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Purpose: To compare by intravascular ultrasound (IVUS) the efficacy of delivering the prescribed dose to the adventitia between two commonly used dose prescriptions for intracoronary radiotherapy. Methods and Materials: In 59 human postangioplasty coronary vessels, one IVUS cross-section (1 mm thick) with the highest plaque burden was used for creating dose-volume histograms with different hypothetical positions of the source. Results: On average, prescription to 1 mm beyond lumen surface resulted in delivery of the prescribed dose (20 Gy ± 20%) to a higher fraction of adventitial volume than with the prescription to 2 mm from the source, with source placed in vessel center, lumen center, or in the IVUS catheter position. Source placement in the lumen center resulted in a low dose heterogeneity to the adventitia and the least dose heterogeneity to the intima. Conclusions: Prescription to 1 mm beyond lumen surface appeared more effective in delivering the prescribed dose to the adventitia than the American Association of Physicists in Medicine (AAPM) recommended prescription to 2 mm from the source center. Moreover, centering the source in the lumen provides the better balance of effective adventitial targeting and intimal dose homogeneity. Modification of the current AAPM recommendation for dose prescription for intracoronary radiotherapy should be considered.

Background —The data on the long-term safety and efficacy of intracoronary β-radiation in animal models are limited. Methods and Results —A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by β-radiation from a centered 32 P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n=2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15±0.17 versus 1.80±0.08 mm 2 , P =0.06) and larger external elastic lamina areas (3.32±0.21 versus 2.62±0.10 mm 2 , P =0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58±0.33, 3.16±0.35, and 8.12±0.42 mm 2 for irradiated vessel segments; these values were not different from those in controls (3.21±0.15, 2.84±0.27, and 7.76±0.28 mm 2 , respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen. Conclusion —In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary β-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment.

A 62-year–old man presented with progressive exertional dyspnea and angina. His past medical history is notable for coronary artery disease, for which he underwent a coronary artery bypass graft surgery 8 years earlier. A few years afterward, he underwent aortic valve (AV) bypass (AVB) surgery for severe aortic stenosis (AS) using an apicoaortic conduit to the descending aorta consisting of a 16-mm connector and an 18-mm valved conduit (Hancock valve; Medtronic, Minneapolis, MN; Figures 1 and 2; online-only Data Supplement Movie I). After a period of initial improvement in symptoms, the patient developed progressive dyspnea and angina and was referred for additional cardiac workup. Figure 1. An ECG-gated thin-slice contrast-enhanced cardiac computed tomography scan showing a heavily calcified native aortic valve (AV), hypertrophied left ventricle (LV), and the apical LV insertion site of the apicoaortic valved conduit. Figure 2. A 3-dimensional cardiac computed tomography reconstruction image showing the apicoaortic valved conduit, extending from its apical insertion site into the left ventricle (LV) to its insertion site into the descending aorta. Arrow , Conduit valve. The patient underwent a bicycle ergometer test, which showed a diminished functional capacity and was stopped because of fatigue and a hypotensive response. He underwent a 2-dimensional transthoracic echocardiogram with gradual dobutamine infusion. He was found to have a heavily calcified AV (online-only Data Supplement Movie II) with a rest mean transvalvular gradient of 34 mm Hg and velocity of 3.5 m/s, which increased to 50 mm Hg and 4.8 m/s, respectively, at peak dobutamine dose (Figure 3). This corresponded with a …

BACKGROUND Gene therapy has been proposed as a possible solution to the problem of restenosis after coronary angioplasty. The current study was undertaken to assess conventional methods of gene transfer and to develop percutaneous techniques for introducing genes directly into the coronary arteries of large mammals. Since the anticipated targets of gene therapy against restenosis include atherosclerotic and previously instrumented arteries, we also evaluated gene transfer in atherosclerotic coronary arteries and in two porcine models of restenosis: one using intracoronary stents and a second using balloon overstretch angioplasty. METHODS AND RESULTS The conventional method of using perforated balloon catheters to deliver Lipofectin-DNA complexes directly into the coronary arteries of intact animals was applied to 18 porcine coronary arteries including normal arteries, hypercholesterolemic arteries, and those simulating restenosis. The results of this study were consistent with previously published results indicating that only low levels of luciferase gene expression could be obtained by Lipofectin-mediated gene transfer. We therefore undertook a second, parallel study to evaluate percutaneous transluminal in vivo gene transfer using a replication-deficient adenoviral vector. A comparison of the two studies revealed that the mean level of reporter gene expression in the cohort undergoing adenoviral infection was 100-fold higher than in the cohort undergoing Lipofection. Analysis of luciferase activity over time in normal arteries revealed that recombinant gene expression was half-maximal after 1 day, peaked within 1 week, was still half-maximal at 2 weeks, and declined to low levels by 4 weeks. Histochemical analysis of coronary arteries treated with a second adenovirus expressing a nuclear-localized beta-galactosidase gene demonstrated gene transfer to a limited number of cells in the media and adventitia. Immunohistochemical analysis of Ad5-infused arteries using a monoclonal antibody directed against CD44 identified a periadventitial infiltrate composed of leukocytes. CONCLUSIONS The recombinant adenoviral vectors proved to be far more effective than Lipofectin at delivering foreign genes directly into the coronary arteries of living mammals. Furthermore, the influences of hypercholesterolemia and arterial injury appeared to have little effect on the levels of gene expression obtained using either method. The results demonstrate that low-level recombinant gene expression, the major obstacle impeding gene therapy for the prevention of restenosis, can potentially be overcome by using adenoviral vectors to mediate coronary gene transfer in vivo. The duration of gene expression provided by these vectors and their effective deployment in atherosclerotic, balloon-overstretched, and stented coronary arteries suggest that recombinant adenovirus may have potential for evaluating gene therapy in the clinically informative porcine models of coronary restenosis.

