmias but in spite of this still have a high associated mortality. associated mortality.

Minimising risk of SCD is by good control of basic Minimising risk of SCD is by good control of basic parameters such as parameters such as fluid balancefluid balance, , electrolyteselectrolytes and and blood pressureblood pressure, along with careful , along with careful assessment of all patients for evidence of assessment of all patients for evidence of coronary artery disease coronary artery disease and and heart failure heart failure is the is the mainstay of management of the CKD patient.mainstay of management of the CKD patient.

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With regards to drug therapy, the following With regards to drug therapy, the following key points are noted: key points are noted: 

• • Beta-blockers are advised, but sotalol Beta-blockers are advised, but sotalol should be avoided.should be avoided.

• • Drugs which are not affected by renal Drugs which are not affected by renal metabolism may still have an altered metabolism may still have an altered distribution or binding in CKD.distribution or binding in CKD.

• • All drug treatment must be closely All drug treatment must be closely monitored and possible interactions sought monitored and possible interactions sought thoroughlythoroughly

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Chronic Kidney Disease and Mortality in Chronic Kidney Disease and Mortality in Implantable Cardioverter-Defibrillator RecipientsImplantable Cardioverter-Defibrillator Recipients

Cardiology Research and Practice. Volume 2010 Cardiology Research and Practice. Volume 2010 

Incidence of sudden cardiac death (SCD) in end-Incidence of sudden cardiac death (SCD) in end-stage renal disease (ESRD) remains high. stage renal disease (ESRD) remains high. Limited data is available about whether Limited data is available about whether implantable cardioverter-defibrillators (ICDs) can implantable cardioverter-defibrillators (ICDs) can prevent arrhythmic death in patients with chronic prevent arrhythmic death in patients with chronic kidney disease (CKD). The purpose of this kidney disease (CKD). The purpose of this retrospective study was to determine the impact retrospective study was to determine the impact of CKD on all-cause and sudden cardiac death in of CKD on all-cause and sudden cardiac death in ICD recipients.ICD recipients.

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441 pts were evaluated who underwent ICD 441 pts were evaluated who underwent ICD implantation. Mortality rate was higher in patients implantation. Mortality rate was higher in patients with eGFR < 6 0 mL/min and those with ESRD on with eGFR < 6 0 mL/min and those with ESRD on hemodialysis (43%,  and 54%, resp.) than in hemodialysis (43%,  and 54%, resp.) than in patients with eGFR ≥ 6 0 mL/min patients with eGFR ≥ 6 0 mL/min (23%;   < . 0 0 0 5). 𝑃(23%;   < . 0 0 0 5). 𝑃The SCD rate was also higher in the patients with The SCD rate was also higher in the patients with ESRD (50%) than in CKD patients not on dialysis ESRD (50%) than in CKD patients not on dialysis (10.2%;   < . 0 0 0 5). Mortality rate for single-𝑃(10.2%;   < . 0 0 0 5). Mortality rate for single-𝑃chamber ICDs was 56.8% in comparison with chamber ICDs was 56.8% in comparison with dual-chamber ICDs (38.1%) and for biventricular dual-chamber ICDs (38.1%) and for biventricular ICDs (5.0%) (  < . 0 0 0 5).𝑃ICDs (5.0%) (  < . 0 0 0 5).𝑃

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The enrolled subjects had ICD implantation based on The enrolled subjects had ICD implantation based on the following criteria. (1) the following criteria. (1) Nonsustained VT Nonsustained VT in patients in patients with coronary artery disease (CAD), previous myocardial with coronary artery disease (CAD), previous myocardial infarction (MI), left ventricular (LV) dysfunction, and infarction (MI), left ventricular (LV) dysfunction, and EF <35% who had induced sustained monomorphic VT EF <35% who had induced sustained monomorphic VT that was nonsuppressible with anti-arrhythmic drug. that was nonsuppressible with anti-arrhythmic drug.

(2) (2) EF ≤30% EF ≤30% in patients with a history of MI (MADIT II) . in patients with a history of MI (MADIT II) . (3) (3) VF or sustained VT with syncope, or sustained VT VF or sustained VT with syncope, or sustained VT with an LVEF <40% with an LVEF <40% and severe symptoms (syncope, and severe symptoms (syncope, near syncope, CHF, angina) suggestive of hemodynamic near syncope, CHF, angina) suggestive of hemodynamic compromise. (4) compromise. (4) Syncope of unknown origin in CAD Syncope of unknown origin in CAD patients, and severe LV dysfunction who had inducible patients, and severe LV dysfunction who had inducible sustained monomorphic VT sustained monomorphic VT with hemodynamic with hemodynamic compromise at EP study.compromise at EP study.

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Potassium level changes – arrhythmia Potassium level changes – arrhythmia contributing factor in chronic contributing factor in chronic

kidney disease patientskidney disease patientsRom J Morphol Embryol 2011, 52(3 Suppl):1047–1050Rom J Morphol Embryol 2011, 52(3 Suppl):1047–1050

The aim of the study was to determine in which The aim of the study was to determine in which degree the serum potassium changes are degree the serum potassium changes are implicated in arrhythmias development in CKD implicated in arrhythmias development in CKD patients. patients.

Methods: ECG , HolterMethods: ECG , Holter

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Results: we noticed, in our predialysis group, an Results: we noticed, in our predialysis group, an important correlation between important correlation between hyper-/hypokalemia and arrhythmias appearance, hyper-/hypokalemia and arrhythmias appearance,

more frequent during hypokalemia episodes more frequent during hypokalemia episodes (OR=4.04, respectively OR=7.5). The same (OR=4.04, respectively OR=7.5). The same

situation was observed in chronic dialysis groupsituation was observed in chronic dialysis group . .

