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Benefits of 1-Year Lifestyle Modification Program on Exercise Capacity and Diastolic Function Among Coronary Artery Disease Men With and Without Type 2 Diabetes.
Piché, ME, Poirier, P, Marette, A, Mathieu, P, Lévesque, V, Bibeau, K, Larose, É, Després, JP
Metabolic syndrome and related disorders. 2019;(3):149-159
Abstract
BACKGROUND To assess the benefits of a 1-year lifestyle modification program on exercise capacity and diastolic function in men with left ventricular (LV) diastolic dysfunction (LVDD) and coronary artery disease (CAD), according to glucose tolerance status. METHODS Fifty-three men (62 ± 8 years; BMI: 27.3 ± 3.5 kg/m2) with LVDD and CAD were enrolled in a 1-year lifestyle modification program based on dietary management and increased physical activity. Patients were classified by using a 75 grams oral glucose tolerance test as having normal glucose tolerance (n = 16), prediabetes (n = 23), or type 2 diabetes mellitus (T2DM) (n = 14). Cardiac morphology and function, visceral fat, and cardiac fat depots were measured using magnetic resonance imaging, whereas exercise capacity [cardiorespiratory fitness (CRF)] (VO2peak) was assessed with a maximal treadmill test. RESULTS The 1-year lifestyle modification program was associated with reductions in body weight, and visceral and cardiac fat levels (all P < 0.05). CRF increased by 13% (24.9 ± 4.1 vs. 28.2 ± 4.8 mL O2/kg/min, P < 0.0001). Moreover, half of patients (53%) improved LV diastolic function in response to the lifestyle intervention. Multiple regression analyses revealed that age (partial R2 = 26.9, P < 0.0001) and presence of T2DM (partial R2 = 5.9, P = 0.04) were the stronger predictors of change in diastolic function, while favorable change in LV remodeling index was the best predictor of improvement in LV diastolic function after the lifestyle intervention (R2 = 21.9, P = 0.002). CONCLUSIONS Irrespective of glucose tolerance status, a 1-year lifestyle modification program in men with LVDD and CAD is associated with significant improvements in exercise capacity and LV diastolic function in more than half of patients.
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Comparative effectiveness of torasemide versus furosemide in symptomatic therapy in heart failure patients: Preliminary results from the randomized TORNADO trial.
Balsam, P, Ozierański, K, Marchel, M, Gawałko, M, Niedziela, Ł, Tymińska, A, Sieradzki, B, Sieradzki, M, Fojt, A, Bakuła, E, et al
Cardiology journal. 2019;(6):661-668
Abstract
BACKGROUND Recent reports suggest that torasemide might be more beneficial than furosemide in patients with symptomatic heart failure (HF). The aim was to compare the effects of torasemide and furosemide on clinical outcomes in HF patients. METHODS This study pilot consisted of data from the ongoing multicenter, randomized, unblinded endpoint phase IV TORNADO (NCT01942109) study. HF patients in New York Heart Association (NYHA) II-IV class with a stable dose of furosemide were randomized to treatment with equipotential dose of torasemide (4:1) or continuation of unchanged dose of furosemide. On enrollment and control visit (3 months after enrollment) clinical examination, 6-minute walk test (6MWT) and assessment of fluid retention by ZOE Fluid Status Monitor were performed. The primary endpoint was a composite of improvement of NYHA class, improvement of at least 50 m during 6MWT and decrease in fluid retention of at least 0.5 W after 3-months follow-up. RESULTS The study group included 40 patients (median age 66 years; 77.5% male). During follow-up 7 patients were hospitalized for HF worsening (3 in torasemide and 4 in furosemide-treated patients). The primary endpoint reached 15 (94%) and 14 (58%) patients on torasemide and furosemide, respectively (p = 0.03). CONCLUSIONS In HF patients treated with torasemide fluid overload and symptoms improved more than in the furosemide group. This positive effect occurred already within 3-month observation.
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Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Chronic Heart Failure and Iron Deficiency.
