Long-term prognosis in unstable angina. The importance of early risk stratification using continuous ST segment monitoring.

AIMS: To assess the ability of clinical characteristics, admission ECG and continuous ST segment monitoring in determining long-term prognosis in unstable angina. METHODS: Two hundred and twelve patients with unstable angina (mean age 59 years), presenting within 24 h of an acute episode of angina were recruited at three hospitals and treated with standardized medical therapy. All patients kept chest pain charts and underwent ST segment monitoring for 48 h. The occurrence of death, myocardial infarction, and need for revascularization was assessed over a median follow-up of 2.6 years. RESULTS: The risk of death of myocardial infarction was greatest in the first 6-8 weeks after admission. Admission ECG ST depression and the presence of transient ischaemia predicted increased risk of subsequent death or myocardial infarction, whereas a normal ECG predicted a good prognosis. In 14 patients, ST segment monitoring provided the only evidence of recurrent ischaemia, and 72% of this group suffered an adverse event. Transient ischaemia and a history of hypertension were the most powerful independent predictors of death or myocardial infarction. CONCLUSIONS: Adverse events in unstable angina occur early after admission and can be predicted by clinical and ECG characteristics, and by the presence of transient ischaemia during ST segment monitoring. Risk stratification by these simple assessments can identify patients with unstable angina at high risk.

Calcium-channel antagonists in cardiovascular disease.

In the last 2 years there has been considerable controversy over the safety of certain calcium antagonists. This article discusses recent drug developments, summarizes the publications that sparked the controversy, highlights results of the l latest trials of calcium antagonists and considers the range of clinical conditions in which calcium antagonists may play a useful role.

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.

Endothelial control of lower limb blood flow in chronic heart failure.

BACKGROUND: Limitation of the blood supply to skeletal muscle in chronic heart failure may contribute to the symptoms of fatigue and diminished exercise capacity. The pathophysiology underlying this abnormality is not known. The purpose of this study was to assess the effect of endothelium dependent and independent vasodilator agents on blood flow in the leg of patients with heart failure. METHODS AND RESULTS: Blood flow in the leg was measured in patients with heart failure (n = 20) and compared with that in patients with ischaemic heart disease and normal left ventricular function (n = 16) and patients with chest pain and normal coronary arteries (n = 8). External iliac artery blood flow was measured using intravascular Doppler ultrasound and quantitative angiography. Flow was recorded at rest and in response to bolus doses of the endothelium independent vasodilator, papaverine. Endothelium dependent responses were measured by infusion of acetylcholine and substance P. Mean (SEM) baseline blood flow was reduced at rest (2.9 (0.4) v 4.5 (0.3) ml/s, P < 0.001) and vascular resistance was raised (37.4 (3.6) v 27.1 (3.0) units, P < 0.05) in patients with heart failure compared with that in controls. The peak blood flow response to papaverine (8 mg), acetylcholine (10(-7)-10(-5) mol/l), and substance P (5 pmol/min) was reduced in heart failure, with greater impairment of the response to acetylcholine than substance P. There was a correlation between baseline blood flow in the heart failure group and diuretic dose (r = -0.62, P = 0.003), New York Heart Association classification (r = -0.65, P = 0.002), and left ventricular ejection fraction (r = 0.80, P = 0.0004). CONCLUSIONS: There is reduced blood flow and raised vascular resistance at rest in the legs of patients with heart failure. The degree of impaired blood flow in the leg correlates with the severity of heart failure. There is impairment of the response to both endothelium dependent and independent vasodilators. Abnormal function of the vascular myocyte in heart failure may explain these results as would structural abnormalities of the resistance vessels.

Early continuous ST segment monitoring in unstable angina: prognostic value additional to the clinical characteristics and the admission electrocardiogram.

