Frederick S. Ling

A Randomized Controlled Trial of Angiography Versus Intravascular Ultrasound-Directed Bare-Metal Coronary Stent Placement (The AVID Trial)

Background—AVID (Angiography Versus Intravascular ultrasound-Directed stent placement) is a multicenter, randomized controlled trial designed to assess the effect of intravascular ultrasound (IVUS)-directed stent placement on the 12-month rate of target lesion revascularization (TLR). Methods and Results—After elective coronary stent placement and an optimal angiographic result (<10% stenosis), 800 patients were randomized to Angiography- or IVUS-directed therapy. Blinded IVUS was performed in the Angiography group without further therapy. In the IVUS group, IVUS criteria for optimal stent placement (<10% area stenosis, apposition, and absence of dissection) were applied. Final minimum stent area was 6.90±2.43 mm2 in the Angiography group and 7.55±2.82 mm2 in the IVUS group (P=0.001). In the IVUS group, only 37% with inadequate expansion (<90%) received further therapy. The 12-month TLR rate was 12.0% in the Angiography group and 8.1% in the IVUS group (P=0.08, 95% confidence level [CI], [−8.3% to 0.5%]). When vessels with a distal reference diameter <2.5 mm by core laboratory angiography measurement were excluded from analysis, the 12-month TLR rate was 10.1% in the Angiography group and 4.3% in the IVUS group (P=0.01, 95% CI, [−10.6% to −1.2%]). With a prestent angiographic stenosis of ≥70%, the TLR rate was lower in the IVUS group compared with the Angiography group (3.1% versus 14.2%; P=0.002; 95% CI, [−18.4% to −4.2%]). Conclusions—IVUS-directed bare-metal stent placement results in larger acute stent dimensions without an increase in complications and a significantly lower 12-month TLR rate for vessels ≥2.5 mm by angiography and for vessels with high-grade prestent stenosis. However, for the entire sample analyzed on an intention-to-treat basis, IVUS-directed bare-metal stent placement does not significantly reduce the 12-month TLR rate when compared with stent placement guided by angiography alone. In addition, IVUS evaluation of adequate stent expansion is underutilized by experienced operators.

Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction.

Sixty-one patients with ST elevation acute myocardial infarction were randomized to receive open-label tirofiban in the emergency room before primary angioplasty versus glycoprotein IIb/IIIa inhibitors administered after initial coronary angiography. Early administration of tirofiban before primary angioplasty resulted in nonsignificant improvement in initial coronary flow (Thrombolysis In Myocardial Infarction trial grade 2 or 3 flow, 39% vs 27%, p >0.20). Patients receiving early tirofiban treatment were more likely to achieve complete (>70%) ST-segment resolution at 90 minutes (69% vs 44%, p = 0.07).

Emergency room administration of Eptifibatide before primary angioplasty for st elevation acute myocardial infarction and its effect on baseline coronary flow and procedure outcomes

