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Articles, see p 2218 and p 2227 Peripheral artery disease affects >200 million individuals worldwide, and those with exertional leg discomfort, rest pain, and tissue or limb loss have significantly impaired functional status and quality of life. Despite their lower associated risk of repeat revascularization, open surgical procedures have been largely supplanted by endovascular intervention for symptomatic peripheral artery disease given the lower associated morbidity and mortality.1 Although standalone plain-old percutaneous transluminal angioplasty (PTA) was previously the standard endovascular strategy for these patients, high procedural failure and restenosis rates led to the development of new therapeutic technologies.2 Stent implantation improved procedural success,3 and a recent meta-analysis of randomized trials suggests that bare metal stenting (BMS) results in half as much restenosis as PTA. Nevertheless, restenosis after femoropopliteal BMS occurs in up to 37% of patients within 12 months,4 and observational data suggest that by 5 years, primary patency rates are roughly equivalent (41±4% for BMS versus 36±3% for PTA; P =0.31).5 Drug-coated balloons (DCBs) were developed as means to further reduce restenosis rates.6 Currently available DCBs carry the antiproliferative agent paclitaxel, which stabilizes microtubules, preventing mitotic spindle formation and ultimately resulting in reduced neointimal hyperplasia. Paclitaxel doses range from 2 to 3.5 μg/mm2 of balloon surface area, and carrier molecules (“excipients”) facilitate drug delivery to the vessel wall. LEVANT 2 (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis 2) demonstrated that in patients with intermittent claudication or rest pain due to femoropopliteal disease, a low-dose paclitaxel (2 μg/mm2) DCB with polysorbate/sorbitol excipient (Lutonix, Bard, Tempe, AZ) was superior to PTA for primary patency (65.2% versus 52.6%; P =0.02), equivalent to PTA for clinically driven target lesion revascularization (TLR; 12.3% versus16.8%; P =0.21), and noninferior to PTA on its primary safety end …

Supplemental Digital Content is available in the text., Background: Numerous studies have reported favorable outcomes using drug-coated balloons (DCBs) for treatment of symptomatic peripheral artery disease of the superficial femoral and popliteal arteries. However, the treatment effect compared with an uncoated balloon has differed greatly among the randomized trials, with better outcomes observed with higher-dose DCBs. This European trial was designed to assess the safety and effectiveness of a next-generation low-dose (2-µg/mm2 surface dose of paclitaxel) DCB. Methods: This was a prospective, randomized, multicenter, single-blinded trial. Patients were randomized (3:1) to treatment with a low-dose DCB or an uncoated percutaneous transluminal angioplasty (PTA) balloon. The primary safety end point was a composite of freedom from device- and procedure-related death through 30 days after the procedure and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months after the procedure. The primary effectiveness end point was primary patency at 12 months. Results: Patients were randomized to treatment with a DCB (222 patients, 254 lesions) or uncoated PTA balloon (72 patients, 79 lesions) after successful predilatation. Mean lesion length was 7.2 and 7.1 cm, and 19.2% and 19.0% of lesions represented total occlusions, respectively. The primary safety end point was met, and superiority was demonstrated; freedom from a primary safety event was 94.1% (193 of 205) with DCB and 83.3% (50 of 60) with PTA, for a difference of 10.8% (95% confidence interval, 0.9%–23.0%). The primary effectiveness end point was met, and superiority of DCB over PTA was achieved (83.9% [188 of 224] versus 60.6% [40 of 66]; P

Percutaneous therapies for peripheral artery disease continue to evolve with new techniques and devices. Although guidelines-recommended therapies have impacted cardiovascular morbidity and mortality, endovascular interventions have been shown to reduce limb pain, improve quality of life, and prolong walking distance for those with claudication and to reduce amputation rates among those with critical limb ischemia. Novel devices such as drug-eluting stents and drug-coated balloons have improved patency for moderate-length lesions, whereas others allow treatment of heavily calcified and tortuous segments. New adjunctive devices to cross lesions and reduce or modify associated plaque have also been developed, although level 1 data regarding their efficacy are sparse. There has also been a better mechanistic understanding of lower extremity endovascular treatment using tools such as intravascular ultrasound. This information has highlighted the need for better stent size selection for the femoropopliteal arterial segments and larger balloon diameters for the tibial arteries. Moreover, a wound perfusion approach with direct in-line flow, the so-called angiosome approach, and reconstruction of the pedal loop have been advocated for improved wound healing. Technical advances such as the tibiopedal access and reentry methods have allowed crossing of lesions that were considered no option for the endovascular approach in the past. Collectively, there has been increased awareness, interest, and commitment by various specialty societies and organizations to advance the treatment of peripheral artery disease and critical limb ischemia. This is also evident by the recent coalition of 7 professional societies and organizations that represented >150 000 allied health professionals and millions of patients with peripheral artery disease at the 2015 Centers for Medicaid and Medicare Services Medicare Evidence Development and Coverage Analysis Committee meeting. The percutaneous therapies for peripheral artery disease continue to evolve with longer follow-up with randomized data and larger prospective registries. In the future, it is hopeful that we will treat the lower extremity arteries according to segments, taking into account plaque morphology, luminal versus subintimal crossing, location, and stenotic versus occlusive disease. Until then, we must identify the most cost-effective, efficacious, and safe treatment for each patient. The goal of this article is to aid the practicing vascular specialist consider the optimal choices for the management of patients with vascular disease.

Background: Atherosclerosis in the superficial femoral artery is common in patients suffering from peripheral artery disease. Paclitaxel-eluting balloon (PEB) angioplasty, stenting, and directional atherectomy (DA) have provided new options for the treatment of superficial femoral artery disease; however, the comparative efficacy of these interventional strategies remains uncertain. Methods: One hundred and fifty-five patients with symptomatic peripheral artery disease due to de novo superficial femoral artery stenotic or occlusive lesions were randomized to treatment with plain balloon angioplasty (BA) followed by PEB angioplasty and stenting (n=48), BA and stenting (n=52), or DA with distal protection and bailout stenting (n=55). The primary end point of the study was percentage diameter stenosis after 6 months measured by angiography. Other end points included target lesion revascularization, thrombosis, ipsilateral amputation, binary restenosis, and all-cause mortality at 6 and 24 months. Results: Baseline and lesion characteristics were comparable in all groups with a mean lesion length of 65.9±46.8 mm and 56% total occlusions. At 6 months angiography, the percent diameter stenosis was significantly lower in patients treated by PEB angioplasty and stenting (34±31%) as compared with BA angioplasty and stenting (56±29%, P =0.009) or DA (55±29%, P =0.007). Similarly, binary restenosis was significantly lower after treatment with PEB and stenting as compared with BA and stenting or DA. Clinical follow-up at 24 months revealed a lower risk for target lesion revascularization after PEB angioplasty and stenting as compared with BA and stenting or DA. We found no difference in terms of target lesion thrombosis and mortality among groups, and no patient underwent amputation. Conclusions: Treatment of de novo superficial femoral artery lesions with PEB angioplasty and stenting is superior to BA angioplasty and stenting or DA in terms of angiographic diameter stenosis at 6 months and target lesion revascularization at 24 months. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00986752.

Percutaneous transluminal angioplasty is a minimally invasive therapy for the treatment of patients with peripheral artery disease who suffer from intermittent claudication or critical limb ischemia. The main advantages of the endovascular approach are a low complication rate ranging between 0.5% and 4%, a high technical success rate approaching 90% even in long occlusions, and an acceptable clinical outcome.1,2 Traditionally, percutaneous transluminal angioplasty (PTA) has been the standard for revascularization in aortoiliac, femoropopliteal, and below-the-knee arteries,1 and in many interventional centers, PTA still is the first and most frequently used methodology. However, high rates of failure resulting from an unacceptable incidence of restenosis, particularly in long and complex disease, are the main limitations of PTA.3 Modern bare metal stents (BMS), nitinol self-expanding stents, and cobalt-chromium balloon-expanding stents improved the durability of endovascular interventions, particularly in certain lower-limb indications. Advantages of self-expanding nitinol stents include acceptable radial strength combined with shape-memory characteristics, crush recoverability, and reduced foreshortening, which allows precise placement. Self-expanding nitinol stents are used mainly for external iliac and femoropopliteal indications but have its limitation in ostial common iliac artery lesions. Advantages of cobalt-chromium balloon-expanding stents are high radial strength, specifically for ostial iliac lesions with reduced strut thickness, allowing smaller introducer sizes. These properties of both stents types were expected to improve patency rates compared with PTA and earlier types of stents.4,5 However, the main obstacle of these BMS remains exaggerated neointimal hyperplasia, leading to in-stent restenosis in 25% to 50% within 12 to 24 months, depending on the location of implantation.6,7 New developments over the last several years include drug-eluting balloons (DEBs), new types of stents such as drug-eluting stents (DES) and covered stent grafts, and novel atherectomy systems. These are designed to reduce restenosis and …

