Search Results (111)

Arrhythmogenic cardiomyopathies (ACMs) are a phenotypically and etiologically heterogeneous group of myocardial disorders characterized by fibrotic or fibro-fatty replacement of ventricular myocardium, electrical instability, and an elevated risk of sudden cardiac death. Initially identified as a right ventricular disease, ACMs are now recognized to include biventricular and left-dominant forms. Genetic causes account for a substantial proportion of cases and include desmosomal variants, non-desmosomal variants, and familial gene-elusive forms with no identifiable pathogenic mutation. Nongenetic etiologies, including post-inflammatory, autoimmune, and infiltrative mechanisms, may mimic the phenotype. In many patients, the disease remains idiopathic despite comprehensive evaluation. Cardiac magnetic resonance imaging has emerged as a key tool for identifying non-ischemic scar patterns and for distinguishing arrhythmogenic phenotypes from other cardiomyopathies. Emerging classifications propose the unifying concept of scarring cardiomyopathies based on shared structural substrates, although global consensus is evolving. Risk stratification remains challenging, particularly in patients without overt systolic dysfunction or identifiable genetic markers. Advances in tissue phenotyping, multi-omics, and artificial intelligence hold promise for improved prognostic assessment and individualized therapy. Full article

Transmembrane protein 43 (TMEM43 or LUMA) encodes a highly conserved protein found in the nuclear and endoplasmic reticulum membranes of many cell types and the intercalated discs and adherens junctions of cardiac myocytes. TMEM43 is involved in facilitating intra/extracellular signal transduction to the nucleus via the linker of the nucleoskeleton and cytoskeleton complex. Genetic mutations may result in reduced TMEM43 expression and altered TMEM43 protein cellular localization, resulting in impaired cell polarization, intracellular force transmission, and cell–cell connections. The p.S358L mutation causes arrhythmogenic right ventricular cardiomyopathy type-5 and is associated with increased absorption of lipids, fatty acids, and cholesterol in the mouse small intestine, which may promote fibro-fatty replacement of cardiac myocytes. Mutations (p.E85K and p.I91V) have been identified in patients with Emery–Dreifuss Muscular Dystrophy-related myopathies. Other mutations also lead to auditory neuropathy spectrum disorder-associated hearing loss and have a negative association with cancer progression and tumor cell survival. This review explores the pathogenesis of TMEM43 mutation-associated diseases in humans, highlighting animal and in vitro studies that describe the molecular details of disease processes and clinical, histologic, and molecular manifestations. Additionally, we discuss TMEM43 expression-related conditions and how each disease may progress to severe and life-threatening states. Full article

Brugada syndrome (BrS) has been traditionally considered a pure electrical disorder without an underlying structural substrate. However, early ECG studies showed the presence of depolarization abnormalities in this condition, while many studies based on advanced imaging have suggested the presence of subtle structural alterations. On the other hand, electrophysiological study (EPS) and electroanatomic mapping (EAM) techniques have provided important data regarding right ventricular functional and structural arrhythmic substrate. More recently, histology and immunology shed light on the possible role of fibrotic and inflammatory substrates in BrS. Notably, a significant overlap between electro anatomical and structural features in BrS and arrhythmogenic cardiomyopathy has been proposed. In this review, we summarized the physio pathological pathways and substrate underlying BrS. A deeper knowledge of the structural abnormalities involved in the pathogenesis of this disease could improve our diagnostic and prognostic approach, while novel findings regarding the role of inflammation and immune activation could potentially lead to new therapeutic strategies for BrS. Full article

