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Aims To evaluate arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) in affected families with desmosome mutations on the basis of the recently revised Task Force Criteria (TFC). Methods and results One hundred and three consecutive carriers of pathogenic desmosome mutations and 102 mutation-negative relatives belonging to 22 families with dominant and 14 families with recessive ARVC/D were evaluated according to the original and revised TFC. Serial cardiac assessment with 12-lead, signal-averaged, and 24 h ambulatory ECG and two-dimensional echocardiography was performed. Clinical events and outcome were prospectively analysed up to 24 years (median 4 years). With the revised criteria, 16 carriers were newly diagnosed on the basis of ECG abnormalities in 100%, ventricular arrhythmias in 79%, and functional/structural alterations in 31%, increasing diagnostic sensitivity from 57 to 71% (P = 0.001). Task Force Criteria specificity improved from 92 to 99% (P = 0.016). In dominant mutation carriers, penetrance changed significantly (61 vs. 42%, P = 0.001); no changes were observed in recessive homozygous carriers (97 vs. 97%, P = 1.00). Affected carriers according to the revised TFC (n = 73) had 12-lead ECG abnormalities in 96%, ventricular arrhythmias in 91%, and functional/structural alterations fulfilling echocardiographic criteria in 76%. Cumulative and event-free survival did not differ significantly between dominant and recessive affected carriers, being at 78.6 vs. 76 and 51.7 vs. 55.4%, respectively, by the age of 40 years. Conclusion Revised TFC increased diagnostic sensitivity particularly in dominant ARVC/D. Serial family evaluation may rely on electrocardiography which seems to have the best diagnostic utility particularly in early disease that is not detectable by two-dimensional echocardiography. [ABSTRACT FROM PUBLISHER]

Naxos disease is a rare autosomal recessive condition combining arrhythmogenic right ventricular cardiomyopathy, woolly hair, and palmoplantar keratoderma. The first identified causative variant was in the gene encoding the desmosomal protein plakoglobin. Naxos disease exhibits fibro-fatty myocardial replacement with immunohistological abnormalities in cardiac protein and signaling pathways, highlighting the role of inflammation and potential anti-inflammatory treatments. Childhood cutaneous signs precede cardiac features, which are diagnosed by familial and genetic evaluation, electrocardiography and cardiac imaging. Disease progression necessitates holistic care with risk management and lifestyle adjustments, often needing treatment for arrhythmia and heart failure. Similar phenotypes have been linked to desmoplakin and rarely desmocollin2 gene variants, highlighting the importance of familial and genetic evaluation. This document summarizes current knowledge on Naxos disease and related cardiocutaneous syndromes and initiates an international endeavor to collect and study all global cases, aiming to improve understanding, treatment, and patient care through shared data and research., Competing Interests: Dr Protonotarios holds consulting agreements with Tenaya Therapeutics and Avidity Biosciences. Dr Crisci has received a research grant by the CardioPath program from Federico II University of Naples, Italy. Dr Abrams is a consultant/scientific advisory board for Thryv Therapeutics, Rockets Pharmaceuticals, Solid Biosciences. Dr Anastasakis is on the advisory board of Pfizer, Genesis, Takeda, Sanofi, and BMS. Dr Mestroni has received grant support from Tenaya Therapeutics, Pfizer, AstraZeneca, Owkin, Greenstone Bioscience, and Bristol Myers Squibb; and is a member of the scientific advisory board of Tenaya Therapeutics. Dr Saffitz is consultant for Implicit Bioscience and Rocket Pharmaceuticals. Dr McKenna is a scientific advisor to Health in Code and to Tenaya Therapeutics. Dr Elliott holds consultancies in Biomarin, Pfizer, BMS, and the Patent: US Pat No 62/903,103: GENE THERAPY COMPOSITIONS AND TREATMENT OF RIGHT VENTRICULAR ARRYTHMOGENIC CARDIOMYOPATHY. Dr Kaski has consultancy/advisory board activities with Tenaya Therapeutics, Cytokinetics, Lexeo, Avidity Biosciences, and Accord Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Aims: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC)., Methods and Results: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function., Conclusion: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC., Competing Interests: Conflict of interest: P.M.E. declares consultancies for Pfizer, Sarepta. G.S. declares consultancies at Novartis, Bayer, Astrazeneca, Boston Scientific, Vifor Pharma, Menarini, Akcea Therapeutics. The other authors declare that there is no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aims: To determine the incidence and the causes of sudden death (SD) in persons aged 1-35 years old and the diagnostic yield of clinically guided genetic screening in the sudden arrhythmic death syndrome (SADS) victims' families., Methods and Results: Incidence and causes of SD in the Attica region of Greece in 2002-10 were determined using death certificates and autopsy reports. We evaluated clinically consecutive families of SADS victims and if a clinical diagnosis was established, we proceeded to targeted genetic analysis. Out of 6030 deaths, 56% were due to traumatic or violent causes, 40.5% were natural deaths, and 3.3% were of undetermined cause. There were 349 SD cases. Cardiovascular causes accounted for 65%, non-cardiovascular causes for 17%, and SADS for 18%. Clinical evaluation identified an inherited heart disease in 5/20 SADS families (25%). Targeted genetic analysis identified a causative mutation in all of the five screened families and reconfirmed the diagnosis in three of five proband victims. Clinical and genetic evaluation of 28 family members identified eight affected carriers and eight non-affected carriers. Molecular autopsy failed to identify any of these families., Conclusion: Sudden death in the young is of cardiovascular origin in the majority of cases. A considerable rate of SD cases remains of unknown cause on post-mortem. Apart from channelopathies, subclinical forms of inherited structural heart diseases would appear to be implicated in SADS. Clinically guided genetic screening has a significant diagnostic yield and identifies affected families that would have been missed by the current suggested molecular autopsy panel., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.)

