Pulmonary responses following cardiac rehabilitation and the relationship with functional outcomes in children and young adults with heart disease.

Introduction: Patients with congenital heart disease (CHD) often have pulmonary abnormalities and exercise intolerance following cardiac surgery. Cardiac rehabilitation (CR) improves exercise capacity in patients with CHD, but minimal study has been performed to see if resting and dynamic pulmonary performance improves following CR in those with prior cardiac surgery. Methods: This was a retrospective cohort study of all patients who completed ≥12 weeks of CR from 2018 through 2022. Demographic, cardiopulmonary exercise test (CPET), spirometry, 6-minute walk, functional strength measures, and outcomes data were collected. Data are presented as median[IQR]. A Student's t-test was used for comparisons between groups and serial measurements were measured with a paired t-test. A p < 0.05 was considered significant. Results: There were a total of 37 patients [age 16.7 (14.2-20.1) years; 46% male] included. Patients with prior surgery (n = 26) were more likely to have abnormal spirometry data than those without heart disease (n = 11) (forced vital capacity [FVC] 76.7 [69.1-84.3]% vs. 96.4 [88.1-104.7]%, p = 0.002), but neither group experienced a significant change in spirometry. On CPET, peak oxygen consumption increased but there was no change in other pulmonary measures during exercise. Percent predicted FVC correlated with hand grip strength (r = 0.57, p = 0.0003) and percent predicted oxygen consumption (r = 0.43, p = 0.009). The number of prior sternotomies showed negative associations with both percent predicted FVC (r = -0.43, p = 0.04) and FEV1 (r = -0.47, p = 0.02). Discussion: Youth and young adults with a prior history of cardiac surgery have resting and dynamic pulmonary abnormalities that do not improve following CR. Multiple sternotomies are associated with worse pulmonary function.

Facility-Based and Virtual Cardiac Rehabilitation in Young Patients with Heart Disease During the COVID-19 Era.

Cardiac rehabilitation (CR) is an important tool for improving fitness and quality of life in those with heart disease (HD). Few pediatric centers use CR to care for these patients, and virtual CR is rarely used. In addition, it is unclear how the COVID-19 era has changed CR outcomes. This study assessed fitness improvements in young HD patients participating in both facility-based and virtual CR during the COVID-19 pandemic. This retrospective single-center cohort study included new patients who completed CR from March 2020 through July 2022. CR outcomes included physical, performance, and psychosocial measures. Comparison between serial testing was performed with a paired t test with P < 0.05 was considered significant. Data are reported as mean ± standard deviation. There were 47 patients (19 ± 7.3 years old; 49% male) who completed CR. Improvements were seen in peak oxygen consumption (VO2, 62.3 ± 16.1 v 71 ± 18.2% of predicted, p = 0.0007), 6-min walk (6 MW) distance (401 ± 163.8 v 480.7 ± 119.2 m, p = < 0.0001), sit to stand (16.2 ± 4.9 v 22.1 ± 6.6 repetitions; p = < 0.0001), Patient Health Questionnaire-9 (PHQ-9) (5.9 ± 4.3 v 4.4 ± 4.2; p = 0.002), and Physical Component Score (39.9 ± 10.1 v 44.9 ± 8.8; p = 0.002). Facility-based CR enrollees were less likely to complete CR than virtual patients (60%, 33/55 v 80%, 12/15; p = 0.005). Increases in peak VO2 (60 ± 15.3 v 70.2 ± 17.8% of predicted; p = 0.002) were seen among those that completed facility-based CR; this was not observed in the virtual group. Both groups demonstrated improvement in 6 MW distance, sit-to-stand repetitions, and sit-and-reach distance. Completion of a CR program resulted in fitness improvements during the COVID-19 era regardless of location, although peak VO2 improved more for the in-person group.

Effects of a zero-gravity treadmill on body composition and cardiorespiratory fitness after Achilles surgery in a Masters runner.

