Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

BACKGROUND: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population. METHODS: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease. RESULTS: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers. CONCLUSION: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Physical fitness in male adolescents and atherosclerosis in middle age: a population-based cohort study.

OBJECTIVES: To examine the associations between physical fitness in male adolescents and coronary and carotid atherosclerosis in middle age. METHODS: This population-based cohort study linked physical fitness data from the Swedish Military Conscription Register during adolescence to atherosclerosis data from the Swedish CArdioPulmonary bioImage Study in middle age. Cardiorespiratory fitness was assessed using a maximal cycle-ergometer test, and knee extension muscular strength was evaluated through an isometric dynamometer. Coronary atherosclerosis was evaluated via Coronary Computed Tomography Angiography (CCTA) stenosis and Coronary Artery Calcium (CAC) scores, while carotid plaques were evaluated by ultrasound. The associations were analysed using multinomial logistic regression, adjusted (marginal) prevalences and restricted cubic splines. RESULTS: The analysis included 8986 male adolescents (mean age 18.3 years) with a mean follow-up of 38.2 years. Physical fitness showed a reversed J-shaped association with CCTA stenosis and CAC, but no consistent association was observed for carotid plaques. After adjustments, compared with adolescents in the lowest tertile of cardiorespiratory fitness and muscular strength, those in the highest tertile had 22% (OR 0.78; 95% CI 0.61 to 0.99) and 26% (OR 0.74; 95% CI 0.58 to 0.93) lower ORs for severe (≥50%) coronary stenosis, respectively. The highest physical fitness group (high cardiorespiratory fitness and muscular strength) had 33% (OR 0.67; 95% CI 0.52 to 0.87) lower OR for severe coronary stenosis compared with those with the lowest physical fitness. CONCLUSION: This study supports that a combination of high cardiorespiratory fitness and high muscular strength in adolescence is associated with lower coronary atherosclerosis, particularly severe coronary stenosis, almost 40 years later.

Cardiorespiratory dysautonomia in post-COVID-19 condition: Manifestations, mechanisms and management.

A significant proportion of COVID-19 patients experience debilitating symptoms for months after the acute infection. According to recent estimates, approximately 1 out of 10 COVID-19 convalescents reports persistent health issues more than 3 months after initial recovery. This 'post-COVID-19 condition' may include a large variety of symptoms from almost all domains and organs, and for some patients it may mean prolonged sick-leave, homestay and strongly limited activities of daily life. In this narrative review, we focus on the symptoms and signs of post-COVID-19 condition in adults - particularly those associated with cardiovascular and respiratory systems, such as postural orthostatic tachycardia syndrome or airway disorders - and explore the evidence for chronic autonomic dysfunction as a potential underlying mechanism. The most plausible hypotheses regarding cellular and molecular mechanisms behind the wide spectrum of observed symptoms - such as lingering viruses, persistent inflammation, impairment in oxygen sensing systems and circulating antibodies directed to blood pressure regulatory components - are discussed. In addition, an overview of currently available pharmacological and non-pharmacological treatment options is presented.

Defining left ventricular remodeling using lean body mass allometry: a UK Biobank study.

PURPOSE: The geometric patterns of ventricular remodeling are determined using indexed left ventricular mass (LVM), end-diastolic volume (LVEDV) and concentricity, most often measured using the mass-to-volume ratio (MVR). The aims of this study were to validate lean body mass (LBM)-based allometric coefficients for scaling and to determine an index of concentricity that is independent of both volume and LBM. METHODS: Participants from the UK Biobank who underwent both CMR and dual-energy X-ray absorptiometry (DXA) during 2014-2015 were considered (n = 5064). We excluded participants aged ≥ 70 years or those with cardiometabolic risk factors. We determined allometric coefficients for scaling using linear regression of the logarithmically transformed ventricular remodeling parameters. We further defined a multiplicative allometric relationship for LV concentricity (LVC) adjusting for both LVEDV and LBM. RESULTS: A total of 1638 individuals (1057 female) were included. In subjects with lower body fat percentage (< 25% in males, < 35% in females, n = 644), the LBM allometric coefficients for scaling LVM and LVEDV were 0.85 ± 0.06 and 0.85 ± 0.03 respectively (R2 = 0.61 and 0.57, P < 0.001), with no evidence of sex-allometry interaction. While the MVR was independent of LBM, it demonstrated a negative association with LVEDV in (females: r = - 0.44, P < 0.001; males: - 0.38, P < 0.001). In contrast, LVC was independent of both LVEDV and LBM [LVC = LVM/(LVEDV0.40 × LBM0.50)] leading to increased overlap between LV hypertrophy and higher concentricity. CONCLUSIONS: We validated allometric coefficients for LBM-based scaling for CMR indexed parameters relevant for classifying geometric patterns of ventricular remodeling.

