Maximal Exercise Research Articles

O2 consumption overshoot in patients with heart failure: crossing the line

Abstract Background Cardiopulmonary exercise testing (CPET) is among the most valuable clinical tools for evaluating disease severity and physical activity limitations in heart failure (HF) patients. Peak oxygen uptake (pVO2) reflects maximal cardiac output during exercise, and it is considered a major parameter in selecting candidates for cardiac transplantation. VO2 overshoot, a transient increase in VO2 during recovery from maximal exercise, has been frequently observed in HF patients and is attributed to the transient increase in cardiac output caused by the mismatch between cardiac contractility and afterload reduction. However, the prognostic significance of this phenomenon remains to be fully established. Purpose This study aimed to characterize the prognostic significance of VO2 overshoot following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF, with left ventricular ejection fraction (LVEF) <50%, who underwent CPET between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sitting passively for 2 minutes). VO2 overshoot kinetics during recovery were measured and described as the time until post-exercise VO2 fell below pVO2 for at least 15 seconds. Please refer to Figure 1A for an example of normal and prolonged VO2 overshoot. The study endpoint was time to cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) over 1-year follow-up. Results A total of 254 patients were included (mean age 59 ± 12 years; 83% males; mean LVEF 34 ± 9%; 70% with ischemic HF; 77% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean predicted pVO2% 52 ± 16%; mean VE/VCO2 slope 41 ± 13). The VO2 overshoot had a normal distribution (Figure 1B) and lasted on average for 45 ± 33 seconds. There were no differences between patients that had an overshoot higher and below average. Overall, during follow-up, 25 patients met the composite endpoint (12 CV deaths, 9 urgent heart transplants, and 4 LVAD). Univariate analysis showed a significant relationship between VO2 overshoot and the outcome of interest (HR 1.01, 95% CI 1.00 – 1.02, p=0.027). In multivariate analysis, this association remained significant, even after adjusting for pVO2 and VE/VCO2 slope (HR 1.01, CI 95% 1.00– 1.02, p=0.026). Conclusion This study delves into the intriguing phenomenon of VO2 overshoot in patients with heart failure, shedding light on its potential prognostic significance. The independent association between VO2 overshoot and the composite endpoint suggests that this transient increase in oxygen consumption may carry prognostic value. Further studies should confirm these findings.

The role of myocardial bridging in athletes with ST-segment depression or T-wave inversion on exercise testing

Abstract Background Myocardial bridging (MB) is a congenital anomaly in which a myocardial band partially or completely covers a coronary artery. It is a common finding in the general population, but it is more frequent in athletes. MB can cause ST-segment depression on exercise testing, which can be misinterpreted as coronary artery disease and generate the prohibition of sports. Aim To evaluate the presence of Myocardial Bridging (MB) through Multi-Slice Tomography Angiography in Moderate to High Intensity Athletes with Electrocardiographic changes and normal parietal motility in Stress Ultrasound with Exercise Methods This study included 159 athletes who had ST-segment depression or T-wave inversion on exercise testing. All participants underwent coronary angiography and/or multislice computed tomography coronary angiography. In addition, follow-up was 36 months (+/- 18 months) to assess the presence of major adverse cardiovascular events (MACE). Results A total of 3790 stress tests were requested from the Cardiology and Sports Clinic: 3631 (95.8%) were completely normal (no ST changes and normal parietal motility) and 159 (4.2%) showed ST segment depression. Of the 159 athletes, 42 (1.11%) had ST depression in the inferior and/or lateral segments and abnormal parietal motility at maximal exercise and were referred for invasive coronary angiography. The remaining 117 (3.09%) had the following ECG changes: 88 (72.21%) inferior and/or lateral ST segment depression and 29 (24.78%) T wave inversion without ST segment depression. Ninety-two (78.64%) of the above 117 athletes were diagnosed with 1 or more MBs in the coronary arteries. One hundred and forty-three MBs were found. The most common location was the anterior descending coronary artery (n=61; 42.6%) in its middle and distal third, followed by findings in the diagonal (n=30; 20.9%), circumflex (n=28; 19.5%) and marginal (n=24; 16.7%) branches. No MACE was recorded during the follow-up period and no further complex diagnostic studies were required. Conclusions Our study suggests that MB is a common cause of ST-segment depression and/or T-wave inversion on exercise testing in athletes. MB is usually benign and does not increase the risk of cardiovascular events. Therefore, athletes with MB should be allowed to continue participating in sports.ECG during maximal exercise stress echocTMSC of athlete

Exercise stress testing recovery kinetics: the forgotten phase

Abstract Background Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters. Purpose The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF with left ventricular ejection fraction (LVEF) <50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year. Results A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 >1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p<0.001), and higher NYHA (p<0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 <1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p<0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014). Conclusion Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.

