Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Unmasking obstruction in hypertrophic cardiomyopathy with postprandial resting and treadmill stress echocardiography.

BACKGROUND: Latent left ventricular outflow tract obstruction (LVOTO) is an important cause of symptoms in patients with hypertrophic cardiomyopathy (HCM) but can be challenging to provoke. OBJECTIVES AND METHODS: To examine the value of postprandial resting and stress echocardiography and utilization of invasive or enhanced drug therapies (surgical myectomy, alcohol septal ablation, disopyramide and mavacamten) in patients with postprandial LVOTO. Consecutive HCM patients without LVOTO underwent routine and postprandial echocardiography at rest, with provocation (Valsalva and standing) and after symptom-limited treadmill stress. RESULTS: Among 252 patients (mean age 58 years, 39% women), postprandial LVOT gradients were higher compared with routine echocardiography at rest (median 9.0 [0-38.0] vs 0 [0-14.0] mmHg, p<0.0001) and with provocation (18.5 [0-70.3] vs 1.5 [0-41.0] mmHg, p<0.0001). Postprandial exercise (PPXSE) gradients were higher in a subset of 44 patients who underwent both postprandial and fasting stress echocardiography, (47.0 [5.3-81.0] vs 17.5 [0-46.0] mmHg, p<0.0001). In total, 49 (19.5%) patients achieved the ≥50 mmHg threshold under routine conditions (rest/provocation); 90 (35.7%) additional patients achieved postprandial gradients ≥50 mmHg (rest/provocation/exercise), 38 (15.1%) with PPXSE alone. A total of 71 patients were treated with 91 invasive or enhanced drug therapies, 32 (45.1%) of whom had gradients ≥50 mmHg only after eating (rest/provocation) and 8 (11.3%) only with PPXSE, with symptom relief in the majority. CONCLUSIONS: Postprandial echocardiography was useful at unmasking LVOTO in more than one third of patients who did not have high gradients otherwise. Eating before echocardiography is a powerful provocative tool in the evaluation of patients with HCM.

Machine learning predicts peak oxygen uptake and peak power output for customizing cardiopulmonary exercise testing using non-exercise features.

PURPOSE: Cardiopulmonary exercise testing (CPET) is considered the gold standard for assessing cardiorespiratory fitness. To ensure consistent performance of each test, it is necessary to adapt the power increase of the test protocol to the physical characteristics of each individual. This study aimed to use machine learning models to determine individualized ramp protocols based on non-exercise features. We hypothesized that machine learning models will predict peak oxygen uptake ( V ˙ O2peak) and peak power output (PPO) more accurately than conventional multiple linear regression (MLR). METHODS: The cross-sectional study was conducted with 274 (♀168, ♂106) participants who performed CPET on a cycle ergometer. Machine learning models and multiple linear regression were used to predict V ˙ O2peak and PPO using non-exercise features. The accuracy of the models was compared using criteria such as root mean square error (RMSE). Shapley additive explanation (SHAP) was applied to determine the feature importance. RESULTS: The most accurate machine learning model was the random forest (RMSE: 6.52 ml/kg/min [95% CI 5.21-8.17]) for V ˙ O2peak prediction and the gradient boosting regression (RMSE: 43watts [95% CI 35-52]) for PPO prediction. Compared to the MLR, the machine learning models reduced the RMSE by up to 28% and 22% for prediction of V ˙ O2peak and PPO, respectively. Furthermore, SHAP ranked body composition data such as skeletal muscle mass and extracellular water as the most impactful features. CONCLUSION: Machine learning models predict V ˙ O2peak and PPO more accurately than MLR and can be used to individualize CPET protocols. Features that provide information about the participant's body composition contribute most to the improvement of these predictions. TRIAL REGISTRATION NUMBER: DRKS00031401 (6 March 2023, retrospectively registered).

Skin sympathetic nerve activity and ST-segment depression in women.

