Comparing the Physiological Responses to the 6-Minute Walk Test, Timed Up and Go Test, and Treadmill Cardiopulmonary Exercise Test.

Purpose: To compare physiological responses during a treadmill cardiopulmonary exercise test (CPX), 6-minute walk test (6MWT), and timed up and go test (TUGT) in individuals referred for unexplained breathlessness and symptom limited treadmill exercise testing. Methods: Heart rate (HR), oxygen consumption (V̇O2), carbon dioxide production (V̇CO2), respiratory exchange ratio (RER), minute ventilation (V̇E), systolic blood pressure (SBP), and rating of perceived exertion (RPE) were recorded throughout each test. Results: Each test demonstrated a significant increase (p < 0.01) in the cardiopulmonary (V̇O2, V̇CO2 and V̇E, RPE, SBP, and HR) and perceptual (RPE) responses from rest to end exercise. The increase in cardiopulmonary and perceptual responses was greatest for the CPX with significantly smaller responses demonstrated during the 6MWT (p < 0.01) and even smaller responses for the TUGT (p < 0.01 vs CPX and 6MWT). Conclusion: Not surprisingly, the treadmill CPX results is the greatest physiological response in our group. Despite being of short duration, the TUGT results in an increased physiological response.

Recalibrated FRIEND equation for peak oxygen pulse is accurate in endurance athletes: the NOODLE study.

Peak oxygen pulse (O2Ppeak) is an important index of cardiorespiratory fitness (CRF). The FRIEND database is a global source of reference values for CRF. However, no reference equation is tailored for endurance athletes (EA) to predict O2Ppeak. Here, we adjusted the well-established FRIEND equation for O2Ppeak to the characteristics of the EA population. 32 (34.0%) female EA and 62 (66.0%) male well-trained EA underwent maximal cardiopulmonary exercise test on a treadmill. V̇O2max was 4.5 ± 0.5 L min-1 in males and 3.1 ± 0.4 L min-1 in females. O2Ppeak was 23.6 ± 2.8 mL beat-1 and 16.4 ± 2.0 mL beat-1 for males and females, respectively. Firstly, we externally validated the original FRIEND equation. Secondly, using multiple linear regression, we adjusted the FRIEND equation for O2Ppeak to the population of EA. The original FRIEND equation underestimated O2Ppeak for 2.9 ± 2.9 mL beat-1 (P < .001) in males and 2.2 ± 2.1 mL beat-1 (P < .001) in females. The updated equation was 1.36 + 1.07 (23.2 · 0.09 · age - 6.6 [if female]). The new equation explained 62% of the variance and significantly predicted O2Ppeak (R2 = 0.62, ß = 0.78, P < .001). The error of the EA-adjusted model was 0.1 ± 2.9 mL beat-1 (P = .82) and 0.2 ± 2.1 mL beat-1 (P = .65) for males and females respectively. Recalibration of the original FRIEND equation significantly enhances its accuracy among EA. The error of the EA-adjusted model was negligible. A new recalibrated equation should be used to predict O2Ppeak in the population of EA.

Sex-Based Differences in Pulmonary Function and Cardiopulmonary Response 30 Months Post-COVID-19: A Brazilian Multicentric Study.

Aim: (I) to verify if there are sex differences in respiratory function, respiratory muscle strength, and effort limitation in individuals recovered from severe acute COVID-19 30 months after the initial infection, and (II) to evaluate the influence of length of stay on cardiorespiratory capacity among men and women. Methods: Cross-sectional observational multicentric study with participants from five Brazilian states (São Paulo, Amazonas, Minas Gerais, Bahia, and Brasília). We assessed lung function and respiratory muscle strength by maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and cardiorespiratory fitness by cardiopulmonary exercise test (CPET). Results: 86 individuals were stratified by sex (48 women and 38 men). Females had significantly longer hospitalization for acute COVID-19 (p < 0.05) and showed a marked reduction in MIP (cmH2O and % predicted). Regarding the CPET, women presented lower V˙O2% predicted, O2 pulse, and oxygen uptake efficiency slope (OUES, % predicted) (p < 0.05). In addition, women also had greater abnormal combinations between RER < 1.10, OUES < 80% predicted, VE/VVM < 15% [3 (6.2%)] and V˙O2% predicted < 80%, V˙E/V˙CO2 slope and V˙O2/workload < 8.4 mL/min/W [8 (17%)]. The regression analysis showed a significant influence of age, length of hospitalization (< and >10 days), and FEV1/FVC (%) on the V˙O2 peak (mL·kg-1·min-1). Secondarily, we found that women hospitalized for more than 10 days had worse O2 pulse (p = 0.03), OUES % predicted (p < 0.001), and worse V˙O2% predicted (p < 0.009). Conclusion: Women exhibited more pronounced impairments in several key indicators of cardiopulmonary function 30 months post-infection.

