Provocative testing with ergonovine to assess the efficacy of treatment with nifedipine, diltiazem and verapamil in variant angina.
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Biomedical subjects
Publications and source records attributed to D D Waters.
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This study describes the results of ergonovine testing in 100 consecutive patients who underwent this procedure in a coronary care unit. All patients had recently undergone coronary arteriography. A bolus injection of ergonovine was administered at 5 minute intervals in the following doses (mg): 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4. The criterion for a positive test was the appearance of S-T elevation greater than 1 mm. The test was positive in all 17 patients known to have variant angina and in 18 (40 percent) of 45 patients who had a history of chest pain judged strongly suggestive of variant angina but who had no electrocardiogram recorded during pain. Of 38 patients with a history of chest pain classified as not entirely typical of variant angina, only 1 (2.6 percent) had a positive test. Of the 64 patients with a negative ergonovine test, 47 had chest pain and 25 had nausea but none had more serious complications. Ventricular arrhythmia accompanied S-T elevation in 18 of the 36 patients with a positive test but occurred in only 4 of the 64 with a negative test (p < 0.0005). No patient needed treatment with antiarrhythmic drugs. Four of the 36 patients with a positive test had serious complications: severe transient hypotension (2 patients), recurrent episodes of angina with S-T elevation (1 patient) and a subendocardial infarction (1 patient). Thus, ergonovine testing is useful in patients with a typical clinical history of variant angina but without an electrocardiogram recorded during pain. In this study, a small but definite incidence of serious complications occurred during a positive test.
A young man with a single left coronary artery and refractory variant angina is described. Spontaneous coronary artery spasm developed during coronary arteriography at the site of a 50% fixed left anterior descending coronary artery stenosis. Frequent episodes of rest angina with transient ST segment elevation persisted in hospital in spite of treatment with three different calcium antagonist drugs. Symptoms disappeared only when the combination of nifedipine, diltiazem, isosorbide dinitrate, and nitroglycerin ointment were given. Ergonovine testing was used to objectively assess the response to treatment.
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Variant angina was diagnosed after coronary artery bypass surgery in six patients over a 22-month period. Although all six patients had at least occasional angina at rest preoperatively, all but one had predominantly exertional angina. After surgery, rest angina with transient ST-segment elevation appeared in all six after an asymptomatic interval of 1 week to 4 years. In two patients the involved artery had not been bypassed, in two patients it was perfused by a patent graft and in two patients the graft to the involved vessel was occluded. Treatment with calcium antagonist drugs (four cases) or isosorbide dinitrate (one case) eliminated symptoms; one patient spontaneously became asymptomatic. The diagnosis of variant angina should be considered when rest angina occurs after bypass surgery, particularly if exertional angina is absent and grafts are patent.
In this study, the systemic and coronary hemodynamic changes associated with the administration of diltiazem, a recent calcium antagonist, were evaluated in three different situations as follows: following a 200 microgram/kg intravenous bolus of the drug in 12 open-chest anesthetized dogs; following two successive intravenous infusions of diltiazem (15 microgram/kg/min and 30 microgram/kg/min), each for a period of ten minutes, in eight patients with angina pectoris investigated by coronary arteriography; and following a single oral dose of 120 mg of diltiazem in 17 patients undergoing hemodynamic monitoring in the coronary care unit after a recent myocardial infarction. Diltiazem was found to be a coronary vasodilator acting on the large coronary arteries and on collaterals. Its effects on myocardial oxygen requirements were variable; as a rule, the predominant effect was a drop in systemic vascular resistance or in heart rate. When systemic vascular resistance changed little, heart rate tended to decrease significantly; however, when systemic vascular resistance decreased notably, heart rate remained unchanged because of a relfex attempt to increase systemic blood pressure. Cardiac performance and left ventricular end-diastolic pressure were not affected and this lack of change in cardiac inotropism may confer and advantage to diltiazem over other calcium antagonistic drugs in patients with coronary heart disease.
The hemodynamic effects of a single oral dose of 20 mg of nifedipine were studied in 21 stable patients after an acute myocardial infarction before withdrawal of Swan-Ganz and intra-arterial catheters. The drug appears safe, and no significant untoward effects were noted. Significant hemodynamic changes were present between 15 and 120 minutes after ingestion with a peak at 60 minutes. Mean arterial pressure decreased from 81+/-2.7 (SEM) to 71+/-2.3 mm Hg (P<0.001), and systemic vascular resistances decreased from 1438+/-88 to 1144+/-63 dynes/sec/cm5 (P<0.001). Cardiac index increased from 2.7+/-0.1 to 3.1+/-0.1 L/min/sq m (P<0.01) and heart rate from 79 +/- 3 to 82 +/- 4 (P<0.01). The pressure-rate product decreased from 10.3 X 10(3) to 9.5 X 10(3) (P<0.05), and pulmonary wedge pressure was unchanged from 12 mm Hg. The hemodynamic changes were similar whether patients were receiving propranolol or not. The afterload reducing effect was potentially most beneficial in the subgroup of patients with depressed left ventricular function where cardiac index increased by 20 percent.
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The prognostic value of a limited treadmill exercises test performed one day before hospital discharge after acute myocardial infarction was studied in 210 consecutive patients who had no over heart failure and had been free of chest pain for at least four days. No complications occurred. During a one-year follow-up period 28 of 43 patients (65 per cent) who had chest pain during the test reported angina, as compared with 60 of 167 (36 per cent) who had no chest pain during test (P less than 0.001). The one-year mortality rates were 2.1 per cent (three of 146) in patients without changes in the S-T segment during exercise and 27 per cent (17 of 64) in those with depression of the S-T segment (P less than 0.001). Sudden death occurred in one of 146 (0.7 per cent) patients who showed no change in the S-T segment and in 10 of 64 (16 per cent) with depression of the segment (P less than 0.001). Thus, a limited treadmill exercise test performed before hospital discharge after acute myocardial infarction is safe and can predict mortality in the subsequent year.
A patient with Prinzmetal angina and ST segment elevation in the anterior ECG leads became asymptomatic after a 50% left anterior descending coronary artery stenosis was bypassed. However, seven years later Prinzmetal angina recurred but with ST segment elevation in the inferior ECG leads. Although the coronary bypass graft had remained patent, the proximal and distal left anterior descending coronary artery was occluded. No significant stenosis was present in the right coronary artery. Perhexiline maleate controlled his symptoms but when the drug was stopped because of side effects an acute inferior myocardial infarction occurred.
This report describes a 70-year-old woman with biventricular failure following an anteroseptal infarction complicated by interventricular septal rupture. Treatment with nitroprusside followed by oral hydralazine eliminated the failure and reduced the shunt from 2.75 to 1 to 1.7 to 1. She is asymptomatic post-discharge. Chronic medical therapy including oral vasodilators may be an acceptable alternative to surgery in a small minority of patients with this complication of myocardial infarction.
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