Efecto de la terapia de resincronización ventricular en los parámetros de disfunción endotelial y función sistólica izquierda en pacientes con insuficiencia cardíaca crónica y bloqueo completo de rama izquierda / Endothelial dysfunction, left ventricular function, and chronic heart failure with complete left bundle branch block: effect of resynchronization therapy

Resumen: Introducción: La insuficiencia cardíaca crónica (ICC) es una condición compleja asociada a inflamación sistémica y a disfunción endotelial (DE) cuya patogénesis no es bien comprendida. Objetivo: Evaluar una posible relación entre marcadores de DE periférica con la respuesta a terapia de resincronización ventricular (TRV). Método: 20 pacientes con ICC, QRS ≥120ms y fracción de eyección ventricular izquierda (FEVI) ≤35% se estudiaron pre y 6 meses post-TRV con: Minnesota Living with Heart Failure Questionnaire (MLHFQ); test de marcha (TM-6min); Ecocardiografía-2D y SPECT de perfusión gatillado en reposo; proteína C-reactiva ultra sensible (us-PCR); péptido natriurético cerebral (pro-BNP); células endoteliales circulantes (CEC); moléculas de adhesión soluble vascular (sVCAM) e intercelular (sICAM); interleukina-6 (IL-6) y Factor von Willebrand (FvW). Se clasificaron como respondedores o no a TRV según criterios preestablecidos. Resultados: Promedios basales: pro-BNP 5.290pg/ml; us-PCR 1,7ug/mL; MLHFQ 72; TM-6min 391 metros. Las CEC y sICAM estaban sobre límites normales. Post-TRV, el 50% fue respondedor: 11/20 mejoraron ≥1 clase NYHA y ≥10% del TM-6min; ML-HFQ disminuyó (p<0.0001); FEVI mejoró (p=0.003); volumen final sistólico disminuyó (p=0.008) y también pro-BNP (p=0.03). En los respondedores, las CEC disminuyeron, persistiendo elevadas, sobre lo normal. Existieron correlaciones entre cambios de pro-BNP con TM-6min y entre us-PCR con MLHFQ y FvW (p≤0.004 en todas). Conclusiones: En ICC existe evidencia de significativa DE, expresada por sICAM y CEC, biomarcador periférico sensible. Estas disminuyeron 6 meses post-TRV, persistiendo sobre el límite normal. Otros parámetros funcionales e inflamatorios se correlacionaron en el grupo total, sin diferencias entre grupos respondedores y no respondedores.

Abstract: Introduction: Chronic heart failure (CHF) is a complex condition associated with systemic inflammation and endothelial dysfunction (ED) whose pathogenesis is not well understood. Objective: to evaluate a possible relationship between peripheral ED markers and response to cardiac resynchronization therapy (CRT). Method: 20 patients with CHF, QRS ≥120ms and left ventricular ejection fraction (LVEF) ≤35% were studied before and 6 months post-CRT. Minnesota Living with Heart Failure Questionnaire (MLHFQ); walking test (6min-WT); 2D-echocardiography and gated perfusion SPECT at rest; ultra-sensitive C-reactive protein (us-CRP); brain natriuretic peptide (pro-BNP); circulating endothelial cells (CEC); vascular soluble adhesion (sVCAM) and intercellular adhesion molecules (sICAM); interleukin-6 (IL-6) and von Willebrand Factor (vWF) were measured in all subjects. They were classified as responders or not to CRT, according to pre-established criteria. Results: Basal means: pro-BNP 5,290 pg / ml; us-CRP 1.7 ug/mL; MLHFQ 72; 6min-WT 391 meters. The CEC and IL-6 were above normal limits. Post-CRT, 50% were responders: 11/20 improved ≥1 NYHA class and ≥10% increase in 6min-WT; MLHFQ decreased (p <0.0001); LVEF improved (p = 0.003); final systolic volume decreased (p = 0.008) and also pro-BNP (p= 0.03). In responders CEC decreased, persisting over normal limits. There were correlations between changes of pro-BNP with TM-6min and between us-PCR with MLHFQ and vWF (p≤0.004 in all). Conclusions: In CHF there is evidence of significant ED, expressed by sICAM and CEC, a sensitive peripheral biomarker that decreased 6 months post-CRT although persisting above normal limits. Other functional and inflammatory parameters were correlated in the total group, without differences between responders and non-responders.