Maximum heart rate prediction equations based on field-tests with adequate clinical applicability for aerobic exercise prescription to individuals after stroke.

OBJECTIVES: 1) to develop two maximum heart rate (HRmax) prediction equations for individuals after stroke; 2) to investigate its validity. METHODS: The HRmax was obtained by a Cardiopulmonary Exercise Test (CPET). Participants also completed the Six-minute Walking Test (6MWT) and the Incremental Shuttle Walking Test (ISWT). RESULTS: 60 individuals (54(12) years; 64(69) months after stroke) were included. Twenty individuals (58(10) years; 67(61) months after stroke) were included in the cross-validation group. For the first model, the following equation was generated (equation-1): HRmax= 87.655 + 0.726 (HRpeak in the 6MWT) - 0.386 (age in years), (R2=0.53; Standard Error of the Estimate (SEE)= 15.35; p < 0.0001). For the second model, the following equation was generated (equation-2): HRmax= 96.523 + 0.681 (HRpeak in the ISWT) - 0.039 (walking distance in meters in the ISWT) - 0.400 (age in years), (R2=0.53; SEE = 15.51; p < 0.0001). Significant and high magnitude agreement was found between the HRmax obtained by the CPET and the predicted HRmax by equation-1 (ICC= 0.85; 95% CI= 0.63 - 0.94) and equation-2 (ICC= 0.72; 95% CI= 0.29 - 0.89). CONCLUSIONS: Two HRmax prediction equations have been developed and showed adequate validity. Professionals will have the option of choosing one of the two equations to use.

Two maximum heart rate prediction equations, with clinical applicability and adequate validity, were provided for individuals after strokeTo apply the equations, it is necessary to perform the Six-Minute Walking Test or the Incremental Shuttle Walking Test.Both equations are valid and suitable for use in this population for the prescription of aerobic exercise intensity in clinical practice.

Cardiorespiratory fitness and working memory in persons with traumatic brain injury: a cross-sectional analysis.

INTRODUCTION: Cognitive impairment is a highly impactful consequence of traumatic brain injury (TBI) and there are limited evidence-based treatment practices to combat these impairments. Evidence from other populations suggest that aerobic exercise training (AET) is beneficial for a variety of cognitive deficits, but the research in persons with TBI to date is equivocal. One potential reason is the heterogeneity of exercise prescriptions and outcome measures. This stems from the fact that studies have not been designed based on previous data supporting a specific AET prescription to target a cognitive domain. The primary purpose of this cross-sectional analysis was to examine the relationship between cardiorespiratory fitness (CRF), as a cross-sectional surrogate of AET, and cognition in persons with TBI to inform future research. METHODS: Cross-sectional analysis was conducted on baseline data of persons with TBI who completed neuropsychological assessments to evaluate several cognitive domains and a cardiopulmonary exercise test (CPET) to measure CRF. Based on the normal distribution of an outcome, Pearson's r or Spearman's ρ was calculated to measure the relationship between CRF and cognition. RESULTS: Data were analyzed for all participants who demonstrated valid CPETs (n = 21 of 29). Based on the cycle ergometer-based norms of CRF, males in this sample were in the 69th percentile and females in this sample were in the 56th percentile, with high variability across individuals. Higher CRF, as measured by peak power output (Wpeak), was significantly associated with greater working memory (ρ = 0.465, p = 0.017), even after post-hoc corrections. CONCLUSIONS: These data suggest average and highly variable CRF in persons with TBI of all severity and support cycle ergometry-based CPET testing in this population. Further, these data provide support for future research applying AET to target working memory and possibly other executive functions in persons with TBI. This research is a small step toward large-scale randomized controlled trials that can directly impact clinical care to treat cognitive symptoms post-TBI.