Enhancing students' understanding of cardiac physiology by using 4D visualization.

Difficulties in achieving knowledge about physiology and anatomy of the beating heart highlight the challenges with more traditional pedagogical methods. Recent research regarding anatomy education has mainly focused on digital three-dimensional models. However, these pedagogical improvements may not be entirely applicable to cardiac anatomy and physiology due to the multidimensional complexity with moving anatomy and complex blood flow. The aim of this study was therefore to evaluate whether high quality time-resolved anatomical images combined with realistic blood flow simulations improve the understanding of cardiac structures and function. Three time-resolved datasets were acquired using time-resolved computed tomography and blood flow was computed using Computational Fluid Dynamics. The anatomical and blood flow information was combined and interactively visualized using volume rendering on an advanced stereo projection system. The setup was tested in interactive lectures for medical students. Ninety-seven students participated. Summative assessment of examinations showed significantly improved mean score (18.1 ± 4.5 vs 20.3 ± 4.9, p = 0.002). This improvement was driven by knowledge regarding myocardial hypertrophy and pressure-velocity differences over a stenotic valve. Additionally, a supplementary formative assessment showed significantly more agreeing answers than disagreeing answers (p < 0.001) when the participants subjectively evaluated the contribution of the visualizations to their education and knowledge. In conclusion, the use of simultaneous visualization of time-resolved anatomy data and simulated blood flow improved medical students' results, with a particular effect on understanding of cardiac physiology and these simulations may be useful educational tools for teaching complex anatomical and physiological concepts.

Disease prevalence and number of health care visits among members of a nationwide sports organization compared to matched controls.

BACKGROUND: Physical activity has positive effects on several diseases and may reduce the risk of morbidity and the mortality rate. Whether the prevalence of disease and health care consumption differ between the members of sports organizations and the general population has not been established. Hence, this pilot study aimed to compare the prevalence of diseases known to be associated with physical inactivity and health care consumption in members of a large non-profit sports organization and an age-, sex- and geographically matched random sample from the general population. METHODS: Subjects in two Swedish cities who exercised at least once a week and had been members for at least two years in the non-profit sports organization Friskis&Svettis were invited. A randomized age-, sex- and geographically matched sample was drawn from the general population. Data on disease prevalence (by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes) and health care consumption were retrieved using the members' personal identification numbers through a regional health care database. Between-group differences in the prevalence of disease were compared using chi2-tests and logistic regression between members and controls. Health care consumption was defined as the number of visits, stratified by primary and hospital care, and was compared using chi2-tests and Mann-Whitney U-tests. RESULTS: In total, 3015 subjects were included in each group (response rate 11%). Controls had higher prevalence rates of musculoskeletal diseases (13.3% vs. 11.6%, p = 0.047), metabolic disease (10.4% vs. 5.4%, p < 0.001), hypertension (16.6% vs. 11.7%, p < 0.001), psychiatric diseases (8.9% vs. 7.1%, p = 0.012) and lung cancer (0.4% vs. 0%, p = 0.001) than the members. The total number of health care contacts was 22% higher in the controls than in the members, whereas the proportion of subjects with at least one health care visit was larger in the members (89% vs. 79%, p < 0.001). CONCLUSIONS: The prevalence rates of lifestyle diseases related to musculoskeletal, metabolic and psychiatric diseases, hypertension and lung cancer, and the overall health care consumption, were lower among members of a sports organization than among controls. However, longitudinal studies are needed to establish a cause-effect relationship between membership and disease development.

