Atrial Support Pacing in Heart Failure: Results from the Multicenter PEGASUS CRT Trial

Atrial Pacing in Heart Failure. Introduction: Cardiac resynchronization therapy (CRT) efficacy trials to date used atrial‐synchronous biventricular pacing wherein there is no or minimal atrial pacing. However, bradycardia and chronotropic incompetence are common in this patient population. This trial was designed to evaluate the effect of atrial support pacing among heart failure patients receiving a CRT defibrillator. Methods and Results: PEGASUS CRT was a multicenter, 3‐arm, randomized study. At 6 weeks, patients were randomized to DDD mode at a lower rate of 40 bpm (DDD‐40; control arm), or one of the following 2 treatment arms: DDD‐70, or DDDR‐40. The primary endpoint was a clinical composite endpoint that included all‐cause mortality, heart failure events, NYHA functional class, and patient global self‐assessment. Subjects were classified as improved, unchanged, or worsened at 12 months. There were 1,433 patients randomized, of whom 66% were male, mean age was 67 ± 11 years, and mean left ventricular ejection fraction was 23 ± 7%. The average follow‐up time was 10.5 ± 3.5 months and 1,309 patients contributed to the primary endpoint. No significant differences were observed in the composite endpoint between either of the 2 treatment arms compared to the control arm (P>0.05 for both comparisons). Additionally, there were no differences among the groups in mortality or heart failure events. Conclusion: In advanced heart failure patients treated with CRT, atrial support pacing did not improve clinical outcomes compared to atrial tracking. However, atrial pacing did not adversely affect mortality or heart failure events. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1317‐1325, December 2012)     

Lessons learned from a pediatric clinical trial: the Pediatric Heart Network angiotensin-converting enzyme inhibition in mitral regurgitation study

BACKGROUND: Mitral regurgitation is the most common indication for reoperation in children following repair of atrioventricular septal defect (AVSD). We hypothesized that angiotensin-converting enzyme inhibitor therapy would decrease the severity of mitral regurgitation and limit left ventricular volume overload in children following AVSD repair. METHODS: The Pediatric Heart Network designed a placebo-controlled randomized trial of enalapril in this population. The primary aim was to test the effect of enalapril on the change in left ventricular end-diastolic dimension body surface area-adjusted z score. Before the launch of the trial, a feasibility study was performed to estimate the number of patients with at least moderate mitral regurgitation following AVSD repair. TRIAL EXPERIENCE: Seventeen months after the start of the study, 349 patients were screened, 8 were trial eligible, and only 5 were enrolled. The study was subsequently terminated because of low patient accrual. Several factors led to the problems with patient accrual, including (1) the use of criteria to assess disease severity in the feasibility study that were not identical to those used in the trial, (2) failure to achieve equipoise for the study among clinicians and referring physicians, (3)?reliance on methodology developed in adult populations with different disease mechanisms, and (4) absence of adequate data to define the natural history of the disease process under study. Progress in the treatment of children with cardiovascular disease will depend on the future of multicenter collaborative clinical trials. The lessons learned from this study may contribute to improvements in this research.     

Exercise capacity and impact of exercise training in patients after a Fontan procedure: a review

After a successful Fontan procedure, children and adolescents should improve their exercise capacity. However, several studies have shown that these children have a reduced maximal oxygen consumption compared with healthy children. The lower exercise performance in these patients was mainly explained by a reduced cardiorespiratory functional capacity. However, it has recently been reported that the lower exercise performance may also be related to altered skeletal muscle function. Moreover, exercise training had a beneficial impact on several parameters related to exercise tolerance in these patients. The main studies supporting these observations are reviewed, with a focus on the physiological adaptation and limitation of the exercise performance as well as the benefits of exercise training in patients after a Fontan procedure.     

Use of Implantable Cardioverter-Defibrillators in Congenital Heart Disease and Pediatric Patients: Results from the German National Registry for Congenital Heart Defects

Background: Sudden cardiac death is a leading cause of death in patients with congenital heart disease (CHD). Risk stratification for implantable cardioverter defibrillators (ICD) remains difficult due to limited data about use and outcome of device therapy in CHD patients in larger community-based cohorts. Methods and results: Out of a dataset with more than 50,000 patients registered at the German National Register for Congenital Heart Defects, 109 patients (median age 35.5; IQR 23.75–46.00), 68 (62%) male) with an ICD were identified and were retrospectively analyzed. Although the number of implantations increased steadily throughout the investigated time interval from 2001 to 2015, only 0.2% of the CHD patients in the national register received an ICD. Indication for ICD implantation was secondary prevention in 84 patients (78%) and primary prevention in 24 patients (22%). 23 patients (21%) of the ICD patients received appropriate ICD therapy. 7 patients (6%) received an inappropriate ICD therapy. In 23 patients (21%) device complications were documented with a high number of lead fractures and insulation defects (n = 14,13%). Conclusion: The current study investigates the clinical uptake and use of ICD therapy based on a large national registry for CHD patients. Despite a steady increase in the number of implanted devices, ICD uptake remains relatively low, particularly for primary prevention. The data suggests a potential reluctance in utilization of device therapy in this patient cohort for primary prevention. Selecting patients in whom benefits outweigh the risks associated with lifelong ICD therapy remains challenging.     