Zero-gravity treadmills allow alterations in training load. Data are lacking on the utilization of this strategy to allow injured Masters-level athletes to return to activity and regain their fitness. A 6-week training program was designed for a 39-year-old male runner recovering from Achilles surgery using a zero-gravity treadmill. Three training sessions per week were performed with gradually increasing loads. Cardiopulmonary exercise testing and bioelectrical impedance analysis were performed before and after program completion. Following the training program, the athlete was able to return to full weight-bearing running. On cardiopulmonary exercise testing, there were improvements in peak oxygen consumption (42.9 vs 47.3 mL/min/kg; 118.6% vs 130.5% of predicted). On bioelectrical impedance analysis, there were small improvements in total weight, skeletal muscle mass, and adiposity felt to be within the standard of error for bioelectrical impedance analysis. In conclusion, load-altering exercise may be helpful for the Masters-level athlete recovering from Achilles tendon surgery.

Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial).

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO2 (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241.

Stable fitness during COVID-19: Results of serial testing in a cohort of youth with heart disease.

Background: Little is known about how sport and school restrictions early during the novel coronavirus 2019 (COVID-19) pandemic impacted exercise performance and body composition in youth with heart disease (HD). Methods: A retrospective chart review was performed on all patients with HD who had serial exercise testing and body composition via bioimpedance analysis performed within 12 months before and during the COVID-19 pandemic. Formal activity restriction was noted as present or absent. Analysis was performed with a paired t-test. Results: There were 33 patients (mean age 15.3 ± 3.4 years; 46% male) with serial testing completed (18 electrophysiologic diagnosis, 15 congenital HD). There was an increase in skeletal muscle mass (SMM) (24.1 ± 9.2-25.9 ± 9.1 kg, p < 0.0001), weight (58.7 ± 21.5-63.9 ± 22 kg, p < 0.0001), and body fat percentage (22.7 ± 9.4-24.7 ± 10.4%, p = 0.04). The results were similar when stratified by age <18 years old (n = 27) or by sex (male 16, female 17), consistent with typical pubertal changes in this predominantly adolescent population. Absolute peak VO2 increased, but this was due to somatic growth and aging as evidenced by no change in % of predicted peak VO2. There remained no difference in predicted peak VO2 when excluding patients with pre-existing activity restrictions (n = 12). Review of similar serial testing in 65 patients in the 3 years before the pandemic demonstrated equivalent findings. Conclusions: The COVID-19 pandemic and related lifestyle changes do not appear to have had substantial negative impacts on aerobic fitness or body composition in children and young adults with HD.

Long-term exercise and pulmonary function outcomes in a contemporary cohort of children with congenital diaphragmatic hernia.

OBJECTIVE: Congenital diaphragmatic hernia (CDH) survivors are at risk for long-term exercise impairment and pulmonary morbidity, but the generalizability of prior reported cohorts are limited by reduced disease severity and older surgical eras. We assessed the mid-childhood exercise and pulmonary function outcomes in a contemporary cohort of CDH survivors. STUDY DESIGN: In this retrospective cohort study, we identified 36 consecutive pediatric CDH survivors who underwent cardiopulmonary exercise testing (CPET) and spirometry from 2014 to 2021. Inferential statistics compared survivors with age-, sex-, and size-matched healthy controls; univariate analyses identified factors associated with abnormal testing. RESULTS: Maximal effort CPET and resting spirometry were completed by 27/36 (75%) and 31/36 (86%) subjects, respectively (median age: 8.1 years [interquartile range: 7.5, 10]; 16 females [44%]). Abnormal CPET (percent predicted [pp] peak VO2 < 80%) was more common in the CDH cohort (12 vs. 1, p < 0.001) and associated with longer neonatal intensive care unit (NICU) stay (p = 0.02) and oxygen therapy at discharge (p = 0.03). Exercise impairment was mild (pp peak VO2 70%-80%), moderate (60%-70%), and severe (<60%) in 6, 4, and 2 survivors, respectively. Abnormal spirometry was more common in the CDH cohort (21 vs. 3, p < 0.001; obstructive [n = 15], restrictive [n = 6]) and associated with decreased gestational age (p = 0.046), longer mechanical ventilation in the NICU (p = 0.02), and orthopedic abnormalities (p = 0.03). CONCLUSION(S): Exercise capacity was normal or mildly impaired in most CDH survivors, however, approximately two-thirds demonstrated abnormal spirometry. Impaired exercise capacity and lung function were associated with severity of lung disease postnatally. These data support cardiopulmonary follow-up throughout childhood.

