James R. Margolis

The role of the exercise test in the evaluation of patients for ischemic heart disease.

A cohort of 1472 patients who underwent both exercise stress testing and coronary angiography within six weeks was examined. The data indicated that a combination of exercise parameters is both diagnostically and prognostically important. Almost all patients (> 97%) who had positive exercise tests at Stage I or Stage II had significant coronary artery disease. More than half of these (> 60%) had three vessel disease and over 25% had significant narrowing (> 50%) of the left main coronary artery. Patients who achieved Stage IV or greater exercise durations with either negative or indeterminate ST-segment response had less than a 15% prevalence of three vessel disease and less than a 1% prevalence of left main coronary artery disease. A low risk subgroup (75% of all nonoperated patients) was identified with a twelve month survival greater than 99%. A high risk subgroup (11% of all nonoperated patients) was identified with a twelve month survival of less than 85%. The exercise test is a noninvasive, reproducible method to assess the presence and extent of anatomic disease and the prognosis when significant disease has been defined. It should be used in conjunction with other noninvasive tests to determine optimal management in patients evaluated for ischemic heart disease.

Restenosis after coronary angioplasty: A multilvariate statistical model to relate lesion and procedure variables to restenosis☆

The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (≤4.6 mm, 33%; >4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (≤73%, 25%; >73%, 43%; p = 0.005), percent stenosis after angioplasty (≤21%, 33%; >21%, 46%; p = 0.017) and arterial diameter (<2.9 mm, 44%; ≥ 2.9 mm, 34%; p = 0.036). Two multivariate models to predict restenosis probability were developed with use of stepwise logistic regression. The preprocedural model, which included only variables whose values were known before angioplasty, entered lesion length, vein graft location, left anterior descending artery location, percent stenosis before angioplasty, eccentric lesion and arterial diameter. The postprocedural model, which also included variables whose values were known after angioplasty was performed, was similar to the preangioplasty model except that it also entered postangioplasty percent stenosis and “optimal” balloon sizing but did not enter eccentric lesion. These data indicate that the probability of restenosis after angioplasty is determined predominantly by the characteristics of the lesion being dilated. They are consistent with the known intimal proliferative mechanism of restenosis, offer a means of identifying lesions at unusually high or low risk of restenosis, and of predicting the likelihood that a particular lesion will restenose after angioplasty and provide a rationale for stratification by restenosis probability in the design of future studies of restenosis.

Clinical features of unrecognized myocardial infarction--silent and symptomatic. Eighteen year follow-up: the Framingham study.

The occurrence, prognosis and characteristics of persons with nonfatal unrecognized myocardial infarction were studied prospectively in a population of 5,127 men and women followed up biennially for 18 years. Of 259 electrocardiographically documented myocardial infarctions, 60 (23 percent) were discovered only by routine electrocardiogram at the time of biennial examination. Of these unrecognized infarctions, 32 (53 percent) were actually silent. In the other 47 percent of cases, the patients gave a history of interim symptoms judged to be compatible with acute infarction. In addition, of the 32 patients judged to have a silent infarction, 22 reported interim illnesses that could have been compatible with myocardial infarction. Only 10 of the 60 patients (17 percent) reported no interim illnesses or symptoms. Of the 28 patients with symptomatic infarction, 6 (21 percent) did not visit their physician despite severe symptoms; 20 gave a history of interim chest pain, 1 a history of epigastric pain and 7 a history of severe dyspnea. Patients who subsequently had unrecognized myocardial infarction typically visited physicians infrequently. Unrecognized myocardial infarction was distinctly rare in patients with prior angina pectoris. Patients with prior diabetes or high blood pressure appeared more likely to have unrecognized infarction. Unrecognized myocardial infarction appears to be as prevalent in the 1970s as it was in the 1950s. The reasons for this prevalence and possible solutions to the problem are discussed.

