Diana R. Holdright

Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina.

OBJECTIVES This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. BACKGROUND Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis. Heparin and aspirin are two drugs used frequently in the treatment of this condition, but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown. METHODS Two hundred eighty-five consecutive patients with unstable angina were randomized to receive either intravenous heparin plus oral aspirin (150 mg once daily) (Group H + A) or aspirin alone (Group A). Patients also received a beta-adrenergic blocking agent, diltiazem and intravenous nitrates. ST segment monitoring was performed for the 1st 48 h of treatment. Patients were followed up for the duration of their in-hospital stay. RESULTS One hundred fifty-four patients (30 women, mean [+/- SEM] age 58.3 +/- 0.8 years) received heparin and aspirin (Group H + A), and 131 patients (26 women, mean age 60.6 +/- 0.8 years) received aspirin only (Group A). ST segment monitoring (11,622 h) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min. There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia (27 [18%] in Group H + A vs. 31 [24%] in Group A), number of episodes (96 in Group H + A vs. 148 in Group A) or total duration of transient myocardial ischemia (2,911 min in Group H + A vs. 4,908 min in Group A). The incidence of in-hospital myocardial infarction or death was significantly higher in patients with transient myocardial ischemia (53% vs. 22%, p < 0.0001). Five of the six deaths occurred in patients with transient myocardial ischemia. Event-free survival from myocardial infarction or death was similar in both treatment groups. Preadmission therapy with aspirin was associated with a lower in-hospital infarction rate (19% vs. 34%, p = 0.01). CONCLUSIONS The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infarction or death in hospital. Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events, nor does it reduce the development of transient myocardial ischemia.

Pathophysiology of Transient Myocardial Ischemia in Acute Coronary Syndromes Characterization by Continuous ST-Segment Monitoring

BACKGROUND Transient ischemia in stable coronary disease peaks in the morning, reflecting increased myocardial oxygen demand and coronary vasomotor tone after walking. In acute coronary syndromes, however, ischemia may result from transient thrombus formation or coronary spasm at the site of a ruptured plaque. We report on the pathophysiological mechanisms underlying transient ischemia in acute coronary syndromes despite optimal therapy, on the basis of analysis of heart rate changes preceding ischemia and its circadian variation. METHODS AND RESULTS Two hundred fifty-six patients with unstable angina or non-Q-wave myocardial infarction underwent continuous ST-segment monitoring for 48 hours while receiving maximal medical therapy. All ischemic episodes were characterized by their timing, duration, association with pain, and heart rate changes before the onset of ischemia. During 10,629 hours of monitoring, 44 patients (17.2%) had 176 episodes of transient ischemia. The mean heart rate at onset of ischemia was 68 +/- 12.8 bpm, and > 55% of ischemic episodes were not preceded by a significant increase in heart rate. Ischemic activity had a single nocturnal peak, with 64% of all episodes occurring between 10 PM and 8 AM, this nocturnal preponderance being evident for episodes with or without a preceding increase in heart rate. The characteristics and timing of transient ischemia were similar in unstable angina and non-Q-wave myocardial infarction, but transient ischemia was more frequent (27.3% versus 15.1%; P < .05) and prolonged (median, 20 versus 13.5 minutes; P < .01) in non-Q-wave myocardial infarction. CONCLUSIONS In acute coronary syndromes, transient ischemia has a low threshold, occurs predominantly without an increase in myocardial oxygen demand, and is present mainly at night rather than in the morning. These findings in patients receiving maximal medical therapy suggest significant pathophysiological differences underlying transient ischemia compared with stable coronary disease.

The ST segment — the herald of ischaemia, the siren of misdiagnosis, or syndrome X?

Syndrome X is the term applied to patients with anginal-type chest pain who, despite a positive exercise stress test, have angiographically normal coronary arteries. Such patients probably belong to a heterogeneous group, and in a proportion the exercise test is falsely positive. With the availability of more accurate techniques for the detection of myocardial ischaemia, it is apparent that some patients can be shown to develop transient myocardial ischaemia with stress. The paradox of normal coronary arteries and a positive exercise test may be resolved by improved understanding of the regulatory control of regional myocardial blood flow, particularly at the level of the microvasculature, and of the metabolic expression of myocardial ischaemia.

Effect of acadesine, a new metabolic agent, on exercise-induced myocardial ischemia in chronic stable angina.

SummaryAcadesine, the first of a class of adenosine-regulating agents, has been shown to possess antiischemic properties in animal models. The aim of the study was to assess the effect of acadesine on exercise-induced myocardial ischemia in patients with chronic stable angina pectoris. Twelve patients with stable angina entered a five-way, randomized double-blind study comparing the effects of four doses of acadesine with placebo on time to 1 mm ST-segment depression and other parameters of exercise tolerance. At each study period patients underwent baseline exercise testing, followed by drug or placebo infusion after a 60 minute rest period. The exercise test was repeated after 30 minutes infusion, which continued throughout recovery. Time to angina, time to 1 mm ST depression, and total exercise time during the placebo infusion were 301.1±45.3, 314.8±50.9, and 399.4±47.6 seconds. The placebo-adjusted percentage change in time to 1-mm ST segment with acadesine 6, 12, 24, and 48 mg/kg was −0.1±6.2%, 11.1±13.8%, 12.9±8.6%, and −3.2±6.8%, respectively (p=NS vs. baseline). Time to angina, total exercise time, and recovery time of the ST segment were not consistently altered by acadesine. The lack of effect across all acadesine doses is consistent with animal data from ischemia-reperfusion injury studies, where a clear dose dependency was present with a loss of effect at higher doses. Alternatively, the extent of ischemia induced by treadmill exercise may have been insufficient for the antiischemic activity of acadesine to be evident.

Significant Differences Between Side-Mounted and End-Mounted Intracoronary Doppler Flow Probes for the Measurement of Blood Flow Velocity

Use of the intracoronary Doppler flow probe is an established method for the assessment of coronary blood flow velocity. The aim of this study was to perform an in vitro compar ison of two commonly used Doppler probes, which differ in the location of the piezo electric crystal (end-mounted vs side-mounted). Blood flow velocity was measured over a wide range of flow rates in a flow simulator using heparinized whole blood. Measurements were made with both Doppler probes assessed in two positions (supported and unsupported) within the tubing. The results were compared with estimated true velocities. Further measurements were made with six side-mounted probes, correcting for the assumed crystal mounting angle and for the angle calculated from magnified images of the individual crystals. Mean velocities for end- and side-mounted probes correlated highly with predicted velocities (all r ≥ 0.99), but the side-mounted probes significantly overestimated velocity by >100%. Estimation of the true crystal mounting angle of the side-mounted probe revealed considerable variability (range 30-42°) and was lower than the recommended angle correction factor of 60 ° . Velocities corrected for the individual crystal mounting angles agreed more closely with predicted mean velocities. Although both probes are adequate for the assessment of relative changes in flow, the side-mounted probe considerably overestimates mean velocity, which is partly explained by the variable mounting angle of the crystal. The demonstrated limitations of the side- mounted Doppler flow probe in vitro should be considered in undertaking measurement of intracoronary blood flow velocity.