Pediatric youth who have obesity have high rates of adult criminal behavior and low rates of homeownership.

Objectives: The social outcomes in adulthood for pediatric patients with obesity are not well-described. This study investigated lifetime criminal behavior and homeownership in youth with obesity. Methods: Retrospective data on all children enrolled in the weight management program from 1999 to 2009 and who completed exercise testing were collected. Demographic and public record collection included body habitus, death records, real estate transactions, and criminal conviction history with comparisons made to published normative data. Results: In the children with obesity studied (N = 716; 12.0 ± 3.1 years old), the now-adult patients (28.5 ± 3.7 years) had a 1.5% mortality rate (11/716). Overall, 9.6% of these adults were convicted of a felony compared to ~7% lifetime prevalence in Ohio (p = 0.03). Also, 14.7% of study patients purchased a home compared to 38.3% of Midwest adults <30 years old (p < 0.0001). Mortality, history of a criminal conviction, or homeownership was associated with any exercise or study parameter. Conclusion: Children with obesity appear to have greater social risk than their peers in adulthood with higher rates of criminal behavior and lower rates of homeownership. This appears to highlight the need for treatment in this vulnerable group of children and young adults.

Arrhythmia Burden and Heart Rate Response During Exercise in Anderson-Fabry Disease.

Patients with Anderson-Fabry disease (AFD) have an elevated incidence of resting arrhythmias and ischemic heart disease, but their exercise arrhythmia burden and ischemic changes are not well understood. In addition, little research has been done on heart rate recovery in these patients. We retrospectively reviewed charts of patients with AFD who underwent maximal effort cardiopulmonary exercise testing (CPET) (n=44; 38.2 ± 13.8 yr; 23 men) from 2012 through 2018. Electrocardiographic, Holter monitoring, echocardiographic, cardiac magnetic resonance imaging, and patient demographic data were collected. No patient had adverse events that necessitated CPET termination, whereas 25 (57%) had ectopy during CPET, including 3 (7%) with frequent premature atrial contractions and 5 (11%) with frequent premature ventricular contractions. The ectopic burden was higher during resting electrocardiographic monitoring before exercise. In addition, 7 patients (16%) had pathologic ST-segment or T-wave changes on CPET, defined as ST-segment changes ≥2 mm. Among the patients who had concurrent cardiac magnetic resonance findings with their CPET (n=27), ST-segment or T-wave changes were associated with left ventricular myocardial mass (r=0.43, P=0.02). Chronotropic incompetence was seen during CPET in 28 patients (64%); however, only 2 patients (4%) had abnormal heart rate recovery at 1 minute. This study shows that patients with AFD can safely undergo exercise testing but have a high incidence of exercise-induced arrhythmias and ischemic changes. Ischemic electrocardiographic changes during exercise testing are associated with myocardial mass. Despite the chronotropic incompetence associated with AFD, heart rate recovery appears to be generally preserved in these patients.

Physical Frailty is Modifiable in Young Cardiac Rehabilitation Patients.

Frailty is a standardized, quantitative metric used to assess multisystem physiologic reserve and vulnerability to poor health outcomes. Cardiac rehabilitation (CR) positively impacts patient outcomes, including frailty, in adult cardiovascular disease (CVD); however, both the frailty paradigm and CR are understudied in pediatric CVD. This retrospective, single-center cohort study aimed to determine baseline composite frailty for pediatric-onset CVD patients and examine its change throughout CR using a proposed frailty assessment tool. Youth with pediatric-onset CVD participating in CR were stratified into five CVD diagnostic groups: post-heart transplant (HTx) (n = 34), post-ventricular assist device (VAD) (n = 12), single ventricle (n = 20) and biventricular (n = 29) congenital heart disease, and cardiomyopathy (n = 25), and frailty was assessed at baseline and every 30 days during CR. Post-HTx and post-VAD groups had significantly higher median frailty scores at baseline (6/10 and 5.75/10, respectively) driven by reduced strength, gait speed, and functional status. All groups except post-VAD displayed a significant absolute reduction in frailty from baseline to 120 days (HTx: - 3.5; VAD: - 3; SV CHD: - 1; BV CHD: - 1; CM: - 1.5), with similar median post-CR scores (1-3/10 in all groups). These improvements did not significantly correlate with number of CR sessions attended. This study established that frailty exhibits discriminatory utility across pediatric-onset CVD groups at baseline and is significantly modifiable over time. Improvements in frailty and other fitness metrics are likely due to a combination of post-operative recovery, post-diagnosis pharmacological and lifestyle changes, and CR. Further study of this frailty tool is needed to explore its prognostic utility.

