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 patiénts, 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.     

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 translent 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.     

S-T segment elevation and coronary spasm in response to exercise

The prevalence rate of exercise-induced S-T segment elevation of 0.1 mV or greater in symptomatic patients is 3.0 to 6.5 percent in most studies. S-T segment elevation is associated with a more severe degree of myocardial ischemia than depression and frequently implies a high grade coronary stenosis in the vessel that supplies the site of ischemia. Leads V₄ to V₆ and bipolar lead CM₅ have been found to be relatively insensitive in detecting exercise-induced S-T segment elevation.

The pathogenesis of S-T segment elevation is different in three clinical patient subsets reviewed. In patients after infarction, the largest of the three subgroups, exercise-induced S-T segment elevation usually appears in leads with Q waves, is more common after anterior myocardial infarction and implies underlying akinetic or dyskinetic wall motion. Of patients with variant angina, 10 to 30 percent have during exercise S-T segment elevation that is most likely provoked by coronary arterial spasm. The natural history of variant angina is cyclic, and clinical observations and laboratory findings are dependent on particular phases in the disease process and treatment. Finally, 0.2 to 1.7 percent of symptomatic patiënts without infarction or variant angina have exercise-induced S-T segment elevation. Although most of the latter have fixed high grade coronary arterial stenoses at angiography, the exact pathogenetic mechanism of S-T segment shift in this patient group is not yet fully understood.     

The variant form of angina: diagnostic and therapeutic implications

A variant form of angina was diagnosed during electrocardiographic monitoring in hospital or during stress testing in five patients. One patient had a severe proximal coronary obstruction. Three patients also had proximal lesions of a coronary artery but of more questionable significance. One patient had a normal coronary arteriogram. An aortocoronary saphenous vein bypass was carried out in four patients with severe unstable angina and coronary lesions. One patient died at operation of unrelated causes and two patients suffered a postoperative myocardial infarction. One patient still has documented attacks of variant angina in spite of a patent vein graft. In these patients, the result of aortocoronary bypass appears less predictable than in patients with classic angina.     

Response to exercise early after uncomplicated acute myocardial infarction in patients receiving no medication: long-term follow-up

Cardiovascular function and prognosis have not been adequately defined early after an uncomplicated acute myocardial infarction in patients given no medication. Ninety such patients were studied with treadmill testing submaximally at 3 weeks and maximally at 8 weeks after infarction. The exercise heart rate, rate-pressure product and oxygen uptake were, respectively, 120 ± 17 beats/min, 179 ± 43 and 17.4 ± 1.0 ml/kg per min at 3 weeks and 157 ± 20, 271 ± 55 and 24.3 ± 3.7 at 8 weeks. Exercise variables at submaximal equivalent exercise work did not change from 3 to 8 weeks. At maximal exercise 15.6 percent of patients had S-T changes alone, 8.9 percent had angina alone and 12.2 percent had both. Patients were followed up for a mean of 23.7 months for complications—death, reinfarction, bypass grafting and progression to functional class III and IV. Complications occurred in 27 percent of patients with both angina and S-T changes, 29 percent of those with S-T changes alone, 25 percent of those with angina alone, 8 percent of those with ventricular arrhythmia alone, 12 percent of those with a normal 8 week treadmill test and in 17 percent of the group as a whole. Another 18 patients who were given no medication and whose course was uncomplicated could not perform a maximal 8 week treadmill test because of angina pectoris or S-T segment depression, or both, and 56 percent of these had long-term complications.In conclusion, these reference values serve as safe limits in performing treadmill testing early after acute myocardial infarction. S-T changes or angina, or both, and inability to complete a maximal 8 week treadmill test identify patients at risk for later complications even though these patients may have been considered to be in a low risk category clinically.     

