Showing papers by "Stephen G. Ellis published in 2002"

Clinical characteristics and outcome of patients with early ( 4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction.

Abstract: Aims We examined the clinical characteristics and outcome of patients with early ( 4h) presentation treated by primary angioplasty or thrombolytic therapy for acute myocardial infarction. Methods and Results We studied 2635 patients enrolled in 10 randomized trials of primary angioplasty (n=1302) vs thrombolytic therapy (n=1333) in acute myocardial infarction, and baseline characteristics of the two groups were comparable. Increase in presentation delay is associated with older age, female gender, diabetes and an increased heart rate. We classified the patients according to the time delay from symptom onset to presentation into three categories: early presentation (<2h), intermediate presentation (2–4h), and late presentation (≥4h). At 30 days the combined rate of death, non-fatal reinfarction and stroke in patients presenting early was 5·8% in the angioplasty group vs 12·5% in the thrombolysis group, in patients with intermediate presentation, 8·6% vs 14·2%, respectively, and in patients presenting late 7·7% vs 19·4%, respectively. With increasing time from symptom onset to presentation, all major adverse cardiac event rates show a trend to a larger increase in the thrombolysis group compared to the angioplasty group, both at 30 days and at 6 months after the acute event. Conclusions Major adverse cardiac event rates are lower after angioplasty compared to thrombolysis, irrespective of time to presentation. With increasing time to presentation major adverse cardiac event rates increase after thrombolysis but appear to remain relatively stable after angioplasty.

A target-mediated model to describe the pharmacokinetics and hemodynamic effects of recombinant human vascular endothelial growth factor in humans.

Abstract: Background The Vascular Endothelial Growth Factor (VEGF) in Ischemiafor Vascular Angiogenesis (VIVA) trial was a double-blind, placebo-controlled, phase II clinical trial designed to evaluate the safety, efficacy, and pharmacokinetics of combinedintracoronary and intravenous infusions of recombinant human vascular endothelial growth factor (rhVEGF165) for therapeutic angiogenesis. This study describes the use of a mechanism-based model to characterize the nonlinear kinetics observed after intravenous administration of rhVEGF165. The model predicts that rhVEGF165 distribution occurs through both saturable binding to high-affinity receptors and reversible interactions with low-affinity binding sites. Methods In this trial, rhVEGF165 was administered to patients with coronary artery disease at a dose rate of 17 or 50 ng/kg/min by means of intracoronary infusion for 20 minutes, followed by three 4-hour intravenous infusions on days 3, 6, and 9. Pharmacokinetic samples and blood pressure measurements were collected at baseline, during infusion, and for 6 hours after infusion. Results The plasma clearance, steady-state volume of distribution, and terminal half-life after a 4-hour intravenous infusion of rhVEGF165 at the high dose were 19.1 ± 5.7 mL/min/kg, 960 ± 260 mL/kg, and 33.7 ± 13 minutes, respectively. The duration of hypotension that occurred after rhVEGF165 administration appeared to be related to the model-predicted VEGF165 concentration associated with the high-affinity receptor compartment. Conclusions This mechanism-based model accurately predicted VEGF concentrations and allowed for the simulation of various rhVEGF165 dose regimens that may aid in optimization of drug delivery for future clinical trials. Clinical Pharmacology & Therapeutics (2002) 72, 20–32; doi: 10.1067/mcp.2002.126179

Long-Term Clinical Outcomes After Unprotected Left Main Trunk Percutaneous Revascularization in 279 Patients

Abstract: Background Percutaneous coronary revascularization (PCI) has been increasingly applied to unprotected left main trunk (LMT) lesions, with varied long-term success. This study attempts to define the predictors of outcome in this population. Methods and Results Two hundred seventy-nine consecutive patients who had LMT PCI at 1 of 25 sites between 1993 and 1998 were studied. Forty-six percent of these patients were deemed inoperable or at high surgical risk. Thirty-eight patients (13.7%) died in hospital, and the rest were followed up for a mean of 19 months. The 1-year incidence was 24.2% for all-cause mortality, 20.2% for cardiac mortality, 9.8% for myocardial infarction, and 9.4% for CABG. Independent correlates of all-cause mortality were left ventricular ejection fraction ≤30%, mitral regurgitation grade 3 or 4, presentation with myocardial infarction and shock, creatinine ≥2.0 mg/dL, and severe lesion calcification. For the 32% of patients 30% and ...