The Role of Atrial Premature Complexes in Exercise Test in Predicting Atrial Fibrillation in Patients Without Obstructive Coronary Artery Disease.

BACKGROUND: Atrial fibrillation (AF) is usually triggered by frequent atrial premature complexes (APC) and atrial tachycardias originated in the pulmonary veins. The aim of the current study is to clarify the relationship between AF and APCs observed during treadmill exercise testing through long-term patient follow-up. MATERIAL AND METHODS: Our study only examined the data of patients who did not have any obstructive coronary artery disease and had an exercise test. In total, 1559 patients were included in this research. The study data were divided into two groups according to the development of AF during follow-up. The patients who developed any type of AF during the follow-up period were classified as AF (+). Mean follow-up time for AF (+) and (-) groups were 48 and 47 months, respectively. RESULTS: In the univariable analysis, age, LAAP, and the presence of APCs (HR: 3.906, 95% CI: 2.848-5.365, p < 0.001) during the treadmill exercise test were significantly associated with the development of AF. In the multivariable analysis, age (adjusted HR: 1.063, 95% CI: 1.043-1.083, p < 0.001) and the presence of APCs during the treadmill exercise test (adjusted HR: 2.504, 95% CI: 1.759-3.565, p < 0.001) emerged as independent risk factors for the development of AF. The AF-free survival was significantly lower in the APCs (+) patients compared with the APCs (-) patients (log rank p < 0.001). CONCLUSION: Our study revealed that individuals without obstructive CAD who exhibited frequent APCs during treadmill exercise tests were more likely to develop AF.

Rating of perceived exertion as a tool for managing exercise intensity during pregnancy: a scoping review.

OBJECTIVE: During pregnancy, international guidelines recommend ≥150 min of moderate-intensity aerobic physical activity per week, with an intensity perceived as fairly light to somewhat hard on the Borg Rating of Perceived Exertion (RPE) scale (ranging from 6 'no exertion' to 20 'maximal exertion', corresponding to 60% to 80% of maximum heart rate). However, the determination and monitoring of exercise intensity seem to be a particular source of confusion, and the most effective method to monitor exercise intensity remains uncertain. This study aimed to examine existing research on the correlation between the Borg RPE scale and maternal heart rate (MHR) for monitoring exercise intensity during pregnancy. DESIGN: Scoping review using the mixed methods appraisal tool (MMAT) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. DATA SOURCES: PubMed, Web of Science and SPORTDiscus were searched from 16-17 April 2023, with a subsequent search on 1 November 2023. ELIGIBILITY CRITERIA: We included studies investigating the correlation between perceived intensity on the Borg RPE scale (6-20) and MHR during exercise in pregnant individuals and written in English/Scandinavian language. There were no restrictions on publication year or study design. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened the articles based on title and abstract. Selected articles were read in full text and reference lists of screened articles were also checked. Out of 120 studies screened, six articles met the inclusion criteria after removing one duplicate. The results were qualitatively summarised to provide an overview of common themes and variations between studies. MMAT and GRADE assessed the risk of bias and the certainty of the evidence. RESULTS: The six studies involved a total of 260 healthy pregnant individuals (gestational week: from 16 to 38), with various exercise protocols (cycling, walking, running and resistance exercise) and intensities (from light to moderate). Three studies supported the Borg RPE scale to estimate exercise intensity during pregnancy, while three found no correlation between this scale and MHR. The certainty of the evidence was graded as low to moderate, with a potential risk of bias due to small sample sizes, incomplete outcome data and inconsistencies across studies. CONCLUSION: The mixed results highlight the complexity of monitoring exercise intensity during pregnancy. Using both the Borg RPE scale and MHR might be better than using them separately for monitoring exercise intensity during pregnancy. Due to limited and inconsistent research, more extensive studies are needed.

