Functional training improves peak oxygen consumption and quality of life of individuals with heart failure: a randomized clinical trial.

BACKGROUND: Functional training may be an effective non-pharmacological therapy for heart failure (HF). This study aimed to compare the effects of functional training with strength training on peak VO2 and quality of life in individuals with HF. METHODS: A randomized, parallel-design and examiner-blinded controlled clinical trial with concealed allocation, intention-to-treat and per-protocol analyses. Twenty-seven participants with chronic HF were randomly allocated to functional or strength training group, to perform a 12-week physical training, three times per week, totalizing 36 sessions. Primary outcomes were the difference on peak VO2 and quality of life assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Questionnaire, respectively. Secondary outcomes included functionality assessed by the Duke Activity Status Index and gait speed test, peripheral and inspiratory muscular strength, assessed by hand grip and manovacuometry testing, respectively, endothelial function by brachial artery flow-mediated dilation, and lean body mass by arm muscle circumference. RESULTS: Participants were aged 60 ± 7 years, with left ventricular ejection fraction 29 ± 8.5%. The functional and strength training groups showed the following results, respectively: peak VO2 increased by 1.4 ± 3.2 (16.9 ± 2.9 to 18.6 ± 4.8 mL.kg-1.min-1; p time = 0.011) and 1.5 ± 2.5 mL.kg-1.min-1 (16.8 ± 4.0 to 18.6 ± 5.5 mL.kg-1.min-1; p time = 0.011), and quality of life score decreased by 14 ± 15 (25.8 ± 14.8 to 10.3 ± 7.8 points; p time = 0.001) and 12 ± 28 points (33.8 ± 23.8 to 19.0 ± 15.1 points; p time = 0.001), but no difference was observed between groups (peak VO2: p interaction = 0.921 and quality of life: p interaction = 0.921). The functional and strength training increased the activity status index by 6.5 ± 12 and 5.2 ± 13 points (p time = 0.001), respectively, and gait speed by 0.2 ± 0.3 m/s (p time = 0.002) in both groups. CONCLUSIONS: Functional and strength training are equally effective in improving peak VO2, quality of life, and functionality in individuals with HF. These findings suggest that functional training may be a promising and innovative exercise-based strategy to treat HF. TRIAL REGISTRATION: NCT03321682. Registered date: 26/10/2017.

Uso do Modelo de Risco ADHERE como Preditor de Piora Intra-Hospitalar de Insuficiência Cardíaca em uma Coorte / Use of the ADHERE Risk Model as a Predictor of Risk of in-Hospital Worsening Heart Failure in a Cohort

Resumo Fundamento Pacientes hospitalizados com insuficiência cardíaca (IC) aguda descompensada estão sujeitos a desenvolver episódios de piora que requerem intervenções mais complexas. O modelo de predição de risco "Acute Decompensated Heart Failure National Registry" (ADHERE) foi desenvolvido nos Estados Unidos para prever o risco de piora intra-hospitalar da IC. Objetivo Utilizar o modelo de predição de risco ADHERE para avaliar o risco de piora intra-hospitalar da IC e determinar a sua sensibilidade e especificidade em pacientes hospitalizados. Métodos O presente estudo de coorte foi realizado em um hospital universitário público brasileiro e os dados de 2013 a 2020 foram coletados retrospectivamente. Foram considerados estatisticamente significativos valores de p < 0,05. Resultados Foram incluídos 890 pacientes com idade média de 74 ± 8 anos. O modelo mostrou que no grupo de 490 pacientes de risco, 254 (51,8%) desenvolveram piora intra-hospitalar da IC. No grupo de 400 pacientes sem risco, apenas 109 (27,2%) apresentaram piora da IC. Os resultados demonstraram uma curva estatisticamente significativa (área sob a curva = 0,665; erro padrão = 0,018; p < 0,01; intervalo de confiança = 0,609 a 0,701), indicando boa precisão. O modelo apresentou sensibilidade de 69,9% e especificidade de 55,2%, com valor preditivo positivo de 52% e valor preditivo negativo de 72,7%. Conclusões Na presente coorte, demonstramos que o modelo de predição de risco ADHERE foi capaz de discriminar pacientes que, de fato, desenvolveram piora da IC durante o período de internação daqueles que não desenvolveram.