Early and Sustained Survival Benefit Associated With Statin Therapy at the Time of Percutaneous Coronary Intervention

Abstract: Background— Long-term administration of statin therapy has been shown to reduce major coronary events and cardiac mortality within randomized clinical trials. In addition to lowering lipids, statins favorably affect platelet adhesion, thrombosis, endothelial function, inflammation, and plaque stability, which may potentially improve outcome after percutaneous coronary intervention (PCI). Therefore, we hypothesized that statin therapy has an early beneficial effect among patients undergoing PCI. Methods and Results— Each year from 1993 to 1999, we prospectively collected data among the first 1000 patients undergoing PCI. Patients who presented with acute or recent myocardial infarction or cardiogenic shock were excluded from the analysis. Baseline, procedural, and 6-month data of statin-treated and non–statin-treated patients were compared. Propensity score and multivariate survival analysis were used to adjust for heterogeneity between the two groups. Of 5052 patients who completed follow-up, 26.5% were t...

Death Following Creatine Kinase-MB Elevation After Coronary Intervention Identification of an Early Risk Period: Importance of Creatine Kinase-MB Level, Completeness of Revascularization, Ventricular Function, and Probable Benefit of Statin Therapy

Abstract: Background— Creatine kinase (CK)-MB elevation after percutaneous coronary intervention (PCI) has been associated with subsequent cardiac death. The patients at risk, the timing of risk, and potential treatment implications are uncertain. Methods and Results— Eight thousand, four hundred nine consecutive non– acute myocardial infarction patients with successful PCI and no emergency surgery or Q-wave myocardial infarction were followed for 38±25 months; 1446 (17.2%) had post-PCI CK-MB above normal on routine ascertainment. Patients were prospectively stratified into those with CK-MB 1 to 5× or CK-MB >5× normal. No patient with CK-MB 1 to 5× normal died during the first week after PCI, and excess risk of early death for patients with CK-MB elevation occurred primarily in the first 3 to 4 months. The actuarial 4-month risk of death was 8.9%, 1.9%, and 1.2% for patients with CK-MB >5×, CK-MB 1 to 5×, and CK-MB ≤1× normal (P<0.001). Death within 4 months was independently correlated with the degree of CK-MB ele...

Lack of Benefit From Intravenous Platelet Glycoprotein IIb/IIIa Receptor Inhibition as Adjunctive Treatment for Percutaneous Interventions of Aortocoronary Bypass Grafts A Pooled Analysis of Five Randomized Clinical Trials

Abstract: Background— Despite widespread use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts, data supporting this strategy are lacking. Methods and Results— A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed, and outcomes of graft interventions were assessed at 30 days and 6 months. Compared with PCI of native circulation (n=13 158), graft interventions (n=627) were associated with worse outcomes and in particular with a doubling of mortality at 30 days (2.1% versus 1.0%, P=0.006) and 6 months (4.7% versus 2.0%, P<0.001). Revascularization of a graft was identified as an independent predictor of death, myocardial infarction, or revascularization at 6 months (hazard ratio, 1.42; 95% CI, 1.24 to 1.63; P<0.001). Among patients undergoing graft PCI, the incidence of the triple end point at 30 days was 16.5% in the platelet GP IIb/IIIa inhibitor group and 12.6%...

