Molecular Choreography of Acute Exercise.

Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

Sigmoidal heart rate response pattern during exercise in patients with chronic heart failure.

Detailed heart rate (HR) response patterns during exercise in patients with heart failure (HF) and sinus rhythm remain uncertain. We screened consecutive patients with HF who underwent cardiopulmonary exercise tests at a large academic center from November 2013 to July 2023. HR response during exercise was statistically classified using logistic differential equation models. A total of 99 patients were included. Of them, 75 patients were assigned to "sigmoidal pattern" and the other 24 to "exponential pattern." Patients with the sigmoidal pattern were older and exhibited higher plasma B-type natriuretic peptide levels. Increases in HR and oxygen consumption (V̇o2)/kg up to the anaerobic threshold level were not different between both patterns. However, beyond the threshold, the sigmoidal pattern group showed no further increase in HR and significantly lower V̇o2/kg than their counterparts (interactions for P < 0.001). HR response during exercise in patients with heart failure and sinus rhythm was categorized into two unique groups: sigmoidal and exponential patterns. More detailed clarification of the sigmoidal pattern, potentially indicating sinus node dysfunction, should offer new clinical insights for chronotropic incompetence.NEW & NOTEWORTHY Heart rate response patterns can be classified into two groups among patients with chronic heart failure reaching maximal exertion: sigmoidal and exponential.

Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test.

BACKGROUND: Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. METHODS: We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2 , O2 pulse trajectory, and exercise ECG test. RESULTS: Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (ß -27.4, 95% CI -30.74 to -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001). CONCLUSION: Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.

Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations.

BACKGROUND: Post-exertional malaise (PEM), the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), represents a constellation of abnormal responses to physical, cognitive, and/or emotional exertion including profound fatigue, cognitive dysfunction, and exertion intolerance, among numerous other maladies. Two sequential cardiopulmonary exercise tests (2-d CPET) provide objective evidence of abnormal responses to exertion in ME/CFS but validated only in studies with small sample sizes. Further, translation of results to impairment status and approaches to symptom reduction are lacking. METHODS: Participants with ME/CFS (Canadian Criteria; n = 84) and sedentary controls (CTL; n = 71) completed two CPETs on a cycle ergometer separated by 24 h. Two-way repeated measures ANOVA compared CPET measures at rest, ventilatory/anaerobic threshold (VAT), and peak effort between phenotypes and CPETs. Intraclass correlations described stability of CPET measures across tests, and relevant objective CPET data indicated impairment status. A subset of case-control pairs (n = 55) matched for aerobic capacity, age, and sex, were also analyzed. RESULTS: Unlike CTL, ME/CFS failed to reproduce CPET-1 measures during CPET-2 with significant declines at peak exertion in work, exercise time, V ˙ e, V ˙ O2, V ˙ CO2, V ˙ T, HR, O2pulse, DBP, and RPP. Likewise, CPET-2 declines were observed at VAT for V ˙ e/ V ˙ CO2, PetCO2, O2pulse, work, V ˙ O2 and SBP. Perception of effort (RPE) exceeded maximum effort criteria for ME/CFS and CTL on both CPETs. Results were similar in matched pairs. Intraclass correlations revealed greater stability in CPET variables across test days in CTL compared to ME/CFS owing to CPET-2 declines in ME/CFS. Lastly, CPET-2 data signaled more severe impairment status for ME/CFS compared to CPET-1. CONCLUSIONS: Presently, this is the largest 2-d CPET study of ME/CFS to substantiate impaired recovery in ME/CFS following an exertional stressor. Abnormal post-exertional CPET responses persisted compared to CTL matched for aerobic capacity, indicating that fitness level does not predispose to exertion intolerance in ME/CFS. Moreover, contributions to exertion intolerance in ME/CFS by disrupted cardiac, pulmonary, and metabolic factors implicates autonomic nervous system dysregulation of blood flow and oxygen delivery for energy metabolism. The observable declines in post-exertional energy metabolism translate notably to a worsening of impairment status. Treatment considerations to address tangible reductions in physiological function are proffered. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, retrospectively registered, ID# NCT04026425, date of registration: 2019-07-17.

