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Introduction: Radiation reduction measures were incorporated in the Cleveland Clinic Catheterization laboratories to mitigate the hazards from radiation exposure to patients and personnel during diagnostic and interventional coronary procedures. We report our experience with these improved systems over a 10-year period. Methods: Fluoroscopes were modified in 2013 by reducing the default fluoroscopic pulse rate from 10 to 7.5 pules/s, added default low-dose acquisitions, revised field-of-view dose factors, and instructed operators to use larger fields-of-view with appropriate collimation. A retrospective data analysis of all patients undergoing diagnostic catheterization from 2009 to 2012 (pre-initiative group), and 2013 to 2019 (post-initiative group) was done using Siemens CARE analytics software. The effectiveness of radiation reduction measures was assessed by comparing the total air kerma (K a,r ), and fluoroscopy- and acquisition-mode air kerma in patients in the two groups after propensity matching them based on age, sex, BSA, and total fluoroscopic time. Results: The total fluoroscopic time for the pre-initiative group (N=18,181) was 8.02 seconds while that for the post-initiative group (N=25,868) was 8.05 seconds. After matching 18,181 patients in both the groups (mean age, 64 years; 62% males), a significant reduction (54.4%) in the mean K a,r was observed in the post- in comparison to the pre-initiative group (420.94 mGy vs. 921.21 mGy; p-16 ). Further analysis revealed a reduction in the mean acquisition- (59.3%; 217.33 mGy vs. 533.50 mGy; p-16 ) and fluoroscopy-mode (47.5%; 203.61 mGy vs. 387.71 mGy; p-16 ) air kerma in the post-initiative group. A sub-analysis of patients matched on the basis of their exact fluoroscopy and acquisition times also revealed a significant reduction in K a,r , acquisition- and fluoroscopy-mode air kerma in the post-initiative group relative to the pre-initiative group (43.95%, 44.04%, 43.78% respectively). Conclusions: Optimization of imaging systems can significantly reduce patient radiation exposures which directly affect the radiation exposure of the Cath lab personnel. Similar algorithms can be applied in other labs to achieve a reduction in radiation exposure.

Background: The Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) provides early drug delivery and mechanical support similar to those of metallic drug-eluting stents, followed by complete resorption in ≈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, or ischemia-driven target lesion revascularization) at 1 year with BVS compared with cobalt chromium everolimus-eluting stents. Between 1 and 3 years and cumulative to 3 years, adverse event rates (particularly target vessel myocardial infarction and scaffold thrombosis) were increased after BVS. We sought to assess clinical outcomes after BVS through 5 years, including beyond the 3-year time point of complete scaffold resorption. Methods: Clinical outcomes from ABSORB III were analyzed by randomized device (intention to treat) cumulative to 5 years and between 3 and 5 years. Results: Rates of target lesion failure, target vessel myocardial infarction, and scaffold thrombosis were increased through the 5-year follow-up with BVS compared with everolimus-eluting stents. However, between 3 and 5 years, reductions in the relative hazards of the BVS compared with everolimus-eluting stents were observed, particularly for target lesion failure (hazard ratio, 0.83 [95% CI, 0.55–1.24] versus 1.35 [95% CI, 1.02–1.78]; P int =0.052) and scaffold thrombosis (hazard ratio, 0.26 [95% CI, 0.02–2.87] versus 3.23 [95% CI, 1.25–8.30]; P int =0.056) compared with the 0- to 3-year time period. Conclusions: In the ABSORB III trial, cumulative 5-year adverse event rates were increased after BVS compared with everolimus-eluting stents. However, the period of excess risk for BVS ended at 3 years, coincident with complete scaffold resorption. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT01751906.

Background: Although most drug-eluding stent (DES) patients live longer than 10 years, there is no generally accepted clinical tool to predict risk of major adverse cardiac events (MACE) after DES over that period of time. Methods: Local consecutive patients receiving their first limus-eluting DES from 6/04-6/12 were characterized at baseline and prospectively followed. Patients were randomly allocated to a training or validation cohort, and a predictive Cox model using pre-procedural variables was developed in the training set. This model was then retested in a validation cohort. The primary endpoint was the c-index in the validation cohort. CIF and Fine-Gray were used for sensitivity analysis. Results: Patients (n=1321) had mean follow up of 10±3 years (3% were lost to follow up). Baseline characteristics included age=63±11 years, 65% male, SYNTAX Score=10±7, 1st/2nd Gen DES (%)=42.8/57.2, DES length (mm)=33±22. In the training set, MACE was independently correlated with renal insufficiency (p Conclusions: Ten year risk of MACE can be accurately modeled using this simple model, with risk ranging from about 30% to nearly 100%.

Background: The Absorb bioresorbable vascular scaffold (BVS) completely resorbs within 3 years after coronary artery implantation. The safety and effectiveness of BVS through this critical 3-year period have not been characterized. Methods: We performed an individual-patient-data pooled meta-analysis of the 4 randomized ABSORB trials in which 3389 patients with coronary artery disease were randomly assigned to everolimus-eluting Absorb BVS (n=2164) or cobalt-chromium everolimus-eluting stents (n=1225). The primary efficacy outcome measure was target lesion failure (cardiac mortality, target vessel myocardial infarction, or ischemia-driven target lesion revascularization), and the primary safety outcome measure was device thrombosis. Results: BVS compared with cobalt-chromium everolimus-eluting stents resulted in higher 3-year rates of target lesion failure (11.7% versus 8.1%; risk ratio [RR], 1.38; 95% confidence interval [CI], 1.10–1.73; P =0.006), driven by greater target vessel myocardial infarction (7.8% versus 4.2%; RR, 1.72; 95% CI, 1.26–2.35; P =0.0006) and ischemia-driven target lesion revascularization (6.6% versus 4.4%; RR, 1.44; 95% CI, 1.05–1.98; P =0.02), with comparable cardiac mortality (1.1% versus 1.1%; RR, 0.93; 95% CI, 0.47–1.88; P =0.85). Device thrombosis rates through 3 years were also higher with BVS (2.4% versus 0.6%; RR, 3.71; 95% CI, 1.70–8.11; P =0.001). Between 1 and 3 years, target lesion failure rates (6.1% versus 3.9%; P =0.02) and device thrombosis rates (1.1% versus 0.0%; P Conclusions: In the present individual-patient-data pooled meta-analysis of the ABSORB trials, BVS was associated with increased rates of target lesion failure and device thrombosis between 1 and 3 years and cumulatively through 3 years of follow-up compared with everolimus-eluting stents. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifiers: NCT01751906, NCT01844284, NCT01923740, and NCT01425281.

To ensure that guidelines reflect current knowledge, available treatment options, and optimum medical care, existing clinical practice guideline recommendations are modified and new recommendations are added in response to new data, medications or devices. To keep pace with evolving evidence, the American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Clinical Practice Guidelines (“Task Force”) has issued this focused update to revise guideline recommendations on the basis of recently published data. This update is not based on a complete literature review from the date of previous guideline publications, but it has been subject to rigorous, multilevel review and approval, similar to the full guidelines. For specific focused update criteria and additional methodological details, please see the ACC/AHA guideline methodology manual.1 ### Modernization In response to published reports from the Institute of Medicine2,3 and ACC/AHA mandates,4–7 processes have changed leading to adoption of a “knowledge byte” format. This entails delineation of recommendations addressing specific clinical questions, followed by concise text, with hyperlinks to supportive evidence. This approach better accommodates time constraints on busy clinicians, facilitates easier access to recommendations via electronic search engines and other evolving technology (eg, smart phone apps), and supports the evolution of guidelines as “living documents” that can be …

Background: ST-elevation myocardial infarction (STEMI) is a potentially fatal condition that may be complicated by cardiac arrest (CA). However, the impact of CA complicating STEMI on prognosis in the contemporary era of rapid primary PCI is uncertain. Methods: We reviewed consecutive cases of STEMI treated with percutaneous coronary intervention (PCI) at our center between January 1, 2011 and December 31, 2016. Baseline clinical characteristics and in-hospital long-term outcomes were compared between patients with and without CA. Results: Among 1,272 patients with STEMI, 148 (11.6%) had CA (30.4% out-of-hospital, 69.6% after ED arrival). Compared to patients without CA, patients with STEMI+CA were more likely to have a history of heart failure, valve surgery, peripheral and cerebrovascular disease, and chronic kidney disease with a trend towards increased prevalence of left main or left anterior descending culprit vessel. Patients with STEMI+CA had greater creatinine (1.28±0.92 vs. 1.07±0.67, p=0.013, infarct size (CK-MB 171.6±131.6 vs. 139.2±117.0 ng/mL, p=0.010; troponin T 6.2±6.2 vs. 5.0±4.8 ng/mL, p=0.024), door-to-balloon-time (118.1±63.6 vs. 106.8±64.0, p=0.045), and incidence of cardiogenic shock (48.0% vs. 5.9%, p Conclusions: CA is a complication in >1 in 10 patients with STEMI and is associated with significantly higher morbidity and mortality compared with STEMI without CA. Strategies to improve the care and outcomes of STEMI patients with CA are needed.

