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.)

We presented the results of our prospective trial of the Bard CathLink 20 in outpatient therapeutic plasma exchange in May 2000. Since the close of that study, three of the original subjects and one additional subject have received continuous outpatient treatment using the device. We report herein on its long-term use. Four patients with demyelinating polyneuropathy underwent outpatient plasma exchange of 1-1 1/4 plasma volumes using Bard CathLink 20 venous access devices for up to 2 1/2 years. Treatment schedules varied according to the status of the patient's neuropathy. Four men (age 59, 60, 76, 79) underwent 55, 56, 38, and 41 plasma exchanges over 18.5, 18, 20, and 38.5 months, respectively, all in the outpatient setting. Ninety-one percent were completed in <150 min (mean 120 +/- 28 min) with 3,783 +/- 314 ml of plasma removed. Mean access flow rates were approximately 70 +/- 11 ml/min. Plasma flow rates were approximately 38 +/- 6 ml/min. (During our original 6-month prospective trial, access and plasma flow rates were approximately 54 and 32 ml/min, respectively). There were no adverse effects resulting from use of the CathLink and no hospitalizations were needed for plasma exchange. Pressure alarms were infrequent. Access and plasma flow rates achieved with the CathLink 20 have increased by about 30 and 16%, respectively, with long-term use. The conclusion from our prospective trial of this device, that it could conveniently be used for long-term outpatient plasma exchange, is supported by our follow-up experience.

M-proteins are monoclonal immunoglobulins or immunoglobulin fragments that aberrantly accumulate in the plasma. Hemodialysis (HD) patients with M-proteins may, under certain circumstances, also need therapeutic plasma exchange (TPE). We employed a protocol for tandem TPE/HD in patients with M-protein disorders. We followed the urea reduction ratio (URR), a measure of the efficiency of HD, to compare the effect of TPE on HD efficiency during tandem procedures versus the efficiency of HD performed as a stand-alone procedure in the same patients. Three men (J.M., R.T., M.M.) underwent 23, 80, and 25 tandem TPE/HD over 3, 17, and 7 months, respectively, almost all in the outpatient setting. Mean whole blood flow rate (in ml/min) was slower during hemodialysis alone than during TPE/HD for J.M. (289 +/- 24 vs. 332 +/- 22, P < 0.0001) and R.T. (310 +/- 20 vs. 367 +/- 15, P < 0.0001) but not for M.M. (395 +/- 65 vs. 404 +/- 62, P = 0.6844). URR was equivalent during hemodialysis alone and during TPE/HD for J.M. (54 +/- 4.2 vs. 58 +/- 1.4, P = 0.3333), R.T. (69 +/- 4.9 vs. 70 +/- 2.5, P = 0.9804), and M.M. (71 +/- 2.4 vs. 67 +/- 1.5, P = 0.1143). J.M.'s renal function recovered sufficiently to permit discontinuation of hemodialysis. R.T. experienced both subjective and objective improvement of his arthritic symptoms. M.M. achieved hemostatic control but ultimately died of amyloidosis. TPE/HD is feasible using disparate pieces of equipment when the therapeutic plasma exchange circuit is connected in parallel with the low-pressure side of the hemodialysis circuit. Our experience illustrates that therapeutic plasma exchange did not adversely impact hemodialysis when the two procedures were performed in tandem.