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.

Effect of carvedilol and nebivolol on oxidative stress-related parameters and endothelial function in patients with essential hypertension.

Oxidative stress and endothelial dysfunction have been associated with essential hypertension (EH) mechanisms. The purpose of this study was to evaluate the effect of carvedilol and nebivolol on the oxidative stress-related parameters and endothelial function in patients with EH. The studied population included 57 patients, either sex, between 30 and 75 years of age, with mild-to-moderate EH complications. Participants were randomized to receive either carvedilol (12.5 mg) (n = 23) or nebivolol (5 mg) (n = 21) for 12 weeks. Measurements included; 24-hr ambulatory blood pressure (BP), flow-mediated dilatation, levels of nitric oxide estimated as nitrite - a nitric oxide metabolite ( NO2) - in plasma, and oxidative stress-related parameters in plasma and erythrocyte. EH patients who were treated with nebivolol or carvedilol showed systolic BP reductions of 17.4 and 19.9 mmHg, respectively, compared with baseline values (p < 0.01). Diastolic BP was reduced by 13.7 and 12.8 mmHg after the treatment with ebivolol and carvedilol, respectively (p < 0.01) (fig. 2B). Nebivolol and carvedilol showed 7.3% and 8.1% higher endothelium-dependent dilatation in relation to baseline values (p < 0.05). Ferric-reducing ability of plasma (FRAP) and reduced glutathione/oxidized glutathione (GSSH) ratio showed 31.5% and 29.6% higher levels in the carvedilol group compared with basal values; however, nebivolol-treated patients did not show significant differences after treatment. On the other hand, the NO2 plasma concentration was not modified by the administration of carvedilol. However, nebivolol enhanced these levels in 62.1% after the treatment. In conclusion, this study demonstrated the antihypertensive effect of both beta-blockers. However, carvedilol could mediate these effects by an increase in antioxidant capacity and nebivolol through the raise in NO2 concentration. Further studies are needed to determine the molecular mechanism of these effects.

Evaluación ecocardiográfica tardía en pacientes sometidos a terapia de resincronización cardiaca / Late echocardiographic evaluation of patients submitted to cardiac resynchronization therapy

Antecedentes: Numerosos estudios clínicos confirman los beneficios de la terapia de resincronización cardiaca (TRC) en el tratamiento de la insuficiencia cardiaca refractaria a fármacos. El Ecocardiograma (ETT) es la técnica de elección en la evaluación de esta terapia tanto en el período agudo como a largo plazo. Objetivo: Nuestro objetivo fue estudiar los beneficios a largo plazo de la TRC mediante ETT. Método y resultados: Se estudiaron 12 pacientes con ETT con más de un año de resincronización, observándose mejoría significativa en la fracción de eyección, diámetro de la aurícula izquierda y presión sistólica de arteria pulmonar, y variaciones positivas en los diámetros y volúmenes ventriculares, fracción de acortamiento, función diastólica, severidad de la insuficiencia mitral. En 8 pacientes en que se comparó la sincronía al Doppler tisular (DT) strain y tissue synchronization imaging (TSI) se observó coincidencia en 2 de 8 sugiriendo baja especificidad para el TSI. Conclusión: El ETT permite estudiar la remodelación reversa que sufre el ventrículo izquierdo con reducción de diámetros y objetivar la mejoría de parámetros de función sistólica y diastólica. El aporte del Doppler tisular para evaluar sincronía requiere de mayor estudio con un mayor número de pacientes.

Terapia de resincronización ventricular en pacientes portadores de marcapasos definitivo e insuficiencia cardiaca avanzada / Ventricular resynchronization therapy in patients with a previous pacemaker for the management of advanced refractory heart failure

Antecedentes: La Terapia de Resincronización Ventricular (TRV) es un procedimiento aceptado en el tratamiento de la Insuficiencia cardiaca (IC) avanzada y retardo de conducción intraventricular. Existe escasa información de esta terapia en pacientes con IC y Marcapasos (MP) previo. Objetivos: Evaluar el impacto de la TRV en pacientes con MP previo e IC refractaria. Pacientes y método: Entre junio 2000 y agosto 2004, 15 pacientes con MP e IC avanzada, edad 60,9 + 15 años, 12 hombres, fueron sometidos a TRV. En 2 de ellos se efectuó como medida de salvataje y puente al transplante cardíaco. Resultados: En todos se logró implantar un electrodo epicárdico en VI vía seno coronario. Dos pacientes tuvieron complicaciones: 1 neumotórax, 1 desplazamiento de electrodo y posterior fractura del mismo. En el seguimiento de 15 meses hubo disminución del DDVI (68mm versus 63mm, p<0,005) y aumento de la FE (22 por ciento versus 32 por ciento, p<0,0001). Antes de la TRV el 86 por ciento de los pacientes estaba en CF III-IV, y posteriormente el 77 por ciento estaba en CF III (p<0,005). Fallecieron 4 pacientes: 2 por neumonía y 2 por IC refractaria. De los pacientes en que la TRV fue efectuada como puente al transplante, éste se logró realizar en ambos. Conclusiones: La TRV es factible en pacientes con MP previo e IC refractaria, con una baja tasa de complicaciones, y se asocia a una mejoría clínica y de la función de VI significativa. En casos seleccionados podría ser una medida útil como puente al transplante cardíaco.

