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Introduction The contribution of metabolic vs mechanical stimuli related to the group III/IV afferent‐mediated exercise pressor reflex (EPR) remains incompletely understood. High pedal frequency during cycling increases type II muscle fiber recruitment and may contribute to increased anaerobically‐mediated metabolic byproduct accumulation. This may lead to an augmented rise in systolic blood pressure (SBP) and, hence, EPR in humans. Thus, we hypothesized, 1) Mean arterial pressure (MAP) will be increased during exercise with SubRCO vs without NoRCO irrespective of pedal frequency, and 2) MAP will be augmented further during exercise with SubRCO at high pedal frequencies. Methods Healthy adults (N=13; 46% men; age 36±19 yr; BMI 24±4 kg/m 2 ) participated in 2 study visits, each consisting of 2 sessions of fixed load (20 W) recumbent cycle ergometry with bilateral upper thigh pressure tourniquets for 8 min at a fixed pedal frequency of 35 (LOW) or 100 (HIGH) rpm (randomized). Cuffs remained at 0 mm Hg for the first 3 min (CTL), and were then randomized to 0 mm Hg (NoRCO) or 90 mm Hg (SubRCO) for the final 5 min of exercise. SBP and diastolic blood pressure (DBP) were measured via manual sphygmomanometry at the end of CTL and end‐exercise (END). MAP was calculated as (SBP + 2 * DBP)/3. Results There were no between or within condition differences at CTL for MAP (P>0.05). In contrast, for between SubRCO and NoRCO differences at END, MAP was increased in SubRCO vs NoRCO in both HIGH (106±12 vs 92±13 mm Hg, respectively) and LOW (94±9 vs 85±8 mm Hg, respectively) (P<0.05). At END, MAP was increased in HIGH vs LOW within both SubRCO and NoRCO (P<0.01). Within both NoRCO (129 ± 18 vs 117 ± 11 mm Hg) and SubRCO (125 ± 15 vs 113 ± 10 mm Hg) at CTL, SBP was increased in HIGH vs LOW, respectively (P<0.01). At CTL, there were no between SBP NoRCO vs SubRCO differences in HIGH or LOW. Within SBP differences for NoRCO (134 ± 19 vs 113 ± 11 mm Hg) and SubRCO (147 ± 20 vs 127 ± 12 mm Hg) in HIGH vs LOW persisted to END, respectively (P<0.01). SBP increased at END vs CTL within SubRCO for both HIGH and LOW (P<0.02), but not within NoRCO (P>0.05). Lastly, SBP increased in SubRCO vs NoRCO at END in both HIGH and LOW (both P<0.01). There were no differences for DBP at any time point (P>0.05). Conclusion These data support our hypothesis that, independent of pedal frequency, SubRCO provokes increased MAP during fixed‐load submaximal exercise as a function of increased SBP. However, high pedal rate accompanied by SubRCO results in exaggerated SBP‐mediated increased MAP. These data contribute to an improved understanding of the stimuli that activate group III/IV afferents during exercise in humans. Support or Funding Information NHLBI RO1 HL126638; AHA 16POST30260021

Introduction The exercise pressor reflex (EPR) is suggested to be linked to activated group III/IV afferents. However, the predominating mechanical and/or metabolic stimuli by which the EPR is mediated remains unclear. It is suggested that high pedal frequency increases the recruitment of type II muscle fibers, which may result in augmented production of metabolic byproducts as a function of increased anaerobic processes. Therefore, this study tested the hypothesis that compared to low frequency, high pedal frequency will be associated with increased blood pressure during postexercise suprasystolic regional circulatory occlusion (SupraRCO). Further, although subsystolic RCO (SubRCO) during exercise is suggested to provoke venous