Performance of an automated echocardiographic artificial intelligence model. to detect subclinical heart failure with preserved ejection fraction (HFpEF) in community-dwelling older adults

Abstract Background Heart failure (HF) with preserved Ejection Fraction (HFpEF) is common among older adults and associated with a high burden of morbidity and mortality. Early identification of subclinical HFpEF, defined by abnormalities in cardiac structure and function without symptoms of HF, can prompt early initiation of evidence-based therapies to prevent HFpEF. However, scalable strategies for the identification of subclinical HFpEF are lacking. Purpose To evaluate the performance of a validated, automated echocardiographic artificial Intelligence algorithm (Ultromics, UK) to identify subclinical HFpEF among community-dwelling individuals without HF. Methods The study included participants of the Dallas Hearts and Minds Study without HF who underwent cardiovascular phenotyping with resting and exercise echocardiography and maximal cardiopulmonary exercise testing. The resting apical 4C echocardiographic images were analyzed by the AI echo algorithm to identify the HFpEF phenotype (AI-HFpEF). Subclinical HFpEF was defined by E/e’ >14 and Peak exercise oxygen uptake (VO2peak) <25th percentile for the cohort. The performance of the AI algorithm to detect subclinical HFpEF was determined using the area under the receiver operating curve and decision curve analysis and was compared with the previously validated H2FpEF score. The association between the AI-HFpEF phenotype and the presence of subclinical HFpEF, VO2peak, exercise E/e’, left ventricular strain, and left atrial strain was assessed using multivariable-adjusted logistic and linear regression models. Results The study included 511 participants (mean age: 61 y, 57% women, mean VO2peak = 16.9 ml/kg/min). Using the AI echo algorithm, subclinical HFpEF was detected in 10% of participants (n=76), and 10% were non-diagnostic. The participants with (vs. without) AI-HFpEF phenotype were older and had a higher burden of CVD risk factors, left ventricular hypertrophy, and left atrial dilation. Subclinical HFpEF, as defined by the gold standard criteria, was present in 5.3% of participants. The AUROC for diagnosis of subclinical HFpEF using the AI-HFpEF algorithm was 0.85 vs. 0.78 by the H2FpEF score (see Figure). In the adjusted analysis, the AI-HFpEF phenotype was significantly associated with greater odds of subclinical HFpEF by exercise and echocardiographic phenotyping criteria, higher E/e’ with exercise, lower VO2 peak, and worse LV and LA strain (see Table). In decision curve analysis, the AI-HFpEF algorithm identified 23 additional cases of subclinical HFpEF per 1000 screened participants compared with the H2FpEF score. Conclusion The AI-HFpEF algorithm can reliably identify community-dwelling individuals with subclinical HFpEF characterized by diastolic dysfunction at rest or exercise and impaired exercise capacity. Future studies are needed to assess the utility of the AI-HFpEF algorithm in screening for subclinical HFpEF in health systems.

Blood pressure response to exercise in endurance athletes with and without paroxysmal atrial fibrillation.

Abstract Background Atrial fibrillation (AF) is more prevalent among endurance-trained athletes when compared to non-athletes. The underlying pathophysiology and mechanisms for this phenomenon remain unknown but repeated exposure to an exaggerated blood pressure (BP) response during exercise may contribute to the development of AF in this population. Purpose We aimed to assess whether endurance athletes with AF have a higher maximal systolic BP (SBP) or a higher BP relative to exercise intensity compared to endurance athletes without AF. Methods Endurance athletes with paroxysmal AF (n=66, 96% male) from the ProAFHeart, NEXAF Detraining and Master@Heart studies were matched for age and sex to endurance athletes without AF (n=66, 96% male). Participants with a history of hypertension were excluded. All athletes underwent a maximal graded cardiopulmonary exercise test on a cycle ergometer to assess exercise BP using an automated auscultatory BP machine, maximal oxygen uptake (VO2peak) and peak workload. All athletes were in sinus rhythm at the time of testing and BP was measured pre-exercise seated on the bike and every 2 min throughout the test. Exercise BP measurements included the maximum exercise SBP (SBPmax) and the slopes of the relationships between SBP, diastolic BP (DBP) and workload (W) as determined from linear regression analysis (SBP/W-slope and DBP/W-slope, respectively). The resting SBP and DBP were measured in the supine position after 10min of rest. Independent T-test (parametric data) or the Mann-Whitney U-test (non-parametric data) assessed for the differences between the two groups. Results The 66 athletes with AF were of similar age and sex as the 66 athletes without AF, median age (55 [IQR 45, 61] vs 54 [IQR 44, 62] years, p=0.839), 4% female. There was no difference in (mean±SD) VO2peak (46 ±9 vs 49±10 mL/kg/min, p=0.114) and peak workload (365±67 vs 385±83 W, p=0.136), nor resting SBP (131±13 vs 128±13 mmHg, p=0.169) and resting DBP (76±9 vs 75±11 mmHg, p=0.465) between athletes with and without AF respectively (Table 1). Athletes with AF showed no significant difference to athletes without AF for exercise BP responses (Figure 1) including SBPmax (222±22 vs 219±28 mmHg, p=0.479), SBP/W-slope (0.22±0.07 vs 0.24±0.08 mmHg/W, p=0.310) and median DBP/W-slope (-0.01 [IQR -0.02, 0.01] vs -0.01 [IQR -0.03, 0.02] mmHg/W, p=0.703). Conclusion When comparing endurance athletes with and without paroxysmal AF, there were no differences in the maximal BP attained during exercise or in their BP response indexed to external workload (SBP/W-slope) suggesting that exercise-induced hypertension does not explain the athletic predisposition to AF.