Exercise performance in children and adolescents after the Ross procedure

OBJECTIVES: The Ross procedure is increasingly utilized in the treatment of aortic valvar disease in children and adolescents. Our purpose was to compare pre- and post-operative exercise state in this population. METHODS: We included patients who underwent the Ross procedure at our institution between January, 1995, and December, 2003, and in whom we had performed pre- and post-operative exercise stress tests. We used a ramp bicycle protocol to measure consumption of oxygen and production of carbon dioxide. Cardiac output was estimated from effective pulmonary blood flow by the helium acetylene re-breathing technique. RESULTS: We studied 26 patients, having a median age at surgery of 15.7 years, with a range from 7.5 to 24.1 years. The primary indication for surgery in two-thirds was combined aortic stenosis and insufficiency. Median time from the operation to the post-operative exercise stress test was 17.4 months, with a range from 6.7 to 30.2 months. There was a trend toward lower maximal consumption of oxygen after the procedure, at 36.3 plus or minus 7.6 millilitres per kilogram per minute (83.9% predicted) as opposed to 38.6 plus or minus 8.4 millilitres per kilogram per minute (88.5% predicted, p equal to 0.06). Patients after the procedure, however, had significantly increased adiposity, so that there was no difference in maximal consumption of oxygen indexed to ideal body weight before and after the operation. In 20 of the patients, aerobic capacity improved or was stable after the operation. There was no post-operative chronotropic impairment. CONCLUSIONS: In the majority of patients following the Ross procedure, exercise performance is stable and within the normal range of a healthy age and sex matched population, despite sedentary lifestyles and increased adiposity.     

Safety and Feasibility of Melody Transcatheter Pulmonary Valve Replacement in the Native Right Ventricular Outflow Tract: A Multicenter Pediatric Heart Network Scholar Study

Objectives

This study sought to determine the safety and feasibility of transcatheter pulmonary valve replacement (TPVR) using the Melody valve in native (nonconduit) right ventricular outflow tracts (nRVOT), and to identify factors associated with successful TPVR.

Cardiopulmonary exercise performance in adult survivors of the Mustard procedure

Most patients with the Mustard procedure are now adults. To date, however, there have been few reports on resting and exercise hemodynamics in a large population of adults with this circulation. The aim of this study is to describe such parameters in one of the largest and oldest populations of adults with the Mustard procedure. The database of the University of Toronto Congenital Cardiac Centre for Adults was examined to identify 84 adults with the Mustard procedure who have undergone cardiopulmonary exercise tests. Magnetic resonance imaging and echocardiography studies were obtained in order to assess right ventricular size, function and baseline hemodynamics. Patients achieved lower maximum uptake of oxygen, maximal heart rate, forced vital capacity, forced expiratory volume in 1 second, and oxygen saturations at maximal exercise compared to a healthy population. Magnetic resonance imaging showed significantly different right ventricular ejection fractions between patients and controls. There were no effects of operative variables or preoperative hemodynamics on current exercise capacity. Patients after the Mustard procedure have subnormal exercise capacities. Factors such as chronotropic incompetence, peripheral deconditioning, and impaired lung function may be responsible for these results.     

Radionuclide assessment of ventricular contraction at rest and during exercise following the Fontan procedure for either tricuspid atresia or single ventricle

Ventricular contraction was evaluated in 18 patients studied at a mean of 2.6 years after Fontan repair. The diagnosis was tricuspid atresia in 9 patients and single ventricle in 9. Gated first-pass and gated equilibrium radionuclide ventriculography were performed at rest and during exercise. Abnormally low ventricular ejection fraction (EF) at rest was present in 8 of 18 patients by the gated equilibrium technique and 6 of 13 technically adequate gated first-pass studies. An abnormal response to exercise (failure of EF to increase less than or equal to 5% from rest to maximal exercise) was found in 10 of 16 patients by the gated equilibrium technique and in 8 of 12 by the gated first-pass technique. Only 2 patients by each radionuclide technique had both normal EF at rest and normal exercise response. Thus, this study confirms the frequent presence of abnormalities in ventricular contraction after the Fontan procedure at rest or during exercise or both despite absence of symptoms. Both EF response and the hemodynamic response during exercise were more abnormal in the presence of an atriopulmonary than an atrioventricular connection.