Daño endotelial y activación del sistema hemostático asociado al uso crónico de cocaína: estudios ex vivo e in vitro / Endothelial damage and activation of the haemostatic system associated to chronic use of cocaine: an ex vivo and in vitro study

Antecedentes: Usuarios crónicos de cocaína tienen riesgo aumentado de presentar infarto de miocardio, angina,muerte súbita y accidentes cerebrovasculares. Aunque la patogenia del daño vascular es mayormente desconocida, se ha encontrado arterioesclerosis prematura y formación de trombos intravasculares. Objetivo: Demostrar evidencia de daño endotelial y activación del sistema hemostático en usuarios crónicos de cocaína. Métodos: Un grupo de 23 pacientes con criterios de dependencia a cocaína DSM-IV; 19 hombres (edad promedio 32 a), con exposición a la droga dentro de 72 h del estudio. Disfunción endotelial se evaluó por enumeración de las células endoteliales circulantes (CEC) y nivel de sICAM . Para activación del sistema hemostático se incluyó: complejos trombina-antitrombina (TAT) y generación de trombina; NAP-2 y RANTES para activación plaquetaria. In vitro, CE en cultivo (HUVEC), se expusieron a plasma de consumidores o controles. Se midió factor von Willebrand (FVW) en el medio y expresión de FvW y factor tisular (FT) sobre las CE. Adhesión plaquetaria estática se evaluó por microscopía. Resultados: En usuarios de cocaína, con respecto a controles, las CEC estaban significativamente elevadas...

Background: chronic cocaine users have an increased risk of developing myocardial infarction, angina, suddendeath and stroke. Although the pathogenesis of this effect is not completely known, premature atheromatosis and intravascular thrombosis appear to be involved.Aim: to provide evidence for the presence of endothelial damage and activation of the haemostatic system in chronic cocaine users. Methods: 23 subjects (19males, overall mean age 32) with DSM-IV criteria for cocaine dependency and exposure to the drug within 72 hours were studied. Endothelial dysfunction was determined by circulating endothelial cell counts (CEC) and sICAM levels. Thrombin-antithrombin complexes (TAT) and thrombin generation were used to characterize haemostatic status. In vitro, platelet activation was studied by NAP-2 and RANTES. EC in culture (HUVEC) were exposed to plasma from cocaine users and controls. Von Willebrand factor was measured in the culture media as well as its expression along with that of tissue factor in EC. Platelet adhesion was evaluated by microscopy. Results: Compared to controls, EC were significantly increased in cocaine users...

Uso de plasmaféresis en unidades de pacientes críticos / Indications, adverse effects and results of plasmapheresis in critical care patients

Background: Plasmapheresis is a therapeutic alternative for diseases in which a "humoral factor" has pathogenetic relevance. However it is not devoid of adverse effects. Aim: To review the indications, number of procedures, morbidity and clinical evolution of plasmapheresis in critical patients. Patients and Methods: A retrospective and descriptive study in four intensive care units of an University hospital. The severity of patients was evaluated with APACHE II and SOFA scores. Results: Twenty patients were studied. The most common indications of plasmapheresis were thrombotic thrombocytopenic purpura (TTP) in 50% of subjects and small vessel vasculitides in 30%. The number of procedures per patient oscillated between 2 and 14 (mean: 7.1±3.3). The registered adverse effects were hypocalcemia in 50% of patients, hypotension in 42.1%, coagulopathy in 35%, hypokalemia in 29%, rash in 20%, procedure related infections in 18% and fever in 10%. There was a significant decrease of 17±28% in prothrombin time, after the procedures. Seventy five percent of patients had a favorable evolution. Global mortality rate was 15%. All deaths occurred in patients with TTP and were attributed to the progression of the disease. No death was attributed to the procedure. The initial APACHE II and SOFA scores were 12.4±8.4 and 5.3±2.9, respectively. Both scores decreased after the procedure. Among other therapeutic measures, 15% of the patients received immunosuppressant treatment, 27% were dialyzed and 32% were mechanically ventilated. Conclusions: The most common indication of plasmapheresis was TTP. Adverse effects were frequent, however there was no procedure related mortality. The global mortality rate was 15% and all deaths occurred in patients with TTP.