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 ß-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 ß-blocker therapy is superior to ß-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 ß-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 ß-blocker significantly reduced ventricular ectopy during exercise compared with placebo plus ß-blocker and ß-blocker alone. Trial Registration: clinicaltrials.gov Identifier: NCT01117454.

QRS Duration Changes in Patients with Single Ventricle Physiology: Birth to 10 Years.

BACKGROUND: QRS prolongation may be a predictor of mortality in certain forms of congenital heart disease. Minimal data exist describing changes in QRS duration in patients with single ventricles (SVs). The goal was to describe changes in QRS duration in patients with SV and to determine if differences existed between single right ventricle (sRV) versus single left ventricle (sLV) patients. METHODS: Chart review was performed on patients with SV physiology. Patients were divided into sRV and sLV groups. QRS durations were measured monthly for the first 6 months, at 1 year, and then yearly until 10 years. t-tests were used for analysis. RESULTS: One hundred sixty patients were evaluated (95 sRV, 65 sLV). The greatest change in QRS duration for the entire cohort occurred in the first 6 months of life versus 6 months to 10 years of age (1.81 ms/month vs 0.20 ms/month). sRV QRS durations were significantly longer than sLV QRS durations at 1 year (78.9 ± 12.6 ms vs 73.2 ± 11.9 ms), 2 year (81.7 ± 14.7 ms vs 73.4 ± 12.5 ms), 4 year (84.2 ± 12.1 ms vs 77.9 ± 16.4 ms), 6 year (90.8 ± 12.7 ms vs 83.4 ± 13.4 ms), 7 year (90.8 ± 16.5 ms vs 81.2 ± 16.6 ms), and 8 year (96.7 ± 13.6 ms vs 84.8 ± 13.9 ms) time points. CONCLUSION: The greatest change in QRS duration in SV patients occurred in the first 6 months of life when these patients' ventricles were volume loaded. Differences in QRS duration between sRV and sLV patients occurred early in life. Further studies are needed to determine if minimizing volume load early in life decreases the rate of change in QRS duration.

Fascicular and nonfascicular left ventricular tachycardias in the young: an international multicenter study.

INTRODUCTION: The aim of this study was to evaluate the clinical presentation and outcomes of pediatric patients with ventricular tachycardia (VT) originating from left heart structures. METHODS AND RESULTS: This international multicenter retrospective study including 152 patients (age 10.0 ± 5.1 years, 62% male), divided into those with fascicular VT (85%, 129/152) and nonfascicular LV VT (15%, 23/152). All patients had a normal heart structure or only a minor cardiac abnormality. Adenosine was largely ineffective in both groups (tachycardia termination in 4/74 of fascicular VT and 0/5 of nonfascicular LV VT). In fascicular VT, calcium channel blockers were effective in 80% (74/92); however, when administered orally, there was a 21% (13/62) recurrence rate. In nonfascicular LV VT, a variety of antiarrhythmic therapies were used with no one predominating. Ablation procedures were successful in 71% (72/102) of fascicular VT and 67% (12/18) of nonfascicular LV VT on an intention to treat analysis. Major complications occurred in 5 patients with fascicular VT and 1 patient with nonfascicular LV VT. After a follow-up period of 2 years (1 day to 15 years), 72% of all patients with fascicular VT were off medications with no tachycardia recurrence. One patient died of noncardiac causes. In nonfascicular LV VT, follow-up was 3.5 years (0.5-15 years), P = 0.38. A total of 65% of these patients were free from arrhythmias. Two patients died suddenly (P < 0.01). CONCLUSION: The clinical course and outcomes of pediatric patients with fascicular VT and nonfascicular LV VT are varied. Catheter ablation procedures can be curative.

QRS duration changes in patients with hypoplastic left heart syndrome undergoing hybrid palliation: prehybrid to post-Fontan.

