What happened
Primary prevention ICD implantation did not reduce sudden cardiac death or hemodynamically significant ventricular arrhythmia compared to an implantable loop recorder (HR 0.76; 95% CI 0.37-1.58).
Multiple clinicians agree the trial is negative on its primary endpoint and that scar detected on CMR does not, by itself, establish a new indication for ICD therapy in patients with mid-range LVEF.
Experts largely read CMR GUIDE as a negative trial that does not support scar-guided ICD implantation in mid-range LVEF, though they split on whether intriguing subgroup signals in younger patients and reduced sudden cardiac death deserve clinical weight or are simply hypothesis-generating findings from an underpowered study.
Most cardiologists and electrophysiologists agree the trial missed its primary endpoint and that scar on CMR alone is not enough to justify an ICD in this population. The community divides, however, on the secondary signals: some see the reduction in sudden cardiac death and benefit in younger patients as clinically meaningful cues for shared decision-making, while others warn against over-interpreting underpowered subgroups from a clearly null trial. The live question is whether these signals warrant a larger, adequately powered trial or a more refined patient-selection strategy before changing practice.
Whether the reduction in sudden cardiac death alone (HR 0.26) and the benefit in patients under 70 will be tested in a larger, adequately powered trial.
It also remains unresolved whether the paradox of more recorded ventricular arrhythmias in the ICD arm reflects ICDs converting fatal events into survived ones or a detection artifact.
The role of competing risks, device complications, and quality of life in this mid-range LVEF population needs further study.
“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.”
News-Medical.net ↗From published coverage, not an answer posted here.
This is a decidedly null trial and should not be over-interpreted
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Signals for reduced SCD and benefit in younger patients have real-world relevance for EP practice
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Clinically relevant question but results are negative and the trial was likely underpowered
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A negative trial, but it advances the field from LVEF-based selection toward individualized arrhythmic risk assessment
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Scar alone does not extend ICD benefit to mid-range LVEF
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Primary endpoint neutral but SCD lower with ICD, with a prespecified subgroup signal in patients under 70
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Scar-guided ICD did not significantly reduce the primary composite despite a signal for reduced SCD
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Primary prevention ICD did not reduce the composite outcome in a mostly white male, ischemic population
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Asks whether LVEF is the sole criterion to decide primary ICD, framing CMR GUIDE as addressing that question.
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Notes that across all age groups, ICD did not significantly reduce the primary endpoint in LVEF 36-50% with CMR-defined scar.
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Summarizes the neutral primary finding: ICD did not significantly reduce the composite outcome in patients with LVEF 36-50% and myocardial scar.
X post ↗Martha Gulati
ContextCardiologistHighlights trial design and asks whether myocardial scar, not just EF, should help determine who gets a primary prevention ICD.
X post ↗peterkistler MBBS PhD FHRS
@peterkistler3“@drjohnm CMR GUIDE is informative. It may be underpowered but is reassuring that LVEF 36-50% with scar do NOT show mortality with ICDs & reports Cx of & impact on Mini living with HF of ICDs. Also reinforces low event rates in the current era with GDMT”
X ↗Mohammed Al-Qadami
@mohamme76294268“MR GUIDE found no significant reduction in sudden cardiac death or haemodynamically significant ventricular arrhythmia with a scar-guided ICD strategy in patients with LVEF 36–50% and CMR-defined scar. HR 0.76, 95% CI 0.37–1.58, P=0.47.”
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Why the trial, key points, tables, limitations, PICO, abstract, media & sources
Why the trial?
Primary-prevention ICDs are restricted to ejection fractions of 35% or below, yet most sudden cardiac deaths occur in patients with higher ejection fractions. CMR GUIDE asked whether CMR-detected myocardial scar identifies patients with mild-moderate systolic dysfunction (LVEF 36-50%) who benefit from a defibrillator.
Does a primary prevention implantable cardioverter-defibrillator (ICD) reduce the composite of sudden cardiac death or hemodynamically significant ventricular arrhythmia in adults with cardiomyopathy, LVEF 36-50%, and CMR-defined myocardial scar?
| Outcome | ICD | ILR |
|---|---|---|
| Sudden cardiac death or HSVA | 14 (7.8%) | 16 (9.2%) |
| HR 0.76 (95% CI 0.37-1.58) - not significant | ||
| Sudden cardiac death | 3 (1.7%) | 10 (5.8%) |
| Also a secondary outcome - lower with ICD (HR 0.26, 0.07-0.95) | ||
| Significant ventricular arrhythmia (HSVA) | 12 (6.7%) | 6 (3.5%) |
| Numerically higher with ICD (HR 1.77, 0.65-4.81); components moved in opposite directions | ||
| Primary outcome, age <70 years | 3.3% | 10.0% |
| Prespecified subgroup - HR 0.28 (0.09-0.89); reversed at >=70 (HR 2.33); P=.01 for interaction | ||
Statistical certainty
only 30 primary events occurred; the wide CI (0.37-1.58) allows meaningful benefit or harm.
Representation
participants were 82% men and 72% had an ischemic etiology.
Design limitations
the trial was open-label.
Does a primary prevention implantable cardioverter-defibrillator (ICD) reduce the composite of sudden cardiac death or hemodynamically significant ventricular arrhythmia in adults with cardiomyopathy, LVEF 36-50%, and CMR-defined myocardial scar?
In patients with an LVEF of 36% to 50% and CMR-defined myocardial scar, prophylactic ICD implantation did not significantly reduce the composite of sudden cardiac death or hemodynamically significant ventricular arrhythmia compared to an implantable loop recorder.
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Expert reaction
JAMA · ESC Congress 2026
What 5 experts said about this trial's result
Expert labels are toward CMR GUIDE's result, from named public quotes (n=5). As of Oct 11, 2026.