Influence of partial sympathetic denervation on the results of myocardial revascularization in variant angina

Poor results of the aortocoronary bypass graft operation in the treatment of variant angina have been ascribed to recurrent vasospastic activity due to autonomic imbalance. Cardiac sympathetic denervation (plexectomy) may represent a rational approach in the prevention of vasospasm. To test the value of plexectomy in the treatment of variant angina, 31 patients were studied, 17 of whom (Group 1) underwent conventional coronary artery grafting whereas the remaining 14 (Group 2) underwent cardiac sympathetic denervation also. The 2 groups were similar with respect to age (54 +/- 8 versus 50 +/- 7 years), sex distribution (male/female ratio 12/5 versus 9/5), prevalence of coexisting effort angina (10 versus 12 patients), previous myocardial infarction (7 versus 4 patients), and duration of variant angina (3.3 +/- 5.4 versus 2.4 +/- 2.7 months). The left ventricular ejection fraction was comparable in both groups (60 +/- 11 versus 60 +/- 4%) as were left ventricular end-diastolic pressure (15 +/- 4 versus 13 +/- 5 mm Hg) and extent of coronary artery disease (65 versus 71% prevalence of multivessel disease). The average duration of follow-up was 23 +/- 15 months in Group 1 and 22 +/- 18 months in Group 2 (p = not significant [NS]). There were no operative deaths. Four patients, 2 in each group, had a perioperative myocardial infarction. Seven patients in Group 1 and 1 patient in Group 2 had recurrent variant angina. There was sudden death and 2 infarcts in Group 1. Actuarial curves showed the cumulative probability of recurrent variant angina to be significantly lower (p less than 0.05 and p less than 0.001 at 6 and 10 months, respectively) in Group 2. This study suggests that cardiac sympathetic denervation may prevent recurrent vasospastic activity in variant angina.     

Factors influencing the clinical course and the long-term prognosis of patients with variant angina

The purpose of this study was to clarify the factors influencing the clinical course and prognosis in variant angina. Also, the mechanism of acute myocardial infarction in variant angina is reviewed. The subjects were 110 patients with variant angina who, after the initial visit or admission, were observed for a period of at least 2 months, the average observation period being 68 +/- 49 months (range: 2 months-16 years). The incidence of acute myocardial infarction was 21.8% of these patients and 87.5% of the infarctions occurred within 1 month of the initial visit or admission. In variant angina, the average rate over 1 year was 2.2%; however, in classical angina the rate was 3.7% and in postinfarction angina 5.0%. The mortality rate was 5.5%, with death in the majority of cases occurring within 1 month, as in myocardial infarction. When treatment was stopped, spontaneous remission occurred in at least 26 of the 110 cases (23.6%). Beyond 3 months, the remission continued in 19 of these 26 cases. Seven cases had acute myocardial infarction in spite of the suppression of anginal attacks with administration of calcium antagonists. Apparently coronary spasm is the cause of anginal attacks, and the cause of acute myocardial infarction in patients with variant angina appears to be coronary thrombus formation.     

Detection of acute right ventricular infarction by right precordial electrocardiography

The value of 0.1 mV or greater of S-T segment elevation in at least one right precordial lead (V₄R to V₆R) in defining right ventricular myocardial infarction was assessed prospectively in 43 subjects (33 consecutive patients with enzymatically confirmed infarction of varying type and location, 4 patients with unstable angina and 6 healthy volunteers). Patients with acute myocardial infarction were studied with radionuclide ventriculography and technetium-99m stannous pyrophosphate myocardial scintigraphy 18.2 ± 14.3 (mean ± standard deviation) and 85.1 ± 18.0 hours after the onset of symptoms, respectively. Eleven patients (Group A: 9 patients with transmural inferior infarction, 1 with transmural inferolateral infarction and 1 with transmural anteroseptal infarction) demonstrated right precordial S-T segment elevation and 22 patients (Group B: 6 patients with transmural inferior infarction, 2 with transmural posterior infarction, 3 with transmural inferolateral infarction, 3 with transmural anteroseptal infarction, 3 with transmural extensive anterior infarction, 4 with subendocardial anterior infarction and 1 with unclassified infarction) did not. Right ventricular ejection fraction was significantly lower in Group A (0.47 ± 0.11) than in Group B (0.60 ± 0.12) (p < 0.01). Right ventricular total wall motion score was 63.8 ± 15.6 percent of normal in Group A versus 94.3 ± 8.5 percent in Group B (p < 0.001). Technetium-99m pyrophosphate uptake (2+ or greater) over the right ventricle occurred in nine patients (81.8 percent) in Group A and in one patient (4.5 percent) in Group B (p < 0.001). No patient with unstable angina and no healthy volunteer had S-T segment elevation in a right precordial lead. S-T segment elevation of 0.1 mV or greater in one or more of leads V₄R to V₆R is both highly sensitive (90 percent) and specific (91 percent) in identifying acute right ventricular infarction.     

