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Background: This study aimed to examine the effects of a six-week of concurrent training using high-intensity interval plus resistance training on flow-mediated dilation and pulse wave velocity in hypertensive, elevated blood pressure, or normotensive. A secondary goal was to analyze the inter-individual variability., Methods: A randomized controlled clinical trial was executed with 60 adult participants distributed across six groups: three control groups of hypertensive, elevated blood pressure, or normotensive and other three experimental hypertensive, elevated blood pressure, and normotensive groups, each comprising n=10 individuals. Participants underwent a six-week intervention of concurrent exercise using high-intensity interval plus resistance training three-weekly. Flow mediated dilation and pulse wave velocity and secondary vascular assessments were conducted before and after the intervention., Results: The hypertensive exercise group exhibited a significant increase in flow mediated dilation (Δ+7.7%; p=0.003) and a reduction in pulse wave velocity (Δ-1.2ms -1 ; p<0.0001). The normotensive exercise group also showed a significant increase in flow mediated dilation (Δ+8.4%, p=0.002)., Conclusion: The six-week concurrent exercise using high-intensity interval plus resistance training protocol, characterized by its clinical time-efficiency, was effective in improving endothelial function, as demonstrated by increased flow mediated dilation, and in reducing arterial stiffness, indicated by decreased pulse wave velocity., (Copyright © 2024 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Central blood pressure (BP) and BP variability are associated with cardiovascular disease risk. However, the influence of exercise on these hemodynamic parameters is unknown among patients with resistant hypertension. The EnRicH (The Exercise Training in the Treatment of Resistant Hypertension) was a prospective, single-blinded randomized clinical trial (NCT03090529). Sixty patients were randomized to a 12-week aerobic exercise program or usual care. The outcome measures include central BP, BP variability, heart rate variability, carotid-femoral pulse wave velocity, and circulating cardiovascular disease risk biomarkers including high-sensitivity C-reactive protein, angiotensin II, superoxide dismutase, interferon gamma, nitric oxide, and endothelial progenitor cells. Central systolic BP decreased by 12.22 mm Hg (95% CI, -1.88 to -22.57, P = 0.022) as did BP variability by 2.85 mm Hg (95% CI, -4.91 to -0.78, P = 0.008), in the exercise (n = 26) compared to the control group (n = 27). Interferon gamma -4.3 pg/mL (95%CI, -7.1 to -1.5, P = 0.003), angiotensin II -157.0 pg/mL (95%CI, -288.1 to -25.9, P = 0.020), and superoxide dismutase 0.4 pg/mL (95%CI, 0.1-0.6, P = 0.009) improved in the exercise compared to the control group. Carotid-femoral pulse wave velocity, heart rate variability, high-sensitivity C-reactive protein, nitric oxide, and endothelial progenitor cells were not different between groups (P > 0.05). In conclusion, a 12-week exercise training program improved central BP and BP variability, and cardiovascular disease risk biomarkers in patients with resistant hypertension. These markers are clinically relevant as they are associated with target organ damage and increased cardiovascular disease risk and mortality., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Exercise oscillatory ventilation (EOV) is an abnormal breathing pattern that occurs in ~20% of patients with heart failure (HF) and is associated with poor prognosis and exercise intolerance. β-blockers (βb) are prescribed for most HF patients; however, their effect on EOV remains unclear. We evaluated the effect of βb on EOV in HF patients with reduced ejection fraction (HFrEF)., Methods: Fifteen patients diagnosed with HF, ejection fraction < 45%, aged from 18 to 65 years, were included before starting βb therapy. Patients underwent clinical evaluation, cardiopulmonary exercise testing, echocardiography, laboratory exams (norepinephrine levels, B type natriuretic peptide) at baseline and after βb therapy optimized for six months. Presence of exercise oscillatory breathing was determined by two experienced observers who were blinded to the moment of the test (pre or post)., Results: Fifteen patients (1 female), aged 49.5 ± 2.5 years, with HFrEF, NYHA I-III enrolled in the study. The etiologies of the HFrEF were idiopathic (n = 8) and hypertensive (n = 7). LVEF increased after βb therapy from 25.9 ± 2.5% to 33 ± 2.6%, P = 0.02; peak VO 2 did not significantly change (21.8 ± 1.7 vs 24.7 ± 1.9, P = 0.4); VE/VCO 2 slope changed from 32.1 ± 10.6-27.5 ± 9.1, P = 0.03. Before βb initiation, nine patients (60%) had EOV, but only two (13%) did after optimized therapy. McNemar test was used to evaluate the significance of the association between the two moments (P = 0.02)., Conclusion: In patients with HF, medical therapy with βb can reverse EOV. This may explain why these patients experience symptom improvement after βb therapy., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Reports suggest that the blood pressure (BP) response to an acute bout of exercise is associated with the BP response to aerobic training in participants with elevated BP. These associations have not been tested among patients with resistant hypertension. This study aimed to determine whether the BP response to acute exercise predicts the 24-h ambulatory BP response to a 12-week exercise training program in patients with resistant hypertension (n = 26, aged 59.3 ± 8.2 years, 24-h ambulatory BP 127.4 ± 12.2/75.6 ± 7.8 mm Hg) who completed the exercise arm of the EnRicH trial. Ambulatory BP measurements were obtained before and after the exercise program to assess the chronic BP response. To assess acute BP changes, resting BP was measured before and 10 min after three exercise sessions in the third week of training and averaged. The resting systolic (9.4 ± 6.7, p < 0.001) and diastolic BP (1.9 ± 3.2, p = 0.005) were reduced after acute exercise. The 24-h systolic (6.2 ± 12.2, p = 0.015) and diastolic BP (4.4 ± 6.1, p = 0.001) were decreased after exercise training. The reductions in systolic BP after acute exercise were associated with the reductions in 24-h systolic BP after exercise training (ß = 0.538, adjusted r 2  = 0.260, P = 0.005). The reductions in diastolic BP after acute exercise (ß = 0.453, adjusted r 2  = 0.187) and baseline 24-h diastolic BP (ß = -0.459, adjusted r 2  = 0. 199) accounted for 38.6% (p = 0.008) of the 24-h diastolic BP response to exercise training. In conclusion, the magnitude of the BP response to acute exercise appears to predict the ambulatory BP response to exercise training among patients with resistant hypertension., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Heart failure (HF) associated with atrial fibrillation increases patients' physical inactivity, worsening their clinical condition and mortality. Exercise training is safe and has clear benefits in HF. However, little is known about the effects of exercise training on patients with HF with reduced ejection fraction and permanent atrial fibrillation (HFAF)., Objective: The purpose of this study was to test the hypothesis that exercise training improves functional capacity, cardiac function, and quality of life in patients with HFAF., Methods: This randomized clinical trial was conducted at the Heart Institute. Patients with HFAF, left ventricular ejection fraction ≤40%, and resting heart rate (HR) ≤80 beats/min were included in the study. Cardiopulmonary testing, echocardiography, nervous system, and quality of life assessment were performed before and after the 12-week protocol period., Results: Twenty-six patients (mean age 58 ± 1 years) were randomized to exercise training (HFAF-trained group; n = 13) or no training (HFAF-untrained group; n = 13). At baseline, no differences between the groups were found. Exercise improved peak oxygen consumption, slope of ventilation per minute/carbon dioxide production, and quality of life. The HFAF-trained group had significantly decreased resting HR (from 73 ± 2 to 69 ± 2 beats/min; P = .02) and recovery HR (from 148 ± 11 to 128 ± 9 beats/min; P = .001). Concomitantly, left ventricular ejection fraction increased (from 31% ± 1% to 36% ± 0.9%; P = .01), left atrial dimension decreased (from 52 ± 1.2 to 47 ± 1 mm; P = .03), and left ventricular end-systolic volume and left ventricular end-diastolic volume deceased (from 69 ± 2 to 64 ± 1.8 mL/m 2 and from 99 ± 2.1 to 91 ± 2 mL/m 2 , respectively; P < .05). No changes were observed in the HFAF-untrained group., Conclusion: Exercise training can improve exercise capacity, quality of life, and cardiac function in patients with HF with reduced ejection fraction and permanent atrial fibrillation., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Skeletal muscle dysfunction is a systemic consequence of heart failure (HF) that correlates with functional capacity. However, the impairment within the skeletal muscle is not well established. We investigated the effect of exercise training on peripheral muscular performance and oxygenation in HF patients., Methods and Results: HF patients with ejection fraction ≤40% were randomized 2:1 to exercise training or control for 12 weeks. Muscle tissue oxygen was measured noninvasively by near-infrared spectroscopy (NIRS) during rest and a symptom-limited cardiopulmonary exercise test (CPET) before and after intervention. Measurements included skeletal muscle oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration, total hemoglobin concentration, VO 2 peak, VE/VCO 2 slope, and heart rate. Muscle sympathetic nerve activity by microneurography, and muscle blood flow by plethysmography were also assessed at rest pre and post 12 weeks. Twenty-four participants (47.5 ± 7.4 years, 58% men, 75% no ischemic) were allocated to exercise training (ET, n = 16) or control (CG, n = 8). At baseline, no differences between groups were found. Exercise improved VO 2 peak, slope VE/VCO 2 , and heart rate. After the intervention, significant improvements at rest were seen in the ET group in muscle sympathetic nerve activity and muscle blood flow. Concomitantly, a significant decreased in Oxy-Hb (from 29.4 ± 20.4 to 15.7 ± 9.0 μmol, p = 0.01), Deoxi-Hb (from 16.3 ± 8.2 to 12.2 ± 6.0 μmol, p = 0.003) and HbT (from 45.7 ± 27.6 to 27.7 ± 13.4 μmol, p = 0.008) was detected at peak exercise after training. No changes were observed in the control group., Conclusion: Exercise training improves skeletal muscle function and functional capacity in HF patients with reduced ejection fraction. This improvement was associated with increased oxygenation of the peripheral muscles, increased muscle blood flow, and decreased sympathetic nerve activity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We sought to assess the residual effects (post 72-h training cessation) on fasting plasma glucose (FPG) and fasting insulin (FI) after 12-weeks of high-intensity interval training (HIIT), resistance training (RT), or concurrent training (CT) in women with insulin resistance (IR). We also aimed to determine the training-induced, post-training residual impact of CT. A total of adult 45 women (age 38.5±9.2years) were included in the final analysis and were assigned to a control (CG; n =13, BMI 28.3±3.6kg/m 2 ), HIIT [ n =14, BMI 28.6±3.6kg/m 2 , three sessions/wk., 80-100% of the maximum heart rate (HR max )], RT [ n =8, BMI 29.4±5.5kg/m 2 , two sessions/wk., 8-10 points of the modified Borg, corresponding to 20 to 50% range of one maximum repetition test (1RM)], or CT group ( n =10, BMI 29.1±3.0kg/m 2 , three sessions/wk., 80-100% of HR max , and 8-10 Borg, or 20 to 50% range of 1RM, to each HIIT and RT compounds), with the latter including both HIIT and RT regimens. Training interventions lasted 12-weeks. The main outcomes were FPG and FI measured at pre- and 24-h and 72-h post-training (FPG 24h , FI 24h , and FPG 72h , FI 72h , respectively). Secondary endpoints were body composition/anthropometry and the adiposity markers waist circumference (WC) and tricípital skinfold (T SF ). The residual effects 72-h post-training [delta (∆)] were significantly poorer (all p <0.01) in the CT group (∆FPG 72h +6.6mg/dl, η 2 : 0.76) than in the HIIT (∆FPG 72h +1.2mg/dl, η 2 : 0.07) and RT (∆FPG 72h +1.0mg/dl, η 2 : 0.05) groups. These findings reveal that HIIT reduces FPG and RT reduces FI 24-h post-training; both exercise interventions alone have remarkably better residual effects on FPG and FI (post-72h) than CT in women with insulin resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alvarez, Ciolac, Guimarães, Andrade, Vasquez-Muñoz, Monsalves-Álvarez, Delgado-Floody, Alonso-Martínez and Izquierdo.)

