Diagnosis Of Arrhythmogenic Right Ventricular Cardiomyopathy Research Articles

Myocarditis: An Important Presentation of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) traditionally presents with ventricular arrhythmias or, less commonly, heart failure. Myocardial inflammation has been implicated in the pathogenesis of ARVC, but clinical myocarditis in ARVC is not well described. We describe myocarditis as a presenting phenotype of ARVC, and hypothesized that patients with this presentation have distinct clinical characteristics. Methods Using the Johns Hopkins ARVC Registry, we examined patients diagnosed with myocarditis at index presentation based on European Society of Cardiology criteria, who were subsequently diagnosed with ARVC by Task Force Criteria (TFC). Results Of the 12 patients (all female, median age 20) initially diagnosed with myocarditis, the majority presented with chest pain (n=7, 58%) or ventricular arrhythmia (n=3, 25%). All patients had troponin elevations and left ventricular function was reduced in 5 (42%). Cardiac magnetic resonance imaging demonstrated LV delayed gadolinium enhancement and/or pericardial enhancement in 10 (83%), however only 3 (25%) patients had RV abnormalities. Treatment of suspected myocarditis during index presentation consisted of steroids (n=3/12, 25%) and/or non-steroidal anti-inflammatory drugs (NSAIDs) (n=4/12, 33%). Pathogenic genetic variants were identified in 11 (92%) patients: 10 desmoplakin (DSP) and 1 desmoglein-2 (DSG2). The clinical course timeline for each patient is shown in Figure 1. Patients were diagnosed with ARVC 1.8 years (IQR 2.7 years) after myocarditis presentation. After diagnosis, an additional 5 (42%) patients were recommended for implantable cardiac defibrillator and screening led to 17 family member diagnoses of ARVC. Conclusions Myocarditis may be the initial presentation of ARVC in some patients. These patients may have distinct characteristics such as female predominance, LV involvement and DSP gene variants. Genetic testing is key to ARVC diagnosis, especially in left ventricle dominant forms, and should be considered in appropriately selected patients presenting with myocarditis.

Relations between genetic background and intracardiac scars characteristics in patients with arrhythmogenic right ventricular cardiomyopathy

Relations between scars characteristics and genetic background in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has not been investigated so far. To investigate if genetic background change the scars characteristics in ARVC. 66 patients with ARVC (24 with culprit mutation) having undergone endocardial mapping have been retrospectively included. Every patient had a diagnosis of ARVC according to the task force criteria. Localisations, surfaces and perimeters of low votage areas (< 1.5 mV in bipolar and < 5.5 mV in unipolar) have been correlated to the existence of a culprit mutation, as well as volumes and ejection fraction of both ventricles by echocardiography, MRI or radionuclide. Mutated patients more often had altered right ventricular ejection fraction (< 0.05) and left ventricular late gadolinium enhancement ( P = 0.01). Right ventricle was more dilated ( P = 0.03), with larger scars in bi and unipolar voltage maps ( P < 0.05). Localisation of scars was linked to the genetic background, with more infero-lateral ( P = 0.01) or multiple scars ( P = 0.01) in mutated patients, while prevalence of outflow tract or apical scars did not differ. In our ARVC population, culprit mutations increase size and number of intracardiac scars and degree of biventricular involvment, and localize scars in infero-lateral areas compared to patients without mutation.

Differentiating hereditary arrhythmogenic right ventricular cardiomyopathy from cardiac sarcoidosis fulfilling 2010 ARVC Task Force Criteria