distension associated with mechanically‐mediated activation of group III/IV afferents, we hypothesized the rise in blood pressure during postexercise SubRCO will be blunted vs postexercise SupraRCO irrespective of pedal frequency. Methods Healthy adults (N=13, 6 male, 7 female), age 36±19 yrs participated in 2 days of testing, each consisting of 3 sessions of recumbent cycle ergometry at pedal frequencies of 100 (HIGH) or 35 (LOW) rpm (randomized) at 20 W for 8 min. At cessation of exercise, bilateral upper thigh pressure tourniquets were inflated to SupraRCO (200 mm Hg), SubRCO (90 mm Hg), or no inflation (NR) for 2 min (randomized). Blood pressure via manual sphygmomanometry was measured at rest, end‐exercise, and 2 min postexercise. Mean arterial pressure (MAP) was calculated as (SBP + 2 * DBP)/3. Results For both rest and end‐exercise, MAP did not differ across repeated transients for either HIGH or LOW (both P>0.05). However, mean MAP across repeated transients was greater in HIGH vs LOW at end‐exercise (P<0.05). At 2 min postexercise in HIGH, compared to NR (89±8 mm Hg), MAP was higher in SupraRCO (105±18 mm Hg; P=0.02), but not in SubRCO (98±9 mm Hg; P=0.38); whereas MAP did not differ between SupraRCO and SubRCO (P=0.70). Similarly, at 2 min postexercise in LOW, MAP was increased in SupraRCO vs NR (96±10 vs 85±7 mm Hg, respectively; P=0.02); whereas there were no differences between SubRCO (88±7 mm Hg) with either NR (P=0.91) or SupraRCO (P=0.23). Lastly, compared to LOW, MAP was greater in HIGH at 2 min postexercise for both SupraRCO (P<0.01) and SubRCO (P<0.01), but not in NR (P=0.59). Conclusions In intact exercising humans it remains challenging to elucidate exact contributions of group III/IV afferents to the EPR. However, these data are consistent with the role of group III/IV afferents in contributing to the EPR in humans. New to this field, our observations suggest that at low fixed workloads, increased pedal frequency augments the postexercise pressor response to both SupraRCO and SubRCO in healthy adults. These data contribute to an improved understanding of specific stimuli associated with the EPR linked to group III/IV afferents in humans. Support or Funding Information NHLBI R25 HL115473; NHLBI RO1 HL126638; AHA 16POST30260021

Introduction Additional oxygen uptake (VO 2 ) beyond muscle oxygen (O 2 ) utilization rates may coincide with exercise at or above the lactate threshold, which may be illustrated using a Phase II to III two‐exponential on‐transient VO 2 kinetics model. This is expected to prolong mean response time (MRT) to VO 2 steady‐state commensurate with increased O 2 deficit (O 2 def), which suggests reduced energy efficiency. Several factors may provoke metabolic acidosis during ergometry including exaggerated pedal frequency related to greater recruitment of type II muscle fibers. Also unclear is whether locomotor subsystolic regional circulatory occlusion (SubRCO), used to study group III/IV afferents during ergometry, accelerates metabolic acidosis due to influences on arterial‐to‐venous gradients. Thus, this study aimed to test the hypothesis that the transition from exercise without SubRCO to with SubRCO during fixed high rate pedaling leads to a Phase III rise in on‐transient VO 2 kinetics and, hence, augmented MRT and O 2 def during hyperbolic submaximal exercise. Methods Healthy adults (N = 15, 53% male; age 36 ± 17 years; BMI 24 ± 4 kg/m 2 ) completed 2 study visits of 3 identical sessions of fixed‐load (20W) ergometry at fixed pedal rates of 35 or 100 rpm (randomized). Sessions began