Background: Physical activity is associated with reduced arterial stiffness, although such a relationship has not been reported in those with resistant hypertension. Therefore, this study aimed to determine the association between daily physical activity and arterial stiffness in patients with resistant hypertension., Methods: Fifty-seven (57) patients with resistant hypertension (50.9% men), aged 58.8±9.4 years, were consecutively recruited. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). Daily physical activity was objectively assessed with accelerometers during 7 consecutive days., Results: Patients had a body mass index of 29.0±4.0 kg/m 2 (84.3% overweight/obese) and were taking an average 4.5 antihypertensive medications. Overall, the cf-PWV was 9.2±2.4 m/s and the majority of participants (n=41, 71.9%) presented a cf-PWV <10 m/s. The cf-PWV showed an inverse correlation with light-intensity physical activity (r = -0.290, p=0.029) and total daily physical activity (r = -0.287, p=0.030). The correlation between light physical activity and cf-PWV remained significant after adjustment for systolic and diastolic blood pressure, but lost significance when further adjusted for age., Conclusions: Higher daily levels of light-intensity and total physical activity were associated with lower arterial stiffness. Nonetheless, this association is weak and attenuated or abolished when adjusted for blood pressure and age. These results suggest that physical activity may play an important role as a lifestyle intervention for patients with resistant hypertension. Future studies with larger samples sizes are necessary to confirm this preliminary data., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Importance: Limited evidence suggests exercise reduces blood pressure (BP) in individuals with resistant hypertension, a clinical population with low responsiveness to drug therapy., Objective: To determine whether an aerobic exercise training intervention reduces ambulatory BP among patients with resistant hypertension., Design, Settings, and Participants: The Exercise Training in the Treatment of Resistant Hypertension (EnRicH) trial is a prospective, 2-center, single-blinded randomized clinical trial performed at 2 hospital centers in Portugal from March 2017 to December 2019. A total of 60 patients with a diagnosis of resistant hypertension aged 40 to 75 years were prospectively enrolled and observed at the hospitals' hypertension outpatient clinic., Interventions: Patients were randomly assigned in a 1:1 ratio to a 12-week moderate-intensity aerobic exercise training program (exercise group) or a usual care control group. The exercise group performed three 40-minute supervised sessions per week in addition to usual care., Main Outcomes and Measures: The powered primary efficacy measure was 24-hour ambulatory systolic BP change from baseline. Secondary outcomes included daytime and nighttime ambulatory BP, office BP, and cardiorespiratory fitness., Results: A total of 53 patients completed the study, including 26 in the exercise group and 27 in the control group. Of these, 24 (45%) were women, and the mean (SD) age was 60.1 (8.7) years. Compared with the control group, among those in the exercise group, 24-hour ambulatory systolic BP was reduced by 7.1 mm Hg (95% CI, -12.8 to -1.4; P = .02). Additionally, 24-hour ambulatory diastolic BP (-5.1 mm Hg; 95% CI, -7.9 to -2.3; P = .001), daytime systolic BP (-8.4 mm Hg; 95% CI, -14.3 to -2.5; P = .006), and daytime diastolic BP (-5.7 mm Hg; 95% CI, -9.0 to -2.4; P = .001) were reduced in the exercise group compared with the control group. Office systolic BP (-10.0 mm Hg; 95% CI, -17.6 to -2.5; P = .01) and cardiorespiratory fitness (5.05 mL/kg per minute of oxygen consumption; 95% CI, 3.5 to 6.6; P < .001) also improved in the exercise group compared with the control group., Conclusions and Relevance: A 12-week aerobic exercise program reduced 24-hour and daytime ambulatory BP as well as office systolic BP in patients with resistant hypertension. These findings provide clinicians with evidence to embrace moderate-intensity aerobic exercise as a standard coadjutant therapy targeting this patient population., Trial Registration: ClinicalTrials.gov Identifier: NCT03090529.