Echocardiographic Assessment of Left Ventricular Remodeling in American Style Footballers.

Several athletic programs incorporate echocardiography during pre-participation screening of American Style Football (ASF) players with great variability in reported echocardiographic values. Pre-participation screening was performed in National Collegiate Athletic Association Division I ASF players from 2008 to 2016 at the Division of Sports Cardiology. The echocardiographic protocol focused on left ventricular (LV) mass, mass-to-volume ratio, sphericity, ejection fraction, and longitudinal Lagrangian strain. LV mass was calculated using the area-length method in end-diastole and end-systole. A total of two hundred and thirty players were included (18±1 years, 57% were Caucasian, body mass index 29±4 kg/m2) after four players (2%) were excluded for pathological findings. Although there was no difference in indexed LV mass by race (Caucasian 78±11 vs. African American 81±10 g/m2, p=0.089) or sphericity (Caucasian 1.81±0.13 vs. African American 1.78±0.14, p=0.130), the mass-to-volume ratio was higher in African Americans (0.91±0.09 vs. 0.83±0.08, p<0.001). No race-specific differences were noted in LV longitudinal Lagrangian strain. Player position appeared to have a limited role in defining LV remodeling. In conclusion, significant echocardiographic differences were observed in mass-to-volume ratio between African American and Caucasian players. These demographics should be considered as part of pre-participation screening.

Vascular Adaptation to Indoor Cycling Exercise in Premenopausal Women.

The early vascular adaptation to indoor cycling, a popular activity at many fitness centres, is incompletely evaluated. Forty two healthy women (21-45 years) underwent measurements of arterial wall properties and geometry as well as a maximal bicycle exercise test before and after a 3 months period during which 21 of the women joined indoor cycling classes at a gym 2-3 times per week, while 21 women served as time controls. Peak work load increased by in average 16% (p<0.001) and ascending aortic diameter by 4% (p<0.01) in the exercise group, while unchanged in control group. The exercise intervention had no significant influence on the local intima-media thickness, blood pressure or the pulse pressure wave configuration while the carotid artery distensibility (p<0.05) was higher after the intervention. There was a positive correlation between change in (Δ) peak work load and Δ-diameter of tubular ascending aorta (r=0.42, p<0.01) in the exercise group. In conclusion, after only 3 months of bicycle exercise training, signs of central arterial remodelling were seen in premenopausal women, which was associated to improvement in exercise capacity.

Left Ventricular Adaptation to 12 Weeks of Indoor Cycling at the Gym in Untrained Females.

Cross-sectional studies provide evidence of larger cardiac dimensions and mass in endurance trained than in untrained females. Much less is known regarding adaptations in cardiac function following training in untrained subjects. We aimed to study left ventricular (LV) adaptation to indoor cycling in previously untrained females, in regard of LV dimensions, mass and function. 42 sedentary females were divided into 2 equally sized groups, either training indoor cycling at regular classes at a local gym for 12 weeks, in average 2.6 times per week, or maintaining their sedentary lifestyle. Echocardiography at rest and a maximal exercise test were performed before and after the intervention. Exercise capacity increased in average 16% in the exercise group (p<0.001), together with decreased heart rate at rest (p<0.05) and at 120 watts steady-state (p<0.001). There were no difference in systolic or diastolic function following the intervention and minimal increases in LV internal diameter in diastole (+1 mm, p<0.01). LV mass was unchanged with training (137±25 vs. 137±28 g, p=0.911). Our findings indicate that attending indoor cycling classes at a gym 2-to-3 times per week for 12 weeks is enough to improve exercise capacity, while a higher volume of training is required to elicit cardiac adaptations.

Percent predicted peak oxygen uptake is superior to weight-indexed peak oxygen uptake in risk stratification before lung cancer lobectomy.

