Relentless mechanical work of the heart is powered by continuous oxygen consumption. How the heart uses oxygen is a defining feature of its health. Invasive studies have established that impaired oxygen consumption by the myocardium predicts contractile dysfunction and adverse outcomes. Despite its importance, noninvasive quantification of myocardial oxygen use remains limited. Magnetic resonance imaging (MRI) signal is known to be sensitive to blood oxygenation and has the potential to quantify myocardial oxygen consumption noninvasively, without exogenous contrast agents and free of ionizing radiation. However, its clinical translation has been impeded by the need for complex biophysical calibration, vulnerability to imaging artifacts and consistent vital motions, and the requirement of lengthy acquisition times. Here, we introduce a rapid, self-calibrated cardiac MRI framework that overcomes these barriers through high-resolution, motion-resolved coronary sinus oximetry, which can quantify myocardial oxygen extraction of the whole heart within 3 minutes. We optimized the imaging parameters via numerical simulations and validated them against invasive coronary sinus catheterization in a porcine model. We combined the method with clinical MRI sequences and demonstrated the feasibility of quantifying myocardial oxygen consumption and myocardial oxygen efficiency in patients with and without heart failure secondary to myocardial infarction in a single institution. This needle-free approach establishes a practical framework for noninvasive characterization of myocardial oxygen metabolism. It holds the potential to facilitate early disease detection, inform personalized therapeutic strategies, and guide the development of cardiometabolic therapies aimed at addressing the ongoing heart failure epidemic.

During physiological provocations, relative changes in muscle blood flow and O2 extraction can be estimated using near-infrared diffuse correlation spectroscopy (NIRS-DCS). However, the NIRS-DCS blood flow index (BFI) may underestimate perfusion changes unless changes in hemoconcentration are accounted for. Accordingly, we compared NIRS-DCS calculations of muscle perfusion and O2 extraction against MRI-derived arterial spin labeling (ASL) and MR susceptometry-based venous oximetry (SvO2), respectively. Thirteen healthy young adults (5 F) completed an ischemic-reperfusion test and plantarflexion exercise inside the bore of a 3 T MRI scanner. NIRS-DCS BFI was either 1) unadjusted (BFI), or converted into a muscle perfusion index (MPI) by 2) scaling BFI linearly for changes in hemoconcentration (MPILIN), or 3) scaling BFI for changes in hemoconcentration squared (MPISQR). Compared with ASL MRI, peak DCS perfusion was significantly lower during postischemic reperfusion when using BFI but not when using MPILIN or MPISQR. Similarly, end-exercise perfusion from BFI was significantly lower than ASL following plantarflexion exercise, whereas no difference was observed when comparing MPILIN and MPISQR to ASL. NIRS estimations of SvO2 were lower than MRI after 8 mins of ischemia, but similar following moderate-intensity plantarflexion exercise. However, following high-intensity exercise, NIRS estimations of SvO2 were similar to MRI only after accounting for changes in hemoconcentration. Collectively, these results highlight the importance of accounting for changes in hemoconcentration when using NIRS-DCS to estimate changes in muscle perfusion during physiological provocations such as ischemic reperfusion and exercise.NEW & NOTEWORTHY We compared changes in skeletal muscle blood flow estimated by NIRS-DCS against arterial spin-labeling MRI during ischemic reperfusion and exercise. NIRS-DCS blood flow index underestimated relative changes in muscle perfusion across all procedures unless the calculations were adjusted for changes in hemoconcentration and total heme content, which resulted in a muscle perfusion index (MPI) that was almost superimposed on ASL-MRI. These results demonstrate that NIRS-DCS MPI noninvasively quantifies changes in muscle perfusion in humans.

