Exercise Performance In Patients Research Articles

Adverse Effect of Bundle Branch Block on Exercise Performance in Patients with Fontan Physiology: From the Pediatric Heart Network Fontan Public Data Set.

Patients with Fontan physiology have reduced exercise performance compared to their peers as well as a higher incidence of bundle branch block (BBB). This study aims to investigate the association between BBB and exercise performance in the Fontan population through a retrospective review of the Pediatric Heart Network Fontan study public use dataset. "Low Performers" were defined as ≤ 25th percentile (for Fontan patients) for each exercise parameter at anaerobic threshold (AT) for gender and age and "Normal Performers" were all other patients. A total of 303 patients with Fontan physiology who underwent exercise testing reached AT and had complete data for BBB. BBB occurred more frequently in Low Performers for VO2 [OR (95% CI): 2.6 (1.4, 4.8)] and Work [OR (95% CI): 2.7 (1.4, 5.1)], suggesting that BBB in the Fontan population is associated with reduced exercise performance. This data adds to the existing clinical evidence of the adverse effects of conduction abnormalities on single ventricle cardiac output and adds support for consideration of cardiac resynchronization and multi-site ventricular pacing in this patient population.

Efficacy and Safety of Bisoprolol in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

To evaluate the clinical efficacy and safety of bisoprolol in patients with chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: Pulmonary function(FEV1, FEV1%, FVC), 6-minute walking distance (6MWD), adverse events and inflammatory cytokines(IL-6, IL-8, CRP). Thirty-five studies were included with a total of 3269 study participants, including 1650 in the bisoprolol group and 1619 in the control group. The effect of bisoprolol on lung function in patients with COPD, FEV1, MD (0.46 [95% CI, 0.27 to 0.65], P=0.000), FEV1%, MD (-0.64 [95% CI, 0.42 to 0.86], P=0.000), FVC, MD (0.20 [95% CI, 0.05 to 0.34], P=0.008), the results all showed a statistically significant result. The effect of bisoprolol on 6MWD in COPD patients, MD (1.37 [95% CI, 1.08 to 1.66], P=0.000), which showed a statistically significant result. The occurrence of adverse events in COPD patients treated with bisoprolol, RR (0.83 [95% CI, 0.54 to 1.26], P=0.382), resulted in no statistical significance. The effect of bisoprolol on inflammatory cytokines in COPD patients, IL-6, MD (-1.16 [95% CI, -1.67 to -0.65], P=0.000), IL-8, MD (-0.94 [95% CI, -1.32 to -0.56], P=0.000), CRP, MD (-1.74 [95% CI, -2.40 to -1.09], P=0.000), the results were statistically significant. We performed a subgroup analysis of each outcome indicator according to whether the patients had heart failure or not, and the results showed that the therapeutic effect of bisoprolol on COPD did not change with the presence or absence of heart failure. Bisoprolol is safe and effective in the treatment of COPD, improving lung function and exercise performance in patients with COPD, and also reducing inflammatory markers in patients with COPD, and this effect is independent of the presence or absence of heart failure.

The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design

BackgroundHeart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). MethodsThis clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P < 0.05 with 1-β>0.80. DiscussionThe iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future ‘pivotal’, phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.

Sacubitril/valsartan improves exercise performance in patients with heart failure: a dose-dependent effect

Abstract Funding Acknowledgements Type of funding sources: None. Background Sacubitril/Valsartan therapy has become a cornerstone of heart failure with reduced ejection fraction (HFrEF) pharmacological therapy due to its positive prognostic impact. However, conflicting results have emerged on the effects of sacubitril/valsartan on exercise performance assessed by cardiopulmonary exercise test (CPET). Purpose The aim of this study was to prospectively evaluate the effects of sacubitril/valsartan on prognostically significant CPET parameters in a larger population of HFrEF patients at different drug doses. Methods We prospectively enrolled HFrEF outpatients eligible to start sacubitril/valsartan according to 2016 ESC Guidelines in 3 Heart Failure Units. Patients underwent CPET at baseline (before sacubitril/valsartan treatment), after 1, 2, 3 months (respectively after a month taking the 24/26 – 49/51 – 97/103mg doses), and 6 months after the maximum tolerated dose was reached (end-study). The subjective impression of disease-related limitation was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). Results 113 patients were enrolled (age 64.5±9.7, 81% males) (Table 1). Peak oxygen intake (peakVO2) improved at each step from 15.0±4.5 mL/min/kg at baseline to 16.5±4.9 mL/min/kg at end study visit, corresponding to 61.5±16.0 and 67.9±17.4 % of predicted, respectively (p&amp;lt;0.05). Minute ventilation/carbon dioxide production relationship (VE/VCO2 slope) reduced from 39.6±5.5 to 35.9±7.1 (p = 0.005) in the 39 patients (42%) with pathological VE/VCO2≥34 at baseline. KCCQ improved significantly since the first visit with an overall summary score increase from 47.9±11.1 to 52.6±9.8 (p&amp;lt;0.001). Conclusions These findings suggest that sacubitril/valsartan benefits on exercise capacity are immediately evident at the lowest dose and progressively improve as the dose increases.

