1. Outcome of Patients with Advanced Heart Failure who Receive Device- Based Therapy for Primary Prevention of Sudden Cardiac Death, G. Amit, N. Samniah, A. Pekar, S. Ben-Zvi, R. Rosso, N. Gavrielov-Yusim, I. Marai, I. Goldenberg, M. Glikson M. Suleiman, G. Amit, N. Samniah, A. Pekar, S. Ben-Zvi, R. Rosso, N. Gavrielov-Yusim, I. Marai, I. Goldenberg, M. Glikson April 23, 2013

2. BackgroundBackground Approximately 50% of deaths among patients with HF are sudden. The percentage of SCD decreases as NYHA class increases It is widely believed that patients with more advanced HF symptoms are less likely to die from a VA and therefore would not benefit from ICD implantation Results of landmark ICD trials were inconsistent Approximately 50% of deaths among patients with HF are sudden. The percentage of SCD decreases as NYHA class increases It is widely believed that patients with more advanced HF symptoms are less likely to die from a VA and therefore would not benefit from ICD implantation Results of landmark ICD trials were inconsistent Sweeney MO. Pacing Clin Electrophysiol 2001;24:871-88. Kjekshus J. Am J Cardiol 1990;65:42I-48I.

3. PurposePurpose To examine the effect of HF functional class on the outcome of patients who receive device therapy in a real world setting.

4. MethodsMethods Israeli ICD Registry Database Israeli ICD Registry Database Period: Jul 2010-June 2012 Period: Jul 2010-June 2012 2108 primary prevention patients 2108 primary prevention patients Study end points Death Appropriate ICD therapies for VA Readmission to hospital for HF The combined endpoints of HF or death, VA or death Israeli ICD Registry Database Israeli ICD Registry Database Period: Jul 2010-June 2012 Period: Jul 2010-June 2012 2108 primary prevention patients 2108 primary prevention patients Study end points Death Appropriate ICD therapies for VA Readmission to hospital for HF The combined endpoints of HF or death, VA or death

5. Baseline Characteristics Variable NYHA class I+II (n=1185, 56%) III+IV (n=923, 44%) p Age, mean ± SD64±1266±11 <0.001 Female gender (%)1421<0.001 Ethnicity (%) 0.87 Jews5644 Arabs5644 Medical History Old MI (%) 68630.28 CABG (%) 30340.002 PCI (%) 58550.86 Dilated CM (%) 2130<0.001

6. Baseline Characteristics Variable NYHA class I+II (n=1185, 56%) III+IV (n=923, 44%) p Atrial fibrillation 1628<0.001 Cerebrovascular disease 7100.02 Diabetes 3347<0.001 Hypertension 63650.20 Dyslipidemia 5261<0.001 Chronic lung disease 816<0.001 Chronic kidney disease (GFR<60) 2847<0.001 Currently on dialysis 250.006 Smoker 33290.02 Sleep apnea 513<0.001

7. Baseline Characteristics Variable NYHA class I+II (n=1185, 56%) III+IV (n=923, 44%) p Meds on admission, % Beta Blockers 8087<0.001 ACE- inhibitors/ARB ant 75800.006 Diuretics 6490<0.001 Oral anticoagulants 12150.02 Anti-arrhythmic drugs 914<0.001 Amiodaron 5100.01

8. Baseline Characteristics Variable NYHA class I+II (n=1185, 56%) III+IV (n=923, 44%) p Diagnostic studies LVEF, mean (%) 29±1125 ± 10 <0.001 LVEF<30% 609 (52%)680 (74%)<0.001 QRS dur, mean (ms) 110± 26136± 30 <0.001 QRS>120 ms 313 (27%)572 (62%)<0.001 Electrophysiologic study 273 (23%)108 (12%)<0.001

9. Device implanted P<0.001

10. OutcomesOutcomes 1016 unselected registry patients were prospectively followed for the occurrence of clinical outcomes.

11. Death o HF in the General Population

12. Death or HF According to Device Type In ICD recipients In RCTD recipients

13. Death or VA in the General Population

14. Change in NYHA class during 1-year of follow-up in the ICD and the CRTD groups

15. Multivariate analysis: Risk of endpoints by NYHA class ≥III vs. <III EndpointTotal PopulationICD RecipientsCRTD Recipients HRp P p HF or death ┼ NYHA class ≥III vs. <III 3.21 <0.001 3.28 <0.001 0.97 0.92 HF NYHA class ≥III vs. <III 2.53 0.005 4.58 <0.001 1.42 0.42 VT/VF or death NYHA class ≥III vs. <III 0.52 0.04 0.81 0.80 0.43 0.01 VT/VF NYHA class ≥III vs. <III 0.34 0.02 0.34 0.23 0.36 0.03

16. Multivariate analysis: Risk of VA/Death by age category (reference group =age<65) EndpointTotal PopulationICD RecipientsCRTD Recipients HRp P p VT/VF or death Age 66-75 1.95 0.003 2.62 0.001 1.01 0.82 Age>75 2.78<0.0013.61<0.0012.070.04 VT/VF Age 66-75 2.08 0.01 2.17 0.02 1.72 0.33 Age>75 2.070.022.250.021.750.35

17. Main Findings Of new ICDs and CRTDs implanted in Israel, >50% are in patients >65 yo and >20% in patients >75 yo Elderly patients have higher risk profile more likely to receive CRTD device > secondary prevention indication Of new ICDs and CRTDs implanted in Israel, >50% are in patients >65 yo and >20% in patients >75 yo Elderly patients have higher risk profile more likely to receive CRTD device > secondary prevention indication

18. Main Findings Our data add to and support the existing evidence from previous studies that the association between advanced age and adverse clinical outcomes is attenuated in elderly patients implanted with CRT-D devices.

19. Main Findings Elderly patients implanted with ICDs experienced a significant increase in the cumulative probability of the combined end- points of appropriate ICD therapy or death and HF or death In contrast, the risk of both HF and arrhythmic outcomes was attenuated among elderly patients implanted with CRT-D devices. Elderly patients implanted with ICDs experienced a significant increase in the cumulative probability of the combined end- points of appropriate ICD therapy or death and HF or death In contrast, the risk of both HF and arrhythmic outcomes was attenuated among elderly patients implanted with CRT-D devices.