An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of CASQ2-Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Genetic variants in calsequestrin-2 (CASQ2) cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of CASQ2-CPVT was sought through an international multicenter collaboration. METHODS: Genotype-phenotype segregation in CASQ2-CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models. Putative dominant CASQ2 missense variants and the established recessive CASQ2-p.R33Q variant were evaluated using oligomerization assays and their locations mapped to a recent CASQ2 filament structure. RESULTS: A total of 112 individuals, including 36 CPVT probands (24 homozygotes/compound heterozygotes and 12 heterozygotes) and 76 family members possessing at least 1 presumed pathogenic CASQ2 variant, were identified. Among CASQ2 homozygotes and compound heterozygotes, clinical penetrance was 97.1% and 26 of 34 (76.5%) individuals had experienced a potentially fatal arrhythmic event with a median age of onset of 7 years (95% CI, 6-11). Fifty-one of 66 CASQ2 heterozygous family members had undergone clinical evaluation, and 17 of 51 (33.3%) met diagnostic criteria for CPVT. Relative to CASQ2 heterozygotes, CASQ2 homozygote/compound heterozygote genotype status in probands was associated with a 3.2-fold (95% CI, 1.3-8.0; P=0.013) increased hazard of a composite of cardiac syncope, aborted cardiac arrest, and sudden cardiac death, but a 38.8-fold (95% CI, 5.6-269.1; P<0.001) increased hazard in genotype-positive family members. In vitro turbidity assays revealed that p.R33Q and all 6 candidate dominant CASQ2 missense variants evaluated exhibited filamentation defects, but only p.R33Q convincingly failed to dimerize. Structural analysis revealed that 3 of these 6 putative dominant negative missense variants localized to an electronegative pocket considered critical for back-to-back binding of dimers. CONCLUSIONS: This international multicenter study of CASQ2-CPVT redefines its heritability and confirms that pathogenic heterozygous CASQ2 variants may manifest with a CPVT phenotype, indicating a need to clinically screen these individuals. A dominant mode of inheritance appears intrinsic to certain missense variants because of their location and function within the CASQ2 filament structure.

Pregnancy in Catecholaminergic Polymorphic Ventricular Tachycardia.

OBJECTIVES: This investigation was a retrospective study of catecholaminergic polymorphic ventricular tachycardia (CPVT) patients in Canada and the Netherlands to compare pregnancy, postpartum, and nonpregnant event rates. BACKGROUND: CPVT is characterized by life-threatening arrhythmias during exertion or emotional stress. The arrhythmic risk in CPVT patients during pregnancy is unknown. METHODS: Baseline demographics, genetics, treatment, and pregnancy complications were reviewed. Event rate calculations assumed a 40-week pregnancy and 24-week postpartum period. RESULTS: Ninety-six CPVT patients had 228 pregnancies (median 2 pregnancies per patient; range: 1 to 10; total: 175.4 pregnant patient-years). The median age of CPVT diagnosis was 40.7 years (range: 12 to 84 years), with a median follow-up of 2.9 years (range: 0 to 20 years; total 448.1 patient-years). Most patients had pregnancies before CPVT diagnosis (82%). Pregnancy and postpartum cardiac events included syncope (5%) and an aborted cardiac arrest (1%), which occurred in patients who were not taking beta-blockers. Other complications included miscarriages (13%) and intrauterine growth restriction (1 case). There were 6 cardiac events (6%) during the nonpregnant period. The pregnancy and postpartum event rates were 1.71 and 2.85 events per 100 patient-years, respectively, and the combined event rate during the pregnancy and postpartum period was 2.14 events per 100 patient-years. These rates were not different from the nonpregnant event rate (1.46 events per 100 patient-years). CONCLUSIONS: The combined pregnancy and postpartum arrhythmic risk in CPVT patients was not elevated compared with the nonpregnant period. Most patients had pregnancies before diagnosis, and all patients with events were not taking beta-blockers at the time of the event.

Genetic testing in cardiomyopathies: an update on indications and benefits.

