Olson, Thomas P.

Study objective: Heart failure (HF) syndrome is associated with pulmonary system abnormalities that have a direct impact on mortality. Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are distinct subtypes of HF with different pathophysiologies, clinical presentations, and treatment approaches. Obesity is highly prevalent in HFpEF and significantly contributes to its development. Importantly, obesity and high abdominal adiposity can have significant effects on pulmonary function. Therefore, HFpEF patients may have more pronounced pulmonary function impairment than HFrEF patients in part due to higher prevalence of upper body adiposity. Hypothesis: We hypothesized that lung volumes would be lower in patients with HFpEF compared to those with HFrEF and CTL. Further, we hypothesized that higher upper body adiposity (measured as trunk fat by dual-energy X-ray absorptiometry) would be associated with lower lung volumes in patients with HFpEF. Methods: HFpEF patients (n=26), HFrEF patients (n=26) and CTL (n=36) performed pulmonary function tests according to ATS/ERS guidelines. Total lung capacity (TLC), residual volume (RV), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) were measured and absolute and % predicted values are reported. Dual-energy X-ray absorptiometry scans quantified % trunk fat. Absolute lung volumes were compared across groups using ANCOVA with age as a covariate and % predicted lung volumes were compared using one-way ANOVA. Results: HFpEF patients were older than HFrEF patients and CTL (HFpEF: 71±9 vs. HFrEF: 65±9 vs. CTL: 63±11 yrs, both p<0.05) while no differences were present among groups for sex, height, or BMI (all, p>0.05). HFpEF patients had higher % trunk fat than CTL (p<0.01), while no differences were present between HFrEF and HFpEF or CTL (p>0.05) (HFpEF: 46±11 vs. HFrEF: 42±8 vs. CTL: 38±11%). HFpEF patients had lower FVC (HFpEF: 3.0±0.7 vs. HFrEF: 3.7±1.0 vs. CTL: 3.8±0.8 L), FEV1 (HFpEF: 2.3±0.5 vs. HFrEF: 2.8±0.8 vs. CTL: 2.9±0.6 L), TLC (HFpEF: 5.5±1.3 vs. HFrEF: 6.3±1.4 vs. CTL: 6.4±1.1 L), and % predicted TLC than CTL (all, p<0.05). HFpEF and HFrEF patients had lower % predicted FVC and % predicted FEV1 than CTL (p<0.05). All other pulmonary function parameters were not different among groups (p>0.05). There was a negative relationship between % trunk fat and TLC for HFpEF patients (r= -0.51, p<0.05). There were negative relationships between % trunk fat and FVC for CTL (r= -0.37) and HFpEF patients (r= -0.50) (both, p<0.05), with statistically different y-intercepts (p<0.01). There were no other significant relationships (all, p>0.05). Conclusion: These findings demonstrate that patients with HF have smaller lung volumes than CTL. Further, our findings suggest that upper body adiposity may be an important contributing factor to these pulmonary system abnormalities in HFpEF. None. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction: Cardiac rehabilitation (CR) is known to improve peak oxygen uptake (VO 2 peak) and body composition (BC). However, not all CR patients improve VO 2 peak and it remains unclear if non-responders also exhibit limited improvement in BC. This study aimed to examine if non-responders to VO 2 peak also demonstrate limited improvement in BC and whether BC is related to VO 2 peak changes in CR patients. Methods: Retrospective analysis of patients who completed CR between 2015 and 2022 at Mayo Clinic. The study included 143 patients who completed both dual-energy X-ray absorptiometry and cardiopulmonary exercise testing before and after CR. Patients were grouped by VO 2 peak response to CR (36 non-responders=Δ≤0 vs 107 responders=Δ>0 mL/kg/min). Within and between-group differences were assessed by paired and independent t-tests respectively. Regression models were used to evaluate whether baseline BC or ΔBC predict VO 2 peak changes. Results: As an entire cohort there were significant mean improvements in VO 2 peak and BC (Table 1, p<0.05). VO 2 peak increased in 75% of patients (responders: Δ 2.9±2 vs non-responders: Δ -2.1 ±2, mL/kg/min, p<0.05). There were no significant differences in baseline characteristics between groups including BC (Table 2, p>0.05); however, non-responders had significantly shorter duration and exercise sessions compared to responders (Table 2, p<0.001). Non-responders for VO 2 peak exhibited a significant improvement in body fat mass, body lean percentage, body fat percentage, and fat mass index (all p<0.001), with no differences in ΔBC between groups (Table 3). Regression models revealed no significant BC predictors for VO 2 peak. Conclusion: Despite significant improvements in BC, 25% of patients did not improve VO 2 peak with CR. These data suggest VO 2 peak improvement is not related to baseline BC or change in BC. These findings suggest the need for additional strategies to maximize improvements in VO 2 peak for patients undergoing CR.

