We report a novel SCN5A missense variant (c.655C>T (p.Arg219Cys)) in a family with non-dilated left ventricular cardiomyopathy, broadening the spectrum of SCN5A-related structural cardiac diseases. The proband, a 35-year-old man, presented with embolic stroke and myocardial fibrosis in the absence of ventricular dilation. He exhibited a significant arrhythmic burden, including premature ventricular complexes and a non-sustained ventricular tachycardia, prompting prophylactic subcutaneous defibrillator implantation. Genetic testing identified a heterozygous SCN5A variant, also present in five relatives with myocardial fibrosis of variable extent on cardiac magnetic resonance imaging. The variant affects a highly conserved residue within the voltage-sensing domain of the Nav1.5 channel and, according to ACMG criteria, is best classified as a variant of uncertain significance. Nevertheless, its segregation with disease and the established functional importance of this region of Nav1.5 suggest a possible role in the observed phenotype. This report highlights a structural cardiomyopathy phenotype potentially linked to SCN5A dysfunction and supports the growing recognition of overlap between ion channelopathies and cardiomyopathies.

Background: Late cardiotoxicity is a recognized complication in survivors of childhood cancer treated with potentially cardiotoxic agents, particularly anthracyclines. These therapies may cause progressive myocardial injury through mechanisms involving oxidative stress, mitochondrial dysfunction, and cardiomyocyte apoptosis. Over time, this process can lead to ventricular remodeling, dilated cardiomyopathy, and heart failure. Advanced ventricular dilation frequently results in functional mitral and tricuspid regurgitation, further worsening hemodynamic burden and clinical outcomes. Case summary: We report the case of a 42-year-old man with a history of non-Hodgkin lymphoma diagnosed in childhood and treated with chemotherapy, without subsequent cardiologic follow-up. From the age of 29, he developed progressive heart failure symptoms. Transthoracic echocardiography revealed severe functional mitral regurgitation with mixed mechanism (Carpentier type I due to annular dilation and type IIIa due to leaflet restriction) and massive tricuspid regurgitation, associated with severe atrial dilation, grade III diastolic dysfunction, and pulmonary hypertension. Left ventricular systolic dysfunction was documented with an ejection fraction of 36% and markedly reduced global longitudinal strain (−11%), consistent with non-ischemic dilated cardiomyopathy. The patient underwent mitral valve replacement and tricuspid valve repair but developed intraoperative cardiac arrest and postoperative mixed shock. Persistent severe ventricular dysfunction (LVEF 26%, GLS −8%) and multiple complications were observed. Conclusion: This case highlights the importance of long-term cardiovascular surveillance in childhood cancer survivors and the role of strain imaging in detecting chemotherapy-related cardiomyopathy.

Rationale:Arrhythmogenic left ventricular cardiomyopathy (ALVC) is an arrhythmogenic cardiomyopathy characterized by nonischemic left-ventricular scar, ventricular arrhythmias, and risk of sudden cardiac death. Diagnosis is often guided by cardiac magnetic resonance (CMR) and clinical criteria.Patient concerns:A 51-year-old man presented with 10 months of intermittent chest tightness and dyspnea, which worsened over 1 month, and 1 episode of syncope.Diagnoses:Transthoracic echocardiography showed severe left ventricular systolic dysfunction (left ventricular ejection fraction 19%). CMR demonstrated nonischemic subepicardial fibrosis and diffuse left ventricular free-wall thinning consistent with ALVC. Coronary angiography revealed no significant stenosis. A clinical cardiomyopathy panel test reported findings supportive of ALVC.Interventions:Guideline-directed medical therapy was initiated, and a cardiac resynchronization therapy defibrillator was implanted for left ventricular dysfunction with dyssynchrony and arrhythmic risk.Outcomes:Ten days after discharge, a localized device-pocket infection occurred and was managed with debridement, negative-pressure therapy, and intravenous vancomycin, with full recovery. At 3 and 6 months, left ventricular ejection fraction improved to 27% and 36%, respectively, and device interrogation documented no malignant ventricular arrhythmias.Lessons:This case underscores the diagnostic value of CMR and supports the combined strategy of cardiac resynchronization therapy defibrillator in left ventricular–dominant disease with dyssynchrony, aligning with contemporary guidelines.

