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There is a paucity of data on the burden of in-stent restenosis (ISR) in the United States as well as on its presentation and appropriate treatment strategies.This study aims to provide an analysis of the temporal trends, clinical presentation, treatment strategies, and in-hospital outcomes of patients undergoing percutaneous coronary intervention (PCI) for ISR in the United States.This study is a retrospective analysis of data collected in the Diagnostic Catheterization and Percutaneous Coronary Intervention (CathPCI) registry of the National Cardiovascular Data Registry (NCDR) between 2009 and 2017. Of the total patients undergoing PCI, we identified those undergoing PCI for ISR lesions. For comparison of in-hospital outcomes, propensity-score matching was employed.Among the 5,100,394 patients undergoing PCI, 10.6% of patients underwent PCI for ISR lesions. Patients with bare-metal stent ISR declined from 2.6% in 2009 Q3 to 0.9% in 2017 Q2 (p 0.001), and drug-eluting stent ISR rose from 5.4% in 2009 Q3 to 6.3% in 2017 Q2 (p 0.001). Patients with ISR PCI were less likely to present with non-ST-segment elevation myocardial infarction (MI) (18.7% vs. 22.5%; p 0.001) or ST-segment elevation MI (8.5% vs. 15.7%; p 0.001). In the propensity-matched population of patients, there were no significant differences between patients with ISR and non-ISR PCI for in-hospital complications and hospital length of stay.ISR represents approximately 10% of all PCI and is treated most commonly with another stent. Approximately 25% of patients present with acute MI. In-hospital outcomes of patients with ISR PCI are comparable with those undergoing non-ISR PCI.

Rotational atherectomy (RA) is an established tool in interventional cardiology for treatment of calcified coronary lesions. Over 3 decades of clinical experience and research, techniques have matured and outcomes have improved. Heterogeneity exists, however, in RA utilization and technique. We assembled a group of experienced RA operators and device experts to summarize and critique key elements of contemporary RA technique, to identify areas of consensus and controversy, and to offer recommendations for optimal performance for the practicing interventional cardiologist. Evolution in RA strategy toward a focus on lesion modification to facilitate balloon angioplasty and stenting has underpinned major advances in procedural safety, including opportunity to use smaller caliber equipment and radial access. Optimal technique and improved safety have permitted exploratory use of RA for different lesion types and reevaluation of procedural requirements, including flush solution composition and transvenous pacing. Preparedness to manage complications remains paramount and recommendations for operators and institutions are outlined.

BACKGROUND In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve longterm outcomes. METHODS In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt–chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. RESULTS Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, −0.5 to 3.9; P = 0.007 for noninferiority and P = 0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P = 0.29), targetvessel myocardial infarction (6.0% and 4.6%, respectively; P = 0.18), or ischemiadriven target-lesion revascularization (3.0% and 2.5%, respectively; P = 0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P = 0.13). CONCLUSIONS In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt–chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.)

The Absorb everolimus-eluting poly-L-lactic acid-based bioresorbable vascular scaffold (BVS) provides early drug delivery and mechanical support functions similar to metallic drug-eluting stents (DES), followed by complete bioresorption in approximately 3 years with recovery of vascular structure and function. The ABSORB III trial demonstrated noninferior rates of target lesion failure (cardiac death, target vessel myocardial infarction [TVMI], or ischemia-driven target lesion revascularization) at 1 year in 2,008 patients with coronary artery disease randomized to BVS versus cobalt-chromium everolimus-eluting stents (EES).This study sought to assess clinical outcomes through 3 years following BVS implantation.Clinical outcomes from the ABSORB III trial were analyzed by randomized treatment assignment cumulative through 3 years, and between 1 and 3 years.The primary composite endpoint of target lesion failure through 3 years occurred in 13.4% of BVS patients and 10.4% of EES patients (p = 0.06), and between 1 and 3 years in 7.0% versus 6.0% of patients, respectively (p = 0.39). TVMI through 3 years was increased with BVS (8.6% vs. 5.9%; p = 0.03), as was device thrombosis (2.3% vs. 0.7%; p = 0.01). In BVS-assigned patients, treatment of very small vessels (those with quantitatively determined reference vessel diameter 2.25 mm) was an independent predictor of 3-year TLF and scaffold thrombosis.In the ABSORB III trial, 3-year adverse event rates were higher with BVS than EES, particularly TVMI and device thrombosis. Longer-term clinical follow-up is required to determine whether bioresorption of the polymeric scaffold will influence patient prognosis. (ABSORB III Randomized Controlled Trial [RCT] [ABSORB-III]; NCT01751906).

Background The PLATINUM randomized trial enrolled 1530 patients treated with either the platinum chromium PROMUS Element everolimus-eluting stent (PtCr-EES; Boston Scientific, Natick, MA, USA) or the predicate cobalt chromium PROMUS/XIENCE V EES (CoCr-EES; manufactured as XIENCE V by Abbott Vascular, Santa Clara, CA, USA also distributed as PROMUS by Boston Scientific), including 124 patients from Japanese sites. This substudy examines 2-year outcomes in the Japanese and non-Japanese cohorts. Methods Patients with 1 or 2 de novo native coronary artery lesions (baseline vessel diameter ≥2.50 mm to ≤4.25 mm and length ≤24 mm) were randomized 1:1 to PtCr-EES ( N = 63 patients in Japan) versus CoCr-EES ( N = 61 patients in Japan). Results Several significant differences were noted in baseline demographics, lesion characteristics, and procedural technique between Japanese and non-Japanese patients, including longer fluoroscopy time, less use of contrast, and greater post-dilatation usage and maximum pressure in Japan. Dual antiplatelet usage at 2 years was also higher in Japan. Despite these differences, the 2-year rates of target lesion failure were comparable in patients treated with PtCr-EES and CoCr-EES both in Japan (3.2% vs 5.0% respectively, p = 0.68) and outside Japan (4.7% vs 5.9% respectively, p = 0.33; p for interaction = 0.82). Conclusions This PLATINUM study subanalysis suggests that the PtCr-EES and CoCr-EES provide comparable safety and efficacy in both Japanese and non-Japanese patients.

Background Transapical (TA) aortic valve replacement was an integral part of the Placement of Transcatheter Aortic Valves (PARTNER) trial. Enrollment during the randomized trial included 104 transapical (premarket approval TA [PMA-TA]) and 92 surgical aortic valve replacements (SAVR) within the TA cohort. On completion of the trial, enrollment continued in a nonrandomized continued access (NRCA) program. We compared the outcomes of NRCA-TA procedures with those of PMA-TA and SAVR. Methods In 22 centers, 975 patients underwent TA aortic valve replacement as part of the NRCA registry. Inclusion and exclusion criteria were unchanged from the previously reported PARTNER trial. All patients were followed up for at least 1 year. Results Thirty-day or in-hospital mortality was 8.8% for the NRCA-TA cohort, compared with 10.6% and 12.0% for the PMA-TA and SAVR patients, respectively ( p = 0.54). One-year mortality in the NRCA-TA cohort was 22.1%, not significantly lower than the mortality in PMA-TA and SAVR patients at 29.0% and 25.3%, respectively ( p = 0.27). Thirty-day or in-hospital stroke was 2.2% among NRCA-TA patients in contrast to the 6.7% stroke rate observed in the PMA-TA group and 5.4% in SAVR patients ( p = 0.008). Lower rates of neurologic adverse events in the NRCA-TA group persisted at 1 year compared with the PMA-TA and SAVR patients. Conclusions Among the 975 patients in the NRCA-TA cohort, rates of major outcomes including death and stroke compared favorably with outcomes of PMA-TA and SAVR patients enrolled in the PARTNER trial. This trend toward improved outcomes may be attributed to improved patient selection, individual centers surmounting the procedural learning curve, and refinements in surgical technique.

