Jeremy P. Moore

Isoproterenol Administration During General Anesthesia for the Evaluation of Children With Ventricular Preexcitation

Background—Rapid anterograde conduction in the setting of ventricular preexcitation is associated with an increased risk of sudden cardiac death. The effect of isoproterenol in this setting is unclear, particularly in younger anesthetized patients. The aim of this study was to determine the effect of isoproterenol on accessory-pathway conduction in children undergoing general anesthesia and its role in the risk-stratification process. Methods and Results—The records of 151 pediatric patients with preexcitation undergoing electrophysiologic study under propofol anesthesia during a 5-year period were reviewed. Data included accessory-pathway effective refractory period, minimum 1:1 accessory pathway conduction with atrial pacing, and shortest preexcited R-R interval in atrial fibrillation. Measurements were repeated after administration of low-dose isoproterenol (mean, 0.013 &mgr;g/kg per min; range, 0.003 to 0.027). All accessory-pathway characteristics were significantly shortened with isoproterenol (P<0.001). Accessory-pathway effective refractory period increased modestly with age, both in the baseline state (r=0.172, P=0.04) and with isoproterenol (r=0.267, P<0.01) as did minimum 1:1 accessory pathway conduction with atrial pacing (r=0.178, P=0.034, and r=0.175, P<0.01, respectively). Accessory-pathway effective refractory period ⩽250 ms was observed in only 5% of patients at baseline vs 25% after isoproterenol, and Shortest preexcited R-R interval in atrial fibrillation ⩽250 ms was noted in 16% vs 41%. Tachycardia was induced in 48 of 151 patients before and in 102 of 151 after isoproterenol. Conclusions—In anesthetized children with ventricular preexcitation, accessory pathways display shorter conduction properties at younger ages and important adrenergic sensitivity at all ages. Use of low-dose isoproterenol resulted in a substantial increase in the number of patients who would otherwise meet typical criteria for ablation.

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.

Characterization of Anatomic Ventricular Tachycardia Isthmus Pathology after Surgical Repair of Tetralogy of Fallot

Background— Although catheter ablation has been used to target the critical isthmuses for re-entrant monomorphic ventricular tachycardia in tetralogy of Fallot, the anatomy and histology of these regions have not been fully characterized. Autopsy hearts with tetralogy of Fallot were evaluated to clarify the pathological substrate. Methods and Results— Twenty-seven hearts with the diagnosis of tetralogy of Fallot were examined. Anatomically defined isthmuses included (1A) ventriculotomy-to-tricuspid annulus, (1B) ventriculotomy-to-ventricular septal defect patch, (2) ventriculotomy-to-pulmonary annulus, (3) pulmonary annulus-to-ventricular septal defect patch, and (4) ventricular septal defect patch-to-tricuspid annulus. Length and wall thickness were measured for all specimens, and light microscopy was performed for those surviving surgery. For subjects ≥5 years at death, isthmuses 1A and 1B were present in 88%, isthmus 2 in 25%, isthmus 3 in 94%, and isthmus 4 in 13%. Isthmus 1A had the greatest dimensions (mean length, 3.9±1.08; thickness, 1.5±0.3 cm), isthmus 1B intermediate dimensions (mean length, 2.4±0.8; thickness, 1.1±0.4 cm), and isthmuses 2, 3, and 4 the smallest dimensions (mean length, 1.5±0.5, 1.4±0.8, and 0.6±0.4 cm; thickness, 0.5±0.2, 0.6±0.2, and 0.3±0.04 cm, respectively). Histological examination (n=7) revealed increased fibrosis in anatomic isthmuses relative to nonisthmus controls. Conclusions— Consistencies in isthmus dimensions and histology are found among patients with repaired tetralogy of Fallot. Isthmus 1A is associated with the largest morphological dimensions, whereas the nearby newly described isthmus 1B is significantly smaller. Of isthmuses with the smallest dimensions, isthmus 3 is the most common.