Acute heart failure (AHF) is a complex clinical syndrome characterized by the rapid or gradual onset of symptoms and/or signs of heart failure (HF), leading to an unplanned hospital admission or an emergency department visit. AHF is the leading cause of hospitalization in patients over 65 years, thus significantly impacting public health care. However, its prognosis remains poor with high rates of mortality and rehospitalization. Many pre-existing cardiac conditions can lead to AHF, but it can also arise de novo due to acute events. Therefore, understanding AHF etiology could improve patient management and outcomes. Cardiomyopathies (CMPs) are a heterogeneous group of heart muscle diseases, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), non-dilated cardiomyopathy (NDLVC), and arrhythmogenic right ventricular cardiomyopathy (ARVC), that frequently present with HF. Patients with CMPs are under-represented in AHF studies compared to other etiologies, and therefore therapeutic responses and prognoses remain unknown. In DCM, AHF represents the most frequent cause of death despite treatment improvements. Additionally, DCM is the first indication for heart transplant (HT) among young and middle-aged adults. In HCM, the progression to AHF is rare and more frequent in patients with concomitant severe left ventricle (LV) obstruction and hypertrophy or severe LV systolic dysfunction. HF is the natural evolution of patients with RCM and HF is associated with poor outcomes irrespective of RCM etiology. Furthermore, while the occurrence of AHF is rare among patients with ARVC, this condition in NDLVC patients is currently unknown. In this manuscript, we assessed the available evidence on AHF in patients with CMPs. Data on clinical presentation, therapeutic management, and clinical outcomes according to specific CMPs are limited. Future HF studies assessing the clinical presentation, treatment, and prognosis of specific CMPs are warranted. Full article

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by structural abnormalities, arrhythmias, and a spectrum of genetic and clinical manifestations. Clinically, ARVC is structurally distinguished by right ventricular dilation due to increased adiposity and fibrosis in the ventricular walls, and it manifests as cardiac arrhythmias ranging from non-sustained ventricular tachycardia to sudden cardiac death. Its prevalence has been estimated to range from 1 in every 1000 to 5000 people, with its large range being attributed to the variability in genetic penetrance from asymptomatic to significant burden. It is even suggested that the prevalence is underestimated, as the presence of genotypic mutations does not always lead to clinical manifestations that would facilitate diagnosis. Additionally, while set criteria have been in place since the 1990s, newer understanding of this condition and advancements in cardiac technology have prompted multiple revisions in the diagnostic criteria for ARVC. Novel discoveries of gene variants predisposing patients to ARVC have led to established screening techniques while providing insight into genetic counseling and management. This review aims to provide an overview of the genetics, pathophysiology, and clinical approach to ARVC. It will also focus on clinical presentation, ARVC diagnostic criteria, electrophysiological findings, including electrocardiogram characteristics, and imaging findings from cardiac MRI, 2D, and 3D echocardiogram. Current management options—including anti-arrhythmic medications, device indications, and ablation techniques—and the effectiveness of treatment will also be reviewed. Full article

Background: An electrocardiogram (ECG) is an essential and easily available diagnostic test in the management of cardiomyopathies and channelopathies. Different strategies based on ECG have been recommended for general population and athlete screening. Objectives: The purpose of this study was to explore the value of the ECG for the diagnosis of sudden cardiac death (SCD) cases. Methods: ECGs from 50 (aged 37.6 ± 19.9 years, 37 men) resuscitated cardiac arrest (26, 52%) and SCD cases (24, 48%) were analyzed. Relevant medical history and results from clinical tests were reviewed. ECG findings were compared with the final diagnosis. Results: Final ECG classification was as follows: 9 (18%) normal, 15 (30%) unspecific, 14 (28%) suggestive, and 12 (24%) diagnostic. Amongst 13 hypertrophic cardiomyopathy patients, ECGs were diagnostic in 6 (46%) and suggestive in 1 (8%). Arrhythmogenic right ventricular cardiomyopathy was diagnosed in seven patients, two (28%) with suggestive ECG. Dilated cardiomyopathy was diagnosed in four patients, two (50%) with suggestive ECG. Six patients had Brugada syndrome: four (66%) had diagnostic ECGs, and two (33%) had suggestive ECG. Long QT syndrome was diagnosed in four cases; only one (25%) had a diagnostic ECG. Three patients had other cardiomyopathies. After the complete study, 13 (26%) patients remained with a non-conclusive diagnosis; their ECGs were unspecific or normal. Conclusion: ECG can be unspecific or normal in an important percentage of SCD cases (48%). Furthermore, a significant proportion of SCD cases after a comprehensive study remain without a definite diagnosis (26%). These findings should be considered when planning SCD preventive strategies. Full article

