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Cardiac physiologic pacing (CPP) after atrioventricular node (AVN) ablation for persistent atrial fibrillation (AF) has improved outcomes in patients with heart failure with reduced and preserved ejection fraction (HFpEF). Emerging evidence suggests patients with HFpEF benefit from higher heart rates, yet the optimal pacing rate after AVN ablation remains unknown. Optimal Pacing Rate for cardiac resynchronization therapy after atrioventricular node ablation in persistent Atrial Fibrillation and heart failure (OPT-RATE AF) is a prospective, randomized crossover study of patients with HFpEF after AVN ablation for persistent AF (NCT06445439). Approximately 60 patients with AF and AVN ablation, CPP, and HF with left ventricular ejection fraction ≥50% will be enrolled. Participants will be randomly assigned 1:1 to a pacing lower rate limit of 60 beats/min for 3 months and then switched to a rate of 80 beats/min for 3 months and vice versa. The primary end point is the change in exercise capacity assessed using the 6-minute walk test. Notable secondary outcomes will include changes in the Kansas City Quality of Life Questionnaire (KCCQ-12), creatinine and natriuretic peptide, and clinical events. Patient mortality and HF hospitalizations will be recorded at each phase. Electrocardiogram, echocardiogram, pacemaker interrogation, and primary and secondary outcomes will be recorded at baseline, 3 months, and 6 months. Study enrollment is ongoing and estimated to be completed by 2026. OPT-RATE AF is a randomized clinical trial that will determine the effect of a higher pacing rate in patients with persistent AF and HFpEF after AVN ablation and/or CPP. Study findings will provide insight on the role of chronotropy in improving quality of life and other important cardiovascular outcomes., Competing Interests: Declaration of competing interest Drs. Weintraub and Thomaides have received unrestricted research grants from Medtronic. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although cardiopulmonary exercise testing (CPET) parameters have known prognostic value in adults after Fontan palliation, there are limited data correlating treadmill CPET with invasive exercise hemodynamics. Furthermore, the invasive hemodynamic underpinnings of exercise limitations have not been thoroughly investigated. This is a retrospective analysis of 55 adults (age ≥18 years) with prior Fontan palliation who underwent treadmill CPET before invasive exercise hemodynamic testing using a supine cycle protocol between November 2018 and April 2023. The median age was 32.2 (IQR 24.1; 37.2) years. The peak heart rate (HR) was 139.7 ± 28.1 beats per minute and the peak oxygen consumption (VO 2 ) was 19.1 ± 5.7 ml/kg/min (47.4 ± 13.5% predicted). VO 2 /HR was directly related to exercise stroke volume index (r = 0.50, p = 0.0002), whereas no association was seen with exercise arterio-mixed venous O 2 content difference (r = 0.14, p = 0.32). Peak HR was inversely related to exercise pulmonary artery (PA) pressures (r = -0.61, p <0.0001) and PA wedge pressures (PAWP) (r = -0.61, p <0.0001). Moreover, %predicted VO 2 was inversely related to exercise PA pressures (r = -0.50, p <0.0001) and PAWP (r = -0.55, p <0.0001). Peak VO 2 ≤19.1 ml/kg/min had a sensitivity of 81% and a specificity of 76% (area under the curve 0.82) for predicting a ΔPAWP/ΔQs ratio >2 mmHg/L/min and/or a ΔPA/ΔQp >3 mmHg/L/min, whereas a predicted peak VO 2 ≤48% had a sensitivity of 74% and a specificity of 81% (area under the curve 0.79) for the same parameters. In summary, lower peak HR and peak VO 2 were associated with higher exercise PAWP and PA pressure. Peak VO 2 ≤48% predicted provided the optimal cutoff for predicting increased indexed exercise PAWP or PA pressures; therefore, low peak VO 2 should alert clinicians of abnormal underlying hemodynamics., Competing Interests: Declaration of competing interest Dr. Egbe is supported by National Heart, Lung, and Blood Institute grants (K23 HL141448, R01 HL158517, and R01 160761)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Diastolic dysfunction plays a major role in precipitating congestive heart failure in patients with hypertrophic cardiomyopathy (HCM). In many such patients, symptoms are unmasked only during exercise because left ventricular (LV) filling pressure is normal at rest but increase with exercise. We sought to establish whether abnormal postexercise diastolic parameters are associated with reduced exercise capacity in patients with HCM. We examined 590 patients with asymptomatic/minimally symptomatic HCM (age 54 ± 14 years, 57% men, body mass index 30 ± 6 kg/m 2 , 84% on β blockers) with HCM by 2-dimensional and Doppler echocardiography at rest and after maximal treadmill exercise echocardiography (TSE). A complete echocardiogram (including LV ejection fraction, LV thickness, LV outflow tract [LVOT] gradient, degree of mitral regurgitation) was recorded. Diastolic parameters (septal and lateral [e'] velocities of the mitral annulus, peak early [E] and late [A] mitral inflow velocity, E/A ratio, E/e', right ventricular systolic pressure [RVSP], and left atrial volume index) were recorded at rest and after TSE. Exercise functional capacity was recorded and divided into <85% or >85% of age-gender predicted metabolic equivalents (AGP-METs). After maximal exercise, 32% patients had at least moderate mitral regurgitation, mean LVOT gradient was 61 ± 59 mm Hg, E/A ratio was 1.2 ± 1.0, average E/e' ratio 12.9 ± 1.0, and peak RVSP was 36 ± 15 mm Hg. Only 42% of patients achieved >85% of AGP-METs; the mean METs was 7 ± 3. On multivariable logistic regression analysis, higher body mass index (odds ratio [OR] 1.05), β-blocker use (OR 2.58), higher left atrial volume index (OR 1.02), higher peak stress LVOT gradient (LVOTG) (OR 1.06), peak stress E/e' (OR 1.04), and higher RVSP (OR 1.03) were independently associated with <85% AGP-METs achieved (all p <0.05). In conclusion, in patients with asymptomatic/minimally symptomatic HCM who underwent TSE, there is a significant and independent association between abnormal diastolic response to exercise and reduced exercise capacity in HCM. Incorporating diastolic parameters during stress echocardiography could provide incremental diagnostic utility in deciphering the exact etiology of dyspnea in such patients., Competing Interests: Declaration of competing interest Dr. Milind Desai is a consultant and has research agreements with Bristol Myers Squibb, Cytokinetics, Tenaya, Viz-AI, and Edgewise. No industry support was utilized in the conduct of this study. The remaining authors have no competing interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sedentary lifestyle is reported to be associated with diminished exercise capacity, resulting in increased cardiovascular risk in adults with congenital heart disease (CHD). This cross-sectional study examined the association between objectively measured physical activity (PA) and exercise capacity in children and adolescents with CHD. Therefore, 107 patients (aged 13.0 ± 2.7 years, 41 girls) with various CHD performed a cardiopulmonary exercise test to quantify their peak oxygen uptake (peakV'O2). Moderate to vigorous PA (MVPA) and daily step count were assessed using Garmin vivofit jr. (Garmin, Germany) for 7 consecutive days. For association between PA and submaximal exercise capacity, Spearman correlation was performed. Patients with CHD showed almost normal values compared with the reference (79.5 ± 17.2% [31.6 to 138.1] %peakV'O2 predicted), with roughly normal ventilatory anerobic thresholds (50.6 ± 14.0% [20.3 to 97.9] % oxygen uptake at ventilatory anaerobic threshold [VATV'O2]). Step counts are below the recommendations (9,304 ± 3,792 steps/day [1,701 to 20,976]), whereas MVPA data are above the recommendations for children with ≥60 min/day (83.6 ± 34.6 min/day [10.1 to 190.9]). The Spearman rho showed significant positive correlations to VATV'O2 (r = 0.353, p <0.001) and %VATV'O2 (r = 0.307, p = 0.001), with similar results regarding MVPA (VATV'O2: r = 0.300, p = 0.002 and %VATV'O2: r = 0.270, p = 0.005). In conclusion, submaximal exercise capacity and PA correlate positively, making both assessments relevant in a clinical setting: PA in the context of cardiovascular prevention and peakV'O2 as the strongest predictor for morbidity and mortality., Competing Interests: Declaration of competing interest JH and LW received an unrestricted grant from Stiftung KinderHerz Deutschland gGmbH. The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Left ventricular diastolic dysfunction exists in patients with heart failure with reduced ejection fraction and causes activity restriction and a poor prognosis, but there have been few reports about exercise tolerance in patients with diastolic dysfunction, regardless of left ventricular ejection fraction (LVEF). In this study, 294 cardiovascular disease patients who performed a cardiopulmonary exercise test (CPX) with an adequate examination by echocardiography at Fukuoka University Hospital from 2011 to 2020 were investigated. Patients were divided into groups with grade I and grade II or III diastolic dysfunction according to diagnostic criteria, regardless of LVEF, by echocardiography. After adjusting for age, gender, body mass index, smoking, and LVEF