Introduction: So far, no studies have been performed regarding the epidemiology and management of acute coronary syndromes (ACS) in Cyprus. The aim of the present study was to enroll a representative sample of patients in order to study the epidemiology and management of ACS in the Mediterranean island of Cyprus., Methods: For a period of 12 months, all patients admitted to Nicosia General Hospital with an ACS were studied. The calculation of the annual incidence of ACS was based on the number of all ACS cases registered during one year in the Nicosia district. The results from the province of Nicosia can be considered as representative of the whole ACS profile in Cyprus., Results: The annual incidence of ACS in the Nicosia district was 160 per 100,000 inhabitants (41 per 100,000 women and 282 per 100,000 men). This percentage translates into 1342 ACS episodes annually among the Cypriot population. The ratio of men to women was 6.8:1. More female ACS patients than men had hypertension (67.3% vs. 46.3%, p=0.005) and were passive smokers (53.8% vs. 47.7%, p=0.4), while male patients with ACS included a significantly greater percentage of smokers compared to women (51.3% vs. 13.5%, p<0.001). Regarding the type of ACS, 45% of patients were diagnosed with STEMI, 41.3% with NSTEMI and 13.7% with unstable angina. The majority of patients with STEMI were treated with medical reperfusion. The in-hospital mortality rate was 3.5%., Conclusions: The annual incidence of ACS in Cyprus is below the European average. The management of ACS is similar to that in southern Europe. The majority of patients with STEMI are treated with pharmacological reperfusion. The small geographical area of the island provides the advantage of early reperfusion to the majority of patients, which results in very low in-hospital mortality.

Introduction: Increased levels of homocysteine are known to be associated with coronary artery disease (CAD). The most common form of genetic hyperhomocysteinemia results from MTHFR polymorphisms. To examine the role of homocysteine levels and MTHFR polymorphisms in premature CAD and acute myocardial infarction (MI) in the Cypriot population, a case control study was performed in Nicosia General Hospital., Methods: Sixty-three male patients less than 50 years old who presented with MI in Nicosia General Hospital were compared with 54 controls without CAD. Fasting homocysteine and lipids were tested within 24 hrs from admission, while MTHFR C677T and A1298C polymorphisms were also tested., Results: Mean homocysteine levels were 14.5 mol/L in patients and 12.3 mol/L in controls (p=0.017). Mutant homozygous MTHFR C677T was present in 17.7% of the patients and 19.2% of the controls (p=0.838), while mutant homozygous MTHFR A1298C was found in 16.1% of patients and 13.5% of controls (p=0.690). Mean homocysteine levels were 12.6 mol/L in patients with single-vessel CAD and 15.5 mol/L in patients with multi-vessel CAD (p=0.025). Lower HDL appeared to be associated with higher levels of homocysteine with an odds ratio of 0.901, indicating that for each unit increase in HDL, the expected odds of having high homocysteine levels decreased by approximately 10%., Conclusions: Higher levels of homocysteine are associated with acute MI and multi-vessel disease in Cypriot patients under the age of 50. The existence and extent of disease are not associated with MTHFR polymorphisms. Lower HDL is associated with higher levels of homocysteine.

Penetrating heart injuries can be lethal. Here we report a case of self-inflicted cardiac injury with glass fragments by a psychiatric patient. The patient presented with cardiogenic shock and was initially treated surgically for a large pneumothorax and cardiac tamponade. A few days later she presented with dyspnoea and hypotension. An echo-Doppler study was performed and an acquired post-traumatic ventricular septal defect (VSD) with left-to-right shunt was diagnosed. The patient was transferred to theatre where the defect was successfully repaired. Post-traumatic VSD is a rare complication of penetrating heart injuries and has a tendency to present late. Follow up of such cases is recommended with repeat echocardiography.