PURPOSE OF REVIEW: As rapid genetic testing has become increasingly accessible in a timely fashion, more genetic mutations are identified in inherited conditions such as cardiomyopathies. Understanding when to consider genetic testing is an important part of the management of patients whose presentations vary from decompensated heart failure to sudden cardiac death. RECENT FINDINGS: We describe the benefits of genetic testing for risk stratification of family members, prognostication of probands, and identification of novel disease-causing mutations and examine the possible role of genetic predisposition in seemingly acquired cardiomyopathies such as peripartum and anthracycline-induced cardiomyopathy. SUMMARY: Genetic screening for the recognition of family members who have inherited a cardiomyopathy is important, and testing may identify patients at higher risk of sudden death. However, genetic testing does have its limitations, such as the identification of variants of unknown significance that often complicate the clinical picture.

Patient Outcomes From a Specialized Inherited Arrhythmia Clinic.

BACKGROUND: Patients with inherited arrhythmia syndromes are at an increased risk of sudden cardiac death (SCD). Specialized inherited arrhythmia clinics were founded to optimize management and prevention of SCD in this population. However, the clinical effectiveness of these clinics has never been evaluated. METHODS AND RESULTS: Clinical outcome data of patients referred to a specialized inherited arrhythmia clinic between 2005 and 2014 for a possible primary electric syndrome or arrhythmogenic right ventricular cardiomyopathy were analyzed. Of 720 patients evaluated, 278 received a definite or probable diagnosis and received long-term management in the inherited arrhythmia clinic. All patients diagnosed with long QT syndrome and catecholaminergic polymorphic ventricular tachycardia received routine ß-blocker therapy and demonstrated >90% long-term compliance. In patients with arrhythmogenic right ventricular cardiomyopathy, those demonstrating an arrhythmia burden on Holter or treadmill testing received ß-blocker therapy (17%). In diagnosed channelopathy or arrhythmogenic right ventricular cardiomyopathy index cases, 44 patients received secondary prevention implantable cardioverter-defibrillators (long QT syndrome, 9; Brugada syndrome, 8; catecholaminergic polymorphic ventricular tachycardia, 3; short QT syndrome, 1; and arrhythmogenic right ventricular cardiomyopathy, 23). Median follow-up was 4.1 years with 43% having a follow-up period of >5 years. SCD occurred in a single patient (annualized risk of SCD, 0.1% per year). In individuals determined to have clinical or genetic disease by cascade screening, no SCD has occurred over a median follow-up of 5.6 years (55%, >5 years). Low event rates occurred despite a low rate (4.0%) of primary prevention implantable cardioverter-defibrillator utilization. CONCLUSIONS: Longitudinal care in a specialized inherited arrhythmia clinic is associated with a low incidence of SCD and a low rate of primary implantable cardioverter-defibrillator utilization in patients with inherited arrhythmia syndromes.

The establishment of core competencies for canadian genetic counsellors: validation of practice based competencies.

Numerous groups of health professionals have undertaken the task of defining core competencies for their profession. The goal of establishing core competencies is to have a defined standard for such professional needs as practice guidelines, training curricula, certification, continuing competency and re-entry to practice. In 2006, the Canadian Association of Genetic Counsellors (CAGC) recognized the need for uniform practice standards for the profession in Canada, given the rapid progress of genetic knowledge and technologies, the expanding practice of genetic counsellors and the increasing demand for services. We report here the process by which the CAGC Practice Based Competencies were developed and then validated via two survey cycles, the first within the CAGC membership, and the second with feedback from external stakeholders. These competencies were formally approved in 2012 and describe the integrated skills, attitudes and judgment that genetic counsellors in Canada require in order to perform the services and duties that fall within the practice of the profession responsibly, safely, effectively and ethically.