Rate-Adaptive Atrial Pacing for Heart Failure With Preserved Ejection Fraction

Reduced heart rate during exercise is common and associated with impaired aerobic capacity in heart failure with preserved ejection fraction (HFpEF), but it remains unknown if restoring exertional heart rate through atrial pacing would be beneficial. To determine if implanting and programming a pacemaker for rate-adaptive atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence. Single-center, double-blind, randomized, crossover trial testing the effects of rate-adaptive atrial pacing in patients with symptomatic HFpEF and chronotropic incompetence at a tertiary referral center (Mayo Clinic) in Rochester, Minnesota. Patients were recruited between 2014 and 2022 with 16-week follow-up (last date of follow-up, May 9, 2022). Cardiac output during exercise was measured by the acetylene rebreathe technique. A total of 32 patients were recruited; of these, 29 underwent pacemaker implantation and were randomized to atrial rate responsive pacing or no pacing first for 4 weeks, followed by a 4-week washout period and then crossover for an additional 4 weeks. The primary end point was oxygen consumption (V̇o2) at anaerobic threshold (V̇o2,AT); secondary end points were peak V̇o2, ventilatory efficiency (V̇e/V̇co2 slope), patient-reported health status by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Of the 29 patients randomized, the mean age was 66 years (SD, 9.7) and 13 (45%) were women. In the absence of pacing, peak V̇o2 and V̇o2 at anaerobic threshold (V̇o2,AT) were both correlated with peak exercise heart rate (r = 0.46-0.51, P < .02 for both). Pacing increased heart rate during low-level and peak exercise (16/min [95% CI, 10 to 23], P < .001; 14/min [95% CI, 7 to 21], P < .001), but there was no significant change in V̇o2,AT (pacing off, 10.4 [SD, 2.9] mL/kg/min; pacing on, 10.7 [SD, 2.6] mL/kg/min; absolute difference, 0.3 [95% CI, -0.5 to 1.0] mL/kg/min; P = .46), peak V̇o2, minute ventilation (V̇e)/carbon dioxide production (V̇co2) slope, KCCQ-OSS, or NT-proBNP level. Despite the increase in heart rate, atrial pacing had no significant effect on cardiac output with exercise, owing to a decrease in stroke volume (-24 mL [95% CI, -43 to -5 mL]; P = .02). Adverse events judged to be related to the pacemaker device were observed in 6 of 29 participants (21%). In patients with HFpEF and chronotropic incompetence, implantation of a pacemaker to enhance exercise heart rate did not result in an improvement in exercise capacity and was associated with increased adverse events. ClinicalTrials.gov Identifier: NCT02145351.

Relation of non-exercise walking activity with exercise performance in patients with peripheral artery disease: NEW activity for PAD

