Chandra Bomma

Arrhythmogenic Right Ventricular Dysplasia: A United States Experience

Background— Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by right ventricular dysfunction and ventricular arrhythmias. The purpose of our study was to describe the presentation, clinical features, survival, and natural history of ARVD in a large cohort of patients from the United States. Methods and Results— The patient population included 100 ARVD patients (51 male; median age at presentation, 26 [interquartile range {IQR}, 18 to 38; range, 2 to 70] years). A familial pattern was observed in 32 patients. The most common presenting symptoms were palpitations, syncope, and sudden cardiac death (SCD) in 27%, 26%, and 23% of patients, respectively. Among those who were diagnosed while living (n=69), the median time between first presentation and diagnosis was 1 (range, 0 to 37) year. During a median follow-up of 6 (IQR, 2 to 13; range, 0 to 37) years, implantable cardioverter/defibrillators (ICD) were implanted in 47 patients, 29 of whom received an appropriate ICD discharge, including 3 patients who received the ICD for primary prevention. At follow-up, 66 patients were alive, of whom 44 had an ICD in place, 5 developed signs of heart failure, 2 had a heart transplant, and 18 were on drug therapy. Thirty-four patients died either at presentation (n=23: 21 SCD, 2 noncardiac deaths) or during follow-up (n=11: 10 SCD, 1 of biventricular heart failure), of whom only 3 were diagnosed while living and 1 had an ICD implanted. On Kaplan-Meier analysis, the median survival in the entire population was 60 years. Conclusions— ARVD patients present between the second and fifth decades of life either with symptoms of palpitations and syncope associated with ventricular tachycardia or with SCD. Diagnosis is often delayed. Once diagnosed and treated with an ICD, mortality is low. There is a wide variation in presentation and course of ARVD patients, which can likely be explained by the genetic heterogeneity of the disease.

Electrocardiographic features of arrhythmogenic right ventricular dysplasia/cardiomyopathy according to disease severity: A need to broaden diagnostic criteria

Background—The purpose of this study was to systematically study diagnostic and prognostic electrocardiographic (ECG) characteristics of arrhythmogenic right ventricle dysplasia/cardiomyopathy (ARVD/C). Methods and Results—The patient population included 50 patients with ARVD/C (27 males, 23 females; mean age 38±15 years). We also analyzed the ECG of 50 age- and gender-matched normal control subject and 28 consecutive patients who presented with right ventricular outflow tract (RVOT) tachycardia. Right bundle-branch block (RBBB) was present in 11 patients (22%). T-wave inversions in V1 through V3 were observed in 85% of ARVD/C patients in the absence of RBBB compared with none in RVOT and normal controls, respectively (P<0.0001); epsilon waves were seen in 33%, and a QRS duration ≥110 ms in V1 through V3 was present in 64% of patients. Among those without RBBB, our newly proposed criterion of “prolonged S-wave upstroke in V1 through V3” ≥55 ms was the most prevalent ECG feature (95%) and correlated with disease severity and induction of VT on electrophysiological study. This feature also best distinguished ARVD/C (diffuse and localized) from RVOT. Conclusions—A prolonged S-wave upstroke in V1 through V3 is the most frequent ECG finding in ARVD/C and should be considered as a diagnostic ECG marker.

Clinical Features of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Associated With Mutations in Plakophilin-2

Background— Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterized by right ventricular dysfunction and ventricular arrhythmias. A recent study reported mutations in PKP2, encoding the desmosomal protein plakophilin-2, associated with ARVD/C. The purpose of our study was to validate the frequency of PKP2 mutations in another large series of ARVD/C patients and to examine the phenotypic characteristics associated with PKP2 mutations. Methods and Results— DNA from 58 ARVD/C patients was sequenced to determine the presence of mutations in PKP2. Clinical features of ARVD/C were compared between 2 groups of patients: those with a PKP2 mutation and those with no detectable PKP2 mutation. Thirteen different PKP2 mutations were identified in 25 (43%) of the patients. Six of these mutations have not been reported previously; 4 occurred in multiple, apparently unrelated, families. The mean age at presentation was lower among those with a PKP2 mutation (28±11 years) than in those without (36±16 years) (P<0.05). The age at median cumulative symptom-free survival (32 versus 42 years) and at the median cumulative arrhythmia-free survival (34 versus 46 years) was lower among patients with a PKP2 mutation than among those without a PKP2 mutation (P<0.05). Inducibility of ventricular arrhythmias on an electrophysiology study, diffuse nature of right ventricular disease, and presence of prior spontaneous ventricular tachycardia were identified as predictors of implanted cardioverter/defibrillator (ICD) intervention only among patients without a PKP2 mutation (P<0.05). Conclusions— Our study highlights the clinical relevance of PKP2 mutations in ARVD/C. Presence of a PKP2 mutation in ARVD/C correlates with earlier onset of symptoms and arrhythmia. Patients with a PKP2 mutation experience ICD interventions irrespective of the classic risk factors determining ICD intervention in ARVD/C patients.

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.

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.

Magnetic resonance and computed tomography imaging of arrhythmogenic right ventricular dysplasia

Arrhythmogenic right ventricular dysplasia (ARVD) is a familial cardiomyopathy that causes fibro‐fatty replacement of the right ventricle (RV), leading to sudden death due to ventricular arrhythmias. The disease is an important cause of sudden death in individuals younger than 35 years of age. Structural and functional abnormalities of the RV constitute an important diagnostic criterion for the disease. Diagnosis of ARVD is often a challenge as conventional imaging modalities have significant limitations to visualize the RV. Recently, magnetic resonance imaging (MRI) and computed tomographic (CT) imaging have emerged as robust clinical tools for evaluation of myocardial pathology. In addition to providing morphologic and functional information, both imaging modalities have the ability to demonstrate intramyocardial fat, which is the pathological hallmark in ARVD. This article discusses the current status and role of MRI and CT imaging in the diagnosis of ARVD. J. Magn. Reson. Imaging 2004;19:848–858.

