Bonikowske, Amanda R.

Background: Exercise stress testing uses metabolic equivalents of tasks (METs) to measure the energy cost of activities, aiding in the assessment of exercise capacity and cardiovascular health. Despite its significance, the correlation between calf muscle pump function (CPF) and exercise stress testing remains unexplored. We aimed to evaluate the relationship between CPF and peak METs as determined by cardiopulmonary treadmill exercise stress testing. Methods: The study included adults who underwent exercise cardiopulmonary stress testing and venous plethysmography at Mayo Clinic between April 2017 and March 2020. The protocols other than Bruce, Mayo, Modified Naughton, and Naughton protocols were excluded. The CPF ejection fraction (EF) was calculated per leg based on refill volumes post-exercise as a percentage of passive drain refill. The classification of CEAP (Clinical-Etiology-Anatomy-Pathophysiology) was utilized to better understand chronic venous insufficiency (CVI). Results: A total of 155 patients who underwent both exercise stress testing and venous plethysmography were included, with a mean age of 61.31 ± 14.03 years, and 84 (54.2%) were male. The peak measured METs for normal, unilaterally reduced, and bilaterally reduced CPF were 8.5 (2.5), 7.3 (2.1), and 7.1 (2.4), respectively (p=0.004, Figure 1). Multiple linear regression models were developed with METs as the outcome to determine if CPF was an independent predictor of METs on cardiopulmonary exercise stress testing. IIn model 1, the following independent variables were included: resting heart rate, peak heart rate, peak systolic blood pressure, recovery heart rate at minute 1, and worst EF (Table 1). In model 1, with only exercise parameters, lower EF was associated with lower METs (p=0.03). In a second analysis, variables identified as statistically significant with METs in the initial model were included, along with CEAP class (model 2) and CCI (model 3) (Table 2). In model 2, CEAP class 3 or higher was associated with decreased METs on the exercise stress test. This correlation implies that individuals with moderate to severe CVI may influence exercise capacity, demonstrating the interconnectedness of the cardiovascular system. Moreover, in model 3, the CCI, a predictor for mortality, was not significantly associated with METs. Conclusion: Our findings revealed that more severe CVI (CEAP class and reduced CPF) was associated with reduced exercise capacity after accounting for other factors.

Background. Frailty is a modifiable risk factor for morbidity and mortality among kidney transplant (KT) candidates. We previously demonstrated that an 8-wk center-based exercise intervention is associated with improved frailty parameters in patients with advanced chronic kidney disease. This study aimed to adapt the intervention for home-based delivery and examine its feasibility, safety, and acceptability in a multicenter cohort of KT candidates. Methods. We conducted a prospective pilot study between January 2021 and November 2023 involving KT candidates from Mayo Clinic in Minnesota and Baylor St. Luke’s Medical Center in Texas. Adults approved for KT who were (1) frail or prefrail by the Physical Frailty Phenotype and/or (2) had a Short Physical Performance Battery score ≤10 were enrolled. The exercise intervention consisted of an individualized exercise prescription provided by a Mayo Clinic exercise physiologist followed by 8 weekly phone calls. Feasibility was assessed via retention rates, adverse events were recorded, and acceptability was assessed via survey. Results. Baseline characteristics of the 15 enrolled participants included a median age of 64 y, 73.3% were men, and 73.3% were of White race. Sixty percent of participants completed the intervention. No unanticipated adverse events occurred. Most participants strongly agreed that the exercise intervention was beneficial to their overall health. Conclusions. This pilot study demonstrates that a home-based 8-wk exercise intervention is a promising prehabilitation strategy in KT candidates and provides important preliminary data for future larger, randomized studies.

Background: The Metabolically Obese Normal Weight (MONW) phenotype has been described as a unique subgroup of individuals with metabolic dysregulation similar to obese individuals, but not considered obese per se . In theory, these individuals have an adiposity-independent substrate predisposing them to metabolic dysregulation. We tested whether central obesity explains the metabolic abnormalities in persons with MONW in a prospective population-based cohort in the Czech Republic. Methods: We used data from Kardiovize Brno 2030 study, a prospective community-based cohort in Central Europe. We defined obesity using World Health Organization categories for body mass index (BMI) and central obesity by waist circumference (WC≥ 94 cm in men and ≥ 80 cm in women). Metabolically obese (MO) was defined using AHA criteria by having three or more of the following: Hypertriglyceridemia (≥ 1.7 mmol/l); HDL cholesterol level <1.0 mmol/l in men or <1.3 mmol/l in women; elevated blood pressure (systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg) or antihypertensive drug treatment or history of hypertension; elevated fasting plasma glucose ≥ 5.6 mmol/l; or drug treatment and central obesity. Results: Of the 2,056 participants (46% men; mean age= 47.2 years, SD=11.2) included in the current analysis, 975 (47.4%) had normal weight and 696 (33.8%) were overweight. Prevalence of MO in the overall sample was 20.6% (n=424), 3.7% (n=36) among those with normal BMI and 9.9% (n=204) among overweight individuals. From the 36 subjects with MONW, 33 (91.6%) had central obesity by WC, while 201/204 (98.5%) with metabolically obese overweight, had central obesity by WC. Remarkably, in a subgroup of people with no metabolic obesity factors nobody had central obesity, see Figure . Conclusions: Metabolic dysregulation in people labeled as MONW can be explained by excessive visceral adiposity and not by an inherent predisposition, independent of adiposity.These findings underscore the importance of identifying central obesity in clinical practice even if BMI is below the obese criteria.