Experts largely read CMR GUIDE as a negative trial that does not support scar-guided ICD implantation in mid-range LVEF, though they split on whether intriguing subgroup signals in younger patients and reduced sudden cardiac death deserve clinical weight or are simply hypothesis-generating findings from an underpowered study.
Most cardiologists and electrophysiologists agree the trial missed its primary endpoint and that scar on CMR alone is not enough to justify an ICD in this population. The community divides, however, on the secondary signals: some see the reduction in sudden cardiac death and benefit in younger patients as clinically meaningful cues for shared decision-making, while others warn against over-interpreting underpowered subgroups from a clearly null trial. The live question is whether these signals warrant a larger, adequately powered trial or a more refined patient-selection strategy before changing practice.
Multiple clinicians agree the trial is negative on its primary endpoint and that scar detected on CMR does not, by itself, establish a new indication for ICD therapy in patients with mid-range LVEF.
Null trial, stop over-interpreting vs. important signals that should shape clinical conversations
What they’re arguing about
supportiveneutralcautiouscritical
Counts are expert takes we classified by axis. Tap a row to see the takes behind its count.
Whether the reduction in sudden cardiac death alone (HR 0.26) and the benefit in patients under 70 will be tested in a larger, adequately powered trial. It also remains unresolved whether the paradox of more recorded ventricular arrhythmias in the ICD arm reflects ICDs converting fatal events into survived ones or a detection artifact. The role of competing risks, device complications, and quality of life in this mid-range LVEF population needs further study.
“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.”
Mandrola argues there is neither evidence for ICD benefit in patients with LVEF 36-50% and scar nor support for the scar theory of selecting patients for devices. He cautions against reading clinical meaning into a clearly null result.
As an electrophysiologist associated with the trial, Ganesan sees a nuanced message: the primary endpoint was not positive, but the reductions in sudden cardiac death and the signal in younger patients are important for discussions with patients about ICD therapy. He calls it a key trial for the EP field providing the first randomized data in this population.
Does not support primary prevention ICD in LVEF 36-50% with scar; challenges CMR late gadolinium enhancement alone for defibrillator selection.
Importance: Current guidelines do not recommend primary prevention implantable cardioverter-defibrillators (ICDs) unless a patient's left ventricular ejection fraction (LVEF) is 35% or less. Many sudden cardiac deaths (SCD) occur when LVEF is 36% to 50%. Myocardial scar (a key arrhythmic substrate) can be assessed by late gadolinium enhancement on cardiovascular magnetic resonance (CMR), but robust evidence is lacking regarding a scar-based approach to ICD insertion. Objective: To determine whether implantation of ICDs reduces SCD or hemodynamically significant ventricular arrhythmia (HSVA) in patients with an LVEF of 36% to 50% and myocardial scar. Design, Setting, and Participants: An open-label randomized clinical trial enrolled adults between 2015 and 2022 who had ischemic or nonischemic cardiomyopathy, an LVEF of 36% to 50%, CMR-defined myocardial scar, and were receiving guideline-directed medical therapy at 18 sites in Australia, Germany, and the UK. Follow-up assessments were completed in 2026. Interventions: A primary prevention ICD (n = 180) vs an implantable loop recorder (ILR) (n = 173). Main Outcomes and Measures: The primary composite outcome was SCD or HSVA. Five secondary outcomes were evaluated: SCD, HSVA, heart failure-related hospitalization, cardiovascular mortality, and all-cause mortality. Results: Of 353 patients randomized (median age, 65 years [IQR, 57-61 years]; 18% female; and 72% had an ischemic etiology), 70% had an LVEF of 40% or greater. The median follow-up was 6.3 years (IQR, 4.8-7.6 years). The primary composite outcome occurred in 14 patients (7.8%) in the ICD group compared with 16 patients (9.2%) in the ILR group (hazard ratio [HR], 0.76 [95% CI, 0.37-1.58]). For the individual components of the primary composite outcome, SCD occurred in 3 patients (1.7%) vs 10 patients (5.8%) in the ILR group (HR, 0.26 [95% CI, 0.07-0.95]) and HSVA occurred in 12 patients (6.7%) vs 6 patients (3.5%), respectively (HR, 1.77 [95% CI, 0.65-4.81]). The rates for all-cause mortality, cardiovascular mortality, and heart failure-related hospitalization were similar between groups. In a prespecified analysis of 6 subgroups, the primary outcome occurred less often in patients younger than 70 years in the ICD group (3.3%) vs patients in the ILR group (10.0%) (HR, 0.28 [95% CI, 0.09-0.89]) but not in those aged 70 years or older (16.9% vs 7.5%, respectively) (HR, 2.33 [95% CI, 0.75-7.26]; P = .01 for interaction). Conclusions and Relevance: Implantation of an ICD did not reduce the composite outcome of SCD or HSVA in patients with an LVEF of 36% to 50% and myocardial scar. Trial Registration: ClinicalTrials.gov Identifier: NCT01918215.
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Selvanayagam et al. (2026) conducted an RCT in Ischemic or nonischemic cardiomyopathy with LVEF 36% to 50% and myocardial scar (n=353). Primary prevention implantable cardioverter-defibrillator (ICD) vs. Implantable loop recorder (ILR) was evaluated on Composite of sudden cardiac death (SCD) or hemodynamically significant ventricular arrhythmia (HSVA) (HR 0.76, 95% CI 0.37-1.58). Primary prevention ICD implantation did not reduce sudden cardiac death or hemodynamically significant ventricular arrhythmia compared to an implantable loop recorder (HR 0.76; 95% CI 0.37-1.58).
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