Inherited arrhythmia syndromes include several different diseases, as well as Brugada syndrome (BrS), long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and short QT syndrome (SQTS). They represent, together with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), an important cause of sudden cardiac death in the young. Most arrhythmia syndromes are inherited in an autosomal dominant manner, and genetic studies are suggested.: to report the spectrum of genetic variations and clinical phenotype in an Italian cohort with confirmed inherited arrhythmia syndromes and arrhythmogenic cardiomyopathy using whole-exome sequencing (WES). Patients with confirmed inherited arrhythmia syndromes and hereditary cardiomyopathy were recruited at the Cardiology Unit, University Polyclinic Hospital of Foggia, Italy and were included in this study. Genomic DNA samples were extracted from peripheral blood and conducted for WES. The variants were annotated using BaseSpace Variant Interpreter Annotation Engine 3.15.0.0 (Illumina). Reported variants were investigated using ClinVar, VarSome Franklin and a literature review. They were categorised agreeing to the criteria of the American College of Medical Genetics and Genomics. Overall, 62 patients were enrolled. Most of them had a clinical diagnosis of BrS (n 48, 77%). The remaining patients included in the present study had diagnosis of confirmed LQT (n 7, 11%), AR-DCM (n 4, 6.5%), ARVD (n 2, 3%), and SQT (n 1, 1.6%). Using the WES technique, 22 variants in 15 genes associated with Brugada syndrome were identified in 21 patients (34%). Among these, the SCN5A gene had the highest number of variants (6 variants, 27%), followed by KCNJ5 and CASQ2 (2 variants). Only one variant was identified in the remaining genes. In 27 patients with a clinical diagnosis of BrS, no gene variant was detected. In patients with confirmed LQT, SQT, 10 variants in 9 genes were identified. Among patients with ARVD and AR-DCM, 6 variants in 5 genes were found. Variants found in our cohort were classified as pathogenic (6), likely pathogenic (3), of uncertain significance (26), and benign (1). Two additional gene variants were classified as risk factors. In this study, 13 novel genetic variations were recognized to be associated with inherited arrhythmogenic cardiomyopathies. Our understanding of inherited arrhythmia syndromes continues to progress. The era of next-generation sequencing has advanced quickly, given new genetic evidence including pathogenicity, background genetic noise, and increased discovery of variants of uncertain significance. Although NGS study has some limits in finding the full genetic data of probands, large-scale gene sequencing can promptly be applied in real clinical practices, especially in inherited and possibly fatal arrhythmia syndromes. Full article

Background and Objectives: The pathophysiology of arrhythmogenic cardiomyopathy (ACM), previously known as arrhythmogenic right ventricular cardiomyopathy (ARVC), and its specific biological features remain poorly understood. High-throughput plasma proteomic profiling, a powerful tool for gaining insights into disease pathophysiology at the systems biology level, has not been used to study ACM. This study aimed at characterizing plasmatic protein changes in patients with ACM, which were compared with those of healthy controls, and at exploring the potential role of the identified proteins as biomarkers for diagnosis and monitoring. Materials and Methods: Blood samples were collected from six ACM patients, four patients with other cardiomyopathies, and two healthy controls. Plasma was processed to remove high-abundance proteins and analyzed by two-dimensional gel electrophoresis. Differential protein expressions were assessed using PDQuest software, Bio-Rad US version 8.0.1. Results: The analysis revealed several proteins with altered expressions between ACM patients and controls, including plakophilin-2, junctional plakoglobin, desmoplakin, desmin, transmembrane protein 43, and lamin A/C. Conclusions: The plasma proteomic profiling of ACM suggests that ACM is a distinct disease entity characterized by a unique dysregulation of desmosomal proteins. The identification of plasma biomarkers associated with ACM underscores their potential to improve diagnostic accuracy and facilitate early intervention strategies. Further exploration of mutations in desmosomal proteins and their phosphorylation states may provide deeper insights into the pathophysiology of ACM. Full article

