Primary angina pectoris: significance of clinical, bicycle ergometric and coronarographic data in the prognosis of ischemic heart disease remission

By the first year of a follow-up, spontaneous clinical remissions (no anginal and ischemic episodes as evidenced by Holter monitoring, negative bicycle ergometric tests) in 52 (26%) out of 200 patients with primary angina pectoris. Possible predictors such as clinical signs, bicycle ergometric and coronary angiographic parameters were examined. A multifactorial stepwise discriminant analysis showed that the independent predictors of the clinical remission were heart rate and exercise power attained on bicycle ergometry, number of diseased coronary artery segments with 70% of more stenoses, disease pattern in the first month, existing and prior smoking, and myocardial infarction in the first 3 months of the disease onset.     

Results of the conservative treatment of patients with unstable stenocardia

The results of conservative treatment were reviewed in 100 patients with unstable angina. In hospital, the condition was stabilized in 73% of patients, acute myocardial infarction developed in 24%, and fatal outcomes resulted in 7%. In the first year since the diagnosis of unstable angina was made, the incidence of acute myocardial infarction was 32%, with 14% mortality. Further prognosis for unstable angina was basically similar to that for chronic coronary heart disease. A clear-cut correlation was demonstrated between the frequency of anginal attacks, total ST displacement, the severity of coronary-bed and myocardial lesions and the incidence of acute myocardial infarction and death.     

The long-term outcome of patients who suffered and survived an acute myocardial infarction in the midst of recurrent attacks of variant angina

Twenty-one patients, ranging in age between 28 and 59 years, who survived hospitalization for an acute myocardial infarction in association with repetitive attacks of variant angina, were followed prospectively for 59.1 +/- 5.1 (SEM) (range 17-120) months. Four patients died, one of sudden death 17 months after admission, one of congestive heart failure at 33 months, and two of cancer at 43 and 45 months of follow-up. Three patients had four new myocardial infarctions at 22, 32, 33, and 61 months of follow-up. Six patients were readmitted for angina or other cardiac reasons. Twelve patients remained asymptomatic throughout the follow-up and one more patient was asymptomatic before and after his recurrent myocardial infarction. No relapse of variant angina was documented. Thus, the long-term course of patients with variant angina culminating in acute myocardial infarction is relatively benign, despite the highly unstable features of their initial presentation.     

Long-term prognosis of “variant” angina with medical treatment

One hundred thirty-eight patients with “variant angina” were followed up for periods of 2 to 8 years. All patients had a history of angina at rest, and 42 percent also had exertional angina. Normal coronary arteries were found in 9 of the 107 patients who underwent coronary arteriography; the remainder had stenosis greater than 50 percent in diameter of at least one major vessel. Coronary vasospasm was demonstrated in all 37 patients studied with coronary arteriography during angina at rest. Twenty-eight patients had acute myocardial infarction and five patients died within 1 month of admission to hospital. Of the 133 surviving patients, 120 were treated medically and 13 underwent coronary arterial surgery. In the medically treated group, only seven patients died and only four had acute myocardial infarction during the remainder of the follow-up period. Symptoms became less frequent and less severe; approximately 50 percent of the patients remained completely asymptomatic for at least 12 months by the end of the 4th year. Death, acute myocardial infarction and persistence of symptoms were more frequent in those patients with more severe coronary atherosclerotic disease although, even in this group, the overall incidence of death and acute myocardial infarction was small. It is concluded that the prognosis of patients with “variant” angina receiving appropriate medical therapy is reasonably good after the acute phase, even in the presence of severe coronary atherosclerosis.     

New-onset stenocardia: the detection of clinical variants of ventricular arrhythmia

A total of 130 patients with angina of new onset (ANO), i.e. first three months after the onset of anginal attacks, were investigated by means of 24- and 48-hour Holter's electrocardiographic monitoring. All the patients underwent selective coronarography. Ventricular arrhythmias (isolated and paired extrasystoles, ventricular tachycardias) and their correlation to acute myocardial ischemia were analysed. Ventricular tachycardia was more common in unstable ANO, as compared to stable angina, and in patients with signs of coronary spasm, as compared to anginal patients showing no such signs. The combination of unstable angina with signs of coronary spasm is the least favorable ANO variant in terms of the risk of grave ventricular arrhythmias.     

