Oxygen Consumption and Heart Rate Responses in Graded Exercise during Long-Duration Space Flight

U.S. and non-Russian International Partner astronauts who participate in long-term International Space Station (ISS) expeditions perform submaximal cycle exercise tests before, during, and after space flight. The heart rate (HR) and oxygen uptake (VO2) responses to exercise are used to estimate peak VO2 (EVO2pk). Purpose: To determine if the following factors are associated with the preflight-to-post flight change in EVO2pk: gender, age, body weight (BW), number of aerobic exercise sessions/wk- during flight, length of flight, EVO2pk measured before and late during the flight, ISS Expedition number and time between landing and the first post flight test. Methods: Records of 37 ISS astronauts (30 male, BW=81.6 plus or minus 8.6 kg; 7 female BW=66.1 plus or minus 4.9 kg [mean plus or minus SD]), age 46 plus or minus 4 years, were retrospectively examined. Peak HR and VO2 were measured approximately 9 months before flight to establish the test protocol. The submaximal cycle test consisted of three 5-minute stages designed to elicit 25, 50, and 75% of VO2pk. EVO2pk was calculated using linear least-squares extrapolation of average HR and VO2 during the last minute of each stage to predict VO2 at maximal HR. VO2 was not measured during flight and was assumed to not be different from preflight. Testing was performed 45 days before launch, late during flight, and during the week after landing. A random-intercept multivariate model was used to determine which characteristics significantly contributed to post flight EVO2pk. Results: In-flight aerobic exercise averaged 5.4 plus or minus 1.2 sessions/wk. ISS flight duration averaged 163 plus or minus 39 d. Mean EVO2pk values were 3.41 plus or minus 0.64 L (raised dot) per minute before flight, 3.09 plus or minus 0.57 L (raised dot) per minute late in flight, and 3.02 plus or minus 0.65 L (raised dot) per minute after flight. Late- and after-flight values were lower (p less than 0.05) than preflight values and did not differ from each other. Time between landing and post flight testing was 4.5 plus or minus 1.6 days. The only factor significantly associated with the post flight EVO2pk value was the late-flight EVO2pk score. Conclusion: Testing performed late during a mission provides a prediction of EVO2pk after landing. This approach may be implemented during longer missions.

There is paucity of scientific information on sex differences in heart rate (HR) responses during and after a sub-maximal exercise test in young adults. We assessed sex differences in normal HR responses during and after a sub-maximal-effort cycle ergometer exercise test in apparently healthy young adults. One hundred young adults (50 males and 50 females) participated in the study. Subjects performed a sub-maximal exercise at an intensity that produced 60–85% of a pre-determined age-predicted maximum HR. Measurements of subjects’ HR were done at rest, during exercise and post exercise recovery periods. The present data indicated that after adjusting for covariates, greater (P<0.05) HR responses (delta HR 2 min, delta HR 5 min, delta peak HR) were observed in men relative to women. Males also indicated significantly higher (P<0.05) %HRmax and %HRreserve compared to females. Variables of HR response during post-exercise recovery did not differ between males and females. HR responses during exercise were greater in young adult males compared to females while HR responses at post-exercise recovery were similar between the two groups. The present findings may be useful in interpreting more accurately the significance of HR responses during and after exercise in healthy young adults according to sex.

Prognostic Value of Late Heart Rate Recovery After Treadmill Exercise

This editorial refers to ‘Chronotropic response to exercise testing is associated with carotid atherosclerosis in healthy middle-aged men’† by S.Y. Jae et al., on page 954 Jae et al. 1 report on the association between the chronotropic response during exercise testing and carotid atherosclerosis in a large cohort of 8959 healthy middle-aged men. Importantly, the association between an attenuated heart rate (HR) response to exercise and a measurement of sub-clinical atherosclerosis by ultrasonography was independent of age, conventional cardiac risk factors, and parameters of inflammation. The HR response to exercise is related to several parameters including age, resting HR, functional capacity, cardiac function, extent of coronary artery disease, and the autonomic nervous system. A common definition of an abnormal HR response during exercise is the failure to achieve 85% of the age-predicted maximal HR (defined by 220 bpm minus the patient's age). This method may, however, be confounded by the resting HR and functional capacity. Therefore, the concept of HR reserve was introduced. The HR reserve is defined as the difference between maximal predicted HR (or 220 bpm minus the patient's age) and resting HR. Failure to use 80% of HR reserve is considered as chronotropic incompetence. To take into account the functional capacity, the chronotropic index can … *Corresponding author. Tel: +32 9 240 58 26; fax: +32 9 240 44 32. E-mail address: johan.desutter{at}ugent.be