by propensity score matching, we compared the results of CPX between the grade I and grade II/III groups. There were no significant differences in hemodynamic parameters, or in the respiratory exchange ratio, oxygen uptake per body weight, oxygen uptake per heart rate, or parameters of ventilatory volume. Ventilatory equivalents per oxygen uptake and per carbon dioxide output were significantly worse in the grade II/III group from the rest to peak periods during CPX. In conclusion, left ventricular diastolic dysfunction worsens ventilatory efficacy during CPX. This effect potentially contributes to a poor prognosis in left ventricular diastolic dysfunction., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The improving ATTENDance (iATTEND) to cardiac rehabilitation (CR) trial tested the hypotheses that hybrid CR (HYCR) (combination of virtual and in-facility CR sessions) would result in greater attendance compared with traditional, facility-based only CR (FBCR) and yield equivalent improvements in exercise capacity and health status. Patients were randomized to HYCR (n = 142) or FBCR (n = 140), stratified by gender and race. Attendance was assessed as number of CR sessions completed within 6 months (primary end point) and the percentage of patients completing 36 CR sessions. Other end points (tested for equivalency) included exercise capacity and self-reported health status. HYCR patients completed 1 to 12 sessions in-facility, with the balance completed virtually using synchronized, 2-way audiovisual technology. Neither total number of CR sessions completed within 6 months (29 ± 12 vs 28 ± 12 visits, adjusted p = 0.94) nor percentage of patients completing 36 sessions (59 ± 4% vs 51 ± 4%, adjusted p = 0.32) were significantly different between HYCR and FBCR, respectively. The between-group changes for exercise capacity (peak oxygen uptake, 6-minute walk distance) and health status were equivalent. Regarding safety, no sessions required physician involvement, there was 1 major adverse event after a virtual session, and no falls required medical attention. In conclusion, although we rejected our primary hypothesis that attendance would be greater with HYCR versus FBCR, we showed that FBCR and HYCR resulted in similar patient attendance patterns and equivalent improvements in exercise capacity and health status. HYCR which incorporates virtually supervised exercise should be considered an acceptable alternative to FBCR. NCT Identifier: 03646760; The Improving ATTENDance to Cardiac Rehabilitation Trial - Full-Text View - ClinicalTrials. gov; https://classic.clinicaltrials.gov/ct2/show/NCT03646760., Competing Interests: Declaration of competing interest Dr. Lanfear is a consultant for Abbott Laboratories, Astra Zeneca, Cytokinetics, Illumina (Lilly), Janssen, and Duke Clinical Research Institute (Novartis) and has participated in clinical research from Amgen, Akros, AstraZeneca, Bayer, Cytokinetics, Illumina, Pfizer (New York, New York, United States), and Janssen. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Patients with heart failure with preserved ejection fraction (HFpEF) often receive β-blocker (BB) therapy for management of co-morbidities. However, the association of BB therapy with exercise capacity and health-related quality of life (HRQL) in HFpEF is not well-studied. In this post hoc analysis of the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF (RELAX) trial, which included patients with chronic stable HFpEF with peak exercise capacity assessment at baseline and at 12 and 24 weeks of follow-up, we evaluated the association of BB use with the measures of exercise capacity (peak exercise oxygen uptake), anaerobic threshold, and HRQL (Minnesota living with heart failure questionnaire). Separate linear mixed-effect models were constructed for each outcome with adjustment for treatment arm, demographics, medical history, left ventricular ejection fraction, and duration of heart failure. Of the 216 study participants (median age 69 years, 48.2% women), 76% reported BB use at baseline. Participants with (vs without) BB therapy were older (70 vs 63.5 years, p = 0.001) and had a higher prevalence of ischemic heart disease (44% vs 23%, p = 0.01). In the adjusted linear mixed model, BB use over time was not associated with peak exercise oxygen uptake (β 95% confidence interval [CI] 0.2 (-0.31 to 0.7), p = 0.5) and 6-minute walk distance (β 95% CI 14.69 [-14.25 to 43.63], p = 0.3). However, BB use was associated with a higher anaerobic threshold (β 95% CI 0.32 (0.02 to 0.62), p = 0.036) and better HRQL (lower quality of life as assessed by Minnesota living with heart failure questionnaire score) (β 95% CI -6.68 [-10.96 to -2.4], p = 0.002). Future trials are needed to better evaluate the effects of BB on exercise capacity in patients with chronic stable HFpEF., Competing Interests: Declaration of competing interest Dr. Chandra has received grant funding outside the present study from August Health. Dr. Pandey has received grant funding outside the present study from Applied Therapeutics and Gilead Sciences; has received honoraria outside the present study as an advisor/consultant for Tricog Health Inc and Lilly, Rivus, and Roche Diagnostics; and has received nonfinancial support from Pfizer and Merck. Dr. Segar reports speaker fees from Merck & Co and grant support from the American Heart Association outside the present study. The remaining authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The study aimed to examine the effects of inspiratory muscle training (IMT) in patients with pulmonary hypertension (PH). A total of 24 patients with PH were included in the randomized controlled evaluator-blind study. IMT was performed at 40% to 60% of the maximal inspiratory pressure for 30 min/d, 7 d/wk (1 day supervised) for 8 weeks. Respiratory muscle strength, dyspnea, diaphragm thickness (DT), pulmonary functions, 24-hour ambulatory blood pressure (BP), arterial stiffness, exercise capacity, upper extremity functional exercise capacity, physical activity levels, fatigue, anxiety-depression levels, activities of daily living (ADL), and quality of life were evaluated. A total of 24 patients (treatment = 12, control = 12) completed the 8-week follow-up. There was no significant difference between the patient groups in terms of demographic and clinical characteristics (p >0.05). Considering the change between the groups in the treatment and control groups, brachial and central BP, dyspnea, respiratory muscle strength, DT in total lung capacity, knee extension muscle strength, functional exercise capacity, upper extremity functional exercise capacity, physical activity, ADL, fatigue, anxiety, and quality of life improved in favor of the IMT group (p <0.05). In conclusion, IMT has improved brachial and central BP, dyspnea, respiratory muscle strength, DT in total lung capacity, knee extension muscle strength, functional exercise capacity, upper extremity functional exercise capacity, physical activity, ADL, fatigue, anxiety, and quality of life compared with the control group. IMT is an effective method in cardiopulmonary rehabilitation for patients with PH., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Decreased exercise capacity portends a poor prognosis in heart failure with preserved ejection fraction (HFpEF). The hemodynamic gain index (HGI) is an integrated marker of hemodynamic reserve measured during exercise stress testing and is associated with survival. The goal of this study was to establish the association of HGI with exercise capacity, serum biomarkers, and echocardiography features in subjects with HFpEF. In 209 subjects with HFpEF enrolled in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial who underwent cardiopulmonary exercise testing, we calculated the HGI ([peak heart rate [HR] × peak systolic blood pressure [SBP]-[HR at rest × SBP at rest])/(HR at rest × SBP at rest) and tested associations with outcomes of interest. The median (interquartile range) HGI was 0.94 (0.5 to 1.3) beats per min/mm Hg. In multivariable-adjusted linear regression, higher HGI was associated with greater peak oxygen consumption (VO 2 ), VO 2 at anaerobic threshold, peak minute ventilation, and 6-minute walk distance (all p <0.001). Higher HGI was associated with lower serum high-sensitivity troponin I, pro-collagen III, N-terminal pro-B-type natriuretic peptide, and creatinine (all p <0.05) and with longer deceleration time, lower E/A ratio, and lower left atrial volume index by echocardiography (all p <0.05). In conclusion, higher HGI in stable HFpEF was associated with greater exercise capacity, a biomarker profile indicating less myocardial injury and fibrosis and less kidney dysfunction, and with less severe diastolic dysfunction. These results suggest that HGI, an easily calculated metric from routine exercise testing, is a marker of functional capacity and disease severity in HFpEF and may serve as a surrogate for VO 2 parameters for use in treadmill testing without gas exchange capability., Competing Interests: Disclosures Dr. Grodin reports personal fees from Pfizer, Alnylam, Eidos, and Sarepta. Dr. Tang reports personal fees from Sequana Medical AG, Cardiol Therapeutics Inc, Genomics plc, Springer Nature, and the American Board of Internal Medicine for exam writing committee participation - all unrelated to the subject and contents of this study. