Endothelial biomarkers (Von willebrand factor, BDCA3, urokinase) as predictors of mortality in COVID-19 patients: cohort study.

BACKGROUND: SARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality. METHODS: From May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction. RESULTS: We recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32-12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively. CONCLUSION: The risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Impact of Body Composition and Sarcopenia on Mortality in Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have alterations in body composition, such as low cell integrity, body cell mass, and disturbances in water distribution evidenced by higher impedance ratio (IR), low phase angle (PhA), as well as low strength, low muscle mass, and sarcopenia. Body composition alterations are associated with adverse outcomes. However, according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), the impact of these alterations on mortality in COPD patients is not well-established. Our aims were to evaluate whether low strength, low muscle mass, and sarcopenia impacted mortality in COPD patients. METHODS: A prospective cohort study performance was conducted with COPD patients. Patients with cancer, and asthma were excluded. Body composition was assessed by bioelectrical impedance analysis. Low strength and muscle mass, and sarcopenia were defined according to EWGSOP2. RESULTS: 240 patients were evaluated, of whom 32% had sarcopenia. The mean age was 72.32 ± 8.24 years. The factors associated with lower risk of mortality were handgrip strength (HR:0.91, CI 95%; 0.85 to 0.96, p = 0.002), PhA (HR:0.59, CI 95%; 0.37 to 0.94, p = 0.026) and exercise tolerance (HR:0.99, CI 95%; 0.992 to 0.999, p = 0.021), while PhA below the 50th percentile (HR:3.47, CI 95%; 1.45 to 8.29, p = 0.005), low muscle strength (HR:3.49, CI 95%; 1.41 to 8.64, p = 0.007) and sarcopenia (HR:2.10, CI 95%; 1.02 to 4.33, p = 0.022) were associated with a higher risk of mortality. CONCLUSION: Low PhA, low muscle strength, and sarcopenia are independently associated with poor prognosis in COPD patients.

Plasma Endothelial and Oxidative Stress Biomarkers Associated with Late Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) is a significant public health problem worldwide. COVID-19 increases the risk of non-pulmonary complications such as acute myocardial injury, renal failure, thromboembolic events, and multi-organic damage. Several studies have documented increased inflammation molecules, endothelial dysfunction biomarkers, and dysregulation of coagulation factors in COVID-19 patients. In addition, endothelium dysfunction is exacerbated by the oxidative stress (OxS) promoted by endocrine and cardiovascular molecules. Our objective was to evaluate whether endothelial and OxS biomarkers were associated with mortality in hospitalized COVID-19 patients. METHODS: A prospective cohort study was performed. Patients ≥18 years old with confirmed COVID-19 that required hospitalization were included in a prospective cohort study. Endothelium and oxidative stress biomarkers were collected between 3 and 5 days after admission. RESULTS: A total of 165 patients were evaluated; 56 patients succumbed. The median follow-up was 71 days [23-129]. Regarding endothelial dysfunction and OxS biomarkers, patients who did not survive had higher levels of nitrates (0.4564 [0.1817-0.6761] vs. 0.2817 [0.0517-0.5], p = 0.014), total nitrates (0.0507 [-0.0342-0.1809] vs. -0.0041 [-0.0887-0.0909], p = 0.016), sE-Selectin (1.095 [0.86-1.495] vs. 0.94 [0.71-1.19], p = 0.004), and malondialdehyde (MDA) (0.50 [0.26-0.72] vs. 0.36 [0.23-0.52], p = 0.010) compared to patients who survived. Endothelial and OxS biomarkers independently associated with mortality were sE-selectin (HR:2.54, CI95%; from 1.11 to 5.81, p = 0.027), nitrates (HR:4.92, CI95%; from 1.23 to 19.63, p = 0.024), and MDA (HR: 3.05, CI95%; from 1.14 to 8.15, p = 0.025). CONCLUSIONS: Endothelial dysfunction (sE-selectin and nitrates) and OxS (MDA) are independent indicators of a worse prognosis in COVID-19 patients requiring hospitalization.

Body composition and risk factors associated with sarcopenia in post-COVID patients after moderate or severe COVID-19 infections.