Cardiogenetics aims to identify the genetic causes of inherited cardiac diseases, with significant implications for early diagnosis, clinical management, and prevention of sudden cardiac death in both patients and their relatives. In Italy, however, access to structured cardiogenetic services remains uneven and is often limited to tertiary care centers, partly due to economic sustainability constraints. We developed a second-level outpatient model that integrates telemedicine to facilitate access to genetic testing. The pathway includes pre-test genetic counseling performed by the cardiologist based on clinical and instrumental phenotype assessment, molecular analysis through blood sample collection and referral to the Medical Genetics Unit of Ferrara, and post-test counseling conducted as a teleconsultation, involving remote participation of a geneticist via a dedicated telemedicine platform (c4C Dedalus). In case of a positive result, the patient undergoes an in-person cardiology consultation in Piacenza, while negative or uncertain results are managed through further phenotypic or familial investigations as needed. In the first year of activity, 78 probands and 20 first-degree relatives underwent genetic testing. The positivity rates, including relevant variants of uncertain significance, were 44% for hypertrophic cardiomyopathy, 75% for non-dilated left ventricular cardiomyopathy, 20% for dilated cardiomyopathy, 100% for arrhythmogenic right ventricular cardiomyopathy, 100% for long QT syndrome, and 50% for Brugada syndrome. This model demonstrates that telemedicine can be an effective and sustainable tool to extend access to specialized genetic counseling in peripheral settings, improving equity of care and optimizing the use of resources for the management of inherited cardiomyopathies.

Effectiveness of upgrading to left bundle branch area pacing compared with biventricular pacing in patients with right ventricular pacing-induced cardiomyopathy.

We present the case of a 58-year-old man with negative T waves in the inferior and lateral leads observed on a routine ECG in the context of persistent peripheral eosinophilia, 6 months after an intestinal parasitic infection. The diagnostic workup excluded coronary artery disease and led to a diagnosis of endomyocardial fibrosis with apical thrombosis. Endomyocardial fibrosis, also known as Loeffler endocarditis, represents the cardiac involvement of the hypereosinophilic syndrome, resulting in a cardiomyopathy with a restrictive phenotype. After initiating specific therapy, further investigations identified chronic eosinophilic leukemia as the underlying cause of hypereosinophilia. The patient remained asymptomatic regarding heart failure manifestations. Additionally, diastolic function was pseudo normal on transthoracic echocardiography, with no restrictive pattern, and troponin and natriuretic peptide levels were only mildly elevated. The moderate peripheral eosinophilia was firstly attributed to the recent parasitic infection, supported by the decrease in eosinophil count following treatment with metronidazole. Cardiac involvement occurred relatively shortly after the onset of peripheral eosinophilia (approximately 6 months). Early diagnosis through advanced cardiac imaging allowed the detection of this condition before irreversible myocardial damage occurred and facilitated the initiation of targeted therapy for both ventricular thrombosis and cardiomyopathy.