S randomized trials and a meta-analysis have shown the superiority of primary angioplasty over thrombolytic therapy for treatment of ST elevation acute myocardial infarction (AMI).1–4 Two large registries representative of practice in a community setting, however, failed to confirm a significant benefit for primary angioplasty over thrombolytic therapy.5,6 It has been postulated that a major reason for the discrepancy in the randomized trial data and so-called “real-world” primary angioplasty is an increased delay in treatment in the less controlled settings.7 Furthermore, primary angioplasty is not available to many patients due to initial presentation to a hospital without angioplasty or cardiac catheterization facilities. Recently, there has been interest in facilitated primary angioplasty, where patients are treated with fibrinolytic agents, glycoprotein (GP) IIb/IIIa inhibitors, or a combination of these agents before baseline angiography. One potential advantage of these strategies is widening of the therapeutic window for revascularization by the provision of partial reperfusion. The present study evaluates the effects of emergency room administration of the GP IIb/IIIa inhibitor, eptifibatide, before primary angioplasty on baseline coronary flow, procedure results, and in-hospital outcomes. • • • The treatment group (group 1) consisted of 30 consecutive patients who presented to our institution with AMI within 6 hours of symptom onset, were referred for primary angioplasty, and provided informed consent from December 1999 to April 2000. The controls (group 2) included 30 patients who were treated with primary angioplasty, including GP IIb/ IIIa inhibitors at the time of angioplasty, at our institution from January 1999 to November 1999. Group 2 patients were matched 1:1 with group 1 patients for age, AMI location, diabetes, gender, and time from onset of symptoms to presentation in descending order of priority. Eptifibatide was administered as a bolus of 180 mg/kg followed by a 2 mg/kg/min infusion. Patients were then referred to the cardiac catheterization laboratory and the bolus dose of eptifibatide was repeated on arrival. Baseline quantitative angiography was performed using a computer edge detection system (Artrek, Quinton Imaging, Bothell, Washington), and Thrombolysis in Myocardial Infarction (TIMI) flow grade and corrected TIMI frame counts8 were assessed by independent review of the study angiograms by 1 investigator who was blinded to the type of treatment. The primary end point was the percentage of patients with TIMI 2 or TIMI 3 coronary flow at baseline angiography. Secondary end points included percentage of patients with TIMI 3 flow, mean corrected TIMI frame count, time from baseline angiography to first balloon inflation, total procedure time, total fluoroscopy time, and total stent length per lesion. Continuous variables were compared using Student’s t test. Frequencies were compared using the chi-square test or Fisher’s exact test. Mean age was 57 years and 25% of patients were women. Comparative baseline clinical and angiographic characteristics are listed in Tables 1 and 2, respectively. Baseline TIMI 2 or TIMI 3 flow was present in 57% (95% confidence intervals 39% to 74%) of group 1 patients compared with 13% (95% confidence intervals 1% to 26%) of group 2 patients (p ,0.01) (Figure 1). The mean time from baseline angiography to initial balloon inflation and total procedure times were significantly less for group 1 patients. This difference in time to first balloon inflation was also evident for patients with persistent total occlusion of the infarctrelated artery (TIMI grade 0 flow, 11.3% vs 21.6%, p ,0.01). Other procedural outcomes are listed in Table 3 and in-hospital outcomes are shown in Table 4.5 • • • The results of this study show that for patients undergoing primary angioplasty for ST elevation AMI, a strategy of administering the GP IIb/IIIa inhibitor, eptifibatide, early after presentation and before arrival in the cardiac catheterization laboratory provides partial reperfusion and may decrease procedure complexity. Of 30 patients who received eptifibatide administered as a double bolus of 180 mg/kg with the initial bolus given 51 6 27 minutes before baseline angiography, 17 (56.7%) had TIMI 2 or 3 flow. In addition, the time from baseline angiography to first balloon inflation was significantly less for these paFrom the Department of Medicine and Cardiology Unit, University of Rochester Medical Center, Rochester, New York. This study was supported by an educational grant from COR Therapeutics, South San Francisco, California. Dr. Cutlip’s address is: Cardiology Unit, Box 679, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642. E-mail: donald_cutlip@urmc.rochester. edu. Manuscript received October 24, 2000; revised manuscript received and accepted February 1, 2001.

Randomized controlled trial of topical hemostasis pad use for achieving vascular hemostasis following percutaneous coronary intervention.

Objectives: We conducted a randomized trial to determine the efficacy of two topical hemostasis pads in promoting vascular hemostasis following PCI, and to assess the appropriate level of anticoagulation for sheath removal. Background: Pads coated with procoagulant materials are widely marketed and used to augment vascular hemostasis following PCI, yet clinical effectiveness and safety data are lacking. Methods: 184 patients who underwent PCI using the femoral approach were randomized to one of four methods of sheath removal: (1) at ACT < 250 using the Chito‐Seal™ pad; (2) at ACT < 250 using the Clo‐Sur PAD™; (3) at ACT < 250 using manual compression alone; (4) at ACT < 170 using manual compression alone. Results: Time to hemostasis was significantly shorter in the hemostasis pad groups compared to the conventional compression groups (16.2 ± 4.9, 16.0 ± 5.3, 19.3 ± 7.8, and 18.3 ± 5.7 min, respectively, P = 0.027), however overall bed rest times following intervention were not reduced by use of either hemostasis pad. The incidence of major or minor bleeding complications did not differ among groups. Irrespective of hemostasis pad use, removal of sheaths at higher ACT levels allowed shorter time to ambulation following PCI without an increase in bleeding events. Conclusions: The hemostasis pads tested shortened time to hemostasis compared to standard manual compression, although the absolute reduction in time to hemostasis was relatively small and did not translate into a reduction in overall bed rest time. Independent of hemostasis pad use, removal of arterial sheaths at higher than conventional activated clotting times was safe and resulted in significant reductions in time to ambulation.