INTRODUCTION:Coronary microvascular dysfunction (CMD) has been proposed as a pathophysiological contributor to heart failure with preserved ejection fraction (HFpEF). Elevated left ventricular end-diastolic pressure (LVEDP) is often present in patients with CMD. HYPOTHESIS:We hypothesized that CMD-mediated impairment in LV relaxation may contribute to elevated LVEDP. METHODS:Women (n = 253) with signs and symptoms of ischemia and no obstructive coronary artery disease (INOCA) underwent invasive coronary functional testing (CFT) for measurement of resting LVEDP and coronary microvascular function. A pre-defined sequential subset of these women underwent cardiac MRI (CMRI). Two sample t-test, Fisher's exact test and Spearman correlation were performed. RESULTS:Group mean LVEDP was 14.4 ± 5.0 mmHg, with 150 women (59%) having LVEDP >12 mmHg. LVEDP directly related with body mass index (BMI) (r = 0.324, p < 0.001), and systolic blood pressure (r = 0.176, p = 0.01) at time of CFT, as well as time to peak filling rate (r = 0.13, p = 0.050). There were no relationships between LVEDP and invasive or non-invasive measures of CMD. CONCLUSIONS:Among women with suspected CMD, elevated resting LVEDP is associated with higher BMI and systolic blood pressure. There were no significant associations between LVEDP and measurements of CMD. Further analyses are needed to further evaluate LVEDP, CMD and development of HFpEF.

The planet is experiencing an unprecedented growth in its human population aged 65 years and older, underscoring the urgent need for comprehensive aging-centered biobehavioral data to guide public health interventions. The Arlington Study of Healthy Aging (ASHA) is a multidisciplinary community cohort study designed to investigate the biological, psychological, and social mechanisms underlying age-related functional decline. Here, we present the study’s rationale, design, and methodological framework. Utilizing a comprehensive, multi-modal assessment strategy—including whole-body MRI, vascular function testing, venous blood biomarkers, cognitive and physical function evaluations, DEXA scans, and continuous remote monitoring of activity, sleep, blood pressure, and glucose—the study captures both quantitative and qualitative dimensions of aging across multiple organ systems (brain, heart, muscle, liver, adipose tissue). A central aim is to identify modifiable risk factors and protective mechanisms that influence aging trajectories. Through interdisciplinary collaboration, ASHA seeks to generate actionable insights to enhance longevity, independence, and quality of life among older adults. NCT 06857877, 2024-09-24.

Heart failure with preserved ejection fraction (HFpEF) disproportionately affects females; however, the influence of sex on peripheral contributors to exercise intolerance remains poorly understood. Forty-three patients with HFpEF (71 ± 7 yr, 28 females; 38.3 ± 6.7 kg/m2) performed incremental single-leg knee extension (SLKE) exercise to determine peak leg blood flow (BF; duplex Doppler ultrasound), arterial-to-venous oxygen content difference (a-vO2) (femoral venous catheter), leg oxygen consumption (V̇o2), and muscle oxygen diffusive conductance (DMO2). Whole body and thigh adiposity and lean mass (TLM) were determined by DXA, and myosteatosis (TLM/fat ratio) by MRI. After adjusting for differences in TLM, females had ∼30% lower peak exercise leg V̇o2/TLM (P < 0.001) and ∼15% lower BF/TLM compared with males (P = 0.024). However, when normalized to V̇o2, the leg BF/leg V̇o2 slope was higher in females (9.5 ± 2.3 vs. 8.1 ± 2.1, P = 0.017) and was associated with markedly lower a-vO2 difference (P < 0.001) and ∼40% lower DMO2 (3.6 ± 1.6 vs. 6.4 ± 1.7, P < 0.0001). Metrics of muscle adiposity were not correlated with peak leg V̇o2 or its determinants (P > 0.150 for all). Females with HFpEF have lower muscle oxygen diffusive conductance during peak SLKE compared with males. However, peripheral determinants of aerobic capacity were not differentially related to adiposity in males and females with HFpEF. Interventions to improve muscle quality and diffusive capacity are of particular importance for improving peripheral limitations to exercise in females with obesity and HFpEF. This study was registered as a clinical trial on https://www.clinicaltrials.gov (NCT04068844).NEW & NOTEWORTHY Females with heart failure with preserved ejection fraction have lower muscle oxygen diffusive conductance during peak exercise compared with males. Interventions to improve muscle quality and diffusive capacity are of particular importance for improving peripheral limitations to exercise in females with HFpEF.

