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.

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.

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.

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

Abstract 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.

Ventilatory efficiency in combination with peak oxygen uptake improves risk stratification in patients undergoing lobectomy.

Objective: We aimed to evaluate whether or not using the slope of the increase in minute ventilation in relation to carbon dioxide (VE/VCo2-slope), with a cutoff value of 35, could improve risk stratification for major pulmonary complications or death following lobectomy in lung cancer patients at moderate risk (Vo2peak = 10-20 mL/kg/min). Methods: Single center, retrospective analysis of 146 patients with lung cancer who underwent lobectomy and preoperative cardiopulmonary exercise testing in 2008-2020. The main outcome was any major pulmonary complication or death within 30 days of surgery. Patients were categorized based on their preoperative cardiopulmonary exercise testing as: low-risk group, peak oxygen uptake >20 mL/kg/min; low-moderate risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope <35; and moderate-high risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope ≥35. The frequency of complications between groups was compared using χ2 test. Logistic regression was used to calculate the odds ratio with 95% CI for the main outcome based on the cardiopulmonary exercise testing group. Results: Overall, 25 patients (17%) experienced a major pulmonary complication or died (2 deaths). The frequency of complications differed between the cardiopulmonary exercise testing groups: 29%, 13%, and 8% in the moderate-high, low-moderate, and low-risk group, respectively (P = .023). Using the low-risk group as reference, the adjusted odds ratio for the low-moderate risk group was 3.44 (95% CI, 0.66-17.90), whereas the odds ratio for the moderate-high risk group was 8.87 (95% CI, 1.86-42.39). Conclusions: Using the VE/VCo2-slope with a cutoff value of 35 improved risk stratification for major pulmonary complications following lobectomy in lung cancer patients with moderate risk based on a peak oxygen uptake of 10 to 20 mL/kg/min. This suggests that the VE/VCo2-slope can be used for preoperative risk evaluation in lung cancer lobectomy.

Donor and Recipient Size Matching in Heart Transplantation With Predicted Heart and Lean Body Mass.

Donor and recipient size matching during heart transplant can be assessed using weight or predicted heart mass (PHM) ratios. We developed sex-specific allomteric equations for PHM and predicted lean body mass (PLBM) using the United Kingdom Biobank (UKB) and evaluated their predictive value in the United Network of Organ Sharing database. Donor and recipient size matching was based on weight, PHM and PLBM ratios. PHM was calculated using the Multiethnic Study of Atherosclerosis and UKB equations. PLBM was calculated using the UKB and National Health and Nutrition Examination Survey equations. Relative prognostic utility was compared using multivariable Cox analysis, adjusted for predictors of 1-year survival in the Scientific Registry of Transplant Recipients model. Of 53,648 adult patients in the United Network of Organ Sharing database between 1996 and 2016, 6528 (12.2%) died within the first year. In multivariable analysis, undersized matches by any metric were associated with increased 1-year mortality (all P < 0.01). Oversized matches were at increased risk using PHM or PLBM (all P < 0.01), but not weight ratio. There were significant differences in classification of size matching by weight or PHM in sex-mismatched donor-recipient pairs. A significant interaction was observed between pulmonary hypertension and donor undersizing (hazard ratio 1.15, P = 0.026) suggesting increased risk of undersizing in pulmonary hypertension. Donor and recipient size matching with simplified PHM and PLBM offered an advantage over total body weight and may be more important for sex-mismatched donor-recipient pairs. Donor undersizing is associated with worse outcomes in patients with pulmonary hypertension.

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.

Workload-indexed blood pressure response is superior to peak systolic blood pressure in predicting all-cause mortality.

AIMS: The association between peak systolic blood pressure (SBP) during exercise testing and outcome remains controversial, possibly due to the confounding effect of external workload (metabolic equivalents of task (METs)) on peak SBP as well as on survival. Indexing the increase in SBP to the increase in workload (SBP/MET-slope) could provide a more clinically relevant measure of the SBP response to exercise. We aimed to characterize the SBP/MET-slope in a large cohort referred for clinical exercise testing and to determine its relation to all-cause mortality. METHODS AND RESULTS: Survival status for male Veterans who underwent a maximal treadmill exercise test between the years 1987 and 2007 were retrieved in 2018. We defined a subgroup of non-smoking 10-year survivors with fewer risk factors as a lower-risk reference group. Survival analyses for all-cause mortality were performed using Kaplan-Meier curves and Cox proportional hazard ratios (HRs (95% confidence interval)) adjusted for baseline age, test year, cardiovascular risk factors, medications and comorbidities. A total of 7542 subjects were followed over 18.4 (interquartile range 16.3) years. In lower-risk subjects (n = 709), the median (95th percentile) of the SBP/MET-slope was 4.9 (10.0) mmHg/MET. Lower peak SBP (<210 mmHg) and higher SBP/MET-slope (>10 mmHg/MET) were both associated with 20% higher mortality (adjusted HRs 1.20 (1.08-1.32) and 1.20 (1.10-1.31), respectively). In subjects with high fitness, a SBP/MET-slope > 6.2 mmHg/MET was associated with a 27% higher risk of mortality (adjusted HR 1.27 (1.12-1.45)). CONCLUSION: In contrast to peak SBP, having a higher SBP/MET-slope was associated with increased risk of mortality. This simple, novel metric can be considered in clinical exercise testing reports.

Blood pressure in athletic preparticipation evaluation and the implication for cardiac remodelling.

