Effect of implantable cardioverter-defibrillators in patients with non-ischaemic systolic heart failure and concurrent coronary atherosclerosis

Abstract

Aims: Prophylactic implantable cardioverter-defibrillators (ICD) reduce mortality in patients with ischaemic heart failure (HF), whereas the effect of ICD in patients with non-ischaemic HF is less clear. We aimed to investigate the association between concomitant coronary atherosclerosis and mortality in patients with non-ischaemic HF and the effect of ICD implantation in these patients.

Methods and results: Patients were included from DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-Ischaemic Systolic Heart Failure on Mortality), randomizing patients to ICD or control. Study inclusion criteria for HF were left ventricular ejection fraction ≤ 35% and increased levels (>200 pg/mL) of N-terminal pro-brain natriuretic peptide. Of the 1116 patients from DANISH, 838 (75%) patients had available data from coronary angiogram and were included in this subgroup analysis. We used Cox regression to assess the relationship between coronary atherosclerosis and mortality and the effect of ICD implantation. Of the included patients, 266 (32%) had coronary atherosclerosis. Of these, 216 (81%) had atherosclerosis without significant stenoses, and 50 (19%) had significant stenosis. Patients with atherosclerosis were significantly older {67 [interquartile range (IQR) 61-73] vs. 61 [IQR 54-68] years; P < 0.0001}, and more were men (77% vs. 70%; P = 0.03). During a median follow-up of 64.3 months (IQR 47-82), 174 (21%) of the patients died. The effect of ICD on all-cause mortality was not modified by coronary atherosclerosis [hazard ratio (HR) 0.94; 0.58-1.52; P = 0.79 vs. HR 0.82; 0.56-1.20; P = 0.30], P for interaction = 0.67. In univariable analysis, coronary atherosclerosis was a significant predictor of all-cause mortality [HR, 1.41; 95% confidence interval (CI), 1.04-1.91; P = 0.03]. However, this association disappeared when adjusting for cardiovascular risk factors (age, gender, diabetes, hypertension, smoking, and estimated glomerular filtration rate) (HR 1.05, 0.76-1.45, P = 0.76).

Conclusions: In patients with non-ischaemic systolic heart failure, ICD implantation did not reduce all-cause mortality in patients either with or without concomitant coronary atherosclerosis. The concomitant presence of coronary atherosclerosis was associated with increased mortality. However, this association was explained by other risk factors.

Keywords: Coronary atherosclerosis; Implantable cardioverter defibrillator; Mortality; Non-ischaemic systolic heart failure.

Figure 1

Cumulative incidence curves of all‐cause mortality according to ICD treatment and the presence of coronary atherosclerosis. Patients with coronary atherosclerosis had an increased risk of all‐cause mortality hazard ratio 1.41 (95% confidence interval, 1.04–1.91); P = 0.03. ICD, implantable cardioverter defibrillators.

Figure 2

Coronary atherosclerosis association with all‐cause mortality. eGFR denotes estimated glomerular filtration rate. CI, confidence interval.

Figure 3

Cumulative incidence curves of the risk of cardiovascular death according to ICD treatment and the presence of coronary atherosclerosis. The presence of coronary atherosclerosis was not associated with the risk of cardiovascular death HR 0.92 (95% CI, 0.63–1.36); P = 0.69. ICD, implantable cardioverter defibrillators.

Figure 4

Cumulative incidence curves of the risk of sudden cardiac death according to ICD treatment and the presence of coronary atherosclerosis. The presence of coronary atherosclerosis was not associated with the risk of cardiovascular death hazard ratio 0.71 (95% confidence interval, 0.37–1.35); P = 0.29. ICD, implantable cardioverter defibrillators; SCD, sudden cardiac death.