mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, abnormal results on exercise stress testing are predictive of heart failure outcomes. Our goal was to determine whether an abnormal exercise response is associated with adverse outcomes in pediatric patients with HCM. METHODS: In an international cohort study including 20 centers, phenotype-positive patients with primary HCM who were <18 years of age at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response and new or worsened ST- or T-wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of abnormal exercise test results with transplant and SCD event-free survival. RESULTS: Of 724 eligible patients, 630 underwent at least 1 exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8 years (interquartile range, 4.7 years); 78% were male and 39% were receiving beta-blockers. A total of 175 (28%) had abnormal test results. Patients with abnormal test results had more severe septal hypertrophy, higher left atrial diameter z scores, higher resting left ventricular outflow tract gradient, and higher frequency of myectomy compared with participants with normal test results (P<0.05). Compared with normal test results, abnormal test results were independently associated with lower 5-year transplant-free survival (97% versus 88%, respectively; P=0.005). Patients with exercise-induced ischemia were most likely to experience all-cause death or transplant (hazard ratio, 4.86 [95% CI, 1.69-13.99]), followed by those with an abnormal blood pressure response (hazard ratio, 3.19 [95% CI, 1.32-7.71]). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (hazard ratio, 3.32 [95% CI, 1.27-8.70]). Exercise-induced ectopy was not associated with survival. CONCLUSIONS: Exercise abnormalities are common in childhood HCM. An abnormal exercise test result was independently associated with lower transplant-free survival, especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.

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

BACKGROUND: Detailed heart rate (HR) response patterns during exercise in patients with heart failure and sinus rhythm remains uncertain. METHODS: We screened consecutive heart failure patients 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. RESULTS: 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 VO2/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 VO2/kg than their counterparts (interactions for p<0.001). CONCLUSIONS: 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.

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.

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.

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.

Animal Models of Exercise From Rodents to Pythons.

Acute and chronic animal models of exercise are commonly used in research. Acute exercise testing is used, often in combination with genetic, pharmacological, or other manipulations, to study the impact of these manipulations on the cardiovascular response to exercise and to detect impairments or improvements in cardiovascular function that may not be evident at rest. Chronic exercise conditioning models are used to study the cardiac phenotypic response to regular exercise training and as a platform for discovery of novel pathways mediating cardiovascular benefits conferred by exercise conditioning that could be exploited therapeutically. The cardiovascular benefits of exercise are well established, and, frequently, molecular manipulations that mimic the pathway changes induced by exercise recapitulate at least some of its benefits. This review discusses approaches for assessing cardiovascular function during an acute exercise challenge in rodents, as well as practical and conceptual considerations in the use of common rodent exercise conditioning models. The case for studying feeding in the Burmese python as a model for exercise-like physiological adaptation is also explored.

Paradoxical breathing during sleep is associated with increased sleep apnea and reduced ventilatory capacities in high-level spinal cord injury.

Sleep-disordered breathing is highly prevalent in individuals with high-level spinal cord injury. In addition, chest mechanics are known to be altered, leading to paradoxical breathing. Here we investigated the interaction between paradoxical breathing and sleep quality in these patients, and its association with measurements of respiratory function, hypercapnic ventilatory response and peak exercise ventilation. Home-based polysomnography was performed in 13 patients with spinal cord injury (C4 to T4) untreated for sleep-disordered breathing. We defined paradoxical breathing as counterphase between thoracic and abdominal movements during slow-wave and rapid eye movement sleep. Sleep quality, pulmonary function, hypercapnic ventilatory responses and peak exercise ventilation were compared between those with and without paradoxical breathing. Half of individuals presented with nocturnal paradoxical breathing. Despite similar age, body mass index, injury level, time since injury, and respiratory function, those with paradoxical breathing had higher apnea-hypopnea index (13 ± 8 versus 5 ± 3 events per hr) and average sleep heart rate (67 ± 12 versus 54 ± 4 bpm; p < 0.05). Moreover, paradoxical breathing was associated with lower hypercapnic ventilatory response (slope: 0.35 ± 0.17 versus 0.96 ± 0.38) and lower peak exercise ventilation (33 ± 4 versus 48 ± 12 L min-1 ; p < 0.05). Nocturnal respiratory muscle desynchronization could play a role in the pathophysiology of sleep apnea, and could relate to low ventilatory responses to both hypercapnia and exercise in high-level spinal cord injury. Polysomnography may be an important diagnostic tool for these patients for whom therapeutic approaches should be considered to treat this abnormality.