Effect of Thromboxane A2 Blockade on Clinical Outcome and Restenosis After Successful Coronary Angioplasty Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART II)

BACKGROUND Antithromboxane therapy with aspirin reduces acute procedural complications of coronary angioplasty (PTCA) but has not been shown to prevent restenosis. The effect of chronic aspirin therapy on long-term clinical events after PTCA is unknown, and the utility of more specific antithromboxane agents is uncertain. The goal of this study was to assess the effects of aspirin (a nonselective inhibitor of thromboxane A2 synthesis) and sulotroban (a selective blocker of the thromboxane A2 receptor) on late clinical events and restenosis after PTCA. METHODS AND RESULTS Patients (n = 752) were randomly assigned to aspirin (325 mg daily), sulotroban (800 mg QID), or placebo, started within 6 hours before PTCA and continued for 6 months. The primary outcome was clinical failure at 6 months after successful PTCA, defined as (1) death, (2) myocardial infarction, or (3) restenosis associated with recurrent angina or need for repeat revascularization. Neither active treatment differed significantly from placebo in the rate of angiographic restenosis: 39% (73 of 188) in the aspirin-assigned group, 53% (100 of 189) in the sulotroban group, and 43% (85 of 196) in the placebo group. In contrast, aspirin therapy significantly improved clinical outcome in comparison to placebo (P = .046) and sulotroban (P = .006). Clinical failure occurred in 30% (49 of 162) of the aspirin group, 44% (73 of 166) of the sulotroban group, and 41% (71 of 175) of the placebo group. Myocardial infarction was significantly reduced by antithromboxane therapy: 1.2% in the aspirin group, 1.8% in the sulotroban group, and 5.7% in the placebo group (P = .030). CONCLUSIONS Thromboxane A2 blockade protects against late ischemic events after angioplasty even though angiographic restenosis is not significantly reduced. While both aspirin and sulotroban prevent the occurrence of myocardial infarction, overall clinical outcome appears superior for aspirin compared with sulotroban. Therefore, aspirin should be continued for at least 6 months after coronary angioplasty.

Relationships among ventricular arrhythmias, coronary artery disease, and angiographic and electrocardiographic indicators of myocardial fibrosis.

SUMMARYThis study was performed to determine the relationships among angiographic, hemodynamic, clinical, and electrocardiographic data and premature ventricular contractions (PVCs). Arrhythmias were analyzed by 24 hour Holter monitor in 244 patients evaluated for chest pain by coronary angiography and left ventriculography. Using a categorical linear model, the presence of myocardial fibrosis as indicated by both abnormal left ventricular contraction (LVC) and abnormal initial QRS on electrocardiogram was found to be the only independent predictor of both frequent and complex ventricular arrhythmias (P < .0001). All other descriptors, including the number of diseased vessels (.75% obstruction), were dependent upon abnormal LVC in their association with PVCs. When the right anterior oblique view of the left ventriculogram was divided into nine segments to allow automated quantitative analysis of LVC, the prevalence of frequent PVCs was directly related to the number of abnormally contracting segments. Of patients with 0 abnormal segments, 11% had > 2 PVC/hr, in contrast to 44%, 73% and 100% of patients with 1-3, 4-6, and 7-9 abnormal wall segments, respectively (P < 0.01). A similar quantitative relationship was found between premature ventricular contractions and abnormal initial forces indicating previous myocardial infarction on the electrocardiogram.

Percutaneous excimer laser coronary angioplasty

To determine the efficacy of percutaneous excimer laser coronary angioplasty as an adjunct or alternative to conventional balloon angioplasty, 55 patients were studied in a multicenter trial. These patients underwent the procedure using a modification of conventional balloon angioplasty technique. A first-generation, 1.6-mm diameter catheter constructed of 12 individual silica fibers concentrically arranged around a guidewire lumen was used. Catheter tip energy density varied from 35 to 50 mJ/mm2. The mean number of pulses delivered at 20 Hz was 1,272 +/- 1,345. Acute success was defined as a greater than or equal to 20% increase in stenotic diameter and a lumen of greater than or equal to 1 mm in diameter after laser treatment. Acute success was achieved in 46 of 55 (84%) patients. Adjunctive balloon angioplasty was performed on 41 patients (75%). The percent diameter stenosis as determined by quantitative angiography decreased from a baseline of 83 +/- 14 to 49 +/- 11% after laser treatment and to 38 +/- 12% in patients undergoing adjunctive balloon angioplasty. The mean minimal stenotic diameter increased from a baseline of 0.5 +/- 0.4 to 1.6 +/- 0.5 mm after laser treatment and to 2.1 +/- 0.5 mm after balloon angioplasty. There were no deaths and no vascular perforations. One patient (1.8%) required emergency coronary bypass surgery. These data suggest that excimer laser energy delivered percutaneously by specially constructed catheters can safely ablate atheroma and reduce coronary stenoses.

