Jim W. Cheung

Reversal of Cardiomyopathy in Patients With Repetitive Monomorphic Ventricular Ectopy Originating From the Right Ventricular Outflow Tract

Background—Tachycardia-induced cardiomyopathy caused by ventricular tachycardia is a well-defined clinical entity. Less well appreciated is whether simple ventricular ectopy can result in cardiomyopathy. We sought to examine a potential causal relationship between repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract and cardiomyopathy and the role of ablation in reversing this process. Methods and Results—The study consisted of 27 patients (11 men; age, 47±15 years) with repetitive monomorphic ventricular ectopy, including 8 patients (30%) with depressed ventricular function (ejection fraction ≤45%). All patients underwent assessment of cardiac structure and function. The burden of ectopy was quantified through 24-hour Holter monitoring. Patients then underwent ablation guided by 3D mapping. After ablation, patients underwent repeated Holter monitoring and reassessment of cardiac function. Patients with depressed ventricular function were more likely to be older than patients with normal function (58±14 versus 42±18 years; P=0.013). However, the burden of ventricular ectopy was similar in patients with (17 859±13 488 ectopic beats per 24 hours) and without (17 541±11 479 ectopic beats per 24 hours; P=0.800) preserved ventricular function. Successful ablation was performed in 23 patients (85%), including 7 of 8 patients with depressed ventricular function. In this latter group, ventricular function improved in all patients (from 39±6% to 62±6%; P=0.017). Conclusions—Repetitive monomorphic ventricular ectopy (in the absence of sustained ventricular tachycardia) originating from the right ventricular outflow tract is an underappreciated cause of unexplained cardiomyopathy. Successful ablation of the focal source of ventricular ectopy results in normalization of left ventricular function. Patients with ectopy-induced cardiomyopathy are significantly older than patients with preserved ventricular function, which suggests either that older patients are more susceptible to the development of a cardiomyopathy or that the cardiomyopathy has had a longer period of time in which to evolve.

Right and left ventricular outflow tract tachycardias : Evidence for a common electrophysiologic mechanism

Introduction:“Idiopathic” ventricular arrhythmias most often arise from the right ventricular outflow tract (RVOT), although arrhythmias from the left ventricular outflow tract (LVOT) are also observed. While previous work has elucidated the mechanism and electropharmacologic profile of RVOT arrhythmias, it is unclear whether those from the LVOT share these properties. The purpose of this study was to characterize the electropharmacologic properties of RVOT and LVOT arrhythmias.

Newly Detected Atrial Fibrillation Following Dual Chamber Pacemaker Implantation

Introduction: Pacemaker (PPM)‐detected atrial high‐rate episodes (AHREs) of even 5‐minute duration may identify patients at increased risk for stroke and death. In this study, we sought to determine the incidence of newly detected atrial fibrillation (AF defined as an AHRE ≥5 minutes) in patients following dual‐chamber PPM implantation and to define the clinical predictors of developing AF.

Temporal Associations Between Thoracic Volume Overload and Malignant Ventricular Arrhythmias: A Study of Intrathoracic Impedance

Volume Overload and Ventricular Arrhythmias. Background: Acute exacerbations of heart failure (HF) are believed to trigger malignant ventricular arrhythmias, but the temporal association between fluid accumulation and ventricular arrhythmias has not been evaluated in an objective manner. We hypothesized that increased intrathoracic fluid accumulation in patients with HF, as measured by an index of intrathoracic impedance, is associated with an increased risk of ventricular arrhythmias.

Ubiquitous myocardial extensions into the pulmonary artery demonstrated by integrated intracardiac echocardiography and electroanatomic mapping: changing the paradigm of idiopathic right ventricular outflow tract arrhythmias.