Postexercise circulatory occlusion (PECO) stimulates metabolically sensitive afferents, activating the muscle metaboreflex and eliciting a greater blood pressure response in males than females, possibly owing to greater absolute exercise workloads that contribute to disproportionate increases in stroke volume (SV). We tested the hypotheses that isometric handgrip exercise (EX) and PECO would increase SV greater in males than females, and accounting for strength would negate differences. Ten males and 10 females underwent cardiac MRI during rest, EX, and PECO. SV, end-systolic (ESV) and end-diastolic volume (EDV), all indexed to body surface area, and wall stress, systolic blood pressure (SBP), and total peripheral resistance (TPR) were measured. EX and PECO lowered stroke volume index (SVi) in males (both P < 0.001) but not females (both P = 0.998). The reduction in SVi during EX and PECO in males remained with analysis of covariance (covariate handgrip strength; P = 0.020). EX increased end-systolic volume index (ESVi) in both sexes (P ≤ 0.018), whereas ESVi increased during PECO in males (P < 0.001) but not females (P ≥ 0.092). EX and PECO increased end-diastolic volume index, SBP, TPR, and wall stress (all P ≤ 0.015) in both sexes. The SVi response to PECO was negatively related to ESVi responses in males (r = -0.822, P = 0.004) but not females (P = 0.216). PECO lowers SVi in males but not females independent of handgrip strength, despite comparable pressor responses. These novel findings support differential afterload sensitivity on SV between sexes in response to the exercise pressor and muscle metaboreflex. Remarkably, SV is not augmented as part of the pressor response elicited by isometric handgrip exercise or muscle metaboreflex activation in either sex.NEW & NOTEWORTHY Moderate-intensity isometric handgrip exercise and postexercise circulatory occlusion decrease stroke volume in males but not females, even after accounting for handgrip strength. Sex differences in the stroke volume response to isometric handgrip exercise and the muscle metaboreflex appear driven by greater male sensitivity to ventricular afterload. In an isolated handgrip exercise-circulatory occlusion model, stroke volume does not increase as a component of the pressor response elicited by exercise or the muscle metaboreflex in either sex.

Ischemia with no obstructive coronary artery disease (INOCA), often due to coronary microvascular dysfunction (CMD), disproportionately affects women and may be linked to cognitive impairment and increased risk of dementia. While CMD and cerebral small vessel disease (CSVD) share similar risk factors and may contribute to cognitive decline, the mechanistic pathways connecting these conditions in women remain unclear. We conducted a cross-sectional observational study with a planned enrollment of 100 women aged 18 years and older with symptoms of INOCA and suspected CMD, recruited from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation–Pre-Heart Failure with Preserved Ejection Fraction study (ClinicalTrials.gov identifier: NCT03876223) and the Microvascular Aging and Eicosanoids–Women’s Evaluation of Systemic Aging Tenacity (MAE-WEST) (“You are never too old to become younger!”) Specialized Center for Research Excellence (SCORE) (U54AG065141) studies at Cedars–Sinai Medical Center and the University of Florida. Each participant underwent a comprehensive assessment protocol, including advanced brain magnetic resonance imaging to quantify markers of CSVD, cardiac MRI to evaluate CMD, non-mydriatic retinal imaging, peripheral vascular function testing, and an extensive battery of cognitive assessments. Clinical, sociodemographic, and vascular risk factor data were collected. We analyzed cross-sectional associations between multimodal imaging biomarkers and cognitive performance. This protocol describes the first multidimensional, imaging-based investigation to integrate assessments of CMD, CSVD, retinal microvasculature, and cognitive function in women at risk for INOCA. Findings will enhance our understanding of the shared vascular mechanisms underlying cognitive decline and inform strategies for early intervention in at-risk women.

