PURPOSE:Most studies applying repeated neuromuscular electrical stimulation (NMES) to assess intrinsic contractile properties employ frequencies considerably greater than the mean motor unit discharge rate (MUDR) for a given force level. It is hypothesized that force loss increases with stimulation frequency, but this has not been evaluated in the same pool of participants when other parameters are unchanged. Furthermore, there is a paucity of research investigating possible sex-based differences for force loss during an NMES protocol, with the presence or absence of a group difference seemingly dependent on stimulation frequency. To address these limitations, we compared force loss of electrically evoked contractions at (10 Hz), slightly above (15 Hz), and well above (30 Hz) the expected mean MUDR of the quadriceps at 25% maximal voluntary force. METHODS:On three separate occasions, 24 participants (12 females) received 3 min of intermittent NMES (10, 15, or 30 Hz) over the quadriceps of the dominant leg. RESULTS:Force impairment increased with NMES frequency (19.8 ± 14.5, 42.6 ± 8.1, and 52.9 ± 4.7 for 10, 15, and 30 Hz, respectively), with no significant differences between sexes. Relative to the start of each task, the rates of force development (RFD) and relaxation (RFR) slowed markedly during the 10-, 15-, and 30-Hz fatiguing protocols (RFD: 42.1 ± 13.5, 61.6 ± 13.2, and 75.9 ± 9.8; RFR: 38.0 ± 13.9, 64.2 ± 9.1, and 80.4 ± 5.0, respectively). RFD impairment was less at 10 compared with 15 and 30 Hz, whereas the slowing of RFR increased with NMES frequency. Post-hoc analysis revealed no sex-based differences at any time point for RFD or RFR. CONCLUSIONS:These findings underscore the impact of stimulus frequency on muscle fatigability and highlight a lack of sex-based differences for electrically evoked force loss, emphasizing the need for appropriate frequency selection in NMES protocols.

Intrathoracic pressure modulates cardiac loading conditions, which then influence left ventricular (LV) chamber function, and may occur with underlying myocardial mechanical alterations. We investigated the independent effects of inspiratory negative and expiratory positive intrathoracic pressure on septal geometry, LV chamber function, and rotation, twist, and strain indices. After baseline, 20 healthy adults (11M/9F, 23 ± 4 yr) performed resistive breathing to manipulate inspiratory (-30, -20, -10 cmH2O) or expiratory (+10, +20 cmH2O) intrathoracic pressure. Echocardiography was used to acquire LV-focused two-dimensional (2-D) images, and mitral Doppler inflow and annular tissue velocity spectra. Images were analyzed for LV chamber volumes, tissue velocities, transmitral filling velocities, and speckle tracking-derived LV longitudinal, radial, and circumferential strain and strain-rate, basal and apical rotation, and twist. Across negative pressure trials, most profoundly at -30 cmH2O, we observed progressive end-diastolic septal flattening (3.9 ± 0.4 vs. 3.2 ± 0.4 cm, P < 0.05) and decreases in LV end-diastolic volume (103 ± 23 vs. 115 ± 25 mL, P < 0.05) and stroke volume, whereas end-systolic volume was unchanged. However, LV apical and basal rotation, twist (13.3° ± 3.6° vs. 13.9° ± 3.7°, P = 0.890), and circumferential, radial, and longitudinal strain indices were largely unchanged. During positive pressure trials, we observed main effects for septal flattening (P = 0.014) confined to inspiration, and modestly reduced LV end-diastolic volume (P < 0.001), end-systolic volume (P = 0.033), and stroke volume. Again, myocardial mechanics parameters changed little. Collectively, our data suggest that both positive and negative intrathoracic pressures can exacerbate direct ventricular interaction through opposing mechanisms that attenuate LV end-diastolic volume and stroke volume, but without specific changes in myocardial mechanics or mitral inflow.NEW & NOTEWORTHY Incrementally more negative or positive intrathoracic pressures, relative to normal dynamic breathing, progressively attenuate left ventricular end-diastolic volume and stroke volume in healthy younger adults. Incrementally more negative or positive intrathoracic pressures were each associated with progressive septal flattening during inspiration, indicating direct ventricular interaction. However, left ventricular transmitral inflow velocities, and myocardial rotation, twist, and circumferential, longitudinal, and radial strain parameters changed little.

