Identifying the Mechanisms of a Peripherally Limited Exercise Phenotype in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation. METHODS: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO2) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO2 slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO2, and muscle oxygen diffusive conductance. In a subset of participants (n=36), phosphocreatine recovery time was measured by magnetic resonance spectroscopy to determine skeletal muscle oxidative capacity. RESULTS: Peak VO2 during cardiopulmonary exercise testing was not different between groups (central: 13.9±5.7 versus peripheral: 12.0±3.1 mL/min per kg; P=0.135); however, the peripheral group had a lower peak arterial-to-venous oxygen content difference (central: 13.5±2.0 versus peripheral: 11.1±1.6 mLO2/dL blood; P<0.001). During single leg knee extension, there was no difference in peak leg VO2 (P=0.306), but the peripherally limited group had greater blood flow/VO2 ratio (P=0.024), lower arterial-to-venous oxygen content difference (central: 12.3±2.5 versus peripheral: 10.3±2.2 mLO2/dL blood; P=0.013), and lower muscle oxygen diffusive conductance (P=0.021). A difference in magnetic resonance spectroscopy-derived phosphocreatine recovery time was not detected (P=0.199). CONCLUSIONS: Peripherally limited patients with heart failure with preserved ejection fraction identified by cardiopulmonary exercise testing have impairments in oxygen transport and utilization at the level of the skeletal muscle quantified by invasive knee extension exercise testing, which includes an increased blood flow/V̇O2 ratio and poor muscle diffusive capacity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04068844.

Racial Disparities in Sports Cardiology: A Review.

Importance: Racial disparities in cardiovascular health, including sudden cardiac death (SCD), exist among both the general and athlete populations. Among competitive athletes, disparities in health outcomes potentially influenced by social determinants of health (SDOH) and structural racism remain inadequately understood. This narrative review centers on race in sports cardiology, addressing racial disparities in SCD risk, false-positive cardiac screening rates among athletes, and the prevalence of left ventricular hypertrophy, and encourages a reexamination of race-based practices in sports cardiology, such as the interpretation of screening 12-lead electrocardiogram findings. Observations: Drawing from an array of sources, including epidemiological data and broader medical literature, this narrative review discusses racial disparities in sports cardiology and calls for a paradigm shift in approach that encompasses 3 key principles: race-conscious awareness, clinical inclusivity, and research-driven refinement of clinical practice. These proposed principles call for a shift away from race-based assumptions towards individualized, health-focused care in sports cardiology. This shift would include fostering awareness of sociopolitical constructs, diversifying the medical team workforce, and conducting diverse, evidence-based research to better understand disparities and address inequities in sports cardiology care. Conclusions and Relevance: In sports cardiology, inadequate consideration of the impact of structural racism and SDOH on racial disparities in health outcomes among athletes has resulted in potential biases in current normative standards and in the clinical approach to the cardiovascular care of athletes. An evidence-based approach to successfully address disparities requires pivoting from outdated race-based practices to a race-conscious framework to better understand and improve health care outcomes for diverse athletic populations.

Simulating ultrafast transient absorption spectra from first principles using a time-dependent configuration interaction probe.

Transient absorption spectroscopy (TAS) is among the most common ultrafast photochemical experiments, but its interpretation remains challenging. In this work, we present an efficient and robust method for simulating TAS signals from first principles. Excited-state absorption and stimulated emission (SE) signals are computed using time-dependent complete active space configuration interaction (TD-CASCI) simulations, leveraging the robustness of time-domain simulation to minimize electronic structure failure. We demonstrate our approach by simulating the TAS signal of 1'-hydroxy-2'-acetonapthone (HAN) from ab initio multiple spawning nonadiabatic molecular dynamics simulations. Our results are compared to gas-phase TAS data recorded from both jet-cooled (T ∼ 40 K) and hot (∼403 K) molecules via cavity-enhanced TAS (CE-TAS). Decomposition of the computed spectrum allows us to assign a rise in the SE signal to excited-state proton transfer and the ultimate decay of the signal to relaxation through a twisted conical intersection. The total cost of computing the observable signal (∼1700 graphics processing unit hours for ∼4 ns of electron dynamics) was markedly less than that of performing the ab initio multiple spawning calculations used to compute the underlying nonadiabatic dynamics.

