Kathleen Gear

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.

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.

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 T1 signal (fat) in the myocardium, and (e) location of high T1 signal (fat) on a Likert scale with formatted responses. Results: Readers indicated that the Task Force ARVC/D cases had significantly more (χ2 = 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 (χ2= 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 (χ2 = 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 (χ2 = 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.

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.

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) A Multidisciplinary Study: Design and Protocol

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a relatively newly recognized disease. A clinical profile of patients with this condition was first published in 1982.1 In that report, it was observed that the majority of patients were male. Patients presented with ventricular tachycardia of left bundle-branch block morphology. An enlarged right ventricle due to fibrofatty infiltration of the right ventricular free wall and a familial association were noted. It was considered to be a rare disease of unknown cause. Since then, it has been diagnosed with increasing frequency and has been reported to account for 3% to 5% of unexplained sudden cardiac death under the age of 65 years.2,3 Evidence of the disease is found in 30% to 50% of family members who are studied by noninvasive tests, including ECG, echocardiography, and signal-averaged ECG.4,5 It has been suggested that MRI may also be used for diagnostic purposes, but this remains controversial.6,7 Six genetic loci have been reported to be associated with ARVD/C, and 3 genes have been identified: ryanodine receptor (RyR2),8 plakoglobin (JUP),9and desmoplakin (DSM).10 There is autosomal dominant transmission with all the genetic forms except Naxos disease8 and Carvahal syndrome,11 both of which have autosomal recessive transmission. These 2 autosomal recessive disorders are variants of ARVD/C that are associated with skin and hair abnormalities. The cardiac presentation in Carvahal syndrome is that of a left ventricular cardiomyopathy and arrhythmias. With the recognition that ARVD/C is frequently familial and can cause arrhythmic death, the clinical challenge is how to definitively identify individuals with ARVD/C who have mild or minimal structural abnormalities of the right ventricle. Definite identification of minimal structural abnormalities of the right ventricle can be difficult because of the irregular shape and asymmetrical contractile pattern …

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.

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.

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Abstract—Arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) is a heart muscle disease characterized by peculiar RV involvement and electrical instability that precipitates vent...

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. CHD = coronary heart disease; DSM-IV = Diagnostic and Statistical Manual, Fourth Edition; ICD = implantable cardioverter defibrillator; IVF = idiopathic ventricular fibrillation; IVF-US = Idiopathic Ventricular Fibrillation Registry of the United States; UCARE = Unexplained Cardiac Arrest Registry of Europe.