Ventricular arrhythmias during coronary angiography in patients with angina pectoris or chest pain syndromes

Of 7,915 patients undergoing coronary angiography from 1978 to 1983, 39 (25 men and 14 women with a mean age of 57 years [range 37 to 79]) had sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) during the procedure. Nine patients had atypical chest pain and 30 had typical angina. Fifteen had had a previous myocardial infarction. One patient had a history of VT or VF. Electrocardiograms taken at rest revealed a prolonged QT interval in 14. A normal ejection fraction was found in 79%. Coronary angiography revealed that 10 patients had 3-vessel disease, 15 had 1- or 2-vessel disease and 14 had normal coronary arteries. The VT or VF was seen with injection of contrast medium into the right coronary artery in 24, the left coronary artery in 10 and vein bypass grafts in 5 patients. Of the episodes of VT or VF, 67% occurred after injection of contrast medium into a minimally diseased coronary artery. In patients in whom VT or VF occurred after injection into a minimally diseased coronary artery, the arrhythmia was preceded by bradycardia, usually with pronounced widening of the QRS and QT intervals. This response was significantly different from that in patients in whom VT or VF occurred after injection into a coronary artery with significant stenosis; in these patients, VT or VF was initiated by a single premature ventricular contraction on a T wave. VT or VF was successfully cardioverted in all instances, without further arrhythmias.     

Ventricular arrhythmias in chronic stable angina pectoris with surgical or medical treatment.

Since both propranolol therapy and saphenous-vein bypass surgery have become accepted treatments for patients with symptomatic coronary-artery disease, it is important to determine if either influences the prevalence of ventricular arrhythmias in these patients. Six-hour dynamic electrocardiography was done on 130 patients with chronic stable angina pectoris at least 1 year after being randomized to surgical or medical therapy. All surgical patients had saphenous-vein grafting; 90% of the medical patients received propranolol. Data analysis showed that even though the overall prevalence of premature ventricular contractions was no different in medical and surgical patients, the prevalence of complex premature ventricular contractions was significantly higher in surgically treated patients not receiving propranolol than in propranolol-treated medical patients (p less than 0.05). However, the survival rate was no different in either group, and the quality of life in the surgical patients remained superior.     

Treatment of unstable angina pectoris.

Unstable angina pectoris may be manifested as new-onset angina, a change in the anginal pattern, pain at rest with associated electrocardiographic (ECG) changes, or postinfarction angina. Of these, pain at rest with ischemic ECG changes is known to be associated with the poorest prognosis. The pathogenesis of unstable angina pectoris involves a combination of a fixed atherosclerotic obstruction and a dynamic component related to coronary vasoconstriction, thrombus formation, or both. Long-acting nitrates, inhibitors of platelet aggregation, beta blockers, and calcium antagonists are among the agents that have been shown to be effective in the medical management of unstable angina. A study now in progress is evaluating the routine use of thrombolytic therapy for this indication. Although alleviation of symptoms and prevention of death and myocardial infarction are important therapeutic goals, the overall efficacy of a particular medical therapy can best be assessed by objective evaluation of its ability to control ischemia, using such techniques as exercise scintigraphy and ambulatory ECG monitoring. Cardiac catheterization and revascularization are indicated for patients with unstable angina who continue to experience symptoms or who show evidence of silent ischemia despite medical therapy. A study is under way to determine the advisability of routine revascularization of such patients. Revascularization will provide symptomatic relief in most patients with unstable angina and may prolong survival and improve left ventricular function in certain subsets.     

Ventricular arrhythmias during ergonovine-induced episodes of variant angina

Of 95 consecutive patients with active variant angina who underwent ergonovine testing in the coronary care unit while off treatment, 24 (25%) developed serious ventricular arrhythmias: ventricular tachycardia in eight, bigeminy in seven, pairs in five, and frequent ventricular extrasystoles in four. Ergonovine-induced arrhythmias were observed more often in patients with anterior than inferior ST segment elevation (p less than 0.05). ST segment elevation was significantly higher (10.3 +/- 8.1 vs 3.1 +/- 2.1 mm) in patients who developed arrhythmias. All ventricular arrhythmias began within 3 minutes after the onset of ST segment elevation. The intravenous administration of nitroglycerin eliminated arrhythmias in 22 of 24 cases; in only two patients did ventricular arrhythmias develop after the administration of nitroglycerin. Serious ventricular arrhythmias were found during spontaneous variant angina attacks in 14 of 24 patients with ergonovine-induced arrhythmias compared to 16 of 71 patients without ergonovine-induced arrhythmias (p less than 0.001). We conclude that arrhythmias during ergonovine testing are most often caused by ischemia and not reperfusion. Patients with arrhythmias during ergonovine-induced attacks are more likely to have arrhythmias during spontaneous attacks.     

The management of unstable angina pectoris.