The clinical presentation of cardiac sarcoidosis (CS) may resemble that of arrhythmogenic right ventricular cardiomyopathy (ARVC). The purpose of this study was to identify clinical variables to better discriminate between patients with genetically determined ARVC and those with CS fulfilling definite 2010 ARVC Task Force Criteria (TFC). In this multicenter study, 10 patients with CS fulfilling definite 2010 ARVC TFC were age and gender matched with 10 genetically proven ARVC patients. A cardiac 18F-fluorodeoxyglucose positron emission tomographic (18F-FDG PET) scan was required for patients to be included in the study. The 2010 ARVC TFC did not reliably differentiate between the 2 diseases. CS patients presented with longer PR intervals, advanced atrioventricular block (AVB), and longer QRS duration (P<.001 and P = .009, respectively), whereas T-wave inversions (TWIs) in the peripheral leads were more common in ARVC patients (P = .009). CS patients presented with more extensive left ventricular involvement and lower left ventricular ejection fraction (LVEF), whereas ARVC patients had a larger right ventricular outflow tract (RVOT) (P = .044). PET scan positivity was only present in CS patients (90% vs 0%). The 2010 ARVC TFC do not reliably differentiate between CS patients fulfilling 2010 ARVC TFC and those with hereditary ARVC. Prolonged PR interval, advanced AVB, longer QRS duration, right ventricular apical involvement, reduced LVEF, and positive 18F-FDG PET scan should raise the suspicion of CS, whereas larger RVOT dimensions, subtricuspid involvement and peripheral TWI favor a diagnosis of hereditary ARVC.

Precordial T-Wave Inversions in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy Who Present with the Initial Features of Right Ventricular Outflow Tract Arrhythmia.

Precordial T-wave inversion (TWI) is an important diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aimed to characterize the initial repolarization features of definite ARVC in patients who first presented with right ventricular outflow tract ventricular arrhythmia (RVOT-VA) and TWI. Patients who presented with RVOT-VA and TWI ≥ V2 were retrospectively assessed. The initial characteristics of repolarization between patients with and without a final diagnosis of definite ARVC during follow-up were compared. TWI ≥ V2 was observed in 61 of 553 patients (mean age: 44.1 ± 14.7 years; 14 men) with RVOT-VAs. After an average follow-up time of 54.9 ± 33.7 months, 31 (50.8%) patients were classified into the definite ARVC group and 30 (49.2%) into the non-definite ARVC group. The disappearance of precordial TWI ≥ V2 was observed in eight (13.1%) patients after the elimination of RVOT-VAs. In a multivariate analysis of the initial electrocardiogram features, only fragmented QRS [odds ratio (OR): 15.45, 95% confidence interval (CI): 1.61-148.26, p = 0.02] and precordial V2 TpTe interval (OR: 1.03, 95% CI: 1.01-1.06, p = 0.02) could independently predict definite ARVC during longitudinal follow-up. An initial V2 TpTe cutoff value > 88.5 ms could predict the final diagnosis of definite ARVC, with a sensitivity and specificity of 74.2% and 78.6%, respectively. Despite the high risk of ARVC in RVOT-VAs and TWI ≥ V2, "normalization" of TWI was observed after ventricular arrhythmia elimination in 13.1% of the patients. Fragmented QRS and longer V2 TpTe interval were associated with definite ARVC during longitudinal follow-up.

Pregnancies, ventricular arrhythmias, and substrate progression in women with arrhythmogenic right ventricular cardiomyopathy in the Nordic ARVC Registry.

Women with arrhythmogenic right ventricular cardiomyopathy (ARVC) are at relatively lower risk of ventricular arrhythmias (VAs) than men, but the physical burden associated with pregnancy on VA risk remains insufficiently studied. We aimed to assess the risk of VA in relation to pregnancies in women with ARVC. We included 199 females with definite ARVC (n = 121) and mutation-positive family members without ascertained ARVC diagnosis (n = 78), of whom 120 had at least one childbirth. Ventricular arrhythmia-free survival after the latest childbirth was compared between women with one (n = 20), two (n = 67), and three or more (n = 37) childbirths. Cumulative probability of VA for each pregnancy (n = 261) was assessed from conception through 2 years after childbirth and compared between those pregnancies that occurred before (n = 191) or after (n = 19) ARVC diagnosis and in mutation-positive family members (n = 51). The nulliparous women had lower median age at ARVC diagnosis (38 vs. 42 years, P < 0.001) and first VA (22 vs. 41 years, P < 0.001). Ventricular arrhythmia-free survival after the latest childbirth was not related to the number of pregnancies. No pregnancy-related VA was reported among the family members. Women who gave birth after ARVC diagnosis had elevated risk of VA postpartum (hazard ratio 13.74, 95% confidence interval 2.9-63, P = 0.001), though only two events occurred during pregnancies. In women with ARVC, pregnancy was uneventful for the overwhelming majority and the number of prior completed pregnancies was not associated with VA risk. Pregnancy-related VA was primarily related to the phenotypical severity rather than pregnancy itself.

