Daniel J. Diver

A Clinical Trial Comparing Three Antithrombotic-Drug Regimens after Coronary-Artery Stenting

Background Antithrombotic drugs are used after coronary-artery stenting to prevent stent thrombosis. We compared the efficacy and safety of three antithrombotic-drug regimens — aspirin alone, aspirin and warfarin, and aspirin and ticlopidine — after coronary stenting. Methods Of 1965 patients who underwent coronary stenting at 50 centers, 1653 (84.1 percent) met angiographic criteria for successful placement of the stent and were randomly assigned to one of three regimens: aspirin alone (557 patients), aspirin and warfarin (550 patients), or aspirin and ticlopidine (546 patients). All clinical events reflecting stent thrombosis were included in the prespecified primary end point: death, revascularization of the target lesion, angiographically evident thrombosis, or myocardial infarction within 30 days. Results The primary end point was observed in 38 patients: 20 (3.6 percent) assigned to receive aspirin alone, 15 (2.7 percent) assigned to receive aspirin and warfarin, and 3 (0.5 percent) assigned to rece...

The Electrocardiogram Predicts One-Year Outcome of Patients With Unstable Angina and Non–Q Wave Myocardial Infarction: Results of the TIMI III Registry ECG Ancillary Study

OBJECTIVES We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non-Q wave myocardial infarction (MI). BACKGROUND Although the ECG is the most widely used test for evaluating patients with unstable angina and non-Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy. METHODS ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non-Q wave MI. RESULTS New ST segment deviation > or = 1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients with > or = 1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p < 0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of either > or = 1 mm or > or = 0.5 mm remained independent predictors of death or MI by 1 year. CONCLUSIONS The admission ECG is very useful in risk stratifying patients with non-Q wave MI. The new criteria of not only > or = 1-mm ST segment deviation but also > or = 0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.

Angiographic and clinical outcome of intracoronary stenting: Immediate and long-term results from a large single-center experience

OBJECTIVES The purpose of this study was to determine the immediate and long-term angiographic and clinical results of coronary stenting. BACKGROUND Although preliminary trials of endovascular stenting have demonstrated promising results, lack of long-term follow-up has limited the critical evaluation of the role of coronary stenting in the treatment of obstructive coronary artery disease. METHODS A total of 250 procedures using the Palmaz-Schatz stent, performed in 220 patients between June 1988 and July 1991, were examined. Minimal lumen diameter of the treated segments was measured on angiograms obtained before, after and 6 months after intervention. RESULTS Stent placement was successful in 246 (98%) of 250 lesions, reducing diameter stenosis from 77% to -2.5%. There were no deaths or Q wave myocardial infarctions. One patient (0.4%) required emergency bypass surgery and one (0.4%) developed subacute thrombosis. Femoral vascular complications occurred in 36 patients (16%). Six-month angiographic follow-up was obtained in 91% of eligible patients. The overall angiographic restenosis rate (stenosis greater than or equal to 50%) was 25%. By univariable analysis, the rate of restenosis was significantly higher for stents in the left anterior descending versus the right coronary artery (44% vs. 12%; p = 0.002); in diabetic patients (56% vs. 20%; p = 0.006), and in vessels with post-stent lumen diameter less than 3.31 mm (34% vs. 16%; p = 0.05). Stenting of the left anterior descending artery was the strongest predictor (p = 0.01) of restenosis in a multivariable model. Total survival was 97% and event-free survival (freedom from death, myocardial infarction or revascularization) was 70% at 36 months. CONCLUSIONS Palmaz-Schatz stents can be placed successfully with a low incidence of major complications. The angiographic restenosis rate was 25%, and 70% of patients remained free of cardiovascular events at 3 years. Diabetes, small postprocedure lumen diameter and stenting of the left anterior descending artery are associated with higher rates of restenosis.