Reference Values for Cardiorespiratory Fitness in Patients Aged 6 to 18 Years.

OBJECTIVE: To develop reference values for cardiorespiratory fitness, as quantified by peak oxygen uptake (VO2peak) and treadmill time, in patients aged 6 through 18 years referred for cardiopulmonary exercise testing (CPET). STUDY DESIGN: We reviewed a clinical pediatric CPET database for fitness data in children aged 6-18 years with no underlying heart disease. CPET was obtained via the Bruce protocol utilizing objectively confirmed maximal effort via respiratory exchange ratio. Fitness data (VO2peak and treadmill test duration) were analyzed to determine age- and sex-specific reference values for this pediatric cohort. RESULTS: Data from 2025 pediatric CPETs (53.2% female) were included in the analyses. VO2peak increased with age in males, but not females. Treadmill test duration increased with age in both males and females. Fitness was generally higher in males when compared with females in the same age groups. CONCLUSIONS: Our study provides extensive reference values for both VO2peak and total treadmill test time via the Bruce protocol for a pediatric population without known cardiac disease. Furthermore, the inclusion of objectively confirmed maximal exercise effort increases confidence in these findings compared with prior studies in this area. Clinicians performing CPET in pediatric populations can utilize these reference values to characterize test results according to representative peer data.

Exercise-Induced Pulmonary Hypertension in Long-Term Survivors of Congenital Diaphragmatic Hernia.

OBJECTIVE: To determine the prevalence of exercise-induced pulmonary hypertension (PH) among long-survivors of congenital diaphragmatic hernia repair. STUDY DESIGN: This is a single-center, retrospective cohort study of CDH survivors who underwent exercise stress echocardiography (ESE) at Boston Children's Hospital from January 2006 to June 2020. PH severity was assessed by echocardiogram at baseline and after exercise. Patients were categorized by right ventricular systolic pressure (RVSP) after exercise: Group 1 - no or mild PH; and Group 2 - moderate or severe PH (RVSP ≥ 60 mmHg or ≥ ½ systemic blood pressure). RESULTS: Eighty-four patients with CDH underwent 173 ESE with median age 8.1 (4.8 - 19.1) years at first ESE. Sixty-four patients were classified as Group 1, 11 as Group 2, and 9 had indeterminate RVSP with ESE. Moderate to severe PH after exercise was found in 8 (10%) patients with no or mild PH at rest. Exercise-induced PH was associated with larger CDH defect size, patch repair, use of ECMO, supplemental oxygen at discharge, and higher WHO functional class. Higher VE/VCO2 slope, lower peak oxygen saturation, and lower percent predicted FEV1, and FEV1/FVC ratio were associated with Group 2 classification. ESE changed management in 9/11 Group 2 patients. PH was confirmed in all 5 Group 2 patients undergoing cardiac catheterization after ESE. CONCLUSIONS: Among long-term CDH survivors, 10% had moderate-severe exercise-induced PH on ESE, indicating ongoing pulmonary vascular abnormalities. Further studies are needed to optimally define PH screening and treatment for patients with repaired CDH.

The Child Opportunity Index 2.0 and Disparities in Pediatric Cardiorespiratory Fitness.