Patients with unstable angina should first be medically managed with the maximally effective drug regimen. Cardiac catheterization is called for if the angina continues. Surgical intervention may be more effective if preceded by intensive medical management. You should be aware, however, that patients with unstable angina and significant left main coronary disease require immediate coronary bypass surgery.     

Medical therapy of unstable angina pectoris.

The pathophysiologic mechanisms responsible for the clinical syndrome known as unstable angina pectoris are complex but provide a framework for a rational medical approach to this ischemic condition. The combined use of nitrates, beta-blockers, calcium antagonists, antiplatelet agents, and anticoagulants has been shown to reduce recurrent ischemia, and the latter therapies have reduced the incidence of progression to myocardial infarction and death. A rational risk stratification scheme, which utilizes the presenting symptoms, electrocardiographic, and anatomic information to identify patients for whom additional revascularization procedures are warranted, is presented.     

Management of unstable angina pectoris

The diagnosis of unstable angina may be confirmed if an ECG taken during an episode of pain demonstrates ST-segment changes that resolve when the pain is relieved. An intra-aortic balloon device should be used in the rare patient who has recurrent episodes of ischemia despite maximum drug therapy. Coronary angiography should be performed as soon as possible after the device is inserted.     

Role of nitrates in unstable angina pectoris.

Unstable angina pectoris is a clinically heterogeneous process with patient symptoms varying between reduced threshold for exertional angina and the occurrence of multiple episodes of rest pain. The major factors in the pathogenesis of unstable angina appear to be intracoronary platelet aggregation and thrombus formation secondary to fissuring or rupture of atheromatous plaques, with associated coronary vasoconstriction due to release of constrictor materials from aggregating platelets and deficiency of endothelium-related vasodilator activity. The latter factor is of particular interest in view of the similar biochemical mechanisms of action of nitroglycerin (NTG) and endothelium-derived relaxing factor (EDRF). The efficacy of NTG in limiting platelet aggregation is also of particular interest in this condition. Medical therapy in patients with unstable angina usually requires use of multiple agents. In the short term, there is a strong case for the use of intravenous heparin both to relieve pain and to reduce the risk of acute myocardial infarction. Aspirin is perhaps less effective in the short term, but very useful in long-term treatment of such patients. Despite their widespread clinical use, beta-adrenoceptor antagonists are probably only marginally beneficial, whereas dihydropyridine calcium antagonists such as nifedipine are potentially harmful as monotherapy and of questionable use in combination with other drugs. Other agents that are effective in relieving ischemic symptoms are the nondihydropyridine calcium antagonists verapamil and diltiazem and the oxygen-sparing agent perhexiline maleate. Despite a paucity of controlled trial data, nitrates are used in the vast majority of patients with unstable angina.     

The nature of ventricular arrhythmias during ergonovine-induced vasospastic angina pectoris

The peak incidence of ventricular fibrillation in acute myocardial infarction usually occurs during the first hours after the onset. Electrophysiological changes immediately after the onset have been studied in animal models, but are still incompletely understood in humans. For clarification of the characteristic features of ventricular arrhythmias during acute myocardial ischemia, ventricular arrhythmias were studied in 81 patients with vasospastic angina pectoris induced by ergonovine. Ventricular arrhythmias occurred in 45 of these patients, including ventricular tachycardia in 15, and ventricular fibrillation requiring repeated DC defibrillation in two patients. Most ventricular extrasystoles occurred before the ST segment reached maximum elevation, while reperfusion arrhythmias were less common. In many patients the coupling intervals varied, and the configuration was multiform. It is concluded that ventricular arrhythmias occurring during ergonovine-induced coronary spasm show different characteristics from those occurring during chronic ischemia. As the arrhythmias in this study seem, in some ways, to resemble arrhythmias occurring at the onset of myocardial infarction, the results might provide useful information on ventricular arrhythmias in myocardial ischemia in humans.     

Angiographic morphology in unstable angina pectoris

Complex morphology occurs frequently in unstable angina; however, its relation to symptomatic presentation, timing of angiography and hospital outcome has not been investigated. Accordingly, coronary angiography was performed 5 +/- 2 days after qualifying rest pain in 101 consecutive patients presenting with acute coronary insufficiency (n = 67) or crescendo angina (n = 34). Significant coronary artery disease was defined as any greater than or equal to 50% stenosis, and complex morphology as any stenosis with irregularity, overhang or thrombus. Eight of the 67 patients presenting with acute coronary insufficiency later proved to have a myocardial infarction as the qualifying event (creatine kinase twice normal with elevation of MB fraction). There were no myocardial infarctions in the crescendo angina group. Complex morphology occurred in 61% of patients. Thrombus alone occurred in 27% of patients with unstable angina without myocardial infarction, with similar frequencies between the 2 clinical groups. In contrast, intraluminal thrombi were identified in 78% of patients with acute coronary insufficiency who later proved to have a myocardial infarction as the qualifying event. The need for urgent catheterization (less than 48 hours) prompted by recurrent symptoms was associated with the angiographic findings of intraluminal thrombus (46%) and complex morphology (83%). The presence of complex morphology and intracoronary thrombus was associated with a higher incidence of in-hospital cardiac events, i.e., revascularization, myocardial infarction and death, independent of the incidence of multivessel disease.     