BACKGROUND: QRS prolongation has been shown to be a predictor of mortality in patients with certain forms of congenital heart disease. QRS changes have not been well described in patients with single ventricle physiology, particularly in those undergoing the hybrid procedure. OBJECTIVE: To describe QRS changes in a cohort of patients with hypoplastic left heart syndrome (HLHS) who underwent hybrid palliation and to evaluate if QRS duration is associated with mortality. METHODS: Chart review of 54 patients with HLHS who underwent hybrid procedure between 2002 and 2009 was performed. Patients awaiting surgical palliation were excluded. Patients who survived Fontan completion (HLHS-S, n = 30) were compared to non-survivor (HLHS-NS, n = 24). Electrocardiograms were reviewed for maximal QRS duration (ms) at three pre- and postsurgical stages: (1) hybrid procedure, (2) comprehensive stage 2 procedure, and (3) Fontan procedure. RESULTS: In HLHS-S, there was a significant increase in QRS from birth to Fontan completion (15.6 ± 9.3 ms). QRS duration increased 8.5 ± 8.9 ms between posthybrid to precomprehensive stage 2, and 5.4 ± 9.7 ms between postcomprehensive stage 2 to Fontan. Following Fontan procedure, mean QRS decreased 4.3 ± 8.5 ms. There was no significant mean difference in QRS change between HLHS-S and HLHS-NS following hybrid procedure. Pre- and posthybrid and pre- and postcomprehensive stage 2 QRS durations were not different between HLHS-S and HLHS-NS who underwent a comprehensive stage 2 procedure. There was a significant difference in QRS difference following comprehensive stage 2 in HLHS-S (0.9 ± 7.1 ms) compared to HLHS-NS (-7.1 ± 10.0 ms). CONCLUSIONS: QRS duration significantly increased from hybrid to Fontan completion in HLHS-S. There was a significant decrease in QRS duration in patients who died following comprehensive stage 2 procedure. Larger studies are needed to assess the significance of these QRS changes.

The study of antiarrhythmic medications in infancy (SAMIS): a multicenter, randomized controlled trial comparing the efficacy and safety of digoxin versus propranolol for prophylaxis of supraventricular tachycardia in infants.

BACKGROUND: Supraventricular tachycardia (SVT) is one of the most common conditions requiring emergent cardiac care in children, yet its management has never been subjected to a randomized controlled clinical trial. The purpose of this study was to compare the efficacy and safety of the 2 most commonly used medications for antiarrhythmic prophylaxis of SVT in infants: digoxin and propranolol. METHODS AND RESULTS: This was a randomized, double-blind, multicenter study of infants <4 months with SVT (atrioventricular reciprocating tachycardia or atrioventricular nodal reentrant tachycardia), excluding Wolff-Parkinson-White, comparing digoxin with propranolol. The primary end point was recurrence of SVT requiring medical intervention. Time to recurrence and adverse events were secondary outcomes. Sixty-one patients completed the study, 27 randomized to digoxin and 34 to propranolol. SVT recurred in 19% of patients on digoxin and 31% of patients on propranolol (P=0.25). No first recurrence occurred after 110 days of treatment. The 6-month recurrence-free status was 79% for patients on digoxin and 67% for patients on propranolol (P=0.34), and there were no first recurrences in either group between 6 and 12 months. There were no deaths and no serious adverse events related to study medication. CONCLUSIONS: There was no difference in SVT recurrence in infants treated with digoxin versus propranolol. The current standard practice may be treating infants longer than required and indicates the need for a placebo-controlled trial. Clinical Trial Registration Information- http://clinicaltrials.gov; NCT-00390546.

Changes in hemodynamic parameters and cerebral saturation during supraventricular tachycardia.

