Roberto Concepción

Serum uric acid correlates with extracellular superoxide dismutase activity in patients with chronic heart failure.

Increased serum uric acid has been identified as an independent risk factor for cardiovascular disease. However, because of its antioxidant capacity, uric acid may play a beneficial role in endothelial function. This paradoxical relationship between uric acid and endothelial function in chronic heart failure patients remains poorly understood. Thirty‐eight chronic heart failure patients (New York Heart Association functional class II–III, mean age 58±10 years and mean left ventricular ejection fraction 25±8%) and twelve age‐and‐sex‐matched healthy controls were studied. Chronic heart failure patients showed higher uric acid levels (7.3±2.3 mg/dL vs. 6.1±0.2 mg/dL, p<0.05) and lower extracellular superoxide dismutase activity (136±36 U ml−1 min−1 vs. 203±61 U ml−1 min−1, p<0.01) and endothelium‐dependent vasodilatation (4.0±1.6% v. 9.1±3.0%, p<0.01) when compared with control subjects. In chronic heart failure patients, correlations between both uric acid levels and extracellular superoxide dismutase activity (r=0.45; p<0.01), and uric acid and endothelium‐dependent vasodilatation (r=0.35; p=0.03) were detected. These correlations were not observed in healthy individuals, suggesting a positive effect of uric acid on endothelial function partially mediated by modulation of extracellular superoxide dismutase activity in chronic heart failure.

Effects of trimetazidine in nonischemic heart failure: a randomized study.

OBJECTIVES Heart failure (HF) is associated with changes in myocardial metabolism that lead to impairment of contractile function. Trimetazidine (TMZ) modulates cardiac energetic efficiency and improves outcomes in ischemic heart disease. We evaluated the effects of TMZ on left ventricular ejection fraction (LVEF), cardiac metabolism, exercise capacity, O2 uptake, and quality of life in patients with nonischemic HF. METHODS AND RESULTS Sixty patients with stable nonischemic HF under optimal medical therapy were included in this randomized double-blind study. Patients were randomized to TMZ (35 mg orally twice a day) or placebo for 6 months. LVEF, 6-minute walk test (6MWT), maximum O2 uptake in cardiopulmonary exercise test, different markers of metabolism, oxidative stress, and endothelial function, and quality of life were assessed at baseline and after TMZ treatment. Left ventricular peak glucose uptake was evaluated with the use of the maximum standardized uptake value (SUV) by 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). Etiology was idiopathic in 85% and hypertensive in 15%. Both groups were similar in age, functional class, LVEF, and levels of N-terminal pro-B-type natriuretic peptide at baseline. After 6 months of TMZ treatment, no changes were observed in LVEF (31 ± 10% vs 34 ± 8%; P = .8), 6MWT (443 ± 25 m vs 506 ± 79 m; P = .03), maximum O2 uptake (19.1 ± 5.0 mL kg(-1) min(-1) vs 23.0 ± 7.2 mL kg(-1) min(-1); P = .11), functional class (percentages of patients in functional classes I/II/III/IV 10/3753/0 vs 7/40/50/3; P = .14), or quality of life (32 ± 26 points vs 24 ± 18 points; P = .25) in TMZ versus placebo, respectively. In the subgroup of patients evaluated with (18)FDG-PET, no significant differences were observed in SUV between both groups (7.0 ± 3.6 vs 8.2 ± 3.4 respectively; P = .47). CONCLUSIONS In patients with nonischemic HF, the addition of TMZ to optimal medical treatment does not result in significant changes of LVEF, exercise capacity, O2 uptake, or quality of life.

Estrés oxidativo e inflamación en insuficiencia cardiaca: Mecanismos de daño y alternativas terapéuticas

Despite advances in treatment, chronic heart failure still is associated with a poor prognosis and remains a leading cause of cardiovascular death. Cumulating evidence suggests that imbalances in redox state lead to a higher generation of reactive oxygen species. This phenomenon, along with pro-inflammatory cytokine activation and extra cellular matrix alterations with reactive fibrosis, play an important role in the pathogenesis and progression of heart failure, through the development of endothelial and myocardial dysfunction. The understanding of the underlying phenomena and the metabolic pathways involved will allow further development of therapies aiming to change the natural history of heart failure.

Inflamación y disfunción endotelial en pacientes con insuficiencia cardiaca crónica

14 years (80% male) with a CHF in functional capacity II-III (New York HeartAssociation) and an ejection fraction (EF) <40% were consecutively studied. Patients wereclassified according to the presence or absence of ED, evaluated by reactive vasodilationmeasured by ultrasound, after brachial artery compression. Circulating levels of highly sensitiveC reactive protein (usCRP), tumor necrosis factor

Relationship between mechanical and metabolic dyssynchrony with left bundle branch block: evaluation by 18-fluorodeoxyglucose positron emission tomography in patients with non-ischemic heart failure.

