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BACKGROUND The long-term outcomes of diabetic patients presenting with ST-segment elevation myocardial infarction (STEMI) in contemporary practice have received limited study. METHODS We evaluated the clinical characteristics and outcomes of STEMI patients with and without diabetes in a large regional STEMI program designed to facilitate timely primary percutaneous coronary intervention (PCI) (Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, MN). The primary and secondary outcome measures were in-hospital mortality, 1-year major adverse cardiovascular events (MACE) (stroke, myocardial infarction, unplanned PCI or coronary artery bypass graft [CABG] surgery, and all-cause mortality), and 5-year mortality. RESULTS Of the 6292 patients included, 1158 (18.4%) had Diabetes Mellitus (DM) (95.3% Type II, 4.7% Type I). Patients with DM were older (mean age 66 vs. 62.8 years, p < 0.01), had more co-morbidities and were more likely to receive medical therapy without reperfusion (13% vs. 10%, p = 0.003). Patients with DM had higher in-hospital (8% vs. 5%, p = 0.001), 1-year (8% vs. 4%, p < 0.001) and 5-year mortality (16% vs. 9%, p < 0.001) compared to non-diabetics. On Cox proportional hazards analysis, DM was independently associated with worse mortality (hazard ratio: 1.70, 95% confidence interval (CI): 1.32-2.19, p < 0.001) and MACE [HR: 1.63 (95% (CI)): 1.28-2.08, p < 0.001]. CONCLUSIONS Despite advancements in medical therapy and revascularization strategies for STEMI, DM remains independently associated with higher short- and long-term morbidity and mortality in contemporary practice.

BackgroundThe prognosis of ST-segment elevation myocardial infarction with non-obstructive coronaries (STE-MINOCA) is largely unknown.MethodsThe objective of this study is to evaluate the prevalence, characteristics, and 5-year mortality of patients with STE-MINOCA compared to STEMI with coronary artery obstruction (STEMI-Obstruction) using a multicenter cohort of consecutive STEMI patients at 3 regional Midwest STEMI programs from 2003 to 2020. STE-MINOCA was defined based on (1) coronary stenosis < 60% by visual estimation, (2) ischemia with elevated troponin, and (3) no alternative diagnosis. STE-MINOCA was further classified based on American Heart Association (AHA) definition as AHA STE-MINOCA and AHA STE-MINOCA Mimicker.Results8,566 STEMI patients, including 420 (4.9%) STE-MINOCA (26.9% AHA STE-MINOCA and 73.1% AHA STE-MINOCA Mimicker) were followed for a median of 7.1 years. Compared to STEMI-Obstruction, STE-MINOCA were younger, more often female, had fewer cardiovascular risk factors, and were less likely to be discharged on cardiac medications. At five years, mortality was higher in STE-MINOCA compared with STEMI-Obstruction (18% vs. 15%, p=0.033). In propensity score-matched analysis, STE-MINOCA had a 1.4-fold (95% CI: 1.04-1.89, p=0.028) higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Furthermore, 5-year mortality risk was significantly higher in AHA STE-MINOCA Mimicker (19% vs. 15%, p=0.043) but similar in AHA STE-MINOCA (17% vs. 15%, p=0.42) compared with STEMI-Obstruction.ConclusionsIn this large multicenter STEMI cohort, nearly 5% of patients presented with STE-MINOCA. At five years, mortality approached 20% among patients with STE-MINOCA. Despite the lower risk profile, STE-MINOCA patients were at 40% higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Additionally, 5-year all-cause mortality risk was higher in AHA STE-MINOCA Mimicker but similar in AHA STE-MINOCA compared to STEMI-Obstruction.

The outcomes of patients with previous coronary bypass graft surgery (CABG) presenting with ST-segment elevation acute myocardial infarction (STEMI) have received limited study. We compared the clinical and procedural characteristics and outcomes of STEMI patients with and without previous CABG in a contemporary multicenter STEMI registry between 2003 and 2020. The primary outcomes of the study were mortality and major cardiac adverse events (MACE: death, MI or stroke). Survival curves were derived using the Kaplan-Meier method and compared with the log-rank test. Of the 13,893 patients included in the analyses, 7.2% had previous CABG. Mean age was 62.4 ± 13.6 years, most patients (71%) were men and 22% had diabetes. Previous CABG patients were older (69.0 ± 11.7 vs 61.9 ± 13.6 years, p0.001) and more likely to have diabetes (40% vs 21%, p0.001) compared with patients without previous CABG. Previous CABG patients had higher mortality and MACE at 5 years (p0.001). Outcomes were similar with saphenous vein graft vs native coronary culprits. Previous CABG remained associated with mortality from discharge to 18 months (p = 0.044) and from 18 months to 5 years (p0.001) after adjusting for baseline characteristics. Long term outcomes after STEMI were worse among patients with previous CABG compared with patients without previous CABG, even after adjustment for baseline characteristics.

Background The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). Objectives The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. Methods A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. Results As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p, Central Illustration

Aims Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial. Methods and results We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) ≤45% and LV scar size ≥15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients. Conclusion Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs. Trial registration Clinicaltrials.gov identifier: NCT01458405.

Background Contemporary real‐world data on stroke in patients presenting with ST‐segment–elevation myocardial infarction (STEMI) are scarce. Methods and Results We evaluated the incidence, trends, cause, and predictors of stroke from 2003 to 2019 in 4 large regional STEMI programs in the upper Midwest that use similar transfer and treatment protocols. We also evaluated the long‐term impact of stroke on 5‐year mortality. Multivariate logistic and Cox regression analysis was used to identify variables independently associated with stroke in patients presenting with STEMI and identify variables associated with 5‐year mortality. A total of 12 868 patients presented with STEMI during the study period. Stroke occurred in 98 patients (0.76%). The incidence of stroke remained stable over time (0.5% in 2003, 1.2% in 2019; P ‐trend=0.22). Most (75%) of strokes were ischemic, with a median time to stroke symptoms of 14 hours after primary percutaneous coronary intervention (interquartile range, 4–72 hours), which led to a small minority (3%) receiving endovascular treatment and high in‐hospital mortality (18%). On multivariate regression analysis, age (increment of 10 years) (odds ratio [OR], 1.32; 95% CI, 1.10–1.58; P ‐value=0.003) and preintervention cardiogenic shock (OR, 2.03; (95% CI, 1.03–3.78; P =0.032)) were associated with a higher risk of in‐hospital stroke. In‐hospital stroke was independently associated with increased risk of 5‐year mortality (hazard ratio, 2.01; 95% CI, 1.13–3.57; P =0.02). Conclusions In patients presenting with STEMI, the risk of stroke is low (0.76%). A stroke in patients presenting with STEMI is associated with significantly higher in‐hospital (18%) and long‐term mortality (35% at 5 years). Stroke was associated with double the risk of 5‐year death.