OBJECTIVE: To evaluate the effect of neighborhood-level characteristics on cardiorespiratory fitness (CRF) via peak oxygen consumption (VO2peak) for healthy pediatric patients. STUDY DESIGN: The institutional cardiopulmonary exercise testing (CPET) database was analyzed retrospectively. All patients aged ≤ 18 years without a diagnosis of cardiac disease and with a maximal effort CPET were included. Patients were divided into three self-identified racial categories: White, Black, and Latinx. The Child Opportunity Index (COI) 2.0 was used to analyze social determinants of health. CRF was evaluated based on COI quintiles and race. Assessment of the effect of COI on racial disparities in CRF was performed using ANCOVA. RESULTS: A total of 1753 CPETs met inclusion criteria. The mean VO2peak was 42.1 ± 9.8 mL/kg/min. The VO2peak increased from 39.1 ± 9.6 mL/kg/min for patients in the very low opportunity cohort to 43.9 ± 9.4 mL/kg/min for patients in the very high opportunity cohort. White patients had higher percent predicted VO2peak compared with both Black and Latinx patients (P < .01 for both comparisons). The racial differences in CRF were no longer significant when adjusting for COI. CONCLUSION: In a large pediatric cohort, COI was associated with CRF. Racial disparities in CRF are reduced when accounting for modifiable risk factors.

A Comprehensive Assessment of the Chinese Version of the Duke Activity Status Index in Patients with Cardiovascular Diseases.

Background: Exercise capacity serves as a direct representation of cardiac function. The Duke Activity Status Index (DASI), a self-administered 12-item questionnaire, covers aspects of daily living, household tasks, sexual function, and physical activity. Although widely used to evaluate exercise capacity, its validation in Chinese cardiovascular disease (CVD) patients has not been thoroughly explored. Considering the significant cultural and lifestyle differences between China and Western countries, which may influence Chinese patients' comprehension and responses to DASI, our objective is to culturally adapt DASI for Chinese patients with CVD to ensure its precision in assessing exercise capacity. Methods: The cultural adaptation of the original DASI questionnaire into Chinese followed a rigorous process to ensure its validity, reliability, and sensitivity to Chinese CVD patients. The study included 107 outpatients diagnosed with CVD who completed the DASI and cardiopulmonary exercise testing (CPET). Cronbach's alpha, Spearman correlation, and factor analysis were utilized to test reliability and validity. Receiver operating characteristic (ROC) curve analysis was employed to assess the prognostic utility of the DASI. Results: Participants had a mean DASI score of 39.40 ± 10.75 and a peak oxygen uptake (Peak VO 2 ) of 19.53 ± 5.89 mL/min/kg. The Chinese version of the DASI exhibited satisfactory reliability and validity in CVD patients, with a Chronbach's alpha coefficient of 0.706. The DASI score demonstrated a moderate correlation with Peak VO 2 measured by CPET (r = 0.67, p < 0.001). Factor analysis yielded three factors, accounting for 56.76% of the total variance, with factor 1 contributing to 26.38% of the variance. ROC curve analysis demonstrated that the DASI exhibited discriminative utility in the identification of patients with improved long-term prognosis (p < 0.001). The ROC curve had an area of 0.788 [95% confidence interval (CI) = 0.704-0.871]. The DASI score ≥ 36.85 served as the optimal threshold for enhanced long-term prognosis, exhibiting a sensitivity of 0.80 and a specificity of 0.69. Conclusions: The culturally adapted DASI questionnaire is a straightforward and efficient tool for reasonably evaluating exercise capacity in Chinese CVD patients.

Cardiopulmonary exercise test to detect cardiac dysfunction from pulmonary vascular disease.

BACKGROUND: Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease. METHODS: We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT). We correlated CPET-determined O2·pulseAT/O2·pulserest with RHC-determined SVAT/SVrest. We evaluated the sensitivity and specificity of O2·pulseAT/O2·pulserest to detect SVAT/SVrest below the lower limit of normal (LLN). For comparison, we performed similar analyses comparing echocardiographically-measured peak tricuspid regurgitant velocity (TRVpeak) with SVAT/SVrest. RESULTS: From July 2018 through February 2023, 83 simultaneous RHC and CPET were performed. Thirty-six studies measured O2·pulse and SV at rest and at AT. O2·pulseAT/O2·pulserest correlated highly with SVAT/SVrest (r = 0.72, 95% CI 0.52, 0.85; p < 0.0001), whereas TRVpeak did not (r = -0.09, 95% CI -0.47, 0.33; p = 0.69). The AUROC to detect SVAT/SVrest below the LLN was significantly higher for O2·pulseAT/O2·pulserest (0.92, SE 0.04; p = 0.0002) than for TRVpeak (0.69, SE 0.10; p = 0.12). O2·pulseAT/O2·pulserest of less than 2.6 was 92.6% sensitive (95% CI 76.6%, 98.7%) and 66.7% specific (95% CI 35.2%, 87.9%) for deficient SVAT/SVrest. CONCLUSIONS: CPET detected deficient SV augmentation more accurately than echocardiography. CPET-determined O2·pulseAT/O2·pulserest may have a prominent role for noninvasive screening of patients at risk for pulmonary vascular disease, such as patients with persistent dyspnea after pulmonary embolism.

Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Maximal Exercise Tolerance, Objective Trunk Strength, and Mobility Measurements in Axial Spondyloarthritis.

OBJECTIVE: Although exercise therapy is safe, effective, and recommended as a nonpharmacological treatment for axial spondyloarthritis (axSpA), there is a lack of guidelines regarding type and dosage. Insufficient knowledge about physical and physiological variables makes designing effective exercise programs challenging. Therefore, the goal of this study was to simultaneously assess trunk strength, spinal mobility, and the cardiorespiratory fitness of patients with axSpA. METHODS: In a cross-sectional study, 58 patients with axSpA (mean age 40.8 yrs, 50% male, mean symptom duration 10.3 yrs) performed maximal cervical and trunk mobility and isometric strength tests in all planes (using David Back Concept devices) and a maximal cardiopulmonary bicycle exercise test (n = 25). Mobility and strength data were compared to healthy reference data. Cut-off values for clinical cardiopulmonary exercise testing interpretation were used to judge normality. Patients were compared based on radiographic involvement and symptom duration. RESULTS: Both strength (P ≤ 0.02) and mobility (P ≤ 0.001) were significantly lower for the patients with axSpA compared to the reference. Strength deficits were comparable between the radiographic and nonradiographic groups (P > 0.05, except trunk extension [P = 0.03]), whereas mobility showed higher deficits in the radiographic group (cervical extension [P = 0.02] and rotation [P = 0.01], and trunk extension [P = 0.03] and rotation [P = 0.03]), regardless of symptom duration. Similarly, symptom duration positively affected oxygen pulse (P = 0.03), relative anaerobic threshold (P = 0.02), and aerobic capacity (P = 0.02). CONCLUSION: In patients with axSpA, strength is more affected than mobility when compared to healthy controls. Likewise, mainly the metabolic component of aerobic capacity is impaired, affecting cardiopulmonary fitness. These findings indicate that future personalized exercise programs in patients with axSpA should incorporate exercises for cardiopulmonary fitness next to strength and mobility training.

Cardiopulmonary exercise testing prior to radical cystectomy: a systematic review and meta-analysis.

OBJECTIVE: To identify the association between cardiopulmonary exercise testing (CPET) and outcomes of radical cystectomy (RC), as RC is historically associated with high rates of short- and long-term morbidity and mortality. METHODS: This quantitative systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. An electronic literature search was conducted to identify all relevant studies evaluating the relationship between CPET parameters and RC outcomes. The primary outcome was short-term mortality. Secondary outcomes included hospital length of stay (LOS) and rate of serious adverse events as defined by the Clavien-Dindo classification. RESULTS: The search identified six studies for inclusion. A total of 546 patients underwent CPET prior to RC. There were significantly more deaths following RC observed in patients with poorer cardiopulmonary function (risk ratio RR 5.80, 95% confidence interval 4.96-6.78). There was no significant association between CPET parameters and adverse events or hospital LOS. CONCLUSIONS: The present systematic review and meta-analysis identified a greater risk of 90-day mortality in patients with poorer cardiorespiratory function, as measured by CPET. However, there remains a paucity of robust clinical data and further high-quality studies are required to verify these results.

