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.
Diagnosis of Arrhythmogenic CardioMyopathy (ACM) is challenging and often late after disease onset. No circulating biomarkers are available to date. Given their involvement in several cardiovascular ...diseases, plasma microRNAs warranted investigation as potential non-invasive diagnostic tools in ACM. We sought to identify circulating microRNAs differentially expressed in ACM with respect to Healthy Controls (HC) and Idiopathic Ventricular Tachycardia patients (IVT), often in differential diagnosis. ACM and HC subjects were screened for plasmatic expression of 377 microRNAs and validation was performed in 36 ACM, 53 HC, 21 IVT. Variable importance in data partition was estimated through Random Forest analysis and accuracy by Receiver Operating Curves. Plasmatic miR-320a showed 0.53 ± 0.04 fold expression difference in ACM vs. HC (p < 0.01). A similar trend was observed when comparing ACM (n = 13) and HC (n = 17) with athletic lifestyle, a ACM precipitating factor. Importantly, ACM patients miR-320a showed 0.78 ± 0.05 fold expression change vs. IVT (p = 0.03). When compared to non-invasive ACM diagnostic parameters, miR-320a ranked highly in discriminating ACM vs. IVT and it increased their accuracy. Finally, miR-320a expression did not correlate with ACM severity. Our data suggest that miR-320a may be considered a novel potential biomarker of ACM, specifically useful in ACM vs. IVT differentiation.
The heart of dystrophinopathies Sinagra, Gianfranco; Dal Ferro, Matteo; Gigli, Marta
European journal of heart failure,
August 2021, 2021-08-00, 20210801, Letnik:
23, Številka:
8
Journal Article
Objective
Natural history of cardiac amyloidosis (CA) is poorly understood. We aimed to examine the changing mortality of different types of CA over a 30-year period.
Patients and methods
Consecutive ...patients included in the “Trieste CA Registry” from January 1, 1990 through December 31, 2021 were divided into a historical cohort (diagnosed before 2016) and a contemporary cohort (diagnosed after 2016). Light chain (AL), transthyretin (ATTR) and other forms of CA were defined according to international recommendations. The primary and secondary outcome measures were all-cause mortality and cardiac death, respectively.
Results
We enrolled 182 patients: 47.3% AL-CA, 44.5% ATTR-CA, 8.2% other etiologies. The number of patients diagnosed with AL and ATTR-CA progressively increased over time, mostly ATTR-CA patients (from 21% before 2016 to 67% after 2016) diagnosed non-invasively. The more consistent increase in event-rate was observed in the long-term (after 50 months) in ATTR-CA compared to the early increase in mortality in AL-CA. In the contemporary cohort, during a median follow up of 16 4–30 months, ATTR-CA was associated with improved overall and cardiac survival compared to AL-CA. At multivariable analysis, ATTR-CA (HR 0.42,
p
= 0.03), eGFR (HR 0.98,
p
= 0.033) and ACE-inhibitor therapy (HR 0.24,
p
< 0.001) predicted overall survival in the contemporary cohort.
Conclusion
Incidence and prevalence rates of ATTR-CA and, to a less extent, of AL-CA have been increasing over time, with significant improvements in 2-year survival of ATTR-CA patients from the contemporary cohort. Reaching an early diagnosis and starting disease-modifying treatments will improve long-term survival in CA.
Background
Hereditary cardiovascular diseases comprise several different entities. In this study, we focused on cardiomyopathies (i.e., hypertrophic, dilated, arrhythmogenic, and left ventricular ...non‐compaction), channelopathies (i.e., Brugada syndrome and long QT syndrome), and aortopathies and pulmonary arterial hypertension (i.e., thoracic/abdominal aortic aneurysm and pulmonary arterial hypertension), and genetically characterized 200 Italian patients affected by these diseases.
Methods
We employed whole‐exome sequencing (WES), focused on four in silico gene panels, and the MLPA method for hypertrophic and arrhythmogenic right ventricular cardiomyopathy cases.