Introduction: There are significant differences in body composition by sex; however, differences by sex on the association of BMI with cardiovascular outcomes after STEMI remains poorly understood. Methods: The Midwest STEMI Consortium consists of 15,039 consecutive STEMI activations. 4,682 patients with 1-year follow-up were included to examine sex-differences in characteristics, treatment, in-hospital and 1-year MACE and mortality risk by BMI groups: normal (18.5-24.9 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ), and obese (≥30.0 kg/m 2 ). Results: Among 4,682 patients, 30% were women and 70% were men. Among women, 28% had normal BMI, 30% were overweight, and 42% obese. In normal BMI patients women were significantly older, had higher rates of HTN, lower rates of smokers, lower peak troponin, and longer door-to-balloon times compared to men. Women had lower risk of 30-day MACE (1.1% vs. 3%, p=0.045) but there were no sex-differences in 1-year MACE or mortality. Among overweight patients, women were significantly older, had higher rates of HTN and diabetes, and lower rates of smokers. Bleeding complication was more common in women (38% vs. 32%, p=0.03) as was cardiogenic shock pre-PCI (13% vs. 8.8%, p=0.02) but no sex-differences were seen in 1-year MACE or mortality. Among obese patients, women were significantly older and had higher rates of HTN, diabetes and stroke. Women had lower rates of out of hospital cardiac arrest (8.8% vs. 13%, p=0.005) and more bleeding complication (39% vs. 33%, p=0.025). Women had higher risk of 30-day death (2% vs. 0.8%, p=0.02), 1-year stroke (2.4% vs. 0.7%, p=0.004), and 1-year MACE and mortality (Figure). Discussion: Among STEMI patients, we found that obese women were at increased risk of MACE and mortality. Interestingly, there were no differences in MACE or mortality between men and women of normal and overweight BMI ranges, suggesting the importance of BMI when risk stratifying patients, particularly women, that warrants further research.

BackgroundMost cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.MethodsIn this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF ResultsIn total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (−0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of −0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04).ConclusionsIn patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI.Trial registration numberNCT01458405.

Introduction: Cell therapy failed to improve global LV ejection fraction (LVEF) in most trials of post-MI LV dysfunction. LVEF does not consider the effect of cell therapy on different segments of the myocardium, which may be heterogeneous across different myocardial regions in patients with regional MI. Hypothesis: Allogeneic cardiosphere-derived cells (CDCs) improve segmental (but not global) myocardial function indexed as circumferential strain by MRI. Methods: In this randomized double-blind trial, 142 post-MI patients with LVEF Results: In total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3(10.8) and 108 (87.1%) males). Segmental Ecc improvement was significantly greater in patients receiving CDC (-0.5%(4.0)) compared to placebo (0.2%(3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of -0.7% (3.5) in patients receiving CDC vs. 0.04% (3.7) in the placebo group, p=0.04). The beneficial effect of CDCs for improving segmental Ecc was greater in patients with LV ejection fraction18.8% or LV end-diastolic volume index>100 [mixed effect regression coefficients of -0.92(p=0.02),-0.78(p=0.03), and -1.16(p=0.004) respectively versus -0.58(p=0.05) for the entire cohort]. Conclusions: In patients with post-MI LV dysfunction, allogeneic CDC administration resulted in improved segmental myocardial function. This CDC induced improvement in segmental myocardial function was greater in patients with severe LV dysfunction, dilated LV and greater infarct size. (clinicaltrials.gov Identifier: NCT01458405).

Introduction: There has been conflicting data regarding the impact of hypertriglyceridemia (HTG) on STEMI outcomes, including reports of a “lipid paradox” defined as lower event rates in patients with HTG. Therefore, the association between HTG and outcomes in STEMI deserves further investigation especially given the results of REDUCE-IT trial. Methods: A prospective, multicenter database of the Midwest STEMI Consortium was examined. The Midwest STEMI Consortium is a unique association of 4 large STEMI systems of care: Iowa Heart Center, Minneapolis Heart Institute Foundation, Prairie Cardiovascular, and The Christ Hospital. We included all consecutive STEMI patients between age of 40 and 75. Those with missing TG levels were excluded (23%). We compared 3 groups of TG levels: normal (500 mg/dl) for MACE (death, MI, or stroke) and all-cause mortality. Results: Of 6492 consecutive STEMI patients from 03/2003 to 01/2020, 3760 (58%) met inclusion criteria. The mean (SD) age was 59.1 ± 9.2 and male gender was predominant (76%). A little over one-third of the study participants had moderate HTG (35%). Patients with higher TG levels had lower HDL levels and increased rates of history of premature CAD, DM, and HTN (Table). Moderate HTG was not a risk factor for MACE or all-cause mortality. Severe HTG was significantly associated with increased in-hospital (p=0.016) but not 1-year all-cause mortality (p=0.21) (Figure). Conclusions: In STEMI patients, higher TG levels were associated with increased in-hospital but not 1-year all-cause mortality.