Nondilated left ventricular cardiomyopathy (NDLVC) has emerged as a new entity within the spectrum of nonischemic cardiomyopathies, characterized by impaired left ventricular (LV) systolic function in the absence of LV dilatation. This study aimed to compare baseline differences in characteristics between NDLVC and dilated cardiomyopathy (DCM), and to identify predictors of heart failure (HF) and sustained ventricular arrhythmias (VA) (VT/VF) hospitalization within the NDLVC subgroup. Patients with both DCM and NDLVC were eligible in this prospective observational cohort, with diagnostic classification being performed via cardiac magnetic resonance-derived volumes. Univariable and multivariable logistic regression models were used to identify differences in baseline characteristics and indices associated with HF and VA hospitalization. There were 122 patients in the study (NDLVC [n = 60], DCM [n = 62]). Compared to DCM, NDLVC patients had significantly smaller left-ventricular end-diastolic volume index (91 vs 103 ml/m², p = 0.015), shorter QRS duration (104 vs 115 ms, p = 0.02), and were more often in New York Heart Association class I (70% vs 45%, p = 0.004). In multivariable models, the NDLVC phenotype was independently associated with late potentials (odds ratio [OR] 2.82, 95% confidence intervals [CI] [1.25,6.69], p = 0.015), lower left-ventricular end-diastolic volume index (OR 0.97, 95% CI [0.95,0.99], p = 0.005), and shorter QTc (OR 0.98, 95% CI [0.96,0.99], p < 0.001). Among NDLVC patients and after a median follow-up of 41 months, 6/60 (10%) experienced HF, and 10/60 (17%) VA hospitalization. In multivariable models, HF hospitalization was associated with worse New York Heart Association class (OR 19.9, 95% CI [2.14,108.9] p = 0.006), reduced right ventricular ejection fraction (OR 0.81, 95% CI [0.60,0.95] p = 0.006), and lower indexed right-ventricular end-diastolic volume (OR 0.87, 95% CI [0.71,0.98] p = 0.014). VA hospitalization was independently associated with premature ventricular complexes >1,000/24 hours (OR=20.1, 95% CI [2.66,336], p = 0.002), right ventricular ejection fraction ≤45% (OR 0.85, 95% CI [0.71,0.96], p = 0.008) and prolonged QTc (OR 1.06, 95% CI [1.01,1.12], p = 0.005). In conclusion, NDLVC represents a distinct cardiomyopathy phenotype with preserved LV geometry and favorable functional status compared to DCM, yet a significant subset remains at-risk for adverse events, particularly VA. RV dysfunction and arrhythmic burden are key risk markers in NDLVC and warrant focused monitoring.

The introduction of non-dilated left ventricular cardiomyopathy (NDLVC) represents one of the key highlights of the 2023 European Society of Cardiology guidelines on cardiomyopathies. NDLVC is defined by the presence of left ventricular systolic dysfunction in the absence of ventricular dilation and/or non-ischemic myocardial fibrosis detectable by cardiac magnetic resonance. The clinical manifestation may be arrhythmogenic, with a risk of life-threatening ventricular arrhythmias even in patients with preserved ejection fraction. The phenotypic heterogeneity and variability in clinical expression reflect the complex interplay between genetic predisposition (involving variants in genes such as FLNC, DSP, and LMNA) and environmental, epigenetic, or inflammatory factors. A synergistic approach combining comprehensive clinical and family assessment, electrocardiographic and echocardiographic findings, advanced imaging, and genetic testing enables more accurate phenotypic characterization, definitive diagnosis, and consequently, tailored therapeutic strategies.

Atrial failure is an emerging clinical syndrome that results from an underlying atrial cardiomyopathy and is characterized by impaired atrial haemodynamic and/or electrical function that is sufficient to cause symptoms, adverse clinical outcomes or both. Similar to ventricular cardiomyopathy, atrial cardiomyopathy refers to a structural, functional and/or electrophysiological tissue abnormality, whereas atrial failure denotes the stage at which it manifests clinically. Atrial failure can be classified as primary, when driven by intrinsic atrial pathology, or secondary, when atrial dysfunction arises from sustained haemodynamic or electrical stress imposed by ventricular, valvular or systemic disease. Increasing evidence indicates that atrial failure might not be merely a bystander, but a key determinant of symptoms and prognosis in cardiovascular conditions. Atrial failure can act as a primary driver of heart failure with preserved ejection fraction, promote atrial arrhythmias through adverse electrical remodelling, and potentially increase thromboembolic risk independently of atrial fibrillation. In this Review, we detail the pathophysiological mechanisms and clinical phenotypes of atrial failure and highlight the role of multimodality imaging in diagnosing and phenotyping atrial cardiomyopathy and clinical atrial failure. Finally, we summarize emerging therapeutic strategies aimed at potentially reversing atrial adverse remodelling and discuss future directions for integrating atrial failure into clinical practice.