Care and Outcomes of Asian-American Acute Myocardial Infarction Patients: Findings From the American Heart Association Get With The Guidelines-Coronary Artery Disease Program

Background— Asian-Americans represent an important United States minority population, yet there are limited data regarding the clinical care and outcomes of Asian-Americans following acute myocardial infarction (AMI). Using data from the American Heart Association Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) program, we compared use of and trends in evidence-based care AMI processes and outcome in Asian-American versus white patients. Methods and Results— We analyzed 107 403 AMI patients (4412 Asian-Americans, 4.1%) from 382 United States centers participating in the Get With The Guidelines-Coronary Artery Disease program between 2003 and 2008. Use of 6 AMI performance measures, composite “defect-free” care (proportion receiving all eligible performance measures), door-to-balloon time, and in-hospital mortality were examined. Trends in care over this time period were explored. Compared with whites, Asian-American AMI patients were significantly older, more likely to be covered by Medicaid and recruited in the west region, and had a higher prevalence of diabetes, hypertension, heart failure, and smoking. In-hospital unadjusted mortality was higher among Asian-American patients. Overall, Asian-Americans were comparable with whites regarding the baseline quality of care, except that Asian-Americans were less likely to get smoking cessation counseling (65.6% versus 81.5%). Asian-American AMI patients experienced improvement in the 6 individual measures (P⩽0.048), defect-free care (P<0.001), and door-to-balloon time (P<0.001). The improvement rates were similar for both Asian-Americans and whites. Compared with whites, the adjusted in-hospital mortality rate was higher for Asian-Americans (adjusted relative risk: 1.16; 95% confidence interval: 1.00–1.35; P=0.04). Conclusions— Evidence-based care for AMI processes improved significantly over the period of 2003 to 2008 for Asian-American and white patients in the Get With The Guidelines-Coronary Artery Disease program. Differences in care between Asian-Americans and whites, when present, were reduced over time.

Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack

Background: Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. Methods: We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. Results: The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54–0.94; P=0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40–0.96; log-rank P=0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58–1.91; P=0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22–0.87; P=0.02), but not smaller MIs. Conclusions: Among patients with insulin resistance without diabetes mellitus, pioglitazone reduced the risk for acute coronary syndromes after a recent cerebrovascular event. Pioglitazone appeared to have its most prominent effect in preventing spontaneous type 1 MIs. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00091949.

Coronary artery fenestration prior to stenting in spontaneous coronary artery dissection

Percutaneous coronary intervention (PCI) in patients with spontaneous coronary artery dissection is associated with high rates of complications and suboptimal long‐term outcomes. Coronary artery fenestration with cutting balloon angioplasty prior to stenting can prevent the expansion of intramural hematoma and optimize PCI outcomes in this patient population.

Triggering of ST-elevation myocardial infarction by ambient wood smoke and other particulate and gaseous pollutants

We previously observed increased odds of ST-elevation myocardial infarctions (STEMIs) associated with increased ambient fine particulate matter (PM2.5) in the previous hour. However, data are lacking on the effects of specific PM sources. Using data from 362 patients, a case–crossover design, and conditional logistic regression, we estimated the relative odds of STEMI associated with increased Delta-C (wood smoke), black carbon (BC; traffic), PM2.5, and gaseous pollutants in the previous 1–72 h. We did not observe increased odds of STEMIs associated with increased Delta-C or BC. We did observe increased odds associated with each 7.1 μg/m3 increase in PM2.5 (OR (95% CI): 1.17 (0.99, 1.39)) and each 19.9 p.p.b. increase in ozone (O3; 1.27 (1.00, 1.63)) in the previous hour, and each 0.22 p.p.m. increase in 48-h carbon monoxide (CO) concentrations (1.32 (1.00, 1.73]). Larger relative odds were associated with PM2.5 in May–October, and O3 and CO in November–April. Increased PM2.5, O3, and CO, but not wood smoke or BC, were associated with increased odds of STEMI, and effects may differ by season. Studies using spatially adjusted pollution estimates are needed, as well as studies further examining O3 and CO effects on the risk of STEMI.

