Cardiopulmonary Exercise Test and Daily Physical Activity in Pediatric Congenital Heart Disease: an Exploratory Analysis.

Sedentary lifestyle is reported to be associated with diminished exercise capacity, resulting in increased cardiovascular risk in adults with congenital heart disease (CHD). This cross-sectional study examined the association between objectively measured physical activity (PA) and exercise capacity in children and adolescents with CHD. Therefore, 107 patients (aged 13.0 ± 2.7 years, 41 girls) with various CHD performed a cardiopulmonary exercise test to quantify their peak oxygen uptake (peakV'O2). Moderate to vigorous PA (MVPA) and daily step count were assessed using Garmin vivofit jr. (Garmin, Germany) for 7 consecutive days. For association between PA and submaximal exercise capacity, Spearman correlation was performed. Patients with CHD showed almost normal values compared with the reference (79.5 ± 17.2% [31.6 to 138.1] %peakV'O2 predicted), with roughly normal ventilatory anerobic thresholds (50.6 ± 14.0% [20.3 to 97.9] % oxygen uptake at ventilatory anaerobic threshold [VATV'O2]). Step counts are below the recommendations (9,304 ± 3,792 steps/day [1,701 to 20,976]), whereas MVPA data are above the recommendations for children with ≥60 min/day (83.6 ± 34.6 min/day [10.1 to 190.9]). The Spearman rho showed significant positive correlations to VATV'O2 (r = 0.353, p <0.001) and %VATV'O2 (r = 0.307, p = 0.001), with similar results regarding MVPA (VATV'O2: r = 0.300, p = 0.002 and %VATV'O2: r = 0.270, p = 0.005). In conclusion, submaximal exercise capacity and PA correlate positively, making both assessments relevant in a clinical setting: PA in the context of cardiovascular prevention and peakV'O2 as the strongest predictor for morbidity and mortality.

Body plethysmography - additional information on exercise capacity in patients with congenital heart disease?

AIMS: In each cardiopulmonary exercise test (CPET), resting spirometry is performed in advance. In patients with a congenital heart defect (CHD), lung volumes are often impaired. This study investigates correlations between lung volumes and CPET parameters and determines, whether body plethysmography provides substantial additional information for these patients. METHODS: Data from 102 patients (23.8 ± 10.4 years of age, 39 female) with various forms of CHD were examined from April 2018 to October 2022. All patients underwent spirometry (measuring forced vital capacity, FVC and forced expiratory volume in 1 s, FEV1), body plethysmography (measuring total lung capacity, TLC) and an exhausting CPET. Data is presented as the median and interquartile range (z-scores) and correlated with Spearman's rho. RESULTS: Fifty-five% of all patients had normal results in lung function and 45% had normal peak oxygen uptake (≥ 80% predicted in peak VO2). Patients with impaired lung function were significantly more likely to have low exercise capacity (Fisher's exact test: p = 0.028). FVC z-values and %predicted peak VO2 (r = 0.365, p < 0.001) correlated significantly as well as FEV1_z and %predicted peak VO2 (r = 0.320, p = 0.001), and TLC z-values and %predicted peak VO2 (r = 0.249, p = 0.012). No correlation was found between FEV1/FVC z-values and %predicted peak VO2 (r = -0.043, p = 0.670). CONCLUSION: Spirometry and exercise capacity positively correlate, also in CHD patients. However, body plethysmography does not provide additional or improved prediction and is therefore only recommended in noteworthy results in spirometry to exclude further lung co-morbidities.

Reference Values of Cardiopulmonary Exercise Test Parameters in the Contemporary Paediatric Population.

