Background-We compared the therapeutic potential of purified mobilized human CD34ϩ cells with that of mobilized total mononuclear cells (tMNCs) for the preservation/recovery of myocardial tissue integrity and function after myocardial infarction (MI). Methods and Results-CD34ϩ cells were purified from peripheral blood tMNCs of healthy volunteers by magnetic cell sorting after a 5-day administration of granulocyte colony-stimulating factor. Phosphate-buffered saline (PBS), 5ϫ10 5 CD34

Background-A growing population of patients with coronary artery disease experiences angina that is not amenable to revascularization and is refractory to medical therapy. Preclinical studies have indicated that human CD34 ϩ stem cells induce neovascularization in ischemic myocardium, which enhances perfusion and function. Methods and Results-Twenty-four patients (19 men and 5 women aged 48 to 84 years) with Canadian Cardiovascular Society class 3 or 4 angina who were undergoing optimal medical treatment and who were not candidates for mechanical revascularization were enrolled in a double-blind, randomized (3:1), placebo-controlled dose-escalating study. Patients received granulocyte colony-stimulating factor 5 g · kg Ϫ1 · d Ϫ1 for 5 days with leukapheresis on the fifth day. Selection of CD34ϩ cells was performed with a Food and Drug Administration-approved device. Electromechanical mapping was performed to identify ischemic but viable regions of myocardium for injection of cells (versus saline). The total dose of cells was distributed in 10 intramyocardial, transendocardial injections. Patients were required to have an implantable cardioverterdefibrillator or to temporarily wear a LifeVest wearable defibrillator. No incidence was observed of myocardial infarction induced by mobilization or intramyocardial injection. The intramyocardial injection of cells or saline did not result in cardiac enzyme elevation, perforation, or pericardial effusion. No incidence of ventricular tachycardia or ventricular fibrillation occurred during the administration of granulocyte colony-stimulating factor or intramyocardial injections. One patient with a history of sudden cardiac death/ventricular tachycardia/ventricular fibrillation had catheter-induced ventricular tachycardia during mapping that required cardioversion. Serious adverse events were evenly distributed. Efficacy parameters including angina frequency, nitroglycerine usage, exercise time, and Canadian Cardiovascular Society class showed trends that favored CD34 ϩ cell-treated patients versus control subjects given placebo. Conclusions-A randomized trial of intramyocardial injection of autologous CD34ϩ cells in patients with intractable angina was completed that provides evidence for feasibility, safety, and bioactivity. A larger phase IIb study is currently under way to further evaluate this therapy. (Circulation. 2007;115:3165-3172.)

Background Multicenter longitudinal objective data for Fontan patients surviving into adulthood are lacking. Objectives Describe transplant-free survival and explore relationships between laboratory measures of ventricular performance and functional status over time. Methods Exercise testing, echocardiography, B-type natriuretic peptide (BNP), functional health assessment, and medical history abstraction were repeated 9.4 ± 0.4 years after the Fontan Cross-Sectional Study (Fontan 1) compared to previous values. Cox regression analysis explored risk factors for interim death or cardiac transplantation. Results From the original cohort of 546 subjects, 466 were recontacted and 373 (80%) were enrolled at 21.2 ± 3.5 years of age. Among subjects with paired testing, percent predicted maximum VO2 decreased (69 ± 14 vs. 61 ± 16, p <0.001, n = 95), ejection fraction decreased (58 ± 11 vs. 55 ± 10, p <0.001, n=259), and BNP increased (Median (IQR) 13 (7,25) vs. 18 (9,36) pg/mol, p <0.001, n = 340). At latest follow-up lower Pediatric Quality of Life Inventory (PedsQL) physical summary score was associated with poorer exercise performance (R2 adjusted = 0.20, p <0.001, n = 274). Cumulative complications since the Fontan included additional cardiac surgery (32%), catheter intervention (62%), arrhythmia treatment (32%), thrombosis (12%), and protein losing enteropathy (8%). Since Fontan 1, 54 subjects (10%) have received a heart transplant (n = 23) or died without transplantation (n = 31). The interval risk of death/transplantation was associated with poorer ventricular performance and functional health status assessed at Fontan 1, but was not associated with ventricular morphology, subject age or type of Fontan connection. Conclusions Interim transplant-free survival over 12 years in this Fontan cohort was 90% and was independent of ventricular morphology. Exercise performance decreased and was associated with worse functional health status. Future interventions might focus on preserving exercise capacity. (Clinical Trials Registration #: NCT00132782)

Objectives To describe growth patterns in infants with single ventricle physiology and determine factors influencing growth. Study design Data from 230 subjects enrolled in the Pediatric Heart Network Infant Single Ventricle Enalapril Trial were used to assess factors influencing change in weight-for-age z-score (Δz) from study enrollment (0.7 ± 0.4 months) to pre-superior cavopulmonary connection (SCPC) (5.1 ± 1.8 months, period 1), and pre-SCPC to final study visit (14.1 ± 0.9 months, period 2). Predictor variables included patient characteristics, feeding regimen, clinical center, and medical factors during neonatal (period 1) and SCPC hospitalizations (period 2). Univariate regression analysis was performed, followed by backward stepwise regression and bootstrapping reliability to inform a final multivariable model. Results Weights were available for 197/230 subjects for period 1 and 173/197 for period 2. For period 1, greater gestational age, younger age at study enrollment, tube feeding at neonatal discharge, and clinical center were associated with a greater negative Δz (poorer growth) in multivariable modeling (adjusted R2 = 0.39, p < 0.001). For period 2, younger age at SCPC and greater daily caloric intake were associated with greater positive Δz (better growth) (R2 = 0.10, p = 0.002). Conclusions Aggressive nutritional support and earlier SCPC are modifiable factors associated with a favorable change in weight-for-age z-score.