P1077Late gadolinium enhancement with cardiac magnetic resonance imaging demonstrates left ventricular involvement is under-recognized in arrhythmogenic right ventricular cardiomyopathy

Abstract Funding Acknowledgements The study is partially funded by Medtronic and the Minneapolis Heart Institute Foundation. Background/Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by replacement of the myocardium with fibrous and fatty tissue that may lead to an increased risk of ventricular arrhythmias and heart failure. Although left ventricular (LV) and biventricular forms have been identified post-mortem resulting in the increased use of the term arrhythmogenic cardiomyopathy, there is only inclusion of right ventricular wall motion abnormalities in the taskforce diagnostic criteria. Purpose The aim of our study was to examine the utility of cardiac magnetic resonance (CMR) imaging in characterizing LV or biventricular involvement with late gadolinium enhancement (LGE) in a large cohort of patients with suspected ARVC. Methods Retrospective, single-institution, chart review of 76 patients diagnosed with ARVC between January 2009 and July 2019. Data collection and analysis included baseline demographics and parameters specific to diagnosis (definite, borderline, or possible) and risk stratification of ARVC based on 2019 modified taskforce criteria, as well as detailed CMR evaluation. Results Of the 76 patients with ARVC, 66 (87%) had at least one CMR with gadolinium administered. In that subset of patients, 27 (41%) had LGE. Of those with LGE, LV involvement was identified in 23 (85%) patients. The pattern of LGE was not localized to one myocardial region but demonstrated variable LV enhancement patterns including anterior, inferior, lateral, septal, basal, mid, apical, and from the sub-epicardium into the mid-myocardium. Conclusions Left ventricular involvement reflected by LGE was identified in a high percentage of patients with suspected ARVC, and there was significant variation in the pattern of distribution in terms of region and depth of myocardial involvement. While post-mortem examination of patients with ARVC demonstrates a high prevalence of left ventricular involvement, this study shows that CMR can consistently detect late gadolinium enhancement, and ARVC should be considered in the differential diagnosis for biventricular cardiomyopathy. The identification of variable locations of LGE within the LV suggests there is more than one phenotype, and this imaging modality may help to clarify the implications of left ventricular involvement in disease progression.

Presence and prognostic value of ventricular diastolic function in arrhythmogenic right ventricular cardiomyopathy.

Limited data exist regarding the presence and importance of diastolic parameters in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We sought to evaluate RV diastolic parameters and echo-based diastolic predictors of major adverse cardiovascular events (MACE). 48 patients with a definitive diagnosis of ARVC were included and followed for 6-18months. A comprehensive standard two-dimensional (2D) transthoracic echocardiography (TTE) with precise evaluation of systolic and diastolic indices of both ventricles was done. RV isovolumetric relaxation time (IVRT), RV myocardial performance index (MPI), and right atrial (RA) volume were evaluated. 48 patients (mean age=38.5±14years; 79.2% male) were enrolled. 27.3% had grade I, 68.2% had grade II, and 4.5% had grade III RV diastolic dysfunction. In 12-month follow-up, 12 patients (25%, with mean RV3DEF=24.8±9%) experienced MACE and required hospitalization: ventricular tachyarrhythmia in 7 patients (14.6%), RV clot in 2 subjects (4.2%), and right-sided failure in 3 cases (6.3%). In logistic regression analysis, tissue Doppler velocity of tricuspid annulus (e' TV) (P=.02, OR=0.581, CI=0.368-0.917), peak E mitral valve (P=.043, OR=0.95, CI=0.913-0.999), tissue Doppler velocity of septal e' (P=.052, OR=0.733, CI=0.536-1.003), and MPI (P=.009, OR=95, CI=3.083-2942) were powerful predictors of MACE. In our study, RV diastolic function parameters including e' TV and e' MV, RA volume and area, and RV MPI were powerful predictors of MACE and may be considered during the baseline and follow-up of the ARVC patients.

The arrhythmogenic right ventricular cardiomyopathy in comparison to the athletic heart.