Background: ST-segment depression (ST depression) on exercise electrocardiogram (ECG) and ambulatory ECG monitoring may occur without myocardial ischemia. The mechanisms of nonischemic ST depression remain poorly understood. Objective: The study sought to test the hypothesis that the magnitudes of skin sympathetic nerve activity (SKNA) correlate negatively with the ST-segment height (ST height) in ambulatory participants. Methods: We used neuECG (simultaneous recording of SKNA and ECG) to measure ambulatory ST height and average SKNA (aSKNA) in 19 healthy women, 6 women with a history of Takotsubo syndrome (TTS), and 4 women with ischemia and no obstructive coronary arteries (INOCA). Results: Baseline aSKNA was similar between healthy women, women with TTS, and women with INOCA (1.098 ± 0.291 µV, 0.980 ± 0.061 µV, and 0.919 ± 0.0397 µV, respectively; P = .22). The healthy women had only asymptomatic upsloping ST depression. All participants had a significant (P < .05) negative correlation between ST height and aSKNA. Ischemic episodes (n = 15) were identified in 2 TTS and 4 INOCA participants. The ischemic ST depression was associated with increased heart rate and elevated aSKNA compared with baseline. An analysis of SKNA burst patterns at similar heart rates revealed that SKNA total burst area was significantly higher during ischemic episodes than nonischemic episodes (0.301 ± 0.380 µV·s and 0.165 ± 0.205 µV·s; P = .023) in both the TTS and INOCA participants. Conclusion: Asymptomatic ST depression in ambulatory women is associated with elevated SKNA. Heightened aSKNA is also noted during ischemic ST depression in women with TTS and INOCA. These findings suggest that ST segment depression is a physiological response to heightened sympathetic tone but may be aggravated by myocardial ischemia.

Blood pressure response during exercise testing in individuals with and without hypertension: The value of the recovery phase.

BACKGROUND: Hypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE. METHODS: 800 patients aged 17-90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre-existent hypertension. RESULTS: Of the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (ß [95% CI] 8.0 [4.9-11.1]) and diastolic (2.4 [0.4-4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2-9.4]) and diastolic BP (4.5 [1.9-7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1-7.5]) and fully adjusted (5.5 [1.1-10.0]) models. There was no difference in maximum diastolic BP between groups. CONCLUSION: In this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase.

Oxygen uptake efficiency plateau is unaffected by fitness level - the NOODLE study.

BACKGROUND: Endurance athletes (EA) are an emerging population of focus for cardiovascular health. The oxygen uptake efficiency plateau (OUEP) is the levelling-off period of ratio between oxygen uptake (VO2) and ventilation (VE). In the cohort of EA, we externally validated prediction models for OUEP and derived with internal validation a new equation. METHODS: 140 EA underwent a medical assessment and maximal cycling cardiopulmonary exercise test. Participants were 55% male (N = 77, age = 21.4 ± 4.8 years, BMI = 22.6 ± 1.7 kg·m- 2, peak VO2 = 4.40 ± 0.64 L·min- 1) and 45% female (N = 63, age = 23.4 ± 4.3 years, BMI = 22.1 ± 1.6 kg·m- 2, peak VO2 = 3.21 ± 0.48 L·min- 1). OUEP was defined as the highest 90-second continuous value of the ratio between VO2 and VE. We used the multivariable stepwise linear regression to develop a new prediction equation for OUEP. RESULTS: OUEP was 44.2 ± 4.2 mL·L- 1 and 41.0 ± 4.8 mL·L- 1 for males and females, respectively. In external validation, OUEP was comparable to directly measured and did not differ significantly. The prediction error for males was - 0.42 mL·L- 1 (0.94%, p = 0.39), and for females was + 0.33 mL·L- 1 (0.81%, p = 0.59). The developed new prediction equation was: 61.37-0.12·height (in cm) + 5.08 (for males). The developed model outperformed the previous. However, the equation explained up to 12.9% of the variance (R = 0.377, R2 = 0.129, RMSE = 4.39 mL·L- 1). CONCLUSION: OUEP is a stable and transferable cardiorespiratory index. OUEP is minimally affected by fitness level and demographic factors. The predicted OUEP provided promising but limited accuracy among EA. The derived new model is tailored for EA. OUEP could be used to stratify the cardiorespiratory response to exercise and guide training.