IntroductionCommunity-based structured exercise training (CB-SET) programs are beneficial for patients with peripheral artery disease (PAD). However, the impact of lower levels of walking activity accumulated separately from formal exercise is unclear. The aim of this study was to determine the relation of non-exercise walking (NEW) activity with exercise performance in PAD. MethodsThis was a post hoc analysis from twenty patients with PAD enrolled in a 12 week CB-SET program using diaries and accelerometry. Formal exercise (3 sessions·week−1) was detected using patient-reported diary entries that corresponded with accelerometer step data. NEW activity was characterized as steps completed over five days each week, excluding steps achieved during formal exercise sessions. The primary exercise performance outcome was peak walking time (PWT) assessed on a graded treadmill. Secondary performance outcomes included claudication onset time (COT) from the graded treadmill and peak walking distance (PWD) achieved during the six-minute walk test (6MWT). Partial Pearson correlations evaluated the relation of NEW activity (step·week−1) with exercise performance outcomes using exercise session intensity (step·week−1) and duration (min·week−1) as covariates. ResultsNEW activity demonstrated a moderate, positive correlation with change in PWT (r=0.50, p=0.04). Other exercise performance outcomes were not significantly related to NEW activity (COT: r=0.14; 6MWT PWD: r=0.27). ConclusionsA positive association was demonstrated between NEW activity and PWT following 12 weeks of CB-SET. Interventions to increase physical activity levels outside of formal exercise sessions may be beneficial for patients with PAD.

Challenging the Hemodynamic Hypothesis in Heart Failure With Preserved Ejection Fraction: Is Exercise Capacity Limited by Elevated Pulmonary Capillary Wedge Pressure?

Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP should improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin to acutely lower PCWP during exercise in patients with HFpEF. Thirty patients with HFpEF (70±6 years of age; 63% female) underwent 2 bouts of upright, seated cycle exercise dosed with sublingual nitroglycerin or placebo control every 15 minutes in a single-blind, randomized, crossover design. PCWP (right heart catheterization), oxygen uptake (breath × breath gas exchange), and cardiac output (direct Fick) were assessed at rest, 20 Watts (W), and peak exercise during both placebo and nitroglycerin conditions. PCWP increased from 8±4 to 35±9 mm Hg from rest to peak exercise with placebo. With nitroglycerin, there was a graded decrease in PCWP compared with placebo at rest (-1±2 mm Hg), 20W (-5±5 mm Hg), and peak exercise (-7±6 mm Hg; drug × exercise stage P=0.004). Nitroglycerin did not affect oxygen uptake at rest, 20W, or peak (placebo, 1.34±0.48 versus nitroglycerin, 1.32±0.46 L/min; drug × exercise P=0.984). Compared with placebo, nitroglycerin lowered stroke volume at rest (-8±13 mL) and 20W (-7±11 mL), but not peak exercise (0±10 mL). Sublingual nitroglycerin lowered PCWP during submaximal and maximal exercise. Despite reduction in PCWP, peak oxygen uptake was not changed. These results suggest that acute reductions in PCWP are insufficient to improve exercise capacity, and further argue that high PCWP during exercise is not by itself a limiting factor for exercise performance in patients with HFpEF. URL: https://www. gov; Unique identifier: NCT04068844.

Human skeletal muscle nitrate and nitrite in individuals with peripheral arterial disease: Effect of inorganic nitrate supplementation and exercise.

Skeletal muscle may act as a reservoir for N-oxides following inorganic nitrate supplementation. This idea is most intriguing in individuals with peripheral artery disease (PAD) who are unable to endogenously upregulate nitric oxide. This study analyzed plasma and skeletal muscle nitrate and nitrite concentrations along with exercise performance, prior to and following 12-weeks of exercise training combined with oral inorganic nitrate supplementation (EX+BR) or placebo (EX+PL) in participants with PAD. Non-supplemented, at baseline, there were no differences in plasma and muscle nitrate. For nitrite, muscle concentration was higher than plasma (+0.10nmol.g-1 ). After 12 -weeks, acute oral nitrate increased both plasma and muscle nitrate (455.04 and 121.14 nmol.g-1 , p < 0.01), which were correlated (r=0.63, p < 0.01), plasma nitrate increase was greater than in muscle (p < 0.01). Nitrite increased in the plasma (1.01 nmol.g-1 , p < 0.05) but not in the muscle (0.22 nmol.g-1 ) (p < 0.05 between compartments). Peak walk time (PWT) increased in both groups (PL + 257.6s;BR + 315.0s). Six-minute walk (6MW) distance increased only in the (EX+BR) group (BR + 75.4m). We report no substantial gradient of nitrate (or nitrite) from skeletal muscle to plasma, suggesting a lack of reservoir-like function in participants with PAD. Oral nitrate supplementation produced increases in skeletal muscle nitrate, but not skeletal muscle nitrite. The related changes in nitrate concentration between plasma and muscle suggests a potential for inter-compartmental nitrate "communication". Skeletal muscle did not appear to play a role in within compartment nitrate reduction. Muscle nitrate and nitrite concentrations did not appear to contribute to exercise performance in patients with PAD.