Balloon angioplasty versus new device intervention: Clinical outcomes. A comparison of the NHLBI PTCA and NACI registries

OBJECTIVES We sought to compare outcomes of patients treated in the National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) and New Approaches to Coronary Intervention (NACI) registries. BACKGROUND Coronary angioplasty has numerous shortcomings. New devices for performing coronary interventions have been introduced in an effort to improve clinical outcomes. METHODS Under the sponsorship of the NHLBI, a registry of consecutive patients treated with PTCA during 1985 to 1986 was established. In 1990, the NHLBI funded a second registry, the NACI. The two registries used the same data coordinating center to collect detailed baseline and follow-up information. RESULTS Patients enrolled in the NACI registry were older, had undergone more previous bypass surgery procedures and had more stenoses located in bypass grafts than patients in the NHLBI PTCA registry. Procedural success was achieved in 72.1% and 82.6% of patients in the PTCA and NACI registries, respectively; however, in-hospital and 1-year mortality rates were 1.0% versus 1.8% and 3.1% versus 5.9% for the PTCA versus NACI registries, respectively. After risk adjustment, there was no difference in 1-year mortality. Rates of target lesion revascularization (TLR) were 21.5% for the PTCA registry and 24.2% for the NACI registry. NACI registry patients had a higher risk for TLR and the composite end point of death, myocardial infarction or revascularization (relative risk 1.28 and 1.23, respectively). However, the NACI registry patients who received stents tended to have a lower adjusted TLR rate. CONCLUSIONS This comparative study found no overall superiority of these newer devices in terms of patient survival or freedom from TLR after adjustment for baseline risk profiles. Although technologic improvements (especially improved stenting) continue, these observations highlight the importance of careful assessment of clinical results in the broad population of patients in whom interventions are used.

Aortocoronary Bypass Surgery: Correlation of Angiographic, Symptomatic and Functional Improvement at 1 Year

Angiographic changes in the coronary circulation were evaluated in 60 patients 1 year after aortocoronary bypass surgery, and their relation to the postoperative clinical status was examined. Of 124 grafts implanted, 26 were closed, 7 stenotic and 91 (74 percent) patent at 1 year. Progression of occlusive disease occurred in 21 of 57 (37 percent) nongrafted and 78 of 123 (63 percent) grafted vessels. On the basis of location and severity of progression, significant lesions bypassed and patency of grafts, postoperative coronary perfusion was considered optimal in 16 patients (Group I), better in 24 (Group III). Complete freedom from chest pain or lessening of pain (improvement by two New York Heart Association functional classes) occurred in 88 and 79 percent of patients in Group III. Positive preoperative treadmill stress tests became negative after surgery in five of six patients in Group I, five of eight in Grojp II and three of eight in Group III. This study demonstrates that when progression of disease, graft patency and extent of revasculariztion are considered in combination, the postoperative angiographic status of the coronary circulation correlates well with clinical improvement at 1 year. These findings support the hypothesis that improved blood supply to ischemic myocardium is a major factor contributing to relief of angina pectoris after saphenous vein bypass surgery.

Clinical and angiographic outcome in the laser angioplasty for restenotic stents (LARS) multicenter registry.