Introduction . The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains a challenging task. Despite the revised 2010 criteria of the ITF Task Force, most patients still face difficulties in establishing this diagnosis. Objective . To assess the clinical and genetic characteristics of patients with a preliminary diagnosis of “ARVC,” with a focus on the final diagnosis established after re-evaluation at the Republican Scientific and Practical Center of Cardiology (RSPC “Cardiology”). Material and methods . Twenty-eight patients (53.6% male, median age 35 [24; 43] years) with a preliminary diagnosis of ARVC referred to the RSPC “Cardiology” were examined. The clinical and instrumental evaluation included 12-lead ECG, 24-hour Holter monitoring, transthoracic echocardiography (TTE), and cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE). The ARVC diagnosis was based on the 2010 ITF criteria and classified into definite, borderline, and possible categories. Genetic testing for mutations in genes associated with cardiomyopathies and inherited rhythm disorders was performed using next-generation sequencing (NGS). Results . Among the 28 patients with a preliminary diagnosis of ARVC, only 7 (25%) were diagnosed with definite ARVC according to the 2010 ITF criteria and confirmed by genotyping (mutations in the PKP2 and DSG genes in 5 patients, mutation in the non-desmosomal TMEM43 gene in 1 patient, and mutations in ILK and RBM20 genes in 1 patient). Eight (28.6%) patients were diagnosed with borderline ARVC, and 4 (14.3%) with possible ARVC. In 9 (32.1%) patients, the diagnosis of ARVC was ruled out due to misinterpretation of cardiac MRI. Genotyping revealed no ARVC-associated mutations in the borderline, possible, or excluded groups. A total of 7 (25%) patients received an ICD; of these, 6 were deemed appropriate, while 1 was considered inappropriate due to an unconfirmed ARVC diagnosis. Conclusions . A misdiagnosis of ARVC was found in 32.1% of patients suspected of having the condition. The most common reason for false suspicion was misinterpretation of cardiac MRI results, particularly regional dyskinesia/akinesia of the right ventricular wall due to factors such as pericardial constriction, right ventricular diverticulum, pectus excavatum, right ventricular enlargement in athletes, or frequent arrhythmias causing artifacts. Genotyping proved helpful in timely confirmation of the ARVC diagnosis in this patient cohort.

Machine Learning Models Enhance Detection of Arrhythmogenic Right Ventricular Cardiomyopathy, Quansah, Kwaku, Murphy, Sean, Kwon, Esther, Anderson, Emma, Tichnell, Crystal, Murray, Brittney, Gaine, Sean, Gasperetti, Alessio, James, Cynthia, Calkins, Hugh, Carrick, Richard, Kwon, Chulan

The article presents a review of literary scientific sources from the MEDLINE database on PubMed, Web of Science, Scopus, and Google Scholar platforms, focusing on arrhythmia in patients with arrhythmogenic cardiomyopathy. In accordance with international guidelines, the definition of arrhythmogenic right ventricular cardiomyopathy, arrhythmogenic left ventricular cardiomyopathy, and biventricular heart damage are provided. An algorithm of the diagnostic process based on the Padua criteria is presented to verify the types of arrhythmogenic cardiomyopathy. The electrocardiographic characteristics of supraventricular and ventricular arrhythmias and their clinical manifestation in patients with arrhythmogenic cardiomyopathy are described. The significance of genotype in the formation of arrhythmic phenotype in cardiomyopaties is emphasized in accordance with modern data. Treatment strategies for arrhythmias include pharmacotherapy and invasive methods. The indications for prescribing antiarrhythmic drugs to patients with arrhythmogenic cardiomyopaties are highlighted, taking into account clinical situations. The role of ablation of arrhythmogenic substrate and implantation of cardioverter-defibrillator in the prevention of sudden cardiac death of patients is shown.