Background— With the availability of transcatheter aortic valve replacement, management of coronary artery disease in patients with severe aortic stenosis (AS) is posing challenges. Outcomes of percutaneous coronary intervention (PCI) in patients with severe AS and coronary artery disease remain unknown. We sought to compare the short-term outcomes of PCI in patients with and without AS. Methods and Results— From our PCI database, we identified 254 patients with severe AS who underwent PCI between 1998 and 2008. Using propensity matching, we found 508 patients without AS who underwent PCI in the same period. The primary end point of 30-day mortality after PCI was similar in patients with and without severe AS (4.3% [11 of 254] versus 4.7% [24 of 508]; hazard ratio, 0.93; 95% confidence interval, 0.51–1.69; P =0.2). Patients with low ejection fraction (≤30%) and severe AS had a higher 30-day post-PCI mortality compared with those with an ejection fraction >30% (5.4% [7 of 45] versus 1.2% [4 of 209]; P P Conclusions— PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ≤30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement.

Background: Acute ischemic mitral regurgitation (MR) is a detrimental complication of ST elevation myocardial infarction (STEMI). We studied a) patient characteristics in acute ischemic MR in anterior versus inferior STEMI and b) its impact on outcomes. Methods: We retrospectively studied all patients presenting with STEMI complicated by acute ischemic MR to our center from 1994-2014. Patients were divided into two groups: anterior and inferior STEMI. Endpoints were 30-day and 1-year mortality. All cases with new development of > 2+ MR on baseline echo within 3 days of index MI were analyzed. Results: Out of 4005 STEMI patients, there were 221 patients (52.5% males) with acute MR at an incidence of 5.5% [74/1666 (4.4%) in anterior vs 147/2306 (6.4%) in inferior STEMI, p=0.02]. At baseline, there were no significant differences between anterior vs. inferior STEMI in age, co-morbidities or degree of MR (Table). Mean ejection fraction (EF) was 31±14 vs 45±13% (p Conclusion: Acute ischemic MR is seen more commonly with inferior yet has worse outcomes in anterior STEMI with increased short and long term mortality. Further, old age, low EF, higher degree of MR, shock on presentation, and need for blood transfusion are associated with worse outcomes.

Background: The clinical and angiographic predictors of outcomes after percutaneous coronary intervention (PCI) in patients with cancer and radiation associated coronary artery disease (CAD) are not well established. Methods: In this retrospective cohort study, 157 patients with thoracic malignancy and external beam radiation therapy (XRT) prior to PCI were identified. The rates of major adverse cardiovascular and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, repeat revascularization, or stroke) were compared across patient characteristics. Results: During follow-up of 5.4±4.5 years, 91 (58%) patients had MACCE; 59 (38%) died, of which 23 (39%) were cardiac deaths, 23 (39%) due to cancer or other causes, and 13 (22%) unknown. By Kaplan-Meier analysis, MACCE were more frequent with coronary artery calcification (p=0.023), ostial stenosis (p=0.049), target vessel diameter ≥ 3.0 mm (p=0.018), a SYNTAX score ≥ the median of 11 (p=0.014), or bare metal stenting (BMS) compared to drug-eluting stenting (DES) (p=0.006) (Figure). Cardiac death was more frequent in patients with SYNTAX score ≥ 11 (p=0.028) or BMS (p=0.043). After multivariable adjustment, independent predictors of MACCE were chronic kidney disease (CKD) (p=0.006), New York Heart Association (NYHA) class ≥ 3 (p=0.024), and BMS (p=0.008) (Table). Conclusions: In patients with radiation associated CAD treated with PCI, MACCE is more frequent in those with target vessel calcification, ostial stenosis, large vessel diameter, or SYNTAX score ≥ 11. BMS placement is independently associated with greater MACCE than DES, and other risk factors for MACCE include CKD and NYHA class ≥ 3.

The latest statistics from the American Heart Association are disturbing: In 2004, an estimated 865 000 Americans will develop a new acute coronary syndrome. Another 700 000 will have a stroke. Unfortunately, the contribution of percutaneous coronary intervention (PCI) to prevent such catastrophic outcomes has been limited. To date, intervention cardiologists have been constrained to the treatment of obstructive atherosclerosis disease in certain regions of the coronary tree. This approach has a clear benefit in reducing ischemia and symptoms but minimal direct impact on patients’ survival. The coming decade in interventional cardiology will be characterized by continued advances and interplay between structural materials and biomaterials, as well as by erosion of the barriers between medical disciplines, including vascular medicine, heart failure and genetics. Advances in imaging technology are on the verge of a clinical debut, which will enhance our screening capabilities to detect subclinical yet hazardous atherosclerosis disease. An expansion of indications for PCI as well as the development and establishment of new therapeutic modalities also are expected in the coming years (Figure 1). Figure 1. Factors promoting (+) or limiting (-) the expansion of interventional cardiology. A comprehensive review of the entire field of intervention cardiology would be impractical. Progress in the areas of drug-eluting stents, detection of vulnerable plaques, percutaneous management of selected patients with stroke and valvular heart disease, angiogenesis and stem cell treatment of congestive heart failure, and increased use of the predictive capacity of genetic markers likely will be pivotal. The goal of this article is to provide an overview of recent achievements in specific areas that may change thinking in the field in the near future (Figure 1). The BENESTENT (BElgian NEtherlands STENT) and STRESS (STent REStenosis Study) trials paved the way for the “stent era” in coronary revascularization.1,2 In-stent restenosis, however, …

Background— The safety and efficacy of the slow-release, polymer-based, paclitaxel-eluting stent after implantation in a broad cross section of de novo coronary lesions at 1 year are unknown. Methods and Results— In the TAXUS-IV trial, 1314 patients with single de novo coronary lesions 10 to 28 mm in length, with reference-vessel diameter 2.5 to 3.75 mm, coverable by a single study stent, were prospectively randomized to the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or an identical-appearing bare-metal EXPRESS stent. By actuarial analysis, the TAXUS stent compared with the bare-metal stent reduced the 12-month rates of target-lesion revascularization by 73% (4.4% versus 15.1%, P P P P P =0.007), target-vessel revascularizations (2.4% versus 5.8%, P =0.002), and major adverse cardiac events (2.4% versus 6.3%, P =0.0009) in the paclitaxel-eluting stent than in the control stent group, respectively. Conclusions— The relative efficacy reported at 9 months for the polymer-based, paclitaxel-eluting TAXUS stent compared with the EXPRESS stent is preserved and continues to increase at 1 year, with no safety concerns apparent.

Background— Beyond lipid lowering, statins are known to possess antiinflammatory and antithrombotic properties. Recent studies suggested an association between statins and early reduction in death or myocardial infarction (MI) after percutaneous coronary interventions (PCIs). We sought to examine the interrelationship between inflammation, statin use, and PCI outcomes. Methods and Results— In the year 2000, 1552 consecutive United States residents underwent elective or urgent PCI at the Cleveland Clinic and were prospectively followed for 1 year. Preprocedural serum high-sensitivity C-reactive protein (hsCRP) levels were routinely measured. Patients who had statins initiated before the procedure (39.6%) had a lower median hsCRP level (0.40 versus 0.50 mg/dL, P =0.012) independent of the baseline cholesterol levels and had less frequent periprocedural MI (defined by CKMB ≥3×upper limit of normal, 5.7% versus 8.1%, P =0.038). At 1 year, statin pretreatment was predictive of survival predominantly among patients within the highest hsCRP quartile (mortality rate with statin pretreatment versus no pretreatment when hsCRP ≥1.11 mg/dL, 5.7% versus 14.8%, P =0.009). Using multivariate analysis, preprocedural hsCRP level remained an independent predictor for 1-year death or MI only in patients without statin therapy (hazard ratio, 1.32/quartile; P =0.001). After adjusting for the propensity of receiving statins, statin pretreatment was an independent predictor for 1-year survival within the highest hsCRP quartile (hazard ratio, 0.44; P =0.039). Conclusions— Statin therapy before PCI is associated with a marked reduction in mortality among patients with high hsCRP levels. A hsCRP-guided strategy may improve targeting of statin therapy and clinical outcome among patients undergoing PCI.

