Peter F. Aziz

Genotype- and mutation site-specific QT adaptation during exercise, recovery, and postural changes in children with long-QT syndrome.

Background— Exercise stress testing has shown diagnostic utility in adult patients with long-QT syndrome (LQTS); however, the QT interval adaptation in response to exercise in pediatric patients with LQTS has received little attention. Methods and Results— One-hundred fifty-eight patients were divided into 3 groups: Those with LQTS type 1 (LQT1) or LQTS type 2 (LQT2) and normal control subjects without cardiovascular disease. Each patient underwent a uniform exercise protocol with a cycle ergometer followed by a 9-minute recovery phase with continuous 12-lead ECG monitoring. Each patient underwent a baseline ECG while resting in the supine position and in a standstill position during continuous ECG recording to determine changes in the QT and RR intervals. Fifty patients were gene-positive for LQTS (n=29 for LQT1 and n=21 for LQT2), and the control group consisted of 108 patients. QT interval adaptation was abnormal in the LQT1 patients compared with LQT2 and control patients (P<0.001). A corrected QT interval (QTc) >460 ms in the late recovery phase at 7 minutes predicted LQT1 or LQT2 versus control subjects with 96% specificity, 86% sensitivity, and a 91% positive predictive value. A recovery &Dgr;QTc(7 min−1 min) >30 ms predicted LQT2 versus LQT1 with 75% sensitivity, 82% specificity, and a 75% positive predictive value. The postural &Dgr;QT was significantly different between LQTS and control groups (P=0.005). Conclusions— Genotype-specific changes in repolarization response to exercise and recovery exist in the pediatric population and are of diagnostic utility in LQTS. An extended recovery phase is preferable to assess the repolarization response after exercise in the pediatric population.

Congenital long QT syndrome and 2:1 atrioventricular block: An optimistic outcome in the current era

BACKGROUND Previous studies of patients with long QT syndrome (LQTS) and 2:1 atrioventricular block (AVB) have reported a mortality rate greater than 50% during infancy. OBJECTIVE The purpose of this study was to determine the outcome of this high-risk population in the current era. METHODS A retrospective study from four tertiary care pediatric centers assessed patients with congenital LQTS and 2:1 AVB from January 2000 to January 2009. All neonates who presented with 2:1 AVB and prolonged QTc unrelated to medication were included in the study. Statistical analysis was performed using a paired t-test. Medical records were reviewed for ECG findings, genotype, medications, and device therapy. RESULTS Twelve patients that met the inclusion criteria were identified. All patients underwent diagnostic ECG in the first 24 hours of life. The average QTc interval prior to therapy was 616 +/- 99 ms (range 531-840 ms). Over a follow-up period of 71 +/- 45 months (range 15-158 months), 11 of 12 patients received devices (8 permanent pacemaker, 3 implantable cardioverter-defibrillator). Average age of device placement was 48 months (median 2 months, range 3 days to 10.5 years). All patients were treated with beta-blockers; mexiletine was added in three patients, and mexiletine and flecainide were added in one patient. Three (25%) patients experienced torsades de pointes while receiving beta-blockers, one of which was refractory to medical therapy. This patient underwent left cardiac sympathetic denervation and implantable cardioverter-defibrillator placement. Genotyping was available for 6 (50%) patients (2 SCN5A mutation, 4 KCNH2 mutation). At last follow-up, no mortality was observed. Follow-up QTc intervals had decreased (mean 480 +/- 20 ms, range 450-507 ms, P <.002). CONCLUSION Management of patients with LQTS and 2:1 AVB presents unique challenges. Despite historical data indicating poor prognosis, our study represents a cohort of high-risk LQTS patients with a relatively optimistic outcome. This finding reflects early diagnosis and intervention, coupled with improved management strategies, in the current era.

Compound Heterozygous Mutations in the SCN5A-Encoded Nav1.5 Cardiac Sodium Channel Resulting in Atrial Standstill and His-Purkinje System Disease

An 11-year-old girl on evaluation for syncope was found to have progressive sinus node dysfunction and His-Purkinje system disease with atrial standstill. Genetic analysis revealed compound heterozygous mutations of the SCN5A gene in a novel combination.

Relation of Ventricular Ectopic Complexes to QTc Interval on Ambulatory Electrocardiograms in Williams Syndrome

Williams syndrome (WS) is a congenital, developmental disorder affecting 1 in 8,000 live births. The corrected QT (QTc) interval is prolonged in 13% of patients with WS. No data exist characterizing the ambulatory electrocardiographic findings in WS. A retrospective review of all patients with WS evaluated at our institution from January 1, 1980 to December 31, 2007 was performed. Patients with ≥1 ambulatory electrocardiogram (AECG) with sinus rhythm and measurable intervals were included. QTc measurements were made at the minimum and maximum heart rate. Logistic regression analysis was used to evaluate the correlation of ventricular ectopic complexes with QTc measurements. A statistical probability of p <0.05 was considered significant. Of 270 patients identified, 32 had AECGs available for review. Complete data were available for 56 AECGs from 26 patients (15 female; 58%). Their mean age was 15.6 ± 7.2 years at the initial AECG and 20.6 ± 8.6 years for all AECGs. The QTc interval increased with increasing heart rate. Ventricular premature complexes occurred in 40 (73%) of 56 AECGs and 21 (81%) of 26 patients. Ventricular tachycardia occurred in 5 (9%) of 56 AECGs and 4 (15%) of 26 patients. The mean length of ventricular tachycardia was 3.6 ± 0.5 beats at a rate of 171 ± 40 beats/min. The QTc interval at the minimum heart rate correlated directly with age (p <0.001), total ventricular premature complexes (p = 0.007), ventricular couplets (p = 0.002), and ventricular tachycardia (p = 0.011). The QTc interval at the maximum heart rate correlated directly with age (p <0.001), total ventricular premature complexes (p = 0.016), and ventricular couplets (p = 0.006). In conclusion, the QTc interval correlated with ventricular ectopic complexes in patients with WS. The type of ventricular ectopic complexes suggested an alternate etiology of the QTc prolongation seen in WS from that seen in congenital long QT syndrome.