Background: Exercise testing is routinely performed in arrhythmogenic right ventricular cardiomyopathy (ARVC), particularly given the disease’s strong association with exercise and competitive sport (James et al., 2013). However, the prognostic value of test-derived variables remains uncertain. Premature ventricular contractions (PVCs) during exercise and recovery have been linked to adverse events, though replication is limited (Castrichini et al., 2025). Heart rate responses may reflect autonomic imbalance, a contributor to arrhythmic risk, but it remains unclear whether these variables independently predict major adverse cardiac events (MACE) in ARVC (Jouven &amp; Courbon, 2005; Nishime, 2000). Purpose: To determine whether heart rate dynamics and PVC burden during exercise testing are associated with future cardiac events in adults with definite ARVC. Methods: Patients with definite ARVC according to the 2010 Task Force Criteria (Marcus et al., 2010) were retrospectively identified. Heart rate metrics included HRmax, resting heart rate, heart rate reserve (peak minus resting), and heart rate recovery at 30 seconds and minutes 1–5. PVC burden was calculated as total PVCs divided by phase duration. MACE included sustained ventricular tachycardia, ventricular fibrillation and tachycardia, appropriate implantable therapy, arrhythmic syncope, survived sudden cardiac death, heart transplantation, and death. Time-to-event analysis used Kaplan–Meier curves and Cox models, with follow-up censored at five years. Both continuous and ROC-derived categorical variables were evaluated. Results: Forty-five patients were included (mean age 49.1 ± 16.8 years, 37.8% female, 40% PKP2, 66.7% on beta-blockers). Among the 17 patients (37.8%) who experienced MACE, the median time to occurrence was 1.7 years (IQR 0.6–2.7). Baseline clinical and exercise variables did not differ significantly by outcome. HRmax was 146 ± 23 bpm, resting heart rate 67 ± 14 bpm, heart rate reserve 78 ± 19 bpm, and 1-minute heart rate recovery 23 ± 10 bpm. PVC burden increased from exercise to recovery (1.7 vs. 4.4 PVCs/min; p = 0.006), but neither predicted 5-year MACE (exercise: HR 1.05, 95% CI 0.96–1.15, p = 0.30; recovery: HR 1.04, 95% CI 0.99–1.10, p = 0.14). Higher heart rate reserve was associated with increased MACE risk (HR per 1-bpm increase 1.04; 95% CI 1.01–1.07; p = 0.024), remaining significant after adjustment for beta-blocker therapy and PVC burden. Heart rate recovery was most prognostic at minute three (HRR3). ROC analysis identified an HRR3 cutoff of 53 bpm; patients with HRR3 ≥ 53 bpm had greater MACE risk (HR 3.79; 95% CI 1.20–11.98; p = 0.023; AUC = 0.717), independent of beta-blocker therapy. Conclusions: Heart rate reserve and late heart rate recovery, particularly HRR3, are independently associated with 5-year MACE in ARVC, whereas PVC burden during exercise and recovery is not associated with MACE. Exercise test–derived autonomic markers may enhance arrhythmic risk stratification beyond conventional clinical parameters. Larger multicenter studies are needed to validate these findings.

Anthracyclines, notably doxorubicin, are potent cytotoxic agents that substantially improved outcomes across numerous malignancies. However, their use is restricted by their cardiotoxicity, a dose-dependent adverse effect that manifests acutely, during treatment, or years post-therapy. It encompasses a spectrum of phenotypes including asymptomatic ventricular dysfunction, heart failure, arrhythmias, and cardiomyopathy, contributing to considerable morbidity and mortality as cancer survival rates improve. This narrative review summarises current insights into anthracycline-induced cardiotoxicity pathophysiology and evaluates pharmacologic strategies for its prevention and management. A comprehensive literature search was conducted through August 2025, prioritizing randomised controlled trials, meta-analyses, observational studies, and guideline statements addressing pharmacologic interventions to mitigate anthracycline cardiotoxicity. Anthracycline cardiotoxicity arises from various mechanisms, including oxidative stress, mitochondrial dysfunction, topoisomerase IIβ-induced DNA damage, calcium dysregulation, and reticulum stress. Neurohormonal modulation with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers has shown modest preservation of left ventricular ejection fraction, especially when initiated early in high-risk patients; spironolactone appears more effective than eplerenone among mineralocorticoid receptor antagonists. Sacubitril/valsartan demonstrates promising superiority in preclinical and early clinical cohorts, though further randomised control trials are ongoing. Metabolic modulators such as metformin and sodium-glucose cotransporter 2 inhibitors exhibit cardio-protectivity via AMPK activation, attenuation of oxidative and inflammatory pathways, but evidence in non-diabetic cancer populations is limited. Statins have shown reduced left ventricular ejection fraction decline and lower cardiotoxicity rates in randomised studies, while dexrazoxane-through iron chelation and topoisomerase IIβ inhibition-remains the only approved agent for anthracycline-induced cardiotoxicity prevention, strongly supported by adult and paediatric data. Several pharmacologic strategies offer potential benefit in limiting anthracycline-induced cardiotoxicity and preserving cardiac function. Tailored, risk-based approaches that incorporate cardioprotective therapies early in anthracycline treatment-guided by biomarkers and imaging-are most promising. Further large-scale randomised studies are required to establish optimal combinations and confirm long-term benefit.