Impaired myocardial energetics and lower cardiac reserve in response to exercise stress in adults born preterm

Abstract Background/Introduction Preterm birth (<37 weeks’ gestation) affects 10% of live births globally and associates with an increased risk of heart failure, early cardiovascular-related mortality, and altered cardiac morphology. At rest, left ventricular (LV) ejection fraction (EF) is similar between adults born preterm and term, but right ventricular (RV) EF is lower in preterm-born adults. Exercise stress uncovers LVEF impairment in preterm-born adults but RVEF response to exercise stress has not been studied. The underlying cause of the impaired LVEF reserve and lower RVEF at rest in preterm-born adults remains uncertain and whether altered myocardial energetics contribute to this cardiac dysfunction is currently unknown. Purpose To measure resting myocardial energetics and ventricular function at rest and during exercise stress to determine whether reduced cardiac reserve in preterm-born adults may be explained by impaired myocardial energetics. Methods We conducted a cross-sectional, observational, case-control study of preterm (n=64; mean gestational age =31 weeks) and term-born (n=36) adults aged 34±5 years to compare myocardial energetics and ventricular function. Following maximal cardiopulmonary exercise testing (CPET), participants underwent 31-phosphorus magnetic resonance (MR) spectroscopy (31-P MRS) and cardiovascular MR imaging (CMR) on a 3-Tesla Siemens MR scanner. 31-P MRS was used to measure myocardial phosphocreatine to adenosine triphosphate ratio (PCr/ATP) as a measure of myocardial energetics. We obtained CMR-derived LVEF and RVEF at rest and during 40% peak wattage exercise (determined from CPET) using a MR compatible cardio-step module and steady-state free precession real-time cine imaging. Outcomes were analysed using unpaired Student’s t-tests and presented as mean±standard deviation. Results Age, body mass index, and sex did not differ between groups (p>0.05). PCr/ATP was 1.8±0.4 in preterm-born adults and 2.0±0.4 in term-born adults (p=0.01, Figure 1). Preterm-born adults had a similar LVEF versus term-born adults at rest (60.3±7.6 versus 62.1±4.5; p=0.19) though resting RVEF was lower in preterm-born adults (53.4±6.7 versus 55.9±4.5; p=0.05). LVEF increased by 6.5±5.5% in preterm-born adults and 10.9±6.0% in term-born adults from rest to 40% peak exercise (p<0.001), while RVEF increased by 9.2±6.3% in preterm-born adults versus 12.0±6.3% in term-born adults (p=0.06) (Figure 2). PCr/ATP associated with resting RVEF in preterm-born adults (R²=0.27, p=0.002), but was not associated with resting LVEF or the delta change in LVEF and RVEF with exercise stress. Conclusions Resting myocardial energetics is impaired in adults born preterm relative to term-born adults, with both the LV and RV demonstrating reduced functional reserve when challenged with low to moderate exercise stress. Metabolic modulators may help prevent progression to heart failure in preterm-born adults.Figure 1Figure 2

Peak oxygen pulse response during maximal cardiopulmonary exercise testing on a treadmill: applicability analysis of the FRIEND registry prediction equation in a Brazilian healthy sample

Abstract Background Peak oxygen uptake (VO2peak), measured by cardiopulmonary exercise test (CPET), is an established variable for prognostic assessment. Other VO2peak-derived variables, such as the peak oxygen pulse (peakO2pulse), also provide valuable information for risk stratification in patients with cardiac diseases. For individualized assessment, the measured peakO2pulse can be compared to reference standards using predictive equations, such as the FRIEND Registry [peakO2pulse = 23.2 – (0.09 × Age) – (6.6 × Sex (female:1; male: 0)]. However, the applicabilty of this equation in a Brazilian population sample has never been evaluated. Purpose To conduct an external validation of the FRIEND registry prediction equation for treadmill peakO2pulse in a sample of healthy Brazilian individuals. Methods Cross-sectional study involving subjects assessed by treadmill CPET in the Brazilian Midwest region from January 2011 to March 2020. Inclusion criteria: healthy individuals aged ≥ 20 years with a peak respiratory exchange ratio ≥ 1.00. Exclusion criteria: history of cardiovascular or pulmonary disease, presence of cardiovascular risk factors (hypertension, diabetes mellitus, current smoking, and obesity), and abnormalities on CPET. Variables were described as median and interquartile range (IQR). Statistical comparisons between measured and predicted values were conducted using the Wilcoxon signed rank test, including the calculation of the median differences and the 95% confidence interval (CI). Furthermore, Bland-Altman agreement analysis was utilized to assess the concordance between measured and estimated values. Results A total of 7,843 CPETs were performed. After applying inclusion and exclusion criteria, 3,544 assessments were included (1,574 females and 1,970 males) aged between 20 to 80 years. In the females, the median and IQR of measured peakO2pulse and predicted values were 10.4 (9.0; 12.1) and 13.1 (12.3; 13.7) ml/beat, respectively. This difference was statistically significant (p < 0.001), with a median difference of 2.54 mL/beat (95% CI: 2.40; 2.69). For males, the measured and predicted values were 17.3 (15.1; 19.7) and 19.7 (19.0; 20.2) ml/beat, respectively. The median difference was statistically significant at 2.26 mL/beat (95% CI: 2.11; 2.46) (p < 0.001) (Figure 1). Bland-Altman agreement analysis indicated a bias of 2.33 mL/beat (95% limits of agreement: -2.17 to 6.83) in females and 2.15 mL/beat (95% limits of agreement: -4.34 to 8.65) in males (Figure 2). Conclusions The study reveals that measured median peakO2pulse values are consistently lower than predicted across both sexes, highlighting a significant bias, which limits the applicability of the FRIEND registry prediction equation in the Brazilian population and underscores the international heterogeneity of the variable. The findings advocate for the development of region-specific reference standards to enhance accuracy in predicting peakO2pulse values.