Percutaneous intervention for peripheral artery disease has evolved from balloon angioplasty for simple focal lesions to multimodality techniques that enable treatment of severe arterial insufficiency. This technological expansion comes without a standard approach or algorithm, which makes the decision-making process more subjective than objective. Nevertheless, clinical tools are available that can have a favorable effect on patient care, and these promote usage. So, when are standard endovascular techniques (such as balloon and stents) good enough, and when are the latest advances (eg, atherectomy, drug-eluting stents) more appropriate? This section will address these questions for acute limb ischemia (ALI) and chronic critical limb ischemia (CLI). It will also delineate the problem of restenosis, particularly of the superficial femoral artery (SFA), and describe treatment alternatives. The discussion will review the role of drug-eluting stents, atherectomy devices, reentry catheters, and brachytherapy, as well as their potential complications and appropriate remedies. Treatment algorithms for aortoiliac and infrainguinal disease are provided in Figures 1 through 3⇓⇓. Figure 1. Treatment algorithm for acute lower-limb ischemia. *Short infusion of thrombolytic therapy proximal to occlusion can be used to facilitate wire traversal. Figure 2. Simplified treatment algorithm for symptomatic aortoiliac disease in patients deemed candidates for revascularization. In patients with multilevel disease, the aortoiliac segment should be addressed first. TASC indicates TransAtlantic Inter-Society Consensus; AI, aortoiliac; PTA, percutaneous transluminal angioplasty; PE, physical examination; ABI, ankle-brachial index; and U/S, ultrasound. Figure 3. Simplified treatment algorithm for symptomatic infrainguinal peripheral arterial disease, assuming concomitant aortoiliac disease has been treated and the patient is an acceptable candidate for revascularization. *Alternative therapies to PTA include cryotherapy, atherectomy (directional, rotational, ablative), and cutting balloon. †Alternative stent options include stent (graft, balloon expanding, and self expanding) and drug-eluting stent. PTA indicates percutaneous transluminal angioplasty; TASC, TransAtlantic Inter-Society Consensus; PE, physical examination; …

Background: Contemporary outcome data regarding effects of atherectomy in lower extremity arterial revascularization is lacking. Methods: We queried HCUP’s Nationwide Inpatient Sample (NIS) for 2012 using the appropriate primary ICD 9-CM diagnostic code for peripheral vascular disease and procedural codes 39.90 (bare metal stent - BMS), 00.55 (drug eluting stent - DES), 17.56 (peripheral artherectomy) and 39.50 for angioplasty. Only procedures performed in patients >= 18 years were included. Hierarchical mixed effects logistic regression models were generated to evaluate multivariate predictors of outcomes. Results: In total 13,206 (weighted: 66,030) lower extremity arterial revascularization were analyzed (65.5% white, 56.2% Male & 97.4% angioplasty). Atherectomy utilization (23.2%) was associated with significant reduction in amputation (11.5% vs 13.4%), any complications (13.2% vs 16.3%) and in hospital morality (0.8% vs 1.4%) compared to no atherectomy group (p < 0.001). Multivariate analysis showed similar results with decrease amputation (OR, 95% CI; p - value) (0.83, 0.71 - 0.97, p = 0.02) and in hospital mortality/any complication (0.79, 0.69 - 0.90, p = 0.001) with atherectomy (similar results were observed with propensity score matching). “Atherectomy only” was utilized only in 2.3%. post-hoc analysis also shows better outcomes when atherectomy was used with either angioplasty or stenting (figure a & b). subgroup multivariate analysis shows significant reduction in amputation when atherectomy was utilized in chronic limb ischemia (0.74, 0.59 - 0.93, p = 0.01) and with angioplasty (0.72, 0.60 - 0.87, p = 0.001) and trend towards advantage while used along with stents but not reaching statistical significant. Conclusion: Lower extremity atherectomy utilization was associated with significant reduction in amputation and overall complication. We observed better outcomes when atherectomy was used in conjunction with angioplasty.

The femoropopliteal segment is increasingly treated via an endovascular-first approach for both lifestyle-limiting claudication and critical limb ischemia. Nitinol stents have been shown to be superior to percutaneous transluminal angioplasty (PTA) and have become one of the primary modalities for the treatment of femoropopliteal obstructive atherosclerotic disease because of the improved structural integrity and conformability of newer devices.1–3 Current nitinol stents have low rates of stent fracture and excellent clinical patency out to 3 years.2,4 Despite these advances, femoropopliteal in-stent restenosis (FP-ISR) remains an important clinical problem, occurring in up to 19% to 37% of cases after stenting of moderate-length (up to 150 mm) lesions and more frequently after treatment of longer lesions.1,2,5 Article see p 2230 Tosaka and colleagues6 have described the angiographic patterns of FP-ISR. Class I FP-ISR consists of focal ( 50 mm) within the stent body or stent edge. Class III FP-ISR lesions consist of total occlusion within the stent. They described the outcomes of PTA for the treatment of FP-ISR and found that in-stent occlusion (class III FP-ISR) was a significant predictor of recurrent restenosis (84.8%) and reocclusion (64.6%) at 2 years. Two-year outcomes for patients with focal (class I) and diffuse (class II) ISR were similar, with recurrent restenosis in 49.9% and 53.3% and stent occlusion in 15.9% and 18.9%, respectively. These results highlighted the lack of efficacy of PTA for FP-ISR, particularly for in-stent occlusion. In a follow-up to that study, we evaluated a multimodality approach to the treatment of FP-ISR.7 Seventy-five patients underwent endovascular treatment of FP-ISR using a variety of adjunctive devices, including laser atherectomy, excisional atherectomy, …

“Does it make economic sense to completely abandon a therapy that works well for 85% to 90% of the population for a new therapy costing four times as much to treat a transient health condition with no impact on either death or myocardial infarction?” J.M. Brophy and L.J. Erickson1 Since Andreas Gruntzig performed the first percutaneous coronary intervention (PCI) in 1977,2 the cost-effectiveness of this procedure has engendered major controversy. Debates have erupted over the clinical value and cost-effectiveness of each new device or therapy that has become available. Controversies have arisen regarding the cost of atherectomy, bare metal stents (BMS), brachytherapy, distal protection devices, glycoprotein IIb/IIIa inhibitors, and intravascular ultrasound.3–6 Drug-eluting stents (DES) are the most recent devices to have their cost scrutinized.7–12 Response by Ryan and Cohen p 1754 Balloon angioplasty is associated with restenosis rates of 30% to 40%, whereas PCI with BMS is associated with rates of 20% to 30%,13,14 and PCI with DES is associated with rates in the single digits.15,16 My colleagues and I pooled the results of 11 DES trials involving >5000 patients using a hierarchical Bayesian random-effects model.17 We found that, compared with BMS, DES reduce angiographic restenosis from 29.3% to 8.9% (Table 1 and Figure 1). There was no difference between DES and BMS in terms of mortality (0.9% versus 0.9%, respectively) or myocardial infarction (2.7% versus 2.9%, respectively). There was a suggestion that restenosis was less with sirolimus-eluting stents (SES) compared with polymeric paclitaxel-eluting stents (PES) (6.2% for SES versus 36.9% for BMS; 7.1% for PES versus 23.5% for BMS), a finding that was subsequently identified in another meta-analysis.18 View this table: TABLE 1. Clinical Events and Restenosis Rates in Randomized Clinical Trials Investigating DESs Figure 1. Forest plot comparing rates of angiographic restenosis for …

Despite early perceptions that distal embolization of atherosclerotic plaque contents was a rare event during balloon angioplasty, it has now become clear that manipulation of atherosclerotic lesions with wires, balloons, atherectomy catheters, or stents does liberate plaque debris. The tendency of this liberated debris to cause clinical manifestations depends on the amount of debris, the size of particles, and the sensitivity of the perfused organ. Additionally, clinical experience with various embolic protection devices (EPDs) has shown that the capture and retrieval of potentially embolic debris reduce adverse events in situations where the amount of debris is largest (eg, saphenous vein grafts [SVGs]) and where the end organ is most sensitive (myocardium, with no reflow and creatine kinase [CK]-MB release; brain with new lesions on magnetic resonance imaging or clinical stroke). In contrast, other adjunctive medical therapies such as glycoprotein IIb/IIIa receptor antagonists, which have been shown to reduce overall rates of CK-MB release during other coronary interventional procedures, have failed to mitigate the impact of distal embolization in SVG intervention.1–3 Embolic protection is thus now firmly established as a routine component of SVG and carotid stenting, although randomized trials have not been performed for the latter indication.4,5 Although it is almost certain that atherosclerotic or atherothrombotic debris is released during other interventions on peripheral, renal, and native coronary arteries, the link between such embolization and clinical events (and hence the rationale for embolic protection) has been more difficult to demonstrate. This may be due to smaller amounts of embolic debris, less sensitive metrics of end-organ damage, or less complete capture of debris by devices tested to date in those locales. For example, initial trials of distal embolic protection in native coronaries during primary angioplasty for acute myocardial infarction have shown retrieval of smaller amounts of debris than seen …

Introduction: The percutaneous treatment of heavily calcified coronary lesions remains suboptimal and often requires debulking with Rotational Atherectomy (RA) which is often underutilized due to a steep learning curve. Although a novel approach using Orbital Atherectomy (OA) has been introduced, which has an easier set-up and easier learning curve, a comparative assessment of both techniques in real world cohort has not been performed METHODS: Retrospective analysis of our prospectively collected database between October 2013 to May 2014 for patients undergoing atherectomy in heavily calcified lesions at our center retrieved 105 OA and 196 RA procedures RESULTS: There were no significant differences in patient demographics.The maximal stent diameter was significantly larger in OA vs RA (3.41 mm 2 vs 3.28 mm 2 , p=0.02).There was a trend towards RA showing better Procedural success defined as successful stent deployment with TIMI 3 flow ( 95.9% vs 90.5%, p = 0.06) and Clinical Success which is procedural success without death, stroke or CABG ( 95.9% vs 90.5%, p = 0.06). Two cases of failed initial OA underwent successful RA. Procedural complications (≥ grade 3 dissection, side branch closure, perforation, slow flow/no flow or vessel closure), In-hospital MACE (a composite of death, stroke, CABG or CKMB>5X), 30 day readmission rates and 30 day MACE were not statistically significant[See Table 1 and Figure 1]. CONCLUSION: OA demonstrated a similar safety and efficacy profile to RA with a trend towards lower procedural success but comparable complications and 30 day outcomes, suggesting OA may serve as an alternative to RA in PCI of heavily calcified lesions.

