Henry A. Liberman

Influence of Diabetes Mellitus on Early and Late Outcome After Percutaneous Transluminal Coronary Angioplasty

BACKGROUND Although patients with diabetes mellitus constitute an important segment of the population undergoing coronary angioplasty, the outcome of these patients has not been well characterized. METHODS AND RESULTS Data for 1133 diabetic and 9300 nondiabetic patients undergoing elective angioplasty from 1980 to 1990 were analyzed. Diabetics were older and had more cardiovascular comorbidity. Insulin-requiring (IR) diabetics had diabetes for a longer duration and worse renal and ventricular functions compared with non-IR subjects. Angiographic and clinical successes after angioplasty were high and similar in diabetics and nondiabetics. In-hospital major complications were infrequent (3%), with a trend toward higher death or myocardial infarction in IR diabetics. Five-year survival (89% versus 93%) and freedom from infarction (81% versus 89%) were lower, and bypass surgery and additional angioplasty were required more often in diabetics. In diabetics, only 36% survived free of infarction or additional revascularization compared with 53% of nondiabetics, with a marked attrition in the first year after angioplasty, when restenosis is most common. Multivariate correlates of decreased 5-year survival were older age, reduced ejection fraction, history of heart failure, multivessel disease, and diabetes. IR diabetics had worse long-term survival and infarction-free survival than non-IR diabetics. CONCLUSIONS Coronary angioplasty in diabetics is associated with high success and low complication rates. Although long-term survival is acceptable, diabetics have a higher rate of infarction and a greater need for additional revascularization procedures, probably because of early restenosis and late progression of coronary disease. The most appropriate treatment for these patients remains to be determined.

Acute Myocardial Infarction Temporally Related to Cocaine Use: Clinical, Angiographic, and Pathophysiologic Observations

Ischemic chest pain syndromes and myocardial infarction occurred within minutes to hours of cocaine use in nine persons ages 23 to 39 years. Five developed symptoms after taking cocaine intranasally; three, after intravenous use; and one, after smoking cocaine. Four were habitual users and five were recreational users; eight also smoked cigarettes heavily. Ischemic syndromes recurred in five who continued to use cocaine. Coronary arteriography showed an abnormal infarct-related vessel (more than 50% stenosis, total occlusion, or intraluminal thrombus) in seven patients. The noninfarct-related vessels were normal in eight patients. The left anterior descending coronary artery and the anteroapical left-ventricular wall were involved in all patients. After three patients had successful thrombolysis of the obstructed infarct-related vessel, angiography showed a normal underlying vessel.

A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (activase) in acute myocardial infarction.

A new, predominantly single chain preparation of recombinant tissue-type plasminogen activator was evaluated to determine coronary thrombolytic efficacy in 100 patients with acute myocardial infarction. At 3.6 +/- 1.2 hours (mean +/- SD) from symptom onset, patients received either intravenous tissue plasminogen activator (1.25 mg/kg body weight over 3 hours) or placebo on a 3:1 randomized, double-blind basis. Coronary angiography, performed 68 +/- 13 minutes after initiation of the study drug infusion, demonstrated patency of the infarct-related artery in 40 (57%) of 70 patients in the tissue plasminogen activator group compared with 3 (13%) of 23 patients in the placebo group (p less than 0.001). Patients in the placebo group were then eligible to receive intracoronary streptokinase. At 90 minutes the patency was observed in 49 (69%) of 71 tissue plasminogen activator patients compared with 5 (24%) of 21 placebo patients (p less than 0.001). At 120 minutes patency was observed in 59 (79%) of 75 patients of the tissue plasminogen activator group and in 10 (40%) of 25 in the intracoronary streptokinase/placebo group. A nadir value of less than 100 mg/dl fibrinogen occurred in 8 (11%) of 73 patients receiving tissue plasminogen activator versus 8 (40%) of 20 patients treated with intracoronary streptokinase (p = 0.002). Moderate or severe bleeding episodes occurred in 39% of patients treated with tissue plasminogen activator compared with 32% of patients who received placebo/intracoronary streptokinase (p = NS). Thus, this tissue plasminogen activator preparation achieves a high rate of recanalization and, at the doses employed, exhibits increased fibrinogen sparing compared with intracoronary streptokinase.