Novel approach to the analysis of restenosis after the use of three new coronary devices

Restenosis after coronary intervention has remained a vexing problem despite the introduction of nearly 24 newer coronary interventional devices. To more clearly evaluate the potential impact of three such new devices on restenosis, coronary lumen diameters were measured before, immediately after and at 6 months after intervention, and restenosis was analyzed using continuous geometric techniques. Lumen diameters were measured before and immediately after intervention in 223 coronary vessels treated with one of three new devices: a single Palmaz-Schatz stent (n = 87), directional atherectomy (n = 125) and laser balloon angioplasty (n = 11); 184 (83%) of the patients underwent follow-up angiography 6 months after treatment. The immediate increase in lumen diameter produced by the intervention (acute gain) and the subsequent reduction in lumen diameter between the time of intervention to 6 month follow-up study (late loss) were examined. For each of the three interventions, the restenosis rate at follow-up study was analyzed using a traditional dichotomous definition (greater than or equal to 50% diameter stenosis), as well as a novel graphic technique. Although the apparent restenosis rates differed significantly among the three interventions (19% for stents, 31% for atherectomy and 50% for laser balloon angioplasty; p = 0.02), late loss among the three interventions was equivalent (average 1 mm; p = 0.91). There were, however, marked differences in the acute gain achieved by the three interventions: 2.6 mm for stents, 2.2 mm for atherectomy and 2 mm for laser balloon angioplasty; p less than 0.001). It was these differences in acute gain rather than late loss that explained the observed differences in restenosis rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon aortic valvuloplasty in 170 consecutive patients

Between October 1, 1985, and April 1, 1988, we performed balloon aortic valvuloplasty in 170 patients (mean age [+/- SD], 77 +/- 5 years) who had symptomatic aortic stenosis. The procedure was completed successfully in 168 patients and resulted in significant increases in the mean (+/- SD) aortic-valve area (from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2) and cardiac output (from 4.6 +/- 3.4 to 4.8 +/- 1.4 liters per minute) and decreases in the peak aortic-valve pressure gradient (from 71 +/- 20 to 36 +/- 14 mm Hg) (P less than 0.01 for all three comparisons). There were six in-hospital deaths, and five patients required early aortic-valve replacement. Follow-up data were available for all patients, for a period averaging 9.1 months. In addition to the 6 patients who died in the hospital, 25 patients died an average of 6.4 +/- 5.3 months after discharge. Symptoms recurred in 44 patients; they were managed by repeat valvuloplasty in 16 patients, by aortic-valve replacement in 17, and by medical therapy in 11. At the most recent follow-up examination, the symptoms of 103 patients had improved after valvuloplasty; this number includes 15 patients with restenosis who successfully underwent redilation. Life-table analysis indicates that the probability of survival 12 months after the procedure was 74 percent. We conclude that balloon aortic valvuloplasty is an effective palliative therapy for some elderly patients with symptomatic aortic stenosis. Symptoms improve in the majority of patients; although restenosis is common, it can be managed in some patients by repeat balloon dilation.

Clinical and arteriographic characterization of patients with unstable angina without critical coronary arterial narrowing (from the TIMI-IIIA Trial)

Previous studies have reported that some patients presenting with unstable angina are found at coronary angiography to have no critical coronary stenosis. This study evaluated the clinical presentation and arteriographic findings in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI-IIIA) trial, which assessed the effect of tissue-type plasminogen activator added to conventional therapy on the coronary arteriographic findings in patients presenting with ischemic pain at rest. Three hundred ninety-one patients were enrolled in the TIMI-IIIA trial and underwent coronary arteriography within 12 hours of enrollment. Fifty-three patients (14%) had no luminal diameter stenosis of a major coronary artery of > or = 60% on the baseline arteriogram. Compared with patients with unstable angina with an identifiable culprit lesion, patients without critical coronary obstruction were more likely to be women and non-white and less likely to have ST-segment deviation on the presenting electrocardiogram. Arteriography in such patients revealed no visually detectable coronary stenosis in half of the group; the remaining patients had noncritical coronary narrowing (i.e., < 60% luminal diameter stenosis) without morphologic features (ulceration or thrombus) suggestive of unstable or active coronary plaque. Nearly one third of the patients without critical coronary stenosis had impaired angiographic filling, suggesting a possible pathophysiologic role for coronary microvascular dysfunction. These patients with unstable angina and no critical coronary obstruction had an excellent short-term prognosis; 2% died or had myocardial infarction compared with 18% of patients with critical obstruction.

