Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterised by increased left ventricle (LV) wall thickness caused by mutations in sarcomeric genes. Finding a causal mutation can help to better assess the proband&rsquo;s risk, as it allows the presence of the mutation to be evaluated in relatives and the follow-up to be focused on carriers. We performed an observational study of patients with HCM due to the novel p.Arg652Lys variant in the MYH7 gene. Eight families and 59 patients are described in the follow-up for a median of 63 months, among whom 39 (66%) carry the variant. Twenty-five (64%) of carriers developed HCM. A median maximum LV wall thickness of 16.5 mm was described. The LV hypertrophy was asymmetric septal in 75% of cases, with LV outflow tract obstruction in 28%. The incidence of a composite of serious adverse cardiovascular events (sudden death, aborted sudden death, appropriate implantable cardiac defibrillator discharge, an embolic event, or admission for heart failure) was observed in five (20%) patients. Given the finding of the p.Arg652Lys variant in patients with HCM, but not in controls, with evident segregation in patients with HCM from eight families and the location in an active site of the protein, we can define this variant as likely pathogenic and associated with the development of HCM

New Variant in Placophilin-2 Gene Causing Arrhythmogenic Myocardiopathy

Introduction: Arrhythmogenic cardiomyopathy (ACM) is an inherited disease characterized by progressive fibroadipose replacement of cardiomyocytes. Its diagnosis is based on imaging, electrocardiographic, histological and genetic/familial criteria. The development of the disease is based mainly on desmosomal genes. Knowledge of the phenotypic expression of each of these genes will help in both diagnosis and prognosis. The objective of this study is to describe the genotype&ndash;phenotype association of an unknown PKP2 gene variant in a family diagnosed with ACM. Methods: Clinical and genetic study of a big family carrying the p.Tyr168* variant in the PKP2 gene, in order to demonstrate pathogenicity of this variant, causing ACM. Results: Twenty-two patients (proband and relatives) were evaluated. This variant presented with high arrhythmic load at an early age, but without evidence of structural heart disease after 20 years of follow-up, with low risk in predictive scores. We demonstrate evidence of its pathogenicity. Conclusions: The p.Tyr168* variant in the PKP2 gene causes ACM with a high arrhythmic load and with an absence of structural heart disease. This fact emphasizes the value of knowing the phenotypic expression of each variant

Changes in surgicaL behaviOrs dUring the CoviD-19 pandemic. The SICE CLOUD19 Study

BACKGROUND: The spread of the SARS-CoV2 virus, which causes COVID-19 disease, profoundly impacted the surgical community. Recommendations have been published to manage patients needing surgery during the COVID-19 pandemic. This survey, under the aegis of the Italian Society of Endoscopic Surgery, aims to analyze how Italian surgeons have changed their practice during the pandemic.METHODS: The authors designed an online survey that was circulated for completion to the Italian departments of general surgery registered in the Italian Ministry of Health database in December 2020. Questions were divided into three sections: hospital organization, screening policies, and safety profile of the surgical operation. The investigation periods were divided into the Italian pandemic phases I (March-May 2020), II (June-September 2020), and III (October-December 2020).RESULTS: Of 447 invited departments, 226 answered the survey. Most hospitals were treating both COVID-19-positive and -negative patients. The reduction in effective beds dedicated to surgical activity was significant, affecting 59% of the responding units. 12.4% of the respondents in phase I, 2.6% in phase II, and 7.7% in phase III reported that their surgical unit had been closed. 51.4%, 23.5%, and 47.8% of the respondents had at least one colleague reassigned to non-surgical COVID-19 activities during the three phases. There has been a reduction in elective (>200 procedures: 2.1%, 20.6% and 9.9% in the three phases, respectively) and emergency (<20 procedures: 43.3%, 27.1%, 36.5% in the three phases, respectively) surgical activity. The use of laparoscopy also had a setback in phase I (25.8% performed less than 20% of elective procedures through laparoscopy). 60.6% of the respondents used a smoke evacuation device during laparoscopy in phase I, 61.6% in phase II, and 64.2% in phase III. Almost all responders (82.8% vs. 93.2% vs. 92.7%) in each analyzed period did not modify or reduce the use of high-energy devices.CONCLUSION: This survey offers three faithful snapshots of how the surgical community has reacted to the COVID-19 pandemic during its three phases. The significant reduction in surgical activity indicates that better health policies and more evidence-based guidelines are needed to make up for lost time and surgery not performed during the pandemic