BACKGROUND Ventricular dyssynchrony is a common finding in patients with heart failure (HF), especially in the presence of conduction delays. The loss of ventricular synchrony leads to progressive impairment of contractile function, which may be explained in part by segmental abnormalities of myocardial metabolism. However, the association of these metabolic disarrangements with parameters of ventricular dyssynchrony and electrocardiography (ECG) findings has not yet been studied. METHODS Our aim was to determine the correlation between the presence of left bundle branch block (LBBB) with left ventricular (LV) mechanical synchrony assessed by multiple-gated acquisition scan (MUGA) and with patterns of 18-fluorodeoxyglucose (18FDG) uptake in patients with non-ischemic heart failure. Twenty-two patients with non-ischemic cardiomyopathy, LV ejection fraction (LVEF) ≤45% and New York Heart Association (NYHA) Functional Class II or III symptoms under standard medical therapy were included, along with 10 healthy controls matched for age and gender. A 12-lead ECG was obtained to measure the length of the QRS. Mechanical LV synchrony was assessed by MUGA using phase analysis. All patients and controls underwent positron emission tomography with 18FDG to determine the distribution of myocardial glucose uptake. The standard deviation of peak (18)FDG uptake was used as an index of metabolic heterogeneity. Students t-test and Pearsons correlation were used for statistical analysis. RESULTS The mean age of the patients with HF was 54 ± 12 years and 72% were male. The length of the QRS was 129 ± 31 milliseconds and LBBB was present in 9 patients. Patients with HF had decreased LV 18FDG uptake compared with controls (7.56 ± 3.36 vs. 11.63 ± 4.55 standard uptake value; p = 0.03). The length of the QRS interval correlated significantly with glucose uptake heterogeneity (r = 0.62; p = 0.002) and mechanical dyssynchrony (r = 0.63; p = 0.006). HF patients with LBBB showed marked glucose uptake heterogeneity compared with HF patients without LBBB (41.4 ± 10 vs 34.7 ± 4.9 ml/100 g/min, respectively; p = 0.01). CONCLUSIONS Patients with non-ischemic heart failure exhibit a global decrease in myocardial glucose uptake. Within this group, subjects who also have LBBB exhibit a marked heterogeneity in segmental glucose uptake, which directly correlates with QRS duration.

Determinaciones de niveles de creatina y lípidos mediante espectroscopia por resonancia magnética en miocardio de pacientes con insuficiencia cardiaca no isquémica

Heart failure (HF) is characterized, among other features, by the development of alterations in myocardial energy metabolism, involving a decrease in glucose utilization and increased free fatty acid uptake by cardiomyocytes, associated with decreased deposits of high-energy phosphates (creatine phosphate/ creatine transporter). Magnetic resonance (MR) imaging allows a direct and noninvasive assessment of myocardial metabolites.

Influencia de factores socio-culturales en la evolución alejada de pacientes con insuficiencia cardíaca

Objetivo: Evaluar el impacto de los factores socioculturales (SC) en las caracteristicas del cuidado de la insuficiencia cardiaca (IC) y la evolucion post alta en pacientes admitidos con diagnostico de IC descompensada a hospitales del registro ICARO en el periodo 2006-2008. Metodo: Registro prospectivo de 14 hospitales. Se incorporaron en forma consecutiva pacientes admitidos con el diagnostico de IC descompensada entre enero 2006 y mayo 2008. La mortalidad al fin del seguimiento se determino por la base de datos del Servicio Nacional de Registro Civil e Identificacion. Se definio como terapia optima la combinacion de un betabloqueador con cualquiera de los siguientes: inhibidores de la enzima convertidora de angiotensina (IECA), antagonistas del receptor de angiotensina II (ARAII), hidralazina/isosorbide o espironolactona. Las caracteristicas de los pacientes se compararon mediante t de Student o chi cuadrado segun correspondia. La sobrevida se evaluo mediante Kaplan-Meier. Resultados: Los pacientes de bajo nivel SC son de mayor edad (71±11 v/s 66±15 anos respectivamente, p de 70 anos, HR=2,17 (1,55-3,03), un bajo nivel SC, HR=1,57(1,17-2,09), una fraccion de eyeccion < a 50%, HR=1,49 (1,04-2,14) y la ausencia de una terapia optima al alta, HR=0,52 (0,41-0,66). La supervivencia fue marcadamente inferior en el grupo con menor nivel SC (mediana 761±47.9 v/s 975±82.3, log rank test p=0,02). Conclusion: La poblacion con IC y menor nivel SC y edad avanzada constituye un grupo especialmente vulnerable. Los resultados ponen en evidencia la necesidad de intervenciones destinadas a asegurar accesos igualitarios a las prestaciones de salud e implementar estrategias para mejorar la adherencia a las guias de tratamiento de la IC.