Percutaneous transluminal coronary angioplasty in women compared with men

OBJECTIVES This study compares in-hospital and long-term outcome after angioplasty in women and men. BACKGROUND The recognition that coronary artery disease is the most common cause of death in women has increased interest in outcome studies of coronary artery disease in women. METHODS Patients who had previous coronary revascularization and those who underwent angioplasty in the setting of acute myocardial infarction were excluded. Angioplasty was performed with standard methods. Clinical data were retrieved from a clinical data base and analyzed with standard statistical methods. RESULTS There were 2,845 women and 7,940 men. The women were older (62 +/- 11 vs. 57 +/- 10 years) and had more hypertension (54.5% vs. 40.1%), diabetes (19.3% vs. 11.7%), grade III to IV angina (71.5% vs. 58.4%) and congestive failure (4.3% vs. 2.1%) than men (all p < 0.0001). More men had a previous myocardial infarction (35.4% vs. 31.0%) and were taller and weighed more (all p < 0.0001). The men had lower ejection fractions and more multivessel disease (31.0% vs. 25.2%) (both p < 0.0001). In women there was a trend toward more Q wave myocardial infarctions (1.1% vs. 0.75%, p = 0.10), and hospital mortality was higher (0.7% vs. 0.1%, p < 0.0001). Angina at follow-up was more common in women 40.2% vs. 26.7%, p < 0.0001). The multivariate correlates of in-hospital death were short stature, reduced ejection fraction and multivessel disease, with trends for older age and female gender. Five-year survival was 95% in men and 92% in women (p = 0.0002). However, female gender was not a multivariate correlate of long-term survival and was accounted for by other characteristics, primarily age. The multivariate correlates of long-term survival were older age, congestive failure, reduced ejection fraction, multivessel disease, diabetes, hypertension and a trend for severe angina. No difference between women and men was noted in long-term freedom from myocardial infarction. There were more additional procedures in men than in women. CONCLUSIONS Despite higher in-hospital mortality, long-term mortality and clinical outcome were similar in both genders when age and body habitus were accounted for.

Antimyosin imaging in acute transmural myocardial infarctions: Results of a multicenter clinical trial

Murine monoclonal antimyosin antibody has been shown experimentally to bind selectively to irreversibly damaged myocytes. To evaluate the safety and efficacy of monoclonal antimyosin for identifying acute transmural infarction, 50 patients with acute Q wave myocardial infarction were entered into a phase I/II multicenter trial involving three clinical sites. Indium-111 antimyosin was prepared from an instant kit formulation containing 0.5 mg of diethylene triamine pentaacetic acid (DTPA)-coupled Fab fragment (R11D10) and 1.2 to 2.4 mCi of indium-111. Average labeling efficiency was 92%. Antimyosin was injected 27 +/- 16 h after the onset of chest pain. Planar or tomographic imaging was performed 27 +/- 9 h after injection in all patients, and repeat imaging was done 24 h later in 39 patients. Of the 50 patients entered, 46 showed myocardial uptake of antimyosin (sensitivity 92%). Thirty-one of 39 planar scans performed at 24 h were diagnostic; 8 showed persistent blood pool activity that cleared by 48 h. Focal myocardial uptake of antimyosin corresponded to electrocardiographic infarct localization. No patient had an adverse reaction to antimyosin. In addition, 125 serum samples, including 21 collected greater than 42 days after injection, were tested for human antimouse antibodies, and all samples were assessed as having undetectable titers. Intensity of antimyosin uptake was correlated with infarct location and the presence or absence of collateral vessels. There was a significant correlation between faint uptake and inferoposterior infarct location. In 21 patients who had coronary angiography close to the time of antimyosin injection, there was a significant correlation between faint tracer uptake and closed infarct-related vessel with absent collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term clinical follow-up in patients with angiographic restudy after successful angioplasty.

