Jennifer N.A. Silva

Cardiac Electrophysiological Substrate Underlying the ECG Phenotype and Electrogram Abnormalities in Brugada Syndrome Patients

Background— Brugada syndrome (BrS) is a highly arrhythmogenic cardiac disorder, associated with an increased incidence of sudden death. Its arrhythmogenic substrate in the intact human heart remains ill-defined. Methods and Results— Using noninvasive ECG imaging, we studied 25 BrS patients to characterize the electrophysiological substrate and 6 patients with right bundle-branch block for comparison. Seven healthy subjects provided control data. Abnormal substrate was observed exclusively in the right ventricular outflow tract with the following properties (in comparison with healthy controls; P<0.005): (1) ST-segment elevation and inverted T wave of unipolar electrograms (2.21±0.67 versus 0 mV); (2) delayed right ventricular outflow tract activation (82±18 versus 37±11 ms); (3) low-amplitude (0.47±0.16 versus 3.74±1.60 mV) and fractionated electrograms, suggesting slow discontinuous conduction; (4) prolonged recovery time (381±30 versus 311±34 ms) and activation-recovery intervals (318±32 versus 241±27 ms), indicating delayed repolarization; (5) steep repolarization gradients (&Dgr;recovery time/&Dgr;x=96±28 versus 7±6 ms/cm, &Dgr;activation-recovery interval/&Dgr;x=105±24 versus 7±5 ms/cm) at right ventricular outflow tract borders. With increased heart rate in 6 BrS patients, reduced ST-segment elevation and increased fractionation were observed. Unlike BrS, right bundle-branch block had delayed activation in the entire right ventricle, without ST-segment elevation, fractionation, or repolarization abnormalities on electrograms. Conclusions— The results indicate that both slow discontinuous conduction and steep dispersion of repolarization are present in the right ventricular outflow tract of BrS patients. ECG imaging could differentiate between BrS and right bundle-branch block.

Cardiac resynchronization therapy in pediatric congenital heart disease: insights from noninvasive electrocardiographic imaging.

BACKGROUND Electrocardiographic imaging (ECGI) is a novel electrophysiologic imaging modality that may help guide patient selection and lead placement for cardiac resynchronization therapy (CRT). OBJECTIVE The purpose of this study was to apply noninvasive ECGI to pediatric heart failure patients with congenital heart disease (CHD) undergoing evaluation for CRT. METHODS ECGI was applied in eight patients with CHD who were either being evaluated for CRT or undergoing CRT. An electrical dyssynchrony (ED) index was computed from the ECGI epicardial activation maps as the standard deviation of activation times at 500 epicardial sites of the systemic ventricle. A normal ED of 20 +/- 4 ms was calculated from a control group of normal pediatric patients. RESULTS Four patients had an ECGI assessment for ED but did not undergo CRT implant. Two other patients had ECGI assessment pre-CRT that demonstrated abnormal ED and went on to CRT implant. In both cases, the resynchronization lead was placed at the site of latest electrical activation (as determined by ECGI) in pre-CRT baseline rhythm. A total of four patients (two responders, two nonresponders) were studied with post-CRT in multiple rhythms. Responders had an average ED of 22 ms in optimal CRT conditions. The nonresponder had very elevated ED (37 ms) in all rhythms including optimal CRT settings. ED and ECG QRS duration showed weak correlation (r = 0.58). CONCLUSIONS ECGI can be used in pediatric heart failure patients to evaluate ventricular ED and identify suitable candidates for CRT. In addition, ECGI can guide resynchronization lead placement to the area of latest electrical activation. It could also be used in noninvasive follow-ups for assessing synchrony and the electrophysiological substrate over time.

Electrophysiologic substrate and intraventricular left ventricular dyssynchrony in nonischemic heart failure patients undergoing cardiac resynchronization therapy

BACKGROUND Electrocardiographic imaging (ECGI) is a method for noninvasive epicardial electrophysiologic mapping. ECGI previously has been used to characterize the electrophysiologic substrate and electrical synchrony in a very heterogeneous group of patients with varying degrees of coronary disease and ischemic cardiomyopathy. OBJECTIVE The purpose of this study was to characterize the left ventricular electrophysiologic substrate and electrical dyssynchrony using ECGI in a homogeneous group of nonischemic cardiomyopathy patients who were previously implanted with a cardiac resynchronization therapy (CRT) device. METHODS ECGI was performed during different rhythms in 25 patients by programming their devices to biventricular pacing, single-chamber (left ventricular or right ventricular) pacing, and native rhythm. The electrical dyssynchrony index (ED) was computed as the standard deviation of activation times at 500 sites on the LV epicardium. RESULTS In all patients, native rhythm activation was characterized by lines of conduction block in a region with steep activation-recovery interval (ARI) gradients between the epicardial aspect of the septum and LV lateral wall. A native QRS duration (QRSd) >130 ms was associated with high ED (≥30 ms), whereas QRSd <130 ms was associated with minimal (25 ms) to large (40 ms) ED. CRT responders had very high dyssynchrony (ED = 35.5 ± 3.9 ms) in native rhythm, which was significantly lowered (ED = 23.2 ± 4.4 ms) during CRT. All four nonresponders in the study did not show significant difference in ED between native and CRT rhythms. CONCLUSION The electrophysiologic substrate in nonischemic cardiomyopathy is consistent among all patients, with steep ARI gradients co-localizing with conduction block lines between the epicardial aspect of the septum and the LV lateral wall. QRSd wider than 130 ms is indicative of substantial LV electrical dyssynchrony; however, among patients with QRSd <130 ms, LV dyssynchrony may vary widely.