Exercise testing in asymptomatic gene carriers exposes a latent electrical substrate of arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: The aim of this study was to determine if exercise testing could expose a latent electrical substrate of arrhythmogenic right ventricular cardiomyopathy (ARVC) in asymptomatic gene carriers. BACKGROUND: Management of asymptomatic ARVC gene carriers is challenging because of variable penetrance of disease and the recognition that sudden cardiac death may be the first clinical manifestation. METHODS: Exercise-induced abnormalities during exercise treadmill testing (ETT) were initially compared in 60 subjects: 30 asymptomatic ARVC gene carriers and 30 healthy controls. In phase 2 of the study, ETT results of 25 patients with ARVC with histories of sustained ventricular arrhythmia or cardiac arrest were evaluated to determine if ETT abnormalities in asymptomatic gene carriers were common to patients with a malignant electrical form of the disease. RESULTS: Depolarization abnormalities during ETT were found to develop more frequently in asymptomatic gene carriers compared with healthy controls: epsilon waves appeared in 4 of 28 (14%) compared with 0 of 30 (0%) (p = 0.048), premature ventricular contractions in 17 of 30 (57%) compared with 3 of 30 (10%) (p = 0.0003), and new QRS terminal activation duration ≥ 55 ms in 7 of 22 (32%) compared with 2 of 29 (7%) (p = 0.03). Superior axis premature ventricular contractions occurred only in gene carriers. In the second phase of the study, the frequency of these abnormalities was found to be high in patients with symptomatic ARVC: new epsilon waves appeared in 3 of 18 (17%), superior axis premature ventricular contractions in 21 of 25 (84%), and new terminal activation duration ≥ 55 ms in 8 of 12 (67%). CONCLUSIONS: Exercise testing exposes a latent electrical substrate in asymptomatic ARVC gene carriers that is shared by patients with ARVC with histories of ventricular arrhythmia. ETT may be useful in guiding treatment decisions, exercise prescription, and prioritizing medical surveillance in asymptomatic ARVC gene carriers.

Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper.

The era of gene discovery and molecular medicine has had a significant impact on clinical practice. Knowledge of specific genetic findings causative for or associated with human disease may enhance diagnostic accuracy and influence treatment decisions. In cardiovascular disease, gene discovery for inherited arrhythmia syndromes has advanced most rapidly. The arrhythmia specialist is often confronted with the challenge of diagnosing and managing genetic arrhythmia syndromes. There is now a clear need for guidelines on the appropriate use of genetic testing for the most common genetic conditions associated with a risk of sudden cardiac death. This document represents the first ever published recommendations outlining the role of genetic testing in various clinical scenarios, the specific genes to be considered for testing, and the utility of test results in the management of patients and their families.

Inherited cardiomyopathies mimicking arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents an inherited cardiomyopathy that manifests clinically with malignant ventricular arrhythmias, sudden cardiac death, and less commonly heart failure. The condition is characterized by replacement of the myocardium, primarily of the right ventricle, with fibrofatty tissue. Extensive fibrofatty replacement of the myocardium has been previously thought to be pathognomonic of ARVC; however, this report details two other forms of inherited cardiomyopathy, namely hypertrophic cardiomyopathy (HCM) and the PRKAG2 cardiac syndrome, that were found to have significant fibrofatty myocardial replacement at pathologic examination. This report represents the first documentation of inherited cardiomyopathies mimicking ARVC and highlights the concept that other cardiac conditions can be associated with fibrofatty replacement of the myocardium.

A pilot study to assess the feasibility of a multicenter cluster randomized trial for the management of asymptomatic persons with a thrombophilia.

There is controversy whether asymptomatic first-degree relatives (FDRs) of patients with venous thromboembolism (VTE) and thrombophilia should be screened, followed, and prescribed prophylaxis during risk periods. We recruited consecutive probands with idiopathic VTE and thrombophilia from our thrombosis clinics. Those FDRs with thrombophilia were randomized in family clusters to receive one-time verbal counseling and no organized follow-up or counseling, educational material, reminder aids and follow-up. Only 203 of 1,129 FDRs were eligible and consented. Dropouts were common; 1 FDR (1.7%) developed VTE. VTE risk, ability to treat and prevent were underestimated by the participants. Patients with VTE and thrombophilia and their FDRs are often not interested in thrombophilia testing. Despite education to inform their knowledge, interest and follow-up were less than ideal. The question of the best educational approach in these patients remains unanswered. The value of testing and following asymptomatic carriers of probands with VTE and thrombophilia remains unknown.

Gain-of-function mutation of Nav1.5 in atrial fibrillation enhances cellular excitability and lowers the threshold for action potential firing.