Practices and Procedures in Clinical Pediatric Exercise Laboratories in North America.

Interinstitutional differences in clinical pediatric exercise laboratory (CPEL) practices may affect patient care and efficacy of multicenter research. PURPOSE: To describe current practices/procedures in CPELs and explore differences in CPELs employing exercise physiologists to those that do not. METHODS: A 40-item survey was distributed to CPELs in North America focusing on (1) staffing; (2) exercise stress testing (EST) volumes, reporting, and interpretation; and (3) EST procedures/protocols. RESULTS: Of the 55 responses, 89% were in the United States, 85% were children's hospitals with university affiliation, and 58% were cardiology specific. Exercise physiologists were employed in 56% of CPELs, and 78% had master's degrees or higher. Certifications were required in most CPELs (92% emergency life-support, 27% professional, and 21% clinical). Median volume was 201 to 400 ESTs per year, 80% used treadmill, and 10% used cycle ergometer as primary modalities. Ninety-three percent of CPELs offered metabolic ESTs, 87% offered pulmonary function testing, 20% used institution-specific EST protocols, and 72% offered additional services such as cardiac/pulmonary rehabilitation. CPELS staffing exercise physiologists performed higher volumes of ESTs (P = .004), were more likely to perform metabolic ESTs (P = .028), participated in more research (P < .001), and provided services in addition to ESTs (P = .001). CONCLUSIONS: Heterogeneity in CPELs staffing and operation indicates need for standardization.

Abnormal Maximal and Submaximal Cardiopulmonary Exercise Capacity in Pediatric Stem Cell Transplant Recipients Despite Normal Standard Echocardiographic Parameters: A Pilot Study.

Left ventricular systolic dysfunction is a known complication of stem cell transplantation (SCT). There has been minimal research to determine whether subclinical cardiac dysfunction exists in SCT patients using tools other than standard echocardiography, such as maximal and submaximal effort cardiopulmonary exercise testing (CPET) and vascular function studies. The objective of this study was to determine the rate of subclinical cardiac dysfunction in patients with normal ejection fraction after SCT, identified by abnormal values by CPET, tissue-Doppler imaging, and arterial stiffness measurements and to further describe submaximal exercise test measures in this population. A prospective cohort study of SCT survivors who were at least 3 years after SCT without prior anthracycline or radiation exposure and with preserved systolic function (left ventricular ejection fraction > 50%) was performed to evaluate for abnormalities in exercise, vascular function, and diastolic function in an effort to detect subclinical dysfunction in SCT patients. Eleven patients (12.4 ± 3.8 years old) were included in the study. No patients had diastolic dysfunction. All patients completed a maximal effort exercise test, and 73% (8/11) had abnormal peak oxygen consumption (Vo2 peak), which is a measure of aerobic fitness. However, during submaximal effort CPET, 45% (5/11) had an abnormal Vo2 at anaerobic threshold (i.e., the point in exercise where aerobic transitions to anaerobic metabolism and fatigue starts), and 64% (7/11) had an abnormal oxygen uptake efficiency slope (a measure that relates Vo2 peak to total ventilation). Eighty-six percent (6/7) of the patients with an abnormal oxygen uptake efficiency slope ultimately had an abnormal Vo2 peak. There were no vascular function abnormalities. Pediatric survivors of SCT often have abnormal maximal and submaximal exercise capacity without vascular or cardiac dysfunction.

Dynamic exercise changes in venous pressure and liver stiffness in Fontan patients: effects of Treprostinil.