Clinical Experience With the Subcutaneous Implantable Cardioverter–Defibrillator in Adults With Congenital Heart Disease

Background—Sudden cardiac death is a major contributor to mortality for adults with congenital heart disease. The subcutaneous implantable cardioverter–defibrillator (ICD) has emerged as a novel tool for prevention of sudden cardiac death, but clinical performance data for adults with congenital heart disease are limited. Methods and Results—A retrospective study involving 7 centers over a 5-year period beginning in 2011 was performed. Twenty-one patients (median 33.9 years) were identified. The most common diagnosis was single ventricle physiology (52%), 9 palliated by Fontan operation and 2 by aortopulmonary shunts: d-transposition of the great arteries after Mustard/Senning (n=2), tetralogy of Fallot (n=2), aortic valve disease (n=2), and other biventricular surgery (n=4). A prior cardiac device had been implanted in 7 (33%). The ICD indication was primary prevention in 67% and secondary in 33% patients. The most common reason for subcutaneous ICD placement was limited transvenous access for ventricular lead placement (n=10) followed by intracardiac right-to-left shunt (n=5). Ventricular arrhythmia was induced in 17 (81%) and was converted with ⩽80 Joules in all. There was one implant complication related to infection, not requiring device removal. Over a median follow-up of 14 months, 4 patients (21%) received inappropriate and 1 (5%) patient received appropriate shocks. There was one arrhythmic death related to asystole in a single ventricle patient. Conclusions—Subcutaneous ICD implantation is feasible for adults with congenital heart disease patients. Most candidates have single ventricle heart disease and limited transvenous options for ICD placement. Despite variable anatomy, this study demonstrates successful conversion of induced ventricular arrhythmia and reasonable rhythm discrimination during follow-up.

Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial

Importance Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal genetic arrhythmia syndrome characterized by polymorphic ventricular tachycardia with physical or emotional stress, for which current therapy with &bgr;-blockers is incompletely effective. Flecainide acetate directly suppresses sarcoplasmic reticulum calcium release—the cellular mechanism responsible for triggering ventricular arrhythmias in CPVT—but has never been assessed prospectively. Objective To determine whether flecainide dosed to therapeutic levels and added to &bgr;-blocker therapy is superior to &bgr;-blocker therapy alone for the prevention of exercise-induced arrhythmias in CPVT. Design, Setting, and Participants This investigator-initiated, multicenter, single-blind, placebo-controlled crossover clinical trial was conducted from December 19, 2011, through December 29, 2015, with a midtrial protocol change at 10 US sites. Patients with a clinical diagnosis of CPVT and an implantable cardioverter-defibrillator underwent a baseline exercise test while receiving maximally tolerated &bgr;-blocker therapy that was continued throughout the trial. Patients were then randomized to treatment A (flecainide or placebo) for 3 months, followed by exercise testing. After a 1-week washout period, patients crossed over to treatment B (placebo or flecainide) for 3 months, followed by exercise testing. Interventions Patients received oral flecainide or placebo twice daily, with the dosage guided by trough serum levels. Main Outcomes and Measures The primary end point of ventricular arrhythmias during exercise was compared between the flecainide and placebo arms. Exercise tests were scored on an ordinal scale of worst ventricular arrhythmia observed (0 indicates no ectopy; 1, isolated premature ventricular beats; 2, bigeminy; 3, couplets; and 4, nonsustained ventricular tachycardia). Results Of 14 patients (7 males and 7 females; median age, 16 years [interquartile range, 15.0-22.5 years]) randomized, 13 completed the study. The median baseline exercise test score was 3.0 (range, 0-4), with no difference noted between the baseline and placebo (median, 2.5; range, 0-4) exercise scores. The median ventricular arrhythmia score during exercise was significantly reduced by flecainide (0 [range, 0-2] vs 2.5 [range, 0-4] for placebo; P < .01), with complete suppression observed in 11 of 13 patients (85%). Overall and serious adverse events did not differ between the flecainide and placebo arms. Conclusions and Relevance In this randomized clinical trial of patients with CPVT, flecainide plus &bgr;-blocker significantly reduced ventricular ectopy during exercise compared with placebo plus &bgr;-blocker and &bgr;-blocker alone. Trial Registration clinicaltrials.gov Identifier: NCT01117454

Catheter ablation of supraventricular tachyarrhythmia after extracardiac Fontan surgery