with 5 min of rest, followed by 3 min of exercise without SubRCO, and immediately transitioning to a 5 min period of exercise+SubRCO at 90 mm Hg bilateral‐thigh cuff inflation pressure. A metabolic system integrated with gas mass‐spectrometry was used to measure breath‐by‐breath VO 2 . Data were linearly interpolated to 1 sec intervals and ensemble averaged across 3 sessions/day for each participant prior to modeling. Models included: single exponential, VO 2REST + A [1 − e −(t‐TD)/τ ]; two exponential, VO 2REST + A [1 − e −(t‐TD)/τ ] + A 2 [1 − e −(t‐TD2)/τ2 ]; O 2 def, [A • 8 min] − ∫ VO 2 dt; MRT, τ + TD; where τ = time constant; A = asymptote; TD = time delay; ∫ VO 2 dt = integral of actual VO 2 across 8 min. Results Single vs two exponential model sums of squares were similar within sessions of 35 (0.05 ± 0.03 vs 0.05 ± 0.03, P = 0.15) and 100 rpm (0.15 ± 0.07 vs 0.14 ± 0.07, P = 0.59), respectively; suggesting an absent Phase III response. Thus, MRT and O 2 def were derived using single exponential models beginning at t = 0. At 35 rpm, MRT = 56 ± 22 sec, and O 2 def = 0.36 ± 0.13 L; which differed significantly from 100 rpm, MRT = 43 ± 13 sec, and O 2 def = 0.70 ± 0.21 L (all P<0.05). Conclusions While these observations demonstrate shortened MRT but increased O 2 def in high versus low pedaling, these data do not suggest locomotor SubRCO provokes worsening of these parameters relating to marked dissociation between VO 2 and muscle O 2 utilization rates during low intensity ergometry in healthy adults. Similarly, although O 2 def demonstrates sensitivity to pedal rate, an absent Phase III rise in VO 2 commensurate with a shortened MRT during high rate pedaling does not suggest an uncoupling of pulmonary and muscle O 2 increases from early to end‐exercise in healthy adults. Support or Funding Information NHLBI RO1 HL126638; AHA 16POST30260021

Introduction Although used as an experimental approach to stimulate group III/IV afferents by causing venous congestion, locomotor subsystolic regional circulatory occlusion (SubRCO) during exercise may lead to accelerated local metabolic acidosis, whilst complicating the interpretation of cardiovascular reflexes using this technique. Moreover, compared to low pedal rate, greater type II fiber recruitment is expected during high pedal rate cycling. Thus, inordinate changes in muscle blood flow and muscle oxygen requirements provoked by augmented energy demands should elicit delayed or absent steady‐state oxygen uptake (VO 2 ), which would not be adequately described using a single‐component exponential on‐transient VO 2 kinetics model. This study aimed to test the hypothesis that increased pedal rate combined with SubRCO during low intensity hyperbolic exercise would shift the exponential fit of on‐transient VO 2 kinetics from a single to a two‐component model. Methods Healthy adults (N = 15, 53% male; age 36 ± 17 years; BMI 24 ± 4 kg/m 2 ) completed 2 study visits of 3 identical sessions of fixed‐load (20W) ergometry at fixed pedal rates of 35 or 100 rpm (randomized). Sessions began with 5 min of rest, followed by 3 min of exercise without SubRCO, and immediately transitioning to a 5 min period of exercise+SubRCO at 90 mm Hg bilateral‐thigh cuff inflation pressure. A metabolic system integrated with gas mass‐spectrometry was used to measure breath‐by‐breath VO 2 . Data were linearly interpolated to 1 sec intervals and ensemble averaged across 3 sessions/day for each participant prior to modeling. All models excluded the cardiodynamic phase. Exponential models were: single‐component, VO 