Objectives The aim of this study was to evaluate the 5-year clinical safety and efficacy outcomes of patients treated for in-stent restenosis of bare-metal stents (BMSs). Background The SISR trial is a prospective, randomized trial that compared the safety and efficacy of sirolimus-eluting stent (SES) vs vascular brachytherapy (VBT) for the treatment of BMS in-stent restenosis. Methods A total of 384 patients with BMS in-stent restenosis were randomized to treatment with SES (n = 259) or VBT (n = 125) and were followed for 5 years. Results At 5 years, the rates of target lesion revascularization (TLR) had narrowed and were nonsignificant between the SES and VBT groups, with TLR rates of 24.7% and 31.2% (95% CI −16.3% to 2.8%, P = .179) respectively. Target vessel failure was 33.6% vs 36.8% (95% CI −13.5% to 6.7% P = .568) for SES compared with VBT. The rate of major adverse cardiac event at 5 years was 34.0% vs 36.8% (95% CI −13.1% to7.1%, P = .648) for the SES compared with VBT. There were no differences between SES and VBT in terms of survival free from TLR (72.9% vs 66.4%, log-rank P = .08) or from target vessel failure (64.4% vs 61.3%, log-rank P = .349). There were no significant differences in the rates of definite/probable stent thrombosis (5.9% vs 2.5%, 95% CI −7.9% to 1.3%, P = .182) between the 2 groups. Conclusions At a 5-year follow-up, no differences in safety or efficacy outcomes were observed for treatment of BMS restenosis with SES vs VBT. There were no significant differences in survival free from TLR, target vessel revascularization, or major adverse cardiac events between the 2 groups at 5 years. Sirolimus-eluting stent is a viable treatment option compared with VBT for BMS restenosis.

Data have emerged demonstrating the safety and efficacy of percutaneous coronary intervention (PCI) of the unprotected left main (ULM) artery. The 2009 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions focused guidelines for PCI no longer state that ULM PCI is contraindicated in patients with anatomic conditions that are associated with a low risk of procedural complications and clinical conditions that predict an increased risk of adverse surgical outcomes. ULM PCI should be performed by operators with experience in the management of the anatomic complexities of left main and multivessel disease, specifically in issues relating to bifurcation disease, calcification, and hemodynamic support. Patients with ostial or shaft disease have lower risk of restenosis compared with distal bifurcation disease. Drug-eluting stents (DES) should be used whenever possible as they reduce clinical restenosis. Intravascular ultrasound is an integral component of the procedure as it provides accurate assessment of lesion severity and can confirm optimal stent expansion and apposition. Compliance with dual antiplatelet therapy for at least 12 months is essential if DES are used. A collaborative, multidisciplinary approach with a "Heart Team" represented by a cardiac surgeon, interventional cardiologist, and non-invasive cardiologist may optimize patient education and objective decision making when obtaining informed consent. Application of clinical and angiographic variables into risk models facilitates appropriate patient selection. Randomized clinical trials will address unanswered issues and help build consensus between cardiology and surgical societies to inform clinical decision making and optimize the outcomes for patients with ULM coronary artery disease.

AIMS: Assess clinical, angiographic, and intravascular ultrasound results in lesions treated with the PROMUS Element platinum chromium everolimus-eluting stent (EES). METHODS AND RESULTS: Patients (N=100) with one de novo target lesion ≤ 34 mm long and reference vessel diameter (RVD) ≥ 2.25-≤ 4.25 mm were enrolled at 14 sites. The primary endpoint was the 30-day composite of cardiac death, myocardial infarction, target lesion revascularisation (TLR), or definite/probable stent thrombosis (ST). The efficacy endpoint of 9 month in-stent late loss in workhorse lesions (defined as RVD ≥ 2.5-≤ 4.25 mm, lesion ≤ 24 mm) was compared to a performance goal based on historical results with TAXUS Express paclitaxel-eluting stents. Post-procedure incomplete stent apposition (ISA) was compared to a performance goal based on results with the PROMUS/XIENCE V EES in SPIRIT III. Mean age was 61.8 ± 9.9 years; 77.0% were male; 19% had medically treated diabetes. Baseline RVD was 2.72 ± 0.53 mm; lesion length was 15.4 ± 7.0 mm. The primary endpoint occurred in one patient (periprocedural ST with TLR) with no additional major clinical events through one year. Nine-month in-stent late loss in workhorse lesions (0.17 ± 0.25 mm, N=73) and post-procedure ISA (5.7%, 5/88) were below performance goals (p

ObjectivesThe objective of this study was to evaluate the antiplatelet effect of clopidogrel 150 mg/day in patients with high on-treatment reactivity (OTR) and to further assess this effect according to CYP2C19 genotype.BackgroundHigh OTR is associated with ischemic events in clopidogrel-treated patients after percutaneous coronary intervention. Alternative dosing regimens might enhance platelet inhibition.MethodsPatients with high OTR receiving a standard clopidogrel regimen were identified with the VerifyNow P2Y12 assay and administered clopidogrel 150 mg daily for 7 days, after which OTR was reassessed. Comprehensive CYP2C19 genotyping was performed with the BeadXpress platform (Illumina, San Diego, California) for the *2, *3, *4, *5, *6, *7, *8, and *17 variants.ResultsA total of 41 subjects were enrolled, 20 of whom were carriers of a CYP2C19 loss-of-function (LoF) allele. High-dose clopidogrel significantly reduced OTR from 285 ± 47 P2Y12 reaction units (PRU) to 220 ± 91 PRU (p < 0.001). There were no significant differences in antiplatelet effect according to CYP2C19 status, although the reduction in reactivity was minimal in the small number of patients homozygous for LoF alleles (n = 3, 28 ± 31 PRU, p = NS). Increasing body mass index was independently and negatively associated with the reduction in OTR (p = 0.009).ConclusionsIn patients with high OTR, clopidogrel 150 mg/day results in a significant reduction in platelet reactivity. Carriage of an LoF CYP2C19 polymorphism does not seem to have a major influence on dose effect. The observed lack of effect in patients with 2 copies of a CYP2C19 LoF allele must be confirmed by larger studies.

Percutaneous coronary intervention with drug-eluting stents (DES) may achieve midterm outcomes comparable to coronary artery bypass grafting (CABG) for unprotected left main coronary artery disease, but few real-world, long-term studies have been reported. In this study, 376 patients with unprotected left main coronary artery disease who underwent DES implantation (n = 131) or CABG (n = 245) were evaluated, and outcomes were compared using propensity analyses to adjust for baseline differences. Overall, 367 patients (98%) had complete clinical follow-up for a median of 4.0 years (interquartile range 3.2 to 4.7). Although the overall sample size was limited, there was a trend toward lower mortality with DES versus CABG in unadjusted (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.20 to 1.22, p = 0.13), multivariate-adjusted (HR 0.37, 95% CI 0.13 to 1.09, p = 0.07), and propensity score-adjusted (HR 0.34, 95% CI 0.12 to 1.03, p = 0.06) analyses. Treatment with DES was associated with a higher rate of target-vessel revascularization (TVR; 18% vs 9%, p = 0.02). However, ischemic TVR was not significantly different between the 2 groups (25% vs 39%, p = 0.15) in patients who received angiographic follow-up. No differences were detected in the occurrence of composite major adverse cardiac and cerebrovascular events between DES and CABG (27% vs 22%, p = 0.42). In conclusion, during 4-year follow-up, overall composite major adverse cardiac and cerebrovascular events were similar after DES and CABG treatment of unprotected left main coronary artery disease, with a trend toward lower mortality after percutaneous coronary intervention with DES. DES were associated with a higher rate of TVR compared to CABG, but ischemic TVR was not significantly different between the 2 groups.