BACKGROUND: Post-COVID-19 syndrome is characterized by diverse symptoms and abnormalities that persist beyond 12 weeks from the onset of acute COVID-19. Severity disease has been associated with more musculoskeletal alterations such as muscle weakness, dyspnea, and distance walking. The aim was to evaluate the impact of invasive mechanical ventilation (IMV) on body composition and investigate risk factors associated with sarcopenia in post-COVID-19 patients three months after moderate or severe COVID-19 infections. METHODS: Cross-sectional study. 530 patients with PCR-confirmed diagnoses of moderate to severe COVID-19, > 18 years old, oxygen saturation ≤ 93%, PaO2/FiO2 ratio < 300, who required hospitalization and were discharged were included. We excluded those who died before the follow-up visit, declined to participate, or could not be contacted. RESULTS: The mean age was 53.79 ± 12.90 years. IMV subjects had lower phase angle and handgrip strength and higher impedance index, frequency of low muscle mass, and low muscle strength than those without IMV. The risk factors of sarcopenia were > 60 years of age, diabetes, obesity, IMV, and prolonged hospital stay. The multivariate model showed that age > 60 years (OR: 4.91, 95% CI: 2.26-10.63), obesity (OR: 3.73, 95% CI: 1.21-11.54), and interaction between prolonged length of hospital stay and IMV (OR: 2.92; 95% CI: 1.21-7.02) were related to a higher risk of sarcopenia. CONCLUSION: Obesity and the interaction between prolonged length of hospital stay and IMV are associated with a higher risk of sarcopenia at 3 months after severe or moderate COVID-19 infection.

Association between body composition, sarcopenia and pulmonary function in chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation. Different factors that modify pulmonary function include age, sex, muscular strength, and a history of exposure to toxic agents. However, the impact of body composition compartments and sarcopenia on pulmonary function is not well-established. This study aimed to evaluate how body composition compartments and sarcopenia affect pulmonary function in COPD patients. METHODS: In a cross-sectional study, patients with a confirmed diagnosis of COPD, > 40 years old, and forced expiratory volume in the first second /forced vital capacity ratio (FEV1/FVC) < 0.70 post-bronchodilator were included. Patients with cancer, HIV, and asthma were excluded. Body composition was measured with bioelectrical impedance. Sarcopenia was defined according to EWGSOP2, and pulmonary function was assessed by spirometry. RESULTS: 185 patients were studied. The mean age was 72.20 ± 8.39 years; 55.14% were men. A linear regression adjusted model showed associations between body mass index, fat-free mass, skeletal muscle mass index, appendicular skeletal muscle mass index, and phase angle (PhA), and sarcopenia with FEV1 (%). As regards FVC (%), PhA and exercise tolerance had positive associations. CONCLUSION: Body composition, especially PhA, SMMI, ASMMI, and sarcopenia, has a significant impact on pulmonary function. Early detection of disturbances of these indexes enables the early application of such therapeutic strategies in COPD patients.

The impact of hydration status and fluid distribution on pulmonary function in COPD patients.

Chronic Obstructive Pulmonary Disease (COPD) patients have alterations in body composition. Bioelectrical impedance analysis (BIA) evaluates body composition, hydration status, and fluid distribution. Subjects with fluid disturbances have been found to have lower FEV1, respiratory muscle strength, and poor prognosis. We aimed to evaluate the effect of hydration status and fluid distribution on pulmonary function in COPD patients. A cross-sectional study, 180 patients with a confirmed diagnosis of COPD were included. Patients with asthma, advanced renal or liver disease, acute HF, exacerbation of COPD, or pacemakers were excluded. Hydration status variables (TBW, ECW, ICW) and disturbance of fluid distribution [impedance ratio (IR) > 0.84 and phase angle (PhA)] were evaluated by BIA. Pulmonary function was assessed by spirometry. The mean population age was 71.55 ± 8.94 years; 55% were men. Subjects were divided into two groups according to the IR ≥ 0.84 or < 0.84. The group with higher IR ≥ 0.84 had lower FEV1, FVC, FEV1/FVC, DLCO and, PhA compared to those with IR < 0.84. After adjusting for confounding variables TBW, ECW, IR ≥ 0.84, PhA, and resistance/height increase were associated with decreased FEV1. In the same way, with IR ≥ 0.84, edema index ≥ 0.48, trunk and abdominal IR were negatively associated with FVC, and PhA had a positive association with FVC. Fluid distribution, especially IR and PhA, could be a useful parameter for predicting pulmonary function in COPD patients.