Induced supraventricular tachycardia (SVT) during electrophysiology studies (EPS) can be associated with hemodynamic changes. Traditionally, invasive arterial blood pressure has been used for continuous monitoring of these changes. This prospective study evaluated the efficacy of near-infrared spectroscopy (NIRS) monitoring during SVT. The use of NIRS has expanded with evidence of its accuracy and benefit in detecting cerebral hypoperfusion. This study aimed first to determine the hemodynamic changes associated with electrophysiology testing for SVT and second to determine whether the hemodynamic changes are associated with similar changes in the cerebral saturation as determined by NIRS. The study enrolled 30 patients 5-20 years of age with a history of SVT who underwent an EPS. The demographic data included age, gender, weight, height, and type of SVT. Hemodynamic data (invasive blood pressure and heart rate), NIRS, bispectral index (BIS), end-tidal carbon dioxide, and pulse oximetry were collected before and during three episodes of induced SVT. The linear correlation coefficient (r) was measured to calculate the relationship of the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) to the changes in NIRS values during the SVT episodes. Data from 22 patients were collected. The induction of SVT was associated mainly with a change in SBP and a less prominent change in DBP and MAP from baseline. The changes in hemodynamic status were associated with minimal changes in cerebral saturations, as evidenced by an average absolute change in NIRS of <1 from baseline value. The changes in hemodynamics were correlated linearly with cerebral saturation. Changes in SBP, DBP, and MAP were correlated positively with changes in NIRS, as denoted by (r) values of 0.52, 0.57, and 0.67 respectively, and a P value less than 0.05 for all three association tests. Induction of SVT during electrophysiology testing is associated with hemodynamic changes, mainly in SBP. In this study, these hemodynamic changes resulted in a minimal decrease in cerebral perfusion, as evidenced by minimal changes in the cerebral saturation measured by NIRS (0.7% from baseline). Although the changes in the cerebral saturation were minimal, these changes were linearly correlated with the changes in the hemodynamics. This study is the first to demonstrate the possible application of NIRS monitoring during EPS and to document that despite changes in the hemodynamic status, the changes in cerebral oxygenation are minimal, thereby confirming the safety of EPS for SVT.

Optimization of biventricular pacing via strain dyssynchrony measurements in a paediatric patient.

Cardiac resynchronization therapy is increasingly being used in the paediatric population as a tool for managing patients with heart failure. Various non-invasive parameters have been used to optimize the settings on the biventricular pacemaker. We describe implantation of a biventricular pacemaker in a nineteen-month-old child because of intractable heart failure. By analysing a 17-segment model using strain analysis of the left ventricle, we were able to place the left ventricular lead at the latest activated segment. Furthermore, we were able to minimize the dyssynchrony of the left ventricle when evaluating a range of pacemaker settings.

Changes in near-infrared spectroscopy and the bispectral index during tilt-table examination.

The head-upright tilt-table test is an important tool for the diagnosis of vasodepressor or neurocardiogenic syncope. The use of noninvasive near-infrared spectroscopy (NIRS) monitoring and bispectral index (BIS) monitoring during these cases can add another tool to the real-time monitoring and aid in their diagnosis. The authors report their experience using NIRS and BIS monitoring during tilt-table testing to investigate syncope in a 14-year-old adolescent. In this case, changes in the NIRS occurred earlier than changes in either blood pressure or the development of clinical symptoms. The change in the NIRS and BIS values correlated with the patient's level of consciousness. One major advantage of monitors such as the BIS, and more importantly, the NIRS is that they provide an instantaneous and continuous noninvasive measure of cerebral perfusion.

Rate of inducible ventricular arrhythmia in adults with congenital heart disease.