Relationship between chronotropic incompetence and β-blockers based on changes in chronotropic response during cardiopulmonary exercise testing

Exercise is one of the most common noninvasive stressors used to risk stratify patients with suspected or established coronary disease. Functional capacity, time to onset of demand-induced ischemic ST-segment shifts or angina, complex ventricular arrhythmias, a progressive fall in systolic blood pressure during exercise, and abnormal heart rate (HR) responses either during or after exercise are all well-established independent predictors of long-term outcome and, when used in combination, have the potential to identify prognostic high-risk patients who may be candidates for coronary angiography and coronary revascularization.1 Among HR variables tested that are predictive of mortality, the most common include the ability to augment HR to age-predicted maximum (chronotropic response), the HR recovery response in the immediate postexercise phase, and the ST-segment response corrected for HR. 2,3 Article p 468 A normal increase in HR during exercise and the ability to slow HR in the immediate postexercise phase are dependent on the autonomic nervous system and the ability of the cardiac conduction tissue to normally propagate the electrical impulse. The vasomotor center, located in the reticular substance of the medulla and pons, has the capability to transmit parasympathetic impulses through the vagus nerves to the heart that slow HR and can modulate excitatory impulses through the sympathetic nervous system that increase HR and contractility.4 Regulation of the vasomotor center is affected by higher nervous centers that can excite or inhibit the center, as well as by circulatory reflexes initiated by aortic arch and carotid sinus baroreceptors that stimulate the vagal parasympathetic center. During the early phases of exercise in normal subjects, increased HR is mediated predominantly by decreased parasympathetic tone and in the later stages of exercise by a marked increase in sympathetic tone and circulating catecholamines. Thus, an exaggerated initial HR response to exercise (eg, first 1 to 2 minutes of exercise) could signal autonomic dysfunction, a condition associated with increased mortality. In 2005, Falcone et al5 published a report in Circulation indicating that a rapid HR increase at the onset of exercise (HR 1 minute 12 bpm) predicts increased adverse cardiac events and cardiovascular mortality in patients with coronary artery disease even after adjustment for potential prognostic confounders. This finding is important because the observation would allow potential risk stratification of patients after only 1 minute of exercise, a useful parameter for patients who cannot perform more strenuous exertion. Notably, the authors comment that their findings require validation in a separate data set. In this issue of Circulation, Leeper et al6 examined initial HR responses using multiple different definitions, including HR15 seconds, HR2 METS,, and HR1 minute, and report that a rapid initial increase in HR predicts decreased total and cardiovascular mortality and that peak exercise HR is the most powerful predictor of cardiovascular prognosis after adjustment for prognostic confounders. How can both welldone studies reach the exact opposite conclusions? A careful analysis provides useful insight. The exercise protocol that Falcone et al 5 used was a symptom-limited semisupine bicycle ergometer with an initial workload of 25 W and fixed stepwise 25-W increments every 2 minutes. The 458 patients were selected for exercise testing after a cardiac catheterization had been performed and coronary disease confirmed. Presumably, patients with highrisk coronary disease were excluded from the study and referred for revascularization. -Blockers and calcium antagonists were withdrawn before testing in 69% of subjects. Patients with signs or symptoms of heart failure, with impaired left ventricular ejection fraction, on digitalis, with evidence of valvular or congenital heart disease, and with a pacemaker or noninterpretable ECG were excluded from the study. Patients were followed up for a median of 6 years, and the cardiovascular end points tested were a composite of cardiac death (n15) and nonfatal myocardial infarction (n56). The overall mortality was very low (3.3% after a median of 6 years), indicating a low-risk population of patients with coronary artery disease.

During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 μm; 95% CI, 28.5-42.9 μm; P < .001; mean choroidal thickness change on flight day 150: 43 μm; 95% CI, 35-46 μm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.