BACKGROUND AND OBJECTIVE: In unstable angina, clinical characteristics, resting electrocardiography, and early continuous ST segment monitoring have been individually reported to identify subgroups at increased risk of adverse outcome. It is not known, however, whether continuous ST monitoring provides additional prognostic information in such a setting. DESIGN: Observational study of 212 patients with unstable angina without evidence of acute myocardial infarction admitted to district general hospitals, who had participated in a randomised study comparing heparin and aspirin treatment versus aspirin alone. METHODS: Clinical variables and a 12 lead electrocardiogram (ECG) were recorded at admission, and treatment was standardised to include aspirin, atenolol, diltiazem, and intravenous glyceryl trinitrate, in addition to intravenous heparin (randomised treatment). Continuous ST segment monitoring was performed for 48 h and all inhospital adverse events were recorded. RESULTS: The admission ECG was normal in 61 patients (29%), showed ST depression in 59 (28%) (17 > or = 0.1 mV), and T wave changes in a further 69 (33%). The remaining 23 had Q waves (18), right bundle branch block (four), or ST elevation (one). During 8963 h of continuous ST segment monitoring (mean 42.3 h/patient), 132 episodes of transient myocardial ischaemia (104 silent) were recorded in 32 patients (15%). Forty patients (19%) had an adverse event (cardiac deaths (n = 3), non-fatal myocardial infarction (n = 6) and, emergency revascularisation (n = 31)). Both admission ECG ST depression (P = 0.02), and transient ischaemia (P < 0.001) predicted an increased risk of non-fatal myocardial infarction or death, while no patients with a normal ECG died or had a myocardial infarction. Adverse outcome was predicted by admission ECG ST depression (regardless of severity) (odds ratio (OR) 3.41) (P < 0.001), and maintenance beta blocker treatment (OR 2.95) (P < 0.01). A normal ECG predicted a favourable outcome (OR 0.38) (P = 0.04), while T wave or other ECG changes were not predictive of outcome. Transient ischaemia was the strongest predictor of adverse prognosis (OR 4.61) (P < 0.001), retaining independent predictive value in multivariate analysis (OR 2.94) (P = 0.03), as did maintenance beta blocker treatment (OR 2.85) (P = 0.01) and admission ECG ST depression, which showed a trend towards independent predictive value (OR 2.11) (P = 0.076). CONCLUSIONS: Patients with unstable angina and a normal admission ECG have a good prognosis, while ST segment depression predicts an adverse outcome. Transient myocardial ischaemia detected by continuous ST segment monitoring in such patients receiving optimal medical treatment provides prognostic information additional to that gleaned from the clinical characteristics or the admission ECG.

Acute effect of oestrogen replacement therapy on treadmill performance in postmenopausal women with coronary artery disease.

The significant reduction in cardiovascular morbidity and mortality following oestrogen replacement therapy in postmenopausal women is only partly explained by an improved lipid profile. Given acutely, oestradiol causes vasodilatation and increases coronary blood flow and, in large doses, improves treadmill performance in postmenopausal women with coronary artery disease. However, the significance of oestrogen-mediated vasodilatation is unknown since the acute effects of oestradiol in doses and preparations commonly used clinically have not been tested. The aim of this study was to evaluate the acute effects of conventional replacement therapy with 17 beta-oestradiol on treadmill performance in 16 postmenopausal women with angina in a randomized, double-blind, placebo-controlled cross-over trial. Following baseline treadmill testing a transdermal oestrogen patch releasing 50 micrograms oestradiol. 24 h-1 or matching placebo was applied and the exercise test repeated 24 h later. The patch was then removed. Seven to 14 days later the sequence was repeated using the alternative patch. The changes in time to angina, time to 1 mm ST segment depression and total exercise time for each treatment compared with the corresponding baseline test were calculated. Plasma 17 beta-oestradiol increased with active therapy from 56 +/- 30 pmol.l-1 to 204 +/- 90 pmol.l-1, indicating adequate replacement. Compared with their respective baseline exercise tests there were no differences between active and placebo patches for time to angina (active: 13 +/- 55 s vs placebo: 10 +/- 47 s), time to 1 mm ST segment depression (active: -30 +/- 52 s vs placebo: 24 +/- 71 s) or total exercise time (active: 14 +/- 45 s vs placebo: 13 +/- 35 s). Despite the recognized acute vasodilator action of larger doses of oestrogen, doses conventionally used in hormone replacement therapy had no acute effect on treadmill performance in this group of postmenopausal women with coronary artery disease.

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 comparison of two commonly used Doppler probes, which differ in the location of the piezoelectric 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 > or = 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 degrees) and was lower than the recommended angle correction factor of 60 degrees. 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.