OBJECTIVE: Despite significant interest in bone marrow cell mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have shown only modest benefit. However, select patients show improvements after autologous BMC therapy for unknown reasons. The purpose of this study was to identify BMC characteristics associated with infarct size reduction following STEMI. METHODS: This study evaluated prospectively the cohort of patients enrolled in the CCTRN TIME trial who agreed to their BMCs being stored and used for further analyses at the CCTRN Biorepository. Analyses were pre-specified and the core laboratories were blinded to clinical data and treatment assignments. The changes in infarct size between baseline (three days after PCI) and 6 months was measured by cMRI. BMC product underwent phenotype analysis using FACS identifying cells expressing CD45, CD34, CD31, CD133, CXCR4, CD3, CD11, CD14, and CD19 and functional analysis with the CFU-Hill, ECFC and CFU-F assays. RESULTS: Quantification of BMC characteristics and infarct size was available in 101 patients. The patients’ mean age was 56.5 years, with a mean screening ejection fraction of 37% and mean baseline cMRI ejection fraction of 45%. At 6 months, 75 (74.3%) patients had reductions in infarct size (mean -21.0% ± 17.6%). Multiple regression analysis revealed that, regardless of treatment allocation, an increased percentage of BMC that expressed CD31 (p=0.046) was associated with greater reductions in infarct size. Greater reductions in infarct size also were associated with more rapid growth rates for BMC functional assays (CFU-Hill, ECFC) (p=0.033, p=0.032, respectively). CONCLUSIONS: This study demonstrates a correlation between characteristics of BMCs in the acute STEMI phase and subsequent changes in infarct size. These data suggest that resident BMCs (specifically, endothelial precursors) play an important role in regenerating infarcted myocardium irrespective of treatment with autologous BMC transplantation.

Background: A significant proportion of patients presenting with ST segment elevation myocardial infarction (STEMI) have newly diagnosed diabetes mellitus (DM). Hypothesis: Our aim was to identify patients with previously undiagnosed DM and compare their outcomes to those with known DM and without DM after STEMI. Methods: Consecutive patients undergoing primary PCI for STEMI at our center between Jan 2005 - Dec 2012 were included. Routinely performed admission Glycated hemoglobin (HbA1c) was utilized to identify patients with previously undiagnosed DM (HbA1c ≥ 6.5 and no history of DM or diabetes therapy). Patients were compared for in-hospital and long-term mortality based on follow up data from our institutional PCI registry. Results: 1,734 consecutive patients underwent primary PCI for STEMI and follow up data was available for 1,566 (90%) patients. Mean age was 60 years and 67.3% were males. A quarter of the patients (24.3%, n = 382) had prior history of DM and 8% (n=95) of the remainder had undiagnosed DM. Median follow up was 35 months. Mortality was comparable in patients with known DM and newly diagnosed DM both in hospital (11.2% vs. 12.5%, p=0.87) and at long term follow up (Figure 1, 2). Mortality was significantly worse with both groups when compared with patients with no DM (In-hospital mortality 5.6%; p Conclusions: One in twelve patients presenting with STEMI have previously undiagnosed DM. Cardiologists have a unique opportunity for identification and initiation of diabetic therapy in this vulnerable population. Patients with newly diagnosed DM have similar short and long-term outcomes when compared with patients with a prior history of DM.

Background β-blocker (BB) use reduces infarct size in spontaneously occurring nonreperfused infarcts but probably does not change infarct size in patients treated with reperfusion therapy. A recent observational study suggested that BB use concurrent with percutaneous coronary intervention (PCI) decreased the risk of creatine kinase (CK)-MB elevation. The cogency of such a conclusion is dependent on the ability to risk-adjust for the multiple differences in patients treated with and without BBs. Methods and Results Using propensity score and multivariate regression analyses, 6200 consecutive patients were analyzed to assess the relationship between BB use before PCI and per protocol-measured CK and CK-MB rise. There were several highly significant ( P P =0.011 and P =0.021 for CK and CK-MB, respectively). After adjustment for significant differences in baseline characteristics there was no difference in either maximum CK rise ( P =0.21) or maximum CK-MB rise ( P =0.99). Conclusions The results of this large observation study do not support the contention that BB use before PCI decreases myocardial injury.

Background Percutaneous coronary revascularization (PCI) has been increasingly applied to unprotected left main trunk (LMT) lesions, with varied long-term success. This study attempts to define the predictors of outcome in this population. Methods and Results Two hundred seventy-nine consecutive patients who had LMT PCI at 1 of 25 sites between 1993 and 1998 were studied. Forty-six percent of these patients were deemed inoperable or at high surgical risk. Thirty-eight patients (13.7%) died in hospital, and the rest were followed up for a mean of 19 months. The 1-year incidence was 24.2% for all-cause mortality, 20.2% for cardiac mortality, 9.8% for myocardial infarction, and 9.4% for CABG. Independent correlates of all-cause mortality were left ventricular ejection fraction ≤30%, mitral regurgitation grade 3 or 4, presentation with myocardial infarction and shock, creatinine ≥2.0 mg/dL, and severe lesion calcification. For the 32% of patients 30% and without shock, the prevalence of these adverse risk factors was low. No periprocedural deaths were observed in this low-risk subset, and the 1-year mortality was only 3.4%. Conclusions Patients undergoing unprotected LMT PCI have frequent serious comorbidities and consequently have high event rates. PCI may be an alternative to CABG for a select proportion of elective patients and may also be appropriate for highly symptomatic inoperable patients. Meticulous follow-up of hospital survivors is required because of the rather high mortality during the first few months after treatment.

Background —Platelet inhibition at the time of a percutaneous coronary intervention has consistently been shown to decrease the risk of thrombotic adverse events but not restenosis. The role of enhanced antiplatelet protection through pretreatment with the platelet ADP-receptor antagonist ticlopidine in preventing both the early and late complications of coronary stenting has not previously been explored. Methods and Results —In the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, ≈1600 patients were randomized to stenting with either placebo or abciximab in addition to aspirin and heparin. All stented patients also received ticlopidine after the procedure, but 58% of these patients were given ticlopidine before stenting at the discretion of the investigating physician. Among patients randomized to placebo, ticlopidine pretreatment was associated with a significant decrease in the incidence of the composite end point of death, myocardial infarction, or target vessel revascularization (TVR) at 1 year (adjusted hazard ratio, 0.73; 95% CI, 0.54 to 0.98; P =0.036). Ticlopidine pretreatment did not significantly influence the risk of death or myocardial infarction in patients randomized to abciximab. Controlling for patient characteristics and for the propensity of being on ticlopidine, Cox proportional hazards regression identified ticlopidine pretreatment as an independent predictor of the need for TVR at 1 year (hazard ratio, 0.62; 95% CI, 0.43 to 0.89; P =0.010) in both placebo-treated and abciximab-treated patients. Conclusions —In the EPISTENT trial, among patients randomized to stenting, starting ticlopidine before the percutaneous coronary intervention was associated with a significant decrease in the incidence of the 12-month composite end point for patients not receiving abciximab and the need for TVR among all patients.

