Berger, Peter B.

Background— Percutaneous coronary interventions (PCIs) in saphenous vein grafts (SVGs) with thrombus have a high frequency of distal embolization. Acolysis (therapeutic ultrasound) can break up thrombus in vitro in animal models and humans. Whether this is beneficial during percutaneous SVG interventions is unknown. Methods and Results— We performed a trial of coronary ultrasound thrombolysis in which patients with an acute coronary syndrome undergoing PCI in SVGs were randomly assigned to receive acolysis or abciximab. The primary end point was a successful procedure, defined as final luminal diameter stenosis 30% or less with Thrombolysis In Myocardial Infarction grade 3 flow and freedom from major adverse cardiac events (composite of death, Q-wave, and non–Q-wave myocardial infarction [MI], emergency bypass procedure, disabling stroke, and target lesion revascularization). Of 181 enrolled, 92 received acolysis and 89 abciximab. Angiographic procedural success was achieved in 63% of acolysis patients and 82% of abciximab patients ( P =0.008). Incidence of major adverse cardiac events at 30 days was 25% with acolysis and 12% with abciximab ( P =0.036), attributable mainly to a greater frequency of non–Q-wave MI with acolysis (19.6% versus 7.9%, P =0.03). The incidence of Q-wave MI was also higher with acolysis (5.4% versus 2.2%, P =nonsignificant). The primary end point was achieved in 53.8% of acolysis patients and 73.1% of abciximab patients ( P =0.014). Conclusions— Use of therapeutic ultrasound in vein graft lesions in patients with acute coronary syndrome had poor angiographic outcome and increased the incidence of acute ischemic complications.

AbstractAlthough hyperhomocysteinemia is an independent risk factor for cardiovascular disease, a direct role for homocysteine (Hcy) in this disease remains to be shown. Whereas diet-induced hyperhomocysteinemia promotes atherosclerosis in animal models, the effects of Hcy on atherogenesis in the absence of dietary perturbations is not known. We have generated double knock-out mice with targeted deletions of the genes for apolipoprotein E (apoE) and cystathionine β-synthase (CBS), which converts Hcy to cystathionine. ApoE−/−/CBS−/− mice developed aortic lesions even in the absence of dietary manipulation; lesion area and lesion cholesteryl ester (CE) and triglyceride (TG) contents increased with animal age and plasma Hcy levels. Plasma total cholesterol was significantly increased, whereas high density lipoprotein (HDL) cholesterol and TG concentrations of apoE−/−/CBS−/− mice were decreased. Cholesterol esterification and activities of enzymes catalyzing CE or TG formation in the vessel wall and in peritoneal macrophages were not changed by hyperhomocysteinemia. However, uptake of human acetyl-LDL, but not native low density lipoprotein (LDL), by mouse peritoneal macrophages was higher in the presence of hyperhomocysteinemia. These results suggest that isolated hyperhomocysteinemia is atherogenic and alters hepatic and macrophage lipoprotein metabolism, in part, by enhancing uptake of modified LDL.

Background — Although severe chronic kidney disease (CKD) is an independent predictor of mortality among patients with coronary artery disease, the impact of mild CKD on morbidity and mortality has not been fully defined. Methods and Results — Morbidity and mortality for the 3608 patients with multivessel coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation randomized trial and registry were compared on the basis of the presence and absence of CKD, defined as a preprocedure serum creatinine level of >1.5 mg/dL. Seventy-six patients had CKD. Patients with renal insufficiency were older and more likely to have a history of diabetes, hypertension, and other comorbidities. Among patients undergoing PTCA, patients with CKD had a greater frequency of in-hospital death and cardiogenic shock ( P <0.05 and 0.01, respectively). There was a trend toward a larger proportion of patients with CKD experiencing angina at 5 years ( P =0.079). Patients with CKD had more cardiac admissions ( P =0.003 and <0.0001 for patients undergoing PTCA and CABG, respectively) and a shorter time to subsequent CABG after initial revascularization than patients without CKD ( P =0.01). CKD was associated with a higher risk of death at 7 years, both of all causes (relative risk 2.2, P <0.001) and of cardiac causes (relative risk 2.8, P <0.001). Conclusions — CKD is associated with an increased risk of recurrent hospitalization, subsequent CABG, and mortality. This increased risk of death is independent of and additive to the risk associated with diabetes.

Background — In patients undergoing percutaneous coronary intervention (PCI) in the modern era, the incidence and prognostic implications of acute renal failure (ARF) are unknown. Methods and Results — With a retrospective analysis of the Mayo Clinic PCI registry, we determined the incidence of, risk factors for, and prognostic implications of ARF (defined as an increase in serum creatinine [Cr] >0.5 mg/dL from baseline) after PCI. Of 7586 patients, 254 (3.3%) experienced ARF. Among patients with baseline Cr <2.0, the risk of ARF was higher among diabetic than nondiabetic patients, whereas among those with a baseline Cr >2.0, all had a significant risk of ARF. In multivariate analysis, ARF was associated with baseline serum Cr, acute myocardial infarction, shock, and volume of contrast medium administered. Twenty-two percent of patients with ARF died during the index hospitalization compared with only 1.4% of patients without ARF ( P <0.0001). After adjustment, ARF remained strongly associated with death. Among hospital survivors with ARF, 1- and 5-year estimated mortality rates were 12.1% and 44.6%, respectively, much greater than the 3.7% and 14.5% mortality rates in patients without ARF ( P <0.0001). Conclusions — The overall incidence of ARF after PCI is low. Diabetic patients with baseline Cr values <2.0 mg/dL are at higher risk than nondiabetic patients, whereas all patients with a serum Cr >2.0 are at high risk for ARF. ARF was highly correlated with death during the index hospitalization and after dismissal.