Background: Myocardial disease is an important component of the wide field of cardiovascular disease. However, the phenomenon of multiple myocardial diseases in a single patient remains understudied. Aim: To investigate the prevalence and impact of myocarditis in patients with genetic cardiomyopathies and to evaluate the outcomes of myocarditis treatment in the context of cardiomyopathies. Methods: A total of 342 patients with primary cardiomyopathies were enrolled. The study cohort included 125 patients with left ventricular non-compaction (LVNC), 100 with primary myocardial hypertrophy syndrome, 70 with arrhythmogenic right ventricular cardiomyopathy (ARVC), 60 with dilated cardiomyopathy (DCM), and 30 with restrictive cardiomyopathy (RCM). The diagnosis of myocarditis was based on data from myocardial morphological examination or a non-invasive diagnostic algorithm consisting of an analysis of clinical presentation, anti-cardiac antibody (Ab) titres, and cardiac MRI. Results: The prevalence of myocarditis was 74.3% in ARVC, 56.7% in DCM, 54.4% in LVNC, 37.5% in RCM, and 30.9% in HCM. Myocarditis had a primary viral or secondary autoimmune nature and manifested with the onset or worsening of chronic heart failure (CHF) and arrhythmias. Treatment of myocarditis in cardiomyopathies has been shown to stabilise or improve patient condition and reduce the risk of adverse outcomes. Conclusions: In cardiomyopathies, the genetic basis and inflammation are components of a single continuum, which forms a complex phenotype. In genetic cardiomyopathies, myocarditis should be actively diagnosed and treated as it is an important therapeutic target. Full article

Background/Objectives: ¹²³Iodo-metaiodobenzylguanidine single photon emission computed tomography/computed tomography (¹²³I-MIBG SPECT/CT) is used to evaluate the cardiac sympathetic nervous system in cardiac diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and α-synucleinopathies such as Parkinson’s diseases. A common feature of these diseases is denervation. We aimed to compare quantitative and semi-quantitative cardiac sympathetic innervation using ¹²³I-MIBG imaging of ARVC and α-synucleinopathies. Methods: Cardiac innervation was assessed using ¹²³I-MIBG SPECT/CT in 20 patients diagnosed with definite ARVC and 8 patients with clinically diagnosed α-synucleinopathies. Heart-to-mediastinum-ratio (H/M-ratio), as semi-quantitative, was evaluated. Additionally, standardized uptake value (SUV), as quantitative, was measured as SUV_median, SUV_max, and SUV_peak in the left ventricle (LV), the right ventricle (RV), and in the global heart, based on a CT scan following quantitative image reconstruction. Results: The quantification of ¹²³I-MIBG uptake in the LV, the RV, and the global heart was feasible in patients suffering from α-synucleinopathies. SUV_median, and SUV_peak demonstrated a significant difference between ARVC and α-synucleinopathies across all regions, with the α-synucleinopathy group showing a lower uptake. In addition, the H/M ratio showed significantly lower uptake in patients with α-synucleinopathies than in patients with ARVC. Conclusions: Patients with α-synucleinopathies demonstrate significantly lower cardiac innervation in semi-quantitative and quantitative examinations than ARVC patients. The comparison of semi-quantitative and quantitative examinations suggests that quantitative examination offers an advantage. Quantitative analysis can be performed separately for the LV, RV, and global heart. However, analyzing the LV or RV does not provide additional benefit over analyzing the global heart in distinguishing between α-synucleinopathies and ARVC. Considering the different clinical manifestations of these two diseases, the absolute SUV values should not be generalized across different pathologies, and disease-specific ranges should be used instead. Full article

Background: The aim of this study was to evaluate the performance of the diagnostic pathway proposed by the European Society of Cardiology (ESC) guidelines for identifying the underlying aetiology of sudden cardiac death (SCD) through the screening of first-degree family members of patients with SCD who either had a negative autopsy or no autopsy performed. Methods: To be eligible for enrolment, patients had to meet the following inclusion criteria: a family history of SCD in a first-degree relative under the age of 50 years; the SCD decedents must not have undergone an autopsy, or if an autopsy was performed, non-cardiac and structural cardiac causes must have been excluded. Patients underwent a comprehensive assessment, including the evaluation of family and medical history, electrocardiography (ECG) and ECG with high precordial leads, Holter ECG monitoring, echocardiography, cardiac magnetic resonance imaging, and exercise stress testing. A sodium channel blocker test (i.e., flecainide test) was performed when other clinical investigations were negative and the suspicion of Brugada syndrome was high. Results: Forty-one patients from 25 different families fulfilled the inclusion criteria and represented the final study cohort. After the comprehensive diagnostic work-up, a total of seven patients from five different families (5/25, 20%) were diagnosed with an inherited cardiac condition: two families with arrhythmogenic right ventricular cardiomyopathy, one with dilated cardiomyopathy, one with non-dilated left ventricular cardiomyopathy, and one with long QT syndrome. Conclusions: The comprehensive cardiologic work-up of relatives of mainly young SCD victims results in the diagnosis of inherited cardiac conditions in one-fifth of cases. Full article