Intense exercise-induced right ventricular remodeling is a potential adaptation of cardiac function and structure. The features of the remodeling may overlap with those of a very early form of arrhythmogenic right ventricular cardiomyopathy (ARVC): at this early stage, it could be difficult to discriminate ARVC, from exercise-induced cardiac adaptation that may develop in normal individuals. The purpose of this paper is to discuss which exercise-induced remodeling may be a pathological or a physiological finding. A complete evaluation may be required to identify the pathological features of ARVC that would include potential risk of sudden cardiac deathduring sport or, to avoid the false diagnosis of ARVC. The most recent expert assessment of arrhythmogenic cardiomyopathy focuses on endurance athletes presenting with clinical features indistinguishable from ARVC.

Novel risk calculator performance in athletes with arrhythmogenic right ventricular cardiomyopathy

Disease progression and ventricular arrhythmias (VAs) in arrhythmogenic right ventricular cardiomyopathy (ARVC) are correlated with physical exercise, and clinical detraining and avoidance of competitive sport practice are suggested for ARVC patients. An algorithm assessing primary arrhythmic risk in ARVC patients was recently developed by Cadrin-Tourigny etal. Data regarding its transferability to athletes are lacking. The purpose of this study was to assess the reliability of the Cadrin-Tourigny risk prediction algorithm in a cohort of athletes with ARVC and to describe the impact of clinical detraining on disease progression. All athletes undergoing clinical detraining after ARVC diagnosis at our institution were enrolled. Baseline and follow-up clinical characteristics and data on VA events occurring during follow-up were collected. The Cadrin-Tourigny algorithm was used to calculate the a priori predicted VA risk, which was compared with the observed outcomes. Twenty-five athletes (age 36.1 ± 14.0 years; 80% male) with definite ARVC who were undergoing clinical detraining were enrolled. Over median (interquartile range) follow-up of 5.3 (3.2-6.6) years, a reduction in premature ventricular complex (PVC) burden (P = .001) was assessed, and 10 VA events (40%) were recorded. The a priori algorithm-predicted risk seemed to fit with the observed cohort arrhythmic risk [mean observed-predicted risk difference over 5 years -0.85% (interquartile range -4.8% to +3.1%); P = .85]. At 1-year follow-up, 11 patients (44%) had an improved stress ECG response, and no significant changes in right ventricular ejection fraction were observed. Clinical detraining is associated with PVC burden reduction in athletes with ARVC. The novel risk prediction algorithm does not seem to require any correction for its application to ARVC athletes.

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.

Late Presentation of Arrhythmogenic Right Ventricular Cardiomyopathy : Role of Non Invasive Modalities for The Diagnosis

Background : Arrhythmogenic right ventricular cardiomyopathy(ARVC) is an inherited myocardial disease affecting predominantly young people and manifests as sustained ventricular tachycardia, sudden cardiac death (SCD) or heart failure. However, its first manifestation in older patients is infrequent. Diagnosis of ARVC remains a clinical challenge and need further investigation. Our case report investigated role of non invasive modalities for diagnosis of ARVC patient.&#x0D; Case Presentation : A 65 year old man was admitted to the hospital with symptoms of palpitationand near syncope. An Electrocardiogram (ECG) showed a sustained VT with LBBB morphology and inferior axis. The patient was cardioverted to sinus rhytm with a single 100J shock. Postcardioversion ECG showed an epsilon wave in right precordial leads. Echocardiography revealed extensive RV enlargement and reduce function. Our patient had three major (RV aneurysm, epsilon wave and T wave inversion) and one minor criteria (sustained LBBB type-VT with inferior axis)making the diagnosis of ARVC definite according to the revised Task Forced Criteria.&#x0D; Conclusion: ARVC may have a very late presentation and this diagnosis should be considered as a potential cause of sustained VT of RV origin among the elderly. ECG and echocardiography as non invasive modalities have an important role for the diagnosis of patients with suspected ARVC.&#x0D; Keywords :Arrhythmogenic right ventricular cardiomyopathy,ventricular tachycardia, sudden cardiac death, diagnosis.