BACKGROUND: Systemic venous hypertension and low cardiac output are believed to be important mediators of liver injury after the Fontan procedure. Pulmonary vasodilators have the potential to improve such haemodynamics. The aim of this study was to assess the acute effects of exercise on liver stiffness and venous pressures and to assess the impact of inhaled Treprostinil on this response. METHODS: In this prospective, double-blind, placebo-controlled, crossover trial, 14 patients with a Fontan circulation were randomised to inhalation of placebo and Treprostinil. Incremental and constant work rate exercise tests were performed to assess the effect of Treprostinil on exercise tolerance. Venous pressures were measured throughout and liver stiffness at rest and immediately after peak exercise. RESULTS: Mean age was 27.8 ± 7.9 years and 66% were females. Exercise acutely increased liver stiffness by 30% (mean shear wave speed: 2.38 ± 0.71 versus 2.89 ± 0.51 ms, p = 0.02). Peripheral venous pressures increased acutely during both incremental (12.1 ± 2.4 versus 22.6 ± 8.0 mmHg, p < 0.001) and constant work rate exercise (12.5 ± 2.5 versus 23.4 ± 5.2 mmHg, p < 0.001). Overall, Treprostinil failed to attenuate exercise-induced increases in liver stiffness. Compared with placebo, Treprostinil did not significantly impact venous pressure responses, VO2peak, nor exercise endurance times. CONCLUSIONS: Peripheral venous pressure increased acutely during exercise by an average of 88% above baseline and was not altered by administration of inhaled Treprostinil. Liver stiffness measured immediately post-exercise increased acutely by an average of 30%, with no attenuation following Treprostinil inhalation.

Peripheral venous pressure changes during exercise are associated with adverse Fontan outcomes.

OBJECTIVE: Elevated central venous pressure (CVP) plays an important role in the development of adverse Fontan outcomes. Peripheral venous pressure (PVP) has been validated as a surrogate for CVP in Fontan patients. We hypothesised that PVP in response to exercise will be associated with a greater prevalence of Fontan morbidity. METHODS: Adult Fontan patients had cardiopulmonary exercise testing (CPET) with PVP monitoring in the upper extremity between 2015 and 2018. PVP at rest, during unloaded cycling and at peak exercise was compared between those with and without adverse Fontan outcomes including arrhythmia, unscheduled hospital admissions, heart failure requiring diuretics, need for reintervention and a composite outcome of the above morbidities, heart transplantation and death. RESULTS: Forty-six patients with a mean age at CPET of 26.9±9.5 years. During exercise, PVP increased from 13.6±3.5 mm Hg at rest, to 16.5±3.9 mm Hg during unloaded cycling, to 23.0±5.5 mm Hg at peak exercise. Unloaded and peak PVP were more strongly associated than resting PVP with all adverse outcomes, except reintervention (composite outcome: resting PVP: OR 2.8, p=0.023; unloaded PVP: OR 6.1, p=0.001; peak PVP: OR 4.0, p<0.001). Cut-offs determined using ROC curve analysis had high specificity for the composite outcome (88% unloaded PVP ≥18 mm Hg; 89% peak PVP ≥25 mm Hg). CONCLUSION: Higher PVP at unloaded and peak exercise was strongly associated with a higher prevalence of adverse Fontan outcomes. Minimally invasive PVP monitoring during CPET may serve as a useful tool for risk stratifying individuals with a Fontan.

The Adaptation of Pediatric Exercise Testing Programs to the Coronavirus/COVID-19 Pandemic.

OBJECTIVE: Response to the coronavirus/COVID-19 pandemic has resulted in several initiatives that directly impact hospital operations. There has been minimal information on how COVID-19 has affected exercise testing in pediatric patients. DESIGN: A web-based survey was designed and sent to pediatric exercise testing laboratories in the United States and Canada. Questions were designed to understand the initial and ongoing adaptations made by pediatric exercise testing laboratories in response to COVID-19. Results were analyzed as frequency data. RESULTS: There were responses from 42% (35/85) of programs, with 68% (23/34) of laboratories discontinuing all exercise testing. Of the 23 programs that discontinued testing, 15 (65%) are actively working on triage plans to reopen the exercise laboratory. Personal protective equipment use include gloves (96%; 25/26), surgical masks (88%; 23/26), N-95 masks (54%; 14/26), face shields (69%; 18/26), and gowns (62%; 16/26). Approximately 47% (15/32) of programs that typically acquire metabolic measurements reported either ceasing or modifying metabolic measurements during COVID-19. Additionally, 62% (16/26) of the programs that previously obtained pulmonary function testing reported either ceasing or modifying pulmonary function testing. Almost 60% of respondents expressed a desire for additional guidance on exercise laboratory management during COVID-19. CONCLUSIONS: Pediatric exercise testing laboratories largely closed during the early pandemic, with many of these programs either now open or working on a plan to open. Despite this, there remains heterogeneity in how to minimize exposure risks to patients and staff. Standardization of exercise testing guidelines during the COVID-19 pandemic may help reduce some of these differences.

