Long-term outcome of patients treated with repeat percutaneous coronary intervention after failure of gamma-brachytherapy for the treatment of in-stent restenosis.

BACKGROUND: Although (192)Ir intracoronary brachytherapy has been demonstrated to dramatically reduce the recurrence of in-stent restenosis, up to 24% of these patients will still require repeat target-vessel revascularization. The short- and long-term outcomes of repeat percutaneous intervention in this population have not been characterized. METHODS AND RESULTS: Analysis was performed of all patients enrolled in the GAMMA-I and GAMMA-II brachytherapy trials who underwent repeat percutaneous target lesion revascularization (TLR) because of restenosis. Subjects were divided into 2 cohorts: those who had received (192)Ir brachytherapy and those randomized to placebo. Forty-five (17.6%) of a total of 256 patients whose index treatment was intracoronary radiation therapy and 36 (29.8%) of 121 patients whose index treatment was placebo required repeat percutaneous TLR. The mean time to this first TLR was 295+/-206 days in the irradiated group and 202+/-167 days in the placebo group (P=0.03). Acute procedural success occurred in 100% of irradiated patients and 94% of placebo controls (P=0.19). After the first TLR, a subsequent TLR was required in 15 (33.3%) of 45 brachytherapy patients versus 17 (47.2%) of 36 placebo failure patients (P=0.26). There was no significant difference in time to second TLR between the 2 groups. Other long-term major adverse event rates in both groups were comparable to those of other contemporary angioplasty/stenting series. CONCLUSIONS: In those patients who "fail" (192)Ir intracoronary brachytherapy for in-stent restenosis, treatment with (192)Ir delays the time to first TLR. Additionally, repeat percutaneous intervention in these patients is safe and efficacious in the short term, with acceptable long-term results.

Comparison of rotational atherectomy with conventional balloon angioplasty in the prevention of restenosis of small coronary arteries: results of the Dilatation vs Ablation Revascularization Trial Targeting Restenosis (DART).

BACKGROUND: The optimum treatment of obstructive coronary disease in small (<3.0 mm diameter) arteries remains unknown. Rotational atherectomy is an approved treatment that might reduce the vascular injury during percutaneous coronary intervention compared with angioplasty. We report on a multicenter, randomized, blinded end point trial comparing rotational atherectomy with balloon angioplasty in the prevention of restenosis of obstructed small coronary arteries. METHODS: A total of 446 patients with myocardial ischemia associated with an angiographic stenosis in a native coronary artery 2 to 3 mm in diameter and < or =20 mm in length without severe calcification were randomly assigned to receive rotational atherectomy (n = 227) or balloon angioplasty (n = 219). The primary end point was target vessel failure at 12 months (defined as the composite of death, Q-wave myocardial infarction, and clinically driven repeat revascularization of the target vessel). RESULTS: The mean reference vessel diameter was 2.46 +/- 0.40 mm, the mean lesion length was 9.97 +/- 5.59 mm, and the prevalence of diabetes mellitus was 32%. Acute procedural success (91.6% for rotational atherectomy, 94.1% for balloon angioplasty, P =.36) and target vessel failure at 12 months were not significantly different (30.5% vs 31.2%, P =.98). At 8 months, there were no significant differences in minimum lumen diameter (1.28 +/- 0.63 mm vs 1.19 +/- 0.54 mm, P =.26), percent diameter stenosis (28% +/- 12% vs 29% +/- 15%, P =.59), binary restenosis rate (50.5% vs 50.5%, P = 1.0), or late loss index (0.57 vs 0.62, P =.7). No Q-wave myocardial infarctions occurred in either arm of the study, and non-Q-wave myocardial infarctions (defined as creatine kinase level >2 times normal with an elevated creatine kinase-myocardial band isoenzyme level) occurred in 2.2% and 1.4% of the patients in the rotational atherectomy and balloon angioplasty groups, respectively (P =.72). CONCLUSION: Rotational atherectomy was found to be safe in the treatment of obstructed small arteries, but lower rates of target vessel failure were not achieved compared with balloon angioplasty. Because the acute gain and loss index ratios of the 2 treatments were similar, there was no evident beneficial antirestenosis mechanism seen for rotational atherectomy.

Cutting balloon angioplasty for the prevention of restenosis: results of the Cutting Balloon Global Randomized Trial.