Background: We tested the hypothesis that the 6 to 20 rating of perceived exertion (RPE) is a cost-effective tool similar to heart rate (HR) response to cardiopulmonary exercise test for prescribing and self-regulating high-intensity interval exercise (HIIE). In this context, we analyzed if health-related responses to exercise are similar between HIIE prescribed and self-regulated by RPE (HIIERPE) and HIIE prescribed and regulated by HR response to cardiopulmonary exercise test (HIIEHR)., Methods: Twelve young (21±2 years) sedentary or insufficiently active individuals (weekly levels ˂150 minutes or 75 minutes of moderate- or vigorous-intensity physical activity, respectively) were randomly assigned to perform HIIERPE (25 minutes), HIIEHR (25 minutes) and control session (25 minutes of seated resting). Blood pressure, HR, and arterial stiffness (pulse wave velocity) were measured before, immediately after, and 30 minutes after each intervention. HR, speed, and distance were measured during exercise sessions. 24-hours ambulatory blood pressure was measured after each intervention., Results: Exercise HR, speed, and distance, as well as blood pressure response to exercise were not different between HIIERPE and HIIEHR. Pulse wave velocity reduced (P<0.05) at postintervention in both HIIERPE (0.28±0.17 m/s) and HIIEHR (0.27±0.11 m/s). However, pulse wave velocity at recovery was lower than pre-intervention only during HIIERPE (0.30±0.10 m/s)., Conclusions: These results suggest that RPE is a cost-effective tool for prescribing self-regulating HIIE and improving health-related variables in young individuals.

Heart transplantation (HTx) is a therapeutic option for a selected group of patients with end-stage heart failure. Although secondary prevention including exercise therapy is recommended in the management of patients following HTx, little information is available on their metabolic and physiological consequences in HTx. Therefore, we aimed to conduct a contemporary review the effectiveness of exercise therapy on functional capacity, cardiovascular health and health-related quality of life for adult HTx patients. We searched the database MEDLINE for articles published between January 2015 and October 2020 and were able to include 6 studies involving 202 patients. Larger improvements in exercise capacity were seen after high-intensity interval training and in patients with evidence of cardiac reinnervation. Clinically relevant reductions were observed for daytime and 24 h ambulatory blood pressure after exercise training and following a single bout of aerobic exercise. Finally, limited data suggest that quality of life is higher in HTx patients following high-intensity training. In summary, the available evidence shows the potential for exercise as a vital treatment in patients following HTx. Yet, the scant data calls for more well-designed and adequately powered studies to support its effectiveness and to unravel optimal exercise characteristics, which would allow for more effective and person-tailored exercise prescription., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate the hemodynamic and cardiorespiratory adaptations to exercise in individuals with heart transplantation with evidence of cardiac reinnervation (cardiac reinnervation group) versus without evidence of cardiac reinnervation (no cardiac reinnervation group)., Methods: Sedentary individuals with heart transplantation (age = 45.5 ± 2.2 years; time elapsed since surgery = 6.7 ± 0.7 years) were divided into the cardiac reinnervation ( n  = 16) and no cardiac reinnervation ( n  = 17) groups according to their heart rate response to cardiopulmonary exercise testing. The 24-hour ambulatory blood pressure, carotid-femoral pulse wave velocity, and cardiorespiratory fitness were assessed before and after 12 weeks of a thrice-weekly exercise program (five minutes of warm-up, 30 min of endurance exercise, one set of 10-15 reps in five resistance exercises, and five minutes of cool-down)., Results: The cardiac reinnervation group had reduced ( p  < 0.01) 24-hour systolic/diastolic blood pressure (7/9 mm Hg), daytime systolic/diastolic blood pressure (9/10 mm Hg) and nighttime diastolic blood pressure (6 mm Hg) after training. The no cardiac reinnervation group reduced ( p  < 0.05) only 24-hour (5 mm Hg), daytime (5 mm Hg) and nighttime (6 mm Hg) diastolic blood pressure after training. Hourly analysis showed that the cardiac reinnervation group reduced systolic/diastolic blood pressure for 10/21 h, while the no cardiac reinnervation group reduced systolic/diastolic blood pressure for only 3/11 h. The cardiac reinnervation group also improved both maximal oxygen consumption (10.8%) and exercise tolerance (13.4%) after training, but the no cardiac reinnervation group improved only exercise tolerance (9.9%). Pulse wave velocity did not change in both groups., Conclusion: There were greater improvements in ambulatory blood pressure and maximal oxygen consumption in the cardiac reinnervation than the no cardiac reinnervation group. These results suggest that cardiac reinnervation associates with hemodynamic and cardiorespiratory adaptations to exercise training in individuals with heart transplantation.

Purpose: To investigate the effect of high-intensity interval training (HIIT) versus moderate-intensity continuous exercise training (MICE) on hemodynamic and functional variables in individuals with Parkinson's disease., Methods: Twenty participants (13 men) were randomly assigned to a thrice-weekly HIIT (n = 12) or MICE (n = 8) for 12 weeks. Hemodynamic (resting heart rate and blood pressure, carotid femoral pulse wave velocity, endothelial reactivity, and heart rate variability) and functional variables (5-time sit-to-stand, timed up and go, and 6-min walking tests) assessed before and after training., Results: Demographic, hemodynamic and functional variables were similar between groups at baseline. Endothelial reactivity tended to increase after HIIT, but not after MICE, resulting in improved level (∼8%, P < .01) of this variable in HIIT versus MICE during follow-up. Six-minute walking test improved after HIIT (10.4 ± 3.8%, P < .05), but did not change after MICE. Sit to stand improved similarly after HIIT (27.2 ± 6.1%, P < .05) and MICE (21.5 ± 5.4%, P < .05). No significant changes were found after HIIT or MICE in any other variable assessed., Conclusion: These results suggest that exercise intensity may influence training-induced adaptation on endothelial reactivity and aerobic capacity in individuals with Parkinson's disease.

We tested the hypothesis that rating of perceived exertion (RPE) is a tool as efficient as the heart rate (HR) response to the cardiopulmonary exercise test (CPX) for prescribing and self-regulating high-intensity interval exercise (HIIE), and that metabolic and hemodynamic response to HIIE is superior than to continuous moderate-intensity exercise (MICE) in individuals with type 2 diabetes mellitus (T2DM). Eleven participants (age = 52.3 ± 3 years) underwent HIIE prescribed and self-regulated by RPE (HIIE RPE ; 25 min), HIIE prescribed and regulated by an individual's HR response to CPX (HIIE HR ; 25 min), MICE prescribed and self-regulated by RPE (30 min) and control (30 min of seated resting) intervention in random order. HR, blood pressure (BP), capillary glucose, endothelial reactivity, and carotid-femoral pulse wave velocity were assessed before, immediately after, and 45 min after each intervention. Exercise HR, speed, and distance were measured during exercise sessions. Twenty-four-hour ambulatory BP was measured after each intervention. Exercise HR, speed, and distance were similar between HIIE RPE and HIIE HR . BP response was not different among HIIE RPE , HIIE HR , and MICE. Capillary glycaemia reduction was greater (P < 0.05) after HIIE RPE (48.6 ± 9.6 mg/dL) and HIIE HR (47.2 ± 9.5 mg/dL) than MICE (29.5 ± 11.5 mg/dL). Reduction (P < 0.05) in 24-h (6.7 ± 2.2 mm Hg) and tendency toward reduction (P = 0.06) in daytime systolic (7.0 ± 2.5 mm Hg) ambulatory BP were found only after HIIE RPE . These results suggest that HIIE is superior to MICE for reducing glycaemia and ambulatory BP, and that the 6-20 RPE scale is a useful tool for prescribing and self-regulating HIIE in individuals with T2DM.