Exercise-induced inflammatory and thrombotic acute phase response in hypertensive patients

Abstract Background/Introduction Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. Purpose The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers. Methods After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity were measured. Results All biomarkers increased with exercise, except PAI-1, which decreased (P<0.05 for the change between resting and peak exercise for all biomarkers). The normotensive group had less marked (P<0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P=NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%) (see also Figure). Conclusion(s) In conclusion, the exercise-induced inflammatory and thrombotic acute phase response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. The effect of blood-pressure lowering treatment on the exercise-induced acute phase response remains to be elucidated.Figure

The impact of exogenous ketone body suppletion on energy and pH balance in skeletal muscle during exercise in chronic heart failure patients: a prospective randomized double-blind cross-over study

Abstract Background Heart Failure (HF) is characterized by impediments in exercise capacity. Disruptions in the energy metabolism of skeletal muscle contribute to this condition. Pre-clinical and clinical evidence showed that reductions in carbohydrate and FA metabolism in HF may be partially overcome by a compensatory increase in ketone body oxidation and suggest that suppletion of ketone bodies (KB) may improve energy metabolism in HF. Purpose We tested the effect of exogenous KB suppletion on energy and pH balance during cycling exercise using 31P Magnetic Resonance (MR) Spectroscopy of the exercising quadriceps muscle in patients with HF. Methods In a randomized, double-blind, placebo-controlled cross-over study, 14 stable HF patients with reduced ejection fraction and diminished exercise capacity underwent maximal exercise testing in a MR scanner fitted with a cycling ergometer after KB or placebo treatment. Phosphocreatine (PCr) and inorganic phosphate (Pi) resonance amplitudes and frequencies were measured continuously in the quadriceps muscle during rest, exercise and recovery using in-vivo 31P MR spectroscopy (Figure 1). Results Patients had a median age of 66 [53 – 75] years, were 14% female, had a median LVEF of 37% [27 – 40] and circulating NT-pro BNP levels of 411 [182 – 946] pg/mL. Peak oxygen uptake (VO2) was 18.2 [15.2 – 20.3] ml/kg/min, which is 68% [62 – 78%] of predicted. After treatment, exercise performance in terms of cycling duration and workload were comparable between treatment arms (Figure 2). Quadriceps acidification during exercise was larger after KB suppletion compared to placebo (ΔpH: -0.2 [-0.3 - -0.1] vs -0.1 [-0.3 - -0.1] respectively; p=0.041) while quadriceps energy depletion during exercise was not altered by treatment (ΔPi/PCr 0.77 [0.55 – 2.51] vs 0.66 [0.46 – 0.81] respectively; p=0.087). Post-exercise mitochondrial oxidative function was similar between treatment arms (KB: PCr resynthesis rate 48 sec [25 – 59] versus placebo: 42 sec [36 – 63]; p=0.767). Conclusions Ketone body suppletion increased acidification and did not improve energy balance in skeletal muscle during exercise or mitochondrial function during recovery in patients with chronic HF. These results question the value of ketone bodies as treatment to boost muscular energy metabolism during exercise in HF.31P MRS Spectrum during exercise in HFExercise and energy parameters

Invasive hemodynamic response to exercise in hemodynamically significant aortic stenosis with preserved left ventricular ejection fraction