Background— Diabetes mellitus predisposes to thrombotic and proliferative vascular remodeling, to which thrombin contributes via activation of protease-activated receptor (PAR) 1. However, the use of PAR-1 inhibitors to suppress remodeling may be limited by severe bleeding. We recently reported upregulation of an additional thrombin receptor, PAR-4, in human vascular smooth muscle cells exposed to high glucose and have now examined PAR-4 as a novel mediator linking hyperglycemia, hypercoagulation, and vascular remodeling in diabetes mellitus. Methods and Results— PAR-4 expression was increased in carotid atherectomies and saphenous vein specimens from diabetic versus nondiabetic patients and in aorta and carotid arteries from streptozotocin-diabetic versus nondiabetic C57BL/6 mice. Vascular PAR-1 mRNA was not increased in diabetic mice. Ligated carotid arteries from diabetic mice developed more extensive neointimal hyperplasia and showed greater proliferation than arteries from nondiabetic mice. The augmented remodeling response was absent in diabetic mice deficient in PAR-4. At the cellular level, PAR-4 expression was controlled via the mRNA stabilizing actions of human antigen R, which accounted for the stimulatory actions of high glucose, angiotensin II, and H 2 O 2 on PAR-4 expression, whereas cicaprost via protein kinase A activation counteracted this effect. Conclusions— PAR-4 appears to play a hitherto unsuspected role in diabetic vasculopathy. The development of PAR-4 inhibitors might serve to limit mainly proliferative processes in restenosis-prone diabetic patients, particularly those patients in whom severe bleeding attributed to selective PAR-1 blockade or complete thrombin inhibition must be avoided or those who do not require anticoagulation.

Background —Lipid-rich, inflamed atherosclerotic lesions are associated with plaque rupture and thrombosis, which are the most important causes of death in patients with diabetes mellitus. This study was designed to quantify lipid composition and macrophage infiltration in the coronary lesions of patients with diabetes mellitus. Methods and Results —A total of 47 coronary atherectomy specimens from patients with diabetes mellitus were examined and compared with 48 atherectomy specimens from patients without diabetes. Plaque composition was characterized by trichrome staining. Macrophage infiltration was characterized by immunostaining. Clinical and demographic data were similar in both groups. The percentage of total area occupied by lipid-rich atheroma was larger in specimens from patients with diabetes (7±2%) than in specimens from patients without diabetes (2±1%; P =0.01), and the percentage of total area occupied by macrophages was larger in specimens from patients with diabetes (22±3%) than in specimens from patients without diabetes (12±1%; P =0.003). The incidence of thrombus was also higher in specimens from patients with diabetes than in specimens from patients without diabetes (62% versus 40%; P =0.04). Plaque composition, macrophage infiltration, and thrombus were similar in lesions from diabetic patients treated with insulin compared with lesions from patients treated with sulfonylureas or diet. Conclusions —Coronary tissue from patients with diabetes exhibits a larger content of lipid-rich atheroma, macrophage infiltration, and subsequent thrombosis than tissue from patients without diabetes. These differences suggest an increased vulnerability for coronary thrombosis in patients with diabetes mellitus.

Background —Coronary stenting has reduced restenosis in focal de novo lesions, but its impact has been less pronounced in complex lesion subsets. Preliminary data suggest a role for plaque burden in promoting intimal hyperplasia after stent implantation. The aim of this study was to test the hypothesis that plaque removal with directional atherectomy before stent implantation may lower the intensity of late neointimal hyperplasia, reducing the incidence of in-stent restenosis. Methods and Results —Seventy-one patients with 90 lesions underwent directional atherectomy before coronary stenting. Intravascular ultrasound–guided stenting was performed in 73 lesions (81%). Clinical success was achieved in 96% of patients. Procedural complications were as follows: emergency bypass surgery in 1 patient (1.4%), who died 2 weeks later; Q-wave myocardial infarction in 2 patients (2.8%); and non–Q-wave myocardial infarction in 8 patients (11.3%). None of the patients had stent thrombosis at follow-up. Angiographic follow-up was performed in 89% of eligible patients at 5.7±1.7 months. Loss index was 0.33 (95% CI, 0.26 to 0.40), and angiographic restenosis was 11% (95% CI, 5% to 20%). Clinical follow-up was performed in all patients at 18±3 months. Target lesion revascularization was 7% (95% CI, 3% to 14%). Conclusions —Directional atherectomy followed by coronary stenting could be performed with good clinical success rate. Also, these data point to a possible reduction in angiographic restenosis and a significant reduction in the need for repeated coronary interventions. Therefore, a randomized clinical trial seems appropriate to test the validity of this approach.

Background —After angioplasty, major complications and ischemic events occur more frequently in diabetic than nondiabetic patients. To determine whether treatment with abciximab is effective in reducing these events in diabetics, we analyzed characteristics and outcomes of diabetic patients enrolled in a large multicenter study (EPILOG). Methods and Results —Of 2792 patients enrolled, 638 (23%) were diabetic. Diabetic patients were older, shorter, and heavier; more likely to be female and have three-vessel disease, prior coronary artery bypass graft surgery, a history of hypertension, or a recent myocardial infarction; and less likely to be current smokers than their nondiabetic counterparts. During hospitalization, death, myocardial infarction, or urgent revascularization occurred in 7.1% of diabetics and 7.5% of nondiabetics. By 6 months, the composite of death and myocardial infarction had occurred in 8.8% of diabetic patients and 7.4% of nondiabetics, whereas death, myocardial infarction, or revascularization had occurred in 27.2% and 22.6%, respectively. Abciximab treatment reduced death or myocardial infarction among diabetic and nondiabetic patients (hazard ratios, 0.28 [95% confidence interval (CI), 0.13 to 0.57] and 0.47 [95% CI, 0.33 to 0.70] at 30 days for diabetics and nondiabetics, respectively, and 0.36 [95% CI, 0.21 to 0.61] and 0.60 [95% CI, 0.44 to 0.82] at 6 months for diabetics and nondiabetics, respectively). Abciximab reduced target vessel revascularization among nondiabetic patients (hazard ratio, 0.78 [95% CI, 0.63 to 0.96]) but not among diabetics (hazard ratio, 1.4 [95% CI, 0.94 to 2.08]). When standard- and low-dose heparin adjuncts were compared, diabetics receiving abciximab with standard-dose heparin had marginally greater reductions in the composite of death and myocardial infarction and in target vessel revascularization than diabetics assigned to abciximab with low-dose heparin. Conclusions —Abciximab treatment in diabetic patients led to a reduction in the composite of death and myocardial infarction, which was at least as great as that seen in nondiabetic patients. However, target vessel revascularization was reduced in nondiabetic but not diabetic patients. This effect may be associated in part with lower doses of heparin. These differences may be related to differences in the platelet and coagulation systems between diabetics and nondiabetics, the greater extent of coronary artery disease in diabetics, or patient selection and management factors.

Background —The clinical and angiographic demographics of patients requiring unplanned coronary stent deployment and the optimal adjunct pharmacotherapy in this population are not well described. This report details the EPILOG trial experience with unplanned coronary stent deployment and the effect of abciximab platelet glycoprotein IIb/IIIa blockade to improve clinical outcomes during 6 months of follow-up. Methods and Results —After randomization in the EPILOG double-blind, placebo-controlled trial of abciximab therapy during percutaneous coronary intervention, 326 (12%) of 2792 patients required unplanned coronary stent deployment. Although stented patients were not distinguished by clinical variables, they had greater coronary lesion complexity by American Heart Association/American College of Cardiology criteria ( P =.003) and greater incidence of lesion length >10 mm ( P =.002), lesion eccentricity ( P =.027), irregular lesion contour ( P =.001), and bifurcation involvement ( P =.019) than nonstented patients. Unplanned stents were required less often in patients treated with abciximab and low-dose, weight-adjusted heparin than in patients receiving placebo and standard-dose heparin (9.0% versus 13.7%; P =.001). Although adverse clinical outcomes including target-vessel revascularization and bleeding events were more frequent in patients requiring unplanned coronary stent deployment, abciximab therapy reduced adverse outcomes in these patients at 30 days and 6 months to a greater extent than was observed in patients not requiring stent placement. Among stented patients, abciximab therapy did not increase bleeding events. Conclusions —Patients requiring unplanned coronary stent deployment have more complex coronary lesion morphology and a more complicated clinical course after coronary intervention. Abciximab therapy both reduces the need for unplanned stent deployment and confers clinical benefit to patients requiring an unplanned stent, without increasing bleeding complications.

Background —Previous directional coronary atherectomy (DCA) trials have shown no significant reduction in angiographic restenosis, more in-hospital complications, and higher 1-year mortality than conventional balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA]). DCA, however, has subsequently evolved toward a more “optimal” technique (larger devices, more extensive tissue removal, and routine postdilation to obtain diameter stenosis Methods and Results —The Balloon vs Optimal Atherectomy Trial (BOAT) was conducted to evaluate whether optimal DCA provides short- and long-term benefits compared with balloon angioplasty. One thousand patients with single de novo, native vessel lesions were randomized to either DCA or PTCA at 37 participating centers. Lesion success was obtained in 99% versus 97% ( P =.02) of patients to a final residual diameter stenosis of 15% versus 28% ( P 3× normal was more common with DCA (16% versus 6%; P P =.016). Clinical follow-up to 1 year showed nonsignificant 13% to 17% reductions in the DCA arm of the study for mortality rate (0.6% versus 1.6%; P =.14), target-vessel revascularization (17.1% versus 19.7%; P =.33), target-site revascularization (15.3% versus 18.3%; P =.23), and target-vessel failure (death, Q-wave myocardial infarction, or target-vessel revascularization, 21.1% versus 24.8%; P =.17). Conclusions —Optimal DCA provides significantly higher short-term success, lower residual stenosis, and lower angiographic restenosis than conventional PTCA, despite failing to reach statistical significance for reducing late clinical events compared with PTCA with stent backup.