Blood pressure (BP) and hemodynamic response to heated water-based (HEx) vs. land-based exercise (LEx) were assessed in 15 (6 men) older hypertensives (age 66.4±4.9 yr) under pharmacological treatment. Participants were randomly assigned to perform 30 min of moderate-intensity HEx (walking inside the pool), LEx (walking on a treadmill) and non-exercise control (CON) intervention. Resting BP, arterial stiffness, endothelial reactivity and heart rate variability (HRV) were measured before, immediately after, and 45 min after interventions. 24-h ambulatory BP monitoring was performed after interventions. Resting systolic (but not diastolic) BP reduced 9.9±3.1 mmHg ( P <0.01) 45 min after HEx only. 24-h systolic and diastolic, daytime diastolic and nightime systolic BP were lower ( P <0.05) after HEx than both LEx and CON. Daytime systolic BP was also lower ( P <0.05) after HEx than CON. Nighttime diastolic was not different between interventions. HEx-induced ambulatory BP reduction ranged 4.5±1.3 mmHg (24-h diastolic BP) to 9.5±3.0 mmHg (nighttime systolic BP), and persisted for 18/11 h in systolic/diastolic BP, when compared with CON. No significant changes in arterial stiffness, endothelial reactivity and HRV were found during any intervention. These results suggest that HEx may have important implications for managing BP in older hypertensive under pharmacological treatment., Competing Interests: All authors have no conflicts of interest to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aims: The SHIFT trial showed that ivabradine reduced heart rate (HR) and the risk of cardiovascular outcomes. Concerns remain over the efficacy and safety of ivabradine on heart failure (HF) due to Chagas disease (ChD). We therefore conducted a post hoc analysis of the SHIFT trial to investigate the effect of ivabradine in these patients., Methods and Results: SHIFT was a randomized, double-blind, placebo-controlled trial in symptomatic systolic stable HF, HR ≥ 70 b.p.m., and in sinus rhythm. The ChD HF subgroup included 38 patients, 20 on ivabradine, and 18 on placebo. The ChD HF subgroup showed high prevalence of bundle branch right block and, compared with the overall SHIFT population, lower systolic blood pressure; higher use of diuretics, cardiac glycosides, and antialdosterone agents; and lower use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or target daily dose of beta-blocker. ChD HF presented a poor prognosis (all-cause mortality at 2 years was ~60%). The mean twice-daily dose of ivabradine was 6.26 ± 1.15 mg and placebo 6.43 ± 1.55 mg. Ivabradine reduced HR from 77.9 ± 3.8 to 62.3 ± 10.1 b.p.m. (P = 0.005) and improved functional class (P = 0.02). A trend towards reduction in all-cause death was observed in ivabradine arm vs. placebo (P = 0.07). Ivabradine was not associated with serious bradycardia, atrioventricular block, hypotension, or syncope., Conclusions: ChD HF is an advanced form of HF with poor prognosis. Ivabradine was effective in reducing HR in these patients and improving functional class. Although our results are based on a very limited sample and should be interpreted with caution, they suggest that ivabradine may have a favourable benefit-risk profile in ChD HF patients., (© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Heart transplantation (HTx) is considered an efficient and gold-standard procedure for patients with end-stage heart failure. After surgery, patients have lower aerobic power (VO2max) and compensatory hemodynamic responses. The aim of the present study was to assess through a systematic review with meta-analysis whether high-intensity interval training (HIIT) can provide benefits for those parameters. This is a systematic review with meta-analysis, which searched the databases and data portals PubMed, Web of Science, Scopus, Science Direct and Wiley until December 2016 (pairs). The following terms and descriptors were used: "heart recipient" OR "heart transplant recipient" OR "heart transplant" OR "cardiac transplant" OR "heart graft". Descriptors via DeCS and Mesh were: "heart transplantation'' OR "cardiac transplantation". The words used in combination (AND) were: "exercise training" OR "interval training" OR "high intensity interval training" OR "high intensity training" OR "anaerobic training" OR "intermittent training" OR "sprint training". The initial search identified 1064 studies. Then, only those studies assessing the influence of HIIT on the post-HTx period were added, resulting in three studies analyzed. The significance level adopted was 0.05. Heart transplant recipients showed significant improvement in VO2peak, heart rate and peak blood pressure in 8 to 12 weeks of intervention.

Background In patients with heart failure, inflammation has been associated with worse functional capacity, but it is uncertain whether it could affect their response to exercise training. We evaluated whether inflammatory biomarkers are related to differential effect of exercise on the peak oxygen uptake (V˙O 2 ) among patients with heart failure. Design Open, parallel group, randomized controlled trial. Methods Patients with heart failure and ejection fraction ≤0.4 were randomized into exercise training or control for 12 weeks. Patients were classified according to: 1) inflammatory biomarkers blood levels, defined as 'low' if both interleukin-6 and tumor necrosis factor-alpha blood levels were below median, and 'high' otherwise; and 2) galectin-3 blood levels, which also reflect pro-fibrotic processes. Results Forty-four participants (50 ± 7 years old, 55% men, 25% ischemic) were allocated to exercise training ( n = 28) or control ( n = 16). Exercise significantly improved peak V˙O 2 among participants with 'low' inflammatory biomarkers (3.5 ± 0.9 vs. -0.7 ± 1.1 ml/kg per min, p = 0.006), as compared with control, but not among those with 'high' inflammatory biomarkers (0.4 ± 0.6 vs. -0.2 ± 0.7 ml/kg per min, p = 0.54, p for interaction = 0.009). Similarly, exercise improved peak V˙O 2 among participants with below median (2.4 ± 0.8 vs. -0.3 ± 0.9 ml/kg per min, p = 0.032), but not among those with above median galectin-3 blood levels (0.3 ± 0.7 vs. -0.7 ± 1.0 ml/kg per min, p = 0.41, p for interaction = 0.053). Conclusion In patients with heart failure, levels of biomarkers that reflect pro-inflammatory and pro-fibrotic processes were associated with differential effect of exercise on functional capacity. Further studies should evaluate whether exercise training can improve clinical outcomes in patients with heart failure and low levels of these biomarkers.

Introduction: Ambient air pollution is associated with adverse cardiovascular events. This meta-analysis aimed to investigate the short-term association between air pollution and cardiovascular effects on healthy volunteers., Methods: We searched databases to identify randomized trials with controlled human exposures to either of two models for studying ambient particulate matter: diesel-exhaust or concentrated ambient particles. Estimates of size effect were performed using standardized mean difference (SMD). Heterogeneity was assessed with I 2 statistics. Outcomes were vascular function estimated by forearm blood flow (FBF), blood pressure, heart rate, and blood analysis., Results: Database searches yielded 17 articles (n = 342) with sufficient information for meta-analyses. High levels of heterogeneity for the some outcomes were analyzed using random-effects model. The pooled effect estimate showed that short-term exposure to air pollution impaired FBF response from 2.7 to 2.5 mL/100 mL tissue/min (SMD 0.404; p = .006). There was an increase in 5000 platelet/mm 3 following pollution exposure (SMD 0.390; p = .050) but no significant differences for other outcomes., Conclusion: Controlled human exposures to air pollution are associated with the surrogates of vascular dysfunction and increase in platelet count, which might be related to adverse cardiovascular events. Given the worldwide prevalence of exposure to air pollution, these findings are relevant for public health. KEY MESSAGES Controlled exposure to air pollution impairs vasomotor response, which is a surrogate for adverse cardiovascular events. This is the first meta-analysis from randomized clinical trials showing short-term association between air pollution and cardiovascular effects on healthy volunteers. Given the worldwide prevalence of exposure to air pollution, this finding is important for public health.