Thrombosis-related markers in unstable angina pectoris

While thrombus formation has been implicated in the pathogenesis of unstable angina, the value of thrombus-related markers for distinguishing unstable from stable angina is not well defined. Fibrin D-dimer and plasminogen activator inhibitor were prospectively analyzed in the peripheral blood of 46 patients (26 with unstable angina and 20 with stable angina or normal coronary arteries). Baseline blood samples were drawn within 24 h after rest pain in patients with unstable angina and in 19 of these 26 patients in less than 6 h. In patients with unstable angina, mean +/- SD (median) values for fibrin D-dimer and plasminogen activator inhibitor values measured 0.09 +/- 0.06 (0.07) microgram/ml and 9.1 +/- 9.6 (5.9) IU, respectively, compared to 0.11 +/- 0.10 (0.05) microgram/ml and 5.5 +/- 1.9 (5.0) IU/ml, in patients in the control group (p = NS for all comparisons between the two groups). Recurrent in-hospital pain, coronary anatomy and need for intervention showed no relation to the levels of these markers. In 19 additional patients (9 with unstable angina and 10 control patients) samples from the coronary sinus and the peripheral blood were also analyzed. Again, in patients with unstable angina all samples were drawn less than 24 h after rest pain; in six of nine patients samples were drawn in less than 6 h. A coronary sinus to peripheral blood gradient for either of these markers could not be demonstrated. The differences between peripheral and coronary sinus D-dimer and plasminogen activator inhibitor concentrations were also similar in patients with unstable angina and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Additional molsidomine in refractory unstable angina pectoris

Summary In a prospective single-blind study we examined the effects of additional molsidomine in 20 patients (63±10 years; 15 males, 5 females) with unstable resting angina (3 attacks/24 hours) refractory to triple therapy (nitrates, calcium antagonists, and beta blockers) combined with heparin or aspirin. All but one patient had coronary artery disease documented by coronarography (n=17) or by recent myocardial infarction (n=3). Two patients had angiographically documented severe coronary spasms. Patients entered the study if coronary bypass surgery or PTCA could not be performed within 3 days after angiography (n=9) or was not feasible due to anatomical or technical reasons (n=6), concomitant malignant disease (n=2), or age greater than 75 years (n=3). All patients received molsidomine orally 12 to 24 mg/day. In 15 of the 20 patients molsidomine was given i.v. initially, starting with 20 mg i.v., followed by infusion of 1 to 4 mg/hour. Heart rate and blood pressure did not change significantly, and eight patients had a slight decrease of systolic and diastolic blood pressure. Severe adverse effects did not occur, and moderate headaches were reported by five patients. In 13 patients, unstable angina could be stabilized, and they remained free of resting angina; five had a marked reduction of the frequency of anginal attacks. In two patients, molsidomine was without demonstrable beneficial effects. After a follow-up of 4 weeks, nine patients were free of symptoms after bypass surgery or PTCA, 10 continued to have angina NYHA class II or III, and one patient died due to acute myocardial infarction and cardiogenic shock 4 days after starting additional molsidomine. We conclude that molsidomine is well tolerated and has a marked beneficial effect in patients with refractory unstable angina. Molsidomine should therefore be considered for routine therapy of unstable angina, especially in those patients who are suspected of tolerance to nitrate therapy.     

Usefulness of esmolol in unstable angina pectoris

Esmolol is a new cardioselective β blocker with unique pharmacokinetic properties resulting in a half-life of only 9 minutes. The present multicenter, randomized, placebo-controlled study examined the hemodynamic and antiischemic effects of this compound given as an adjunctive to conventional medical therapy in 113 patients with unstable angina. Fifty-nine patients received esmolol and 54 received matching placebo infusions. Esmolol was titrated in a step-wise manner at dosages of 2 to 24 mg/min until a 25% reduction in the double product was achieved; thereafter, esmolol was continuously infused for up to 72 hours. Esmolol caused a significant and persistent decline in heart rate and blood pressure throughout the entire study period. Clinical events, such as development of acute myocardial infarction or the need for urgent revascularization, occurred in 3 esmolol compared with 9 placebo patients (p = 0.06). There was also a trend toward reduction of silent ischemia as judged by Holter monitoring (mean [± standard deviation] duration/patient/24 hours, 21 ± 81 minutes in the esmolol and 35 ± 128 minutes in the placebo groups). Esmolol-related adverse effects were mostly cardiovascular in origin and could be managed promptly by downward dose titration or cessation of drug infusion. Thus, esmolol appears to be a safe and effective drug for patients with unstable angina because it permits a large degree of flexibility in adapting the desired level of β blockade to the patient's changing clinical presentation.     