Study objective: Hypertrophic cardiomyopathy (HCM) is the most common genetic myocardial disorder increasingly characterized by concomitant metabolic syndrome. Cardiac rehabilitation (CR) has been shown to improve metabolic parameters in populations with heart failure and myocardial infarction. However, there is a paucity of data on the impact of CR in the HCM population with metabolic syndrome. We designed the REHABHCM study to explore the feasibility, safety, and efficacy of CR in HCM patients with metabolic syndrome. Design: Prospective observation cohort study. Setting: A multi-disciplinary HCM clinic and Multidisciplinary Exercise-based Cardiac Rehabilitation program. Participants: Patients aged 18-80 years old diagnosed with HCM and metabolic syndrome, defined by the American Heart Association and American College of Cardiology guidelines, and the National Cholesterol Education Adult Treatment Panel III (NCEP-ATP III) criteria. Intervention: A structured 3-month CR program with 6 months extended follow-up of physical activity levels. Main outcome measures: Feasibility (e.g., attendance), safety (e.g., major adverse events and exercise-related harms), and efficacy pertaining to long term improvements in physical activity levels, metabolic health, cardiorespiratory fitness, quality of life, and systemic and cellular markers of inflammation. Conclusion: This prospective cohort study will address an important knowledge gap by evaluating the effect of an organized CR program in HCM patients and metabolic syndrome. It is anticipated that exercise and CR will be feasible and beneficial for this complex patient population without significant exercise-related harms.

Rationale: Despite increasing complexity and disease severity of critical illness admissions to the intensive care unit (ICU), more people are surviving critical illness than in previous decades; however, post intensive care mortality remains high. There are currently no prognostic tools that are used to predict long-term outcomes in post-ICU survivors. Functional status, a measure of an individual's physical independence, is used prognostically to inform clinical decision making in diseases with high risk of long-term mortality, such as cardiorespiratory diseases and cancer. Thus, the purpose of this study was to investigate the prognostic significance of ICU functional status to predict long-term mortality in critical illness survivors. Methods: Using a retrospective design, functional status measured daily in patients who were in the ICU at St. Paul's Hospital in Vancouver, B.C. between 2019-2022 were collected. Patients were classified as having a high peak ICU functional status (i.e., standing or walking; n=311) or a low peak functional status (peak mobility of awake but supine; n=328). Patients were excluded if they were admitted to the ICU for <48 hours and if there were multiple admissions for an individual, only the index admission was included. Kaplan Meier estimates were performed to determine the independent association between functional status and survival. A multivariable cox proportional model was used to determine risk of all-cause mortality with adjustment for important covariates such as age, ICU length of stay, disease severity at ICU entry (APACHE II score), length of mechanical ventilation, the use of vasoactive drugs, and the presence of delirium. Results: There was a total of 2584 admissions to the ICU between 2019-2022. Of those, 311 were classified as having a high functional status and 328 as having low functional status. Median follow-up time was 24 months; 244 deaths were reported during this period. High ICU functional status was an independent predictor of overall survival in the Kaplan Meier analysis (p=0.024). Compared with low ICU functional status, the adjusted Hazard Ratio (HR) for all-cause mortality was 0.76 (CI, 0.58-0.9) for the high functional status group. Conclusions: Peak ICU functional status predicts long-term survival probability. Individuals with high ICU functional status experience a significantly lower risk of mortality after ICU discharge.

Although the gross morphology of the heart is conserved across mammals, subtle interspecific variations exist in the cardiac phenotype, which may reflect evolutionary divergence among closely-related species. Here, we compare the left ventricle (LV) across all extant members of the Hominidae taxon, using 2D echocardiography, to gain insight into the evolution of the human heart. We present compelling evidence that the human LV has diverged away from a more trabeculated phenotype present in all other great apes, towards a ventricular wall with proportionally greater compact myocardium, which was corroborated by post-mortem chimpanzee (Pan troglodytes) hearts. Speckle-tracking echocardiographic analyses identified a negative curvilinear relationship between the degree of trabeculation and LV systolic twist, revealing lower rotational mechanics in the trabeculated non-human great ape LV. This divergent evolution of the human heart may have facilitated the augmentation of cardiac output to support the metabolic and thermoregulatory demands of the human ecological niche.

