The Seattle Institute for Cardiac Research

Background: The MADIT-ICD Benefit Score (MIBS) predicts ICD VT/VF shocks vs. non-arrhythmic death and divides patients into three predicted ICD benefit groups. Objective: The actual utility of the MIBS in primary prevention ICDs clinical trial with a control has not been evaluated. Methods: MIBS continuous score and categories (lowest, intermediate and highest ICD benefit) were derived for patients in SCD-HeFT in ICD and control arms. VT/VF therapy (Shock) vs. non-arrhythmic death (NAD) was compared across risk categories. The observed ICD hazard ratio for all-cause mortality was calculated for categories. SCD-HeFT ICD programming was 18 of 24 beats with a single rate zone of 188 bpm. Comparison was made with the Seattle Proportional Risk Model (SPRM) quartiles (predicts proportion of sudden vs. non-sudden death). Results: MIBS ranged from 2-91 with mean of 54±18 with lowest (<25), intermediate (25-75), and highest (>75) ICD benefit categories of 17%, 68% and 15%. The first event was a Shock (62%) vs. NAD (38%). The MIBS Category with highest ratio of Shock/NAD was the intermediate group with 2-fold difference due to higher Shock rates. Shock vs. NAD was similar in the lowest and highest ICD benefit groups. SPRM had a 10-fold difference in the Shock/NAD, due 90% lower NAD. The ICD benefit was least in the Intermediate MIBS group (interaction P=0.69) and the lowest quartile of the SPRM (interaction P<0.001). The ICD hazard ratio was similar for MIBS <50 (n=503, 0.72) vs. >50 (n=1173, 0.76) with a nonsignificant interaction p value (0.78). Conclusion: The MADIT-ICD Benefit Score did not validate for VT/VF Shock and Non-arrhythmic death or predict a variable ICD benefit for all-cause mortality in SCD-HeFT. The SPRM had a 10-fold difference in the ratio of Shock/NAD and a significant difference in ICD benefit. Reasons for this difference may be due to different patient populations, therapies (CRT or not), ICD programming, or background medications. Application: MADIT-ICD Benefit Score should be validated in other ICD trials to ascertain the utility of the risk model in predicting ICD benefit.

The recent introduction of subcutaneous implantable cardioverter defibrillator (S-ICD) has raised attention about the potential of this technology for clinical use in daily clinical practice. We review the methods and results of the four studies conducted in humans for approval of this innovative technology for daily practice. Two studies using a temporary S-ICD system (acute human studies) were conducted to search for an appropriate lead configuration and energy requirements. For this purpose, 4 S-ICD configurations were tested in 78 patients at the time of transvenous (TV)-ICD implantation. The optimal configuration was tested in 49 more patients to comparatively assess the subcutaneous defibrillation threshold (S-DFT) versus the standard TV-ICD. Long-term implants were evaluated in 55 patients using an implanted system (chronic human study). The acute humans studies led to an optimal S-ICD configuration comprising a parasternal electrode and left anterolateral thoracic pulse generator. Both configurations successfully terminated 98% of induced ventricular fibrillation (VF), but significantly higher energy levels were required with S-ICD than with TV-ICD systems (36.6 ± 19.8 J vs. 11.1 ± 8.5 J). In the chronic study, all 137 VF episodes induced at time of implant were detected with a 98% conversion rate. Two pocket infections and four lead revisions were required during 10 ± 1 months of follow-up. During this period, survival was 98%, and 12 spontaneous ventricular tachyarrhythmias were detected and treated by the device. These data show that the S-ICD systems here consistently detected and converted VF induced at time of implant as well as sustained ventricular tachyarrhythmias occurring during follow-up (248).

The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction < or =35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death. ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. [corrected] URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.

Implantable cardioverter-defibrillator (ICD) therapy significantly prolongs life in patients at increased risk for sudden death from depressed left ventricular function. However, whether this increased longevity is accompanied by deterioration in the quality of life is unclear. In a randomized trial, we compared ICD therapy or amiodarone with state-of-the-art medical therapy alone in 2521 patients who had stable heart failure with depressed left ventricular function. We prospectively measured quality of life at baseline and at months 3, 12, and 30; data collection was 93 to 98% complete. The Duke Activity Status Index (which measures cardiac physical functioning) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being) were prespecified primary outcomes. Multiple additional quality-of-life outcomes were also examined. Psychological well-being in the ICD group, as compared with medical therapy alone, was significantly improved at 3 months (P=0.01) and at 12 months (P=0.003) but not at 30 months. No clinically or statistically significant differences in physical functioning among the study groups were observed. Additional quality-of-life measures were improved in the ICD group at 3 months, 12 months, or both, but there was no significant difference at 30 months. ICD shocks in the month preceding a scheduled assessment were associated with a decreased quality of life in multiple domains. The use of amiodarone had no significant effects on the primary quality-of-life outcomes. In a large primary-prevention population with moderately symptomatic heart failure, single-lead ICD therapy was not associated with any detectable adverse quality-of-life effects during 30 months of follow-up.