Dialysis-Dependent Cardiomyopathy Patients Demonstrate Poor Survival Despite Reverse Remodeling With Cardiac Resynchronization Therapy Evan Adelstein, MD, FHRS John Gorcsan III, MD Samir Saba, MD, FHRS University of Pittsburgh Heart and Vascular Institute
Dialysis and Sudden Death Dialysis is associated with increased risk of sudden death and ventricular tachyarrhythmias. Arrhythmias comprise 60% of cardiac deaths and 25% of all deaths. Primary cardiac causes: High incidence of structural heart disease (coronary artery disease, LV hypertrophy, and cardiomyopathy). Secondary non-cardiac causes: Electrolyte derangements and fluctuations. Risk increases with longer duration of dialysis dependence.
Prior Studies of ICDs in Dialysis Patients ICDs decrease mortality 42% in secondary prevention patients, but only 50% of patients survive 2 years. ICDs may not decrease mortality in primary prevention patients. MADIT-2 demonstrated U-shaped mortality curve based upon comorbid illnesses. Several small single-center retrospective studies. Increased risk of device-related complications. Vascular access, bleeding, infection. Herzog CA et al. Kidney International 2005; 68: 818-5. Goldenberg I et al. J Am Coll Cardiol 2008; 51: 288-96. Hreybe H et al. PACE 2007; 30: 1091-5. Khan F et al. J Interv Card Electrophysiol 2010; 28: 117-23. Amin MS et al. J Cardiovasc Electrophysiol 2008; 19: 1275-80. Dasgupta A et al. Am J Kidney Dis 2007; 49: 656-63.
Prior Studies of CRT in Dialysis Patients
Study Objectives Is a CRT-defibrillator (CRT-D) associated with a survival advantage compared to a standard ICD in dialysis-dependent patients? Do patients on dialysis who receive CRT undergo cardiac reverse remodeling?
Methods: Patient Selection All patients referred for CRT-D at UPMC between July 2000 - September 2011 meeting following criteria were screened: 1. LV ejection fraction (LVEF) 35 % 2. QRS duration 120 ms 3. NYHA class 2-4 HF
Methods: Patient Cohorts We identified four cohorts (n=600): 1. All dialysis-dependent patients who received CRT- D (n=18). 2. All dialysis-dependent patients who had an unsuccessful LV lead implant and received an ICD (n=10). 3. Non-dialysis patients who received CRT-D and either died within 6 months or had a follow-up echocardiogram 6 months after CRT (n=472). 4. All non-dialysis patients who had an unsuccessful LV lead implant and received an ICD (n=100).
Methods: Prespecified Outcomes Primary endpoint: death from any cause Secondary outcomes in CRT patients who had a follow-up echocardiogram 6 months after CRT: Absolute LVEF change Relative LV end-systolic volume (LVESV) change
Results: Survival Follow-up: 45 ± 30 months 250 (42%) deaths in entire population
CRT-D Dialysis ICD Dialysis P-value* (n=18) (n=10) Age, y 64 ± 10 56 ± 11 0.05 Male, n 15 (83%) 10 (100%) 0.5 Ischemic etiology, n 12 (67%) 6 (60%) 1.0 Diabetes, n 9 (53%) 6 (60%) 1.0 Prior atrial fibrillation, n 7 (41%) 6 (60%) 0.4 NYHA class 3.1 ± 0.3 3.3 ± 0.3 0.3 QRS duration, ms 154 ± 36 167 ± 33 0.3 RBBB, n 0 2 (20%) 0.1 ACE-I or ARB, n 9 (53%) 7 (70%) 0.4 b-blocker, n 12 (71%) 5 (50%) 0.4 LVEF, % 20 ± 7 25 ± 10 0.2 LVEDD, mm 61 ± 10 60 ± 7.5 0.8 LVESD, mm 50 ± 11 50 ± 11 1.0 *2-sided Fisher s exact test for categorical variables