Patients with adult congenital heart disease are at increased risk of ventricular arrhythmia (VA) and sudden cardiac death, although no clear predictors have been found. Ventricular programmed stimulation has been shown to predict clinical ventricular tachycardia and sudden death events, but the role of screening electrophysiology studies (S-EPSs) in this population remains poorly defined. Therefore, we sought to determine the prevalence of inducible VA and to evaluate the clinical predictors in a heterogeneous group of patients with adult congenital heart disease (> or =18 years old) undergoing S-EPSs at preoperative or interventional cardiac catheterization. Studies for the primary evaluation of clinical VA were excluded. The demographic, clinical, and diagnostic findings were compared between the patients with positive and negative findings. From 2005 to 2009, 80 patients (mean age 30 +/- 9 years) underwent S-EPSs, and 23 had inducible VA. The diagnoses for those with studies positive for VA included tetralogy of Fallot (n = 12), d-transposition of the great arteries (n = 6), pulmonary stenosis (n = 2), double outlet right ventricle (n = 1), double inlet left ventricle (n = 1), and Ebstein's anomaly (n = 1). Men were significantly more likely to have a S-EPS positive for VA (p = 0.015). Increasing QRS duration, decreasing peak oxygen uptake (percentage of predicted), and ventricular fibrosis with cardiovascular magnetic resonance imaging were significantly associated with studies positive for VA (p <0.05). Combined fibrosis and a peak oxygen uptake <80% of predicted had 100% sensitivity for positive VA findings. In conclusion, almost 30% of those with adult congenital heart disease undergoing S-EPSs had inducible VA. A prolonged QRS duration, diminished exercise capacity, and the presence of ventricular fibrosis were significantly associated with findings positive for VA and might improve patient selection for screening evaluations.

Tissue doppler changes in pediatric complete heart block patients who are chronically paced.

INTRODUCTION: Pediatric patients with complete heart block (CHB) often require pacemaker therapy. Adult studies have shown chronic right ventricular pacemaker therapy may be associated with decreased echocardiographic parameters and increased brain natriuretic peptide (BNP) values. The goal of this study was to determine if there are echocardiographic or BNP changes in a pediatric population that is chronically paced. METHODS: Patients were recruited if they had CHB and had a pacemaker. Patients were excluded if they had congenital structural heart disease. Standard two-dimensional echocardiograms, including tissue Doppler imaging (TDI), were performed. BNP values were obtained. Nonparametric Spearman's rank correlation was used for analysis. Rho < or = 0.05 was considered significant. RESULTS: Eighteen patients (16.4 +/- 7.3 years) with CHB were studied. Age at implant was 8.6 +/- 6.6 years and length of pacing was 7.8 +/- 6.6 years. Pacing mode was VDD, DDD, DDDR, or VVIR. All patients were ventricularly paced >95% of the time. Ejection fraction was 58.5 +/- 7.5%. All BNP values were <40 pg/mL. There was no correlation between ejection fraction or BNP level with the length of pacing years. Pacing years significantly correlated with mitral and tricuspid E/A ratios (rho =-0.56, -0.56, respectively). Pacing years also correlated with right ventricular and interventricular TDI a wave (rho = 0.61 and 0.68, respectively). Furthermore, pacing years correlated with right ventricular TDI e/a ratio (rho =-0.58). CONCLUSIONS: Ejection fraction and BNP levels were not sensitive parameters in evaluating pediatric patients who are chronically paced. Subtle diastolic changes, especially of the right ventricle, were detected by TDI.

Managed ventricular pacing in pediatric patients and patients with congenital heart disease.

Ventricular dyssynchrony induced by ventricular pacing (VP) may predispose patients to congestive heart failure. The detrimental effects of VP are directly related to the cumulative percentage of VP (Cum%VP). Managed VP (MVP) is a novel pacing algorithm developed to minimize unnecessary VP by uncoupling atrial pacing from VP. This retrospective analysis assessed the feasibility of using MVP in pediatric patients and patients with congenital heart disease (CHD). A multicenter review evaluated all pediatric patients <22 years old and older patients with CHD that had an implanted device using a MVP algorithm. Primary outcome variables were Cum%VP and adverse events. A subgroup analysis evaluated patients that had a DDD(R) pacemaker before a MVP device and compared Cum%VP before and after initiation of MVP. From 6 centers 62 patients (mean age 21.5 +/- 9.6 years) were included; 64% had CHD. With a MVP device, mean Cum%VP was 4.3 +/- 14.6% (range 0 to 83.7): Eleven patients were eligible for subgroup analysis. Compared with DDD(R), Cum%VP significantly decreased with MVP (67.1 +/- 29.4% vs 9.2 +/- 24.8%, p = 0.002). One MVP-related adverse event occurred; a patient with intermittent atrioventricular block had symptoms with frequent nonconducted atrial depolarizations and was reprogrammed to DDD. In conclusion, MVP can be used safely and can significantly reduce unnecessary VP in pediatric patients and patients with CHD.