2REST + A [1 − e −(t−TD)/τ ]; two‐component, VO 2REST + A [1 − e −(t−TD)/τ ] + A 2 [1 − e − (t−TD2)/τ2 ]; where τ = time‐constant; A = asymptote; TD = time delay. Results Best‐fit residuals for single vs. two‐component models did not differ within either 35 rpm (0.031 ± 0.009 vs 0.028 ± 0.007, P = 0.15) or 100 rpm (0.052 ± 0.013 vs 0.050 ± 0.013, P = 0.48) sessions, respectively; suggesting SubRCO does not influence on‐transient VO 2 kinetics. Thus, 35 rpm single‐component parameters were: τ = 48 ± 24 sec, A = 0.32 ± 0.04 L/min, and TD = 12 ± 10 sec, which differed significantly vs 100 rpm single‐component parameters: τ = 25 ± 20 sec, A = 0.87 ± 0.12 L/min, and TD = 1 ± 9 sec (all P<0.05), suggesting an independent effect of pedal rate on on‐transient VO 2 kinetics. Conclusions These data do not support our hypothesis, whilst suggesting that the oxygen requirement during hyperbolic exercise for a transition from low‐intensity ergometry without SubRCO to a longer period with SubRCO is not exaggerated to appreciably evoke a phase III on‐transient VO 2 kinetic response in healthy adults. Therefore, if on‐transient VO 2 kinetics mirror muscle oxygen utilization patterns at steady‐state moderate exercise, these data suggest locomotor SubRCO during moderate exercise does not exacerbate local metabolic acidosis in healthy adults. Support or Funding Information NHLBI R01 HL126638; AHA 16POST30260021

Introduction A disproportionate increase in ventilation relative to carbon dioxide output (V E /VCO 2 ) slope is a strong prognostic indicator in heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) patients. Similarly, secondary pulmonary hypertension also poses a profound mortality risk in these patients. Exaggerated ventilation and pulmonary pressures appear to parallel one another during exercise in HF. However, an underlying pathophysiologic mechanism relating these two outcomes remains incompletely understood. Thus, the aim of this study was to determine associations between anatomical and physiologic metrics of ventilatory control and pulmonary pressures during exercise in HFrEF and HFpEF. Methods 32 HFpEF and 33 HFrEF (EF: 62±2 vs 22±1%; male: 17 and 31; age: 70±2 and 55±2 yrs; BMI: 34±1 and 28±1 kg/m 2 ; weight: 98±4 and 86±3 (all P <0.05), respectively, participated in cardiopulmonary exercise testing during right heart catheterization. Measures of pulmonary pressures included: systolic (PASP); diastolic (PADP); mean (mPAP); wedge (PCWP); pulse (PP); transpulmonary gradient (TPG). Partial pressure of arterial oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) were measured via radial arterial catheterization. Ventilation was measured continuously using a breath by breath metabolic measurement system. We calculated dead space to tidal volume [Vd/Vt=(V E ×PaCO 2 )‐(863×VCO 2 )/(V E ×PaCO 2 )] and Alveolar‐arterial oxygen gradient (A‐a)=PAO 2 ‐PaO 2 ; V E /VCO 2 slope=rest to peak exercise. Results At rest, pulmonary pressures did not differ between groups ( P >0.05); whereas Vd/Vt was lower in HFpEF vs HFrEF (0.42±0.02 vs 0.48±0.01, respectively, P =0.03). At peak exercise, HFpEF had higher PCWP (34.8±1.2 vs 30.2±1.5 mm Hg, P =0.02) and PADP (35.4±1.3 vs 29.8±1.6 mm Hg, P =0.02), but lower Vd/Vt (0.32±0.02 vs 0.38±0.01, P =0.03) and V E /VCO 2 slope (35.3±1.6 vs 43.5±2.0, P <0.01) vs HFrEF. At peak in HFpEF, Vd/Vt was related to PASP (r=0.40, P =0.03), PP (r=0.44, P =0.01), and TPG (r=0.53, P <0.01), and A‐a was related to PASP (r=0.43, P =0.01), PP (r=0.44, P =0.01), and TPG (r=0.46, P <0.01). At peak in HFrEF, Vd/Vt