D. P. Murray

Plasma catecholamine levels in acute myocardial infarction: Influence of beta-adrenergic blockade and relation to central hemodynamics

In a prospective study, 20 patients with acute myocardial infarction were randomly assigned in a double-blind fashion to treatment with intravenous metoprolol followed by oral metoprolol or placebo. All patients underwent hemodynamic monitoring for 24 hours. Plasma adrenaline and noradrenalin levels were estimated at baseline (mean 6.0 +/- 0.9 hours from onset of symptoms) and at 1 and 24 hours after the start of therapy. Plasma adrenaline and noradrenalin levels were elevated in all but one patient, with a further increase at 1 hour after administration of metoprolol (p less than 0.05). At baseline pulmonary capillary wedge pressure was directly related to both plasma adrenaline (r = -0.44; p less than 0.05) and noradrenalin levels (r = -0.44; p less than 0.05). There was also an inverse relationship between stroke volume index and the plasma noradrenalin level (r = -0.44; p less than 0.05) but not the plasma adrenaline level. These relationships were lost after the baseline measurements. However, between baseline and 1 hour there was a close relationship between the change in systemic vascular resistance and the changes in both adrenaline (r = -0.48; p less than 0.05) and noradrenalin levels (r = -0.66; p less than 0.01). Thus, in the early stages of myocardial infarction high plasma catecholamine levels are associated with the hemodynamic markers of severe left ventricular damage. Beta-adrenergic blockade with metoprolol produced a further increase in catecholamine levels that was associated with an increase in systemic vascular resistance.

Does beta adrenergic blockade influence the prognostic implications of post-myocardial infarction exercise testing?

The influence of beta blockade on the ability of ST depression, during pre-discharge exercise testing, to predict coronary anatomy and subsequent complications was studied in 300 consecutive post-infarct patients, 125 of whom underwent cardiac catheterisation. At the time of exercise 62 patients were taking a beta blocker. The exercise test had a higher sensitivity in predicting multivessel disease in patients who were not taking beta blockers than in patients who were (95% v 76%). beta Blockade did not, however, influence the ability of the test to identify patients at risk of subsequent cardiac events (sensitivity 84% and 85% respectively). These results suggest that it is not necessary to stop treatment with beta blockers before predischarge exercise testing of patients who have had an acute myocardial infarction.

Which exercise test variables are of prognostic importance post-myocardial infarction?

The prognostic value of parameters noted on pre-discharge exercise testing was assessed in 300 survivors of acute myocardial infarction. Exercise testing was performed at a mean of 9 days post-infarction. Each patients data were studied for the presence of ST-segment depression or elevation greater than or equal to 0.1 mV in any of the 12 leads recorded, angina pectoris, exertional hypotension and duration of exercise. The patients were followed for a mean of 12 months and the incidence of death, reinfarction, angina pectoris, heart failure and coronary revascularization procedures was noted. All variables studied, other than the presence of exercise-induced ST-segment elevation, were significantly associated with the occurrence of subsequent cardiac events (P less than 0.001). Exercise-induced ST-segment depression identified 80% of patients who developed complications and was significantly more sensitive than any of the other variables as a prognostic marker (P less than 0.05). The finding of angina pectoris, an abnormal blood pressure response or a limited exercise tolerance in association with exercise-induced ST-segment depression heightened the prognostic implications of this variable.

Does acute-phase beta-blockade reduce mortality in acute myocardial infarction by limiting infarct size?

The mechanism by which early intervention with beta-blockers reduces mortality in acute myocardial infarction is unclear. Therefore the effects of intravenous, followed by oral, metoprolol on indices of infarct size were studied in a double-blind fashion with a median delay of 6.75 hours from onset of symptoms. In 129 patients peak enzyme release and QRS score on the electrocardiogram were assessed, while myocardial perfusion score on thallium-201 scintigraphy was studied in 45 patients. There was a close correlation between all the indices of infarct size. While the correlation coefficients did not appear to be influenced by metoprolol treatment, the slope of the regression was affected. Peak aspartate aminotransferase and lactic dehydrogenase were lower by 11 and 7%, respectively, in the metoprolol-treated group, but no reduction was noted in QRS score or in thallium-201 perfusion defect size in the actively treated group. Thus, it seems likely that early intervention with metoprolol in acute myocardial infarction reduces mortality, not by limiting infarct size, but by some other mechanism.