Electrophysiologic Substrate in Congenital Long QT Syndrome Noninvasive Mapping With Electrocardiographic Imaging (ECGI)

Background— Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. Methods and Results— Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation–recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation–recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P <0.05). Conclusions— LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification. # CLINICAL PERSPECTIVE {#article-title-34}Background— Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. Methods and Results— Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation–recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation–recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P<0.05). Conclusions— LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification.

Predictors of myocardial recovery in pediatric tachycardia-induced cardiomyopathy

BACKGROUND Tachycardia-induced cardiomyopathy (TIC) carries significant risk of morbidity and mortality, although full recovery is possible. Little is known about the myocardial recovery pattern. OBJECTIVE The purpose of this study was to determine the time course and predictors of myocardial recovery in pediatric TIC. METHODS An international multicenter study of pediatric TIC was conducted. Children ≤18 years with incessant tachyarrhythmia, cardiac dysfunction (left ventricular ejection fraction [LVEF] <50%), and left ventricular (LV) dilation (left ventricular end-diastolic dimension [LVEDD] z-score ≥2) were included. Children with congenital heart disease or suspected primary cardiomyopathy were excluded. Primary end-points were time to LV systolic functional recovery (LVEF ≥55%) and normal LV size (LVEDD z-score <2). RESULTS Eighty-one children from 17 centers met inclusion criteria: median age 4.0 years (range 0.0-17.5 years) and baseline LVEF 28% (interquartile range 19-39). The most common arrhythmias were ectopic atrial tachycardia (59%), permanent junctional reciprocating tachycardia (23%), and ventricular tachycardia (7%). Thirteen required extracorporeal membrane oxygenation (n = 11) or ventricular assist device (n = 2) support. Median time to recovery was 51 days for LVEF and 71 days for LVEDD. Two (4%) underwent heart transplantation, and 1 died (1%). Multivariate predictors of LV systolic functional recovery were age (hazard ratio [HR] 0.61, P = .040), standardized tachycardia rate (HR 1.16, P = .015), mechanical circulatory support (HR 2.61, P = .044), and LVEF (HR 1.33 per 10% increase, p=0.005). For normalization of LV size, only baseline LVEDD (HR 0.86, P = .008) was predictive. CONCLUSION Pediatric TIC resolves in a predictable fashion. Factors associated with faster recovery include younger age, higher presenting heart rate, use of mechanical circulatory support, and higher LVEF, whereas only smaller baseline LV size predicts reverse remodeling. This knowledge may be useful for clinical evaluation and follow-up of affected children.

Congenital Long QT 3 in the Pediatric Population

There is insufficient knowledge concerning long-QT (LQT) 3 in the pediatric population to determine whether recommendations for more aggressive therapy in these patients are appropriate. An international multicenter review of 43 children with cardiac sodium channel (SCN5A) mutations and clinical manifestations of LQT syndrome without overlap of other SCN5A syndromes was undertaken to describe the clinical characteristics of LQT3 in children. Patients were aged 7.6 ± 5.9 years at presentation and were followed for 4.7 ± 3.9 years. There was significant intrasubject corrected QT interval (QTc) variability on serial electrocardiography. Forty-two percent presented with severe symptoms or arrhythmia and exhibited longer QTc intervals compared to asymptomatic patients. None of the 14 patients who underwent primary prevention implantable cardioverter-defibrillator (ICD) implantation received appropriate shocks in 41 patient-years of follow-up, while 2 of 6 patients who underwent secondary prevention ICD implantation received appropriate shocks in 30 patient-years of follow-up. Half of patients who underwent ICD implantation experienced inappropriate shocks or ICD-related complications. Mexiletine significantly shortened the QTc interval, and QTc shortening was greater in patients with longer pretreated QTc intervals. Two ICD patients with frequent appropriate ICD shocks showed immediate clinical improvement, with elimination of appropriate ICD shocks after mexiletine loading. In conclusion, severe symptoms are common in children with LQT3 and are associated with longer QTc intervals. ICD implantation is associated with significant morbidity. Mexiletine shortens the QTc interval, and it may be beneficial.