BackgroundObstructive coronary disease remains a leading cause of sudden cardiac death (SCD). The management of SCD therefore involves coronary angiography. Our aim was to evaluate whether the non-hyperemic angiography-derived microcirculatory resistance index (NH-IMRangio) could be an easy-to-use tool for identifying patients with electrical heart disease (EHD) from patients with other causes of SCD.MethodsA retrospective study was carried out on 30 patients who survived from SCD with no significant coronary lesions on coronary angiography. Etiological investigations enabled the classification of patients with myocardial disease (Group 1, n=20) and those with EHD without myocardial disease (Group 2, n=10). Myocardial disease was investigated by cardiac magnetic resonance imaging (CMR). NH-IMRangio was determined based on standard coronary angiographic views with 3-dimensional-modeling and computational analysis of the coronary flow.ResultsPatients were 46.4±15.9 years old and mostly male (73%). Group 1 included patients with dilated cardiomyopathy (n=7), non-dilated left ventricular cardiomyopathy (n=6), hypertrophic cardiomyopathy (n=2), arrhythmogenic right ventricular cardiomyopathy (n=1), myocardial infarction with non-obstructive coronary arteries (MINOCA) disease due to vasospastic angina (n=1), myocarditis (n=2), chemotherapy-induced cardiomyopathy (n=1). Group 1 presented a significantly higher NH-IMR angio compared to group 2 (46.5±13.1 vs. 34.1±10.8, P<0.02). An NH-IMR angio cut-off of 41.5 enabled an optimal classification of patients with or without myocardial disease.ConclusionsA high NH-IMRangio could represent a useful tool for guiding the etiological diagnosis of SCD towards myocardial disease rather than EHD.

Premature Ventricular Complexes (PVCs) are among the most frequent ventricular arrhythmias observed in daily cardiology practice. Although often benign, sustained high ectopic activity can result in left ventricular dysfunction known as PVC-induced Cardiomyopathy (PVC-CMP), a condition that is frequently reversible when the arrhythmia is effectively suppressed. The underlying mechanisms are multifaceted, involving electromechanical dyssynchrony, contractile inefficiency, abnormal calcium cycling, neurohormonal activation, and progressive structural remodeling. The likelihood of developing PVC-CMP varies among individuals and is influenced by electrophysiological and structural factors. Diagnosis relies on prolonged rhythm monitoring, comprehensive multimodality imaging, and demonstration of ventricular recovery after reducing the ectopic burden, which, in turn, confirms causality. Over the past decade, major advances in electrocardiographic mapping, cardiac imaging, and ablation therapy have transformed this field, demonstrating excellent efficacy and safety profiles. In parallel, artificial intelligence and computational mapping are emerging as powerful tools for prediction and procedural guidance. Recognition of PVC-CMP as a distinct, treatable cardiomyopathy highlights the importance of early detection and individualized therapy, offering the prospect of complete functional recovery and the prevention of heart failure progression.