The clinical presentation of acute myocardial infarction predicts the severity of the lesion in the infarct-related artery

The purpose of this study was to correlate the clinical presentation of acute myocardial infarction with the patency rate and degree of residual stenosis of the infarct-related artery. One hundred and forty-five patients who underwent angiography after acute myocardial infarction were divided into two groups according to the time of onset of anginal pain prior to infarction. Group A comprised 119 patients, (109 men, 10 women, aged 53 +/- 9 years) who did not experience any symptoms before infarction or with anginal pain of less than 5 days preceding myocardial infarction, and group B 26 patients (all men, aged 54 +/- 12 years) with previous stable angina for greater than or equal to 1 year. Twenty-two days after acute myocardial infarction, 68 of the 145 patients (47%) had a patent infarct-related artery: 64 patients in group A (54%) and four patients in group B (15.4%) (P less than 0.006). Furthermore, 19 patients in group A (16%) and none in group B had less than 70% stenosis in the infarct-related artery (P less than 0.02). The mean residual stenosis in group A was 83.3 +/- 27% whereas in group B it was 98.1 +/- 4% (P less than 0.001). These results indicate that a long-standing history of angina before acute myocardial infarction is often related to a severe pre-existing atheromatous obstruction, which would account for the higher incidence of total coronary occlusion observed in group B. Thus angina of recent onset preceding acute myocardial infarction is associated with a higher patency rate of the infarct-related artery and frequent less than 70% residual lesions.     

Assessment of plexectomy in the treatment of severe coronary spasm in patients with normal coronary arteries

Surgical denervation of the heart by plexectomy was performed in 3 patients with variant angina, documented coronary spasm, and normal findings on coronary angiography. In all cases, spasm had already been responsible, preoperatively, for myocardial infarction and recurred thereafter in another territory despite medical therapy with a combination of nitrates and calcium antagonists. Plexectomy was performed using a standardized technique. The effectiveness of surgical suppression of cardiac autonomic innervation was confirmed postoperatively by pharmacologic tests. In 2 patients inferior myocardial infarction developed in the early postoperative period; in the third patient, coronary spasm recurred 3 weeks after plexectomy. Thus plexectomy, despite an adequate suppression of autonomic innervation, was ineffective in all cases and may even have been harmful in 2 patients. These data contradict the good results obtained by plexectomy associated with aortocoronary bypass in patients with variant angina and fixed stenotic coronary arteries. This discrepancy may be accounted for by a different pathophysiologic mechanism of vasospasm in normal coronary arteries and in diseased arteries at the site of the atheromatous stenosis. Thus, plexectomy should not be considered in the treatment of vasospasm involving normal coronary arteries, even if medical therapy fails to achieve satisfactory control of variant anginal attacks.     

Regional myocardial perfusion in ischemic heart disease assessed by myocardial contrast echocardiography

Myocardial contrast echocardiography is a new cardiovascular imaging technique that can be used to evaluate regional myocardial perfusion. Regional myocardial perfusion was studied in 12 patients with normal coronary arteries, 14 patients with old myocardial infarction, four patients with acute myocardial infarction, and 15 patients with effort angina. Conventional two-dimensional echo imaging was obtained during intracoronary injections of relatively small volumes (2 ml) of agitated Urografin-76. The echo intensities were measured before and after injecting contrast agents and the subtraction images were composed by a high-speed image processor (NEXUS 6400). Clear myocardial images were obtained in 10 of 12 the patients with normal coronary arteries, and they reflected well the epicardial arterial architecture by coronary angiography. In cases of old myocardial infarction, the infarcted areas appeared as contrast defects in seven and as slightly enhanced areas in three of the 10 patients. In cases of acute myocardial infarction, contrast defect areas in the myocardial images were less in two cases of successful early coronary thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). However, contrast defects remained unchanged despite good recanalization in one case of delayed PTCA. In cases of effort angina, anginal attacks were successfully induced by rapid atrial pacing in six of the 15 patients. In four of the six patients, contrast enhancement in myocardial imaging during anginal attack decreased more in the endocardial than in the epicardial myocardium, possibly reflecting subendocardial ischemia. It is concluded that this technique can identify regional myocardial perfusion, which is not revealed by coronary angiography, and it is therefore useful for the clinical analysis of ischemic heart disease.     

