The "Hypertension Approaches in the Elderly: a Lifestyle study" multicenter, randomized trial (HAEL Study): rationale and methodological protocol.

BACKGROUND: Hypertension is a clinical condition highly prevalent in the elderly, imposing great risks to cardiovascular diseases and loss of quality of life. Current guidelines emphasize the importance of nonpharmacological strategies as a first-line approach to lower blood pressure. Exercise is an efficient lifestyle tool that can benefit a myriad of health-related outcomes, including blood pressure control, in older adults. We herein report the protocol of the HAEL Study, which aims to evaluate the efficacy of a pragmatic combined exercise training compared with a health education program on ambulatory blood pressure and other health-related outcomes in older individuals. METHODS: Randomized, single-blinded, multicenter, two-arm, parallel, superiority trial. A total of 184 subjects (92/center), ≥60 years of age, with no recent history of cardiovascular events, will be randomized on a 1:1 ratio to 12-week interventions consisting either of a combined exercise (aerobic and strength) training, three times per week, or an active-control group receiving health education intervention, once a week. Ambulatory (primary outcome) and office blood pressures, cardiorespiratory fitness and endothelial function, together with quality of life, functional fitness and autonomic control will be measured in before and after intervention. DISCUSSION: Our conceptual hypothesis is that combined training intervention will reduce ambulatory blood pressure in comparison with health education group. Using a superiority framework, analysis plan prespecifies an intention-to-treat approach, per protocol criteria, subgroups analysis, and handling of missing data. The trial is recruiting since September 2017. Finally, this study was designed to adhere to data sharing practices. TRIAL REGISTRATION: NCT03264443 . Registered on 29 August, 2017.

Tai Chi Chuan improves functional capacity after myocardial infarction: A randomized clinical trial.

BACKGROUND: Patients with a recent myocardial infarction (MI) present a reduction in functional capacity expressed as a decrease in peak oxygen consumption (Vo2 peak). The impact of a Tai Chi Chuan (TCC) cardiac rehabilitation program for patients recovering from recent MI has yet to be assessed. Our goal is to evaluate functional capacity after a TCC-based cardiac rehabilitation program in patients with recent MI. METHODS: A single-blind randomized clinical trial was conducted. The researchers who performed the tests were blinded to group allocation. Between the 14th and 21st days after hospital discharge, all patients performed a cardiopulmonary exercise testing and a laboratory blood workup. Mean age was similar (56±9 years in the TCC group and 60±9 years in the control group). Patients allocated to the intervention group performed 3 weekly sessions of TCC Beijin style for 12 weeks (n=31). The control group participated in 3 weekly sessions of full-body stretching exercises (n=30). RESULTS: After the 12-week study period, participants in the TCC group experienced a significant 14% increase in Vo2 peak from baseline (21.6 ± 5.2 to 24.6 ± 5.2 mL/kg per minute), whereas control participants had a nonsignificant 5% decline in Vo2 peak (20.4 ± 5.1 to 19.4 ± 4.4 mL/kg per minute). There was a significant difference between the 2 groups (P<.0001). CONCLUSIONS: Tai Chi Chuan practice was associated with an increase in Vo2 peak in patients with a recent MI and may constitute an effective form of cardiac rehabilitation in this patient population.

Pro- and Anti-inflammatory Biomarkers Responses after Aerobic Training in Heart Transplant Recipients: A Systematic Review and Meta-analysis.