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.

Blood Pressure Responses During Exercise: Physiological Correlates and Clinical Implications.

BACKGROUND: Abnormal blood pressure (BP) responses to exercise can predict adverse cardiovascular outcomes, but their optimal measurement and definitions are poorly understood. We combined frequently sampled BP during cardiopulmonary exercise testing with vascular stiffness assessment to parse cardiac and vascular components of exercise BP. METHODS: Cardiopulmonary exercise testing with BP measured every two minutes and resting vascular tonometry were performed in 2858 Framingham Heart Study participants. Linear regression was used to analyze sex-specific exercise BP patterns as a function of arterial stiffness (carotid-femoral pulse wave velocity) and cardiac-peripheral performance (defined by peak O2 pulse). RESULTS: Our sample was balanced by sex (52% women) with mean age 54±9 years and 47% with hypertension. We observed variability in carotid-femoral pulse wave velocity and peak O2 pulse across individuals with clinically defined exercise hypertension (peak systolic BP [SBP] in men ≥210 mm Hg; in women ≥190 mm Hg). Despite similar resting SBP and cardiometabolic profiles, individuals with higher peak O2 pulse displayed higher peak SBP (P≤0.017) alongside higher fitness levels (P<0.001), suggesting that high peak exercise SBP in the context of high peak O2 pulse may in fact be favorable. Although both higher (favorable) O2 pulse and higher (adverse) arterial stiffness were associated with greater peak SBP (P<0.0001 for both), the magnitude of association of carotid-femoral pulse wave velocity with peak SBP was higher in women (sex-carotid-femoral pulse wave velocity interaction P<0.0001). In sex-specific models, exercise SBP measures accounting for workload (eg, SBP during unloaded exercise, SBP at 75 watts, and SBP/workload slope) were directly associated with the adverse features of greater arterial stiffness and lower peak O2 pulse. CONCLUSIONS: Higher peak exercise SBP reflects a complex trade-off between arterial stiffness and cardiac-peripheral performance that differs by sex. Studies of BP responses to exercise accounting for vascular and cardiac physiology may illuminate mechanisms of hypertension and clarify clinical interpretation of exercise BP.

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.

Evaluation of novel indices of walking performance taking oxygen desaturation into account during six-minute walk test in cardiovascular disease patients.

In pulmonary disease patients since oxygen desaturation during 6-min walk test (6MWT) affects walk distance (6MWD), some novel indices such as desaturation/distance ratio [DDR, oxygen desaturation area (DAO2)/6MWD] and distance-saturation product [DSP, 6MWD × minimum peripheral oxygen saturation (SpO2)] are evaluated. However, there has been no study examining these indices that consider exercise-induced desaturation (EID) in patients with cardiovascular disease. In 94 cardiovascular disease patients without pulmonary complications, 6MWT and echocardiography were performed at the entry of cardiac rehabilitation. SpO2 was measured during 6MWT using a continuously monitorable pulse oximeter, and DSP and DDR were calculated using minimum SpO2 and DAO2 [sum of (100-SpO2) per second during 6MWT], respectively. EID was defined as SpO2 decrease of ≥ 4% or minimum SpO2 of < 90% during 6MWT. DSP was slightly lower and DDR was markedly higher in patients with EID than in those without. When examining correlations of DSP and DDR with their components, DSP was correlated with 6MWD much closely than minimum SpO2, while DDR was correlated as closely with DAO2 as 6MWD. Furthermore, DAO2, but not minimum SpO2, had a direct correlation with 6MWD. As for associations with cardiac function, DSP was correlated with several cardiac parameters, but DDR was not correlated with any of these parameters. Our findings suggest that oxygen desaturation during 6MWT affects walking distance in cardiovascular disease patients even without pulmonary complications and that DDR is more appropriate than DSP as an index of walking performance that takes EID into consideration, independently of cardiac function.