In‐stent restenosis (ISR), when treated with balloon angioplasty (PTCA) alone, has an angiographic recurrence rate of 30%–85%. Ablating the hypertrophic neointimal tissue prior to PTCA is an attractive alternative, yet the late outcomes of such treatment have not been fully determined. This multicenter case control study assessed the angiographic and clinical outcomes of 157 consecutive procedures in 146 patients with ISR at nine institutions treated with either PTCA alone (n = 64) or excimer laser assisted coronary angioplasty (ELCA, n = 93)) for ISR. Demographics were similar except more unstable angina at presentation in ELCA‐treated patients (74.5% vs. 63.5%; P = 0.141). Lesions selected for ELCA were longer (16.8 ± 11.2 mm vs. 11.2 ± 8.6 mm; P < 0.001), more complex (ACC/AHA type C: 35.1% vs. 13.6%; P < 0.001), and with compromised antegrade flow (TIMI flow < 3: 18.9% vs. 4.5%; P = 0.008) compared to PTCA‐treated patients. ELCA‐treated patients had similar rate of procedural success [93 (98.9% vs. 62 (98.4%); P = 1.0] and major clinical complications [1 (1.1%) vs. 1 (1.6%); P = 1.0]. At 30 days, repeat target site coronary intervention was lower in ELCA‐treated patients (1.1% vs. 6.4% in PTCA‐treated patients; P = 0.158), but not significantly so. At 1 year, ELCA‐treated patients had similar rate of major cardiac events (39.1% vs. 45.2%; P = 0.456) and target lesion revascularization (30.0% vs. 32.3%; P = 0.646). These data suggest that ELCA in patients with complex in‐stent restenosis is as safe and effective as balloon angioplasty alone. Despite higher lesion complexity in ELCA‐treated patients, no increase in event rates was observed. Future studies should evaluate the relative benefit of ELCA over PTCA alone for the prevention of symptom recurrence specifically in patients with complex in‐stent restenosis. Cathet Cardiovasc Intervent 2001;52:24–34.

Excimer laser coronary angioplasty

BackgroundPercutaneous transluminal coronary angioplasty (PICA) of aorto-ostial stenosis has been associated with a lower rate of acute success, a high risk of vessel closure, and late restenosis. The purpose of this report is to document a prospective multicenter trial of excimer laser coronary angioplasty (ELCA) of aorto-ostial stenosis involving the coronary arteries and saphenous vein grafts. Methods and ResultsBetween December 1989 and May 1992, 206 aorto-ostial ELCA procedures were performed on 209 stenoses in 200 patients. Canadian Cardiovascular Society class III or IV angina was present in 76%. The distribution of stenosis locations was left main coronary (LM) in 26 (12%), right coronary (RCA) in 124 (59%/o), and vein grafts (VG) in 59 (28%). Adjunctive PTCA was performed in 72%. Procedure success defined as .50%, diameter stenosis without major complications was achieved in 90% (LM, 92%; RCA, 89%; VG, 90%o). Quantitative angiographic analysis documented an improvement in stenosis diameter from 0.8±0.5 mm or 76±14% at baseline to 2.1±0.6 mm or 36±15% at completion (P<.01). The majority of the acute gain in diameter (1.0±0.6 mm) resulted from ELCA. A major complication during hospitalization occurred in 3.9% (death, 0%; Q-wave myocardial infarction, 0.5%; bypass surgery, 3.4%). The only logistic regression univariate and multivariate predictor of procedure failure was female gender. Six-month angiographic follow-up, available in 51% of eligible patients, documented an average lumen diameter of 1.7±1.0 mm and mean diameter stenosis of 46±26%. Restenosis (>50%o diameter stenosis) occurred in 39%o (LM, 64%; RCA, 35%; VG, 35%). Restenosis was less likely when residual stenosis was <35% (28% versus 53%, P<.05). Clinical events at follow-up were death, 2.7%; bypass surgery, 6.5%; myocardial infarction, 2.2%; and repeat angioplasty, 16.2%. Of the remainder, 78% were asymptomatic, class I or II for anginal symptoms. An adverse event during follow-up was more than twice as likely in the group with LM (50.0% versus 21.1%, P<.02). ConclusionsELCA is acutely effective and safe therapy in patients with aorto-ostial stenosis. Six-month restenosis, adverse-event rates were higher and functional status was poorer in the group with LM stenosis. ELCA may be considered as an alternative to bypass surgery in carefully selected patients with isolated aorto-ostial stenosis of the RCA and saphenous vein grafts.