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The purpose of this study was to test the hypothesis that an individualized exercise training target heart rate (HR) based on a maximal graded exercise test (GXT) is associated with greater improvements in exercise tolerance during cardiac rehabilitation (CR) compared with no GXT. In this retrospective study, we identified patients who completed 9 to 36 visits of CR between 2001 and 2016, with a length of stay ≤18 weeks and a visit frequency of 1 to 3 days per week. Patients were grouped based on whether their exercise was guided by a target HR determined from a GXT. To assess the relation between GXT and change in exercise training metabolic equivalents of task (METs), we used generalized linear models adjusted for age, gender, race, referral reason, CR visits, CR frequency, METs at start, CR location, and year of participation. Out of 4,455 patients (37% female, 48% White, median age = 62 years), 53% were prescribed a target HR based on a GXT. Compared with no GXT, a GXT was associated with a significantly greater increase in covariate-adjusted METs during CR and percentage change from start (+0.44 METs [95% confidence interval [CI] 0.38 to 0.51] and +17% [95% CI 14% to 19%], respectively). In a sensitivity analysis limited to patients with 24 to 36 visits at ≥2 days per week (n = 1,319), a GXT was associated with a significantly greater increase in covariate-adjusted exercise training METs (+0.51 [95% CI 0.36 to 0.66]; +19% [95% CI 13% to 24%]). In conclusion, to maximize the potential increase in exercise capacity during CR, patients should undergo a GXT to determine an individualized exercise training target HR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Interleukin-1 (IL-1) blockade is an anti-inflammatory treatment that may affect exercise capacity in heart failure (HF). We evaluated patient-reported perceptions of exertion and dyspnea at submaximal exercise during cardiopulmonary exercise testing (CPET) in a double-blind, placebo-controlled, randomized clinical trial of IL-1 blockade in patients with systolic HF (REDHART [Recently Decompensated Heart Failure Anakinra Response Trial]). Patients underwent maximal CPET at baseline, 2, 4, and 12 weeks and rated their perceived level of exertion (RPE, on a scale from 6 to 20) and dyspnea on exertion (DOE, on a scale from 0 to 10) every 3 minutes throughout exercise. Patients also answered 2 questionnaires to assess HF-related quality of life: the Duke Activity Status Index and the Minnesota Living with Heart Failure Questionnaire. From baseline to the 12-week follow-up, IL-1 blockade significantly reduced RPE and DOE at 3- and 6-minutes during CPET without changing values for heart rate, oxygen consumption, and cardiac workload at 3- and 6-minutes. Linear regression identified 6-minute RPE to be a strong independent predictor of both physical symptoms (Minnesota Living with Heart Failure Questionnaire; β = 0.474, p = 0.002) and perceived exercise capacity (Duke Activity Status Index; β = -0.443, p = 0.008). In conclusion, patient perceptions of exertion and dyspnea at submaximal exercise may be valuable surrogates for quality of life and markers of response to IL-1 blockade in patients with HF., Competing Interests: Disclosures Dr. Van Tassell and Dr. Abbate were co-prinicpal investigators on the NIH funding for this study. Please list both of them as receiving financial support from NIH., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Exercise stress testing is routinely performed to evaluate suspected coronary artery disease in older adults. However, the available data to predict and compare relative exercise capacity in the general population were developed using predominantly younger, healthy cohorts with few or no women. This study aimed to describe the exercise capacity of patients older than 75 years who underwent a clinically indicated Bruce protocol exercise stress test. This was a retrospective, cross-sectional study of 2,041 consecutive patients older than 75 years who performed a Bruce protocol exercise stress echocardiogram that was terminated because of maximal effort without ischemia at Columbia University Medical Center between April 10, 2009, and July 30, 2020. The analytic sample included 2,041 exercise stress tests in 786 women (median [interquartile range] age 79 [77 to 81] years) and 1,255 men (median [interquartile range] age 79 [77 to 82] years). Cardiovascular risk factors and clinical coronary disease were common and more prevalent in men than women. The median exercise time for men aged 76 to 80 years was 7:22 (minutes:seconds) and for women was 6:00 and significantly decreased in both genders as age increased (p <0.001). The mean (SD) METs achieved for women and men were 6.5 (1.6) and 7.7 (1.7), respectively. Most women (85%) and men (95%) completed the first stage, whereas only 32% of women and 64% of men completed the second stage. It was uncommon for women (3%) or men (15%) to complete the third stage. Fewer than 1% of patients completed the fourth stage, and none completed the fifth stage. At all ages, women had a lower exercise capacity than men. These data allow physicians to compare the exercise capacity of older patients who underwent a Bruce protocol exercise stress test more accurately to a representative sample of similarly aged adults., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderate-good systolic ventricular function. Fontan patients between 8 and 18 years with moderate-good systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B-type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 ± 0.1 mg/kg/d. A total of 6 patients (21%) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B-type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Comprehensive geriatric assessment (CGA)-based cardiac rehabilitation (CR) program is essential for patients before and after transcatheter aortic valve implantation (TAVI). This study aimed to explore the values of CGA and exercise capacity in CR for patients referred to TAVI. A retrospective analysis was conducted in 90 patients referred to TAVI from January to October 2019. CR strategies started before TAVI. The association between clinical characteristics, CGA, and change in six-minute walk distance (Δ6MWD) was analyzed with multivariate regression models. Most of patients had cognitive impairment (50%), malnutrition (61%), and frailty (83%). After the CR, the proportion of cognitive impairment, malnutrition, and frail patients was significantly decreased by 21%, 40%, and 57%, respectively (p = 0.002, p <0.001, p <0.001). The 6MWD at a month after discharge (291.9 ± 98.8 m) was significantly improved than that at discharge after TAVI (218.8 ± 114.3m, p <0.001). The multivariate regression analysis indicated body mass index (BMI; Δ6MWD:12.0, 95% confidence interval [CI] 0.3 to 23.8, p = 0.045), frailty (Δ6MWD: -57.9, 95% CI -81.8 to -34.1, p <0.001) and malnutrition (Δ6MWD: -25.1, 95% CI -47.0 to -3.2, p = 0.026) as the associated predictors of Δ6MWD. In conclusion, functional status in patients referred to TAVI could be improved by CGA-based CR. BMI, frailty, and malnutrition were associated with the efficacy of CR on exercise capacity. CGA can play the important role in the evaluation and making strategies for CR in patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Heart rate reserve (HRR) during physical or pharmacological stress is a sign of cardiac autonomic function and sympathetic reserve, but it can be reduced during exercise for confounders such as poor motivation, drugs or physical fitness. In this study we sought to assess the prognostic meaning of HRR during dipyridamole stress echocardiography (DSE) in patients with abnormal chronotropic response to exercise. From 2004 to 2019, we prospectively acquired and retrospectively analyzed 379 patients (age 62 ± 11 years; ejection fraction 60 ± 5%) with suspected (n = 243) or known (n = 136) chronic coronary syndromes, referred to DSE for chronotropic incompetence during upright bicycle exercise-electrocardiography test defined as HRR used [(peak HR - rest HR) / (220 - age) - rest HR] ≤80% in patients off and ≤62% in patients on beta-blockers. All patients were in sinus rhythm and underwent DSE (0.84 mg/kg) within 3 months of exercise testing. During DSE, age-independent HRR (peak/rest HR) ≤1.22 was considered abnormal. All patients were followed-up. All-cause death was the only outcome measure. HRR during DSE was normal in 275 (73%) and abnormal in 104 patients (27%). During a follow-up of 9.0 ± 4.2 years, 67 patients (18%) died. The 15-year mortality rate was 23% in patients with normal and 61% in patients with abnormal HRR (p < 0.0001). At multivariable analysis a blunted HRR during DSE was an independent predictor of outcome (hazard ratio 2.01, 95% confidence intervals 1.23-3.29; p = 0.005) with age and diabetes, while neither inducible ischemia nor ongoing beta-blocker therapy were significant predictors. In conclusion, a blunted HRR during DSE predicts a worse survival in patients with chronotropic incompetence during exercise test. HRR during DSE is an appealingly simple biomarker of cardiac autonomic dysfunction independent of imaging, exercise and beta-blocker therapy., (Copyright © 2021. Published by Elsevier Inc.)