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic disorder associated with an elevated risk of life-threatening arrhythmias and progressive ventricular impairment. Risk stratification is essential to prevent major adverse cardiac events (MACE). Our study aimed to investigate the incremental value of strain measured by two-dimensional speckle-tracking echocardiography in predicting MACE in ARVC patients compared to conventional echocardiographic parameters. Methods and Results This was a retrospective, single-centre cohort study of 83 patients with ARVC (51% males, median age 37 years (IQR: 23, 53)) under the care of the Inherited Cardiac Conditions clinic at University Hospital Birmingham. MACE was defined as one of the following: sustained ventricular tachycardia (Sus VT), ventricular fibrillation (VF), appropriate implantable cardio-defibrillator (ICD) therapy [shock/anti-tachycardia pacing (ATP)], heart failure (defined as decompensated heart failure, cardiac index by heart catheter, HF medication, and symptoms), cardiac transplantation, or cardiac death. Echocardiography images were analysed by a single observer for right ventricle (RV) and left ventricular (LV) global longitudinal strain (GLS). Multivariable Cox regression was performed in combination with RV fractional area change and tricuspid annular plane systolic excursion. During three years of follow-up, 12% of patients suffered a MACE. ARVC patients with MACE had significantly reduced RV GLS (−13 ± 6% vs. −23 ± 6%, p < 0.001) and RV free wall longitudinal strain (−15 ± 5% vs. −25 ± 7%, p < 0.001) compared to those without MACE. Conclusions Right ventricular free wall longitudinal strain (RVFWLS) may be a more sensitive predictor of MACE than conventional echocardiographic parameters of RV function. Moreover, RV-free wall longitudinal strain may have superior predictive value compared to RV GLS. Full article

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder responsible for nearly a quarter of sports-related sudden cardiac deaths. ACM cases caused by mutations in desmosome proteins lead to right ventricular enlargement, the loss of cardiomyocytes, and fibrofatty tissue replacement, disrupting electrical and mechanical stability. It is currently unknown how paracrine factors secreted by infiltrating fatty tissues affect ACM cardiomyocyte electrophysiology. Methods: A normal and a PKP2 mutant (c.971_972InsT) ACM hiPSC line were cultivated and differentiated into cardiomyocytes (CMs). Adipocytes were differentiated from human adipose stem cells, and adipocyte conditioned medium (AdCM) was collected. Optical mapping and phenotypic analyses were conducted on human iPSC-cardiomyocytes (hiPSC-CMs) cultured in cardiac maintenance medium (CMM) and either with AdCM or specific cytokines. Results: Significant differences were observed in voltage parameters such as the action potential duration (APD₈₀, APD₃₀), conduction velocity (CV), and CV heterogeneity. When cultured in AdCM relative to CMM, the APD₈₀ increased and the CV decreased significantly in both groups; however, the magnitudes of changes often differed significantly between 1 and 7 days of cultivation. Cytokine exposure (IL-6, IL-8, MCP-1, CFD) affected the APD and CV in both the normal and PKP2 mutant hiPSC-CMs, with opposite effects. NF-kB signaling was also found to differ between the normal and PKP2 mutant hiPSC-CMs in response to AdCM and IL-6. Conclusions: Our study shows that hiPSC-CMs from normal and mPKP2 ACM lines exhibit distinct molecular and functional responses to paracrine factors, with differences in RNA expression and electrophysiology. These different responses to paracrine factors may contribute to arrhythmogenic propensity. Full article

