Bonnie H. Weiner

Unexplained chest pain in patients with normal coronary arteriograms: a follow-up study of functional status

Approximately 10 per cent of patients referred for coronary arteriography because of chest pain have angiographically normal coronary arteries and no other heart disease. We examined the functional status of 57 patients who had undergone catheterization (23 men and 34 women), all of whom were told that their hearts were normal, that their pain was noncardiac, and that no limitation on activity was necessary. At a mean follow-up time of 16 +/- 7.7 months, 27 of the 57 patients (47 per cent) still described their activity as limited by chest pain (before catheterization, 42 of 57 or 74 per cent); 29 of 57 (51 per cent) were unable to work (before catheterization, 36 of 57 or 63 per cent); and 25 of 57 (44 per cent) still believed that they had heart disease (before catheterization, 45 of 57 or 79 per cent). Use of medical facilities was significantly reduced after catheterization (P < 0.001). At follow-up the physician was more likely than the patient to believe that the symptoms had improved. We conclude that many of these patients remain limited in activity and may benefit from further efforts at comunication and rehabilitation.

Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

Do fish oils prevent restenosis after coronary angioplasty

BACKGROUND The omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA). METHODS AND RESULTS From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a > 30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with < 50% luminal diameter remaining. In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P = .37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates. CONCLUSIONS This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids.

Non–High-Density Lipoprotein Cholesterol Levels Predict Five-Year Outcome in the Bypass Angioplasty Revascularization Investigation (BARI)

Background—Current National Cholesterol Education Program guidelines recommend that non–high-density lipoprotein cholesterol (non-HDL-C) be considered a secondary target of therapy among individuals with triglycerides >2.26 mmol/L. It is not known whether non-HDL-C relates to prognosis among patients with coronary heart disease. Methods and Results—Lipid levels were available at baseline among 1514 patients (73% men; mean age, 61 years) enrolled in the Bypass Angioplasty Revascularization Investigation (BARI); all had multivessel coronary artery disease. Patients were followed for 5 years. Outcomes of death, nonfatal myocardial infarction, and death or myocardial infarction were modeled using univariate and multivariate time-dependent proportional hazards methods; angina pectoris at 5 years was modeled using univariate and multivariate logistic regression. Non-HDL-C was a strong and independent predictor of nonfatal myocardial infarction (multivariate relative risk, 1.049 [95% confidence intervals, 1.006 to 1.093] for every 0.26 mmol/L increase) and angina pectoris (multivariate odds ratio, 1.049 [95% confidence intervals, 1.004 to 1.096] for every 0.26 mmol/L increase), but it did not relate to mortality. HDL-C and LDL-C did not predict events during follow-up. Conclusions—Among patients with lipid values in BARI, non-HDL-C is a strong and independent predictor of nonfatal myocardial infarction and angina pectoris at 5 years, even after consideration of powerful clinical variables. Our data suggest that non-HDL-C is an appropriate treatment target among patients with coronary heart disease.

Late stent thrombosis: Considerations and practical advice for the use of drug‐eluting stents: A report from the Society for Cardiovascular Angiography and Interventions drug‐eluting stent task force

Recent analyses have suggested that implantation of drug-eluting stents (DES) is associated with a higher rate of very late stent thrombosis when compared with bare metal stents. This complication is evident with both sirolimus-eluting stents as well as polymer-based paclitaxel-eluting stents, but the precise magnitude of this risk and whether this applies to all patients or only a subset of those who have received DES is incompletely characterized. This alert is designed to provide the practicing interventional cardiologist with practical advice in light of this new information. It is not the purpose of this document to provide an exhaustive review of the literature on DES and the risk of stent thrombosis; however a brief summary is appropriate. While exact definitions have been variable in different trials, late stent thrombosis generally refers to stent thrombosis occurring at least 1 month following stent implantation, while very late stent thrombosis refers to events occurring more than 12 months following stent placement. Following bare metal stent implantation, stent thrombosis is rare after 2 weeks, and dual antiplatelet therapy (aspirin and a thienopyridine) was typically prescribed for 3–6 weeks. In contrast, sporadic reports of late stent thrombosis in patients receiving DES have occurred over the past few years. These events often (but not always) occurred in the setting of premature discontinuation of dual antiplatelet therapy. In March 2006, the BASKET-LATE trial was reported, describing a significantly greater composite occurrence of cardiac death and non-fatal myocardial infarction in patients treated with DES when compared with bare-metal stents after clopidogrel had been discontinued at 6 months [1]. Other meta-analyses of the existing DES trials also showed an increase in late events in the DES cohort although these analyses were limited by incomplete data in publications, abstracts, and Internet sources [2,3]. In October 2006, an independent patient-level meta analysis of the four pivotal randomized Cypher stent trials and the five pivotal randomized Taxus stent trials was publicly presented. These analyses demonstrated an increased rate of stent thrombosis with both sirolimus-eluting and paclitaxelJ_ID: Z7V Customer A_ID: 06-0418 Cadmus Art: CCI 21093 Date: 5-JANUARY-07 Stage: I Page: 1