BackgroundRestenosis remains a critical limitation after coronary angioplasty. There is little information comparing long-term prognosis in patients who suffer from restenosis and others who do not. The purpose of this paper is to determine the clinical events in patients with restenosis or continued patency documented by restudy coronary arteriography. Methods and ResultsThe source of data was the clinical data base at Emory University. Patients who had previous coronary surgery and patients who underwent angioplasty in the setting of acute myocardial infarction were excluded. A total of 3,363 patients undergoing angiographic restudy 4 months to 1 year after angioplasty were compared with 3,858 not undergoing restudy. In the restudy population, 1,570 had restenosis and 1,793 had patent arteries at all sites dilated. The restenosis patients were older and had more hypertension, more diabetes, more severe angina, more multivessel coronary artery disease, more severe stenoses, and less satisfactory original results. At restudy, in patients without restenosis, 38.7% had angina versus 70.7% in patients with restenosis (p<0.0001). There were few deaths in the first 6 months. At 6 years, the survival rate was 0.95 without restenosis and 0.93 with restenosis (p=0.16). At 6 months and 6 years, freedom from myocardial infarction was 0.97 and 0.88 without restenosis and 0.93 and 0.85 with restenosis (p=0.0001). On multivariate analysis, restenosis was an independent correlate of myocardial infarction but not mortality. At 6 months and 6 years, freedom from coronary bypass surgery was 0.99 and 0.94 without restenosis and 0.91 and 0.78 with restenosis (p<0.0001). At 6 months and 6 years, freedom from repeat angioplasty was 0.96 and 0.76 without restenosis and 0.44 and 0.20 with restenosis (p=0.0001). The highest event rates were noted in the patients with restenosis with recurrent chest pain. Patients not undergoing restudy differed somewhat from the study group, and there were far fewer repeat revascularization procedures in the group not undergoing restudy. ConclusionsPatients with restenosis are more likely to have recurrent angina pectoris. Although there is no or little difference in survival, there is a difference in myocardial infarction rate in the patients with and without restenosis. The low myocardial infarction and death rates in the group suffering restenosis may be related to repeat revascularization in these patients; the principal events in the restenosis population are frequent repeat revascularization procedures.

Angioplasty or Surgery for Multivessel Coronary Artery Disease: Comparison of Eligible Registry and Randomized Patients in the EAST Trial and Influence of Treatment Selection on Outcomes

The Emory Angioplasty versus Surgery Trial (EAST) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass surgery (CABG) had equivalent 3-year outcomes regarding survival, myocardial infarction, and major myocardial ischemia. Patients eligible for the trial who were not randomized because of physician or patient refusal were followed in a registry. This study compares the outcomes of the randomized and registry patients. Of the 842 eligible patients, 450 did not enter the trial. Their baseline features closely resembled those of the randomized patients and follow up was performed using the same methods. In the registry there was a bias toward selecting CABG in patients with 3-vessel disease (84%) and PTCA in patients with 2-vessel disease (54%). Three-year survival for the registry patients was 96.4%, which was better than the randomized patients, 93.4% (p = 0.044). Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry (12.4%) than PTCA randomized patients (19.6%) (p = 0.079). Thus, the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup. Since baseline differences were small, improved survival in the registry may be due to treatment selection. Physician judgment, even in patients judged appropriate for clinical trials, remains a potentially important predictor of outcomes.

Improved Late Clinical Safety With Zotarolimus-Eluting Stents Compared With Paclitaxel-Eluting Stents in Patients With De Novo Coronary Lesions: 3-Year Follow-Up From the ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) Trial

OBJECTIVES The increased frequency of very late (>1 year) stent thrombosis (VLST) has raised concerns with regard to the safety of sirolimus-eluting stents and paclitaxel-eluting stents (PES). BACKGROUND Experimental and preliminary clinical findings with the zotarolimus-eluting stent (ZES) have suggested a favorable safety profile. METHODS The ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) trial is a single-blind randomized ZES versus PES clinical trial in 1,548 patients with de novo native coronary lesions; the primary end point-9-month target vessel failure-was previously reported, annual clinical follow-up is planned for 5 years, and this report describes the 3-year outcomes. RESULTS The ZES compared with PES reduced target vessel failure (12.3% vs. 15.9%, hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.58 to 1.00, p = 0.049), myocardial infarctions (MI) (2.1% vs. 4.9%, HR: 0.44, 95% CI: 0.25 to 0.80, p = 0.005), and cardiac death plus MI (3.6% vs. 7.1%, HR: 0.52, 95% CI 0.32 to 0.82, p = 0.004). Although the overall 3-year rate of Academic Research Consortium definite/probable stent thrombosis did not differ significantly (1.1% vs. 1.7%, HR: 0.67, 95% CI 0.28 to 1.64, p = 0.380), VLST (between 1 and 3 years) was significantly reduced in ZES patients (1 event vs. 11 events; 0.1% vs. 1.6%, HR: 0.09, 95% CI: 0.01 to 0.71, p = 0.004). Ischemia-driven target lesion revascularization at 3 years was similar with ZES versus PES (6.5% vs. 6.1%, HR: 1.10, 95% CI: 0.73 to 1.65, p = 0.662). CONCLUSIONS Three-year follow-up results from the ENDEAVOR IV trial indicate similar antirestenosis efficacy but improved clinical safety associated with ZES compared with PES, due to significantly fewer peri-procedural and remote MIs associated with fewer VLST events. (A Randomized, Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions; NCT00217269).