PURPOSE:Research on intermittent training has mainly focused on the effects of exercise intensity while overlooking the specific effect of the modulations associated with alternating exercise and recovery. This study investigated how the frequency of modulations during moderate-intensity exercise affects postexercise vagal reactivation. METHODS:Healthy, active females and males 18-39 yr old were recruited for the study. Participants completed three treadmill running sessions on separate days. Each moderate-intensity session accumulated 30 min at 90% of the intensity associated with the second ventilatory threshold and was performed as either high-frequency intermittent (HiFi; 15 × [2 min + 2 min recovery]), low-frequency intermittent (LoFi; 5 × [6 min + 2 min recovery]), or moderate-intensity continuous training (MICT; 1 × 30 min). Heart rate recovery (HR rec ) at 1 min and heart rate variability recovery (HRV rec ; lnRMSSD) were assessed in response to submaximal constant-speed tests performed before (CST1) and after (CST2) each of the exercise sessions. HR rec , HRV rec , blood lactate (BLa), and blood pressure were also collected during the exercise sessions. RESULTS:Twenty-one individuals (8 females, 13 males) participated in the study. HR rec from CST2 was faster in HiFi versus MICT ( P < 0.001), whereas HRV rec post-CST2 was higher after HiFi versus both LoFi ( P = 0.024) and MICT ( P < 0.001). BLa increased in all conditions ( P = 0.007) but remained lower during HiFi compared with LoFi and MICT (both P < 0.001). Diastolic blood pressure did not change during exercise with HiFi ( P = 0.939) but decreased during LoFi ( P = 0.006) and MICT ( P = 0.008). CONCLUSIONS:Exercise pattern influences the physiologic response to exercise. Higher frequencies of modulations can preserve vagal activity and expedite postexercise recovery, suggesting moderate-intensity intermittent exercise as a potential strategy to mitigate autonomic impact and acute physiological stress while maintaining total work performed.

Pulmonary arterial hypertension affects females more frequently than males, and there are known sex-related differences in the lungs. However, normal sex-related differences in pulmonary vascular structure remain incompletely described. We aimed to contrast computed tomography-derived pulmonary vascular volume and its distribution within the lungs of healthy adult females and males. From the CanCOLD Study, we retrospectively identified healthy never-smokers. We analyzed full-inspiration computed tomography images, using vessel and airway segmentation to generate pulmonary vessel volume, vessel counts, and airway counts. Vessels were classified by cross-sectional area >10, 5-10, and <5 mm2 into bins, with volume summed within each area bin and in total. We included 46 females and 36 males (62 ± 9 years old). Females had lower total lung volume, total airway counts, total vessel counts, and total vessel volume (117 ± 31 vs. 164 ± 28 mL) versus males (all p < 0.001). Females also had lower vessel volume >10 mm2 (14 ± 8 vs. 27 ± 9 mL), vessel volume 5-10 mm2 (35 ± 11 vs. 55 ± 10 mL), and vessel volume <5 mm2 (68 ± 18 vs. 82 ± 19 mL) (all p < 0.001). Normalized to total vessel volume, vessel volume >10 mm2 (11 ± 4 vs. 16 ± 4%, p < 0.001) and 5-10 mm2 (30 ± 6 vs. 34 ± 5%, p = 0.001) remained lower in females but vessel volume <5 mm2 relative to total volume was 18% higher (59 ± 8 vs. 50 ± 7%, p < 0.001). Among healthy older adults, pulmonary vessel volume is distributed into smaller vessels in females versus males.

Exercise training requires the careful application of training dose to maximize adaptation while minimizing the risk of illness and injury. High-intensity interval training (HIIT) is a potent method for improving health and fitness but generates substantial autonomic imbalance. Assuming a supine posture between intervals is a novel strategy that could enhance physiological readiness and training adaptations. This study aimed to establish the safety and feasibility of supine recovery within a HIIT session and explore its acute effects. Fifteen healthy, active males (18–34 years) underwent assessment of cardiopulmonary fitness. Participants completed two identical HIIT treadmill sessions (4 x [3 min at 95

