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Background The NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry followed 1345 consecutive patients with first PTCA between 1977 and 1981 (registry 1) and 2136 consecutive patients with PTCA between 1985 and 1986 (registry 2). Changes in patient selection and in immediate and 1-year outcome are presented. This report extends to 5 years the comparison of the effects of early and more recent management with PTCA. Methods and Results Sixteen participating centers entered consecutive patients who had angioplasty for the first time between 1977 and 1981 and between 1985 and 1986. Patients with recent myocardial infarction (MI) were excluded. Vessel disease was defined according to the Coronary Artery Surgery Study. Successful dilatation required ≥20% reduction in luminal narrowing and <50% lumen diameter stenosis after intervention. Routine annual follow-up was conducted by telephone interview. The product-limit method was used to estimate freedom from untoward events, Cox regression analysis to model relative risk and adjusted relative risk of events between the two registries, and logistic regression when the exact time of outcome (such as recurrence of symptoms) was not known. Long-term event rates were computed by vessel disease for all patients and for the cohort of patients with initially successful PTCA. After adjustment for extent of disease, diabetes, prior bypass surgery (CABG), hypertension, age, and sex, the 5-year risk of death was similar in the two registry cohorts. However, rates of MI, CABG, and a combined outcome measure of death, MI, and/or CABG were significantly lower in the registry 2 cohort both for all patients and for patients who were initially treated successfully. Use of repeated PTCA was higher, and freedom from symptoms without adverse events was significantly better in the latter cohort. Conclusions Compared with registry 1, the management of the registry 2 cohort resulted in lower 5-year morbid event rates and reduced CABG operations. Mortality rates remained similar. When symptomatic status was considered in combination with events, a significantly better outcome was seen overall and in the initially successful cohort. In registry 2, repeated PTCA was used with much greater frequency early after the initial procedure.

BACKGROUND In acute myocardial infarction, residual flow to the infarct zone either through antegrade flow in the infarct-related coronary artery or collateral flow from the non-infarct-related arteries is often present before reperfusion therapy. The purpose of this study was to assess the influence of antegrade flow in the infarct-related artery and/or collateral flow to the infarct zone before successful direct angioplasty on infarct size and myocardial salvage in patients with acute evolving myocardial infarction. METHODS AND RESULTS Sixty patients with acute evolving myocardial infarction underwent direct successful angioplasty without prior thrombolytic therapy. The myocardium at risk of infarction, the final infarct size, and myocardial salvage were measured by tomographic perfusion imaging with 99mTc sestamibi. Antegrade flow in the infarct-related artery before intervention was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study group classification. Collateral flow to the infarct zone before angioplasty was also graded (0 through 3, 0 being no collateral flow). The presence of even minimal antegrade flow before angioplasty (TIMI grade 1) in the infarct-related artery compared with absent flow was associated with a significant reduction in final infarct size (9 +/- 17% versus 23 +/- 19% of left ventricle, P = .02) and a significant increase in myocardial salvage (23 +/- 16% versus 14 +/- 13% of left ventricle, P = .05) after angioplasty. When antegrade flow in the infarct-related artery was absent before angioplasty, the presence of collateral flow before angioplasty resulted in a significantly smaller final infarct size (P = .01) and more myocardial salvage (P = .05) after angioplasty. Both antegrade infarct-related artery flow and collateral flow to the infarct zone had significant independent ability to predict infarct size after angioplasty. When collateral grade and TIMI grade were added to provide an estimate of residual flow, a model including residual flow, myocardium at risk, and the interaction of residual flow and infarct site explained 83% of the variability in infarct size after angioplasty. CONCLUSIONS The presence of antegrade flow in the infarct-related artery and/or collateral flow to the infarct zone before direct angioplasty in acute evolving infarction results in a smaller infarct size after direct successful angioplasty.