BACKGROUND: The evaluation of health status by cardiopulmonary exercise test (CPET) has shown increasing interest in the paediatric population. Our group recently established reference Z-score values for paediatric cycle ergometer VO2max, applicable to normal and extreme weights, from a cohort of 1141 healthy children. There are currently no validated reference values for the other CPET parameters in the paediatric population. This study aimed to establish, from the same cohort, reference Z-score values for the main paediatric cycle ergometer CPET parameters, apart from VO2max. RESULTS: In this cross-sectional study, 909 healthy children aged 5-18 years old underwent a CPET. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best CPET parameters Z-scores, according to anthropometric parameters (sex, age, height, weight, and BMI). This study provided Z-scores for maximal CPET parameters (heart rate, respiratory exchange ratio, workload, and oxygen pulse), submaximal CPET parameters (ventilatory anaerobic threshold, VE/VCO2 slope, and oxygen uptake efficiency slope), and maximum ventilatory CPET parameters (tidal volume, respiratory rate, breathing reserve, and ventilatory equivalent for CO2 and O2). CONCLUSIONS: This study defined paediatric reference Z-score values for the main cycle ergometer CPET parameters, in addition to the existing reference values for VO2max, applicable to children of normal and extreme weights. Providing Z-scores for CPET parameters in the paediatric population should be useful in the follow-up of children with various chronic diseases. Thus, new paediatric research fields are opening up, such as prognostic studies and clinical trials using cardiopulmonary fitness outcomes. Trial registration NCT04876209-Registered 6 May 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04876209 .

Reference values of aerobic fitness in the contemporary paediatric population.

AIMS: There has been a growing interest in the use of markers of aerobic physical fitness (VO2max assessed by cardiopulmonary exercise test (CPET)) in the follow-up of paediatric chronic diseases. The dissemination of CPET in paediatrics requires valid paediatric VO2max reference values to define the upper and lower normal limits. This study aimed to establish VO2max reference Z-score values, from a large cohort of children representative of the contemporary paediatric population, including those with extreme weights. METHODS AND RESULTS: In this cross-sectional study, 909 children aged 5 to 18 years old from the general French population (development cohort) and 232 children from the general German and US populations (validation cohort) underwent a CPET, following the guidelines on high-quality CPET assessment. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best VO2max Z-score model. Predicted and observed VO2max values using the VO2max Z-score model, and the existing linear equations were compared, in both development and validation cohorts. For both sexes, the mathematical model using natural logarithms of VO2max, height, and BMI was the best fit for the data. This Z-score model could be applied to normal and extreme weights and was more reliable than the existing linear equations, in both internal and external validity analyses (https://play.google.com/store/apps/details?id=com.d2l.zscore). CONCLUSION: This study established reference Z-score values for paediatric cycloergometer VO2max using a logarithmic function of VO2max, height, and BMI, applicable to normal and extreme weights. Providing Z-scores to assess aerobic fitness in the paediatric population should be useful in the follow-up of children with chronic diseases. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04876209.

Abnormalities in pulmonary function and volumes in patients with CHD: a systematic review.

BACKGROUND: Lung function and cardiac function are naturally correlated by sharing the thoracic cage and handling the whole cardiac output sequentially. However, lung function studies are rare in patients with CHD, although results worthy of investigation could be expected. This review summarises existing studies with the lung function parameters (spirometry and body plethysmography) in CHD patients during the last decade. METHODS: A systematic review was performed in the relevant database (PubMed, Cochrane, and Scopus) in studies including paediatric and adult patients with CHD where lung parameters (spirometry, body plethysmography) were investigated from January 2010 to December 2020. Two independent reviewers evaluated the studies according to the Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung, and Blood Institute. RESULTS: Eight studies investigated patients with Fontan palliation including 704 patients (306 female). Four studies included patients after repaired tetralogy of Fallot examining 219 patients (103 female), with one study using double. Further six studies included 3208 (1324 female) children and adults with various CHDs. Overall, four studies were categorised as "good", ten as "fair", and four as "poor". While the measurements were consistently standardised, references to calculate %predicted differed substantially across all studies. All evaluated studies showed reduced forced vital capacity in the majority of CHD patients. CONCLUSIONS: Many CHD patients have a reduced forced vital capacity independent of their underlying defect. Spirometry should not only follow a standardised measure according to ATS (update 2019) but also stick to the 2012 GLI reference values.