Application of noninvasive signal-averaged electrocardiogram analysis in predicting the requirement of epicardial ablation in patients with arrhythmogenic right ventricular cardiomyopathy

Signal-averaged electrocardiogram (SAECG) provides not only diagnostic information but also the prognostic implication of ablation in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aimed to validate the role of SAECG in identifying arrhythmogenic substrates requiring an epicardial approach in ARVC. Ninety-one patients with a definite diagnosis of ARVC who underwent successful ablation for drug-refractory ventricular arrhythmia were enrolled and classified into 2 groups: group 1 who underwent successful ablation at the endocardium only and group 2 who underwent successful ablation requiring an additional epicardial approach. The baseline characteristics of patients and SAECG parameters were obtained for analysis. Male predominance, worse right ventricular (RV) function, higher incidence of syncope, and depolarization abnormality were observed in group 2. Moreover, the number of abnormal SAECG criteria was higher in group 2 than in group 1. After a multivariate analysis, the independent predictors of the requirement of epicardial ablation included the number of abnormal SAECG criteria (odds ratio 2.8, 95% confidence interval 1.4-5.4; P = .003) and presence of syncope (odds ratio 11.7; 95% confidence interval 2.7-50.4; P = .001). In addition, ≥2 abnormal SAECG criteria were associated with larger RV endocardial unipolar low-voltage zone (P < .001), larger RV endocardial/epicardial bipolar low-voltage zone/scar (P < .05), and longer RV endocardial/epicardial total activation time (P < .001 and P = .004, respectively). The number of abnormal SAECG criteria was correlated with the extent of diseased epicardial substrates and could be a potential surrogate marker for predicting the requirement of epicardial ablation in patients with ARVC.

Prevalence and Electronic Health Record-Based Phenotype of Loss-of-Function Genetic Variants in Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Genes.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with variants in desmosome genes. Secondary findings of pathogenic/likely pathogenic variants, primarily loss-of-function (LOF) variants, are recommended for clinical reporting; however, their prevalence and associated phenotype in a general clinical population are not fully characterized. From whole-exome sequencing of 61 019 individuals in the DiscovEHR cohort, we screened for putative loss-of-function variants in PKP2, DSC2, DSG2, and DSP. We evaluated measures from prior clinical ECG and echocardiograms, manually over-read to evaluate ARVC diagnostic criteria, and performed a PheWAS (phenome-wide association study). Finally, we estimated expected penetrance using Bayesian inference. One hundred forty individuals (0.23%; 59±18 years old at last encounter; 33% male) had an ARVC variant (G+). None had an existing diagnosis of ARVC in the electronic health record, nor significant differences in prior ECG or echocardiogram findings compared with matched controls without variants. Several G+ individuals satisfied major repolarization (n=4) and ventricular function (n=5) criteria, but this prevalence matched controls. PheWAS showed no significant associations of other heart disease diagnoses. Combining our best genetic and disease prevalence estimates yields an estimated penetrance of 6.0%. The prevalence of ARVC loss-of-function variants is ≈1:435 in a general clinical population of predominantly European descent, but with limited electronic health record-based evidence of phenotypic association in our population, consistent with a low penetrance estimate. Prospective deep phenotyping and longitudinal follow-up of a large sequenced cohort is needed to determine the true clinical relevance of an incidentally identified ARVC loss-of-function variant.

P5653Atrial fibrillation in arrhythmogenic right ventricular cardiomyopathy and its association with left atrial volume index

