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Cardiovascular Magnetic Resonance to Guide Defibrillator Implantation for LVEF of 36% to 50%
Key result
Primary prevention ICD fails to reduce sudden cardiac death or significant ventricular arrhythmias versus ILR.
- HR 0.76
- 95% CI 0.37-1.58
- n=353
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?
Population
353 patients LVEF 36-50% + CMR myocardial scar
Comparison
Primary prevention ICD vs implantable loop recorder
Design
Open-label multicenter randomized trial (18 sites; Australia, Germany, UK)
Follow-up
Median 6.3 years (IQR 4.8-7.6)
Authors
Discussion
Key questions
No takes yet. Share an insight, caveat, or question.
Where experts stand
Experts broadly read CMR GUIDE as a negative trial that does not justify extending ICD implantation to patients with mid-range LVEF and scar alone, though they split on whether intriguing subgroup signals in younger patients and reduced sudden death deserve further pursuit.
Most cardiologists and electrophysiologists agree the trial missed its primary endpoint and that scar on CMR does not yet earn a new ICD indication. A vocal minority, particularly those close to the trial, argues the reduction in sudden cardiac death and the benefit seen in younger patients are clinically meaningful signals worth building on. The live question is whether these secondary findings justify a larger trial or whether the overall null result should close the door on scar-guided ICD selection in this population.
Agreement
Multiple clinicians agree that the trial is clearly negative on its primary endpoint and that scar alone does not currently justify expanding ICD implantation to patients with LVEF 36-50%.
4 clinicians say this directly
Main debate
Mandrola calls it a decisively null result with no support for the scar theory. Ganesan and Flett see nuanced, clinically meaningful signals that deserve further investigation.
Decidedly null, no support for scar theory1
There is neither evidence for ICD benefit in this group nor support for selecting patients by scar.vs
Important signals for SCD and younger patients2
The reductions in sudden cardiac death and benefit in patients under 70 are nuanced signals that should inform clinical discussions and future study.+1Not placed6 reporting, watching, or context only
What they’re arguing about
supportiveneutralcautiouscritical
Counts are expert takes we classified by axis. Tap a row to see the takes behind its count.
Still unclear
Whether the reduction in sudden cardiac death alone and the age-based subgroup finding in patients under 70 can be confirmed in a larger, adequately powered trial. It also remains open whether scar characterization needs to be combined with other risk markers beyond LGE presence to identify a population that truly benefits from ICD implantation. Overall and cardiovascular mortality were similar between groups, raising the question of whether ICD therapy shifts the mode of death without changing total outcomes.
Key expert perspectives
This is a decidedly null trial with no evidence for ICD benefit or the scar hypothesis
Mandrola argues the trial should not be over-interpreted. He sees neither evidence supporting ICD benefit in patients with LVEF 36-50% and scar nor support for selecting patients by scar on CMR.
Distilled from their postX post
The trial has important signals about SCD reduction and ICD benefit in younger patients
As an electrophysiologist associated with the trial, Ganesan emphasizes the nuanced signals for clinical practice. He highlights the positive signal in younger patients and the reductions in sudden cardiac death as important discussions to have with patients about ICD therapy.
Andrew FlettHeart Failure / Cardiomyopathy · University Hospital Southampton NHS Foundation TrustEndpoint critiqueAug 31A landmark trial that is negative but thought-provoking on its components
Flett calls CMR GUIDE the first randomised test of a CMR scar-guided ICD approach and a landmark for the field. He notes the primary endpoint was not met but finds the component split thought-provoking: fewer sudden deaths with ICD but numerically more haemodynamically significant VA. He questions whether the trial challenges the scar hypothesis or simply shows how hard it is to demonstrate ICD benefit when absolute SCD risk is low.
Implication
Does not support primary prevention ICD in LVEF 36-50% with scar; challenges CMR late gadolinium enhancement alone for defibrillator selection.
Key Points
- To determine whether primary prevention implantable cardioverter-defibrillators reduce sudden cardiac death or hemodynamically significant ventricular arrhythmias in patients with moderately reduced left ventricular ejection fraction and cardiovascular magnetic resonance-detected myocardial scar.
- Open-label randomized clinical trial (NCT01918215) conducted at 18 sites across Australia, Germany, and the UK enrolling 353 adults with ischemic or nonischemic cardiomyopathy, an LVEF of 36% to 50%, and CMR-defined myocardial scar receiving guideline-directed medical therapy.
- Participants were randomly assigned to receive either a primary prevention implantable cardioverter-defibrillator (ICD; n = 180) or an implantable loop recorder (ILR; n = 173) and followed for a median of 6.3 years.
- The primary composite outcome of sudden cardiac death or hemodynamically significant ventricular arrhythmia occurred in 7.8% (14/180) of the ICD group vs 9.2% (16/173) of the ILR group (HR, 0.76; 95% CI, 0.37–1.58).
- Sudden cardiac death alone occurred in 1.7% of the ICD group vs 5.8% of the ILR group (HR, 0.26; 95% CI, 0.07–0.95), whereas hemodynamically significant ventricular arrhythmia occurred in 6.7% vs 3.5%, respectively (HR, 1.77; 95% CI, 0.65–4.81).
- All-cause mortality, cardiovascular mortality, and heart failure hospitalizations were similar between groups, though a prespecified subgroup analysis showed fewer primary events in patients younger than 70 years receiving ICDs (3.3% vs 10.0%; HR, 0.28; 95% CI, 0.09–0.89; P = .01 for interaction).
Evidence details
What drove the result?
| 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 | ||
Limitations & tradeoffs
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.
Structured PICO
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?
P
Population
353 adults with ischemic or nonischemic cardiomyopathy, LVEF 36% to 50%, and CMR-defined myocardial scar, followed for a median of 6.3 years.
I
Intervention
Primary prevention implantable cardioverter-defibrillator (ICD) (n=180)
C
Comparator
Implantable loop recorder (ILR) (n=173)
O
Outcome
Composite of sudden cardiac death (SCD) or hemodynamically significant ventricular arrhythmia (HSVA)composite
Main Result
Hazard Ratio: 0.76 (95% CI 0.37–1.58)
Absolute Event Rate: 7.8% vs 9.2%
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.
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
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).