Heart-Focused Anxiety Is Prevalent in Adults With Congenital Heart Disease and Associated With Reduced Exercise Capacity.

PURPOSE: Psychological distress and anxiety are increased among adults with congenital heart disease (CHD). However, heart-focused anxiety (HFA) and its impact on peak oxygen uptake (V˙ o2peak ) have not yet been studied in this patient cohort. This study investigates HFA in adults with CHD and whether HFA is associated with V˙ o2peak in these patients. METHODS: In this cross-sectional study, HFA was assessed in 984 adults with various CHD (34.2 ± 11.2 yr, 44% female) by the cardiac anxiety questionnaire. In 708 of those (33.5 ± 10.6 yr, 42% female), additional cardiopulmonary exercise testing was performed to assess exercise capacity by measurement of V˙ o2peak . RESULTS: Compared with the general population, this adult CHD population showed higher HFA in the total cardiac anxiety questionnaire score ( z score; 1.32 ± 1.17; P < .001), as well as in the three subdomains anxiety, avoidance, and attention (all P < .001). The higher the HFA, the lower was the V˙ o2peak % predicted ( r = -0.280, P < .001) independent of CHD diagnosis, CHD severity, and surgical status. The V˙ o2peak % predicted significantly differed between patients with no (85.9 ± 18.4% predicted), slight (80.4 ± 18.4% predicted), and severe HFA (74.2 ± 18.4% predicted) independent of CHD diagnosis, CHD severity, and surgical status ( P < .001). CONCLUSION: This study shows that HFA is a common sequela in adults with CHD, and high HFA is associated with reduced V˙ o2peak . Psychological screening and counseling for HFA therefore seem indicated in the aftercare of adults with CHD.

Peak Oxygen Uptake on Cardiopulmonary Exercise Test Is a Predictor for Severe Arrhythmic Events during Three-Year Follow-Up in Patients with Complex Congenital Heart Disease.

Patients with congenital heart disease (CHD) are at increased risk for severe arrhythmia and sudden cardiac death (SCD). Although implantable cardioverter defibrillators (ICD) effectively prevent SCD, risk stratification for primary prophylaxis in patients with CHD remains challenging. Patients with complex CHD undergoing CPET were included in this single-center study. Univariable and backwards stepwise multivariable logistic regression models were used to identify variables associated with the endpoint of severe arrhythmic event during three years of follow-up. Cut-off values were established with receiver operating characteristic (ROC) curve analysis. Survival analysis was conducted via Kaplan-Meier plots. Severe Arrhythmia was documented in 97 of 1194 patients (8.1%/3 years). Independent risk factors for severe arrhythmia during follow-up were old age and a low peak oxygen uptake (V.O2peak) on multivariable analysis. Patients with more advanced age and with V.O2peak values of less than 24.9 mL/min/kg were at significantly increased risk for the occurrence of severe arrhythmias during follow-up. The combined analysis of both risk factors yielded an additional benefit for risk assessment. Age at CPET and V.O2peak predict the risk for severe arrhythmic events and should be considered for risk stratification of SCD in patients with complex CHD.

Cardiovascular Function and Exercise Capacity in Childhood Cancer Survivors.