Background —Stenting likely decreases the need for target-vessel revascularization procedures in diabetic patients compared with balloon angioplasty. However, the efficacy of stenting with platelet glycoprotein IIb/IIIa blockade has not yet been assessed in diabetics. Methods and Results —We analyzed the outcomes of 491 diabetic patients within the multicenter Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT). Diabetic patients were a prospectively defined subset: 173 were randomized to stent-placebo, 162 to stent-abciximab, and 156 to balloon angioplasty–abciximab. The main end point for this analysis was combined 6-month death, myocardial infarction (MI), or target-vessel revascularization (TVR). The composite end point occurred in 25.2% of stent-placebo, 23.4% of balloon-abciximab, and 13.0% of stent-abciximab patients ( P =0.005). Abciximab therapy, irrespective of revascularization strategy (stent or balloon angioplasty), resulted in a significant reduction in the 6-month death or MI rate: 12.7% for stent-placebo, 7.8% for balloon angioplasty–abciximab, and 6.2% for the stent-abciximab group ( P =0.029). The 6-month TVR rate was 16.6% for stent-placebo, 18.4% for balloon-abciximab, and 8.1% for stent-abciximab ( P =0.021). Compared with stent-placebo, stent-abciximab therapy was associated with a significant increase in angiographic net gain (0.88 versus 0.55 mm; P =0.011) and a decrease in the late loss index (0.40 versus 0.60 mm; P =0.061). The 1-year mortality rate for diabetics was 4.1% for stent-placebo and 1.2% for stent-abciximab patients ( P =0.11). Conclusions —The combination of stenting and abciximab therapy among diabetics resulted in a significant reduction in 6-month rates of death, MI, and TVR compared with stent-placebo or balloon-abciximab therapy.

Background —The currently used American College of Cardiology/American Heart Association lesion classification scheme dates from an era when balloon angioplasty was the only percutaneous treatment available and major complications occurred in ≈7% of patients. Major advances in treatment options would suggest that this scheme may be outmoded, but the schemes that have been suggested to update lesion classification have not been widely accepted. Methods and Results —Four thousand one hundred eighty-one consecutive patients (6676 lesions) formed a training set and 2146 patients (4231 lesions) formed a validation set treated from 1995 to 1997 at a single center used by 3 hospital groups. Twenty-seven pretreatment candidate variables were analyzed with the use of stepwise proportional logistic regression, and 9 (nonchronic total occlusion with TIMI flow 0, degenerated vein graft, vein graft age >10 years, lesion length ≥10 mm, severe calcium, lesion irregularity, large filling defect, angulated ≥45 degrees plus calcium, and eccentricity) were independently correlated ( P P =0.010 vs old scheme), respectively. Conclusions —Appreciation of these contemporary risk factors for complications of coronary intervention may assist in patient selection and in risk adjustment for comparison of outcomes between providers.

Background —Time to treatment with thrombolytic therapy is a critical determinant of mortality in acute myocardial infarction. Little is known about the relationship between the time to treatment with direct coronary angioplasty and clinical outcome. The objectives of this study were to determine both the time required to perform direct coronary angioplasty in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) trial and its relationship to clinical outcome. Methods and Results —Patients randomized to direct coronary angioplasty (n=565) were divided into groups based on the time between study enrollment and first balloon inflation. Patients randomized to angioplasty who did not undergo the procedure were also analyzed. The median time from study enrollment to first balloon inflation was 76 minutes; 19% of patients assigned to angioplasty did not undergo an angioplasty procedure. The 30-day mortality rate of patients who underwent balloon inflation ≤60 minutes after study enrollment was 1.0%; 61 to 75 minutes after enrollment, 3.7%; 76 to 90 minutes after enrollment, 4.0%; and ≥91 minutes after enrollment, 6.4%. The mortality rate of patients assigned to angioplasty who never underwent the procedure was 14.1% ( P =0.001). Logistic regression analysis revealed that the time from enrollment to first balloon inflation was a significant predictor of mortality within 30 days; after adjustment for differences in baseline characteristics, the odds of death increased 1.6 times ( P =0.008) for a movement from each time interval to the next. Conclusions —The time to treatment with direct PTCA, as with thrombolytic therapy, is a critical determinant of mortality.

To the Editor: The multicenter report by Dr Ellis and colleagues1 of 107 patients with left main coronary obstruction who were not candidates for surgery and in whom an attempt was made to reopen the left main coronary vessel by percutaneous techniques with different devices has significant implications for the cardiac surgeon when the patient is a candidate for a surgical procedure. Ellis et al deserve to be congratulated for this important piece of information. There have been numerous reports of patients who have undergone direct attempts to widen the left main trunk of the coronary artery to provide antegrade flow when the distal branches are not significantly involved with obstructions. One of the main complications of this approach is early restenosis of the vessel and, occasionally, total occlusion, with fatal consequences for the patient. It appears that the main trunk of the coronary artery reacts unfavorably to endarterectomy procedures or any type of trauma damaging the …

Coronary artery bypass graft surgery improves survival for certain subsets of patients with coronary artery disease and has been accepted as the revascularization “gold standard” since the 1970s. PTCA, introduced by Gruentzig in 1977, was initially envisioned as a potentially serial treatment for patients with focal coronary artery disease to prevent the development of complex disease severe enough to require CABG. By the mid-1980s, however, expertise and technology had improved to the point that PTCA could, apparently with reasonable success and safety, be brought to bear on anatomic situations previously considered to be solely the realm of the cardiovascular surgeon. To ascertain whether PTCA for patients with moderately advanced disease was truly an appropriate alternative to CABG, several RCTs were undertaken. At the time, it appeared that both revascularization alternatives were sufficiently mature that the long-term results would be relevant when they became available 5 to 10 years later. In aggregate, 4310 patients with multivessel disease thought to be suitable for either form of revascularization (thereby excluding many patients with far advanced disease) were enrolled in six RCTs between 1986 and 1991. The overall trial results were remarkably concordant. CABG was associated with a slight but not statistically significant survival advantage, less angina, and far fewer later revascularizations. PTCA led to a slight but insignificant reduction in myocardial infarction over the ensuing 2 to 5 years.1 2 3 4 5 6 Critics of RCTs often contest the generalizability of the treatment outcomes reported. They question whether it might be an oversimplification to apply the overall results of a trial both to all of its component patients and also to all similar but nonrandomized patients. In fact, given the general homogeneity engendered by the focus of most clinical trials, it is unusual for some patients to benefit and others to …

Background Clinical studies have demonstrated the efficacy of intravenous administration of agents that block platelet glycoprotein IIb/IIIa receptors in the setting of percutaneous coronary revascularization. Although the optimal duration of treatment has not been determined, more prolonged receptor blockade has been associated with increased efficacy. Orally active glycoprotein IIb/IIIa receptor antagonists may be advantageous and required for chronic therapy. Methods and Results Thirty patients with unstable angina who were undergoing percutaneous coronary interventions were randomized to placebo or Xemilofiban 35 mg orally before and 20 to 25 mg TID for 30 days after angioplasty. Bleeding events, platelet aggregation, and pharmacokinetic and hematologic parameters were assessed during hospitalization and at 2 and 4 weeks after drug initiation. Xemilofiban produced a rapid, sustained, marked inhibition of platelet aggregation. ADP-induced platelet aggregation at 2 hours after the initial dose at 2 and 4 weeks was 15%, 8%, and 11% in the Xemilofiban group compared with 80%, 68%, and 69% in the placebo group. Among 20 patients randomized to Xemilofiban there was 1 death after emergency coronary bypass surgery complicated by severe bleeding diathesis, and 3 patients had major bleeding events. Patients on Xemilofiban for 30 days reported episodes of mild mucocutaneous bleeding. Conclusions Xemilofiban, an orally active glycoprotein IIb/IIIa receptor inhibitor, produced rapid, sustained, extensive inhibition of platelet aggregation for a period of up to 30 days. At the dose initially tested, however, acute major bleeding and mucocutaneous bleeding during chronic administration were encountered.