Abstract Background Recent studies in arrhythmogenic right ventricular cardiomyopathy (ARVC) support atrial involvement in the disease progression and consider atrial fibrillation (AF) as one of the primary manifestations of ARVC. We aimed to assess clinical factors, components of 2010 Task Force criteria (TFC2010) and echocardiographic characteristics of atria associated with AF in the Scandinavian cohort of ARVC patients. Methods Study sample comprised of 106 definite ARVC patients by TFC2010 from three tertiary care centers participating in the Nordic ARVC Registry (33% females, median age at ARVC diagnosis 41 years [IQR 30–54 years]). No concomitant diseases were observed in 90 patients (85%) while 16 patients had one or more comorbidities: hypertension (n=6), diabetes mellitus (n=5), coronary artery disease (n=5) or congestive heart failure (n=9). AF was included in the registry protocol as a pre-specified clinical event and verified by processing of the electronic ECG databases which contains all ECG recordings from the involved hospitals catchment areas (earliest ECG from 1988). Left (LA) and right atrial (RA) dimensions were obtained by revisiting cardiac ultrasound examinations performed at the time of ARVC diagnosis. Association between AF and clinical characteristics was assessed using multivariable logistic regression analysis adjusted for age and gender. Results AF was diagnosed in 29 patients (27%) at a median age of 53 (IQR 38–63) years, 7 females (24%). Median time from ARVC diagnosis to AF onset was 8 (IQR 2–12) years. AF was univariately associated with right ventricular structural abnormalities meeting the definition of major imaging criterion by 2010TFC, ventricular tachycardia (VT) with superior axis (major criterion) and LA volume index. Significantly associated variables were included in a multivariate model, in which LA volume index (OR=1.07, 95% CI 1.01–1.14, p=0.021) and superior axis VT (OR=7.45, 95% CI 1.82–30.55, p=0.005) remained independently associated with AF. In receiver operating characteristic (ROC) curve analysis, LA volume index was significantly associated with AF (AUC=0.703, p=0.005) and with superior axis VT (AUC=0.703, p=0.021). AF was not associated with either RA volume index (univariate OR=1.03, 95% CI 0.99–1.06, p=0.203) or left ventricular ejection fraction (OR=0.97, 95% CI 0.92–1.03, p=0.299). Conclusion In patients with ARVC,AF is primarily associated with LA structural abnormalities without indication of RA involvement and is strongly associated with ventricular arrhythmias thus indicating parallel development of atrial and ventricular arrhythmic substrate.

P3683Diagnosis of arrhythmogenic cardiomyopathy and overlap with cardiac adaptation to exercise: insights from a cardiac magnetic resonance study

Abstract Background The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging and some structural abnormalities typical of the disease may overlap with changes reflective of cardiac adaptation to exercise. Purpose The aim of the study was to assess the performance of the cardiac magnetic resonance (CMR) 2010 Task Force Criteria (TFC) in a cohort of patients with definite diagnosis of ARVC and define the overlap with a cohort of highly trained athletes of similar age and sex. Methods We compared the CMR features of 43 patients (mean age 49±17 years, 49% males, 32 (74%) genotyped) with a definite diagnosis of ARVC according to the revised TFC to 97 (mean age 45±16 years, 61% males) highly-trained athletes of similar age and sex, in whom cardiac disease was excluded after comprehensive work-up. Results The CMR was abnormal in 37 (86%) patients. The right ventricle (RV) was affected in isolation in 17 (39%) patients, with 18 (42%) patients exhibiting biventricular involvement and 2 (5%) patients showing isolated left ventricular (LV) involvement. The most common RV abnormalities were regional wall motion abnormalities (RWMA) (n=34; 79%), RV dilatation fulfilling a major or minor volume TFC (n=18; 42%), impaired systolic function (RV ejection fraction (EF) ≤45%: n=17; 40%) and myocardial fibrosis (n=13; 30%). The predominant LV abnormality was myocardial fibrosis (n=20; 47%), with a small proportion of patients exhibiting RWMA (n=6; 14%) and impaired systolic function (LVEF &lt;50%: n=6; 14%). Twenty-three (53%) patients fulfilled a major (n=14; 32%) or a minor (n=9; 21%) CMR TFC. Sixteen (16%) athletes exceeded the cut-off values for RV volumes used as a major (n=10; 10%) or a minor (n=6; 6%) TFC with an inverse relationship between age and RV volumes (r=−41, p=0.001). None of the athletes fulfilled the TFC for RV ejection fraction. Applying the CMR TFC to the ARVC patient population showed a sensitivity of 33% for the major and 28% for the minor criteria. Applying the RV volume and systolic function TFC values in the entire study population showed a sensitivity of 53%, a specificity between 83% and an accuracy of 0.68. Conclusions The great majority (86%) of patients with ARVC demonstrates structural abnormalities suggestive of cardiomyopathy on CMR but only 53% fulfills any of the CMR TFC. Only a small proportion (16%) of older athletes demonstrate significant RV dilatation that overlaps with the volume criteria for ARVC, in juxtaposition to younger athletes who exhibit a greater degree of overlap. The emergence of ARVC as a biventricular disease provides an opportunity to re-evaluate the diagnostic criteria and include LV involvement in conjunction with RV involvement to improve diagnostic accuracy. Acknowledgement/Funding CRY (Cardiac Risk in the Young) charity