BACKGROUND:Despite the known interplay between blood flow and function, to our knowledge, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound to quantify relative diaphragm blood flow (Q˙DIA) in humans and assessed the technique's efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that: (1) Q˙DIA would linearly increase with pressure generation, and (2) that there would be good test-retest reliability and interanalyzer reproducibility. RESEARCH QUESTION:Can we validate what is, to our knowledge, the first minimally invasive method to measure relative diaphragm blood flow in humans? STUDY DESIGN AND METHODS:Quantitative contrast-enhanced ultrasound of the costal diaphragm was performed in healthy participants (10 male participants, 6 female participants; mean age 28 ± 5 years; BMI 22.8 ± 2.0 kg/m) during unloaded breathing and three stages of loaded breathing on two separate days. Gastric and esophageal balloon catheters measured transdiaphragmatic pressure. Ultrasonography was performed during a constant-rate IV infusion of lipid-stabilized microbubbles following each stage. Ultrasound images were acquired after a destruction-replenishment sequence and diaphragm specific time-intensity data were used to determine Q˙DIA by two individuals. RESULTS:Transdiaphragmatic pressure for unloaded and each loading stage were 15.2 ± 0.8, 26.1 ± 0.8, 34.6 ± 0.8, and 40.0 ± 0.8 percentage of the maximum, respectively. Q˙DIA increased with each stage of loading (3.1 ± 3.1, 6.9 ± 3.6, 11.0 ± 4.9, and 13.5 ± 5.4 acoustic units/s; P < .0001). The linear relationship between diaphragmatic flow and pressure was reproducible from day to day. Q˙DIA had good to excellent test-retest reliability (0.86 [0.77, 0.92]; P < .0001) and excellent interanalyzer reproducibility (0.93 [0.90, 0.95]; P < .0001) with minimal bias. INTERPRETATION:Relative Q˙DIA measurements had valid physiological underpinnings, were reliable day-to-day, and were reproducible analyzer-to-analyzer. This study indicated that contrast-enhanced ultrasound is a viable, minimally invasive method for assessing costal Q˙DIA in humans and may provide a tool to monitor diaphragm hemodynamics in clinical settings.

Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardiovagal arms. Since sympathetic postganglionic neurons also innervate the left ventricle (LV), it is often assumed that the LV produces a sympathetically mediated increase in contractility during baroreceptor unloading, but this has not been characterized using a load-independent index of contractility. We aimed to determine 1) whether LV contractility increases in response to baroreceptor unloading and 2) whether such increases are mediated via the sympathetic or parasympathetic arm of the autonomic nervous system. Ten male Wistar rats were anesthetized (urethane) and instrumented with arterial and LV pressure-volume catheters to measure mean arterial pressure (MAP) and load-independent LV contractility [maximal rate of increase in pressure adjusted to end-diastolic volume (PAdP/dtmax)], respectively. Rats were placed in a servo-controlled lower-body negative pressure (LBNP) chamber to reduce MAP by 10% for 60 s to mechanically unload baroreceptors under control conditions. LBNP was repeated in each animal following infusions of cardiac autonomic blockers using esmolol (sympathetic), atropine (parasympathetic), and esmolol + atropine. Under control conditions, PAdP/dtmax increased during baroreceptor unloading (26 ± 6 vs. 31 ± 9 mmHg·s-1·μL-1, P = 0.031). During esmolol, there was no increase in LV contractility during baroreceptor unloading (11 ± 2 vs. 12 ± 2, P = 0.125); however, during atropine, there was an increase in LV contractility during baroreceptor unloading (26 ± 6 vs. 31 ± 9, P = 0.019). During combined esmolol and atropine, there was a small increase in contractility versus control (13 ± 3 vs. 15 ± 4, P = 0.046). Our results demonstrate that, in anesthetized rats, LV contractility increases in response to baroreceptor unloading, which is largely sympathetically mediated.NEW & NOTEWORTHY This study empirically demonstrates a sympathetically mediated increase in LV contractility in response to baroreceptor unloading using a load-independent index of cardiac contractility in the anesthetized rat.

