José A. Moro

What is the best biomarker for diagnosis of rejection in heart transplantation

Abstract: Introduction:  Acute cellular rejection is a major cause of graft loss in heart transplantation (HT). Endomyocardial biopsy remains the gold standard for its diagnosis, but it is an invasive procedure not without risk. A proinflammatory state exists in rejection that could be assessed by determining plasma levels of inflammatory biomarkers.

Follow-up Study on the Utility of von Willebrand Factor Levels in the Diagnosis of Cardiac Allograft Vasculopathy

BACKGROUND Cardiac allograft vasculopathy (CAV) is the major cause of late death in patients undergoing heart transplantation (HT). The most validated method for its diagnosis is intravascular ultrasound (IVUS), and there are no sufficiently reliable non-invasive methods. von Willebrand factor (vWF) is a marker of endothelial dysfunction/activity that is rarely studied in the context of CAV. The purpose of this study was to determine whether patients with higher levels of vWF in the first year post-transplant will develop a greater degree of CAV. METHODS A prospective study of 113 consecutive cardiac transplant recipients was initiated in January 2002. vWF determinations were performed at 1, 2, 4, 6, 9 and 12 months post-transplant, at the same time as biopsies. Coronary arteriography and IVUS were performed on the first and last follow-up visits. Heart-lung transplants, retransplants and pediatric transplants were excluded from the study. Patients who died in the first month and those who refused consent were also excluded. The final analysis included 72 patients and 405 vWF determinations. CAV was defined as an intimal thickening of >or=0.5 mm on follow-up versus baseline IVUS. Patients with CAV (n = 41) and without CAV (n = 31) after 1 year of follow-up were compared. RESULTS Patients who developed CAV had a higher prevalence of prior dyslipidemia, ischemic heart disease as the cause of HT, and rate of rejection, as well as higher vWF levels (321 +/- 122 vs 243 +/- 100%, p < 0.05). The receiver-operator characteristic (ROC) curve showed that vWF values of 150% provided a sensitivity of 91%, and values of 400% a specificity of 91% (p < 0.0001). The variables associated with CAV in the multivariate analysis were prior dyslipidemia, rejections and vWF, both linearly and by groups. vWF levels of 300% to 400% increased the probability of developing CAV by 390%, and levels >400% by 500%, versus levels <200%. CONCLUSIONS vWF levels determined in the first year post-transplant help to distinguish a subgroup of patients with a higher incidence of CAV.

Analysis of Echocardiographic Alterations Observed in Sleep Apnea-Hypopnea Syndrome and How They Are Influenced by Hypertension

INTRODUCTION AND OBJECTIVES Sleep apnea-hypopnea syndrome (SAHS) is associated with significant effects on the heart, which can be assessed using noninvasive methods such as transthoracic echocardiography. However, it is not clear whether these effects are due to the condition itself or are influenced by associated factors, such as high blood pressure (HBP). The objective of this study was to investigate the echocardiographic alterations observed in SAHS patients and how they are affected by the presence of concomitant HBP. METHODS The study involved 103 consecutive patients (49 with HBP and 54 without) with SAHS and an indication for continuous positive airways pressure treatment and 24 controls matched for age and body mass index. Doppler echocardiography was performed in a blinded manner. Both morphology (i.e., wall thickness, and diameters) and function (i.e., ejection fraction, peak E and A wave velocities, mitral deceleration time, and Tei index) were assessed. Results were compared using ANOVA and Bonferronis test. RESULTS Hypertensive patients had larger morphological changes characteristic of left ventricular hypertrophy (i.e., increased septal and posterior wall thicknesses) than nonhypertensive patients, who in turn had larger changes than controls (septal thickness: HBP-SAHS, 12 [2] mm; non-HBP SAHS, 11 [2] mm, and controls, 9.5 [5] mm; 1 vs. 2, P=.038; 1 vs. 3, P=.0001, 2 vs. 3, P=.034) (posterior wall thickness: HBP-SAHS, 11 [2] mm; non-HBP SAHS, 10 [1] mm, and controls, 9 [1.5] mm; 1 vs. 2, P=.5; 1 vs. 3, P=.0001; 2 vs. 3, P=.001). In addition, there were also greater changes in ventricular filling patterns on the left (HBP-SAHS, 92%; non-HBP SAHS, 72%, controls, 29%; P=.0001) and on the right (HBP-SAHS, 72%; non-HBP SAHS, 58%; controls, 25%; P=.001). There was a trend towards a larger left ventricular Tei index (HBP-SAHS, 0.56 [0.2]; non-HBP SAHS, 0.54 [0.12]; controls, 0.5 [0.1]; 1 vs. 2, P=.8; 1 vs. 3, P=.09; 2 vs. 3, P=.7). CONCLUSIONS From the time of diagnosis, SAHS was associated with left ventricular hypertrophy and impaired biventricular filling, even in the absence of concomitant HBP. The abnormalities observed were more severe when HBP was present.

