DSP-Related Cardiomyopathy as a Distinct Clinical Entity? Emerging Evidence from an Italian Cohort.

Variants in desmoplakin gene (DSP MIM *125647) have been usually associated with Arrhythmogenic Cardiomyopathy (ACM), or Dilated Cardiomyopathy (DCM) inherited in an autosomal dominant manner. A cohort of 18 probands, characterized as heterozygotes for DSP variants by a target Next Generation Sequencing (NGS) cardiomyopathy panel, was analyzed. Cardiological, genetic data, and imaging features were retrospectively collected. A total of 16 DSP heterozygous pathogenic or likely pathogenic variants were identified, 75% (n = 12) truncating variants, n = 2 missense variants, n = 1 splicing variant, and n = 1 duplication variant. The mean age at diagnosis was 40.61 years (IQR 31-47.25), 61% of patients being asymptomatic (n = 11, New York Heart Association (NYHA) class I) and 39% mildly symptomatic (n = 7, NYHA class II). Notably, 39% of patients (n = 7) presented with a clinical history of presumed myocarditis episodes, characterized by chest pain, myocardial enzyme release, 12-lead electrocardiogram abnormalities with normal coronary arteries, which were recurrent in 57% of cases (n = 4). About half of the patients (55%, n = 10) presented with a varied degree of left ventricular enlargement (LVE), four showing biventricular involvement. Eleven patients (61%) underwent implantable cardioverter defibrillator (ICD) implantation, with a mean age of 46.81 years (IQR 36.00-64.00). Cardiac magnetic resonance imaging (CMRI) identified in all 18 patients a delayed enhancement (DE) area consistent with left ventricular (LV) myocardial fibrosis, with a larger localization and extent in patients presenting with recurrent episodes of myocardial injury. These clinical and genetic data confirm that DSP-related cardiomyopathy may represent a distinct clinical entity characterized by a high arrhythmic burden, variable degrees of LVE, Late Gadolinium Enhancement (LGE) with subepicardial distribution and episodes of myocarditis-like picture.

Sport activity in patients with cardiomyopathies: a review.

Exercise has undisputable benefits and is an important therapy component for most cardiovascular diseases, with a proven role in reducing mortality. On the contrary, exercise may paradoxically trigger sudden cardiac arrest in patients with cardiomyopathies requiring refrain from competitive sports participation. The 2020 European guidelines for patients with cardiovascular disease provided indication for sports participation for patients with cardiac conditions, including cardiomyopathies. Although in some cases, the knowledge of the natural history of the disease and the risk of death during intensive exercise is more robust, in others, the evidence is scarce. Therefore, recommendations are not available for all possible scenarios with several uncertainties. In addition, many patients aspire to continue competitive sports or practise recreational activities after a diagnosis of cardiomyopathy. These aspects generate concern for the physician, who should make complex decisions, and confronts the request to design specific exercise programmes without specific indications. This article will review the available evidence on the sports-related risk of sudden cardiac death or cardiovascular events and the progression of the disease in cardiomyopathies.

Thromboembolism after COVID-19 vaccine in patients with preexisting thrombocytopenia.

While vaccination is the single most effective intervention to drastically reduce severe disease and death following SARS-CoV-2 infection, as shown in UK and Israel, some serious concerns have been raised for an unusual adverse drug reaction (ADR), including vaccine-induced immune thrombotic thrombocytopenia (VITT) with concurrent low platelets as well as capillary leak syndrome. In fact, the overall safety of the vaccine is highlighted by the low frequency of ADR considering that in UK, by the early June, 40 million first doses and 29 million second doses have been injected; nonetheless, 390 thrombotic events, including 71 fatal events have been reported. Interestingly, the cases reported low platelet counts with the presence of anti-platelet factor-4 (PF4) antibodies, indicating an abnormal clotting reaction. Here, out of three referred cases, we report a post-vaccine clinical case of fatal thrombosis with postmortem examination and whole exome sequencing (WES) analysis, whose pathogenesis appeared associated to a preexisting condition of thrombocytopenia due to myelodysplasia.

Clinical Features of LMNA-Related Cardiomyopathy in 18 Patients and Characterization of Two Novel Variants.

Dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease. Mutations in LMNA gene, encoding for lamin A/C, account for 10% of familial DCM. LMNA-related cardiomyopathies are characterized by heterogeneous clinical manifestations that vary from a predominantly structural heart disease, mainly mild-to-moderate left ventricular (LV) dilatation associated or not with conduction system abnormalities, to highly pro-arrhythmic profiles where sudden cardiac death (SCD) occurs as the first manifestation of disease in an apparently normal heart. In the present study, we select, among 77 DCM families referred to our center for genetic counselling and molecular screening, 15 patient heterozygotes for LMNA variants. Segregation analysis in the relatives evidences other eight heterozygous patients. A genotype-phenotype correlation has been performed for symptomatic subjects. Lastly, we perform in vitro functional characterization of two novel LMNA variants using dermal fibroblasts obtained from three heterozygous patients, evidencing significant differences in terms of lamin expression and nuclear morphology. Due to the high risk of SCD that characterizes patients with lamin A/C cardiomyopathy, genetic testing for LMNA gene variants is highly recommended when there is suspicion of laminopathy.

Neurovascular manifestations in connective tissue diseases: The case of Marfan Syndrome.

Patients with connective tissue diseases (CTDs) are suspected to be at higher risk for cerebrovascular involvement, such as intracranial aneurysms, dissections and strokes, than the general population. Particularly, Marfan Syndrome (MFS) has been reported as associated with an increased risk of cerebrovascular alterations. Literature data report different prevalence of intracranial aneurysms in MFS, ranging from 4 % to 29 %, suggesting a role of genetic cause that involves the regulation of the TGF-ß signaling. Ischemic and hemorrhagic strokes have been also reported in MFS, but with an estimated prevalence from 3 % to 4 %. However, the aetiology of both events appears to be reliable more to a cardiac source than to the primary connective tissue defect. Finally, the available literature suggests that MFS patients have a higher prevalence of arterial tortuosity of neck and head vessels and these findings may be related to an enhanced chance of dissection. Overall, despite of the lack of studies, we could affirm that it may exists an increased prevalence of some neurovascular findings in MFS patients. Nevertheless, further studies are required to determine the true prevalence of these features and investigate specific gene mutations involved in MFS.