The predictive value of 201Tl rest-redistribution and 18F-fluorodeoxyglucose SPECT for wall motion recovery after recent reperfused myocardial infarction.

UNLABELLED: 201Tl and 18F-FDG are useful for acute myocardial infarction (MI) assessment. The goal of this study was to compare their predictive value for wall motion recovery in the culprit area after a recent reperfused MI using SPECT technique. METHODS: Forty-one patients (mean age: 56 +/- 12 years) were included, 81% of them male; all were studied within 1-24 days post MI. They underwent angioplasty in 27 cases (12 primary); bypass grafting in 10 cases and successful thrombolysis in 4. SPECT 201Tl injected at rest and redistribution (R-R) and also 18F-FDG, were performed on different days. Processed tomograms were interpreted blinded to clinical or angiographic data. Segmental wall motion assessed with echocardiography at baseline was compared with the 3 month follow up. RESULTS: Sensitivity [Confidence Interval] for 201Tl R-R was 74.6% [60.5-84.5], for FDG it was 82.1% [70.8-90.4]; specificities were 73% [64.3-80.5] and 54.8% [45.6-63.7], respectively. 18F-FDG tended to be more sensitive than 201Tl R-R, but the latter was more specific (p < 0.0004). Both 201Tl RR and 18F-FDG presented high negative predictive value (p: ns). CONCLUSION: In recent MI, SPECT 201Tl R-R is a valuable and widely available technique for viability detection, with similar sensitivity and significant better specificity than SPECT 18F-FDG.

[Results of intraventricular resynchronization in patients with severe cardiac failure]. / Resultados clínicos de la resincronización ventricular en pacientes con insuficiencia cardíaca severa.

BACKGROUND: Intraventricular resynchronization with pacemakers is a promising therapy for patients with refractory cardiac failure and intraventricular conductions delay. However its long term effects are not well known. AIM: To report the results of this therapy in patients with cardiac failure. PATIENTS AND METHODS: Fourteen patients (11 male), whose mean age was 68 years, with a severe and refractory cardiac failure, have been treated in our unit using intraventricular resynchronization with pacemakers. Eight had a coronary heart disease and six a dilated myocardiopathy. The pacemaker was implanted transvenously, with conventional stimulation in atrium and right ventricle. The left ventricle was stimulated through an epicardial vein, accessed through the coronary sinus. RESULTS: In one patient the high thresholds did not allow a left ventricular stimulation. In the other 13 patients, a clinical improvement was observed in 11 (85%), that has been sustained for a mean of 8.2 months. The ejection fraction improved form 23.5 to 32.4% (p < 0.001), the 6 min walking test improved from 347 to 437 m (p = 0.003) and the functional capacity changes from 3.3 to 2.7 (p < 0.001). Three patients died during follow up. One was the patient in whom the stimulation failed and two had a sudden death. No complications of the procedure were observed. CONCLUSIONS: In this series, intraventricular resynchronization with pacemakers was effective in 11 of 13 patients, improving functional capacity and ejection fraction. Sudden death could be avoided adding a defibrillator to the pacemaker system.

FDG F18 / Rest Tl 201 SPECT patterns in recent myocardial infarction: predictive value for regional function recovery