BACKGROUND Coronary revascularization with bypass has been shown to improve survival in patients with coronary artery disease and left ventricular dysfunction. In these patients, use of nonsurgical revascularization with percutaneous transluminal coronary angioplasty (PTCA) is increasing, although their long-term outcome has not been well delineated. The purpose of this investigation was to characterize the outcome of angioplasty in patients with decreased left ventricular function and contrast it with the results in patients with normal left ventricular function. METHODS AND RESULTS In the 1985-1986 National Heart, Lung, and Blood Institute's PTCA Registry, of 1,802 patients undergoing PTCA, 244 patients (13.5%) had an ejection fraction of < or = 45% (mean, 39.6 +/- 6.8%). These patients had a higher incidence of prior infarction, a longer and worse history of manifestations of coronary disease, and more extensive coronary artery disease than patients with well-preserved function; 88% and 91%, respectively, had successful dilation of at least one lesion (nonsignificant difference). However, patients with decreased left ventricular function had a decreased frequency of successful dilation of all lesions in which PTCA was attempted (76% versus 84%, p < 0.01). There were no statistically significant differences in in-hospital complications--death occurred in 0.8% and 0.7%, nonfatal myocardial infarction occurred in 4.9% and 4.5%, and emergency surgical revascularization was performed in 4.5% and 3.2%, respectively. Patients were followed for a mean of 4.1 years; during this time, patients with decreased left ventricular function had significantly worse survival and combined event-free survival. Despite this, at 4 years, 87% of the patients with a mean ejection fraction of 39.6% remained alive, and 77% were alive and had not experienced infarction or required bypass. CONCLUSIONS PTCA is effective in selected patients with depressed left ventricular function. Initial outcome and risk-benefit ratio are excellent. Successful dilation of at least one vessel was achieved in 88% of patients with depressed left ventricular function and in 91% of patients with more normal left ventricular function. The former group, however, had a decreased incidence of successful dilation in all lesions in which dilation was attempted (76% versus 84%, p < 0.01). There was no significant difference in in-hospital complications between the two groups. During follow-up, patients with decreased left ventricular function had worse event-free survival, although 77% were alive without infarction or bypass grafting at 4 years.

BACKGROUND Complete revascularization after coronary artery bypass surgery is a logical goal and improves symptomatic outcome and survival. However, the impact of complete revascularization in patients with three-vessel coronary disease with varying severities of angina and left ventricular dysfunction has not been clearly defined. METHODS AND RESULTS The study was performed as a retrospective analysis of 3,372 nonrandomized surgical patients from the Coronary Artery Surgery Study (CASS) Registry who had three-vessel coronary disease. Group 1 (894 patients) had class I or II angina (Canadian Cardiovascular Society criteria) and group 2 (2,478 patients) had class III or IV angina. In group 1, adjusted cumulative 4-year survivals according to the number of vessels bypassed were 85% (one vessel), 94% (two vessels), 96% (three vessels), and 96% (more than three vessels) (log rank, p = 0.022). Adjusted event-free survival (death, myocardial infarction, definite angina, or reoperation) was not influenced by the number of vessels bypassed, nor was the anginal status among patients remaining alive after 5 years. In group 2, adjusted cumulative 5-year survivals were 78% (one vessel), 85% (two vessels), 90% (three vessels), and 87% (more than three vessels) (log rank, p = 0.074). Adjusted event-free survivals after 6 years were 23% (one vessel), 23% (two vessels), 29% (three vessels), and 31% (more than three vessels) (p = 0.025); at 5 years, those with more complete revascularization were more likely to be asymptomatic or free of severe angina. Among group 2 patients with ejection fractions less than 0.35, 6-year survival was 69% for those with grafts to three or more vessels versus 45% for those with grafts to two vessels (p = 0.04). Placing grafts to three or more vessels was independently associated with improved survival and event-free survival in group 2 but not group 1 patients. The case-fatality rates among 529 patients experiencing a myocardial infarction during follow-up was significantly higher for patients with less complete revascularization. CONCLUSIONS Complete revascularization (grafts to three or more vessels) in patients with three-vessel coronary disease appears to most benefit those with severe angina and left ventricular dysfunction.

BACKGROUND Experimental animal studies have demonstrated that myocardium at risk, residual collateral flow, and duration of coronary artery occlusion are important determinants of final infarct size. The present study examined these variables in patients with acute myocardial infarction in relation to final infarct size. METHODS AND RESULTS Myocardium at risk was assessed with hexakis(2-methoxyisobutyl isonitrile) technetium (I) (99mTc sestamibi) in 89 patients with first-time myocardial infarction (anterior, 48 patients; inferior, 41 patients). All patients had successful reperfusion therapy with either intravenous thrombolysis (32 patients) or primary coronary angioplasty (57 patients) within 24 hours of the onset of chest pain (4.7 +/- 3.9 hours; range, 0.5-21.5 hours) documented by coronary angiography. 99mTc sestamibi was injected intravenously before reperfusion therapy, and tomographic imaging was performed 1-6 hours later. Myocardium at risk was quantitated for each patient and expressed as a percentage of the left ventricle: 35 +/- 19%; range, 2-73%. Collateral flow was estimated by both invasive and noninvasive methods. Fifty-three patients with TIMI grade 0 or I flow who underwent primary coronary angioplasty had collateral flow graded angiographically (0-3) before the first balloon inflation. All patients had collateral flow estimated noninvasively from the acute sestamibi short-axis profile curve by three methods that assess the severity of the perfusion defect. Each of these three methods was significantly associated with angiographic collateral grade. Final infarct size was determined at hospital discharge by a second sestamibi study (17 +/- 17%; range, 0-59%). Myocardium at risk (r = 0.61, p less than 0.0001), angiographic collateral grade (p = 0.0003), and radionuclide estimates of collateral flow (r = 0.69-0.70, all p less than 0.0001) were all significantly associated with final infarct size. The time to reperfusion therapy was not significantly associated with final infarct size by univariate analysis (r = 0.18, p = 0.10). Two multivariate models were constructed to determine which variables were independently associated with final infarct size. In the invasive model, myocardium at risk, angiographic collateral grade with an interaction term for infarct location, and time to reperfusion were all independently significant and accounted for 70% of the variability in final infarct size. The noninvasive model, which substituted a radionuclide estimate of collateral flow for angiographic collateral grade, showed nearly identical results, accounting for 68% of the variability in infarct size in patients where the infarct artery was known to be occluded. When all patients were included (patients with and without acute angiography), the noninvasive model accounted for 59% of the variability in infarct size. CONCLUSIONS Myocardium at risk, collateral flow, and duration of coronary occlusion are each independently associated with final infarct size and account for most of its variability. Ideally, all three parameters should be examined in evaluation of the efficacy of new treatment strategies for acute myocardial infarction.