Cutting balloon angioplasty for the prevention of restenosis: results of the Cutting Balloon Global Randomized Trial ☆

The cutting balloon (CB) is a specialized device designed to create discrete longitudinal incisions in the atherosclerotic target coronary segment during balloon inflation. Such controlled dilatation theoretically reduces the force needed to dilate an obstructive lesion compared with standard percutaneous transluminal coronary angioplasty (PTCA). We report a multicenter, randomized trial comparing the incidence of restenosis after CB angioplasty versus conventional balloon angioplasty in 1,238 patients. Six hundred seventeen patients were randomized to CB treatment, and 621 to PTCA. The mean reference vessel diameter was 2.86 +/- 0.49 mm, mean lesion length 8.9 +/- 4.3 mm, and prevalence of diabetes mellitus in patients was 13%. The primary end point, the 6-month binary angiographic restenosis rate, was 31.4% for CB and 30.4% for PTCA (p = 0.75). Acute procedural success, defined as the attainment of <50% diameter stenosis without in-hospital major adverse cardiac events, was 92.9% for CB and 94.7% for PTCA (p = 0.24). Freedom from target vessel revascularization was slightly higher in the CB arm (88.5% vs 84.6%, log-rank p = 0.04). Five coronary perforations occurred in the CB arm only (0.8% vs 0%, p = 0.03). At 270 days, rates of myocardial infarction, death, and total major adverse cardiac events for CB and PTCA were 4.7% versus 2.4% (p = 0.03), 1.3% versus 0.3% (p = 0.06), and 13.6% versus 15.1% (p = 0.34), respectively. In summary, the proposed mechanism of controlled dilatation did not reduce the rate of angiographic restenosis for the CB compared with conventional balloon angioplasty. CB angioplasty should be reserved for difficult lesions in which controlled dilatation is believed to provide a better acute result compared with balloon angioplasty alone.

Survival Following Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Anatomic Subsets in Which Coronary Artery Bypass Surgery Improves Survival Compared With Medical Therapy Results From the Bypass Angioplasty Revascularization Investigation (BARI)

OBJECTIVES We sought to compare survival after coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) in high-risk anatomic subsets. BACKGROUND Compared with medical therapy, CABG decreases mortality in patients with three-vessel disease and two-vessel disease involving the proximal left anterior descending artery (LAD), particularly if left ventricular (LV) dysfunction is present. How survival after PTCA and CABG compares in these high-risk anatomic subsets is unknown. METHODS In the Bypass Angioplasty Revascularization Investigation (BARI), 1,829 patients with multivessel disease were randomized to an initial strategy of PTCA or CABG between 1988 and 1991. Stents and IIb/IIIa inhibitors were not utilized. Since patients in BARI with diabetes mellitus had greater survival with CABG, separate analyses of patients without diabetes were performed. RESULTS Seven-year survival among patients with three-vessel disease undergoing PTCA and CABG (n = 754) was 79% versus 84% (p = 0.06), respectively, and 85% versus 87% (p = 0.36) when only non-diabetics (n = 592) were analyzed. In patients with three-vessel disease and reduced LV function (ejection fraction <50%), seven-year survival was 70% versus 74% (p = 0.6) in all PTCA and CABG patients (n = 176), and 82% versus 73% (p = 0.29) among non-diabetic patients (n = 124). Seven-year survival was 87% versus 84% (p = 0.9) in all PTCA and CABG patients (including diabetics) with two-vessel disease involving the proximal LAD (n = 352), and 78% versus 71% (p = 0.7) in patients with two-vessel disease involving the proximal LAD with reduced LV function (n = 72). CONCLUSION In high-risk anatomic subsets in which survival is prolonged by CABG versus medical therapy, revascularization by PTCA and CABG yielded equivalent survival over seven years.

