Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high-risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high-risk arrhythmogenic gene variants in DCM patients. METHODS AND RESULTS: In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non-sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high-risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF] <35%). During a median follow-up of 6 years (interquartile range 1.6-12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present. CONCLUSION: In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life-threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes.

Sex-Specific Prognostic Implications in Dilated Cardiomyopathy After Left Ventricular Reverse Remodeling.

BACKGROUND: Women affected by Dilated Cardiomyopathy (DCM) experience better outcomes compared to men. Whether a more pronounced Left Ventricular Reverse Remodelling (LVRR) might explain this is still unknown. AIM: We investigated the relationship between LVRR and sex and its long-term outcomes. METHODS: A cohort of 605 DCM patients with available follow-up data was consecutively enrolled. LVRR was defined, at 24-month follow-up evaluation, as an increase in left ventricular ejection fraction (LVEF) ≥ 10% or a LVEF > 50% and a decrease ≥ 10% in indexed left ventricular end-diastolic diameter (LVEDDi) or an LVEDDi ≤ 33 mm/m2. Outcome measures were a composite of all-cause mortality/heart transplantation (HTx) or ventricular assist device (VAD) and a composite of Sudden Cardiac Death (SCD) or Major Ventricular Arrhythmias (MVA). RESULTS: 181 patients (30%) experienced LVRR. The cumulative incidence of LVRR at 24-months evaluation was comparable between sexes (33% vs. 29%; p = 0.26). During a median follow-up of 149 months, women experiencing LVRR had the lowest rate of main outcome measure (global p = 0.03) with a 71% relative risk reduction compared to men with LVRR, without significant difference between women without LVRR and males. A trend towards the same results was found regarding SCD/MVA (global p = 0.06). Applying a multi-state model, male sex emerged as an independent adverse prognostic factor even after LVRR completion. CONCLUSIONS: Although the rate of LVRR was comparable between sexes, females experiencing LVRR showed the best outcomes in the long term follow up compared to males and females without LVRR. Further studies are advocated to explain this difference in outcomes between sexes.

Contemporary survival trends and aetiological characterization in non-ischaemic dilated cardiomyopathy.

AIM: Contemporary survival trends in dilated cardiomyopathy (DCM) are largely unknown. The aim of this study is to investigate clinical descriptors, survival trends and the prognostic impact of aetiological characterization in DCM patients. METHODS AND RESULTS: Dilated cardiomyopathy patients were consecutively enrolled and divided into four groups according to the period of enrolment (1978-1984; 1985-1994; 1995-2004; and 2005-2015). A subset of patients with DCM of specific aetiology, enrolled from 2005 to 2015, was also analysed. Over a mean follow-up of 12 ± 8 years, 1284 DCM patients (52 in the 1978-1984 group, 326 in the 1985-1994 group, 379 in the 1995-2004 group, and 527 in the 2005-2015 group) were evaluated. Despite older age (mean age 51 ± 15, 43 ± 15, 45 ± 14, and 52 ± 15 years for the 1978-1984, 1985-1994, 1995-2004, and 2005-2015 groups, respectively; P < 0.001), most of the baseline clinical characteristics improved in the 2005-2015 group, suggesting a less advanced disease stage at diagnosis. Similarly, at competing risk analysis, the annual incidence of all outcome parameters progressively decreased over time (global P < 0.001). At multivariable analysis, the last period of enrolment emerged as independently associated with a reduction in all-cause mortality/heart transplantation (HTx)/ventricular assist device (VAD) implantation (1.46 events/100 patients/year), cardiovascular death/HTx/VAD implantation (0.82 events/100 patients/year) and sudden cardiac death (0.15 events/100 patients/year). Lastly, in 287 patients with DCM of specific aetiology, patients with environmental, toxic, or removable factors appeared to have different phenotypes and prognosis compared to those with genetic, post-myocarditis, or idiopathic DCM (P < 0.001). CONCLUSIONS: Contemporary survival trends in DCM significantly improved, mainly due to a reduction of cardiovascular events. Appropriate aetiological characterization might help in prognostication of DCM patients.

Sex Differences in the Long-term Prognosis of Dilated Cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) represents a specific phenotype of heart failure. Sex differences in the long-term prognosis of patients with DCM are unknown. The aim of this study is to investigate the long-term prognostic role of gender in a large cohort of patients with DCM. METHODS: A total of 1113 patients with DCM were prospectively enrolled. To investigate the impact of sex, a propensity score-matching analysis was performed on a sample of 586 patients. Univariable and multivariable Cox models and competing-risk analyses were estimated on both cohorts for the following outcome measures: (1) all-cause mortality/heart transplantation (HTx)/ventricular assist device (VAD); (2) cardiovascular mortality/HTx/VAD; and (3) sudden cardiac death or malignant ventricular arrhythmias. RESULTS: Women were older than men (50 ± 15 years vs 47 ± 15 years, respectively, P = 0.004) and more frequently had moderate to severe left ventricular dilation (P < 0.001) and left bundle branch block (P = 0.019). At multivariable analyses, male sex was independently associated with all considered outcome measures in the total cohort. At propensity score-matching analysis, over a median follow-up of 126 months (interquartile range, 62-201), 96 men (33%) vs 66 women (22%) experienced all-cause mortality/HTx/VAD (P = 0.03), 95 men (32%) vs 57 women (20%) experienced cardiovascular mortality/HTx/VAD (P = 0.025), and 46 men (16%) vs 28 women (10%) experienced sudden cardiac death/malignant ventricular arrhythmias (P = 0.07). CONCLUSION: The long-term outcomes of women affected by DCM are more favourable than those of men, and sex emerged as an important independent factor, particularly for cardiovascular outcomes.