Maximal cardiopulmonary exercise testing in glioblastoma patients undergoing chemotherapy: assessment of feasibility, safety, and physical fitness status.

PURPOSE: Maximal cardiopulmonary exercise testing (max. CPET) provides the most accurate measurement of cardiorespiratory fitness. However, glioblastoma (GBM) patients often undergo less intensive tests, e.g., 6-min walk test or self-rating scales. This study aims to demonstrate feasibility and safety of max. CPET in GBM patients, concurrently evaluating their physical fitness status. METHODS: Newly diagnosed GBM patients undergoing adjuvant chemotherapy were offered participation in an exercise program. At baseline, max. CPET assessed cardiorespiratory fitness including peak oxygen consumption (VO2peak), peak workload, and physical work capacity (PWC) at 75% of age-adjusted maximal heart rate (HR). Criteria for peak workload were predefined based on threshold values in HR, respiratory quotient, respiratory equivalent, lactate, and rate of perceived effort. Data were compared to normative values. Adverse events were categorized according to standardized international criteria. Further, self-reported exercise data pre- and post-diagnosis were gathered. RESULTS: All 36 patients (median-aged 60; 21 men) met the predefined criteria for peak workload. Mean absolute VO2peak was 1750 ± 529 ml/min, peak workload averaged 130 ± 43 W, and mean PWC was 0.99 ± 0.38 W/kg BW, all clinically meaningful lower than age- and sex-predicted normative values (87%, 79%, 90%, resp.). Only once (3%) a minor, transient side effect occurred (post-test dizziness, no intervention needed). Self-reported exercise decreased from 15.8 MET-h/week pre-diagnosis to 7.2 MET-h/week post-diagnosis. CONCLUSION: Max. CPET in this well-defined population proved feasible and safe. GBM patients exhibit reduced cardiorespiratory fitness, indicating the need for tailored exercise to enhance health and quality of life. CPET could be essential in establishing precise exercise guidelines.

Distinct effects of type 2 diabetes and obesity on cardiopulmonary performance.

AIM: Effort intolerance is frequent in patients with overweight/obesity and/or type 2 diabetes (T2D) free from cardiac and respiratory disease. We sought to quantify the independent effects of T2D and body mass index (BMI) on cardiopulmonary capacity and gain insights on the possible pathophysiology by case-control and regression analyses. METHODS: Patients at high/moderate cardiovascular risk, with or without T2D, underwent spirometry and combined echocardiography-cardiopulmonary exercise test as part of their clinical workup. Subjects with evidence of cardiopulmonary disease were excluded. The effects of T2D and obesity were estimated by multivariable models accounting for known/potential confounders and the major pathophysiological determinants of oxygen uptake at peak exercise (VO2peak ) normalized for fat-free mass (FFM). RESULTS: In total, 109 patients with T2D and 97 controls were included in the analysis. The two groups had similar demographic and anthropometric characteristics except for higher BMI in T2D (28.6 ± 4.6 vs. 26.3 ± 4.4 kg/m2 , p = .0003) but comparable FFM. Patients with T2D achieved lower VO2peak than controls (18.5 ± 4.4 vs. 21.7 ± 8.3 ml/min/kg, p = .0006). Subclinical cardiovascular dysfunctions were observed in T2D: concentric left ventricular remodelling, autonomic dysfunction, systolic dysfunction and reduced systolic reserve. After accounting for confounders and major determinants of VO2peakFFM , T2D still displayed reduced VO2peak by 1.0 (-1.7/-0.3) ml/min/kgFFM , p = .0089, while the effect of BMI [-0.2 (-0.3/0.1) ml/min/kgFFM , p = .06 per unit increase], was largely explained by a combination of chronotropic incompetence, reduced peripheral oxygen extraction, impaired systolic reserve and ventilatory (in)efficiency. CONCLUSIONS: T2D is an independent negative determinant of VO2peak whose effect is additive to other pathophysiological determinants of oxygen uptake, including BMI.