Intravascular brachytherapy may cause "exaggerated" vessel remodeling with late incomplete apposition in segments that have little disease, which are exposed to higher radiation doses. The long-term clinical impact of this finding is unclear.

Importance The US Food and Drug Administration recently approved the use of a transcatheter aortic valve in patients for whom traditional valve replacement surgery poses a high or prohibitive risk. Our hospital was one of the first Veterans Affairs facilities to launch a transcatheter aortic valve replacement (TAVR) program. Objective To evaluate our early experience with transfemoral TAVR. Design and Setting We retrospectively reviewed the records of all patients who underwent TAVR during the first year of our program at the Department of Cardiothoracic Surgery, Michael E. DeBakey Veterans Affairs Medical Center. Participants The mean (SD) age of the patients was 77 (9) years, and their mean (SD) Society of Thoracic Surgeons predicted risk of mortality score was 8.8 (10.7). Interventions All patients underwent TAVR with the SAPIEN transcutaneous valve. Main Outcome Measures We evaluated operative mortality and major operative morbidity (stroke, myocardial infarction, renal failure necessitating dialysis, and requirement for mechanical circulatory support, as well as vascular complications and requirement for permanent pacemaker), in addition to length of hospital stay and discharge status. Results Between December 21, 2011, and December 13, 2012, a total of 19 transfemoral TAVR procedures were performed at our center. Implantation was successful in all cases. There were no reports of operative (30-day) mortality, prosthetic valve endocarditis, renal failure necessitating dialysis, perioperative myocardial infarction or stroke, or conversion to surgical aortic valve replacement. Seven patients (37%) had mild paravalvular leak, 3 patients (16%) had moderate paravalvular leak, 2 patients (11%) had groin wound complications, 2 patients (11%) required a permanent pacemaker, 1 patient (5%) had a vascular access complication requiring endovascular repair, and 1 patient (5%) required temporary circulatory support (with extracorporeal membrane oxygenation). The mean (SD) length of hospital stay after TAVR was 8.0 (5.9) days. All patients were discharged home. Conclusions and Relevance Transcatheter aortic valve replacement can be performed safely and with good outcomes at a Veterans Affairs facility with a committed multidisciplinary team and substantial experience in heart valve and endovascular therapies.

Side branch occlusion may occur in the course of percutaneous transluminal coronary angioplasty (PTCA), particularly if complicated by site dissection. Concern that the additional placement of a stent may further jeopardize side branches is logical. Consequently, this study analyzed pre-PTCA, post-PTCA, poststent, and 6-month follow-up angiograms of 100 consecutive patients in whom 103 Gianturco-Roubin stents were implanted for acute or threatened closure after PTCA. Side branches were defined as major (>50% of the stented vessel diameter) and minor ( 50% stenosis), and 129 minor branches were analyzed. Seven major branches (6%), all of which were diseased before PTCA, and 23 minor branches (18%) were lost after PTCA. Immediately after stent insertion, only 1 additional major and 1 minor branch were lost, whereas 2 of 7 major (29%) and 9 of 23 minor (39%) branches reappeared. At follow-up angiography, 7 major branches (6%) were more stenosed and 6 (6%) were improved compared with the angiogram before PTCA. Only 2 major (2%) and 5 minor (4%) branches remained occluded. Additionally, 2 major and 1 minor branch, which were patent after PTCA and stenting, were occluded at follow-up as a result of total occlusion of the stented segment. It is concluded that: (1) stent implantation is rarely associated with side branch loss; (2) more typically, recovery of patency of branches occluded by PTCA occurs immediately after stenting; (3) as a delayed effect, a stent may facilitate later reopening of branches occluded after PTCA; and (4) excellent patency of branches of the stented segment is maintained in the followup period.