Treatment of chronic stable angina: follow-up study with nifedipine gastrointestinal therapeutic system. SENIOR Study Group

OBJECTIVE: To gather information about efficacy and tolerability of nifedipine GITS in patients with stable angina, and its impact on the patient quality of life. PATIENTS AND METHODS: 1076 patients of both sexes (63.5 +/- 12.8 year old) with stable angina (classes I to III of the CCVS) and evidence of coronary disease (43.3% previous myocardial infarction) were included. The treatment with nifedipine GITS 30-60 mg/day (monotherapy or combination) lasted for 6 months. The study variables were: weekly rate of anginal attacks, short-acting nitrate consumption, changes in the antianginal drug treatment, tolerability, and changes in the questionnaire score concerning the quality of life. RESULTS: A decrease in the number of the anginal attacks and in the short-acting nitrates consumption by 80.7% and 83.3%, respectively (both, p = 0.001), was found. Furthermore, the proportion of patients experiencing anginal attacks the week before the assessment visit fell from 71.7% to 10.9% (p < 0.001). At the end of the study, a remarkable decrease in the use of other antianginal medications was seen. Side effects were reported by 10.9% of the patients, 2.7% of which were withdrawn from the study for this reason. A favourable change in the patient quality of life was also noted. CONCLUSION: In patients with stable angina, nifedipine GITS is an effective, safe and well tolerated drug that remarkably enhances the patient quality of life.     

Myocardial infarction indicated by angina pectoris of effort or by brief attacks of angina of rest,with remarks on premonitory pain

This is a report of sixteen cases in which there was clinical and laboratory evidence suggestive of myocardial infarction, although characteristic, severe, and protracted anginal attacks were lacking. In nine cases, myocardial infarction was indicated by the sudden onset or aggravation of angina of effort; in seven instances, it was clinically signalized by brief attacks of angina of rest, lasting up to twenty minutes. Similar observations are quoted from the literature.The seriousness of such atypical anginal manifestations is often unrecognized, and proper management of the patients is neglected. Sudden death is frequent among this group of cases. A painstaking history, including an accurate estimate of the functional capacity of the heart and a comparison of present and past performances, furnishes the most significant diagnostic data. An increase in the sedimentation rate is often a more sensitive index of myocardial necrosis than are electrocardiographic changes. Lack of the latter should never be considered as conclusive evidence against serious myocardial involvement.Anginal pain like that in the cases in our report has often been designated as “premonitory pain,” which precedes the development of “actual myocardial infarction.” Our own experience and reports in the literature prove that “premonitory pain” is not invariably followed by typical anginal attacks signifying myocardial infarction. Moreover, “premonitory pain” is often by itself associated with evidence of myocardial necrosis. Hence, it appears that the distinction between “premonitory pain” and “actual myocardial infarction” is inappropriate. A sudden onset or aggravation of angina of effort, or brief attacks of angina of rest indicates progressive coronary insufficiency, and is in the majority of cases, associated with ischemic myocardial necrosis.     