Balloon dilation of mitral stenosis in adult patients: postmortem and percutaneous mitral valvuloplasty studies.

Preliminary reports have documented the utility of percutaneous balloon valvuloplasty of the mitral valve in adult patients with mitral stenosis, but the mechanism of successful valve dilation and the effect of mitral valvuloplasty on cardiac performance have not been studied in detail. Accordingly, mitral valvuloplasty was performed in five postmortem specimens and in 18 adult patients with rheumatic mitral stenosis, using either one (25 mm) or two (18 and 20 mm) dilation balloons. Postmortem balloon dilation resulted in increased valve orifice area in all five postmortem specimens, secondary to separation of fused commissures and fracture of nodular calcium within the mitral leaflets. In no case did balloon dilation result in tearing of valve leaflets, disruption of the mitral ring or liberation of potentially embolic debris. Percutaneous mitral valvuloplasty in 18 patients with severe mitral stenosis (including 9 with a heavily calcified valve) resulted in an increase in cardiac output (4.3 +/- 1.1 to 5.1 +/- 1.5 liters/min, p less than 0.01) and mitral valve area (0.9 +/- 0.2 to 1.6 +/- 0.4 cm2, p less than 0.0001), and a decrease in mean mitral pressure gradient (15 +/- 5 to 9 +/- 4 mm Hg, p less than 0.0001), pulmonary capillary wedge pressure (23 +/- 7 to 18 +/- 7 mm Hg, p less than 0.0001) and mean pulmonary artery pressure (36 +/- 12 to 33 +/- 12 mm Hg, p less than 0.01). Left ventriculography before and after valvuloplasty in 14 of the 18 patients showed a mild (less than or equal to 1+) increase in mitral regurgitation in five patients and no change in the remainder.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of left ventricular and aortic valve function after aortic balloon valvuloplasty in adult patients with critical aortic stenosis.

Preliminary reports have documented the utility of balloon aortic valvuloplasty as a palliative treatment for high-risk patients with critical aortic stenosis, but the effect of this procedure on cardiac performance has not been studied in detail. Accordingly, 32 patients (mean age 79 years) with long-standing, calcific aortic stenosis were treated at the time of cardiac catheterization with balloon dilatation of the aortic valve, and serial changes in left ventricular and valvular function were followed before and after valvuloplasty by radionuclide ventriculography, determination of systolic time intervals, and Doppler echocardiography. Prevalvuloplasty examination revealed heavily calcified aortic valves in all patients, a mean peak-to-peak aortic valve gradient of 77 +/- 27 mm Hg, a mean Fick cardiac output of 4.6 +/- 1.4 liters/min, and a mean calculated aortic valve area of 0.6 +/- 0.2 cm2. Subsequent balloon dilatation with 12 to 23 mm valvuloplasty balloons resulted in a fall in aortic valve gradient to 39 +/- 15 mm Hg, an increase in cardiac output to 5.2 +/- 1.8 liters/min, and an increase in calculated aortic valve area to 0.9 +/- 0.3 cm2. Individual hemodynamic responses varied considerably, with some patients showing major increases in valve area, while others demonstrated only small increases. In no case was balloon dilatation accompanied by evidence of embolic phenomena. Supravalvular aortography obtained in 13 patients demonstrated no or a mild (less than or equal to 1+) increase in aortic insufficiency. Serial radionuclide ventriculography in patients with a depressed left ventricular ejection fraction (i.e., that less than or equal to 55%) revealed a small increase in ejection fraction from 40 +/- 13% to 46 +/- 12% (p less than .03). In addition, for the study group as a whole there was a decrease in left ventricular end-diastolic volume index (113 +/- 38 to 101 +/- 37 ml/m2, p less than .003), a fall in stroke-volume ratio (1.49 +/- 0.44 to 1.35 +/- 0.33, p less than .04), and no immediate change in left ventricular peak filling rate (2.05 +/- 0.77 to 2.21 +/- 0.65 end-diastolic counts/sec, p = NS). Serial M mode echocardiography and phonocardiography showed an increase in aortic valve excursion (0.5 +/- 0.2 to 0.8 +/- 0.2 cm, p less than .001), a decrease in time to one-half carotid upstroke (80 +/- 30 to 60 +/- 10 msec, p less than .001), and a small decrease in left ventricular ejection time (0.44 +/- 0.03 to 0.42 +/- 0.02 sec, p less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical and angiographic results of balloon-expandable intracoronary stents in right coronary artery stenoses