Abstract Background Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. Purpose To describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%, and to identify the variables associated with the steepness of the pulmonary capillary wedge pressure (PCWP)/cardiac output (CO) slope defined as (peak exercise PCWP-rest PCWP)/(peak exercise CO-rest CO). Methods Patients with aortic valve area (AVA) ≤1.5 cm² underwent right heart catheterization at rest and during maximal exercise measuring pulmonary artery pressures, PCWP, CO and PCWP/CO slope. Patients were stratified in three groups: 1) discordant LG AS (AVA ≤1.0 cm² and mean gradient <40 mmHg); 2) moderate AS (AVA >1.0 cm²) and 3) high-gradient severe AS (AVA ≤1.0 cm² and mean gradient ≥40 mmHg). Results Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) high-gradient severe AS. The PCWP/CO slope was significantly steeper in discordant LG: median 3.3 mmHg/L/min (interquartile range: 2.2 mmHg/L/min) and high-gradient severe AS: 2.7 mmHg/L/min (1.5 mmHg/L/min) compared to moderate AS: 1.9 mmHg/L/min (2.0 mmHg/L/min), p=0.004. In a linear regression model adjusted for age, sex and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO slope. Furthermore, patients with discordant LG AS had a leftward and upward shift in the PCWP/CO slope. Conclusions Discordant LG and high-gradient severe AS had similar hemodynamic response to exercise with steeper PCWP/CO slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left-upward shift in PCWP/CO slope for discordant LG compared to high-gradient severe AS indicates that, this group also has latent heart failure with preserved ejection fraction physiology.

Effect of alcohol septal ablation on exercise hemodynamics, symptoms and quality of life in patients with obstructive hypertrophic cardiomyopathy

Abstract Background The comprehensive impact of septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy (HCM), including exercise hemodynamics and quality of life (QoL), remains poorly understood. Purpose The aim of this study was to evaluate the effect of alcohol septal ablation (ASA) in mitigating left ventricular outflow tract (LVOT) obstruction, reducing filling pressures during exercise, and the effect on QoL in patients with obstructive HCM. Methods This prospective study enrolled 24 patients with obstructive HCM referred for ASA. Evaluations included right-heart catheterization and echocardiography performed at rest and during exercise, before and approximately six months post-ASA. The primary outcome was the difference in filling pressures assessed by pulmonary capillary wedge pressure (PCWP) at 75 Watt (W). Secondary outcome assessed LVOT gradients, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and exercise capacity. Results ASA significantly reduced PCWP at 75 W (24 ± 10 mmHg vs 33 ± 9 mmHg; P = 0.0001) (Figure 1), decreased LVOT gradients at rest (49 mmHg (24-90) vs 17 mmHg (14-27); P=0.002), at peak exercise (45 mmHg (29-90) vs 32 mmHg (21-61); P = 0.02), and post-exercise (96 mmHg (34-161) vs 28 mmHg (21-62); P=0.004). The KCCQ-OSS score was also significantly reduced (75.6 ± 18.8 vs 64.7 ± 16; P = 0.006), without affecting peak oxygen consumption (19.9 ± 4.8 ml/kg/min vs 18.7 ± 3.6 ml/kg/min; P = 0.26). The improvement in the KCCQ score was confirmed by changes in NYHA functional class. Before ASA treatment, 54% of patients were in NYHA functional class III compared to 13% after ASA (P < 0.0005). Conclusion ASA substantially reduces exercise-induced filling pressures, reduces LVOT obstruction, and improves symptoms and QoL in obstructive HCM, without impacting maximal exercise capacity.

Treadmill exercise test as a screening tool in the development of hypertension

Abstract Background Guidelines promote screening people with high normal BP for the presence of end-organ damage because their presence is associated with a 2- to 3-fold increase in the risk of CVD. Purpose Office blood pressure measurements may be unable to detect early subclinical cardiac damage of adverse prognostic significance in subjects with high normal blood pressure. Methods 100 consecutive subjects with high normal BP [systolic BP=130-139mmHg and/or diastolic BP=85-89mmHg] were examined for early signs of hypertension-mediated organ damage (HMOD). They underwent an echocardiographic study, a negative for ischemia treadmill exercise test (Bruce protocol) where the index SBP/MET-slope [(peak SBP—resting SBP)/(peakMET-1)] was used. Arterial stiffness was evaluated based on carotid-femoral pulse wave velocity (PWV). The sympathetic drive was assessed by MSNA. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in the office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advice to lower their BP. The endpoint was the development of HTN either with Office BP or ABPM. Results Of 100 subjects (54±8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg), 40 developed HTN in 3 years. 34 subjects developed Hypertensive Response to Exercise (HRE) (BP >210mmHg in men and >190mmHg in women) and all of them developed HTN. The SBP/MET-slope in future hypertensives was increased in all stages till peak exercise independently of sex type (stage1: 6.7vs4.9 p=0.049, stage2: 8.4vs4.8 p=0.001, peak: 6.7vs4.9, p=0.001). Their exercise capacity was reduced (10vs11.3METs, p=0.002) as well as their maximum exercise heart rate (156vs164, p=<0.0001). Those with HRE had higher 24hSBP (124vs121mmHg, p=0.009), Night SBP (117vs111mmHg, p<0.001), Day SBP (127vs124mmHg, p=0.012) Office Pulse Pressure (51vs47mmHg, p=0.01). Additionally, they had increased PWV (8.3vs7.5m/sec, p=<0.0001), MSNA levels (36vs28 bursts, p=<0.0001), LVMI (38vs34 gr/m2.7, p=0.02), and a statistically significant deterioration of 2021 CKD-EPI eGFR (90 vs 97 mL/min/1.73 m², p=0.02). All of them correlated with development of hypertension (p=0.002), while they did not differ regarding their metabolic profile at the follow-up. Conclusion Detecting exaggerated blood pressure response and specifically an increased SBP/MET-slope in the end of second stage of Bruce protocol at treadmill exercise test is associated with increased systemic vascular resistance and early subclinical HMOD which may upgrade an individual’s cardiovascular disease (CVD) risk as they progress to HTN indicating a need for instituting a BP-lowering strategy.

