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.

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.

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.

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: 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 to 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. RESULTS: We included 3,895 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 to incident HTN, particularly the SBP/W-slope calculated as supine-to-peak SBP (HRadjusted 1.25 [1.19-1.31] per 1 mmHg/10W). 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 response during maximal bicycle exercise testing in individuals without hypertension or established cardiovascular disease, and found that: When applying reference values for peak systolic blood pressure during cycling exercise, accounting for age, sex, resting blood pressure and exercise capacity, exceeding the upper limit of normal was associated with twice as high relative risk of future hypertension, compared to having a peak systolic blood pressure within normal limits. A steep increase in exercise blood pressure in relation to the increase in work rate was also associated with future hypertension but did not always coincide with elevated peak systolic blood pressure.

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.

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.

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.

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.

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.

Defining post-acute COVID-19 syndrome (PACS) by an epigenetic biosignature in peripheral blood mononuclear cells.

Post-acute COVID-19 syndrome (PACS) has been defined as symptoms persisting after clearance of a COVID-19 infection. We have previously demonstrated that alterations in DNA methylation (DNAm) status persist in individuals who recovered from a COVID-19 infection, but it is currently unknown if PACS is associated with epigenetic changes. We compared DNAm patterns in patients with PACS with those in controls and in healthy COVID-19 convalescents and found a unique DNAm signature in PACS patients. This signature unravelled modified pathways that regulate angiotensin II and muscarinic receptor signalling and protein-protein interaction networks that have bearings on vesicle formation and mitochondrial function.

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.

Systolic Blood Pressure Response to Exercise in Endurance Athletes in Relation to Oxygen Uptake, Work Rate and Normative Values.

Work rate has a direct impact on the systolic blood pressure (SBP) during aerobic exercise, which may be challenging in the evaluation of the SBP response in athletes reaching high work rates. We aimed to investigate the exercise SBP response in endurance athletes in relation to oxygen uptake (VO2), work rate and to recent reference equations for exercise SBP in the general population. Endurance athletes with a left-ventricular end-diastolic diameter above the reference one performed a maximal bicycle cardiopulmonary exercise test. The increase in SBP during exercise was divided by the increase in VO2 (SBP/VO2 slope) and in Watts, respectively (SBP/W slope). The maximum SBP (SBPmax) and the SBP/W slope were compared to the predicted values. In total, 27 athletes (59% men) were included; mean age, 40 ± 10 years; mean VO2max, 50 ± 5 mL/kg/min. The mean SBP/VO2 slope was 29.8 ± 10.2 mm Hg/L/min, and the mean SBP/W slope was 0.27 ± 0.08 mm Hg/W. Compared to the predicted normative values, athletes had, on average, a 12.2 ± 17.6 mm Hg higher SBPmax and a 0.12 ± 0.08 mm Hg/W less steep SBP/W slope (p < 0.01 and p < 0.001, respectively). In conclusion, the higher SBPmax values and the less steep SBP/W slope highlight the importance of considering work rate when interpreting the SBP response in endurance athletes and suggest a need for specific normative values in athletes to help clinicians distinguish physiologically high maximal blood pressure from a pathological blood pressure response.

Prognostic implications of structural heart disease and premature ventricular contractions in recovery of exercise.

Premature ventricular contractions (PVCs) during recovery of exercise stress testing are associated with increased cardiovascular mortality, but the cause remains unknown. We aimed to evaluate the association of PVCs during recovery with echocardiographic abnormalities, and their combined prognostic performance. Echocardiographic abnormalities [reduced left ventricular (LV) ejection fraction, valvular heart disease, LV dilatation, LV hypertrophy, or increased filling pressures] and PVCs during recovery were identified among patients having undergone both echocardiography and exercise stress test. Among included patients (n = 3106, age 59 ± 16 years, 55% males), PVCs during recovery were found in 1327 (43%) patients, among which the prevalence of echocardiographic abnormalities was increased (58% vs. 43%, p < 0.001). Overall, PVCs during recovery were associated with increased cardiovascular mortality (219 total events, 7.9 [5.4-11.1] years follow-up; adjusted hazard ratio (HR [95% confidence interval]) 1.6 [1.2-2.1], p < 0.001). When analyzed in combination with either presence or absence of echocardiographic abnormalities, PVCs during recovery were associated with increased risk when such were present (HR 3.3 [1.9-5.5], p < 0.001) but not when absent (HR 1.5 [0.8-2.8], p = 0.22), in reference to those with neither. Our findings provide mechanistic insights to the increased CV risk reported in patients with PVCs during recovery.