Clinician's Corner: Counseling Patients with Pulmonary Vascular Disease Traveling to High Altitude

Ulrich, Silvia, Mona Lichtblau, Simon R. Schneider, Stéphanie Saxer, and Konrad E. Bloch, Clinician's corner: counseling patients with pulmonary vascular disease traveling to high altitude. High Alt Med Biol. 23:201-208, 2022.-Pulmonary vascular diseases (PVDs) with precapillary pulmonary hypertension (PH), such as pulmonary arterial or chronic thromboembolic PH, impair exercise performance and survival in patients. Vasodilators and other treatments improve quality of life and prognosis to an extent in patients who have PVDs as chronic disorders. Obviously, patients with PVD wish to participate in usual daily activities, including travel to popular settlements and mountainous regions located at high altitude. However, the pulmonary hemodynamic impairment due to PVD leads to blood and tissue hypoxia, particularly during exercise and sleep. It is thus of concern that alveolar hypoxia at higher altitude may exacerbate patients' symptoms and lead to decompensation. Current PH guidelines discourage high-altitude exposure for fear of altitude-related adverse health effects. However, several recent well-designed prospective and randomized trials show that despite altitude-induced hypoxemia, pulmonary hemodynamic changes and impairment of exercise performance in patients with PVD are similar to the responses in healthy people or in patients with mild chronic obstructive pulmonary disease. The vast majority of patients with PVD can tolerate short-term exposure to moderate altitudes up to 2,500 m. For the roughly 10% of patients with stable disease who develop severe hypoxemia when ascending to 2,500 m, they respond well to low-level supplemental oxygen support. The best low-altitude predictors for adverse health effects at high altitude are the known clinical risk factors for PVD such as symptoms, functional class, exercise capacity, and exertional oxygen desaturation, whereas hypoxia altitude simulation testing is of little additive value. In any case, patients should be instructed that altitude-related adverse health effects may be difficult to predict and that in case of worsening symptoms, immediate accompanied descent to lower altitude and oxygen therapy are required. Patients with severe hypoxemia near sea level may safely visit high-altitude regions up to 1,500-2,000 m while continuing oxygen therapy and avoiding strenuous exercise. All PH patients should be counseled before any high-altitude sojourn by doctors with experience in PVD and high-altitude medicine and have an action plan for the occurrence of severe hypoxemia and other altitude-related conditions such as acute mountain sickness.

Evaluation of maximal exercise capacity through the incremental shuttle walking test in lymphangioleiomyomatosis

BackgroundThe cardiopulmonary exercise test (CPET) is the gold standard for assessing aerobic fitness; however, it is expensive, not widely available, and requires specialized equipment and staff. The incremental shuttle walking test (ISWT) is an exercise field test used to evaluate exercise capacity and may be an alternative to CPET in patients with lymphangioleiomyomatosis (LAM). ObjectiveTo investigate whether the ISWT can be used to assess maximal aerobic capacity in patients with LAM. MethodsForty-five women were evaluated on two days, and they randomly performed the CPET and ISWT. The maximum oxygen uptake (peak VO2) was evaluated using gas analyzers in both tests. The carbon dioxide production (VCO2), respiratory exchange ratio (RER), and heart rate (HR) were compared during peak exercise. Pearson's correlation and Bland-Altman assessed the association and agreement, respectively. The intraclass correlation coefficient (ICC) was used to assess the reliability of the data. ResultsAll patients (46.1 ± 10.2 years) presented similar peak VO2, RER, and peak HR during the CPET and ISWT (15.6 ± 4.6 vs. 15.7 ± 4.4 ml·kg−1·min−1; 1.15±0.09 vs. 1.17±0.12; and 142.2 ± 18.6 vs. 141.5 ± 22.2 bpm, respectively; p>0.05). A good linear correlation (r = 0.79; p<0.001) and ICC (0.86; 95%CI 0.74−0.93) were observed between the peak VO2 in both tests. Predictive peak VO2 equations based on the ISWT performance are also presented. ConclusionOur results suggest that the ISWT can be used to assess maximal exercise performance in patients with LAM, and it is a valuable option to be used as an alternative to the CPET and predict maximal exercise capacity.

