Risk Stratification in Arrhythmic Right Ventricular Cardiomyopathy Without Implantable Cardioverter-Defibrillators.

OBJECTIVES: The primary objective of this study is risk stratification of patients with arrhythmic right ventricular cardiomyopathy (ARVC). BACKGROUND: There is a need to identify those who need an automatic implantable defibrillator (ICD) to prevent sudden death. METHODS: This is an analysis of 88 patients with ARVC from three centers who were not treated with an ICD. RESULTS: Risk factors for subsequent arrhythmic deaths were pre-enrollment sustained or nonsustained ventricular tachycardia (VT) and decreased left ventricular function. CONCLUSION: These factors serve as proposed guidelines for implantation of an ICD in patients with ARVC to prevent sudden death.

Ventricular arrhythmias in the North American multidisciplinary study of ARVC: predictors, characteristics, and treatment.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with sudden cardiac death. However, the selection of patients for implanted cardioverter-defibrillators (ICDs), as well as programming of the ICD, is unclear. OBJECTIVES: The objective of this study was to identify predictors, characteristics, and treatment of ventricular arrhythmias in patients with ARVC. METHODS: The Multidisciplinary Study of Right Ventricular Cardiomyopathy established the North American ARVC Registry and enrolled patients with a diagnosis of ARVC. Patients were followed prospectively. RESULTS: Of 137 patients enrolled, 108 received ICDs. Forty-eight patients had 502 sustained episodes of ventricular arrhythmias, including 489 that were monomorphic and 13 that were polymorphic. In the patients with ICDs, independent predictors of ventricular arrhythmias in follow-up included spontaneous sustained ventricular arrhythmias before ICD implantation and T-wave inversions inferiorly. The only independent predictor for life-threatening arrhythmias, defined as sustained ventricular tachycardia (VT) ≥240 beats/min or ventricular fibrillation, was a younger age at enrollment. Anti-tachycardia pacing (ATP), independent of the cycle length of the VT, was successful in terminating 92% of VT episodes. CONCLUSIONS: In the North American ARVC Registry, the majority of ventricular arrhythmias in follow-up are monomorphic. Risk factors for ventricular arrhythmias were spontaneous ventricular arrhythmias before enrollment and a younger age at ICD implantation. ATP is highly successful in terminating VT, and all ICDs should be programmed for ATP, even for rapid VT.

Right ventricular volume analysis by angiography in right ventricular cardiomyopathy.

Imaging of the right ventricle (RV) for the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is commonly performed by echocardiography or magnetic resonance imaging (MRI). Angiography is an alternative modality, particularly when MRI cannot be performed. We hypothesized that RV volume and ejection fraction computed by angiography would correlate with these quantities as computed by MRI. RV volumes and ejection fraction were computed for subjects enrolled in the North American ARVC/D Registry, with both RV angiography and MRI studies. Angiography was performed in the 30° right anterior oblique (RAO) and 60° left anterior oblique (LAO) views. Angiographic volumes were computed by RAO view and two-view (RAO and LAO) formulae. 17 subjects were analyzed (11 men and 6 women), with 15 subjects classified as affected, and two as unaffected by modified Task Force criteria. The correlation coefficient of MRI to the two-view angiographic analysis was 0.72 (P = 0.003) for end-diastolic volume and 0.68 (P = 0.005) for ejection fraction. Angiographically derived volumes were larger than MRI derived volume (P = 0.009) and with the slope in a linear relationship equal to 0.8 for end diastolic volume, and 0.9 for RV ejection fraction (P < 0.001), computed by the two view formula. End-diastolic volumes and ejection fractions of the RV obtained by dual view angiography correlate with these quantities by MRI. RV end-diastolic volumes are larger by RV angiography in comparison with MRI.

Electrocardiographic comparison of ventricular arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy and right ventricular outflow tract tachycardia.