OBJECTIVE: To improve preoperative risk stratification in lung cancer lobectomy by identifying and comparing optimal thresholds for peak oxygen uptake (VO2peak) presented as weight-indexed and percent of predicted values, respectively. METHODS: This was a longitudinal cohort study including national registry data on patients scheduled for cancer lobectomy that used available data from preoperative cardiopulmonary exercise testing. The measured VO2peak was indexed by body mass (mL/kg/min) and also compared with 2 established reference equations (Wasserman-Hansen and Study of Health in Pomerania, respectively). By receiver operating characteristic analysis, a lower 90% specificity and an upper 90% sensitivity threshold were determined for each measure, in relation to the outcome of any major complication or death. For each measure and based on these thresholds, patients were categorized as low risk, intermediate risk, or high risk. The frequency of complications was compared between groups using χ2. RESULTS: The frequency of complications differed significantly between the proposed low-, intermediate-, and high-risk groups when using % predicted Study of Health in Pomerania (5%, 21%, 35%, P = .007) or % predicted Wasserman-Hansen (5%, 25%, 35%, P = .002) but not when using the weight-indexed VO2peak groups (7%, 23%, 15%, P = .08). Nonsignificant differences were found using the threshold <15 mL/kg/min (P = .34). CONCLUSIONS: This study showed that weight-indexed VO2peak was of less use as a marker of risk at the lower range of exercise capacity, whereas % predicted VO2peak was associated with a continuously increasing risk of major complications, also at the lower end of exercise capacity. As identifying subjects at high risk of complications is important, % predicted VO2peak is therefore preferable.

VE/VCO2 slope threshold optimization for preoperative evaluation in lung cancer surgery: identifying true high- and low-risk groups.

Background: Cardiopulmonary exercise testing (CPET) enables measurement of the slope of the increase in minute ventilation in relation to carbon dioxide elimination during exercise (the VE/VCO2 slope). Several studies have shown that the VE/VCO2 slope is a strong marker for postoperative complications and mortality. However, current thresholds for adverse outcomes are generated from historical data in heart failure patients. Methods: This was a retrospective analysis of 158 patients with lung cancer who underwent lobectomy or pneumonectomy during 2008-2020. The main outcome was major pulmonary complications (MPC) or death ≤30 days of cancer surgery. Patients were first categorized using two different single threshold approaches; the traditional threshold of 35 and the highest Youden value from the receiver operating curve (ROC) analysis. Secondly, patients were categorized into three risk groups using two thresholds. These two thresholds were determined in an ROC analysis, where the VE/VCO2 slope values generating either a 90% sensitivity (lower threshold) or a 90% specificity (upper threshold) for the main outcome were chosen. The frequency of complications was compared using Chi2. The overall model quality was evaluated by an area under the curve (AUC) analysis. Positive predictive values (PPVs) and negative predictive values (NPVs) are presented. Results: The two thresholds, <30 (90% sensitivity) and >41 (90% specificity), created three risk groups: low risk (VE/VCO2 slope <30, n=44, 28%); intermediate risk (VE/VCO2 slope 30-41, n=95, 60%) and high risk (VE/VCO2 slope >41, n=19, 12%). The frequency of complications differed between groups: 5%, 16% and 47% (P<0.001). Using two thresholds compared to one threshold increased the overall model quality (reaching AUC 0.70, 95% confidence interval: 0.59-0.81), and identified a high sensitivity threshold (VE/VCO2 slope <30) which generated a NPV of 95% but importantly, also a high specificity threshold (VE/VCO2 slope >41) with a PPV of 47%. Conclusions: Risk stratification based on three risk groups from the preoperative VE/VCO2 slope increased the model quality, was more discriminative and generated better PPV and NPV compared to traditional risk stratification into two risk groups.

Peak oxygen uptake in combination with ventilatory efficiency improve risk stratification in major abdominal surgery.