Emergency Coronary Artery Bypass Surgery in the Contemporary Percutaneous Coronary Intervention Era

Abstract: Background— Since the advent of percutaneous coronary interventions (PCIs), technological advances, adjunctive pharmacotherapy, and increasing operator experience have contributed to lowering the occurrence of major complications. However, emergency coronary artery bypass surgery (CABG) for failed PCI is still associated with important morbidity and mortality, even in the era of coronary stenting. We sought to determine the prevalence, indications, predictors, and complications of emergency CABG after PCI in the past decade. Methods and Results— We reviewed 18 593 PCIs performed from 1992 through 2000. There was a need for emergency CABG in 113 (0.61%) cases. The major indications were extensive dissection (n=61, 54%), perforation/tamponade (n=23, 20%), and recurrent acute closure (n=23, 20%). Prevalence of emergency CABG decreased from 1.5% of PCIs in 1992 to 0.14% in 2000 (P<0.001). Independent predictors of the need for emergency CABG included the worst ACC/AHA scoring of the intervened lesion (P<0.001...

Frequency and long-term impact of myonecrosis after coronary stenting

Abstract: Aims To study the frequency of creatine kinase MB elevation in stent recipients and to correlate the magnitude of myonecrosis with long-term ischaemic events. Methods and Results We evaluated the frequency and impact (major adverse ischaemic events) of creatine kinase MB elevation in 3478 patients undergoing planned coronary stenting and divided them in five strata according to peak creatine kinase MB: normal, 1–3×, 3–5×, 5–10× and >10× above upper limit of normal. Graft intervention was done in 15% and 61% received platelet glycoprotein IIb/IIIa receptor inhibitors. The average follow-up period was 15±15 (range 1–72) months. Creatine kinase MB elevation above upper limit of normal occurred in 24% and in 5·3% it was greater than 5×upper limit of normal. The unadjusted rates of actuarial mortality in the five strata were: 7·5% (198/2637), 8·0% (40/502), 11·0% (17/155), 10·8% (11/102) and 29·3% (24/82), respectively, P <0·001. Logistic regression analysis including 18 demographic and procedural variables revealed that, in addition to age, extent of coronary disease, ventricular function and coronary risk profile, creatine kinase MB elevation was associated with a significant increase in major ischaemic events at follow-up. The excess risk was concentrated mainly in the highest stratum of creatine kinase MB elevation. Conclusions Thus, in the era of stenting and aggressive adjunctive pharmacology, peri-procedural myonecrosis still remains frequent and has an important impact on long-term event-free survival. Intensive efforts to reduce creatine kinase MB elevation after revascularization are warranted and should lead to important benefits. Copyright 2001 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved

Impact of mitral regurgitation on long-term survival after percutaneous coronary intervention.

Abstract: In patients with coronary artery disease, mitral regurgitation (MR) may be due to acute or chronic papillary muscle ischemia, left ventricular (LV) dilation, or papillary muscle rupture. Patients with moderate or severe MR and early LV dysfunction may benefit from surgical repair or replacement of the mitral valve, with or without coronary bypass surgery. 1‐ 4 There are reports of improvement in MR after percutaneous coronary intervention (PCI), especially in patients with acute myocardial ischemic syndromes. 5‐9 The prognostic importance of MR in patients with coronary artery disease selected to undergo PCI outside of the setting of acute myocardial infarction has not been studied. In this observational analysis we sought to determine the independent prognostic impact of moderate to severe MR on subsequent survival in a cohort of consecutive patients who underwent PCI from 1994 to 1997.

Long-term mortality benefit with the combination of stents and abciximab for cardiogenic shock complicating acute myocardial infarction.

