Using a double-blind protocol, we investigated the use of propranolol in patients with coronary artery spasm as assessed by subjective and objective variables. Both low-dose (40 mg every 6 hours) and high-dose (160 mg every 6 hours) propranolol were administered. At both doses, the duration of angina attacks was significantly prolonged but the frequency was not. We conclude that propranolol at doses up to 160 mg every 6 hours as single therapy is frequently detrimental in angina pectoris due to coronary artery spasm and should not be used as the sole treatment of this disorder.

Exacerbation of vasotonic angina pectoris by propranolol.

A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome; 16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block. Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites. In contrast to findings in patients manifesting only typical exertional angina, the hemodynamic findings during spasm were those of a hypodynamic state. Left ventricular systolic pressure decreased from 138.9 ± 6.0 (mean ± standard error of the mean) to 113.2 ± 6.2 mm Hg; left ventricular end-diastolic pressure did not change significantly. Myocardial lactate extraction during spasm was invariably markedly reduced: −53.19 percent ± 15.44 ( P The respective roles of medical and surgical intervention are uncertain. Only 3 patients had a completely satisfactory pharmacologic response to nitrates alone or in combination with propranolol, and the condition of 5 others was partially improved; the remaining 21 patients were judged intractable to medical management. Coronary bypass surgery was performed as the ultimate recourse in 18 patients. However, short-term results reveal that only nine (50 percent) showed improvement, four (22 percent) had myocardial infarction during or after surgery and four (22 percent) died. These studies confirm that coronary arterial spasm is a definite pathogenetic factor in a variety of acute myocardial ischemic syndromes. The incidence and full clinical significance of this functional disorder remain to be determined.

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases

We compared patients with variant angina (ST-segment elevation during pain) who had normal or near normal coronary arteriograms (Group 1) with 20 in whom variant angina occurred in the presence of obstructive coronary lesions (Group 2). A long history of nonexertional angina without angina of effort or previous infarction was the rule in Group 1, whereas recent-onset unstable angina preceded by effort angina and infarction predominated in Group 2 (P<0.001). Normal electrocardiograms at rest, with ischemic ST-segment elevation in the inferior leads, and ischemia-induced heart block and bradycardia, characterized Group 1, whereas abnormal electrocardiograms, ischemic involvement of anterolateral leads and ventricular tachycardia or fibrillation were more common in Group 2 (P<0.001). Variant angina with normal coronary arteriogram generally has a benign course and is probably unrelated to atherosclerosis. (N Engl J Med 295:1343–1347, 1976)

Clinical Syndrome of Variant Angina with Normal Coronary Arteriogram

Twenty patients are described with the variant angina syndrome (recurrent angina at rest with S-T segment elevations occurring only during pain and no evolution of infarction). In contrast to patients previously reported on, all but one had progressive unstable angina before hospitalization. Angina was frequently associated with arrhythmias, including ventricular fibrillation (2 instances), ventricular tachycardia (4), frequent ventricular premature beats (5), atrioventricular block (4), sinus bradycardia (2), sinoatrial exit block (1) and supraventricular tachycardia (1). Seventeen patients had significant proximal stenosis of one or more coronary arteries with good distal vessels. Bypass surgery in 15 of these patients resulted in one noncardiac postoperative death, one perioperative infarction and relief of pain in all 14 survivors. After a 17 month mean follow-up period (range 4 to 38 months), all survivors are pain-free. Three patients had no significant coronary disease; one of these became asymptomatic with medical therapy, one continues to have angina and one died suddenly. Patients with normal coronary arteries could not be distinguished clinically or by electrocardiogram from those with severe obstructive lesions. This experience suggests that all patients with the variant angina syndrome should be studied by coronary angiography, and that most patients with significant fixed coronary lesions will do well after coronary bypass surgery.

Variant angina pectoris: Clinical and anatomic spectrum and results of coronary bypass surgery

Twenty-six patients with variant angina pectoris (VAP) were studied 1) to determine whether the degree of ST-segment elevation and R-wave changes correlate with the development of arrhythmias; and 2) to evaluate the relationship between the prevalence of arrhythmias, the severity of coronary artery disease, left ventricular function and wall motion. Serious arrhythmias were found in 12 patients (46%) (ventricular fibrillation in two, ventricular tachycardia in four, ventricular premature complexes [VPCs] [> 5 VPCs/min, multifocal and R-on-T phenomenon] in four, and secondand third-degree atrioventricular block in three). All twelve patients with arrhythmias had ST-segment elevation > 0.4 mV during VAP (range 0.4-1.6 mV). R-wave amplitude was compared before and during episodes of VAP and expressed as %AR. An increase in R 10% was seen in 10 of 12 patients with arrhythmias (group 1) and in only six of 14 patients without arrhythmias (group 2) (p < 0.05). Twenty-three of the 26 patients underwent coronary angiography and ventriculography, and one was examined by autopsy. Sixteen patients in this group had single or multiple high-grade obstructive lesions, while the remaining eight had normal coronary arteriograms. Arrhythmias were more common in the group with coronary obstructive disease (66%) than in the group with normal coronary arteriograms (44%). There was no significant difference between patients with arrhythmias (group I) and those without arrhythmias (group 2) in the coronary arteriographic score or left ventricular ejection fraction. The data suggest that arrhythmias occur frequently during VAP and correlate well with the degree of STsegment elevation and %AR. In patients with VAP, arrhythmias are not contingent upon preexisting coronary artery disease or left ventricular ejection fraction, and are more commonly detected in patients with normal coronary arteriograms.

Arrhythmias in variant angina pectoris. Relationship of arrhythmias to ST-segment elevation and R-wave changes.

Prinzmetal's variant angina: A clinical and electrocardiographic study

An experimental model of a prolapsing left atrial tumor mass has been utilized In dogs to study the hemodynamic events of the cardiac cycle and the cineangiographic and echocardiographic manifestations of this condition. The characteristic ventricular notch has been correlated with the timing of the expulsion of the simulated tumor mass from the left ventricle to the left atrium. The early notch seen with small simulated tumors delays aortic ejection by 0.02 to 0.03 second and results in abbreviated aortic ejection time and minimal distortion of the E-F slope of anterior mitral leaflet motion in the echocardiogram. Larger masses lead to late ventricular notching, transiently interrupt aortic flow and may displace the anterior mitral leaflet until It impinges on the interventricular septum in mid-diastole and at the onset of systole. A transient systolic Increment of coronary flow is observed after expulsion of the tumor from the left ventricle into the left atrium. There is an echo-free interval immediately after opening of the mitral valve, indicating that tumor motion lags perceptibly behind the initial blood flow through the mitral orifice. The sudden expulsion of the mass from the ventricle to the atrium early in systole represents an in vivo example of the quick release phenomenon.

Monty Bodenheimer

Papers

Prinzmetal's variant angina: A clinical and electrocardiographic study

Simulated left atrial tumor: A hemodynamic, echocardiographic and cineangiographic study