Uncertainty regarding the appropriate duration of dual antiplatelet therapy (DAPT) with aspirin and a thienopyridine challenges every clinician involved in the care of patients considered for or treated with drug-eluting stents (DES). Despite guideline recommendations for extended (or =12 months) DAPT following percutaneous coronary revascularization with DES, few data are available to guide clinical decision-making beyond consensus opinion. Yet considering the clinical implications of stent thrombosis (ST) and its unpredictability in late occurring events, comprehensive assessment of the relationship between DAPT duration and ST over the long-term is a focus for DES-related clinical trials and an essential public health measure. Despite the potential for prolonged DAPT to reduce late-term cardiovascular events related to the progression of atherosclerosis, few studies have formally examined the safety and efficacy of extended DAPT and its impact on late ST events. The purpose of this paper is to appraise the existing evidence regarding the relationship between long-term DAPT and late cardiovascular events; address outstanding (and unstudied) dilemmas related to DAPT in DES-treated patients; and propose considerations for both trial design and clinical practice.

Small studies have indicated that drug-drug interactions and such clinical characteristics as diabetes mellitus may increase residual platelet reactivity in patients on clopidogrel therapy. The independent contribution of these variables to high residual platelet reactivity (HRPR) is not well studied. Residual platelet reactivity was assessed using the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, California) in 377 patients with stable coronary artery disease on maintenance clopidogrel therapy. HRPR was defined using a threshold previously shown to predict adverse clinical outcomes. Residual platelet reactivity was significantly higher in women (220 +/- 82 vs 200 +/- 77 P2Y12 reaction units [PRU]; p = 0.041), non-Caucasians (229 +/- 79 vs 202 +/- 78 PRU; p = 0.047), patients with diabetes mellitus (220 +/- 73 vs 196 +/- 80 PRU; p = 0.005), and those treated with nitrates (233 +/- 70 vs 200 +/- 80 PRU; p = 0.018) or proton-pump inhibitors (218 +/- 79 vs 198 +/- 78 PRU; p = 0.02), whereas residual platelet reactivity was significantly lower in active smokers (168 +/- 82 vs 208 +/- 77 PRU; p = 0.006). Independent predictors of HRPR were female gender (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.14 to 3.19, p = 0.014), non-Caucasian ethnicity (OR 3.05, 95% CI 1.49 to 6.28, p = 0.002), use of proton-pump inhibitors (OR 1.64, 95% CI 1.03 to 2.59, p = 0.035), and active smoking (OR 0.37, 95% CI 0.14 to 0.94, p = 0.037). HRPR was associated with increased 6-month mortality rates (3.0% vs 0%; p = 0.016). In conclusion, our findings support the hypothesis that clopidogrel nonresponsiveness is primarily the result of genetic mechanisms and factors that may influence activity of the cytochrome P-450 system.

In the early 1970s, coronary artery bypass graft (CABG) was found to improve late survival in comparison to medical therapy in patients with significant left main stenosis.1–3 Once CABG became the standard of care for left main disease, a distinction between “protected”—by at least 1 patent bypass graft to the left coronary artery—and “unprotected left main (UPLM)”— no patent bypass graft to the left coronary artery—was made. In the 1980s, early attempts at balloon angioplasty of UPLM stenoses were associated with poor early outcomes because of coronary dissection, abrupt closure, and restenosis. Mortality rates as high as 30% at 1 year were reported.4–6 In the 1990s, bare metal stents were introduced and soon used to treat UPLM disease. Several small registries found a low rate of procedural complications, but repeat revascularization rates of 20% to 30% because of restenosis were considered unacceptable.7–12 Early bare metal stent registries for UPLM also found high mortality rates, particularly in high-risk patients, such as patients with acute coronary syndromes and poor left ventricular function. Importantly, high-risk subgroups often presented with late sudden death after stenting.11,13 In the early 2000s, the introduction of drug-eluting stents (DES), with the promise of vastly reduced rates of restenosis,14–17 raised the possibility of improved late outcomes in this challenging patient group. Response by Smith p 1033 Clinical outcomes after treatment of UPLM disease with either the sirolimus-eluting stent or the paclitaxel-eluting stent from >20 small registries have been published. Results reported in these registries vary widely.18–40 As depicted in Table 1, cardiac mortality between 6 and 12 months after the procedure ranges from 0% to 11%. Target lesion revascularization (TLR) or target vessel revascularization (TVR) rates range from 2% to 38%. This wide variation in clinical outcome appears largely because of variation …

Proteinuria was associated with cardiovascular events and mortality in community-based cohorts. The association of proteinuria with mortality and cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) was unknown. The association of urinary dipstick proteinuria with mortality and cardiovascular events (composite of death, myocardial infarction, or nonhemorrhagic stroke) in 5,835 subjects of the EXCITE trial was evaluated. Dipstick urinalysis was performed before PCI, and proteinuria was defined as trace or greater. Subjects were followed up for 210 days/7 months after enrollment for the occurrence of events. Multivariate Cox regression analysis evaluated the independent association of proteinuria with each outcome. Mean age was 59 years, 21% were women, 18% had diabetes mellitus, and mean estimated glomerular filtration rate was 90 ml/min/1.73 m(2). Proteinuria was present in 750 patients (13%). During follow-up, 22 subjects (2.9%) with proteinuria and 54 subjects (1.1%) without proteinuria died (adjusted hazard ratio 2.83, 95% confidence interval [CI] 1.65 to 4.84, p

The Food and Drug Administration convened a special public meeting of the Circulatory System Devices Advisory Panel in late 2006 in response to data suggesting a small but potentially significant increased risk of stent thrombosis with drug-eluting stents (DES). This panel concluded that "off-label" DES use was associated with an increased risk of adverse outcomes compared with "on-label" use. In this commentary, we will discuss the role of product labeling in clinical decision-making during percutaneous coronary intervention, elucidate the issues that may arise from the conflation of the responsibilities of regulatory bodies and physicians, and offer a potential framework for their resolution.

A clopidogrel loading dose before percutaneous coronary intervention may reduce ischemic events but can increase bleeding risk and result in delayed treatment in patients who subsequently require surgical revascularization. The goal of this study was to examine the dynamics of platelet functional recovery after the common clinical scenario of a single 600-mg loading dose of clopidogrel. Fourteen volunteers were administered clopidogrel 600 mg. Platelet reactivity was measured before exposure, 4 hours after exposure, and then daily for 8 days using the VerifyNow P2Y12 assay. Percentage inhibition (PI) was calculated as the relative change in P2Y12 reaction units from baseline. One day after clopidogrel, the median PI was 39.9% (range 8.5% to 97.7%). Before day 5, the number of days after exposure was significantly but weakly correlated with PI (Pearson's coefficient = 0.45, R2 = 0.20, p = 0.001), while most of the variance in PI on each day of recovery was explained by the PI that was observed the previous day (Pearson's coefficient = 0.95, R2 = 0.92, p0.001). The decay in PI over time was exponential, with a common ratio of 17% relative reduction per day (95% confidence interval 10% to 23%). Similar findings were observed when the effect of clopidogrel was defined by residual platelet reactivity or by the adenosine diphosphate-prostaglandin E1/iso-thrombin receptor-activating peptide ratio. In conclusion, platelet inhibition on each day after a loading dose varies considerably among subjects. The level of inhibition depends less on the number of days after exposure than on the magnitude of initial inhibition after loading. A strategy of individual platelet function monitoring should be examined in patients requiring cardiac surgery after clopidogrel loading.