Genetic mutations of the cardiac sodium channel (SCN5A) specific only to the phenotype of atrial fibrillation have recently been described. However, data on the biophysical properties of SCN5A variants associated with atrial fibrillation are scarce. In a mother and son with lone atrial fibrillation, we identified a novel SCN5A coding variant, K1493R, which altered a highly conserved residue in the DIII-IV linker and was located six amino acids downstream from the fast inactivation motif of sodium channels. Biophysical studies of K1493R in tsA201 cells demonstrated a significant positive shift in voltage-dependence of inactivation and a large ramp current near resting membrane potential, indicating a gain-of-function. Enhanced cellular excitability was observed in transfected HL-1 atrial cardiomyocytes, including spontaneous action potential depolarizations and a lower threshold for action potential firing. These novel biophysical observations provide molecular evidence linking cellular "hyperexcitability" as a mechanism inducing vulnerability to this common arrhythmia.

Discrepant DNA analysis in three patients with inherited arrhythmia: molecular genetic test results deserve a second glance.

Molecular results provide a basis for diagnosis, risk assessment, medical management and genetic counseling. Unlike other areas of laboratory medicine, molecular genetic tests are rarely repeated. We describe three patients with suspected inherited arrhythmia in whom genetic testing was arranged via clinical and/or research laboratories. In all three instances, initial test results appeared falsely negative, with no deleterious mutations detected by various methodologies in selected long-QT or catecholaminergic polymorphic ventricular tachycardia-related genes. Discordant results emerged upon repeat analysis in separate laboratories. The cases highlight the importance of clinical judgment and assessment of genetic test results and methodology, in addition to the role of re-testing in molecular genetic medicine, particularly in the case of uninformative negative results.

Molecular autopsy in the sudden cardiac death of a young woman: a first Canadian report.

Standard autopsy of young victims with sudden cardiac death commonly does not identify a specific pathological diagnosis. In such cases, sudden cardiac death may be secondary to a genetic condition predisposing the patient to ventricular arrhythmias. Failure to identify a genetic etiology for an unexpected sudden death may leave surviving family members at risk for a similar tragedy. The case of a 21-year-old woman who died suddenly while at rest is presented. Molecular genetic analysis of tissue retrieved from the regional coroner's office identified a novel missense mutation in the KCNH2 gene, a gene known to cause the long QT syndrome.

Findings on magnetic resonance imaging of idiopathic right ventricular outflow tachycardia.

We evaluated 20 patients with idiopathic ventricular tachycardia for structural abnormalities using magnetic resonance imaging (MRI) and compared them with 20 controls. Two experienced observers interpreted the MRIs. There were no differences in incidence of qualitative MRI findings in patients compared with controls. These findings do not favor an association between anatomic abnormalities and arrhythmia in these patients.

Arrhythmogenic right ventricular dysplasia: ex vivo and in vivo fat detection with black-blood MR imaging.

PURPOSE: To assess electrocardiographically gated spin-echo (SE) and double inversion-recovery fast SE magnetic resonance (MR) imaging in the depiction of intramyocardial fat in cadaveric heart specimens and patients with arrhythmogenic right ventricular dysplasia (ARVD). MATERIALS AND METHODS: A phantom was used to determine the effective in-plane spatial resolution of SE and fast SE MR imaging protocols. Two cadavers with proved ARVD were imaged with identical sequences with spectrally selected fat suppression. Contrast-to-noise ratios (CNRs) of intramyocardial fat in the right ventricle (RV) were compared by using analysis of variance and Student t test with Bonferroni correction. Eleven patients with ARVD and 10 control subjects underwent fast SE MR imaging. Two blinded readers semiquantitatively evaluated images for fat conspicuity and image quality. RESULTS: Fast SE MR imaging achieved better spatial resolution but lower CNR than that of gated SE imaging. CNRs in cadaveric specimens were higher for double R-R than for single R-R fast SE sequences for all section thicknesses (P <.0001). Absolute CNR values were higher for fat-suppressed fast SE sequences than for those without fat suppression. Cadaveric specimens demonstrated fatty infiltration from epicardium toward endocardium of the RV free wall. Intramyocardial fat was detected in eight of 11 (73%) patients with ARVD and in no control subjects (P <.001). CONCLUSION: Intramyocardial fat detection in ARVD was better with fast SE MR imaging alone and combined with fat suppression than was gated SE MR imaging. When fast SE imaging is applied in vivo, however, breath-holding constraints limit the spatial resolution for RV fat detection.