Associations between ambient wood smoke and other particulate pollutants and biomarkers of systemic inflammation, coagulation and thrombosis in cardiac patients

Background: Increased particulate air pollution has been associated with both an increased risk of myocardial infarction (MI) and adverse changes in cardiac biomarkers. Up to 30% of ambient wintertime fine particles (PM2.5) in Rochester, NY are from wood burning. Our study examined associations between ambient levels of a marker of wood smoke (Delta‐C) and other particulate air pollutants and biomarkers of inflammation, coagulation and thrombosis. Methods: We measured blood concentrations of C‐reactive protein (CRP), D‐dimer, fibrinogen, P‐selectin, platelet factor 4 (PF‐4), von Willebrand factor (vWF), and myeloperoxidase (MPO) of 135 patients undergoing cardiac catheterization during the winters of 2011–2013. We coupled these data with hourly ambient concentrations of Delta‐C, black carbon (BC; marker of traffic pollution), and ultrafine (10–100 nm; UFP), accumulation mode (100–500 nm; AMP), and fine particles (<2.5 &mgr;m; PM2.5). Using linear regression models, we estimated the change in each biomarker associated with increased pollutant concentrations at intervals between 1 and 96 h preceding blood collection. Results: Each 0.13 &mgr;g/m3 increase in Delta‐C concentration in the prior 12 h was associated with a 0.91% increase in fibrinogen levels (95% CI=0.23%, 1.59%), but unexpectedly in the prior 48 h, each 0.17 &mgr;g/m3 increase in Delta‐C concentration was associated with a 2.75% decrease in MPO levels (95% CI=−5.13%,−0.37%). We did not see associations between Delta‐C concentrations and any other biomarkers. Interquartile range (IQR) increases in PM2.5, BC, UFP, and AMP concentrations were generally associated with increased CRP and fibrinogen, but not PF4, D‐dimer, vWF, or P‐selectin. Conclusions: In a population of cardiac patients, we noted adverse changes in fibrinogen associated with increased concentrations of a marker of wood smoke. Increases in PM2.5, BC, AMP, and UFP concentrations in the previous 96 h were also associated with adverse changes in markers of systemic inflammation and coagulation, but not with markers of endothelial cell dysfunction or platelet activation. HighlightsBiomarkers in 135 cardiac patients were matched to air pollution in prior four days.Increased particulate pollution and wood smoke associated with increased fibrinogen.No changes in biomarkers related to endothelial dysfunction or platelet activation.More research needed for association between wood smoke and inflammation/coagulation.

Patient and physician perspectives on public reporting of mortality ratings for percutaneous coronary intervention in New York state

Background— Public reporting of physician-specific outcome data for procedures, such as percutaneous coronary intervention (PCI), can influence physicians to avoid high-risk patients who may benefit from treatment. Prior physician attitudes toward public scorecards in New York State (NYS) have been studied, but the exclusion criteria have evolved. Additionally, patient perceptions toward such reports remain poorly understood. This study evaluates (1) whether exclusion of certain high-risk patients from public reporting of PCI outcomes in NYS has influenced physician attitudes, (2) current patient awareness and use of publicly reported outcome data, and (3) differences in physician and patient attitudes toward public reporting. Methods and Results— A questionnaire was administered to interventional cardiologists in NYS with specific emphasis on how modifications in publicly reported outcome data have influenced their practice. The results were compared with a 2003 survey administered by our group. A separate questionnaire regarding the publicly available NYS PCI Report was administered to patients referred to our center for possible PCI. The majority of interventional cardiologists indicated that the exclusion of patients with anoxic brain injury and refractory cardiogenic shock from public reporting has made them more likely to perform PCI for these subgroups. While patient awareness of the NYS PCI Report was low, patients were significantly more likely than physicians to think that publication of physician-specific mortality data can provide an accurate measure of physician quality, serve to improve patient care, and provide useful information in terms of physician selection. Conclusions— The study provides further evidence that public reporting of physician-specific outcome data influences physician behavior and indicates that significant discrepancies exist in how scorecards are perceived by physicians versus patients.