Diagnosis Of Arrhythmogenic Right Ventricular Cardiomyopathy Research Articles

Arrhythmogenic right ventricular cardiomyopathy: the importance of biventricular strain in risk-stratification

Abstract Background Despite Arrhythmogenic right ventricular cardiomyopathy (ARVC) being a predominant right ventricle (RV) disease, concomitant left ventricle (LV) involvement has been recognized. ARVC diagnosis is made through the RV-centric 2010 Task Force Criteria (TFC), but previous studies already suggested the use of echocardiographic strain measures to better depict RV and LV dysfunction in these patients. No data however is available on the additional value of combining biventricular strain in ARVC for risk stratification. Purpose To assess the prognostic value of measuring both LV global longitudinal strain (GLS) and RV free wall strain (FWLS) analysis in patients with ARVC. Methods A total of 204 patients who met the TFC for the ARVC spectrum were included. Patients were categorized based on a cut-off of -18% for strain impairment in both ventricles. The end-point was a composite of all-cause mortality, arrhythmic events, ICD therapy and heart failure events. Results Patients (age 41 ± 17 years, 55% males) were divided into impaired (n=33), discordant (either RV or LV impaired, n=70), and normal (n=101) strain groups (Fig. 1A). Definite and borderline ARVC were diagnosed in 78% and 39%, respectively, at the time of first available echocardiography. During a follow-up of 87 [24-136] months, 60 (29%) experienced the combined outcome, and a significant difference in event-free survival was observed (p<0.001) between the 3 groups (Fig. 1B). In the multivariate analysis (Fig. 2), the strain grouping remained associated with outcome (p=0.040) after adjusting for age, gender, history of syncope and definite ARVC diagnosis, which were also significantly associated with the endpoint at the univariate analysis. A sub-analysis including only definite and borderline ARVC patients confirmed that the strain grouping was an independent predictor of the composite endpoint (p=0.027). Conclusion Biventricular involvement by strain analysis has additional prognostic value in ARVC patients and outcome is worse for those with both RV and LV involvement.Strain groups and Kaplan Meier curvesMultivariate analysis

Clinical value of anti-DSG2 antibodies in arrhythmogenic right ventricular cardiomyopathy: a real-life experience

Abstract Background/Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease leading to ventricular arrhythmias and heart failure. The diagnosis is challenging and currently based on a set of clinical criteria with limited sensitivity and specificity. Anti-desmoglein-2 (DSG2) antibodies were previously found in patients diagnosed with ARVC, while they were absent in both healthy controls and athletes. Purpose The study aimed to evaluate the diagnostic value of anti-DSG2 antibodies by comparing their concentration in patients with ARVC and other right ventricular diseases. Additionally, the prognostic value of the biomarker was assessed. Methods A cohort of 101 patients with a definite diagnosis of ARVC according to the 2010 Task Force criteria was enrolled (64 males, mean age 47 ± 16 years). The control group included patients with Ebstein anomaly and Eisenmenger syndrome (16 and 21 subjects, respectively). Anti-DSG2 antibody concentration was assessed using enzyme-linked immunosorbent assay (ELISA). After that, an ARVC cohort was followed for 3.9 ± 1.6 years for the occurrence of the primary endpoint of cardiac death or heart transplantation (HTx) and major arrhythmic events (MAEs) defined as ventricular fibrillation, sustained ventricular tachycardia (sVT) or appropriate implantable cardioverter-defibrillator intervention. Results The median anti-DSG2 antibody concentration presented as ELISA optical density (OD) reached 1.36 [0.54-2.15] in the ARVC cohort, while it was 0.4 [0.34-0.54] in Ebstein anomaly group and 0.36 [0.28-0.58] in the Eisenmenger syndrome group. There was a significant difference in antibody levels between ARVC and both control groups (p < 0.001, Figure 1). The cutoff value for the diagnosis of ARVC was 0.774, with 72.3% sensitivity and 100% specificity (AUC = 0.823). After dividing the ARVC cohort according to the designated cutoff point, the anti-DSG2-positive subgroup was significantly younger (44.5 ± 15.4 vs. 52.8 ± 15.5 years, p = 0.017) and more likely to have a history of sVT (68.5% vs. 46.4%, p = 0.041). There was no difference regarding sex, presence of PKP2 or DSG2 mutations, previous sports activities, history of sudden cardiac arrest or syncope, right ventricular dimensions and systolic function, left ventricular ejection fraction and heart failure symptoms. This threshold was not predictive for the primary endpoint and MAEs. However, a more stringent cutoff value for anti-DSG2 level (1.021) was found to predict death or HTx (HR [95% CI] 4.56 [1.05-19.76], p = 0.026, Figure 2). Conclusions The concentration of anti-DSG2 antibodies is significantly higher in ARVC compared to other right ventricular diseases. A high antibody level is prognostic for death or HTx in ARVC.Figure 1Figure 2