OBJECTIVES: To explore blood pressure (BP) in athletes at preparticipation evaluation (PPE) in the context of recently updated US and European hypertension guidelines, and to determine the relationship between BP and left ventricular (LV) remodelling. METHODS: In this retrospective study, athletes aged 13-35 years who underwent PPE facilitated by the Stanford Sports Cardiology programme were considered. Resting BP was measured in both arms; repeated once if ≥140/90 mm Hg. Athletes with abnormal ECGs or known hypertension were excluded. BP was categorised per US/European hypertension guidelines. In a separate cohort of athletes undergoing routine PPE echocardiography, we explored the relationship between BP and LV remodelling (LV mass, mass/volume ratio, sphericity index) and LV function. RESULTS: In cohort 1 (n=2733, 65.5% male), 34.3% of athletes exceeded US hypertension thresholds. Male sex (B=3.17, p<0.001), body mass index (BMI) (B=0.80, p<0.001) and height (B=0.25, p<0.001) were the strongest independent correlates of systolic BP. In the second cohort (n=304, ages 17-26), systolic BP was an independent correlate of LV mass/volume ratio (B=0.002, p=0.001). LV longitudinal strain was similar across BP categories, while higher BP was associated with slower early diastolic relaxation. CONCLUSION: In a large contemporary cohort of athletes, one-third presented with BP levels above the current US guidelines' thresholds for hypertension, highlighting that lowering the BP thresholds at PPE warrants careful consideration as well as efforts to standardise measurements. Higher systolic BP was associated with male sex, BMI and height and with LV remodelling and diastolic function, suggesting elevated BP in athletes during PPE may signify a clinically relevant condition.

Cardiopulmonary exercise testing for evaluation of a randomized exercise training intervention following aortic valve replacement.

Aortic valve surgery is the definitive treatment for aortic stenosis (AS). No specific recommendation is available on how exercise training should be conducted and evaluated after aortic valve replacement (AVR). This study aimed to examine the effect of aerobic exercise training on exercise capacity following AVR. In addition to our primary outcome variable, peak oxygen uptake (peakVO2 ), the effect on submaximal cardiopulmonary variables including oxygen uptake kinetics (tau), oxygen uptake efficiency slope (OUES) and ventilatory efficiency (VE/VCO2 slope) was evaluated. Following AVR due to AS, 12 patients were randomized to either a group receiving 12 weeks of supervised aerobic exercise training (EX) or a control group (CON). Exercise capacity was assessed by a maximal cardiopulmonary exercise test (CPET). There was a significant increase in peak load (+28%, P = 0·031) and in peakVO2 (+23%, P = 0·031) in EX, corresponding to an increase in achieved percentage of predicted peakVO2 from 88 to 104% (P = 0·031). For submaximal variables, there were only non-statistically significant trends in improvement between CPETs in EX. In CON, there were no significant differences in any maximal or submaximal variable between CPETs. We conclude that 12 weeks of supervised aerobic exercise training induces significant adaptations in cardiopulmonary function following AVR, especially in regard to maximal variables including peakVO2 . In addition, we provide novel data on the effect on several submaximal variables following exercise training in this group of patients.

Låg följsamhet till rekommenderad hjärtscreening av elitidrottare - Lägesanalys i Östergötland.

Low adherence to recommended pre-participation cardiac evaluation of Swedish athletes Pre-participation cardiac evaluation of athletes is recommended by international organizations like the European Society of Cardiology and the American Heart Association, as well as by the Swedish Sports Confederation. The purpose of the evaluation is to prevent sudden cardiac death in athletes by early identification of individuals at risk. To our knowledge, no previous study has been made regarding the implementation of pre-participation cardiac evaluation of athletes in Sweden. We performed an electronical survey addressing sports clubs in one out of 21 districts in which the Swedish Sports Confederation is geographically divided. Only four out of 22 responding clubs with elite athletes preformed cardiac evaluation. Lack of knowledge about the recommendations as well as how to perform the evaluation were mentioned as reasons not to evaluate the athletes. Our results indicate the need for more information about pre-participation cardiac evaluation of athletes in Sweden.

Decreased aerobic capacity 4 years after aortic valve replacement in male patients operated upon for chronic aortic regurgitation.

Exercise testing is underutilized in patients with valve disease. We have previously found a low physical work capacity in patients with aortic regurgitation 6 months after aortic valve replacement (AVR). The aim of this study was to evaluate aerobic capacity in patients 4 years after AVR, to study how their peak oxygen uptake (peakVO(2)) had changed postoperatively over a longer period of time. Twenty-one patients (all men, 52±13 years) who had previously undergone cardiopulmonary exercise testing (CPET) pre- and 6 months postoperatively underwent maximal exercise testing 49 ± 15 months postoperatively using an electrically braked bicycle ergometer. Breathing gases were analysed and the patients' physical fitness levels categorized according to Åstrand's and Wasserman's classifications. Mean peakVO(2) was 22·8 ± 5·1 ml × kg(-1) × min(-1) at the 49-month follow-up, which was lower than at the 6-month follow-up (25·6 ± 5·8 ml × kg(-1) × min(-1), P = 0·001). All but one patient presented with a physical fitness level below average using Åstrand's classification, while 13 patients had a low physical capacity according to Wasserman's classification. A significant decrease in peakVO(2) was observed from six to 49 months postoperatively, and the decrease was larger than expected from the increased age of the patients. CPET could be helpful in timing aortic valve surgery and for the evaluation of need of physical activity as part of a rehabilitation programme.