Historically, it was thought that healthy humans predominantly described their breathing as a sense of increased work or effort (W/E) during maximal exercise. However, emerging data show that many healthy adults select unpleasant dyspnea descriptors such as "unsatisfied inspiration" (UI), with relatively more females selecting UI than males. We hypothesized that males and females who select UI would report higher dyspnea intensity ratings during exercise, select more distressing dyspnea qualities post exercise, and have greater inspiratory constraints than those who do not. Sixty-four healthy, nonsmokers (32 males:32 females; 23 ± 5 yr) completed questionnaires, pulmonary function tests, and maximal incremental cycling with detailed dyspnea evaluation. Males in UI and non-UI subgroups reported similar Borg 0-10 dyspnea intensity ratings of W/E, UI, and unsatisfied expiration (UE) (all P > 0.05). Females in the UI subgroup reported significantly higher UI and UE ratings than females in the non-UI subgroup (both P < 0.01). Both UI subgroups reported greater air hunger, chest tightness, and mental breathing effort than non-UI participants (all P < 0.05). In males only, masculine gender was negatively correlated (ρ = -0.402, P = 0.02) and anxiety positively correlated (ρ = 0.363, P = 0.04) with submaximal UI ratings. Females with UI had smaller peak tidal volume (Vt) [1.74 (0.32) vs. 2.06 (0.33) L, P = 0.03] than non-UI females; and Vt was negatively correlated with submaximal (ρ = -0.496, P = 0.004) and peak (ρ = -0.495, P = 0.004) UI ratings in all females. There were no differences in Vt or correlations between Vt and dyspnea in male subgroups. Absolute lung volumes and psychosocial factors appear important in understanding sex differences in the perception of UI during exercise.NEW & NOTEWORTHY The mechanisms of sex-based differences in the sensation of unsatisfied inspiration (UI) in healthy humans during exercise are poorly understood. We found that females who selected UI at peak exercise had worse dyspnea intensity ratings throughout exercise. Both sexes who selected UI at peak exercise also reported more distressing dyspnea qualities post exercise. Psychosocial factors appeared to influence male dyspnea perception, whereas smaller absolute lung volumes correlated with worse UI ratings in females.

ABSTRACT Purpose The purpose of this study is to evaluate the prevalence of abnormal cardiopulmonary responses to exercise and pathophysiological mechanism(s) underpinning exercise intolerance across the continuum of breast cancer (BC) care from diagnosis to metastatic disease. Methods Individual participant data from four randomized trials spanning the BC continuum ([1] prechemotherapy [ n = 146], [2] immediately postchemotherapy [ n = 48], [3] survivorship [ n = 138], and [4] metastatic [ n = 47]) were pooled and compared with women at high-risk of BC (BC risk; n = 64). Identical treadmill-based peak cardiopulmonary exercise testing protocols evaluated exercise intolerance (peak oxygen consumption; V̇O 2peak ) and other resting, submaximal, and peak cardiopulmonary responses. The prevalence of 12 abnormal exercise responses was evaluated. Graphical plots of exercise responses were used to identify oxygen delivery and/or uptake mechanisms contributing to exercise intolerance. Unsupervised, hierarchical cluster analysis was conducted to explore exercise response phenogroups. Results Mean V̇O 2peak was 2.78 ml O 2 . kg −1 ·min −1 (95% confidence interval [CI], −3.94, −1.62 mL O 2 . kg −1 ·min −1 ; P < 0.001) lower in the pooled BC cohort (52 ± 11 yr) than BC risk (55 ± 10 yr). Compared with BC risk, the pooled BC cohort had a 2.5-fold increased risk of any abnormal cardiopulmonary response (odds ratio, 2.5; 95% confidence interval, 1.2, 5.3; P = 0.014). Distinct exercise responses in BC reflected impaired oxygen delivery and uptake relative to control, although considerable inter-individual heterogeneity within cohorts was observed. In unsupervised, hierarchical cluster analysis, six phenogroups were identified with marked differences in cardiopulmonary response patterns and unique clinical characteristics. Conclusions Abnormal cardiopulmonary response to exercise is common in BC and is related to impairments in oxygen delivery and uptake. The identification of exercise response phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions.