The association of coronary artery disease with heart rate at anaerobic threshold and respiratory compensatory point.

Background: There is limited knowledge regarding the association between heart rate (HR) during different exercise phases and coronary artery disease (CAD). This study aimed to evaluate the relationship between four exercise-related HR metrics detected by cardiopulmonary exercise testing (CPET) and CAD. These metrics include HR at the anaerobic threshold (HRAT), HR at respiratory compensatory point (HRRCP), maximal HR (HRmax), and HR 60 s post-exercise (HRRec60s). Methods: The 705 participants included 383 with CAD and 322 without CAD in Beijing Hospital, who underwent CPET between January 2021 and December 2022. The Logistic regression analysis was applied to estimate the odds ratio and the 95% confidence interval. Additionally, the multivariable Logistic regression analyses with restricted cubic splines were conducted to characterize the dose-response association and explore whether the relationship was linear or nonlinear. Results: Our primary finding indicates that for each one-beat increase in HRAT, there is a 2.8% reduction in the adjusted risk of CAD in the general population. Similarly, a one-beat increase in HRRCP corresponds to a 2.6% reduction in the adjusted risk of CAD. Subgroup analyses revealed significant interactions between HRAT and factors such as sex, hypertension, and lung cancer, as well as between HRRCP and sex and hypertension, in relation to CAD. The dose-response analysis further confirmed that higher HRAT and HRRCP are associated with a reduced risk of CAD. Conclusion: These results are suggestive of a good association between HRAT, HRRCP, and CAD. The lower HRAT, and HRRCP are signs of poor HR response to exercise in CAD. HRAT and HRRCP are potentially good indicators of poor HR response to exercise without considering maximal effort.

Investigation of exertional dyspnoea by cardiopulmonary exercise testing with continuous laryngoscopy.

OBJECTIVES: Abnormal breathlessness at maximal exercise may be caused by a range of conditions, including exercise-induced bronchospasm, breathing pattern disorder, or exercise-induced laryngeal obstruction. These three disorders may not be detected on standard cardiopulmonary exercise testing. The aim of this study was to describe diagnostic outcomes of an expanded protocol during cardiopulmonary exercise testing. DESIGN: Retrospective cohort study. METHODS: Patients presenting with abnormal breathlessness on maximal exercise underwent continuous laryngoscopy with cardiopulmonary exercise testing on a stationary cycle ergometer. Breathing pattern disorder was evaluated by video and ventilatory data. Pre- and post-exercise spirometry was performed. RESULTS: 24 adult patients were evaluated; 10 were professional athletes. Mean age was 40 years (range 18-73). Nine of 24 (38 %) were diagnosed with exercise-induced laryngeal obstruction and referred for speech pathology. Six of these had supraglottic exercise-induced laryngeal obstruction; all were aged <30 years; 5/6 were professional athletes. One patient had breathing pattern disorder and was referred for physiotherapy; one had exercise-induced bronchospasm, requiring escalation of asthma medication; one had muscle tension dysphonia resulting in referral to an otolaryngologist who administered a laryngeal injection of botulinum toxin. A further four patients had unexplained lower maximal oxygen consumption with cardiac limitation and were referred for further cardiac investigation. CONCLUSIONS: In patients reporting abnormal breathlessness at maximal exercise, this expanded exercise protocol provided diagnostic information in 66.7 % cases which contributed to further personalised management.

Effects of sildenafil on gas exchange, ventilatory, and sensory responses to exercise in subjects with mild-to-moderate COPD: A randomized cross-over trial.