Right heart failure as a risk factor for severe exacerbation in patients with chronic obstructive pulmonary disease: Prospective cohort study.

BACKGROUND: The prognosis in patients with Chronic Obstructive Pulmonary Disease (COPD) depends, in large part, on the frequency of exacerbations. Cardiovascular diseases, including heart failure (HF), are the risk factors for exacerbations. However, the importance of HF type over the exacerbations in COPD patients is unknown. OBJECTIVE: To determine whether right heart failure (RHF) is an independent risk factor for severe exacerbations in patients with COPD. METHODS: A prospective cohort study of 133 patients diagnosed with COPD with a follow-up period from 2010 to 2016. Patients with bronchial hyperreactivity, asthma, or pulmonary embolism were excluded. RESULTS: The mean age was 74.7 ± 8.2 years and 43.6% were men, 69.9% had severe exacerbations during follow-up. Subjects with RHF had lower FEV1 (50.2 ± 19.9 vs 57.4 ± 16.9, P = .006) and greater incidence of stroke (15.4% vs 1.8%, P = .009) compared to those without RHF. Subjects with RHF were at higher risk of severe exacerbations (HR, 2.46; CI 95%, 1.32-4.58, P = .005) compared to those without RHF after adjusting for confounding variables. CONCLUSION: In patients with COPD, RHF is an independent risk factor for suffering severe exacerbations.

A randomized control trial for reduction of caloric and non-caloric sweetened beverages in young adults: effects in weight, body composition and blood pressure.

INTRODUCTION: Recently has been documented that the consumption of sweetened non-caloric beverages has increased as an option to weight control, however randomized control trials have demonstrated a modest weight loss. OBJECTIVE: To evaluate the effect of reducing consumption of beverage with caloric and non-caloric sweeteners on weight, body composition and blood pressure in young Mexican adults. METHODS: In an experimental study 148 nursing students were randomly assigned to one of 3 groups: 1) no sweetened beverages were permitted, only plain water, tea or coffee without sugar; 2) consumption of beverages with non-caloric sweeteners was allowed; and 3) no restriction of sweetened beverages was imposed. All groups were given individualized isocaloric diets monitored by a 24-hour record of consumption and food frequency questionnaire and blood pressure, weight, waist circumference and body composition by tetrapolar bioelectric impedance were taken at the beginning of the study and three and six months later. RESULTS: Differences between groups were found in body mass index at 3 months that decrease in group 1 and 2 and increase in group 3 (-1.75 vs.-0.61 vs.0.54% of change, p < 0.001). At six months there were also statistical differences in waist circumference (-4.07 vs.-1.23 vs. 0.62% of change, p < 0.001) and sugar consumption (-62.0 vs.-54.61 vs.11.08% of change, p < 0.001) in groups 1, 2 and 3 respectively. CONCLUSIONS: The reduction in consumption of both caloric and non-caloric sweetened beverages contributes to signifi cant body mass index loss and waist circumference.

A randomized control trial for reduction of caloric and non-caloric sweetened beverages in young adults: effects in weight, body composition and blood pressure / Ensayo clínico controlado para evaluar el efecto de la reducción de bebidas dulces calóricas y no calóricas sobre peso, composición corporal y presión arterial

Introduction: Recently has been documented that the consumption of sweetened non-caloric beverages has increased as an option to weight control, however randomized control trials have demonstrated a modest weight loss. Objective: To evaluate the effect of reducing consumption of beverage with caloric and non-caloric sweeteners on weight, body composition and blood pressure in young Mexican adults. Methods: In an experimental study 148 nursing students were randomly assigned to one of 3 groups: 1) no sweetened beverages were permitted, only plain water, tea or coffee without sugar; 2) consumption of beverages with non-caloric sweeteners was allowed; and 3) no restriction of sweetened beverages was imposed. All groups were given individualized isocaloric diets monitored by a 24-hour record of consumption and food frequency questionnaire and blood pressure, weight, waist circumference and body composition by tetrapolar bioelectric impedance were taken at the beginning of the study and three and six months later. Results: Differences between groups were found in body mass index at 3 months that decrease in group 1 and 2 and increase in group 3 (-1.75 vs. -0.61 vs. 0.54% of change, p < 0.001). At six months there were also statistical differences in waist circumference (-4.07 vs. -1.23 vs. 0.62% of change, p < 0.001) and sugar consumption (-62.0 vs. -54.61 vs. 11.08% of change, p < 0.001) in groups 1, 2 and 3 respectively. Conclusions: The reduction in consumption of both caloric and non-caloric sweetened beverages contributes to significant body mass index loss and waist circumference (AU)

