ABSTRACT
Cell therapy is an evolving option for patients with end-stage heart failure. First-generation cell therapy trials have had marginal success. Our goal was to evaluate retrograde delivery of allogeneic umbilical cord subepithelial cells (UCSECs) in patients with heart failure. A prospective open-label dose escalation study of the safety and feasibility of UCSECs infused retrogradely into the coronary sinus was performed. Patients received a single dose of either 100 million (M), 200M, or 400M cells. The patients were followed for 2 years. Twenty-four patients were successfully enrolled in the study. The patients had UCSEC infusion without procedure-related complications. The ejection fraction in patients receiving UCSECs demonstrated improvement compared to baseline; from 25.4% (±5.5) at screening to 34.9% (±4.1) at 12 months. End-systolic diameter decreased significantly from 59.9 (±5.3) mm to 52.6 (±2.7) mm (p < 0.05). Retrograde UCSEC delivery was safe and feasible in all three dosage groups. Patients receiving 200M and 400M UCSECs showed signs of early improvement in left ventricular ejection fraction (LVEF) and remodeling. This study provides the basis for a larger clinical trial in heart failure (HF) patients using the middle or high dose of UCSECs.
Subject(s)
Cell- and Tissue-Based Therapy/methods , Heart Failure/therapy , Umbilical Cord/cytology , Aged , Cell- and Tissue-Based Therapy/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Stroke Volume/physiology , Treatment Outcome , Ventricular Function, Left/physiologyABSTRACT
BACKGROUND: Chronic refractory angina is a challenging clinical problem with limited treatment options. The results of early cardiovascular stem cell trials using ABMMC have been promising but have utilized intracoronary or intramyocardial delivery. The goal of the study was to evaluate the safety and early efficacy of autologous bone marrow derived mononuclear cells (ABMMC) delivered via percutaneous retrograde coronary sinus perfusion (PRCSP) to treat chronic refractory angina (CRA). METHODS: From May 2005 to October 2006, 14 patients, age 68 +/- 20 years old, with CRA and ischemic stress-induced myocardial segments assessed by SPECT received a median 8.19*10(8) ± 4.3*10(8) mononuclear and 1.65*10(7) ± 1.42*10(7) CD34(+) cells by PRCSP. RESULTS: ABMMC delivery was successful in all patients with no arrhythmias, elevated cardiac enzymes or complications related to the delivery. All but one patient improved by at least one Canadian Cardiovascular Society class at 2 year follow-up compared to baseline (p < 0.001). The median baseline area of ischemic myocardium by SPECT of 38.2% was reduced to 26.5% at one year and 23.5% at two years (p = 0.001). The median rest left ventricular ejection fraction by SPECT at baseline was 31.2% and improved to 35.5% at 2 year follow up (p = 0.019). CONCLUSIONS: PRCSP should be considered as an alternative method of delivery for cell therapy with the ability to safely deliver large number of cells regardless of coronary anatomy, valvular disease or myocardial dysfunction. The clinical improvement in angina, myocardial perfusion and function in this phase 1 study is encouraging and needs to be confirmed in randomized placebo controlled trials.
Subject(s)
Angina Pectoris/therapy , Bone Marrow Transplantation/adverse effects , Coronary Sinus/pathology , Leukocytes, Mononuclear/transplantation , Perfusion/methods , Aged , Angina Pectoris/physiopathology , Chronic Disease , Coronary Sinus/physiopathology , Demography , Exercise , Feasibility Studies , Female , Humans , Male , Myocardial Perfusion Imaging , Tomography, Emission-Computed, Single-Photon , Transplantation, Autologous , Treatment Outcome , Ventricular Function, Left/physiologyABSTRACT
Fueron evaluadas 39 variables clínicas en 185 pacientes con diagnóstico definitivo de Infarto Agudo de Miocardio (I.A.M.). La mortalidad global dentro de los 30 días de iniciado el cuadro fue del 15.6 por ciento. La Clase Funcional Hemodinámico Clínica III (CFHC-III), I.A.M. con Onda Q, las complicaciones intrahospitalarias dentro de la primera semana: Arritmia Ventricular, BAV 3er G; Angina Post-infarto y extensión del infarto a la cara anterior, se correlacionan significativamente con una mortalidad intrahospitalaria elevada y por lo tanto son los mejores predictores de mortalidad a corto plazo. Pacientes admitidos al hospital dentro de las primeras 3 horas de iniciado el cuadro clínico y la presencia de Síntomas Neurovegetativos en la fase aguda se correlacionan significativamente con una menor mortalidad intrahospitalaria y por lo tanto son los mejores predictores de sobrevida a corto plazo. Se establece una tabla porcentual de mortalidad de acuerdo a la CFHC y demás covariables pronósticas permitiendo establecer cuatro niveles de estimación de riesgo de muerte: bajo, medio, alto y extremo. Determinar el tipo de I.A.M. y la CFHC al momento de la admisión hospitalaria y reconocer y vigilar la aparición de complicaciones inmediatas nos permitirá identificar pacientes de alto riesgo de muerte luego del I.A.M. para orientar una apropiada y oportuna intervención en el tratamiento médico y decidir una rápida y oportuna transferencia a la Unidad de Cuidados Coronarios (UCC), así como una mejor utilización de nuestros recursos.