Navigating the Uncommon: Case Report of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Successfully Managed with Implantable Cardioverter Defibrillator (ICD)

With a high risk of sudden cardiac mortality, arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited cardiomyopathy characterized by right ventricular dysfunction and ventricular arrhythmias (VA). In this case study, a 35-year-old presented with palpitations and revealed epsilon waves on the right precordial electrocardiogram (ECG) leads which led to the suspicion of ARVC. A 24-hour Holter monitoring revealed frequent ventricular extrasystoles (>500 per 24 hours), a CMRI revealed RV dyskinesia and transmural LGE in the apical RV, and an electrophysiologic study detected spontaneous polymorphic ventricular tachycardia (VT) despite the presence of induction ventricle fibrillation (VF). These results validated the diagnosis of ARVC and indicated that an implantable cardioverter defibrillator was necessary treatment. The ability to identify potential ARVC’s ECG abnormalities, the timing to pursue further studies, and determining necessary treatment execution are critical. The evaluation of cardiac, electrophysiological, and clinical imaging parameters is essential for the risk stratification, diagnosis, and management of patients with ARVC.

Ventricular Angiography: A Forgotten Diagnostic Tool?

A 76-year-old male patient presented to the emergency room with acute decompensated right heart failure and presyncope episodes. Upon admission, his electrocardiogram (ECG) showed sustained monomorphic ventricular tachycardia at 180 bpm, which was electrically cardioverted, and the patient was subsequently admitted to the intensive care unit. The echocardiography showed a very dilated right ventricle (RV) with global systolic dysfunction and akinetic anterior and lateral walls. The coronary angiography was normal. The cardiac magnetic resonance showed signs of fibro-fatty replacement of the RV myocardium. Furthermore, the ECG after cardioversion showed inverted T waves and an epsilon wave in V1-V3 leads and late potentials by signal-averaged ECG. As such, a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) was suspected. However, he presented no familial history of ARVC, was 76 years of age at the time of diagnosis and was asymptomatic until now. Given these considerations, we performed a right ventricular angiography which showed dilatation of the RV with akinetic/dyskinetic bulging, creating the "pile d'assiettes" image suggestive of ARVC. In the case of this patient, the RV angiography contributed to establish a diagnosis of ARVC with a very late presentation, to our knowledge the latest presentation in terms of age described in the literature.

Diagnostic and Prognostic Value of Right Ventricular Fat Quantification from Computed Tomography in Arrhythmogenic Right Ventricular Cardiomyopathy.

Background: In arrhythmogenic right ventricular cardiomyopathy (ARVC) non-invasive scar evaluation is not included among the diagnostic criteria or the predictors of ventricular arrhythmias (VA) and sudden death (SD). Computed tomography (CT) has excellent spatial resolution and allows a clear distinction between myocardium and fat; thus, it has great potential for the evaluation of myocardial scar in ARVC. Objective: The objective of this study is to evaluate the feasibility, and the diagnostic and prognostic value of semi-automated quantification of right ventricular (RV) fat replacement from CT images. Methods: An observational case-control study was carried out including 23 patients with a definite (19) or borderline (4) ARVC diagnosis and 23 age- and sex-matched controls without structural heart disease. All patients underwent contrast-enhanced cardiac CT. RV images were semi-automatically reconstructed with the ADAS-3D software (ADAS3D Medical, Barcelona, Spain). A fibrofatty scar was defined as values of Hounsfield Units (HU) <-10. Within the scar, a border zone (between -10 HU and -50 HU) and dense scar (<-50 HU) were distinguished. Results: All ARVC patients had an RV scar and all scar-related measurements were significantly higher in ARVC cases than in controls (p < 0.001). The total scar area and dense scar area showed no overlapping values between cases and controls, achieving perfect diagnostic performance (sensitivity and specificity of 100%). Among ARVC patients, 16 (70%) had experienced sustained VA or aborted SD. Among all clinical, ECG and imaging parameters, the dense scar area was the only one with a statistically significant association with VA and SD (p = 0.003). Conclusions: In ARVC, RV myocardial fat quantification from CT is feasible and may have considerable diagnostic and prognostic value.