Body Composition and Exercise Performance in Youth With a Fontan Circulation: A Bio-Impedance Based Study.

Background Adults with a Fontan circulation tend to have myopenia and elevated adiposity when measured by dual energy x-ray absorptiometry. Bioelectrical impedance analysis is an alternative validated approach to assess body composition. We used bioelectrical impedance analysis to compare body composition between pediatric patients with a Fontan circulation and control individuals without heart disease. Methods and Results A retrospective chart review identified all patients aged <22 years with a Fontan circulation who presented for cardiopulmonary exercise testing and bioelectrical impedance analysis from April 2019 to January 2020. Data were compared with control subjects tested during the same period. We studied 47 patients with a Fontan circulation (53% boys; 15±3.1 years) and 165 controls (48% boys; 14.4±2.5 years). Fontan status was associated with shorter height, but similar age, sex, and overall body mass. Patients with Fontan had lower lean body mass (-12.0±22%, Z-score -0.5±1, P=0.005), skeletal muscle mass (-13.6±1.4%; Z-score, -0.5±1; P=0.004), skeletal muscle indexed to height (-10.3±13.3%; Z-score, -0.5±1; P=0.005), and higher percent body fat (+13.8±18.6%; Z-score, 0.4±1.2; P=0.03). Greater skeletal muscle mass was associated with higher peak oxygen consumption (r2=0.52, P<0.0001) and oxygen pulse (r2=0.68, P<0.0001). Patients who had suffered a late complication (ie, heart transplant referral or evidence of extracardiac organ dysfunction) of the Fontan operation (13 of 47, 27.7%) had lower skeletal muscle mass (P=0.048) and higher body fat percentage (P=0.003). Conclusions The Fontan circulation is associated with marked myopenia and increased adiposity. Higher muscle mass was associated with better exercise capacity. Fontan complications are associated with lower muscle mass and increased adiposity.

Probenecid Improves Cardiac Function in Subjects with a Fontan Circulation and Augments Cardiomyocyte Calcium Homeostasis.

Subjects with functionally univentricular circulation who have completed staged single ventricle palliation, with the final stage culminating in the Fontan procedure, are often living into adulthood. However, high morbidity and mortality remain prevalent in these patients, as diastolic and systolic dysfunction of the single systemic ventricle are linked to Fontan circulatory failure. We presently investigated the effects of probenecid in post-Fontan patients. Used for decades for the treatment of gout, probenecid has been shown in recent years to positively influence cardiac function via effects on the Transient Receptor Potential Vanilloid 2 (TRPV2) channel in cardiomyocytes. Indeed, we observed that probenecid improved cardiac function and exercise performance in patients with a functionally univentricular circulation. This was consistent with our findings from a retrospective cohort of patients with single ventricle physiology where TRPV2 expression was increased. Experiments in isolated cardiomyocytes associated these positive actions to augmentation of diastolic calcium homeostasis.

Implementation of a Pediatric Chest Pain Local Consensus Guideline Decreases the Total Tests Performed Without Negatively Affecting the Yield of Abnormal Cardiac Results.

Pediatric chest pain is common and though usually benign often leads to unnecessary diagnostic testing. There is limited evidence as to whether a local consensus guideline can decrease testing frequency without negatively affecting the overall yield. In addition, it is unknown whether the addition of pulmonary function testing to a cardiopulmonary exercise test increases the diagnostic yield in pediatric patients with chest pain. A retrospective chart review was performed on all new pediatric patients who presented with chest pain at our academic center's pediatric cardiology clinic 18 months before and after the implementation of a standard management guideline. Data from the encounter-associated echocardiogram, cardiopulmonary exercise test, and pulmonary function test, when available, were analyzed. There were no significant differences in patient volume or demographic characteristics in the 18 months before (n = 768) and after (n = 778) guideline implementation. There were significant reductions in the number of ordered echocardiograms (n = 131; 17% vs. n = 75; 9.6%, p < 0.001) and cardiopulmonary exercise tests (n = 46; 6% vs. n = 29; 4%, p = 0.04) with no concerning pathology discovered in either group. Associated pulmonary function testing performed prior to with exercise testing discovered abnormalities in 19% of the total patients tested. The implementation of a local consensus guideline for pediatric chest pain results in fewer unnecessary tests ordered. There was no concerning pathology before or after guideline implementation, therefore conclusions regarding the diagnostic yield of these guidelines are unfeasible. The addition of pulmonary function testing to cardiopulmonary exercise tests increases the potential diagnostic yield in these patients.