The role of the plasmon in interfacial charge transfer.

The lack of a detailed mechanistic understanding for plasmon-mediated charge transfer at metal-semiconductor interfaces severely limits the design of efficient photovoltaic and photocatalytic devices. A major remaining question is the relative contribution from indirect transfer of hot electrons generated by plasmon decay in the metal to the semiconductor compared to direct metal-to-semiconductor interfacial charge transfer. Here, we demonstrate an overall electron transfer efficiency of 44 ± 3% from gold nanorods to titanium oxide shells when excited on resonance. We prove that half of it originates from direct interfacial charge transfer mediated specifically by exciting the plasmon. We are able to distinguish between direct and indirect pathways through multimodal frequency-resolved approach measuring the homogeneous plasmon linewidth by single-particle scattering spectroscopy and time-resolved transient absorption spectroscopy with variable pump wavelengths. Our results signify that the direct plasmon-induced charge transfer pathway is a promising way to improve hot carrier extraction efficiency by circumventing metal intrinsic decay that results mainly in nonspecific heating.

Impaired longitudinal systolic-diastolic coupling and cardiac response to exercise in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), impaired augmentation of stroke volume and diastolic dysfunction contribute to exercise intolerance. Systolic-diastolic (S-D) coupling characterizes how systolic contraction of the left ventricle (LV) primes efficient elastic recoil during early diastole. Impaired S-D coupling may contribute to the impaired cardiac response to exercise in patients with HCM. METHODS: Patients with HCM (n = 25, age = 47 ± 9 years) and healthy adults (n = 115, age = 49 ± 10 years) underwent a cardiopulmonary exercise testing (CPET) and echocardiogram. S-D coupling was defined as the ratio of LV longitudinal excursion of the mitral annulus during early diastole (EDexc) and systole (Sexc) and compared between groups. Peak oxygen uptake (peak V̇O2) (Douglas bags), cardiac index (C2H2 rebreathe), and stroke volume index (SVi) were assessed during CPET. Linear regression was performed between S-D coupling and peak V̇O2, peak cardiac index, and peak SVi. RESULTS: S-D coupling was lower in HCM (Controls: 0.63 ± 0.08, HCM: 0.56 ± 0.10, p < 0.001). Peak V̇O2 and stroke volume reserve were lower in patients with HCM (Peak VO2 Controls: 28.5 ± 5.5, HCM: 23.7 ± 7.2 mL/kg/min, p < 0.001, SV reserve: Controls 39 ± 16, HCM 30 ± 18 mL, p = 0.008). In patients with HCM, S-D coupling was associated with peak V̇O2 (r = 0.47, p = 0.018), peak cardiac index (r = 0.60, p = 0.002), and peak SVi (r = 0.63, p < 0.001). CONCLUSION: Systolic-diastolic coupling was impaired in patients with HCM and was associated with fitness and the cardiac response to exercise. Inefficient S-D coupling may link insufficient stroke volume generation, diastolic dysfunction, and exercise intolerance in HCM.

Physical Activity and Progression of Coronary Artery Calcification in Men and Women.