CHARACTERISATION OF THE 12–LEAD ECG IN PAEDIATRIC CARRIERS OF PLAKOPHILLIN–2 GENE VARIANTS

Abstract Background and Aim The PKP2 gene encodes the desmosomal protein Plakophilin–2, vital for cellular adhesion between cardiomyocytes. It is associated with classical Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a cardiac disorder that can cause malignant ventricular arrhythmias and sudden cardiac death in the young. The 12–lead electrocardiogram (ECG) is an important tool for diagnosis of ARVC but ECG patterns in paediatric carriers of PKP2 variants have not been previously systematically assessed. Methods The retrospective study enrolled paediatric (&amp;lt;18 years) PKP2 gene carriers referred to Great Ormond Street Hospital between 2005 and 2023. Their ECGs were analysed and compared with an age and gender–matched healthy population using paired two–tailed χ2–test. Results 28 PKP2 variant carriers (54% females) were identified, of which 2 (7%) were diagnosed with ARVC at the time of the ECG, with a mean age of 13.6 +∕– 4.8 years. These were compared to 28 healthy controls (mean age of 12.7 +/– 4.4 years). 17 carriers (60%) had low QRS voltages in the lateral leads, compared to 4 controls (16%). Fractioned QRS complexes were seen in the lateral leads in 19 (67%) and in the septal leads in 20 (71%), compared to 1 and 2 controls (3.5% and 7%, respectively). Abnormal T wave inversion (TWI) for age was found in 54% of the patients (29% in lateral leads) and flat T waves in 22 patients (78%); but these were not statistically–significantly different to controls. Conclusions Paediatric carriers of PKP2 gene variants are more likely to have low QRS voltages and QRS fractionation in the lateral and anterior leads than normal controls, but the presence of abnormally inverted or flat T waves did not discriminate between gene carriers and controls. Our findings suggest that paediatric–specific ECG features may represent early phenotypic expression of PKP2 gene variants.

Long-Term Freedom From Ventricular Arrhythmias in ARVC With Endocardial Only Ablation: Predictors of Success

BackgroundAlthough the epicardial predominance of substrate abnormalities has been well demonstrated in early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC), endocardial (ENDO) ablation may suffice to eliminate ventricular tachycardia (VT) in some patients. ObjectivesThis study aimed to report the long-term outcomes of ENDO-only ablation in ARVC patients and factors that predict VT-free survival. MethodsWe included consecutive patients with Task Force Criteria diagnosis of ARVC undergoing a first ENDO-only VT ablation between 1998 and 2020. Ablation was predominantly guided by activation/entrainment mapping for mappable VTs and pace mapping/targeting abnormal electrograms for unmappable VTs. The primary endpoint was freedom from any recurrent sustained VT after the last ENDO-only ablation. ResultsSeventy-four ARVC patients underwent ENDO-only VT ablation. VT noninducibility was achieved in 49 (66%) patients. During median follow-up of 6.6 years (Q1-Q3: 3.4-11.2 years), 40 (54.1%) patients remained free from any VT recurrence with rare VT ≤2 episodes in additional 12.2%. Among patients with noninducibility, VT-free survival was 75.5% during long-term follow-up. In multivariable analysis, >45 y of age at diagnosis (HR: 0.41; 95% CI: 0.17-0.98) and VT noninducibility (HR: 0.36; 95% CI: 0.16-0.80) were predictors of VT-free survival. ConclusionsLong-term VT-free survival can be achieved in over half of ARVC patients following ENDO-only VT ablation, increasing to over 75% if VT noninducibility is achieved. Our results support consideration of a stepwise ENDO-only approach before proceeding to epicardial ablation if VT noninducibility can be achieved particularly in older patients.