Background Extended sedentary behavior is a risk factor for chronic disease and mortality, even among those who exercise regularly. Given the time constraints of incorporating physical activity into daily schedules, and the high likelihood of sitting during office work, this environment may serve as a potentially feasible setting for interventions to reduce sedentary behavior. Methods and Results A randomized cross‐over clinical trial was conducted at an employee wellness center. Four office settings were evaluated on 4 consecutive days: stationary or sitting station on day 1 (referent), and 3 subsequent active workstations (standing, walking, or stepper) in randomized order. Neurocognitive function (Selective Attention, Grammatical Reasoning, Odd One Out, Object Reasoning, Visuospatial Intelligence, Limited‐Hold Memory, Paired Associates Learning, and Digit Span) and fine motor skills (typing speed and accuracy) were tested using validated tools. Average scores were compared among stations using linear regression with generalized estimating equations to adjust standard errors. Bonferroni method adjusted for multiple comparisons. Healthy subjects were enrolled (n=44), 28 (64%) women, mean±SD age 35±11 years, weight 75.5±17.1 kg, height 168.5±10.0 cm, and body mass index 26.5±5.2 kg/m 2 . When comparing active stations to sitting, neurocognitive test either improved or remained unchanged, while typing speed decreased without affecting typing errors. Overall results improved after day 1, suggesting habituation. We observed no major differences across active stations, except decrease in average typing speed 42.5 versus 39.7 words per minute with standing versus stepping ( P =0.003). Conclusions Active workstations improved cognitive performance, suggesting that these workstations can help decrease sedentary time without work performance impairment. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06240286.

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.

Introduction: Cardiac rehabilitation (CR) is a cornerstone of secondary prevention for cardiovascular disease (CVD). CR participation is associated with improvements in secondary CVD risk factor management. However, it is unclear if CR participation is associated with maintained improvements in CVD risk factor management following CR completion. Purpose: The aim of this study was to assess the impact of CR participation on CVD risk factor management at 1 and 3 years following CR completion. Methods: This retrospective study analyzed 911 patients (73% male) enrolled in the CR program at Mayo Clinic from 2013 to 2020. Patient demographics, clinical characteristics, and CVD risk factor management were examined pre and post CR as part of clinical practice and assessed passively at 1 and 3 years following CR. Secondary prevention CVD risk factor goals included total cholesterol (<200 mg/dL), HDL cholesterol (>40 mg/dL), LDL cholesterol (<100 mg/dL), triglycerides (<150 mg/dL), systolic and diastolic blood pressure (<130 and <80 mmHg), and body mass index (BMI) (18.5-24.9 kg/m 2 ). Results: The mean age was 66±12 years and on average 33±9 CR sessions were attended. Table 1 shows the percentage (%) of patients meeting the secondary prevention CVD risk factor goals. The % of patients meeting the goals for total cholesterol, LDL, triglycerides, and diastolic blood pressure were higher post than pre CR. There were no changes in the % of patients meeting the goals for total cholesterol or LDL at 1 and 3 year follow up compared to post CR. At 1 and 3 year follow up, there was a lower % of patients meeting the goals for systolic and diastolic blood pressure and triglycerides (at 1 year follow up only) than post CR. No changes were present in the % of patients meeting the goals for HDL and BMI at any timepoint (all, p>0.09). Conclusions: CR participation was associated with maintained improvements in lipid management, but not in triglycerides or blood pressure control at 1 and 3 years following CR.