Abstract Background Patients admitted with acute decompensated heart failure (HF) are subject to developing worsening episodes that require more complex interventions. The Acute Decompensated Heart Failure National Registry (ADHERE) risk model was developed in the United States to predict the risk of in-hospital worsening HF. Objective To use the ADHERE risk model in the assessment of risk of in-hospital worsening HF and to determine its sensitivity and specificity in hospitalized patients. Methods This cohort study was conducted at a Brazilian public university hospital, and data from 2013 to 2020 were retrospectively collected. P values < 0.05 were considered statistically significant. Results A total of 890 patients with a mean age of 74 ± 8 years were included. The model showed that, in the group of 490 patients at risk, 254 (51.8%) developed in-hospital worsening HF. In the group of 400 patients not at risk, only 109 (27.2%) experienced worsening HF. The results demonstrated a statistically significant curve (area under the curve = 0.665; standard error = 0.018; P < 0.01; confidence interval = 0.609 to 0.701), indicating good accuracy. The model had a sensitivity of 69.9% and a specificity of 55.2%, with a positive predictive value of 52% and a negative predictive value of 72.7%. Conclusions In this cohort, we showed that the ADHERE risk model was able to discriminate patients who in fact developed worsening HF during the admission period, from those who did not.

C-Reactive Protein and Frailty in Heart Failure.

Frailty commonly coexists with heart failure and although both have been associated with neurohormonal dysregulation, inflammation, catabolism, and skeletal muscle dysfunction, there are still no defined biomarkers to assess frailty, especially from the perspective of populations with cardiovascular diseases. This is a cross-sectional study with 106 outpatients with heart failure, aged ≥60 years, which aimed to assess frailty through a physical (frailty phenotype) and multidimensional (Tilburg Frailty Indicator) approach and to analyze its association with inflammatory and humoral biomarkers (high sensitivity C-reactive protein [hs-CRP], interleukin 6, tumor necrosis factor-α, insulin-like growth factor-1, and total testosterone), clinical characteristics, and functional capacity. In univariate analysis, hs-CRP was associated with frailty in both phenotype and Tilburg Frailty Indicator assessment (PR = 1.005, 95% confidence interval [CI] 1.001 to 1.009, p = 0.027 and PR = 1.015, 95% CI 1.006 to 1.024, p = 0.001, respectively), which remained significant in the final multivariate model in the frailty assessment by the phenotype (PR = 1.004, 95% CI 1.001 to 1.008, p = 0.025). There was no statistically significant difference between the groups for other biomarkers analyzed. Frailty was also associated with worse functional capacity, nonoptimized pharmacological treatment and a greater number of drugs in use, age, female gender, and a greater number of comorbidities. In conclusion, frailty is associated with higher levels of hs-CRP, which can indicate it is a promising frailty biomarker.

Electromyographical and Physiological Correlation in Patient with Heart Disease

Abstract Background: Walking is an economic activity, the more efficient the mechanical contribution, the less metabolic energy is necessary to keep walking. Patients with chronic heart failure and heart transplant present peripheral musculoskeletal disorders, dyspnea, and fatigue in their activities. Objective: In this scenario, the present study sought to verify the correlations between metabolic and electromyographic variables in chronic heart failure, heart transplant patients, and healthy controls. Methods: Regression and correlation between cost of transport and electromyographic cost, as well as correlation between oxygen consumption and muscle coactivation in patients and controls at five different walking speeds have been performed, with alpha = 0.05. Results: Strong correlation values (r controls: 0.99; chronic heart failure: 0.92; heart transplant: 0.88) indicate a linear relationship between the cost of transport and electromyographic cost. Oxygen consumption was significantly correlated to muscle activation in all groups. Conclusion: These results suggested that dynamic muscle coactivation was an important factor, especially for CHF and HT. These data support the idea that peripheral muscle limitations play an important role in people with CHF and HT. These findings indicate a strong relation between metabolic and electromyographic variables. For chronic heart failure and heart transplant patients, it can help to explain some difficulties in daily activities and aid in physical rehabilitation.

Donor-recipient predicted heart mass ratio and right ventricular-pulmonary arterial coupling in heart transplant.