Conclusions: Conclusions: HypokalemiaHypokalemia is a stronger risk is a stronger risk factor than factor than hyperkalemiahyperkalemia, but all together, any , but all together, any minimal changes in serum potassium levelsminimal changes in serum potassium levels

could determine arrhythmia in CKD patientscould determine arrhythmia in CKD patients . .

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Knowledge GapKnowledge Gap

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Excessive bleeding has been noted in pts Excessive bleeding has been noted in pts administered warfarin in therapeutic administered warfarin in therapeutic doses. The clinical dilemma is that stroke doses. The clinical dilemma is that stroke risk increases with declining kidney risk increases with declining kidney function, but bleeding risk increases function, but bleeding risk increases during warfarin anticoagulationduring warfarin anticoagulation..

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Risk of arrhythmic and nonarrhythmic death Risk of arrhythmic and nonarrhythmic death in patients with heart failure and chronic in patients with heart failure and chronic

kidney diseasekidney diseaseAmerican Heart Journal American Heart Journal Volume 161, Issue 1 , Pages 204- , Pages 204-

209.e1, January 2011209.e1, January 2011

Among 6,378 patients without an ICD (age 60 ± Among 6,378 patients without an ICD (age 60 ± 10, LVEF 27 ± 6, male 86%), there were 421 10, LVEF 27 ± 6, male 86%), there were 421 arrhythmic and 1188 nonarrhythmic deaths over a arrhythmic and 1188 nonarrhythmic deaths over a median follow-up of 34 months. median follow-up of 34 months.

Worse HF or CKD stages were associated with Worse HF or CKD stages were associated with increased risk of both arrhythmic and increased risk of both arrhythmic and nonarrhythmic deathnonarrhythmic death

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The increase in the risk of nonarrhythmic death The increase in the risk of nonarrhythmic death in the worst HF stage was disproportionately in the worst HF stage was disproportionately higher than that of arrhythmic death, and this higher than that of arrhythmic death, and this disproportionate effect was more exaggerated in disproportionate effect was more exaggerated in the presence of more advanced CKD.the presence of more advanced CKD.

ConclusionConclusion

While advanced CKD and HF stages are While advanced CKD and HF stages are associated with increased risk of arrhythmic and associated with increased risk of arrhythmic and nonarrhythmic death, benefits of ICDs in patients nonarrhythmic death, benefits of ICDs in patients with more advanced disease may be limited by with more advanced disease may be limited by the preponderance of nonarrhythmic death.the preponderance of nonarrhythmic death.

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Figure  shows the association of HF and CKD stage with  shows the association of HF and CKD stage with arrhythmic death. Subjects with the most advanced arrhythmic death. Subjects with the most advanced stages of HF and CKD (HF 4/CKD 4) had 13.0 times stages of HF and CKD (HF 4/CKD 4) had 13.0 times (95% CI 4.9-34.2) the hazard of dying of an arrhythmia (95% CI 4.9-34.2) the hazard of dying of an arrhythmia compared with patients in the least advanced stages compared with patients in the least advanced stages (HF 1/CKD 1).(HF 1/CKD 1). 2323

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Summary of Studies on Noninvasive Risk Summary of Studies on Noninvasive Risk Assessment in Dialysis PatientsAssessment in Dialysis Patients

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StudiesInvestigated

MarkerOutcome Measure

Patient Characteristics

Salient Findings

Krane et al, 200924LVHSCD

1253 patients with type 2

diabetes on HD

LVH associated with a 60% higher relative risk of SCD

Nishimura et al37HRV+LVHSCD

196 asymptomatic HD patients with LVH

LF/HF ratio in HRV was an

independent predictor of SCD

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Questions:Questions:-What are the predictors of SD in CKD?What are the predictors of SD in CKD?-What are the indications of ICD in CKD? What are the indications of ICD in CKD? Answer :slide 13Answer :slide 13- What is the appropriate INR in Marevan What is the appropriate INR in Marevan treated CKD pts? Answer: 2treated CKD pts? Answer: 2-What are suitable antiarrhythmic drugs in What are suitable antiarrhythmic drugs in CKD pts? Answer : Amiodarone, CKD pts? Answer : Amiodarone, Propafenon (if LV wall< 14 mm)Propafenon (if LV wall< 14 mm)

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What are the predictors of SD in CKD?What are the predictors of SD in CKD?-LVHLVH-LVFLVF-HR VariabilityHR Variability-Mutlivessel coronary diseaseMutlivessel coronary disease-Acute myocardial infarctionAcute myocardial infarction-K hyper or hypoK hyper or hypo-WithdrawalWithdrawal-CardiomyopathyCardiomyopathy

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CONCLUSIONSCONCLUSIONS

Chronic kidney disease was associated with Chronic kidney disease was associated with an increased risk of stroke or systemic an increased risk of stroke or systemic

thromboembolism and bleeding among thromboembolism and bleeding among patients with atrial fibrillation. Warfarin patients with atrial fibrillation. Warfarin

treatment was associated with a decreased treatment was associated with a decreased risk of stroke or systemic thromboembolism risk of stroke or systemic thromboembolism among pnts with CKD, whereas warfarin among pnts with CKD, whereas warfarin and aspirin were associated with an and aspirin were associated with an increased risk of bleeding. increased risk of bleeding.

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