Introducción: recientemente se ha documentado que el consumo de bebidas dulces calóricas y no calóricas ha incrementado como una opción para el control de peso. Sin embargo, algunos ensayos clínicos han demostrado solo pérdidas de peso modestas. Objetivo: evaluar el efecto de la reducción del consumo de bebidas con endulzantes calóricos y no calóricos en el peso, composición corporal y presión arterial en adultos jóvenes mexicanos. Métodos: en un ensayo clínico controlado fueron asignados al azar 148 estudiantes de enfermería a 3 grupos: 1) no se permitió consumo de bebidas endulzadas, solo agua simple, café o infusiones sin azúcar; 2) consumo de bebidas con endulzantes no calóricos; y 3) ninguna restricción en el consumo de bebidas. A todos los grupos se les proporcionó una dieta individualizada isocalórica que fue monitoreada mediante un recordatorio de 24 horas y un cuestionario de frecuencia consumo de alimentos. Al inicio del estudio, tres y seis meses después se tomó la presión arterial, peso, circunferencia de cintura y composición corporal mediante impedancia bioeléctrica tetrapolar. Resultados: se encontraron diferencias estadísticamente significativas en el cambio del índice de masa corporal a los tres meses, el cual disminuyó en los grupos 1 y 2 y aumentó en el grupo 3 (-1,75 vs. -0,61 vs. 0,54% de cambio, p < 0,001). A los 6 meses se encontraron diferencias en el cambio de la circunferencia de cintura (-4,07 vs. -1,23 vs. 0,62% de cambio, p < 0,001) y en el consumo de azúcar (-62,0 vs. -54,61 vs. 11,08% de cambio, p < 0,001) en los grupo 1, 2 y 3 respectivamente. Conclusiones: la reducción del consumo de bebidas endulzadas calóricas y no calóricas contribuye a una reducción significativa del índice de masa corporal y la circunferencia de cintura (AU)

Changes in body composition in heart failure patients after a resistance exercise program and branched chain amino acid supplementation.

BACKGROUND & AIMS: Heart Failure (HF) is a complex syndrome, which can include the physiological, neural hormonal and metabolic complications known as "Cardiac Cachexia" (CC). In the development of CC there is a release of catabolic cytokines (Tumor Necrosis Factor-α, interleukins 1 and 6) that cause a decrease of fat free mass and fat mass. These changes in body composition might be reversed with a therapeutic combination of resistance exercise and branched chain amino acid supplementation (BCAA). AIM: Evaluate changes in body composition after a resistance exercise program and BCAA supplementation in patients with HF. METHODS: In a randomized clinical trial with 3 month of follow-up anthropometric body composition analysis and stress tests were evaluated at the beginning and in the end of the study. Patients were divided into two groups; the experimental group performed the resistance exercise program and received 10 g/day BCAA supplementation, and the control group only performed the resistance exercise program. Both groups were provided with individualized diets and conventional medical treatment. RESULTS: Changes were found in hip circumference between the groups (p = 0.02), and muscle strength was increased in the experimental group (8%) and the control group (11.4%) with no difference between them. METS and VO2Max also increased in experimental and control groups (16.6% and 50.1% respectively). Regarding changes in symptoms, improvements in fatigue (45.4%), decubitus intolerance (21.8%) and dyspnea (25.4%) were observed in the overall sample. CONCLUSION: Improvements in physical and functional capacities are attributed to resistance exercise program but not to the BCAA supplementation. CLINICAL TRIALS IDENTIFIER: NCT02240511.

Risk factors for asymptomatic ventricular dysfunction in rheumatoid arthritis patients.

Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients.

Abnormal myocardial perfusion and risk of heart failure in patients with type 2 diabetes mellitus.