Misdiagnosis of ARVC leading to inappropriate ICD implant and subsequent ICD removal - lessons learned.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited progressive cardiomyopathy characterized by frequent life-threatening arrhythmias. The diagnosis of ARVC is challenging and is on the basis of a set of major and minor criteria as described by the modified Task Force Criteria (TFC). We report our clinical experience in a series of patients who were misdiagnosed with ARVC and subsequently underwent removal of their implantable cardioverter defibrillator (ICD) after a re-evaluation at our center. We studied 12 patients who were misdiagnosed with ARVC and had ICD implantation before our assessment. All patients had a repeat evaluation and were scored according to TFC before ICD removal. Cardiac magnetic resonance imaging (CMR) studies performed at outside institutions during the initial evaluation were reported abnormal and classified as meeting major TFC in ninety percent of patients. The most common abnormality reported was fatty infiltration of the right ventricular (RV) free wall and/or presence of focal intra-myocardial fat in six patients (50%). On re-evaluation, none of these findings fulfilled the TFC for the diagnosis. This study demonstrated that high dependence on misinterpretation of CMR along with a misunderstanding of the TFC evaluation are the main reasons for the misdiagnosis of ARVC. Despite the updated criteria for almost a decade, this study reminds that the diagnosis of ARVC is complex and hence careful TFC evaluation and consideration of multiple cardiac test results should be the focused approach for clinicians when confronted with suspected ARVC patients.

Atrial fibrillation as a clinical characteristic of arrhythmogenic right ventricular cardiomyopathy: Experience from the Nordic ARVC Registry

BackgroundRecent studies in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have drawn attention to atrial fibrillation (AF) as an arrhythmic manifestation of ARVC and as an indicator of atrial involvement in the disease progression. We aimed to assess the prevalence of AF in the Scandinavian cohort of ARVC patients and to evaluate its association with disease clinical manifestations. MethodsStudy sample comprised of 293 definite ARVC patients by 2010 Task Force criteria (TFC2010) and 141 genotype-positive family members (total n = 434, 43% females, median age at ARVC diagnosis 41 years [interquartile range (IQR) 28–52 years]). ARVC diagnostic score was calculated as the sum of major (2 points) and minor (1 point) criteria in all categories of the TFC2010. ResultsAF was diagnosed in 42 patients (10%): in 41 patients with definite ARVC diagnosis (14%) vs in one genotype-positive family member (1%), p < 0.001. The median age at AF onset was 51 (IQR 38–58) years. The prevalence of AF was related to the ARVC diagnostic score: it significantly increased starting with the diagnostic score 4 (2% in those with score 3 vs 13% in those with score 4, p = 0.023) and increased further with increased diagnostic score (Somer's d value is 0.074, p < 0.001). ConclusionAF is seen in 14% of definite ARVC patients and is related to the severity of disease phenotype thus suggesting AF being an arrhythmic manifestation of this cardiomyopathy indicating atrial myocardial involvement in the disease progression.

Association of Echocardiographic Parameters of Right Ventricular Remodeling and Myocardial Performance With Modified Task Force Criteria in Adolescents With Arrhythmogenic Right Ventricular Cardiomyopathy.