Excess exercise ventilation (high ventilation (V̇E)/carbon dioxide output (V̇CO2)) contributes significantly to dyspnea and exercise intolerance since the earlier stages of chronic obstructive pulmonary disease (COPD). A selective pulmonary vasodilator (inhaled nitric oxide) has shown to increase exercise tolerance secondary to lower V̇E/V̇CO2 and dyspnea in this patient population. We aimed to assess whether a clinically more practical option - oral sildenafil - would be associated with similar beneficial effects. In a randomized, placebo-controlled study, twenty-four patients with mild-to-moderate COPD completed, on different days, two incremental cardiopulmonary exercise tests (CPET) one hour after sildenafil or placebo. Eleven healthy participants performed a CPET in a non-interventional visit for comparative purposes with patients when receiving placebo. Patients (FEV1= 69.4 ± 13.5 % predicted) showed higher ventilatory demands (V̇E/V̇CO2), worse pulmonary gas exchange, and higher dyspnea during exercise compared to controls (FEV1= 98.3 ±11.6 % predicted). Contrary to our expectations, however, sildenafil (50 mg; N= 15) did not change exertional V̇E/V̇CO2, dead space/tidal volume ratio, operating lung volumes, dyspnea, or exercise tolerance compared to placebo (P>0.05). Due to the lack of significant beneficial effects, nine additional patients were trialed with a higher dose (100 mg). Similarly, active intervention was not associated with positive physiological or sensory effects. In conclusion, acute oral sildenafil (50 or 100 mg) failed to improve gas exchange efficiency or excess exercise ventilation in patients with predominantly moderate COPD. The current study does not endorse a therapeutic role for sildenafil to mitigate exertional dyspnea in this specific patient subpopulation. Clinical trial registry: https://ensaiosclinicos.gov.br/rg/RBR-4qhkf4 Web of Science Researcher ID: O-7665-2019.

Determinants of Longitudinal Changes in Exercise Capacity in Patients with Independent Functioning on Hemodialysis.

OBJECTIVE: Patients with chronic kidney disease reportedly have decreased muscle oxygen utilization, which most substantially decreases exercise capacity, followed by cardiac reserve. However, determinants of longitudinal changes in exercise capacity in patients on hemodialysis and the effects of long-term exercise interventions are unknown. This study was conducted to clarify these concerns. METHODS: This was a prospective cohort study. Patients on hemodialysis that were not hospitalized were followed from baseline up to 2 years, and cardiopulmonary exercise testing results, including peak oxygen uptake, peak work rate, heart rate reserve, and ventilatory equivalent for carbon dioxide slope, as well as implementation of exercise interventions were assessed. Based on the 2-year change in peak oxygen uptake, they were divided into improvement or declined groups. RESULTS: Forty-five patients who were not hospitalized completed the follow-up were analyzed. In the improvement group, the variation was determined by an increase in peak work rate, which is a peripheral factor (partial regression coefficient 0.08 [95% CI = 0.01 to 0.16]), while in the decline group, the variation was determined by a decrease in the ventilatory equivalent for carbon dioxide slope, which is a cardiac factor (partial regression coefficient = -0.12; 95% CI = -0.21 to -0.03). Moreover, exercise intervention was associated with the change in peak oxygen uptake (partial regression coefficient = 3.09; 95% CI = 1.45 to 4.72). CONCLUSION: Exercise intolerance even in patients on hemodialysis that were not hospitalized and stable progressed over time with deterioration of cardiac reserve, whereas exercise interventions were associated with improved exercise capacity through enhanced peripheral function. IMPACT: The results support the early measurement of cardiopulmonary or skeletal muscle reserve through cardiopulmonary exercise testing and the implementation of long-term exercise interventions based on the measurement results to address the potential deterioration in exercise capacity associated with reduced cardiac reserve, even in patients on hemodialysis that are asymptomatic and stable.

Changes in Cerebral Oxygenation in the Prefrontal Cortex During Cardiopulmonary Exercise Testing in Patients After Cardiovascular Surgery.

Oxygenated haemoglobin (O2Hb) and total haemoglobin (THb) concentrations rise with increasing exercise load during the cardiopulmonary exercise test (CPX); however, this elevated response is impaired in patients with chronic heart failure. Furthermore, the changes occurring in patients during the acute phase of cardiac surgery are unknown. This study aimed to measure cerebral oxygenation in the prefrontal cortex (PFC) during CPX in patients during the acute post-operative phase following cardiovascular surgery. Fourteen patients in the acute phase of post-cardiovascular surgery period were enrolled. CPX was administered between the post-operative period and discharge. The protocol employed the ramp method (10 W/min) after 3-min rest and 3-min warm-up periods. Levels of O2Hb, deoxygenated haemoglobin (HHb), THb, and the regional cerebral oxygen saturation (rSO2) in the PFC were measured from the resting state through the end of CPX using near-infrared spectroscopy. The mean values of O2Hb, HHb, and THb levels and rSO2 were compared at rest, warm-up, anaerobic threshold, and peak points. At the peak, O2Hb and rSO2 declined significantly, and HHb rose significantly compared to the respective values at rest; no significant changes were observed in THb. These findings suggest that the oxygen supply to the PFC is reduced in patients with reduced cardiac function following cardiovascular surgery.