Background Although an inverse relation between physician caseload and complications has been conclusively demonstrated for several surgical procedures, such data are lacking for percutaneous coronary intervention, and the ACC/AHA guidelines requiring ≥75 cases per year for operator “competency” are considered by some physicians to be arbitrary. Methods and Results From quality-controlled databases at five high-volume centers, models predictive of death and the composite outcome of death, Q-wave infarction, or emergency bypass surgery were developed from 12 985 consecutively treated patients during 1993 through 1994. Models had moderate to high discriminative capacity (area under ROC curves, 0.65 to 0.85), were well calibrated, and were not overfitted by standard tests. These models were used for risk adjustment, and the relations between both yearly caseload and years of interventional experience and the two adverse outcome measures were explored for all 38 physicians with ≥30 cases per year. The average physician performed a mean±SD of 163±24 cases per year and had been practicing angioplasty for 8±5 years. Risk-adjusted measures of both death and the composite adverse outcome were inversely related to the number of cases each operator performed annually but bore no relation to total years of experience. Both adverse outcomes were more closely related to the logarithm of caseload (for death, r =.37, P =.01; for death, Q-wave infarction, or bypass surgery, r =.58, P Conclusions In this analysis, high-volume operators had a lower incidence of major complications than did lower-volume operators, but the difference was not consistent for all operators. If these data are validated, their implications for hospital, physician, and payer policy will require exploration.

Background Platelet activation and aggregation may be key components of thrombolytic failure to restore and maintain perfusion in acute myocardial infarction. We performed a placebo-controlled, dose-ranging trial of Integrilin, a potent inhibitor of platelet aggregation, with heparin, aspirin, and accelerated alteplase. Methods and Results We assigned 132 patients in a 2:1 ratio to receive a bolus and continuous infusion of one of six Integrilin doses or placebo. Another 48 patients were randomized in a 3:1, double-blind fashion to receive the highest Integrilin dose from the first phase or placebo. All patients received accelerated alteplase, aspirin, and intravenous heparin infusion; all but two groups also received an intravenous heparin bolus. The highest Integrilin dose group from the nonrandomized phase and the randomized patients were pooled for analysis and compared with placebo-treated patients. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 90-minute angiography. Secondary end points were time to ST-segment recovery, an in-hospital composite (death, reinfarction, stroke, revascularization procedures, new heart failure, or pulmonary edema), and bleeding variables. The highest Integrilin dose groups had more complete reperfusion (TIMI grade 3 flow, 66% versus 39% for placebo-treated patients; P =.006) and a shorter median time to ST-segment recovery (65 versus 116 minutes for placebo; P =.05). The groups had similar rates of the composite end point (43% versus 42% for placebo-treated patients) and severe bleeding (4% versus 5%, respectively). Conclusions The incidence and speed of reperfusion can be enhanced when a potent inhibitor of the glycoprotein IIb/IIIa integrin receptor, such as Integrilin, is combined with accelerated alteplase, aspirin, and intravenous heparin.

Background Basic fibroblast growth factor (bFGF) has been shown to reduce infarct size in canine acute myocardial infarction; however, the mechanism of tissue salvage remains uncertain. We evaluated the effect of bFGF on infarct size in a model of acute infarction in which coronary occlusion was followed by prolonged reperfusion and sought to determine whether reperfusion attenuates the stimulus for myocardial neovascularization. Methods and Results Anesthetized dogs undergoing 4-hour balloon occlusion of the left anterior descending coronary artery were treated with intracoronary bFGF (n=8) or vehicle (n=6). Ten-microgram doses of bFGF were administered 10 minutes after occlusion and again immediately before reperfusion. Left ventriculograms were obtained before occlusion, after reperfusion, and preceding euthanasia on day 7. Infarct size, expressed as a percentage of the area at risk, was reduced in bFGF-treated dogs (13.7±2.1% versus 28±3.4%; P =.002). Changes in left ventricular ejection fraction, capillary density, and cellular proliferation—assessed immunohistochemically with factor VIII and proliferating cell nuclear antigen antibodies—were similar in both groups. To assess coronary vasomotor responses to bFGF, a separate hemodynamic study was performed in five anesthetized nonischemic dogs in which incremental bFGF doses up to 100 μg induced no vasodilator response. Conclusions Treatment with bFGF was associated with a reduction in infarct size without hemodynamic effects or evidence of neovascularization. These data suggest that bFGF mediates myocardial salvage independently of angiogenesis and that reperfusion after infarction may attenuate the stimulus for neovascularization.

Background The relation among the coagulation cascade, its individual proteins, and the response to vascular injury is largely undefined. We have evaluated the effect of four probes that block specific levels of coagulation cascade on neointimal hyperplasia in the atherosclerotic rabbit arterial injury model. Methods and Results Focal femoral atherosclerosis was induced by air-desiccation injury and hypercholesterolemic diet in 48 New Zealand White rabbits, followed by balloon angioplasty. Active-site inactivated factor VII a (DEGR-VII a ), which blocks the binding of factor VII a to tissue factor, was administered (n=12 arteries) by intravenous bolus (1 mg/kg) at the time of balloon angioplasty and followed by infusion of 50 μg · kg −1 · h −1 for 3 days; for the control (n=13 arteries), 150 U heparin was injected as bolus and followed by infusion of saline at 50 μL · kg −1 · min −1 . Recombinant tissue factor pathway inhibitor (TFPI), which binds factor X a and inhibits the tissue factor–factor VII a complex and factor X a , was given as a 1 mg/kg bolus followed by 15 μg · kg −1 · min −1 infusion for 3 days (n=17 arteries). Recombinant tick anticoagulant peptide (TAP; n=15 arteries) and hirudin (n=14 arteries), which block factor X a and thrombin, respectively, were administered as a 1 mg/kg bolus followed by 5 μg · kg −1 · min −1 infusion for 3 days. These three groups had their own controls (n=14 arteries). There were no differences among treatment groups in preangioplasty and postangioplasty minimal luminal diameter (MLD) by angiography. The mean MLD 21 days after balloon angioplasty was significantly different between control and DEGR-VII a –treated groups (0.74±0.25 and 1.24±0.27 mm, respectively; P =.0001) and between the TFPI-treated group and others (0.88±0.21 mm for control, 0.97±0.22 mm for hirudin-treated, 0.98±0.14 mm for TAP-treated, and 1.32±0.21 mm for TFPI-treated arteries; P =.0001 by ANOVA). By quantitative histological analysis, the ratio of neointimal cross-sectional area compared with the area of internal elastic lamina in the DEGR-VII a –treated group was significantly less than control (0.48±0.12 versus 0.67±0.12, P =.0001), and the ratio of neointimal cross-sectional area to the area demarcated by the internal elastic lamina of the TFPI-treated group was significantly reduced compared with the other groups (0.46±0.20 for TFPI-treated, 0.67±0.15 for hirudin-treated, 0.61±0.15 for TAP-treated, and 0.64±0.13 for control groups; P =.003). Conclusions Treatment with DEGR-VII a or TFPI for 3 days in this rabbit atherosclerotic injury model reduced angiographic restenosis and decreased neointimal hyperplasia compared with controls. These findings highlight the importance of early initiators of the extrinsic coagulation pathway, especially factor VII and tissue factor, in the response to arterial injury.

Background An adjunctive pharmacological strategy to thrombolytic therapy that is tailored to limit reperfusion injury after thrombolysis could further maximize the unquestioned benefit of restoring flow to ischemic myocardium. Ischemia–reperfusion injury exhibits features characteristic of an acute inflammatory response, including the rapid activation and infiltration of neutrophils. The initial process of neutrophil migration from the circulation to injured tissue is modulated by a group of adhesion molecules called selectins. The purpose of the present study was to assess the efficacy of a selectin blocker (CY 1503) given as an adjunct to thrombolytic therapy to interfere with the inflammatory response after ischemia–reperfusion and subsequently reduce myocardial infarct size in the electrolytic canine model. Methods and Results A fully occlusive thrombus was formed in the left circumflex coronary artery by electrolytic injury in 20 anesthetized open-chest dogs. After occlusion, an infusion of 1 mg/kg recombinant tissue-type plasminogen activator (rTPA) was administered over 20 minutes with either a bolus of placebo or the selectin blocker CY 1503 (40 mg/kg). At the onset of reperfusion, 20 μg/kg per minute rTPA was administered for 1 hour to prevent reocclusion. After 1 hour of reperfusion, infarct size, myocardial myeloperoxidase activity, and reperfusion arrhythmias were measured. In CY 1503–treated dogs, there was a significant 69% reduction in infarct size when expressed as a percentage of the area at risk (6.7±8.4% versus 21.8±13.6%; P =.008) and a marked reduction in myeloperoxidase activity (0.014±0.009 versus 0.0370±0.025 U/min per gram; P =.02) compared with the placebo group. There was no difference between the groups in the occurrence of reperfusion arrhythmias. Conclusions Selectin blockade as an adjunct to rTPA-mediated thrombolysis significantly reduces infarct size and myocardial neutrophil infiltration well beyond thrombolysis alone in the electrolytic canine model. These data suggest that selectin blockade is extremely effective at reducing ischemia–reperfusion injury and myocardial infarct size in this model and that the neutrophil is a potent mediator of ischemia–reperfusion injury.