Objectives The aim of this study was to evaluate long-term outcome of patients treated for in-stent restenosis of bare-metal stents (BMS). Background Treatment of restenosis of BMS is characterized by high recurrence rates. Vascular brachytherapy (VBT) improved outcome although late catch-up events were documented. Drug-eluting stents tested against VBT in this setting were found superior for at least the first year; superiority at longer follow-up is uncertain. Methods We evaluated 3-year outcome of the multicenter SISR (Sirolimus-Eluting Stents Versus Vascular Brachytherapy for In-Stent Restenosis) trial, which randomized patients with restenosis of BMS to either a sirolimus-eluting stents (SES) or VBT. Results Target vessel failure (cardiac death, infarction, or target vessel revascularization [TVR]) at 9 months as previously reported was significantly improved with SES. Kaplan-Meier analysis at 3 years documented that survival free from target lesion revascularization (TLR) and TVR continues to be significantly improved with SES: freedom from TLR 81.0% versus 71.6% (log-rank p = 0.018), and TVR 78.2% versus 68.8% (log-rank p = 0.022), SES versus VBT. At 3 years, target vessel failure and major adverse cardiac events (death, infarction, emergency coronary artery bypass grafting, or repeat TLR) remained improved with SES, but did not reach statistical significance. There was no statistically significant difference in definite or probable stent thrombosis (3.5% for SES, 2.4% for VBT; p = 0.758). Conclusions At 3 years of follow-up, after treatment of in-stent restenosis of BMS, patients treated with SES have improved survival free of TLR and TVR compared with patients treated with VBT. Stent thrombosis rates are not different between the 2 groups but are higher than reported in trials of treatment of de novo lesions.

Aims The aim of this study was to determine whether platelet reactivity on clopidogrel therapy, as measured by a point-of-care platelet function assay, is associated with thrombotic events after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Methods and results Platelet reactivity on clopidogrel (post-treatment reactivity) was measured with the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, CA, USA) in 380 patients undergoing PCI with sirolimus-eluting stents. Receiver-operating characteristic curve analysis was used to derive the optimal cut-off value for post-treatment reactivity in predicting 6 month out-of-hospital cardiovascular (CV) death, non-fatal MI, or stent thrombosis. The mean post-treatment reactivity was 184 ± 85 PRU (P2Y12 reaction units). The optimal cut-off for the combined endpoint was a post-treatment reactivity ≥235 PRU [area under the curve 0.711 (95% confidence interval 0.529–0.893), P = 0.03], which was similar to the threshold of the upper tertile (231 PRU). Patients with post-treatment reactivity greater than the cut-off value had significantly higher rates of CV death (2.8 vs. 0%, P = 0.04), stent thrombosis (4.6 vs. 0%, P = 0.004), and the combined endpoint (6.5 vs. 1.0%, P = 0.008). Conclusion High post-treatment platelet reactivity measured with a point-of-care platelet function assay is associated with post-discharge events after PCI with DES, including stent thrombosis. Investigation of alternative clopidogrel dosing regimens to reduce ischaemic events in high-risk patients identified by this assay is warranted.

Udgivelsesdato: 2008-Feb BACKGROUND: Cardiac surgery is the standard treatment for unprotected left main disease (ULM). Drug-eluting stent (DES) implantation has been recently reported in patients with ULM but with unclear results. We systematically reviewed outcomes of percutaneous DES implantation in ULM. METHODS: Several databases were searched for clinical studies reporting on > or = 20 patients and > or = 6-month follow-up. The primary end point was major adverse cardiovascular events (MACEs; ie, death, myocardial infarction, or target vessel revascularization [TVR]) at the longest follow-up. Incidence and adjusted risk estimates were pooled with generic inverse variance random-effect methods (95% CIs). RESULTS: From 823 initial citations, 16 studies were included (1278 patients, median follow-up 10 months). Eight were uncontrolled registries, 5 nonrandomized comparisons between DES and bare-metal stents and 3 nonrandomized comparisons between DES and CABG, with no properly randomized trial. Meta-analysis for DES-based PCI showed, at the longest follow-up, rates of 16.5% (11.7%-21.3%) MACE, 5.5% (3.4%-7.7%) death, and 6.5% (3.7%-9.2%) TVR. Comparison of DES versus bare-metal stent disclosed adjusted odds ratios for MACE of 0.34 (0.16-0.71), and DES versus CABG showed adjusted odds ratios for MACE plus stroke of 0.46 (0.24-0.90). Meta-regression showed that disease location predicted MACE (P = .001) and TVR (P = .020), whereas high-risk features predicted death (P = .027). CONCLUSIONS: Clinical studies report apparently favorable early and midterm results in selected patients with ULM. However, given their limitations in validity and the inherent risk for DES thrombosis, results from randomized trials are still needed to definitely establish the role of DES implantation instead of the reference treatment, surgery.

Percutaneous coronary intervention (PCI) has played an integral role in the therapeutic management strategies for patients who present with either acute coronary syndromes or stable angina pectoris. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial enrolled patients with chronic stable angina and at least 1 significant (or =70%) angiographic coronary stenosis who were randomly assigned to an initial treatment of either PCI in conjunction with optimal medical therapy or optimal medical therapy alone. Although the initial management strategy of PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events, improvement in angina-free status and a reduction in the requirement for subsequent revascularization was observed. An in-depth analysis of the COURAGE trial design and execution is provided.

Objective: The goal of this study was to determine whether three-dimensional (3D) reconstruction of traditional coronary angiography could optimize the choice of drug-eluting stent (DES) length and number during percutaneous coronary intervention (PCI). Background: Coronary angiography is subject to significant foreshortening artifact that limits the ability of the operator to accurately determine lesion length. Methods: The angiographic images of the target vessels of consecutive PCI procedures were postprocessed using a 3D reconstruction algorithm. The appropriate length and optimal number of DES to span each target lesion were calculated and compared with the number and length of DES actually chosen by the operator. Results: A total of 42 target vessels were analyzed, and 3D reconstruction was successful in 38/42 (90.5%) of cases. The results of 3D analysis would have changed operator decision making in six cases (16%): in four cases, the stent chosen by the operator was too short requiring an additional DES; in two cases, the chosen DES was too long and exchanged for a shorter one. In each of these six cases, 3D analysis would have determined the correct stent length prior to stent selection. The optimal stent number derived by 3D reconstruction was significantly less than the actual number of stents per lesion used by the operator (1.31 6 0.47 versus 1.54 6 0.68, P = 0.01), and the optimal stent length trended less than the actual stented length (27.5 6 12.8 mm versus 28.7 6 14.7 mm, P = 0.23). Conclusions: 3D reconstruction algorithm of standard coronary angiography is a promising technique to improve DES utilization during PCI. ' 2006 Wiley-Liss, Inc.

The optimal treatment for sirolimus-eluting stent (SES) restenosis is not known. This study evaluated the safety and clinical outcome of paclitaxel-eluting stent (PES) implantation for SES restenosis. From March 2004 to July 2005, PESs were implanted in 125 patients with 140 lesions with SES restenosis. Acute and 6-month clinical outcomes were determined through review of the medical record and/or telephone interview. In-hospital major adverse cardiac events (death, nonfatal myocardial infarction, or repeat revascularization) occurred in 14 patients (11.2%), driven entirely by postprocedure non-Q-wave myocardial infarction. At a mean clinical follow-up of 7.2 +/- 1.8 months, the incidence of target lesion revascularization (TLR) was 14.0%, and the rate of major adverse cardiac events was 17.2%. Subacute thrombosis occurred in 2 patients (1.6%). Length of PES implanted, postprocedure diameter stenosis, and total occlusion of the target lesion were independent predictors of TLR. In patients with de novo SES restenosis, TLR was only 8.7%. In conclusion, at medium-term follow-up, PES implantation for SES failure appears to be safe and effective, although efficacy is decreased in the setting of total occlusions, greater residual diameter stenosis, and longer PESs.

A randomized, controlled clinical trial demonstrated that intravenous (IV) fenoldopam did not prevent further deterioration in renal function after contrast administration in patients with chronic renal insufficiency. This lack of effect may have been a consequence of the inability to administer an effective renal dose of IV fenoldopam. This study sought to determine whether compared with IV administration, selective intrarenal (IR) fenoldopam would increase local concentration, leading to a higher glomerular filtration rate (GFR), and, because of first-pass renal elimination, result in lower systemic drug levels and less decrease in systemic blood pressure (BP). A randomized, controlled, open-label, partial crossover design trial was conducted in which 33 patients who underwent coronary angiography were randomized in a 1:2 ratio to control or fenoldopam (initially IV, then crossed over to IR through a bifurcated renal infusion catheter). Compared with IV fenoldopam, IR administration was associated with a significantly higher GFR (73.7 +/- 3.1 vs 62.6 +/- 2.5 ml/min, p = 0.0007) and renal plasma flow (537.2 +/- 34.0 vs 494.0 +/- 35.5 ml/min, p0.01), lower fenoldopam plasma levels (3.3 +/- 0.3 vs 4.8 +/- 0.3 ng/ml, p0.0001), and greater nadir systolic BP (125.5 +/- 3.6 vs 117.4 +/- 2.8 mm Hg, p0.0001). Two hours after drug discontinuation after contrast administration, GFRs in the patients who received IR fenoldopam remained higher than in controls (+15.0 ml/min [+25%] vs -8.0 ml/min [-14.0%], p0.05). In conclusion, this pilot trial demonstrates that the IR infusion of fenoldopam is safe and practical, producing greater renal effect and less reduction of BP than IV infusion. It would be appropriate to restudy this renal vasodilator for the prevention of contrast nephropathy, using selective IR delivery.

Objectives This study was performed to evaluate the clinical and serial angiographic outcomes of patients undergoing sirolimus-eluting stent (SES) implantation for unprotected left main coronary artery (LMCA) stenosis. Background The efficacy of SES has led to their expanded use for off-label indications, including LMCA disease. Methods Unprotected LMCA intervention with SES was attempted in 50 patients. Surveillance angiography was performed at three and nine months’ follow-up. Results The target lesion involved the distal LMCA in 47 patients (94%). In-lesion restenosis occurred in 21 patients (42%), was focal in 85% of cases, and in 82% involved the branch ostia, sparing the LMCA itself. Target lesion revascularization (TLR) occurred in 19 patients (38%) over a mean follow-up of 276 ± 57 days; TLR was ischemia-driven in 7 patients (14%). Late loss was significantly greater within the left circumflex (LCX) ostium compared to the parent vessel (PV) of the LMCA bifurcation (0.83 ± 0.89 mm vs. 0.49 ± 0.72 mm, p = 0.04). Late loss continued to increase between three- and nine-month follow-up. Final minimal luminal diameter and maximal balloon pressure were independent predictors of restenosis of the PV. Conclusions Restenosis is a frequent finding when serial angiographic follow-up is performed after SES implantation for unprotected distal LMCA lesions. Restenosis is usually focal, most often involves the LCX ostium, and often occurs without symptoms.

In Part I of this article, the definitions, prevalence, and clinical presentation of chronic total occlusions (CTOs) were reviewed, the histopathology of CTOs was examined, efforts to replicate human CTOs with experimental models were appraised, and the clinical relevance and rationale for CTO revascularization were evaluated.1 In Part II, we summarize the technical approach to and outcomes after percutaneous coronary intervention (PCI) of occluded coronary arteries, describe the novel devices and drugs approved and undergoing investigation for CTO recanalization, and conclude with practical perspectives on managing the patient with 1 or more chronic coronary occlusions. ### Patient Selection and Revascularization Strategies PCI of CTOs constitutes as many as 20% of all angioplasty procedures at selected centers,2 although a rate of &10% is more typical,3–6 suggesting that CTO angioplasty is attempted in 50 000 to 100 000 patients per year in the United States. Many more CTOs are present for which PCI is never attempted, representing one of the most common causes for referral to bypass surgery rather than PCI.6–8 Furthermore, a large proportion of patients with CTOs are managed medically, the prognosis of whom may vary depending on the extent of viable myocardium and ischemia, concomitant atherosclerosis in other coronary and noncoronary vascular territories, and other comorbid conditions. The decision to attempt PCI of a CTO (versus continued medical therapy or surgical revascularization) requires an individualized risk/benefit analysis, encompassing clinical, angiographic, and technical considerations. Clinically, the patient’s age, symptom severity, associated comorbidities (eg, diabetes mellitus and chronic renal insufficiency), and overall functional status are major determinants of treatment strategy. Angiographically, the extent and complexity of coronary artery disease (eg, single-vessel versus multivessel disease, single versus multiple total occlusions, likelihood for complete revascularization), left ventricular function, and the presence and degree of valvular heart disease should be considered. The technical probability of achieving …

Background— Revascularization strategies often hinge on the presence and degree of left anterior descending coronary artery (LAD) stenosis. A decision for bypass surgery is often based on the durability of surgical LAD revascularization compared with percutaneous approaches. By decreasing restenosis, drug-eluting stents may have reduced the “reintervention gap” between surgery and percutaneous intervention, making the percutaneous route preferable. Methods and Results— Of the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized to percutaneous intervention with either sirolimus-eluting or bare-metal stents. Baseline demographic, clinical, and angiographic data were obtained. Patients had 1-year clinical and 8-month angiographic follow-up. Baseline characteristics were similar in both groups. The majority of lesions were tubular type B lesions (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P P P =NS). Conclusions— Sirolimus-eluting stents significantly decrease revascularization rates in LAD lesions. At 1 year, sirolimus-eluting stent revascularization rates are comparable to historic single vessel bypass surgery revascularization rates.

The management of diabetic patients with restenosis after percutaneous coronary intervention remains a significant challenge. Diabetic patients remain at significant risk of restenosis despite stent implantation. This retrospective analysis was performed to determine the extent to which vascular brachytherapy improves late clinical and angiographic outcomes in diabetic patients compared to conventional therapy and compared to patients' nondiabetic counterparts.Pooled data from two studies (START [Stents and Radiation Trial] and START-40 trials) of patients (204 diabetic, 477 nondiabetic) receiving vascular brachytherapy (VBT) with a (90)Sr/(90)Y source after conventional percutaneous coronary intervention for in-stent restenosis comprise the study population. The radiation delivery system used in both studies was the Beta-Cath system. The prescribed dose at 2 mm from the centerline of the source axis was 18.4 Gy or 23 Gy, depending on vessel diameter. The reference vessel diameter, minimal lumen diameter, and percent diameter stenosis were measured before the intervention, at the conclusion of the procedure, and at the 8-month follow-up examination. The Breslow-Day test was used to formally assess the similarity of treatment effect between diabetic and nondiabetic patients.Target lesion and target vessel revascularization rates and angiographic restenosis rates in diabetic and nondiabetic patients treated with beta radiation or placebo were analyzed. Diabetic patients were more likely to have longer and more complex coronary lesions. In-hospital outcomes in diabetic and nondiabetic patients were similar, irrespective of treatment status. At 8 months, patients treated with beta radiation exhibited less target lesion revascularization (diabetic: 10.9% vs. 22.7%, p = 0.02; nondiabetic: 12.8% vs. 22.3%, p = 0.007) and less target vessel revascularization (diabetic: 14.7% vs. 25.3%, p = 0.06; nondiabetic: 16.6% vs. 23.6%, p = 0.06) compared to placebo. In-stent binary angiographic restenosis was lower in irradiated patients (diabetic: 19.4% vs. 37.3% for placebo, p = 0.01; nondiabetic: 12.9% vs. 43% for placebo, p0.001). However, restenosis beyond the stent site reduced the impact of VBT, regardless of diabetic status. The magnitude of the treatment effect for target lesion and target vessel revascularization rates was similar between diabetic and nondiabetic patients.Previously published institutional experiences have suggested that diabetic patients benefit from the use of VBT in the management of in-stent restenosis. This analysis now provides direct evidence to support the role of beta radiation VBT in this patient population. Diabetic patients undergoing this therapy are just as likely to benefit from it as their nondiabetic counterparts.