Exaggerated exercise blood pressure (BP) is linked to cardiovascular disease (CVD). Although evening chronotypes have greater CVD risk than morning (Morn) types, it is unknown if exercise BP differs in intermediate (Int) types. Adults with obesity were classified as either Morn [n = 23 (18 females), Morning-Eveningness Questionnaire (MEQ) = 63.96 ± 1.0, 54.74 ± 1.4 yr, 33.7 ± 0.6 kg/m2] or Int [n = 23 (19 females), MEQ = 51.36 ± 1.1, 55.96 ± 1.8 yr, 37.2 ± 1.2 kg/m2] chronotype per MEQ. A graded, incremental treadmill test to maximal aerobic capacity (V̇o2max) was conducted. Systolic (SBP) and diastolic (DBP) blood pressure and mean arterial pressure (MAP), rate pressure product (RPP), heart rate (HR), and rate of perceived intensity (RPE) were determined at baseline, 4 min, 6 min, and maximal stages. HR recovery (HRR; maximum postexercise) was determined at 1 and 2 min postexercise. Preexercise fasted aortic waveforms (applanation tonometry), plasma leptin, nitrate/nitrite (nitric oxide bioavailability), and body composition (dual X-ray, DXA) were also collected. Int had lower V̇o2max and plasma nitrate (both P ≤ 0.02) than Morn. No difference in preexercise BP, aortic waveforms, or body composition were noted between groups, although higher plasma leptin was seen in Int compared with Morn (P = 0.04). Although Int had higher brachial DBP and MAP across exercise stages (both P ≤ 0.05) and higher HR, RPE, and RPP at 6 min of exercise (all P ≤ 0.05), covarying for V̇o2max nullified the BP, but not HR or RPE, difference. HRR was greater in Morn independent of V̇o2max (P = 0.046). Fasted leptin correlated with HR at exercise stage 4 (r = 0.421, P = 0.041) and 6 min (r = 0.593, P = 0.002). This observational study suggests that Int has exaggerated BP and HR responses to exercise compared with Morn, although fitness abolished BP differences.NEW & NOTEWORTHY This study compares blood pressure and heart rate responses with graded, incremental exercise between morning and intermediate chronotype adults with obesity. Herein, blood pressure responses to exercise were elevated in intermediate compared with morning chronotype, although V̇o2max abolished this observation. However, heart rate responses to exercise were higher in intermediate vs. morning chronotypes independent of fitness. Collectively, this exercise hemodynamic response among intermediate chronotype may be related to reduced aerobic fitness, altered nitric oxide metabolism, and/or elevated aortic waveforms.

Detailed heart rate (HR) response patterns during exercise in patients with heart failure (HF) and sinus rhythm remain uncertain. We screened consecutive patients with HF who underwent cardiopulmonary exercise tests at a large academic center from November 2013 to July 2023. HR response during exercise was statistically classified using logistic differential equation models. A total of 99 patients were included. Of them, 75 patients were assigned to "sigmoidal pattern" and the other 24 to "exponential pattern." Patients with the sigmoidal pattern were older and exhibited higher plasma B-type natriuretic peptide levels. Increases in HR and oxygen consumption (V̇o2)/kg up to the anaerobic threshold level were not different between both patterns. However, beyond the threshold, the sigmoidal pattern group showed no further increase in HR and significantly lower V̇o2/kg than their counterparts (interactions for P < 0.001). HR response during exercise in patients with heart failure and sinus rhythm was categorized into two unique groups: sigmoidal and exponential patterns. More detailed clarification of the sigmoidal pattern, potentially indicating sinus node dysfunction, should offer new clinical insights for chronotropic incompetence.NEW & NOTEWORTHY Heart rate response patterns can be classified into two groups among patients with chronic heart failure reaching maximal exertion: sigmoidal and exponential.