Background Successful reversal of abrupt vessel closure without resultant major ischemic complications (death, Q-wave myocardial infarction, or coronary artery bypass graft surgery) is achieved in nearly half of all cases of abrupt vessel closure. The long-term outcome of these patients has not been previously addressed, and it is not clear whether they have a different prognosis than that of patients who have a successful procedure not associated with transient vessel closure. Methods and Results We examined 4863 consecutive patients who underwent successful percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA). Eighty-eight patients had an uncomplicated, successfully reversed transient in-laboratory vessel closure (group 2) and were compared with 4775 patients who had a successful procedure not associated with transient in-laboratory closure (group 1). Clinical follow-up was available in 4839 patients (99.5%), with a mean duration of 41±23 months (range, 1 to 104 months). Survival analysis showed that successfully treated, uncomplicated transient vessel closure per se does not have an adverse effect on long-term prognosis (death, myocardial infarction, or coronary interventions). However, when the procedure (PTCA or DCA) was associated with an increase in creatine kinase–MB (CK-MB), there was a significant adverse effect on long-term outcome. By multivariate logistic regression, an increase in postprocedure CK-MB was the most significant correlate for cardiac death (risk ratio, 1.25; P P =.0005). Conclusions Transient, uncomplicated in-laboratory vessel closure per se does not have an adverse long-term effect. However, a concomitant elevation of postprocedure cardiac enzymes has an important and significant adverse effect on long-term outcome. This study suggests that periprocedural creatine kinase isoenzyme determination in patients experiencing in-laboratory coronary closure has important prognostic implications.

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.

We appreciate the interest in our article1 shown by Dr Khawaja and colleagues. We agree that the majority of percutaneous coronary interventions (PCIs) are performed in patients with severe aortic stenosis (AS) who are undergoing transcatheter aortic valve replacement (TAVR) in the context of stable coronary artery disease (CAD) and not acute coronary syndromes. We stratified our data by distinct clinical subgroups based on the indication for PCI and found no difference in the 30-day mortality after PCI among patients with and without AS and with unstable angina (5 of 105 [5%] vs 11 of 185 [6%], respectively; P =0.67), non-ST-elevation myocardial infarction (3 of 48 [6%] vs 7 of 90 [8%], respectively; P =0.74), and ST …

BACKGROUND Thrombosis has been implicated as central to the clinical complications of coronary angioplasty (PTCA). Chimeric monoclonal 7E3 Fab (c7E3 Fab) is the first of a new class of antiplatelet drugs directed at the platelet glycoprotein IIb/IIIa integrin. This study was performed to determine the pharmacodynamics of c7E3 Fab administration during PTCA and to gain an initial clinical experience with this novel agent. METHODS AND RESULTS The study was a multicenter, open-label, dose-escalation study conducted in two stages. Enrollment included 56 patients scheduled for elective PTCA who were estimated to be at moderate to high risk of sustaining ischemic complications. All patients were given aspirin and heparin. The study drug was given at least 10 minutes before PTCA. In stage 1, increasing bolus doses of c7E3 Fab were given to 15 patients; a bolus dose of 0.25 mg/kg was found to result in blockade of > 80% of the receptors and reduce platelet aggregation to < 20% compared with baseline, establishing this dose as that necessary to sufficiently suppress platelet activity. In stage 2, additional c7E3 Fab was administered by continuous infusion to 32 patients for progressively longer periods of time (up to 24 hours) to confirm that platelet inhibition could be maintained with prolonged drug infusion. Also, 9 patients otherwise meeting entry criteria were given placebo. There were no thrombotic events among patients receiving c7E3 Fab. Overall procedural and clinical success and complication rates as well as rates of bleeding were statistically similar among groups. However, minor bleeding was more frequent with administration of the active drug. CONCLUSIONS The novel antiplatelet agent c7E3 Fab can be administered during PTCA in combination with aspirin and heparin. Suppression of platelet activity is dose dependent and can be maintained for up to 24 hours. Further evaluation will be required to determine the extent of improvement in ischemic complication and restenosis rates and to provide additional insight into the safety profile of this potent monoclonal platelet antibody.

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).

Alice K. Jacobs, MD, FACC, FAHA, Chair Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect Nancy Albert, PhD, CCNS, CCRN, FAHA Mark A. Creager, MD, FACC, FAHA Steven M. Ettinger, MD, FACC Robert A. Guyton, MD, FACC Jonathan L. Halperin, MD, FACC, FAHA Judith S. Hochman, MD, FACC, FAHA

BACKGROUND Coronary angioplasty is frequently performed in the United States, with more than 300,000 procedures in 1990. Despite the high rate of use of the procedure, there have been few studies addressing practice patterns. METHODS AND RESULTS From a private insurance claims data base of 5.4 million individuals, a total of 2,101 patients who underwent coronary angioplasty during 1988-1989 were identified. Using their 4,578 hospital admission records and 87,578 outpatient claim records, with an average follow-up of 332 +/- 182 days, we compared patients' outcomes and charges according to whether they had an exercise stress test before the procedure, by sex, by region of the country, and by whether the angioplasty was performed in an institution with a training program. Only 29% of the study cohort had exercise testing before angioplasty; patients in the West (p = 0.001), those undergoing multivessel angioplasty (p = 0.00001), and those whose procedures were performed at sites with training programs (p = 0.04) were more likely to have a screening test, whereas women (p = 0.008) and those with a recent myocardial infarction (p = 0.00001) were less likely to have a screening test. The average length of stay for patients without myocardial infarction as a primary diagnosis was 5.6 days, with a total hospital charge of $15,027. In follow-up, 15.1% had coronary artery bypass surgery and 15% had at least one additional angioplasty procedure; the average follow-up charges were $4,879. Charges varied according to sex, region of the country, and academic status of the angioplasty institution. Certain outcomes showed variation by region of the country and academic status of the angioplasty institution. CONCLUSIONS The relative lack of an objective definition of myocardial ischemia and the marked variability of use of procedures according to geographic region suggest the need for further implementation of established guidelines.

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 To assess the likelihood of intermediate-term event-free survival (freedom from death, coronary artery bypass surgery, and myocardial infarction) in patients with multivessel coronary disease undergoing coronary angioplasty, 350 consecutive patients from four clinical sites were carefully evaluated and followed for 22 +/- 10 months. METHODS AND RESULTS Eight clinical variables were evaluated at the clinical sites, and 23 angiographic variables describing the number, morphology, and topography of coronary stenoses were evaluated at a core angiographic laboratory. Most patients had Canadian Cardiovascular Society class III or IV angina (72%), two-vessel coronary disease (68%), and well-preserved left ventricular function (mean ejection fraction, 58 +/- 12%; range, 18-85%). Follow-up was complete in 99% of patients. At 2 years, event-free survival was 72%, overall survival was 96%, freedom from bypass surgery was 82%, and freedom from nonfatal myocardial infarction without surgery was 96%. Sequential Cox proportional hazards regression analyses allowing stepwise entry of variables prospectively coded as simple, as of intermediate complexity, or as complex found event-free survival to be independently predicted by low Canadian Cardiovascular Society angina class, no diabetes, no proximal left anterior descending stenoses, and the sum of stenosis simplified risk-territory scores of 15 or less. In the absence of class IV angina and these risk factors, 2-year event-free survival was 87% and overall survival was 100%. In the presence of two or more of these risk factors, event-free survival was less than 50%. CONCLUSIONS Recognition of risk factors for poor long-term outcome in this setting may improve clinical decision making and provide a framework on which to base meaningful subgroup analyses in randomized trials assessing the efficacy of coronary angioplasty.

