Cardiac magnetic resonance-based phenotyping, genetic architecture, and outcomes in dilated and non-dilated left ventricular cardiomyopathy
A B M Heymans, M F G H M Venner, A G Raafs, N J Beelen, S L V M Stroeks, R M A Ter Bekke, K Vernooy, S R B Heymans, J A J VerdonschotAbstract
Background
Non-dilated left ventricular cardiomyopathy (NDLVC) is recognized as a distinct phenotype, but comparative data with dilated cardiomyopathy (DCM) remain limited.
Purpose
To compare clinical, imaging, and genetic characteristics of DCM and NDLVC, and assess disease-specific predictors for life-threatening ventricular arrhythmia (LTVA) and heart failure (HF).
Methods
Clinical characteristics, echocardiography, cardiac magnetic resonance (CMR) including late gadolinium enhancement (LGE, 17-segment model), and pathogenic/likely pathogenic (P/LP) variants in DCM/arrhythmogenic cardiomyopathy-associated genes were collected in patients with DCM or NDLVC. Multivariable Cox regression, based on clinical relevance and univariable significance, evaluated predictors of a composite LTVA/HF endpoint separately for each phenotype. Holter variables were excluded from multivariable models due to limited availability.
Results
We included 1130 patients (DCM n=812, NDLVC n=318). Age at diagnosis was comparable (DCM vs NDLVC; 56 vs 57 years, p=0.251), but NDLVC patients were more often male (58.7 vs 71.7%, p<0.001), had higher left ventricular ejection fraction (LVEF 32.03 vs 41.43%, p<0.001) and more LGE presence (26.8 vs 37.4%, p<0.001). Over a median follow-up of 6.2 years, composite event rates were similar between phenotypes (DCM 23.40% vs NDLVC 22.33%, p=0.716). LGE independently predicted outcomes in NDLVC (p=0.036), whereas male sex (p=0.040) and increasing left atrial volume index (p=0.044) were predictive in DCM. LVEF was not independently associated with outcomes in either phenotype (p=0.830, p=0.948). Lateral LGE prevalence was comparable, while septal LGE was more common in DCM and associated with adverse outcomes (p=0.036) (Fig. 1-2). Importantly, the prevalence of P/LP variants, including arrhythmogenic variants, was similar in DCM and NDLVC, with variants in TTN being the most prevalent in both groups (10.3 vs 9.2%). LMNA (2 vs 3.6%) and MYH7 variants (0.5 vs 2.6%) were more prevalent in NDLVC, while FLNC variants were observed only in DCM (1.4%) (Fig. 1-2). P/LP arrhythmogenic variants were independently associated with outcomes in both phenotypes (p=0.040, p=0.012). At baseline, atrial fibrillation (AF) was more prevalent in NDLVC (p<0.001), whereas DCM had a higher 24-hour premature ventricular complex (PVC) burden (p=0.017). Baseline PVC burden (p=0.005, p=0.024) and NSVT (p=0.003, p<0.001) were univariably associated with outcomes in both phenotypes, without significant differences in progression during follow-up.
Conclusion
Despite more preserved ventricular structure and function at diagnosis, NDLVC had long-term event rates comparable to DCM. Both phenotypes showed similar prevalence of genetic variants, where the presence of arrhythmogenic variants and myocardial fibrosis, rather than conventional parameters such as LVEF, emerged as key determinants of outcome, supporting CMR- and genotype-guided risk stratification.DCM: genetics, LGE patterns, outcomeFor image description, please refer to the figure legend and surrounding text.NDLVC: genetics, LGE patterns, outcomeFor image description, please refer to the figure legend and surrounding text.