van Veldhuisen, DJ, Ponikowski, P, van der Meer, P, Metra, M, Böhm, M, Doletsky, A, Voors, AA, Macdougall, IC, Anker, SD, Roubert, B, et al
Circulation. 2017;(15):1374-1383
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Abstract
BACKGROUND Iron deficiency is common in patients with heart failure (HF) and is associated with reduced exercise capacity and poor outcomes. Whether correction of iron deficiency with (intravenous) ferric carboxymaltose (FCM) affects peak oxygen consumption [peak VO2], an objective measure of exercise intolerance in HF, has not been examined. METHODS We studied patients with systolic HF (left ventricular ejection fraction ≤45%) and mild to moderate symptoms despite optimal HF medication. Patients were randomized 1:1 to treatment with FCM for 24 weeks or standard of care. The primary end point was the change in peak VO2 from baseline to 24 weeks. Secondary end points included the effect on hematinic and cardiac biomarkers, quality of life, and safety. For the primary analysis, patients who died had a value of 0 imputed for 24-week peak VO2. Additional sensitivity analyses were performed to determine the impact of imputation of missing peak VO2 data. RESULTS A total of 172 patients with HF were studied and received FCM (n=86) or standard of care (control group, n=86). At baseline, the groups were well matched; mean age was 64 years, 75% were male, mean left ventricular ejection fraction was 32%, and peak VO2 was 13.5 mL/min/kg. FCM significantly increased serum ferritin and transferrin saturation. At 24 weeks, peak VO2 had decreased in the control group (least square means -1.19±0.389 mL/min/kg) but was maintained on FCM (-0.16±0.387 mL/min/kg; P=0.020 between groups). In a sensitivity analysis, in which missing data were not imputed, peak VO2 at 24 weeks decreased by -0.63±0.375 mL/min/kg in the control group and by -0.16±0.373 mL/min/kg in the FCM group; P=0.23 between groups). Patients' global assessment and functional class as assessed by the New York Heart Association improved on FCM versus standard of care. CONCLUSIONS Treatment with intravenous FCM in patients with HF and iron deficiency improves iron stores. Although a favorable effect on peak VO2 was observed on FCM, compared with standard of care in the primary analysis, this effect was highly sensitive to the imputation strategy for peak VO2 among patients who died. Whether FCM is associated with an improved outcome in these high-risk patients needs further study. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01394562.
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High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study.
Angadi, SS, Mookadam, F, Lee, CD, Tucker, WJ, Haykowsky, MJ, Gaesser, GA
Journal of applied physiology (Bethesda, Md. : 1985). 2015;(6):753-8
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Exercise training is an established adjuvant therapy in heart failure; however, the effects of high-intensity interval training (HIIT) in HFpEF are unknown. We compared the effects of HIIT vs. moderate-intensity aerobic continuous training (MI-ACT) on peak oxygen uptake (V̇o₂peak), left ventricular diastolic dysfunction, and endothelial function in patients with HFpEF. Nineteen patients with HFpEF (age 70 ± 8.3 yr) were randomized to either HIIT (4 × 4 min at 85-90% peak heart rate, with 3 min active recovery) or MI-ACT (30 min at 70% peak heart rate). Fifteen patients completed exercise training (HIIT: n = 9; MI-ACT: n = 6). Patients trained 3 days/wk for 4 wk. Before and after training patients underwent a treadmill test for V̇o₂peak determination, 2D-echocardiography for assessment of left ventricular diastolic dysfunction, and brachial artery flow-mediated dilation (FMD) for assessment of endothelial function. HIIT improved V̇o₂peak (pre = 19.2 ± 5.2 ml·kg(-1)·min(-1); post = 21.0 ± 5.2 ml·kg(-1)·min(-1); P = 0.04) and left ventricular diastolic dysfunction grade (pre = 2.1 ± 0.3; post = 1.3 ± 0.7; P = 0.02), but FMD was unchanged (pre = 6.9 ± 3.7%; post = 7.0 ± 4.2%). No changes were observed following MI-ACT. A trend for reduced left atrial volume index was observed following HIIT compared with MI-ACT (-3.3 ± 6.6 vs. +5.8 ± 10.7 ml/m(2); P = 0.06). In HFpEF patients 4 wk of HIIT significantly improved V̇o₂peak and left ventricular diastolic dysfunction. HIIT may provide a more robust stimulus than MI-ACT for early exercise training adaptations in HFpEF.
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Phlebotomy eliminates the maximal cardiac output response to six weeks of exercise training.
Bonne, TC, Doucende, G, Flück, D, Jacobs, RA, Nordsborg, NB, Robach, P, Walther, G, Lundby, C
American journal of physiology. Regulatory, integrative and comparative physiology. 2014;(10):R752-60
Abstract
With this study we tested the hypothesis that 6 wk of endurance training increases maximal cardiac output (Qmax) relatively more by elevating blood volume (BV) than by inducing structural and functional changes within the heart. Nine healthy but untrained volunteers (Vo2max 47 ± 5 ml·min(-1)·kg(-1)) underwent supervised training (60 min; 4 times weekly at 65% Vo2max for 6 wk), and Qmax was determined by inert gas rebreathing during cycle ergometer exercise before and after the training period. After the training period, blood volume (determined in duplicates by CO rebreathing) was reestablished to pretraining values by phlebotomy and Qmax was quantified again. Resting echography revealed no structural heart adaptations as a consequence of the training intervention. After the training period, plasma volume (PV), red blood cell volume (RBCV), and BV increased (P < 0.05) by 147 ± 168 (5 ± 5%), 235 ± 64 (10 ± 3%), and 382 ± 204 ml (7 ± 4%), respectively. Vo2max was augmented (P < 0.05) by 10 ± 7% after the training period and decreased (P < 0.05) by 8 ± 7% with phlebotomy. Concomitantly, Qmax was increased (P < 0.05) from 18.9 ± 2.1 to 20.4 ± 2.3 l/min (9 ± 6%) as a consequence of the training intervention, and after normalization of BV by phlebotomy Qmax returned to pretraining values (18.1 ± 2.5 l/min; 12 ± 5% reversal). Thus the exercise training-induced increase in BV is the main mechanism increasing Qmax after 6 wk of endurance training in previously untrained subjects.