BACKGROUND: Physical exercise (PE) may improve plasma concentration of interleukin- 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and adiponectin (adpN) in heart transplant (HT) patients. However, no consistent data is available on this population. AIM: Thus, we aimed to conduct a systematic review and meta-analysis on the effects of PE over these pro- and anti-inflammatory biomarkers in HT patients. METHODS: Following the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, we conducted a systematic literature search in the PubMed, Cochrane, and Scopus databases. Outcomes included IL-6, TNF-alpha, and adpN. Effect size (ES) was calculated using the standardized mean difference with a 95% confidence interval (CI). RESULTS: The PE group (aerobic modality) was associated with reduced IL-6 compared to the control group (ES: -0.53; 95% CI: -0.99 to -0.06 pg/mL; P = 0.026). However, the PE group did not show a significant effect on TNF-alpha and adpN levels (ES: -0.33; 95% CI: -0.79 to 0.13; P = 0.16 and ES: -0.20; 95% CI: -0.70 to 0.30 pg/mL; P = 0.444, respectively). CONCLUSION: PE is associated with IL-6 reductions, although TNF alpha and adpN did not change after this intervention in HT patients. Therefore, PE is an effective intervention to downregulate IL-6 in post-HT patients.

Independent and Added Value of Cardiopulmonary Exercise Testing to New York Heart Association Classification in Patients With Heart Failure.

PURPOSE: The objective of this study was to evaluate the independent and added value of a cardiopulmonary exercise test (CPX) to New York Heart Association (NYHA) functional analysis in patients with heart failure (HF) and ejection fraction (EF) <50%. METHODS: Patients (n = 613) with HF and EF < 50% underwent CPX and were followed for 28 ± 17 mo with respect to primary outcomes (death or heart transplantation). RESULTS: Mean patient age was 56 ± 12 yr, and 64% were male. Most patients were classified as NYHA class II (41%). The composite rate of primary outcomes was 12%; death occurred in 9%, and heart transplant in 4%. Independent predictors of primary outcomes were: EF (HR = 0.95: 95% CI, 0.92-0.98; P = .001) and NYHA (HR = 2.06: 95% CI, 1.54-2.75; P < .0001). When added to the model, peak oxygen uptake (V˙ O2peak ) was an independent predictor (HR = 0.90: 95% CI, 0.84-0.96; P = .001), as was the percentage of predicted V˙ O2peak (HR = 0.03: 95% CI, 0.007-0.147; P < .001), minute ventilation/carbon dioxide production slope (HR = 1.02: 95% CI, 1.01-1.04; P = .012), and CPX score (HR = 1.16: 95% CI, 1.06-1.27; P = .001). CONCLUSIONS: CPX variables were independent predictors of HF prognosis, even when controlled by NYHA functional class. Despite being independent predictors, the value added to NYHA classification was modest and lacked statistical significance.

Prognostic value of right ventricular strain and peak oxygen consumption in heart failure with reduced ejection fraction.

Our purpose is to evaluate the combined predictive value of cardiopulmonary exercise testing (CPET) and echocardiographic evidence of left ventricular (LV) and right ventricular (RV) strain in predicting mortality and heart transplant (HTx) in a series of outpatients with heart failure with reduced ejection fraction (HFrEF). A retrospective cohort study of 66 patients with HFrEF (median age, 57 years; 51% women) who underwent CPET and echocardiography (up to 90 days apart) to assess prognosis. The primary outcome was a composite of death and need for HTx. At a median follow-up of 27 [20-39] months, 19 patients (29%) experienced the primary outcome. In unadjusted analysis, most echocardiographic and CPET parameters were associated with the primary outcome, including percentage of predicted peak oxygen consumption (ppVO2), VE/VCO2 slope, LV ejection fraction, and LV and RV longitudinal strain. After adjusting for other clinical, echocardiographic and CPET variables, RV free wall longitudinal strain and ppVO2 remained significantly associated with the primary outcome. Kaplan-Meier survival curves for death and HTx, based on the best cutoff values, showed lower survival rates in patients with impairment in both ppVO2 and RV FW-LS than in those with one or neither parameter impaired (p < 0.001). RV dysfunction and low cardiorespiratory fitness were independent markers of death and need for HTx. Impairment of both ppVO2 and RV FW-LS had a strong additive impact on prognostic assessment in this cohort of patients with HFrEF.

Pre-percutaneous coronary intervention sudden cardiac arrest in ST-elevation myocardial infarction: Incidence, predictors, and related outcomes.