Transplant vasculopathy significantly limits the survival of cardiac transplant patients and occurs in 50% of patients by 5 years posttransplant. We report our experience with six cardiac transplant patients who underwent intracoronary brachytherapy for in-stent restenosis. At four centers, six patients underwent intracoronary radiation for in-stent restenosis. All patients received extended antiplatelet therapy with clopidogrel and aspirin. Follow-up angiography was performed in all patients. Two of the six patients underwent subsequent target lesion revascularization. Patient 1 presented with total occlusion of her radiated lesion. She had a complex procedure requiring stenting for a dissection after the radiation dwell. Patient 2 had high-grade restenosis following brachytherapy. Patient 3 had a 50% restenotic lesion. Patients 4, 5, and 6 had follow-up angiography that showed no evidence of restenosis. There are few good options to treated accelerated transplant vasculopathy. Radiation therapy may be a viable option in this difficult patient population.

OBJECTIVES We analyzed the effects of vascular brachytherapy (VBT) on ostial in-stent restenosis (ISR). BACKGROUND In-stent restenosis has a high recurrence rate after percutaneous reintervention. The recurrence rate of ostial ISR lesions and the impact of VBT remain unknown. METHODS We evaluated 133 patients with native coronary ostial ISR from a pooled database of 990 patients enrolled in randomized VBT trials. Independent quantitative angiography was performed at baseline and follow-up in 45 gamma, 27 beta, and 61 placebo patients. RESULTS Binary restenosis was significantly higher in placebo than radiated patients (75.4% vs. 17.8% in gamma vs. 22.2% in beta, p < 0.0001). The treatment effect of both gamma (odds ratio [OR] 0.06; 95% confidence interval [CI] 0.02 to 0.17) and beta VBT (OR 0.10; 95% CI 0.03 to 0.31) was maintained after controlling for differences in baseline lesion length. Proximal and distal radiation edge restenosis rates were similar among the groups. Vascular brachytherapy of true aorto-ostial lesions (n = 34) was similarly beneficial: restenosis rates of placebo versus gamma or beta patients of 83.3% versus 6.7% versus 28.6%, p = 0.0002. CONCLUSIONS Conventional treatment of ostial ISR is associated with a recurrence rate of over 75%. Vascular brachytherapy with either gamma or beta sources results in significant and similar reductions in restenosis compared with placebo. Similar benefits after VBT prevail in true aorto-ostial lesions.

Background Therapy with either low-molecular-weight heparin (LMWH) or glycoprotein (GP) IIb/IIIa receptor antagonists is of benefit to patients with acute coronary syndromes (ACSs). However, algorithms that define how LMWH may be used in patients, proceeding from medical management to intervention and in conjunction with GP IIb/IIIa inhibitors, are lacking. The objectives of this task force were to formulate recommendations based on all available data for the use of LMWH, both with and without GP IIb/IIIa receptor antagonists, and to provide seamless integration of care during the transition from medical to interventional management. Methods and Results An international task force of 14 cardiologists with extensive experience in clinical trials was convened in New York in February 2001 to address issues related to the use of LMWH in patients with non-ST-elevation ACS. Evidence from randomized trials, observational studies, and other reports was discussed, and consensus recommendations were formulated. Conclusions Substantial evidence exists that patients receiving LMWH for an ACS can safely undergo cardiac catheterization and percutaneous coronary intervention. Concerns regarding the transition of these patients from the medical service to the cardiac catheterization laboratory should therefore not impede the upstream use of LMWH. Furthermore, LMWH and GP IIb/IIIa receptor antagonists can be used safely in combination, with no apparent increase in the risk of major bleeding. Consensus algorithms for therapy are presented. (Am Heart J 2002;144:615-24.)

Background — Recently, several randomized trials have demonstrated that intracoronary brachytherapy can reduce the rates of both angiographic and clinical restenosis in patients undergoing percutaneous coronary intervention (PCI) for in-stent restenosis. Whether this practice is cost-effective is unknown. Methods and Results — Between December 1997 and July 1998, 252 patients with in-stent restenosis were randomized to receive brachytherapy or placebo after successful PCI as part of the Gamma-1 trial. We collected detailed resource utilization and cost data for each patient’s initial hospitalization and for 1 year after randomization. Compared with conventional treatment, intracoronary brachytherapy increased procedure duration, physician services, and equipment costs. As a result, initial costs were increased by nearly $4100 per patient ($15 724 versus $11 675, P P =0.46). In a sensitivity analysis that incorporated recent technical modifications and the use of prolonged antiplatelet therapy to prevent late thrombotic occlusion, follow-up cost savings increased to $3600/patient, and 1-year costs were slightly lower with brachytherapy ($26 352 versus $26 729, P =0.87). Subgroup analysis demonstrated significant cost savings in patients with diabetes and patients who did not undergo repeat stenting. Conclusions — As performed in the Gamma-1 trial, coronary brachytherapy for in-stent restenosis improved clinical outcomes but increased 1-year costs compared with standard therapy. If late thrombosis can be eliminated, however, this technology has the potential to reduce overall medical care costs.

Background — Several clinical trials indicate that intracoronary radiation is safe and effective for treatment of restenotic coronary arteries. We previously reported 6-month and 3-year clinical and angiographic follow-up demonstrating significant decreases in target lesion revascularization (TLR) and angiographic restenosis after γ radiation of restenotic lesions. The objective of this study was to document the clinical outcome 5 years after treatment of restenotic coronary arteries with catheter-based iridium-192 ( 192 Ir). Methods and Results — A double-blind, randomized trail compared 192 Ir to placebo sources in patients with restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192 Ir and 29 to placebo. At 5-year follow-up, TLR was significantly lower in the 192 Ir group (23.1% versus 48.3%; P =0.05). There were 2 TLRs between years 3 and 5 in patients in the 192 Ir group and none in patients in the placebo group. The 5-year event-free survival rate (freedom from death, myocardial infarction, or TLR) was greater in 192 Ir-treated patients (61.5% versus 34.5%; P =0.02). Conclusions — Despite apparent mitigation of efficacy over time, there remains a significant reduction in TLR at 5 years and an improvement in event-free survival in patients treated with intracoronary 192 Ir. The early clinical benefits after intracoronary γ radiation with 192 Ir seem durable at 5-year clinical follow-up.

OBJECTIVES We sought to evaluate the safety and efficacy of percutaneous transmyocardial revascularization (PTMR) in patients with refractory angina caused by one or more chronic total occlusions (CTOs) of a native coronary artery. BACKGROUND Previous unblinded, randomized trials of PTMR in patients with end-stage coronary artery disease and refractory angina have demonstrated significant relief of angina and increased exercise duration. Whether such benefits would be realized in blinded patients with less extensive coronary artery disease is unknown. METHODS A total of 141 consecutive patients with class III or IV angina caused by one or more chronically occluded native coronary arteries in which a percutaneous coronary intervention (PCI) had failed were prospectively randomized, at 17 medical centers, in the same procedure, to PTMR plus maximal medical therapy (MMT) (n = 71) or MMT only (n = 70). Blinding was achieved through heavy sedation, dark goggles and the concurrent performance of PCI in all patients. RESULTS Baseline characteristics were similar between the two groups. A median number of 20 laser channels were created in patients randomized to PTMR. At six months, the anginal class improved by two or more classes in 49% of patients assigned to PTMR and in 37% of those assigned to MMT (p = 0.33). The median increase in exercise duration from baseline to six months was 64 s with PTMR versus 52 s with MMT (p = 0.73). There were no differences in the six-month rates of death (8.6% vs. 8.8%), myocardial infarction (4.3% vs. 2.9%) or any revascularization (4.3% vs. 5.9%) in the PTMR and MMT groups, respectively (p = NS for all). CONCLUSIONS In patients with class III or IV angina caused by nonrecanalizable CTOs, the performance of PTMR does not result in a greater reduction in angina, improvement in exercise duration or survival free of adverse cardiac events, as compared with MMT only.

