A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia.

BACKGROUND: Critical limb ischemia portends a risk of major amputation of 25% to 35% within 1 year of diagnosis. Preclinical studies provide evidence that intramuscular injection of autologous CD34+ cells improves limb perfusion and reduces amputation risk. In this randomized, double-blind, placebo-controlled pilot study, we evaluated the safety and efficacy of intramuscular injections of autologous CD34+ cells in subjects with moderate or high-risk critical limb ischemia, who were poor or noncandidates for surgical or percutaneous revascularization (ACT34-CLI). METHODS AND RESULTS: Twenty-eight critical limb ischemia subjects were randomized and treated: 7 to 1 × 10(5) (low-dose) and 9 to 1 × 10(6) (high-dose) autologous CD34+ cells/kg; and 12 to placebo (control). Intramuscular injections were distributed into 8 sites within the ischemic lower extremity. At 6 months postinjection, 67% of control subjects experienced a major or minor amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.137). This trend continued at 12 months, with 75% of control subjects experiencing any amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.058). Amputation incidence was lower in the combined cell-treated groups compared with control group (6 months: P=0.125; 12 months: P=0.054), with the low-dose and high-dose groups individually showing trends toward improved amputation-free survival at 6 months and 12 months. No adverse safety signal was associated with cell administration. CONCLUSIONS: This study provides evidence that intramuscular administration of autologous CD34+ cells was safe in this patient population. Favorable trends toward reduced amputation rates in cell-treated versus control subjects were observed. These findings warrant further exploration in later-phase clinical trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00616980.

Midterm outcomes from the TALON Registry: treating peripherals with SilverHawk: outcomes collection.

PURPOSE: To determine midterm clinical outcomes among patients with lower extremity peripheral arterial disease who underwent revascularization with catheter-based plaque excision (PE). METHODS: Between August 2003 and February 2005, 19 institutions participating in the observational, nonrandomized, multicenter TALON registry enrolled 601 consecutive patients (353 men; mean age 70+/-11, range 36-98) with 1258 symptomatic lower extremity atherosclerotic lesions (748 limbs) treated by plaque excision with the SilverHawk catheter. Approximately 50% of the patients had diabetes, and nearly one third of the procedures were indicated for Rutherford ischemia category > or =4. Mean lesion lengths above and below the knee, respectively, were 62.5+/-68.5 mm (interquartile range [IQR], 20.0-80.0) and 33.4+/-42.7 mm (IQR 15.0-37.5). The primary endpoints of the study were target lesion revascularization (TLR) at 6 and 12 months. RESULTS: The device achieved < or =50% residual diameter stenosis in 94.7% of lesions; procedural success was 97.6%. Nearly half (41.9%) of the procedures involved PE of > or =2 lesions. Nearly three quarters (73.3%) of the lesions did not require adjunctive therapy, and stent placement following PE occurred in only 6.3% of lesions. The 6- and 12-month rates of survival free of TLR were 90% and 80%, respectively. Rates of TLR were similar among patients with diabetes (11%) and without diabetes (9%). In the multivariate analysis, significant predictors of TLR at 6 months were a history of MI or coronary revascularization (HR 5.49, 95% CI 1.87 to 16.10, p=0.0008), multiple (> or =2) lesions (HR 1.37, 95% CI 1.11 to 1.70, p=0.0019), and increasing Rutherford category (HR 1.84, 95% CI 1.28 to 2.65, p=0.0003). Lesion length >50 mm was associated with a 2.9-fold increased risk for TLR (HR 2.88, 95% CI 1.18 to 7.01, p=0.012); lesion length >100 mm was associated with a 3.3-fold increase in TLR (HR 3.32, 95% CI 1.15 to 9.56, p=0.016). CONCLUSION: In patients undergoing revascularization for lower extremity atherosclerotic disease, catheter-based PE achieves favorable procedural success and avoids the need for repeat revascularization at midterm follow-up. These findings support PE as a primary endovascular therapy for patients undergoing lower extremity arterial revascularization.

Durable clinical benefit following Sr90 Beta irradiation therapy for in-stent restenosis in high-volume community practice.

Although randomized clinical trials have demonstrated efficacy of coronary irradiation versus placebo for the treatment of in-stent restenosis (ISR), durable long-term benefit in community practice is less well defined. From January 1, 2001, through June 30, 2002, consecutive percutaneous coronary intervention (n = 3,869) were analyzed at our center with a total of 330 patients undergoing coronary irradiation for ISR (53, Ir192; 12, P32; 265 Novoste Sr90). Novoste Sr90 was successfully performed in 265 of 270 (98%) of patients attempted by 10 operators. The mean patient age was 63 years (range 35 90) with 55% male (145/265) and 45% female (120/265). ISR anatomic subsets included multi-lesion (45/265; 17%), multi-vessel (27/265; 10.0%) and saphenous vein graft (16/265; 6.0%) interventions. At a mean follow-up of 10.5 2.8 (SD) months, fifty-three (20%) of the Novoste Sr90 treated patients had returned for symptoms requiring repeat angiography. Of these, 23 patients had repeat percutaneous coronary intervention (PCI) including 2 target site revascularizations (TSR), twelve non-TSR (distinct from the radiated segment of the target vessel), and 9 non-target vessel revascularizations (TVR). Coronary artery bypass surgery was performed in 11 total patients, 4 due to TSR, and 7 due to non-TVR. Clinical TSR was 2.3% (6/265) and TVR was 6.8% (18/265). In conclusion, the Novoste SR90 Beta-Cath System for the treatment of ISR is associated with a high procedural success rate and low TSR and TVR. Revascularization in follow-up is predominantly due to progressive disease outside the radiated segment and aggressive secondary prevention, especially prolonged anti-platelet therapy, appear critical to long-term procedural success.