Hypertension and sleep apnea–hypopnea syndrome: changes in echocardiographic abnormalities depending on the presence of hypertension and treatment with CPAP☆

INTRODUCTION Sleep apnea-hypopnea syndrome (SAHS) is an emerging disease with high prevalence. There is controversy as to whether cardiac abnormalities are due to the disease itself or to the arterial hypertension frequently associated with this disease. OBJECTIVES To analyze echocardiographic abnormalities in a population of SAHS patients depending on the presence or absence of hypertension at the time of diagnosis and after six months of treatment with continuous positive airway pressure (CPAP). METHODS We studied 85 consecutive patients diagnosed with SAHS who required treatment with CPAP (Hypertensive: 43, nonhypertensive: 42). We performed a baseline echocardiogram after six months of treatment. We analyzed morphological (wall thickness, diameters, ejection fraction) and functional (peak E- and A-wave velocities, deceleration time, Tei index) parameters of the left and right ventricles. RESULTS Hypertensive patients were older and had higher blood pressure values, but there were no differences between groups in other clinical parameters. The hypertensive group had greater septal thickness (hypertensive: 12.1+/-2.3; nonhypertensive: 10.8+/-2.1mm; p=0.01). There were also differences in impairment of left (hypertensiveHT: 92.9%, nonhypertensive: 65%, p=0.002) and right (hypertensive: 74.4%, nonhypertensive: 42.1%, p=0.006) ventricular filling. After six months of treatment, an improvement of the myocardial performance index was noted in nonhypertensive patients (baseline Tei: 0.55+/-0.1 vs. 6-month Tei: 0.49+/-0.1; p=0.01), whereas no significant change was observed in hypertensive patients. CONCLUSIONS Cardiac abnormalities in SAHS patients are increased in the presence of associated hypertension. Treatment with CPAP for six months improves cardiac abnormalities in nonhypertensive patients but not in hypertensive patients.

Correlation between beta-adrenoceptors and G-protein-coupled receptor kinases in pretransplantation heart failure.

INTRODUCTION Prolonged catecholamine overstimulation of the myocardium in chronic heart failure causes a reduction in the number and functionality of beta1-adrenoceptors (beta1-AR) of the heart. Desensitization of beta1-AR is mediated by their phosphorylation by a group of cytosolic kinases (G-protein-coupled receptor kinases GRK). In advanced heart failure, an increase in GRK levels associated with the severity of the disease has been observed. OBJECTIVE The objective of this study was to analyze messenger RNA (mRNA) levels of beta1-AR in the myocardium of patients who underwent transplantation for advanced heart failure and their correlation with expression of the major cardiac isoenzymes of GRK. MATERIALS AND METHODS Myocardial tissue samples were obtained from the left ventricles of 14 explanted hearts of patients who underwent transplantation for dilated (n = 7) and ischemic (n = 7) cardiomyopathy. RT-PCR techniques were used to analyze mRNA levels of beta1-AR and the isoenzymes GRK2, GRK3, and GRK5. RESULTS We observed a significant correlation between beta1-AR and the 3 subtypes of GRK (R(2) = 0.668, 0.71, and 0.318, respectively). CONCLUSIONS In patients with advanced heart failure pretransplantation, we observed a significant correlation between beta1-AR and GRK2 and GRK3 levels. GRK5, the subtype predominantly expressed in the myocardium, showed a lesser correlation with beta1-AR levels.

Alteraciones ecocardiográficas asociadas al síndrome de apnea-hipopnea del sueño en función de su gravedad

Introduccion y objetivos El sindrome de apnea-hipopnea del sueno (SAHS) es una enfermedad muy prevalente con repercusiones cardiovasculares conocidas. Sin embargo, son pocos los estudios ecocardiograficos publicados que evaluan estas alteraciones en el momento del diagnostico y su relacion con la gravedad del sindrome. Nuestro objetivo fue analizar parametros morfologicos, funcionales y de rendimiento miocardico en estos pacientes. Metodos Analizamos a 110 pacientes consecutivos diagnosticados, entre junio de 2005 y 2006, de SAHS con indicacion de presion positiva continua en la via aerea (CPAP), divididos en 2 grupos segun la gravedad. Realizamos una ecocardiografia basal y analizamos variables morfologicas y funcionales, comparando los resultados entre grupos mediante analisis univariable y multivariable. Resultados La muestra presentaba una edad media de 54 ± 13 anos, un indice de masa corporal de 32 ± 6, una comorbilidad del 51% y un porcentaje de varones del 74%. Los pacientes con SAHS grave (indice apnea-hipopnea [IAH] ≥ 30) presentaron mayor tabaquismo activo, consumo de alcohol y perimetro de cuello. No encontramos diferencias entre grupos al analizar los parametros morfologicos. En los parametros funcionales, los pacientes graves presentaron menor tiempo de eyeccion aortico (IAH Conclusiones El rendimiento miocardico esta disminuido en pacientes SAHS. Tanto el indice de Tei como los tiempos de eyeccion se asocian con gravedad. El tiempo de eyeccion pulmonar es una variable predictora independiente de gravedad de la enfermedad.