BACKGROUND Coronary balloon angioplasty of chronic total occlusions is associated with relatively low success rates and a high incidence of restenosis. Whether there is long-term benefit in performing angioplasty of these lesions is unknown. The purpose of the present report was to analyze the long-term outcome of a large series of patients undergoing this procedure. METHODS AND RESULTS A computerized database analysis of 354 consecutive patients (from 1979 to 1990) who underwent coronary angioplasty of a chronic total coronary occlusion was performed (mean age, 62.3 years). Initial technical success was achieved in 69%; in 66%, success was achieved without procedural death or need for coronary artery surgery. During hospitalization, six patients suffered myocardial infarction, nine required emergency bypass surgery, and nine patients died. During a mean follow-up period of 2.7 years, no difference was found in survival or freedom from myocardial infarction among 234 successfully dilated patients compared with 120 patients with a failed attempt. However, the use of coronary artery bypass surgery was significantly less after successful dilation (p less than 0.0001 versus failed attempt). No significant difference in the cumulative incidence of severe angina was observed between these two patient populations, with the majority remaining asymptomatic. Restenosis occurred in 59% of 69 patients who returned for follow-up angiography. CONCLUSIONS Successful recanalization is achieved in the majority of patients undergoing angioplasty of chronic total occlusions and reduces the need for coronary artery bypass surgery. However, no major impact on either survival or incidence of myocardial infarction was noted after successful recanalization when patients with surgery were included.

BACKGROUND Patients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation. METHODS AND RESULTS Tc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1-6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20 +/- 15% of the left ventricle; range, 2-53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery. CONCLUSIONS Patients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy.

Background —Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. Methods and Results —Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events ( P <0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. Conclusions —Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.

BACKGROUND Prior studies based on autopsy data suggest that infarction of more than 40% of the left ventricle necessitates cardiogenic shock and death. METHODS AND RESULTS Technetium-99m Sestamibi tomography was used prospectively to measure infarct size at discharge in 166 patients with acute myocardial infarction. Patients with previous myocardial infarction or revascularization were excluded from the trial. Sixteen patients were identified with final infarct sizes > 40% of the left ventricle despite acute reperfusion therapy. These 16 patients (13 men) had a mean age of 63 +/- 10 years; 44% had a previous history of angina. Ten patients had emergent coronary angioplasty only (mean time to percutaneous transluminal coronary angioplasty [PTCA], 6.0 +/- 3.0 hours); 6 had thrombolysis (mean time to tissue plasminogen activator, 4.0 +/- 1.5 hours), of which 2 had rescue PTCA (5 and 3 hours from onset of pain). Of 15 patients who had angiograms after therapy, 15 had open infarct-related arteries. The left anterior descending artery was the infarct-related artery in 14 (9 proximal and 5 distal lesions). Half the patients had only single-vessel disease. Infarct size measured 50 +/- 7% of the left ventricle (range, 42% to 68%). Ejection fraction by radionuclide angiogram was 0.33 +/- 0.09 and 0.38 +/- 0.07 at discharge and 6 weeks, respectively. Hospital complications included shock (1 patient), pulmonary edema (2), angina (3), symptomatic nonsustained ventricular tachycardia (1), transient complete heart block (2), and transient bifascicular block (1). At follow-up (13 +/- 9 months), the patient with shock had died, but the remaining 15 patients were asymptomatic (1 had late PTCA for angina). CONCLUSIONS In the interventional and thrombolytic era, patients with large residual myocardial infarctions can survive without heart failure.

Purpose In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007. Patients and Methods Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate. Results Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy. For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, “B” symptoms, and nodular sclerosis histology were risk factors for inferior EFS. Conclusion With a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in EFS but no improvement in OS. For individual patients, the relative risks of relapse versus late effects of IFRT must be considered. Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT.