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Nondilated left ventricular cardiomyopathy (NDLVC) has been recently differentiated from dilated cardiomyopathy (DCM). A comprehensive characterization of these 2 entities using cardiac magnetic resonance (CMR) and genetic testing has never been performed. This study sought to provide a thorough characterization and assess clinical outcomes in a large multicenter cohort of patients with DCM and NDLVC. A total of 462 patients with DCM (227) or NDLVC (235) with CMR data from 4 different referral centers were retrospectively analyzed. The study endpoint was a composite of sudden cardiac death or major ventricular arrhythmias. In comparison to DCM, NDLVC had a higher prevalence of pathogenic or likely pathogenic variants of arrhythmogenic genes (40% vs 23%; P < 0.001), higher left ventricular (LV) systolic function (LV ejection fraction: 51% ± 12% vs 36% ± 15%; P < 0.001) and higher prevalence of free-wall late gadolinium enhancement (LGE) (27% vs 14%; P < 0.001). Conversely, DCM showed higher prevalence of pathogenic or likely pathogenic variants of nonarrhythmogenic genes (23% vs 12%; P = 0.002) and septal LGE (45% vs 32%; P = 0.004). Over a median follow-up of 81 months (Q1-Q3: 40-132 months), the study outcome occurred in 98 (21%) patients. LGE with septal location (HR: 1.929; 95% CI: 1.033-3.601; P = 0.039) was independently associated with the risk of sudden cardiac death or major ventricular arrhythmias together with LV dilatation, older age, advanced NYHA functional class, frequent ventricular ectopic activity, and nonsustained ventricular tachycardia. In a multicenter cohort of patients with DCM and NDLVC, septal LGE together with LV dilatation, age, advanced disease, and frequent and repetitive ventricular arrhythmias were powerful predictors of major arrhythmic events. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) affects an estimated 1:500 individuals and is largely considered to be a disease of the sarcomere. However, disease-causative genetic variants in PLN -encoded phospholamban and JPH2 -encoded junctophilin-2 cause HCM via perturbations in intracellular calcium handling (ICH). Given recent case reports describing asymmetric left ventricular hypertrophy (LVH) in patients with arrhythmogenic cardiomyopathy (ACM)-predisposing genetic variants in PKP2 -encoded plakophilin-2, a gene known to play a role in ICH, we sought to examine the prevalence and clinical impact of an HCM phenotype in PKP2-ACM patients. In this retrospective study, review of 771 genotype-positive ACM patients evaluated between 01/2015 and 04/2024 was used to identify those with a pathogenic/likely pathogenic (P/LP) variant in PKP2. Pertinent demographic, electrocardiographic, imaging and outcome data was extracted from the electronic medical record. HCM was defined by the presence of maximal end-diastolic wall thickness of >15 mm anywhere in the left ventricle. Advanced heart failure (HF) and major VA outcomes [sudden cardiac arrest (SCA), sustained VT, and appropriate implantable cardioverter-defibrillator (ICD) shocks] were analyzed. Collectively, an HCM phenotype was observed in 9 (7.8%) of the 115 P/LP variant-positive patients (mean age 38±36; 51 (44%) male, and 57 with a ACM phenotype). Of note sigmoid subtype HCM was noted in 8/9 (89%) and left ventricular outflow tract obstruction present in 7/9 (78%; mean gradient of 57±48 mmHg). In comparison to PKP2-ACM patients without HCM, PKP2-HCM patients with HCM were older and less likely to have a family history of any cardiomyopathy (Table). Interestingly, in the patients with a positive phenotype, non-sustained VT and major VA outcomes were less prevalent in the HCM patients (Table). Nearly 8% of individuals with a P/LP variant in PKP2 have a concomitant HCM phenotype. Whether this observation reflects abnormal calcium handling in the setting of PKP2 haploinsufficiency or selection bias in the setting of the combined prevalence of HCM (1:500) and PKP2 loss-of-function (1:695) requires further studies. [ABSTRACT FROM AUTHOR]