Importance: Prior cross-sectional studies have suggested that very high levels of physical activity (PA) are associated with a higher prevalence of coronary artery calcium (CAC). However, less is known regarding the association between high-volume PA and progression of CAC over time. Objective: To explore the association between PA (measured at baseline and during follow-up) and the progression of CAC over time. Design, Setting, and Participants: This cohort study included data from 8771 apparently healthy men and women 40 years and older who had multiple preventive medicine visits at the Cooper Clinic (Dallas, Texas), with a mean (SD) follow-up time of 7.8 (4.7) years between the first and last clinic visit. Participants with reported PA and CAC measurements at each visit during 1998 to 2019 were included in the study. Data were analyzed from March 2023 to February 2024. Exposures: PA reported at baseline and follow-up, examined continuously per 500 metabolic equivalent of task minutes per week (MET-min/wk) and categorically: less than 1500, 1500 to 2999, 3000 or more MET-min/wk. Main Outcomes and Measures: Negative binomial regression was used to estimate the rate of mean CAC progression between visits, with potential modification by PA volume, calculated as the mean of PA at baseline and follow-up. In addition, proportional hazards regression was used to estimate hazard ratios for baseline PA as a predictor of CAC progression to 100 or more Agatston units (AU). Results: Among 8771 participants, the mean (SD) age at baseline was 50.2 (7.3) years for men and 51.1 (7.3) years for women. The rate of mean CAC progression per year from baseline was 28.5% in men and 32.1% in women, independent of mean PA during the same time period. That is, the difference in the rate of CAC progression per year was 0.0% per 500 MET-min/wk for men and women (men: 95% CI, -0.1% to 0.1%; women: 95% CI, -0.4% to 0.5%). Moreover, baseline PA was not associated with CAC progression to a clinically meaningful threshold of 100 AU or more over the follow-up period. The hazard ratio for a baseline PA value of 3000 or more MET-min/wk vs less than 1500 MET-min/wk to cross this threshold was 0.84 (95% CI, 0.66 to 1.08) in men and 1.16 (95% CI, 0.57 to 2.35) in women. Conclusions and Relevance: This study found that PA volume was not associated with progression of CAC in a large cohort of healthy men and women who were initially free of overt cardiovascular disease.

Coherence mapping to identify the intermediates of multi-channel dissociative ionization.

Identifying the short-lived intermediates and reaction mechanisms of multi-channel radical cation fragmentation processes remains a current and important challenge to understanding and predicting mass spectra. We find that coherent oscillations in the femtosecond time-dependent yields of several product ions following ultrafast strong-field ionization represent spectroscopic signatures that elucidate their mechanism of formation and identify the intermediate(s) they originate from. Experiments on endo-dicyclopentadiene show that vibrational frequencies from various intermediates are mapped onto their resulting products. Aided by ab initio methods, we identify the vibrational modes of both the cleaved and intact molecular ion intermediates. These results confirm stepwise and concerted fragmentation pathways of the dicyclopentadiene ion. This study highlights the power of tracking the femtosecond dynamics of all product ions simultaneously and sheds further light onto one of the fundamental reaction mechanisms in mass spectrometry, the retro-Diels Alder reaction.

Respiratory symptom perception during exercise in patients with heart failure with preserved ejection fraction.

We investigated whether central or peripheral limitations to oxygen uptake elicit different respiratory sensations and whether dyspnea on exertion (DOE) provokes unpleasantness and negative emotions in patients with heart failure with preserved ejection fraction (HFpEF). 48 patients were categorized based on their cardiac output (Q̇c)/oxygen uptake (V̇O2) slope and stroke volume (SV) reserve during an incremental cycling test. 15 were classified as centrally limited and 33 were classified as peripherally limited. Ratings of perceived breathlessness (RPB) and unpleasantness (RPU) were assessed (Borg 0-10 scale) during a 20 W cycling test. 15 respiratory sensations statements (1-10 scale) and 5 negative emotions statements (1-10) were subsequently rated. RPB (Central: 3.5±2.0 vs. Peripheral: 3.4±2.0, p=0.86), respiratory sensations, or negative emotions were not different between groups (p>0.05). RPB correlated (p<0.05) with RPU (r=0.925), "anxious" (r=0.610), and "afraid" (r=0.383). While DOE provokes elevated levels of negative emotions, DOE and respiratory sensations seem more related to a common mechanism rather than central and/or peripheral limitations in HFpEF.

Coronary Artery Calcification and High-Volume Physical Activity: Role of Lower Intensity versus Longer Duration of Exercise.