was related to PADP (r=0.41, P =0.02), and A‐a was related to PASP (r=0.43, P <0.01), PADP (r=0.42, P =0.01), and mPAP (r=0.44, P <0.01). There were no significant relationships between measures of pulmonary pressures and PaCO 2 . Remaining correlations between pulmonary pressures and anatomical or physiologic metrics of ventilatory control were negligible in both groups ( P >0.05). Conclusion These data suggest pulmonary pressures play a role in dead space ventilation during exercise in HF. Moreover, as suggested by the A‐a gradient, augmented pulmonary pressures may contribute to an exacerbation of ventilation/perfusion mismatch during exercise in both HFrEF and HFpEF patients. Support or Funding Information None

Background Neurophysiological coupling between ventilation and locomotor muscle group III/IV muscle afferent fibers during exercise is an important relationship that favorably influences ventilation in young healthy adults. In contrast, we have shown that group III/IV locomotor muscle afferents provoke aberrant ventilation in aging heart failure patients, which is suggested to be a primary effect of heart failure. However, there remains a limited understanding of the effect of aging in the absence of cardiovascular disease on the group III/IV muscle afferent pathway. Subsystolic circulatory occlusion to elicit venous distension has been suggested to stimulate locomotor muscle afferent neurologic feedback. The purpose of this study was to compare ventilatory responses in young vs aging healthy adults during submaximal constant‐load exercise with intermittent bilateral subsystolic occlusion of locomotor muscles. Methods Healthy adults completed 2 visits (10 young [YNG] vs 9 OLD; age 22±1 vs 66±3 yrs, BSA 1.8±0.1 vs 1.9±0.1 m 2 ; % predicted peak VO 2 99±7 vs 115±7 %; peak workload 188±16 vs 144±9 W, respectively; age and workload P <0.05). Visit 1: peak exercise ergometry test. Visit 2: constant‐load cycle ergometry at 30% peak workload (YNG=56±5 vs OLD=43±3 W, P <0.05) with the first 3 min without cuffing (0 mm Hg) and intermittent subsystolic bilateral thigh cuff inflations to 20, 40, 60, 80, or 100 mm Hg for 2 min (randomized), with 2 min deflation between occlusions thereafter. Minute ventilation (V E ), respiratory rate (RR), tidal volume (V T ), oxygen uptake (VO 2 ) indexed to weight, carbon dioxide output (VCO 2 ), respiratory exchange ratio (RER), V E /VCO 2 , and end tidal partial pressure CO 2 (P ET CO 2 ) were measured continuously via breath by breath system. Results At rest, V E , RR, V T , or RER did not differ in YNG vs OLD ( P >0.05); whereas VO 2 (6.3±0.3 vs 3.9±0.2 mL/kg/min) and VCO 2 (0.3±0.0 vs 0.2± 0.0 L/min) were higher in YNG vs OLD (respectively, P <0.05). During all exercise occlusions, V E was higher in YNG vs OLD, with the largest difference at 100 mm Hg (36.7±1.7 vs 30.2±1.6 L/min, respectively, P <0.05). However, the % change from rest to 0 mm Hg or each cuff occlusion resulted in no differences in YNG vs OLD for V E ( P >0.05). In contrast, in YNG vs OLD, the largest % change from 0 mm Hg to the cuff occlusion resulting in between group differences included V E (3.3±3.0 vs 17.3±3.6 at 80 mm Hg, P <0.05), VCO 2 (2.3±2.3 vs 20.8±3.4 at 100 mm Hg, P <0.05) and V E /VCO 2 (7.0±2.6 vs 0.5±1.8 at 100 mm Hg, P <0.05). In addition, there was a trend for significant differences between YNG and OLD for V T (−1.2±4.4 vs 5.9±4.1 % at 80 mm Hg, P =0.15), VO 2 (−2.1±1.5 vs 3.3±1.8 %, at 100 mm Hg, P =0.09) and P ET CO 2 (−6.4±1.9 vs −2.3±1.4 % at 100 mm Hg, P =0.11). Conclusions These data suggest that aging is associated with altered ventilatory responses to venous occlusion of locomotor muscles during constant load submaximal exercise. These changes may be a result of an increased contribution of locomotor muscle afferents on ventilatory control with aging. Support or Funding Information none