An 8-week Forced-rate Aerobic Cycling Program Improves Cardiorespiratory Fitness in Persons With Chronic Stroke: A Randomized Controlled Trial.

OBJECTIVE: To examine the cardiorespiratory effects of a forced-rate aerobic exercise (FE) intervention among individuals with chronic stroke compared with an upper extremity repetitive task practice (UE RTP) control group. DESIGN: Secondary analysis of data from a randomized controlled trial. SETTING: Research laboratory. PARTICIPANTS: Individuals with chronic stroke (N=60). INTERVENTIONS: Participants completed 24 sessions of FE followed by RTP (FE+RTP, N=30) or time matched RTP alone (N=30). The FE+RTP group was prescribed exercise at 60%-80% of heart rate reserve on a motorized stationary cycle ergometer for 45 minutes followed by 45 minutes of RTP. The control group completed 90 minutes of RTP. MAIN OUTCOME MEASURES: Metabolic exercise stress tests on a cycle ergometer were conducted at baseline and post-intervention. Outcomes included peak oxygen consumption (peak V̇o2) and anaerobic threshold (AT). RESULTS: Fifty participants completed the study intervention and pre/post stress tests. The FE+RTP group demonstrated significantly greater improvements in peak V̇o2 from 16.4±5.7 to 18.3±6.4 mL/min/kg compared with the RTP group (17.0±5.6 to 17.2±5.6 mL/min/kg, P=.020) and significantly greater improvements in AT from 10.3±2.8 to 11.5±3.6 mL/min/kg compared with the RTP group (10.8±3.9 to 10.4±3.2 mL/min/kg, P=.020). In analyzing predictors of post-intervention peak V̇o2, the multivariable linear regression model did not reveal a significant effect of age, sex, body mass index, or beta blocker usage. Similarly, bivariate linear regression models for the FE group only did not find any exercise variables (aerobic intensity, power, or cycling cadence) to be significant predictors of peak V̇o2. CONCLUSIONS: While the aerobic exercise intervention was integrated into rehabilitation to improve UE motor recovery, it was also effective in eliciting significant and meaningful improvements in cardiorespiratory fitness. This novel rehabilitation model may be an effective approach to improve motor and cardiorespiratory function in persons recovering from stroke.

Clinimetric Properties of the Steep Ramp Test to Assess Cardiorespiratory Fitness, Its Underlying Physiological Responses, and Its Current Applications: A Scoping Review.

OBJECTIVE: Providing an overview of the clinimetric properties of the steep ramp test (SRT)-a short-term maximal exercise test-to assess cardiorespiratory fitness (CRF), describing its underlying physiological responses, and summarizing its applications in current clinical and research practice. DATA SOURCES: MEDLINE (through PubMed), CINAHL Complete, Cochrane Library, EMBASE, and PsycINFO were searched for studies published up to July 2023, using keywords for SRT and CRF. STUDY SELECTION: Eligible studies involved the SRT as research subject or measurement instrument and were available as full text articles in English or Dutch. DATA EXTRACTION: Two independent assessors performed data extraction. Data addressing clinimetric properties, physiological responses, and applications of the SRT were tabulated. DATA SYNTHESIS: In total, 370 studies were found, of which 39 were included in this study. In several healthy and patient populations, correlation coefficients between the work rate at peak exercise (WRpeak) attained at the SRT and oxygen uptake at peak exercise during cardiopulmonary exercise testing (CPET) ranged from .771-.958 (criterion validity). Repeated measurements showed intraclass correlation coefficients ranging from .908-.996 for WRpeak attained with the first and second SRT (test-retest reliability). Physiological parameters, like heart rate and minute ventilation at peak exercise, indicated that the SRT puts a lower burden on the cardiopulmonary system compared to CPET. The SRT is mostly used to assess CRF, among others as part of preoperative risk assessment, and to personalize interval training intensity. CONCLUSIONS: The SRT is a practical short-term maximal exercise test that is valid for CRF assessment and to monitor changes in CRF over time in various healthy and patient populations. Its clinimetric properties and potential applications make the SRT of interest for a widespread implementation of CRF assessment in clinical and research practice and for personalizing training intensity and monitoring longitudinal changes in CRF.