Intracoronary radiation therapy is effective in reducing the recurrence of in-stent stenosis in native coronary arteries. We examined the effects of intravascular gamma radiation in patients with in-stent restenosis of saphenous-vein bypass grafts.A total of 120 patients with in-stent restenosis in saphenous-vein grafts, the majority of whom had diffuse lesions, underwent balloon angioplasty, atherectomy, additional stenting, or a combination of these procedures. If the intervention was successful, the patients were randomly assigned in a double-blind fashion to intravascular treatment with a ribbon containing either iridium-192 or nonradioactive seeds. The prescribed dose, delivered at a distance of 2 mm from the source, was 14 to 15 Gy in vessels that were 2.5 to 4.0 mm in diameter and 18 Gy in vessels with a diameter that exceeded 4.0 mm. The primary end points were death from cardiac causes, Q-wave myocardial infarction, revascularization of the target vessel, and a composite of these events at 12 months.Revascularization and radiation therapy were successfully accomplished in all patients. At six months, the restenosis rate was lower in the 60 patients assigned to the iridium-192 group than in the 60 assigned to the placebo group (21 percent vs. 44 percent, P=0.005). At 12 months, the rate of revascularization of the target lesion was 70 percent lower in the iridium-192 group than in the placebo group (17 percent vs. 57 percent, P0.001), and the rate of major cardiac events was 49 percent lower (32 percent vs. 63 percent, P0.001).The results of our study support the use of gamma-radiation therapy for the treatment of in-stent restenosis in patients with bypass grafts.

The Scripps Trial was a randomized study of intracoronary artery radiation therapy with iridium 192 used to treat restenotic vessels. We used the intravascular ultrasound data from the Scripps Trial to investigate whether a lumen-centered gamma or beta radiation source would reduce radiation dose heterogeneity compared with the noncentered source position used.Analysis included 28 patients with stent placement in 20 native vessels and 8 saphenous vein grafts enrolled in this trial. Radiation dosimetry for gamma radiation was calculated to deliver 800 cGy to the far field target, provided the maximum dose to the near field target did not exceed 3000 cGy. Prescribed dosimetry for beta radiation by use of yttrium 90 was 1600 cGy at 2 mm distance from the source.The calculated average minimum source to target distance by use of a lumen-centered source increased by 0.18 mm from 1.70 +/- 0.25 to 1.88 +/- 0.36 mm, whereas the maximum distance decreased by 0.17 mm from 3.64 +/- 0.60 to 3.47 +/- 0.43 mm (P.05). On the basis of these distances, the maximum radiation dose, as well as radiation dose heterogeneity (ratio of maximum to minimum), would have been reduced in 22 of 28 patients by use of a lumen-centered gamma or beta source (P.005). The reduction in dose heterogeneity was substantially greater with a beta source compared with a gamma source (48% vs 16% reduction).Centering of the intracoronary artery radiation therapy delivery catheter within the vessel lumen can significantly reduce radiation dose heterogeneity when compared with a noncentered source position. This dose reduction is substantially greater for a beta compared with a gamma source.

Long-term clinical outcomes after exposure to non-ionic iso-osmolar contrast medium (IOCM) or ionic low-osmolar CM (LOCM) in patients with chronic kidney disease (CKD) undergoing coronary angiography are unclear.The ICON trial was a prospective, double-blinded, multicentre study that randomly assigned 146 patients with CKD undergoing coronary angiography with or without percutaneous coronary intervention to the non-ionic IOCM Iodixanol or the ionic LOCM Ioxaglate. We report the 1-year clinical outcomes.After randomization, baseline and procedural characteristics were well-matched between the two groups. At 1 year, three deaths (4.1%) occurred in the ioxaglate and nine deaths in the iodixanol group (13.6%, P = 0.07). The cardiac death rate at 1 year was 2.7% in the ioxaglate group and 9.1% in the iodixanol group (P = 0.07). There were no significant differences in the rates of myocardial infarction (1.4% vs. 1.5%; P = 1.00) and repeated revascularization (6.8% vs. 9.1%; P = 0.75).The use of ionic LOCM ioxaglate was associated with a numerically lower mortality at 1 year as compared to iodixanol in patients who underwent cardiac catheterization. Future studies evaluating long-term safety following exposure to different types of CM are warranted.

This study sought to determine whether outcomes for transfemoral (TF) transcatheter aortic valve replacement (TAVR) differ between the randomized controlled trial (RCT) and the subsequent NRCA (Nonrandomized Continued Access) registry of the PARTNER (Placement of AoRTic TraNscathetER Valves) trial.The PARTNER RCT demonstrated that TAVR with the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) is noninferior to surgery in high-risk patients and superior to standard therapy for inoperable patients.The inclusion and exclusion criteria, data collection, monitoring, and core laboratories were the same for the RCT and NRCA registry. Baseline characteristics, procedural results, and 1-year outcomes were compared between patients undergoing TF-TAVR as part of the RCT and as part of the NRCA registry.In the RCT, 415 patients underwent TF-TAVR, whereas in the NRCA, 1,023 patients did. At 30 days, death, cardiac death, stroke, and transient ischemic attacks were not different in the NRCA registry than in the RCT. Major vascular complications (8.0% vs. 15.7%, p 0.0001) and major bleeding (6.8% vs. 15.3%, p 0.0001) were significantly lower in the NRCA registry. At 1 year, death rates were significantly lower in the NRCA cohort (19.0% vs. 25.3%, p = 0.009) and cardiac death tended to be lower (8.4% vs. 11.1%, p = 0.12). Stroke or transient ischemic attack (6.2% vs. 8.7%, p = 0.10) and stroke alone (5.0% vs. 7.1%, p = 0.13) also tended to be lower.The large NRCA registry demonstrates further improvement in procedural and longer-term outcomes after TF-TAVR when compared with the favorable results from the PARTNER RCT. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

To report 1- and 2-year clinical outcomes of patients receiving platinum chromium everolimus-eluting stents (PtCr-EES) in the prospective, single-arm PLATINUM small vessel (SV) and long lesion (LL) studies.Small vessel diameter and long lesion length are independently associated with increased risk of adverse cardiac events after drug-eluting stent implantation.The PLATINUM SV study enrolled 94 patients with coronary artery lesions in vessels ≥2.25 mm to2.50 mm in diameter and ≤28 mm in length. The PLATINUM LL study enrolled 102 patients with lesions24 to ≤34 mm long in vessels ≥2.50 to ≤4.25 mm in diameter. The primary endpoint for both studies was target lesion failure (TLF) at 1 year compared to a prespecified performance goal based on outcomes with the TAXUS Express paclitaxel-eluting stent in small vessels and long lesions.One-year TLF rates with the PtCr-EES were significantly (P0.001) lower than the predetermined performance goals: 2.4% versus 21.1% in the SV cohort and 3.2% versus 19.4% in the LL cohort. Cumulative rates of TLF to 2 years were 4.7% in the SV cohort and 8.8% in the LL cohort. No myocardial infarction or ARC definite/probable stent thromboses occurred in either cohort through 2-year follow-up.The clinical efficacy and safety outcomes observed in these small vessel and long lesion cohorts support the use of the PtCr-EES in the treatment of small diameter vessels and long lesions.