The usefulness of echocardiographic indices, including those already used by modified Task Force Criteria (mTFC), and others such as strain imaging, to identify arrhythmogenic right ventricular cardiomyopathy (ARVC) in adolescence is not well established. Echocardiograms from 120 adolescents investigated for ARVC (13±4 years) were retrospectively analyzed. According to the mTFC, patients were classified into definite (n=38), borderline (n=39), or possible (n=43) ARVC. Results were compared with 35 healthy controls. mTFC echocardiographic parameters were analyzed, as well as comprehensive right ventricular (RV) and left ventricular assessment of function including parameters not included in mTFC such as pulsed-wave tissue Doppler and RV 2-dimensional speckle strain. mTFC parameters indexed for body surface area were significantly more abnormal in patients with possible, borderline, or definite ARVC compared with controls for parasternal long-axis view of the RV outflow tract. RV end-diastolic diameters were significantly larger in patients versus controls, a difference that increased with likelihood of ARVC. Left ventricular ejection fraction, tricuspid annular peak systolic excursion, and systolic and diastolic pulsed-wave tissue Doppler imaging indices were similar to controls for all groups. Average and segmental RV peak longitudinal systolic strain was significantly lower in patients with definite ARVC (-21±4%) and disease subgroups versus controls (-25±3%). Multivariable risk analysis showed that reduced RV strain was significantly associated with ARVC diagnosis and its likelihood (multivariable odds ratio [95% CI]=1.23 [1.1-1.37]; P<0.001) as was increased end-diastolic diameter at the apical third of the RV (multivariable odds ratio [95% CI]=1.51 [1.33-1.72]; P<0.001). mTFC echocardiographic criteria are significantly different between patients and controls and between the different diagnostic groups. However, in our cohort, current echocardiographic mTFC are not met by the majority of adolescent ARVC patients, particularly when indexed to body surface area. Measurement of RV apical dimensions and strain may increase the diagnostic yield of echocardiography for ARVC.

Subcutaneous implantable cardioverter defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy: Results from an Italian multicenter registry

BackgroundDespite expanding indication of the subcutaneous implantable cardioverter defibrillator (S-ICD) in clinical practice, limited data exists on safety and efficacy of S-ICD in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. The aim of this multicenter study was to evaluate the safety and efficacy of S-ICD in ARVC patients. MethodsThe study population included 44 consecutive patients with definite ARVC diagnosis according to the 2010 ITF criteria (57% male, mean age 37 ± 17 years [range 10–75 years]) who received an S-ICD. Eighteen (41%) patients were implanted for secondary prevention. ResultsAt implant, all inducible patients (34/44) had conversion of ventricular fibrillation at 65 J. No early complications occurred. During a median follow-up of 12 months (7–19), 3 (6.8%) patients experienced complications requiring surgical revision. No local or systemic device-related infections were observed. Six patients (14%) received a total of 61 appropriate and successful shocks on ventricular arrhythmias. Six (14%) patients experienced 8 inappropriate shocks for oversensing of cardiac signal (4 cases) and non-cardiac signal (4 cases) with one patient requiring device explantation. No patients had the device explanted due to the need for antitachycardia pacing. ConclusionsThe study shows that S-ICD provides safe and effective therapy for termination of both induced and spontaneous malignant ventricular tachyarrhythmias with high energy shocks in ARVC patients, but the risk of inappropriate shocks and complications needing surgical revision should be considered.

Primary Prevention of Sudden Cardiac Death With Implantable Cardioverter-Defibrillator Therapy in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Implantable cardioverter-defibrillator (ICD) therapy remains a corner stone of sudden cardiac death (SCD) prevention in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to assess predictors of appropriate ICD therapies in the Scandinavian cohort of ARVC patients who received ICD for primary prevention of SCD. Study group comprised of 79 definite ARVC patients by 2010 Task Force criteria (60% male, age at ICD implant 39 ± 14 years) who were enrolled in the Nordic ARVC Registry and received an ICD for primary SCD prevention. The primary end point of appropriate ICD shock or death from any cause was assessed and compared with 137 definite ARVC patients who received ICD for secondary SCD prevention (74% male, age at ICD implant 42 ± 15 years). In the study group, 38% were ≤35 years of age at baseline, 25% had nonsustained ventricular tachycardia, and 29% had syncope at baseline. Major repolarization abnormality (hazard ratio = 4.00, 95% confidence interval 1.30 to 12.30, p = 0.015) and age ≤35 years (hazard ratio = 4.21, 95% confidence interval 1.49 to 11.85, p = 0.001) independently predicted the primary end point. The outcome did not differ between the primary prevention patients with either of these risk factors and the secondary prevention cohort (2% to 4% annual event rate) whereas patients without risk factors did not have any appropriate ICD shocks during follow-up. In conclusion, young age at ARVC diagnosis and major repolarization abnormality independently predict ICD shocks or death in the primary prevention ICD recipients and associated with the event rate similar to the one observed in the secondary prevention cohort. Our data indicate the benefit of ICD for primary prevention in patients with any of these risk factors.