Michael G. McBride

Impact of Oral Sildenafil on Exercise Performance in Children and Young Adults After the Fontan Operation A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Background— Children and young adults with single-ventricle physiology have abnormal exercise capacity after the Fontan operation. A medication capable of decreasing pulmonary vascular resistance should allow improved cardiac filling and improved exercise capacity. Methods and Results— This study was a double-blind, placebo-controlled, crossover trial conducted in children and young adults after Fontan. Subjects were randomized to receive placebo or sildenafil (20 mg three times daily) for 6 weeks. After a 6-week washout, subjects crossed over for an additional 6 weeks. Each subject underwent an exercise stress test at the start and finish of each phase. After taking sildenafil, subjects had a significantly decreased respiratory rate and decreased minute ventilation at peak exercise. At the anaerobic threshold, subjects had significantly decreased ventilatory equivalents of carbon dioxide. There was no change in oxygen consumption during peak exercise, although there was a suggestion of improved oxygen consumption at the anaerobic threshold. Improvement at the anaerobic threshold was limited to the subgroup with single left or mixed ventricular morphology and to the subgroup with baseline serum brain natriuretic peptide levels ≥100 pg/mL. Conclusions— In this cohort, sildenafil significantly improved ventilatory efficiency during peak and submaximal exercise. There was also a suggestion of improved oxygen consumption at the anaerobic threshold in 2 subgroups. These findings suggest that sildenafil may be an important agent for improving exercise performance in children and young adults with single-ventricle physiology after the Fontan operation. Clinical Trial Registration— URL: . Unique identifier: [NCT00507819][1]. # Clinical Perspective {#article-title-31} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00507819&atom=%2Fcirculationaha%2F123%2F11%2F1185.atomBackground— Children and young adults with single-ventricle physiology have abnormal exercise capacity after the Fontan operation. A medication capable of decreasing pulmonary vascular resistance should allow improved cardiac filling and improved exercise capacity. Methods and Results— This study was a double-blind, placebo-controlled, crossover trial conducted in children and young adults after Fontan. Subjects were randomized to receive placebo or sildenafil (20 mg three times daily) for 6 weeks. After a 6-week washout, subjects crossed over for an additional 6 weeks. Each subject underwent an exercise stress test at the start and finish of each phase. After taking sildenafil, subjects had a significantly decreased respiratory rate and decreased minute ventilation at peak exercise. At the anaerobic threshold, subjects had significantly decreased ventilatory equivalents of carbon dioxide. There was no change in oxygen consumption during peak exercise, although there was a suggestion of improved oxygen consumption at the anaerobic threshold. Improvement at the anaerobic threshold was limited to the subgroup with single left or mixed ventricular morphology and to the subgroup with baseline serum brain natriuretic peptide levels ≥100 pg/mL. Conclusions— In this cohort, sildenafil significantly improved ventilatory efficiency during peak and submaximal exercise. There was also a suggestion of improved oxygen consumption at the anaerobic threshold in 2 subgroups. These findings suggest that sildenafil may be an important agent for improving exercise performance in children and young adults with single-ventricle physiology after the Fontan operation. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00507819.

Position statement on youth resistance training: the 2014 International Consensus

The current manuscript has been adapted from the official position statement of the UK Strength and Conditioning Association on youth resistance training. It has subsequently been reviewed and endorsed by leading professional organisations within the fields of sports medicine, exercise science and paediatrics. The authorship team for this article was selected from the fields of paediatric exercise science, paediatric medicine, physical education, strength and conditioning and sports medicine.

Exercise performance after the arterial switch operation for d-transposition of the great arteries