Arrhythmogenic right ventricular cardiomyopathy: Unveiling clinical presentations, CMR insights and prognosis in a single-center retrospective study

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a hereditary condition with a prevalence ranging from 1 in 2000 to 1 in 5000 individuals. ARVC is a significant contributor to sudden cardiac death, particularly in young individuals and athletes, and remains challenging to diagnose definitively. We conducted a single-center retrospective study to evaluate the presentations, electrocardiogram findings, and imaging characteristics of ARVC patients evaluated at our center between 2021 and 2023. Notably, our study is the second investigation of ARVC conducted in Pakistan. We report divergent symptom prevalence as compared to the current literature and have incorporated the Task Force Criteria. Despite limited access to cardiac magnetic resonance (CMR) facilities worldwide, our findings underscore the critical role ofCMR in ARVC diagnosis. Our cohort had a mortality rate of 17 % highlighting the importance of early detection and the need for improved diagnostic facilities for ARVC in the region.

Right ventricular scalloping index as cardiac magnetic resonance-derived marker for diagnosis of arrhythmogenic right ventricular cardiomyopathy.

The cardiac magnetic resonance (CMR) evaluation of right ventricular (RV) morphologic abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is subjective. Here, we aimed to use a quantitative index, the right ventricular scalloping index (RVSI), to standardize the measurement of RV free wall scalloping and aid in the imaging diagnosis. We retrospectively included 15 patients with definite ARVC and 45 age- and sex-matched patients with idiopathic right ventricular outflow tract ventricular arrhythmia (RVOT-VA) as controls. The RVSI was measured from cine images on four-chamber view to evaluate its ability to distinguish between ARVC and RVOT-VA patients. Other cardiac functional parameters including strain analysis were also performed. The RVSI was significantly higher in the ARVC than RVOT-VA group (1.56 ± 0.23 vs 1.30 ± 0.08, p < 0.001). The diagnostic performance of the RVSI was superior to the RV global longitudinal, circumferential, and radial strains, RV ejection fraction, and RV end-diastolic volume index. The RVSI demonstrated high intraobserver and interobserver reliability (intraclass correlation coefficient, 0.94 and 0.96, respectively). RVSI was a strong discriminator between ARVC and RVOT-VA patients (area under curve [AUC], 0.91; 95% CI, 0.82-0.99). A cutoff value of RVSI ≥1.49 provided an accuracy of 90.0%, specificity of 97.8%, sensitivity of 66.7%, positive predictive value (PPV) of 90.9%, and a negative predictive value (NPV) of 89.8%. In a multivariable analysis, a family history of ARVC or sudden cardiac death (odds ratio, 38.71; 95% CI, 1.48-1011.05; p = 0.028) and an RVSI ≥1.49 (odds ratio, 64.72; 95% CI, 4.58-914.63; p = 0.002) remained predictive of definite ARVC. RVSI is a quantitative method with good performance for the diagnosis of definite ARVC.

Enhancing Arrhythmogenic Right Ventricular Cardiomyopathy Detection and Risk Stratification: Insights from Advanced Echocardiographic Techniques.

The echocardiographic diagnosis criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are highly specific but sensitivity is low, especially in the early stages of the disease. The role of echocardiographic strain in ARVC has not been fully elucidated, although prior studies suggest that it can improve the detection of subtle functional abnormalities. The purposes of the study were to determine whether these advanced measures of right ventricular (RV) dysfunction on echocardiogram, including RV strain, increase diagnostic value for ARVC disease detection and to evaluate the association of echocardiographic parameters with arrhythmic outcomes. The study included 28 patients from the Heart Institute of São Paulo ARVC cohort with a definite diagnosis of ARVC established according to the 2010 Task Force Criteria. All patients were submitted to ECHO's advanced techniques including RV strain, and the parameters were compared to prior conventional visual ECHO and CMR. In total, 28 patients were enrolled in order to perform ECHO's advanced techniques. A total of 2/28 (7%) patients died due to a cardiovascular cause, 2/28 (7%) underwent heart transplantation, and 14/28 (50%) patients developed sustained ventricular arrhythmic events. Among ECHO's parameters, RV dilatation, measured by RVDd (p = 0.018) and RVOT PSAX (p = 0.044), was significantly associated with arrhythmic outcomes. RV free wall longitudinal strain < 14.35% in absolute value was associated with arrhythmic outcomes (p = 0.033). Our data suggest that ECHO's advanced techniques improve ARVC detection and that abnormal RV strain can be associated with arrhythmic risk stratification. Further studies are necessary to better demonstrate these findings and contribute to risk stratification in ARVC, in addition to other well-known risk markers.