Background: Autoantibodies against Desmoglein-2 desmosomal protein (anti-DSG2-ab) were identified in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) by Enzyme-Linked ImmunoSorbent Assay (ELISA); anti-intercalated disk autoantibodies (AIDAs) were identified in myocarditis and (ARVC) by indirect immunofluorescence (IFL). We aim to assess: (1) anti-DSG2-ab specificity in ARVC and myocarditis, (2) accuracy of anti-DSG2-ab detection by ELISA versus AIDA by IFL, and (3) clinical correlates of anti-DSG2-ab in ARVC. Methods: We included 77 patients with ARVC, 91 with myocarditis/dilated cardiomyopathy (DCM), 27 with systemic immune-mediated diseases, and 50 controls. Anti-heart antibodies (AHAs) and AIDAs were assessed by IFL, and anti-DSG2-ab by ELISA (assessed both by optical density, OD, and U/L). Receiving operator curve (ROC) analysis was used to assess ELISA diagnostic accuracy. Results: A relevant proportion (56%) of ARVC patients was anti-DSG2-ab-positive, with higher anti-DSG2-ab levels than controls. Anti-DSG2-ab titer was not different between ARVC and myocarditis/DCM patients (48% anti-DSG-ab positive). Frequency of anti-DSG2 positivity by ELISA was higher in AIDA-positive cases by IFL than AIDA-negative cases (p = 0.039 for OD, p = 0.023 for U/L). In ARVC, AIDA-positive patients were more likely to be AHA-positive (p < 0.001), had pre-syncope (p = 0.025), and abnormalities in cardiac rhythm (p = 0.03) than ARVC AIDA-negative patients, while anti-DSG2-ab positivity did not have clinical correlates. Conclusions: Anti-DG2-ab detection in ARVC and myocarditis/DCM reflects immune-mediated pathogenesis to desmosomal proteins. Higher frequency of anti-DSG2-ab positivity by ELISA by U/L was higher in AIDA-positive cases by IFL than AIDA-negative cases, in keeping with the hypothesis that DSG2 is one of AIDA autoantigens. In ARVC, AIDA status but not anti-DSG2-ab showed distinct clinical correlates, possibly reflecting a wider AIDA autoantigenic spectrum. Full article

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterised by progressive fibrosis predominantly of the right ventricular (RV) myocardium, resulting in life-threatening arrhythmias and heart failure. The diagnosis is challenging due to a wide spectrum of clinical symptoms. The important role of ECG was covered in the current diagnostic criteria. The role of the epsilon wave (EW) is still under discussion. Aim: The aim of the study was to examine a potential association between the EW and late ventricular potentials (LPs) in ARVC patients (pts). The correlation between RV dilatation or dysfunction and LPs/EW was also analysed. Methods: The ARVC group consisted of 81 pts (53 men, aged 20–78 years) fulfilling 2010 International Task Force Criteria. 12-lead ECG, LPs, Holter, and ECHO were performed in all pts. The presence of EW was analysed in ECG by 3 investigators. LPs were detected by signal-averaged ECG (SAECG). SAECG was considered positive for LPs when at least two of the three following criteria were met: (1) the filtered QRS duration (fQRS) ≥ 114 msec; (2) the duration of the final QRS fragment in which low-amplitude signals lower than 40 μV are recorded (LAS-40 > 38 msec); and (3) the root mean square amplitude of the last 40 milliseconds of the fQRS complex (RMS-40 < 20 μV). The results were compared with a reference group consisting of 53 patients with RV damage in the course of atrial septum defect (ASD) or Ebstein’s Anomaly (EA). Results: In the ARVC group, a significant relationship was observed between the occurrence of EW and the presence of LPs. EW was more common in the LP+ than in the LP- patients (48.1% vs. 6.9%, p < 0001; OR 12.5; 95% CI [2.691–58.063]). In ARVC pts, RVOT > 36 mm, RVIT > 41 mm, and RV S’ < 9 cm/s were observed significantly more often in the LPs+ than in the LPs− group (OR [95% CI]: 8.3 [2.9–1.5], 6.4 [2.2–19.0] and 3.6 [1.1–12.2], respectively). In the ARVC group, any of fQRS > 114 ms, LAS > 38 ms, and RMS < 20 μV were significantly more frequent in EW+ pts. In multivariate analysis, the independent factors of the EW were LAS-40 and RV S’. In the LPs− subgroup, RVOT > 36 mm was more frequent in ASD/EA than in ARVC (70.4% vs. 25%, p = 0.002). Similarly, in the LPs− subgroup, RVIT > 41 mm was encountered more frequently in ASD/EA than in ARVC (85.2% vs. 48.3%, p = 0.004). Conclusions: In ARVC, there is an association between EW and LPs, with both probably resulting from the same process of fibrofatty substitution of the RV myocardium. Although RV dilatation is common in ASD and EA, it does not correlate with LPs. Full article