Background— Idiopathic ventricular arrhythmias of left bundle branch block inferior axis morphology are usually localized to the right ventricular outflow tract (RVOT), presumably below the pulmonic valve (PV). However, the PV location is usually not confirmed by direct visualization. Methods and Results— Intracardiac echocardiography was used to visualize and tag the PV annulus, which was then integrated with 3-dimensional voltage maps of the RVOT. Distances were measured from the furthest extent of myocardial signal (bipolar voltage ≥1.5 mV) to the PV annulus. This was performed in 24 control patients and 24 prospective patients with RVOT arrhythmias. Myocardial signal beyond the PV was found in 92% of controls and 88% of RVOT arrhythmia patients ( P =1.000). Average myocardial extension was further on the septal side than on the free wall side for control patients (5.6 mm; interquartile range [IQR], 3.6–7.7, versus 1.7 mm; IQR (−)0.1 to (+)4.0; P =0.002) and RVOT arrhythmia patients (5.7 mm; IQR, 2.7–7.7, versus 1.4 mm; IQR, (−)0.8 to (+)4.8; P =0.004). Eleven (46%) RVOT arrhythmia foci were localized beyond the valve in the pulmonary artery (median 8.2 mm above PV; IQR, 6.6–10.3 mm); these locations were confirmed as supravalvular by direct intracardiac echocardiography visualization. Conclusions— Myocardial voltage extension into the pulmonary artery in humans is ubiquitous and can be demonstrated in vivo using 3-dimensional integrated intracardiac echocardiography to localize the PV. These extensions frequently serve as origins of presumed RVOT arrhythmias; intracardiac echocardiography localization of the PV allows reclassification of these as pulmonary arterial arrhythmias.Background—Idiopathic ventricular arrhythmias of left bundle branch block inferior axis morphology are usually localized to the right ventricular outflow tract (RVOT), presumably below the pulmonic valve (PV). However, the PV location is usually not confirmed by direct visualization. Methods and Results—Intracardiac echocardiography was used to visualize and tag the PV annulus, which was then integrated with 3-dimensional voltage maps of the RVOT. Distances were measured from the furthest extent of myocardial signal (bipolar voltage ≥1.5 mV) to the PV annulus. This was performed in 24 control patients and 24 prospective patients with RVOT arrhythmias. Myocardial signal beyond the PV was found in 92% of controls and 88% of RVOT arrhythmia patients (P=1.000). Average myocardial extension was further on the septal side than on the free wall side for control patients (5.6 mm; interquartile range [IQR], 3.6–7.7, versus 1.7 mm; IQR (−)0.1 to (+)4.0; P=0.002) and RVOT arrhythmia patients (5.7 mm; IQR, 2.7–7.7, versus 1.4 mm; IQR, (−)0.8 to (+)4.8; P=0.004). Eleven (46%) RVOT arrhythmia foci were localized beyond the valve in the pulmonary artery (median 8.2 mm above PV; IQR, 6.6–10.3 mm); these locations were confirmed as supravalvular by direct intracardiac echocardiography visualization. Conclusions—Myocardial voltage extension into the pulmonary artery in humans is ubiquitous and can be demonstrated in vivo using 3-dimensional integrated intracardiac echocardiography to localize the PV. These extensions frequently serve as origins of presumed RVOT arrhythmias; intracardiac echocardiography localization of the PV allows reclassification of these as pulmonary arterial arrhythmias.

Frequent recurrent polymorphic ventricular tachycardia during sleep due to managed ventricular pacing.

We report a case of a patient with an implantable cardioverter defibrillator and no prior history of heart block with managed ventricular pacing (MVP) programmed who had frequent recurrent episodes of polymorphic ventricular tachycardia. All of the episodes were initiated by transient atrioventricular block which resulted in short‐long‐short sequences permitted by MVP. This case illustrates that MVP should be used with caution not only in patients with complete heart block, but also in patients at risk for brief heart block due to such states as hypervagatonia due to sleep apnea. (PACE 2010; 641–644)

Short-coupled polymorphic ventricular tachycardia at rest linked to a novel ryanodine receptor (RyR2) mutation: Leaky RyR2 channels under non-stress conditions

BACKGROUND Ryanodine receptor (RyR2) mutations have largely been associated with catecholaminergic polymorphic ventricular tachycardia (PMVT). The role of RyR2 mutations in the pathogenesis of arrhythmias and syncope at rest is unknown. We sought to characterize the clinical and functional characteristics associated with a novel RyR2 mutation found in a mother and daughter with PMVT at rest. METHODS AND RESULTS A 31-year-old female with syncope at rest and recurrent short-coupled premature ventricular contractions (PVCs) initiating PMVT was found to be heterozygous for a novel RyR2-H29D mutation. Her mother, who also had syncope at rest and short-coupled PMVT, was found to harbor the same mutation. Human RyR2-H29D mutant channels were generated using site-directed mutagenesis and heterologously expressed in HEK293 cells together with the stabilizing protein calstabin2 (FKPB12.6). Single channel measurements of RyR2-H29D mutant channels and wild type (WT) RyR2 channels were compared at varying concentrations of cytosolic Ca(2+). Binding affinities of the RyR2-H29D channels and RyR2-WT channels to calstabin2 were compared. Functional characterization of the RyR2-H29D mutant channel revealed significantly higher open probability and opening frequency at diastolic levels of cytosolic Ca(2+) under non-stress conditions without protein kinase A treatment. This was associated with a modest depletion of calstabin2 binding under resting conditions. CONCLUSIONS The RyR2-H29D mutation is associated with a clinical phenotype of short-coupled PMVT at rest. In contrast to catecholaminergic PMVT-associated RyR2 mutations, RyR2-H29D causes a leaky channel at diastolic levels of Ca(2+) under non-stress conditions. Leaky RyR2 may be an under-recognized mechanism for idiopathic PMVT at rest.