Usefulness of carvedilol in unstable angina pectoris

The safety and efficacy of adding oral carvedilol (25 mg twice daily) to standardized treatment of unstable angina was assessed in a multicenter, randomized, double-blind, placebo- controlled trial on 116 patients with acute unstable angina. Patients were monitored in an intensive care unit and underwent 48-hour Holter monitoring to assess transient ischemia. Carvedilol as adjunctive therapy resulted in a significant reduction of median heart rate (65 vs 75 beats/min, p <0.05), mean systolic blood pressure (133 vs 130 mm Hg, p <0.05), and mean rate-pressure product (8,337 vs 10,042, p <0.05). Carvedilol reduced the ischemic burden during 48 hours of treatment by 75% (49 vs 204 minutes), including a 36% reduction of patients with ischemic episodes (p <0.05), a 66% reduction of the mean number of ischemic episodes (8 vs 24, p <0.05), and a 76% reduction in the mean duration of ischemic episodes (50 vs 205 minutes, p <0.05). Side effects occurred in 8 of 59 patients (13.6%) in the carvedilol group and in 5 of 54 patients (8.8%) given placebo. Although not significant, the early onset of maximal blood pressure reduction and the delayed effect on heart rate were closely correlated to drug-induced hypotension and bradycardia in the carvedilol group. Thus, carvedilol as an adjunctive to standardized treatment effectively reduces heart rate and blood pressure, and thus the ischemic burden in patients with unstable angina pectoris, but requires close monitoring of patients at risk for bradycardia or hypotension.     

血脂康治疗不稳定心绞痛疗效观察

目的:探讨血脂康的非调脂功能。方法:比较治疗组(血脂康组)与对照组治疗冠心病不稳定型心绞痛的疗效,包括心绞痛发作情况和心电图变化。结果:与对照组比较,治疗组显著减少心绞痛发作(P<0.05)和改善心电图变化(P<0.05)。结论:血脂康治疗不仅可用于高脂血症的治疗,且对冠心病不稳定型心绞痛也有一定的疗效。     

The heart in fatal unstable angina pectoris

Compared to patients with sudden coronary death and acute myocardial infarction, relatively little morphologic data has been reported in patients with unstable angina pectoris. This article reviews necropsy data collected from one laboratory on unstable angina pectoris. From these data, several observations are appropriate: (1) Patients with unstable angina as a group have more coronary narrowing by atherosclerotic plaque than do patients with sudden coronary death or acute or healed myocardial infarction. (2) Patients with unstable angina have a much higher frequency of severe narrowing of the left main coronary artery than do patients in other coronary subsets. (3) The coronary atherosclerotic plaques in unstable angina consist primarily of fibrous tissue, and they are more similar to those found in patients with sudden coronary death than in patients with acute myocardial infarction. (4) The frequency of acute coronary lesions (thrombi, plaque rupture, and plaque hemorrhage) is similar to that observed in patients with sudden coronary death and significantly less than that observed in acute myocardial infarction. (5) The frequency of multiluminal channels throughout the major coronary arteries is significantly higher in unstable angina compared to sudden coronary death or acute myocardial infarction. (6) The major epicardial arteries and the heart are smaller in patients with unstable angina than in patients with sudden coronary death or acute myocardial infarction. (7) The left ventricular cavity is usually of normal size in patients with unstable angina and therefore left ventricular function is usually normal.     

Thallium-201 scintigraphy in unstable angina pectoris

Thallium-201 scintigraphy was performed during the pain free period in 98 patients with unstable angina. Scintiscans were positive in 39 patients, questionable in 27 patients and normal in 32 patients. Eighty-one patients responded favorably to treatment (group I). Seventeen patients had complicated courses (group II) and despite maximal treatment with propranolol either developed infarction (six patients) or continued to have angina necessitating coronary surgery (11 patients). In group I during the pain free period 26 of 81 patients had positive thallium-201 scans, whereas 20 patients had an abnormal ECG at that time; during angina 18 patients had transient ECG changes. In group II during the pain free period 13 of 17 patients had positive scans, whereas two patients had abnormal ECG at that time; during angina 12 patients showed transient ECG changes. The sensitivity to recognize group II was 76% for thallium-201 scintigraphy, 11% for ECG during the pain free period; 70% for ECG during angina; 94% for the combination of either positive scans or abnormal ECG. Thus, 1) positive thallium-201 scans occur in patients with unstable angina, 2) positive scans can be obtained during the pain free period, 3) thallium-201 scans are more frequently positive in patients with complicated course.