Introduction: There is limited data regarding the frequency, predictors and impact of repeat, unplanned coronary angiography following successful reperfusion with primary PCI in STEMI pts. Methods: We used the prospective, multicenter Midwest STEMI Consortium database, which was created by unique consolidation of 4 large STEMI systems of care: Iowa Heart Center, Minneapolis Heart Institute Foundation, Prairie Cardiovascular, and The Christ Hospital. Each center has similar, well-established standardized STEMI protocols with collaboration over 100 non-PCI-capable hospitals in Midwest. We included all consecutive STEMI pts who underwent repeat, unplanned coronary angiography within 48-hour of successful primary PCI. We excluded pts who underwent a planned or staged coronary angiography. We compared pts with repeat, unplanned coronary angiography to a propensity-score matched (1:2) pts without repeat coronary angiography within 48-hour. Results: Among 6507 STEMI pts treated with primary PCI from 03/2003 to 01/2020, only 136 (2.1%) underwent repeat, unplanned coronary angiography. These pts had higher rates of LAD culprit, history of prior MI, poor pre-PCI TIMI flow (0 or 1) and lower EF. Nearly half of the repeat, unplanned coronary angiographies revealed patent stent (63/136). There were only 32 (24%) in-stent thrombosis and 30 (22%) new occlusions. Compare to the control group, pts with repeat, unplanned coronary angiography were more likely to have major bleeding and longer LOS (p=(Table). Conclusions: Repeat, unplanned coronary angiography is relatively uncommon after contemporary primary PCI for STEMI pts and is more common with larger, anterior MIs.

Background Over the past 20 years, the development of regional ST-elevation myocardial infarction (STEMI) care systems has led to remarkable progress in achieving timely coronary reperfusion with attendant improvement in clinical outcomes, including survival. Despite this progress, contemporary STEMI care does not consistently meet the national guideline-recommended goals, which offers an opportunity for further improvement in STEMI outcomes. The lack of single, comprehensive, national STEMI registry complicates our ability to improve STEMI outcomes in particular for high-risk STEMI subsets such as cardiac arrest (CA) and/or cardiogenic shock (CS). Objectives To address this need, the Midwest STEMI Consortium (MSC) was created as a collaboration of 4 large, regional STEMI care systems to provide a comprehensive, multicenter, and prospective STEMI registry without any exclusionary criteria. Methods The MSC is a collaboration of 4 large, regional STEMI care systems: Iowa Heart Center in Des Moines, IA; Minneapolis Heart Institute Foundation in Minneapolis, MN; Prairie Heart Institute in Springfield, IL; and The Christ Hospital in Cincinnati, OH. Each has similar standardized STEMI protocol and together include 6 percutaneous coronary intervention (PCI)-capable hospitals and over 100 non-PCI-capable hospitals. Each center had a prospective database that was transferred to a data coordinating center to create the multicenter database. The comprehensive database includes traditional risk factors, cardiovascular history, medications, time to treatment data, detailed angiographic characteristics, and short- and long-term clinical outcomes up to 5-year for myocardial infarction, stroke, and cardiovascular and all-cause mortality. Ten-year mortality rates were assessed by using national death index. Results Currently, the comprehensive database (03/2003-01/2020) includes 14,911 consecutive STEMI patients with mean age of 62.3 ± 13.6 years, female gender (29%), and left anterior descending artery as the culprit vessel (34%). High risk features included: Age >75 years (19%), left ventricular ejection fraction, Highlights • There is no single, comprehensive, and national STEMI registry. In particular, detailed information regarding high-risk STEMI patients including cardiac arrest (CA) and cardiogenic shock (CS) are frequently missing. • Midwest STEMI Consortium is a unique registry of over 15,000 consecutive patients from 4 large regional STEMI systems. • Unique aspects of the registry include: • Consecutive STEMI activations without exclusions. • Detailed data on high-risk (CA/CS) cohorts. • Detailed angiographic data. • Detailed long-term follow up including mortality to 10 years.

Objective To evaluate the impact of COVID‐19 pandemic migitation measures on of ST‐elevation myocardial infarction (STEMI) care. Background We previously reported a 38% decline in cardiac catheterization activations during the early phase of the COVID‐19 pandemic mitigation measures. This study extends our early observations using a larger sample of STEMI programs representative of different US regions with the inclusion of more contemporary data. Methods Data from 18 hospitals or healthcare systems in the US from January 2019 to April 2020 were collecting including number activations for STEMI, the number of activations leading to angiography and primary percutaneous coronary intervention (PPCI), and average door to balloon (D2B) times. Two periods, January 2019–February 2020 and March–April 2020, were defined to represent periods before (BC) and after (AC) initiation of pandemic mitigation measures, respectively. A generalized estimating equations approach was used to estimate the change in response variables at AC from BC. Results Compared to BC, the AC period was characterized by a marked reduction in the number of activations for STEMI (29%, 95% CI:18–38, p

The Door to Unload Trial is a novel interventional trial proposing to treat anterior ST-elevation myocardial infarction (STEMI) by unloading the left ventricle (LV) with impella for 30 minutes prior to performing percutaneous coronary intervention (PCI). Our goal was to identify patients (pts) who