Diagnostic value of late gadolinium enhancement at cardiovascular magnetic resonance to distinguish arrhythmogenic right ventricular cardiomyopathy from differentials

BackgroundWhile late gadolinium enhancement (LGE) is proposed as a diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC), the potential of LGE to distinguish ARVC from differentials remains unknown. We aimed to assess the diagnostic value of LGE for ARVC diagnosis. MethodsWe included 132 subjects (60% male, 47±11 years) who had undergone cardiac magnetic resonance imaging with LGE assessment present for ARVC or ARVC-differentials. ARVC was diagnosed as per 2010 Task Force Criteria (n=55). ARVC-differentials consisted of familial/genetic dilated cardiomyopathy (n=25), myocarditis (n=13), sarcoidosis (n=20), and amyloidosis (n=19). The diagnosis of all differentials was based upon the most current golden standard. Presence of LGE was evaluated using a 7-segment RV and 17-segment LV model. Subsequently, we assessed LGE patterns for every patient individually for fulfilling LV- and/or RV-LGE per Padua criteria, independent of their clinical diagnosis (i.e. phenotype). Diagnostic values were analysed using sensitivity and specificity for any RV-LGE, any LV-LGE, RV-LGE per Padua criteria, and prevalence graphs for LV-LGE per Padua criteria. Optimal integration of LGE for ARVC diagnosis was determined using classification-and-regression-tree analysis. Resultsone-third (38%) of ARVC patients had RV-LGE, while half (51%) had LV-LGE. RV-LGE was less frequently observed in ARVC vs. non-ARVC patients (38% vs. 58%, p=0.034) leading to a poor discriminatory potential (any RV-LGE: sensitivity 38%, specificity 42%; RV-LGE per Padua criteria: sensitivity 36%, specificity 44%). Compared to ARVC patients, non-ARVC patients more often had LV-LGE (91% vs. 51%, p<0.001) which was also more globally distributed (median 9 [IQR: 3-13] vs. 0 [IQR: 0-3] segments, p<0.001). Absence of anteroseptal and absence of extensive (≥5 segments) mid- mid-myocardial LV-LGE, and absence of moderate (≥2 segments) mid-myocardial LV-LGE predicted ARVC with good diagnostic performance (sensitivity 93%, specificity 78%). ConclusionsLGE is often present in ARVC differentials and may lead to false positive diagnoses when used without knowledge of LGE patterns. Moderate RV-LGE without anteroseptal and mid-myocardial LV-LGE is typically observed in ARVC.

Progression of definite and non-definite Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and risk of major adverse cardiac events

Abstract Background In patients with Arrhythmogenic right ventricular cardiomyopathy (ARVC, also called"Arrhythmogenic Cardiomyopathy"), it is a challenge to predict those at greatest risk of major adverse cardiac events (MACE). Our hypothesis is that risk of arrhythmia may be preceded by change in ventricular structure and function. Purpose To assess the association between change in ventricular structure and function over time and risk of (MACE) in ARVC. Methods 101 definite and non-definite ARVC patients (defined as per Revised Task Force criteria (TFC)) were included with at least two sequential echocardiography and ECGs between 2010 and 2022. Structural progression was defined as development of new 2010 TFC on echocardiography during follow-up. MACE were defined as ventricular fibrillation (VF), sustained ventricular tachycardia (Sus VT), appropriate implantable cardio-defibrillator (ICD) therapy (shock/anti-tachycardia pacing (ATP)), heart failure, cardiac transplantation and death. Results Of the 101 patients, 51 had a definite diagnosis of ARVC, and 50 had a non-definite ‘early’ diagnosis, of whom a total of 66 (68%) carried a pathogenic variant associated with ARVC. Most were male 58 (57%), and the median age at presentation was 39 years (IQR: 27 - 53). Palpitations 41 (41%) and syncope 25 (25%) were the most common symptoms at baseline. 21 (23%) of the entire population were engaged in competitive exercise. At baseline, 22/101 (22%) patients presented with MACE, in which 20 (91%) definite patients met either minor or major imaging criteria at inclusion. During 4 years follow up (IQR: 2 – 6), 22 patients experienced MACE, in which 11 with history of MACE and 11 without, of those (15 (68%)) had structural progression. Additionally, 9 patients had structural progression of which 5 patients had history of MACE and no second event during follow up and 4 patients had no MACE at baseline or during follow up. Results showed that the odds of structural progression were significantly higher in patients with MACE than without (Table 1). Conclusion Structural progression was strongly associated with MACE events. This finding raises the possibility that tracking change over time identifies those patients at greatest risk of arrhythmia, with significant changes in right ventricular measurements.