Background —Previous clinical trials of directional coronary atherectomy (DCA) have failed to show significant improvement in early or late outcomes compared with balloon angioplasty (PTCA). The present study tested the hypothesis that more aggressive “optimal” atherectomy could be performed safely to produce larger initial lumen diameters and a lower late restenosis rate. Methods and Results —The present study was a prospective multicenter registry of consecutive patients undergoing optimal DCA of de novo or restenotic lesions in 3.0- to 4.5-mm native coronary arteries. Optimal DCA was defined as using a 7F atherectomy device and adjunctive PTCA if necessary to achieve a 3 times normal) occurred in 14% of patients. Mean reference vessel diameter was 3.28 mm. Mean diameter stenosis was reduced from 63.5% to a final stenosis of 7%. Late 1-year clinical follow-up revealed one cardiac death and a target lesion revascularization rate of 17.8%. The angiographic restenosis rate at 6 months was 28.9%, with the major predictor of restenosis being a smaller postprocedure lumen diameter. Conclusions —Optimal DCA produced a low residual percent diameter stenosis and a lower restenosis rate than seen in previous trials without an increase in early or late major adverse events.

Background Recently, long-term constriction of the vessel has been suggested as an alternative mechanism of restenosis after coronary angioplasty. Methods and Results To understand remodeling of human coronary arteries undergoing coronary angioplasty or atherectomy, serial intravascular ultrasonographic examinations were performed at preintervention and postintervention examinations and at 24 hours, 1 month, and 6 months. Complete serial data were obtained in 61 lesions (balloon angioplasty, 35 lesions; directional atherectomy, 26 lesions). Lumen area improved from 6.81±2.24 mm 2 after intervention to 8.22±2.79 mm 2 at 1 month ( P =.0001) and decreased to 4.88±2.86 mm 2 at 6 months ( P =.0001). Vessel area enlarged from 17.32±5.35 mm 2 after intervention to 19.39±5.33 mm 2 at 1 month ( P =.0001) and decreased to 16.33±5.54 mm 2 at 6 months ( P =.0001). Plaque+media area increased significantly from postintervention examination to 24 hours (10.51±4.38 versus 10.96±4.49 mm 2 , P =.0008) and from 24 hours to 6 months (10.96±4.49 versus 11.45±4.45 mm 2 , P =.03). Changes in lumen area in each study interval correlated more closely with changes in vessel area than with changes in plaque+media area. Restenotic lesions compared with nonrestenotic lesions had a greater decrease in the vessel area between 1 month and 6 months (−4.33±2.73 versus −2.49±2.15 mm 2 , P =.006) and greater increase in the plaque+media area both within 24 hours (0.84±1.22 versus 0.27±0.38 mm 2 , P =.04) and between 24 hours and 6 months (1.19±2.19 versus 0.18±1.46 mm 2 , P =.04). Conclusions Remodeling after coronary angioplasty or atherectomy was characterized by early adaptive enlargement and late constriction of the vessel.

Background Treatment of calcified (in contrast to simple) lesions with PTCA has been associated with a lower success rate and more procedural complications. Rotablation can improve acute results, but the high restenosis rate remains a problem. The purpose of this study was to evaluate the clinical and angiographic outcome of patients with complex and calcified lesions treated with a combination of rotablation and stenting. Methods and Results Seventy-five consecutive patients with 106 lesions had rotablation prior to coronary stenting. Intravascular ultrasound–guided stenting was used without subsequent anticoagulation in 93% of patients. Procedural success was achieved in 93.4% of lesions. Acute stent thrombosis occurred in two lesions (1.9%), and subacute stent thrombosis in one lesion (0.9%). Angiographic follow-up was performed in 82.5% of lesions at 4.6±1.9 months with an angiographic restenosis rate of 22.5%. Clinical follow-up was performed in all patients at 6.4±3 months; target lesion revascularization was needed in 18% of lesions, Q-wave myocardial infarction occurred in 1.3%, coronary bypass surgery in 4.0%, and death in 1.3%. Conclusions Optimal coronary stenting after rotablation in calcified and complex lesions can be performed with a high success rate, an acceptable rate of procedural complications, and a low rate of stent thrombosis. This approach was associated with a low incidence of angiographic restenosis compared with results usually obtained with other interventional strategies in calcified and complex lesion subsets.

Background The pathophysiology of phenotypic modulation of smooth muscle cells (SMCs) involved in restenosis after angioplasty is not well understood. Smooth muscle myosin heavy chain (SM MHC) isoforms (SM1 and SM2) are specific markers for SMC differentiation. In particular, SM2 is useful as a marker of mature SMCs. SMemb is a nonmuscle myosin heavy chain (NM MHC) whose expression is upregulated in immature or activated SMC. Methods and Results To determine SMC phenotypes in neointimal tissues after percutaneous transluminal coronary angioplasty (PTCA), we performed immunohistochemistry on human coronary arteries with antibodies against α-SM actin, SM1, SM2, and SMemb. Tissues were obtained from six autopsied patients and from atherectomy specimens from 16 patients who had undergone PTCA. Medial SMCs were positive for α-actin, SM1, and SM2. Expression of SM1 and SM2 in the neointima varied with the time after intervention, whereas α-actin was constitutively expressed in all cases studied. Neointimal cells at 16 and 20 days after PTCA contained α-actin but little or no SM1 or SM2, indicating that these cells modulated their phenotype to the immature state. Neointimal SMCs recovered SM MHC expression, first SM1 and then SM2, by 6 months after PTCA. Increased expression of SMemb was found in the neointima but without apparent relationship to the time after PTCA. Conclusions Neointimal SMCs show features of an undifferentiated state, indicated by altered expression of SM MHC, and undergo redifferentiation in a time-dependent manner. The expression of SM MHC isoforms provides insight into the biology of healing after angioplasty and furnishes useful tools for the understanding of the roles of differentiation and phenotypic modulation of SMCs in human vascular lesions.

Background The purpose of this study was to assess serial changes in coronary blood flow velocity before and after Rotablator atherectomy and after adjunctive percutaneous transluminal coronary angioplasty (PTCA). Since Rotablator atherectomy results in luminal enlargement by plaque pulverization and distal embolization, improvement in coronary blood flow could be attenuated despite luminal enlargement. Methods and Results Intracoronary Doppler blood flow velocity measurements were obtained with a Doppler Flowire. Basal average peak velocity (bAPV), hyperemic APV (hAPV), diastolic/systolic velocity ratio (DSVR), and coronary flow reserve (CFR) were assessed before intervention, after Rotablator, and after adjunctive PTCA. Complete clinical, angiographic, and Doppler data were obtained in 22 patients. There was a small but significant difference ( P =.02) in resting heart rate and mean arterial pressure before and after Rotablator and after adjunctive PTCA. Minimum lumen diameter increased from 0.8±0.1 to 1.5±0.2 to 2.0±0.1 mm ( P P P 30 cm/s was the best Doppler correlate of angiographic success. Conclusions Rotablator atherectomy and adjunctive PTCA significantly improve distal coronary blood flow velocity and DSVR but not CFR. Failure to normalize CFR could be secondary to parallel increases in bAPV and hAPV, “acquired” microvascular disease due to distal microembolization or spasm, and/or angiographically inapparent dissection or residual stenosis. Adjunctive PTCA contributes significantly to the overall physiological benefit of a combined procedure.

Background Vascular myocyte apoptotic cell death has been reported in human atherectomy and endarterectomy specimens and for neointimal smooth muscle cells (SMCs) in balloon-injured rat carotid arteries between 7 and 30 days after injury. However, the immediate effect of balloon injury on medial SMC viability has not been examined. Methods and Results Rat carotid arteries were harvested at the time of balloon injury (T=0) and at 0.5, 1, 2, and 4 hours after injury. Uninjured vessels or vessels harvested at the time of injury (T=0) did not display evidence of apoptosis. However, as early as 30 minutes after injury, 70% of medial SMCs appeared apoptotic by TdT-mediated dUTP nick end labeling (TUNEL) analysis and by the appearance of condensed chromatin. High frequencies of TUNEL-positive cells were also observed at 1 and 2 hours after injury but not at 4 hours. Transmission electron microscopy revealed many cells with morphological characteristics of apoptosis in the injured sections. A marked decrease in bcl-X expression was detected in the most luminal layers of the media. To corroborate these findings in a second animal model, rabbit external iliac arteries were analyzed after balloon angioplasty. Apoptotic cell death was evident in rabbit arteries at 30 minutes and at 4 hours after injury. Conclusions As early as 30 minutes after balloon injury, myocytes appear to undergo apoptotic cell death at a high frequency as shown by TUNEL staining, chromatin condensation, and the appearance of morphological features in electron micrographs. The induction of apoptosis coincides with a marked downregulation of bcl-X expression.