Effects of different inspiratory muscle training protocols on functional exercise capacity and respiratory and peripheral muscle strength in patients with chronic kidney disease: a randomized study.

BACKGROUND: Pathological changes were observed in the diaphragm due to abnormal renal function in chronic kidney disease (CKD). Inspiratory muscle training (IMT) has been suggested for patients with CKD; however, the most appropriate intensity for IMT has not been determined. Therefore, this study aimed to investigate the effects of different IMT protocols on respiratory muscle strength, quadriceps femoris muscle strength (QMS), handgrip muscle strength (HGS), functional exercise capacity, quality of life (QoL), pulmonary function, dyspnoea, fatigue, balance, and physical activity (PA) levels in patients with CKD. METHODS: This randomized, controlled, single-blind study included 47 patients and they were divided into three groups: Group 1 (n = 15, IMT with 10% maximal inspiratory pressure (MIP)), Group 2 (n = 16, IMT with 30% MIP), and Group 3(n = 16; IMT with 60% MIP). MIP, maximal expiratory pressure (MEP), 6-min walking test (6-MWT), QMS, HGS, QoL, pulmonary function, dyspnoea, fatigue, balance, and PA levels were assessed before and after eight weeks of IMT. RESULTS: Increases in MIP, %MIP, 6-MWT distance, and %6-MWT were significantly higher in Groups 2 and 3 than in Group 1 after IMT (p < 0.05). MEP, %MEP, FEF25-75%, QMS, HGS, and QoL significantly increased; dyspnoea and fatigue decreased in all groups (p < 0.05). FVC, PEF, and PA improved only in Group 2, and balance improved in Groups 1 and 2 (p < 0.05). CONCLUSIONS: IMT with 30% and 60% MIP similarly improves inspiratory muscle strength and functional exercise capacity. IMT with 30% is more effective in increasing PA. IMT is a beneficial method to enhance peripheral and expiratory muscle strength, respiratory function, QoL and balance, and reduce dyspnoea and fatigue. IMT with %30 could be an option for patients with CKD who do not tolerate higher intensities. TRIAL REGISTRATION: This study was retrospectively registered (NCT06401135, 06/05/2024).

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge.

BACKGROUND: SARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients. METHODS: In a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin). RESULTS: Out of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups. CONCLUSIONS: The study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

Echocardiographic assessment for cardiopulmonary function in patients with congenital heart disease-related pulmonary arterial hypertension.

BACKGROUND: For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity. METHODS: A cohort of 70 patients contributed a total of 110 paired echocardiogram and CPET results to this study, with 1 year interval for repeated examinations. Echocardiography and exercise testing were conducted following standardized procedures, and the data were collected together with clinically relevant indicators for subsequent statistical analysis. Demographic comparisons were performed using t-tests and chi-square tests. Univariate and multivariate analyses were conducted to identify potential predictors of peak oxygen uptake (peak VO2) and the carbon dioxide ventilation equivalent slope (VE/VCO2 slope). Receiver operating characteristic (ROC) analysis was used to assess the performance of the parameters. RESULTS: The ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) was found to be the only independent indicator significantly associated with both peak VO2 and VE/VCO2 slope (both p < 0.05). Additionally, left ventricular ejection fraction (LVEF) and right ventricular fractional area change (FAC) were independently correlated with the VE/VCO2 slope (both p < 0.05). TAPSE/PASP showed the highest area under the ROC curve (AUC) for predicting both a peak VO2 ≤ 15 mL/kg/min and a VE/VCO2 slope ≥ 36 (AUC = 0.91, AUC = 0.90, respectively). The sensitivity and specificity of TAPSE/PASP at the optimal threshold exceeded 0.85 for both parameters. CONCLUSIONS: TAPSE/PASP may be a feasible echocardiographic indicator for evaluating exercise tolerance.