Influence of immunosuppressive regimens on short-term morbidity and mortality in heart transplantation

Abstract:  Background:  The goal of immunosuppressive therapy in heart transplantation is to maximize safety and efficacy while minimizing morbidity and mortality. We now have numerous drug combinations, but few have been compared with each other.

Impacto de la diabetes mellitus en el paciente con trasplante cardiaco

Introduccion y objetivos Actualmente, el impacto de la diabetes mellitus en los pacientes con trasplante cardiaco es controvertido y su efecto sobre la mortalidad y otras complicaciones, como las infecciones y los rechazos, no esta completamente aclarado. El objetivo de este estudio es analizar estos efectos en nuestra poblacion de pacientes trasplantados. Metodos Se ha estudiado a una poblacion de 365 pacientes consecutivos con trasplante cardiaco desde noviembre de 1987 hasta mayo de 2003, dividiendolos en 3 grupos en funcion de la presencia de diabetes pretrasplante (grupo 1), diabetes de novo (grupo 2) y no diabeticos (grupo 3). Se analizaron variables tanto basales como de complicaciones evolutivas, y los resultados se compararon mediante test t de Student, test χ 2 y metodo de Kaplan-Meier para la supervivencia. Resultados No apreciamos diferencias entre grupos en la supervivencia al ano (p = 0,24) ni a 5 anos (p = 0,32). Los pacientes de los grupos con diabetes mellitus pretrasplante y de novo tenian mayor edad (54,6 frente a 54,9 frente a 50,6 anos; p = 0,04), mayor prevalencia de hipertension arterial (el 48, el 36 y el 23%; p = 0,001) y mayor porcentaje de tratamiento con tacrolimus (el 10, el 12 y el 4%; p = 0,04) y esteroides (el 92, el 86 y el 70%; p = 0,001). Evolutivamente, estos 2 grupos presentan mayor incidencia de rechazo (el 64, el 70 y el 45%; p = 0,001). Conclusiones La diabetes previa al trasplante o de novo no tuvo impacto negativo sobre la supervivencia de nuestros pacientes trasplantados. Su presencia se asocial al tratamiento con esteroides y tacrolimus. En estos pacientes seria deseable realizar un ajuste individualizado de la inmunodepresion.

Valor pronóstico de la tasa de filtración glomerular al año del trasplante cardiaco

Introduccion y objetivos Uno de los problemas mas relevantes tras el trasplante cardiaco es el desarrollo de insuficiencia renal. La heterogeneidad en su definicion hace que la estimacion de su prevalencia sea variable. Por otro lado, su impacto en la mortalidad no ha sido suficientemente estudiado. El objetivo fue evaluar la relacion entre la tasa de filtracion glomerular al ano (TFG) y la mortalidad en el seguimiento. Metodos Se analizo la TFG de 316 pacientes vivos al ano del trasplante mediante la formula abreviada Modification of Diet in Renal Disease Study. Se clasificaron en tres grupos segun su TFG ( Resultados No hubo diferencias en el numero de rechazos ni infecciones durante el primer ano en los tres grupos. En el seguimiento medio (6,3 anos) fallecio el 74% de los pacientes con TFG Conclusiones La disfuncion grave de la funcion renal al ano es un predictor independiente de mortalidad por todas las causas a largo plazo en el paciente con trasplante cardiaco.

Prognostic Value of Glomerular Filtration Rate 1 Year After Heart Transplantation

INTRODUCTION AND OBJECTIVES The development of renal failure is one of the most important problems after heart transplantation (HT), but the wide range of definitions means that estimates of its prevalence vary considerably. Furthermore, its impact on mortality has not been adequately studied. The objective was to investigate the relationship between the glomerular filtration rate (GFR) 1 year after transplantation and mortality during follow-up. METHODS The GFR was determined in 316 patients still living 1 year after transplantation using the abbreviated Modification of Diet in Renal Disease Study formula. Patients were divided into three groups according to GFR (i.e. <30, 30-59 and > or =60 mL/min per 1.73 m2) and pretransplant variables and rejection and infection rates within the first year were analyzed. The association between GFR at 1 year and mortality during follow-up was evaluated and reasons for the association were examined. RESULTS There was no difference in the number of rejections or infections in the first year between the three groups. During a mean follow-up period of 6.3 years, 74% of patients with a GFR <30 mL/min per 1.73 m2 died, compared with 24% and 30% of those with a GFR > or =60 and 30-59 mL/min per 1.73 m2, respectively. Survival analysis (i.e. Cox regression analysis) demonstrated a significant difference between patients with a GFR <30 mL/min per 1.73 m2 and other patients (P< .001). A very low GFR at 1 year was the only independent predictor that remained statistically significant on multivariate analysis (hazard ratio =2.87; 95% confidence interval, 1.52-5.41). CONCLUSIONS Severe renal dysfunction at 1 year was an independent predictor of long-term all-cause mortality in heart transplant patients.