The role of intravenous amiodarone in the management of cardiac arrhythmias

PURPOSE: To review the electropharmacology, clinical applications, side effects, and hemodynamic profile of intravenous amiodarone. DATA SOURCES: The MEDLINE database was searched for English-language material, including reports of clinical trials and in vivo studies, review articles, and abstracts presented at national symposia, that was published between 1985 and 1996. Bibliographies of textbooks and articles were also examined. STUDY SELECTION: Studies that reported on the efficacy, toxicity, and hemodynamic profile of intravenous amiodarone and studies that examined the pharmacologic behavior of intravenous amiodarone in laboratory models were reviewed. DATA EXTRACTION: Study design and quality and relevant data on efficacy of suppression and treatment of arrhythmias with oral and intravenous amiodarone therapy, the reported mechanisms of antiarrhythmic effect, and hemodynamic changes seen with therapy were analyzed. DATA SYNTHESIS: Amiodarone is a unique antiarrhythmic agent that is now available in oral and intravenous forms in the United States. The use of intravenous amiodarone in the short-term treatment of life-threatening or hemodynamically unstable rhythm disturbances has generated much interest. Amiodarone has many electropharmacologic actions, some of which differ between the oral and intravenous forms. The wide clinical application of amiodarone includes treatment and prevention of supraventricular and ventricular arrhythmias and arrhythmias related to myocardial infarction. Intravenous amiodarone is effective for supraventricular and ventricular arrhythmias that are resistant to other antiarrhythmic agents. The effectiveness of intravenous amiodarone as short-term treatment also suggests that the drug has an important role in protocols of advanced cardiac life support. Intravenous amiodarone seems to have an overall favorable hemodynamic profile and does not produce many of the unwanted long-term side effects associated with oral therapy. CONCLUSION: Intravenous amiodarone shows much promise for the short-term treatment of unstable arrhythmias. Its favorable hemodynamic effects and minimal short-term side effects make it an attractive option in the management of cardiac arrhythmias.     

Syncope in bradycardic cardiac arrhythmias

Bradyarrhythmias, depending on the patient population, are the cause of syncope in 3 to 10%. Marked bradycardia or asystole can be due to impaired function of the sinus node (sinus node syndrome) or high-grade AV-conduction block as well as carotid sinus syndrome and pathologic vasodepressor reactions. In particular, in the presence of high-grade AV-block, the diagnosis of bradyarrhythmia-induced syncope can frequently be established on the basis of a standard ECG. One of the most common causes of syncope is functional impairment of the sinus node, in particular, an inadequate permanent sinus bradycardia, sinus node arrest or SA-block and paroxysmal atrial tachycardia alternating with atrial bradycardia. The method of choice for detecting suspected paroxysmal arrthythmias is ambulatory ECG monitoring but interpretation may be encumbered by the absence of concomitant symptoms during the registration. Frequently, the use of non-invasive methods alone, such as detailed history, ambulatory ECG and ECG exercise testing, will not render confirmatory findings to document the cause of syncope, that is, > 3 s pause in sinus rhythm or high-grade AV-block. In this situation, the question arises which patients should undergo electrophysiologic examination. Several studies have shown that in patients with a pathologic resting ECG (first degree AV-block, bundle branch block, inadequate sinus bradycardia) and cardiac disease, electrophysiologic studies will document a cause of syncope in more than 30%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic and molecular basis of cardiac arrhythmias: impact on clinical management parts I and II

Genetic approaches have succeeded in defining the molecular basis of an increasing array of heart diseases, such as hypertrophic cardiomyopathy and the long-QT syndromes, associated with serious arrhythmias. Importantly, the way in which this new knowledge can be applied to managing patients and to the development of syndrome-specific antiarrhythmic strategies is evolving rapidly because of these recent advances. In addition, the extent to which new knowledge represents a purely research tool versus the extent to which it can be applied clinically is also evolving. The present article represents a consensus report of a meeting of the European Working Group on Arrhythmias. The current state of the art of the molecular and genetic basis of inherited arrhythmias is first reviewed, followed by practical advice on the role of genetic testing in these and other syndromes and the way in which new findings have influenced current understanding of the molecular and biophysical basis of arrhythmogenesis.     

