Jadwiga Szlachcic

Is Variant Angina the Coronary Manifestation of a Generalized Vasospastic Disorder

IN VARIANT angina, myocardial ischemia is caused by transient coronary-arterial spasm.1 , 2 Although altered adrenergic activity has been proposed as the cause of coronary spasm3 , 4 and high circu...

Ergonovine testing to detect spontaneous remissions of variant angina during long-term treatment with calcium antagonist drugs

A subgroup of 22 patients with variant angina who had responded well to calcium antagonist drugs were studied to determine if ergonovine testing could help assess the need for continued therapy. Before treatment all 22 patients exhibited angina with S-T elevation during ergonovine testing done in the coronary care unit according to a previously described protocol with sequential ergonovine doses of 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4 mg administered at 5 minute intervals. After 9.4 +/- 4.7 (range 1 to 24) months of treatment (nifedipine 7 patients, diltiazem 3, verapamil 8, perhexiline 3, nifedipine and diltiazem 1), all patients were free from anginal attacks. Medication was discontinued and ergonovine testing repeated 24 to 48 hours later (3 weeks for perhexiline). In 12 of the 22 patients, angina or S-T segment shifts did not occur during the second ergonovine test to a maximal dose of 0.4 mg. Treatment was not restarted in these patients and all 12 remain free of variant anginal attacks 4.2 +/- 2.9 (range 1 to 13) months later. In seven patients angina and S-T elevation occurred during the second ergonovine test, in the same electrocardiographic leads as during the test before treatment. In three patients the ergonovine test induced angina with S-T depression in the leads where S-T elevation had occurred during the previous test. Treatment was reinstituted in these 10 patients with a positive test. No complications resulted from ergonovine testing in any patient. We conclude that in many patients with variant angina, symptoms will disappear spontaneously and the ergonovine test will revert to negative. Treatment with calcium antagonist drugs can probably be safely discontinued in some patients with variant angina; ergonovine testing appears to be helpful in identifying such patients. Longer periods of follow-up are required to confirm that symptoms do not recur.

Provocative testing with ergonovine to assess the efficacy of treatment with nifedipine, diltiazem and verapamil in variant angina.

Twenty-seven hospitalized patients with typical variant angina were studied to evaluate the efficacy of nifedipine, diltiazem and verapamil in blocking ergonovine-induced episodes of variant angina and to determine if the results of incremental ergonovine testing during treatment correlated with the clinical response. The ergonovine test result was positive (that is, with S-T elevation) in all 27 patients during a control period without medication. During a subsequent treatment period with nifedipine (20 mg every 6 hours), the test result converted to negative at the maximal ergonovine dose of 0.4 mg in 11 patients, remained positive but at two or more ergonovine dose levels higher than those during the control test in 11, and was unimproved in 5 other patients. Identical results occurred when ergonovine tests were repeated during treatment with diltiazem, 120 mg every 8 hours. During treatment with verapamil, 160 mg every 8 hours, the test result was negative in 8 patients, positive at two or more ergonovine dose levels higher than those during the control test in 10 patients and positive at a dose similar to that of the control test in the remaining 9. n nVariant anginal attacks occurred during none of the 30 drug treatment periods associated with a negative ergonovine test, during only 1 of the 24 treatment periods associated with a positive test at high ergonovine dose levels (0.2 to 0.4 mg), and during 12 of the 27 treatment periods with a positive test at 0.1 mg or less of ergonovine (p <0.001). During the 7 month (range 1 to 15) follow-up period, 14 of 15 patients treated with a drug that had converted the ergonovine test response to negative remained angina-free, compared with only 4 of 12 treated with a drug associated with a persistently positive test (p <0.01). n nThus, nifedipine, diltiazem and verapamil can partially or totally block ergonovine-induced angina and S-T elevation in most patients with variant angina. The results of ergonovine testing during treatment with these drugs correlate with the clinical response to therapy.

Ergonovine testing in a coronary care unit

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.

Clinical characteristics of patients with variant angina complicated by myocardial infarction or death within 1 month

Of 132 consecutive patients hospitalized during a 5 year period because of active variant angina, 18 died or had a myocardial infarction within 1 month. In 4 patients an episode of pain and S-T elevation unrelieved by calcium antagonist drugs and intravenous nitroglycerin persisted for more than 1 hour, inducing cardiogenic shock and death before the appearance of Q waves and elevated serum enzyme levels. In the other 14 patients myocardial infarction developed in the electrocardiographic leads in which S-T elevation had occurred during attacks of variant angina. Clinical features were not helpful in distinguishing the 18 patients with complications from the other 114. Angina at rest had been present for less than 1 month in 7 of the 18 patients with infarction compared with 31 of 114 in the other group (probability [p] not significant [NS]). Before infarction the artery presumed to be perfusing the involved territory contained a fixed stenosis of 70 percent or more of luminal diameter in 8 of the 14 patients with complications who had coronary arteriograms compared with 50 of 112 in the other group (p = NS). In 13 of the 18 patients, complications occurred in spite of large doses of calcium antagonist drugs. In 11 of these 13, attacks of variant angina were monitored for 3 to 17 days both before and during treatment. All 11 had fewer attacks with treatment and 5 had no attacks. Daily attacks per patient decreased from 4.6 +/- 4.3 to 0.5 +/- 0.7 (mean +/- standard deviation) (p less than 0.01). It is concluded that in variant angina of recent onset myocardial infarction occurs frequently and unpredictably. Myocardial infarction may occur in the absence of severe fixed lesions and in spite of apparent clinical improvement with administration of calcium antagonist drugs.