BACKGROUND: Diabetes is a major risk factor for heart failure (HF), although the pathophysiological processes have not been clarified. OBJECTIVE: To determine the prevalence of HF and of abnormal myocardial perfusion in diabetic patients evaluated using technetium (99m) sestamibi single-photon emission computed tomography. METHODS: An observational cross-sectional study was conducted that included patients with type 2 diabetes mellitus who underwent echocardiography to diagnose HF and a pharmacological stress test with intravenous dipyridamole to examine cardiac scintigraphic perfusion abnormalities. Clinical and biochemical data were also collected. RESULTS: Of the 160 diabetic patients included, 92 (57.6%) were in HF and 68 (42.5%) were not. When patients were stratified according to the presence of abnormal myocardial perfusion, those with abnormal perfusion had a higher prevalence of HF (93%) than those with normal perfusion (44.4%) (P<0.0001). Patients with HF weighed more (P=0.03), used insulin less frequently (P=0.01), had lower total cholesterol (P=0.05) and high-density lipoprotein cholesterol concentrations (P=0.002), and a greater number of their myocardial segments showed abnormal perfusion (P≤0.001). More HF patients had a history of myocardial infarction (P<0.001) compared with those without HF. In a logistic regression analysis, the number of segments exhibiting abnormal myocardial perfusion was an independent risk factor for HF. CONCLUSIONS: The prevalence of HF in diabetic patients was high and HF predominantly occured in association with myocardial ischemia.

Effect of ivabradine on endothelial function in diastolic and right heart failure patients.

Background. Ivabradine is an If ion current inhibitor that has proved to reduce mortality in patients with systolic heart failure by slowing heart rate without decreasing myocardial contractility. Photoplethysmography is a simple, low-cost optical technique that can evaluate vascular function and detect changes in blood flow, pulse, and swelling of tissular microvascular space. Objective. To evaluate the effect of ivabradine on endothelial function by photoplethysmography in diastolic and right heart failure patients. Methodology. 15 patients were included (mean age of 78.1 ± 9.2 years) with optimally treated diastolic and right heart failure. They underwent photoplethysmography before and after induced ischemia to evaluate the wave blood flow on the finger, using the maximum amplitude time/total time (MAT/TT) index. Two measurements were made before and after oral Ivabradine (mean 12.5 mg a day during 6 months of followup). Results. In the study group, the MAT/TT index was 29.1 ± 2.2 versus 24.3 ± 3.2 (P = 0.05) in basal recording and 30.4 ± 2.1 versus 23.3 ± 2.9 (P = 0.002), before versus after ischemia and before versus after Ivabradine intervention, respectively. Conclusions. Ivabradine administration improves endothelial function (shear stress) in diastolic and right heart failure patients.

Low albumin levels and high impedance ratio as risk factors for worsening kidney function during hospitalization of decompensated heart failure patients.

BACKGROUND: Patients hospitalized for decompensated heart failure (DHF) frequently experience worsening of renal function (WRF), leading to volume overload and resistance to diuretics. OBJECTIVE: To investigate whether albumin levels and whole-body impedance ratio, as an indicator of water distribution, were associated with WRF in patients with DHF. METHODS: A total of 80 patients hospitalized for DHF were consecutively included in the present longitudinal study. WRF during hospitalization was defined as an increase of ≥0.3 mg/dL (≥26.52 µmol/L) or 25% of baseline serum creatinine. Clinical and echocardiographic characteristics were assessed at baseline. Whole-body bioelectrical impedance was measured using tetrapolar and multiple-frequency equipment to obtain the ratio of impedance at 200 kHz to that at 5 kHz. Serum albumin levels were also evaluated. Baseline characteristics were compared between patients with and without deteriorating renal function using a t test or χ(2) test. Subsequently, a logistic regression analysis was performed to obtain the independent variables associated with WRF. RESULTS: The incidence of WRF during hospitalization was 26%. Independent risk factors associated with WRF were low serum albumin (RR=0.11; P=0.04); impedance ratio >0.85 (RR=5.3; P=0.05), systolic blood pressure >160 mmHg (RR=12; P=0.02) and maximum dose of continuous intravenous furosemide required >80 mg/day during hospitalization (RR=5.7, P=0.015). CONCLUSIONS: WRF is frequent in patients with DHF. It results from the inability to effectively regulate volume status because hypoalbuminemia induces water loss from the vascular space (high impedance ratio), and high diuretic doses lower circulatory volumes and reduce renal blood flow, leading to a decline in renal filtration function.

Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation.

BACKGROUND: The utility of L-arginine and L-citrulline in treatment of arterial hypertension by increasing vascular oxide nitric availability has been demonstrated. Photoplethysmography, a simple and low-cost optical technique, makes it possible to assess vascular function and to detect changes in blood flow, pulse and swelling of the microvascular tissular space. The aim of the study was to evaluate the effect of L-citrulline supplementation on functional class, ejection fraction and peripheral blood flow in patients with systolic heart failure. METHODS: Thirty-five stable outpatients attending the Heart Failure Clinic at the INCMNSZ underwent clinical evaluation, radioisotopic ventriculography and photoplethysmography before and at the end of 4 months. They were randomized into two groups: experimental group, with oral L-citrulline supplementation (3 g/day, n = 20) and control group, without supplementation (n = 15). RESULTS: In the experimental group the left ventricular ejection fraction (LVEF) increased 20.3% at rest and 12.7% with stress, as well as the right ventricular ejection fraction at rest of 15.10% and 14.88% with stress. In addition, functional class improved in 35%, and the maximum amplitude time/total time (MAT/TT) index decreased 23.1%. These changes were statistically significant compared with the control group. CONCLUSIONS: Citrulline supplementation significantly improved the LVEF, the endothelial function (MAT/TT index) and functional class. Citrulline can be an important co-adjuvant in the treatment of stable and stable systolic heart failure patients.

Bioelectrical impedance phase angle as a prognostic marker in chronic heart failure.

OBJECTIVE: The main purpose of the present study was to assess the prognostic value of the bioelectrical phase angle (PA) in patients with heart failure independently of other parameters of a poor prognosis. METHODS: This retrospective study included 389 patients with heart failure. Anthropometric, body composition, clinical, biochemical, and echocardiographic data were collected from all patients. The quartiles were obtained for the PA, and patients were classified according to the quartiles into four groups. The endpoint was all-cause mortality. A Cox proportional hazards regression analysis was performed to estimate the adjusted relative risks, and 95% confidence intervals were obtained for the potential predictors of death. RESULTS: Patients below the lowest quartile of PA (<4.2°) had decreased mean body mass index, handgrip strength, and hemoglobin values and a larger proportion of patients in New York Heart Association functional class III and renal failure. The Kaplan-Meier survival analysis among PA groups showed a better survival for patients above the highest quartile of PA (≥5.7°), and survival decreased as the PA decreased. The Cox regression analysis found that a PA <4.2 was an independent predictor of mortality (relative risk 3.08, 95% confidence interval 1.06-8.99), adjusting for age, hemoglobin levels, and diabetes, compared with a PA ≥5.7. CONCLUSION: In this study population, a smaller PA was associated with malnutrition markers such as decreased body mass index, handgrip strength, and hemoglobin values and with a poor New York Heart Association functional class and renal failure. Adjusting for age, hemoglobin levels, and diabetes, a PA <4.2 was found to be an independent predictor of all-cause mortality in chronic heart failure.

Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction.

BACKGROUND: The effect of L-arginine and L-citrulline on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction (HFpEF) is unknown. We have therefore evaluated, in a randomized clinical trial, the effect of these aminoacids in chronic outstanding and stable patients with HFpEF. METHODS AND RESULTS: All patients underwent an echocardiogram and radioisotopic ventriculography rest/exercise, and were randomized in a consecutive manner to the L-arginine group (n = 15; 8 g/day); and the citrulline malate group (n = 15; 3 g/day). The duration of follow-up was two months. The principal echocardiographic finding was a statistically significant decrease in pulmonary artery pressure in the L-arginine (56.3 ± 10 vs 44 ± 16.5 mm Hg, p < 0.05) and the citrulline (56.67 ± 7.96 vs 47.67 ± 8.59 mm Hg, p < 0.05) groups. Duration on treadmill and right ventricular ejection fraction post exercise increased, while diastolic and systolic artery pressure decreased significantly in both groups. There were no other statistically significant differences between the groups. CONCLUSIONS: Administration of L-arginine and citrulline to patients with HFpEF improved right ventricular function by increasing right ventricular ejection fraction, and probably decreasing systolic pulmonary artery pressure.