INTRODUCTION: Childhood cancer survivors (CCS) might be at high risk of additional chronic diseases due to cardiotoxic side effects. The aim of this study was to analyze long-term side effects of cancer therapy on vascular structure/function, cardiac biomarkers and on physical activity. METHODS: In total, 68 asymptomatic patients aged 16-30 years with childhood cancer (diagnosed 10.6 ± 3.9 years ago) were examined from 2015-2020. (Central) blood pressure and pulse wave velocity were registered via the oscillometric method, while carotid intima-media thickness (cIMT) was measured non-invasively by ultrasound. cIMT values of patients were compared to healthy controls (n = 68; aged 22.3 ± 3.5 years). Patients' exercise capacity was recorded. The plasma N-terminal pro-brain natriuretic protein (NTproBNP) and troponin levels were measured as cardiac biomarkers. CCS were categorized in groups with low, moderate and high anthracyclines. RESULTS: No differences were found in cIMT between patients and controls as well as between patients with various anthracycline dosage. Patients with high dose anthracyclines showed a significant lower performance versus patients with moderate dose anthracyclines (84.4% of predicted VO2peak; p = 0.017). A total of 11.6% of CCS had abnormal NTproBNP values which correlated with received anthracycline dosage (p = 0.024; r = 0.343). CONCLUSION: NTproBNP levels and exercise capacity might be early markers for cardiovascular dysfunction in CCS and should be included in a follow-up protocol, while cIMT and troponin seem not to be adequate parameters.

Exercise capacity in patients with repaired Tetralogy of Fallot aged 6 to 63 years.

OBJECTIVES: This study aimed to provide a perspective for the interpretation of exercise capacity (peakVO2) in patients with repaired Tetralogy of Fallot (patients with rTOF) by describing the course of peakVO2 from patients aged 6-63 years. METHODS: A retrospective study was performed between September 2001 and December 2016 in the German Heart Centre Munich, Germany, and in the University Medical Centre Groningen, the Netherlands. A total of 1175 cardiopulmonary exercise tests (CPETs) were collected from 586 patients with rTOF, 46% female. Maximal exertion was verified using a respiratory exchange ratio ≥1.00. PeakVO2 was modelled using time-dependent multilevel models for repeated measurements (n=889 in 300 patients), and compared with subject-specific reference values calculated by the models of Bongers et al and Mylius et al. RESULTS: The peakVO2 of patients with rTOF was reduced at all ages. At the age of 6, the peakVO2 was 614 mL/min (70% of predicted (95% CI 67 to 73)). The reduced increase in peakVO2 during adolescence resulted in a significant lower maximum peakVO2 of 1209 mL/min at 25 years (65% predicted, p<0.001). A linear decline after 25 years was observed in patients and references, although patients showed an accelerated decline, with a -0.24% point of predicted (95% CI 0.11 to 0.38) per year without differences between sexes (p=0.263). CONCLUSIONS: This study provides a context for peakVO2 across ages in patients with rTOF under contemporary treatment strategies. It showed that the reduction in peakVO2 originates from childhood and declines over time. Sex differences in patients with rTOF were similar to natural existing sex differences.

Breathing training improves exercise capacity in patients with tetralogy of Fallot: a randomised trial.

OBJECTIVE: Patients with tetralogy of Fallot (ToF) have limited pulmonary blood flow before corrective surgery and ongoing dysfunction of the pulmonary valve and right ventricle throughout life leading to lower exercise capacity and lung volumes in many patients. Inhalation training can increase lung volumes, improve pulmonary blood flow and consequently exercise capacity. This study tests whether home-based daily breathing training improves exercise capacity and lung volumes. METHODS: From February 2017 to November 2018, 60 patients (14.7±4.8 years, 39% female) underwent spirometry (forced vital capacity (FVC); forced expiratory volume in 1 s (FEV1)), cardiopulmonary exercise testing (peak oxygen uptake (peak [Formula: see text]O2)) and breathing excursion measurement. They were randomised into immediate breathing exercise or control group (CG) and re-examined after 6 months. The CG started their training afterwards and were re-examined after further 6 months. Patients trained with an inspiratory volume-oriented breathing device and were encouraged to exercise daily. The primary endpoint of this study was the change in peak [Formula: see text]O2. Results are expressed as mean±SEM (multiple imputations). RESULTS: In the first 6 months (intention to treat analysis), the training group showed a more favourable change in peak [Formula: see text]O2 (Δ0.5±0.6 vs -2.3±0.9 mL/min/kg, p=0.011), FVC (Δ0.18±0.03 vs 0.08±0.03 L, p=0.036) and FEV1 (Δ0.14±0.03 vs -0.00±0.04 L, p=0.007). Including the delayed training data from the CG (n=54), this change in peak [Formula: see text]O2 correlated with self-reported weekly training days (r=0.282, p=0.039). CONCLUSIONS: Daily inspiratory volume-oriented breathing training increases dynamic lung volumes and slows down deconditioning in peak [Formula: see text]O2 in young patients with repaired ToF.