Results: Survival in Dialysis Patients 13 (72%) patients died in dialysis CRT-D group 8 (80%) patients died in dialysis ICD group
Proportion Surviving 1.0 0.8 0.6 50% survival 0.4 0.2 CRT-D, dialysis ICD, dialysis p=0.3 0 1 2 3 Years From Device Implant CRT-D, dialysis 18 10 7 5 ICD, dialysis 10 6 1 0 No difference in survival between dialysis patients with CRT-D vs. ICD: HR 0.64, 95% CI 0.25-1.6, p=0.3 Adding age to model did not affect outcomes: HR 0.65, 95% CI 0.24-1.8, p=0.4
CRT-D No dialysis ICD No dialysis P-value (n=472) (n=100) Age, y 65 ± 12 67 ± 14 0.2 Male, n 335 (71%) 69 (69%) 0.7 Ischemic etiology, n 247 (52%) 62 (62%) 0.08 Diabetes, n 153 (32%) 36 (36%) 0.5 Prior atrial fibrillation, n 235 (50%) 47 (47%) 0.6 NYHA class 3.1 ±0.5 3.0 ± 0.4 0.6 GFR, ml/min 63 ±24 64 ± 25 0.7 GFR <30 ml/min, n 30 (6%) 6 (6%) 0.9 QRS duration, ms 170 ± 31 169 ± 30 0.8 RBBB, n 41 (9%) 17 (17%) 0.009 ACE-I or ARB, n 390 (83%) 84 (84%) 0.7 b-blocker, n 377 (80%) 81 (81%) 0.8 LVEF, % 22 ± 7 23 ± 10 0.3 LVEDD, mm 62 ±9 62 ±7 0.6 LVESD, mm 53 ±10 51 ± 10 0.08
Results: Survival in Non-Dialysis Patients 181 (38%) patients died in CRT-D group 48 (48%) patients died in ICD group
Proportion Surviving 1.0 0.8 CRT-D, no dialysis 0.6 0.4 ICD, no dialysis p=0.01 0.2 0 1 2 3 4 5 Years From Device Implant CRT-D, no dialysis 472 367 293 233 181 127 ICD, no dialysis 100 68 51 36 22 16 In non-dialysis patients, CRT-D was associated with significant survival benefit: HR 0.67, 95% CI 0.49-0.9, p=0.014 Correcting for ischemic HF etiology, RBBB, and LVESD, CRT-D remained significantly associated with survival: HR 0.59, 95% CI 0.40-0.88, p=0.009
p<0.01 Proportion Surviving p<0.01 1.0 0.8 CRT-D, no dialysis 0.6 ICD, no dialysis p=0.4 p=0.01 0.4 0.2 CRT-D, dialysis ICD, dialysis 0 1 2 3 4 5 Years From Device Implant CRT-D, no dialysis 472 367 293 233 181 127 ICD, no dialysis 100 68 51 36 22 16 CRT-D, dialysis 18 10 7 5 3 2 ICD, dialysis 10 6 1 0 0 0
Results: Echocardiography 8/18 (44%) dialysis CRT patients had follow-up echocardiogram. 408/472 (86%) non-dialysis CRT patients had follow-up echocardiogram.
Echocardiographic Findings 20.0 10.0 0.0-10.0-20.0-30.0-40.0 LVEF Change (%) LVESV Change (%) * 15.0 8.0 P=0.1 P=0.08-36.0-17.0 *p=0.05 for change from baseline p<0.01 for change from baseline Dialysis Non-dialysis
Conclusions CRT-defibrillators do not provide a survival benefit over ICDs in dialysis-dependent HF patients despite an association with significant reverse remodeling. CRT-defibrillators do provide survival benefit over ICDs in non-dialysis HF patients. Survival is significantly better in non-dialysis patients, regardless of device type.
Limitations Small sample size of dialysis patients. Limited echocardiographic follow-up in dialysis CRT group. Duration of dialysis not known. Cause of death not known.
Future Directions Randomized trial or multicenter registry of CRT-D patients who are dialysis-dependent. Are LVEF and volumes a valid endpoint in this population? Does volume status alter volumes significantly? Is LVEF a more stable measure of cardiac structural improvement?