Prognostic Value of Integrated Assessment of Cardiac Magnetic Resonance-Derived Global Coronary Flow Reserve and Cardiopulmonary Exercise Testing-Derived Peak Oxygen Consumption in Patients With Acute Myocardial Infarction.

Background: This study investigated the prognostic value of cardiovascular magnetic resonance (CMR)-derived global coronary flow reserve (G-CFR) in addition to cardiopulmonary exercise testing (CPET) variables in patients with acute myocardial infarction (AMI). Methods and Results: We investigated 127 patients with AMI who underwent primary or urgent percutaneous coronary intervention (PCI) and post-intervention CMR and CPET. The incidence of major cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent non-fatal myocardial infarction, re-hospitalization due to congestive heart failure, and stroke, was evaluated (median follow-up, 2.8 years). Patients with MACCE (n=14) had lower ejection fraction (EF) (50 [43-59] vs. 58 [51-63]%; P=0.014), lower G-CFR (1.74 [1.19-2.20] vs. 2.40 [1.61-3.66]; P=0.008), and lower peak oxygen consumption (V̇O2) (15.16±2.64 vs. 17.19±3.70 mL/kg/min; P=0.049) than patients without MACCE. G-CFR<2.33 and peak V̇O2 <15.65 mL/kg/min (cut-off values derived from receiver operating characteristic curve analyses) were significantly associated with the incidence of MACCE (log-rank test, P=0.01). The combination of low G-CFR and low peak V̇O2 improved risk discrimination for MACCE when added to the reference clinical model including age, male sex, post-PCI peak creatine kinase, EF, and left anterior descending artery culprit lesion. Conclusions: G-CFR and peak V̇O2 showed incremental prognostic information compared with the reference model using historically important clinical risk factors, indicating that this approach may help identify high-risk patients who suffer subsequent adverse events.

Prediction of Sudden Cardiac Death With Ultra-Short-Term Heart Rate Fluctuations.

BACKGROUND: Conventional measures of heart rate variability (HRV) have shown only modest associations with sudden cardiac death (SCD). Detrended fluctuation analysis (DFA), with novel methodological developments to evaluate the short-term scaling exponent, is a potentially superior method compared to conventional HRV tools. OBJECTIVES: In this study, the authors studied the analysis of the association between DFA and SCD. METHODS: The investigators studied the predictive value of ultra-short-term heart rate fluctuations (1-minute electrocardiogram samples) with DFA at rest and during different stages of physical exertion for incident SCD among 2,794 participants undergoing clinical exercise testing in the prospective FINCAVAS (Finnish Cardiovascular Study). The novel key DFA measure, the short-scale scaling exponent computed with second-order detrending (DFA2 α1), was the main exposure variable. SCDs were defined by American Heart Association/European Society of Cardiology criteria using death certificates with written accounts of the events. RESULTS: During a median follow-up of 8.3 years (Q1-Q3: 6.4-10.5), 83 SCDs occurred. DFA2 α1 measured at rest (but not in exercise) associated highly significantly with the risk of SCD, with 1-SD lower values associating with a 2.4-fold (Q1-Q3: 2.0-3.0) risk (P < 0.001). The results persisted when adjusting for other major risk factors for SCD, including age, cardiovascular morbidities, cardiorespiratory fitness, heart rate reduction, and left ventricular ejection fraction. Associations between conventional HRV parameters (measured at any stage of exercise or at rest) and SCD were substantially weaker and statistically nonsignificant after adjusting for other risk factors. CONCLUSIONS: Ultra-short-term DFA2 α1, when measured at rest, is a powerful and independent predictor of SCD. The association between DFA2 α1 and SCD is modified by physical exertion.