Comparison of the Stanford ECG Left Atrial Criteria With the International ECG Criteria for Sports Screening.

OBJECTIVE: Because the International left atrial enlargement electrocardiographic (ECG) screening criteria (ECG-LAE) for athletes are rarely fulfilled in young athletes, we compared it with evidence-based criteria from a recent clinical outcome study of ECG left atrial abnormality (ECG-LAA). DESIGN: Retrospective analyses. SETTING: Routine preparticipation ECG screening in California. PARTICIPANTS: Four thousand four hundred thirty-eight young individuals (18.5 ± 5.4 years, 40% women). ASSESSMENT OF RISK FACTORS: The International criteria for ECG-LAE were applied: prolonged P wave duration of ≥120 ms in leads I or II AND negative portion of ≥1 mm in depth in lead V1. This was compared with Stanford criteria for ECG-LAA: prolonged P wave duration of ≥140 ms odds ratio (OR) negative portion in V1 and V2 greater than 1 mm. MAIN OUTCOME MEASURES: Differences in the classification of abnormal ECGs between the 2 criteria applied to the same population of young athletes. RESULTS: Only 33 (0.7%) of our subjects fulfilled the International criteria for ECG-LAE while 110 (2.5%) fulfilled the ECG-LAA criteria. Adding our new ECG-LAA criterion and considering it a major criterion raised the abnormal ECG prevalence and athletes referred for further evaluation from 2.9% to 4.4%. CONCLUSIONS: The Stanford evidence-based criterion for ECG-LAA incorporating V2 and replacing "or" for "and" regarding P wave duration increased the yield of abnormal classification for P waves. Future follow-up studies are needed to confirm that this new criterion should be included in future ECG screening consensus documents.

Reduced Parasympathetic Activity in Patients With Different Types of Congenital Heart Disease and Associations to Exercise Capacity.

PURPOSE: Current research indicates an imbalance in the autonomic nervous system (ANS) pathway activities in patients with congenital heart disease (CHD). The heart rate variability (HRV) is a measure to quantify activities of the parasympathetic and sympathetic branches. This study evaluated the parasympathetic activity by means of HRV in patients with CHD, regarding diagnostic subgroups and CHD severity, and the association to exercise capacity. METHODS: From July 2016 to August 2018, a total of 222 patients with different types of CHD (28.4 ± 10.1 yr; 44% female) received breathing-controlled HRV measurement in the supine position. Based on 130 adjacent heartbeats, the root mean square of successive differences (RMSSD), a parasympathetic activity surrogate was estimated and log-transformed. Additionally, all patients underwent a cardiopulmonary exercise test. For comparison, a control group (CG) of 57 (29.0 ± 7.1 yr; 61% female) healthy volunteers was recruited. RESULTS: Patients with CHD exhibited reduced parasympathetic activity in comparison to the CG (lnRMSSD CHD: 3.55 ± 0.57 ms vs CG: 3.93 ± 0.55 ms; P < .001), with the lowest parasympathetic activity in patients with Fontan circulation (3.07 ± 0.54 ms; P < .001). Complex CHD (3.40 ± 0.54 ms) had worse values compared with patients with simple (3.87 ± 0.55 ms; P < .001) and moderate severity (3.74 ± 0.54 ms; P < .001). Better parasympathetic activity in CHD patients was associated with increased exercise capacity (r = 0.322; P < .001). CONCLUSIONS: Impaired parasympathetic activity suggests limited function of the ANS in patients with CHD. Further studies should focus on the association of exercise capacity and ANS to possibly improve parasympathetic activity and functional outcomes.