Background: Life's Simple 7 (LS7) have been identified as key health factors aimed at achieving ideal cardiovascular health (CVH) and improving healthy life expectancy; however, it is unclear if different patient populations respond similarly to optimization of health behaviors. We sought to quantify the contribution of sex and age differences to changes in LS7 components in patients participating in cardiac rehabilitation. Methods: We included 937 adult patients who participated in CR from January 2018 to September 2020. LS7 metrics at baseline (pre-CR) and completion of CR (post-CR) were collected and changes in LS7 components (body mass index (BMI), diet, smoking, physical activity (PA), blood pressure (PB), cholesterol, glucose) were assessed by sex and age groups (<65 vs ≥65 years old). Each LS7 component was assigned 0 (poor), 1 (intermediate), or 2 (ideal) points and a final score was computed to estimate an individual’s level of CVH (0-14 pts): 0-6 = poor, 7-8= intermediate, 9 -14= ideal. Results: The mean age was 64±13 years, and 34% were female. Patients attended a mean of 11.1±12.5 CR sessions. LS7 components with the highest proportion within the poor category were HbA1c (41%) and BMI (50%) at the time of CR enrollment; neither women nor men showed improvement on either component. The trend towards improvement from poor to intermediate range on cholesterol and BP metrics was seen only in older patients (Table 1). Mean LS7 score improvement was greater in the older group, P=.01 (Fig 1). Both women and men equally improved LS7 scores (Table 2, Fig 2). Conclusions: Patients participating in CR demonstrated improvement in overall LS7 scores regardless of sex and age. However, age disparities exist in LS7 metrics, with exacerbated differences noted by a lack of improvement in LS7 components such as BP and cholesterol in younger patients. Our insights provide opportunities to explore equitable CVH.

Background Innovative restructuring of cardiac rehabilitation (CR) delivery remains critical to reduce barriers and improve access to diverse populations. Destination Cardiac Rehab is a novel virtual world technology‐based CR program delivered through the virtual world platform, Second Life, which previously demonstrated high acceptability as an extension of traditional center‐based CR. This study aims to evaluate efficacy and adherence of the virtual world–based CR program compared with center‐based CR within a community‐informed, implementation science framework. Methods Using a noninferiority, hybrid type 1 effectiveness‐implementation, randomized controlled trial, 150 patients with an eligible cardiovascular event will be recruited from 6 geographically diverse CR centers across the United States. Participants will be randomized 1:1 to either the 12‐week Destination Cardiac Rehab or the center‐based CR control groups. The primary efficacy outcome is a composite cardiovascular health score based on the American Heart Association Life's Essential 8 at 3 and 6 months. Adherence outcomes include CR session attendance and participation in exercise sessions. A diverse patient/caregiver/stakeholder advisory board was assembled to guide recruitment, implementation, and dissemination plans and to contextualize study findings. The institutional review board–approved randomized controlled trial will enroll and randomize patients to the intervention (or control group) in 3 consecutive waves/year over 3 years. The results will be published at data collection and analyses completion. Conclusions The Destination Cardiac Rehab randomized controlled trial tests an innovative and potentially scalable model to enhance CR participation and advance health equity. Our findings will inform the use of effective virtual CR programs to expand equitable access to diverse patient populations. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05897710.