Previous reports have suggested that an attenuated exercise heart rate response may be associated with coronary heart disease risk and with mortality. These observations may parallel the association between reduced heart rate variability during normal activities and adverse outcome. This investigation was designed to look at the prognostic implications of exercise heart rate response in a population-based sample. In this prospective cohort investigation, 1575 male participants (mean age, 43 years) in the Framingham Offspring Study who were free of coronary heart disease, who were not taking beta-blockers, and who underwent submaximal treadmill exercise testing (Bruce protocol) were studied. Heart rate response was assessed in three ways: (1) failure to achieve 85% of the age-predicted maximum heart rate, which has been the traditional definition of chronotropic incompetence; (2) the actual increase in heart rate from rest to peak exercise; and (3) the ratio of heart rate to metabolic reserve used by stage 2 of exercise ("chronotropic response index"). Proportional hazards analyses were used to evaluate the associations of heart rate responses with all-cause mortality and with coronary heart disease incidence during 7.7 years of follow-up. Failure to achieve target heart rate occurred in 327 (21%) subjects. During follow-up there were 55 deaths (14 caused by coronary heart disease) and 95 cases of incident coronary heart disease. Failure to achieve target heart rate, a smaller increase in heart rate with exercise, and the chronotropic response index were predictive of total mortality and incident coronary heart disease (P <.01). Failure to achieve target heart rate remained predictive of incident coronary heart disease even after adjusting for age, ST-segment response, physical activity, and traditional coronary disease risk factors (adjusted hazard ratio, 1.75; 95% confidence interval, 1.11 to 2.74; P=.02). After adjusting for the same factors, the increase in exercise heart rate remained inversely predictive of total mortality (P=.04) and coronary heart disease incidence (P=.0003). The chronotropic response index also was predictive of total mortality (P=.05) and incident coronary heart disease (P=.001) after adjusting for age and other risk factors. An attenuated heart rate response to exercise, a manifestation of chronotropic incompetence, is predictive of increased mortality and coronary heart disease incidence.

This paper is devoted to the problem of real-time heart rate (HR) response modelling during treadmill exercise. A novel recursive constrained parameter estimation method is developed which in contrast to the conventional parameter estimation schemes (e.g. recursive least squares (RLS) method) can avoid the occurrence of the so-called blowup phenomena. By incorporation of a weighting upon 1) parameter variation relative to a priori HR response knowledge, 2) one-step parameter variation, into the objective function, an estimation scheme is obtained that in the absence of exciting data can avoid blowup. The proposed estimation scheme were experimentally verified using eight healthy male subjects and the results demonstrated that the designed scheme is able to identify the HR response of the exercising subjects in a real-time manner. As HR response is naturally a time-varying dynamics, the proposed online modelling method is of importance for the HR regulation during exercises, using a feedback controller with a desirable level of performance.

AimsThe mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF.Methods and resultsWe prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO2). The mean (standard deviation) peak VO2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta‐HR (HR at peak exercise − HR at rest), chronotropic index (CI) = (HR at peak exercise − resting HR)/[(220 − age) − resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise − HR at rest)/[119 + (HR at rest/2) − (age/2) − 5 − HR at rest]. In a bivariate setting, peak VO2 was positively and significantly correlated with Delta‐HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO2. We found a linear relationship between Delta‐HR and peak VO2 (β coefficient of 0.03; 95% confidence interval: 0.004–0.05; P = 0.030); conversely, the association among CIs and peak VO2 was exponentially shaped.ConclusionsIn patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity.

This study aimed to achieve two objectives: firstly, to analyze the relationships between aerobic fitness, as represented by the VIFT, and the heart rate and locomotor responses of youth male soccer players across various teams; and secondly, to compare players with lower and higher VIFT in terms of performance outcomes extracted during small-sided games (SSGs). A total of twenty-six youth male soccer players, aged 16.5 ± 0.32 years, with 3.4 ± 1.1 years of experience, voluntarily participated in the study. These players belonged to two regional-level tier 2 teams (trained/developmental). In the initial week of observation, the 30–15 Intermittent Fitness Test was implemented to measure the final velocity (VIFT) achieved by the players. Subsequently, the 5v5 format of play was conducted twice a week over two consecutive weeks, during which heart rate responses and locomotor demands were measured. The Pearson product-moment correlation test revealed a significant correlation between VIFT and the total distance covered during the 5v5 format (r = 0.471 [95% CI: 0.093; 0.721], p = 0.015). Conversely, small and non-significant correlations were identified between VIFT and mean heart rate (r = 0.280 [95% CI: − 0.126; 0.598]; p = 0.166), VIFT and peak heart rate (r = 0.237 [95% CI: − 0.170; 0.569]; p = 0.243), as well as VIFT and high-speed running (r = 0.254 [95% CI: − 0.153; 0.580]; p = 0.211). Players with higher VIFT demonstrated a significantly greater total distance, with a large effect size (+ 6.64%; p = 0.015; d = 1.033), compared to those with lower VIFT. Our findings suggest that improved performance in VIFT may lead to covering more distance in 5v5 matches. However, the lack of significant associations between VIFT and heart rate levels during SSGs suggests that they are not strongly correlated, possibly because VIFT is more closely linked to locomotor profile. As a practical implication, coaches may consider organizing players during SSGs based on their VIFT if the goal is to standardize locomotor demands.