Background: Diverse genetic backgrounds often lead to phenotypic heterogeneity in cardiomyopathies (CMPs). Previous genotype-phenotype studies have primarily focused on the analysis of a single phenotype, and the diagnostic and prognostic features of the CMP genotype across different phenotypic expressions remain poorly understood.Objectives: We sought to define differences in outcome prediction when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of patients with CMPs and positive genetic testing.Methods: Dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, and biventricular arrhythmogenic cardiomyopathy were examined in this study. A total of 281 patients (80% DCM) with pathogenic or likely pathogenic variants were included. The primary and secondary outcomes were: 1) all-cause mortality (D)/heart transplant (HT); 2) sudden cardiac death/major ventricular arrhythmias (SCD/MVA); and 3) heart failure-related death (DHF)/HT/left ventricular assist device implantation (LVAD).Results: Survival analysis revealed that SCD/MVA events occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA, and FLNC variants. However, after adjustment for age and sex, genotype-based classification, but not phenotype-based classification, was predictive of SCD/MVA. LMNA showed the worst trends in terms of D/HT and DHF/HT/LVAD.Conclusions: Genotypes were associated with significant phenotypic heterogeneity in genetic cardiomyopathies. Nevertheless, in our study, genotypic-based classification showed higher precision in predicting the outcome of patients with CMP than phenotype-based classification. These findings add to our current understanding of inherited CMPs and contribute to the risk stratification of patients with positive genetic testing. [ABSTRACT FROM AUTHOR]

[Display omitted] • Concurrent assessment of physician prescriptions and patient adherence is mandatory. • The rate of HF drug treatments in our study was in line with previous observations. • Patient adherence to drug therapy resulted unsatisfactorily. • Patient adherence is associated with a lower risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Little is known about the role of different types of atrial fibrillation (AF) in dilated cardiomyopathy (DCM). We investigated the epidemiological and prognostic impact of different types of AF in DCM during long-term follow-up. We evaluated consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry. Uni- and multivariable, extended Kaplan-Meier and propensity score-matching analyses were performed for a composite outcome including death/heart transplantation/ventricular-assist device implantation. Out of 1181 DCM patients (71% males, age 49 ± 15 years, left ventricular ejection fraction 33 ± 11%), 46 (3.9%) had baseline permanent AF (permAF), while 66 (5.6%) had a history of paroxysmal/persistent AF. Compared with sinus rhythm (SR) patients, permAF patients were older (48 ± 15 vs. 61 ± 11 respectively, p = 0.001), were more frequently in NYHA class III-IV (18% vs. 30%, p = 0.002) and had larger left atrium diameter (40 ± 8 vs. 50 ± 10 mm, respectively). Paroxysmal/persistent AF patients had intermediate characteristics between permAF and SR. During a median follow-up of 135 (75–210) months, 63 patients developed permAF (0.45 new cases/100patients/year). At multivariable analysis, permAF as a time-dependent variable was an independent outcome predictor (HR 2.45; 95% C.I. 2.61–3.63, p < 0.001), together with creatinine, NYHA class, restrictive filling pattern and moderate-severe mitral regurgitation, while paroxysmal/persistent AF was neutral. Propensity score-matching analysis confirmed the higher rate of primary outcome events in patients with baseline or incident permAF versus patients without permAF during a very long-term follow-up (70% vs. 20%, p < 0.001). PermAF in a large DCM cohort had low prevalence and incidence but had a relevant. prognostic role on hard outcomes. Patients with non-dilated left atrium and without permAF (upper figure) are those with the best prognosis. LA enlargement (middle figure) is associated with adverse outcome. The worst prognosis is proper of patients with permAF at baseline (bottom figure) or incident at follow-up. Patients with dilated atria are at higher risk for permAF incidence. The arrow on the right represents the prognosis (green: favourable outcome; red: adverse outcome). Legend. LA: left atrium. Unlabelled Image • DCM is a particular HF setting where AF is relatively infrequent. • The prognostic role of AF depends on the type of AF. • Paroxysmal or persistent AF do not significantly affect prognosis. • Permanent AF, at baseline or incident, carries a relevant negative prognostic impact. • Dilated atria increase the risk of permanent AF incident. [ABSTRACT FROM AUTHOR]