Objectives To compare outcomes of fractional flow reserve (FFR) to angiography (ANGIO) guided percutaneous coronary intervention (PCI). Background The results of a recent randomized controlled trial reported unfavorable effects of routine measurement of FFR, thereby questioning its validity in improving clinical outcomes. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were queried from January, 2000 through December, 2016 and studies comparing FFR and ANGIO guided PCI were included. Clinical endpoints assessed during hospitalization and at follow-up (>9 months) included: myocardial infarction (MI), major adverse cardiovascular events (MACE), target lesion revascularization (TLR), and all-cause mortality. Additional endpoints included number of PCIs performed, procedure cost, procedure time, contrast volume, and fluoroscopy time. Results A total of 51,350 patients (age 65 years, 73% male) were included from 11 studies. The use of FFR was associated with significantly lower likelihood of MI during hospitalization (OR 0.54, 95% CI: 0.39 to 0.75, P = 0.0003) and at follow-up (OR 0.53, 95% CI: 0.40 to 0.70, P = 0.00001). Similarly, FFR-PCI was associated with lower in-hospital MACE (OR 0.51, 95% CI: 0.37 to 0.70, P = 0.0001) and follow-up MACE (OR 0.63, 95% CI: 0.47 to 0.86, P = 0.004). In-hospital TLR was lower in the FFR-PCI group (OR 0.62, 95% CI: 0.40 to 0.97, P = 0.04), but not at follow-up (OR 0.83, 95% CI: 0.50 to 1.37, P = 0.46). There was no difference of in-hospital (OR 0.58, 95% CI: 0.31 to 1.09, P = 0.09) or follow-up all-cause mortality (OR 0.84, 95%CI: 0.59 to 1.20, P = 0.34). FFR-PCI was associated with significantly less PCI (OR 0.04, 95% CI: 0.01 to 0.15, P = 0.00001) with lower procedure cost (Mean Difference −4.27, 95% CI: −6.61 to −1.92, P = 0.0004). However, no difference in procedure time (Mean Difference 0.79, 95% CI: −2.41 to 3.99, P = 0.63), contrast use (Mean Difference −8.28, 95% CI: −24.25 to 7.68, P = 0.31) or fluoroscopy time (Mean Difference 0.38, 95% CI: −2.54 to 3.31, P = 0.80) was observed. Conclusions FFR-PCI as compared to ANGIO-PCI is associated with lower in-hospital and follow-up MI and MACE rates. Although, in-hospital TLR was lower in the FFR-PCI group, this benefit was not present after 9 months. FFR-PCI group was also associated with less PCI and lower procedure costs with no effect on procedure time, contrast volume or fluoroscopy time.

KILO tested 2 novel weight-based eptifibatide dosing strategies compared with standard dosing in obese patients undergoing elective percutaneous coronary intervention (PCI). Eptifibatide dosing is weight adjusted for patients up to 121 kg. Patients above this weight receive the same maximal dose, although it is unknown if this provides adequate eptifibatide concentration or platelet inhibition.Sixty-seven patients weighing ≥125 kg undergoing elective PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using a weight of 121 kg, actual body weight (ABW)-based dosing with no upper limit, or ideal body weight (IBW)-based dosing. Boluses of 180 μg/kg were given 10 minutes apart, followed by a 2.0 μg/kg per minute infusion. Plasma eptifibatide concentrations were drawn at 12 to 18 hours after initiating the infusion. Platelet aggregation was assessed at baseline and 10 minutes after the second bolus.Sixty-seven patients were randomized to standard (n = 22), ABW (n = 23), or IBW (n = 22) dosing. The median (25th, 75th) steady-state plasma eptifibatide concentrations were 1,740 ng/mL (1,350, 2,350), 1,780 ng/mL (1,510, 2,350), and 1,055 ng/mL (738, 1,405), respectively (P.001). Ten-minute median (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20), respectively (P = .001).Actual body weight eptifibatide dosing leads to higher plasma concentrations and greater platelet inhibition than standard or IBW dosing in obese patients undergoing PCI. Current recommendations for eptifibatide dosing may be inadequate in patients121 kg. Further study is warranted to define the optimal dosing of eptifibatide and other medications in obese patients.

Background— Circadian rhythms with regard to time of symptom onset for patients with acute myocardial infarction have been observed, although their relationship to outcomes has been debated. We evaluated these rhythms in patients with ST-elevation myocardial infarction as a function of the 24-hour circadian cycle. Methods and Results— The relationship between onset of symptoms during the 24-hour circadian cycle and prehospital delays from symptom onset to hospital arrival, timeliness of reperfusion, and in-hospital death was assessed in 2143 patients with ST-elevation myocardial infarction presenting from 2004–2008 at 1 of 3 tertiary-care healthcare ST-elevation myocardial infarction systems. There was a significant association between time of onset and the circadian cycle, with the greatest percentage (39%) of patients experiencing onset between 8 am and 3 pm ( P am to 5:59 am had median prehospital delays of 121 minutes versus 70 minutes from 12 pm to 5:59 pm ( P am to 5:59 am had median door-to-balloon times of 75 minutes versus 60 minutes from 6 am to 11:59 am ( P Conclusions— Patients with ST-elevation myocardial infarction exhibit significant circadian patterns in symptom onset, prehospital delay, and timeliness of reperfusion. Patients who develop symptoms from 12 am to 5:59 am present with longer prehospital delays and have longer door-to-balloon times. After multivariable adjustment, there was no significant association between circadian patterns of time of onset and in-hospital death.

Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk/benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. Unpublished clinical trial results have not been taken into account. A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk/benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2 . The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period …

Background— In Europe, interhospital transfer of ST-elevation myocardial infarction (STEMI) patients for primary percutaneous coronary intervention (PCI) from non–PCI-capable (STEMI-referral) to PCI-capable (STEMI-accepting) facilities has been shown to be a superior reperfusion strategy compared with on-site fibrinolysis. The feasibility of such programs in the United States remains poorly defined. Methods and Results— We describe an observational cohort of 230 consecutive presumed STEMI patients who underwent interhospital transfer between January 2005 and March 2007 among 6 STEMI-referral and 2 STEMI-accepting hospitals in rural central Illinois. A standard treatment protocol using rapid interhospital transfer for primary PCI or rescue PCI after full-dose intravenous fibrinolysis (in event of unanticipated transfer delays) was initiated by the STEMI-referral emergency department physician. Three time intervals were evaluated: STEMI-referral care (door 1 to departure), transport time (door 1 departure to STEMI-accepting hospital arrival [door 2]), and STEMI-accepting hospital care (door 2 to balloon). Primary PCI was performed in 165 STEMI-confirmed patients (87.7%), whereas fibrinolysis was required in 16 patients (8.5%), with 56% undergoing rescue PCI. The median door 1–to-departure time was 46 minutes (25th and 75th percentiles, 32 and 62 minutes); approximately two thirds of this delay was attributable to the wait for transport arrival and departure. The transport and door 2–to-balloon times were 29 minutes (25th and 75th percentiles, 25 and 35 minutes) and 35 minutes (25th and 75th percentiles, 32 and 46 minutes), respectively. The door 1–to-balloon time was 117 minutes (25th and 75th percentiles, 98 and 137 minutes), with 12.2% and 58% of patients achieving a time of ≤90 and ≤120 minutes, respectively. No adverse clinical events occurred during interhospital transport. Conclusion— In rural US communities, emergency department physician–initiated interhospital transfer of STEMI patients for primary or rescue PCI is feasible and was safely executed with achievement of timely reperfusion when performed within coordinated healthcare networks.