The cutting balloon (CB) is a specialized device designed to create discrete longitudinal incisions in the atherosclerotic target coronary segment during balloon inflation. Such controlled dilatation theoretically reduces the force needed to dilate an obstructive lesion compared with standard percutaneous transluminal coronary angioplasty (PTCA). We report a multicenter, randomized trial comparing the incidence of restenosis after CB angioplasty versus conventional balloon angioplasty in 1,238 patients. Six hundred seventeen patients were randomized to CB treatment, and 621 to PTCA. The mean reference vessel diameter was 2.86 +/- 0.49 mm, mean lesion length 8.9 +/- 4.3 mm, and prevalence of diabetes mellitus in patients was 13%. The primary end point, the 6-month binary angiographic restenosis rate, was 31.4% for CB and 30.4% for PTCA (p = 0.75). Acute procedural success, defined as the attainment of <50% diameter stenosis without in-hospital major adverse cardiac events, was 92.9% for CB and 94.7% for PTCA (p = 0.24). Freedom from target vessel revascularization was slightly higher in the CB arm (88.5% vs 84.6%, log-rank p = 0.04). Five coronary perforations occurred in the CB arm only (0.8% vs 0%, p = 0.03). At 270 days, rates of myocardial infarction, death, and total major adverse cardiac events for CB and PTCA were 4.7% versus 2.4% (p = 0.03), 1.3% versus 0.3% (p = 0.06), and 13.6% versus 15.1% (p = 0.34), respectively. In summary, the proposed mechanism of controlled dilatation did not reduce the rate of angiographic restenosis for the CB compared with conventional balloon angioplasty. CB angioplasty should be reserved for difficult lesions in which controlled dilatation is believed to provide a better acute result compared with balloon angioplasty alone.

The clinical evaluation of the Endeavor zotarolimus-eluting coronary stent in Japanese patients with de novo native coronary artery lesions: primary results and 3-year follow-up of the Endeavor Japan study.

BACKGROUND: Angiographic and clinical outcomes associated with coronary stents eluting the new molecular entity zotarolimus have been well characterized in a variety of geographies and patient subsets. The Endeavor Japan study is the first prospective clinical trial to evaluate the safety and efficacy of the Endeavor zotarolimus-eluting stent (ZES) in the treatment of Japanese patients with single de novo lesions in native coronary arteries. METHODS AND MATERIALS: This nonrandomized, prospective, multicenter, single-arm trial of 99 subjects with inclusion criteria (elective percutaneous revascularization of single native de novo coronary artery lesions with length ≥14 and ≤27 mm with reference vessel diameters between 2.25 and 3.5 mm) selected to enhance statistical comparability to the ENDEAVOR II randomized study as historical control. The primary end point was target vessel failure (TVF) at 9 months. RESULTS: At 9 months, the TVF rate was 5.2%, compared with 7.9% in the ZES arm of ENDEAVOR II (P=.412). Notable baseline differences between the Endeavor Japan and ENDEAVOR II populations were mean age (68.2 vs. 61.6 years; P<.001), diabetes (38.4% vs. 18.2%; P<.001), and unstable angina (4.6% vs. 30.3%; P<.001). Despite cohort differences, acute, 9-month, and 3-year clinical outcomes were similar in the two groups, as were 8-month angiographic indices. Finally, out to 3 years, no stent thrombosis was observed in Japanese subjects. CONCLUSIONS: These findings demonstrate that, in a Japanese population, the Endeavor ZES has similar safety and efficacy compared with other geographies, with sustained clinical benefit and safety to 3 years.

First-in-human study of the Endeavor ABT-578-eluting phosphorylcholine-encapsulated stent system in de novo native coronary artery lesions: Endeavor I Trial.

AIMS: The Endeavor I study was the first clinical study evaluating the safety and feasibility of the Endeavor stent system in the treatment of symptomatic coronary artery disease. The Endeavor Stent System comprises a new cytostatic, antiproliferative and immunosuppressive agent in the same class of drugs as sirolimus, (ABT-578), a phosphorylcholine polymer-based coating, and an established cobalt-alloy stent with thin struts, (Driver stent). METHODS AND RESULTS: One hundred consecutive patients with symptomatic ischemic heart disease due to de novo, obstructive lesions of native coronary arteries were treated with the Endeavor stent system at eight centers in Australia and New Zealand according to contemporary practice. The acute lesion, procedure, and device-deployment success rates were all 100%. Independent core laboratories analyzed quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) data immediately after stent implantation, and at 4 and 12 month follow-up. At 12 months, in-stent late lumen loss was 0.61+/-0.44 mm; in-segment late lumen loss was 0.43+/-0.44 mm, and neointimal hyperplasia volume was 14.2+/-11.8 mm3 (corresponding to a percent volume obstruction of 9.7%+/-8.5%). By QCA and IVUS, the pattern of neointimal hyperplasia was greatest within stent and not at the stent edges. The binary angiographic restenosis rate (defined as >50% diameter stenosis) at 4 and 12 months was 2.1% (2/97) and 5.4% (5/93) respectively. The cumulative incidence of major adverse cardiac events (MACE, defined as death, myocardial infarction, emergent cardiac surgery or repeat revascularization of the index lesion), was 1% at 30 days and 2% at 4 and 12 months. CONCLUSION: This 100 patient pilot study demonstrates that the Endeavor stent system is a reliable and safe treatment for obstructive coronary disease, providing durable event free clinical outcomes to 12 months by suppression of neointimal proliferation of the target lesion. The results support further pivotal evaluation in larger randomized clinical trials.

