Frailty Burden Effects Efficacy of Cardioverter-Defibrillator in HFrEF

Implantable cardioverter-defibrillator (ICD) efficacy related to mortality among patients with heart failure with reduced ejection fraction (HFrEF) is significantly improved by a low baseline frailty burden, according to findings published in JACC: Heart Failure.

Investigators sought to assess the effect of baseline frailty burden on the efficacy of ICD therapy for preventing death among patients with HFrEF. All-cause mortality was the primary outcome. Cardiovascular (CV) death, sudden cardiac death (SCD), and all-cause hospitalization were secondary outcomes.

They conducted a post hoc analysis using participant-level data from 1676 participants with HFrEF (mean age, 59±12 years; 23% women) from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). SCD-HeFT was a multicenter, randomized controlled trial that included participants with HF and left ventricular ejection fraction of no greater than 35% and New York Heart Association functional class II or III. Participants were randomly assigned in a 1:1:1 ratio to ICD therapy, amiodarone, or placebo. ICD therapy consisted of a shock-only single-lead device programmed to detect tachycardia (defined as 18 or 24 beats at a rate of 187 beats/min or higher). In the post hoc analysis, participants from the amiodarone treatment arm were excluded.

The investigators of the post hoc analysis used the Rockwood Frailty Index (FI) to estimate baseline frailty, then participants were stratified into high vs low frailty burden groups (FI > median vs FI ≤ median, respectively). At baseline, participants in the high frailty group vs low frailty group tended to be younger, with a higher burden of HF symptoms, traditional CV risk factors, and worse functional status.

Median FI for the high frailty group was 0.54 (IQR, 0.47-0.60) and median FI for the low frailty group was 0.30 (IQR, 0.23-0.37). In adjusted multivariable Cox models, the investigators found the treatment effect of ICD therapy for risk of all-cause mortality was significantly modified by baseline frailty status (P_interaction =.047). The treatment effect was significant for CV mortality (P_interaction =.02) but not statistically significant for sudden cardiac death (P_interaction =.11) or all-cause readmission (P_interaction =.54).

Median follow-up was 3.4 years (IQR, 2.5-4.0 years) and 25.4% of participants died during follow-up. Participants with high frailty vs low frailty had a significantly higher cumulative incidence of all-cause mortality. High vs low frailty burden was associated with a 45% higher risk of all-cause mortality (HR, 1.45; 95% CI, 1.20-1.76; P <.001) in unadjusted analysis.

Among participants with low frailty burden, ICD therapy was associated with a lower risk of all-cause mortality (hazard ratio [HR], 0.56; 95% CI, 0.40-0.78) compared with participants with high frailty burden (HR, 0.86; 95% CI, 0.68-1.09).

Limitations of the analysis include lack of generalizability beyond patients who meet SCD-HeFT enrollment criteria and SCD-HeFT was conducted more than 20 years ago, therefore the analysis cannot account for evolving medical therapy.

“Among participants with HFrEF enrolled in SCD-HeFT, frailty modified the effect of ICD therapy on all-cause mortality such that adults with a lower vs higher burden of frailty appeared to derive greater benefit,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.