Coronary artery bypass grafting (CABG) often causes physiological changes in patients. Although functional changes, such as lung function and exercise capacity changes, are observed in patients, there are no detailed studies examining this. The aim was to compare preoperative and postoperative pulmonary function and exercise capacity in patients undergoing on-pump CABG with a multidimensional index (BODE index). Demographic and surgical characteristics of patients were recorded. Pulmonary function test, six-minute walk test (6MWT), and modified Medical Research Council (mMRC) dyspnea score were assessed and BODE index were calculated in preoperative and at six months postoperatively. A total of 75 patients were included with a mean ± standard deviation age of 59.8±10.0 years. The male to female ratio was 57/18. There was a statistically significant decrease in the forced expiratory flow at 25-75% (FEF 25-75 %) value after CABG. Other pulmonary function test values were also lower in the postoperative period compared to the preoperative period, but these changes were not significant. The mean distance achieved in the 6MWT (p=0.02) and the mMRC dyspnea score (p=0.001) were significantly better postoperatively. The BODE index, which combines these parameters, had increased in the postoperative period. Age (OR 1.09; 95% CI: 1.008-1.181) and postoperative FEF 25-75 % (OR -0.96; 95% CI: 0.938-0.988) were the independent predictors of BODE score ≥3 in multivariate analysis. Despite the decrease in pulmonary function in patients undergoing CABG, there was an improvement in exercise capacity and dyspnea score., Competing Interests: Conflicts of Interest The Authors declare that there are no financial disclosures or conflict of interest associated with this study. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Patients with diabetes mellitus (DM) frequently present reduced exercise capacity. We aimed to explore the extent to which peripheral extraction relates to exercise capacity in asymptomatic patients with DM. We prospectively enrolled 98 asymptomatic patients with type-2 DM (mean age of 59 ± 11 years and 56% male sex), and compared with 31 age, sex and body mass index-matched normoglycemic controls. Cardiopulmonary exercise testing with resting followed by stress echocardiography was performed. Exercise response was assessed using peak oxygen uptake (peak VO 2 ) and ventilatory efficiency was measured using the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO 2 ). Peripheral extraction was calculated as the ratio of VO 2 to cardiac output. Cardiac function was evaluated using left ventricular longitudinal strain, E/e', and relative wall thickness. Among patients with DM, 26 patients (27%) presented reduced percent-predicted-peak VO 2 (<80%) and 18 (18%) presented abnormal VE/VCO 2 slope (>34). There was no significant difference in peak cardiac output; however, peripheral extraction was lower in patients with DM compared to controls. Higher peak E/e' (beta = -0.24, p = 0.004) was associated with lower peak VO 2 along with age, sex and body mass index (R 2  = 0.53). A cluster analysis found left ventricular longitudinal strain, E/e', relative wall thickness and peak VO 2 in different clusters. In conclusion, impaired peripheral extraction may contribute to reduced peak VO 2 in asymptomatic patients with DM. Furthermore, a cluster analysis suggests that cardiopulmonary exercise testing and echocardiography may be complementary for defining subclinical heart failure in patients with DM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In the pediatric population, exercise capacity differs between females and males and the gap widens through adolescence. However, specific age- and sex-based changes in adolescents with congenital heart disease and Fontan palliation have not been reported. The purpose of the current study is to identify age- and sex-specific changes in exercise performance at peak and ventilatory anaerobic threshold (AT) for adolescents with Fontan physiology. Retrospective review of the Pediatric Heart Network Fontan cross sectional study (Fontan 1) public use dataset. Comparisons were made for peak and AT exercise parameters for females and males at 2-year age intervals. In addition, normative values were generated by sex and age at 2-year intervals. χ 2 test was used for comparison for categorical variables. Changes in exercise parameters between age groups by sex were compared by ANOVA with post-hoc analysis. Exercise testing was performed in 411 patients. AT was reached in 317 subjects (40% female), of whom, 166 (43% female) reached peak exercise. Peak oxygen consumption decreased 32% through adolescence in females and did not have the typical increase through adolescence for males. Oxygen consumption at AT also decreased with age in both sexes. In conclusion, age- and sex-based exercise performance for adolescents with Fontan physiology are predictably low, but there are additional significant decreases through adolescence for this population, especially in females. We have established normative exercise values for several parameters for this population which will better identify at risk patients and allow for earlier intervention., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Exercise testing represents the preferred stress modality for individuals undergoing evaluation of suspected myocardial ischemia. Patients with limited functional status may be unable to achieve an adequate exercise stress, thus influencing the diagnostic sensitivity of the results. The Duke Activity Status Index (DASI) is a clinically applicable tool to estimate exercise capacity. The purpose of the current study was to assess the utility of the DASI to identify patients unable to achieve an adequate exercise stress result. Patients referred for exercise stress testing were administered the DASI pre-exercise. Baseline characteristics and exercise variables were evaluated including DASI-metabolic equivalents (DASI-METs), peak METs, exercise time (ET), and %-predicted maximal heart rate (%PMHR). Criteria for determining adequate exercise stress was defined as ≥85%PMHR or ≥ 5-METs at peak exercise. In 608 cardiovascular stress tests performed during the study period; 314 were exercise stress. The median DASI-METs (8.4 [interquartile range; 6.7 to 9.9]) was associated with estimated peak exercise METs (R=0.50, p <0.001), ET (R=0.29, p <0.001), and %PMHR (R=0.19, p = 0.003). DASI-METs were different between those with < or ≥85%PMHR (7.9 [6.6-9.0] vs. 8.9 [7.1-9.9], P=0.025) and those with < or ≥5-METs (5.8 [4.6 to 6.6] versus 8.9 [7.3-9.9], p <0.001). Receiver operating characteristic curve analysis identified a DASI-MET threshold of ≤/>7.4 to optimally predict adequate exercise stress (sensitivity=93%, specificity=71%). In conclusion, the DASI correlates with peak METs, ET, and %PMHR among patients referred for exercise testing and can be used to identify patients with an increased likelihood of an inadequate stress test result., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Several studies have reported aortic dilation and increased stiffness of the ascending aorta in patients after repair of congenital heart disease (CHD), which may be a predominant cardiovascular risk. However, the clinical significance has not been described in detail. In this retrospective study, 175 repaired patients with complex CHD achieving biventricular circulation and age-matched 39 control subjects were reviewed (median age: 14.9 and 15.7 years, respectively). We measured the diameters of the ascending aorta and descending aorta from catheterization angiograms to yield Z-scores and stiffness indexes (β) using diameter fluctuations corresponding to pulsatile pressures. Clinical profile, peak oxygen uptake during the cardiopulmonary exercise test, and incidence of unscheduled hospitalization during follow-up was also reviewed. Compared with controls, patients with complex CHD, except for those with aortic coarctation, exhibited significant dilation and increased stiffness of the aortic root and ascending aorta, but not of the descending aorta. In this CHD population (n = 147, including 112 conotruncal anomalies), exercise capacities correlated independently with the diameter Z-score and stiffness index of the ascending aorta along with the history of repetitive thoracotomies, reduced forced vital capacity, and right ventricular hypertension. During a follow-up period (median 15.6 years), either dilation (Z-score >3.5) or increased stiffness (β >6.0) of the ascending aorta stratified morbidity, but no synergistic impact was detected. In conclusion, in repaired patients with complex CHD, a stiffened and dilated ascending aorta was frequently found, exerting significant adverse impacts on diminished exercise capacity and morbidity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In order to show that reduced functional capacity in subclinical heart failure portends a higher risk of clinically overt (stage C) heart failure, we obtained the Duke activity status index (DASI) and 6-minute walk distance (6MWD) in 814 patients (age 70 [interquartile range 67 to 74] years, 51% female) with nonischemic subclinical heart failure. Reduced functional capacity was defined as: (1) DASI-derived metabolic equivalents <7, (2) 6MWD <2 standard deviations below the age-based normative mean (excluding those with mobility impairment) and (3) reduced 6MWD with reclassification where DASI was discordant. Based on reduced functional capacity and left ventricular dysfunction (LVD), subjects were classified into; (1) Stage A heart failure (436 with neither LVD nor reduced functional capacity), (2) Stage A with reduced functional capacity (n = 80), (3) Stage B heart failure (182 with LVD but preserved functional capacity) and (4) early stage C heart failure (52 with LVD and reduced functional capacity). Outcome was assessed by Kaplan-Meier survival estimates and Cox proportional hazard ratios. After a median follow-up of 13 months [interquartile range 11 to 19]), 76 (9%) developed heart failure - 6% of Stage A, 10% of Stage A-reduced functional capacity, 9% of Stage B and 37% of early Stage C (p < 0.001). After adjustment (for heart failure risk score, atrial fibrillation, pulmonary disease and therapy), the hazard ratio for development of overt heart failure in early Stage C was 5.92 (95% confidence intervals 2.92 to 11.54, p < 0.001) compared with Stage A and 3.08 (95% confidence intervals 1.47 to 6.47, p = 0.003) compared with Stage B., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Peak exercise oxygen consumption (pVO 2 ) is an important predictor of prognosis in patients with heart failure (HF). The association between pretransplant pVO 2 and post-transplantation outcomes in HF patients has not been previously studied. We identified adult OHT recipients with available pVO 2 in the United Network for Organ Sharing registry (2000 to 2015). Patients were divided into 3 categories using Weber classification: class B (pVO 2 16 to 20 ml/kg/min), class C (pVO 2 10 to 16 ml/kg/min), and class D (pVO 2 <10 ml/kg/min). Postoperative outcomes (mortality, renal failure, rejection) were compared between the groups. A total of 9,623 patients were included in this analysis; the mean age was 54 ± 11 years, 74% were male, 75% were white and 59% had nonischemic etiology of HF. The mean pVO 2 was 11.7 ± 3.6 ml/kg/min: 1,202 (12.5%) in class B, 6,055 (62.9%) in class C, and 2,366 (24.6%) were in class D. At a median follow-up of 6.1 years, 2,730 (28.4%) died. Post-transplantation survival decreased with decreasing pVO 2 ; 1 and 5-year survival: B (92%, 80%), C (90%, 79%), and D (87%, 75%), p <0.001 by log-rank. After multiple adjustments, patients in class D had significantly higher post-transplantation mortality compared with class C (Hazard Ratio (HR) 1.21 [1.03 to 1.43], p = 0.02). When analyzed as a continuous variable, each 1 ml/kg/min increase in pVO 2 was associated with 2% decrease in mortality during follow-up (adjusted HR 0.98 [0.96 to 0.99], p <0.001). Patients in class D had significantly prolonged (>14 days) hospitalization (adjusted Odds Ratio (OR) 1.42 [1.20 to 1.68], p <0.001) and a trend toward increased need for dialysis (adjusted OR 1.36 [1.00 to 1.84], p = 0.05) compared with patients in class B. In this large cohort, lower pretransplant pVO 2 was associated with greater mortality and morbidity after OHT. These results suggest that earlier transplantation might improve post-transplantation outcomes in advanced HF patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Jugular venous pressure (JVP) has been established for the assessment of central venous pressure in patients with heart failure (HF), but data are limited regarding the response of JVP to exercise because of its complicated methods. Simplifying the estimation