Echocardiographic deformation imaging as a substitute for cardiac magnetic resonance imaging in arrhythmogenic right ventricular cardiomyopathy risk prediction

Abstract Background &amp; aims Echocardiography has a central role in diagnosis and follow-up of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). It is however not included in the risk calculator for ventricular arrhythmia (VA) which was recently developed and validate, since traditional echo parameters were outperformed by RV ejection fraction (RVEF) measured by CMR. CMR is however not as widely available as echocardiography. We aimed to investigate whether echocardiographic RV deformation imaging could be used as a substitute for RVEF by CMR in arrhythmic risk prediction in ARVC. Methods &amp; results From two referral centres, 150 consecutive patients with a definite ARVC diagnosis, no prior sustained VA and an echocardiogram suitable for deformation analysis were included (aged 41 ± 17 years, 50% female). During a median follow-up of 6.3 (IQR 3.1-9.8) years, 37 (25%) experienced a first-time sustained VA. The current ARVC risk calculator, including RVEF by CMR performed well in this cohort, with an optimism corrected C-statistic of 0.77 (95% CI 0.71 – 0.84). When RVEF was replaced by RV free wall longitudinal strain, the latter was an independent predictor (p = 0.005) and C-statistic changed to 0.80 (95% CI 0.74 – 0.86). The model including RV deformation imaging reduced the Akaike information criterion by &amp;gt;2. Conclusions This study showed that echocardiographic RV deformation imaging is able to replace RVEF by CMR in ARVC risk prediction without losing discriminative power. In clinical use, repeated yearly risk assessment using echocardiography could be alternated with a CMR every few years.

The added value of abnormal regional myocardial function for risk prediction in arrhythmogenic right ventricular cardiomyopathy

Abstract Background &amp; aims A risk calculator for individualized prediction of first-time sustained ventricular arrhythmia (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients has recently been developed and validated. This study aimed to investigate whether regional functional abnormalities, measured by echocardiographic deformation imaging, can provide additional prognostic value. Methods &amp; results From two referral centres, 150 consecutive patients with a definite ARVC diagnosis, no prior sustained VA and an echocardiogram suitable for deformation analysis were included (aged 41 ± 17 years, 50% female). During a median follow-up of 6.3 (IQR 3.1-9.8) years, 37 (25%) experienced a first-time sustained VA. All tested left and right ventricular (LV, RV) deformation parameters were univariate predictors for first-time VA. While LV function did not add predictive value in multivariate analysis, two RV deformation parameters did; RV free wall longitudinal strain and regional RV deformation patterns remained independent predictors after adjusting for the calculator-predicted risk (HR 1.07 [1.02-1.11]; p = 0.004 and 4.45 [1.07-18.57]; p = 0.040, respectively) and improved its discriminative value (from C-statistic 0.78 to 0.82 in both. Akaike information criterion change &amp;gt;2). Importantly, all patients who experienced VA within 5 years from the echocardiographic assessment had abnormal regional RV deformation patterns at baseline. Conclusions This study showed that regional functional abnormalities measured by echocardiographic deformation imaging can further refine personalized arrhythmic risk prediction when added to the ARVC risk calculator. The excellent negative predictive value of normal RV deformation could support a watchful waiting strategy regarding ICD implantation in intermediate risk patients.Added value of functional abnormalities

Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent “non-ischemic” myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the “Padua criteria” were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late‑gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other “non-scarring” myocardial disease. The “ring-like’ pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.

Electroanatomical voltage mapping with contact force sensing for diagnosis of arrhythmogenic right ventricular cardiomyopathy