A pilot crossover trial assessing the exercise performance patients with chronic obstructive pulmonary disease

Noninvasive ventilation improves exercise performance in patients with chronic obstructive pulmonary disease (COPD). However, the effect of helmet ventilation (HV) on the short-term self-paced exercise performance of patients with COPD remains unclear. This study investigated the use of HV during a 6 min walk test (6MWT) and analyzed its short-term cardiopulmonary outcomes in patients with stable COPD. A single-site crossover trial was conducted in a pulmonary rehabilitation outpatient department. A total of 20 stable patients with COPD without disability were enrolled. The participants performed 6MWTs with and without HV on two consecutive days. The outcome measures were the distance walked in the 6MWT and the physiological and cardiopulmonary parameters. The mean difference in meters walked between the HV-aided and unaided walk tests was 15.4 ± 37.2 (95% confidence interval: − 2.03 to 32.8 m; p = .145). During the 6MWT, the peak heart rate was significantly higher when walking was aided by HV than when it was unaided (p < .001). The energy expenditure index, walking speed, oxygen saturation nadir, and hemodynamic parameters were comparable. Although carbon dioxide levels inside the helmet increased after the walk test, the participants’ transcutaneous carbon dioxide measurements remained unchanged. HV did not improve the short-term self-paced exercise performance in patients with stable mild-to-moderate COPD. Further research should focus on noninvasive ventilation delivered via helmets in exercise training to determine the setting strategy, breathing circuit configuration, and effects of regular exercise.ClinicalTrial.gov: NCT04156724; IRB number: C108032.

Sex related differences in exercise performance in patients with hypertrophic cardiomyopathy: Hemodynamic insights through non-invasive pressure volume analysis

BackgroundWomen with HCM have worse cardiopulmonary exercise performance compared to men. We used non-invasive pressure-volume (PV) analysis to delineate sex related hemodynamic differences in HCM. MethodsPV loops were constructed from echocardiograms using left ventricular (LV) volumes indexed to body surface area, Doppler estimates of LV end-diastolic pressure and blood pressure. The end-systolic PV relationship (ESPVR) and end-diastolic PV relationship (EDPVR) were derived from validated single-beat techniques. The area between the ESPVR and EDPVR (isovolumetric PV area), was indexed to an LV end-diastolic pressure of 30 mmHg (PVAiso30), as the integrated metric of LV function. LV volume at an end-diastolic pressure of 30 mmHg (V30) indexed ventricular capacity. Results202 patients were included, 56 women. Women were older (51 vs 44 years, p = 0.012) and had reduced exercise capacity (5.6 vs 6.9 METs, p < 0.001). Only 32 patients (16%) had a peak gradient >30 mmHg at rest with no sex differences. Women had significantly lower indexed PVAiso30 (9094 vs 10,255 mmHg*mL/m2, p = 0.02) driven by reduced ventricular capacitance (V30 54 vs 62 mL/m2, p < 0.001). In multivariable linear regression indexed V30 was an independent predictor of exercise capacity. ConclusionImpaired exercise capacity in women with HCM appears associated with abnormalities in passive diastolic properties, suggesting a unique pathophysiology compared to men, and a potential difference in viable therapeutic molecular targets.

Predictors of Prolonged Cardiopulmonary Exercise Impairment After COVID-19 Infection: A Prospective Observational Study.