of JVP may be applied in such situations. JVP was assessed before and after the 6-minute walk test (6MWT) in 81 patients with HF using a simple method by which the JVP was considered high when the internal jugular venous pulsation on the right side was visually identified above the right clavicle in the sitting position. The primary outcome was a composite of cardiovascular death and hospitalization for worsening HF. None of the patients exhibited high JVP before the 6MWT and 11 patients (14%) had a high JVP after. The 6MWT distances were lower in patients with a high JVP after the 6MWT (338 ± 114 m) than those in patients without a high JVP (417 ± 78 m, p = 0.04). During a follow-up period of 13.4 ± 6.9 months, 11 patients died and 8 patients were hospitalized for worsening HF. The incidence of adverse cardiac events was higher in patients with a high JVP after the 6MWT (64%) than in patients without a high JVP after (64% vs 17%; hazard ratio, 7.52; 95% confidence interval, 2.69 to 20.83; p <0.001). In conclusion, high JVP after exercise was associated with exercise intolerance and poor prognosis. The response of JVP to exercise using this simple technique of physical examination may be a new approach for patients with HF for risk assessment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Impaired cardiorespiratory fitness (CRF) in heart failure (HF) is influenced by a complex array of cardiac and extracardiac factors. The study aimed to identify clinical determinants of CRF measured as peak oxygen consumption (peak VO 2 ) in HF patients, and to determine a peak VO 2 prediction model using regression equations. Retrospective analysis of 200 HF patients who completed treadmill cardiopulmonary exercise testing and underwent Doppler echocardiography and/or biomarker analysis on the same day was performed. After univariate linear regression analysis, a multivariate peak VO 2 prediction model was developed using significant variables in a stepwise linear regression analysis. In subjects with repeated testing, Pearson's correlation was used to assess correlations between measured and predicted change in peak VO 2 (Δpeak VO 2 ) over time. Mean age was 57 years, with 55% being male. Stepwise linear regression was used to generate a weighted model for peak VO 2 : 30.895 + (-0.112•age[years]) + (0.296•hemoglobin [g/dl]) + (-0.101•E/e'[unit change]) + (-0.202• body mass index [kg/m 2 ]) + (-0.593• N-terminal pro-brain natriuretic peptide [log N pg/ml])) + (-1.349•CRP [log mg/L]). Predicted peak VO 2 correlated strongly with measured peak VO 2 in HF with reduced ejection fraction and HF with preserved ejection fraction patients (r = +0.63, p <0.001; r = +0.64, p <0.001, respectively). Predicted Δpeak VO 2 correlated with measured Δpeak VO 2 (r = +0.23, p <0.001). In conclusion, in patients with HF across a wide range of left ventricular ejection fraction, age, systemic inflammation, oxygen carrying capacity, obesity, and elevated filling pressures are the strongest predictors of impaired CRF. The proposed CRF model allows prediction of peak VO 2 in HF patients and may be used to estimate peak VO 2 changes over time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Despite the known benefits of regular exercise, the majority of adults with congenital heart disease (CHD) fail to meet recommended standards for physical activity. We aimed to evaluate the factors associated with exercise frequency in adults with CHD, which remain largely unknown. From September 2015 to December 2016, 446 adults with CHD completed clinical questionnaires regarding exercise frequency. Questionnaires also measured related demographic and psychosocial variables. Retrospective chart review was utilized to determine cardiac function and cardiopulmonary exercise capacity. Exercise frequency was classified as none (33%), low (<3×/month, 2%), occasional (<2×/week, 8%), or frequent (≥2×/week, 57%). Frequent exercisers were more highly educated (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.06 to 2.57), reported improved sleep quality, with decreased nocturnal awakenings and sleep latency (OR 0.52, 95% CI 0.32 to 0.83), and had a lower prevalence of depression (OR 0.30, 95% CI 0.12 to 0.75). There was no significant association between exercise frequency and disease complexity or cardiac function. Of the original cohort, 74 patients completed exercise testing within 1 year of their visit. Frequent exercisers (n = 46) had better indicators of cardiovascular capacity, including higher peak maximal oxygen consumption [VO 2 ] (28.8 ± 8.5 vs 24.6 ± 8.4, p = 0.04). After controlling for exercise frequency, higher educational attainment independently predicted an improved exercise capacity (peak [VO 2 ]: OR = 1.09, 95% CI 1.01 to 1.18). In conclusion, frequent exercise in adults with CHD is associated with improved cardiopulmonary exercise capacity and psychosocial functioning, irrespective of underlying cardiac disease complexity and severity. Increased physical activity levels and improved exercise capacity were observed in more highly educated patients, highlighting the potential importance of socioeconomic influences on physical and mental functioning., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In primary prevention, addition of C-reactive protein and family history to standard risk factor assessment (Reynolds Risk Score or RRS) provides superior risk stratification for future cardiovascular (CV) events. We sought to assess whether addition of functional capacity to RRS provided incremental prognostic value. This was a prospective observational cohort study of 3,964 consecutive asymptomatic adults without documented CV disease (mean age 51 years, 78% men) evaluated between 2005 and 2013, who underwent clinical and treadmill stress testing at baseline. RRS was calculated; % age-gender predicted metabolic equivalents (AGP-METs) achieved and heart rate recovery (HRR) were recorded. End point was death and myocardial infarction. Findings were tested in derivation (n = 1,982) and validation samples (n = 1,982). Mean RRS and C-reactive protein were 3.7 ± 4 and 2 ± 4 mg/dl. Nine percent had family history of premature CV disease. %AGP-METs achieved, and HRR were 113 ± 20 and 24 ± 8 beats/min. Forty-six percent achieved <110% AGP-METs, whereas 41% had RRS ≥3. At 7.3 ± 3 years, there were 83 (2%) events (39 in derivation and 44 in validation samples). In derivation group, on multivariable survival analysis, higher RRS (Hazard ratio or HR 1.27 [1.07 to 1.39]), lower % AGP METs (HR 1.21 [1.09 to 1.34]) achieved and abnormal (<12 beats/min) HRR (HR 1.15 [1.02 to 1.23]) were associated with increased longer-term events (all p <0.01). Findings were similar in validation group. Cutoffs of RRS >3 and %AGP-METs <110 were associated with increased longer-term events on spline analysis in the derivation group. The continuous net reclassification improvement for longer-term events, when %AGP-METs was added to RRS was 0.79 (95% confidence interval 0.52 to 1.05; p <0.01). Findings were confirmed in validation group. In conclusion, in primary prevention, addition of exercise capacity to RRS (incorporating traditional risk factors, family history, and inflammation) provides incremental prognostic value., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fontan failure remains a significant problem, especially in patients with an atriopulmonary Fontan. Fontan baffle volume change during the cardiac cycle (Fontan baffle stroke volume) may affect outcomes in Fontan circulation. Assuming that increased Fontan baffle stroke volume is associated with increased energy loss in the baffle, we hypothesized that higher baffle stroke volume is associated with worse exercise capacity and increased incidence of Fontan failure. Patients from 6 centers with an atriopulmonary or lateral tunnel Fontan operation were included if they had a cardiac magnetic resonance (CMR) study and an adequate cardiopulmonary exercise test. Fontan baffle stroke volume was defined as the difference between maximum and minimum Fontan baffle volumes. Fontan failure was defined as death, listing for transplantation, heart failure symptoms requiring medications, or peak VO 2 below 16 ml/kg/min. The study group consisted of 107 patients (median age 19 years, interquartile range, 14 to 29 years). Most patients (84%) had lateral tunnel procedure. During a median follow-up period of 6.8 [interquartile range: 3.2 to 8.8] years after the CMR, 25 (23%) patients had Fontan failure (7 deaths, 3 listed for transplantation, and 15 with heart failure symptoms). Predictors of Fontan failure on multivariable analysis were ventricular tachycardia, protein losing enteropathy, and additionally in atriopulmonary Fontan only, larger Fontan baffle stroke volume. Predictors of lower peak VO 2 on multivariable analysis were older age at CMR and additionally in atriopulmonary Fontan only, larger Fontan baffle stroke volume. In conclusion, larger Fontan baffle stroke volume was independently associated with lower peak VO 2 and Fontan failure in atriopulmonary Fontan., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Clinical guidelines advocate for customization of exercise testing to address patient-specific diagnostic goals, including reproduction of presenting exertional symptoms. However, the diagnostic yield of adding customized exercise testing to graded exercise in patients presenting with exertional complaints has not been rigorously examined and is the focus of this study. Using prospectively collected data, we analyzed the diagnostic yield of customized additional exercise provocation following inconclusive graded exercise test with measurement of gas exchange. Additional testing was defined as "positive" if it revealed a clinically-actionable diagnosis related to the chief complaint or reproduced symptoms in the absence of an explanatory diagnosis or pathology. Of 1,110 patients who completed a graded test, 122 (11%) symptomatic patients underwent additional customized exercise testing (e.g., sprint intervals and race simulations). Compared with those who did not undergo additional testing, this group was younger (29 [interquartile range 19 to 45] vs 46 [25 to 58] year old) and disproportionately female (43% vs 27%). Presenting symptoms included palpitations (46%), lightheadedness/syncope (25%), chest pain (14%), dyspnea (11%), and exertional intolerance (3%). Additional testing was "positive" in 48 of 122 (39%) of patients by revealing a clinically actionable diagnosis in 26 of 48 (54%) or reproducing symptoms without an explanatory diagnosis in 22 of 48 (46%). In conclusion, while patient-centered customization of exercise testing is suggested by clinical guidelines, these data are the first to demonstrate that the selective addition of customized exercise provocation following inconclusive graded exercise testing improves the diagnostic yield of exercise assessment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although atrial fibrillation/atrial flutter (AF/AFL) and heart failure with preserved ejection fraction (HFpEF) frequently coexist, the influence of AF/AFL on physical activity, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life in HFpEF is unclear and could have relevance to HFpEF trial design. We evaluated the association between AF/AFL and volitional physical activity, functional performance, NT-proBNP, and quality of life in patients with HFpEF in the Nitrate's Effect on Activity Tolerance (NEAT)-HFpEF trial. Of 99 patients with accelerometer data, 35 (35%) had AF/AFL. There were no differences between AF/AFL versus no AF/AFL in baseline average daily accelerometer units (ADAUs; 9.06 ± 0.54 vs 9.06 ± 0.48, p = 0.75), hours active per day (9.7 ± 2.3 vs 9.2 ± 2.2, p = 0.86), or 6-minute walk distance (6MWD; 307 ± 136m vs 321 ± 110m, p = 0.85). AF/AFL status was associated with higher baseline NT-proBNP (586 [25th to 75th percentile: 291 to 1254] pg/ml vs 154 [25th to 75th percentile: 92 to 288] pg/ml, p <0.001) and Kansas City Cardiomyopathy Questionnaire scores (69 [25th to 75th percentile: 46 to 88] vs 48 [25th to 75th percentile: 37 to 70], p = 0.01). Although treatment responses to isosorbide mononitrate measured by change in ADAUs, hours active per day, or 6MWD did not vary by AF/AFL status (interaction p >0.05 for all), AF/AFL patients had greater reductions in NT-proBNP after isosorbide mononitrate than patients without AF/AFL (interaction p <0.001), possibly due to regression to the mean. In conclusion, baseline measures and treatment-related changes in volitional physical activity (ADAUs) and functional performance (6MWD) did not differ by AF/AFL in NEAT-HFpEF, whereas NT-proBNP did. In HFpEF-where AF/AFL prevalence is high-functional measures may be superior to natriuretic peptides as trial endpoints., (Copyright © 2019 Elsevier Inc. All rights reserved.)