Skeletal muscle atrophy, dysfunction, and fatigue are important complications of chronic obstructive pulmonary disease (COPD). Greater reliance on glycolytic metabolism and increased type III/IV muscle afferent activity increase ventilatory drive, promote ventilatory constraint, amplify exertional dyspnea, and limit exercise tolerance. To investigate whether muscular adaptation with resistance training (RT) could improve exertional dyspnea, exercise tolerance, and intrinsic neuromuscular fatigability in individuals with COPD (n = 14, FEV1 = 62 ± 21% predicted), we performed a proof-of-concept single-arm efficacy study utilizing 4 wk of individualized lower-limb RT (3 times/wk). At baseline, dyspnea (Borg scale), ventilatory parameters, lung volumes (inspiratory capacity maneuvers), and exercise time were measured during a constant-load test (CLT) at 75% maximal workload to symptom limitation. On a separate day, fatigability was assessed using 3 min of intermittent stimulation of the quadriceps (initial output of ∼25% maximal voluntary force). Following RT, the CLT and fatigue protocols were repeated. Compared with baseline, isotime dyspnea was reduced (5.9 ± 2.4 vs. 4.5 ± 2.4 Borg units, P = 0.02) and exercise time increased (437 ± 405 s vs. 606 ± 447 s, P < 0.01) following RT. Isotime tidal volume increased (P = 0.01), whereas end-expiratory lung volumes (P = 0.02) and heart rate (P = 0.03) decreased. Quadriceps force, relative to initial force, was higher at the end of the stimulation protocol posttraining (53.2 ± 9.1 vs. 46.8 ± 11.9%, P = 0.04). This study provides evidence that 4 wk of RT attenuates exertional dyspnea and improves exercise tolerance in individuals with COPD, which in part, is likely due to delayed ventilatory constraint and reduced intrinsic fatigability. A pulmonary rehabilitation program beginning with individualized lower-limb RT may help mitigate dyspnea before performing aerobic training in individuals with COPD.NEW & NOTEWORTHY This study presents the novel finding that 4-wk resistance training (RT) focused specifically on the lower limbs can reduce exertional dyspnea during constant-load cycling, improve exercise tolerance, and reduce intrinsic fatigability of the quadriceps in individuals with COPD.

In healthy younger adults, the Mueller maneuver transiently reduces left atrial filling and passive emptying during the reservoir and conduit phases, respectively. Corresponding reductions are seen in left atrial reservoir and conduit phase longitudinal myocardial strain and strain rate. However, left atrial pump phase active function and mechanics are largely preserved compared with baseline. Rapid changes in LA chamber volumes and myocardial strain with recurrent forceful inspiratory efforts and relaxation may reflect acute LA stress.

AIMS:The most appropriate timing of exercise therapy to improve cardiorespiratory fitness (CRF) among patients initiating chemotherapy is not known. The effects of exercise therapy administered during, following, or during and following chemotherapy were examined in patients with breast cancer. METHODS AND RESULTS:Using a parallel-group randomized trial design, 158 inactive women with breast cancer initiating (neo)adjuvant chemotherapy were allocated to receive (1:1 ratio): usual care or one of three exercise regimens-concurrent (during chemotherapy only), sequential (after chemotherapy only), or concurrent and sequential (continuous) (n = 39/40 per group). Exercise consisted of treadmill walking three sessions/week, 20-50 min at 55%-100% of peak oxygen consumption (VO2peak) for ≈16 (concurrent, sequential) or ≈32 (continuous) consecutive weeks. VO2peak was evaluated at baseline (pre-treatment), immediately post-chemotherapy, and ≈16 weeks after chemotherapy. In intention-to-treat analysis, there was no difference in the primary endpoint of VO2peak change between concurrent exercise and usual care during chemotherapy vs. VO2peak change between sequential exercise and usual care after chemotherapy [overall difference, -0.88 mL O2·kg-1·min-1; 95% confidence interval (CI): -3.36, 1.59, P = 0.48]. In secondary analysis, continuous exercise, approximately equal to twice the length of the other regimens, was well-tolerated and the only strategy associated with significant improvements in VO2peak from baseline to post-intervention (1.74 mL O2·kg-1·min-1, P < 0.001). CONCLUSION:There was no statistical difference in CRF improvement between concurrent vs. sequential exercise therapy relative to usual care in women with primary breast cancer. The promising tolerability and CRF benefit of ≈32 weeks of continuous exercise therapy warrant further evaluation in larger trials.