Clinical and functional characteristics of patients with ischemic heart disease in long-term remission of angina pectoris]

Long-term (5-15-year) prospective surveys of 171 angina patients have yielded clinical, coronarographic, and bicycle ergometric criteria for predicting the favourable course of the disease. A prolonged (at least 3 years) clinical anginal remission was observed in 43 (25.1%) patients. The patients had typical features: a short (less than 6-9 months) history of classical angina, the age at the onset of CHD under 50 years; high performance during bicycle ergometric test, lack of angina after sustained so-called "accomplished" myocardial infarction. The coronarograms of patients with a long-term anginal remission most frequently displayed severe stenosis or occlusion of "unsafe" site of a large coronary artery. The duration of remission was less than 10 years if atherosclerosis also affected the remaining coronary arteries. That of remission was more than 10-15 years, if the remaining coronary arteries proved completely intact.     

Pure arrhythmic form of the pre-infarction syndrome or spasm responsible for myocardial necrosis

A 74 years old man was admitted as an emergency for syncopal attacks due to recurrent ventricular fibrillation (VF). These attacks were observed at the height of myocardial ischaemia as shown by ST elevation in Leads II, III and RV without associated anginal pain. Inferior myocardial infarction occurred during recurrent VF on the 4th day; the outcome was favourable. Coronary angiography was performed on the 10th day and showed double vessel disease; ergometrine (0.2 mg) induced anginal pain and ST elevation in Leads II, III and AVF. A good clinical result was obtained by calcium antagonists with an 18 months follow-up. Coronary spasm, documented in this case by the ergometrine provocation test, is now recognised as a cause of resting angina, effort angina and also some cases of myocardial infarction. This report suggests that coronary spasm may also induce apparently isolated severe ventricular arrhythmias without associated chest pain, which raises the question as to whether arrhythmias induced by spasm could play a primary role in aggravating myocardial ischaemia, leading to myocardial infarction.     

Autopsy findings of the coronary arteries of variant angina with Raynaud's phenomenon of the tongue

A 42 year old man with variant angina occasionally associated with syncopal attacks died of acute myocardial infarction 17 months after the onset of angina. Prior to the onset of variant angina, he had Raynaud's phenomenon of the tongue for 2 years. Both Valsalva maneuver and hyperventilation could repeatedly provoke chest pain and ST segment elevation in leads II, III and aVF. The infusion of prostaglandin E1 at a rate of 0.05 microgram/kg/min, was able to prevent the attack of variant angina induced by these maneuvers. Although coronary angiography performed 15 months prior to death revealed no organic lesions except for complete spastic occlusion at segment 1 following intravenous ergonovine, autopsy revealed marked intimal proliferation and accumulation of abundant glycosaminoglycans in three coronary vessels, as well as in small and muscular arteries of other organs. This suggests that a rapid systemic progression of narrowing due to proliferation of the intima might occur in some cases of variant angina.     

Increased fibrinopeptide A during anginal attacks in patients with variant angina

It is not known whether coronary vasospasm is associated with coronary thrombosis. In this study, plasma levels of fibrinopeptide A during anginal attacks in 24 patients with variant angina were examined. A hyperventilation test was used to induce angina. Hyperventilation induced angina and ST segment elevation (AST: 0.32 +/- 0.14 mV, p less than 0.01) in eight patients with variant angina. Fibrinopeptide A increased from 0.75 +/- 0.27 at control to 7.8 +/- 4.4 ng/ml (p less than 0.01) during anginal attacks in these eight patients. In addition, four patients had spontaneous attacks of angina; they also had elevated levels of fibrinopeptide A during attacks (from 2.0 +/- 1.2 at control to 21.9 +/- 18.0 ng/ml [p less than 0.01] during attacks). Hyperventilation did not induce either angina or ST segment elevation in 12 of the patients with variant angina. Fibrinopeptide A levels did not change with hyperventilation in these patients. To determine whether elevated plasma levels of fibrinopeptide A were associated with angina, the plasma levels of fibrinopeptide A were examined during exercise-induced angina in seven additional patients with stable effort angina. They all developed angina with treadmill exercise; however, plasma fibrinopeptide A did not change. Therefore, only the patients with variant angina demonstrated elevated levels of fibrinopeptide A during anginal attacks. These findings suggest that coronary vasospasm associated with myocardial ischemia may induce stasis of blood, resulting in fibrinogen-fibrin conversion in the coronary vessels.     