Implantable cardioverter-defibrillators in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

OBJECTIVES: The aim of this study was to assess the outcome of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients treated with an implantable cardioverter-defibrillator (ICD). BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is associated with tachyarrhythmia and an increased risk of sudden death. METHODS: This study included 42 ARVD/C patients with ICDs (52% male, age 6 to 69 years, median 37 years) followed at our center. RESULTS: Mean follow-up was 42 +/- 26 months (range 4 to 135 months). Complications associated with ICD implantation included need for lead repositioning (n = 3) and system infection (n = 2). During follow-up, one patient died of a brain malignancy and one had heart transplantation. Lead replacement was required in six patients as a result of lead fracture and insulation damage (n = 4) or change in thresholds (n = 2). During this period, 33 of 42 (78%) patients received a median of 4 (range 1 to 75) appropriate ICD interventions. The median period between ICD implantation and the first firing was 9 months (range 0.1 to 66 months). The ICD firing storms were observed in five patients. Inappropriate interventions were seen in 10 patients. Predictors of appropriate firing were induction of ventricular tachycardia (VT) during electrophysiologic study (EPS) (84% vs. 44%, p = 0.024), detection of spontaneous VT (70% vs. 15%, p = 0.001), male versus female gender (91% vs. 65%, p = 0.04), and severe right ventricular dilation (39% vs. 0%, p = 0.013). Using multivariate analysis, VT induction during EPS was associated with increased risk for firing in ARVD/C patients; odds ratio 11.2 (95% confidence interval 1.23 to 101.24, p = 0.031). CONCLUSIONS: Patients with ARVD/C have a high arrhythmia rate requiring appropriate ICD interventions. The ICD therapy appears to be well tolerated and important in the management of patients with ARVD/C.

Misdiagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

INTRODUCTION: Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has major implications for the management of patients and their first-degree relatives. Diagnosis is based on a set of criteria proposed by the International Task Force for Cardiomyopathies. We report our experience in providing a re-evaluation for patients who previously have been diagnosed with ARVD/C. METHODS AND RESULTS: We studied 89 patients who requested a re-evaluation for diagnosis of ARVD/C at our center. Each of these patients had been diagnosed with ARVD/C at their initial evaluation. Each patient was re-evaluated with clinical history, physical examination, and noninvasive testing at our center. Invasive testing, which included electrophysiologic testing, right ventricular angiography, and endomyocardial biopsy, was performed when clinically indicated. Sixty (92%) of the 65 patients who had undergone magnetic resonance imaging (MRI) at an outside institution were reported to have an abnormal MRI consistent with ARVD/C. Among these patients, the only abnormality identified was the qualitative finding of intramyocardial fat/wall thinning in 46 patients. On re-evaluation, these qualitative findings were not confirmed. None of these 46 patients ultimately were diagnosed with ARVD/C. Among the entire patient group, only 24 (27%) of the 89 patients met the Task Force criteria for ARVD/C. CONCLUSION: This study demonstrates that the high frequency of "misdiagnosis" of ARVD/C is due to over-reliance on the presence of intramyocardial fat/wall thinning on MRI, incomplete diagnostic testing, and lack of awareness of the Task Force criteria. Diagnosis of ARVD/C cannot rely solely upon qualitative features on MRI.

Filtered QRS duration on signal-averaged electrocardiography predicts inducibility of ventricular tachycardia in arrhythmogenic right ventricle dysplasia.