OBJECTIVES: The purpose of this study was to evaluate whether electrocardiographic characteristics of ventricular arrhythmias distinguish patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) from those with right ventricular outflow tract tachycardia (RVOT-VT). BACKGROUND: Ventricular arrhythmias in RVOT-VT and ARVD/C-VT patients can share a left bundle branch block/inferior axis morphology. METHODS: We compared the electrocardiographic morphology of ventricular tachycardia or premature ventricular contractions with left bundle branch block/inferior axis pattern in 16 ARVD/C patients with that in 42 RVOT-VT patients. RESULTS: ARVD/C patients had a significantly longer mean QRS duration in lead I (150 ± 31 ms vs. 123 ± 34 ms, p = 0.006), more often exhibited a precordial transition in lead V(6) (3 of 17 [18%] vs. 0 of 42 [0%] with RVOT-VT, p = 0.005), and more often had at least 1 lead with notching (11 of 17 [65%] vs. 9 of 42 [21%], p = 0.001). The most sensitive characteristics for the detection of ARVD/C were a QRS duration in lead I of ≥120 ms (88% sensitivity, 91% negative predictive value). QRS transition at V(6) was most specific at 100% (100% positive predictive value, 77% negative predictive value). The presence of notching on any QRS complex had 79% sensitivity and 65% specificity of (55% positive predictive value, 85% negative predictive value). In multivariate analysis, QRS duration in lead I of ≥120 ms (odds ratio [OR]: 20.4, p = 0.034), earliest onset QRS in lead V(1) (OR: 17.0, p = 0.022), QRS notching (OR: 7.7, p = 0.018), and a transition of V(5) or later (OR: 7.0, p = 0.030) each predicted the presence of ARVD/C. CONCLUSIONS: Several electrocardiographic criteria can help distinguish right ventricular outflow tract arrhythmias originating from ARVD/C compared with RVOT-VT patients.

Value of the signal-averaged electrocardiogram in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited disease that causes structural and functional abnormalities of the right ventricle (RV). The presence of late potentials as assessed by the signal-averaged electrocardiogram (SAECG) is a minor task force criterion. OBJECTIVE: The purpose of this study was to examine the diagnostic and clinical value of the SAECG in a large population of genotyped ARVC/D probands. METHODS: We compared the SAECGs of 87 ARVC/D probands (age 37 ± 13 years, 47 males) diagnosed as affected or borderline by task force criteria without using the SAECG criterion with 103 control subjects. The association of SAECG abnormalities was also correlated with clinical presentation, surface ECG, ventricular tachycardia (VT) inducibility at electrophysiologic testing, implantable cardioverter-defibrillator therapy for VT, and RV abnormalities as assessed by cardiac magnetic resonance imaging (cMRI). RESULTS: Compared with controls, all three components of the SAECG were highly associated with the diagnosis of ARVC/D (P <.001). They include the filtered QRS duration (97.8 ± 8.7 ms vs 119.6 ± 23.8 ms), low-amplitude signal (24.4 ± 9.2 ms vs 46.2 ± 23.7 ms), and root mean square amplitude of the last 40 ms of the QRS (50.4 ± 26.9 µV vs 27.9 ± 36.3 µV). The sensitivity of using SAECG for diagnosis of ARVC/D was increased from 47% using the established 2 of 3 criteria (i.e., late potentials) to 69% by using a modified criterion of any 1 of 3 criteria, while maintaining a high specificity of 95%. Abnormal SAECG as defined by this modified criterion was associated with a dilated RV volume and decreased RV ejection fraction detected by cMRI (P <.05). SAECG abnormalities did not vary with clinical presentation or reliably predict spontaneous or inducible VT and had limited correlation with ECG findings. CONCLUSION: Using 1 of 3 SAECG criteria contributed to increased sensitivity and specificity for the diagnosis of ARVC/D. This finding is incorporated in the recent modification of the task force criteria.

Usefulness of precordial T-wave inversion to distinguish arrhythmogenic right ventricular cardiomyopathy from idiopathic ventricular tachycardia arising from the right ventricular outflow tract.

The 2 predominant causes of ventricular tachycardia (VT) arising from the right ventricle are arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic VT arising from the right ventricular outflow tract (RVOT). These arrhythmias can be adrenergically mediated and may be difficult to distinguish clinically. A minor criterion for the diagnosis of ARVC is T-wave inversion (TWI) in the right precordial leads during sinus rhythm. However, there have been reports of precordial TWI identified in patients with RVOT tachycardia. The purpose of this study was to determine whether patterns of precordial TWI could differentiate between the 2 groups. A multicenter registry of 229 patients with VT of right ventricular origin was evaluated. After appropriate exclusions (n = 29), 79 patients (58% men, mean age 40 +/- 14 years) had ARVC, and 121 patients (41% men, mean age 48 +/- 14 years) had RVOT tachycardia. During sinus rhythm, 37 patients (47%) with ARVC and 5 patients (4%) with RVOT tachycardia had TWI in leads V(1) to V(3). For the diagnosis of ARVC, TWI in leads V(1) to V(3) had sensitivity of 47% and specificity of 96%. In conclusion, in patients with VT of right ventricular origin, the presence of TWI in electrocardiographic leads V(1) to V(3) supports the diagnosis of ARVC.

Pitfalls in the diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia.

The diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia is determined according to Task Force Criteria published in 1994 that included imaging abnormalities of the right ventricle and diagnostic pathologic evaluation findings of the right ventricular myocardium by endomyocardial biopsy. These have recently been modified to include evaluation using cardiac magnetic resonance imaging. In addition, quantitative criteria for the percentage of fibrosis and the decrease in myocytes have been included in the new criteria. The pitfalls of determining the presence of arrhythmogenic right ventricular cardiomyopathy/dysplasia at autopsy and the difficulty in assessing the presence of this disease in family members are well illustrated in the present report. In conclusion, we have illustrated the need to subscribe to the modified criteria to avoid misdiagnosis.

Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria.

BACKGROUND: In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. METHODS AND RESULTS: Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. CONCLUSIONS: The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00024505.

Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria.

BACKGROUND: In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. METHODS AND RESULTS: Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. CONCLUSIONS: The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. Clinical Trial Registration clinicaltrials.gov Identifier: NCT00024505.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: results from the North American Multidisciplinary Study.

BACKGROUND: Prior reports on patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) focused on individuals with advanced forms of the disease. Data on the diagnostic performance of various testing modalities in newly identified individuals suspected of having ARVC/D are limited. OBJECTIVE: The purpose of the Multidisciplinary Study of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia was to study the clinical characteristics and diagnostic evaluation of a large group of patients newly identified with ARVC/D. METHODS: A total of 108 newly diagnosed patients with suspected ARVC/D were prospectively enrolled in the United States and Canada. The patients underwent noninvasive and invasive tests using standardized protocols that initially were interpreted by the enrolling center and adjudicated by blind analysis in six core laboratories. Patients were followed for a mean of 27 +/- 16 months (range 0.2-63 months). RESULTS: The clinical profile of these newly diagnosed patients differs from the profile of reported patients with more advanced disease. There was considerable difference in the initial and final classification of the presence of ARVC/D after the diagnostic tests were evaluated by the core laboratories. Final clinical diagnosis was 73 affected, 28 borderline, and 7 unaffected. Individual tests agreed with the final diagnosis in 50% to 70% of the 73 patients with a final classification of affected. CONCLUSION: The clinical profile of 108 newly diagnosed probands with suspected ARVC/D indicates that a combination of diagnostic tests is needed to evaluate the presence of right ventricular structural, functional, and electrical abnormalities. Echocardiography, right ventricular angiography, signal-averaged ECG, and Holter monitoring provide optimal clinical evaluation of patients suspected of ARVC/D.

Quantitative assessment of angiographic right ventricular wall motion in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C).

INTRODUCTION: Angiography of the right ventricle (RV) is a standard, reference technique to diagnose wall motion abnormalities in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). RV wall motion is usually assessed by qualitative, visual impression, and has lacked a quantitative basis for defining abnormalities. Since the normal RV has a markedly asymmetric movement, angiographic interpretation can differ, even among experienced clinicians. The purpose of this study was to quantify RV wall motion based on contrast ventriculography in patients with ARVD/C and to specify the severity and location of wall motion abnormalities, as compared with normal subjects. METHODS AND RESULTS: We analyzed the angiographic contours of the RV in three views from 19 normal subjects and 23 subjects with ARVD/C. Contour area movement during contraction was calculated circumferentially and further analyzed in nine zones. RV ejection fraction was also computed. Wall motion in ARVD/C was depressed by more than 30% at the tricuspid valve and inferior wall regions (P < 0.001) and significantly reduced at the apex (P = 0.003). However, the RVOT and anterior wall motion were not significantly reduced. RV ejection fraction was depressed from 60 +/- 11% in normal subjects to 41 +/- 12% in ARVD/C patients (P < 0.001). CONCLUSION: Wall motion abnormalities in ARVD/C can be quantified and compared with normal controls, showing primarily reduced movement in the tricuspid and inferior wall regions. This study delineates objective measurements that can be used to aid in the diagnosis of ARVD/C. In addition, they may be incorporated in future refinements of criteria to diagnose ARVD/C.

Do patients with right ventricular outflow tract ventricular arrhythmias have a normal right ventricular wall motion? A quantitative analysis compared to normal subjects.

