Interpreting CMR GUIDE’s Mixed Results for ICD Implantation, With Joseph Selvanayagam, MBBS

The CMR GUIDE trial failed to achieve its primary endpoint, but managed to effectively reduce sudden cardiac death among younger patients with implantable cardioverter-defibrillators (ICDs) for heart failure (HF).1

These data were presented at the European Society of Cardiology (ESC) Congress 2026, in Munich, Germany, by Joseph Selvanayagam, MBBS, professor of cardiovascular medicine at Flinders University and director of cardiac imaging at SA Health. In an interview with HCPLive, Selvanayagam discussed the trial’s final results – and how they influence the question of ICDs in patients with myocardial scarring.1

“In totality, I think there is enough for informed decision-making in a clinical context for your individual patient,” Selvanayagam said. “Whether this shifts the needle on guidelines in the future based on CMR-GUIDE, that’s not for me to say. That is for the field to dissect and discuss.”

The CMR GUIDE trial investigated the efficacy of ICD implantation in patients with a left ventricular ejection fraction (LVEF) between 36 and 50%, as well as myocardial scar identified by cardiovascular magnetic resonance (CMR), to reduce sudden cardiac death or hemodynamically significant ventricular arrhythmia (HSVA). Patients were randomly assigned in a 1:1 ratio to receive either an ICD or an implantable loop recorder (ILR).1,2

The study’s primary outcome was a composite of HSVA and sudden cardiac death. HSVA was defined as a ventricular arrhythmia that either produced syncope or was associated with hypotension. Secondary outcomes included each component independently, as well as all-cause mortality, cardiovascular mortality, quality of life, and HF-related hospitalization.1

Of the 352 patients ultimately enrolled in the trial, 159 received an ICD and 163 received an ILR. An additional 25 patients were enrolled in a concurrent observational registry. By the end of the trial, 131 patients in the ICD group and 118 in the ILR arm were still alive and still had functional implants. After a median follow-up of 6.3 years, the primary composite outcome occurred in 14 of 180 patients in the ICD arm and 16 of the 173 in the ILR arm. This difference was not statistically significant.1

However, sudden cardiac death did indicate a potential reduction, as 3 ICD recipients and 10 ILR recipients exhibited this secondary outcome. Additionally, of the patients enrolled in the trial, 68% were <70 years old, and Selvanayagam and colleagues concluded that these patients were less likely to experience the composite primary outcome. This highlights a potentially protective effect, which Selvanayagam suggests as a focus of future studies.1

Selvanayagam also discussed his impression of how these data should be reflected in the clinic. Although the data did not display overall efficacy in this population, it did display a reduction in sudden cardiac death; however, it also reflected a worse quality of life. Patients assigned to the ICD arm during the trial reported modestly lower health-related quality of life during follow-up, which is consistent with prior trials indicating that defibrillator therapy may be associated with increased treatment burden.1

“What I think is worth more of a discussion with your patient based on our data is the reduced quality of life in the ICD arm compared with the ILR arm,” Selvanayagam said. “I think that you have to discuss with your patient the potential trade-off of risk versus benefit. You have to mention that the same trial that showed this reduction of sudden death also shows that you’re likely to feel worse, have a worse quality of life.”

Editors’ Note: Selvanayagam reports disclosures with AstraZeneca, Bayer, Biotronik, Boehringer-Ingelheim, Novartis, Pfizer, and others.

References

1. Selvanayagam JB, Cleland JGF, Hillis GS, et al. Cardiovascular Magnetic Resonance to Guide Defibrillator Implantation for LVEF of 36% to 50%: The CMR GUIDE Randomized Clinical Trial. JAMA. Published online August 28, 2026. doi:10.1001/jama.2026.17078

2. Flinders University. Cardiac Magnetic Resonance GUIDEd Management of Mild-moderate Left Ventricular Systolic Dysfunction (CMR_GUIDE). ClinicalTrials.gov Identifier: NCT01918215. Updated July 8, 2026. Accessed September 18, 2026. https://clinicaltrials.gov/study/NCT01918215?id=NCT01918215&viewType=Card&rank=1