Moving from bench to bedside in the development of the monoclonal antibody 7E3, directed against the platelet GPIIb/IIIa receptor, from a basic science laboratory reagent to an antithrombotic drug was a long, incremental process. From the beginning, we hoped that this powerful new agent would allow us to define better the biochemistry of the GPIIb/IIIa receptor and its role in platelet physiology and pathology, and we dreamed that we might be able to use it to improve the therapy of patients with vascular disease. I first review the evolution of our understanding of platelet physiology since the 1960s and why the platelet GPIIb/IIIa receptor appeared to be a logical target for antithrombotic therapy. I then describe our studies with 7E3 to block the receptor in experimental animal models of thrombosis. The results of these studies encouraged us to try to develop 7E3 as a human therapeutic agent. The development was a monumental effort conducted by hundreds of people working for nearly a decade and culminated in the approval by the Food and Drug Administration of c7E3 Fab (abciximab [ReoPro]) in December 1994 as conjunctive therapy for use in patients undergoing high-risk coronary artery angioplasty and atherectomy. A detailed description of the developmental process is beyond the scope of this essay, so it is only briefly described. My experience in moving back and forth from the academic medical center research bench to the world of drug development has allowed me to reflect on the processes involved, and at the end of this essay, I share some of my thoughts and concerns. The choice of the GPIIb/IIIa receptor as a therapeutic target rests on an enormous amount of basic and clinical research by many investigators working in what might appear to be quite disparate fields, including platelet-fibrinogen interactions, the rare blood platelet …

Background Apoptosis has been recognized in normal, including rapidly proliferating, cell populations and is inferred to be potentially responsible for the maintenance of stable cell numbers in tissues with various degrees of proliferative activity. Previous studies performed in rats indicated that despite the persistence of a relatively high level of injury-induced proliferative activity, total arterial smooth muscle content at 12 weeks remained unchanged from that measured at 2 weeks, suggesting that accrual of vascular smooth muscle cells is mitigated by cell death. The extent to which apoptosis may be observed in human atherosclerosis and/or restenosis, however, has not been previously established. Methods and Results We performed immunohistochemical studies on 56 specimens retrieved from patients undergoing directional atherectomy for primary atherosclerotic lesions or recurrent arterial narrowing after percutaneous revascularization (restenosis). Immunohistochemical staining disclosed evidence of apoptosis in 35 (63%) of the 56 specimens studied. When present, immunohistochemical evidence of apoptosis was typically limited to P =.0046). Among coronary arterial specimens, apoptosis was observed in 12 (86%) of 14 specimens from patients with restenosis versus 6 (29%) of 14 specimens from patients with primary obstructions ( P Conclusions Apoptosis is a feature of human vascular pathology, including restenotic lesions and, to a lesser extent, primary atherosclerotic lesions. The findings of the present study suggest that apoptosis may modulate the cellularity of lesions that produce human vascular obstruction, particularly those with evidence of more extensive proliferative activity.

Background Directional atherectomy is a frequently used percutaneous revascularization strategy, but its long-term outcomes have not previously been compared with those of balloon angioplasty in a prospective trial. Methods and Results The 1012 patients enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT I) were followed for at least 1 year after randomization. Analyses of predetermined end points were performed, including a detailed analysis of the 14 patients who died. At 1 year, 11 patients had died in the atherectomy group compared with 3 in the angioplasty group (2.2% versus 0.6%, P =.035), with an excess of out-of-hospital deaths (2.2% versus 0.2%, P =.01) and late cardiac deaths (1.6% versus 0%, P =.01). Univariate predictors of death included age, abrupt closure, periprocedural enzyme elevation, and peripheral vascular complications. There was no evidence that the excess of deaths after atherectomy was linked to perforation, ectasia, or deep resection. Cumulative rates of myocardial infarction were higher in those who had been randomized to atherectomy than in those randomized to angioplasty (8.9% versus 4.4%, P =.005) with a trend toward excess Q-wave and non–Q-wave infarctions. By multivariate analysis, atherectomy was the only variable predictive of the combined end point of death or myocardial infarction. No clinical or angiographic characteristics added to this index. Rates of repeat percutaneous intervention at the target site (24.4% after atherectomy versus 25.9% after angioplasty), coronary artery bypass surgery (9.3% versus 9.1%), hospitalization (50% versus 47.1%), and stroke (1% in both groups) were not significantly different. Conclusions Long-term follow-up of the 1012 patients randomized to atherectomy or angioplasty has revealed a statistically significant excess of deaths after directional atherectomy that was not evident at 6 months. This difference could be due to the chance occurrence of a low mortality rate in those randomized to angioplasty. The excess of myocardial infarctions after atherectomy remains statistically significant at 1 year. Further investigation is warranted to improve the safety of atherectomy.

Background Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque, leading to intracoronary thrombosis and clinical sequelae. The proximate cause of plaque rupture is unknown. Accordingly, we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family in acute coronary ischemia. Methods and Results Coronary atherectomy specimens from patients with atherosclerosis and an acute ischemic syndrome consistent with recent plaque rupture (unstable angina) (n=12) were immunostained for the presence of 92-kD gelatinase; the results were compared with those obtained by identical study of atherectomy specimens from patients with atherosclerosis and angina but without acute ischemia (stable angina) (n=12). Positive immunostaining for 92-kD gelatinase was present in 83% of specimens from both unstable and stable angina patients. However, intracellular localization of enzyme (indicating active synthesis) was documented in 10 of 10 positively stained specimens from patients with unstable angina compared with 3 of 10 positively stained specimens from patients with stable angina. Macrophages and smooth muscle cells were the major sources of 92-kD gelatinase in all specimens examined by immunostaining of adjacent sections. Conclusions 92-kD gelatinase is commonly expressed in coronary arterial atherosclerotic lesions. Active synthesis of 92-kD gelatinase by macrophages and smooth muscle cells in atherosclerotic lesions may play a pathogenic role in the development of acute coronary ischemia.

Background Unstable angina is most frequently caused by coronary thrombosis, with or without plaque fissure, but the mechanisms underlying these events are still speculative. Since cytomegalovirus (CMV) antigens and DNA encoding CMV major immediate-early (MIE) gene have been detected in atherosclerotic arterial walls, the active replication of CMV may be responsible for plaque instability. Therefore the expression of CMV MIE gene mRNA, an early marker of viral replication, was assessed in coronary atherectomy specimens from patients with stable or unstable angina. Methods and Results Twenty patients with unstable angina (12 men and 8 women; mean age, 62 years; range, 44 to 89 years) and 20 patients with stable angina (16 men and 4 women; mean age, 62 years; range, 43 to 81 years) who underwent successful directional coronary atherectomy were enrolled in the study. The efficiency of mRNA extraction, transcription, and amplification from each coronary atherectomy specimen was assessed by performance of reverse transcription and thermal cycling amplification of a 548-bp human β-actin cDNA segment. After Southern blotting and hybridization with a specific probe, all specimens but one showed a positive hybridization signal. The negative sample was excluded from the study. Reverse transcription and thermal cycling amplification of a 145-bp CMV cDNA segment of the MIE gene were then carried out. After Southern blotting and hybridization with a specific probe, none of the specimens showed a positive hybridization signal. Plasmid pACYC 184 containing the Xba I–inserted MIE gene cDNA was used as a positive control: as few as 10 molecules of the plasmid per reaction were detectable after amplification. Conclusions Our results do not support the hypothesis that, in patients with unstable angina, replication of CMV in coronary atherosclerotic plaques is a major cause of plaque instability. These findings suggest that the research for the causes of unstable angina should be directed toward processes other than CMV replication.

Background Directional coronary atherectomy and percutaneous transluminal coronary angioplasty have both been used in symptomatic patients with coronary saphenous vein bypass graft stenoses. The relative merits of plaque excision and removal versus balloon dilatation remain uncertain. We compared outcomes after directional coronary atherectomy or angioplasty in patients with de novo bypass graft stenoses. Methods and Results Fifty-four North American and European sites randomized 305 patients with de novo vein graft lesions to atherectomy (n=149) or angioplasty (n=156). Quantitative coronary angiography at a core laboratory assessed initial and 6-month results. Initial angiographic success was greater with atherectomy (89.2% versus 79.0%), as was initial luminal gain (1.45 versus 1.12 mm, P P =.012), and a trend was shown toward more non–Q-wave myocardial infarction ( P =.09). Although the 6-month net minimum luminal diameter gain was 0.68 mm for atherectomy and 0.50 mm for angioplasty, the restenosis rates were similar, 45.6% for atherectomy and 50.5% for angioplasty ( P =.491). At 6 months, there was a trend toward decreased repeated target-vessel interventions for atherectomy ( P =.092); in addition, 13.2% of patients treated with atherectomy versus 22.4% of the angioplasty patients ( P =.041) required repeated percutaneous intervention of the initial target lesion. Conclusions Atherectomy of de novo vein graft lesions was associated with improved initial angiographic success and luminal diameter but also with increased distal embolization. There was no difference in 6-month restenosis rates, although primary atherectomy patients tended to require fewer target-vessel revascularization procedures.

BACKGROUND Rupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes. METHODS AND RESULTS Hematoxylin and eosin and immunostaining with anti-human macrophage monoclonal antibody (PG-M1) were performed. Computerized planimetry was used to analyze 26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myocardial infarction. Total plaque area was 417 +/- 87 mm2 x 10(-2) in patients with stable angina, 601 +/- 157 mm2 x 10(-2) in patients with unstable angina, and 499 +/- 87 mm2 x 10(-2) in patients with non-Q-wave myocardial infarction (P = NS). The macrophage-rich area was larger in plaques from patients with unstable angina (61 +/- 18 mm2 x 10(-2)) and non-Q-wave myocardial infarction (87 +/- 32 mm2 x 10(-2)) than in plaques from patients with stable angina (14 +/- 5 mm2 x 10(-2)) (P = .024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3 +/- 5.6%) and non-Q-wave myocardial infarction (14.6 +/- 4.6%) than in patients with stable angina (3.14 +/- 1%) (P = .018). Macrophage-rich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67 +/- 30 mm2 x 10(-2)) and unstable angina (55 +/- 19 mm2 x 10(-2)) than in patients with stable angina (11.5 +/- 4.1 mm2 x 10(-2)) (P = .046). Macrophage-rich atheromatous gruel was also largest in patients with non-Q-wave myocardial infarction (15 +/- 4 mm2 x 10(-2)) than in patients with unstable angina (3.3 +/- 1.7 mm2 x 10(-2)) or stable angina (2.4 +/- 1.2 mm2 x 10(-2)) (P = .026). CONCLUSIONS Macrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes.