Females have better metabolic flexibility in different metabolically challenging stimuli.

The first aim was to explore the difference in metabolic flexibility between sexes in response to changing exercise intensity under control conditions. The second aim was to evaluate metabolic flexibility between sexes in response to exercise intensity adding two different metabolically challenging stimuli (glycogen depletion and heat). Eleven males (22±3 years, 176.2±4cm, 68.4±4.9kg, and 60.2±4.1mL/kg FFM/min) and nine females (22±2 years, 166.7±4.5cm, 61.9±2.9kg, and 64.2±5.6mL/kg FFM/min) performed a maximal incremental exercise test (30W every 3min) on a cycle ergometer under three conditions: control (24h high-carbohydrate diet followed by the incremental test), glycogen depletion (glycogen-depletion protocol followed by 24h low-carbohydrate diet and then the incremental test), and heat (24h high-carbohydrate diet followed by 30min passive heating and then the incremental test in heat). In the last minute of each step, lactate was analysed, fat (FATox/FFM) and carbohydrate oxidation (CHox/FFM), and energy expenditure (EE/FFM) normalized to fat-free mass (FFM) was estimated by indirect calorimetry. Females presented a greater FATox/FFM as exercise intensity increases across conditions (control, glycogen depletion, and heat) (p=0.006). In contrast, CHox/FFM was not significantly different between sexes at any specific intensity across conditions (p>0.05). Consequently, EE/FFM was higher in females throughout the different intensities across conditions (p=0.002). Finally, lactate concentration was not different between sexes at the same intensities across conditions (p=0.87). In conclusion, females present a greater metabolic flexibility, due to the higher FATox/FFM throughout the different intensities, regardless of whether the test is performed in conditions emphasizing the oxidative pathway (glycogen depletion) or the glycolytic pathway (heat). Clinical trials: NCT05703100.

Ventilatory thresholds in professional female soccer players.

This study investigated the ventilatory thresholds (VT1 and VT2) along with the corresponding heart rates, velocities and % of V̇O2 max at which these thresholds are reached in professional female soccer players. It also examined positional differences in the aforementioned parameters. Thirty-three professional players from two teams (age range 18-31 years) were recruited. The players underwent maximal exercise testing on the treadmill for the detection of VT1 (V̇E versus V̇O2 plot) and VT2 (V̇E versus V̇CO2 plot). The test began at a speed of 6km/h and was increased by 2 km/h every 3.15 minutes, with the inclination constant at 1%. Results indicated that the players had an average V̇O2 max of 50.24 ml·kg- 1.min- 1. VT1 (% max) and VT2 (% max) were shown at 72.87% and 91.26% of V̇O2 max, respectively. The respective velocities at VT1 and VT2 were indicated at 10.85 km/h and 12.91 km/h, respectively, while the average VV̇O2 max was 14.61 km/h. The average heart rates at VT1, VT2 and V̇O2 max were 159.33, 185.15 and 192.85 beats per minute, respectively. Furthermore, analysis of variance ANOVA indicated significant differences in velocity at V̇O2max. This study provides important normative data regarding the ventilatory thresholds of female soccer players.

Clinical and Electrocardiographic Predictors of Cardiac Resynchronization Therapy Response That Correlate with the 6 min Walking Test.

Background: Cardiac resynchronization therapy is an essential treatment for heart failure patients. Candidates typically have cardiomyopathy accompanied by delayed electrical activation in the left ventricular lateral wall, causing uncoordinated contractions and worsening heart failure. Heart failure severity can be assessed with functional tests: the cardiopulmonary test, which is a maximal exercise test, remains the gold standard, but the 6 min walk test has emerged as an easier, faster, and more comfortable alternative to be used by clinicians to adjust treatment protocols for cardiovascular and pulmonary conditions. Methods: This is a prospective observational study that included 69 patients from a single healthcare facility, and the purpose was to determine if the 6 min walk test results could be associated with changes in various electrocardiographic, clinical, functional, and demographic parameters. All the parameters and the 6 min walk distance were recorded at four key time moments: before the procedure and after 6, 9, and 12 months. The electrocardiographic parameters were obtained from the patients' electrocardiograms recorded in the four key moments and included variables such as QRS area, duration, percentage of biventricular pacing, and many others, while the functional variables included the monitored intraprocedural systolic blood pressure and the end-systolic left ventricular volume. We also aimed to check if clinical conditions such as diabetes and chronic kidney disease and demographic variables such as age or sex have any impact. Results and Conclusions: All this research was performed in order to identify which parameters hold a predictive value and can serve as future criteria for better patient selection and for defining a proper resynchronization outcome. The study shows that parameters such as diabetes and QRS duration have an impact over the 6 min walk distance. Also, newer variables such as the QRS area and the R/S ratio may represent a direction worth studying in order to predict the outcomes of cardiac resynchronization therapy.