The purpose of this study was to examine the effects of Ramadan fasting on body composition, aerobic exercise performance and blood lactate, heart rate and perceived exertion in regularly trained young soccer players. Sixteen male soccer players participated in this study. Mean age, stature, body mass and training age of the players were 17.4±1.2 years, 175.4±3.6 cm, 69.6±4.3 kg and 5.1±1.3 years, respectively. During the Ramadan period, all subjects voluntarily chose to follow the fasting guidelines and abstained from eating and drinking from sunrise to sunset. Body composition, hydration status, dietary intake and sleep duration were assessed on four occasions: before Ramadan, at the beginning of Ramadan, at the end of Ramadan and 2 weeks after the end of Ramadan. On each occasion, aerobic exercise performance and blood lactate, heart rate and rating of perceived exertion responses of players were also determined during an incremental running test. Repeated measures of ANOVA revealed that body mass, percentage of body fat, fat-free mass, hydration status, daily sleeping time and daily energy and macronutrient intake of players did not vary significantly throughout the study period (p>0.05). However, players experienced a small but significant decrease in skinfold thicknesses over the course of the study (p<0.05). Although ratings of perceived exertion at submaximal workloads increased during Ramadan (p<0.05), blood lactate and heart rate responses had decreased by the end of Ramadan (p<0.05). In line with these changes, peak running performance and running velocity at anaerobic threshold also improved by the end of Ramadan (p<0.05). Improvements in aerobic exercise performance with time were probably due to the effects of pre-season training program that was performed after the break of the fast (Iftar) during the month of Ramadan. The results of the present study suggest that if regular training regimen, body fluid balance, daily energy intake and sleep duration are maintained as before Ramadan, Ramadan fasting does not have detrimental effects on aerobic exercise performance or body composition in young soccer players.

Obstructive sleep apnea (OSA) is characterized by repetitive collapse of the upper airway during sleep with intermittent hypoxia, hypercapnia, and stressful arousals to re-establish breathing. OSA also causes persistent sympathetic activation which contributes to the pathogenesis of hypertension (HTN). The exercise test is an established diagnostic and prognostic tool in clinical cardiology, but its utility in risk assessment for OSA has received little attention. PURPOSE: To evaluate whether cardiovascular responses to exercise testing and post-exercise recovery are altered in overweight young men with OSA. METHODS: Fourteen overweight men (BMI: Mean + SD = 32.0 + 3.7, age = 22.4 + 2.8 yr) with OSA determined via unattended polysomnography screening (Embletta pds; Embla, Broomfield, CO), 16 men without OSA (BMI = 31.4 + 3.7, age = 21.4 + 2.6), and 14 normal weight controls (BMI = 22.0+ 1.3, age 21.4+ 2.1) performed maximal cycle ergometry tests utilizing a 15 watts/min ramp. Exercise measurements included heart rate (HR), blood pressure (BP), and oxygen consumption (VO2). Recovery HR data were converted to a HR difference (i.e., HRpeak - HR 1-min recovery), and BP data converted to a recovery ratio for each minute. RESULTS: While relative VO2 did not differ between the two overweight groups at any level of exercise, values were higher in the normal weight group at all exercise intensities (repeated measures ANOVA; p < 0.05). However, when these results were adjusted for lean body mass, none of the groups differed in the VO2 response to exercise. During exercise, no group differences were noted in the HR or BP responses at any intensity. In contrast, post-exercise HR recovery was attenuated in the OSA group through minutes 1–5 (p = 0.009). BP recovery did not differ between groups. CONCLUSIONS: OSA is associated with attenuated HR recovery in young men following maximal exercise testing. This may indicate an imbalance in autonomic regulation of HR and provide an early clinical sign of OSA. Results suggest that, for young overweight men, the clinical exercise test may be helpful for risk stratification and patient selection for diagnostic testing with polysomnography. Supported by a grant from ResMed Sleep Disordered Breathing Foundation, Poway, CA. Additional support provided by Sensormedics, Yorba Linda, CA.