Cardiovascular risk factors and cardiac disorders in long‐term survivors of pediatric liver transplantation

The MetS and cardiovascular disease are leading causes of late morbidity in adult liver transplantation recipients; however, limited data are available in pediatric liver transplantation. A single‐center retrospective review was undertaken for patients who had a liver transplantation before 18 yr of age and were >5 yr post‐transplantation, to study the prevalence of MetS, its components, and cardiac disorders. Fifty‐eight patients were included in the study with a mean age at transplantation of 6.3 ± 6.1 yr and mean follow‐up of 14.1 ± 6.0 yr. Of the study group, 41.4% were overweight or obese, with ongoing prednisone use and increased duration of follow‐up being significant risk factors. Fifty‐three patients had sufficient data for determining MetS, which was present in 17% of the patients. Although the prevalence of MetS is low in pediatric liver transplant recipients, it is associated with CKD and prednisone therapy (p < 0.05). Echocardiography data were available for 23 patients, of whom 43.4% had LVH and 13% had evidence of PH. The spectrum of cardiac disorders in this population is much wider than in adults.

2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry

Ambulatory ECG (AECG) is very commonly employed in a variety of clinical contexts to detect cardiac arrhythmias and/or arrhythmia patterns which are not readily obtained from the standard ECG. Accurate and timely characterization of arrhythmias is crucial to direct therapies that can have an important impact on diagnosis, prognosis or patient symptom status. The rhythm information derived from the large variety of AECG recording systems can often lead to appropriate and patient‐specific medical and interventional management. The details in this document provide background and framework from which to apply AECG techniques in clinical practice, as well as clinical research.

The evolution of sports participation guidelines and the influence of genotype-phenotype correlation in long QT syndrome.

Congenital Long QT Syndrome (LQTS) results in abnormal ventricular repolarization in patients with otherwise structurally normal hearts. Following the initial clinical descriptions of LQTS, there has been a great deal of investigation into the genetic etiology and pathophysiology of these entities, with the goal of improved screening tools and understanding of associated risks. Through this work, heart rhythm experts continue to revise their recommendations regarding sports eligibility. We review the evolution of sports participation recommendations for LQTS.

Use of dofetilide in adult patients with atrial arrhythmias and congenital heart disease: A PACES collaborative study

BACKGROUND Arrhythmia management has become the major treatment challenge in adult patients with congenital heart disease (ACHD). OBJECTIVE We sought to investigate the utility and safety profile of dofetilide for atrial arrhythmias in ACHD. METHODS A retrospective chart review was performed. We included patients (age ≥18 years) with congenital heart disease who had atrial fibrillation (AF) or intra-atrial reentrant tachycardia treated with dofetilide. RESULTS We identified 64 patients with a mean age at initiation of 42 ± 14 years. ACHD type included single ventricle (n = 19, 30%), transposition of the great arteries (n = 14, 22%), atrial septal defect (n = 9, 14%), tetralogy of Fallot (n = 8, 12%), atrioventricular canal defect (n = 5, 8%), mitral/aortic stenosis (n = 7, 11%), and other (n = 2, 3%). Thirty-five (55%) had atrial fibrillation, and 29 (45%) had intra-atrial reentrant tachycardia. A total of 3 (4.7%) patients had major inpatient adverse events: torsades de pointes (n = 1, 1.5%), ventricular tachycardia (n = 1, 1.5%), and corrected QT prolongation requiring discontinuation (n = 1, 1.5%). Dofetilide was discontinued in 1 patient because of sinus node dysfunction, and another patient discontinued therapy before discharge because of persistent arrhythmia. Of the patients who were discharged on dofetilide (n = 59, 92%), 40 (68%) had adequate rhythm control and 19 (32%) had partial rhythm control. After a median follow-up of 3 years, 29 (49%) patients remained on dofetilide and 2 (3%) patients died. Reasons for discontinuation included waning effect (n = 16, 57%), side effects (n = 5, 18%), noncompliance (n = 2, 7%), successful ablation (n = 3, 11%), high cost (n = 1, 3.5%), and unknown (n = 1, 3.5%). CONCLUSION Dofetilide remains a viable antiarrhythmic drug option in this challenging population. At 3 years, 49% remained on dofetilide. Close monitoring of renal function, concomitant medications, and corrected QT interval is required.

Genotype-phenotype correlation in long QT syndrome

Congenital long QT syndrome, caused by a cardiac channelopathy, is a leading cause of sudden cardiac death in the young population. In total, 16 genes have been implicated in this condition, with three genes being the most commonly affected. Long QT syndrome is one of the earliest conditions for which a genotype specific treatment was designed. This genotype-phenotype correlation extends to involve the clinical presentation, electrocardiographic manifestation and treatment strategies. It is necessary for the clinician treating these patients to be cognizant of the important role played by the genotype in order to best provide counseling and treatment options to this unique population.

Do LQTS gene single nucleotide polymorphisms alter QTc intervals at rest and during exercise stress testing

The impact of harboring, genetic variants or single nucleotide polymorphisms (LQT‐PM) on the repolarization response during exercise and recovery is unknown.