Clinical and Functional Outcomes Associated with Quality of Life in Patients with Lymphangioleiomyomatosis: A Cross-Sectional Study.

Lymphangioleiomyomatosis (LAM) is a rare (twenty-one per million female inhabitants) neoplastic cystic lung disease that impairs health-related quality of life (HRQoL). However, the factors associated with impaired quality of life in patients with LAM are poorly understood. To assess the clinical, psychosocial, and functional characteristics associated with impaired quality of life in patients with LAM. This was a cross-sectional study performed on two nonconsecutive days. HRQoL (SF-36 and CRQ), lung function tests, anxiety and depression symptoms (HADS), maximal (CPET and ISWT), and submaximal exercise capacity (6MWT) were assessed. Linear associations among outcomes were assessed using Pearson's correlation and multivariate tests. Forty-five women with LAM (46 ± 10.years; FEV1,74%pred) were evaluated. The lowest SF-36 scores were observed for general health and vitality and the highest for the physical and social domains. The lowest CRQ scores were observed for dyspnea and fatigue, and the highest were for the emotional function and self-control domains. Sixteen (35%) women had anxiety, and 8 (17%) had depression symptoms. Most of the SF-36 and CRQ domains were associated with anxiety and depression symptoms (from r = 0.4 to r = 0.7; p < 0.05) and exercise capacity (from r = 0.3 to r = 0.5; p < 0.05). Lung function parameters were weakly or not associated with quality of life domains. After multiple linear regression, HRQoL was independently associated with depression symptoms and physical capacity but not with lung function. Our results show that aerobic capacity and depression symptoms are the main factors, rather than lung function, related to quality of life in patients with LAM.

Validity and Reliability of a New Wearable Chest Strap to Estimate Respiratory Frequency in Elite Soccer Athletes.

Assessing respiratory frequency (fR) is practical in monitoring training progress in competitive athletes, especially during exercise. This study aimed to validate a new wearable chest strap (wCS) to estimate fR against ergospirometry as a criterion device in soccer players. A total of 26 elite professional soccer players (mean [standard deviation]: 23.6 [4.8] years; 180.6 [5.7] cm; 77.2 [5.4] kg) from three Italian Serie A League teams participated in this cross-sectional study. The sample included attackers, midfielders, and defenders. fR was assessed during a maximal cardiopulmonary exercise test (CPET) on a treadmill using (i) a breath-by-breath gas exchange analyzer (Vyntus® CPX, Vyaire Medical) and (ii) a novel wCS with sensors designed to assess breath frequency following chest expansions. Pearson's correlation coefficient (r), adjusted coefficient of determination (aR2), Bland-Altman plot analysis, and Lin's concordance correlation coefficient (ρc) were used for comparative analysis (correlation and concordance) among the methods. The repeated measures correlation coefficient (rrm) was used to assess the strength of the linear association between the methods. The intraclass correlation coefficient (ICC) and the Finn coefficient (rF) were used for inter-rater reliability. All statistical analyses were performed within the R statistical computing environment, with 95% confidence intervals (95% CIs) reported and statistical significance set at p < 0.05. A total of 16529 comparisons were performed after collecting the CPET data. The robust time series analysis with Hodges-Lehmann estimation showed no significant differences between both methods (p > 0.05). Correlation among devices was statistically significant and very large (r [95% CI]: 0.970 [0.970, 0.971], p < 0.01; aR2 [95% CI]: 0.942 [0.942, 0.943], p < 0.01) with strong evidence supporting consistency of the new wCS (BF10 > 100). In addition, a high concordance was found (ρc [95% CI]: 0.970 [0.969, 0.971], bias correction factor: 0.999). VyntusTM CPX, as a standard criterion, showed moderate agreement with wCS after Bland-Altman analysis (bias [95% lower to the upper limit of agreement]; % agree: 0.170 [-4.582 to 4.923] breaths·min-1; 69.9%). A strong association between measurements (rrm [95% CI]: 0.960 [0.959, 0.961]), a high absolute agreement between methods (ICC [95% CI]: 0.970 [0.970, 0.971]), and high inter-rater reliability (rF: 0.947) were found. With an RMSE = 2.42 breaths·min-1, the new wCS seems to be an valid and reliable in-field method to evaluate fR compared to a breath-by-breath gas exchange analyzer. Notwithstanding, caution is advised if methods are used interchangeably while further external validation occurs.