PURPOSE:Premature birth (< 37 weeks gestation) is associated with lower exercise capacity. However, the specific underlying mechanisms remain poorly defined. This study investigated the mechanisms of exercise limitation across the oxygen transport chain in preterm-born adults with normal resting cardiopulmonary function but exertional dyspnea. METHODS:10 preterm born (6F, age: 30 ± 5 years, body mass index [BMI]: 27.0 ± 6.3 kg/m2, gestational age: 30 ± 3 weeks) and 8 term born (3F, age: 29 ± 5 years, BMI: 25.4 ± 4.6 kg/m2, gestational age: 40 ± 0 weeks) adults performed resting spirometry and a cardiopulmonary exercise test, consisting of two 5-min submaximal cycling exercises (30 and 60 W), followed by an incremental protocol to exhaustion. We measured breath-by-breath gas exchange (custom designed system), heart rate (HR, 12-lead ECG), cardiac output (Q̇c, acetylene rebreathe), and calculated arterial-venous oxygen difference (a-vO2diff, Fick equation). RESULTS:Oxygen uptake (V̇O2) was similar between groups at rest, 30 and 60 W. At peak, compared to term-born peers, preterm adults showed lower power output (108 ± 18 vs. 208 ± 69 W, p < 0.001), V̇O2 (1.58 ± 0.29 vs. 2.52 ± 0.85 L/min, p = 0.017), Q̇cindex (7.5 ± 1.0 vs. 8.9 ± 1.6 L/min/m2, p = 0.057), while a-vO2diff (12.6 ± 1.7 vs. 14.1 ± 1.6 mL/dL, p = 0.096) and HR were similar between groups (175 ± 16 vs. 185 ± 8 bpm, p = 0.104). The increase in stroke volume index from rest to peak exercise was blunted in preterm compared to term-born adults (8 ± 7 vs. 15 ± 6 mL/m2, p = 0.032). CONCLUSION:Preterm born adults present with lower exercise capacity compared to age-matched peers born at term. Central mechanisms, primarily stroke volume, underlie exercise limitation in this population.

RATIONALE: Preterm birth (<37 weeks completed gestation) is associated with exercise intolerance. Reduced stroke volume (SV) reserve is a primary contributor to exercise intolerance in this population, although the underlying mechanisms remain to be clarified. Therefore, this study aimed to investigate biventricular volumes and cardiac hemodynamics during exercise in term born and preterm born adults. METHODS: 9 preterm born (6F, age: 30 ± 5 years, body mass index (BMI): 27 ± 6 kg/m2, gestational age: 30 ± 3 weeks) and 7 term born (3F, age: 29 ± 5 years, BMI: 26.5 ± 3.9 kg/m2, gestational age: 40 ± 0 weeks) adults completed two 8-min submaximal supine stepping exercises (30W and 60W) inside an MRI scanner. Short- and long-axis cine images were acquired to determine left (LV) and right (RV) ventricular end-diastolic (EDV) and end-systolic (ESV) volumes. LV mass, EDV (EDVi), ESV (ESVi) and SV (SVi) were indexed for body surface area. LV mass index in term and preterm born adults was compared via unpaired t-test. Group differences in LV and RV volumes and cardiac hemodynamics were compared by two-way repeated measures ANOVA. RESULTS: LV mass index was similar between term and preterm born adults (49 ± 8 vs. 48 ± 4 g/m2, P = 0.771). Resting and exercise cardiac hemodynamics are shown in Table 1. Compared with term born peers, preterm adults showed lower LVSVi (Rest: 46 ± 5 vs. 43 ± 4; 30W: 51 ± 7 vs. 43 ± 5; 60W: 51 ± 10 vs. 43 ± 5 mL/m2, main group effect: P = 0.036), RVEDVi (Rest: 82 ± 13 vs. 73 ± 4; 30W: 85 ± 13 vs. 69 ± 8; 60W: 77 ± 18 vs. 65 ± 6 mL/m2, main group effect: P = 0.024) and RVSVi (Rest: 48 ± 8 vs. 44 ± 5; 30W: 52 ± 8 vs. 42 ± 5; 60W: 52 ± 12 vs. 42 ± 5 mL/m2, main group effect: P = 0.031). LVEDVi was also lower in preterm adults (Rest: 80 ± 13 vs. 72 ± 5; 30W: 83 ± 15 vs. 70 ± 7; 60W: 79 ± 17 vs. 70 ± 8 mL/m2, main group effect: P = 0.067), though with greater variability. ESVi and heart rate were similar between groups. CONCLUSION: Preterm born adults present with impaired SV augmentation during exercise. Our results highlight smaller biventricular end-diastolic volumes in adults born preterm, with similar cardiac function during physiologic stress.