BACKGROUND The clinical guidelines for unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) published in 1994 by the Agency for Health Care Policy Research (AHCPR) were intended to help improve treatment. No large study, however, has evaluated the effect of the guidelines on clinical practice METHODS We compared the treatment of 3,318 patients admitted with UA/NSTEMI in the preguideline Thrombolysis in Myocardial Infarction (TIMI) III Registry (1990-1993) and 2,948 patients enrolled in the postguideline Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry (1995-1996). RESULTS More patients in GUARANTEE received guideline-recommended medication than did those in TIMI III, specifically beta-blockers (50.9% vs. 40.7%, P < 0.001), heparin (63.3% versus 57.5%, P < 0.001), and the combination of aspirin, heparin, and beta-blockers on admission plus aspirin at discharge (26.9% vs. 18.8%, P < 0.001). These changes were similar in all subgroups, but the greatest improvement in medication use was seen in patients admitted to a tertiary care hospital and in those with a final diagnosis of NSTEMI, i.e., with positive cardiac markers. Conversely, fewer patients in GUARANTEE who fulfilled AHCPR criteria for catheterization underwent the procedure (62.3% in GUARANTEE tertiary centers vs. 44.6% in GUARANTEE nontertiary centers vs. 66.0% in TIMI, P < 0.001). CONCLUSION After publication of clinical guidelines for UA/NSTEMI, more patients received appropriate pharmacologic treatment, but a significant number of patients remained under-treated. Efforts to improve compliance with guideline recommendations via education and critical pathways are warranted, especially in nontertiary care settings.

Background Pharmacodynamics of eptifibatide, a cyclic heptapeptide antagonist of platelet glycoprotein IIb/IIIa, are substantially altered by anticoagulants that chelate calcium, resulting in overestimation ex vivo of the in vivo effects of this agent. We conducted a dose-ranging study to characterize the pharmacodynamics and pharmacokinetics of eptifibatide under physiological conditions. Methods and Results Patients (n=39) undergoing elective percutaneous coronary intervention were randomly assigned to an eptifibatide bolus followed by an infusion (180-μg/kg bolus followed by 2 μg/kg per minute or 250-μg/kg bolus followed by 3 μg/kg per minute) for 18 to 24 hours. In a 2:1 ratio, these patients received either a second bolus of eptifibatide (90 μg/kg or 125 μg/kg for the initial 180-μg/kg or 250-μg/kg groups, respectively) or placebo 30 minutes after the initial bolus. Bleeding times, ex vivo platelet aggregation, receptor occupancy, and plasma eptifibatide levels at baseline and at 1, 2, 3, 4, 6, and 8 hours were evaluated. Platelet inhibition was dose dependent and >80% in all groups by steady state. The single-bolus regimens had a transient loss of inhibition at 1 hour, consistent with rapid distribution and drug elimination. Pharmacokinetic modeling suggested that optimal dosing of eptifibatide would be obtained with a 180-μg/kg bolus and a 2-μg/kg per minute infusion followed by a second 180-μg/kg bolus 10 minutes later. Conclusions A novel higher-dose, double-bolus regimen of eptifibatide in coronary intervention attains and maintains >90% inhibition of platelet aggregation in >90% of patients, providing the pharmacodynamic construct for the design of the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of adjunctive eptifibatide in coronary stent implantation.

Background and Methods: Because time to presentation to the hospital affects time to treatment and is known to be important in acute myocardial infarction, we evaluated this variable in patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). Among 2909 consecutive patients with UA/NSTEMI admitted to 35 hospitals in 6 geographic regions of the United States, we compared patients with acute (onset of pain 12 hours) unstable angina.

Background —Absolute coronary flow velocity reserve (CVR) after stenting may remain abnormal as a result of several different mechanisms. Relative CVR (rCVR=CVR target /CVR reference ) theoretically normalizes for global microcirculatory disturbances and facilitates interpretation of abnormal CVR. Methods and Results —To characterize potential mechanisms of poststent physiology, CVR was measured using a Doppler-tipped angioplasty guidewire in 55 patients before and after angioplasty, after stenting, and in an angiographically normal reference vessel. For the group, the percent diameter stenosis decreased from 75±13% to 40±18% after angioplasty and to 10±9% (all P P P stent ≤2.0, increased basal coronary flow, rather than attenuated hyperemia, was responsible in large part for the lower CVR stent compared with patients having CVR stent >2.0. In 8 patients with CVR stent stent Conclusions —Although a majority of patients after stenting normalize CVR for the individual circulation (ie, normal CVR or normal rCVR), in those with impaired CVR stent , the analysis of coronary flow dynamics suggests several different physiological mechanisms. Additional assessment may be required to fully characterize the physiological result for such patients to exclude remediable luminal abnormalities.

Background Prior studies, usually conducted with the use of insurance databases, have shown differences in the use of cardiac procedures between black patients and white patients hospitalized with various types of coronary artery disease. However, few data are available in prospectively collected cohorts of patients with unstable angina or on the use of appropriate medications or interventions. Methods and Results We evaluated 2948 consecutive patients with unstable angina admitted to 35 hospitals across the United States in 1996, comparing nonwhite and white patients. Seventy-seven percent of patients were white, 14% were black, 4% were Hispanic, 1% were Asian, and 3% were other or unknown race. Differences were seen in coronary risk profile, with a higher incidence of hypertension and diabetes mellitus in nonwhites. Cardiac catheterization was performed less often in nonwhites compared with whites (36% vs 53%, P = .001). Even in patients meeting the criteria for appropriate catheterization in the Agency for Health Care Policy Research unstable angina guidelines, fewer nonwhites underwent catheterization (44% vs 61%, P = .001), but among these, fewer nonwhites had significant coronary stenosis (72% vs 90%, P = .001). However, among patients catheterized who had indications for revascularization, angioplasty and coronary artery bypass grafting were performed equally often in nonwhites and whites. Conclusions Current guidelines would recommend more aggressive use of cardiac catheterization for nonwhite patients. However, our findings suggest that racial differences may need to be included in the diagnostic and interventional algorithms. (Am Heart J 1999;138:1065-72.)

