Rationale A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function. Objective Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options. Methods and Results In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×105 or 5×105 cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P=0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P=0.014; 12 months: 140±171 versus 58±146 seconds, P=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients. Conclusions Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (105 cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.

Background and objectives: Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time.Design and setting: A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument.Results: Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role-physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 ؎ 10.2; female: 37.7 ؎ 10.8; P < 0.0001; diabetic: 37.3 ؎ 10.6; nondiabetic: 41.6 ؎ 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 ؎ 9.7; no: 40.3 ؎ 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 ؎ 10.0; no: 40.2 ؎ 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities.Conclusions: These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention.

Secular trends in dialysis therapy delivery require a frequent re-examination of outcomes in patients on renal replacement modalities. We examined four large cohorts of patients initiating peritoneal dialysis (PD) in 2000-2003 (total of >40 000 patients) to ascertain trends in patient outcomes, technique success, and predictors of both parameters of interest. Age, end-stage renal disease vintage, and diabetes were clear predictors of patient survival. Technique success was higher in patients on automated PD than in patients on continuous ambulatory PD. Center size was a powerful predictor of technique success. We conclude that the current state of PD in the United States is characterized by improving patient outcomes, higher technique success, and a predominance of use of cycler-based therapy. Several opportunities for improving technique success amenable to practice interventions have been identified.

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.)