Background: ST-segment elevation myocardial infarction (STEMI) is a frequent cause of sudden cardiac arrest (SCA) and early percutaneous coronary intervention (PCI) is associated with increased survival. Despite constant improvements in SCA management, survival remains poor. We aimed to assess pre-PCI SCA incidence and related outcomes in patients admitted with STEMI. Methods: This was a prospective cohort study of patients admitted with STEMI in a tertiary university hospital over 11 years. All patients were submitted to emergency coronary angiography. Baseline characteristics, details of the procedure, reperfusion strategies, and adverse outcomes were assessed. The primary outcome was in-hospital mortality. The secondary outcome was 1-year mortality after hospital discharge. Predictors of pre-PCI SCA was also assessed. Results: During the study period 1,493 patients were included; the mean age was 61.1 years (±12), and 65.3% were male. Pre-PCI SCA was present in 133 (8.9%) patients. In-hospital mortality was higher in the pre-PCI SCA group (36.8% vs. 8.8%, p < 0.0001). In multivariate analysis, anterior MI, cardiogenic shock, age, pre-PCI SCA and lower ejection fraction remained significantly associated with in-hospital mortality. When we analyzed the interaction between pre-PCI SCA and cardiogenic shock upon admission there is a further increase in mortality risk when both conditions are present. For predictors of pre-PCI SCA, only younger age and cardiogenic shock remained significantly associated after multivariate analysis. Overall 1-year mortality rates were similar between pre-PCI SCA survivors and non-pre-PCI SCA group. Conclusion: In a cohort of consecutive patients admitted with STEMI, pre-PCI SCA was associated with higher in-hospital mortality, and its association with cardiogenic shock further increases mortality risk. However, long-term mortality among pre-PCI SCA survivors was similar to non-SCA patients. Understanding characteristics associated with pre-PCI SCA may help to prevent and improve the management of STEMI patients.

Long-term reduced functional capacity and quality of life in hospitalized COVID-19 patients.

Background: Persistent symptoms and exercise intolerance have been reported after COVID-19, even months after the acute disease. Although, the long-term impact on exercise capacity and health-related quality of life (HRQoL) is still unclear. Research question: To assess the long-term functional capacity and HRQoL in patients hospitalized due to COVID-19. Study design and methods: This is a prospective cohort study, conducted at two centers in Brazil, that included post-discharge COVID-19 patients and paired controls. The cohort was paired by age, sex, body mass index and comorbidities, using propensity score matching in a 1:3 ratio. Patients were eligible if signs or symptoms suggestive of COVID-19 and pulmonary involvement on chest computed tomography. All patients underwent cardiopulmonary exercise testing (CPET) and a HRQoL questionnaire (SF-36) 6 months after the COVID-19. The main outcome was the percentage of predicted peak oxygen consumption (ppVO2). Secondary outcomes included other CPET measures and HRQoL. Results: The study sample comprised 47 post-discharge COVID-19 patients and 141 healthy controls. The mean age of COVID-19 patients was 54 ± 14 years, with 19 (40%) females, and a mean body mass index of 31 kg/m2 (SD, 6). The median follow-up was 7 months (IQR, 6.5-8.0) after hospital discharge. PpVO2 in COVID-19 patients was lower than in controls (83% vs. 95%, p = 0.002) with an effect size of 0.38 ([95%CI], 0.04-0.70). Mean peak VO2 (22 vs. 25 mL/kg/min, p = 0.04) and OUES (2,122 vs. 2,380, p = 0.027) were also reduced in the COVID-19 patients in comparison to controls. Dysfunctional breathing (DB) was present in 51%. HRQoL was significantly reduced in post COVID patients and positively correlated to peak exercise capacity. Interpretation: Hospitalized COVID-19 patients presented, 7 months after discharge, with a reduction in functional capacity and HRQoL when compared to historical controls. HRQoL were reduced and correlated with the reduced peak VO2 in our population.

Direct-Acting Oral Anticoagulants in Atrial Fibrillation: What's New in the Literature.