OBJECTIVES We examined the procedural and 30-day clinical outcomes among patients receiving aspirin and either ticlopidine or clopidogrel during coronary stenting. BACKGROUND Ticlopidine-plus-aspirin has become standard antiplatelet therapy for the prevention of thrombotic complications after coronary stenting. Clopidogrel has a similar mechanism of action as ticlopidine, but both its efficacy and its safety as a pharmacologic adjunct to coronary stenting have not been well described. METHODS This single-center, prospective analysis examined the in-hospital procedural and 30-day clinical outcomes among 875 consecutive patients undergoing coronary stenting who received adjunctive aspirin and either clopidogrel (n = 514; 58.7%) or ticlopidine (n = 361; 41.3%) therapy. RESULTS Procedural success rates were similar among the clopidogrel- (99.6%) and ticlopidine-treated patients (99.4%). Subacute stent thrombosis (i.e., >24 h ≤30 days) occurred in one clopidogrel-treated (0.2%) and in one ticlopidine-treated (0.3%) patient (p = 0.99). By 30 days following the index procedure, the combined rates of death, nonfatal myocardial infarction and need for target vessel revascularization were similar among patients who received either clopidogrel (2.1%) or ticlopidine (1.4%; p = 0.57) therapy. CONCLUSIONS In this analysis the antiplatelet combination therapy of aspirin-plus-clopidogrel was an effective regimen for preventing thrombotic complications and major adverse cardiovascular events among a broad spectrum of patients undergoing coronary artery stenting.

Few data are available in prospectively collected cohorts of patients with unstable angina pectoris or on the use of appropriate medications or interventions. Accordingly, we evaluated 2,948 consecutive patients with unstable angina admitted to 35 hospitals in the United States in 1996, and comparing men and women (39% of the patients were women). Differences were seen in coronary risk profiles with a higher incidence of systemic hypertension, diabetes mellitus, and a family history of coronary disease in women. Women were less likely to receive Agency for Health Care Policy Research (AHCPR) recommended pharmacologic treatment than men. Cardiac catheterization, coronary angioplasty, and bypass was performed less often in women compared with men (44% vs. 53%, p = 0.002; 12% vs. 18%, p = 0.02; 7% vs. 10%, p = 0.001, respectively). At catheterization, women were more likely to have no significant coronary artery disease (25% vs. 14%, p = 0.001). Although fewer women than men fulfilled the AHCPR criteria for cardiac catheterization (54% vs. 64%, p = 0.001), a similar rate of men and women with positive criteria underwent catheterization and angioplasty. However, fewer women with positive criteria underwent bypass surgery (36% vs. 46%, p = 0.03). More men "ruled-in" for a myocardial infarction at admission (13% vs. 8%, p = 0.001), but there was no difference in recurrent angina, in-hospital myocardial infarction, or death. Despite different epidemiologic profiles and less evidence of coronary artery disease by noninvasive and invasive tests, women and men had similar outcomes.

Objectives. The purpose of this study was to investigate whether or not there is an association between managed care insurance and the delivery and outcome of care in patients presenting with unstable angina. Background. The proportion of U.S. patients with managed care health insurance is increasing. This may be associated with recent improvements in the control of health care costs. It is unknown whether or not there is a difference in process of care in angina patients presenting with managed care versus fee-for-service health insurance. Methods. We compared baseline characteristics, process and outcome of care in 636 patients with managed care insurance (MC) and 1,404 patients with fee-for-service (FFS) insurance who presented with unstable angina to 35 hospitals participating in the global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry. Results. Although, there was little difference in baseline characteristics and hospital treatments between cohorts, MC patients were more likely to be discharged on guideline-recommended medications (aspirin and beta-adrenergic blocking agents). In addition, FFS patients were more likely to undergo cardiac catheterization (odds ratio = 1.25 95% confidence interval = 1.1 to 1.5), but not revascularization during the hospitalization. There was no difference in hospital mortality (0.9% versus 1.2% in MC versus FFS; p = 0.60). Conclusions. In patients admitted with suspected unstable angina, MC patients are less likely to undergo coronary angiography, but are more likely to be discharged on indicated medications.

Objectives. This study was designed to identify potential predictors of vascular access site (VAS) complications in the large-scale Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor inhibitor (eptifibatide).Background. GP IIb/IIIa receptor inhibition during coronary interventions has been associated with excess VAS complications. If other predictors of VAS complications could be identified, they might be manipulated to reduce complications.Methods. A total of 4,010 patients undergoing percutaneous transluminal coronary revascularization (PTCR) were randomized into one of three bolus/20- to 24-h infusion arms: placebo bolus/placebo infusion; 135-μg/kg body weight eptifibatide bolus/0.5-μg/kg per min eptifibatide infusion; or 135-μg/kg eptifibatide bolus/0.75-μg/kg per min eptifibatide infusion. Heparin during the procedure was weight adjusted and stopped 4 h before sheaths were removed. Logistic regression modeling was used to identify independent predictors of VAS complications.Results. VAS complications were more common in patients treated with eptifibatide (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer time to sheath removal (p = 0.0002), stent placement (with intense post-stent anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009), major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04) as independent predictors of VAS complications.Conclusions. VAS complications may be reduced by early sheath removal, by avoiding placement of venous sheaths and by limiting heparin dosing to avoid excessive activated clotting times. Early sheath removal during inhibition of platelet aggregation by eptifibatide is feasible.