Cardiotoxicity is associated with the chronic use of doxorubicin leading to cardiomyopathy and heart failure. Identification of cardiotoxicity-specific miRNA biomarkers could provide clinicians with a valuable prognostic tool. The aim of the study was to evaluate circulating levels of miRNAs in breast cancer patients receiving doxorubicin treatment and to correlate with cardiac function. This is an ancillary study from "Carvedilol Effect on Chemotherapy-induced Cardiotoxicity" (CECCY trial), which included 56 female patients (49.9±3.3 years of age) from the placebo arm. Enrolled patients were treated with doxorubicin followed by taxanes. cTnI, LVEF, and miRNAs were measured periodically. Circulating levels of miR-1, -133b, -146a, and -423-5p increased during the treatment whereas miR-208a and -208b were undetectable. cTnI increased from 6.6±0.3 to 46.7±5.5 pg/mL (p<0.001), while overall LVEF tended to decrease from 65.3±0.5 to 63.8±0.9 (p=0.053) over 12 months. Ten patients (17.9%) developed cardiotoxicity showing a decrease in LVEF from 67.2±1.0 to 58.8±2.7 (p=0.005). miR-1 was associated with changes in LVEF (r=-0.531, p<0.001). In a ROC curve analysis miR-1 showed an AUC greater than cTnI to discriminate between patients who did and did not develop cardiotoxicity (AUC = 0.851 and 0.544, p= 0.0016). Our data suggest that circulating miR-1 might be a potential new biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients.

Background: Idiopathic dilated cardiomyopathy (IDCM), most common cardiac cause of pediatric deaths, mortality descriptor: a low left ventricular ejection fraction (LVEF) and low functional capacity (FC). FC is never self reported by children., Objective: The aims of this study were (i) To evaluate whether functional classifications according to the children, parents and medical staff were associated. (iv) To evaluate whether there was correlation between VO2 max and Weber's classification., Method: Prepubertal children with IDCM and HF (by previous IDCM and preserved LVEF) were selected, evaluated and compared. All children were assessed by testing, CPET and functional class classification., Results: Chi-square test showed association between a CFm and CFp (1, n = 31) = 20.6; p = 0.002. There was no significant association between CFp and CFc (1, n = 31) = 6.7; p = 0.4. CFm and CFc were not associated as well (1, n = 31) = 1.7; p = 0.8. Weber's classification was associated to CFm (1, n = 19) = 11.8; p = 0.003, to CFp (1, n = 19) = 20.4; p = 0.0001and CFc (1, n = 19) = 6.4; p = 0.04)., Conclusion: Drawing were helpful for children's self NYHA classification, which were associated to Weber's stratification.

Purpose: Heart transplant recipients (HTx) have a high prevalence of hypertension. Although exercise training promotes blood pressure (BP) reduction in HTx, the effects of a single exercise bout are unknown. Thus, we analyzed the acute effects of heated water-based exercise (HEx) versus land-based exercise (LEx) on ambulatory BP (ABP) in HTx., Methods: Eighteen (six females) clinically stable HTx (time since surgery = 5.0 ± 0.7 yr) age 45.7 ± 2.7 yr underwent 30 min of HEx (walking inside the pool), LEx (walking on a treadmill), and nonexercise control (CON) intervention in random order (2-5 d between interventions). HEx and LEx intensity was set at 11-13 in the 6-20 RPE scale. Twenty-four-hour (24-h) ABP monitoring was performed after each intervention., Results: No significant differences between interventions were found in 24-h and nighttime BP. However, daytime diastolic BP was significantly lower after HEx than CON (-4 ± 1.6 mm Hg, P = 0.03), and daytime diastolic BP tended to be lower after LEx than CON (-2.3 ± 1.1 mm Hg, P = 0.052). Hourly analysis showed that systolic and diastolic BP values were lower after HEx (average reductions of 6.6 to 12.3 mm Hg, P < 0.01) and LEx (average reductions of 5 to 8.3 mm Hg, P < 0.05) than after CON in several hours. No significant differences between HEx and LEx were found in any ABP data., Conclusion: HEx and LEx promoted similar reductions in ABP of heart transplant recipients, which suggests that they may be a tool to counteract hypertension in this high-risk population.

Objective: To look for correlations between lung function and cardiac dimension variables in morbidly obese patients, in order to test the hypothesis that the relative size of the small airways is independently correlated with left ventricular hypertrophy., Methods: This was a retrospective study involving 192 medical records containing a clinical protocol employed in candidates for bariatric surgery between January of 2006 and December of 2010., Results: Of the 192 patients evaluated, 39 (10 males and 29 females) met the inclusion criteria. The mean BMI of the patients was 49.2 ± 7.6 kg/m2, and the mean age was 35.5 ± 7.7 years. The FEF25-75/FVC, % correlated significantly with left ventricular posterior wall thickness and relative left ventricular posterior wall thickness, those correlations remaining statistically significant (r = -0.355 and r = -0.349, respectively) after adjustment for weight, gender, and history of systemic arterial hypertension. Stepwise multivariate linear regression analysis showed that FVC and FEV1 were the major determinants of left ventricular mass (in grams or indexed to body surface area)., Conclusions: A reduction in the relative size of the small airways appears to be independently correlated with obesity-related cardiac hypertrophy, regardless of factors affecting respiratory mechanics (BMI and weight), gender, or history of systemic arterial hypertension. However, FEV1 and FVC might be important predictors of left ventricular mass in morbidly obese individuals.

Background: Polypharmacy is a significant economic burden., Objective: We tested whether using reverse auction (RA) as compared with commercial pharmacy (CP) to purchase medicine results in lower pharmaceutical costs for heart failure (HF) and heart transplantation (HT) outpatients., Methods: We compared the costs via RA versus CP in 808 HF and 147 HT patients followed from 2009 through 2011, and evaluated the influence of clinical and demographic variables on cost., Results: The monthly cost per patient for HF drugs acquired via RA was $10.15 (IQ 3.51-40.22) versus $161.76 (IQ 86.05‑340.15) via CP; for HT, those costs were $393.08 (IQ 124.74-774.76) and $1,207.70 (IQ 604.48-2,499.97), respectively., Conclusion: RA may reduce the cost of prescription drugs for HF and HT, potentially making HF treatment more accessible. Clinical characteristics can influence the cost and benefits of RA. RA may be a new health policy strategy to reduce costs of prescribed medications for HF and HT patients, reducing the economic burden of treatment.