To assess the likelihood of procedural success in patients with multivessel coronary disease undergoing percutaneous coronary angioplasty, 350 consecutive patients (1,100 stenoses) from four clinical sites were evaluated. Eighteen variables characterizing the severity and morphology of each stenosis and 18 patient-related variables were assessed at a core angiographic laboratory and at the clinical sites. Most patients had Canadian Cardiovascular Society class III or IV angina (72%) and two-vessel coronary disease (78%). Left ventricular function was generally well preserved (mean ejection fraction, 58 +/- 12%; range, 18-85%) and 1.9 +/- 1.0 stenoses per patient had attempted percutaneous coronary angioplasty. Procedural success (less than or equal to 50% final diameter stenosis in one or more stenoses and no major ischemic complications) was achieved in 290 patients (82.8%), and an additional nine patients (2.6%) had a reduction in diameter stenosis by 20% or more with a final diameter stenosis 51-60% and were without major complications. Major ischemic complications (death, myocardial infarction, or emergency bypass surgery) occurred in 30 patients (8.6%). In-hospital mortality was 1.1%. Stepwise regression analysis determined that a modified American College of Cardiology/American Heart Association Task Force (ACC/AHA) classification of the primary target stenosis (with type B prospectively divided into type B1 [one type B characteristic] and type B2 [greater than or equal to two type B characteristics]) and the presence of diabetes mellitus were the only variables independently predictive of procedural outcome (target stenosis modified ACC/AHA score; p less than 0.001 for both success and complications; diabetes mellitus: p = 0.003 for success and p = 0.016 for complications). Analysis of success and complications on a per stenosis dilated basis showed, for type A stenoses, a 92% success and a 2% complication rate; for type B1 stenoses, an 84% success and a 4% complication rate; for type B2 stenoses, a 76% success and a 10% complication rate; and for type C stenoses, a 61% success and a 21% complication rate. The subdivision into types B1 and B2 provided significantly more information in this clinically important intermediate risk group than did the standard ACC/AHA scheme. The stenosis characteristics of chronic total occlusion, high grade (80-99% diameter) stenosis, stenosis bend of more than 60 degrees, and excessive tortuosity were particularly predictive of adverse procedural outcome. This improved scheme may improve clinical decision making and provide a framework on which to base meaningful subgroup analysis in randomized trials assessing the efficacy of percutaneous coronary angioplasty.

To determine the clinical consequences of reocclusion of an infarct-related artery after reperfusion therapy, we evaluated 810 patients with acute myocardial infarction. Patients were admitted into four sequential studies with similar entry criteria in which patency of the infarct-related artery was assessed by coronary arteriography 90 minutes after onset of thrombolytic therapy. Successful reperfusion was established acutely in 733 patients. Thrombolytic therapy included tissue-type plasminogen activator (t-PA) in 517, urokinase in 87, and a combination of t-PA and urokinase in 129 patients. All patients received aspirin, intravenous heparin and nitroglycerin, and diltiazem during the recovery phase. A repeat coronary arteriogram was performed in 88% of patients at a median of 7 days after the onset of symptoms. Reocclusion of the infarct-related artery occurred in 91 patients (12.4%), and 58% of these were symptomatic. Angiographic characteristics at 90 minutes after thrombolytic therapy that were associated with reocclusion compared with sustained coronary artery patency were right coronary infarct-related artery (65% versus 44%, respectively) and Thrombolysis in Myocardial Infarction (TIMI) flow 0 or 1 (21% versus 10%, respectively) before further intervention. Median (interquartile value) degree of stenosis in the infarct-related artery at 90 minutes was similar between groups: 99% for reoccluded (value, 90/100%) compared with 95% for patent (value, 80/99%). Patients with reocclusion had similar left ventricular ejection fractions compared with patients with sustained patency at follow-up. However, patients with reocclusion at follow-up had worse infarct-zone function at -2.7 (value, -3.2/-1.8) versus -2.4 (SD/chord) (value, -3.1/-1.3) (p = 0.016). The recovery of both global and infarct-zone function was impaired by reocclusion of the infarct-related artery compared with maintained patency; median delta ejection fraction was -2 compared with 1 (p = 0.006) and median delta infarct-zone wall motion was -0.10 compared with 0.34 SD/chord (p = 0.011), respectively. In addition, patients with reocclusion had more complicated hospital courses and higher in-hospital mortality rates (11.0% versus 4.5%, respectively; p = 0.01). We conclude that reocclusion of the infarct-related artery after successful reperfusion is associated with substantial morbidity and mortality rates. Reocclusion is also detrimental to the functional recovery of both global and infarct-zone regional left ventricular function. Thus, new strategies in the postinfarction period need to be developed to prevent reocclusion of the infarct-related artery.

Introduction: Whereas primary PCI is the preferred reperfusion strategy for acute ST elevation MI if performed promptly, treatment delays are common. Methods: We tested the hypothesis in a randomized placebo-controlled double-blind trial of 2452 subjects from 20 countries that early pharmacologic therapy with half dose reteplase and abciximab, followed by PCI would improve the outcome in ST elevation MI patients presenting within 6 hours of symptom onset with anticipated first medical contact to catheterization time of 1– 4 hours, relative to patients receiving abciximab at the time of primary PCI; with a third randomized arm of early abciximab to better evaluate the contribution of reteplase to the combination therapy. The primary study endpoint was a composite of all cause mortality, ventricular fibrillation beyond 48 hours, cardiogenic shock or heart failure requiring re-hospitalization or an emergency room visit within 90 days. A major secondary endpoint was % ST segment resolution (>70%) 60 –90 min after randomization. Final patient enrollment was completed December 30, 2006, and 90 day follow up results will be available fall 2007. Results: Enrollment demographics are as follows: mean age = 62 years (16% ≥75), 26% female, 10% Killip II-IV, 11% prior MI, 16% diabetics, 48% anterior MI and 61% enrolled ≤ 3h after symptom onset. The median times from symptom onset to randomization, and randomization to first balloon inflation by tertiles were 1.5, 2.6, and 4.4 hours and 1.2, 1.8, and 2.6 hours, respectively. Pre specified subgroup analyses for the primary and major secondary study endpoints included time from symptom onset to randomization (≥3 vs >3 hours), randomization time to first balloon inflation (by tertiles), Killip Class (I vs II-IV), gender, age ( Conclusion: The findings from these analyses will supplement the primary study results from this, the largest randomized trial of facilitated angioplasty, to help define the proper management of this important group of high-risk patients.

Background A recent non-blinded, observational landmark study from uncontrolled registry data by Eisenstein et al. suggested that thienopyridine (T) use beyond 1 year may reduce death and MI in patients who have received drug-eluting stents (DES). We performed a similar examination of slow-release paclitaxel-eluting stents (PES) in the prospective, randomized, double-blind TAXUS DES trials. Methods Using data from the TAXUS II-SR, IV and V trials, a landmark analysis was performed on the 2,523 patients who were free of death, MI and stent thrombosis (ST) through 1 year. Patients were divided according to stent type (PES vs bare metal stent [BMS]) and thienopyridine usage at a 1-year landmark point: PES T+ (N=578), PES T− (N=683), BMS T+ (N=574), and BMS T− (N=688). Subsequent events (ST, death, MI) were tabulated for the next 3 years in TAXUS II-SR and IV, and for 1 year in TAXUS V. Results Thienopyridine and aspirin usage were well matched between BMS and PES patients at all time-points. T+ patients at 12 months had no ST events through 4 years, while T− patients had 6 ST events (0.57%; p=0.045, log-rank). This difference was not significant for BMS T+/T− (0.0% versus 0.22%, p=0.49), and borderline significant for PES T+/T− (0.0% versus 0.92%, p=0.056). There was no corresponding difference in death at either 2 or 4 years, but there was a borderline reduction in MI at 2 years for PES T+/T− (0.35% versus 1.49%, p=0.08; interaction term p=0.09 between stent type and thienopyridine use), which disappeared at 4 years (2.79% versus 3.42%, p=0.565; interaction term p=0.35). Conclusions Thienopyridine use at 1 year was associated with fewer subsequent late ST events overall, which was more pronounced for PES than BMS. While there was a borderline reduction in MI at 2 years, no sustained impact on death or MI at 4 years was demonstrated. These data will be updated with one additional year of follow-up in all 2,523 patients at the time of presentation.