Grosor íntima media carotídeo y asociación con factores de riesgo cardiovascular tradicionales y metabólicos

Background: Carotid intima-media thickness (IMT) is a surrogate marker of subclinical atherosderosis and is associated with cardiovascular risk factors (CVRF) Aim: To analyze the association of CVRF and metabolic factors (MF) with IMT, and if the clustering of these factors modify IMT. Material and Methods: Cross sectional study in 187 participants aged 46±10years (53% male) without CV disease. Weight, height, waist circumference (WC), blood pressure, fasting plasma glucose and lipid profile were measured. Abdominal obesity (AOb) was defined by ATP III criteria. Mean carotid IMT was measured at the farwall of the common carotid artery. The cutoff point for an abnormally high IMT was set at the 75th IMT percentile of the sample. Results: The 75th IMT percentile of the sample was 0.67 mm. In a multivariate analysis four factors were significantly related with a high IMT: age (odds ratio (OR): 5.3, confidence intervals (CI): 2.2-12.9), dyslipidemia (OR: 6.4 CI: 2.3-17.9), systolic blood pressure (OR: 2.9, CI: 1.2-7.1) and AOb (OR: 2.9 (IC: 1.1-7.2). The presence of Oto 4 of these factors was associated with an IMT increment from 0.54 to 0.71 mm (p < 0,001). Conclusions: In this sample dyslipidemia, systolic blood pressure and abdominal obesity were the main predictors of a high IMT.BACKGROUND Carotid intima-media thickness (IMT) is a surrogate marker of subclinical atherosclerosis and is associated with cardiovascular risk factors (CVRF) AIM: To analyze the association of CVRF and metabolic factors (MF) with IMT, and if the clustering of these factors modify IMT. MATERIAL AND METHODS Cross sectional study in 187 participants aged 46±10 years (53% male) without CV disease. Weight, height, waist circumference (WC), blood pressure, fasting plasma glucose and lipid profile were measured. Abdominal obesity (AOb) was defined by ATP III criteria. Mean carotid IMT was measured at the far wall of the common carotid artery. The cutoff point for an abnormally high IMT was set at the 75th IMT percentile of the sample. RESULTS The 75th IMT percentile of the sample was 0.67 mm. In a multivariate analysis four factors were significantly related with a high IMT: age (odds ratio (OR): 5.3, confidence intervals (CI): 2.2-12.9), dyslipidemia (OR: 6.4 CI: 2.3-17.9), systolic blood pressure (OR: 2.9, CI: 1.2-7.1) and AOb (OR: 2.9 (IC: 1.1-7.2). The presence of Oto 4 of these factors was associated with an IMT increment from 0.54 to 0.71 mm (p < 0,001). CONCLUSIONS In this sample dyslipidemia, systolic blood pressure and abdominal obesity were the main predictors of a high IMT.

Taquicardiomiopatía, causa reversible de insuficiencia cardiaca: caso clínico

Tachycardiomyopathy is a potentially reversible cause of heart failure. It can be induced by supraventricular or ventricular arrhythmias. When these are treated, systolic function improves or normalizes. We report a 20 year-old male with deterioration of left ventricular function and dilated cardiomyopathy secondary to an incessant atrial tachycardia that was treated with radiofrequency catheter ablation. After the procedure, the patient experienced a significant improvement of his ventricular function.

Factores asociados a fragilidad en pacientes hospitalizados con insuficiencia cardiaca descompensada

Background: Frailty is a geriatric syndrome characterized by a progressive impairment in the subjects’ ability to respond to environmental stress. Frailty is more commonly found in heart failure (HF) patients than in general population and it is an independent predictor of rehospitalization, emergency room visits and death. Aim: To estimate the prevalence of frailty in patients with decompensated HF admitted to four hospitals in Santiago, Chile. Material and methods: Cross-sectional study. Subjects aged 60 or older consecutively admitted for decompensated HF to the study centers between August 2014 and March 2015 were included. Frailty was defined as the presence of three or more of the following criteria: unintended weight loss, muscular weakness, depression symptoms (exhaustion), reduced gait speed and low physical activity. Independent variables were tested for association using simple logistic regression. Variables associated with frailty (p<0.05) were included in a multiple logistic regression model. Results: Seventy-nine subjects were included. The prevalence of frailty was 50.6%. Frail patients were mostly female (52.6%) and older than non-frail subjects (73.7± 7.9 vs 68.2 ± 7.1; p<0.003). Independent predictors of frailty were age (Odds raio (OR) 1.10; 95% confidence intervals (CI): 1.03-1.17), quality of life measured with the Minnesota Living with Heart Failure Questionnaire (OR 1.07; IC95%: 1.03-1.11), previous hospitalizations (OR 2.56; 95%CI: 1.02-6.43) and number of medications (OR 4.46; 95%CI: 1.11-17.32). Conclusions: The prevalence of frailty in patients admitted to the hospital for decompensated heart failure is high. Age, Quality of life, hospitalizations and polypharmacy were factors associated with frailty in this group of participants.