Patients with Single-Ventricle Physiology over the Age of 40 Years.

BACKGROUND: Single-ventricle physiology (SVP) is associated with significant morbidity and mortality at a young age. However, survival prospects have improved and risk factors for a negative outcome are well described in younger cohorts. Data regarding older adults is scarce. METHODS: In this study, SVP patients under active follow-up at our center who were ≥40 years of age at any point between January 2005 and December 2018 were included. Demographic data, as well as medical/surgical history were retrieved from hospital records. The primary end-point was all-cause mortality. RESULTS: Altogether, 49 patients (19 female (38.8%), mean age 49.2 ± 6.4 years) were included. Median follow-up time was 4.9 years (interquartile range (IQR): 1.8-8.5). Of these patients, 40 (81.6%) had undergone at least one cardiac surgery. The most common extracardiac comorbidities were thyroid dysfunction (n = 27, 55.1%) and renal disease (n = 15, 30.6%). During follow-up, 10 patients (20.4%) died. On univariate analysis, renal disease and liver cirrhosis were predictors of all-cause mortality. On multivariate analysis, only renal disease (hazard ratio (HR): 12.5, 95% confidence interval (CI): 1.5-106.3, p = 0.021) remained as an independent predictor. CONCLUSIONS: SVP patients ≥40 years of age are burdened with significant morbidity and mortality. Renal disease is an independent predictor of all-cause mortality.

Tetralogy of Fallot or Pulmonary Atresia with Ventricular Septal Defect after the Age of 40 Years: A Single Center Study.

Background: The population of adults with tetralogy of Fallot (TOF) or pulmonary atresia with ventricular septal defect (PA/VSD) is growing and aging. Data regarding older patients are scarce. Prognostic outcome parameters in adults with TOF or PA/VSD ≥ 40 years were studied. METHODS: This was a retrospective study of patients ≥ 40 years of age during the study period (January 2005-March 2018). Major adverse cardiac events (MACE) were a combined primary endpoint including death from any cause, prevented sudden cardiac death, pacemaker implantation, arrhythmia, and new-onset heart failure. Additionally, MACE II (secondary endpoint) was a combination of death from any cause and prevented sudden cardiac death. RESULTS: 184 (58.7% female, mean age 45.3 ± 7.2 years) patients were included (159 (86.4%) TOF and 25 (13.6%) PA/VSD). During a median follow-up of 3.1 years (IQR: 0.6-6.5), MACE occurred in 35 and MACE II in 13 patients. On multivariable analysis, New York Heart Association class [HR: 2.1, 95% CI: 1.2-3.6, p = 0.009] emerged as an independent predictor for MACE, and age at corrective surgery [HR: 13.2, 95% CI: 1.6-107.1, p = 0.016] for MACE II. CONCLUSIONS: Adults with TOF or PA/VSD ≥ 40 years are burdened with significant morbidity and mortality. New York Heart Association class and age at corrective surgery were independent predictors of outcome.

Children with Congenital Heart Disease Are Active but Need to Keep Moving: A Cross-Sectional Study Using Wrist-Worn Physical Activity Trackers.

OBJECTIVE: To compare daily physical activity of children with congenital heart disease (CHD) with healthy peers measured using wearables bracelets in a large cohort. Additionally, subjectively estimated and objectively measured physical activity was compared. STUDY DESIGN: From September 2017 to May 2019, 162 children (11.8 ± 3.2 years; 60 girls) with various CHD participated in a self-estimated and wearable-based physical activity assessment. Step-count and moderate-to-vigorous physical activity were recorded with the Garmin vivofit jr. for 7 consecutive days and compared with a reference cohort (RC) of 96 healthy children (10.9 ± 3.8 years; 49 girls). RESULTS: Children with CHD were active and 123 (75.9%) achieved 60 minutes physical activity on a weekly average according to the World Health Organization criteria as 81 (84.3%) of the healthy peers did (P = .217). After correction for age, sex, and seasonal effects, only slightly lower step count (CHD: 10 206 ± 3178 steps vs RC: 11 142 ± 3136 steps; P = .040) but no lower moderate-to-vigorous physical activity (CHD: 80.5 ± 25.6 minutes/day vs RC: 81.5 ± 25.3 minutes/day; P = .767) occurred comparing CHD with RC. In children with CHD higher age (P = .004), overweight or obesity (P = .016), complex severity (P = .046), and total cavopulmonary connection (P = .027) were associated with not meeting World Health Organization criteria. Subjective estimation of daily moderate-to-vigorous physical activity was fairly correct in half of all children with CHD. CONCLUSIONS: Even though the majority is sufficiently active, physical activity needs to be promoted in overweight or obese patients, patients with complex CHD severity, and in particular in those with total cavopulmonary connection.