Background— Drug-eluting stents compared with bare metal stents (BMS) may increase late stent thrombosis (ST), although an accompanying increase in the rates of death and myocardial infarction (MI) has not been observed. We hypothesized that the prevention of restenosis-related adverse events by drug-eluting stents might offset some or all of the excess risk from ST. Methods and Results— We analyzed a pooled patient-level database from 4 prospective, double-blind trials in which 3445 patients were randomized to paclitaxel-eluting stents or BMS. The occurrence of death or MI within 7 days of ST or target lesion revascularization was assessed. With a median follow-up of 3.2 years, ST occurred in 34 patients (1.0%), 31 (91.1%) of whom sustained death or MI within 7 days. Target lesion revascularization was performed in 425 patients (12.3%), 15 (3.5%) of whom died or had MI within 7 days. ST occurred in 14 BMS and 20 paclitaxel-eluting stent patients, resulting in 12 and 19 deaths or MIs within 7 days, respectively. Target lesion revascularization was performed in 290 BMS and 135 paclitaxel-eluting stent patients, resulting in 11 and 4 deaths or MI events within 7 days, respectively. In total, 23 patients in both the BMS and paclitaxel-eluting stents groups died or had an MI event within 7 days of either ST or target lesion revascularization. Conclusions— ST, although infrequent, results in a high incident rate of death and MI, whereas the more frequent occurrence of target lesion revascularization is associated with a finite but lower rate of death and MI. The marked reduction in restenosis with drug-eluting stents compared with BMS may counterbalance the potential excess risk from late ST with drug-eluting stents.

Background— The radial artery has been increasingly used in CABG. However, angiographic outcome data have been limited. Methods and Results— We reviewed all coronary angiography procedures from February 1996 to October 2001 and selected patients with a radial artery bypass graft. Angiographic outcomes were divided into groups as (1) occluded, (2) severe disease (≥70% stenosis, or string sign), or (3) patent (P P =0.0016). Radial artery grafts had an occlusion rate of 33.7%, compared with 4.8% for left internal mammary arteries ( P P =0.0003) and 4.8% for left internal mammary arteries ( P P =0.025). A radial artery graft was the most powerful multivariable predictor of severe stenosis or occlusion (χ 2 =28.87, P Conclusions— In patients predominantly presenting with signs and symptoms of myocardial ischemia after CABG, radial artery grafts have lower patency rates than left internal mammary artery and saphenous vein grafts. Selective use of the radial artery is warranted, particularly in women.

Background— Despite widespread use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts, data supporting this strategy are lacking. Methods and Results— A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed, and outcomes of graft interventions were assessed at 30 days and 6 months. Compared with PCI of native circulation (n=13 158), graft interventions (n=627) were associated with worse outcomes and in particular with a doubling of mortality at 30 days (2.1% versus 1.0%, P =0.006) and 6 months (4.7% versus 2.0%, P P P =0.18). At 6 months, 39.4% of patients randomized to GP IIb/IIIa inhibitors and 32.7% of patients allocated to placebo had an ischemic event (hazard ratio, 1.29; 95% CI, 0.97 to 1.72; P =0.07). Conclusions— Intravenous platelet GP IIb/IIIa receptor inhibition does not improve outcomes after PCI of bypass grafts. In the absence of mechanical emboli protection, this procedure is associated with high incidence of death and nonfatal ischemic events.

Background— Since the advent of percutaneous coronary interventions (PCIs), technological advances, adjunctive pharmacotherapy, and increasing operator experience have contributed to lowering the occurrence of major complications. However, emergency coronary artery bypass surgery (CABG) for failed PCI is still associated with important morbidity and mortality, even in the era of coronary stenting. We sought to determine the prevalence, indications, predictors, and complications of emergency CABG after PCI in the past decade. Methods and Results— We reviewed 18 593 PCIs performed from 1992 through 2000. There was a need for emergency CABG in 113 (0.61%) cases. The major indications were extensive dissection (n=61, 54%), perforation/tamponade (n=23, 20%), and recurrent acute closure (n=23, 20%). Prevalence of emergency CABG decreased from 1.5% of PCIs in 1992 to 0.14% in 2000 ( P P P = 0.028), whereas history of prior bypass surgery and use of stents resulted in a decreased need for emergency CABG ( P Conclusions— The need for emergency CABG has considerably decreased over time. Risk factors include female sex and a higher ACC/AHA score of the intervened lesion. However, morbidity and mortality of emergency CABG remain high even in the new millennium.

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

Background— Creatine kinase (CK)-MB elevation after percutaneous coronary intervention (PCI) has been associated with subsequent cardiac death. The patients at risk, the timing of risk, and potential treatment implications are uncertain. Methods and Results— Eight thousand, four hundred nine consecutive non– acute myocardial infarction patients with successful PCI and no emergency surgery or Q-wave myocardial infarction were followed for 38±25 months; 1446 (17.2%) had post-PCI CK-MB above normal on routine ascertainment. Patients were prospectively stratified into those with CK-MB 1 to 5× or CK-MB >5× normal. No patient with CK-MB 1 to 5× normal died during the first week after PCI, and excess risk of early death for patients with CK-MB elevation occurred primarily in the first 3 to 4 months. The actuarial 4-month risk of death was 8.9%, 1.9%, and 1.2% for patients with CK-MB >5×, CK-MB 1 to 5×, and CK-MB ≤1× normal ( P P P P =0.005), and no statin treatment at hospital discharge ( P =0.009) were associated with death. Conclusions— Patients with CK-MB elevation after PCI are at excess risk of death for 3 to 4 months, although prolonging hospitalization for CK-MB 1 to 5× is unlikely to modify risk. CK-MB >5× normal, incomplete revascularization, elevated C-reactive protein, heart failure, the elderly, and hospital discharge without on statin therapy increases risk. Several of these factors suggest that inflammation may play a part in the excess risk of death.

In this issue of Circulation , Rioufol et al1 describe the presence of multiple ruptured atherosclerotic coronary plaques in patients presenting with an acute coronary syndrome (ACS). With the use of intravascular ultrasound (IVUS), the authors systematically examined proximal portions of the entire coronary tree in 24 patients. Ruptured plaques were found at the culprit lesion in 9 patients (37.5%) but, more importantly, distant from the culprit lesion in 19 patients (79%). These additional ruptured plaques were frequently multiple, located in a vessel different from the culprit vessel in 70% of patients and in 2 vessels not related to the acute event in 12% of patients. Both culprit lesions and additional ruptured plaques were characterized by positive remodeling. The authors proceeded with coronary stent placement at the culprit lesion site in 19 patients (86%) and, on the basis of angiographic and IVUS criteria (minimum luminal diameter

Background Established methods of risk assessment in percutaneous coronary intervention have focused on clinical and anatomical lesion characteristics. Emerging evidence indicates the substantial contribution of inflammatory processes to short-term and long-term outcomes in coronary artery disease. Methods and Results Within a single-center registry of contemporary percutaneous coronary revascularization strategies with postprocedural creatine kinase and clinical events routinely recorded, we assessed the association of baseline C-reactive protein with death or myocardial infarction within the first 30 days. Predictive usefulness of baseline C-reactive protein within the context of established clinical and angiographic predictors of risk was also examined. Among 727 consecutive patients, elevated baseline C-reactive protein before percutaneous coronary intervention was associated with progressive increase in death or myocardial infarction at 30 days (lowest quartile, 3.9%, versus highest quartile, 14.2%; P =0.002). Among clinical and procedural characteristics, baseline C-reactive protein remained independently predictive of adverse events, with the highest quartile of C-reactive protein associated with an odds ratio for excess 30-day death or myocardial infarction of 3.68 (95% CI, 1.51 to 8.99; P =0.004). A predictive model that included baseline C-reactive protein quartiles, American College of Cardiology/American Heart Association lesion score, acute coronary syndrome presentation, and coronary stenting appears strongly predictive of 30-day death or myocardial infarction within this population (C-statistic, 0.735) and among individual patients (Brier score, 0.006). Conclusions Elevated baseline C-reactive protein portends heightened risk of 30-day death or myocardial infarction after coronary intervention. Coupled anatomic, clinical, and inflammatory risk stratification demonstrates strong predictive utility among patients undergoing percutaneous coronary intervention and may be useful for guiding future strategies.