Portal Angiogenesis in Chronic Liver Disease Patients Correlates with Portal Pressure and Collateral Formation.

BACKGROUND/AIMS: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. METHODS: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. RESULTS: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-ß, PDGFsRα, PDGF-AB and BB, CD163, TGF-ß VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, -pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.

Echocardiographic evaluation after pediatric heart transplant in Chile: initial application of a functional protocol with global longitudinal strain. / Evaluación ecocardiográfica de pacientes pediátricos post-trasplante cardiaco en Chile: Aplicación inicial de un protocolo funcional con Strain longitudinal global.

INTRODUCTION: The echocardiographic evaluation of patients after heart transplantation is a useful tool. However, it is still necessary to define an optimal follow-up protocol. OBJECTIVE: To describe the results of the application of a functional echocardiographic protocol in patients being followed after pediatric heart transplantation. PATIENTS AND METHOD: Alls patients being followed at our institution after pediatric heart transplantation underwent an echocardiographic examination with a functional protocol that included global longitudinal strain. Contemporaneous endomyocardial biopsy results and hemodynamic data were recorded. RESULTS: 9 patients were evaluated with our echocardiographic functional protocol. Of these patients, only 1 showed systolic left ventricular dysfunction according to classic parameters. However, almost all patients had an abnormal global longitudinal strain. Right ventricular systolic dysfunction was observed in all patients. No epidodes of moderate to severe rejectiom were recorded. No correlation was observed between these parameters and pulmonary artery pressure. CONCLUSIONS: Subclinical biventricular systolic dysfunction was observed in the majority of the patients in this study. No association with rejection episodes or pulmonary hypertension was observed, which may be related to the absence of moderate or severe rejection episodes during the study period, and to the small sample size. Long term follow-up of these patients may better define the clinical relevance of our findings.

[Results of a national program of pediatric heart transplantation: strengths and weakness]. / Resultados de un programa nacional de trasplante cardiaco pediátrico: fortalezas y debilidades.

Pediatric heart transplantation is an effective therapy to treat advanced heart failure in children. OBJECTIVES: To analyze the immediate and mid-term results of pediatric patients listed for heart transplantation. PATIENTS AND METHODS: Registration of patients admitted to our transplant protocol between October 2001 and July 2016 were reviewed, analyzing demographic data, diagnosis, status at the time of listing, waiting time until transplantation, donor data, use of ventricular assist device, hemodynamic data, complications and global mortality. RESULTS: Thirthy patients where included with a mean age of 9.4 years (1 month to 15 years). The most frequent diagnosis was dilated cardiomyopathy in 24 patients (80%). The status was I (urgency) in 19 cases and II in 11 cases. Ten patients died on the waiting list (33.3%) at an average of 52 days (13-139 days). Fourteen were transplanted (46.7%), with a waiting time of 199.6 days (4-586 days). Nine patients required mechanical support (30%). All patients received triple association of immunosuppression. One patient died 16 days post transplant due to primary graft failure (7.1%). The average follow-up was 43 months (0.5-159 months). Two patients died later on (82 and 55 months), both due to secondary rejection because of voluntary cessation of immunosuppressive therapy. Survival at 1 and 5 years was 93% and 74%, respectively. CONCLUSIONS: Our program has successfully transplanted 50% of patients enrolled, with good medium-term survival. A significant proportion of patients were listed as a medical emergency and 34.5% died on the waiting list.

Evaluación ecocardiográfica de pacientes pediátricos post-trasplante cardiaco en Chile: Aplicación inicial de un protocolo funcional con Strain longitudinal global / Echocardiographic evaluation after pediatric heart transplant in Chile: initial application of a functional protocol with global longitudinal strain

Resumen: Introducción: La evaluación ecocardiográfica de pacientes post-trasplante cardiaco pediátrico es una herramienta útil. Sin embargo, aún es necesario definir un protocolo óptimo de seguimiento. Obje tivo: Caracterizar los resultados de la aplicación de un protocolo de evaluación ecocardiográfica fun cional en pacientes en control post-trasplante cardiaco pediátrico ortotópico. Pacientes y Método: Posterior al trasplante cardiaco pediátrico se realizó una ecocardiografía con un protocolo funcional que incluyó strain longitudinal global. Se evaluaron además los datos de la biopsia endomiocárdica y del estudio hemodinámico contemporáneos. Resultados: De un total de 9 pacientes sólo 1 presentó disfunción sistólica de ventrículo izquierdo según parámetros clásicos, pero casi la totalidad presentó un strain longitudinal global alterado. No se observaron episodios de rechazo moderado o severo en estos pacientes. Todos los pacientes presentaban disfunción sistólica ventricular derecha. No se ob servó correlación entre estos parámetros y la presión de arteria pulmonar. Conclusiones: Se observó disfunción sistólica biventricular subclínica en la mayoría de los pacientes de esta serie. No hubo aso ciación con episodios de rechazo o con hipertensión pulmonar, lo que podría estar en relación con la ausencia de episodios de rechazo moderado o severo en la biopsia contemporánea y con el reducido tamaño muestral. Sólo el seguimiento a largo plazo de estos pacientes permitirá definir la relevancia clínica de los hallazgos descritos.

