Influence of late gadolinium enhancement on arrhythmic events in genotype-positive, phenotype-negative carriers of dilated cardiomyopathy
C Gonzalez Maniega, N Ramos-Lopez, B P Halliday, A Paldino, M Garofalo, M A Espinosa-Castro, M L Pena-Pena, F J Bermudez-Jimenez, C Diez-Lopez, M Gallego-Delgado, J Piqueras-Flores, E Zorio-Grima, S Vilches-Soria, J Gonzalez-Mirelis, P Garcia-PaviaAbstract
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.Baseline characteristicsCompeting risks curve