Background. Detecting viability is important after recent myocardial infarction (MI). SPECT FDG/Tl flow-metabolism patterns for predicting functional recovery were analyzed in this setting. Method. Forty-one patients were studied (56ñ12 years; 80 percent males) with Tl 201 at rest and FDG F18 SPECT at a mean of 8.9 days post MI (range:1-24). All had baseline and 3 month follow-up echocardiography (ECHO) and initial coronary angiography. They were submitted to primary PTCA in 12 cases, late PTCA in 15 and bypass surgery in 10 and thrombolysis was performed in 4 patients as only procedure. A total of 345 culprit artery territory segments were interpreted by 3 nuclear independent observers. Analysis included segments with or without abnormal motion. Results. FDG/Tl 201 on patient basis, had: sensitivity 91percent; specificity 56 percent; positive predictive value 88 percent; negative predictive value (NPV) 63 percent and accuracy 83 percent. The analysis of segments with abnormal contractility showed values of 67 percent, 69 percent, 44 percent, 85 percent and 68 percent, respectively. Reverse mismatch with FDG/Tl appears to predict viability similarly to classical mismatch; severe or moderate match was highly associated with no functional recovery (NPV = 85 percent). Conclusion. Flow-perfusion patterns are variable in recent MI. FDG/Tl 201 SPECT has acceptable accuracy for predicting functional recovery and excellent NPV to further exclude viability

[Performance of Thallium 201 rest-redistribution spect to predict viability in recent myocardial infarction]. / Rendimiento del SPECT talio201 reposo-redistribución para predecir viabilidad post infarto reciente del miocardio.

BACKGROUND: The detection of viability after acute myocardial infarction is primordial to select the most appropriate therapy, to decrease cardiac events and abnormal remodeling. Thallium201 SPECT is one of the radionuclide techniques used to detect viability. AIM: To evaluate the use of Thallium201 rest-redistribution SPECT to detect myocardial viability in reperfused patients after a recent myocardial infarction. PATIENTS AND METHODS: Forty one patients with up to of 24 days of evolution of a myocardial infarction were studied. All had angiographically demonstrated coronary artery disease and were subjected to a successful thrombolysis, angioplasty or bypass grafting. SPECT Thallium201 images were acquired at rest and after 4 h of redistribution. These results were compared with variations in wall motion score, studied at baseline and after 3 or 4 months with echocardiography. RESULTS: The sensitivity of rest-redistribution Thallium201 SPECT, to predict recovery of wall motion was 91% when patient analysis was performed and 79% when segmental analysis was done in the culprit region. The figures for specificity were 56 and 73% respectively. CONCLUSIONS: Rest-distribution Thallium201 SPECT has an excellent sensitivity to predict myocardial viability in recent myocardial infarction. The data obtained in this study is similar to that reported for chronic coronary artery disease.

Eficacia de F18_fluorodeoxiglucosa SPECT para evaluar infarto reciente y viabilidad miocárdica / Efficacy of F18_fluorodeoxiglucose SPECT for recent infarction evaluation and myocardial viability

El mejor examen disponible para evaluar viabilidad miocárdica es el Fluor18-fluordeoxiglucosa (F18FDG) que mide metabolismo celular y utilización de glucosa como sustrato. Su asociación a marcadores de flujo miocárdico permiten conocer la existencia y extensión de tejido con función potencialmente recuperable. El objetivo de este trabajo fue evaluar el rendimiento del F18FDG SPECT en pacientes con infarto reciente de miocardio. Material y Método: Se estudiaron preliminarmente 23 pacientes (7M,16H), edad promedio 63 ñ 13 años (rango:40-85), con evolución promedio de 10 días postinfarto (rango:5-24). En 14 casos, el infarto fue anterior y en 9 casos inferior. Se realizó F18FDG en cámara ADAC doble cabezal con colimadores de 511 Kev, con dosis promedio de 211 MBq (rango: 52-444) , con adquisición de las imágenes a los 45 min postinyección. Contemporáneamente, se efectuó Tl201 SPECT reposo redistribución con dosis de 148 MBq y adquisición de imágenes a los 10 min y 3 hrs. Se realizó análisis visual de ambos estudios en forma independiente dividiendo el miocardio en 17 segmentos (total de segmentos: 391). Resultados: Tanto en el SPECT con Tl201 como en el con F18 FDG hubo 21/23 (91 por ciento) de casos con segmentos alterados, en que hubo concordancia de 83 por ciento. En el Tl201 reposo redistribución, se encontraron 32 por ciento de segmentos alterados y en el estudio conjunto Tl201 reposo F18 FDG, se observó un 34 por ciento de segmentos alterados del total de los analizados. En dichos segmentos, el Tl201 reposo redistribución mostró 65 por ciento de segmentos viables y el Tl201 F18 FDG 77 por ciento de segmentos con viabilidad. Conclusión: 1) Tanto el Tl201 como el estudio con F18 FDG tienen buena concordancia, tanto por pacientes como por segmentos, en el infarto reciente de miocardio. 2) El SPECT Tl201 asociado a F18 FDG detecta un mayor número de segmentos viables que el examen de Tl201 reposo- redistribución aislado