BACKGROUND Rotational atherectomy using the Rotablator has recently become available to treat coronary stenoses. This study was performed to determine the relation of patient characteristics, stenosis morphology, and operator technique to procedural outcome to gain insight into which patients might be best treated with this device. METHODS AND RESULTS Four hundred stenoses from 316 patients randomly selected from the initial Rotablator experience at three major referral institutions were analyzed. Angiographic data were assessed at a central angiographic laboratory using standardized morphological criteria and caliper measurement. Patients were somewhat more elderly than most percutaneous transluminal coronary angioplasty (PTCA)-treated groups (mean age, 64 +/- 11 years), 74% were men, and the lesions treated were often complex (modified American College of Cardiology/American Heart Association lesion type A, 24%; B1, 40%; B2, 30%; and C, 6%). Elective adjunctive PTCA was used for 82% of stenoses treated. Procedural success was achieved in 89.8% of stenoses (93.5% if results with creatine kinase two to three times normal are not counted as failures), and major ischemic complications (death, 0.3%; non-Q-wave myocardial infarction, 5.7%; Q-wave myocardial infarction, 2.2%; or emergency bypass surgery, 0.9%) occurred in 8.9% of patients. Complications were due to epicardial coronary obstruction in 3.8% of patients and to delayed coronary runoff ("slow reflow") in 5.1% of patients. Procedural failure was correlated independently with outflow obstruction (success rate, 64%; odds ratio for failure, 5.4; multivariate P = .002), lesion irregularity (76%; odds ratio, 3.3; P = .003), stenosis bend > or = 60 degrees (73%; odds ratio, 3.7; P = .03), and female sex (84%; odds ratio, 2.4; P = .03). Ischemic complications were correlated independently with lesion length (> or = 50% narrowing) > or = 4 mm (complication rate, 12%; odds ratio, 3.6; multivariate P = .005), right coronary artery stenosis (13%; odds ratio, 2.4; P = .02), stenosis bend > or = 60 degrees (27%; odds ratio, 6.1; P = .03), and female sex (13%; odds ratio, 3.0; P = .04). Slow reflow was correlated with total burring duration (odds ratio, 1.005/s; multivariate P = .001), right coronary artery stenosis (incidence, 17%; odds ratio, 4.5; P = .009), and to a lesser extent with recent myocardial infarction in the treated territory (44%; odds ratio, 4.3; P = .08). CONCLUSIONS The procedural outcome of rotational atherectomy is highly correlated with stenosis morphology and location and sex of the patient. After stratification for these parameters, overall outcome with the Rotablator appears to be similar to that with balloon angioplasty and other competing techniques. Short-term outcome with specific subsets of patients may be superior with the Rotablator (calcified stenoses), but this technique might best be avoided in some patients (those with irregular or possibly thrombus-containing stenoses, highly angulated stenoses, and possible right coronary artery stenoses or those associated with impaired distal runoff caused by a recent myocardial infarction or manifest by a fixed thallium defect).

BACKGROUND To be used optimally, new interventional devices (stent, lasers, atherectomy catheters) must be carefully evaluated in terms of optimal patient and lesion selection, technique of use, expected acute success and complications, and long-term results. Sources for that information include single-center and multicenter (single-device) reports, although randomized trials may then be performed to provide a more definitive picture of any clinical benefits. One interim option, however, consists of carefully collected registry data. The purpose of this article is to review data collected in the National Heart, Lung, and Blood Institute-funded New Approaches to Coronary Intervention (NACI) Registry and to compare them with existing reports. METHODS AND RESULTS NACI is an independent, investigator-driven effort that seeks to collect uniform data on patients undergoing treatment with one of several investigational devices and thereby provide an unbiased report of procedure outcome. Between November 1990 and November 1992, 36 participating centers treated a total of 3201 lesions in 2835 patients, using one of seven study devices: directional atherectomy (1084 lesions), transluminal extraction atherectomy (240 lesions), rotational atherectomy (349 lesions), Palmaz-Schatz stent (674 lesions), Gianturco-Roubin stent (213 lesions), and the Advanced Interventional Systems (474 lesions) or Spectranetics (167 lesions) excimer lasers. Data on each procedure were recorded on a unique modular database that captured the reason for (and interim result after) each device use. Device success (defined here as stenosis improvement by > or = 20% and a residual stenosis < 50% after new device use) was 66.5% overall. Adjunctive angioplasty was used in 75.5% of lesions, either before (25.9%) or after (43.5%) new device use, yielding an overall lesion success (> or = 20% stenosis improvement with a final residual stenosis < 50% after all devices) of 92.2%. Adjunctive angioplasty after new device use produced further enlargement in minimal lumen diameter (from 2.2 to 2.7 mm) and further reduction in residual stenosis (26.4% to 16.1%) compared with the results present after use of the new devices themselves. Major complications consisting of death (1.6%), Q-wave myocardial infarction (1.3%), or emergency bypass surgery (1.7%) occurred in 4.0% of patients (range, 2.6% to 8.7% across devices). Procedural success, defined as lesion success in all new device-treated lesions without a major complication, was achieved in 90.8% of patients, with a median length of hospital stay of 4 days. CONCLUSIONS NACI illustrates the type of information that can be obtained in a registry format that examines the acute angiographic and clinical results of new devices according to uniform definitions. Although no registry can substitute for formal interdevice trials, registries such as this can supplement earlier single-center and multicenter reports. In doing so, they can help focus subsequent randomized interdevice comparisons on lesion types for which two or more devices have promising acute results. Given the substantial interdevice differences in baseline patient and lesion characteristics found in NACI, simple "head-to-head" comparison of the results of different devices might give misleading impressions and should be avoided unless such comparisons are restricted to carefully matched patient and lesion subgroups.

BACKGROUND Transluminal extraction coronary (TEC) atherectomy is a relatively new device that has recently been approved by the Food and Drug Administration. Because of its ability to aspirate clot and atheromatous material, TEC atherectomy may be useful in patients with stenoses in saphenous vein bypass grafts. METHODS AND RESULTS TEC atherectomy was performed on 158 saphenous vein graft lesions in 146 consecutive patients with a mean age of 65 +/- 8 years (78% men). Clinical indications for atherectomy included stable angina (37%), unstable angina (54%), and postinfarction angina after recent (< 1 month) myocardial infarction (8%). Patients with acute myocardial infarction and target vessels < 2 mm in diameter were excluded. The mean age of the bypass graft was 8.3 +/- 3.0 years, and 17% were diffusely diseased and degenerated. Complex lesion morphology included total occlusion (6%), eccentricity (64%), ulceration (18%), and thrombus (28%). The TEC atherectomy cutter was successfully advanced through 144 lesions (91%), but technical failures occurred in 14 lesions (9%), and these were subsequently managed by successful balloon angioplasty. Quantitative angiography revealed an increase in lumen diameter from 0.9 +/- 0.5 mm, to 1.5 +/- 0.7 mm after TEC atherectomy, to 2.3 +/- 0.8 mm after percutaneous transluminal coronary angioplasty (PTCA) (P < .001), which corresponded to decreases in diameter stenosis from 75 +/- 14%, to 58 +/- 20% after TEC atherectomy, to 36 +/- 22% after PTCA (P < .001). Device success was achieved in 39.2% (post-TEC atherectomy decrease in diameter stenosis > or = 20%), and procedural success was achieved in 84% (final diameter stenosis < 50% in the absence of a major complication). Angiographic complications were evident in 33 lesions (20.7%) immediately after TEC atherectomy and in 8 lesions (5%) after PTCA, including distal embolization (11.9%), no-reflow (8.8%), and abrupt closure (5.0%), but no perforations. Adjunctive PTCA (and other medical therapy) successfully managed 61% of angiographic complications. Serious clinical complications included in-hospital death in 3 patients (2.0%), emergency bypass surgery in 1 patient who died (0.7%), Q wave myocardial infarction in 3 patients (2.0%), non-Q wave myocardial infarction in 4 patients (2.7%), vascular injury requiring surgical repair and/or blood transfusion in 9 patients (6.1%), and hemorrhagic cerebral infarction in 4 patients (2.7%). Using a composite clinical end point defined as in-hospital death, emergency bypass surgery, or myocardial infarction, the strongest independent correlate (P < .001) of a severe clinical complication was the development of one or more serious angiographic complications (no-reflow, distal embolization, or abrupt closure) immediately after TEC atherectomy. Complete clinical follow-up was available in 118 (92%) of 128 eligible patients at an interval of 6.0 +/- 2.5 months after discharge. Late cardiac outcome included recurrent angina treated with medical therapy (18%), repeat percutaneous intervention on the original target lesion (26%), repeat coronary artery bypass surgery (5%), Q wave myocardial infarction (4%), and late cardiac death (7%). Angiographic follow-up in 105 (80%) of 132 eligible lesions revealed a restenosis rate of 69% (defined as a diameter stenosis > 50%), including 30 lesions (29%) with total occlusion of the original lesion. CONCLUSIONS In patients with stenoses in saphenous vein bypass grafts, TEC atherectomy is limited by the frequent need for adjunctive balloon angioplasty to achieve adequate lumen enlargement and to manage TEC atherectomy-induced complications. Although the incidence of serious clinical complications is similar to that of other percutaneous interventions in vein grafts, there is a high incidence of restenosis and late vessel occlusion. Prospective randomized studies are needed to determine the best revascularization strategy for high-risk patients with old degenerated vein