Treatment of arrhythmogenic right ventricular dysplasia (ARVD) is mostly based on the prevention of sudden cardiac death that results from arrhythmias. A clinical history suggestive of ARVD requires careful evaluation including electrophysiological study. The potential ability to identify those patients who will have inducible VT with electrophysiological study will enable better risk stratification and selection of vulnerable patients for electrophysiologically guided therapy. The purpose of the study was to evaluate the predictive ability of signal-averaged electrocardiography (SAECG) to predict inducibility of VT in patients with ARVD. The patient population consisted of 31 ARVD patients diagnosed with McKenna's criteria who underwent electrophysiological study. Electrophysiological study was considered positive if sustained monomorphic VT was induced. The sensitivity, specificity, and predictive accuracy of various SAECG criteria for inducibility of sustained monomorphic VT were also calculated. Twenty-one patients had inducible VT. The filtered QRS duration (fQRS), duration of signal <40 uV (LAS40), and root mean square voltage in the last 40 ms of QRS duration (RMS40) in ARVD patients induced versus noninduced were 122 +/- 21 and 103 +/- 8 ms (P=0.007), 45 +/- 20 and 28 +/- 14 ms (P=0.02), 19 +/- 19 and 32 +/- 22 uV (0.03), respectively. The ejection fractions were comparable in both groups. fQRS duration > or =110 ms had sensitivity of 91%, specificity of 90%, and a total predictive accuracy of 90% in predicting inducibility of VT in these patients. Filtered QRS duration on SAECG is predictive of electrophysiological study outcome in ARVD. Further studies will be needed to determine if SAECG results can predict the development of ventricular arrhythmias during follow-up.

Utility of SAECG in arrhythmogenic right ventricle dysplasia.

BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by progressive replacement of RV myocardium with fibro-adipose tissue thought to be responsible for the presence of late potentials (LP) detected by SAECG. The general consensus on the role of SAECG in the diagnosis and prognosis of patients with ARVD is lacking. The purpose of this systematic review was to better define the role of SAECG in ARVD. METHODS: An extensive review of literature was done to specifically describe the prevalence of LP in ARVD and its determinants, explore the various options available to improve the diagnostic ability of SAECG, and provide recommendations for proper utilization of this technique. RESULTS: LPs are frequent in ARVD (47-100%), and more prevalent in severe disease and in patients with documented spontaneous VT. SAECG is a useful test in following the characteristic evolutivity of the disease. 4-16% of normal family members of patients with ARVD also have abnormal SAECG results. Detection of LP in ARVD can be improved by employing a high-pass filter of 25 Hz and specifically looking for changes in the Z leads. CONCLUSIONS: SAECG testing should be considered a standard part of the evaluation of patients with known or suspected ARVD. Further research is needed to confirm the value of SAECG testing in predicting arrhythmia risk and assessing the rate of disease progression, as well as to determine if greater prevalence of SAECG abnormalities in family members of patients with ARVD represents early detection of ARVD. The ongoing multidisciplinary study of right ventricular dysplasia will hopefully answer some of these questions.

Magnetic resonance imaging findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia.

INTRODUCTION: Magnet resonance imaging (MRI) findings in patients meeting Task Force criteria for the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) have not been systematically described. We report qualitative and quantitative MRI findings in ARVD using state-of-the-art MRI. METHODS AND RESULTS: MRI was performed on 12 patients with ARVD who were prospectively diagnosed using the Task Force criteria. The imaging protocol included breath-hold double inversion recovery spin-echo and gradient-echo images. Ventricular volumes and dimensions were compared to 10 age- and sex-matched normal volunteers. High intramyocardial T1 signal similar to fat signal was observed in 9 (75%) of the 12 patients and in none of the controls. Right ventricular (RV) hypertrophy was seen in 5 (42%) patients, trabecular disarray in 7 (59%), and wall thinning in 3 (25%). Both the RV end-diastolic diameter and the outflow tract area were significantly higher in ARVD patients compared to controls (51.2 vs 43.2 mm, P < 0.01; and 14.5 vs 9.3 cm2, P < 0.01, respectively). ARVD patients had a higher RV end-diastolic volume index and lower RV ejection fraction compared with controls (127.4 vs 87.5, P < 0.01; and 41.6% vs 57%, P < 0.01, respectively). CONCLUSION: High intramyocardial T1 signal indicative of fat is seen in a high percentage (75%) of patients who meet the Task Force criteria for ARVD. Trabecular disarray is seen more frequently than wall thinning and aneurysms. RV dimensions and volumes differ significantly in ARVD compared to controls, indicating a role for quantitative evaluation in the diagnosis of ARVD.