Younger heart patients benefit from implantable cardioverter-defibrillators in CMR GUIDE trial

An implantable cardioverter-defibrillator did not improve the primary endpoint overall in the CMR GUIDE trial but younger patients appeared to benefit, according to results presented in a Hot Line session today at ESC Congress 2026 and published simultaneously in JAMA.

Sudden death is a devastating complication of heart failure. An implantable cardioverter-defibrillator (ICD) is a small electrical device that monitors the heart rhythm continuously and delivers electrical pulses to correct abnormalities.

ICDs are currently recommended to prevent sudden cardiac death in certain patients with heart failure, namely those with left ventricular ejection fraction (LVEF) that is substantially reduced to 35% or less, despite optimized heart failure medication. However, as noted by Principal Investigator, Professor Joseph Selvanayagam from Flinders University, Flinders Medical Centre, Adelaide, Australia, most sudden cardiac deaths occur in patients with mild-to-moderate LVEF reductions who are not currently eligible for an ICD for primary prevention. "In the CMR GUIDE trial, we assessed whether an ICD could improve outcomes in patients with LVEF 36-50% who have evidence of myocardial scarring, a risk factor for sudden cardiac death," he said.

The trial was conducted at 18 centers in Australia, Germany and the United Kingdom. A total of 353 patients with ischemic or non-ischemic cardiomyopathy, LVEF 36-50% on optimal heart failure therapy and myocardial scarring confirmed by cardiovascular magnetic resonance were included. They were randomized (1:1) to receive an ICD or an implantable loop recorder (ILR), which monitors heart rate only. Most participants were aged over 70 years (68%) and 18% were women.

The primary endpoint of sudden cardiac death or hemodynamically significant ventricular arrhythmias (ventricular arrhythmias producing loss of consciousness or significant drop in blood pressure) was not significantly different between an ICD or an ILR. The primary endpoint occurred in 7.8% of patients assigned to ICDs and 9.2% assigned to ILRs (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.37 to 1.58). In a prespecified subgroup analysis, ICD implantation was associated with a 72% reduction in the primary endpoint in patients younger than 70 years, whereas no benefit was observed in patients aged 70 years or older.

The secondary endpoint of sudden cardiac death was significantly reduced in the ICD group compared with the ILR group (1.7% vs. 5.8%; HR 0.26; 95% CI 0.07 to 0.95).

Overall, the primary endpoint was neutral. However, younger patients appeared to derive clinical benefit from ICDs. We suggest that data from the CMR GUIDE trial are discussed with younger patients in whom ICDs may be an option in a shared decision-making process."

Professor Joseph Selvanayagam, Flinders University

Finally, he remarked that data and insights from CMR GUIDE could be used to inform future trials in a larger number of patients.