OBJECTIVES: Right ventricular-pulmonary arterial (RV-PA) coupling interactions are largely unexplored in heart transplant patients. The outcome of this study was RV-PA coupling at 7 and 30 days after heart transplant and its association with donor-recipient size matching. METHODS: Clinical, echocardiographic and haemodynamic data from a retrospective cohort of heart transplant recipients and respective donors were reviewed. Coupling between RV-PA was examined by assessing the RV fractional area change and pulmonary artery systolic pressure ratio. Donor-recipient size matching was assessed by the predicted heart mass (PHM) ratio, and groups with a PHM ratio <1 and ≥1 were compared. RESULTS: Forty-four heart transplant recipients were included in this study (50 years, 57% male sex). Postoperative RV-PA coupling improved from 7 to 30 days (RV fractional area change/pulmonary artery systolic pressure 0.9 ± 0.3 vs 1.2 ± 0.3; P < 0.001). A positive association was found between an adequate PHM ratio and improvement of RV fractional area change/pulmonary artery systolic pressure at 30 days, independent of graft ischaemic time and pre-existent pulmonary hypertension (B coefficient 0.54; 95% confidence interval 0.11-0.97; P = 0.016; adjusted R2 = 0.24). CONCLUSIONS: These findings highlight the role of PHM as a metric to help donor selection and suggest its impact in RV-PA coupling interactions post-heart transplant.

Safety and Results of Bioelectrical Impedance Analysis in Patients with Cardiac Implantable Electronic Devices.

OBJECTIVE: To analyze the dual interference between cardiac implantable electronic devices (CIEDs) and bioelectrical impedance analysis (BIA). METHODS: Forty-three individuals admitted for CIEDs implantation were submitted to a tetrapolar BIA with an alternating current at 800 microA and 50 kHz frequency before and after the devices' implantation. During BIA assessment, continuous telemetry was maintained between the device programmer and the CIEDs in order to look for evidence of possible electric interference in the intracavitary signal of the device. RESULTS: BIA in patients with CIEDs was safe and not associated with any device malfunction or electrical interference in the intracardiac electrogram of any electrode. After the implantation of the devices, there were significant reductions in BIA measurements of resistance, reactance, and measurements adjusted for height resistance and reactance, reflecting an increase (+ 1 kg; P<0.05) in results of total body water and extracellular water in liter and, consequently, increases in fat-free mass (FFM) and extracellular mass in kg. Because of changes in the hydration status and FFM values, without changes in weight, fat mass was significantly lower (-1.2 kg; P<0.05). CONCLUSION: BIA assessment in patients with CIEDs was safe and not associated with any device malfunction. The differences in BIA parameters might have occurred because of modifications on the patients' body composition, associated to their hydration status, and not to the CIEDs.

Impaired Right Ventricular Function in Heart Transplant Rejection / Disfunção Ventricular Direita e Rejeição em Transplante Cardíaco

Abstract Background: The practice of screening for complications has provided high survival rates among heart transplantation (HTx) recipients. Objectives: Our aim was to assess whether changes in left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) are associated with cellular rejection. Methods: Patients who underwent HTx in a single center (2015 - 2016; n = 19) were included in this retrospective analysis. A total of 170 biopsies and corresponding echocardiograms were evaluated. Comparisons were made among biopsy/echocardiogram pairs with no or mild (0R/1R) evidence of cellular rejection (n = 130 and n = 25, respectively) and those with moderate (2R) rejection episodes (n=15). P-values < 0.05 were considered statistically significant Results: Most patients were women (58%) with 48 ± 12.4 years of age. Compared with echocardiograms from patients with 0R/1R rejection, those of patients with 2R biopsies showed greater LV posterior wall thickness, E/e' ratio, and E/A ratio compared to the other group. LV systolic function did not differ between groups. On the other hand, RV systolic function was more reduced in the 2R group than in the other group, when evaluated by TAPSE, S wave, and RV fractional area change (all p < 0.05). Furthermore, RV GLS (−23.0 ± 4.4% in the 0R/1R group vs. −20.6 ± 4.9% in the 2R group, p = 0.038) was more reduced in the 2R group than in the 0R/1R group. Conclusion: In HTx recipients, moderate acute cellular rejection is associated with RV systolic dysfunction as evaluated by RV strain, as well as by conventional echocardiographic parameters. Several echocardiographic parameters may be used to screen for cellular rejection.