Cardiac magnetic resonance imaging in a patient with implantable cardioverter-defibrillator

The presence of pacemakers and implantable cardioverter‐defibrillators (ICD) is considered historically a contraindication to magnetic resonance (MR) imaging. This image modality has unparalleled soft‐tissue imaging capabilities, and many consider it as the image of choice for patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). ICDs are now smaller, with less magnetic materials and improved electromagnetic interference protection. We tested modern ICDs for heat, force, function and image distortion and found that several of them may indeed be MRI safe. We report here a patient who was suspected of ARVD/C, underwent ICD implantation based on MR safety testing, and underwent intentionally scheduled follow‐up cardiac MR imaging. This is the description of a patient with an ICD who had planned MRI scanning. The scan was safe and most of the MRI images were of high quality.

The apparent inversion time for optimal delayed enhancement magnetic resonance imaging differs between the right and left ventricles.

BACKGROUND Delayed post-contrast magnetic resonance (MR) imaging involves suppression of signal from myocardium using inversion times (TI) between 150-225 ms, when the myocardium appears dark and fibrotic scar appears bright. We noticed that at a TI optimized for signal suppression of the left ventricle (LV), the right ventricle (RV) appeared brighter. PURPOSE The purpose of this study was to evaluate the TI for signal suppression in RV compared to LV, and to try and identify the cause of this observation. Methods. We studied 31 patients (ages ranged from 17-79 years, 11 females) who had an MR scan on a 1.5 T GE scanner. Delayed post-contrast short-axis images were obtained 20 minutes after injection of 0.2 mmol/kg of intravenous gadolinium chelate. TI optimization was performed by acquiring a range of TI times within a single breath hold, in increments of 25 msec. The TI time that resulted in lowest signal for the RV arid LV was recorded. RESULTS With the imaging sequence employed, the TI leading to LV signal suppression ranged from 150-225 ms. At the TI that resulted in LV signal suppression, the corrected signal from the RV was significantly higher as compared to the LV (29 +/- 13 au vs. 15 +/- 8 au, p < 0.001). The findings were similar using only the body coil. The TI required to suppress the RV was usually < or =150 msec. The observation persisted before and after gadolinium infusion. CONCLUSION The TI for myocardial signal suppression appears to be different between LV and RV. Potential mechanisms include partial volume averaging with fat or blood pool (related to increased trabeculation) in the RV. Alternatively, increased blood pool signal (within Thebesian veins or arterioluminal communications) in RV compared to LV leads to altered TI times due to similar partial volume effects.

Right ventricle shape and contraction patterns and relation to magnetic resonance imaging findings

Objective: To analyze and to describe the shape and contraction of the normal right ventricle (RV) as visualized by magnetic resonance imaging (MRI). Methods: Thirty normal volunteers were imaged using cine MRI in axial, short-axis, and long-axis planes. The shape and contraction of the RV were qualitatively evaluated. Quantitative evaluation of RV shape was performed by calculating the angle subtended between the planes of horizontal long-axis view (HLA) and axial view and the RV base-to-apex distance. Multiplanar reformation was used to visualize changes between corresponding views. Results: The spectrum of major RV shape (wedge, box, and round) was more variable on axial images (17%, 43%, and 23%, respectively) than on HLA images (63%, 20%, and 0%, respectively). Focal outpouching of the RV free wall was more frequent on the axial view than on the HLA view. The subtended plane angle and base-to-apex distance showed statistically significant dependence indicative of an artificially foreshortened RV in the axial view with a direct influence on RV variations. Conclusions: With increasing subtended angles, variation of the normal RV appearance is substantially higher on axial views compared with HLA views.

Comparison of left ventricular size by computed tomography with magnetic resonance imaging measures of left ventricle mass and volumes: The multi-ethnic study of atherosclerosis

BACKGROUND A non-contrast-enhanced cardiac computed tomography (NCE-CCT) scan for assessing coronary artery calcification (CAC) is being increasingly used for assessing underlying burden of atherosclerosis. Although many studies document the potential value of measuring CAC, little is known about the other measures such as left ventricular (LV) geometry that can be obtained from the same scan data. OBJECTIVES We sought to evaluate the accuracy of noncontrast CT-derived LV size (LVS; sum of LV volume and mass) compared with magnetic resonance imaging (MRI)-derived measures as the clinical reference standard. METHODS Participants (n = 5004) in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent cardiac MRI studies from August 2000 to September 2002 were included. CT-derived LVS was defined as the sum of LV mass and LV intracavitary volume. The calculated LVS was taken from a measurement of a single slice from noncontrast images. Multivariate analysis adjusting for demographics was used to identify predictors of the relation between CT LVS and MRI LVS, and Bland-Altman analysis was performed comparing MRI-derived measures with CT-derived measure of LVS. RESULTS The mean CT LVS was 187.8 +/- 56.8 mL (range, 33.6-486.4 mL). The correlation was 0.73 (P = 0.01) for MRI-derived LV volume and 0.74 (P = 0.01) for MRI-derived LV mass. The correlation between CT LVS and MRI-derived LV end-diastolic total volume (mass + volume) was 0.79. CONCLUSION A single NCE-CT scan used to detect and quantify coronary calcification can also estimate LVS with reasonable accuracy compared with MRI. This provides a new method to study ventricular size in epidemiologic studies and potentially provide additional information for clinical screening of cardiac risk.