AIM: While high-volume physical activity (PA) has been linked to elevated coronary artery calcification (CAC), the role of intensity versus duration of PA has not been investigated. The purpose of the study was to examine the role of intensity versus duration of PA in relation to CAC. METHODS: Data are from 23,383 apparently healthy men who completed a PA questionnaire and underwent CAC scanning as part of a preventive exam. Self-reported PA was categorized into 4 groups of average intensity and weekly duration of PA and (average intensity: 1, 3-5.9, 6-8.9, and 9-12 metabolic equivalents of task [METs]; weekly duration: 0, > 0-<2, 2-<5, and ≥5 hours/week). Mean CAC and CAC ≥ 100 Agatston Units (AU) were regressed separately on continuous or categorical average intensity and weekly duration of PA. RESULTS: The mean and standard deviation (SD) age was 51.7 (8.3) years, and mean CAC was 174.8 (543.6) AU with 23.5% of men presenting with CAC ≥ 100 AU. Higher average intensity of PA was related to lower mean CAC (-3.1%/MET, 95% confidence interval [CI]: -4.6, -1.6%/MET) and lower relative risk (RR) of CAC ≥ 100 AU (RR: 0.99, 95% CI: 0.98, 1.00/MET). Opposite trend was observed for the duration component wherein higher weekly duration of PA was significantly associated with greater mean CAC and RR of CAC ≥ 100 AU. CONCLUSIONS: Elevated CAC was associated with lower average intensity and longer duration of PA in men, providing new insight into the complex relationship between leisure-time PA behaviors and risk of CAC.

Does greater extent of coronary artery calcification observed at high volumes of leisure time physical activity relate more to the intensity or the duration of the activity? Higher average intensity of activity is associated with less coronary artery calcification at any age and weekly duration of activity.Higher weekly duration of activity is associated with more coronary artery calcification at any age and average intensity of activity.

Prediction challenge: First principles simulation of the ultrafast electron diffraction spectrum of cyclobutanone.

Computer simulation has long been an essential partner of ultrafast experiments, allowing the assignment of microscopic mechanistic detail to low-dimensional spectroscopic data. However, the ability of theory to make a priori predictions of ultrafast experimental results is relatively untested. Herein, as a part of a community challenge, we attempt to predict the signal of an upcoming ultrafast photochemical experiment using state-of-the-art theory in the context of preexisting experimental data. Specifically, we employ ab initio Ehrenfest with collapse to a block mixed quantum-classical simulations to describe the real-time evolution of the electrons and nuclei of cyclobutanone following excitation to the 3s Rydberg state. The gas-phase ultrafast electron diffraction (GUED) signal is simulated for direct comparison to an upcoming experiment at the Stanford Linear Accelerator Laboratory. Following initial ring-opening, dissociation via two distinct channels is observed: the C3 dissociation channel, producing cyclopropane and CO, and the C2 channel, producing CH2CO and C2H4. Direct calculations of the GUED signal indicate how the ring-opened intermediate, the C2 products, and the C3 products can be discriminated in the GUED signal. We also report an a priori analysis of anticipated errors in our predictions: without knowledge of the experimental result, which features of the spectrum do we feel confident we have predicted correctly, and which might we have wrong?

Right ventricular performance during acute hypoxic exercise.

Acute hypoxia increases pulmonary arterial (PA) pressures, though its effect on right ventricular (RV) function is controversial. The objective of this study was to characterize exertional RV performance during acute hypoxia. Ten healthy participants (34 ± 10 years, 7 males) completed three visits: visits 1 and 2 included non-invasive normoxic (fraction of inspired oxygen ( F i O 2 ${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) = 0.21) and isobaric hypoxic ( F i O 2 ${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$  = 0.12) cardiopulmonary exercise testing (CPET) to determine normoxic/hypoxic maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ ). Visit 3 involved invasive haemodynamic assessments where participants were randomized 1:1 to either Swan-Ganz or conductance catheterization to quantify RV performance via pressure-volume analysis. Arterial oxygen saturation was determined by blood gas analysis from radial arterial catheterization. During visit 3, participants completed invasive submaximal CPET testing at 50% normoxic V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ and again at 50% hypoxic V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ ( F i O 2 ${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$  = 0.12). Median (interquartile range) values for non-invasive V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ values during normoxic and hypoxic testing were 2.98 (2.43, 3.66) l/min and 1.84 (1.62, 2.25) l/min, respectively (P < 0.0001). Mean PA pressure increased significantly when transitioning from rest to submaximal exercise during normoxic and hypoxic conditions (P = 0.0014). Metrics of RV contractility including preload recruitable stroke work, dP/dtmax , and end-systolic pressure increased significantly during the transition from rest to exercise under normoxic and hypoxic conditions. Ventricular-arterial coupling was maintained during normoxic exercise at 50% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ . During submaximal exercise at 50% of hypoxic V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ , ventricular-arterial coupling declined but remained within normal limits. In conclusion, resting and exertional RV functions are preserved in response to acute exposure to hypoxia at an F i O 2 ${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}}}$  = 0.12 and the associated increase in PA pressures. KEY POINTS: The healthy right ventricle augments contractility, lusitropy and energetics during periods of increased metabolic demand (e.g. exercise) in acute hypoxic conditions. During submaximal exercise, ventricular-arterial coupling decreases but remains within normal limits, ensuring that cardiac output and systemic perfusion are maintained. These data describe right ventricular physiological responses during submaximal exercise under conditions of acute hypoxia, such as occurs during exposure to high altitude and/or acute hypoxic respiratory failure.