Sarcopenia is independently associated with poor preoperative physical fitness in patients undergoing colorectal cancer surgery.

BACKGROUND: Accurate preoperative risk assessment for major colorectal cancer (CRC) surgery remains challenging. Body composition (BC) and cardiopulmonary exercise testing (CPET) can be used to evaluate risk. The relationship between BC and CPET in patients undergoing curative CRC surgery is unclear. METHODS: Consecutive patients undergoing CPET prior to CRC surgery between 2010 and 2020 were identified between two different UK hospitals. Body composition phenotypes such as sarcopenia, myosteatosis, and visceral obesity were defined using widely accepted thresholds using preoperative single axial slice CT image at L3 vertebrae. Relationships between clinicopathological, BC, and CPET variables were investigated using linear regression analysis. RESULTS: Two hundred eighteen patients with stage I-III CRC were included. The prevalence of sarcopenia, myosteatosis, and visceral obesity was 62%, 33%, and 64%, respectively. The median oxygen uptake at anaerobic threshold (VO2 at AT) was 12.2 mL/kg/min (IQR 10.6-14.2), and oxygen uptake at peak exercise (VO2 peak) was 18.8 mL/kg/min (IQR 15.4-23). On univariate linear regression analysis, male sex (P < 0.001) was positively associated with VO2 at AT. While ASA grade (P < 0.001) and BMI (P = 0.007) were negatively associated with VO2 at AT, on multivariate linear regression analysis, these variables remained significant (P < 0.05). On univariate linear regression analysis, male sex (P < 0.001) was positively associated with VO2 peak, whereas age (P < 0.001), ASA grade (P < 0.001), BMI (P = 0.003), sarcopenia (P = 0.015), and myosteatosis (P < 0.001) were negatively associated with VO2 peak. On multivariate linear regression analysis age (P < 0.001), ASA grade (P < 0.001), BMI (P < 0.001), and sarcopenia (P = 0.006) were independently and negatively associated with VO2 peak. CONCLUSIONS: The novel finding that sarcopenia is independently associated with reduced VO2 peak performance in CPET supports the supposition that reduced muscle mass relates to poor physical function in CRC patients. Further work should be undertaken to assess whether sarcopenia diagnosed on CT can act as suitable surrogate for CPET to further enhance personalized risk stratification.

The roles of exercise stress echocardiography for the evaluation of heart failure with preserved ejection fraction in the heart failure pandemic era.

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly 70% of all HF and has become the dominant form of HF. The increased prevalence of HFpEF has contributed to a rise in the number of HF patients, known as the "heart failure pandemic". In addition to the fact that HF is a progressive disease and a delayed diagnosis may worsen clinical outcomes, the emergence of disease-modifying treatments such as sodium-glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists has made appropriate and timely identification of HFpEF even more important. However, diagnosis of HFpEF remains challenging in patients with a lower degree of congestion. In addition to normal EF, this is related to the fact that left ventricular (LV) filling pressures are often normal at rest but become abnormal during exercise. Exercise stress echocardiography can identify such exercise-induced elevations in LV filling pressures and facilitate the diagnosis of HFpEF. Exercise stress echocardiography may also be useful for risk stratification and assessment of exercise tolerance as well as cardiovascular responses to exercise. Recent attention has focused on dedicated dyspnea clinics to identify early HFpEF among patients with unexplained dyspnea and to investigate the causes of dyspnea. This review discusses the role of exercise stress echocardiography in the diagnosis and evaluation of HFpEF.

Physical Fitness Is Directly Related to Exercise Capacity and Ventilatory Response to Exercise in Men with HFrEF.