Objectives: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting individuals to varying degrees. There is emerging evidence that even patients with mild symptoms will suffer from prolonged physical impairment.Methods: In this prospective observational study, lung function, and cardiopulmonary exercise testing have been performed in 100 patients for 3–6 months after COVID-19 diagnosis (post-CoVG). Depending on the severity of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, patients were divided into asymptomatic, or mild to moderate (mild post-CoVG), and severe post-CoVG [hospitalization with or without intensive care unit/non-invasive ventilation (ICU/NIV)]. Results have been compared with age, sex, and body mass index (BMI) matched control group (CG, N = 50).Results: Both lung function (resting) and exercise capacity (peak workload, Wpeak and peak oxygen uptake, VO2 peak - % predicted) were considerably affected in patients with severe post-CoV (81.7 ± 27.6 and 86.1 ± 20.6%), compared to the mild post-CoVG (104.8 ± 24.0%, p = 0.001 and 100.4 ± 24.8; p = 0.003). In addition, also the submaximal exercise performance was significantly reduced in the severe post-CoVG (predicted VT1/VO2 peak; p = 0.013 and VT2/VO2 peak; p = 0.001). Multiple linear regression analyses revealed that 74 % (adjusted R2) of the variance in relative VO2 peak of patients who had CoV could be explained by the following variables: lower age, male sex, lower BMI, higher DLCO, higher predicted heart rate (HR) peak, lower breathing reserve (BR), and lower SaO2 peak, which were related to higher relative VO2 peak values. Higher NT-proBNP and lower creatinine kinase (CK) values were seen in severe cases compared to patients who experienced mild CoV.Discussion: Maximal and submaximal exercise performance in patients recovering from severe COVID-19 remain negatively affected for 3–6 months after COVID-19 diagnosis. The presented findings reveal that impaired pulmonary, cardiac, and skeletal muscle function contributed to the limitation of VO2 peak in those patients, which may have important implications on rehabilitation programs.

Dietary nitrate supplementation to enhance exercise capacity in hypoxic COPD: EDEN-OX, a double-blind, placebo-controlled, randomised cross-over study

RationaleDietary nitrate supplementation improves skeletal muscle oxygen utilisation and vascular endothelial function. We hypothesised that these effects might be sufficient to improve exercise performance in patients with COPD and hypoxia...

Effect of oxygen therapy on exercise performance in patients with cyanotic congenital heart disease: Randomized-controlled trial

BackgroundPatients with unrepaired cyanotic congenital heart disease (CHD) suffer from aggravated hypoxemia during exercise. We tested the hypothesis that supplemental oxygen improves exercise performance in these patients. MethodsIn this randomized, sham-controlled, single-blind, cross-over trial cyanotic CHD-patients underwent four cycle exercise tests to exhaustion, while breathing either oxygen-enriched (FiO2 0.50, oxygen) or ambient air (FiO2 0.21, air) using incremental (IET) or constant work-rate (CWRET) exercise test protocols (75% of maximal work rate achieved under FiO2 0.21). Pulmonary gas-exchange, electrocardiogram, arterial blood gases, oxygen saturation (SpO2), cerebral and quadriceps muscle tissue oxygenation (CTO and QMTO) by near-infrared spectroscopy were measured. ResultsWe included seven patients with cyanotic CHD (4 Eisenmenger syndrome, 3 unrepaired cyanotic defects, 4 women) median (quartiles) age 36 (32;50) years, BMI 23 (20;26) kg/m2 and SpO2 at rest 87 (83;89) %. When comparing supplemental oxygen with air during exercise, maximal work-rate in IET increased from 76 (58;114) Watts to 83 (67;136) Watts, median difference 9 (0;22) W (p = 0.046) and CWRET-time increased from 412 s (325;490) to 468 s (415;553), median increase 56 (39;126) s (p = 0.018). In both IET and CWRET SpO2 was significantly higher and ventilatory equivalent for carbon dioxide significantly lower at end-exercise with oxygen compared to air, whereas CTO and QMTO did not significantly differ. ConclusionsPatients with cyanotic CHD significantly improved their exercise performance, in terms of maximal work-rate and endurance time along with an improved arterial oxygenation and ventilatory efficiency with supplemental oxygen compared to air.

Myocardial adaptation and exercise performance in patients with pulmonary arterial hypertension assessed with patient-specific computer simulations.