Heart failure (HF) is a significant global health issue, categorized by left ventricular ejection fraction, being either reduced (HFrEF < 0.40) or preserved (HFpEF > 0.50), or in the middle of this range. Although the overall incidence of HF remains stable, HFpEF cases are increasing, representing about 50% of all HF cases. Outcomes for HFpEF are similar to those for HFrEF, leading to substantial health-care resource use. Despite extensive research over the past 2 decades, the prognosis and mortality rates for HFpEF remain high. A key feature of HFpEF is exercise intolerance, characterized by severe exertional dyspnea and fatigue, which significantly impacts quality of life. The underlying mechanisms of exercise intolerance are not fully understood due to the complex pathophysiology and multisystem involvement. Obesity is a common comorbidity in HFpEF, especially in North America, leading to worsening symptoms, hemodynamics, and mortality rates. Increased adiposity leads to inflammation, hypertension, dyslipidemia, and insulin resistance, and impairing cardiac, vascular, pulmonary, and skeletal muscle function. Therefore, managing obesity is crucial in treating HFpEF. In this review we explore the pathophysiologic mechanisms of HFpEF, emphasizing obesity’s role, and we discuss current management strategies while identifying areas needing further research.

Background:Increased aortic pulse wave velocity (aPWV), a marker of arterial stiffness, is associated with poor prognosis in patients with or at risk for heart failure with preserved ejection fraction (HFpEF). Increasingly, advanced imaging using cardiac magnetic resonance imaging (MRI) is used to evaluate cardiac dysfunction, including coronary microvascular dysfunction (CMD). To facilitate investigation linking CMD with HFpEF, we compared MRI-measured aPWV with traditional invasive or noninvasive measurements of aPWV. Methods:We studied 118 participants (90.7% women) with or at risk for HFpEF due to suspected CMD in a cross-sectional design at Cedars-Sinai Medical Center between October 2025 and February 2022. aPWV was measured by: (I) MRI through-plane phase-contrast imaging at the ascending and distal descending aorta (MRI-aPWV) (n=78), (II) invasively via catheter pullback (cath-aPWV) (n=68), and (III) carotid-femoral applanation tonometry (cf-aPWV; SphygmoCor XCEL, Atcor Medical) (n=87). MRI-aPWV was compared to cath-aPWV and cf-aPWV using Pearson correlation and Bland-Altman plots. Results:Mean age was 58±11.8 years, and mean aPWV were 8.48±3.21 m/s (MRI-PWV), 7.51±2.79 m/s (cath-aPWV), and 8.68±1.83 m/s (cf-aPWV). MRI-aPWV strongly correlated with cf-aPWV with r=0.74 [95% confidence interval (CI): 0.61-0.83, P<0.001] with mean difference -0.18 and standard deviation (SD) 2.14. Comparison of MRI-aPWV to cath-aPWV showed a modest correlation of 0.52 (95% CI: 0.29-0.69, P<0.001) with a mean difference of -0.74 and SD 2.78. Conclusions:MRI measurement of aPWV shows good agreement with traditional invasive and noninvasive measurements in participants with or at risk for HFpEF. Reliable measurement of arterial stiffness combined with cardiac MRI measures of ventricular remodeling, fibrosis, scar and perfusion may offer pathophysiology insights and treatment targets for HFpEF.

Background There is increasing recognition that the pathophysiology of coronary microvascular dysfunction (CMD) plays a pivotal role in the development of heart failure with preserved ejection fraction (HFpEF). However, the mechanisms underlying this role are not known. Study design and methods The Women's Ischemia Syndrome Evaluation Mechanisms of Coronary Microvascular Dysfunction Leading to Pre-Heart Failure With Preserved Ejection Fraction (WISE Pre-HFpEF) is a prospective cohort study enrolling 180 women and men undergoing clinically indicated invasive coronary angiography for suspected ischemia with no obstructive coronary artery disease. The study aims to investigate (1) CMD-related ischemia contribution to myocellular damage and impaired left ventricular (LV) relaxation as determined invasively by ultra-high sensitivity cardiac troponin I (u-hscTnI) measurements in the coronary sinus/great cardiac vein and LV pressure-volume loops, respectively, during provocative stress testing with isometric handgrip, and (2) CMD-related ischemic myocellular damage contribution to LV diastolic dysfunction progression as assessed using cardiac magnetic resonance imaging obtained at enrollment and 1-2 years later, along with prospectively repeated ambulatory u-hs-cTnI measurements. Conclusions The WISE pre-HFpEF study is designed to investigate whether ischemic myocardial damage secondary to CMD contributes to the progression of LV diastolic dysfunction. The findings from this study will provide new understanding of the role of CMD in HFpEF development as well as the potential benefits of CMD-directed therapies for the prevention and treatment of HFpEF. Trial registration ClilicalTrial.gov, NCT03876223 (Am HeartJ 2025;284:47-56.)