Management of Pediatric Tachyarrhythmias on Mechanical Support

Background—Pediatric patients with persistent arrhythmias may require mechanical cardiopulmonary support. We sought to classify the population, spectrum, and success of current treatment strategies. Methods and Results—A multicenter retrospective chart review was undertaken at 11 sites. Inclusion criteria were (1) patients <21 years, (2) initiation of mechanical support for a primary diagnosis of arrhythmias, and (3) actively treated on mechanical support. A total of 39 patients were identified with a median age of 5.5 months and median weight of 6 kg. A total of 69% of patients were cannulated for supraventricular tachycardia with a median rate of 230 beats per minute. A total of 90% of patients were supported with extracorporeal membrane oxygenation for an average of 5 days. The remaining 10% were supported with ventricular assist devices for an average of 38 (20–60) days. A total of 95% of patients were treated with antiarrhythmics, with 43% requiring >1 antiarrhythmic. Amiodarone was the most frequently used medication alone or in combination. A total of 33% patients underwent electrophysiology study/transcatheter ablation. Radiofrequency ablation was successful in 9 patients on full flow extracorporeal membrane oxygenation with 3 radiofrequency-failures/conversion to cryoablation. One patient underwent primary cryoablation. A total of 15% of complications were related to electrophysiology study/ablation. At follow-up, 23 patients were alive, 8 expired, and 8 transplanted. Conclusions—Younger patients were more likely to require support in the presented population. Most patients were treated with antiarrhythmics and one third required electrophysiology study/ablation. Radiofrequency ablation is feasible without altering extracorporeal membrane oxygenation flows. There was a low frequency of acute adverse events in patients undergoing electrophysiology study/ablation, while on extracorporeal membrane oxygenation.

Use of smartphone technology in cardiology.

Smartphone-based technologies along with broadband connectivity are changing the way modern cardiology is practiced. The ever broadening connectivity and increasing capabilities of smartphone-based technologies can better monitor, diagnose, and prevent cardiovascular diseases. Researchers can leverage the ubiquitous use of smartphone-based technologies and their constant stream of biometric data to establish large community-based clinical research studies. Patient engagement is enhanced with constant and on-demand access to physicians, daily self-monitoring, and expanding social networks. On the other hand, the exponential growth of smartphone-based technologies invariably disrupts the traditional healthcare model and leaves a vacuum in the infrastructure, medico-legal apparatus, and reimbursement systems that need to be addressed. In this review, we present a comprehensive discussion of the various applications utilizing smartphone-based technologies in cardiology.

SPEAR Trial: Smartphone Pediatric ElectrocARdiogram Trial

Objectives Smartphone-enabled ECG devices have the potential to improve patient care by enabling remote ECG assessment of patients with potential and diagnosed arrhythmias. This prospective study aimed to assess the usefulness of pediatric ECG tracings generated by the AliveCor device (Oklahoma City, OK) and to assess user satisfaction. Study Design Enrolled pediatric patients with documented paroxysmal arrhythmia used the AliveCor device over a yearlong study period. Pediatric electrophysiologists reviewed all transmitted ECG tracings. Patient completed surveys were analyzed to assess user satisfaction. Results 35 patients were enrolled with the following diagnoses: supraventricular tachycardia (SVT, 57%), atrial fibrillation (AF, 11%), ectopic atrial tachycardia (EAT, 6%), atrial tachycardia (AT, 3%), and ventricular tachycardia (VT, 23%). A total of 238 tracings were received from 20 patients, 96% of which were of diagnostic quality for sinus rhythm, sinus tachycardia, SVT, and AF. 126 patient satisfaction surveys (64% from parents) were completed. 98% of the survey responses indicated that it was easy to obtain tracings, 93% found it easy to transmit the tracings, 98% showed added comfort in managing arrhythmia by having the device, and 93% showed interest in continued use of the device after the study period ended. Conclusions Smartphone-enabled ECG devices can generate tracings of diagnostic quality in children. User satisfaction was extremely positive. Use of the device to manage certain patients with AF and SVT showcases the future role of remote ECGs in the successful outpatient management of arrhythmias in children by potentially reducing Emergency Department visits and healthcare costs.

Current management of pediatric dilated cardiomyopathy

Purpose of review American and European guidelines for treatment of adult heart failure have been recently revised. This review will reconcile those guidelines to recent studies and experience in the treatment of pediatric dilated cardiomyopathy. Recent findings Therapy for pediatric dilated cardiomyopathy includes establishing a diagnosis for diagnostic-specific therapies as well as preventive strategies for anthracycline toxicity and muscular dystrophy. Pediatric studies demonstrate safety and efficacy for use of angiotensin-converting enzyme inhibition and beta-blockers in dilated cardiomyopathy. Cardiac resynchronization and mitral annuloplasty represent potential nonpharmacologic therapies. Implantable defibrillator therapy may be of less import in children as compared with adults. Ventricular assist devices (VADs) are now available for all ages, which can improve survival and potentially can lead to recovery. Summary The robust development of new therapies for adult heart failure has been successfully applied to children with dilated cardiomyopathy. Therapies for severe, intractable heart failure have been more widely utilized than therapies for mild-to-moderate heart failure.