Exercise testing early after myocardial infarction: Predictive value for subsequent unstable angina and death

Recently, modified treadmill exercise testing before hospital discharge has been reported to be safe in patients after uncomplicated myocardial infarction. Accordingly, the frequency of treadmill exercise-induced abnormalities and their prognostic value were evaluated in 130 patients with uncomplicated myocardlal infarction. Seventy-eight patients (60 percent) had one or more treadmill exercise-induced abnormalities; 42 had S-T segment depression, 35 had angina and 17 had an inadequate blood pressure response. During the mean follow-up period of 11 months, 27 patients experienced unstable angina, 12 had a recurrent myocardlal infarction and 10 died of cardiac causes. Compared with patients with no exercise-induced abnormality, patients with S-T segment depression, angina pectoris or an inadequate blood pressure response had a significantly greater (p < 0.001) incidence of all cardiac events during the follow-up period. Furthermore, unstable angina pectoris was significantly more frequent (p <0.005) in patients with S-T segment depression or angina pectoris. Finally, when the patients with ischemic treadmill abnormalities were combined with the patients exhibiting an inadequate blood pressure response, they had a statistically greater (p < 0.005) incidence of cardiac death than that of patients with no treadmill abnormalities. Therefore, these three abnormalities during modified treadmill exercise testing before hospital discharge identify patients with uncomplicated myocardial infarction who are at risk for a future cardiac event.     

Prinzmetal's variant angina: Hemodynamic and angiographic observations during pain

Hemodynamic and angiographic data obtained during pain from four patients with Prinzmetal's variant angina are reported. The left ventricular pressure-time index did not increase before or during attacks of angina in three of the four patients; left ventricular systolic performance was impaired during pain in all three. In one of these three patients left ventricular pressure-volume data obtained during angina suggested a reduction in diastolic compliance; in another, pain and S-T segment elevation were present during coronary arterial spasm. The fourth patient had an increase in both arterial blood pressure and heart rate before an attack; in this patient coronary arterial spasm could not be demonstrated during the period of pain and S-T elevation. The data presented suggest that hemodynamic factors that increase the myocardial Oxygen requirements are absent and that coronary arterial spasm is present in some, but not all, patients with variant angina.     

Clinical evidence suggesting vasospastic cause of myocardial infarction

To examine the vasospastic cause of myocardial infarction (MI) we studied 1) the incidence of rest angina before MI, 2) clinical features of postinfarction angina and 3) the occurrence of MI in variant angina. 1) Of 178 patients with MI, 60 (34%) experienced rest angina for 1 day to 10 years before the onset of MI. The incidence of rest angina was significantly higher in patients having milder coronary stenosis of 75% or less (15/30, 50%) than in others having severe stenosis of 90% or more (45/148, 30%), p less than 0.05. 2) Postinfarction angina with ST elevation was observed in 16 patients (9%) and ST elevation developed in leads with pathological Q waves in all patients. The incidence of postinfarction angina was significantly higher in those having milder coronary stenosis than in others having severe stenosis, (27% versus 5%, p less than 0.005). Patients with postinfarction angina experienced rest angina before MI more frequently (81%) than others (29%, p less than 0.005). Sublingual nitroglycerin was effective in relieving postinfarction angina attacks and oral calcium antagonist prevented attacks in all patients. 3) MI developed in 9 of 97 patients with variant angina. Six patients had transmural and 3, non-transmural MI. Pathological Q waves and/or coronary T waves appeared in leads where ST elevation was observed during anginal attack. In 7 patients MI developed when antispastic agents were not used and in 2, when angina persisted even under treatment with calcium antagonist. These data strongly suggest that the coronary spasm can be a cause of MI in some patients.     