During standard cardiovascular magnetic resonance (CMR) the horizontal long-axis cine image (i.e., 4-chamber) is captured which includes a cross-section of the descending aorta. The aortic cross-section can be used to assess aortic stiffness (distensibility; ∆area/pressure) or circumferential strain (percentage vascular deformation). We examined whether descending aortic strain from traditional CMR is sensitive to age- and disease-related (heart failure with preserved ejection fraction; HFpEF) arteriosclerosis. We recruited 83 participants into three groups: (1) 34 young individuals (age: 22 ± 3 years; body mass index (BMI): 24.3 ± 2.8 kg/m2); (2) 19 older individuals (age: 69 ± 5 years; BMI: 26.9 ± 4.7 kg/m2) and (3) 26 patients with HFpEF (age: 69 ± 6 years; BMI: 35.8 ± 6.1 kg/m2). All participants were studied in the same 3 T scanner (Phillips, Achieva). Descending aortic cross-sectional area and circumferential strain were measured using cvi42 software. Blood pressure was measured via a brachial oscillometric cuff. Data were compared via ANOVA. All data are reported as means ± standard deviation. Compared to the young group (71 ± 5 mmHg), mean arterial pressure was higher in the older (83 ± 9 mmHg, P < 0.001) and HFpEF groups (86 ± 10 mmHg, P < 0.001). Minimum and maximum aortic areas were greater in the older and HFpEF groups (both, P < 0.01). Peak descending aortic strain (young: 11.4% ± 2.2%; older: 4.8% ± 1.6%; HFpEF 3.8% ± 1.6%) and absolute distension were lower (all, P < 0.02) in the older and HFpEF groups compared to the young. Peak descending aortic strain and strain rates are sensitive to age and may provide a novel assessment of arterial stiffness for longitudinal studies that utilize or have utilized CMR.

Previous studies have suggested associations between coronary microvascular dysfunction (CMD) and alterations in left ventricular (LV) structure and function Data are however scarce regarding the right ventricular (RV). In the context of CMD, the RV could be affected via mechanisms potentially involving ischemia from CMD, shared pathophysiological milieu leading to adverse ventricular remodeling, and/or increased afterload secondary to increased LV end-diastolic pressure or heart failure with preserved ejection fraction (HFpEF) with pulmonary hypertension. We evaluated the relationship between measures of RV structure/function and invasively measured CMD in individuals with suspected ischemia and no obstructive coronary artery (INOCA) disease. We included 297 participants from the WISE-HFpEF, WISE-preHFpEF and WISE-CVD cohorts, who underwent cardiac magnetic resonance imaging (CMRI) and coronary function testing to measure coronary flow reserve (CFR) in response to adenosine and coronary blood flow change in response to acetylcholine (∆CBF). We assessed the correlation between RV parameters on CMRI and coronary microvascular function (CFR and ∆CBF). Participants had a mean age 54±11 years. Of them, 104 (39%) had hypertension, 31 (11%) had diabetes, and 18 (7%) had chronic obstructive pulmonary disease. Mean RV end-diastolic volume was 66.6±11.0 mL/m2, RV ejection fraction was 62.7%±5.6% and RV longitudinal strain was -27.2%±3.5%. We found no significant correlation between RV parameters and coronary microvascular function. This is the first study to report associations between invasively measured CMD and CMRI parameters of RV structure and function among patients with suspected INOCA. Despite a large sample size, we found no significant relationship between RV structure or function and CMD. These results suggest that RV abnormalities do not precede and are not concurrent with CMD in suspected INOCA participants. Longitudinal prospective studies are needed to evaluate if RV deterioration may occur later during the course of CMD and among patients with HFpEF.