A multicenter experience with novel implantable cardioverter defibrillator configurations in the pediatric and congenital heart disease population.

INTRODUCTION: In pediatric and congenital heart disease patients, transvenous ICD implantation may be limited secondary to patient size, venous, or cardiac anatomy. Epicardial patches require a thoracotomy, and may lead to a restrictive pericardial process. Because of these issues, we have explored novel ICD configurations. METHODS: Retrospective review at 10 centers implanting ICDs without a transvenous shocking coil or epicardial patches. RESULTS: Twenty-two patients underwent implant at a mean age of 8.9 years (range: 0.3-43.5), with a mean weight of 25.5 kg (range: 5.2-70). Diagnoses included complex CHD, intracardiac tumors, cardiomyopathy, idiopathic VT, LV noncompaction, and long QT syndrome. Three configurations were used: subcutaneous array, a transvenous design ICD lead placed on the epicardium, or a transvenous design ICD lead placed subcutaneously. Difficulties were found at implant in 8 patients: 4 had difficulty inducing VT/VF, and 4 had high DFTs. Over a mean follow-up of 2.2 years (range: 0.2-10.5), 7 patients had appropriate shocks. Inappropriate shocks occurred in 4 patients. System revisions were required in 7 patients: 2 generator changes (in 1 patient), 3 pace-sense lead replacement, 1 additional subcutaneous coil placement due to increased DFT, 1 upgrade to a transvenous system, and 1 revision to epicardial patch system. CONCLUSIONS: ICD implantation can be performed without epicardial patches or transvenous high-energy leads in this population, using individualized techniques. This will allow ICD use in patients who have intracardiac shunting or are deemed too small for transvenous ICD leads. The long-term outcome and possible complications are as yet unknown in this population, and they should be monitored closely with follow-up DFTs.

Congenital superior vena cava obstruction causing anasarca and respiratory failure in a newborn: successful transcatheter therapy.

Superior vena cava (SVC) obstruction is a rare entity in the pediatric population. It usually presents in association with either previous cardiac surgery or external compression from a neoplasm. We present the case of an infant born with congenital SVC obstruction and significant bilateral chylothorax and anasarca necessitating mechanical ventilation. Successful placement of an intravascular stent led to resolution of the chylothoraces with rapid clinical improvement.

Diagnostic assessment before Fontan operation in patients with bidirectional cavopulmonary anastomosis: are noninvasive methods sufficient?

OBJECTIVES: This study was designed to determine if a subset of patients who have undergone bidirectional cavopulmonary anastomosis could be identified in which catheterization was of little benefit before completion of the Fontan procedure. BACKGROUND: Diagnostic evaluation before Fontan procedure has typically included cardiac catheterization. However, the overall management strategy for patients with functional single ventricle has evolved to include staging bidirectional cavopulmonary anastomosis in most, and it has become uncommon to exclude patients from Fontan based on catheterization data. METHODS: Patients who underwent bidirectional cavopulmonary anastomosis and had complete echocardiograms and catheterizations within three months of each other between January 1992 and October 1997 were evaluated with a series of clinical and echocardiographic characteristics to identify a subset in whom catheterization was predicted to be of little added value ("no-cath" group). The predictive value and sensitivity of these criteria in excluding patients who required additional intervention, were excluded from Fontan, or died within 30 days of Fontan was determined. RESULTS: A total of 99 patients who underwent bidirectional cavopulmonary anastomosis at 6.7 months (range 2.9 months to 14 years) were studied; 46 met criteria for the "no-cath" group. Noninvasive criteria stratified all patients who died (n = 5) or did not proceed to Fontan (n = 1) and 9 of 11 who required additional interventions to the "cath" group. Thus, the negative predictive value of these criteria was 93%. CONCLUSIONS: Our data suggest that catheterization before Fontan could be avoided in a large percentage of patients without adversely affecting outcome; prospective evaluation of this strategy is warranted.