Introduction: Patients with coronary artery disease (CAD) are at increased risk of cognitive decline. A proposed mechanism is cerebral hypoperfusion related to vascular dysfunction and impaired cerebral blood flow regulation Hypothesis: Patients with CAD will have lower cerebrovascular function than age- and sex-matched controls, assessed as reactivity to a vasodilatory carbon dioxide (CO 2 ) stimulus. Methods: Adults 40-70years old with CAD were recruited on enrollment to a cardiac rehabilitation program following a cardiac event or hospitalization. Age and sex-matched adults without known disease or cardiovascular risk factors were recruited as healthy controls. Cognitive function was assessed by the Fluid Composite of the NIH Cognition Toolbox. Following a familiarization visit, participants underwent a stepped CO 2 protocol (room air, 2% CO 2 , 4% CO 2 , 6% CO 2 ) while continuously measuring middle cerebral artery velocity (MCAv) using transcranial doppler ultrasound, mean arterial pressure (MAP), ventilation (VE), and end-tidal CO 2 . Cerebrovascular conductance (CVCi) was calculated as MCAv/MAP. Cerebrovascular reactivity was calculated as the linear regression slope of CVCi against the change in end-tidal CO 2 . The reactivity of MAP and VE (or chemosensitivity) were also calculated. Results: 19 patients with CAD and 10 healthy controls were recruited ( Table 1 ). Compared with controls, patients with CAD had a 2-fold lower cerebrovascular reactivity (p=0.003), higher MAP reactivity (p<0.05), and a trend towards higher chemosensitivity (p<0.1) ( Table 2 ). There were no group differences in resting CVCi or cognition ( Table 2 ). After adjustment for age and sex, lower cerebrovascular reactivity was associated with lower peak oxygen uptake, diabetes, and smoking history ( Table 3 ). Conclusions: Compared with healthy controls, we report that patients with CAD have significantly lower cerebrovascular function, with no differences in cognitive function.

Background: Data on the occurrence of syncope and presyncope with hemodynamic instability during graded exercise test (GXT) are limited. Methods: We reviewed the Mayo Integrated Stress Center database for non-imaging GXTs performed between January 2006 and December 2010 and registered syncopic/presyncopic episodes. Electronic medical records were reviewed for clinical information, outcomes, and mortality. SAS was used to provide background statistics. Results: During the study period, a total of 40,715 GXTs were performed on 33,885 unique patients, including 16,306 (40.0%) GXTs on patients with known cardiovascular disease (CVD). High risk for cardiac syncope is defined as prior cardiac arrest/ventricular tachycardia, ischemic cardiomyopathy, implanted defibrillator, history of atrial fibrillation, sotalol, amiodarone, LQTS, HOCM, aortic stenosis was identified in 3263 patients (6.0%), while risk factors for non-cardiac syncope (POTS, history of dizziness/spells/syncope, rest SBP < 100 mmHg, age ≥ 80 years, female age < 30 years, beta blocker use) were found in 15,925 patients (39.1%). Despite the presence of so many patients at risk, only 8 episodes of syncope occurred (0.020% per test; 0.023% per individual patient). Another 5 episodes of near-syncope with documented hypotension were aborted by the quick action of the testing staff (0.012% per test; 0.015% per individual patient). Only 1 patient (a 71yo M with severeCAD) required electrical cardioversion for ventricular fibrillation. None of the other patients, including all 6 women, presented with tachyarrhythmias. There were no deaths and no significant musculoskeletal trauma. Conclusion: Despite many patients with risk factors for cardiac and non-cardiac syncope in the cohort, syncope, and near-syncope with hemodynamic instability were very rare findings on guideline-directed GXTs.

Introduction: Arrhythmias commonly occur during clinical exercise stress testing (EST), however there are limited data on prognostic significance, particularly differences between individuals with minor versus significant arrhythmia burden. Hypothesis: We hypothesized that significant but not minor arrhythmia burden during EST would be predictive of future all-cause mortality. Methods: Adults who underwent clinically indicated EST at Mayo Clinic Rochester between September 1993 and April 2017 were included and followed-up until March 2021 using the National Death Index to ascertain survival status. Expert clinician coding pertaining to arrhythmia burden during EST were used to group individuals (see Table 1 ). Cox proportional hazard models adjusted for known predictors of exercise-induced arrhythmias, were used to test the association of arrhythmia burden with all-cause mortality. Results: A total of 30796 individuals were included (age: 55±14yrs; female: 36%; Table 1 ). Mean follow-up was 8.8±3.6yrs, with a total of 2516 deaths. Arrhythmia during EST was associated with all-cause mortality compared with no arrhythmia (HR: 1.72; 95% CI: 1.58-1.88; p<0.001), however significant arrhythmia showed greater association compared with minor arrhythmia (HR: 2.07; 95% CI: 1.81-2.38; p<0.001). Both minor and significant arrhythmia during EST were significant predictors of all-cause mortality compared with no arrhythmia ( Figure, Table 2 ), however, after model adjustments, only significant arrhythmia was associated with all-cause mortality (HR: 1.40; 95% CI: 1.21-1.63; p<0.001) ( Table 2 ). Conclusions: After multivariate adjustment, significant arrhythmia burden during EST showed a 40% increased future risk of all-cause mortality, Conversely, adjusting for age and sex attenuated the effect of minor arrhythmia burden during EST on incidence of death. These results highlight the clinical significance of arrhythmia burden during exercise testing.