Purpose: The objective of this study is to analyze the use of the 6-20 RPE scale for prescribing and self-regulating heated water-based exercise (HEx) and land-based exercise (LEx) in heart transplant recipients., Methods: Fifteen (five females) clinically stable heart transplant recipients (time since surgery = 4.0 ± 2.5 yr) age 46.7 ± 11.8 yr underwent a symptom-limited maximal graded exercise test on a treadmill to determine their HR at anaerobic threshold (HRAT), respiratory compensation point (HRRCP), and maximal effort (HRmax). After a week, patients were randomized to perform 30 min of both HEx (walking inside the pool) and LEx (treadmill walking) sessions at a pace between 11 and 13 on the 6-20 RPE scale and had their HR measured every 4 min. The interval between sessions was 48-72 h., Results: No significant differences between sessions were found in the average HR during HEx and LEx. Patients showed a delay in HR increase during both interventions, with the stabilization beginning after 8 min of exercise. Exercise HR was maintained between the HRAT and HRRCP (in the aerobic exercise training zone) for the most part of both HEx (72% of HR measurements) and LEx (66% of HR measurements). Only a few HR measurements stayed below HRAT (HEx = 9%, LEx = 13%) or above HRRCP (HEx = 19%, LEx = 21%) during both exercise sessions., Conclusion: Exercise HR was maintained in the aerobic exercise training zone (between HRAT and HRRCP) for the most part of both sessions, suggesting that the 6-20 RPE scale may be an efficient tool for prescribing and self-regulating HEx and LEx in heart transplant recipients.

Background: Hypertension is the most prevalent comorbidity after heart transplantation (HT). Exercise training (ET) is widely recommended as a key non-pharmacologic intervention for the prevention and management of hypertension, but its effects on ambulatory blood pressure (ABP) and some mechanisms involved in the pathophysiology of hypertension have not been studied in this population. The primary purpose of this study was to investigate the effects of ET on ABP and arterial stiffness of HT recipients., Methods: 40 HT patients, randomized to ET (n = 31) or a control group (n = 9) underwent a maximal graded exercise test, 24-hour ABP monitoring, and carotid-femoral pulse wave velocity (PWV) assessment before the intervention and at a 12-week follow-up assessment. The ET program was performed thrice-weekly and consisted primarily of endurance exercise (40 minutes) at ~70% of maximum oxygen uptake (Vo2MAX)., Results: The ET group had reduced 24-hour (4.0 ± 1.4 mm Hg, p < 0.01) and daytime (4.8 ± 1.6 mm Hg, p < 0.01) systolic ABP, and 24-hour (7.0 ± 1.4 mm Hg, p < 0.001) daytime (7.5 ± 1.6 mm Hg, p < 0.001) and nighttime (5.9 ± 1.5 mm Hg, p < 0.001) diastolic ABP after the intervention. The ET group also had improved Vo2MAX (9.7% ± 2.6%, p < 0.001) after the intervention. However, PWV did not change after ET. No variable was changed in the control group after the intervention., Conclusions: The 12-week ET program was effective for reducing ABP but not PWV in heart transplant recipients. This result suggests that endurance ET may be a tool to counteract hypertension in this high-risk population., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Context and Objective: Methylphenidate is the most widely used drug for treating attention deficit hyperactivity disorder. However, it has important side effects, such as abdominal pain, insomnia, anorexia and loss of appetite, and also some cases of early severe emphysema after drug abuse have been reported. Our aim was to investigate the development of pulmonary emphysema in rats that were subjected to different doses of methylphenidate., Design and Setting: Experimental study carried out at the laboratory of a public university., Methods: Eighteen male Wistar rats were divided into three groups: control (0.9% saline solution); MP 0.8 (methylphenidate, 0.8 mg/kg); MP 1.2 (methylphenidate, 1.2 mg/kg). After 90 days of daily gavage, the animals were sacrificed and lung tissue samples were prepared for analysis on the mean alveolar diameter (Lm)., Results: The Lm was greater in MP 0.8 (47.91 ± 3.13; P < 0.01) and MP 1.2 (46.36 ± 4.39; P < 0.05) than in the control group (40.00 ± 3.48)., Conclusion: Methylphenidate caused an increase in the alveolar diameter of rats, which was compatible with human pulmonary emphysema.

Objective: To establish the determinants of the peak VO2 in heart transplant recipients., Methods: Patient's assessment was performed in two consecutive days. In the first day, patients performed the heart rate variability assessment followed by a cardiopulmonary exercise test. In the second day, patients performed a resting echocardiography. Heart transplant recipients were eligible if they were in a stable condition and without any evidence of tissue rejection diagnosed by endomyocardial biopsy. Patients with pacemaker, noncardiovascular functional limitations such as osteoarthritis and chronic obstructive pulmonary disease were excluded from this study., Results: Sixty patients (68% male, 48 years and 64 months following heart transplantation) were assessed. Multivariate analysis selected the following variables: receptor's gender (P=0.001), receptor age (P=0.049), receptor Body Mass Index (P=0.005), heart rate reserve (P <0.0001), left atrium diameter (P=0.016). Multivariate analysis showed r=0.77 and r2=0.6 with P <0.001. Equation: peakVO2=32.851 - 3.708 (receptor gender) - 0.067 (receptor age) - 0.318 (receptor BMI) + 0.145 (heart rate reserve) - 0.111 (left atrium diameter)., Conclusion: The determinants of the peak VO2 in heart transplant recipients were: receptor sex, age, Body Mass Index, heart rate reserve and left atrium diameter. Heart rate reserve was the unique variable positively associated with peak VO2. This data suggest the importance of the sympathetic reinnervation in peak VO2 in heart transplant recipients.

The aim of the present study was to analyze the effects of age on cardiorespiratory fitness (CRF), muscle strength and heart rate (HR) response to exercise adaptation in women in response to a long-term twice-weekly combined aerobic and resistance exercise program. 85 sedentary women, divided into young (YG; n=22, 30.3 ± 6.2 years), early middle-aged (EMG; n=28, 44.1 ± 2.5 years), late middle-aged (LMG; n=20, 56.7 ± 3.5 years) and older (OG; n=15, 71.4 ± 6.9 years) groups, had their CRF, muscle strength (1-repetition maximum test) and HR response to exercise (graded exercise test) measured before and after 12 months of combined exercise training. Exercise training improved CRF and muscle strength in all age groups (P<0.05), and no significant differences were observed between groups. Exercise training also improved resting HR and recovery HR in YG and EMG (P<0.05), but not in LMG and OG. Maximal HR did not change in any group. Combined aerobic and resistance training at a frequency of 2 days/week improves CRF and muscle strength throughout the lifespan. However, exercise-induced improvements in the HR recovery response to exercise may be impaired in late middle-aged and older women., (© Georg Thieme Verlag KG Stuttgart · New York.)

Sedentary habits or insufficient activities to promote health benefits can influence the occurrence of chronic diseases. The cardiovascular risk factors arise, at least partially, from the individual-environment interaction during life, and worsen with aging and lack of physical exercise. Health promotion and prevention are among the greatest challenges of public health policies. However, physical activity turns out to be rarely recommended and, thus have a very poor adhesion. In spite of consensus about the benefits of physical activity in both primary and secondary prevention, only 32% of adults and 66% of children and adolescents, according to Healthy People 2010 guideline, practice leisure-time physical activity. Thus, the regular practice of physical activity and healthy habits require changes in basic concepts in government and social policies. The higher involvement of public and private sectors related to health and education, the more expressive would be the reduction in socioeconomic costs and the improvement in quality of life.

High blood pressure (BP) increases the risk of cardiovascular diseases, and its control is a clinical challenge. Regular exercise lowers BP in patients with mild-to-moderate hypertension. No data are available on the effects of heated water-based exercise in hypertensive patients. Our objective was to evaluate the effects of heated water-based exercise on BP in patients with resistant hypertension. We tested the effects of 60-min heated water-based exercise training three times per week in 16 patients with resistant hypertension (age 55±6 years). The protocol included walking and callisthenic exercises. All patients underwent 24-h ambulatory blood pressure monitoring (ABPM) before and after a 2-week exercise program in a heated pool. Systolic office BP was reduced from 162 to 144 mmHg (P<0.004) after heated-water training. After the heated-water exercise training during 24-h ABPM, systolic BP decreased from 135 to 123 mmHg (P=0.02), diastolic BP decreased from 83 to 74 mmHg (P=0.001), daytime systolic BP decreased from 141 to 125 mmHg (P=0.02), diastolic BP decreased from 87 to 77 mmHg (P=0.009), night-time systolic BP decreased from 128 to 118 mmHg (P=0.06), and diastolic BP decreased from 77 to 69 mmHg (P=0.01). In addition, BP cardiovascular load was reduced significantly during the 24-h daytime and night-time period after the heated water-based exercise. Heated water-based exercise reduced office BP and 24-h daytime and night-time ABPM levels. These effects suggest that heated water-based exercise may have a potential as a new therapeutic approach to resistant hypertensive patients.