Clinical predictors of angina following myocardial infarction.

To determine if angina following myocardial infarction could be predicted before hospital discharge we prospectively evaluated 219 consecutive patients admitted to the coronary care unit with acute myocardial infarction. Of the 166 who survived to one year, angina was present before infarction in 53 per cent and after infarction in 61 per cent. Angina did not recur postinfarction in 26 per cent of the patients who had angina before infarction. However, in 47 per cent of those without previous angina it developed postinfarction. Although postinfarction angina correlated with the presence of angina before infarction (p < 0.0005), it did not correlate significantly with age, sex, site of infarction, Killip class on admission nor the presence of a previous infarction.To improve our ability to predict angina after infarction we performed exercise tests to 5 metabolic equivalents (METS), or 70 per cent of age-predicted maximal heart rate, before hospital discharge on all patients less than 70 years old who were without chest pain within four days or without overt heart failure. Of the 105 patients exercised, 31 (86 per cent) of the 36 with positive tests had angina during the subsequent year compared to only 25 (36 per cent) of the 69 with negative tests (p < 0.001). Postinfarction angina occurred in 96 per cent (23 of 24) of the patients who had both angina before infarction and a positive test, but in only 26 per cent (10 of 39) of the patients with neither finding (p < 0.001).We conclude that the presence of angina prior to infarction and a positive limited exercise test performed before hospital discharge are predictive of angina following infarction. Myocardial infarction abolishes angina in a quarter of the patients, but angina develops postinfarction in nearly half of the patients who did not have angina previously.     

Long-term prognosis of vasospastic angina without significant atherosclerotic coronary artery disease

Long-term prognosis of 90 patients with vasospastic angina without significant coronary artery disease (less than 50% reduction in luminal diameter) was examined for a mean follow-up period of 4 years. All patients had episodes of angina at rest and were treated with calcium antagonists. One patient developed myocardial infarction and 2 died suddenly during the follow-up period. In the patient with myocardial infarction, there was an abrupt worsening of angina prior to the infarction despite therapy with a calcium antagonist. One of the sudden death patients discontinued his calcium antagonist before his death. Of the sudden death patients, one had ventricular tachycardia and the other had a complete atrioventricular block during an anginal attack. The incidence of such serious arrhythmias was higher (p less than 0.01) in sudden death patients (2/2) than that in survivors (6/88). The treatment with calcium antagonists reduced the severity and frequency of angina in all patients. These results suggest that long-term prognosis of vasospastic angina without significant coronary artery disease is good as characterized by the low incidence of myocardial infarction and death and the favorable response to treatment with calcium antagonists.     

Circadian variation in variant angina

Thirteen hospitalized patients with variant angina were studied to assess circadian variation in disease activity. Over 48 hours, all angina attacks were noted, a continuous Holter electrocardiogram was recorded and 2 ergonovine tests were performed 12 hours apart, 1 at 4 AM and the other at 4 PM. Only 2 patients gave a clearcut history of more frequent nocturnal or early morning attacks. During the study period, 1.8 +/- 1.6 AM and 0.62 +/- 1.2 PM angina episodes per patient were reported (p less than 0.02), but a circadian pattern was apparent in only 4 patients. However, Holter analysis revealed 5.3 +/- 13.8 AM and 2.6 +/- 8.5 PM episodes of ST elevation per patient (p less than 0.05) and 8.1 +/- 13.9 AM and 3.2 +/- 8.5 PM episodes of ST elevation, ST depression or T-wave pseudonormalization (p less than 0.01). Ten of 11 patients with Holter abnormalities had more frequent AM than PM attacks (p less than 0.01). ST elevation developed during all 13 of the 4-AM and 12 of 13 of the 4-PM ergonovine tests. In 10 cases the ergonovine threshold at which the attack occurred was lower in the morning, in no case was it lower in the afternoon, and in 3 patients the morning and afternoon doses were identical (p less than 0.01). Thus, circadian variation in disease activity both for spontaneous and provoked attacks is present in most patients with variant angina, even though it is often not clinically apparent.     