Implantable cardioverter-defibrillators (ICDs) are the cornerstone of sudden cardiac death prevention in cardiomyopathies, but disease-specific structural and electrophysiological substrates profoundly affect device performance and outcomes. Understanding these distinctions is critical for tailoring therapy and improving patient safety. This review examines current evidence and practical experience regarding ICD implantation, programming, and management in hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and cardiac amyloidosis (CA). We performed a structured narrative synthesis to identify phenotype-specific technical challenges, programming strategies, and complication trends. For HCM, lead placement and programming to minimize inappropriate therapies are emphasized; for ARVC, issues of lead instability, oversensing, and ATP efficacy are explored; and for CA, defibrillation thresholds, sensing difficulties, and individualized indications are discussed. ICD therapy in cardiomyopathies must be individualized, balancing arrhythmic protection against disease-specific risks and device-related complications. Tailored programming, careful system selection, and remote monitoring are key to improving outcomes. Emerging technologies such as modular and extravascular ICD systems promise safer and more phenotype-driven care.

Sjögren’s syndrome is a chronic autoimmune condition in which the majority of patients present with sicca symptoms. About 20% of patients, however, do not have sicca symptoms and instead present predominantly with systemic or extraglandular involvement, posing a diagnostic challenge. Pulmonary Hypertension (PH) manifests as elevated pulmonary arterial pressure due to remodelling of the pulmonary vasculature as a result of various factors, including systemic involvement, infectious agents, connective tissue diseases, or toxin/drug exposure. PH in Sjögren’s syndrome is a dangerous complication that can significantly affect patient outcomes. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a genetic cardiomyopathy characterised by fibrofatty replacement of the right ventricular myocardium, predisposing patients to arrhythmias which may cause abrupt collapse or sudden death. Sjögren’s syndrome and ARVC are two distinct disorders that may lead to grave outcomes when they co-exist. Present case is a rare case of atypical Sjögren’s syndrome with PH and ARVC in a patient who suffered a cardiac arrest during her initial evaluation. Further work-up revealed ARVC, following which appropriate treatment was initiated. This case underlines the need for clinicians to consider Sjögren’s syndrome even in the absence of sicca symptoms, especially when unexplained systemic or cardiovascular findings are present. The co-existence of ARVC added further diagnostic complexity. Overlapping pathophysiology— right ventricular strain from PH combined with intrinsic ARVC-related myocardial damage—may accelerate clinical deterioration.

The classification of left ventricular cardiomyopathies is challenging due to evolving definitions and overlapping phenotypes. The European Task Force Criteria, by incorporating structural, functional, arrhythmic, and genetic parameters, refine the diagnostic criteria for arrhythmogenic cardiomyopathy. This study aimed to characterize the genotype-phenotype features of patients with arrhythmogenic left ventricular/biventricular cardiomyopathy (ALVC/ABVC), dilated cardiomyopathy (DCM), and their potential overlap. We retrospectively evaluated 306 patients with DCM or non-dilated left ventricular cardiomyopathy (NDLVC). Following European Task Force criteria, patients were reclassified as: isolated DCM, isolated ALVC/ABVC and a DCM-ALVC/ABVC overlapping phenotype. NDLVC not fulfilling the criteria, and isolated arrhythmogenic right ventricular cardiomyopathy were excluded. The study endpoint was a composite of cardiac death, sustained ventricular tachycardia, or ventricular fibrillation. Overall, 66, 79 and 76 patients were categorized as DCM, ALVC/ABVC, DCM-ALVC/ABVC, respectively. Genetic likely-pathogenic/pathogenic variants were more frequent in ALVC/ABVC than in DCM and DCM-ALVC/ABVC (50.6% vs 28.8% and 27.6%, p=0.004). DCM-ALVC/ABVC patients presented extensive LGE, higher NT-proBNP, and the highest arrhythmic burden (all p<0.05). Moreover, they had significantly lower event-free survival (log-rank p=0.002). In Cox analysis, LVEF (HR: 0.96, 95% CI 0.94-0.99, p=0.002) and LGE extent (HR: 1.04, 95% CI 1.00-1.07, p=0.016) independently predicted the endpoint. The European Task Force Criteria enabled the identification of an overlapping phenotype associated with increased arrhythmic risk, supporting the clinical utility of multiparametric diagnostic approaches to improve risk stratification and guide therapeutic decisions in patients with cardiomyopathies.

Cardiomyopathy Gene Variants and Polygenic Risk Scores in Atrial Fibrillation: Evidence for an Atrial-First Phenotype.