Efficacy of Wearable Single-Lead ECG Monitoring during Exercise Stress Testing: A Comparative Study.

BACKGROUND AND OBJECTIVES: Few comparative studies have evaluated wearable single-lead electrocardiogram (ECG) devices and standard multi-lead ECG devices during exercise testing. This study aimed to validate the accuracy of a wearable single-lead ECG monitor for recording heart rate (HR) metrics during graded exercise tests (GXTs). METHODS: A cohort of 50 patients at a tertiary hospital underwent GXT while simultaneously being equipped with wearable single- and conventional multi-lead ECGs. The concordance between these modalities was quantified using the intraclass correlation coefficient and Bland-Altman plot analysis. RESULTS: The minimum and average HR readings between the devices were generally consistent. Parameters such as ventricular ectopic beats and supraventricular ectopic beats showed strong agreement. However, the agreement for the Total QRS and Maximum RR was not sufficient. HR measurements across different stages of the exercise test showed sufficient agreement. Although not statistically significant, the standard multi-lead ECG devices exhibited higher noise levels compared to the wearable single-lead ECG devices. CONCLUSIONS: Wearable single-lead ECG devices can reliably monitor HR and detect abnormal beats across a spectrum of exercise intensities, offering a viable alternative to traditional multi-lead systems.

Test-retest reliability of exercise blood pressure and the workload-indexed systolic blood pressure slope in healthy males and females.

The reliability of blood pressure (BP) measured during submaximal and maximal exercise, and confounding effects of biological sex, remain to be fully established but have implications for using exercise BP as a cardiovascular risk factor. We hypothesize that exercise BP test-retest reliability will not differ between sexes but will be higher during submaximal compared to maximal exercise. Eighty-four participants (22±5 years; 36 females) completed two maximal treadmill tests (modified Bruce protocol) separated by ≥2 days. Exercise BP was measured every 90-seconds using automated auscultation (Tango M2 monitor). Breath-by-breath oxygen uptake was analyzed. Test-retest reliability was assessed using two-way, mixed effects, consistency, single-rater intraclass correlation coefficient (ICC) analysis on the total group and separated by sex at submaximal and maximal exercise. Systolic BP during submaximal (ICC=0.65 [0.49-0.76], p<0.01) and maximal (ICC=0.66 [0.52-0.77], p<0.01) exercise both displayed substantial reliability between visits. In contrast, the SBP/MET slope showed poor submaximal (ICC=0.12 [-0.09-0.33], p=0.13) but substantial maximal (ICC=0.63 [0.48-0.75], p<0.01) exercise reliability. Females showed substantial reliability in submaximal systolic BP (ICC=0.73 [0.53-0.85], p<0.01), and peak systolic BP (ICC=0.74 [0.54-0.87], p<0.01) and SBP/MET slope (ICC=0.78 [0.60-0.88], p<0.01); the submaximal SBP/MET slope had fair reliability (ICC=0.28 [-0.06-0.56], p=0.05). Males showed moderate reliability in submaximal systolic BP (ICC=0.53 [0.26-0.72], p<0.01), and peak systolic BP (ICC=0.41 [0.15-0.62], p<0.01) and SBP/MET slope (ICC=0.48 [0.22-0.67], p<0.01); the submaximal SBP/MET slope had poor reliability (ICC=0.06 [-0.18-0.31], p=0.32). Systolic BP showed similar reliability during submaximal and maximal exercise, with females demonstrating higher reliability in exercise systolic BP compared to males.

The chronic heart failure evolutions: Different fates and routes.