The effect of chronic habitual exercise on oxygen carrying capacity and blood compartment volumes in older adults.

Absolute total hemoglobin mass (tHbmass) and blood compartment volumes are often considered to be higher in endurance athletes compared with nonathletes, yet little data support a fitness effect in older age. Therefore, we measured tHbmass and blood compartment volumes (carbon monoxide rebreathing) in 77 healthy individuals (23% female; aged, 60-87 yr). Participants were recruited into groups based upon their lifelong (>25 yr) exercise "dose": 1) 15 sedentary individuals, <2 sessions/wk; 2) 25 casual exercisers, 2-3 sessions/wk; 3) 24 committed exercisers, 4-5 sessions/wk; and 4) 13 competitive Masters athletes, 6-7 sessions/wk, plus regular competitions. Absolute (L/min) and relative (mL/kg/min) V̇o2peak were higher with increasing exercise "dose" (P = 0.0005 and P < 0.0001, respectively). Hemoglobin concentration, hematocrit, and absolute tHbmass and blood compartment volumes were not significantly different between groups (all, P > 0.1328). When scaled to body mass, tHbmass (Sedentary, 9.2 ± 1.7 mL/kg; Casual, 9.2 ± 1.3; Committed, 10.2 ± 1.4; Competitive, 11.5 ± 1.4, ANOVA P < 0.0001) and blood volume were significantly different between groups [Sedentary, 63.4 (59.2-68.5) mL/kg; Casual, 67.3 (64.4-72.6); Committed, 73.5 (67.5-80.2); Competitive, 83.4 (78.9-88.6), ANOVA P < 0.0001], whereby all values were highest in Masters athletes. However, when scaled to fat-free mass (FFM), tHbmass and blood compartment volumes were greater in Competitive compared with Casual exercisers (all, P < 0.0340) and tHbmass and erythrocyte volume were also higher in Committed compared with Casual exercisers (both, P < 0.0134). In conclusion, absolute tHbmass and blood compartment volumes are not different between groups, with dose-dependent differences only among exercisers when scaled for FFM, with the highest tHbmass and blood compartment volumes in competitive Masters athletes.NEW & NOTEWORTHY We observed that absolute oxygen carrying capacity (total hemoglobin mass, tHbmass) and blood compartment volumes were not associated with lifelong exercise dose. However, hematological adaptations associated with lifelong habitual exercise are only present among exercisers, whereby competitive Masters athletes have a greater oxygen carrying capacity (tHbmass) and expanded blood compartment volumes when scaled to fat-free mass.