Resumo Fundamento: A prática de triagem para complicações tem proporcionado altas taxas de sobrevida entre pacientes que receberam transplante cardíaco (TC). Objetivos: Visamos avaliar se alterações no strain longitudinal global (SLG) do ventrículo esquerdo (VE) e do ventrículo direito (VD) estão associadas à rejeição celular. Métodos: Pacientes que foram submetidos à TC em um único centro (2015 - 2016; n = 19) foram incluídos nesta análise retrospectiva. Foram avaliados um total de 170 biópsias com ecocardiogramas correspondentes. Foram realizadas comparações entre pares de biópsia/ecocardiograma com nenhuma ou leve (0R/1R) evidência de rejeição celular (n = 130 e n = 25, respectivamente) e aqueles com episódios de rejeição moderada (2R) (n = 15). Foram considerados estatisticamente significativos os valores de p < 0,05. Resultados: A maioria dos pacientes eram mulheres (58%) com idade média de 48 ± 12,4 anos. Em comparação com os ecocardiogramas dos pacientes com rejeição 0R/1R, os pacientes com biópsias 2R apresentaram maior espessura da parede posterior do VE, relação E/e' e relação E/A, em comparação com o outro grupo. A função sistólica do VE não diferiu entre os grupos. Por outro lado, a função sistólica do VD foi reduzida no grupo 2R em comparação ao outro grupo, quando avaliada por TAPSE, onda S e variação fracional da área do VD. Adicionalmente, SLG VD (−22,97 ± 4,4% no grupo 0R/1R vs. −20,6 ± 4,9% no grupo 2R, p = 0,038) foi reduzido no grupo 2R, em comparação com o grupo 0R/1R. Conclusão: Em pacientes de TC, rejeição celular aguda moderada está associada à disfunção sistólica do VD, avaliado pelo strain do VD, bem como por parâmetros ecocardiográficos convencionais. Vários parâmetros ecocardiográficos podem ser utilizados para realizar triagem para rejeição celular.

Impaired Right Ventricular Function in Heart Transplant Rejection.

BACKGROUND: The practice of screening for complications has provided high survival rates among heart transplantation (HTx) recipients. OBJECTIVES: Our aim was to assess whether changes in left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) are associated with cellular rejection. METHODS: Patients who underwent HTx in a single center (2015 - 2016; n = 19) were included in this retrospective analysis. A total of 170 biopsies and corresponding echocardiograms were evaluated. Comparisons were made among biopsy/echocardiogram pairs with no or mild (0R/1R) evidence of cellular rejection (n = 130 and n = 25, respectively) and those with moderate (2R) rejection episodes (n=15). P-values < 0.05 were considered statistically significant Results: Most patients were women (58%) with 48 ± 12.4 years of age. Compared with echocardiograms from patients with 0R/1R rejection, those of patients with 2R biopsies showed greater LV posterior wall thickness, E/e' ratio, and E/A ratio compared to the other group. LV systolic function did not differ between groups. On the other hand, RV systolic function was more reduced in the 2R group than in the other group, when evaluated by TAPSE, S wave, and RV fractional area change (all p < 0.05). Furthermore, RV GLS (-23.0 ± 4.4% in the 0R/1R group vs. -20.6 ± 4.9% in the 2R group, p = 0.038) was more reduced in the 2R group than in the 0R/1R group. CONCLUSION: In HTx recipients, moderate acute cellular rejection is associated with RV systolic dysfunction as evaluated by RV strain, as well as by conventional echocardiographic parameters. Several echocardiographic parameters may be used to screen for cellular rejection.

Safety and results of bioelectrical impedance analysis in patients with cardiac implantable electronic devices

Abstract Objective: To analyze the dual interference between cardiac implantable electronic devices (CIEDs) and bioelectrical impedance analysis (BIA). Methods: Forty-three individuals admitted for CIEDs implantation were submitted to a tetrapolar BIA with an alternating current at 800 microA and 50 kHz frequency before and after the devices' implantation. During BIA assessment, continuous telemetry was maintained between the device programmer and the CIEDs in order to look for evidence of possible electric interference in the intracavitary signal of the device. Results: BIA in patients with CIEDs was safe and not associated with any device malfunction or electrical interference in the intracardiac electrogram of any electrode. After the implantation of the devices, there were significant reductions in BIA measurements of resistance, reactance, and measurements adjusted for height resistance and reactance, reflecting an increase (+ 1 kg; P<0.05) in results of total body water and extracellular water in liter and, consequently, increases in fat-free mass (FFM) and extracellular mass in kg. Because of changes in the hydration status and FFM values, without changes in weight, fat mass was significantly lower (-1.2 kg; P<0.05). Conclusion: BIA assessment in patients with CIEDs was safe and not associated with any device malfunction. The differences in BIA parameters might have occurred because of modifications on the patients' body composition, associated to their hydration status, and not to the CIEDs.

Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system.

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1-7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male Balb/c mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain ß-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.

Continuous Intravenous Inotropes in Ward Units: Expanding Therapy Outside Intensive Care using a Safety-Oriented Protocol / Inotrópicos Intravenosos Contínuos em Unidades de Enfermaria: Expandindo o Tratamento Além da Unidade de Terapia Intensiva Utilizando um Protocolo Orientado em Segurança

Abstract Selected clinically stable patients with heart failure (HF) who require prolonged intravenous inotropic therapy may benefit from its continuity out of the intensive care unit (ICU). We aimed to report on the initial experience and safety of a structured protocol for inotropic therapy in non-intensive care units in 28 consecutive patients hospitalized with HF that were discharged from ICU. The utilization of low to moderate inotropic doses oriented by a safety-focused process of care may reconfigure their role as a transition therapy while awaiting definitive advanced therapies and enable early ICU discharge.

Resumo Pacientes selecionados com insuficiência cardíaca (IC), clinicamente estáveis que necessitam de terapia inotrópica intravenosa prolongada podem se beneficiar de sua continuidade fora da unidade de terapia intensiva (UTI). Nosso objetivo foi relatar a experiência inicial e a segurança de um protocolo estruturado para terapia inotrópica em unidades de terapia não-intensiva em 28 pacientes consecutivos hospitalizados com IC que receberam alta da UTI. A utilização de doses inotrópicas baixas a moderadas, orientadas por um processo de cuidado focado na segurança, pode reconfigurar seu papel como terapia de transição enquanto aguarda terapias avançadas definitivas e permite a alta precoce da UTI.

Characterization of advanced glycation end products and their receptor (RAGE) in an animal model of myocardial infarction.

Circulating advanced glycation end products (AGE) and their receptor, RAGE, are increased after a myocardial infarction (MI) episode and seem to be associated with worse prognosis in patients. Despite the increasing importance of these molecules in the course of cardiac diseases, they have never been characterized in an animal model of MI. Thus, the aim of this study was to characterize AGE formation and RAGE expression in plasma and cardiac tissue during cardiac remodeling after MI in rats. Adult male Wistar rats were randomized to receive sham surgery (n = 15) or MI induction (n = 14) by left anterior descending coronary artery ligation. The MI group was stratified into two subgroups based on postoperative left ventricular ejection fraction: low (MIlowEF) and intermediate (MIintermEF). Echocardiography findings and plasma levels of AGEs, protein carbonyl, and free amines were assessed at baseline and 2, 30, and 120 days postoperatively. At the end of follow-up, the heart was harvested for AGE and RAGE evaluation. No differences were observed in AGE formation in plasma, except for a decrease in absorbance in MIlowEF at the end of follow-up. A decrease in yellowish-brown AGEs in heart homogenate was found, which was confirmed by immunodetection of N-ε-carboxymethyl-lysine. No differences could be seen in plasma RAGE levels among the groups, despite an increase in MI groups over the time. However, MI animals presented an increase of 50% in heart RAGE at the end of the follow-up. Despite the inflammatory and oxidative profile of experimental MI in rats, there was no increase in plasma AGE or RAGE levels. However, AGE levels in cardiac tissue declined. Thus, we suggest that the rat MI model should be employed with caution when studying the AGE-RAGE signaling axis or anti-AGE drugs for not reflecting previous clinical findings.

Phase angle and mortality: a systematic review.

BACKGROUND/OBJECTIVES: The phase angle, expressed through bioelectrical impedance, has been studied as a prognostic marker in several health conditions. As this issue is still conflicting, the question whether this parameter correlates with mortality in the most diverse clinical situations remains. Therefore, this study aimed to evaluate the relationship between phase angle and mortality through a systematic review of the literature. SUBJECTS/METHODS: This research was conducted in electronic databases (Pubmed, Embase, Cochrane, Lilacs, Scielo, e Scopus), and included studies that had phase angle as a variable of interest and mortality/survival as an outcome. Data were extracted independently by two reviewers and disagreements were assessed by a third reviewer. RESULTS: Forty-eight of 455 papers were assessed and an amount of 42 showed a correlation between phase angle and mortality. CONCLUSIONS: Phase angle seems to be a good indicator for mortality in many clinical situations and can be used in screening individuals prone to this outcome.