Skeletal Muscle Mass Is Linked to Cardiorespiratory Fitness in Youth.

INTRODUCTION: Cardiorespiratory fitness (CRF) measured by oxygen consumption (V˙O2) during exercise is an important marker of health. The traditional method of indexing V˙O2 to total body mass is suboptimal because skeletal muscle mass (SMM), rather than fat and extracellular fluid, is the main contributor to CRF. The traditional estimating equations for peak V˙O2 in youth do not account for this. Bioelectric impedance analysis (BIA) is a noninvasive method to accurately measure body composition. The objectives of this study were to 1) examine the relationship of body composition indices and peak V˙O2 in healthy children, adolescents, and young adults, and 2) derive an optimized estimating equation incorporating BIA and compare its performance with traditional estimating equations. METHODS: A retrospective, cross-sectional, single-center study of patients <21 yr old referred for exercise testing who did not have underlying cardiovascular disease. All patients underwent BIA immediately before exercise testing. Univariable and multivariable linear regression models were constructed and tested for model performance. RESULTS: A total of 165 young healthy people (mean age 14 yr, 48% male) were studied. There was a strong and linear relationship between peak V˙O2 and SMM (R = 0.79). The sex difference in SMM explained the most variability in CRF between boys and girls. A generalized equation using SMM (peak V˙O2 = 302 - (23.7 × age) - (50.3 × [female = 1, male = 0]) + (81.8 × SMM)) had superior performance (R = 0.80) compared with estimating equations currently used in clinical practice (R = 0.67). CONCLUSIONS: SMM is a stronger correlate of CRF than is total body mass in youth and may be a better scaling variable to estimate expected peak V˙O2.

The Unique Clinical Phenotype and Exercise Adaptation of Fontan Patients With Normal Exercise Capacity.

BACKGROUND: Exercise limitation is almost universal among Fontan patients. Identifying unique clinical features in the small fraction of Fontan patients with normal exercise capacity (high-capacity Fontan [HCF]) provides potential to inform clinical strategies for those with low exercise capacity (usual Fontan). METHODS: We performed a retrospective chart review of all patients with single-ventricle physiology palliated with a Fontan operation who underwent incremental cardiopulmonary exercise testing at Cincinnati Children's Hospital Medical Center from 2013 to 2018. Comparison was between patients with peak oxygen uptake < vs ≥ 80% predicted. RESULTS: A total of 22 of 112 patients were classified as HCF (68% were female; aged 18 ± 7 years). During incremental exercise, peak oxygen uptake (86.1% ± 6.1% vs 62% ± 12.2% predicted; P < 0.001) was greater in HCF vs usual Fontan despite similar chronotropic impairment, resulting in a greater oxygen pulse in HCF. Pulmonary function, breathing reserve, and ventilatory equivalent for CO2 output slope were not different between groups. Those in the HCF group were more likely to self-report exercise ≥ 4 days/week for at least 30 minutes (77% vs 10%, P < 0.001), have normal systolic function (95% vs 74%, P = 0.003), have fewer postoperative complications (8% vs 36%, P = 0.04), and have shorter post-Fontan length of stay (8 ± 2.8 vs 12.4 ± 0.9 days, P = 0.04). CONCLUSIONS: Approximately 1 in 5 Fontan patients who undergo cardiopulmonary exercise testing have normal exercise capacity despite chronotropic impairment. This implies a better preserved stroke volume, perhaps due to greater muscle pump-mediated preload. Additionally, a complicated perioperative Fontan course is associated with eventual impaired functional capacity.