Sympathetic Neural Control at Rest and During the Cold Pressor Test in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: We tested the hypothesis that patients with heart failure with preserved ejection fraction (HFpEF) would have greater muscle sympathetic nerve activity (MSNA) at rest and sympathetic reactivity during a cold pressor test compared with non-heart failure controls. Further, given the importance of the baroreflex modulation of MSNA in the control of blood pressure (BP), we hypothesized that patients with HFpEF would exhibit a reduced sympathetic baroreflex sensitivity. METHODS: Twenty-eight patients with HFpEF and 44 matched controls (mean±SD: 71±8 versus 70±7 years; 9 men/19 women versus 16 men/28 women) were studied. BP, heart rate, and MSNA (microneurography) were measured during 6 to 10 minutes of supine rest and the 2-minute cold pressor test. Spontaneous sympathetic baroreflex sensitivity was assessed during supine rest. RESULTS: Patients with HFpEF had higher resting MSNA burst frequency (39±14 versus 31±12 bursts/min; P=0.020) and lower sympathetic baroreflex sensitivity (-2.83±0.76 versus -3.57±1.19 bursts/100 heartbeats/mm Hg; P=0.019) than controls, but burst incidence was not different between groups (56±19 versus 50±20 bursts/100 heartbeats; P=0.179). During the cold pressor test, increases in MSNA indices did not differ between groups (P=0.135-0.998), but patients had a smaller increase in diastolic BP (Δ4±6 versus Δ14±11 mm Hg; P<0.001) compared with controls. CONCLUSIONS: Despite augmented resting MSNA burst frequency, burst incidence was not significantly different between groups, and sympathetic baroreflex sensitivity was reduced in patients with HFpEF. Furthermore, patients had preserved sympathetic reactivity but attenuated diastolic BP responses during the cold pressor test. These data suggest that, during physiological stress, sympathetic reactivity is intact, but the peripheral pathway for sympathetic vasoconstriction may be impaired in HFpEF.

The Tactical Athlete: Definitions, Cardiovascular Assessment, and Management, and "Fit for Duty" Standards.

Tactical athletes are individuals in the military, law enforcement, and other professions whose occupations have significant physical fitness requirements coupled with the potential for exposure to life-threatening situations. Such exposures can have varied hemodynamic effects on the cardiovascular system. It is crucial that their clinical evaluation is inclusive of specific occupational requirements. Safety protocols regarding medical clearance are relatively more stringent for this population than for competitive athletes due to the increased impact to the tactical athlete, their team, and the population they aim to serve and protect should they experience a cardiovascular event on the job.

Attenuated peripheral oxygen extraction and greater cardiac output in women with posttraumatic stress disorder during exercise.

Posttraumatic stress disorder (PTSD) is associated with an increased risk of developing cardiovascular disease, especially in women. Evidence indicates that men with PTSD exhibit lower maximal oxygen uptake (V̇o2max) relative to controls; however, whether V̇o2max is blunted in women with PTSD remains unknown. Furthermore, it is unclear what determinants (i.e., central and/or peripheral) of V̇o2max are impacted by PTSD. Therefore, we evaluated the central (i.e., cardiac output; Q̇c) and peripheral (i.e., arteriovenous oxygen difference) determinants of V̇o2max in women with PTSD; hypothesizing that V̇o2max would be lower in women with PTSD compared with women without PTSD (controls), primarily due to smaller increases in stroke volume (SV), and therefore Q̇c. Oxygen uptake (V̇o2), heart rate (HR), Q̇c, SV, and arteriovenous oxygen difference were measured in women with PTSD (n = 14; mean [SD]: 43 [11] yr,) and controls (n = 17; 45 [11] yr) at rest, and during an incremental maximal treadmill exercise test, and the Q̇c/V̇o2 slope was calculated. V̇o2max was not different between women with and without PTSD (24.3 [5.6] vs. 26.4 [5.0] mL/kg/min; P = 0.265). However, women with PTSD had higher Q̇c [P = 0.002; primarily due to greater SV (P = 0.069), not HR (P = 0.285)], and lower arteriovenous oxygen difference (P = 0.002) throughout exercise compared with controls. Furthermore, the Q̇c/V̇o2 slope was steeper in women with PTSD relative to controls (6.6 [1.4] vs. 5.7 [1.0] AU; P = 0.033). Following maximal exercise, women with PTSD exhibited slower HR recovery than controls (P = 0.046). Thus, despite attenuated peripheral oxygen extraction, V̇o2max is not reduced in women with PTSD, likely due to larger increases in Q̇c.NEW & NOTEWORTHY The current study indicates that V̇o2max is not different between women with and without PTSD; however, women with PTSD exhibit blunted peripheral extraction of oxygen, thus requiring an increase in Q̇c to meet metabolic demand during exercise. Furthermore, following exercise, women with PTSD demonstrate impaired autonomic cardiovascular control relative to sedentary controls. We interpret these data to indicate that women with PTSD demonstrate aberrant cardiovascular responses during and immediately following fatiguing exercise.