Background: Heart failure (HF) patients experience reduced functional fitness level (determining the performance of routine, daily activities) and diminished exercise capacity (linked to more effortful activities). Aim: The aim of the study is to assess this relationship using functional fitness tests compared to peak VO2 and VE/VCO2 slope in the context of exercise capacity and ventilatory response to exercise. Methods: A total of 382 men with stable HFrEF (age: 61 ± 10, NYHA class I/II/III/IV: 16/50/32/2%, LVEF: 30.5 ± 8.3%) underwent cardiopulmonary exercise testing (CPX) and a Senior Fitness Test (SFT). Afterwards, the patients were divided according to the 2capacity with peak VO2 ≥ 18 mL/kg/min, those with higher or lower ventilatory responses (VE/VCO2 slope ≥ 35 vs. <35) to the exercise were compared. Results: Patients who covered shorter distances in the 6 min walking test showed worse results in the functional tests ('stand up and go', 'chair stand' and 'arm curl') and CPX (lower peak VO2, shorter exercise time and higher VE/VCO2 slope). Subjects classified into Class D demonstrated the worst results in all elements of SFT; those in Class A demonstrated the best results. Significant differences that were analogous occurred also between classes B and C. Among the participants who reached peak VO2 ≥ 18 mL/kg/min (n = 170), those with VE/VCO2 slope ≥ 35 were characterized by worse physical fitness as compared to those with VE/VCO2 < 35. Conclusion: Reduced exercise tolerance led to worsening physical function in patients with HFrEF. Moreover, limitations in physical fitness seem to be distinctive for those patients showing excessive ventilatory response to exercise slope VE/VCO2 (≥35). The Senior Fitness Test may be considered as a useful tool for assessing comprehensive functional and clinical status and risk stratification in patients with HFrEF, especially those with extremely low exercise capacity.

The valuable role of cardio-pulmonary exercise testing in the diagnosis of atrial septal defect in a competitive triathlete: a case report.

Background: Atrial septal defect (ASD) is characterized by a diverse clinical presentation influenced by the type, size, and haemodynamics. Endurance athletes with ASD may exhibit higher than normal performance levels, however they face an elevated risk of exercise-induced cardiac volume and pressure strain, potentially expediting a maladaptation of the right heart. Case summary: An asymptomatic 28-year-old female elite triathlete sought a pre-participation sports medical examination. Her past medical history revealed right heart enlargement. Transthoracic echocardiography and magnetic resonance imaging did not ascertain a definitive diagnosis such as shunting. The examination revealed a remarkably high maximum oxygen uptake during cardio-pulmonary exercise testing (CPET), yet an abnormal oxygen uptake/workload slope and a low, plateauing oxygen pulse. The athlete agreed to transoesophageal echocardiography that demonstrated a superior sinus venosus-type ASD. Surgical intervention, conducted with minimally invasive endoscopic robotic technology and a pericardial patch, was performed at a tertiary centre under full cardio-pulmonary bypass. At seven-month follow-up, the patient reported engaging in swim sessions without limitations and participating in high intensity cycling sessions with performances similar to pre-surgery. Cardio-pulmonary exercise testing revealed increased maximum oxygen consumption and normalization of oxygen uptake/workload slope and maximum oxygen pulse. Discussion: Endurance athletes with ASD may have abnormal haemodynamic response during CPET despite an exceptional high maximum oxygen uptake. This underscores the value of CPET in the diagnostic work-up of right heart enlargement.

Understanding and Involving the Perspective of Pregnant Women as Users When Designing the Framework of e-Health and Exercise Interventions during Pregnancy: Preliminary Study.