Modifiable Risk Factors for Vascular Access Site Complications in the IMPACT II Trial of Angioplasty With Versus Without Eptifibatide

Abstract 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 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.

Effect of Supersaturated Oxygen Delivery on Infarct Size After Percutaneous Coronary Intervention in Acute Myocardial Infarction

Background—Myocardial salvage is often suboptimal after percutaneous coronary intervention in ST-segment elevation myocardial infarction. Posthoc subgroup analysis from a previous trial (AMIHOT I) suggested that intracoronary delivery of supersaturated oxygen (SSO2) may reduce infarct size in patients with large ST-segment elevation myocardial infarction treated early. Methods and Results—A prospective, multicenter trial was performed in which 301 patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset were randomized to a 90-minute intracoronary SSO2 infusion in the left anterior descending artery infarct territory (n=222) or control (n=79). The primary efficacy measure was infarct size in the intention-to-treat population (powered for superiority), and the primary safety measure was composite major adverse cardiovascular events at 30 days in the intention-to-treat and per-protocol populations (powered for noninferiority), with Bayesian hierarchical modeling used to allow partial pooling of evidence from AMIHOT I. Among 281 randomized patients with tc-99m-sestamibi single-photon emission computed tomography data in AMIHOT II, median (interquartile range) infarct size was 26.5% (8.5%, 44%) with control compared with 20% (6%, 37%) after SSO2. The pooled adjusted infarct size was 25% (7%, 42%) with control compared with 18.5% (3.5%, 34.5%) after SSO2 (PWilcoxon=0.02; Bayesian posterior probability of superiority, 96.9%). The Bayesian pooled 30-day mean (±SE) rates of major adverse cardiovascular events were 5.0±1.4% for control and 5.9±1.4% for SSO2 by intention-to-treat, and 5.1±1.5% for control and 4.7±1.5% for SSO2 by per-protocol analysis (posterior probability of noninferiority, 99.5% and 99.9%, respectively). Conclusions—Among patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset, infusion of SSO2 into the left anterior descending artery infarct territory results in a significant reduction in infarct size with noninferior rates of major adverse cardiovascular events at 30 days. Clinical Trial Registration—clinicaltrials.gov Identifier: NCT00175058

A simplified lesion classification for predicting success and complications of coronary angioplasty

In 1988, the American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures presented a classification of coronary lesions utilizing 26 lesion features to predict the success and complications of balloon angioplasty. Using data from the Registry of the Society for Cardiac Angiography and Interventions (SCAI) we evaluated the ability of this classification to predict success and complications. Lesion success, death in hospital, emergency cardiac bypass surgery, and major adverse events were evaluated in 41,071 patients who underwent single-vessel angioplasty from January 1993 to June 1996. Logistic models using the ACC/AHA lesion classification, vessel patency, or both, were compared. A new classification based on the interaction of the ACC/AHA classification plus lesion patency was compared with the existing ACC/AHA classification. Vessel patency, added to the ACC/AHA classification, improved prediction of lesion success (p </=0.0001). Class A and patent B lesions had similar success and complication rates, so a simplified classification (SCAI) using only 7 lesion characteristics could be created. This system (I: non-C patent, II: C patent, III: non-C occluded, and IV: C occluded) improved prediction of lesion success compared with the ACC/AHA classification (Bayesian Information Criterion statistic: ACC/AHA 16539, SCAI 15956; and area under the receiver- operating characteristics curve 0.659, 0.693, respectively). The SCAI classification was preferred for predicting major complications and in-hospital death and was similar to the ACC/AHA classification for predicting emergency bypass surgery.