Outcome of Pulmonary Vascular Disease in Pregnancy: A Systematic Overview From 1978 Through 1996

OBJECTIVE--To assess the effects of calcium channel blockers on development of infarcts, reinfarction, and mortality. DESIGN--A systematic overview of all randomised trials of calcium channel blockers in myocardial infarction and unstable angina. PATIENTS--19,000 Patients in 28 randomised trials. RESULTS--In the trials of myocardial infarction 873 deaths occurred among 8870 patients randomised to active treatment compared with 825 deaths among 8889 control patients (odds ratio of 1.06, 95% confidence interval of 0.96 to 1.18). There was no evidence of a beneficial effect on development and size of infarcts or rate of reinfarction. The results were similar in short term trials in which treatment was confined to the acute phase and those in which treatment was started some weeks later and continued for a year or two. There was no evidence of heterogeneity among different calcium channel blockers in their effects on any end point. The results were similar in the unstable angina trials (110 out of 561 patients treated with calcium channel blocker compared with 104 out of 548 controls developed a myocardial infarction; 14 out of 591 treated compared with nine out of 578 controls died). CONCLUSIONS--Calcium channel blockers do not reduce the risk of initial or recurrent infarction or death when given routinely to patients with acute myocardial infarction or unstable angina.

https://www.bmj.com/content/bmj/299/6709/1187.full.pdf

Calcium channel blockers in acute myocardial infarction and unstable angina: an overview.

Diltiazem is an orally and intravenously active calcium channel blocking agent shown to be an effective and well-tolerated treatment for stable angina and angina due to coronary artery spasm Its efficacy in these diseases has generally been similar to that of nifedipine or verapamil - alternative calcium channel blockers with which diltiazem has many electrophysiological, haemodynamic, and antiarrhythmic similarities The antianginal mechanism of diltiazem cannot be precisely described; however, it appears to increase myocardial oxygen supply and decrease myocardial oxygen demand, mainly by coronary artery dilatation and/or via both direct and indirect haemodynamic alterations Diltiazem has also shown substantial efficacy in the treatment of unstable angina, hypertension, and supraventricular tachyarrhythmias, but further study is necessary before its place in the treatment of these diseases may be clearly established Although headache due to peripheral vasodilatation and depression of atrioventricular nodal conduction may be troublesome, side effects occur in only 2 to 10% of patients receiving diltiazem and are generally minor in nature Thus, diltiazem offers a worthwhile alternative to other agents currently available for the treatment of angina pectoris Although the infrequency of serious side effects may offer an advantage, its relative place in therapy compared with that of other calcium channel blockers remains to be clarified

Diltiazem. A review of its pharmacological properties and therapeutic efficacy.

Pulmonary embolism presenting as an isolated syncopal spell can be a difficult clinical correlation to make. We present three cases of pulmonary embolism-induced syncope and review the pathophysiology and diagnostic considerations in this setting. Pulmonary embolism should be considered in the differential diagnosis of every syncopal event that presents to the emergency department, even in the face of cardiac dysrhythmias and normal pulse oximetry values.

Syncope as an emergency department presentation of pulmonary embolism

The calcium antagonists provide a unique tool to reduce myocardial oxygen demand and prevent increases in coronary vasomotor tone. For patients with Prinzmetal's variant angina, diltiazem, nifedipine and verapamil are extremely effective in preventing episodes of coronary vasospasm and symptoms of ischemia. Unstable angina pectoris is a more complex pathophysiologic syndrome with episodes of ischemia due to increases in coronary vasomotor tone, intermittent platelet aggregation or alterations in the underlying atherosclerotic plaque. Each of the calcium antagonists is effective as monotherapy in decreasing the frequency of angina at rest. Nifedipine is the only calcium antagonist that has been studied in a combination regimen with beta blockers and nitrates for patients with unstable angina, and control of angina is better with the combination regimen than with either form of therapy alone. Although symptoms of myocardial ischemia in unstable angina are reduced by calcium antagonists, these agents do not seem to decrease the incidence of adverse outcomes. Antiplatelet therapy appears to improve morbidity and mortality in patients with unstable angina, suggesting that thrombus formation may play a central role in that disorder. Episodes of silent or asymptomatic myocardial ischemia, identified by ST-segment monitoring, occur in a variety of disorders of coronary disease. Among patients with Prinzmetal's variant angina and unstable angina, episodes of silent ischemia appear to be as frequent as episodes of angina and the calcium antagonists are effective in decreasing episodes of ischemia regardless of the presence or absence of symptoms. Persisting episodes of silent ischemia among patients with unstable angina despite maximal medical therapy identify patients at high risk for an early unfavorable outcome. Among patients with stable exertional angina, episodes of silent ischemia may be up to 5 times as frequent as episodes of angina, and may be due to increases in coronary vasomotor tone, transient platelet aggregation or increases in myocardial oxygen demand. Preliminary experience suggests that calcium antagonists and beta blockers are effective in decreasing episodes of silent ischemia in patients with stable exertional angina and that a combination regimen may be more effective than either form of therapy alone.