Health and exercise technology may promote a healthy lifestyle during pregnancy. The objective of this cross-sectional study was to understand and involve the perspective of pregnant women as users in the design of a framework for future e-health and exercise interventions during pregnancy. Pregnant women replied to a questionnaire aimed at understanding their physical activity patterns, needs, and preferences regarding the use of mobile applications (apps). The main results showed that one-third of the women did not practice any type of exercise during pregnancy. Women preferred to exercise in a gym, outdoors, or at home. The majority already had or were currently using a fitness app, but never used any pregnancy-specific app. Most women agreed that it was important to have a specific app for pregnancy to improve knowledge about recommendations on lifestyle, have direct contact with health and exercise professionals, have social interaction with other mothers, and have guidance on preparation for childbirth and postpartum recovery. Understanding and involving the perspective of pregnant women as users will allow researchers to improve the design of a pregnancy-specific app and future e-health and exercise interventions during pregnancy. These preliminary results will lead to the development of the "active pregnancy app" focused on the promotion of an active and healthy lifestyle during pregnancy and postpartum.

Pulmonary responses following cardiac rehabilitation and the relationship with functional outcomes in children and young adults with heart disease.

Introduction: Patients with congenital heart disease (CHD) often have pulmonary abnormalities and exercise intolerance following cardiac surgery. Cardiac rehabilitation (CR) improves exercise capacity in patients with CHD, but minimal study has been performed to see if resting and dynamic pulmonary performance improves following CR in those with prior cardiac surgery. Methods: This was a retrospective cohort study of all patients who completed ≥12 weeks of CR from 2018 through 2022. Demographic, cardiopulmonary exercise test (CPET), spirometry, 6-minute walk, functional strength measures, and outcomes data were collected. Data are presented as median[IQR]. A Student's t-test was used for comparisons between groups and serial measurements were measured with a paired t-test. A p < 0.05 was considered significant. Results: There were a total of 37 patients [age 16.7 (14.2-20.1) years; 46% male] included. Patients with prior surgery (n = 26) were more likely to have abnormal spirometry data than those without heart disease (n = 11) (forced vital capacity [FVC] 76.7 [69.1-84.3]% vs. 96.4 [88.1-104.7]%, p = 0.002), but neither group experienced a significant change in spirometry. On CPET, peak oxygen consumption increased but there was no change in other pulmonary measures during exercise. Percent predicted FVC correlated with hand grip strength (r = 0.57, p = 0.0003) and percent predicted oxygen consumption (r = 0.43, p = 0.009). The number of prior sternotomies showed negative associations with both percent predicted FVC (r = -0.43, p = 0.04) and FEV1 (r = -0.47, p = 0.02). Discussion: Youth and young adults with a prior history of cardiac surgery have resting and dynamic pulmonary abnormalities that do not improve following CR. Multiple sternotomies are associated with worse pulmonary function.

The 1-min sit-to-stand test induces a significant and reliable level of neuromuscular fatigability: insights from a mobile app analysis.

PURPOSE: The performance metric associated with the execution of the 1-min sit-to-stand (1STS) typically relies on the number repetitions completed in 1 min. This parameter presents certain limitations (e.g., ceiling effect, motivational factors) which can impede its interpretation. Introducing additional parameters, such as neuromuscular fatigability level, could enhance the informative value of the 1STS and facilitate its interpretation. This study aimed to assess (i) whether the 1STS induces fatigability and (ii) the reliability of the fatigability level. METHODS: Forty young, healthy, and active participants underwent the 1STS twice during the same session. Isolated sit-to-stand maneuvers were performed before, immediately, and 1 min after completing the 1STS. A mobile app was utilized to obtain time (STST), velocity (STSV), and muscle power (STSP) from these sit-to-stand maneuvers. The pre-post change in these parameters served as the fatigability marker. Reliability was assessed using the intra-class correlation coefficient (ICC) and the coefficient of variation (CV). RESULTS: The mean number of repetitions during the 1STS was 63 ± 9. Significant decline in performance was observed for STST (13 ± 8%), STSV (-11.2 ± 6%), and STSP (-5.2 ± 3%), with more than 74% of participants exhibiting a decline beyond the minimal detectable change. Excellent between-session reliability (ICC ≥ 0.9; CV ≤ 5.3) was observed for the mobile app variables. CONCLUSION: The 1STS induces significant levels of fatigability. The fatigability indicators derived from the mobile app demonstrated remarkable reliability. Utilizing this user-friendly interface for computing fatigability may empower professionals to acquire insightful complementary indicators from the 1STS.

