The impact of implantable cardioverter-defibrillator implantation on health-related quality of life in the DANISH trial.

AIM: The Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators (ICD) in Patients with Non-ischaemic Systolic Heart Failure (HF) on Mortality (DANISH) found no overall effect on all-cause mortality. The effect of ICD implantation on health-related quality of life (HRQoL) remains to be established as previous trials have demonstrated conflicting results. We investigated the impact of ICD implantation on HRQoL in patients with non-ischaemic systolic HF, a prespecified secondary endpoint in DANISH. METHODS AND RESULTS: In DANISH, a total of 1116 patients with non-ischaemic systolic HF were randomly assigned (1:1) to ICD implantation or usual clinical care (control). Patients completed disease-specific HRQoL as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ; 0-105, high indicating worse). Changes in HRQoL 8 months after randomization were assessed with a mixed-effects model. At randomization, MLHFQ was completed by 935 (84%) patients (n = 472 in the ICD group and n = 463 in the control group) and was reassessed in 274 (58%) and 292 (63%) patients, respectively after 8 months for the primary analysis. Patients in the ICD group vs. the control group had similar improvements in MLHFQ after 8 months [least square mean -7.0 vs. -4.2 (P = 0.13)]. A clinically relevant improvement (decrease ≥5) in the MLHFQ overall score at 8 months was observed in 151 patients in the ICD group and 148 patients in the control group [55% vs. 51%, respectively (P = 0.25)]. CONCLUSION: Implantable cardioverter-defibrillator implantation in patients with non-ischaemic systolic HF did not significantly alter HRQoL compared with patients randomized to usual clinical care.

Incidence of atrial fibrillation in patients with either heart failure or acute myocardial infarction and left ventricular dysfunction: a cohort study.

BACKGROUND: We examined the incidence of new-onset atrial fibrillation in patients with left ventricular dysfunction. Patients either had a recent myocardial infarction (with or without clinical heart failure) or symptomatic heart failure (without a recent MI). Patients were with and without treatment with the class III antiarrhythmic drug dofetilide over 36 months. METHODS: The Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies included 2627 patients without atrial fibrillation at baseline, who were randomised to treatment with either dofetilide or placebo. RESULTS: The competing risk analyses estimated the cumulative incidences of atrial fibrillation during the 42 months of follow-up to be 9.6% in the placebo-treated heart failure-group, and 2.9% in the placebo-treated myocardial infarction-group. Cox proportional hazard regression found a 42% significant reduction in the incidence of new-onset AF when assigned to dofetilide compared to placebo (hazard ratio 0.58, 95% confidence interval 0.40-0.82) and there was no interaction with study (p = 0.89). In the heart failure-group, the incidence of atrial fibrillation was significantly reduced to 5.6% in the dofetilide-treated patients (hazard ratio 0.57, 95% confidence interval 0.38-0.86). In the myocardial infarction-group the incidence of atrial fibrillation was reduced to 1.7% with the administration of dofetilide. This reduction was however not significant (hazard ratio 0.61, 95% confidence interval 0.30-1.24). CONCLUSION: In patients with left ventricular dysfunction the incidence of AF in 42 months was 9.6% in patients with heart failure and 2.9% in patients with a recent MI. Dofetilide significantly reduced the risk of developing atrial fibrillation compared to placebo in the entire study group and in the subgroup of patients with heart failure. The reduction in the subgroup with recent MI was not statistically significant, but the hazard ratio was similar to the hazard ratio for the heart failure patients, and there was no difference between the effect in the two studies (p = 0.89 for interaction).

Mineralocorticoid receptor antagonists and cardiovascular mortality in patients with atrial fibrillation and left ventricular dysfunction: insights from the Atrial Fibrillation and Congestive Heart Failure Trial.

BACKGROUND: Patients with heart failure (HF) and atrial fibrillation (AF) may differ from the larger HF population with respect to comorbidities, including renal impairment and overall prognosis. Associated cardiorenal interactions may mitigate the effects of pharmacological agents. Our primary objective was to assess the impact of mineralocorticoid receptor antagonists on cardiovascular mortality in patients with AF and HF enrolled in the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial. METHODS AND RESULTS: All 1376 patients randomized in the AF-CHF trial were included. The median baseline creatinine was 105.2 (Q1 88.4, Q3 125.0) µmol/L, and the median estimated glomerular filtration rate was 62.3 (Q1 49.0, Q3 77.2) mL/min per 1.73 m(2). The renal function was moderately or severely impaired (ie, estimated glomerular filtration rate <60 mL/min per 1.73 m(2)) in 46.5% of patients. In multivariable analyses, increased creatinine was associated with worsening HF but not mortality. Mineralocorticoid receptor antagonists were prescribed in 44.8% and were independently associated with a 1.4-fold increase in total mortality (hazard ratio, 1.4; 95% CI [1.1-1.8]; P=0.005) and a 1.4-fold increase in cardiovascular mortality (hazard ratio, 1.4; 95% CI [1.1-1.9]; P=0.009). This was driven by an increased incidence of sudden cardiac death (hazard ratio, 2.0; 95% CI [1.3, 3.0]; P=0.001). CONCLUSIONS: Renal dysfunction was highly prevalent in patients with AF and HF. Mineralocorticoid receptor antagonists were independently associated with an increased incidence of cardiovascular deaths, predominantly of presumed arrhythmic cause. Although these provocative findings merit prospective validation, they underscore the importance of careful monitoring of renal function and electrolytes in patients with AF and HF receiving mineralocorticoid receptor antagonists.

Maintenance of sinus rhythm and survival in patients with heart failure and atrial fibrillation.

OBJECTIVES: The goal of this study was to evaluate the relationship between the presence of sinus rhythm and outcomes in patients with a history of congestive heart failure (CHF) and atrial fibrillation (AF). BACKGROUND: The value of sinus rhythm maintenance in patients with AF and heart failure (HF) is uncertain. METHODS: A total of 1,376 patients with AF, ejection fraction < or =35%, and heart failure symptoms were randomized to a rhythm- or rate-control strategy. Detailed efficacy analyses were used to evaluate the independent effects of treatment strategy and the presence of sinus rhythm on cardiovascular outcomes. RESULTS: Overall, 445 (32%) patients died and 402 (29%) experienced worsening HF. The rhythm-control strategy was not predictive of cardiovascular mortality (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.70 to 1.16; p = 0.41), all-cause death (HR: 0.86, 95% CI: 0.69 to 1.08; p = 0.19), or worsening HF (HR: 0.86, 95% CI: 0.68 to 1.10; p = 0.23). In analyses devised to isolate the effect of underlying rhythm, sinus rhythm was not associated with cardiovascular mortality [HR: 1.22, 95% CI: 0.80 to 1.87; p = 0.35), total mortality [HR: 1.11, 95% CI: 0.78 to 1.58; p = 0.57), or worsening HF [HR: 0.62, 95% CI: 0.37 to 1.02; p = 0.059). CONCLUSIONS: A rhythm-control strategy or the presence of sinus rhythm are not associated with better outcomes in patients with AF and CHF.