Combination of FLNC and JUP variants causing arrhythmogenic cardiomyopathy in an Iranian family with different clinical features.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) characterized by progressive myocardial loss and replacement with fibro-fatty tissue is a major cause of sudden cardiac death (SCD). In particular, ACM with predominantly left ventricular involvement, known as arrhythmogenic left ventricular cardiomyopathy (ALVC), has a poor prognosis. METHODS: The proband underwent whole-exome sequencing (WES) to determine the etiology of ALVC. Family members were then analyzed using PCR and Sanger sequencing. Clinical evaluations including 12-lead ECG, transthoracic echocardiography, and cardiac MRI were performed for all available first-degree relatives. RESULTS: WES identified two variants in the FLNC (c.G3694A) and JUP (c.G1372A) genes, the combination of which results in ALVC and SCD. CONCLUSION: The present study comprehensively investigates the involvement of two discovered variants of FLNC and JUP in the pathogenesis of ALVC. More study is necessary to elucidate the genetic factors involved in the etiology of ALVC.

Percutaneous versus surgical closure of paravalvular leaks in prosthetic valves: A cross-sectional comparison of clinical outcomes.

Background and Aims: Paravalvular leak (PVL) is a serious complication of prosthetic valve replacement. Both surgical and percutaneous closure techniques are used for PVL closure, but optimal strategies and comparative outcomes are uncertain. This study aimed to compare the efficacy and safety of percutaneous versus surgical PVL closure by analyzing changes in leak severity, functional status, echocardiographic parameters, and clinical outcomes. Methods: A total of 72 patients were included in this retrospective cross-sectional single-center study comparing percutaneous (n = 25) and surgical (n = 47) PVL closure from 2015 to 2022. Demographics, medical history, echocardiograms, laboratory data, complications, and mortality data were extracted from the records. Changes in leak severity, NYHA class, echocardiographic parameters, and clinical outcomes were compared between the percutaneous and surgical groups. Results: Both percutaneous and surgical PVL closure significantly reduced leak severity and improved NYHA class (both p < 0.01), with no difference between the quantity of changes in each group. The 30-day mortality was 4% after percutaneous and 6.4% after surgical closure (p = 0.65). At 90 days, mortality was 24% percutaneous versus 17% surgical (p = 0.48). The length of stay in the hospital and post-procedural decrease in hemoglobin were considerably lower in the percutaneous group. The rate of complication rates was similar between the groups. Echocardiographic changes were also comparable. Conclusion: Percutaneous and surgical PVL closure had similar efficacy in reducing leaks and improving symptoms, with no significant difference in early outcomes. Both options should be considered viable for PVL repair after heart team evaluation.

Cross-cultural validity of the Pulmonary Embolism Quality of Life questionnaire in the quality of life survey after pulmonary embolism: A Persian-speaking cohort.

Background: The Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire is the first disease-specific scale for assessing the quality of life in patients with a history of pulmonary embolism (PE). Objectives: To assess the cross-cultural validity and reliability of the disease-specific PEmb-QoL questionnaire. Methods: The Persian version was prepared through the forward and backward translation of the English questionnaire. Six months after the diagnosis of acute PE, consecutive Persian-speaking patients were asked to complete the PEmb-QoL, the generic 36-item Short Form (SF-36) questionnaires and undertake a 6-minute walk test (6MWT). Acceptability was assessed via item missing rate, reproducibility by the test-retest method, and internal consistency reliability by Cronbach's α and McDonald's ω coefficients. Convergence validity was assessed using the Spearman rank correlation between scores of PEmb-QoL, SF-36, and 6MWT. The questionnaire structure was evaluated through exploratory factor analysis. Results: Ninety-six patients with a confirmed diagnosis of PE completed the questionnaires. The Persian version of PEmb-QoL had good internal consistency (α = 0.95, 3-factor ω = 0.96), inter-item correlation (0.3-0.62), item-total correlation (0.38-0.71), reproducibility (test-retest ICC with 25 participants = 0.92-0.99), and good discriminant validity. Convergence validity was confirmed by the moderate-to-high correlations between PEmb-QoL and SF-36 scores, and a good correlation between the "limitation in daily activities" dimension of the PEmb-QoL questionnaire and 6MWT results. Exploratory factor analysis suggested a 3-component structure with functional (items 1h, 4b-5d, 6, 8, 9i, and 9j), symptoms (1b-h, 7, and 8), and emotional (5a, 6, and 9a-h) components. Conclusion: The Persian version of the PEmb-QoL questionnaire is valid and reliable for measuring the disease-specific quality of life in patients with PE.

Knowledge Gaps for Prophylactic Use of Antithrombotic Agents in Patients with COVID-19: Insights into New SARS-CoV-2 Variants, Vaccination Status, and Emerging Oral Antivirals.

Data suggest that coronavirus disease 2019 (COVID-19) results in a prothrombotic state leading to arterial and venous thromboses. Vaccination, novel antiviral drugs, and emerging variants have changed the course of the disease in many ways; however, their effects on the incidence of thrombotic events and the efficacy of preventative antithrombotic agents have not been yet evaluated. A systematic search was conducted to identify studies reported on the incidence of thrombotic events based on vaccination status, use of novel antiviral drugs, and emerging viral variants. Similarly, we screened the ongoing/published randomized trials of preventative antithrombotic therapy in any COVID-19 population to assess whether subgroup-specific results were reported based on any of these variants. Upon searching a total of 3,451 records, only one entry fulfilled the inclusion criteria of our systematic review, which was a self-controlled case series on 29,121,633 vaccinated individuals, the incidence rate ratio of thrombotic complication after breakthrough infection was 13.86 (95% confidence interval [CI]: 12.76-15.05) compared with 1.10 (95% CI: 1.02-1.18) during the 28-day postvaccination. In conclusion, although the mortality benefit of mass vaccination and the early promising results of the new antiviral therapies are well known, we were unable to find clinical evidence on whether vaccination, the use of novel antiviral agents, and emerging viral variants have affected the incidence rate of thrombotic events or impacted the efficacy of prophylactic antithrombotic therapy in patients with COVID-19. Analyses from existing trials and large-scale registries can provide interim knowledge and any findings of relevance should be incorporated in the design of future trials.