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Two formulations of epoprostenol sodium in the treatment of pulmonary arterial hypertension: EPITOME-1 (epoprostenol for injection in pulmonary arterial hypertension), a phase IV, open-label, randomized study.
Chin, KM, Badesch, DB, Robbins, IM, Tapson, VF, Palevsky, HI, Kim, NH, Kawut, SM, Frost, A, Benton, WW, Lemarie, JC, et al
American heart journal. 2014;(2):218-225.e1
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Abstract
BACKGROUND Epoprostenol sodium with arginine-mannitol excipients (epoprostenol AM; Veletri [Actelion Pharmaceuticals Ltd, Allschwil, Switzerland]) and epoprostenol sodium with glycine-mannitol excipients (epoprostenol GM; Flolan [GlaxoSmithKline, Triangle Park, NC]) are intravenous treatments for pulmonary arterial hypertension (PAH). Epoprostenol AM contains different inactive excipients, resulting in greater stability at room temperature compared with epoprostenol GM. METHODS In this prospective, multicenter, open-label, randomized, phase IV exploratory study, epoprostenol-naïve patients in need of injectable prostanoid therapy were randomized 2:1 to open-label epoprostenol AM or epoprostenol GM. The study period was 28 days, followed by a 30-day safety follow-up. Study aims were to descriptively compare the safety, tolerability, drug metabolite levels, and treatment effects of epoprostenol AM and epoprostenol GM in PAH. Statistical analysis was descriptive only because of the exploratory nature of the study. RESULTS Thirty patients with PAH (18-70 years, 24 women, 20 idiopathic PAH) were randomized to epoprostenol AM (n = 20) or epoprostenol GM (n = 10). Most frequently reported adverse events included jaw pain, headache, nausea, and flushing. Two deaths occurred during the study period, and 1 death occurred during the 30-day safety follow-up period, all in patients receiving epoprostenol AM. All deaths were classified by the treating physician as unrelated to epoprostenol AM. The median (range) change from baseline to day 28 in 6-minute walk distance was 36 m (-127 to 210 m) and 49 m (-44 to 110 m) for the epoprostenol AM and epoprostenol GM groups, respectively. CONCLUSIONS In this randomized clinical study of epoprostenol AM in PAH, use of this novel preparation with greater room temperature stability was well tolerated.
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Total testosterone levels, metabolic parameters, cardiac remodeling and exercise capacity in coronary artery disease patients with different stages of glucose tolerance.
Ukkola, O, Huttunen, T, Puurunen, VP, Piira, OP, Niva, J, Lepojärvi, S, Tulppo, M, Huikuri, H
Annals of medicine. 2013;(3):206-12
Abstract
OBJECTIVE AND METHODS The correlation between total testosterone levels, exercise capacity, and metabolic and echocardiographic parameters was studied in 1097 male subjects with coronary artery disease (CAD) and different stages of glucose tolerance. RESULTS Testosterone level was the lowest among diabetics as compared to prediabetics or controls (P < 0.001). Total and abdominal adiposity were the highest in the subjects with the lowest testosterone. Independent of adiposity, fasting glucose, insulin, and leptin were higher (P < 0.03 to < 0.001) among diabetic and control groups in the lowest, and HbA1c values (P < 0.001) higher among diabetics in the lowest, than in the highest testosterone tertile. Controls and prediabetic subjects with the lowest testosterone levels had the lowest HDL-cholesterol levels, and controls also the highest triglycerides. An association between low testosterone level and low maximal exercise capacity was observed in diabetics (P < 0.001) and controls (P < 0.03). Independent of adiposity and metabolic parameters, low testosterone levels were associated with the highest septal wall thickness (P < 0.03) among diabetics. CONCLUSION A negative correlation between low testosterone and dysmetabolic features was observed. Independent of metabolic status, low plasma testosterone seems to be an indicator of impaired maximal exercise capacity and cardiac hypertrophy among CAD patients with type II diabetes.
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Exercise-induced brachial artery vasodilation: effects of antioxidants and exercise training in elderly men.