BACKGROUND Extracardiac total cavopulmonary connection (E-TCPC) is widely performed for single ventricle palliation, yet there is little experience with catheter ablation in this population. OBJECTIVES We hypothesized that atrial tachycardia substrates after primary E-TCPC would be similar to those in other forms of congenital heart disease and that catheter ablation could be performed effectively using a primarily transconduit approach. METHODS Catheter ablation characteristics of patients with E-TCPC from 9 centers were collected. Acute procedural success was defined as elimination of all sustained supraventricular tachyarrhythmias. Procedural complications, acute success, and recurrences were assessed. RESULTS Forty-six catheter ablation procedures were performed in 36 patients. Access to the atrium was by transconduit puncture in 29 procedures (63%). The most common supraventricular tachyarrhythmia mechanism was intra-atrial reentrant tachycardia (IART) in 21 patients (58%); and for all patients with primary E-TCPC and IART, an isthmus between the atrioventricular valve annulus and the oversewn inferior vena cava was critical for maintenance of tachycardia. Overall, acute success was achieved in 38 procedures (83%). There were 8 complications, with only 1 requiring intervention (epicardial pacemaker) and none related to conduit puncture. Recurrence after the final procedure occurred in 6 patients (17%) over a median follow-up duration of 0.4 years (interquartile range 0.1-1.5 years). CONCLUSION Catheter ablation could be performed effectively in this group of patients with E-TCPC, and the underlying IART substrate after primary E-TCPC appears to be reproducible. Catheter ablation may be a reasonable alternative to long-term antiarrhythmic therapy in this patient group.

Catheter ablation of tachycardia arising from the pulmonary venous atrium after surgical repair of congenital heart disease.

BACKGROUND Tachycardia arising from the pulmonary venous atrium (PVA) has not been adequately characterized in the setting of surgically repaired congenital heart disease (CHD). OBJECTIVE The purpose of this study was to determine the mechanisms, approach, and outcomes of catheter ablation of PVA tachycardia after CHD repair. METHODS The adult CHD procedural database was searched for consecutive ablation procedures over a 4-year period. Procedural characteristics of the population with tachycardia arising from the PVA were compared to those without PVA tachycardia. Groups were classified as (1) biventricular CHD, (2) single ventricle, or (3) d-transposition of the great arteries (DTGA)-baffle. RESULTS Complete 3-dimensional mapping was possible for 113 of 124 sustained tachycardias during 81 procedures. Of these, 31 (19%) arose from the PVA, including 11 (15%) tachycardias in biventricular CHD, 8 (31%) in single ventricle, and 12 (80%) in DTGA-baffle procedures. Intra-atrial reentrant tachycardia was less frequently observed in the PVA vs the systemic venous atrium (SVA) (P = .012). Independent predictors of PVA tachycardia were absence of biventricular CHD (odds ratio 0.19, confidence interval 0.05-0.64, P = .010) and ipsilateral atrial surgery (odds ratio 15.7, confidence interval 4.8-59.9, P <.001). PVA procedure duration was greater than SVA-only procedures (median 5.3 hours vs 4.0 hours, P = .012), but acute success was similar (87% vs 82%, respectively, P = NS). CONCLUSION PVA tachycardia is not unusual after surgical repair of CHD. Predictors include ipsilateral atrial surgery and absence of biventricular CHD. Such procedures involve increased complexity and unique tachycardia substrates but appear equally amenable to catheter ablation.

The corrected QT interval before and after heart transplantation.