Failed elective percutaneous transluminal coronary angioplasty requiring coronary artery bypass surgery. In-hospital and late clinical outcome at 5 years.

This study was performed to define the in-hospital and late clinical outcome at 5 years in 430 patients who had a failed elective percutaneous transluminal coronary angioplasty (PTCA) and underwent coronary artery bypass graft (CABG) surgery during their hospitalization. This group comprised 5.9% of 7,246 patients undergoing elective PTCA. CABG surgery was performed in 346 patients with ongoing myocardial ischemia (80.5%) and in 84 patients without ischemia (19.5%). Their mean age was 56 +/- 9 years, and 76.3% were male. One-vessel disease was present in 72.3%, and the mean left ventricular ejection fraction was 59 +/- 11%. Overall, 1.9 +/- 0.9 bypass grafts were placed. There was increased use of the internal thoracic artery in the nonischemic group. A new nonfatal postprocedural Q wave myocardial infarction occurred in 21.2% and occurred more frequently in the ischemic (25.4%) than in the nonischemic (3.6%) group (p less than 0.0001). There were six in-hospital deaths (1.4%), an incidence that did not differ between the two groups. Follow-up was 99.8% complete. There were 25 deaths (93.2 +/- 1.5%, 5-year survival), including 16 of cardiac cause (95.3 +/- 1.3%, 5-year cardiac survival). Q wave myocardial infarction occurred in 111 patients (91 in-hospital), and freedom from cardiac death or nonfatal myocardial infarction at 5 years was 71 +/- 3%. In the group going to CABG surgery with ongoing ischemia, the 5-year cardiac survival was 94.9 +/- 1.6%, and in the group without ischemia, the corresponding survival was 96.2 +/- 2.2%. By multivariate analysis, the presence of preoperative myocardial ischemia, pre-PTCA diameter stenosis less than 90%, and the presence of multiple-vessel disease correlated with the occurrence of cardiac death or nonfatal myocardial infarction at 5 years. At this large-volume center with extensive PTCA operator and surgical experience, the excellent survival and low event rates over 5 years support the concept that despite the failed elective PTCA procedure, there was little effect on long-term survival provided the patient underwent prompt successful surgical revascularization.

Hybrid Coronary Revascularization Versus Off-Pump Coronary Artery Bypass Grafting for the Treatment of Multivessel Coronary Artery Disease

BACKGROUND Hybrid coronary revascularization (HCR) combines a minimally invasive (3-cm anterolateral thoracotomy), sternal-sparing, off-pump left internal mammary artery-left anterior descending (LIMA-LAD) coronary artery anastomosis with percutaneous coronary intervention (PCI) to non-LAD coronary arteries. We compared outcomes of HCR versus traditional off-pump coronary artery bypass grafting (OPCAB) for the treatment of multivessel coronary artery disease (CAD). METHODS Between October 8, 2003 and April 23, 2010, 147 patients with multivessel coronary disease were treated with HCR at a US academic center. These were matched 4:1 to 588 contemporaneous patients treated with multivessel OPCAB by sternotomy using an optimal matching algorithm with 8 preoperative variables: age, gender, ejection fraction, presence of diabetes, myocardial infarction (MI), number of diseased vessels, left main coronary artery disease, and Society of Thoracic Surgeons (STS) predicted risk of mortality (PROM) score. In-hospital major adverse events (MACCE) and the need for repeated revascularization during follow-up were compared between groups. All-cause mortality was determined using the Social Security Death Index (SSDI). RESULTS Matching produced groups with similar coronary anatomy and statistically similar preoperative risk factors. The incidence of MACCE was similar between groups (3/147 HCR versus 12/588 OPCAB). During a median 3.2 years of follow up, the need for repeated revascularization was higher for HCR than for OPCAB (18/147 [12.2%] versus 22/588 [3.7%]; p < 0.001). The incidence of blood transfusion was higher for the OPCAB group. Estimated 5-year survival was similar between groups (OPCAB, 84.3% versus HCR, 86.8%; p = 0.61). CONCLUSIONS Hybrid coronary revascularization is a minimally invasive treatment for multivessel CAD. Although repeated revascularization was greater with HCR, both in-hospital and midterm outcomes were comparable with those of traditional OPCAB. Further investigation into the comparative effectiveness of this alternative strategy is warranted.