Joseph Selvanayagam, MBBS, is a professor of cardiovascular medicine at Flinders University and the director of cardiac imaging at SA Health.

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 

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

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 

, Selvanayagam discussed the trial’s final results – and how they influence the question of ICDs in patients with myocardial scarring.

“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 

 (HSVA). Patients were randomly assigned in a 1:1 ratio to receive either an ICD or an implantable loop recorder (ILR).

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.

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.

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.

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.

“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.

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. 

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

Videos

Selvanayagam shares his thoughts on whether ICDs’ improvements in sudden cardiac death are worth the reduced quality of life.

Although it failed to achieve its primary endpoint of reducing sudden cardiovascular death or ventricular 

, the CMR GUIDE trial did indicate a patient population that may benefit more from implantable cardioverter-defibrillators (ICDs).

CMR GUIDE Misses Primary Endpoint, Indicates Possible Cardiac Death Reduction With ICDs

 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 

, Selvanayagam discussed the impetus for the trial and the success the investigators found despite the program’s overall failure.

“Guidelines currently do not recommend an ICD in patients with EF 36-50%, yet there is a treatment paradox there,” Selvanayagam told 

. “We treat the patients below 35%, who numerically have fewer sudden cardiac deaths, but we don’t treat the ones above 35%, where the numerical events are high. We need better risk stratifiers.”

CMR GUIDE was a multicenter randomized controlled trial investigating the efficacy of ICD implantation in patients with a left ventricular ejection fraction (LVEF) of 36-50% and cardiovascular magnetic resonance (CMR)-identified myocardial scar to reduce sudden cardiac death or hemodynamically significant ventricular arrhythmia (HSVA). Patients were eligible for inclusion if they had an LVEF within the established range attributable to 

 and evidence of ventricular scar on CMR. Patients were excluded if they had a history of cardiac arrest, cardiomyopathy related to sarcoidosis, or an established indication for an ICD, among other criteria.

Eligible patients were randomly assigned in a 1:1 ratio to either a single-chamber ICD or an implantable loop recorder (ILR). The primary outcome was a composite of sudden cardiac death or HSVA – the latter was defined as a ventricular arrhythmia that produced syncope or was associated with hypotension. Prespecified secondary outcomes included the individual components of sudden cardiac death and HSVA, all-cause mortality, cardiovascular mortality, quality of life, and HF-related hospitalization.

A total of 352 patients were enrolled and randomized; of these, 159 patients received an ICD and 163 received an ILR. The median age between groups was 65 years (interquartile range [IQR], 57-71 years), and 72% of patients had ischemic etiology. Another 25 patients without myocardial scar were also enrolled in a concurrent observational registry.

By the end of the trial, 131 patients in the ICD group and 118 in the ILR group were still alive with active implants. Median follow-up was 6.3 years (IQR, 4.8-7.6 years) – in this time, the primary composite outcome occurred in 14 of 180 patients in the ICD arm and 16 of 173 patients in the ILR arm (unadjusted HR, 0.76; 95% CI, 0.37-1.58; adjusted HR, 0.77; 95% CI, 0.37-1.59). The latter hazard ratio was adjusted for age, sex, cardiomyopathy etiology, and baseline LVEF. Neither endpoint was statistically significant.

Sudden cardiac death occurred in 3 ICD recipients and 10 ILR recipients (HR, 0.26; 95% CI, 0.07-0.95), while HSVA occurred in 12 ICD recipients and 6 ILR recipients (HR, 1.77; 95% CI, 0.65-4.81). Rates were similar for all-cause mortality, cardiovascular mortality, and HF-related hospitalization, regardless of the assigned intervention group. Among the enrolled patients, 68% were <70 years old. These patients were less likely to experience the primary outcome (HR, 0.28; 95% CI, 0.09-0.89; 

 = .01) compared to those ≥70 years (HR, 2.33; 95% CI, 0.75-7.26).

Although the primary endpoint was not achieved, Selvanayagam and colleagues noted the potential reduction in sudden cardiac death found in younger patients with low competing risk from other causes of death. Selvanayagam highlighted this in the interview, suggesting future research into this area to corroborate these findings.

“This was not an overall neutral trial,” Selvanayagam said. “The primary outcome was neutral, but there were certainly enough signals in the deep dive of the data to suggest that we need to think carefully about the design of future trials. That’s the good news – the more challenging news is that this is going to take a long time, as this is a difficult population to enroll.”

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. 

Joseph Selvanayagam, MBBS, discusses the potential of implantable cardioverter-defibrillators to reduce sudden cardiac death among younger patients.

Joseph Selvanayagam, MBBS

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