AIMS: Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk. METHODS AND RESULTS: From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2-year follow-up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow-up paths, as well as specific end-stages conditions of the disease. Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n = 527) and external (n = 777) populations. We analyzed 4876 patients (age = 63 [53-71], male gender n = 3973 (81.5%), NYHA class I-II n = 3576 (73.3%), III-IV n = 1300 (26.7%), LVEF = 33 [25.5-39.9], atrial fibrillation n = 791 (16.2%), peak VO2% pred = 54.8 [43.8-67.2]), with a minimum 2-year follow-up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end-stage points. Clusters survival rate varied from 44% to 100% at 2 years and from 20% to 100% at 5 years, respectively. The event frequency at 5-year follow-up for each study cohort cluster was successfully compared with those in the validation cohorts (R = 0.94 and R = 0.84, P < 0.001, for internal and external cohort, respectively). Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant observed in 22% of cases). CONCLUSIONS: Each HF phenotype has a specific disease progression and prognosis. These findings allow to individualize HF patient evolutions and to tailor assessment.

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

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

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

Right-ventricle heart failure in PAH vs. HFrEF with secondary PH: Hemodynamic, ergospirometric, and organ function correlations.

PURPOSE: The goal of the study was to identify markers of organ function used in daily routines that could potentially aid in the overall evaluation of the cardiovascular system in patients with right-ventricle heart failure due to pulmonary arterial hypertension (PAH) and left-ventricle heart failure. We analyzed correlations between parameters from right heart catheterization (RHC), cardiopulmonary exercise test (CPET), and selected laboratory parameters of thyroid, liver, kidneys function and iron homeostasis. PATIENTS AND METHODS: A retrospective analysis included 107 patients (mean age 57.6 â€‹± â€‹16.2; 34.6 â€‹% women), comprising 57 patients with PAH (mean age 54.0 â€‹± â€‹18.2; 49.1 â€‹% women) and 50 patients with heart failure with reduced ejection fraction (HFrEF) â€‹< â€‹40 â€‹% (mean age 61.6 â€‹± â€‹12.7; 18 â€‹% women). All patients underwent CPET. Each patient in the PAH group had RHC performed. Fifteen patients from the HFrEF group underwent RHC, which confirmed the suspicion of pulmonary hypertension (HFrEF-SPH). RESULTS: CPET and laboratory parameters' analysis showed strong correlations between ventilation/carbon dioxide production (VE/VCO2) slope and NT-proBNP in HFrEF without secondary PH and HFrEF-SPH groups. In the PAH group, VE/VCO2 slope correlated with liver and thyroid function but also with morphological parameters of red-cell system. Analysis of correlations between laboratory and hemodynamic parameters revealed significant correlations between pulmonary arterial pressure, pulmonary vascular resistance (PVR) and red-cell parameters, especially strong with fT4 in the PAH group. CONCLUSIONS: In HFrEF-SPH patients, laboratory parameters strongly correlated with pulmonary pressures and pulmonary capillary wedge pressure (PCWP).

Right Ventricular to Pulmonary Artery Uncoupling Is Associated With Impaired Exercise Capacity in Patients With Transthyretin Cardiac Amyloidosis.

BACKGROUND: Exercise capacity is related to mortality and morbidity in heart failure (HF) patients. Determinants of exercise capacity in transthyretin cardiac amyloidosis (ATTR-CA) have not been established. METHODS AND RESULTS: This single-center study retrospectively evaluated ATTR-CA patients and patients with non-amyloidosis HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) (n=32 and n=51, respectively). In the ATTR-CA group, the median age was 75.5 years (interquartile range [IQR] 71.3-78.8 years), 90.6% were male, and the median left ventricular (LV) ejection fraction was 53.5% (IQR 41.4-65.6%). Cardiopulmonary exercise tests revealed a median peak oxygen consumption and anaerobic threshold of 15.9 (IQR 11.6-17.4) and 10.6 (IQR 8.5-12.0] mL/min/kg, respectively, and ventilatory efficiency (minute ventilation/carbon dioxide production [V̇E/V̇CO2] slope) of 35.5 (IQR 32.0-42.5). Among exercise variables, V̇E/V̇CO2slope has the greatest prognostic value. Univariate analysis revealed a significant correlation between V̇E/V̇CO2slope and age, LV global longitudinal strain, tricuspid annular plain systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and mixed venous oxygen saturation. In multivariate analyses, the TAPSE/PASP ratio was an independent predictor of V̇E/V̇CO2slope (95% confidence interval -44.5, -10.8; P=0.0067). In non-amyloidosis HFpEF/HFmrEF patients, the TAPSE/PASP ratio was not independently correlated with V̇E/V̇CO2slope. CONCLUSIONS: Right ventricular-pulmonary artery coupling estimated by the TAPSE/PASP ratio determines exercise capacity in ATTR-CA patients. This highlights the importance of early therapeutic intervention against underappreciated right ventricular dysfunction associated with ATTR-CA.