Effects of an acute maximal exercise bout on serum insulin-like growth factor-1 in adults with MDD

Exercise has acute, positive effects on mood and can lead to antidepressant effects over time when repeated regularly. The mechanisms underlying the antidepressant effects of exercise training are not well known, limiting the prescription of exercise training for depression. Serum Insulin-Like Growth Factor-1 (IGF-1) appears dysregulated in those with Major Depressive Disorder (MDD), suggesting MDD could inhibit or alter the IGF-1 response to exercise. In healthy individuals, exercise has been shown to acutely increase serum IGF-1, which may act positively on the dysregulated IGF-1 system in MDD. Therefore, the purpose of this study was to examine the sensitivity of serum IGF-1 levels to an acute maximal exercise bout in adults with MDD and healthy controls. Additionally, clinical and behavioral factors of MDD are likely to affect this system, such as depression severity, antidepressant usage and physical activity habits. Baseline data were used from a larger trial in Germany (SPeED Study) collected from individuals with mild to moderate MDD (n=113) and healthy controls (n=34) that were matched for age, sex, and education. Demographics, depression severity (Hamilton Depression Rating Scale-17), self-reported antidepressant usage, MVPA (International Physical Activity Questionnaire-Short Form), and blood draws before and after a maximal exercise test were collected. Multiple linear regressions were conducted to determine relationships between depression severity, antidepressant usage, and physical activity with peripheral IGF-1 levels following acute exercise. Covariates included demographic factors and IGF-1 pre-exercise (baseline levels). Acute IGF-1 changes occurred similarly in depression (mean ± SD; 11.3 ± 12.9) as well as healthy adults (11.3 ± 20.4: p>0.05). Neither depression severity, antidepressant use, nor regular physical activity were significant predictors of peripheral IGF-1 levels at baseline or following exercise. Individuals with MDD are likely to have favorable exercise-induced IGF-1 changes regardless of clinical and behavioral differences. Acute exercise increases peripheral IGF-1 briefly, and in response to repeated exercise bouts, the IGF-1 system could normalize over time. The normalization of the IGF-1 system might be a possible mechanism underlying mood increases that occur during exercise with exercise training research warranted.

Exercise testing in patients with tricuspid regurgitation undergoing transcatheter tricuspid valve intervention.

Transcatheter tricuspid valve intervention (TTVI) has shown promising results with persistent reduction of tricuspid regurgitation (TR) and improvements in functional class and quality of life (QOL). To analyze the impact of TTVI on maximal and submaximal exercise capacity (SEC). Constant work-rate exercise-time (CWRET) testing reflects SEC, which is more likely to be relevant for daily life activities and provides more differentiated physiological insight into the nature of exercise intolerance. Thus, 30 patients undergoing TTVI (21 direct annuloplasty and 9 edge-to-edge repair) received cardiopulmonary exercise testing (CPET) and CWRET (at 75% of maximum work rate in the initial CPET) before and 3months after TTVI. Patients' age was 80.5 [74.8-82.3] years and 53.3% were female. TR reduction ≥ 2 grades was achieved in 93.3% (TR grade ≤ moderate in 83.3%). Echocardiography revealed improved right ventricular (RV) characteristics with decreased RV basal diameter (47.0mm [43.0-54.3] vs. 41.5mm [36.8-48.0]; p < 0.001) and decreased inferior caval vein diameter. CWRET testing showed a significantly improved SEC (246.5s [153.8-416.8] vs. 338.5s [238.8-611.8] p = 0.001). Maximum oxygen uptake showed a positive trend without statistically significant differences (9.9ml/min/kg [8.6-12.4] vs. 11.7ml/min/kg [9.7-13.3]; p = 0.31). In contrast to the six-minute-walking distance (6MWD), SEC correlated moderately with effective regurgitation orifice area reduction (r = 0.385; p = 0.036), increased cardiac output (r = 0.378; p = 0.039), and improved QOL (r = 387; p = 0.035). Improvements in exercise capacity after TTVI mainly occur in the submaximal rather than in the maximal exercise range and correlate with hemodynamic effects and QOL. This may have a methodological impact on assessment of exercise capacity in these patients.

Physical Activity Levels, Cardiorespiratory Fitness, and Physical Literacy in Children With a Chronic Medical Condition.

This study investigated differences in cardiorespiratory fitness (CRF) and other physical literacy domains between children with a chronic medical condition (CMC) who adhered to with the physical activity guideline and those who did not. Forty children with a CMC (7-12years) wore an accelerometer for 7days to measure moderate-to-vigorous physical activity. CRF and muscle power were assessed with a maximal cardiopulmonary exercise test, and motor performance was measured with an exercise course. Motivation, confidence, knowledge, and understanding were assessed with a questionnaire. Children who adhered to the PA guideline (n =13) scored significantly higher for CRF, muscle power, motivation and confidence than children who did not adhere to the PA guideline (n =27). No significant differences were found for motor performance, knowledge and understanding. Future research should investigate the effect of paying specific attention to motivation and confidence in children with a CMC to stimulate their adherence to the PA guideline.