This pilot study aimed to evaluate if peak VO2 and ventilatory efficiency in combination would improve preoperative risk stratification beyond only relying on peak VO2 . This was a single-center retrospective cohort study including all patients who underwent cardiopulmonary exercise testing (CPET) as part of preoperative risk evaluation before major upper abdominal surgery during years 2008-2021. The primary outcome was any major cardiopulmonary complication during hospitalization. Forty-nine patients had a preoperative CPET before decision to pursue to surgery (cancer in esophagus [n = 18], stomach [6], pancreas [16], or liver [9]). Twenty-five were selected for operation. Patients who suffered any major cardiopulmonary complication had lower ventilatory efficiency (i.e., higher VE/VCO2 slope, 37.3 vs. 29.7, p = 0.031) compared to those without complications. In patients with a low aerobic capacity (i.e., peak VO2 < 20 mL/kg/min) and a VE/VCO2 slope ≥ 39, 80% developed a major cardiopulmonary complication. In this pilot study of patients with preoperative CPET before major upper abdominal surgery, patients who experienced a major cardiopulmonary complication had significantly lower ventilatory efficiency compared to those who did not. A low aerobic capacity in combination with low ventilatory efficiency was associated with a very high risk (80%) of having a major cardiopulmonary complication.

Heart rate response and recovery in cycle exercise testing - normal values and association with mortality.

AIM: Chronotropic incompetence and impaired heart rate (HR) recovery are related to mortality. Guidelines lack specific reference values for HR recovery. We defined normal values and studied blunted HR response and recovery, and mortality risk. METHODS: We included 9,917 subjects (45% females) aged 18-85 years who performed a cycle exercise test. We defined normal values for peak HR, HR reserve, and HR recovery at 1 and 2 minutes (HRR1 and HRR2) based on individuals apparently healthy (N=2,242). Associations between blunted HR indices (<5th percentile) and mortality over a median follow-up of 8.6 years were analysed using Cox regression and competing risk analysis. RESULTS: All HR indices were age-dependent and independent predictors of all-cause and CV mortality. The 5th percentiles of HR reserve, HRR1, and HRR2 correlated weakly with existing reference values. HR recovery variables were the strongest predictors of all-cause mortality (HRR1, hazard ratio 1.70 [95% confidence interval, 1.49-1.94] and HRR2, 1.57 [1.37-1.79]), including in subjects with normal exercise capacity (HRR1, 1.96 [1.61-2.39] and HRR2, 1.76 [1.46-2.12]). Combining HR indices appeared to increase the risk of all-cause (HRR1 and HRR2, 1.96 [1.68-2.29] and peak HR and HRR1, 1.87 [1.56-2.23]) and CV mortality, although no specific combination was superior for predicting CV mortality. CONCLUSIONS: All HR variables were age-dependent and associated with all-cause and CV mortality. Blunted HR recovery variables were the strongest predictors of all-cause mortality, even in subjects with normal exercise capacity. Combined blunted HR indices appeared to add prognostic value.

We provide a detailed description on the physiologic HR response and recovery kinetics in a population apparently CV risk-free referred for cycle exercise testing. When assessed in a larger population, blunted HR response and recovery were associated with increased mortality. HR response and recovery are age-dependent. We provide novel reference values.All blunted HR indices (peak HR, HR reserve, HRR1 and HRR2) are strong predictors of all-cause and CV mortality, and combined HR indices appeared to add prognostic value in all the analyses.Blunted HRR1 followed by HRR2 are the strongest predictor of all-cause mortality even in subjects with normal exercise capacity, highlighting the importance of their assessment in standard exercise testing.

Exercise systolic blood pressure response during cycle ergometry is associated with future hypertension in normotensive individuals.

AIMS: We aimed to investigate the association between the exercise systolic blood pressure (SBP) response and future hypertension (HTN) in normotensive individuals referred for cycle ergometry, with special regard to reference exercise SBP values and exercise capacity. METHODS AND RESULTS: In this longitudinal cohort study, data from 14 428 exercise tests were cross-linked with Swedish national registries on diagnoses and medications. We excluded individuals with a baseline diagnosis of cardiovascular disease or HTN. The peak exercise SBP (SBPpeak) was recorded and compared with the upper limit of normal (ULN) derived from SBPpeak reference equations incorporating age, sex, resting SBP, and exercise capacity. To evaluate the impact of exercise capacity, three SBP to work rate slopes (SBP/W-slopes) were calculated, relative to either supine or seated SBP at rest or to the first exercise SBP. Adjusted hazard ratios [HRadjusted (95% confidence interval, CI)] for incident HTN during follow-up, in relation to SBP response metrics, were calculated. We included 3895 normotensive individuals (49 ± 14 years, 45% females) with maximal cycle ergometer tests. During follow-up (median 7.5 years), 22% developed HTN. Higher SBPpeak and SBPpeak > ULN were associated with incident HTN [HRadjusted 1.19 (1.14-1.23) per 10 mmHg, and 1.95 (1.54-2.47), respectively]. All three SBP/W-slopes were positively associated with incident HTN, particularly the SBP/W-slope calculated as supine-to-peak SBP [HRadjusted 1.25 (1.19-1.31) per 1 mmHg/10 W]. CONCLUSION: Both SBPpeak > ULN based on reference values and high SBP/W-slopes were associated with incident HTN in normotensive individuals and should be considered in the evaluation of the cycle ergometry SBP response.