Donato, AJ, Uberoi, A, Bailey, DM, Wray, DW, Richardson, RS
American journal of physiology. Heart and circulatory physiology. 2010;(2):H671-8
Abstract
Aging, vascular function, and exercise are thought to have a common link in oxidative stress. Of the 28 subjects studied (young, 26 +/- 2 yr; old, 71 +/- 6 yr), 12 took part in a study to validate an antioxidant cocktail (AOC: vitamins C, E, and alpha-lipoic acid), while the remaining 8 young and 8 old subjects performed submaximal forearm handgrip exercise with placebo or AOC. Old subjects repeated forearm exercise with placebo or AOC following knee-extensor (KE) exercise training. Brachial arterial diameter and blood velocity (Doppler ultrasound) were measured at rest and during exercise. During handgrip exercise, brachial artery vasodilation in the old subjects was attenuated compared with that in young subjects following placebo (maximum = approximately 3.0 and approximately 6.0%, respectively). In contrast to the previously documented attenuation in exercise-induced brachial artery vasodilation in the young group with AOC, in the old subjects the AOC restored vasodilation (maximum = approximately 7.0%) to match the young. KE training also improved exercise-induced brachial artery vasodilation. However, in the trained state, AOC administration no longer augmented brachial artery vasodilation in the elderly, but rather attenuated it. These data reveal an age-related pro-/antioxidant imbalance that impacts vascular function and show that exercise training is capable of restoring equilibrium such that vascular function is improved and the AOC-mediated reduction in free radicals now negatively impacts brachial artery vasodilation, as seen in the young.
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Improvement in aerobic capacity after an exercise program in sporadic inclusion body myositis.
Johnson, LG, Collier, KE, Edwards, DJ, Philippe, DL, Eastwood, PR, Walters, SE, Thickbroom, GW, Mastaglia, FL
Journal of clinical neuromuscular disease. 2009;(4):178-84
Abstract
OBJECTIVES The study aimed to investigate the effects of a combined functional and aerobic exercise program on aerobic capacity, muscle strength, and functional mobility in a group of patients with sporadic inclusion body myositis (IBM). METHODS Aerobic capacity, muscle strength, and functional capacity assessments were conducted on 7 participants with sporadic IBM before and after a 12-week exercise program, which included resistance exercises and aerobic stationary cycling 3 times per week on alternative days. RESULTS Aerobic capacity of the group increased significantly by 38%, and significant strength improvements were observed in 4 of the muscle groups tested (P < 0.05). The exercise program was well tolerated, and there was no significant change in the serum creatine kinase level after the exercise period. CONCLUSIONS An aerobic exercise program can be safely tolerated by patients with sporadic IBM and can improve aerobic capacity and muscle strength when combined with resistance training. These findings indicate that aerobic and functional muscle strengthening exercise should be considered in the management of patients with IBM.
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Core temperature and metabolic responses after carbohydrate intake during exercise at 30 degrees C.
Horswill, CA, Stofan, JR, Lovett, SC, Hannasch, C
Journal of athletic training. 2008;(6):585-91
Abstract
CONTEXT Carbohydrate ingestion has recently been associated with elevated core temperature during exercise in the heat when testing for ergogenic effects. Whether the association holds when metabolic rate is controlled is unclear. Such an effect would have undesirable consequences for the safety of the athlete. OBJECTIVE To examine whether ingesting fluids containing carbohydrate contributed to an accelerated rise in core temperature and greater overall body heat production during 1 hour of exercise at 30 degrees C when the effort was maintained at steady state. DESIGN Crossover design (repeated measures) in randomized order of treatments of drinking fluids with carbohydrate and electrolytes (CHO) or flavored-water placebo with electrolytes (PLA). The beverages were identical except for the carbohydrate content: CHO = 93.7 +/- 11.2 g, PLA = 0 g. SETTING Research laboratory. PATIENTS OR OTHER PARTICIPANTS Nine physically fit, endurance-trained adult males. INTERVENTION(S): Using rectal temperature sensors, we measured core temperature during 30 minutes of rest and 60 minutes of exercise at 65% of maximal oxygen uptake (Vo(2) max) in the heat (30.6 degrees C, 51.8% relative humidity). Participants drank equal volumes (1.6 L) of 2 beverages in aliquots 30 minutes before and every 15 minutes during exercise. Volumes were fixed to approximate sweat rates and minimize dehydration. MAIN OUTCOME MEASURE(S): Rectal temperature and metabolic response (Vo(2), heart rate). RESULTS Peak temperature, rate of temperature increase, and metabolic responses did not differ between beverage treatments. Initial hydration status, sweat rate, and fluid replacement were also not different between trials, as planned. CONCLUSIONS Ingestion of carbohydrate in fluid volumes that minimized dehydration during 1 hour of steady-state exercise at 30 degrees C did not elicit an increase in metabolic rate or core temperature.