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 Treatment with β‐antagonists in heart failure (HF) elicits known cardioprotective benefits. Recent work has suggested that administration of a β‐agonist can induce lung fluid clearance in healthy subjects and HF patients. However, the impact of β‐antagonists on the diffusing capacity of the lungs for carbon monoxide (DLCO, to assess lung fluid changes) remains unclear. PURPOSE To examine the relationship between β‐antagonist use and lung diffusion in HF patients. METHODS A retrospective analysis was performed on 102 HF patients seen at Mayo Clinic between 1995–2010. Patients were divided into two groups: BB=patients prescribed β‐antagonists (n=70) and NB=patients not prescribed β‐antagonists (n=32). Medical records were examined ±1 year from the time of the most recent exercise stress test for age (yrs), sex, height (cm), weight (kg), body mass index (BMI) and β‐antagonist status. Outcome variables included DLCO, left ventricular ejection fraction (LVEF), cardiac output (Q), and cardiac output corrected for body surface area (CI). Independent‐samples t‐test compared age, height, weight, and BMI between BB and NB. A Chi‐Squared test compared New York Heart Association (NYHA) classification and sex between NB and BB. Comparison of DLCO, LVEF, Q, CI, DLCO corrected for CI (DLCO/CI), and DLCO corrected for Q (DLCO/Q) between NB and BB was performed with an independent‐samples t‐test. Data are reported as mean ± standard deviation (SD) or frequency (percentage) where applicable. RESULTS There were no differences in age (75±12 vs. 76±13yrs), height (172±10 vs. 173±9cm), weight (84±20 vs. 86±18kg), or BMI (28±6 vs. 29±5kg/m 2 ) between NB vs. BB, respectively. Neither NYHA classification (χ 2 =0.159; p =0.98) or sex (χ 2 =0.066; p =0.80) were different between NB and BB groups. No differences were found for LVEF (36.8±17.3 vs. 31.6±15.6%) or DLCO (20.32±7.6 vs. 19.35±5.7ml/min/mmHg) for NB vs. BB, respectively. Compared to NB, the BB group demonstrated lower CI (0.72±0.3 vs. 0.56±0.3, p =0.006) and Q (1.47±0.6 vs. 1.15±0.6, p =0.01), while both DLCO/CI and DLCO/Q were higher in BB (31.32±14.1 vs. 43.84±29.5, p =0.005 and 15.84±7.5 vs. 21.93±16.2, p =0.01, respectively). CONCLUSIONS These data suggest that HF patients prescribed β‐antagonist therapy demonstrate better lung diffusion for a given cardiac output compared to HF patients not prescribed β‐antagonist therapy.

INTRODUCTION Bronchodilator therapy via β‐agonists has been considered a controversial treatment option for patients with cardiovascular disease, including heart failure (HF), due to previous studies suggesting increased rates of mortality. A major limitation to several previous studies is the lack of similar baseline characteristics between groups; therefore, a matched control comparison is yet to be explored. PURPOSE To evaluate the relationship between bronchodilator therapy and survival in HF patients. METHODS A retrospective analysis was performed on 96 HF patients who underwent a cardiopulmonary exercise test between the years 1994–2010. Patients were divided into two groups: 48 patients on bronchodilator therapy (BDT) and 48 matched controls (CTL). Patients were matched based on age (yrs), height (cm), weight (kg), body mass index (BMI), New York Heart Association (NYHA) classification, and cardioselective β‐blocker medication during the time of their cardiopulmonary exercise test. Patients were followed for an average of ten years for an endpoint of cardiovascular mortality. An independent samples t‐test was performed comparing BDT and CTL for age (yrs), height (cm), weight (kg), and BMI, to determine comparable baseline characteristics. A Chi‐Squared test compared NYHA classification, cardioselective β‐blocker status, and sex between BDT and CTL. A log rank test was performed to determine differences in survival distributions between BDT and CTL. RESULTS There were no significant demographic differences between groups (age: 59.8 vs. 60.3yrs; height: 172.1 vs. 171.9cm; weight: 86.9 vs. 86.2kg; and BMI: 28.9 vs. 28.6kg/m 2 for BDT vs. CTL, respectively). NYHA classification (χ 2 =0.00; p =1.0), cardioselective β‐blocker status (χ 2 =0.14; p =0.71) and sex (χ 2 =0.202; p =0.65) were not different between groups. BDT patients demonstrated an event rate of 51.1% compared to 42.6% for CTL patients over the same time period. The survival distribution for BDT compared to CTL was not statistically different, χ 2 (1) = 1.49, p =0.22. CONCLUSION These data suggest that HF patients on bronchodilator therapy demonstrate no significant difference in survival compared to matched HF controls. In contrast to previous work, our data suggests bronchodilator therapy does not elicit increased mortality in these HF patients.