Comprehensive Cardiac Rehabilitation Following Acute Myocardial Infarction Improves Clinical Outcomes Regardless of Exercise Capacity.

BACKGROUND: Reduced exercise capacity is a prognostic indicator of adverse outcomes in patients with acute myocardial infarction (AMI). However, few studies have evaluated the effectiveness of comprehensive cardiac rehabilitation (CR) in this population. This study aimed to clarify the efficacy of comprehensive CR in patients with AMI and reduced exercise capacity. METHODS AND RESULTS: This cohort study included 610 patients with AMI who underwent percutaneous coronary intervention. Major adverse cardiovascular events (MACE) were compared between patients who participated in comprehensive outpatient CR for 150 days (CR group; n=430) and those who did not (non-CR group; n=180). During the mean (±SD) follow-up period of 6.1±4.0 years, the CR group exhibited a lower incidence of MACE (log-rank P=0.002). Multivariable analysis revealed that Killip classification, diuretics at discharge, and participation in comprehensive CR were independently associated with MACE. The CR group was further divided into 2 groups, namely reduced exercise capacity (% predicted peak V̇O2<80%; n=241) and preserved exercise capacity (≥80%; n=147), based on the initial cardiopulmonary exercise test. Despite distinct exercise capacities, the incidence of MACE was comparable and physical parameters improved similarly after comprehensive CR in both groups. CONCLUSIONS: Comprehensive CR in patients with AMI effectively reduced the incidence of MACE regardless of initial exercise capacity. Cardiologists should actively encourage patients with low exercise capacity to participate in comprehensive CR.

Right Ventricular to Pulmonary Artery Uncoupling Is Associated With Impaired Exercise Capacity in Patients With Transthyretin Cardiac Amyloidosis.

BACKGROUND: Exercise capacity is related to mortality and morbidity in heart failure (HF) patients. Determinants of exercise capacity in transthyretin cardiac amyloidosis (ATTR-CA) have not been established. METHODS AND RESULTS: This single-center study retrospectively evaluated ATTR-CA patients and patients with non-amyloidosis HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) (n=32 and n=51, respectively). In the ATTR-CA group, the median age was 75.5 years (interquartile range [IQR] 71.3-78.8 years), 90.6% were male, and the median left ventricular (LV) ejection fraction was 53.5% (IQR 41.4-65.6%). Cardiopulmonary exercise tests revealed a median peak oxygen consumption and anaerobic threshold of 15.9 (IQR 11.6-17.4) and 10.6 (IQR 8.5-12.0] mL/min/kg, respectively, and ventilatory efficiency (minute ventilation/carbon dioxide production [V̇E/V̇CO2] slope) of 35.5 (IQR 32.0-42.5). Among exercise variables, V̇E/V̇CO2slope has the greatest prognostic value. Univariate analysis revealed a significant correlation between V̇E/V̇CO2slope and age, LV global longitudinal strain, tricuspid annular plain systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and mixed venous oxygen saturation. In multivariate analyses, the TAPSE/PASP ratio was an independent predictor of V̇E/V̇CO2slope (95% confidence interval -44.5, -10.8; P=0.0067). In non-amyloidosis HFpEF/HFmrEF patients, the TAPSE/PASP ratio was not independently correlated with V̇E/V̇CO2slope. CONCLUSIONS: Right ventricular-pulmonary artery coupling estimated by the TAPSE/PASP ratio determines exercise capacity in ATTR-CA patients. This highlights the importance of early therapeutic intervention against underappreciated right ventricular dysfunction associated with ATTR-CA.

Impact of an Exercise-Based Cardiac Rehabilitation Program on Cardiopulmonary Test Parameters.