Atrial fibrillation (AF) is considered the most common sustained cardiac arrhythmia, and it is associated with a significant risk of adverse events, especially ischemic stroke. Oral anticoagulation is the cornerstone for stroke prevention in AF; for many years, only vitamin K antagonists were used for this purpose, with an absolute risk reduction >60%. However, these agents have limitations, such as narrow therapeutic margins and drug-food and drug-drug interactions. More recently, 4 direct-acting oral anticoagulants (DOACs)-non-vitamin K antagonists-have become available for patients with AF: dabigatran, rivaroxaban, apixaban, and edoxaban. In addition to a comparable efficacy to warfarin in large randomized controlled trials, DOACs were found to promote a lower risk of intracranial bleeding. The strategic dosage and lack of need for periodic prothrombin-time testing make their use attractive, especially for primary or secondary prevention of stroke in older adults. Furthermore, among patients with AF presenting with acute coronary syndrome or undergoing percutaneous coronary intervention, apixaban is associated with a reduction in serious bleeding events when compared with warfarin. On the other hand, there is no evidence of benefit of DOACs in patients with mechanical prosthetic valves or moderate/severe mitral stenosis. Furthermore, the suitability of DOACs in patients with liver disease is still poorly understood, and their safety in patients requiring renal replacement therapy remains uncertain. This review provides an overview of the main trials of DOACs, their pharmacology and safety profile, clinical implications, and best indications in light of the current evidence.

Acute inspiratory muscle exercise effect on glucose levels, glucose variability and autonomic control in patients with type 2 diabetes: A crossover randomized trial.

Inspiratory muscle exercise (IME) can be an alternative to conventional exercise. We aimed to evaluate the effect of IME on glucose, glucose variability, and autonomic cardiovascular control in type 2 diabetes. Fourteen diabetic subjects were randomly assigned to IME with 2% maximal inspiratory pressure (PImax) or 60% PImax wearing a continuous glucose monitoring system for three days. Glucose variability [glucose variance (VAR), glucose coefficient of variation (CV%), glucose standard deviation (SD), and mean amplitude of glycemic excursions (MAGE)] were evaluated. Glucose reduction was observed in 5 min (60% of PImax 33.2% and 2% of PImax 32.0%), 60 min (60% of PImax 29.6% and 2% of PImax 31.4%) and 120 min (60% of PImax 21.4% and 2% of PImax 24.0%) after IME (vs.1 h before the exercise), with no difference between loads. This reduction in glucose levels was observed in all moments of the IME protocol. Glucose variability was reduced after 12 h and 18 h of the IME (ΔCV: P < 0.001, ΔSD: P < 0.001 and ΔVAR: P < 0.001) for both loads. No difference was found in MAGE (P = 0.594) after IME. Mean arterial pressure and heart rate rose during the exercise session with 60% of PImax. Although sufficiently strong to induce cardiovascular changes, an inspiratory muscle exercise session with 60% of PImax in subjects with type 2 diabetes has failed to induce any significant improvement in glucose, glucose variability and autonomic control, compared to the 2% Plmax exercise session.

Effects of Different Rehabilitation Protocols in Inpatient Cardiac Rehabilitation After Coronary Artery Bypass Graft Surgery: A RANDOMIZED CLINICAL TRIAL.

