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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 (1×10(5) or 5×10(5) 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 (10(5) 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: After conventional treatment of in-stent restenosis, the incidence of recurrent clinical restenosis may approach 40%. We report the first multicenter, blinded, and randomized trial of intracoronary radiation with the use of a 90Sr/90Y beta-source for the treatment of in-stent restenosis., Methods and Results: After successful catheter-based treatment of in-stent restenosis, 476 patients were randomly assigned to receive an intracoronary catheter containing either 90Sr/90Y (n=244) or placebo (n=232) sources. The prescribed dose 2 mm from the center of the source was 18.4 Gy for vessels between 2.70 and 3.35 mm in diameter and 23.0 Gy for vessels between 3.36 and 4.0 mm. The primary end point, ie, clinically driven target-vessel revascularization by 8 months, was observed in 56 (26.8%) of the patients assigned to placebo and 39 (17.0%) of the patients assigned to radiation (P=0.015). The incidence of the composite including death, myocardial infarction, and target-vessel revascularization was observed in 60 (28.7%) of the patients assigned to placebo and 44 (19.1%) of the patients assigned to radiation (P=0.024). Binary 8-month angiographic restenosis (> or =50% diameter stenosis) within the entire segment treated with radiation was reduced from 45.2% in the placebo-treated patients to 28.8% in the 90Sr/90Y-treated patients (P=0.001). Stent thromboses occurred in 1 patient assigned to placebo <24 hours after the procedure and in 1 patient assigned to 90Sr/90Y at day 244., Conclusions: The results of this study demonstrated that beta-radiation using 90Sr/90Y is both safe and effective for preventing recurrence in patients with in-stent restenosis.

Background: Pulmonary sequestration is not believed to be familial. We report two male infants with this anomaly who were born to the same parents., Cases: The prenatal diagnosis of pulmonary sequestration was made in a woman's two consecutive pregnancies by demonstrating systemic arterial supply to an echogenic mass located in the left lower lung of each fetus. Postnatal radiographic evaluation confirmed the prenatal diagnoses., Conclusion: Recurrent pulmonary sequestration in two male offspring from the same parents raises the possibility of a genetic predisposition for this condition.

Background: The presence of angiographically identified intracoronary thrombus has been variably associated with complications after coronary angioplasty. Angiography has been shown to be less sensitive than angioscopy for detecting subtle details of intracoronary morphology, such as intracoronary thrombi. The clinical importance of thrombi detectable by angioscopy but not by angiography is not known., Methods and Results: Percutaneous coronary angioscopy was performed in 122 patients undergoing conventional coronary balloon angioplasty (PTCA) at six medical centers. Unstable angina was present in 95 patients (78%) and stable angina in 27 (22%). Therapy was not guided by angioscopic findings, and no patient received thrombolytic therapy as an adjunct to angioplasty. Coronary thrombi were identified in 74 target lesions (61%) by angioscopy versus only 24 (20%) by angiography. A major in-hospital complication (death, myocardial infarction, or emergency bypass surgery) occurred in 10 of 74 patients (14%) with angioscopic intracoronary thrombus, compared with only 1 of 48 patients (2%) without thrombi (P = .03). In-hospital recurrent ischemia (recurrent angina, repeat PTCA, or abrupt occlusion) occurred in 19 of 74 patients (26%) with angioscopic intracoronary thrombi versus only 5 of 48 (10%) without thrombi (P = .03). Relative risk analysis demonstrated that angioscopic thrombus was strongly associated with adverse outcomes (either a major complication or a recurrent ischemic event) after PTCA (relative risk, 3.11; 95% CI, 1.28 to 7.60; P = .01) and that angiographic thrombi were not associated with these complications (relative risk, 0.85; 95% CI, 0.36 to 2.00; P = .91)., Conclusions: The presence of intracoronary thrombus associated with coronary stenoses is significantly underestimated by angiography. Angioscopic intracoronary thrombi, the majority of which were not detected by angiography, are associated with an increased incidence of adverse outcomes after coronary angioplasty.

