The Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic Heart Failure on Mortality (DANISH) randomized about 1100 patients with symptomatic heart failure, LVEF <35% on optimal medical therapy but without coronary artery disease to implantable cardioverter defibrillator (ICD) therapy without finding any lowering of all cause death with the device. A nonpacing ICD prevents sudden death from arrhythmia, particularly in patients with coronary disease heart failure. The evidence for efficacy of an ICD in nonischemic heart failure is not very robust. DANISH enrolled patients of systolic nonischemic heart failure and an elevated N-terminal probrain natriuretic peptide (NT-proBNP); half received an ICD while the other half were assigned to contemporary heart failure therapy.More than 90% of patients in both groups received beta-blockers, ACE inhibitors or angiotensin receptor blockers (ARBs) and 60% of patients in both groups took mineralocorticoid inhibitors. Almost 58% of patients had a CRT (cardiac resynchronization therapy) pacemaker in them. In fact CRT were implanted in 93% of patients who had left bundle branch block and QRS >150 ms. The median follow up was 67 months.
Death from any cause was near similar in both groups; 120 patients (21.6%) died in the ICD group and 131 patients (23.4%) died in the control group.
Death from cardiovascular causes was also not significantly different; 77 patients (13.8%( died in the ICD arm while (95) patients died on medical therapy.
Sudden cardiac death occurred in 24 patients (4.3%) with an ICD, and this was less than the 46 (8.2%) sudden cardiac deaths recorded in the control group. But this 3.9% difference was not significant (p=0.05).
The DANISH results were quite different from the earlier randomized SCD-HEFT trial, which had recorded significant reduction in mortality with an ICD paving the way for class 1 guideline recommendation for ICDs in patients with heart failure. But the SCD-HEFT trial had only 20% of patients on a mineralocorticoid inhibitor and only 60% of patients were given a beta-blocker. In the DANISH trial almost all patients took a beta-blocker. Also no patient was on CRT in the SCD-HEFT trial.
Almost 58% of patients in the DANISH trial had CRT implantation. It is quite plausible that CRT by increasing LVEF and reversing LV remodeling reduced arrhythmic events.
Crucially patients with nonischemic heart failure as compared to ischemic heart failure are less prone to arrhythmia. Also patients with nonischemic heart failure have lower mortality from all causes.
But age showed a significant interaction with mortality (p=0.009) among those with an ICD. Patients, younger than 59 years, showed a significant 49% drop in all cause mortality. Older patients as they age acquire greater comorbidities burden that overwhelms beneficial effects of an ICD.
So the take home message against the backdrop of under usage of ICDs is that patients below 60 years would be the best candidates for ICD therapy if they had nonischemic heart failure accompanied with an LVEF<35%. The researchers of the DANISH trial concluded that in their trial prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary disease was not associated with a drop in heart rate as compared to usual care.
ICDs have been shown in the last 2 decades to be associated with significant reduction in death and total mortality in patients with ischemic heart disease. But no convincing trial has shown similar benefits in non ischemic heart failure patients. The COMPANION trial did not show any difference in mortality between patients assigned to CRT pacing and CRT alone, but did report significant lowering of death by both devices when compared to medical treatment. The SCD-HEFT trial showed benefit only in patients with NYHA class II heart failure and medical treatment has developed considerably since then.
In the current American Heart Association guidelines, ICD implantation for primary prevention of sudden cardiac death in patients with systolic heart failure is a class 1 A recommendation, without differentiation between patients with ischemic and nonischemic causes. In the European guidelines recommendation for ICD implantation is class 1B for nonischemic heart failure and class 1 A for ischemic heart failure.
Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group. Inappropriate shocks occurred in 33 patients (5.9%) in the ICD group.
ICDs are expensive and do carry adverse effects. They should not be implanted in patients where little benefit is anticipated. The DANISH trial for now has identified young patients with nonischemic symptomatic heart failure for primary prevention with an ICD. ICDs would continue to be used for primary prevention in symptomatic patients with ischemic heart failure.