OBJECTIVESWe performed a multicenter, double-blind placebo-controlled trial to examine the efficacy and safety of enoxaparin in patients at high risk for stent thrombosis (ST).BACKGROUNDThe optimal antithrombotic regimen for such patients is unknown.METHODSWe randomized 1,102 patients with clinical, angiographic or ultrasonographic features associated with an increased risk of ST to receive either twice-daily injections of weight-adjusted enoxaparin or placebo for 14 days after stenting. All patients received aspirin and ticlopidine. The primary end point was a 30-day composite end point of death, myocardial infarction (MI) or urgent revascularization.RESULTSThe target enrollment for the study was 2,000 patients. However, the trial was terminated prematurely at 1,102 patients after interim analysis revealed an unexpectedly low event rate. The primary outcome occurred in 1.8% enoxaparin-treated patients versus 2.7% treated with placebo (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.29 to 1.5, p = 0.30); for death or MI the rates were 0.9% vs. 2.2%, respectively (OR 0.41, 95% CI 0.14 to 1.2, p =0.13); and for MI, 0.4% vs. 1.6%, respectively (OR 0.22, 95% CI 0.05 to 0.99, p = 0.04). The groups had comparable rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p =0.08), but minor nuisance bleeding was increased with enoxaparin (25% vs. 5.1%, p < 0.001).CONCLUSIONSThe clinical outcomes of patients at increased risk of ST are more favorable than previously reported, rendering routine oral antiplatelet therapy adequate for most. However, given its relative safety and potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients.

Although the frequency of restenosis after coronary angioplasty is reduced by stenting, when restenosis develops within a stent, the risk of subsequent restenosis is greater than 50 percent. We report on a multicenter, double-blind, randomized trial of intracoronary radiation therapy for the treatment of in-stent restenosis.Of 252 eligible patients in whom in-stent restenosis had developed, 131 were randomly assigned to receive an indwelling intracoronary ribbon containing a sealed source of iridium-192, and 121 were assigned to receive a similar-appearing nonradioactive ribbon (placebo).The primary end point, a composite of death, myocardial infarction, and the need for repeated revascularization of the target lesion during nine months of follow-up, occurred in 53 patients assigned to placebo (43.8 percent) and 37 patients assigned to iridium-192 (28.2 percent, P=0.02). However, the reduction in the incidence of major adverse cardiac events was determined solely by a diminished need for revascularization of the target lesion, not by reductions in the incidence of death or myocardial infarction. Late thrombosis occurred in 5.3 percent of the iridium-192 group, as compared with 0.8 percent of the placebo group (P=0.07), resulting in more late myocardial infarctions in the iridium-192 group (9.9 percent vs. 4.1 percent, P=0.09). Late thrombosis occurred in irradiated patients only after the discontinuation of oral antiplatelet therapy (with ticlopidine or clopidogrel) and only in patients who had received new stents at the time of radiation treatment.Intracoronary irradiation with iridium-192 resulted in lower rates of clinical and angiographic restenosis, although it was also associated with a higher rate of late thrombosis, resulting in an increased risk of myocardial infarction. If the problem of late thrombosis within the stent can be overcome, intracoronary irradiation with iridium-192 may become a useful approach to the treatment of in-stent restenosis.

Background —The aim of this study was to use serial volumetric intravascular ultrasound to evaluate the effect of γ-radiation on recurrent in-stent restenosis. Methods and Results —After successful reintervention, patients were randomized to receive either 192 Ir or placebo. Intravascular ultrasound studies with motorized pullback (0.5 mm/s) were performed immediately after irradiation and at 8-month follow-up in 70 patients. Paired volumetric analysis of the stented segment and of 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque and media (external elastic membrane minus lumen), stent, and intimal hyperplasia (stent minus lumen). Baseline proximal reference, stent, and distal reference measurements were similar in both groups. The changes in proximal and distal reference measurements of the external elastic membrane, plaque and media, and lumen areas were similar in both groups. However, the decrease in stented segment lumen volume was less in the 192 Ir patients than the placebo patients (–25±34 mm 3 versus –48±42 mm 3 ; P =0.0225), and the increase in the volume of intimal hyperplasia in the stented segment was less in the 192 Ir patients than in the placebo patients (28±37 mm 3 versus 50±40 mm 3 ; P =0.0352). When averaged over the length of the stented segment (32±13 mm versus 33±14 mm; P =0.9), the increase in mean area of intimal hyperplasia was 0.8±1.0 mm 2 in the 192 Ir group and 1.6±1.2 mm 2 in the control group ( P =0.0065). Late stent-vessel wall malapposition was noted in one placebo patient and no 192 Ir patients. Conclusions —γ-Radiation therapy can effectively prevent recurrent in-stent restenosis by inhibiting neointimal formation within the stent. At the stent edge, there were no significant differences between 192 Ir and placebo patients.

Purpose: In this study, the effect of barotrauma due to stent deployment is investigated for several commonly used commercial stents used in endovascular brachytherapy for restenosis prevention. Methods and Materials: Restenosis due to intimal hyperplasia can occur anywhere along the clinical target volume, which is defined as the length of vessel receiving intervention or injury. The injury may be due to angioplasty, atherectomy (tissue removing), stenting, and stent deployment. Manufacturer specifications for several commonly used stents were reviewed and the results were tabulated. Results: The barotrauma length of stents reviewed in this study ranges from 0.5 to 2.5 mm; the average was 1.7 mm. Conclusions: By considering specific barotrauma into the treatment length, one can provide adequate treatment margins to minimize edge failure or to avoid "geographic miss," which may improve the efficacy of endovascular brachytherapy.

The International Commission on Radiation Units and Measurement (IRCU) 50 has clearly defined treatment volumes in radiation therapy in the management of neoplasms. These concepts are applied to the field of endovascular brachytherapy (EVBT) for the prevention of postangioplasty restenosis. The following definitions are proposed: gross target length (GTL) is defined as the narrowed segment of the artery that requires intervention. Clinical target length (CTL) is defined as the intervened or injured length, which could be due to angioplasty, stent strut injury, stent deployment, or debulking procedures. Planning target length (PTL) is the CTL plus a margin to account for heart/catheter movement and uncertainty in target localization. The final treatment length (TL) is the PTL plus the effect of penumbra. The accurate specification of treatment length serves several important purposes. Based on an understanding of the different factors constituting the treatment length, adequate margins can be provided beyond the GTL; this will avoid geographic misses and minimize edge failures. These definitions of target length ensure treatment consistency and provide a standard terminology for communication among practitioners of EVBT, something of critical importance in the conduct of multi-institutional trials in this new and multidisciplinary therapy. Finally, since the efficacy of EVBT is critically dependent on the precision of radiation delivery, these guidelines ensure that the benefits of EVBT seen in prospective randomized trials can be translated into daily clinical practice at the community level.

To identify luminal dimension changes occurring within the stent alone and within the stent + margin segment, we reviewed the quantitative angiographic results obtained from the Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) trial, a prospective randomized trial assessing the effect of iridium-192 (Ir-192) on the prevention of stent restenosis. Fifty-five patients were randomly assigned to receive Ir-192 or placebo sources after successful intervention. Procedural and 6-month follow-up cineangiograms were quantitatively reviewed in 52 patients to identify changes within the stent and the stent + margin segment. The percent diameter stenosis was lower within the stent than within the stent + margin segment after the procedure (6 +/- 22% vs 21+/- 15%, p0.0001) and at follow-up (28 +/- 29% vs 42 +/- 21%, p0.0001). As a result, a lower restenosis rate was found within the stent than within the stent + margin (25% vs 37%, p0.0001); isolated stent margin restenosis occurred in 11.5% of lesions. Treatment with Ir-192 reduced restenosis within the stent (8% vs 39%; p = 0.010) and within the stent + margin segment (17% vs 54%; p = 0.010); the reduction in restenosis at the margin only (8.3% vs 14.3%, p = 0.503) was not significant. The lowest relative risk for restenosis resulting from Ir-192 occurred within the stent (0.21; 95% confidence interval [CI] 0.05 to 0.86) compared with the stent + margin segment (0.31; 95% CI 0.12 to 0.81) or the stent margin (0.58; 95% CI 0.12 to 2.91). In the SCRIPPS trial, 32% of restenosis occurred at the stent margins. Treatment with Ir-192 reduced restenosis primarily within the stent rather than the margin. Whether extending the treatment length to fully include the stent margins will further reduce restenosis requires further study.