Abstract: Cardiogenic shock secondary to ischemic heart disease is associated with a high mortality rate, and recent trials have established the benefit of an early invasive approach. However, the role of adjunctive abciximab and stenting for cardiogenic shock has not been established. We prospectively examined collected data from 96 consecutive patients who underwent emergent percutaneous coronary intervention for cardiogenic shock over the past 7 years. Patients were classified as receiving stent plus abciximab, stent alone, percutaneous transluminal coronary angiopplasty (PTCA) plus abciximab, or PTCA alone. Baseline characteristics of the 4 groups were similar. During 2.5 years of follow-up, the mortality rates for stent plus abciximab, stent only, PTCA plus abciximab, and PTCA alone were 33%, 43%, 61%, and 68%, respectively (log-rank p = 0.028). Achievement of postprocedural Thrombolysis In Myocardial Infarction 3 flow was higher with stent plus abciximab than with the other interventions (85% vs 65%, p = 0.048). By multivariate analysis, absence of stent use (hazard ratio 2.58, 95% confidence interval 1.36 to 4.90, p = 0.004) and left ventricular ejection function

Plaque vulnerability, plaque rupture, and acute coronary syndromes: (Multi)-Focal manifestation of a Systemic disease process

Abstract: In this issue of Circulation , Rioufol et al1 describe the presence of multiple ruptured atherosclerotic coronary plaques in patients presenting with an acute coronary syndrome (ACS). With the use of intravascular ultrasound (IVUS), the authors systematically examined proximal portions of the entire coronary tree in 24 patients. Ruptured plaques were found at the culprit lesion in 9 patients (37.5%) but, more importantly, distant from the culprit lesion in 19 patients (79%). These additional ruptured plaques were frequently multiple, located in a vessel different from the culprit vessel in 70% of patients and in 2 vessels not related to the acute event in 12% of patients. Both culprit lesions and additional ruptured plaques were characterized by positive remodeling. The authors proceeded with coronary stent placement at the culprit lesion site in 19 patients (86%) and, on the basis of angiographic and IVUS criteria (minimum luminal diameter <1.5 mm, minimum luminal cross-sectional-area <4 mm2), at additional sites in 16 patients (72%). See p 804 It is important to consider these findings in the context of the recent literature. Traditional diagnostic criteria of lesion significance define focal, hemodynamically significant plaques that cause acute or chronic impairment of coronary blood flow. These lesions are identified by selective coronary angiography. However, it is well known from angiographic studies that most myocardial infarctions occur at sites that previously caused only mild-to-moderate luminal stenosis.2 In histological studies of patients with coronary artery disease who died suddenly, the plaque at the culprit lesion site shows evidence of rupture in ∼70% of patients and superficial erosion in 30% of patients. 3 Acute superimposed thrombosis leads to luminal obstruction. Similar to the findings of Rioufol et al, 1 other recent studies that used different clinical imaging modalities found evidence of ruptured plaques that were …

Evidence that angiotensin-converting enzyme inhibitor use diminishes the need for coronary revascularization after stenting.

Abstract: Restenosis after stenting, in contrast to balloon angioplasty, is predominantly due to neointima formation. Angiotensin-converting enzyme (ACE) inhibitors diminish neointima formation in animal models of arterial injury. In an observational study, 1,598 patients who were treated from 1994 to 1997 with coronary stents and prospectively followed for clinical events were divided into 2 groups: those receiving ACE inhibitors at the time of stenting (n = 345) and those who did not (n = 1,253). Multivariate logistic regression was used to adjust for imbalances between populations with regard to elements relevant to risk of 12-month coronary revascularization, which was the primary study end point. After adjustment, ACE inhibitor usage remained significantly protective against revascularization (odds ratio [OR] 0.46, 95% confidence interval 0.29 to 0.73, p = 0.001). Protection was not observed in patients treated with balloon angioplasty alone during the same period (OR 1.06, p = 0.33), which is consistent with the results of prior randomized trials. ACE inhibitors appear to decrease late revascularization, possibly due to a reduction in restenosis after coronary stenting.

Effect of catheter-based iridium-192 gamma brachytherapy on the added risk of restenosis from diabetes mellitus after intervention for in-stent restenosis (subanalysis of the GAMMA I Randomized Trial).