Background:Estimated peak oxygen consumption (Vo2peak) is widely used in oncology; however, estimated Vo2peak equations were developed in noncancer settings. Objectives:The aim of this study was to evaluate the validity of estimated Vo2peak in women with primary breast cancer and to develop oncology-specific estimated Vo2peak equations. Methods:Vo2peak was directly measured (TrueOne 2400, Parvo Medics) during 380 cardiopulmonary exercise tests in women previously treated for breast cancer (mean age: 59 ± 10 years; 3.1 ± 1.2 years post-therapy). The American College of Sports Medicine (ACSM), the Fitness Registry and the Importance of Exercise National Database (FRIEND), and heart failure (HF)-FRIEND equations were used to estimate Vo2peak. New equations were developed using patient and peak (Oncpeak) or submaximal (Oncsub) exercise test characteristics. Results:The median differences between measured and estimated Vo2peak were 7.0 mL O2·kg-1·min-1, 3.9 mL O2·kg-1·min-1, and -0.2 mL O2·kg-1·min-1 for ACSM, FRIEND, and HF-FRIEND, respectively. The number of estimated Vo2peak values within ±3.5 mL O2·kg-1·min-1 of the measured values was 70 (18%), 164 (43%), and 306 (81%) for ACSM, FRIEND, and HF-FRIEND, respectively. The Oncpeak and OncSub models included body mass index, age, a history of chemotherapy or radiation, the peak measured heart rate, and the treadmill grade and/or speed. The median differences between measured and estimated Vo2peak were 0.02 mL O2·kg-1·min-1 (Oncpeak) and -0.2 mL O2·kg-1·min-1 (Oncsub). Eighty-six percent (n = 325) and 76% (n = 283) estimated Vo2peak values were within ±3.5 mL O2·kg-1·min-1 of the measured Vo2peak values for Oncpeak and Oncsub, respectively. Conclusions:HF-FRIEND or oncology-specific equations could be applied to estimate Vo2peak in patients previously treated for breast cancer in settings where cardiopulmonary exercise tests are not available. (Trial Comparing the Effects of Linear Versus Nonlinear Aerobic Training in Women With Operable Breast Cancer [EXCITE]; NCT01186367.

Background Exercise limitation in chronic obstructive pulmonary disease (COPD) is commonly attributed to abnormal ventilatory mechanics and/or skeletal muscle function, while cardiovascular contributions remain relatively understudied. To date, the integrative exercise responses associated with different cardiopulmonary exercise limitation phenotypes in COPD have not been explored but may provide novel therapeutic utility. This study determined the ventilatory, cardiovascular, and metabolic responses to incremental exercise in patients with COPD with different exercise limitation phenotypes. Methods Patients with COPD (n = 95, FEV1:23–113%pred) performed a pulmonary function test and incremental cardiopulmonary exercise test. Exercise limitation phenotypes were classified as: ventilatory [peak ventilation (VEpeak)/maximal ventilatory capacity (MVC) ≥ 85% or MVC-VEpeak ≤ 11 L/min, and peak heart rate (HRpeak) < 90%pred], cardiovascular (VEpeak/MVC < 85% or MVC-VEpeak > 11 L/min, and HRpeak ≥ 90%pred), or combined (VEpeak/MVC ≥ 85% or MVC-VEpeak ≤ 11 L/min, and HRpeak ≥ 90%pred). Results FEV1 varied within phenotype: ventilatory (23–75%pred), combined (28–90%pred), and cardiovascular (68–113%pred). The cardiovascular phenotype had less static hyperinflation, a lower end-expiratory lung volume and larger tidal volume at peak exercise compared to both other phenotypes (p < 0.01 for all). The cardiovascular phenotype reached a higher VEpeak (60.8 ± 11.5 L/min vs. 45.3 ± 15.5 L/min, p = 0.002), cardiopulmonary fitness (VO2peak: 20.6 ± 4.0 ml/kg/min vs. 15.2 ± 3.3 ml/kg/min, p < 0.001), and maximum workload (103 ± 34 W vs. 72 ± 27 W, p < 0.01) vs. the ventilatory phenotype, but was similar to the combined phenotype. Conclusion Distinct exercise limitation phenotypes were identified in COPD that were not solely dependent upon airflow limitation severity. Approximately 50% of patients reached maximal heart rate, indicating that peak cardiac output and convective O2 delivery contributed to exercise limitation. Categorizing patients with COPD phenotypically may aid in optimizing exercise prescription for rehabilitative purposes.