Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry

Aims: Dilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non-familial (sporadic) DCM (SDCM) across Europe. Methods and results: Patients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P\ua0<\ua00.01), had less severe disease phenotype at presentation (P\ua0<\ua00.02), more favourable baseline cardiovascular risk profiles (P\ua0 64\ua00.007), and less medication use (P\ua0 64\ua00.042). Outcome at 1\ua0year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25\u20130.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02\u20131.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P\ua0<\ua00.01) and had higher genetic yield (55% vs. 22%, P\ua0<\ua00.01). Conclusions: We observed that FDCM and SDCM have significant differences at baseline but similar short-term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non-marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence

Phenotypic diversity, population structure and stress protein-based capacitoring in populations of Xeropicta derbentina, a heat-tolerant land snail species

The shell colour of many pulmonate land snail species is highly diverse. Besides a genetic basis, environmentally triggered epigenetic mechanisms including stress proteins as evolutionary capacitors are thought to influence such phenotypic diversity. In this study, we investigated the relationship of stress protein (Hsp70) levels with temperature stress tolerance, population structure and phenotypic diversity within and among different populations of a xerophilic Mediterranean snail species (Xeropicta derbentina). Hsp70 levels varied considerably among populations, and were significantly associated with shell colour diversity: individuals in populations exhibiting low diversity expressed higher Hsp70 levels both constitutively and under heat stress than those of phenotypically diverse populations. In contrast, population structure (cytochrome c oxidase subunit I gene) did not correlate with phenotypic diversity. However, genetic parameters (both within and among population differences) were able to explain variation in Hsp70 induction at elevated but non-pathologic temperatures. Our observation that (1) population structure had a high explanatory potential for Hsp70 induction and that (2) Hsp70 levels, in turn, correlated with phenotypic diversity while (3) population structure and phenotypic diversity failed to correlate provides empirical evidence for Hsp70 to act as a mediator between genotypic variation and phenotype and thus for chaperone-driven evolutionary capacitance in natural populations