Background: Antithromboxane therapy with aspirin reduces acute procedural complications of coronary angioplasty (PTCA) but has not been shown to prevent restenosis. The effect of chronic aspirin therapy on long-term clinical events after PTCA is unknown, and the utility of more specific antithromboxane agents is uncertain. The goal of this study was to assess the effects of aspirin (a nonselective inhibitor of thromboxane A2 synthesis) and sulotroban (a selective blocker of the thromboxane A2 receptor) on late clinical events and restenosis after PTCA., Methods and Results: Patients (n = 752) were randomly assigned to aspirin (325 mg daily), sulotroban (800 mg QID), or placebo, started within 6 hours before PTCA and continued for 6 months. The primary outcome was clinical failure at 6 months after successful PTCA, defined as (1) death, (2) myocardial infarction, or (3) restenosis associated with recurrent angina or need for repeat revascularization. Neither active treatment differed significantly from placebo in the rate of angiographic restenosis: 39% (73 of 188) in the aspirin-assigned group, 53% (100 of 189) in the sulotroban group, and 43% (85 of 196) in the placebo group. In contrast, aspirin therapy significantly improved clinical outcome in comparison to placebo (P = .046) and sulotroban (P = .006). Clinical failure occurred in 30% (49 of 162) of the aspirin group, 44% (73 of 166) of the sulotroban group, and 41% (71 of 175) of the placebo group. Myocardial infarction was significantly reduced by antithromboxane therapy: 1.2% in the aspirin group, 1.8% in the sulotroban group, and 5.7% in the placebo group (P = .030)., Conclusions: Thromboxane A2 blockade protects against late ischemic events after angioplasty even though angiographic restenosis is not significantly reduced. While both aspirin and sulotroban prevent the occurrence of myocardial infarction, overall clinical outcome appears superior for aspirin compared with sulotroban. Therefore, aspirin should be continued for at least 6 months after coronary angioplasty.

A multicenter, double-blind, placebo-controlled trial was conducted to determine if corticosteroids influence the development of restenosis after successful percutaneous transluminal coronary angioplasty (PTCA). Either placebo or 1.0 g methylprednisolone (steroid) was infused intravenously 2-24 hours before planned PTCA in 915 patients. The PTCA patient success rate was 87% (mean) in the eight centers. There were no differences in clinical or angiographic baseline variables between the two groups. End-point analysis (angiographic restenosis, death, recurrent ischemia necessitating early restudy, and coronary artery bypass graft surgery) showed that there was no significant difference comparing placebo- with steroid-treated patients. Angiographic restudy showed the lesion restenosis rate to be 39% (120 of 307 lesions) after placebo and 40% (117 of 291) after steroid treatment (p = NS). We conclude that pulse steroid pretreatment does not influence the overall restenosis rate after successful PTCA.

Adaptation to exercise or the "warm up phenomenon" has been observed in some patients with angina pectoris. To investigate adaptation, eleven patients with exertional angina pectoris and angiographic evidence of coronary artery disease underwent two identical bouts of sequential tachycardia stress separated by a brief recovery period. Manifestations of ischemia were less during the second stress, as evidenced by a reduction in the severity of angina pectoris, less ST segment depression, and improved lactate extraction. Peak coronary blood flow during the second stress (81 +/- 20 ml/min) was not significantly different from that during the first (95 +/- 32 ml/min). Regional myocardial oxygen consumption, however, was significantly (p = .03) lower during the second stress (8.8 +/- 2.4 ml O2/min) when compared with the first (11.4 +/- 3.0 ml O2/min). Thus, patients with coronary artery disease can develop anginal tolerance to the stress of tachycardia similar to that observed after repeated bouts of exercise. A relative reduction in myocardial oxygen consumption, rather than an increase in coronary blood flow, appears to account for this phenomenon.