Role of adenosine thallium-201 tomography for defining long-term risk in patients after acute myocardial infarction.

OBJECTIVES: This study prospectively evaluated whether early assessment with adenosine thallium-201 tomography could better refine risk stratification on the basis of absolute extent of myocardial ischemia in postinfarction patients in clinically stable condition. BACKGROUND: Postinfarction patients are at increased risk for subsequent cardiac events. However, identifying high risk patients among those with residual myocardial ischemia is suboptimal. METHODS: All 146 patients enrolled underwent assessment of left ventricular function and had adenosine tomography performed early (mean [+/- SD] 5 +/- 3 days) after infarction. Excluded from analysis were 51 patients with revascularization after scintigraphy and 3 lost to follow-up. Statistical risk models were therefore generated from the remaining 92 patients. RESULTS: Cardiac events occurred in 30 (33%) of 92 patients over 15.7 +/- 4.9 months. Univariate predictors of all events were quantified perfusion defect size (p < 0.0001), absolute extent of left ventricular ischemia (p < 0.000001) and ejection fraction (p < 0.0001). Risk was best predicted by Cox analysis on the basis of 1) absolute extent of ischemia and ejection fraction (chi-square 24.6); 2) percent infarct zone ischemia and ejection fraction (chi-square 24.4); or 3) total perfusion defect size and percent infarct zone ischemia (chi-square 18.9). The variables that predicted all cardiac events were equally powerful at predicting only death and nonfatal reinfarction. Death was best predicted by total perfusion defect size. CONCLUSIONS: Risk analysis of individual patients early after infarction is feasible on the basis of the quantified extent of scintigraphic ischemia and severity of left ventricular dysfunction.

Transdermal nitroglycerin patch therapy reduces the extent of exercise-induced myocardial ischemia: results of a double-blind, placebo-controlled trial using quantitative thallium-201 tomography.

OBJECTIVES: This study prospectively evaluated whether transdermal nitroglycerin patches could limit the extent of exercise-induced left ventricular ischemia as assessed by quantitative thallium-201 tomography. BACKGROUND: Although antianginal medications are effective at reducing chest pain symptoms in patients with coronary artery disease, there is limited evidence that these agents can also reduce myocardial ischemia. METHODS: This was a randomized, double-blind, parallel, placebo-controlled trial evaluating nitroglycerin patch therapy in patients in stable condition with angiographic coronary artery disease and no previous myocardial infarction. All patients were weaned from antianginal agents and had a baseline symptom-limited treadmill test followed by thallium-201 tomography. Forty patients with perfusion defects involving > or = 5% of the left ventricle were randomized to receive either intermittent (12 h on/off) active nitroglycerin patch therapy (0.4 mg/h) or placebo. Exercise tomography was repeated a mean (+/- SD) of 6.1 +/- 1.8 days after randomization. RESULTS: Patients randomized to receive active patch therapy had a significant reduction in their total perfusion defect size (-8.9 +/- 11.1%) compared with placebo-treated patients (-1.8 +/- 6.1%, p = 0.04), which was most apparent in those with the largest (> or = 20%) baseline perfusion defects (-11.4 +/- 13.4% vs. 1.0 +/- 3.6%, respectively, p < 0.02). Furthermore, 7 (33%) of 21 patients receiving active therapy had a > or = 10% decrease in their perfusion defects compared with only 1 (5%) of 19 patients randomized to receive placebo (p = 0.002). Nitrate therapy did not significantly reduce heart rate, blood pressure or double product, indicating benefit through enhancement of coronary blood flow. CONCLUSIONS: Short-term, intermittent nitroglycerin patch therapy significantly reduces myocardial ischemia, particularly in patients with large ischemic perfusion defects. Thallium-201 tomography can be used to assess sequential changes in the extent of exercise-induced left ventricular ischemia.

Effects of low-dose aspirin on in vitro platelet aggregation in the early minutes after ingestion in normal subjects.

Aspirin interferes with platelet aggregation by inhibiting the metabolism of arachidonic acid to thromboxane A2. Although both high- and low-dose aspirin therapies are effective for secondary prophylaxis in patients with atherosclerotic vascular disease, the acute response to low-dose aspirin therapy is controversial. Eighteen volunteer subjects ingested 81, 162, or 324 mg of aspirin in a longitudinal crossover study design. Initial doses were randomly assigned and dosing intervals were separated by 2 weeks. Platelet aggregation in response to 0.9 mM arachidonic acid was measured at baseline, 15, 30, 60, and 90 minutes after ingestion. Thromboxane B2 production was assayed on simultaneously obtained samples after stimulation with arachidonic acid. The median inhibition of aggregation was 97%, 97%, and 97% 15 minutes after ingestion of 81, 162, and 324 mg, respectively. Four subjects had < 20% inhibition 15 minutes after ingesting 81 mg, but all 4 had > 90% inhibition after 30 minutes. Thromboxane B2 production declined by > 93% in all subjects at each dose. There was no difference between doses in inhibition of thromboxane B2 production.

Discontinuation of chronic diuretic therapy in stable congestive heart failure secondary to coronary artery disease or to idiopathic dilated cardiomyopathy.

To assess the feasibility of diuretic discontinuation in patients with stable congestive heart failure (CHF) and to identify risk factors for subsequent development of congestion, a prospective, 12-week clinical trial of unmasked diuretic withdrawal was conducted with continuation of background CHF therapy and double-blind randomization to placebo or lisinopril. Forty-one patients with a history of CHF and continuous diuretic use for > or = 3 months had all diuretic therapy discontinued, and therapy with lisinopril 5 mg (target 20 mg)/day (n = 20) or placebo (n = 21) begun the next day. A diuretic was restarted if new or worsening CHF symptoms and signs developed. Twelve patients (29%) did not require diuretic reinitiation at any time during follow-up, whereas 29 (71%) restarted diuretic therapy after a median of 15 days (range 2 to 42). Fourteen patients taking lisinopril and 15 taking placebo required diuretic drugs (p = NS). The baseline daily furosemide dose of > 40 mg, a left ventricular ejection fraction < or = 0.27, and history of systemic hypertension were independently predictive of early diuretic reinitiation by Cox proportional-hazards analysis. The probability of remaining diuretic-free after 6 weeks was 71% if none of these criteria were present. This trial demonstrates the feasibility of discontinuing diuretic drugs in certain patients with stable CHF and predicts those patients likely to require reinitiation of therapy. Diuretic withdrawal may be warranted when the furosemide dose is < or = 40 mg/day, left ventricular ejection fraction is > 0.27 and when no history of systemic hypertension is present.