Background:Coronary vascular dysfunction (CVaD) contributes to ischemia even in the absence of obstructive coronary artery disease. We hypothesize that abnormal autonomic reactivity to mental stress is a key pathophysiologic mechanism in CVaD compared to non-cardiac chest pain (NCCP) and reference control (RC) groups. Methods:Seventy women (35 with CVaD diagnosed by coronary function testing, 19 with NCCP, and 16 RC) underwent mental stress testing (arithmetic and anger recall) in the Cardiac Autonomic Nervous System study. RC group was asymptomatic with no risk factors and normal exercise treadmill testing. Frequency domain heart rate variability (HRV, ms2) was obtained at baseline and during mental stress, with high frequency (HF) power as an accepted parasympathetic measure. Low frequency (LF)/HF ratio may reflect sympathetic dominance. ANOVA was used for comparisons. Results:CVaD group was older compared to NCCP (57.1 ± 9.6 vs. 50.4 ± 11.3 years, p = 0.025, respectively), but age-matched to RC group (54.6 ± 14.5, p = 0.45). HRV was similar at baseline among the groups. During anger recall, CVaD group had lower HF HRV vs. NCCP (5.03 ± 1.05 vs 6.00 ± 1.17, p = 0.006, respectively), but not vs. RC (5.74 ± 1.02, p = 0.077). During arithmetic, CVaD group had lower HF HRV vs. NCCP (5.06 ± 1.12 vs. 6.00 ± 1.17, p = 0.007, respectively) and RC (6.04 ± 0.83, p = 0.01) groups. LF/HF ratio did not differ among the three groups. Conclusions:Women with CVaD demonstrate a greater stress-induced vagal withdrawal compared to those with NCCP and RC women. Further work to investigate altered autonomic responses as a mechanism in CVaD is warranted.

In the present study, we examined how fatiguing exercise affects O2-based measures of skeletal muscle oxidative capacity in vivo by measuring changes in the rate constant of muscle V̇o2 recovery ([Formula: see text]). Healthy young adults completed isokinetic (120°·s-1), maximal voluntary dynamic contractions (MVDCs) lasting 24 (baseline [Formula: see text]) and 240 s (postfatiguing exercise [Formula: see text]). Vastus lateralis [Formula: see text] was measured using near-infrared diffuse correlation spectroscopy (NIRS-DCS) via the conventional repeated arterial occlusion method (part A, n = 14) or a novel NIRS-DCS "free-flow" method (part B, n = 13). Pulmonary V̇o2 (pV̇o2), muscle V̇o2 (mV̇o2), and surface electromyography (sEMG) measures of muscle activation were also measured throughout the 240-s trial. Compared with the 24-s trial, [Formula: see text] following 240 s of MVDCs was impaired by ∼25% (part A; P = 0.005) and ∼16% (part B; P = 0.017). Moreover, both pV̇o2 and mV̇o2 rapidly increased to maximal levels, where they remained for the duration of the 240-s trial, despite sEMG activity and peak MVDC power declining. These results demonstrate that fatiguing exercise not only impairs O2-based measures of skeletal muscle oxidative capacity, but also that mitochondrial O2 consumption is uncoupled from power output and ATP demand during fatiguing exercise.NEW & NOTEWORTHY We measured rates of skeletal muscle V̇o2 recovery ([Formula: see text]) at baseline and following fatiguing exercise using near-infrared diffuse correlation spectroscopy (NIRS-DCS). Regardless of whether [Formula: see text] was measured via the conventional repeated arterial occlusion method (part A) or a novel NIRS-DCS "free-flow" method (part B), fatiguing exercise impaired [Formula: see text] by ∼15%-25%. Because ATP demand rapidly declines post exercise, the slow [Formula: see text] recovery observed here suggests fatiguing exercise may uncouple the functional relationship between mitochondrial O2 consumption and ATP synthase activity.