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

Objectives. We sought to evaluate the impact of angiographically visible thrombus on short- and long-term clinical outcomes after percutaneous transluminal coronary angioplasty (PTCA). Background. Intracoronary thrombus is frequently seen on angiography in patients with acute ischemic coronary syndromes or complex lesion morphology, or both, and is often considered to predict a higher rate of complications in patients undergoing PTCA. Methods. Prospectively collected data from 2,099 patients undergoing high risk PTCA in the Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial were analyzed. In addition to aspirin and heparin, patients were randomized to receive either abciximab bolus and infusion, abciximab bolus alone or placebo. Based on an angiographic core laboratory interpretation, patients were classified into three groups: thrombus absent, thrombus possible or thrombus present. The primary end point at 30 days was the composite of death, myocardial infarction or urgent revascularization. The 6-month end point was the composite of death, myocardial infarction or any revascularization. Results. Although abrupt closure was most common in patients with thrombus present compared with thrombus absent or possible (13%, 10.0% and 7.4%, respectively), neither the 30-day nor the 6-month clinical end points were different among the three groups (9%, 11% and 11.7%, respectively, and 30%, 34% and 31%, respectively). Most notably, the benefit of treatment with abciximab was present in all three thrombus groups, and the magnitude of benefit was not different among the thrombus groups. Conclusions. In high risk patients undergoing percutaneous coronary revascularization, features of thrombus on the preprocedure angiogram do not indicate an augmented risk of adverse clinical outcomes. Abciximab therapy reduces the rate of adverse outcomes regardless of the presence of thrombus and should therefore not necessarily be reserved for patients whose angiograms have features of intraluminal thrombus.

Objectives. We sought to evaluate whether patients with unstable angina undergoing coronary intervention derive particular clinical benefit from potent platelet inhibition. Background. Plaque rupture and platelet aggregation are pathogenetic processes common to unstable angina and ischemic complications of percutaneous coronary intervention. Methods. Of the 2,099 patients undergoing a coronary intervention in the Evaluation of 7E3 in Preventing Ischemic Complications (EPIC) trial, 489 were enrolled with the diagnosis of unstable angina and randomized to receive placebo, an abciximab (c7E3) bolus immediately before the intervention or an abciximab bolus followed by a 12-h infusion. The primary end point was a composite of death, myocardial infarction (MI) or urgent repeat revascularization within 30 days of randomization. The occurrence of death, MI or any revascularization within 6 months was also assessed. Results. Compared with placebo, the bolus and infusion of abciximab resulted in a 62% reduction in the rate of the primary end point (12.8% vs. 4.8%, p = 0.012) among patients with unstable angina, due primarily to a reduction in the incidences of death (3.2% vs. 1.2%, p = 0.164) and MI (9% vs. 1.8%, p = 0.004). By 6 months, cumulative death and MI were further reduced by abciximab (6.6% vs. 1.8%, p = 0.018 and 11.1% vs. 2.4%, p = 0.002, respectively). The magnitude of the risk reduction with abciximab was greater among the patients with unstable angina than among other patients in the EPIC trial without unstable angina for the end points of death (interaction: p = 0.008 at 30 days, p = 0.002 at 6 months) and MI (interaction: p = 0.004 at 30 days, p = 0.003 at 6 months). Conclusions. The syndrome of unstable angina identifies patients who will experience particularly marked reductions in the risk of death and MI with abciximab during coronary intervention. (J Am Coll Cardiol 1997;30:149–56)

The physiology of a coronary to pulmonary artery fistula has not been well characterized. This case report demonstrates the flow velocity pattern of a coronary fistula to the pulmonary artery which supports the hypothesized physiology that flow is predominantly continuous without a phasic pattern. The flow velocity within a coronary fistula has not been previously demonstrated.

Background This study compared angiographically graded coronary blood flow with intracoronary Doppler flow velocity in patients during percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction. Different TIMI angiographic flow grades (flow grades based on results of the Thrombolysis In Myocardial Infarction trial) have been associated with different clinical results after reperfusion for acute myocardial infarction. However, intracoronary blood flow velocity has not been compared with the angiographic method of determining flow grade in patients. Methods and Results Coronary flow velocity (measured by use of a Doppler guidewire) during primary or rescue PTCA in 41 acute myocardial infarction patients was compared with TIMI grade and cineframes-to-opacification count. Before PTCA, 34 patients had TIMI grade 0 or 1, 5 had TIMI grade 2, and 2 had TIMI grade 3 flow in the infarct artery. Flow velocity was similar among patients with TIMI grades 0, 1, or 2 but was lower than in those with TIMI grade 3 flow (9.4±5.4 versus 16.0±5.4 cm/s for TIMI grades ≤2 versus TIMI grade 3, respectively; P P P r =.45; P Conclusions Determination of flow velocity after reperfusion may enhance patient characterization and provide the physiological rationale for clinical variations after reperfusion therapy.

Percutaneous coronary revascularization in patients with unstable angina and coronary thrombus carries a high complication rate. A new strategy to reduce thrombus burden before revascularization was tested in a multicenter prospective trial. Patients with unstable angina and coronary thrombus (n = 45) received alteplase through an infusion catheter at the proximal aspect of the target lesion and concomitant intracoronary heparin via a standard guiding catheter. Angiography was performed before and alter lesion-directed therapy and post-intervention. Systemic fibrinogen depletion and thrombin activation were not observed, while fibrinolysis was evident for > or = 4 hr after treatment. Target lesion stenosis did not change significantly after lesion-directed therapy, but thrombus score was reduced, particularly among patients who had large thrombi (mean 2.2 vs. 1.6, P = 0.02). Revascularization was successful in 89% of patients. Median final stenosis was 30% and mean final thrombus score was 0.4. Complications included recurrent ischemia (11%), MI (7%), abrupt closure (7%), severe bleeding (4%), and repeat emergency angioplasty (2%). Patients with overt thrombus appeared to derive the most angiographic benefit from lesion-directed alteplase plus intracoronary heparin. Later revascularization was highly successful. This strategy may be a useful adjunct to percutaneous revascularization for patients with unstable angina and frank intracoronary thrombus.