Introduction Healthy aging in adults is associated with attenuated cardiac output (Q) for a given exercise workload compared to younger healthy adults. This is important because skeletal muscle perfusion pressure during exercise is dependent on coordinated adjustments between cardiac and vascular hemodynamics. Cardiac power (CP) quantifies the flow and peripheral pressure generating capacity of the heart, and may be the strongest measure of cardiac function during exercise. Group III/IV muscle afferents are suggested to favorably influence Q and arterial pressure during exercise in young healthy adults. However, the influence of group III/IV afferents on cardiac hemodynamic and arterial pressure coupling during exercise remains unclear across the aging spectrum. Venous distension via subsystolic circulatory occlusion of locomotor muscles is suggested to increase group III/IV afferent outflow. The aim of this study was to assess the influence of subsystolic circulatory occlusion of locomotor muscles on CP in young vs aging healthy adults. Methods Healthy adults completed 2 visits (10 young [YNG] vs 9 OLD; age 22±1 vs 66±3 yrs, BSA 1.8±0.1 vs 1.9±0.1 m 2 ; % predicted peak VO 2 99±7 vs 115±7 %; peak workload 188±16 vs 144±9 W, respectively; age and workload P <0.05). Visit 1: peak exercise test. Visit 2: constant load cycle ergometry at 30% peak workload (YNG=56±5 vs OLD=43±3 W, P <0.05) with the first 3 min without cuffing (0 mm Hg), but thereafter included intermittent subsystolic bilateral thigh cuff inflations to 20, 40, 60, 80, or 100 mm Hg for 2 min (randomized), with 2 min deflation between inflations. Non‐invasive Q and mean arterial (MAP) pressure were measured using continuous hemodynamic photoplethysmography. We calculated CP=Q*MAP. Q and CP were indexed to BSA. Results At rest, MAP did not differ in YNG vs OLD, but Q and CP were higher in YNG vs OLD (P<0.05), which persisted throughout each exercise cuff occlusion. In YNG, the greatest increase in CP from 0 mm Hg occurred at 100 mm Hg (754±48 vs 899±48 L/min/m 2 · mm Hg, P <0.05) due to increased MAP (19±4%, P <0.05) but not Q (1±2%, P >0.05). In OLD, Q, MAP, and CP did not differ between 0 mm Hg and any occlusion ( P >0.05). The % increase in Q from rest to 0, 20, 60, 80, and 100 mm Hg was higher in YNG vs OLD ( P <0.05). The % increase in MAP from rest to any occlusion did not differ in YNG vs OLD ( P >0.05). The % increase in CP from rest to occlusions of 60 (130±9 vs 98±11%), 80 (142±9 vs 108±20%), and 100 (158±11 vs 114±14%) were higher in YNG vs OLD (all P <0.05). Within YNG, the % increase in CP from rest to 100 mm Hg was higher than the % increase from rest to 0, 20, 40, or 60 mm Hg ( P <0.05), driven by increased MAP ( P <0.05). Within OLD, these differences for % increase in CP did not occur despite MAP that was similar to YNG ( P >0.05). Conclusions These data suggest that CP is attenuated in OLD vs YNG healthy adults during subsystolic circulatory occlusion of locomotor muscles during submaximal constant load exercise. The reduced CP generation in older adults is related to a blunted increase in Q mediated by attenuated influence of group III/IV muscle afferents on cardiac function during exercise.

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.