Functional outcome in contemporary children and young adults with tetralogy of Fallot after repair.

OBJECTIVE: Functional outcome measures are of growing importance in the aftercare of patients with congenital heart disease. This study addresses the functional status with regard to exercise capacity, health-related physical fitness (HRPF) and arterial stiffness in a recent cohort of children, adolescents and young adults with tetralogy of Fallot (ToF) after repair. DESIGN: Single-centre, uncontrolled and prospective cohort study. SETTING: Outpatient department of the German Heart Centre Munich; July 2014-January 2018. PATIENTS: One hundred and six patients with ToF after repair (13.5±3.7 years, 40 females) were included. Data were compared with a recent cohort of healthy controls (HCs) (n=1700, 12.8±2.6 years, 833 females). MAIN OUTCOME MEASURES: Patients underwent a symptom-limited cardiopulmonary exercise test, performed an HRPF test (FitnessGram) and had an assessment of their arterial stiffness (Mobil-O-Graph). RESULTS: Compared with HC, patients with ToF showed lower predicted [Formula: see text]O2 peak (ToF: 80.4% ± 16.8% vs HC: 102.6% ± 18.1%, p<0.001), impaired ventilatory efficiency (ToF: 29.6 ± 3.6 vs HC: 27.4 ± 2.9, p<0.001), chronotropic incompetence (ToF: 167 ± 17 bpm vs HC: 190 ± 17 bpm, p<0.001) and reduced HRPF (ToF z-score: -0.65 ± 0.87 vs HC z-score: 0.03 ± 0.65, p<0.001). Surrogates of arterial stiffness, central and peripheral systolic blood pressure, did not differ between the two groups. CONCLUSIONS: Contemporary children, adolescents and young adults with ToF still have functional limitations. How impaired HRPF and limited exercise capacity interact and how they can be modified needs to be evaluated in further intervention studies.

Electrocardiographic left atrial abnormalities predict cardiovascular mortality.

OBJECTIVE: Clinical utilization of electrocardiography for diagnosis of left atrial abnormalities is hampered by variable P-wave morphologies, multiple empiric criteria, and lack of an imaging "gold standard". Our aim was to determine the prevalence of P-wave patterns and demonstrate which components have associations with cardiovascular death (CVD). METHODS: This is a retrospective analysis of 20,827 veterans <56 years of age who underwent electrocardiograms at a Veteran's Affairs Medical Center from 1987 to 1999, followed for a median duration of 17.8 years for CVD. Receiver Operating Characteristic, Kaplan-Meier and Cox Hazard analyses were applied, the latter with adjustment for age, gender and electrocardiography abnormalities. RESULTS: The mean age was 43.3 ±â€¯8 years, and 888 CVD (4.3%) occurred. A single positive deflection of the P-wave (Pattern 1) was present in 29% for V1 and 81% for V2. A singular negative P-wave (Pattern 2) was present in 4.6% for V1 and 1.6% in V2. A P-wave with an upward component followed by downward component (Pattern 3) was present in 64.5% for V1 and 17.5% for V2. When the downward component in Patterns 2 and/or 3 is at least -100 µV, a significant association is observed with CVD (adjusted hazard ratios [HRs] 2.9-4.1, P < 0.001). Total P-wave duration ≥140 ms was also associated with CVD (adjusted HR 2.2, P < 0.001). CONCLUSIONS: A negative P-wave in V1 or V2 ≤-100 µV, and P-wave with a duration of ≥140 ms, all have independent and significant associations with CVD, with HRs comparable to other electrocardiography abnormalities.