Sex- and age-adjusted reference values for dynamic inspiratory constraints during incremental cycle ergometry.

Activity-related dyspnea in chronic lung disease is centrally related to dynamic (dyn) inspiratory constraints to tidal volume expansion. Lack of reference values for exertional inspiratory reserve (IR) has limited the yield of cardiopulmonary exercise testing in exposing the underpinnings of this disabling symptom. One hundred fifty apparently healthy subjects (82 males) aged 40-85 underwent incremental cycle ergometry. Based on exercise inspiratory capacity (ICdyn), we generated centile-based reference values for the following metrics of IR as a function of absolute ventilation: IRdyn1 ([1-(tidal volume/ICdyn)] x 100) and IRdyn2 ([1-(end-inspiratory lung volume/total lung capacity] x 100). IRdyn1 and IRdyn2 standards were typically lower in females and older subjects (p<0.05 for sex and age versus ventilation interactions). Low IRdyn1 and IRdyn2 significantly predicted the burden of exertional dyspnea in both sexes (p<0.01). Using these sex and age-adjusted limits of reference, the clinician can adequately judge the presence and severity of abnormally low inspiratory reserves in dyspneic subjects undergoing cardiopulmonary exercise testing.

Prognostic utility of cardiopulmonary exercise testing with simultaneous exercise echocardiography in heart failure with preserved ejection fraction.

AIMS: Cardiopulmonary exercise testing (CPET) combined with exercise echocardiography (CPETecho) allows simultaneous assessments of cardiac, pulmonary, and ventilation in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to determine whether simultaneous assessment of CPET variables could provide additive predictive value over exercise stress echocardiography in patients with dyspnoea. METHODS AND RESULTS: CPETecho was performed in 443 patients with suspected HFpEF (240 HFpEF and 203 controls without HF). Patients with HFpEF were divided based on peak oxygen consumption (VO2, ≥10 or <10 ml/min/kg) or the slope of minute ventilation to carbon dioxide production (VE vs. VCO2 slope ≥45.0 or <45.0). The primary endpoint was defined as a composite of all-cause mortality, HF hospitalization, unplanned hospital visits requiring intravenous diuretics, or intensification of oral diuretics. During a median follow-up of 399 days, the composite outcome occurred in 57 patients. E/e' ratio during peak exercise was associated with adverse outcomes. Patients with HFpEF and lower peak VO2 had increased risks of the composite event (hazard ratio [HR] 5.05, 95% confidence interval [CI] 2.65-9.62, p < 0.0001 vs. controls; HR 3.14, 95% CI 1.69-5.84, p = 0.0003 vs. HFpEF with higher peak VO2). Elevated VE versus VCO2 slope was also associated with adverse events in HFpEF. The addition of either the presence of abnormal peak VO2 or VE versus VCO2 slope increased the predictive ability over the model based on age, sex, atrial fibrillation, left atrial volume index, and exercise E/e' (p < 0.05). CONCLUSION: These data provide new insights into the role of CPETecho in patients with HFpEF.

Clusters of multidimensional exercise response patterns and estimated heart failure risk in the Framingham Heart Study.