Heart donor candidates have severe neurologic injuries that have been associated with significant prolongation of the corrected QT (QTc) interval. Screening for an underlying abnormality of cardiac repolarization such as the long-QT syndrome thus becomes difficult. The aims of this study were to establish normal values and determine factors associated with prolongation of pre- and post-transplantation QTc intervals in a large cohort of heart transplantation donors and recipients. The medical records of 179 donors and 112 recipients were reviewed for historical, electrocardiographic, and neuroimaging data. After linear regression analysis, gunshot wounds were associated with the shortest mean pre-transplantation QTc interval of 447 +/- 51 ms (p = 0.016), whereas all other mechanisms of brain injury were associated with markedly prolonged QTc intervals. Overall, the mean QTc interval decreased from 467 +/- 58 to 446 +/- 47 ms (p <0.001), the mean QRS duration increased from 87 +/- 16 to 98 +/- 21 ms (p <0.001), and the mean QT dispersion did not change significantly after transplantation. The only factor associated with a prolonged QTc interval in the post-transplantation period was hypokalemia, with a mean QTc of 468 +/- 37 ms (p = 0.047). In conclusion, the mechanism of donor brain injury is associated with alterations in the pre-transplantation QTc interval, with the shortest intervals related to gunshot wounds. Fewer than 5% of the donor population was found to have QTc interval > or =580 ms. For those afflicted by gunshot wounds, <5% had QTc intervals > or =550 ms. This information can be used in pre-transplantation donor assessment, and post-transplantation management can be tailored to avoid the occurrence of ventricular arrhythmia.

Transcaval Puncture for Access to the Pulmonary Venous Atrium after the Extracardiac Total Cavopulmonary Connection Operation

Background—Patients with surgically palliated total cavopulmonary connection are at risk for recurrent atrial arrhythmia requiring catheter ablation. Transcatheter procedures for those with extracardiac conduits (extracardiac-total cavopulmonary connection) are perhaps the most challenging because of exclusion of the venous circulation from the arrhythmia substrate. Puncture through the inferior vena cava to the pulmonary venous atrium may be an effective route for access in these patients. Methods and Results—The pediatric and adult congenital surgical databases were explored for patients with extracardiac-total cavopulmonary connection and postoperative computed tomography imaging to assess for the presence of clinically relevant (>3 mm) apposition between the inferior vena cava and pulmonary venous atrium (cavoatrial overlap). The degree of overlap between the structures was measured by 2 blinded reviewers. Patients were stratified by surgical repair in childhood versus adult congenital heart disease. Thirty-seven patients were identified, with cavoatrial overlap observed in 9 (36%) of pediatric and 1 (9%) of adult congenital heart disease–repaired patients. Time elapsed after surgery was associated with cavoatrial overlap in the pediatric cohort (P=0.034) and was identified in all pediatric patients with computed tomography imaging ≥8 years after surgery. Three patients underwent successful transcaval puncture during the study period without complication. Conclusions—Puncture through a region of overlap between the inferior vena cava and pulmonary venous atrium is feasible. Cavoatrial overlap is present in a substantial proportion of patients undergoing extracardiac-total cavopulmonary connection in childhood and is associated with a longer time elapsed since surgery.

Mechanisms and predictors of recurrent tachycardia after catheter ablation for d-transposition of the great arteries after the Mustard or Senning operation.

BACKGROUND The Senning and Mustard operations for dextro-transposition of the great arteries are associated with an increased risk for supraventricular tachycardia. Catheter ablation has been shown to be acutely successful for achieving rhythm control in this population, but the mechanisms of recurrence are ill-defined. OBJECTIVE We hypothesized that the type and degree of recurrence would vary by the surgical technique used. METHODS All consecutive catheter ablation procedures for dextro-transposition of the great arteries after the Mustard or Senning operation between 2004 and 2016 at a single center were reviewed. Tachycardia mechanisms were determined by complete 3-dimensional mapping in addition to a standard electrophysiological technique for all cases. RESULTS Twenty-eight patients underwent 38 procedures during the study period. The most common mechanism at the index procedure was intra-atrial reentrant tachycardia using the cavotricuspid isthmus. Over a median follow-up period of 1.6 years, 9 patients experienced recurrent tachycardia (32%), all of whom underwent repeat catheter ablation. Tachycardia recurrence was more common after the Senning vs the Mustard operation (6 of 10 [60%] vs 3 of 18 [17%]; P = .034). In addition, substrates for recurrence were different from those encountered at the index procedure in 10 of 13 tachycardias (77%), with the single most common location being the posterior anastomosis after the Senning operation. Complete control was ultimately achieved in 27 patients (96%) when considering all procedures. CONCLUSION Recurrent tachycardia after catheter ablation appears to be more common after the Senning operation and to involve substrates unique to this repair. The posterior anastomosis is commonly implicated and should not be overlooked.