Balloon-expandable stents were placed successfully in 35 (95%) of 37 patients whose right coronary artery lesion was believed to have a poor short- or long-term prognosis with conventional balloon angioplasty because of prior restenosis or adverse lesion morphology. Quantitative angiography showed a reduction in stenosis diameter from 83 +/- 14% to 42 +/- 14% after conventional balloon dilation, with a further reduction to -3 +/- 12% after stent placement (p less than 0.001). There were no acute stent thromboses, but one patient (with two stents and unstented distal disease) developed subacute thrombosis on day 8 after self-discontinuation of warfarin and was treated with thrombolytic therapy and redilation. Follow-up angiography was performed at 4 to 6 months in 25 patients, demonstrating restenosis (83 +/- 13%) in 4 (57%) of 7 patients with multiple stents, but only 3 (17%) of 18 patients with a single stent (p less than 0.05). Six of the seven in-stent restenotic lesions were subtotal (80 +/- 12%) and were subjected to repeat conventional balloon angioplasty (postdilation stenosis 13 +/- 21%). The 18 patients without restenosis had a maximal in-stent diameter stenosis of 29 +/- 15%, corresponding to a maximal focal neointimal thickness of 0.68 +/- 0.26 mm within the stented segment. These preliminary results suggest that the Schatz-Palmaz stent may be a useful adjunctive device in the performance of coronary angioplasty.

Rescue angioplasty in the thrombolysis in myocardial infarction (TIMI) 4 trial

Rescue percutaneous transluminal coronary angioplasty (PTCA) has been used to establish reperfusion after failed thrombolysis, and the goal of this study was to examine the angiographic and clinical outcomes after rescue PTCA performed for an occluded artery 90 minutes after thrombolysis. Four hundred two patients with acute myocardial infarction were randomized to receive either anistreplase (APSAC), recombinant tissue plasminogen activator, or their combination in the Thrombolysis in Myocardial Infarction (TIMI) 4 trial. The angiographic and clinical outcomes of patients with a patent artery 90 minutes after thrombolysis were compared with those of patients with an occluded artery treated in a nonrandomized fashion with either rescue or no rescue PTCA. At 90 minutes, the number of frames required to opacify standard landmarks (corrected TIMI frame count) was significantly lower (i.e., flow was faster) after successful rescue PTCA (27 +/- 11) than that in patent arteries after successful thrombolysis (39 +/- 20, p < 0.001), and the incidence of TIMI grade 3 flow was correspondingly higher after successful rescue PTCA (87% vs 65%, p = 0.002). In-hospital adverse outcomes (death, recurrent acute myocardial infarction, severe congestive heart failure, cardiogenic shock or an ejection fraction <40%) occurred in 29% of successful rescue PTCAs and in 83% of failed rescue PTCAs (p = 0.01). Among all patients in whom rescue PTCA was performed (successes and failures combined), 35% of patients experienced an adverse outcome, which was the same as the 35% incidence observed in patients not undergoing rescue PTCA (p = NS) and tended to be higher than the 23% incidence observed in patients with patent arteries (p = 0.07). Although successful rescue PTCA for an occluded artery at 90 minutes results in restoration of flow that is superior to that of successful thrombolysis, the incidence of adverse events for the strategy of rescue PTCA as a whole was the same as that of undertaking no PTCA.