PURPOSE: Patients undergoing coronary artery bypass graft (CABG) surgery typically experience loss of cardiopulmonary capacity in the post-operative period. The purpose of this study was to evaluate the effects of different rehabilitation protocols used in inpatient cardiac rehabilitation on functional capacity and pulmonary function in patient status post-CABG surgery. METHODS: This was a single-blind randomized controlled trial. The primary endpoint of functional capacity and secondary endpoints of lung capacity and respiratory muscle function were assessed in patients scheduled to undergo CABG. After surgery, 40 patients were randomly assigned across 1 of 4 inpatient cardiac rehabilitation groups: G1, inspiratory muscle training, active upper limb and lower limb exercise training, and early ambulation; G2, same protocol as G1 without inspiratory muscle training; G3, inspiratory muscle training alone; and G4, control. All groups received chest physical therapy and expiratory positive airway pressure. Patients were reassessed on post-operative day 6 and post-discharge day 30 (including cardiopulmonary exercise testing). RESULTS: The 6-min walk distance on post-operative day 6 was significantly higher in groups that included exercise training (G1 and G2), remaining higher at 30 d post-discharge (P < .001 between groups). Peak oxygen uptake on day 30 was also higher in G1 and G2 (P = .005). All groups achieved similar recovery of lung function. CONCLUSION: Protocols G1 and G2, which included a systematic plan for early ambulation and upper and lower limb exercise, attenuated fitness losses while in the hospital and significantly enhanced recovery 1 mo after CABG.

Impact of treatment with glibenclamide or vildagliptin on glucose variability after aerobic exercise in type 2 diabetes: A randomized controlled trial.

AIMS: To evaluate the glucose variability, oxidative stress, metabolic and cardiovascular responses after an aerobic exercise session in diabetic patients on treatment with metformin plus vildagliptin or glibenclamide. METHODS: Parallel clinical trial including patients with type 2 diabetes treated with metformin plus vildagliptin or glibenclamide for 12 weeks. Glucose variability, oxidative stress, metabolic (plasma glucose, insulin and glucagon-like-peptide-1) and cardiovascular responses were evaluated at rest, during and after a 30 min aerobic exercise session (70% of the peak heart rate). RESULTS: Thirteen patients were included, seven in vildagliptin group (METV) and six in glibenclamide group (METG), baseline glycated hemoglobin (HbA1c) 8.8 ±â€¯0.3%. Treatment reduced HbA1c (1.2% and 1.5% for METV and METG, respectively). The aerobic exercise session did not change glucose variability in both groups. A decrease in glucose during exercise recovery was found, with area under the curve lower in the METG vs. METV (p = 0.04). After the intervention, systolic blood pressure (SBP) decreased in both groups. Patients treated with vildagliptin showed lower SBP variability compared to those treated with glibenclamide. CONCLUSIONS: Besides improvement in glucose control and reduction of SBP obtained by both treatments, lower blood pressure variability was observed in patients receiving vildagliptin. Glucose variability remained unaffected by both interventions and the exercise session.

Reduction in Post-Marathon Peak Oxygen Consumption: Sign of Cardiac Fatigue in Amateur Runners?

BACKGROUND: Prolonged aerobic exercise, such as running a marathon, produces supraphysiological stress that can affect the athlete's homeostasis. Some degree of transient myocardial dysfunction ("cardiac fatigue") can be observed for several days after the race. OBJECTIVE: To verify if there are changes in the cardiopulmonary capacity, and cardiac inotropy and lusitropy in amateur marathoners after running a marathon. METHODS: The sample comprised 6 male amateur runners. All of them underwent cardiopulmonary exercise testing (CPET) one week before the São Paulo Marathon, and 3 to 4 days after that race. They underwent echocardiography 24 hours prior to and immediately after the marathon. All subjects were instructed not to exercise, to maintain their regular diet, ingest the same usual amount of liquids, and rest at least 8 hours a day in the period preceding the CPET. RESULTS: The athletes completed the marathon in 221.5 (207; 250) minutes. In the post-marathon CPET, there was a significant reduction in peak oxygen consumption and peak oxygen pulse compared to the results obtained before the race (50.75 and 46.35 mL.kg-1 .min-1; 19.4 and 18.1 mL.btm, respectively). The echocardiography showed a significant reduction in the s' wave (inotropic marker), but no significant change in the E/e' ratio (lusitropic marker). CONCLUSIONS: In amateur runners, the marathon seems to promote changes in the cardiopulmonary capacity identified within 4 days after the race, with a reduction in the cardiac contractility. Such changes suggest that some degree of "cardiac fatigue" can occur.