The purpose of this study was to examine the influence of sequential percutaneous transluminal coronary rotational atherectomy (PTCRA) and coronary angioplasty on coronary blood flow reserve in patients. Rotational coronary atherectomy restores lumen patency by partially ablating fibrocalcific plaque, releasing microparticulate debris into the distal coronary circulation. Adjunctive balloon angioplasty is usually performed to optimize the angiographic luminal dimensions. Serial alterations in coronary physiology have not been reported. Fourteen lesions in 13 patients were treated by sequential rotational atherectomy followed by adjunctive balloon angioplasty. Poststenotic baseline coronary blood flow velocity was measured by using a Doppler flow wire (FloWire, Cardiometrics, Inc., Mountain View, Calif.), and coronary blood flow was calculated by using the distal vessel cross-sectional area obtained by quantitative coronary angiography. Data were acquired at baseline and during hyperemia (12 to 18 microg of intracoronary adenosine), before and after PTCRA, and again after balloon angioplasty. The mean stenosis decreased from 76 percent +/- 12 percent at baseline to 21 percent +/- 11 percent at the completion of the procedure (p0.01). The minimal luminal diameter (by quantitative coronary angiography) was 0.7 +/- 0.4 mm at baseline, increased to 1.9 +/- 0.4 mm after rotational atherectomy (p0.01), and increased to 2.4 +/- 0.5 mm after balloon angioplasty (p0.01 versus baseline and PTCRA). Distal (poststenotic) coronary blood flow at baseline was 47 +/- 23 ml/min and 57 +/- 38 ml/min during hyperemia. After PTCRA, coronary blood flow increased to 104 +/- 59 ml/min and to 132 +/- 73 ml/min with hyperemia. After adjunctive angioplasty, coronary blood flow was 84 +/- 40 ml/min (p=not significant [NS] vs PTCRA) and increased to 143 +/- 81 ml/min with hyperemia (p=NS vs PTCRA). The poststenotic coronary flow reserve increased from an initial value of 1.1 +/- 0.2 ml/min to 1.3 +/- 0.3 ml/min after PTCRA (p=NS vs baseline) and to 1.6 +/- 0.3 ml/min after adjunctive balloon angioplasty (p0.01 vs p=NS vs PTCRA). PTCRA significantly increased resting coronary blood flow. Adjunctive balloon angioplasty did not significantly augment resting or hyperemic coronary blood flow more than that achieved by rotational atherectomy alone. These data demonstrate that PTCRA alone improves baseline coronary blood flow with minimal additional physiologic change after adjunctive balloon angioplasty.

The assessment of flow velocity using the Doppler guidewire provides a means of investigating both antegrade and retrograde blood flow in the coronary artery distal to obstructive lesions and occluding PTCA balloons. This has yielded unique qualitative and quantitative information regarding coronary collateral blood flow, and the responses of collaterals to pharmacological and haemodynamic perturbations. The current study analysed collateral flow velocity recordings obtained during coronary interventions in 46 patients in our laboratory. The mean collateral peak velocity integral distal to the occluding PTCA balloon was 9 +/- 7 units, while antegrade distal coronary peak velocity integral following stenosis relief by PTCA was 27 +/- 12 units. Thus, during PTCA balloon occlusion collaterals were able to supply a mean of 30 +/- 18% of the flow provided antegrade by successful PTCA. Variability in collateral flow velocity was not accounted for by differences in the PTCA artery assessed, the supply artery, the direction of collateral filling, the severity of coronary stenosis, or the angiographic grade of collaterals, and the magnitude of collateral flow velocity did not correlate with preserved left ventricular regional wall motion. The measurement of collateral flow velocity by intravascular Doppler provides unique and quantitative information regarding the coronary collateral circulation.

Intravenous thrombolysis has become a primary mode of reperfusion therapy for selected patients with acute myocardial infarction. The timing and potential benefits of cardiac angiography and coronary revascularization after thrombolysis in patients experiencing an uncomplicated myocardial infarction have been extensively studied, but remain clinically controversial. This review discusses the potential benefits and timing of acute and convalescent phase cardiac catheterization after thrombolytic therapy in patients with acute myocardial infarction.

Background The potential for novel antiplatelet and antithrombin agents to contribute to periprocedural bleeding complications of percutaneous coronary revascularization is poorly defined. In the Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial, the periprocedural use of aspirin, heparin, and a chimeric antibody to the platelet glycoprotein IIb/IIIa integrin c7E3 Fab in 2099 patients significantly reduced postprocedural ischemic complications and 6-month clinical restenosis but was associated with increased procedural bleeding complications. We review these complications and describe clinical and procedural variables associated with increased bleeding complications in the EPIC trial. Methods and Results Patients with high-risk clinical or lesion morphological characteristics were randomized to receive placebo bolus plus placebo infusion, c7E3 Fab bolus plus placebo infusion, or c7E3 Fab bolus plus c7E3 Fab infusion. Patients received periprocedural aspirin and intravenous heparin continued for a minimum of 12 hours after the procedure. Outcomes reflecting bleeding complications were measured: transfusions, decreased hemoglobin, and an index including both parameters. Major bleeding complications unrelated to bypass surgery occurred in 3.3%, 8.6%, and 10.6%, and blood product transfusions were used in 7.5%, 14.0%, and 16.8% of patients treated with placebo, bolus c7E3 Fab, and bolus plus infusion c7E3 Fab, respectively (both P P =.38 and P =.14, respectively). Conclusions Bleeding complications unrelated to bypass surgery were two to three times more frequent in patients receiving c7E3 Fab than in those receiving placebo, but most were transient and well tolerated. Risk-factor analysis and modification of concomitant antithrombotic and antiplatelet treatment strategies may aid in reducing bleeding complications and enhancing clinical benefit in patients receiving c7E3 Fab during percutaneous coronary revascularization.