Early- and intermediate-term results of the arterial switch operation for D-transposition of the great arteries (D-TGA) are encouraging. However, questions remain about the long-term outcome for these patients, especially with regard to exercise performance. Preliminary studies have demonstrated normal endurance time on treadmills. However, data regarding aerobic capacity and cardiopulmonary function are lacking. We report the cardiopulmonary performance of 22 school-age patients with D-TGA who underwent the arterial switch operation. Outcome variables included maximal oxygen consumption (VO2), maximal cardiac index, and peak heart rate. Patient and procedure-related variables were assessed for their association with outcome variables using linear and logistic regression. The mean values of maximal VO2 (113 +/- 19% predicted) and maximal cardiac index (96 +/- 18% predicted) were within normal limits for the pediatric population. Although the mean peak heart rate for the entire group (184 +/- 14 beats/min) was within normal limits, there were 7 subjects (32%) with chronotropic impairment. Significant ST-segment depression was seen in 2 subjects (9%). In regression analysis, surgery subsequent to the arterial switch was associated with lower maximal cardiac index (p = 0.01). Other variables were not significantly associated with maximal VO2, maximal cardiac index, and peak heart rate. In particular, chronotropic impairment was not significantly associated with maximal VO2 or maximal cardiac index. These findings demonstrate that cardiopulmonary performance during exercise is excellent after the arterial switch operation. The finding of ST-segment depression in some subjects supports the role of formal exercise testing in those patients participating in vigorous athletic activities.

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.

Exercise Performance in Tetralogy of Fallot: The Impact of Primary Complete Repair in Infancy

Primary complete repair (PCR) of tetralogy of Fallot (TOF) is now routinely performed in infancy. Although operative results are excellent, the impact on exercise performance is incompletely understood. We reviewed data of all children with TOF who underwent PCR at our institution and had subsequent maximal cycle ergometer exercise testing between January 1995 and December 2000. Of the 193 patients with TOF who underwent PCR, 57 (30%) underwent exercise testing; maximal tests were available for 50 of 57 (88%). Exercise performance of subjects who underwent PCR at <1 YEAR OF AGE WAS COMPARED TO THAT OF THOSE WHO UNDERWENT REPAIR AT >l year of age. The median age at PCR was 10.9 months; 28 subjects (56%) underwent PCR in infancy (<1 year). A transannular incision was employed in the repair in 41 subjects (82%). The mean age at exercise testing was 12.5 ± 3.2 years. The mean maximal VO2 was 94.9 ± 18.8% predicted and the mean maximal work rate was 98.0 ± 20.8% predicted. In multivariate analysis PCR in infancy (age <1 year) was not associated with maximal VO2, peak work rate, peak heart rate, or arrhythmias. Only older age at testing and male gender were significantly associated with higher maximal VO2 (p = 0.005 and p = 0.002, respectively). Intermediate-term exercise performance in subjects who undergo PCR of TOF in early childhood is near normal. Performing PCR in the first year of life does not impact subsequent exercise performance.

Anomalous left coronary artery origin from the opposite sinus of Valsalva: Evidence of intermittent ischemia

FIGURE 1. Electrocardiogram from submaximal exercise stress test o From the Divisions of Cardiology and Cardiothoracic Surgery, The Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pa. Disclosures: None. Received for publication April 14, 2009; accepted for publication June 10, 2009; available ahead of print Aug 31, 2009. Address for reprints: Julie Brothers, MD, Cardiology, Main Building, 8NW75, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104 (E-mail: brothersj@email.chop.edu). J Thorac Cardiovasc Surg 2010;140:e27-9 0022-5223/

Following the arterial switch operation, obese children have risk factors for early cardiovascular disease.

36.00 Copyright 2010 by The American Association for Thoracic Surgery doi:10.1016/j.jtcvs.2009.06.029

Exercise performance and quality of life following surgical repair of anomalous aortic origin of a coronary artery in the pediatric population.