Cardiopulmonary Performance Among Heart Failure Patients Before and After Left Ventricular Assist Device Implantation.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) have persistent impairments in functional capacity after continuous-flow left ventricular assist device (CF-LVAD) implantation. OBJECTIVES: This study aims to characterize longitudinal changes in exercise hemodynamics and functional capacity among patients with HFrEF before and after CF-LVAD implantation. METHODS: Ten patients underwent 3 invasive cardiopulmonary exercise tests on upright cycle ergometry with pulmonary artery catheterization: 1) Visit 1 before CF-LVAD implantation; 2) Visit 2 after device implantation with CF-LVAD pump speed held constant at baseline speed; and 3) Visit 3 with increases in pump speed during exercise (median: 1,050 rpm [IQR: 750-1,150 rpm] and 220 rpm [IQR: 120-220 rpm] for HeartMate 3 and HeartWare VAD, respectively). Hemodynamics and direct Fick cardiac output were monitored using pulmonary artery catheterization. Gas exchange metrics were determined using indirect calorimetry. RESULTS: Maximal oxygen uptake (Visits 1, 2, and 3: 10.8 ± 2.5 mL/kg/min, 10.7 ± 2.2 mL/kg/min, and 11.5 ± 1.7 mL/kg/min; P = 0.92) did not improve after device implantation. Mean pulmonary arterial and pulmonary capillary wedge pressures increased significantly during submaximal and peak exercise on preimplantation testing (P < 0.01 for rest vs peak exercise) and remained elevated, with minimal change on Visits 2 and 3 regardless of whether pump speed was fixed or increased. CONCLUSIONS: Among patients with HFrEF, cardiovascular hemodynamics and exercise capacity were similar after CF-LVAD implantation, regardless of whether patients exercised at fixed or adjusted pump speeds during exercise. Further research is needed to determine methods by which LVADs may alleviate the HFrEF syndrome after device implantation. (Effect of mechanIcal circulatoRy support ON exercise capacity aMong pAtieNts with heart failure [IRONMAN]; NCT03078972).

Cardiovascular remodelling in response to exercise training in patients after the Fontan procedure: a pilot study.

BACKGROUND: The cardiovascular adaptations associated with structured exercise training in Fontan patients remain unknown. We hypothesised that short-term training causes cardiac remodelling and parallel improvement in maximal exercise capacity (VO2 max) in these patients. METHODS AND RESULTS: Five patients, median age 19.5 (17.6-21.3) years, with a history of Fontan operation meeting inclusion/exclusion criteria, participated in a 3-month training programme designed to improve endurance. Magnetic resonance images for assessment of cardiac function, fibrosis, cardiac output, and liver elastography to assess stiffness were obtained at baseline and after training. Maximal exercise capacity (VO2 max) and cardiac output Qc (effective pulmonary blood flow) at rest and during exercise were measured (C2H2 rebreathing) at the same interval. VO2 max increased from median (IQR) 27.2 (26-28.7) to 29.6 (28.5-32.2) ml/min/kg (p = 0.04). There was an improvement in cardiac output (Qc) during maximal exercise testing from median (IQR) 10.3 (10.1-12.3) to 12.3 (10.9-14.9) l/min, but this change was variable (p = 0.14). Improvement in VO2 max correlated with an increase in ventricular mass (r = 0.95, p = 0.01), and improvement in Quality-of-life inventory (PedsQL) Cardiac scale scores for patient-reported symptoms (r = 0.90, p = 0.03) and cognitive problems (r = 0.89, p = 0.04). The correlation between VO2 max and Qc showed a positive trend but was not significant (r = 0.8, p = 0.08). No adverse cardiac or liver adaptations were noted. CONCLUSION: Short-term training improved exercise capacity in this Fontan pilot without any adverse cardiac or liver adaptations. These results warrant further study in a larger population and over a longer duration of time. TRIAL REGISTRATION NUMBER: NCT03263312, Unique Protocol ID: STU 122016-037; Registration Date: 18 January, 2017.