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Dilated cardiomyopathy (DCM) is a common heart disorder caused by genetic and non-genetic etiologies, characterized by left ventricular dilatation and contractile dysfunction. Here, we created a human induced pluripotent stem cell line from peripheral blood mononuclear cells using non-integrating vectors from a patient carrying a heterozygous LMNA variant (c.481G > A, p.Glu161Lys, NM_170707.4). The obtained EURACi015-A line, showed the typical morphology of pluripotent cells, normal karyotype and exhibited pluripotency markers and a trilineage differentiation potential. This cell line can be successfully differentiated into cardiomyocytes and endothelial cells. This line represents a human in vitro model to study the genetic basis of DCM., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessandra Rossini and Serena Zacchigna reports financial support was provided by European Regional Development Fund., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Titin (TTN)-related dilated cardiomyopathy (DCM) has a higher likelihood of left ventricular reverse remodelling compared with other genetic etiologies. No data regarding the evolution of right ventricular dysfunction (RVD) according to genetic background are available., Methods: Consecutive 104 DCM patients with confirmed pathogenic genetic variants (51 TTN-related DCM; 53 other genetic DCM) and a control group of 139 patients with negative genetic testing and available follow-up data at 12-24 months were analysed. RVD was defined as a right ventricular fractional area change (RVFAC) < 35%. The main study end point was the comparison of the evolution of RVD and the change of RVFAC throughout the follow-up according to etiology. A composite of all-cause mortality and heart transplantation was included as outcome measure., Results: At enrollment, RVD was present in 29.1% of genetically positive DCM without differences between genetic cohorts. At 14 months follow-up, 5.9% of TTN-related DCM patients vs 35.8% of other genetic DCM patients had residual RVD after treatment (P < 0.001). Accordingly, RVFAC significantly improved in the TTN-related DCM cohort and remained stably impaired in other genetic DCM patients. However, the evolution of RVD was similar between TTN-related DCM and patients without a genetic mutation. After adjusting for RVD at follow-up, no differences in the outcome measure were seen in the study cohorts., Conclusions: The evolution of RVD in DCM is heterogeneous in different genetic backgrounds. TTN-related DCM is associated with a higher chance of RVD recovery compared with other genetic etiologies., (Copyright © 2021 Canadian Cardiovascular Society. All rights reserved.)

Background: The early diagnosis of genetically determined dilated cardiomyopathy (DCM) could improve the prognosis in mutation carriers. Left ventricular global longitudinal strain (LV GLS) and peak left atrial longitudinal strain (PALS) are promising techniques for the detection of subtle systolic and diastolic dysfunction. We sought to evaluate the prevalence of subtle systolic and diastolic dysfunction by LV GLS and PALS in a cohort of genotype-positive phenotype-negative (GPFN) DCM relatives., Methods and Results: In this retrospective study, we analyzed echocardiograms of forty-one GPFN relatives of DCM patients. They were compared with age and sex matched healthy individuals (control group). Reduced LV GLS and PALS were defined as >18% and <23.1%, respectively. GPFN relatives (37 ± 14 years, 48.8% male) and controls were similar according to standard echocardiographic measurements. Conversely, LV GLS was -18.8 ± 2.7% in the GPFN group vs. -24.0 ± 1.8% in the control group (p < 0.001). Twenty subjects (48.8%) in the GPFN group and no subjects in the control group had a reduced LV GLS. PALS was 29.2 ± 6.7% in the GPFN group vs. 40.8 ± 8.5% in the control group (p < 0.001). Seven subjects (18.4%) in the GPFN group and one (2%) in the control group had a reduced PALS. A cohort of 17 genotype-negative phenotype-negative relatives showed higher values of LV GLS compared to GPFN., Conclusions: Despite standard echocardiographic parameters are within the normal range, LV GLS and PALS are lower in GPFN relatives of DCM patients when compared to healthy individuals, suggesting a consistent proportion of subtle systolic and diastolic dysfunction in this population., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Implantable cardioverter-defibrillators (ICD) have a pivotal role in preventing major arrhythmic events in patients with severely reduced left ventricular ejection fraction (LVEF). Device replacement strategy is still controversial in patients without severely reduced left ventricular ejection fraction (LVEF) at the end of battery life., Objective: To evaluate the long-term arrhythmic outcome of patients with ICD or and cardiac resynchronization therapy defibrillators (CRT-D) with normal or intermediate LVEF at the time of device replacement., Methods: All consecutive patients with reduced ejection fraction heart failure, both from ischemic and non-ischemic origin, implanted with ICD or CRT-D for primary prevention from 2002 to 2009, were considered. The study population included patients without previous ICD interventions and without severe dysfunction (i.e. LVEF ≥ 35%) 60 [53-65] months after implantation (average battery duration). The outcome measure was the occurrence of appropriate ICD interventions in the long-term., Results: Among the 255 patients (150 ICDs; 105 CRT-D) evaluated, 45 (18%) had LVEF ≥ 35% without ICD interventions 5-year follow-up after implantation (15 ICD [10%]; 30 CRT-D [29%]). In the long term, ICD interventions were 4 (27%) in the ICD group and 5 (17%) in the CRT-D group., Conclusions: Despite the absence of severe left ventricular dysfunction at the time of battery replacement, a not negligible number of patients with ICD and CRT-D maintained a high risk of appropriate interventions in the long term, suggesting the opportunity of replacing the ICD regardless the amount of LV dysfunction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Left bundle branch block (LBBB) negatively affects prognosis in heart failure patients with a reduced left ventricular ejection fraction (LVEF). Less is known about the prognostic role of LBBB in dilated cardiomyopathy (DCM) with intermediate LVEF (between 36% and 50%). We sought to assess the role of LBBB in optimally treated DCM patients with mildly to moderately reduced LVEF and to determine the possible variables associated with subsequent LVEF reduction., Methods: We retrospectively analyzed DCM patients with LVEF >35% after 3-to-9 months of optimal medical treatment (OMT) consecutively evaluated from 1990 to 2010. All-cause mortality or heart transplantation (D/HTx) and sudden cardiac death (SCD) or major ventricular arrhythmias (MVA) were considered as outcome measures. LVEF deterioration during follow-up was also considered., Results: Among 280 (49%) patients that met the study criteria, 76 had LBBB (27%). During a mean follow-up of 151 months, the rates of D/HTx and SCD/MVA were similar between LBBB and not LBBB patients (p value = 0.52 and p = 0.39, respectively). Twenty-six out of 76 (34%) patients with LBBB experienced LVEF deterioration below 36%. The persistence of moderate-severe mitral regurgitation (MR), left atrial end-systolic area index and LV end-diastolic volume index emerged as independent predictors of LVEF deterioration and were associated with an increased risk of D/HTx during follow-up., Conclusions: LBBB does not affect mortality in DCM patients with intermediate LVEF after OMT. However, among these patients those with persistent significant MR, left atrial and LV remodeling carries a higher risk of LVEF deterioration during follow-up., (Copyright © 2018 Elsevier B.V. All rights reserved.)