BACKGROUND/AIM: Patients with ventricular ectopy from the right ventricular (RV) outflow tract (RVOT) are often referred for RV angiography to exclude disorders such as arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D). This is usually based on a qualitative assessment of the wall motion. We present a method to quantify the wall motion and to apply this method to compare patients with RVOT ectopy to normal subjects. METHODS: RV angiograms were analyzed from 19 normal subjects and 11 subjects with RVOT ventricular arrhythmias (RVOT arrhythmia subjects) who had no other clinical or other evidence for ARVC/D. By a newly developed computer-based method, RV contours were first traced from multiple frames spanning the entire cardiac cycle. The fractional change in area between contours was then calculated as a serial function of time and location to determine both total contour area change and timing of contour movement. Contour area strain, defined as the differential change in area between nearby regions, was also computed. RESULTS: The contour area change was greatest in the tricuspid valve region and least in the RVOT and midanterior regions. The onset of contraction was earliest in the RVOT region and latest in the apical, inferior, inferoapical, and subtricuspid valve regions. The contour strain was largest in superior tricuspid valve and inferior wall and near zero within the lateral tricuspid valve region. There were significant pairwise differences in contraction area, timing, and strain in the various regions. There were no significant differences between normal subjects and RVOT arrhythmia subjects. CONCLUSIONS: The RV wall motion is nonuniform in contour area change, strain, and timing of motion. Patients with RVOT ventricular ectopy demonstrate wall motion parameters similar to those of normal subjects. This technique should be applicable in analyzing RV wall motion in patients suspected of having ARVC/D.

Psychological stress preceding idiopathic ventricular fibrillation.

OBJECTIVE: Emotional stress is well established as a trigger of sudden death in the context of coronary heart disease (CHD), but its role in patients experiencing cardiac arrest with apparently normal hearts is unknown. This study sought to determine the role of psychosocial stress as a precipitant of cardiac arrest in patients with apparently normal hearts, so-called idiopathic ventricular fibrillation (IVF). METHODS: We interviewed 25 IVF survivors (12 men, 13 women) and 25 matched comparison patients regarding life events during the 6 months and 24 hours preceding the cardiac event. The comparison group consisted of patients with an acute myocardial infarction or angina pectoris requiring angioplasty but without cardiac arrest. Judges independently rated written summaries of these interviews for psychosocial stress at each time point on a three-point scale (low, moderate, severe). RESULTS: During the 6 months before the cardiac event, 20 patients sustaining IVF had severe/moderate stress and five had low stress, whereas 10 comparison patients had severe/moderate stress and 15 had low stress (Fisher exact p = .008). During the preceding 24 hours, nine patients with IVF had severe/moderate stress and 16 had low stress, whereas two comparison patients had severe/moderate stress and 22 had low stress (Fisher exact p = .04) (one silent myocardial infarction could not be precisely dated). CONCLUSION: These data suggest that psychosocial stress is playing a role in otherwise unexplained cardiac arrest.

MR Imaging of arrhythmogenic right ventricular cardiomyopathy: morphologic findings and interobserver reliability.

BACKGROUND: Magnetic resonance (MR) imaging is frequently used to diagnose arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). However, the reliability of various MR imaging features for diagnosing ARVC/D is unknown. The purpose of this study was to determine which morphologic MR imaging features have the greatest interobserver reliability for diagnosing ARVC/D. METHODS: Forty-five sets of films of cardiac MR images were sent to 8 radiologists and 5 cardiologists with experience in this field. There were 7 cases of definite ARVC/D as defined by the Task Force criteria. Six cases were controls. The remaining 32 cases had MR imaging because of clinical suspicion of ARVC/D. Readers evaluated the images for the presence of (a) right ventricle (RV) enlargement, (b) RV abnormal morphology, (c) left ventricle enlargement, (d) presence of high T(1) signal (fat) in the myocardium, and (e) location of high T(1) signal (fat) on a Likert scale with formatted responses. RESULTS: Readers indicated that the Task Force ARVC/D cases had significantly more (chi(2) = 119.93, d.f. = 10, p < 0.0001) RV chamber size enlargement (58%) than either the suspected ARVC/D (12%) or no ARVC/D (14%) cases. When readers reported the RV chamber size as enlarged they were significantly more likely to report the case as ARVC/D present (chi(2)(= )33.98, d.f. = 1, p < 0.0001). When readers reported the morphology as abnormal they were more likely to diagnose the case as ARVC/D present (chi(2) = 78.4, d.f. = 1, p < 0.0001), and the Task Force ARVC/D (47%) cases received significantly more abnormal reports than either suspected ARVC/D (20%) or non-ARVC/D (15%) cases. There was no significant difference between patient groups in the reported presence of high signal intensity (fat) in the RV (chi(2) = 0.9, d.f. = 2, p > 0.05). CONCLUSIONS: Reviewers found that the size and shape of abnormalities in the RV are key MR imaging discriminates of ARVD. Subsequent protocol development and multicenter trials need to address these parameters. Essential steps in improving accuracy and reducing variability include a standardized acquisition protocol and standardized analysis with dynamic cine review of regional RV function and quantification of RV and left ventricle volumes.