BackgroundVentilation as a function of elimination of CO2 during incremental exercise (VE/VCO2 slope) has been shown to be a valuable predictor of complications and death after major non-cardiac surgery. VE/VCO2 slope and partial pressure of end-tidal carbon dioxide (PetCO2) are both affected by ventilation/perfusion mismatch, but research on the utility of PetCO2 for risk stratification in major abdominal surgery is limited. AimWe aimed to determine the correlation between VE/VCO2 slope and PetCO2 measured during preoperative cardiopulmonary exercise testing (CPET) and its association with major cardiopulmonary complications (MCPCs) or death following oesophageal and other major abdominal cancer surgeries. MethodIn a retrospective cohort of 116 patients undergoing preoperative CPET 2008-2023, VE/VCO2 slope and PetCO2 (kPa) were recorded. The main outcome was MCPC during hospitalisation or death <= 90 days of surgery. We determined threshold values for each measure, corresponding to 90% specificity, using receiver operating characteristics analysis. ResultsA strong negative correlation was found between PetCO2 after a 5-minute warm-up and VE/VCO2 slope (Pearson r = -.88). In oesophagus cancer, VE/VCO2 slope >38 and PetCO2 < 4.1 kPa (30.8 mmHg) were both significant thresholds for the main outcome. For other major abdominal surgery patients, threshold analyses were non-significant. The area under the curve to predict outcome was similar using VE/VCO2 slope (0.70, 95% confidence interval 0.51-0.89) as compared to PetCO2 (0.71, 0.53-0-90). ConclusionBoth preoperative VE/VCO2 slope and PetCO2 could identify subjects with a very high risk of complications following oesophageal resection, with similar prognostic utility. PetCO2 can be measured with simpler equipment and could therefore be useful when CPET is not available.

Background

Cardiopulmonary exercise testing (CPET) has a pivotal role in preoperative evaluation of patients before lung cancer surgery. As surgical and perioperative practice and functional diagnostics continuously evolve, it may be time to reevaluate and refine the use of CPET in this setting.

Research Question

Can risk assessment with CPET before lung cancer surgery be improved by combining 2 established CPET variables (percent predicted peak oxygen uptake [Vo2peak], and ventilatory efficiency, measured by minute ventilation []/carbon dioxide elimination [Vco2] slope) while using recently suggested optimal threshold values for these variables?

Study Design and Methods

Single-center, retrospective analysis of 208 patients with lung cancer who underwent preoperative CPET in 2008 to 2020. The main outcome was any major pulmonary complication (MPC) or death within 30 days of surgery. We combined previously suggested threshold values of percent predicted Vo2peak and /Vco2 slope, defined with a focus on high sensitivity and specificity. For each measure, patients were categorized into 3 groups based on these thresholds, yielding a proposed 9-field matrix for risk assessment. The frequency of complications between groups was compared using the χ2 test.

Results

Overall, 29 patients (14%) suffered an MPC and 3 died. The frequency of complications differed between groups based on the 9-field matrix in patients who underwent lobectomy or pulmectomy (P < .001). No patient with both favorable percent predicted Vo2peak and /Vco2 slope values experienced MPC or death, whereas worsening values in both percent predicted Vo2peak and /Vco2 slope were associated with an increasing frequency of adverse outcomes.

Interpretation

The proposed 9-field matrix for risk assessment was able to demonstrate a synergistic effect between /Vco2 slope and percent predicted Vo2peak for identifying patients who suffered major pulmonary complications or death within 30 days of cancer lobectomy or pulmectomy. These results further improve and help nuance risk assessment in these patients.

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 SBP(pea)k 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 SBP(peak )and SBPpeak &gt; 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 &gt; 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.Lay summary 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:center dot 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.center dot 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.

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 &gt;= 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 (&lt; 25% in males, &lt; 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 (R-2 = 0.61 and 0.57, P &lt; 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 &lt; 0.001; males: - 0.38, P &lt; 0.001). In contrast, LVC was independent of both LVEDV and LBM [LVC = LVM/(LVEDV0.40 x 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.

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.

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.

Objectives: This study aimed to evaluate the risk of all-cause mortality and incident cardiovascular disease associated with peak systolic blood pressure (PeakSBP) at clinical exercise testing.

Methods: Data from 10 096 clinical exercise tests (54% men, age 18-85 years) was cross-linked with outcome data from national registries. PeakSBP was compared with recently published reference percentiles as well as expressed as percentage predicted PeakSBP using reference equations.Natural cubic spline modelling and Cox regression were used to analyse data stratified by sex and baseline cardiovascular risk profile.

Results: Median [IQR] follow-up times were 7.9 [5.7] years (all-cause mortality) and 5.6 [5.9] years (incident cardiovascular disease), respectively. The adjusted risk of all-cause mortality [hazard ratio, 95% confidence interval (95% CI)] for individuals with PeakSBP below the 10th percentile was 2.00 (1.59-2.52) in men and 2.60 (1.97-3.44) in women, compared with individuals within the 10th--90th percentile. The corresponding risk for incident cardiovascular disease was 1.55 (1.28-1.89, men) and 1.34 (1.05-1.71, women). For males in the upper 90th percentile, compared with individuals within the 10th--90th percentile, the adjusted risks of all-cause death and incident cardiovascular disease were 0.35 (0.22-0.54) and 0.72 (0.57-0.92), respectively, while not statistically significant in women. Spline modelling revealed a continuous increase in risk with PeakSBP values less than 100% of predicted in both sexes, with no increase in risk more than 100% of predicted.

Conclusion: Low, but not high, PeakSBP was associated with an increased risk of mortality and future cardiovascular disease. Using reference standards for PeakSBP could facilitate clinical risk stratification across patients of varying sex, age and exercise capacity.

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 &gt;20 mL/kg/min; low-moderate risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCO2-slope &lt;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 ?2 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. © 2022 The Author(s)

Background Guidelines recommend considering workload in interpretation of the systolic blood pressure (SBP) response to exercise, but reference values are lacking. Design This was a retrospective, consecutive cohort study. Methods From 12,976 subjects aged 18-85 years who performed a bicycle ergometer exercise test at one centre in Sweden during the years 2005-2016, we excluded those with prevalent cardiovascular disease, comorbidities, cardiac risk factors or medications. We extracted SBP, heart rate and workload (watt) from &gt;= 3 time points from each test. The SBP/watt-slope and the SBP/watt-ratio at peak exercise were calculated. Age- and sex-specific mean values, standard deviations and 90th and 95th percentiles were determined. Reference equations for workload-indexed and peak SBP were derived using multiple linear regression analysis, including sex, age, workload, SBP at rest and anthropometric variables as predictors. Results A final sample of 3839 healthy subjects (n = 1620 female) were included. While females had lower mean peak SBP than males (188 +/- 24 vs 202 +/- 22 mmHg, p &lt; 0.001), workload-indexed SBP measures were markedly higher in females; SBP/watt-slope: 0.52 +/- 0.21 versus 0.41 +/- 0.15 mmHg/watt (p &lt; 0.001); peak SBP/watt-ratio: 1.35 +/- 0.34 versus 0.90 +/- 0.21 mmHg/watt (p &lt; 0.001). Age, sex, exercise capacity, resting SBP and height were significant predictors of the workload-indexed SBP parameters and were included in the reference equations. Conclusions These novel reference values can aid clinicians and exercise physiologists in interpreting the SBP response to exercise and may provide a basis for future research on the prognostic impact of exercise SBP. In females, a markedly higher SBP in relation to workload could imply a greater peripheral vascular resistance during exercise than in males.