Prognostic stratification of patients after myocardial infarction.

An attempt was made to stratify risk of subsequent cardiac events in post-infarct patients according to a combination of the results of clinical assessment, routine diagnostic investigations, and pre-discharge exercise testing in 350 consecutive patients who were followed up for one year. Patients were classified prospectively on the basis of the extent of myocardial damage as assessed by peak enzyme release, reciprocal change on the electrocardiogram at the time of myocardial infarction, Norris prognostic index, ability to perform a pre-discharge exercise test (and test result), and ability to tolerate beta adrenergic blockade on discharge. Of the 50 patients with contraindications to pre-discharge exercise testing, 26% died or had reinfarctions compared with 9% of the 300 exercised patients; the 24 non-exercised patients with evidence of extensive myocardial damage or reciprocal changes on the electrocardiogram were particularly at risk. Similarly, among the 300 exercised patients, extensive myocardial damage, reciprocal change on the electrocardiogram, and ST depression on exercise testing were the major risk markers in that each identified at least 75% of the patients who had subsequent cardiac events. The 63 exercised patients who had all three of these major risk markers constituted a high risk group: 18 (29%) died or had reinfarction. Of the remaining 237 patients, only 9 (4%) had cardiac events. The 35 high risk patients with exercise induced angina pectoris or clinical contraindications to beta blockade were particularly at risk; 15 (43%) died or had reinfarction. This approach to risk stratification identified a small cohort of high risk patients in a large population of myocardial infarction survivors; it also identified a large group with a very low risk of subsequent cardiac events.

Routine exercise testing or thallium-201 scintigraphy for prediction of cardiac events post-myocardial infarction?

The efficacy of 12 lead exercise testing and rest/exercise 201Tl scintigraphy as indicators of coronary anatomy and prognosis was compared in 46 low risk survivors of acute myocardial infarction. The non invasive procedures were performed at discharge, and cardiac catheterization was performed six weeks post discharge. On exercise testing, ST depression in leads remote from the site of infarction was considered to indicate multivessel disease and reversible ischaemia. On 201Tl scintigraphy, a perfusion defect remote from the site of infarction indicated multivessel disease, while a defect which reperfused at rest indicated reversible ischaemia. During the mean follow-up of 13±3 months, 14(30%) patients experienced cardiac events. Thallium scintigraphy was a more sensitive, but less specific, indicator of multivessel disease than exercise testing. Both exercise testing and 201Tl scintigraphy had a similar sensitivity (79% vs 79%), specificity (78% vs 88%) and predictive accuracy (78% vs 85%) for predicting subsequent cardiac events. Thus, in our patient population, 201Tl scintigraphy could not be demonstrated to be superior to routine exercise testing in low risk patients post myocardial infarction.

Prognostic investigations after myocardial infarction: a comparison of radionuclide angiography and 201Tl scintigraphy.

The ability of pre-discharge thallium Tl201 scintigraphy and radionuclide angiography (RNA) to predict subseqeunt cardiac events was investigated in 46 apparently low-risk survivors of a first acute myocardial infarction. All patients underwent selective coronary arteriography at 3 months post-discharge. At the time of the initial investigation, half were beta-blocked, and thereafter, all patients were given prophylactic beta-blockade. During a mean follow-up period of 12±4 months, 14 patients (30%) experienced cardiac events, i.e. recurrent myocardial infarction (3 patients), angina pectoris (13 patients) and coronary surgery (8 patients). No patient died during the follow-up period. Of the 14 with subsequent cardiac events, 11 were identified by the presence of a reversible perfusion defect at 201Tl scintigraphy, while 7 exhibited abnormal left ventricular exercise reserve on RNA. The predictive accuracy of 201Tl (85%) for subsequent cardiac events exceeded that of RNA (56%; P<0.01) and of arteriographic multi-vessel disease (65%; P<0.05). The sensitivity of the non-invasive techniques was not influenced by beta-blockade at the time of investigation. Thus, 201Tl scintigraphy appears to be the more accurate technique for the assessment of the prognosis of apparently low-risk patients following myocardial infarction. The accuracy of the technique was not reduced by beta-adrenergic blockade.