Key result
Late gadolinium enhancement on CMR was not associated with major arrhythmic events in genotype-positive, phenotype-negative DCM carriers (sHR 2.68; 95% CI 0.74-9.68; 5-yr rate 2.2% vs 0.6%, p=0.132).
Why the study?
Late gadolinium enhancement on CMR is a marker of arrhythmic risk in genetic DCM, but its prognostic impact in carriers of DCM variants with LVEF>50% remained uncertain.
Does the presence of late gadolinium enhancement on cardiac magnetic resonance predict major arrhythmic events and dilated cardiomyopathy development in genotype-positive, phenotype-negative carriers of dilated cardiomyopathy variants with LVEF >50%?
Cohort (n=686)
Yes
Does the presence of late gadolinium enhancement on cardiac magnetic resonance predict major arrhythmic events and dilated cardiomyopathy development in genotype-positive, phenotype-negative carriers of dilated cardiomyopathy variants with LVEF >50%?
In genotype-positive, phenotype-negative carriers of DCM variants with preserved LVEF, baseline LGE on CMR independently predicts progression to overt DCM but is not significantly associated with major arrhythmic events prior to DCM onset.
LGE should not guide arrhythmic risk stratification in these carriers; hypothesis-generating for DCM onset and needs prospective validation.
Background Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a well-established marker of arrhythmic risk and adverse outcomes in patients with genetic DCM. However, the prognostic impact of LGE in genetic carriers of DCM variants with LVEF>50% remains uncertain. We sought to evaluate the influence of LGE on major arrhythmic events (MAE) and DCM development among carriers of causative variants for DCM. Methods We conducted a multicenter retrospective study including 686 carriers of pathogenic or likely pathogenic DCM variants with normal systolic function at baseline CMR, from 31 international centers. The primary endpoint was a composite of MAE (sudden cardiac death, sustained ventricular tachycardia, or appropriate ICD therapy). The secondary endpoint was development of DCM during follow-up. Outcomes among patients harboring variants in high arrhythmic risk genes (LMNA, FLNC, TMEM43, PLN, DSP and RBM20; according to 2023 ESC guidelines), were also analyzed for both endpoints (394 individuals, 57%). Results Mean age of the study cohort was 36.6 ± 15.7 years and 53.5% were women (Table 1). LGE was present in 212 (30.9%) individuals. TTN variants were the most prevalent genotype (28%), followed by LMNA (18.7%), DSP (18.2%), and FLNC (16.2%). During a median follow-up of 3.5 years (IQR 1.6–6.4), only 10 (1.5%) individuals had MAE before developing DCM while 121 subjects (17.6%) developed DCM. Genotypes of patients with MAE were: LMNA (6 patients), FLNC (3), DSP (1), and TMEM43 (1). Six out of 10 individuals with MAE exhibited LGE on CMR. The 5-year cumulative incidence of MAE in individuals with LGE was 2.2% (95%CI 0.7–5.2%) vs 0.6% (95%CI 0.1–2.1%) in those without LGE (p=0.132). LGE presence was not associated with MAE (sHR 2.68; 95%CI 0.74–9.68) (Figure 1). However, LGE was independently associated with DCM onset (adjusted HR 2.05; 95% CI 1.43–2.94; p<0.001). Patients with high-risk genotype exhibited similar findings with LGE presence being associated with DCM development (HR 2.52; 95%CI: 1.51 – 4.24; p<0.001) but not with MAE (sHR 1.7; CI95%: 0.47 – 6.19). Conclusions Arrhythmic events are uncommon in genetic carriers of DCM variants with LVEF>50% even among those with LGE on CMR. LGE presence is associated with a higher risk of developing DCM during follow-up but not with MAE. Findings were consistent among carriers of variants in high-risk arrhythmic genes.
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Maniega et al. (2026) conducted a cohort in Genotype-positive, phenotype-negative carriers of dilated cardiomyopathy (DCM) (n=686). Late gadolinium enhancement (LGE) presence on CMR vs. Absence of LGE on CMR was evaluated on Composite of major arrhythmic events (MAE: sudden cardiac death, sustained ventricular tachycardia, or appropriate ICD therapy) (sHR 2.68, 95% CI 0.74-9.68, p=0.132). Late gadolinium enhancement on CMR was not associated with major arrhythmic events in genotype-positive, phenotype-negative DCM carriers (sHR 2.68; 95% CI 0.74-9.68; 5-yr rate 2.2% vs 0.6%, p=0.132).
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