Introduction: Assessment of cardiac function during exercise is critical in the clinical evaluation of patients with heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction. Direct invasive measurement of cardiac power (CP) and stroke work (SW) are robust measures of cardiac function. Non-invasive gas exchange based surrogates may provide practical means of assessing cardiac function in clinical and research settings; however, the relationship between invasive and non-invasive measurement of CP or SW during exercise is unclear in HFpEF and HFrEF. We aimed to assess relationships between invasive and non-invasive measures of CP and SW during exercise in HFpEF and HFrEF. Methods: HFpEF (n=47) and HFrEF (n=29) (age 71±10 vs 55±10 yrs; EF% 62±8 vs 21±6%; BSA 2.1±0.3 vs 2.1±0.2 m 2 ; weight 99±22 vs 87±15 kg; peak work 36±14 vs 37±13 watts (W), respectively; all p<0.05, except peak work) underwent peak exercise testing during right heart catheterization. Invasive measurement of cardiac pressures, hemodynamics, and arterial pressures were recorded at rest, 20 W, and peak work. Continuous measurement of HR and VO 2 occurred from rest to peak work via 12-lead ECG and metabolic measurement system, respectively. Invasive measurements were calculated as, CP=(MAP–RAP) x Q x 2.22х10 -3 ; SW=(MAP–PCWP) x SV I x 0.133; and non-invasive as, CP=VO 2 x MAP; SW=VO 2 /HR x MAP. All indices adjusted for body surface area. Results: At rest, there were moderate relationships between invasive and non-invasive measures of CP and SW in HFpEF (r=0.56 and 0.48) and HFrEF (0.57 and 0.73), respectively (all p<0.05). At 20 W, relationships between invasive and non-invasive measures of CP and SW strengthened in HFpEF (r=0.74 and 0.69) and HFrEF (0.74 and 0.72), respectively (all p<0.05). The relationships noted between invasive and non-invasive measures of CP and SW at 20 W persisted at peak work in HFpEF (r=0.74 and 0.67) and HFrEF (0.78 and 0.69), respectively (all p<0.05). Conclusion: These data suggest that non-invasive estimates of CP and SW correlate closely with invasive measures and may be reasonable surrogates for these indices during peak exercise testing in both HFpEF and HFrEF patients.

Introduction: Invasive measurement of cardiac power (CP) and stroke work (SW) during exercise are robust indices of cardiac function and relate to syndrome severity and prognosis in heart failure patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction. Because invasive measurement via catheterization laboratories are not always readily available, non-invasive cardiopulmonary exercise testing to estimate cardiac function is routinely performed in the clinical evaluation of HFpEF and HFrEF. However, it is unknown how VO 2 relates with CP and SW in HFpEF vs HFrEF. We compared relationships between CP and SW with VO 2 at rest and peak exercise in HFpEF vs HFrEF. Methods: 30 HFpEF and 32 HFrEF (EF: 62±2 vs 22±1%; males: 17 vs 30; age: 70±2 vs 55±2 yrs; BMI: 34±1 vs 28±1 kg/m 2 ; wt: 98±4 vs 86±3 kg (all p<0.05)) participated in exercise testing during right heart catheterization. Oxygen consumption (VO 2 ) was measured continuously from rest to peak work. Invasive measures at rest and peak work included mean radial arterial pressure (MAP), right atrial pressure (RAP), and pulmonary capillary wedge pressure (PCWP). We calculated CP=(MAP–RAP) x Q I x 2.22х10 -3 and SW=(MAP–PCWP) x SV I x 0.133. Results: At rest, R 2 between VO 2 and CP or SW were not different between HFpEF (CP=0.41, SW=0.30) and HFrEF (CP=0.39, SW=0.15). Slopes did not differ significantly between HFpEF (CP=0.13, SW=0.01) and HFrEF (CP=0.16, SW=0.01) for regressions between VO 2 and CP or SW; but, fitted intercepts of the regression showed significantly higher intercepts in HFrEF (CP=0.89, SW=1.16) vs HFpEF (CP=0.05, SW=0.27) for VO 2 vs CP and SW, respectively. At peak exercise, R 2 between VO 2 and CP or SW were not different between HFpEF (CP=0.48, SW=0.64) and HFrEF (CP=0.70, SW=0.67). Slopes did not differ between HFpEF (CP=0.18, SW=0.02) and HFrEF (CP=0.15, SW=0.02) for regressions between VO 2 and CP or SW, whereas the fitted intercepts the slope of the regression were significantly higher in HFrEF (CP=5.1, SW=4.4) vs HFpEF (CP=3.2, SW=2.0) for VO 2 vs CP and SW, respectively. Conclusion: Our data suggest that despite lower VO 2 relative to CP and SW in HFpEF, both the strength of relationship and rate of increase in VO 2 relative to CP and SW are similar between HFpEF and HFrEF at rest and peak exercise.