Abstract: Catheter-based intracoronary radiation therapy using iridium-192 (Ir-192) has been shown to be effective in reducing recurrent coronary restenosis after initial percutaneous treatment of in-stent restenosis. Patients with diabetes mellitus (DM) have a higher risk of recurrent restenosis than nondiabetics for nonstented and in-stent restenosis coronary lesions. The use of Ir-192 for preventing recurrent restenosis in such patients remains undefined. The GAMMA I trial was a prospective, randomized, double-blind, multicenter trial of 252 patients with in-stent restenosis who underwent percutaneous coronary intervention and were assigned to receive either Ir-192 (131 patients) or catheter-based placebo (121 patients). DM was present in 79 patients (31%) (41 patients received Ir-192 and 38 patients received placebo) and was absent in 173 patients (90 patients received Ir-192 and 83 patients received placebo). At 6-month follow-up in the GAMMA I trial, the angiographic in-lesion binary restenosis rate was lower in the Ir-192 arm than in the placebo arm (32.4 vs 55.3, p = 0.01). When patients were stratified by the presence of DM, the antirestenosis effect of Ir-192 was larger for diabetic patients than for nondiabetic patients (absolute in-lesion restenosis rate was reduced by 40% for diabetics and 16% for nondiabetics). Thus, adjunctive Ir-192 intracoronary radiation therapy reduces recurrent restenosis after intervention for in-stent restenosis in patients with and without DM. The relative impact of this treatment is more pronounced in diabetic patients because it appears to neutralize the added risk of recurrent restenosis seen in proliferative diabetic lesions.

Safety of abciximab during percutaneous coronary intervention in patients with chronic renal insufficiency

Abstract: In summary, this study suggests that the use of abciximab in patients with chronic renal dysfunction undergoing PCI is relatively safe and not associated with an increased risk of major bleeding.

Comparison of Long-Term Survival Following Non-Q- Wave Creatine Kinase Elevation After Percutaneous Coronary Intervention in Patients Discharged on a Beta Blocker Versus Those Not So Treated

Abstract: Alarge cohort of consecutively treated patients undergoing percutaneous coronary intervention (PCI) at our institution is routinely followed for up to 5 years, and from this registry came the initial reports of the relation between low level creatine kinase (CK) elevation and subsequent adverse outcome during long-term follow-up after PCI. 1 From more recent experience, we sought to determine whether or not -blocker usage diminished the risk of death or reinfarction after CK elevation with PCI.  Baseline, procedural and outcome data are prospectively recorded on all patients undergoing PCI at the Cleveland Clinic by trained personnel on dedicated case report forms. Consecutive patients are prospectively identified for long-term followup. Patients, family, and if necessary, referring physicians were routinely contacted at 30 days and at 1, 3, and 5 years (standardized written form, followed by phone contact if necessary) after their procedure to ascertain occurrence of death, myocardial infarction, bypass surgery, or PCI. The study cohort consisted of all patients undergoing PCI from 1994 to 1998 with elevated CK-MB after PCI who were identified for follow-up. Patients presenting with acute or recent myocardial infarction with continued elevated CK-MB (n 498) or periprocedural Q-wave infarction (n 12) were excluded. Follow-up was 97.9% complete. Discharge medications were confirmed by chart review. Patients whose charts could not be located to ascertain -blocker status were excluded (n 22). For the purposes of the study, a patient was considered to have been treated with blockers if they were discharged from hospital after PCI on any oral blocker. CK-MB levels were routinely obtained 6 to 8 hours

Rescue Percutaneous Coronary Intervention for Failed Thrombolysis

Abstract: Rescue or salvage percutaneous coronary intervention (PCI) entails mechanical reopening of an infarct-related artery (IRA) after unsuccessful fibrinolytic therapy. Although rescue PCI is commonly performed, data describing clinical outcomes are sparse.