The effect of chronotropic incompetence on physiologic responses during progressive exercise in people with Parkinson's disease.

PURPOSE: Heart rate (HR) response is likely to vary in people with Parkinson's disease (PD), particularly for those with chronotropic incompetence (CI). This study explores the impact of CI on HR and metabolic responses during cardiopulmonary exercise test (CPET) in people with PD, and its implications for exercise intensity prescription. METHODS: Twenty-eight participants with mild PD and seventeen healthy controls underwent CPET to identify the presence or absence of CI. HR and metabolic responses were measured at submaximal (first (VT1) and second (VT2) ventilatory thresholds), and at peak exercise. Main outcome measures were HR, oxygen consumption (VO2), and changes in HR responses (HR/WR slope) to an increase in exercise demand. RESULTS: CI was present in 13 (46%) PD participants (PDCI), who during CPET, exhibited blunted HR responses compared to controls and PD non-CI beyond 60% of maximal workload (p ≤ 0.05). PDCI presented a significantly lower HR at VT2, and peak exercise compared to PD non-CI and controls (p ≤ 0.001). VO2 was significantly lower in PDCI than PD non-CI and controls at VT2 (p = 0.003 and p = 0.036, respectively) and at peak exercise (p = 0.001 and p = 0.023, respectively). CONCLUSION: Although poorly understood, the presence of CI in PD and its effect on HR and metabolic responses during incremental exercise is significant and important to consider when programming aerobic exercises.

Usefulness of cardiopulmonary exercise test combined with exercise stress echocardiography in mild chronic thromboembolic pulmonary disease.

PURPOSE: Chronic thromboembolic pulmonary disease (CTEPD) can lead to exercise limitations even without right ventricular (RV) dysfunction or pulmonary hypertension at rest. Combining exercise stress echocardiography with cardiopulmonary exercise testing (ESE-CPET) for RV function and pressure changes combined measuring overall function may be useful for CTEPD evaluation. This study aims to investigate CPET and ESE results to elucidate the mechanisms of exercise limitation in mild CTEPD cases. METHODS: Among our CTEPD registry, 50 patients who performed both right heart catheterization data of mild disease (less than 30 mm Hg of mean pulmonary arterial pressure (mPAP)) and ESE-CPET were enrolled. Echocardiography and CPET-derived parameters were compared with hemodynamic parameters measured through right heart catheterization. RESULTS: Peak VO2 (maximal oxygen consumption) was decreased in overall population (71.3 ± 16.3% of predictive value). Peak VO2 during exercise was negatively correlate with mPAP and pulmonary vascular resistance at rest. A substantial increase in RV systolic pressure (RVSP) was observed during exercise (RVSP: pre-exercise 37.2 ± 11.8 mm Hg, postexercise 64.3 ± 24.9 mm Hg, p-value < .001). Furthermore, RV function deteriorated during exercise when compared to the baseline (RV fractional area change: 31.5 ± 10.0% to 37.8 ± 7.0%, p-value < .001; RV global longitudinal strain: -17.1 ± 4.2% to -17.7 ± 3.3%, p-value < .001) even though basal RV function was normal. While an excessive increase in RVSP during exercise was noticed in both groups, dilated RV and RV dysfunction during exercise were demonstrated only in the impaired exercise capacity group. CONCLUSION: CTEPD patients with mild PH or without PH exhibited limited exercise capacity alongside an excessive increase in RVSP during exercise. Importantly, RV dysfunction during exercise was significantly associated with exercise capacity. ESE-CPET could aid in comprehending the primary cause of exercise limitation in these patients.