We examined the systolic blood pressure (SBP) response during maximal bicycle exercise testing in individuals without hypertension (HTN) or established cardiovascular disease and found that:When applying reference values for peak SBP during cycling exercise, accounting for age, sex, resting blood pressure (BP), and exercise capacity, exceeding the upper limit of normal was associated with twice as high relative risk of future HTN, compared with having a peak SBP within normal limits.A steep increase in exercise SBP in relation to the increase in work rate was also associated with future HTN but did not always coincide with elevated peak SBP.

Prognostic value of peak work rate indexed by left ventricular diameter.

Left ventricular diameter (LVEDD) increases with systematic endurance training but also in various cardiac diseases. High exercise capacity associates with favorable outcomes. We hypothesized that peak work rate (Wpeak) indexed to LVEDD would carry prognostic information and aimed to evaluate the association between Wpeak/LVEDDrest and cardiovascular mortality. Wpeak/LVEDDrest (W/mm) was calculated in patients with an echocardiographic examination within 3 months of a maximal cycle ergometer exercise test. Low Wpeak/LVEDDrest was defined as a value below the sex- and age-specific 5th percentile among lower-risk subjects. The association with cardiovascular mortality was evaluated using Cox regression. In total, 3083 patients were included (8.0 [5.4-11.1] years of follow-up, 249 (8%) cardiovascular deaths). Wpeak/LVEDDrest (W/mm) was associated with cardiovascular mortality (adjusted hazard ratio (HR) 0.28 [0.22-0.36]), similar to Wpeak in % of predicted, with identical prognostic strength when adjusted for age and sex (C-statistics 0.87 for both). A combination of low Wpeak/LVEDDrest and low Wpeak was associated with a particularly poor prognosis (adjusted HR 6.4 [4.0-10.3]). Wpeak/LVEDDrest was associated with cardiovascular mortality but did not provide incremental prognostic value to Wpeak alone. The combination of a low Wpeak/LVEDDrest and low Wpeak was associated with a particularly poor prognosis.

Reference equations for breathlessness during incremental cycle exercise testing.

Background: Exertional breathlessness is commonly assessed using incremental exercise testing (IET), but reference equations for breathlessness responses are lacking. We aimed to develop reference equations for breathlessness intensity during IET. Methods: A retrospective, consecutive cohort study of adults undergoing IET was carried out in Sweden. Exclusion criteria included cardiac or respiratory disease, death or any of the aforementioned diagnoses within 1 year of the IET, morbid obesity, abnormally low exercise capacity, submaximal exertion or an abnormal exercise test. Probabilities for breathlessness intensity ratings (Borg CR10) during IET in relation to power output (%predWmax), age, sex, height and body mass were analysed using marginal ordinal logistic regression. Reference equations for males and females were derived to predict the upper limit of normal (ULN) and the probability of different Borg CR10 intensity ratings. Results: 2581 participants (43% female) aged 18-90 years were included. Mean breathlessness intensity was similar between sexes at peak exertion (6.7±1.5 versus 6.4±1.5 Borg CR10 units) and throughout exercise in relation to %predWmax. Final reference equations included age, height and %predWmax for males, whereas height was not included for females. The models showed a close fit to observed breathlessness intensity ratings across %predWmax values. Models using absolute W did not show superior fit. Scripts are provided for calculating the probability for different breathlessness intensity ratings and the ULN by %predWmax throughout IET. Conclusion: We present the first reference equations for interpreting breathlessness intensity during incremental cycle exercise testing in males and females aged 18-90 years.