INTRODUCTION: Exercise-based cardiac rehabilitation programs (CRPs) represent a multidisciplinary therapeutic approach tailored to improve cardiorespiratory fitness and overall health-related quality of life, while reducing cardiovascular hospitalizations and mortality. Our aim was to determine changes in exercise capacity and cardiac events according to the left ventricular ejection fraction (LVEF) following a CRP. METHODS: This single-center cohort study included 131 patients who completed a center-based CRP from 2015 to 2022. Cardiopulmonary exercise testing (CPET), transthoracic echocardiography, and laboratory analysis were performed before and after program completion. RESULTS: Of 232 enrolled patients, 131 were included in our cohort analysis, with 36.6% having a reduced LVEF. These patients exhibited higher rates of atrial fibrillation (p = 0.019) and NT-proBNP values (p < 0.001). Patients with reduced LVEF had lower peak VO2 (pVO2) (p = 0.046), percentage of predicted oxygen consumption (ppVO2) (p < 0.001), and VO2 at anaerobic threshold (p = 0.015) during baseline CPET. Completion of the CRP led to comparable improvements in exercise performance between groups, assessed through Δ pVO2 (p = 0.990), Δ ppVO2 (p = 0.610), and Δ VE/VCO2 slope (p = 0.200). In the study population, male gender and hypertension independently predicted variation in VE/VCO2 slope (p = 0.017) and oxygen uptake efficiency slope (p = 0.048), respectively, post-CRP. During follow-up, 9.2% of all patients had hospital admissions for cardiac events, and 3.8% died, with no significant differences between groups. CONCLUSION: Patients with reduced LVEF admitted to our CRP showed lower functional status based on specific CPET parameters. After CRP, both reduced and preserved LVEF groups experienced similar functional improvements. Therefore, strategies to increase participation of patients with reduced LVEF in such programs are warranted.

Effect of body mass index on exercise capacity following pediatric heart transplantation.

BACKGROUND: Obesity and impaired exercise tolerance following heart transplantation increase the risk of post-transplant morbidity and mortality. The aim of this study was to evaluate the effect of body mass index on markers of exercise capacity in pediatric heart transplant recipients and compare this effect with a healthy pediatric cohort. METHODS: A retrospective analysis of cardiopulmonary exercise test data between 2004 and 2022 was performed. All patients exercised on a treadmill using the Bruce protocol. Inclusion criteria included patients aged 6-21 years, history of heart transplantation (transplant cohort) or no cardiac diagnosis (control cohort) at the time of testing, and a maximal effort test. Patients were further stratified within these two cohorts as underweight, normal, overweight, and obese based on body mass index groups. Two-way analyses of variance were performed with diagnosis and body mass index category as the independent variables. RESULTS: A total of 250 exercise tests following heart transplant and 1963 exercise tests of healthy patients were included. Heart transplant patients across all body mass index groups had higher resting heart rate and lower maximal heart rate, heart rate recovery at 1 min, exercise duration, and peak aerobic capacity (VO2peak). Heart transplant patients in the normal and overweight body mass index categories had higher VO2peak and exercise duration when compared to underweight and obese patients. CONCLUSION: Underweight status and obesity are strongly associated with lower VO2peak and exercise duration in heart transplant patients. Normal and overweight heart transplant patients had the best markers of exercise capacity.

Cardiopulmonary exercise testing in long covid shows the presence of dysautonomia or chronotropic incompetence independent of subjective exercise intolerance and fatigue.