Background: Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure., Methods: In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP2), urea transporter (UT-A1), and sodium/hydrogen exchanger 3 (NHE3)., Results: Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo., Conclusions: HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy., Methods and Results: We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas) and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1%) died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34-5.69; p = 0.006), LVEDD (left ventricular end diastolic diameter) (HR 1.07; CI 1.04-1.10; p<0.001), creatinine clearance (HR 0.98; CI 0.97-0.99; p = 0.006) and use of amiodarone (HR 3.05; CI 1.47-6.34; p = 0.003) were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01-1.07; p = 0.005) and use of beta-blocker (HR 0.52; CI 0.34-0.94; p = 0.014) were independently associated with sudden death mortality., Conclusions: In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death., Trial Registration: ClinicalTrials.gov NCT00505050 (REMADHE).

Background: The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of natriuretic peptides in clinical conditions associated with dyspnea, their effect on pulmonary VE and chemoreceptor activity remains unexplored., Methods: We tested in a prospective, placebo-controlled, three-way cross-over, double-blind randomized study the effects of the recombinant form of the natural human B-type natriuretic peptide (R-BNP) in comparison with placebo and levosimendan on chemoreflex sensitivity at rest, as well as their effects on pulmonary VE, systemic blood pressure, heart rate and sympathetic serum activity both at rest and during exercise., Results: Eleven stable chronic HF patients were randomized to sessions of 6-min treadmill-walking tests during placebo, or levosimendan or R-BNP intravenous infusion in the following conditions: room air, hypoxia, and hypercapnia. R-BNP administration determined higher pulmonary ventilatory response at rest and during exercise (P < 0.001) consequent to a boost of respiratory rate (P < 0.001) under room air and hypoxia conditions. Norepinephrine blood levels increased from rest to exercise in all conditions without differences among placebo, levosimendan, and R-BNP effects. BNP blood levels remained unchanged., Conclusions: The novelty of the present findings is that R-BNP infusion in HF patients can boost pulmonary ventilatory response at rest and during exercise., (© 2011 Blackwell Publishing Ltd.)

MicroRNAs (miRNAs) are a class of non-coding small RNAs representing one of the most exciting areas of modern medical science. miRNAs modulate a large and complex regulatory network of gene expression of the majority of the protein-coding genes. Currently, evidences suggest that miRNAs play a crucial role in the pathogenesis of heart failure. Some miRNAs as miR-1, miR-133 and miR-208a are highly expressed in the heart and strongly associated with the development of cardiac hypertrophy. Recent data indicate that these miRNAs as well as miR-206 change their expression quickly in response to physical activity. The differential regulation of miRNAs in response to exercise suggests a potential value of circulating miRNAs (c-miRNAs) as biomarkers of physiological mediators of the cardiovascular adaptation induced by exercise. Likewise, serum levels of c-miRNAs such as miR-423-5p have been evaluated as potential biomarkers in the diagnosis and prognosis of heart failure. On the other hand, the manipulation of miRNAs levels using techniques such as 'miR mimics' and 'antagomiRs' is becoming evident the enormous potential of miRNAs as promising therapeutic strategies in heart failure.

Background: Heart failure (HF) is associated with impaired maximal aerobic capacity as indicated by decreases in peak oxygen uptake (peak VO(2)). Considering that aging by itself has a negative effect on this variable, the evaluation of maximum capacity is often questioned because current predicted peak VO(2) is based on subjects without heart disease or b-blocker therapy. In contrast, if decline in predicted and attained peak VO(2) were age-related, proportionally, loss of aerobic function (predicted peak VO(2), %) would remain stable over time in these patients. The purpose of this investigation is to assess the effects of age on peak VO(2) in HF patients taking b-blockers., Methods: We retrospectively evaluated 483 (132 female) patients (aged 20-88 years, LVEF 31 ± 11%) with non-ischemic (n = 362), ischemic (n = 74) and Chagas-related HF (n = 47) who had been submitted to an incremental cardiopulmonary exercise testing on a motorized treadmill. Linear regression was used to develop the equation to predict peak VO(2), based on age., Results: Peak VO(2) decreased 0.9 mL/min/kg per age-decade, maximum HR also decreased with aging and VE/VCO(2) slope was similar among all decades. The predicted new b-blocker equation to peak VO(2 bb) was 20.934 - 0.092 × age., Conclusions: Clinical interpretation of aerobic capacity impairment is influenced by aging in HF patients. This evidence must be considered when using peak VO(2) for prognostic stratification and clinical decision-making in patients with HF under b-blocker therapy.

Aims: To evaluate the feasibility, safety, and potential beneficial effects of left cardiac sympathetic denervation (LCSD) in systolic heart failure (HF) patients., Methods and Results: In this prospective, randomized pilot study, inclusion criteria were New York Heart Association (NYHA) functional class II or III, left ventricular ejection fraction (LVEF) ≤40%, sinus rhythm, and resting heart rate >65 b.p.m., despite optimal medical therapy (MT). Fifteen patients were randomly assigned either to MT alone or MT plus LCSD. The primary endpoint was safety, measured by mortality in the first month of follow-up and morbidity according to pre-specified criteria. Secondary endpoints were exercise capacity, quality of life, LVEF, muscle sympathetic nerve activity (MSNA), brain natriuretic peptide (BNP) levels and 24 h Holter mean heart rate before and after 6 months. We studied clinical effects in long-term follow-up. Ten patients underwent LCSD. There were no adverse events attributable to surgery. In the LCSD group, LVEF improved from 25 ± 6.6 to 33 ± 5.2 (P = 0.03); 6 min walking distance improved from 167 ± 35 to 198 ± 47 m (P = 0.02). Minnesota Living with Heart Failure Questionnaire (MLWHFQ) score physical dimension changed from 21 ± 5 to 15 ± 7 (P = 0.06). The remaining analysed variables were unchanged. During 848 ± 549 days of follow-up, in the MT group, three patients either died or underwent cardiac transplantation (CT), while in the LCSD group six were alive without CT., Conclusions: LCSD was feasible and seemed to be safe in systolic HF patients. Its beneficial effects warrant the development of a larger randomized trial. Trail registration: NCT01224899.

Background: Conventional cardiac rehabilitation program consist of 15 min of warm-up, 30 min of aerobic exercise and followed by 15 min calisthenics exercise. The Pilates method has been increasingly applied for its therapeutic benefits, however little scientific evidence supports or rebukes its use as a treatment in patients with heart failure (HF)., Purpose: Investigate the effects of Pilates on exercise capacity variables in HF., Methods: Sixteen pts with HF, left ventricular ejection fraction 27 ± 14%, NYHA class I-II were randomly assigned to conventional cardiac rehabilitation program (n = 8) or mat Pilates training (n = 8) for 16 weeks of 30 min of aerobic exercise followed by 20 min of the specific program., Results: At 16 weeks, pts in the mat Pilates group and conventional group showed significantly increase on exercise time 11.9 ± 2.5 to 17.8 ± 4 and 11.7 ± 3.9 to 14.2 ± 4 min, respectively. However, only the Pilates group increased significantly the ventilation (from 56 ± 20 to 69 ± 17 L/min, P = 0.02), peak VO(2) (from 20.9 ± 6 to 24.8 ± 6 mL/kg/min, P = 0.01), and O(2) pulse (from 11.9 ± 2 to 13.8 ± 3 mL/bpm, P = 0.003). The Pilates group showed significantly increase in peak VO(2) when compared with conventional group (24.8 ± 6 vs. 18.3 ± 4, P = 0.02)., Conclusions: The result suggests that the Pilates method may be a beneficial adjunctive treatment that enhances functional capacity in patients with HF who are already receiving standard medical therapy., (© 2011 Blackwell Publishing Ltd.)