Myocardial function and exercise reserve are important determinants of outcome in pulmonary arterial hypertension (PAH) but are incompletely understood. For this study, we performed subject-specific computer simulations, based on invasive measurements and cardiac magnetic resonance imaging (CMR), to investigate whole circulation properties in PAH at rest and exercise and determinants of exercise reserve. CMR and right heart catheterization were performed in nine patients with idiopathic PAH, and CMR in 10 healthy controls. CMR during exercise was performed in seven patients with PAH. A full-circulation computer model was developed, and model parameters were optimized at the individual level. Patient-specific simulations were used to analyze the effect of right ventricular (RV) inotropic reserve on exercise performance. Simulations achieved a high consistency with observed data. RV contractile force was increased in patients with PAH (127.1 ± 28.7 kPa vs. 70.5 ± 14.5 kPa, P < 0.001), whereas left ventricular contractile force was reduced (107.5 ± 17.5 kPa vs. 133.9 ± 10.3 kPa, P = 0.002). During exercise, RV contractile force increased by 1.56 ± 0.17, P = 0.001. In silico experiments confirmed RV inotropic reserve as the important limiting factor for cardiac output. Subject-specific computer simulation of myocardial mechanics in PAH is feasible and can be used to evaluate myocardial performance. With this method, we demonstrate marked functional myocardial adaptation to PAH in the resting state, primarily composed of increased contractile force development by RV myofibers, and we show the negative impact of reduced RV inotropic reserve on cardiac output during exercise.NEW & NOTEWORTHY Computer simulations of the myocardial mechanics and hemodynamics of rest and exercise were performed in nine patients with pulmonary arterial hypertension and 10 control subjects, with the use of data from invasive catheterization and from cardiac magnetic resonance. This approach allowed a detailed analysis of myocardial adaptation to pulmonary arterial hypertension and showed how reduction in right ventricular inotropic reserve is the important limiting factor for an increase in cardiac output during exercise.

Sex related differences in exercise performance in patients with hypertrophic cardiomyopathy: hemodynamic insights through non-invasive pressure volume analysis

Abstract Background Women with HCM have worse cardiopulmonary exercise performance compared to men. We used non-invasive pressure-volume (PV) analysis to delineate sex related hemodynamic differences in HCM. Methods PV loops were constructed from echocardiograms using left ventricular (LV) volumes indexed to body surface area, Doppler estimates of LV end-diastolic pressure and blood pressure. The end-systolic PV relationship (ESPVR) and end-diastolic PV relationship (EDPVR) were derived from validated single-beat techniques. The area between the ESPVR and EDPVR (isovolumetric PV area), was indexed to an LV end-diastolic pressure of 30mmHg (PVAiso30), as the integrated metric of LV function. LV volume at an end-diastolic pressure of 30mmHg (V30) indexed ventricular capacity. Results 202 patients were included, 56 women. Women were older (51 vs 44 yrs, p=0.012) and had reduced exercise capacity (5.6 vs 6.9 METs, p&amp;lt;0.001). Only 32 patients (16%) had a peak gradient &amp;gt;30mmHg at rest with no sex differences. Women had significantly lower indexed PVAiso30 (6577 vs 7767 mmHg·mL/m2, p&amp;lt;0.001) driven by reduced ventricular capacitance (V30 54 vs 62 ml/m2, p&amp;lt;0.001). In multivariable linear regression indexed V30 was an independent predictor of exercise capacity. Conclusion Impaired exercise capacity in women with HCM appears strongly related to abnormalities in passive diastolic properties, suggesting a unique pathophysiology compared to men, and a potential difference in viable therapeutic molecular targets Funding Acknowledgement Type of funding sources: None.

Exercise performance in patients with post-acute sequelae of SARS-CoV-2 infection compared to patients with unexplained dyspnea.

BackgroundDyspnea and exercise intolerance are commonly reported post-acute sequelae of SARS-CoV-2 infection (PASC), but routine diagnostic testing is often normal. Cardiopulmonary exercise testing (CPET) offers comprehensive assessment of dyspnea to characterize pulmonary PASC.MethodsWe performed a retrospective cohort study of CPET performed on patients reporting dyspnea and/or exercise intolerance following confirmed Covid-19 between August 1, 2020 and March 1, 2021, and compared them to age- and sex-matched patients with unexplained dyspnea referred for CPET at the same center in the pre-Covid-19 era.FindingsCompared to matched unexplained dyspnea comparators, PASC patients shared similar medical comorbidities and subjective dyspnea at referral (mMRC score 1.6 ± 0.9 vs. 1.4 ± 0.9, P = 0.5). Fifteen (83.3%) PASC patients underwent high resolution computed tomography of the chest, of which half (46.7%) were normal, and 17 (94.4%) patients had pulmonary function testing, of which the majority (76.5%) were normal. All patients underwent CPET, and 12 (67%) had normal findings. Compared to matched comparators, PASC patients had similar peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, and ventilatory efficiency measured by the minute ventilation to carbon dioxide production (VE/VCO2) slope.InterpretationDespite prominent dyspnea, physiological abnormalities on CPET were mild across a range of initial Covid-19 severity and similar to matched comparators referred for dyspnea without antecedent SARS-CoV-2.FundingThe project was supported by the NHLBI (R01HL131029, R01HL151841, U10HL110337, T32HL116275) and a KL2 award (5KL2TR002542–02) from Harvard Catalyst.