BACKGROUND Children who have undergone the arterial switch operation (ASO) are at risk for premature coronary artery disease due to coronary re-implantation. Obesity may also pose cardiovascular risk. The purpose of this study was to evaluate comorbidities and markers of early cardiovascular disease in obese ASO patients. METHODS Obese [body mass index (BMI) >or= 95th %] and normal weight (NW, BMI < 85th %) ASO patients, and NW controls without heart disease were enrolled, and underwent prospective vascular, echocardiographic, laboratory, exercise, and ambulatory blood pressure (BP) testing. Results were compared between groups. BP load was defined as proportion of recordings >or= 95th %. RESULTS Thirty patients [13.2 years (11.2-16.8), 57% male] were evaluated: 10 obese ASO, 10 NW ASO, and 10 NW controls. Obese ASO patients, in comparison to NW ASO and controls, had higher systolic BP% [96% (90-99) vs. 67% (30-91) P= 0.07 (trend) and 34% (21-43) P= 0.005], night-time diastolic BP load [18% (14-24) vs. 0% (0-0) P= 0.01 and 0% (0-0) P= 0.01], left ventricular mass index [51.7 g/m(2.7) (46.6-53.3) vs. 40.7 g/m(2.7) (29.2-41.6) P < 0.01 and 28.9 g/m(2.7) (27.3-33.7) P < 0.01], and lower brachial artery reactivity [8.7% (6.2-11.9) vs. 14.6% (10.8-23.0) P= 0.03, and 16.7% (12.8-17.8) P= 0.05]. There was a trend toward increased carotid intima-media thickness, and significantly higher triglyceride and lower high-density lipoprotein levels in obese ASO patients. CONCLUSIONS Following the ASO, obese patients have associated comorbidities, and markers of early cardiovascular disease. These may pose additional risk for future cardiovascular events in this unique population who underwent coronary artery re-implantation in infancy.

Chest Compression Quality Over Time in Pediatric Resuscitations

OBJECTIVE We sought to evaluate exercise performance and quality of life in children after surgical repair of anomalous aortic origin of a coronary artery with an interarterial course. METHODS Patients who had surgery from October 2001 to January 2007 were eligible for inclusion. Exercise performance and quality of life were prospectively assessed by maximal exercise tests and age-appropriate questionnaires, respectively. We used t tests to compare pre- and postoperative exercise data and quality-of-life scores to published normative data. We performed linear regression analyses to assess associations between demographic, anatomic, and exercise variables and quality-of-life score. RESULTS Of 25/27 patients, 64% were boys, 68% had anomalous right coronary, 32% were asymptomatic. Average age at surgery was 10.8 (+/-4.1) years; median follow-up was 14.5 (2 to 48) months. Postoperative percent-predicted exercise values were: peak heart rate 97 (+/-6), working capacity 91 (+/-15), maximal oxygen consumption 82 (+/-16). In those who had preoperative exercise testing (n = 11), resting and maximal heart rates decreased significantly without significant change in exercise performance. Average child quality of life was 85/100 (+/-13) and parent-proxy 88 (+/-11) compared with normal scores of 83 (+/-15) and 88 (+/-12), respectively. CONCLUSION There is mild chronotropic impairment in children and adolescents following anomalous coronary artery repair without a decline in exercise performance. This does not appear to impair their overall quality of life. Because long-term effects on heart rate, exercise performance, and quality of life are unknown, serial exercise tests should be included as routine care of these patients.

Safety and feasibility of inpatient exercise training in pediatric heart failure: a preliminary report.

BACKGROUND: Chest compression (CC) quality deteriorates with time in adults, possibly because of rescuer fatigue. Little data exist on compression quality in children or on work done to perform compressions in general. We hypothesized that compression quality, work, and rescuer fatigue would differ in child versus adult manikin models. METHODS: This was a prospective randomized crossover study of 45 in-hospital rescuers performing 10 minutes of single-rescuer continuous compressions on each manikin. An accelerometer recorded compression quality measures over 30-second epochs. Work and power were calculated from recorded force data. A modified visual analogue scale measured fatigue. Data were analyzed by using linear mixed-effects models and Cox regression analysis. RESULTS: A total of 88 484 compression cycles were analyzed. Percent adequate CCs/epoch (rate ≥ 100/minute, depth ≥ 38 mm) fell over 10 minutes (child: from 85.1% to 24.6%, adult: from 86.3% to 35.3%; P = .15) and were <70% in both by 2 minutes. Peak work per compression cycle was 13.1 J in the child and 14.3 J in the adult (P = .06; difference, 1.2 J; 95% confidence interval, −0.05 to 2.5). Peak power output was 144.1 W in the child and 166.5 W in the adult (P < .001; difference, 22.4 W, 95% confidence interval, 9.8–35.0). CONCLUSIONS: CC quality deteriorates similarly in child and adult manikin models. Peak work per compression cycle is comparable in both. Peak power output is analogous to that generated during intense exercise such as running. CC providers should switch every 2 minutes as recommended by current guidelines.