With rising survival rates of patients with congenital heart disease (CHD), functional health variables have become the key aspect in treatment evaluation. The effectiveness of various treatment options on the health-related quality of life (HRQoL) and the objectively measured exercise capacity as peak oxygen uptake (VO 2 peak) remains rather unclear and hence, its investigation is the primary aim of this study. Data from 1014 patients (≥14-years-old, various CHD) were retrospectively reviewed. The patients had completed at least twice the SF-36 questionnaire on HRQoL prior to a cardiopulmonary exercise test. Each patient was assigned to 1 of 4 treatment groups (i.e., surgery, catheter intervention, drug therapy, and surveillance) according to the received treatment between the baseline and the follow-up examination. After 4.0 ± 2.2 years of follow-up, patients with surgery and catheter intervention showed an increase in the physical summary score of HRQoL as compared to the other treatment groups (p <0.001). This effect remained also significant in a multivariable model accounting for anthropometric and baseline data. No significant differences in the mental summary score of HRQoL and the VO 2 peak were evident between the different treatment groups in the multivariable model. No significant correlation was found between the changes in HRQoL and VO 2 peak over time. In conclusion, despite insignificant changes in aerobic capacity, adolescents and adults with CHD report better physical HRQoL following surgery and catheter intervention compared to the other treatment options. HRQoL and exercise capacity need to be considered concurrently in the evaluation of adolescents and adults with CHD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the relation between liver histology, exercise tolerance, and diastolic function in patients with nonalcoholic fatty liver disease (NAFLD). Myocardial remodeling and diastolic dysfunction have been associated with NAFLD. However, its physiological impact and relationship to the histological severity of NAFLD is not known. Cardiopulmonary exercise testing and stress echocardiography was performed in subjects with biopsy-confirmed NAFLD. Maximal aerobic exercise capacity (peak oxygen consumption [VO 2 ]) was related to diastolic function (mitral annulus Doppler velocity e' and ratio of early diastolic filling pressure [E] to e' [E/e']) at rest and peak exercise. Autonomic dysfunction was determined from heart rate recovery after exercise. Independent predictors of cardiac function and exercise capacity were identified by multivariable regression. Thirty-six subjects (nonalcoholic fatty liver [NAFL  =  15], nonalcoholic steatohepatitis [NASH  =  21]) were enrolled. NASH was associated with impaired exercise capacity compared with NAFL (median peak VO 2 17.0 [15.4, 18.9] vs 19.9 [17.4, 26.0], p  =  001); pVO 2 declined with increasing fibrosis (F0  =  22.5, F1  =  19.9, F2  =  19.0, F3  =  16.6 ml·kg -1 ·min -1 ; p  =  0.01). Similarly, E/e' during exercise increased progressively with increasing fibrosis (F0  =  5.6, F1  =  6.5, F2  =  8.7, F3  =  9.8; P  =  0.02). Finally, heart rate recovery, a marker of autonomic function, was blunted in those with higher fibrosis stages (F0  =  25 [20, 30], F1  =  23 [17.5, 27.0], F2  =  17 [11.8, 21.5], F3  =  11 [8.5, 18.0] beats per minute; p <0.01). Fibrosis was an independent predictor of these functional outcomes. In conclusion, NASH is associated with impaired exercise capacity and diastolic dysfunction compared with NAFL. The severity of impairment is directly related to the severity of fibrosis stage in precirrhotic stages of NAFLD., (Copyright © 2018. Published by Elsevier Inc.)

The objective of this study was to evaluate the relation between body mass index (BMI), exercise capacity, and symptoms in patients with hypertrophic cardiomyopathy (HC) and to utilize results of cardiopulmonary exercise tests (CPX) and transthoracic echocardiograms to understand the mechanism(s) of reduced exercise capacity across body mass index groups. Over a 6-year period, 510 consecutive patients with HC seen at a tertiary referral center underwent (CPX) and a transthoracic echocardiogram. Increasing BMI was associated with decreased exercise capacity as assessed by peak VO 2 (ml/kg/min). However, the prevalence of cardiac impairment did not vary by BMI group. In conclusion, these findings suggest that in some patients with hypertrophic cardiomyopathy, cardiac impairment is not the primary cause of exercise limitation and weight loss may result in improved exercise capacity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Previous studies have demonstrated that cardiorespiratory fitness is a strong marker of cardiovascular health. Machine learning (ML) can enhance the prediction of outcomes through classification techniques that classify the data into predetermined categories. The aim of the analysis is to compare the prediction of 10 years of all-cause mortality (ACM) using statistical logistic regression (LR) and ML approaches in a cohort of patients who underwent exercise stress testing. We included 34,212 patients (55% males, mean age 54 ± 13 years) free of coronary artery disease or heart failure who underwent exercise treadmill stress testing between 1991 and 2009 and had complete 10-year follow-up. The primary outcome of this analysis was ACM at 10 years. The probability of 10-years ACM was calculated using statistical LR and ML, and the accuracy of these methods was calculated and compared. A total of 3,921 patients died at 10 years. Using statistical LR, the sensitivity to predict ACM was 44.9% (95% confidence interval [CI] 43.3% to 46.5%), whereas the specificity was 93.4% (95% CI 93.1% to 93.7%). The sensitivity of ML to predict ACM was 87.4% (95% CI 86.3% to 88.4%), whereas the specificity was 97.2% (95% CI 97.0% to 97.4%). The ML approach was associated with improved model discrimination (area under the curve for ML [0.923 (95% CI 0.917 to 0.928)]) compared with statistical LR (0.836 [95% CI 0.829 to 0.846], p<0.0001). In conclusion, our analysis demonstrates that ML provides better accuracy and discrimination of the prediction of ACM among patients undergoing stress testing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The approach to managing asymptomatic or questionably symptomatic patients for aortic stenosis is difficult. We aimed to determine whether cardiopulmonary exercise testing (CPET) is prognostically useful in such patients. Patients judged asymptomatic or questionably symptomatic for aortic stenosis with aortic valve area index <0.6 cm 2 /m 2 and left ventricular ejection fraction ≥0.50 were managed conservatively provided they had either (group 1) normal peak oxygen consumption and peak oxygen pulse (>83% and >95% of the predicted values, respectively) or (group 2) subnormal peak oxygen consumption or peak oxygen pulse but with CPET data pointing to pathologies other than hemodynamic compromise from aortic stenosis. Increase in systolic blood pressure <20 mm Hg, ST depression ≥2 mm, or symptoms during the exercise test were allowed. Unexpected events included cardiac death or hospitalization with heart failure in patients who had not been recommended valve replacement. The median age of the study population (n = 101) was 75 years (interquartile range 65 to 79 years), and 67% were judged questionably symptomatic. During a follow-up at 24 ± 6 months, the rate of unexpected cardiac death and unexpected hospitalization with heart failure was 0% and 6.0%, respectively. All-cause mortality was 4.0% compared with 8.0% in the age- and gender-matched population. For group 1, 26 of 70 (37.1%) succumbed to cardiac death, or were hospitalized because of heart failure, or underwent valve replacement, and for group 2 this was 12 of 31 (38.7%). In conclusion, if CPET does not indicate a significant hemodynamic compromise because of aortic stenosis, an initially conservative strategy results in a good prognosis and an acceptable event rate., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

High exercise capacity (EC) has been associated with a lower risk of incident diabetes, whereas statin therapy has been associated with a higher risk. We sought to investigate whether the association between EC and diabetes risk is modified by statin therapy. This retrospective cohort study included 47,337 patients without diabetes or coronary artery disease at baseline (age 53 ± 13 years, 48% women, 66% white) who underwent clinical treadmill stress testing within the Henry Ford Health System from January 1, 1991, to May 31, 2009. The patients were stratified by baseline statin use and estimated peak METs achieved during exercise testing. Hazard ratios for incident diabetes were calculated using Cox proportional hazards models adjusted for demographic characteristics, co-morbidities, pertinent medications, and stress test indication. We observed 6,921 new diabetes cases (14.6%) over a median follow-up period of 5.1 years (interquartile interval of 2.6 to 8.2 years). Compared with the statin group, the no-statin group achieved higher mean METs (8.9 ± 2.7 vs 9.6 ± 3.0, respectively; p <0.001). After adjustment for covariates, a higher EC was associated with a lower risk of incident diabetes, irrespective of statin use (p-interaction = 0.15). Each 1-MET increment was associated with an 8%, 8%, and 6% relative risk reduction in the total cohort, the no-statin, and the statin groups, respectively (95% confidence interval, 0.91 to 0.93, 0.91 to 0.93, and 0.91 to 0.96, respectively; p <0.001 for all). We conclude that a higher EC is associated with a lower risk of incident diabetes regardless of statin use., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Patients with myocardial infarction with nonobstructive coronary arteries (MINOCA), including Takotsubo syndrome (TS), are considered to have a better survival compared with those with coronary heart disease (CHD). Studies of patients with MINOCA measuring physical and mental function including matched control groups are lacking. The aim of this study was to determine the physical capacity and quality of life in patients with MINOCA. One-hundred patients with MINOCA along with TS (25%) were investigated from 2007 to 2011. A bicycle exercise stress test was performed 6 weeks after hospitalization and QoL was investigated by the Short Form Survey 36 at 3 months' follow-up. Both a healthy and a CHD group that were age and gender matched were used as controls. The MINOCA group had a lower physical capacity (139 ± 42 W) compared with the healthy control group (167 ± 53 W, p <0.001) but better than the CHD control group (124 ± 39 W, p = 0.023). Patients with MINOCA had lower physical and mental component summary scores compared with the healthy controls (p <0.001) and lower mental component summary (p = 0.012), mental health (p = 0.016), and vitality (p = 0.008) scores compared with the CHD controls. In conclusion, the findings of this first study on exercise capacity and QoL in patients with MINOCA showed both physical and mental distress from 6 weeks to 3 months after the acute event similar to CHD controls and in some perspectives even lower scores especially in the mental component of QoL., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The unique, unphysiological Fontan circulation is associated with an impaired functional status of the patients that is suggested to deteriorate over time. Unfortunately, previous studies did not integrate both pulmonary and cardiac determinants of functional status. In addition, a comparison with the natural decrease in exercise capacity in healthy subjects (in both children and adults) is lacking. This single-center study aims to investigate the functional status in a cohort of Fontan patients in relation to time since Fontan completion and to identify its determinants, including cardiac characteristics and pulmonary characteristics. Eighty-five consecutive Fontan patients ≥10 years who performed adequate cardiopulmonary exercise testing (respiratory exchange ratio >1.01) were included. Mean time since Fontan completion was 15 ± 9 years (range 2 to 37 years). New York Heart Association functional class was I in 36 patients (42%), II in 41 patients (48%), and III in 8 patients (9%). Peak oxygen uptake during exercise (VO 2 index) was 25.7 ± 7.9 ml/min/m 2 (58 ± 14% of predicted). New York Heart Association functional class and peak VO 2 index both correlated with time since the Fontan operation; however, peak VO 2 as percentage of predicted (VO 2 (pred)) did not. In multivariate analyses, peak VO 2 (pred) was independently associated with maximum heart rate, oxygen pulse at peak exercise, and forced expiratory volume in 1 second (R 2  = 0.579) but not with cardiac output in rest. In conclusion, the present data suggest that functional status in Fontan patients is impaired already shortly after Fontan completion, whereas its subsequent deterioration seems to follow the natural decline of aging. Furthermore, functional status in Fontan patients correlates with pulmonary function and cardiac functional parameters during exercise but not with conventional cardiac measurements at rest., (Copyright © 2017. Published by Elsevier Inc.)

Idiopathic/heritable pulmonary arterial hypertension has a poor prognosis despite the available therapeutic options. Survival of Japanese patients with this disease entity has not been reported in the multicenter setting. A retrospective study of 141 patients with idiopathic/heritable pulmonary arterial hypertension treated at 3 pulmonary hypertension centers in Japan from 1992 to 2012 investigated survival and determinants of survival. Mean survival time from treatment initiation was 14.7 ± 0.8 years (95% confidence interval, 13.1 to 16.3 years) and the 1-, 3-, 5-, and 10-year survival rates were 97.9%, 92.1%, 85.8%, and 69.5%, respectively. Patients showed significant improvement in exercise capacity and hemodynamics after treatment. Patients with 6-minute walk distance >372 m, mean pulmonary arterial pressure ≤46 mm Hg, and cardiac index >2.5 L/min/m 2 at follow-up had a significantly better prognosis. Most patients (99.2%) were receiving pulmonary hypertension-targeted drugs at follow-up. Use of endothelin receptor antagonists and intravenous epoprostenol were related to survival in the univariate analysis. Among the patients who were on intravenous epoprostenol therapy, those with endothelin receptor antagonists had a significantly better prognosis, whereas patients on warfarin had a significantly worse prognosis. In conclusion, survival of Japanese patients with idiopathic/heritable pulmonary arterial hypertension in this study was good, showing improvement in hemodynamic parameters supported by pulmonary hypertension-targeted drugs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Combining echocardiography and cardiopulmonary stress testing allows noninvasive assessment of hemodynamics, and oxygen extraction (A-VO 2 difference). We evaluated mechanisms of effort intolerance in patients with heart failure with borderline (40% to 49%) left ventricular ejection fraction (EF) (HF and Borderline Ejection fraction). We included 89 consecutive patients with HF and Borderline Ejection fraction (n = 25; 63.6 ± 14 years, 64% men), control subjects (n = 22), patients with HF with preserved EF (n = 26; EF ≥50%), and patients with HF with reduced EF (n = 16; <40%). Various echo parameters (left ventricular volumes, EF, stroke volume, mitral regurgitation [MR] volume, e', right ventricle end-diastolic area, and right ventricle end-systolic area), and ventilatory or combined parameters (peak oxygen consumption [VO 2 ] and A-VO 2 difference) were measured at 4 predefined activity stages. Effort-induced functional MR was frequent and more prevalent in HF and Borderline Ejection fraction than in all the other types of HF. In multivariable analysis heart rate response (p <0.0001), A-VO 2 difference (p = 0.02), stroke volume (p = 0.002), and right ventricle end-systolic area were the only independent predictors of exercise capacity in HF and Borderline Ejection fraction but peak EF was not. In HF and Borderline Ejection fraction exercise intolerance is predominantly due to chronotropic incompetence, peripheral factors, and limited stroke volume reserve, which are related to right ventricle dysfunction and functional MR but not to left ventricular ejection fraction. Combined testing can be helpful in determining mechanisms of exercise intolerance in HF and Borderline Ejection fraction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The incremental cardiopulmonary exercise test (CPET) is an increasingly used diagnostic method that serves to evaluate patients with chief complaint of dyspnea during exercise. Performing maximal symptom-limited CPET can show if the tested subject has a reduced exercise capacity and give clues to the mechanism of such exercise capacity reduction, cardiac, pulmonary, or pulmonary vascular source. In this review, it is suggested that the evaluation of the complex results of CPET should be performed by first determining if myocardial/circulatory insufficiency is present and second if there is gas exchange abnormality. By looking with scrutiny at the oxygen consumption (VO 2 ) versus work rate plot, one can see if oxygen delivery is adequate or if it is hampered by abnormally reduced blood flow through skeletal muscle. Elevated ventilatory equivalent of carbon dioxide at the ventilatory threshold and or arterial oxygen desaturation during effort, strongly suggest gas exchange abnormalities. The absence of circulatory insufficiency and gas exchange abnormalities, almost always suggest normal response to effort or deconditioning whenever peak VO 2 is below the maximal predicted value., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Whether lower heart rate thresholds (defined as the percentage of age-predicted maximal heart rate achieved, or ppMHR) should be used to determine chronotropic incompetence in patients on beta-blocker therapy (BBT) remains unclear. In this retrospective cohort study, we analyzed 64,549 adults without congestive heart failure or atrial fibrillation (54 ± 13 years old, 46% women, 29% black) who underwent clinician-referred exercise stress testing at a single health care system in Detroit, Michigan from 1991 to 2009, with median follow-up of 10.6 years for all-cause mortality (interquartile range 7.7 to 14.7 years). Using Cox regression models, we assessed the effect of BBT, ppMHR, and estimated exercise capacity on mortality, with adjustment for demographic data, medical history, pertinent medications, and propensity to be on BBT. There were 9,259 deaths during follow-up. BBT was associated with an 8% lower adjusted achieved ppMHR (91% in no BBT vs 83% in BBT). ppMHR was inversely associated with all-cause mortality but with significant attenuation by BBT (per 10% ppMHR HR: no BBT: 0.80 [0.78 to 0.82] vs BBT: 0.89 [0.87 to 0.92]). Patients on BBT who achieved 65% ppMHR had a similar adjusted mortality rate as those not on BBT who achieved 85% ppMHR (p >0.05). Estimated exercise capacity further attenuated the prognostic value of ppMHR (per-10%-ppMHR HR: no BBT: 0.88 [0.86 to 0.90] vs BBT: 0.95 [0.93 to 0.98]). In conclusion, the prognostic value of ppMHR was significantly attenuated by BBT. For patients on BBT, a lower threshold of 65% ppMHR may be considered for determining worsened prognosis. Estimated exercise capacity further diminished the prognostic value of ppMHR particularly in patients on BBT., Competing Interests: The authors have no relevant conflicts of interest to