BACKGROUND Several types of atherectomy devices have been developed recently for treatment of patients with ischemic heart disease. METHODS AND RESULTS Mechanical rotational atherectomy (MRA) using a high-speed rotational burr (Rotablator) was performed on 116 lesions in 104 patients. MRA alone was performed in 27 lesions (23%), and conventional balloon angioplasty (PTCA) was performed after MRA in 89 lesions (77%). Diameter stenosis decreased from 70 +/- 13% before MRA to 54 +/- 23% after MRA, and the final diameter stenosis (after MRA alone or with adjunctive PTCA) was 30 +/- 20% (P < .001). Minimal lumen diameter increased from 1.0 +/- 0.5 mm before MRA to 1.4 +/- 0.7 mm after MRA, and the final minimal lumen diameter was 2.3 +/- 0.7 mm (P < .001). MRA resulted in a decrease in diameter stenosis of 20% or more in 44% of lesions, and the final diameter stenosis (after MRA alone or after PTCA) was less than 50% in 75% of lesions. Considering the small diameter of available burrs, the magnitude of lumen enlargement was equal to 91% of the burr diameter, and only 9% of the burr diameter was "lost" due to elastic recoil or spasm. These angiographic results were obtained despite the presence of complex lesion morphology, including the presence of calcification in 17% of lesions and ostial location in 26% of lesions. Significant angiographic complications included abrupt closure (13 lesions, 11.2%), no reflow (8 lesions, 7%), severe coronary vasospasm (16 lesions, 13.8%), and guide wire fracture (3 lesions, 2.7%). There were no coronary artery perforations. Adjunctive therapy, including salvage PTCA, thrombolytic agents, and vasodilators, was successful in treating angiographic complications in 42 of 49 lesions (86%). Clinical complications included Q-wave myocardial infarction (5 patients, 4.8%), non-Q-wave myocardial infarction (3 patients, 2.9%), femoral vascular injury requiring surgery (3 patients, 2.9%) or blood transfusion (8 patients, 7.7%), abrupt closure requiring emergency bypass graft surgery (2 patients, 1.9%), and in-hospital death (1 patient, 1.0%). Angiographic follow-up (mean follow-up interval, 5.0 +/- 2.0 months) was available in 84% of successfully treated patients and revealed a restenosis rate of 51%, defined as a residual diameter stenosis of more than 50%. There was no significant difference in restenosis rates between de novo lesions (50%) and restenosis (54%) lesions. CONCLUSIONS These data suggest that for the treatment of most coronary stenoses, PTCA is required after MRA to achieve satisfactory lumen enlargement or to salvage complications. Angiographic complications appear to be more common after MRA, and salvage PTCA often is required to manage these device-induced complications. The combination of MRA and PTCA does not prevent restenosis.

Dramatic improvements in angioplasty technology have allowed initial patient and lesion selection criteria to expand and to include the treatment of complex lesions in critically ill patients. Most recent estimates indicate that 900 000 patients were treated with a percutaneous approach in the United States in 2000 and 1.7 million patients were treated with one worldwide. As the technology has become more complex with the introduction of a variety of stents, atherectomy devices, capture devices, and filters, among others, interventionists have learned more about the procedures and the patients undergoing them. See p 642 In the early years of balloon angioplasty, success rates were low. In the initial National Heart, Lung and Blood Percutaneous Transluminal Coronary Angioplasty Registry from 1977 and 1981, clinical success, which was defined as a reduction in luminal diameter stenosis by ≥20% and no death, infarction, or coronary bypass surgery, was achieved in 61% of patients.1,2 Failures were often the result of dissection or refractory acute closure, emergency coronary bypass graft surgery (often required), and Q-wave myocardial infarction (often resulted). Nonfatal Q-wave myocardial infarction occurred in 4.9% of patients and death, nonfatal Q-wave myocardial infarction, or emergency surgery occurred in 8.8%.1–3 There was often nothing subtle about an angioplasty complication at that time. As operator experience has improved and improvements in technology have become available, these morbid complications have decreased markedly. The need for emergency surgery has declined from 5.8% (initial registry) to ≈0.5% (today). Satisfaction from these advances has been tempered by the recognition of just how frequently enzyme elevations result from even successful percutaneous revascularization procedures. The issue of cardiac enzyme elevation (or “biomarker” elevation, in the case of the troponins, which are not enzymes) has become increasingly important for 2 reasons.4–10 (1) The definition of acute infarction has changed, and …

BACKGROUND The pathological consequences of cardiovascular laser irradiation have been studied extensively in vitro. Previous in vivo studies of laser-induced injury have included analyses of acute and/or chronic findings in experimental animals. Little information, however, is available regarding the acute effects of laser irradiation of human vascular tissues in vivo. METHODS AND RESULTS To determine the acute pathology resulting from laser irradiation of human vascular tissue in vivo, specimens retrieved from 23 patients by directional atherectomy immediately after laser angioplasty (19 peripheral and four coronary) were examined by light microscopy. Of the 23 patients, three (13.0%) were treated with a metal-capped ("hot-tip") fiber coupled to a continuous-wave neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using up to 18 W power and 18-305 seconds of cumulative exposure time; in all three patients (100%), thermal injury, including frank charring several cell layers thick, was seen along the luminal borders of the atherectomy specimen. In eight of the 23 patients (34.5%), laser angioplasty was performed using a 250-microseconds holmium:YAG laser at fluences up to 2,300 mJ/mm2, a repetition rate of 5 Hz, and 25-200 seconds of cumulative exposure; in seven of eight patients (85.5%), the atherectomy specimen showed signs of vacuolar injury consisting of central and satellite Alcian-blue-negative vacuoles. In two patients (25.0%), there was a "smudged" or "shredded" edge, whereas in one patient, frank signs of thermal injury were observed. Finally, in 12 of the 23 patients (52.2%), laser angioplasty was performed using a 120-nsec excimer laser at fluences up to 60 mJ/mm2, a repetition rate of 25 Hz, and a cumulative exposure time of 21-315 seconds. Pathological findings among these 12 patients were limited to nine patients (75%) in whom a weakly basophilic, smudged, and/or shredded appearance approximately one cell layer thick was observed along the luminal border of the atherectomy specimen and two patients (16.7%) with small foci of vacuolar injury. None of the atherectomy specimens retrieved after excimer laser angioplasty disclosed signs of thermal injury. CONCLUSIONS These findings document that acute pathological alterations resulting from in vivo laser angioplasty are variable, depending on the laser source used, and are similar to that predicted by experimental studies performed previously in vitro. The prognostic implications of these varying pathological features remain to be clarified.

BACKGROUND The successful cultivation of human smooth muscle cells (SMC) from coronary and peripheral atherosclerotic lesions removed by percutaneous directional atherectomy is described. METHODS AND RESULTS Sixty-seven patients in whom plaque material was obtained compose the study population. A total of 73 lesions from both coronary (n = 38) and peripheral (n = 35) arteries of primary (n = 50) and restenotic origin (n = 23) were studied. Successful cultivation was significantly (p less than 0.001) dependent on the quantity of plaque material submitted. Fifty-five percent of patients in whom atherectomy specimens were removed from coronary lesions yielded an adequate SMC population in comparison to 89% of those from peripheral arteries (p less than 0.01). Cultivation was not dependent on the age and sex of patients, lesion origin, risk factors, medications, or incidence of unstable angina. In an attempt to quantify SMC activity, migratory velocity was measured with a computer-assisted motion analysis system. SMC migratory velocity was found to be significantly (p less than 0.001) greater in restenotic than in primary plaque material. This finding was confirmed for both coronary and peripheral lesions. CONCLUSIONS Our data suggest that elevated SMC migratory activity may be an important mechanism in the development of restenotic lesions.

In 458 BC, a prominent Roman leader named Lucius Quintius Cincinnatus was unique in his behavior. Cincinnatus served his country when he was needed and, after fulfilling his duty, he returned to his private life.1 We now see a new medical device, a biodegradable stent, that mimics this historical figure. The 2 main functions of a stent, treatment of dissection and prevention of restenosis, refer to 2 events that occur and progress in a set frame of time. Coronary dissections are effectively contained by stent insertion and undergo a healing process, with the majority of cardiac events occurring in the first 6 months.2 In-stent restenosis also occurs within the first 6 months.3 Therefore, a permanent prosthesis that is in place beyond this initial period has no clear function. Besides lacking a well-defined function, are there any negative aspects related to the presence of a permanent coronary implant? Zidar et al4 stated that one of the main reasons to develop a biodegradable stent was the short-term need for a stent and the potential long-term complications of metal stents. Kimura et al3 demonstrated, with an extended angiographic follow-up of 3 years, that the presence of a metallic stent does not seem to be associated with lesion progression or accelerated atherosclerosis of the treated site after 6 months. In fact, late improvement in luminal diameter seems to occur between 6 months and 3 years. The Belgian Netherlands Stent Study (BENESTENT I) recently extended its follow-up to 5 years and demonstrated a sustained and persistent benefit of the stent.5 If no demonstrable complications exist with a permanent intracoronary implant, can the question be turned around by asking, “What are the benefits of not having a permanent coronary implant?” Two answers can be given. 1. Coronary stenting freezes recoil, …

Background— The molecular regulation for the transition from stable to vulnerable plaque remains to be elucidated. Heme oxygenase 1 (HO-1) and its metabolites have been implicated in the cytoprotective defense against oxidative injury in atherogenesis. In this study, we sought to assess the role of HO-1 in the progression toward plaque instability in carotid artery disease in patients and in a murine model of vulnerable plaque development. Methods and Results— Atherectomy biopsy from 112 patients with clinical carotid artery disease was collected and stratified according to characteristics of plaque vulnerability. HO-1 expression correlated closely with features of vulnerable human atheromatous plaque ( P −/− mice, HO-1 expression was upregulated in vulnerable versus stable lesions. HO-1 induction by cobalt protoporphyrin impeded lesion progression into vulnerable plaques, indicated by a reduction in necrotic core size and intraplaque lipid accumulation, whereas cap thickness and vascular smooth muscle cells were increased. In contrast, inhibition of HO-1 by zinc protoporphyrin augmented plaque vulnerability. Plaque stabilizing was prominent after adenoviral transduction of HO-1 compared with sham virus–treated animals, providing proof that the observed effects on plaque vulnerability were HO-1 specific. Conclusions— Here we demonstrate in a well-defined patient group and a murine vulnerable plaque model that HO-1 induction reverses plaque progression from a vulnerable plaque to a more stable phenotype as part of a compensatory atheroprotective response.