Prognostic implications of early spontaneous angina after acute transmural myocardial infarction

We investigated the clinical, electrocardiographic and hemodynamic features and the prognostic implications of early spontaneous angina in 31 consecutive patients after acute myocardial infarction. Re-elevation of ST segments in the area of infarction occurred during angina and during reinfarction in all but one patient. Depression of ST segments, when present during pain, involved the same leads as in the acute infarction. Blood pressure and double product tended to increase during pain in 23 patients. The magnitude of this change, however, often varied from crisis to crisis and there were no increases in these parameters in one or more attacks in 15 patients. Sublingual nitroglycerin, 1.0 mg, failed to relieve one or all anginal episodes in 17 of the 28 patients in whom it was given. In-hospital mortality rate was 10% (3/31) and always followed reinfarction. In-hospital reinfarction rate was 16% (5/31) and followed a larger number of anginal crises (7.2 +/- 1.3 vs 3.0 +/- 2.1, P less than 0.001) and a higher incidence of transient hypotensive episodes than in the rest of patients (3/5 vs 3/26). Three additional patients died after discharge. Of the remaining 25 patients and during a follow-up of 26 months (16-34) only one developed reinfarction. Early resting angina after a transmural infarction is almost invariably associated with ECG evidence of ischemia in the leads overlying the infarcted zone. The inconsistent changes in blood pressure and heart rate during pain render these hemodynamic changes an unlikely cause of this form of angina. While postinfarction angina did not carry a grave short- or long-term prognosis, patients with recurrent crises demonstrated as high a risk of reinfarction and death as those with spontaneous hypotension.     

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.     

Nifedipine therapy for Prinzmetal's angina.

A case is described in which nifedipine, a new coronary vasodilator, was effective in relieving attacks of Prinzmetal's angina unresponsive to conventional therapy. The extreme frequency of the anginal attacks provided evidence that lower doses of nifedipine lost their effectiveness approximately 4 hours after administration. A month after initiation of nifedipine, nitrates were withdrawn since they had been ineffective in controlling the attacks. A myocardial infarction occurred immediately, presumably due to coronary spasm.     

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.     

Continuous electrocardiographic recording in Prinzmetal's variant angina pectoris. A report of four cases

Four patients with Prinzmetal's variant angina pectoris were subjected to continuous electrocardiographic recording. In three of them several episodes of ST segment elevation unaccompanied by pain were recorded. In one patient, identical electrocardiographic alterations were observed both in presence or in absence of pain, while in the others a good correlation was evident between pain and severity of the electrocardiographic abnormalities. In two patients transmural myocardial infarction complicated the course of the angina. In contrast to the classical findings, in these patients the attacks of chest pain did not cease after the infarction, but became more frequent and severe. The electrocardiographic alterations of the anginal episodes occurred in the same myocardial areas involved by the infarction, so that a reversible superposition of electrocardiographic signs of acute ischaemia on those of recent necrosis was observed.Continuous electrocardiographic recording provided the best means of investigation of these patients with the variant form of angina pectoris.     

Clinical course of ischemic heart disease in arteriosclerotic lesions of the anterior interventricular branch of the left coronary artery

A study of 67 coronary patients with isolated stenosing atherosclerosis of the anterior interventricular branch of the left coronary artery demonstrated proximal arterial stenosis in 2/3 of the cases; it was hemodynamically significant in 83% of those. Clinically, coronary heart disease in this condition was manifested as severe angina pectoris. Fifty-two percent of the patients had a history of myocardial infarction. Long-term conservative treatment, administered in 33 cases, produced an improvement in 67%, and controlled anginal attacks in 20%. Aortocoronary shunting, performed in 34 patients, had a complete antianginal effect in 2/3 of those. Clinical improvement was accompanied with somewhat improved stress tolerance.