Cardiorespiratory fitness components in relation to clinical characteristics, disease state and medication intake: A patient registry study.

BACKGROUND: Interpretation of cardiopulmonary exercise testing (CPET) results requires thorough understanding of test confounders such as anthropometrics, comorbidities and medication. Here, we comprehensively assessed the clinical determinants of cardiorespiratory fitness and its components in a heterogeneous patient sample. METHODS: We retrospectively collected medical and CPET data from 2320 patients (48.2% females) referred for cycle ergometry at the University Hospital Leuven, Belgium. We assessed clinical determinants of peak CPET indexes of cardiorespiratory fitness (CRF) and its hemodynamic and ventilatory components using stepwise regression and quantified multivariable-adjusted differences in indexes between cases and references. RESULTS: Lower peak load and peak O2 uptake were related to: higher age, female sex, lower body height and weight, and higher heart rate; to the intake of beta blockers, analgesics, thyroid hormone replacement and benzodiazepines; and to diabetes mellitus, chronic kidney disease, non-ST elevation myocardial infarction and atrial fibrillation (p < 0.05 for all). Lower peak load also correlated with obstructive pulmonary diseases. Stepwise regression revealed associations of hemodynamic and ventilatory indexes (including heart rate, O2 pulse, systolic blood pressure and ventilation at peak exercise and ventilatory efficiency) with age, sex, body composition and aforementioned diseases and medications. Multivariable-adjusted differences in CPET metrics between cases and controls confirmed the associations observed. CONCLUSION: We described known and novel associations of CRF components with demographics, anthropometrics, cardiometabolic and pulmonary diseases and medication intake in a large patient sample. The clinical implications of long-term noncardiovascular drug intake for CPET results require further investigation.

Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise.

BACKGROUND: Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF. METHODS: Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2. RESULTS: Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 ± 3.8 vs. 32.5 ± 9.8 mL/Kg*min-1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 ± 9.8% for patients with CHF compared to 61.1 ± 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 ± 51.0, 132.0 ± 38.8 and 155.6 ± 45.5s) than in controls (58.08 ± 13.2, 74.3 ± 21.1, 96.7 ± 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 ± 3.3, 41.9 ± 29.1 and 25.0 ± 13.6%) than in controls (10.1 ± 4.6, 62.1 ± 17.7 and 38.7 ± 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF. CONCLUSIONS: Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.

Classification and occurrence of an abnormal breathing pattern during cardiopulmonary exercise testing in subjects with persistent symptoms following COVID-19 disease.

Reduced exercise capacity and several limiting symptoms during exercise have been reported following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. From clinical observations, we hypothesized that an abnormal breathing pattern (BrP) during exercise may be common in these patients and related to reduced exercise capacity. We aimed to (a) evaluate a method to classify the BrP as normal/abnormal or borderline in terms of inter-rater agreement; (b) determine the occurrence of an abnormal BrP in patients with post-COVID; and (c) compare characteristics of post-COVID patients with normal and abnormal BrP. In a retrospective, cross-sectional study of patients referred for CPET due to post-COVID April 2020-April 2021, we selected subjects without a history of intensive care and with available medical records. Three raters independently categorized patients' BrP as normal, abnormal, or borderline, using four traditional CPET plots (respiratory exchange ratio, tidal volume over ventilation, ventilatory equivalent for oxygen, and ventilation over time). Out of 20 patients (11 male), 10 were categorized as having a normal, 7 an abnormal, and three a borderline BrP. Inter-rater agreement was good (Fleiss' kappa: 0.66 [0.66-0.67]). Subjects with an abnormal BrP had lower peak ventilation, lower exercise capacity, similar ventilatory efficiency and a similar level of dyspnea at peak exercise, as did subjects with a normal BrP. Patients' BrP was possible to classify with good agreement between observers. A third of patients had an abnormal BrP, associated with lower exercise capacity, which could possibly explain exercise related symptoms in some patients with post-COVID syndrome.