report, including financial interests, activities, relationships, and affiliations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction; however, the role of cardiac rehabilitation (CR) for patients with SCAD has not been well defined. To further understand CR in patients with SCAD, we studied a large cohort of patients with confirmed SCAD enrolled in the Mayo Clinic SCAD Registry from January 2010 to December 2014 (n = 354). Demographics, clinical characteristics, mental health status, and details about CR participation and experience were collected through medical record review and questionnaires. Participants at time of SCAD were 46 ± 10 years old; 96% were women. Most (76%) attended ≥1 CR sessions, averaging 18 ± 12 sessions. Most reported CR-related physical and emotional benefits (82% and 75%, respectively). Of the CR nonparticipants, 57 of 85 reported not participating because CR was not recommended by their health care provider. Other reasons included inadequate transportation (10 of 85), no insurance coverage (7 of 85), cost (2 of 85), no energy (2 of 85), being too ill (2 of 85), and miscellaneous comments (5 of 85). In conclusion, 3 of 4 of patients with SCAD participated in CR, most of whom reported benefit. Lack of recommendation for CR by a health care provider was the primary reason patients did not participate., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Increasingly end-organ injury is being demonstrated late after institution of the Fontan circulation, particularly liver fibrosis and cirrhosis. The exact mechanisms for these late phenomena remain largely elusive. Hypothesizing that exercise induces precipitous systemic venous hypertension and insufficient cardiac output for the exercise demand, that is, a possible mechanism for end-organ injury, we sought to demonstrate the dynamic exercise responses in systemic venous perfusion (SVP) and concurrent end-organ perfusion. Ten stable Fontan patients and 9 control subjects underwent incremental cycle ergometry-based cardiopulmonary exercise testing. SVP was monitored in the right upper limb, and regional tissue oxygen saturation was monitored in the brain and kidney using near-infrared spectroscopy. SVP rose profoundly in concert with workload in the Fontan group, described by the regression equation 15.97 + 0.073 watts per mm Hg. In contrast, SVP did not change in healthy controls. Regional renal (p <0.01) and cerebral tissue saturations (p <0.001) were significantly lower and decrease more rapidly in Fontan patients. We conclude that in a stable group of adult patients with Fontan circulation, high-intensity exercise was associated with systemic venous hypertension and reduced systemic oxygen delivery. This physiological substrate has the potential to contribute to end-organ injury., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The Fontan operation is a common end point for children born with a single functional ventricle. Fontan patients typically experience physiological deterioration leading to transplant or death in their third or fourth decades of life. This deterioration is partially attributable to progressive increases in pulmonary vascular resistance (PVR) and as such endothelin receptor antagonists, which are known to decrease pulmonary vascular resistance, have been proposed as potentially beneficial in this population. We conducted a single-center, randomized, double-blind, placebo-controlled, crossover study of 12 weeks of ambrisentan therapy (10 mg per day) versus placebo to test the hypothesis that endothelin receptor antagonism will improve cardiopulmonary exercise test parameters and 36-item short form (SF-36) assessed quality of life in adult Fontan patients. Twenty-eight patients entered the trial, 19 patients completed the protocol. Ambrisentan therapy improved peak oxygen consumption by 1.7 ml/kg/min in patients who achieved a respiratory exchange ratio of >0.95 (p = 0.05) and decreased the slope of the ventilatory equivalent ratio for oxygen (-2.8, p = 0.019) in all completers. It did not change SF-36 physical function score compared with placebo (p = 0.28). Ambrisentan therapy resulted in a decrease in (-1.4 g/dl, p <0.001) with no change in liver or renal function. Therapy was generally well tolerated, with no greater rate of side effects than placebo. In conclusion, ambrisentan is well tolerated and improves exercise capacity in adult Fontan patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Clinical status in heart failure is conventionally assessed by the physician's evaluation, patients' own perception of their symptoms, quality of life (QoL) tools, and a measure of functional capacity. These aspects can be measured with tools such as the New York Heart Association functional class, QoL tools such as the EuropeanQoL-5 dimension, the Kansas City Cardiomyopathy Questionnaire, patient global assessment (PGA), and by 6-minute walk test (6MWT), respectively. The ferric carboxymaltose in patients with heart failure and iron deficiency (FAIR-HF) trial demonstrated that treatment with intravenous ferric carboxymaltose in iron-deficient patients with symptomatic heart failure with reduced left ventricular function, significantly improved all 5 outcome measures. This analysis assessed the correlations between the longitudinal changes in the measures of clinical status, as measured by QoL tools and the changes in the measures of functional capacity as measured by the 6MWT. This analysis used the database from the FAIR-HF trial, which randomized 459 patients with chronic heart failure (reduced left ventricular ejection fraction) and iron deficiency, with or without anemia to ferrous carboxymaltose or placebo. The degree of correlation between QoL tools and the 6MWT was assessed at 4, 12, and 24 weeks. The data demonstrate highly significant correlations between QoL and functional capacity, as measured by the 6MWT, at all time points (p <0.001). Changes in PGA, Kansas City Cardiomyopathy Questionnaire, and EuroQoL-5D correlated increasingly over time with changes in 6MWT performance. Interestingly, the strongest correlation at 24 weeks is for the PGA, which is a simple numerical scale (r = -0.57, p <0.001). This analysis provides evidence that QoL assessment show a significant correlation with functional capacity, as measured by the 6MWT. The strength of these correlations increased over time., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose of this retrospective, observational study was to describe the relation between exercise workload during cardiac rehabilitation (CR), expressed as metabolic equivalents of task (METs), and prognosis among patients with coronary heart disease. We included patients with coronary heart disease who participated in CR between January 1998 and June 2007. METs were calculated from treadmill workload. Cox regression analysis was used to describe the relationship between METs and time to a composite outcome of all-cause mortality, nonfatal myocardial infarction, or heart failure hospitalization. Among 1,726 patients (36% women; median age 59 years [interquartile range, 52 to 66]), there were 467 events (27%) during a median follow-up of 5.8 years (interquartile range, 2.6 to 8.7). In analyses adjusted for age, sex, Charlson co-morbidity index, hypertension, diabetes, and CR referral diagnosis, METs were independently related to the composite outcome at CR start (Wald chi-square 43, hazard ratio 0.59 [95% confidence interval 0.51 to 0.70]) and CR end (Wald chi-square 47, hazard ratio 0.68 [95% confidence interval 0.61 to 0.76]). Patients exercising below 3.5 METs on exit from CR represent a high-risk group with 1- and 3-year event rates ≥7% and ≥18%, respectively. In conclusion, METs during CR is available at no additional cost and can be used to identify patients at increased risk for an event who may benefit from closer follow-up, extended length of stay in CR, and/or participation in other strategies aimed at maximizing adherence to secondary preventive behaviors and improving exercise capacity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cardiac rehabilitation (CR) improves functional capacity and reduces mortality in patients with cardiovascular disease. It also improves cardiovascular risk factors and aids in weight reduction. Because of the increase in morbidly obese patients with cardiovascular disease, the prevalence of obesity and patterns of weight change in those undergoing CR merit fresh study. We studied 1,320 participants in a 12-week CR program at our academic medical center. We compared 5 categories: 69 class III obese (body mass index [BMI] ≥40) patients, 128 class II obese patients (BMI 35.0 to 39.9), 318 class I obese patients (BMI 30.0 to 34.9), 487 overweight patients (BMI 25.0 to 29.9), and 318 normal weight patients (BMI 18.5 to 24.9). Exercise capacity in METs, weight, blood pressure, and fasting lipid profile were measured before and after CR. Overall, 131 patients gained weight, 827 had no significant weight change, and 363 lost weight (176 lost 3% to 5% of their baseline weight, 161 lost 5% to 10%, and 26 lost >10%). Exercise capacity, blood pressure, and low-density lipoprotein cholesterol improved in all patients. Class III obese patients had the smallest improvement in peak METs (p <0.001), but the greatest weight loss. Patients who lost >10% of their baseline weight had the greatest improvements in exercise capacity, low-density lipoprotein, and triglycerides. In conclusion, after CR, a minority of patients lost weight. Most patients had no significant weight change and some even gained weight. The greatest loss was seen in class III obese patients. All patient groups showed improvements in exercise capacity and risk factors, regardless of the direction or degree of weight change., (Copyright © 2016 Elsevier Inc. All rights reserved.)