Body Oxygen Level Test (BOLT) is not associated with exercise performance in highly-trained individuals.

Introduction: The analysis of chemoreflex and baroreflex sensitivity may contribute to optimizing patient care and athletic performance. Breath-holding tests, such as the Body Oxygen Level Test (BOLT), have gained popularity as a feasible way to evaluate the reflex control over the cardiorespiratory system. According to its proponents, the BOLT score reflects the body's sensitivity to carbon dioxide and homeostasis disturbances, providing feedback on exercise tolerance. However, it has not yet been scientifically validated or linked with exercise performance in highly-trained individuals. Therefore, we investigated the association of BOLT scores with the results of standard performance tests in elite athletes. Methods: A group of 49 speedskaters performed BOLT, Wingate Anaerobic Test (WAnT), and cardiopulmonary exercise test (CPET) on a cycle ergometer. Peak power, total work, and power drop were measured during WAnT. Time to exhaustion and maximum oxygen uptake were measured during CPET. Spearman's rank correlation and multiple linear regression were performed to analyze the association of BOLT scores with parameters obtained during the tests, age, somatic indices, and training experience. Results: No significant correlations between BOLT scores and parameters obtained during WAnT and CPET were found, r(47) = -0.172-0.013, p = 0.248-0.984. The parameters obtained during the tests, age, somatic indices, and training experience were not significant in multiple linear regression (p = 0.38-0.85). The preliminary regression model showed an R 2 of 0.08 and RMSE of 9.78 sec. Conclusions: Our findings did not demonstrate a significant relationship between BOLT scores and exercise performance. Age, somatic indices, and training experience were not significant in our analysis. It is recommended to interpret BOLT concerning exercise performance in highly-trained populations with a great degree of caution.

Cardiovascular risk and its influencing factors during exercise in apparently healthy Chinese adult population.

BACKGROUND: There are few studies on the safety of sub-maximal exercise testing of aerobic exercise in apparently healthy Chinese populations. The purpose of this study was to explore the frequency of exercise electrocardiography (ECG) abnormalities and the corresponding exercise intensities, as well as the associated influencing factors, during a symptom-limited stepwise incremental cardiopulmonary exercise test (CPET) in an apparently healthy Chinese population. METHODS: A cross-sectional study was done in four communities, one urban and one rural in the North (Beijing) and in the South (Hezhou, Guangxi) of China from 1 January 2017 to 31 December 2018, respectively. Total of 1642 participants was recruited, 918 were eligible and completed demographic indicators, routine blood indicators, physical activity status, symptom-limited CPET and exercise ECG were included in the analysis. RESULTS: Of the exercise ECG outcomes, 10 (1.1%) were positive and occurred at exercise intensities ≥ 62.50% heart rate reserve (HRR); 44 (4.8%) were equivocal and 864 (94.1%) were normal. Individuals with Cardiovascular Disease Risk Factor (CVDRF) = 3-4 were 2.6 times more likely to have a equivocal and abnormal exercise ECG than those with CVDRF = 0-2. Exercise ECGs of individuals with CVDRF = 5-7 were 5.4 times more likely to be positive and abnormal than exercise ECGs of individuals with CVDRF = 0-2. CONCLUSIONS: The exercise intensity of 62.5% HRR can be used as a safe upper limit for safe participation in exercise in apparently healthy Chinese population; the greater the number of CVDRFs, the greater the likelihood of cardiovascular risk during exercise.