Applying current normative data to prognosis in heart failure: The Fitness Registry and the Importance of Exercise National Database (FRIEND).

INTRODUCTION: Percent of predicted peak VO2 (ppVO2) is considered a standard measure for establishing disease severity, however, there are known limitations to traditional normative values. This study sought to compare ppVO2 from the newly derived "Fitness Registry and the Importance of Exercise: a National Database" (FRIEND) registry equation to conventional prediction equations in a clinical cohort of patients undergoing cardiopulmonary exercise testing (CPX). METHODS AND RESULTS: We selected 1094 patients referred for evaluation of heart failure (HF) symptoms who underwent CPX. ppVO2 was calculated using the FRIEND, Wasserman/Hansen and Jones equations. Participants were followed for a median of 4.5 years [Interquartile range 3.5-6.0] for the composite endpoint of death, advanced HF therapy, or acute decompensated HF requiring hospital admission. Mean age was 48 ±â€¯15 years and 62% were female. The FRIEND registry equation predicted the lowest ppVO2 (measured/predicted; 71 ±â€¯31%), compared to the Wasserman/Hansen (74 ±â€¯29%) and Jones equations (83 ±â€¯33%) (p < 0.001). All expressions of peak VO2 were significant as univariate predictors of outcome with no significant differences between equations on pairwise analysis of receiver operating characteristic curves. When compared at a similar threshold of ppVO2 the event rate was significantly lower in the FRIEND registry equation versus the currently used Wasserman and Jones equations. CONCLUSION: The use of the newly derived FRIEND registry equation predicts HF outcomes; however, it appears to predict a higher predicted VO2; the clinical implication being a lower threshold of percent predicted peak VO2 should be considered when risk stratifying patients with HF.

Functional outcome in contemporary children with total cavopulmonary connection - Health-related physical fitness, exercise capacity and health-related quality of life.

OBJECTIVE: Children and adolescents with an univentricular heart after total cavopulmonary connection (TCPC) have functional impairments. This study assesses health-related physical fitness (HRPF) and exercise capacity, as well as their relation to health-related quality of life (HRQoL) in patients with an univentricular heart after total-pulmonary connection (TCPC). PATIENTS AND METHODS: Between July 2014 and October 2016 a total of 78 children and adolescents with TCPC (12.0±3.2years, 21 female) performed a motor test including five tasks for strength and flexibility during their routine follow-up appointment. They also underwent a symptom limited cardio-pulmonary exercise test and filled in a HRQoL questionnaire (KINDL-R). Patients' data were compared to a recent sample of healthy children (n=1650, 12.6±2.4years, 49% female). RESULTS: Multivariable regressions corrected for sex, age and BMI showed that TCPC patients achieved 12.4 repetitions of curl-ups (p<0.001) and 2.6 push-ups (p=0.010) less than healthy counterparts. They had impairments in trunk (-8.5cm; p<0.001), shoulder (-7.5cm; p<0.001) and lower limb flexibility (-4.7cm; p<0.001). Peak oxygen uptake was reduced to 34.8±7.5ml/min/kg and 77.7% respectively, compared to peers (p<0.001). Ventilatory efficiency was also impaired (healthy: 27.5±2.9 vs. TCPC: 31.6±3.3; p<0.001). HRQoL did not differ significantly (p=0.233). CONCLUSIONS: Children and adolescents with TCPC still present impaired HRPF and exercise capacity whereas HRQoL is similar to healthy peers. Since low HRPF may yield to worse motor competence and exercise capacity, early screening for HRPF and early treatment, if indicated, is recommended.