Effect of Breathing Oxygen-Enriched Air on Exercise Performance in Patients With Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction: A Randomized, Placebo-Controlled, Crossover Trial.

Objective: To evaluate the effects of breathing oxygen-enriched air (oxygen) on exercise performance in patients with pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF).Methods: Ten patients with PH-HFpEF (five women, age 60 ± 9 y, mPAP 37 ± 14 mmHg, PAWP 18 ± 2 mmHg, PVR 3 ± 3 WU, resting SpO2 98 ± 2%) performed two-cycle incremental exercise tests (IET) and two constant-work-rate exercise test (CWRET) at 75% maximal work-rate (Wmax), each with ambient air (FiO2 0.21) and oxygen (FiO2 0.5) in a randomized, single-blinded, cross-over design. The main outcomes were the change in Wmax (IET) and cycling time (CWRET) with oxygen vs. air. Blood gases at rest and end-exercise, dyspnea by Borg CR10 score at end-exercise; continuous SpO2, minute ventilation (V'E), carbon dioxide output (V'CO2), and cerebral and quadricep muscle tissue oxygenation (CTO and QMTO) were measured.Results: With oxygen vs. air, Wmax (IET) increased from 94 ± 36 to 99 ± 36 W, mean difference (95% CI) 5.4 (0.9–9.8) W, p = 0.025, and cycling time (CWRET) from 532 ± 203 to 680 ± 76 s, +148 (31.8–264) s, p = 0.018. At end-exercise with oxygen, Borg dyspnea score and V'E/V'CO2 were lower, whereas PaO2 and end-tidal PaCO2 were higher. Other parameters were unchanged.Conclusion: Patients with PH-HFpEF not revealing resting hypoxemia significantly improved their exercise performance while breathing oxygen-enriched air along with less subjective dyspnea sensation, a better blood oxygenation, and an enhanced ventilatory efficiency. Future studies should investigate whether prolonged training with supplemental oxygen would increase the training effect and, potentially, daily activity for PH-HFpEF patients.Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT04157660].

The correlation between quadriceps muscle strength and endurance and exercise performance in patients with COPD.

To determine the association between quadriceps muscle strength (QMS) and endurance (QME) and exercise capacity in patients with COPD after stratification for sex and resting lung function (LF). Data were collected from 3,246 patients with COPD (60% men, 64 ± 9 yr), including measures of exercise capacity [peak aerobic capacity (peakV̇o2), 6-min walk distance (6MWD)] and isokinetic QMS and QME. Patients were stratified for sex, forced expiratory volume in 1 s (>50/≤50% predicted), single breath carbon monoxide diffusing capacity (>50/≤50% predicted), and residual volume (>140/≤140% predicted). After stratification for resting LF, QMS and QME were significantly associated with peakV̇o2 (r range: 0.47-0.61 and 0.49-0.65 for men and 0.53-0.66 and 0.48-0.67 for women, respectively) and 6MWD (r range: 0.29-0.42 and 0.44-0.55 for men and 0.25-0.54 and 0.34-0.55 for women, respectively) (P < 0.001). Regression models demonstrated that QMS and QME were significant determinants of peakV̇o2 (explained variance R2 range: 35.6%-48.8% for men and 36.8%-49.0% for women) and 6MWD (R2 range: 24.3%-43.3% for men and 28.4%-40.3% for women), independent of age and fat-free mass. Quadriceps muscle function was significantly associated with peakV̇o2 and 6MWD in male and female patients with COPD after stratification for resting LF, in which QME appear to be a more important determinant than QMS. This underlines the importance of systematically evaluating both quadriceps muscle strength and endurance in in all patients with COPD.NEW & NOTEWORTHY Our findings identified quadriceps muscle function as an important determinant of exercise capacity across a wide spectrum of lung function. Quadriceps muscle endurance appears to be a more important determinant than quadriceps muscle strength, underlining the importance of including both the measurement of quadriceps muscle strength and endurance in routine assessment for all patient with COPD.