Comparison of coronary arteriographic findings during angina pectoris associated with S-T elevation or depression

Coronary arteriographic findings during an attack of angina pectoris associated with S-T segment elevation and angina associated with S-T depression were compared in 54 patients. Thirty-eight attacks with S-T segment elevation included 2 that were spontaneous, 6 induced by methacholine, 4 by epinephrine with or without propranolol, 9 by arm exercise, 5 by hyperventilation with or without Tris-buffer infusion and 12 by ergonovine maleate. Twenty-nine of the 38 attacks were associated with total occlusion, 8 with subtotal occlusion and 1 with diffuse narrowing of a major coronary artery caused by spasm.Twenty-six attacks with S-T segment depression included 3 induced by methacholine, 13 by arm exercise, 3 by hyperventilation with or without Tris-buffer infusion and 7 by ergonovine maleate. Eight of the 26 attacks were associated with subtotal occlusion and 9 with diffuse narrowing of a major coronary artery caused by spasm; 3 attacks were associated with total occlusion of a major coronary artery well supplied with collateral vessels and 2 with total occlusion of a small coronary branch caused by spasm. Four attacks were associated not with spasm but with fixed subtotal occlusion of a major coronary artery (3 attacks) or total occlusion of a major coronary artery receiving collateral vessels (1 attack).Only 2 of the 31 patients with S-T segment elevation had collateral vessels compared with 8 of the 16 patients with S-T segment depression (p < 0.001). It is concluded that angina pectoris associated with S-T segment elevation usually indicates more severe myocardial ischemia than angina associated with S-T segment depression.     

Transient S-T elevation detected by 24-hour ECG monitoring during normal daily activity

Seven out of 174 patients subjected to continuous 24-hour ECG monitoring because of atypical chest pain and/or palpitations were found to have transient S-T elevation. Two were diagnosed as suffering from neurocirculatory asthenia, three had myocardial infarction, and two suffered, most probably, from Prinzmetal's variant angina pectoris. We believe that the finding of transient S-T elevation is of special significance, because of the pathological and therapeutic implications, and that continuous ECG monitoring during unrestricted daily activities provides a unique opportunity to detect this condition more frequently.     

Long-term follow-up of verapamil and nitrate treatment for coronary artery spasm

Thirty-seven patients with coronary artery spasm and minor coronary atherosclerosis (34) or normal coronary arteries (3) were followed up long-term. All had angina at rest, 32 had nocturnal angina, and 13 had a positive exercise test with S-T elevation. Three had a previous subendocardial infarction; 10 had had serious arrhythmias, which caused syncope in 7. At last review, 21 months (range 1 to 61) after starting therapy, 27 patients continued on verapamil, 314 (120 to 600) mg/day; 4 who did not respond to verapamil were taking nifedipine, 58 (30 to 80) mg/day; and 16 were also taking isosorbide dinitrate, 41 (20 to 80) mg/day. Of the 31 patients on therapy, 21 were asymptomatic, 9 were improved (1 to 4 attacks/month), and 1 had an average of 8 anginal attacks/month; the remaining 6 had stopped therapy and 5 were asymptomatic a mean of 10 (3 to 18) months after stopping. The exercise test became negative in all 12 patients tested on therapy, although 3 required nitrates in addition to verapamil or nifedipine.In 26 supervised treatment withdrawals in the hospital, a mean of 15 (1 to 55) months on therapy, 10 developed angina in less than 48 hours. Angina recurred in all 6 unsupervised, patient-initiated withdrawals. Failure to stop smoking was positively associated with recurrence of angina on treatment withdrawal (p < 0.02).Long-term treatment of coronary artery spasm with verapamil or nifedipine together with isosorbide dinitrate was well tolerated and effectively relieved angina. No documented serious arrhythmias, syncopal episodes, myocardial infarction, or death occurred during follow-up.     