BackgroundThree-dimensional electroanatomical mapping (EAM) can be helpful to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC). Yet, previous studies utilizing EAM have not systematically used contact-force sensing catheters (CFSC) to characterize the substrate in ARVC, which is the current gold standard to assure adequate tissue contact. ObjectiveTo investigate reference values for endocardial right ventricular (RV) EAM as well as substrate characterization in patients with ARVC by using CFSC. MethodsEndocardial RV EAM during sinus rhythm was performed with CFSC in 12 patients with definite ARVC and 5 matched controls without structural heart disease. A subanalysis for the RV outflow tract (RVOT), septum, free-wall, subtricuspid region, and apex was performed. Endocardial bipolar and unipolar voltage amplitudes (BVA, UVA), signal characteristics and duration as well as the impact of catheter orientation on endocardial signals were also investigated. ResultsARVC patients showed lower BVA vs. controls (p = 0.018), particularly in the subtricuspid region (1.4, IQR:0.5–3.1 vs. 3.8, IQR:2.5-5 mV, p = 0.037) and RV apex (2.5, IQR:1.5–4 vs. 4.3,IQR:2.9–6.1 mV, p = 0.019). BVA in all RV regions yielded a high sensitivity and specificity for ARVC diagnosis (AUC 59–78%, p < 0.05 for all), with the highest performance for the subtricuspid region (AUC 78%, 95% CI:0.75–0.81, p < 0.001, negative predictive value 100%). A positive correlation between BVA and an orthogonal catheter orientation (46°-90°:r = 0.106, p < 0.001), and a negative correlation between BVA and EGM duration (r = −0.370, p < 0.001) was found. ConclusionsEAM using CFSC validates previous bipolar cut-off values for normal endocardial RV voltage amplitudes. RV voltages are generally lower in ARVC as compared to controls, with the subtricuspid area being commonly affected and having the highest discriminatory power to differentiate between ARVC and healthy controls. Therefore, EAM using CFSC constitutes a promising tool for diagnosis of ARVC.

Nomogram for predicting cardiac death and heart transplantation in arrhythmogenic right ventricular cardiomyopathy.

In this study, we aimed to develop and validate a competing risk nomogram for predicting cardiac death and heart transplantation (HT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We retrospectively enrolled 149 consecutive patients with ARVC diagnosed at our institution between 2008 and 2022. Cox proportional hazards model was primarily used to identify variables associated with cardiac death and HT. On the basis of these indicators, a competing risk nomogram was developed to predict the 1, 3, and 5 year probabilities of cardiac death and HT. The area under the receiver operating characteristic curve (AUC), Harrell's C-index, and calibration curves were used to evaluate and internally validate the performance of the model. Decision curve analysis was performed to assess the clinical utility of the nomogram. Of the 149 patients with ARVC, the mean age was 38.77 ± 15.94 years, and most of the patients were men (67.11%, 100/149). Fourteen patients experienced cardiac death and nine underwent HT, during a median follow-up period of 5.8 years (interquartile range, 0.62-5.56 years). Multivariable COX analysis revealed that extent of TWI in the anterior and inferior leads (P = 0.0057), right atrial diameter on transthoracic echocardiography (P = 0.0498), RVEF (P = 0.1036), and LVEF (P < 0.001) all showed statistical significance. The 1-, 3-, and 5-year cumulative incidence of cardiac death and HT were 3.35%, 8.05%, and 11.4%, respectively. The area under the receiver operating characteristic curve of the nomogram for predicting cardiac death and HT at 1, 3, and 5years after diagnosis of ARVC were 0.860, 0.935, and 0.956. The value of Harrell's C-index is 0.9273 (95% confidence interval 0.8954-0.9590; P<0.001), indicating that the model had good discriminative ability in internal validation. Decision curve analysis revealed that our model was clinically useful within the entire range of potential treatment thresholds in most cases. The cumulative incidence of the primary outcomes was significantly different between the three risk groups according to nomogram-derived scores (P<0.001). On the basis of a retrospective review of patients with ARVC at a single centre, we developed a novel nomogram for predicting the risk of cardiac death and HT after ARVC diagnosis. This competing risk nomogram based on four readily available clinical parameters (right atrial diameter, right and left ventricular ejection fraction, and T-wave inversion) is a potentially useful tool for individualized prognostic assessment in patients with ARVC.