Differentiation of Papillary Muscle From Fascicular and Mitral Annular Ventricular Arrhythmias in Patients With and Without Structural Heart Disease

Background—Idiopathic left ventricular arrhythmias (VAs) and those caused by structural heart disease can originate from the papillary muscles, fascicles, and mitral annulus. Differentiation of these arrhythmias can be challenging because they present with a right bundle branch block morphology by electrocardiography. We sought to identify clinical, electrocardiographic, and electrophysiological features that distinguish these left VAs in patients with and without structural heart disease. Method and Results—Patients undergoing catheter ablation for papillary muscle, fascicular, or mitral annular VAs were studied. Demographic data and electrocardiographic and electrophysiological findings were analyzed. Fifty-two VAs in 51 patients (32 [63%] male; mean age 61±15 years) with papillary muscle (n=18), fascicular (n=15), and mitral annular (n=19) origins were studied. Patients with papillary muscle VAs were older and had higher prevalence of left ventricular dysfunction (67% versus 13% of fascicular VA patients [P=0.009]) and coronary artery disease (78% versus 37% of mitral annular VA patients [P=0.036]). Papillary muscle VAs were distinguished electrocardiographically from fascicular VAs by longer QRS durations and lower prevalence of r<R′ V1 QRS morphology, and from mitral annular VAs by lower prevalence of positive precordial lead concordance. Using a stepwise electrocardiographic algorithm, the accuracy rates for the diagnosis of papillary muscle VAs, fascicular VAs, and mitral annular VAs were 83%, 87%, and 89%, respectively. Conclusions—Specific electrocardiographic characteristics, including QRS morphology and precordial lead morphology, can help distinguish between papillary muscle, fascicular, and mitral annular VAs.

Reappraisal of Cardiac Magnetic Resonance Imaging in Idiopathic Outflow Tract Arrhythmias

Because of prognostic and therapeutic implications, the distinction between idiopathic right ventricular (RV) outflow tract (iRVOT) and arrhythmogenic RV cardiomyopathy (ARVC) is clinically important. Over the last 2 decades multiple reports have identified RV abnormalities using CMR in patients with idiopathic VT, suggesting a link between these arrhythmias and ARVC. The purpose of this study was to assess for structural abnormalities in patients with iRVOT tachycardia using contemporary cardiac magnetic resonance (CMR) imaging.

Newly detected atrial high rate episodes predict long-term mortality outcomes in patients with permanent pacemakers

BACKGROUND Subclinical atrial high rate episodes (AHREs) detected by implanted devices in patients with no history of atrial fibrillation (AF) have been associated with an increased risk of stroke and systemic embolism. Data regarding the long-term survival of patients with permanent pacemakers and newly detected AHREs are limited. OBJECTIVE This study aimed to assess whether newly detected AHREs in pacemaker patients predict mortality outcomes. METHODS We evaluated 224 patients (mean age 74 ± 12 years; 118 men [53%]) with no history of AF who underwent dual-chamber pacemaker implantation from 2002 through 2004. During follow-up, patients with AHREs of ≥5-minute duration were identified. Mortality data were obtained from the National Death Index. RESULTS Thirty-nine patients (17%) had AHREs of ≥5-minute duration within 6 months of pacemaker implantation. Over a mean follow-up period of 6.6 ± 2.0 years, the rate of all-cause mortality was 29%. In multivariate analysis adjusted for age, sex, and cardiovascular diseases, AHREs were associated with a significant increase in cardiovascular mortality (hazard ratio [HR] 2.80; 95% confidence interval [CI] 1.24-6.31; P = .013) and stroke mortality (HR 9.65; 95% CI 1.56-59.9; P = .015), with a trend toward increased all-cause mortality (HR 1.79; 95% CI 0.98-3.26; P = .059). The subgroup of patients with AHREs of ≥5-minute but <1-day duration still had a significantly increased cardiovascular mortality (HR 3.24; 95% CI 1.37-7.66; P = .007). CONCLUSION AHREs are commonly encountered in pacemaker patients with no history of AF and are independent predictors of cardiovascular mortality.