BACKGROUND: After COVID-19 infection, 10-20% of patients suffer from varying symptoms lasting more than 12 weeks (Long COVID, LC). Exercise intolerance and fatigue are common in LC. The aim was to measure the maximal exercise capacity of the LC patients with these symptoms and to analyze whether this capacity was related to heart rate (HR) responses at rest and during exercise and recovery, to find out possible sympathetic overactivity, dysautonomia or chronotropic incompetence. METHODS: Cardiopulmonary exercise test was conducted on 101 LC patients, who were admitted to exercise testing. The majority of them (86%) had been treated at home during their acute COVID-19 infection. Peak oxygen uptake (VO2peak), maximal power during the last 4 min of exercise (Wlast4), HRs, and other exercise test variables were compared between those with or without subjective exercise intolerance, fatigue, or both. RESULTS: The measurements were performed in mean 12.7 months (SD 5.75) after COVID-19 infection in patients with exercise intolerance (group EI, 19 patients), fatigue (group F, 31 patients), their combination (group EI + F, 37 patients), or neither (group N, 14 patients). Exercise capacity was, in the mean, normal in all symptom groups and did not significantly differ among them. HRs were higher in group EI + F than in group N at maximum exercise (169/min vs. 158/min, p = 0.034) and 10 min after exercise (104/min vs. 87/min, p = 0.028). Independent of symptoms, 12 patients filled the criteria of dysautonomia associated with slightly decreased Wlast4 (73% vs. 91% of sex, age, height, and weight-based reference values p = 0.017) and 13 filled the criteria of chronotropic incompetence with the lowest Wlast4 (63% vs. 93%, p < 0.001), VO2peak (70% vs. 94%, p < 0.001), the lowest increase of systolic blood pressure (50 mmHg vs. 67 mmHg, p = 0.001), and the greatest prevalence of slight ECG-findings (p = 0.017) compared to patients without these features. The highest prevalence of chronotropic incompetence was seen in the group N (p = 0.022). CONCLUSIONS: This study on LC patients with different symptoms showed that cardiopulmonary exercise capacity was in mean normal, with increased sympathetic activity in most patients. However, we identified subgroups with dysautonomia or chronotropic incompetence with a lowered exercise capacity as measured by Wlast4 or VO2peak. Subjective exercise intolerance and fatigue poorly foresaw the level of exercise capacity. The results could be used to plan the rehabilitation from LC and for selection of the patients suitable for it.

Cardiopulmonary function in paediatric post-COVID-19: a controlled clinical trial.

Recently, the importance of post-COVID-19 in children has been recognized in surveys and retrospective chart analysis. However, objective data in the form of cardiopulmonary exercise test as performed in adults suffering from this condition are still lacking. This study aimed to investigate the cardiopulmonary effects of post-COVID-19 on children and adolescents. In this cross-sectional study (the FASCINATE study), children fulfilling the criteria of post-COVID-19 and an age- and sex-matched control group underwent cardiopulmonary exercise testing on a treadmill and completed a questionnaire with regard to physical activity before, during and after the infection with SARS-CoV-2. We were able to recruit 20 children suffering from post-COVID-19 (mean age 12.8 ± 2.4 years, 60% females) and 28 control children (mean age 11.7 ± 3.5 years, 50% females). All participants completed a maximal treadmill test with a significantly lower V ˙ O 2 peak in the post-COVID-19 group (37.4 ± 8.8 ml/kg/min vs. 43.0 ± 6.7 ml/kg/min. p = 0.019). This significance did not persist when comparing the achieved percentage of predicted V ˙ O 2 peak . There were no significant differences for oxygen pulse, heart rate, minute ventilation or breathing frequency.   Conclusion: This is the first study to investigate post-COVID-19 in children using the cardiopulmonary exercise test. Although there was a significantly reduced V ˙ O 2 peak in the post-COVID-19 group, this was not true for the percent of predicted values. No pathological findings with respect to cardiac or pulmonary functions could be discerned. Deconditioning was the most plausible cause for the experienced symptoms.    Trial registration: clinicaltrials.gov, NCT054445531, Low-field Magnetic Resonance Imaging in Pediatric Post Covid-19-Full Text View-ClinicalTrials.gov. What is Known: • The persistence of symptoms after an infection with SARS-CoV 2, so-called post-COVID-19 exists also in children. • So far little research has been conducted to analyze this entity in the pediatric population. What is New: • This is the first study proving a significantly lower cardiopulmonary function in pediatric patients suffering from post-COVID-19 symptoms. • The cardiac and pulmonary function appear similar between children suffering from post-COVID-19 and those who don't, but the peripheral muscles seem affected.