Results
Cardiomyopathies affected 87.5% of analyzed patients, channelopathies 7%, and aortopathies and pulmonary arterial hypertension 5.5%. The molecular diagnosis was confirmed for 21.5% of cases with a higher detection rate in familial forms (34%) than sporadic ones (14%). We highlighted the importance of family segregation to better understand the pathogenic role of the identified variants and their involvement in the clinical phenotype. Negative results could be ascribed to the high genetic and clinical heterogeneity of hereditary cardiovascular diseases; clinical follow‐up and revaluation of WES data will be essential.
Conclusion
This study highlights the importance of a multi‐step approach (WES and MLPA) to characterize hereditary cardiovascular diseases, provides crucial information for clinical management and recurrence risk estimation, and lays the foundation for future personalized therapies.
A total of 200 Italian patients affected by different forms of hereditary cardiovascular diseases were genetically characterized by WES and MLPA analyses. The molecular diagnosis was confirmed for 21.5% of cases, with a higher detection rate in the familial forms than in the sporadic ones. This multi‐step approach is important to well‐characterize hereditary cardiovascular diseases and provide information for clinical management and recurrence risk estimation of these heterogeneous diseases.
Aims
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a high risk of sudden cardiac death. Three different prediction models for the indication of implanted cardioverter ...defibrillator (ICD) are now available: the 5 year ARVC risk score, the International Task Force Consensus (ITFC) criteria, and the Heart Rhythm Society (HRS) criteria. We compared these three prediction models in a validation cohort of patients with definite ARVC.
Methods and results
In a cohort of 140 patients with definite ARVC, the 5 year ARVC risk score and the ITFC and HRS criteria were compared for the prediction of a major combined endpoint of sudden cardiac death, appropriate ICD intervention, resuscitated cardiac arrest, and sustained ventricular tachycardia. During the follow‐up, 65 major events occurred. The 5 year ARVC risk score with a threshold >10%, derived from the maximally selected rank statistic, predicted 62 (95%) events odds ratio (OR) 9.1, 95% confidence interval (CI) 2.6–32, P = 0.0006, the ITFC criteria 53 (81%, OR 4.8, 95% CI 2.2–10.3, P = 0.0001), and the HRS criteria 29 (45%, OR 4.2, 95% CI 1.9–9.3, P = 0.0003). At the analysis of decision curve for ICD implantation, a 5 year ARVC risk score >10% showed a greater net benefit than the ITFC and HRS criteria over a wide range of threshold probability of events. Finally, at multivariate analysis, the 5 year ARVC risk score >10% was the only independent predictor of major events.
Conclusions
The 5 year score with a threshold of >10% was more effective for predicting events than the ITFC and HRS criteria.
Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging ...provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.
Myocarditis: Which Role for Genetics? Baggio, Chiara; Gagno, Giulia; Porcari, Aldostefano ...
Current cardiology reports,
05/2021, Letnik:
23, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Purpose of Review
Myocarditis is a polymorphic disease, both in its presentation and clinical course. Recent data suggests that the genetic background, interacting with environmental factors, could ...be diriment both in the susceptibility and evolution of myocarditis in different clinical presentations. The aim of this paper is to expose the current available evidences and the evolving concepts on this topic, in order to provide insight for improving the clinical management of those patients. In this regard, the main goal is an optimal characterization of each patient’s risk, with the purpose of individualizing the treatment and the follow-up.
Recent Findings
The latest research highlights the possible prognostic role of some pathogenic mutations that could create a vulnerable myocardium prone to myocardial inflammation and also to the development of a long-lasting cardiomyopathy.
Summary
The identification of these genetic defects and of myocarditis patients requiring genetic testing is emerging as a challenge for the future. In fact, identifying a possible genetic background responsible for a particularly high-risk profile could be of extreme importance in improving management of myocarditis. This and many other aspects in the genetics of myocarditis remain uncovered, and further studies are expected based to refine our daily clinical practice.
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