AIMS: New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long-term HF risk in a large community-based cohort. METHODS AND RESULTS: We studied 2532 Framingham Heart Study participants [age 53 ± 9 years, 52% women, body mass index (BMI) 28.0 ± 5.3 kg/m2, peak oxygen uptake (VO2) 21.1 ± 5.9 kg/m2 in women, 26.4 ± 6.7 kg/m2 in men] who underwent maximum effort CPET and were not taking atrioventricular nodal blocking agents. Higher peak VO2 was associated with a lower estimated HF risk score (Spearman correlation r: -0.60 in men and -0.55 in women, P < 0.0001), with an observed overlap of estimated risk across peak VO2 categories. Hierarchical clustering of 26 separate CPET phenotypes (values residualized on age, sex, and BMI to provide uniformity across these variables) identified three clusters with distinct exercise physiologies: Cluster 1-impaired oxygen kinetics; Cluster 2-impaired vascular; and Cluster 3-favourable exercise response. These clusters were similar in age, sex distribution, and BMI but displayed distinct associations with relevant subclinical phenotypes [Cluster 1-higher subcutaneous and visceral fat and lower pulmonary function; Cluster 2-higher carotid-femoral pulse wave velocity (CFPWV); and Cluster 3-lower CFPWV, C-reactive protein, fat volumes, and higher lung function; all false discovery rate < 5%]. Cluster membership provided incremental variance explained (adjusted R2 increment of 0.10 in women and men, P < 0.0001 for both) when compared with peak VO2 alone in association with predicted HF risk. CONCLUSIONS: Integrated CPET response patterns identify physiologically relevant profiles with distinct associations to subclinical phenotypes that are largely independent of standard risk factor-based assessment, which may suggest alternate pathways for prevention.

The prognostic value of peak oxygen uptake in obstructive hypertrophic cardiomyopathy: a literature review to inform economic model development.

AIMS: Patients with obstructive hypertrophic cardiomyopathy (oHCM) experience significant clinical burden which is associated with a high economic burden. Peak oxygen uptake (pVO2), measured by cardiopulmonary exercise testing, is used to quantify functional capacity, and has been studied as a primary endpoint in recent clinical trials. This study aimed to gather evidence to consolidate the prognostic value of pVO2 in oHCM and to assess whether it is feasible to predict health outcomes in an economic model based on changes in pVO2. METHODS: A targeted literature review was conducted in MEDLINE (via PubMed) and Embase databases to identify evidence on the prognostic value of pVO2 as a surrogate health outcome to support future oHCM economic model development. Following screening, study characteristics, population characteristics, and pVO2 prognostic association data were extracted. RESULTS: A total of 4,687 studies were identified. In total, 3,531 and 538 studies underwent title/abstract and full-text screening, respectively, of which 151 were included and nine of these were in hypertrophic cardiomyopathy (HCM); only three studies focused on oHCM. The nine HCM studies consisted of one systematic literature review and eight primary studies reporting on 27 potentially predictive relationships from a pVO2-based metric with clinical outcomes including all-cause mortality, cardiovascular mortality, sudden cardiac death, transplant, paroxysmal, and permanent atrial fibrillation. pVO2 was described as a predictor of single and composite endpoints, in three and six studies, respectively, with one study reporting on both. LIMITATIONS: This study primarily uses systemic literature review methods but does not qualify as one due to not entailing parallel reviewers during title-abstract and full-text stages of review. CONCLUSION: The findings of this study suggest pVO2 is predictive of multiple health outcomes, providing a rationale to use pVO2 in the development of an economic model.

Obstructive hypertrophy cardiomyopathy (oHCM) is a condition where the heart muscle thickens, obstructing blood flow and potentially impacting health. Peak oxygen uptake (pVO2) measures the highest amount of oxygen consumption during peak exercise and serves as an indicator of fitness. pVO2 can be used to assess heart health and predict severe conditions and death, acting as a surrogate endpoint. Surrogate endpoints are valuable in drug investigations since they allow earlier decisions on drug approval and funding before longer-term patient follow-up is available.This study reviewed evidence on the relationship between pVO2 values in patients with heart disease and the risk of becoming sicker or dying. Our goal was to assess if these relationships had been established and whether it is feasible to use them to predict future treatment benefits and support economic evaluations of new treatments. Our review found that most studies reported on patients with heart failure, with only nine focusing on HCM. Evidence indicates that low pVO2 values in patients with heart disease are linked to an increased risk of developing other heart conditions, needing a heart transplant, or dying.