The predictive value of a strongly positive stress test in patients with minimal symptoms

The ability of a strongly positive stress test to predict left main coronary artery disease in people with suspected coronary artery disease but with minimal or no angina was investigated in 40 such patients. Nine had a history of myocardial infarction but no angina. Thirty-one had mild angina or a history of mild angina. The stress electrocardiograms were analyzed according to criteria known to be associated with left main coronary artery disease in moderately or severely symptomatic patients; (1) early S-T segment changes (stage I or II of exercise), (2) 2 mm or more S-T segment depression, (3) downsloping S-T segments, (4) associated exercise-induced hypotension, (5) prolonged S-T segment changes after the test (≥8 minutes) and (6) anterior and inferior S-T segment depression. The prevalence of left main coronary artery disease was 35 percent and that of any severe coronary artery disease 75 percent. The criterion of anterior and inferior electrocardiographic changes with exercise was most predictive of left main coronary artery disease (P < 0.01 by χ²). Exercise electrocardiography is useful in the prediction of left main or other severe coronary artery disease even when performed in patients who have minimal angina or in those who are asymptomatic after myocardial infarction.     

Natural history and prognosis of ischemic heart disease

Forty-four cases with myocardial rupture (33 with free wall rupture, 9 with interventricular septal perforation and 2 with papillary muscle rupture), all of which were ascertained by autopsy and/or at surgery, were analyzed. When the following 7 risk factors were actively managed in the acute stage of myocardial infarction, the incidence of myocardial rupture was significantly reduced: a) high blood pressure on admission, b) physical and emotional instability, c) recurrent chest pain, d) aged females, e) no history of angina or myocardial infarction, f) large myocardial infarction on ECG and g) the first 10 days after the attack of myocardial infarction. If cardiogenic shock occurs, surgery should be performed as soon as possible; if not, it should be delayed 3 weeks. The natural history of ischemic heart disease was analyzed in 400 medically-treated patients with significant coronary artery disease. They had been followed up continuously and periodically for more than one year. The prognosis of the patients with 3-vessel disease or left main trunk disease, those with poor left ventricular function (EF less than 30%) and of old age (greater than or equal to 60) and those who had a history of ischemic heart disease was poor. Follow-up study was done in 30 patients with variant angina. They often had life-threatening arrhythmias during attacks (8 ventricular tachycardia or ventricular fibrillation, 8 serious bradyarrhythmia). All patients with variant angina should be treated medically at first, and only patients with organic coronary artery disease and chest pain on effort in spite of the medical treatment should be considered as candidates for AC bypass surgery.     

Significance of spasm in the pathogenesis of ischemic heart disease.

The role of coronary arterial vasospasm in the pathogenesis of ischemic heart disease is reviewed on the basis of investigations carried out in our laboratory. Patients were selected because they had angina either at rest or both at rest and during exercise. With continuous hemodynamic and electrocardiographic monitoring of these patients, as well as thallium-201 scintigraphy and coronary arteriography during ischemic episodes, we were able to demonstrate a vasospastic origin for the attacks. During anginal episodes, electrocardiographic changes were variable, with S-T segment elevation, S-T segment depression, a rise in T wave potential and pseudonormalization of inverted T waves corresponding to various distributions of myocardial ischemia in different patients and even in the same patient at different times. Increases in hemodynamic variables that control myocardial oxygen consumption never preceded the onset of ischemic episodes, which challenges the theory that the limitation of a possible increase in flow caused by critical organic stenosis is the only cause of myocardial ischemia. In some patients in whom myocardial infarction developed, the lesion was always found in the same area in which the vasospastic phenomena had been seen angiographically. Vasospasm led to serious arrhythmias in some patients. We therefore believe that independent of atherosclerosis or superimposed on it, vasospasm plays an important role in producing myocardial ischemia—angina, myocardial infarction and possibly sudden death. Elucidation of its mechanisms will lead to more appropriate therapy.