Thermoregulatory responses in post-coronary artery bypass surgery and healthy males during moderate exercise in warm and cool environments.

PURPOSE: The purpose of this study was to determine and compare the thermoregulatory and hemodynamic responses to moderate intensity exercise (60% of peak oxygen consumption [.VO(2peak)]) in warm (35 degrees C, 45% relative humidity) and cool (18 degrees C, 65% relative humidity) environments in men who had previously undergone coronary artery bypass graft (CABG) surgery and healthy control subjects, matched for age and body composition. METHODS: Fourteen post-CABG men and 16 healthy control subjects were recruited and walked 40 minutes at a moderate intensity, in randomized order, in warm and cool environments (on separate days). Measures of heart rate, systolic and diastolic blood pressures, rating of perceived exertion, core (rectal)(T(c)) and mean skin temperatures (T(sk)), oxygen consumption (.VO(2peak)), sweat rate, and blood lactate were taken. RESULTS: Both groups showed a larger increase (P <.05) in T(c) and rate-pressure product during exercise in the warm compared with the cool environment. However, T(c) and rate pressure product were significantly lower (P <.05), and systolic blood pressure decreased slightly with exercise duration (P <.05) in the CABG group compared with the control group in the warm environment. Heart rate, T(sk), percent .VO(2peak), blood lactate, sweat rate, and rating of perceived exertion did not differ significantly between the groups in either climate and no subject had ischemia or arrhythmia during test procedures. CONCLUSIONS: These results indicate that clinically stable men with revascularized coronary artery disease are able to cope as well as healthy controls with the thermoregulatory and cardiovascular demands of 40 minutes of moderate intensity exercise in warm and cool environments.

Angiographic outcome after intracoronary X-Sizer helical atherectomy and thrombectomy: first use in humans.

The objective of this study was to evaluate the early angiographic outcome in the first human subjects who underwent intracoronary atherectomy and thrombectomy using the X-Sizer helical cutting and aspiration system. Percutaneous coronary interventions in patients with thrombo-occlusive disease or friable degenerative saphenous vein grafts are associated with considerable periprocedural morbidity and mortality, predominantly related to microscopic distal embolization. X-Sizer catheter system is a novel atherectomy and thrombectomy device that consists of a helix cutter connected to a handheld motor drive unit and a vacuum collection chamber for aspiration of excised atheroma, thrombus, and debris. Quantitative coronary angiography was obtained in 14 patients before and after X-Sizer extraction atherectomy with adjunctive balloon angioplasty and stenting. Thirteen native coronary arteries and one saphenous vein graft were treated. Mean preprocedural reference vessel diameter was 3.06 +/- 0.66 mm. There were 71.4% AHA/ACC type B2 and C lesions. Preprocedural thrombus was present in nine patients and total occlusion in 64% of cases. Minimal luminal diameter was increased from 0.29 +/- 0.47 mm to 1.32 +/- 0.64 mm, a gain of 1.04 +/- 0.69 mm after atherectomy. Final total gain was 1.47 +/- 0.61 mm. Mean diameter stenosis was reduced from 89.3% to a final residual stenosis of 14.4%. Postatherectomy distal embolization occurred in one patient who had heavy preprocedural thrombus burden. No episodes of perforation, distal coronary spasm, abrupt closure, or slow/no-reflow occurred. The angiographic analysis of the first cohort of human subjects suggests that X-Sizer helical atherectomy is a feasible method of removing occlusive tissue or thrombus in coronary artery disease with a low angiographic complication rate. A large-scale randomized phase II clinical trial is underway to determine the ultimate safety and efficacy of this device in thrombo-occlusive native coronary arteries and saphenous vein grafts.