The Value of Strain Echocardiography in Predicting Electrical Progression in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular (RV) cardiomyopathy is a progressive disease characterized by the replacement of the normal myocardium with fibrofatty tissue. This study aimed to determine the value of echocardiographic RV deformation parameters in predicting electrical progression as assessed by serial changes in RV lead sensing and threshold in patients with arrhythmogenic RV cardiomyopathy. The present study recruited 40 patients with a definitive diagnosis of arrhythmogenic RV cardiomyopathy at a mean (SD) age of 38.6 (14.2) years between 2018 and 2020. All patients had received an implantable cardioverter-defibrillator for the primary or secondary prevention of sudden cardiac death. The patients underwent 2-dimensional (2D) and 3-dimensional (3D) transthoracic echocardiographic examinations and RV 2D and 3D strain analyses, comprising free-wall longitudinal strain, global longitudinal strain, and strain rate. They were then followed up for electrical progression. During a mean (SD) follow-up period of 20 (6) months, the RV lead amplitude decreased from 7.95 (IQR, 4.53-10.25) mV to 5.25 (IQR, 2.88-8.55) mV (P < .001), and the lead threshold increased from 0.75 (IQR, 0.50-0.79) V to 0.75 (IQR, 0.75-1.00) V (P < .001). Right ventricular 2D free-wall (ρ = 0.56, P = .01), RV 2D global (ρ = 0.58, P = .007), and RV 3D free-wall (ρ = 0.65; P = .003) longitudinal strain correlated with electrical progression. Right ventricular 2D and 3D deformation parameters were found to be significant predictors of electrical progression during follow-up of patients with arrhythmogenic RV cardiomyopathy. These findings suggest that echocardiography has a pivotal role in predicting patients at high risk for electrical progression.

Exercise does not influence development of phenotype in PLN p.(Arg14del) cardiomyopathy.

Endurance and frequent exercise are associated with earlier onset of arrhythmogenic right ventricular cardiomyopathy (ARVC) and ventricular arrhythmias (VA) in desmosomal gene variant carriers. Individuals with the pathogenic c.40_42del; p.(Arg14del) variant in the PLN gene are frequently diagnosed with ARVC or dilated cardiomyopathy (DCM). The aim of this study was to evaluate the effect of exercise in PLN p.(Arg14del) carriers. In total, 207 adult PLN p.(Arg14del) carriers (39.1% male; mean age 53 ± 15years) were interviewed on their regular physical activity since the age of 10years. The association of exercise with diagnosis of ARVC, DCM, sustained VA and hospitalisation for heart failure (HF) was studied. Individuals participated in regular physical activities with amedian of 1661 metabolic equivalent of task (MET) hours per year (31.9MET-hours per week) until clinical presentation. The 50% most and least active individuals had asimilar frequency of sustained VA (18.3% vs 18.4%; p = 0.974) and hospitalisation for HF (9.6% vs 8.7%; p = 0.827). There was no relationship between exercise and survival free from (incident) sustained VA (p = 0.65), hospitalisation for HF (p = 0.81), diagnosis of ARVC (p = 0.67) or DCM (p = 0.39) during follow-up. In multivariate analyses, exercise was not associated with sustained VA or HF hospitalisation during follow-up in this relatively not-active cohort. There was no association between the amount of exercise and the susceptibility to develop ARVC, DCM, VA or HF in PLN p.(Arg14del) carriers. This suggested unaffected PLN p.(Arg14del) carriers can safely perform mild-moderate exercise, in contrast to desmosomal variant carriers and ARVC patients.

The added value of abnormal regional myocardial function for risk prediction in arrhythmogenic right ventricular cardiomyopathy.

A risk calculator for individualized prediction of first-time sustained ventricular arrhythmia (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients has recently been developed and validated (www.ARVCrisk.com). This study aimed to investigate whether regional functional abnormalities, measured by echocardiographic deformation imaging, can provide additional prognostic value. From two referral centres, 150 consecutive patients with a definite ARVC diagnosis, no prior sustained VA, and an echocardiogram suitable for deformation analysis were included (aged 41 ± 17 years, 50% female). During a median follow-up of 6.3 (interquartile range 3.1-9.8) years, 37 (25%) experienced a first-time sustained VA. All tested left and right ventricular (LV and RV) deformation parameters were univariate predictors for first-time VA. While LV function did not add predictive value in multivariate analysis, two RV deformation parameters did; RV free wall longitudinal strain and regional RV deformation patterns remained independent predictors after adjusting for the calculator-predicted risk [hazard ratio 1.07 (95% CI 1.02-1.11); P = 0.004 and 4.45 (95% CI 1.07-18.57); P = 0.040, respectively] and improved its discriminative value (from C-statistic 0.78 to 0.82 in both; Akaike information criterion change > 2). Importantly, all patients who experienced VA within 5 years from the echocardiographic assessment had abnormal regional RV deformation patterns at baseline. This study showed that regional functional abnormalities measured by echocardiographic deformation imaging can further refine personalized arrhythmic risk prediction when added to the ARVC risk calculator. The excellent negative predictive value of normal RV deformation could support clinicians considering the timing of implantable cardioverter defibrillator implantation in patients with intermediate arrhythmic risk.