Abstract: Introduction: The echocardiographic evaluation of patients after heart transplantation is a useful tool. However, it is still necessary to define an optimal follow-up protocol. Objective: To describe the results of the application of a functional echocardiographic protocol in patients being followed after pediatric heart transplantation. Patients and Method: Alls patients being followed at our institution after pediatric heart transplantation underwent an echocardiographic examination with a functional protocol that included global longitudinal strain. Contemporaneous endomyocardial biopsy results and hemodynamic data were recorded. Results: 9 patients were evaluated with our echocardiographic functional protocol. Of these patients, only 1 showed systolic left ventricular dysfunction according to classic parameters. However, almost all patients had an abnormal global longitudinal strain. Right ventricular systolic dysfunction was observed in all patients. No epidodes of moderate to severe rejectiom were recorded. No correlation was observed between these parameters and pulmonary artery pressure. Conclusions: Subclinical biventricular systolic dysfunction was observed in the majority of the patients in this study. No association with rejection episodes or pulmonary hypertension was observed, which may be related to the absence of moderate or severe rejection episodes during the study period, and to the small sample size. Long term follow-up of these patients may better define the clinical relevance of our findings.

Resultados de un programa nacional de trasplante cardiaco pediátrico: fortalezas y debilidades / Results of a national program of pediatric heart transplantation: strengths and weakness

El trasplante cardiaco pediátrico es una terapia efectiva para tratar la insuficiencia cardiaca avanzada. Objetivos: Analizar los resultados inmediatos y a mediano plazo de niños enlistados para trasplante cardiaco. Pacientes y Método: Se analizó el registro de pacientes enlistados para trasplante, entre octubre de 2001 y julio de 2016, analizando datos demográficos, diagnósticos, status de enlistamiento, tiempo de espera, datos de donantes, uso de asistencia ventricular, complicaciones y mortalidad. Resultados: La serie abarca 30 pacientes con edad promedio de 9,4 años (1 mes a 15 años). El diagnóstico principal fue miocardiopatía dilatada en 24 pacientes (80%). El status de ingreso fue I (urgencia) en 19 casos y II (no urgencia) en 11. Fallecieron 10 en la lista de espera (33,3%) en un promedio de 52 días (13 a 139 días). Catorce pacientes fueron trasplantados (46.7%), con un tiempo de espera de 199,6 días (4 a 586 días). Requirieron asistencia ventricular 9 pacientes (30%). Todos recibieron inmunosupresión tri asociada. Un paciente falleció a los 16 días por falla primaria del injerto (7,1%). El seguimiento promedio fue de 43 meses (0,5 a 159 meses). Dos pacientes fallecieron alejadamente (55 y 82 meses) por rechazo secundario al abandono de tratamiento inmunosupresor. La supervivencia a 1 y 5 años fue 93% y 74%, respectivamente. Conclusiones: Nuestro programa ha trasplantado al 50% de los pacientes enlistados con buena supervivencia a mediano plazo. Una proporción significativa de pacientes se enlistó con carácter de urgencia y un 34.5% de los pacientes fallecieron en la lista de espera.

Pediatric heart transplantation is an effective therapy to treat advanced heart failure in children. Objectives: To analyze the immediate and mid-term results of pediatric patients listed for heart transplantation. Patients and Methods: Registration of patients admitted to our transplant protocol between October 2001 and July 2016 were reviewed, analyzing demographic data, diagnosis, status at the time of listing, waiting time until transplantation, donor data, use of ventricular assist device, hemodynamic data, complications and global mortality. Results: Thirthy patients where included with a mean age of 9.4 years (1 month to 15 years). The most frequent diagnosis was dilated cardiomyopathy in 24 patients (80%). The status was I (urgency) in 19 cases and II in 11 cases. Ten patients died on the waiting list (33.3%) at an average of 52 days (13-139 days). Fourteen were transplanted (46.7%), with a waiting time of 199.6 days (4-586 days). Nine patients required mechanical support (30%). All patients received triple association of immunosuppression. One patient died 16 days post transplant due to primary graft failure (7.1%). The average follow-up was 43 months (0.5-159 months). Two patients died later on (82 and 55 months), both due to secondary rejection because of voluntary cessation of immunosuppressive therapy. Survival at 1 and 5 years was 93% and 74%, respectively. Conclusions: Our program has successfully transplanted 50% of patients enrolled, with good medium-term survival. A significant proportion of patients were listed as a medical emergency and 34.5% died on the waiting list.