BACKGROUND Directional coronary atherectomy has recently become available to treat coronary stenoses. This study was performed to determine the relation of patient characteristics and stenosis morphology to procedural outcome with directional coronary atherectomy to gain insight into which patients might be best treated with this device. METHODS AND RESULTS Four hundred stenoses from 378 patients consecutively treated at six major referral institutions were analyzed. Angiographic data were assessed at a central angiographic laboratory using standardized morphological criteria and computer-assisted quantitative dimensional analyses. Procedural success was achieved in 87.8% of stenoses, and major ischemic complications (death, myocardial infarction, and emergency bypass surgery) occurred in 6.3% of patients. Lesion success and complications were closely correlated with recognized modified American College of Cardiology/American Heart Association Task Force lesion morphological criteria. Observed for type A stenoses were 93% success and 3% complication rates; for type B1 stenoses, 88% success and 6% complication rates; and for type B2 stenoses, 75% success and 13% complication rates, respectively. There were too few type C stenoses treated to analyze. Furthermore, multivariate testing demonstrated stenosis angulation (multivariate p less than 0.001), proximal tortuosity (p less than 0.001), decreased preatherectomy minimum lumen dimension (p = 0.032), and calcification (p = 0.041) to correlate independently with adverse outcome and complex, probably thrombus-associated stenoses to have a favorable outcome (p = 0.055). Operator experience (p = 0.020) and a history of restenosis (p = 0.022) also favorably influenced outcome. CONCLUSIONS The procedural outcome of directional coronary atherectomy is highly associated with coronary stenosis morphology. Furthermore, after appropriate stratification for morphology and clinical presentation, overall atherectomy procedural outcome may be similar to that achieved with coronary angioplasty. However, specific subsets of patients may have relatively better outcome with either atherectomy or balloon angioplasty.

Background— Cannabinoid 1 (CB1) receptor blockade with rimonabant represents a clinical therapeutic strategy for obesity. Recently, the role of the endocannabinoid system has been described in peripheral organs. We sought to determine whether the endocannabinoid system could be involved in human atherosclerosis and whether CB1 receptor blockade could modulate proinflammatory activity in macrophages. Methods and Results— mRNA expression levels of CB1 receptor in coronary atherectomy samples were significantly higher in patients with unstable angina than in those with stable angina (3.62±2.96-fold; n=7; P P P P P P P P Conclusions— Patients with coronary artery disease demonstrated the activation of the endocannabinoid system with elevated levels of blood endocannabinoids and increased expression of CB1 receptor in coronary atheroma. CB1 receptor blockade exhibited antiinflammatory effects on macrophages, which might provide beneficial effects on atherogenesis.

In an effort to enhance long-term patency in the coronary circulation, interventional cardiologists have examined the effects of a plethora of devices designed to improve short-term results and reduce the possibility of restenosis. Two disparate techniques, debulking by means of directional coronary atherectomy (DCA) and arterial scaffolding by stent implantation, have been tested separately in prospective randomized trials with respect to angiographic and clinical restenosis. In this issue of Circulation , Moussa et al1 combine plaque excision and slotted-tube stent placement in an attempt to show that the 2 methods are synergistic. DCA has been tested in several well-designed prospective, randomized comparisons with balloon angioplasty. Two early studies, CAVEAT and CCAT, showed that DCA applied to patients with focal lesions in native coronary arteries resulted in only slight reductions in the rate of restenosis. Specifically, in the CAVEAT trial, in which 1012 patients were randomized to DCA or balloon angioplasty,2 angiographic restenosis was only slightly reduced, from 57% in the balloon group to 50% in DCA group; clinical restenosis was unchanged (34% versus 35%). An unexpected and disturbing finding was the excess mortality at 1 year in the DCA group (2.2% for DCA versus 0.6% for PTCA, P =0.035), a finding possibly attributable to the doubling of periprocedural non–Q-wave infarction in patients treated with atherectomy. In the CCAT trial,3 DCA was performed in patients with isolated stenoses in the proximal left anterior descending coronary artery, and results were similar: a nonsignificant reduction in angiographic restenosis (46% versus 43%) and no decrease in clinical restenosis (30.1% versus 30.6%). DCA was further evaluated in CAVEAT II, a trial in which 305 patients with saphenous vein bypass graft stenoses were randomized to either DCA or balloon angioplasty.4 Although initial angiographic success was superior in the DCA arm, there was …

Directional coronary atherectomy (DCA) was originally developed as a potential replacement for balloon angioplasty. The design of the catheter used to perform DCA offered several unique advantages. First, it was capable of removing obstructive atherosclerotic lesions. Thus rather than rearranging plaque within an artery as occurs with balloon angioplasty, the obstruction was relieved by reduction of the plaque mass. Second, certain lesions with characteristics unfavorable for balloon angioplasty appeared to be ideally suited for DCA. Since the atherectomy catheter had a cutting window that could be positioned rotationally as well as longitudinally within an artery, eccentric plaque could be removed selectively. Similar benefits were anticipated from lesions located at important coronary bifurcations, such as those involving the left anterior descending coronary artery and origin of the diagonal branch. Finally, tissue removed by DCA was available for analysis to expand our knowledge about coronary atherosclerosis. Samples of coronary atheroma could be examined grossly and microscopically1 and studied by immunohistochemistry.2 Initially, the value of DCA was assessed by means of a large registry that catalogued acute and late clinical outcomes.3 When compared with a historical control, the results of DCA appeared comparable to or better than those achieved by balloon angioplasty. There was a sense that the incidence of serious coronary dissection and abrupt occlusion after DCA was less than that after balloon angioplasty.4 DCA became the first of the “new” percutaneous, catheter-based devices approved for the treatment of coronary disease in the United States. Interestingly, unlike current “new devices,” approval did not require the performance of a randomized, clinical trial. DCA was quickly and enthusiastically embraced by the interventional community. During this early phase of its use, DCA was performed without adjunctive balloon angioplasty; that is, the DCA catheter was used alone and not …

Background— Bacterial infection has been discussed as a potential etiologic factor in the pathophysiology of coronary heart disease (CHD). This study analyzes molecular phylogenies to systematically explore the presence, frequency, and diversity of bacteria in atherosclerotic lesions in patients with CHD. Methods and Results— We investigated 16S rDNA signatures in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients with CHD, control material from postmortem patients (n=15), and heart-beating organ donors (n=11) using clone libraries, denaturating gradient gel analysis, and fluorescence in situ hybridization. Bacterial DNA was found in all CHD patients by conserved PCR but not in control material or in any of the normal/unaffected coronary arteries. Presence of bacteria in atherosclerotic lesions was confirmed by fluorescence in situ hybridization. A high overall bacterial diversity of >50 different species, among them Staphylococcus species, Proteus vulgaris , Klebsiella pneumoniae , and Streptococcus species, was demonstrated in >1500 clones from a combined library and confirmed by denaturating gradient gel analysis. Mean bacterial diversity in atheromas was high, with a score of 12.33±3.81 (range, 5 to 22). A specific PCR detected Chlamydia species in 51.5% of CHD patients. Conclusions— Detection of a broad variety of molecular signatures in all CHD specimens suggests that diverse bacterial colonization may be more important than a single pathogen. Our observation does not allow us to conclude that bacteria are the causative agent in the etiopathogenesis of CHD. However, bacterial agents could have secondarily colonized atheromatous lesions and could act as an additional factor accelerating disease progression.

Background— Apoptosis in human atherosclerotic coronary plaques possibly causes plaque destabilization by contributing to the weakening and breaking down of the fibrous cap. We tested the hypothesis that apoptosis is quantitatively increased in unstable atherosclerotic plaques. Methods and Results— We analyzed the expression of apoptotic genes such as BAX , CASP1 , FAS , FAS L , FOS , MDM2 , NFkB2 , P53 , PCNA , TERT , and XRCC1 in coronary plaques collected with directional coronary atherectomy from 15 patients with stable angina and 15 with acute coronary syndromes without ST elevation (ACS). Total RNA was extracted and cDNA was amplified with a specific set of primers and TaqMan probes. Apoptosis was also revealed by DNA laddering. To clarify the source of mRNAs, we performed in situ reverse transcriptase-polymerase chain reaction coupled with immunocytochemistry and found a substantial overlap between the mRNAs of the above genes and vascular smooth muscle cells. Gene expression analysis showed that the proapoptotic genes (ie, BAX , CASP1 , FAS , FAS L , FOS , NFkB2 , P53 , PCNA ) were significantly more expressed ( P MDM2 , TERT , XRCC1 ) were more transcribed ( P Conclusions— Our findings support the idea that ACS plaques are committed to apoptosis through an established meshwork of gene activation and inactivation, whereas stable angina plaques retain active cell homeostasis and repair mechanisms.

A 72-year-old blind woman with pseudoxanthoma elasticum had typical angina pectoris for 6 weeks. She was admitted to our emergency room with signs of anterior myocardial ischemia on ECG. On physical examination there was a remarkable wrinkling of the skin at her neck and elbows. Coronary angiography showed a significant stenosis of the …