Background: Equations to predict maximum heart rate (HR(max)) in heart failure (HF) patients receiving β-adrenergic blocking (BB) agents do not consider the cause of HF. We determined equations to predict HR(max) in patients with ischemic and nonischemic HF receiving BB therapy., Methods and Results: Using treadmill cardiopulmonary exercise testing, we studied HF patients receiving BB therapy being considered for transplantation from 1999 to 2010. Exclusions were pacemaker and/or implantable defibrillator, left ventricle ejection fraction (LVEF) >50%, peak respiratory exchange ratio (RER) <1.00, and Chagas disease. We used linear regression equations to predict HR(max) based on age in ischemic and nonischemic patients. We analyzed 278 patients, aged 47 ± 10 years, with ischemic (n = 75) and nonischemic (n = 203) HF. LVEF was 30.8 ± 9.4% and 28.6 ± 8.2% (P = .04), peak VO(2) 16.9 ± 4.7 and 16.9 ± 5.2 mL kg(-1) min(-1) (P = NS), and the HR(max) 130.8 ± 23.3 and 125.3 ± 25.3 beats/min (P = .051) in ischemic and nonischemic patients, respectively. We devised the equation HR(max) = 168 - 0.76 × age (R(2) = 0.095; P = .007) for ischemic HF patients, but there was no significant relationship between age and HR(max) in nonischemic HF patients (R(2) = 0.006; P = NS)., Conclusions: Our study suggests that equations to estimate HR(max) should consider the cause of HF., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although the impact of exercise on survival of patients with heart failure has been recently questioned, exercise training improves quality of life, functional capacity, inflammation, endothelial and autonomic function. In recent years, interest has increased regarding a group of small non-protein coding RNAs called microRNAs. Studies have shown that the expression of these molecules changes in several pathological conditions, such as myocardial infarction, myocardial ischemia and heart failure, and when clinical improvement occurs, they seem to normalize. With the potential for practical applicability, markers that may be useful in diagnostic and prognostic assessment of heart failure have been identified, such as miR-423-5p. In addition, results of experimental studies have indicated that there are potential therapeutic effects of microRNAs. MicroRNAs are involved in the regulation of gene expression during fetal development and in adult individuals, increasing or decreasing in the heart in response to physiological stress, injury or hemodynamic overload. Thus, the study of the behavior of these molecules in physical exercise has brought important information about the effects of this therapeutic modality and represents a new era in the understanding of heart failure. This review aims to integrate the evidence on microRNAs in heart failure with greater relevance in the study of physical exercise.

MicroRNAs (miRNAs) are a group of newly discovered small RNAs, non-coding, which represent one of the most exciting areas of modern medical science as they modulate a huge and complex regulatory network of gene expression. Lines of evidence have recently suggested that miRNAs play a key role in the pathogenesis of heart failure. Some miRNAs highly expressed in the heart, such as miR-1, miR-133 and miR-208, are strongly associated with the development of cardiac hypertrophy, while the exact role of miR-21 in the cardiovascular system remains controversial. Serum levels of circulating miRNAs such as miR-423-5p are being evaluated as potential biomarkers in the diagnosis and prognosis of heart failure. On the other hand, the manipulation of levels of miRNAs using techniques such as mimicking the miRNAs (miRmimics) and antagonistic miRNAs (antagomiRs) is making increasingly evident the enormous potential of miRNAs as promising therapeutic strategies in heart failure.

Although it is known that obesity, diabetes, and Kawasaki's disease play important roles in systemic inflammation and in the development of both endothelial dysfunction and cardiomyopathy, there is a lack of data regarding the endothelial function of pre-pubertal children suffering from cardiomyopathy. In this study, we performed a systematic review of the literature on pre-pubertal children at risk of developing cardiomyopathy to assess the endothelial function of pre-pubertal children at risk of developing cardiomyopathy. We searched the published literature indexed in PubMed, Bireme and SciELO using the keywords 'endothelial', 'children', 'pediatric' and 'infant' and then compiled a systematic review. The end points were age, the pubertal stage, sex differences, the method used for the endothelial evaluation and the endothelial values themselves. No studies on children with cardiomyopathy were found. Only 11 papers were selected for our complete analysis, where these included reports on the flow-mediated percentage dilatation, the values of which were 9.80±1.80, 5.90±1.29, 4.50±0.70, and 7.10±1.27 for healthy, obese, diabetic and pre-pubertal children with Kawasaki's disease, respectively. There was no significant difference in the dilatation, independent of the endothelium, either among the groups or between the genders for both of the measurements in children; similar results have been found in adolescents and adults. The endothelial function in cardiomyopathic children remains unclear because of the lack of data; nevertheless, the known dysfunctions in children with obesity, type 1 diabetes and Kawasaki's disease may influence the severity of the cardiovascular symptoms, the prognosis, and the mortality rate. The results of this study encourage future research into the consequences of endothelial dysfunction in pre-pubertal children.

Becker muscular dystrophy (BMD) integrates dystrophy occurring due to genetic mutations that express the dystrophin protein in chromosome X. The onset of neuromuscular symptoms usually precedes the impairment of cardiac function, and may conversely happen by heart failure (HF). Physical training is well established in HF, however, when combined with BMD, it is controversial and without any scientific basis. This study presents the case of a patient with BMD associated with HF in cardiac transplant waiting list undergoing a physical training program.

Exercise training is an effective intervention for treating and preventing hypertension, but its effects on heart rate (HR) response to exercise and cardiorespiratory fitness (CRF) of non-hypertensive offspring of hypertensive parents (FH+) has not been studied. We compared the effects of three times per week equal-volume high-intensity aerobic interval (AIT) and continuous moderate-intensity exercise (CME) on HR response to exercise and CRF of FH+. Forty-four young FH+ women (25.0 ± 4.4 years) randomized to control (CON; n = 12), AIT (80-90% of VO(2MAX); n = 16), or CME (50-60% of VO(2MAX); n = 16) performed a graded exercise test (GXT) before and after 16 weeks of follow-up to evaluate HR response to exercise and several parameters of CRF. Resting, maximal, and reserve HR did not change after the follow-up in all groups. HR recovery (difference between HR(MAX) and HR at 1 minute of GXT recovery phase) improved only after AIT (11.8 ± 4.9 vs. 20.6 ± 5.8 bpm, p < 0.01). Both exercise programmes were effective for improving CRF parameters, but AIT was more effective than CME for improving oxygen consumption at the respiratory compensation point (VO(2RCP); 22.1% vs. 8.8%, p = 0.008) and maximal effort (VO(2MAX); 15.8% vs. 8.0%, p = 0.036), as well as tolerance time (TT) to reach anaerobic threshold (TT(AT); 62.0 vs. 37.7, p = 0.048), TT(RCP) (49.3 vs. 32.9, p = 0.032), and TT(MAX) (38.9 vs. 29.2, p = 0.042). Exercise intensity was an important factor in improving HR recovery and CRF of FH+women. These findings may have important implications for designing exercise-training programmes for the prevention of an inherited hypertensive disorder.