Calcium antagonists for Prinzmetal's variant angina, unstable angina and silent myocardial ischemia: Therapeutic tool and probe for identification of pathophysiologic mechanisms

The short-term efficacy of diltiazem (D) has been compared to that of propranolol (P), in a group of 70 patients hospitalized in the Coronary Care Unit for unstable angina, defined as recent (less than one month) appearance or aggravation of spontaneous chest pains.

Among the 70 patients, 24 had angina only at rest. The patients have been divided into two groups according to ST- T changes during chest pain: 29 with ST elevation (group A) and 41 with other repolarization abnormalities (group B). Treatment was then randomized in each group Treatment was considered successful only if spontaneous chest pains disappeared completely. Thirty-four patients were treated with D (282±102 mg/day) and 36 with P (158±81 mg/day).

In the whole group and in groups A and B considered individually, responses to D and P did not differ. Among the 24 patients with angina exclusively at rest, nine successes and four failures were observed with D. There was no symptomatic relief among the 11 patients treated by P (P = 0.001). Moreover, the number of episodes of angina was decreased by D and unchanged by P, while eight out of the 11 failures with P were immediate successes when treatment was replaced with D.

These results suggest that D is preferable to P for management of unstable angina in patients with angina which is exclusively spontaneous.

Comparison of short-term efficacy of diltiazem and propranolol in unstable angina at rest--a randomized trial in 70 patients.

Two cases of pulmonary embolism accompanied by syncope in patients with pre-existing left bundle branch block are reported. Contrary to classical descriptions, the syncopes in these two patients could not be ascribed to cardiovascular collapse, but several arguments (such as the clinical features of the syncope and its coexistence in one case with ECG evidence of complete atrio-ventricular dissociation) were in favour of a paroxysmal disorder of conduction. Right bundle branch block is known to be common in pulmonary embolism and may even be more frequent in patients with left bundle branch block. In such cases, sudden and transient arrest of conduction in the right bundle would complete the left bundle branch block, thus accounting for a paroxysmal atrio-ventricular block.

[Paroxysmal atrioventricular block, cause of syncope in pulmonary embolism. 2 cases].

Two cases of spontaneous delivery at 27 weeks and 38 weeks are reported in two patients with Eisenmenger's syndrome. One case did not present any problems, while the other was followed by maternal death on the 6th day post-partum. The cause of death was similar to that of other cases reported in the literature. The pathophysiological explanation of the terminal clinical condition with refractory hypoxia remains unclear. In view of the maternal mortality of about 50 per cent, these patients should be prescribed effective contraception, free of thrombogenic and infectious risks. The therapeutic approach in patients who become pregnant is not well defined. However, a number of principles should be observed during delivery: oxygen therapy, rapid correction of haemorrhages, the timing and the modalities of anti-coagulation are controversial. The failure of the usual methods of resuscitation in the terminal stage raises the possibility of using fibrinolytics.

[Eisenmenger's syndrome and pregnancy. Apropos of 2 spontaneous deliveries, one of which was fatal].

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Comparison of short-term efficacy of diltiazem and propranolol in unstable angina at rest--a randomized trial in 70 patients.

[Paroxysmal atrioventricular block, cause of syncope in pulmonary embolism. 2 cases].

[Eisenmenger's syndrome and pregnancy. Apropos of 2 spontaneous deliveries, one of which was fatal].