Drug therapy of cardiac arrhythmias 199

Current antiarrhythmic drug therapy is employed in strict compliance with the proper indication, which is itself limited by the side effects of the available drugs, and modified by the increasing success of such non-drug options as electrical ablation and implantable cardioverters/defibrillators. Drug treatment is restricted to 3 major indications, regular paroxysmal supraventricular tachycardias, atrial flutter and fibrillation, and ventricular tachycardias. Class IA and IC agents are used only to treat supraventricular and ventricular arrhythmias with no structural heart disease. Class III drugs, e.g. sotalol and in particular amiodarone are used preferentially to treat the pre-damaged heart, in particular left-ventricular functional impairment and in coronary heart disease in consideration of their side effects. In the case of the most common treatment-requiring arrhythmia-atrial fibrillation-anticoagulation alone may be indicated. For the prevention of sudden death, beta-blockers continue to be the drugs of first choice.     

Cellular electrophysiologic mechanisms of cardiac arrhythmias

Cardiac arrhythmias are caused by alterations in the electrophysiologic properties of the cardiac cells, which affect the characteristics of the transmembrane potentials. The electrophysiologic properties that cause arrhythmias are automaticity, triggered activity, and reentrant excitation. Each of these mechanisms is described in terms of the characteristics of the transmembrane potentials and how these influence the appearance of the arrhythmia on the electrocardiogram.     

Recognition, understanding, and current management of cardiac lesions with decreased pulmonary blood flow

Congenital heart lesions can be classified according to hemodynamic characteristics related to pulmonary blood flow patterns: increased, normal, or decreased, lesions with decreased pulmonary blood flow characteristically present with cyanosis. This article briefly reviews differential diagnoses for the presenting sign of cyanosis. Additionally, this article provides a comprehensive overview of cardiac physiology of lesions with decreased pulmonary blood flow. This information provides a foundation of knowledge for the recognition of acute symptoms in the newborn period and an understanding of immediate stabilization and medical and surgical interventions related to each diagnosis.     

Catheter ablation and implantable atrial defibrillators in supraventricular cardiac arrhythmias

This study was designed to evaluate drug use and drug costs of treatment of 1112 AIDS patients at the Infectious Diseases Unit at F. Houphou?t Boigny Hospital in Marseilles, France, between January 1, 1990 and December 31, 1994. All drug expenditures directly or indirectly related to AIDS treatment were recorded for both inpatients and outpatients. There were 1952 hospital stays. For each stay baseline characteristics including age, sex risk factors, costs, and duration of hospitalization were noted. Patients were mainly young male drug addicts around thirty years of age. Reason for admission was also noted. The overall number of admissions per year has decreased since 1991 probably due to development of outpatient care. The number of stays per patient per year has decreased since 1993 because of the use of more appropriate therapeutic and prophylactic protocols. The number of drugs used was high increasing from 750 in 1990 to 868 in 1994. Cost of treatment doubled between 1990 and 1994 due to the introduction of many expensive new drugs. Closer analysis showed that the greatest increase in expenditure involved 'antibiotic/antiviral', 'psychiatry/neurology' and 'specialized therapy'. Although not frequently prescribed, costly drugs such as immunoglobulins, hematopoietic growth factors, and parenteral nutrition solutions accounted for a high proportion of total costs. Since AZT, ddI and ddC were used mainly for outpatient treatment, their cost was low in inpatients. Cytomegalovirus-related retinitis, tuberculosis, and multiple infections were cost-intensive complications. The increasing number of cytomegalovirus infections underlines the need for cost evaluation and surveillance of this complication. This study demonstrates that cost of treating AIDS patients is rising due to the use of more and costlier drugs. This finding underlines the need to evaluate and compare new therapeutic modalities in terms of cost effectiveness.     

Treatment of cardiac arrhythmias during pregnancy: safety considerations

Adult spinal cats were trained to perform bipedal hindlimb locomotion on a treadmill for 6-12 wk. After each animal acquired the ability to step, locomotor training was withheld, and stepping was reexamined 6 and 12 wk after training ended. The performance characteristics, hindlimb muscle electromyographic activity patterns, and kinematic characteristics of the step cycle that were acquired with training were largely maintained when training was withheld for 6 wk. However, after 12 wk without training, locomotor performance declined, i.e., stumbling was more frequent, and the ability to consistently execute full weight-bearing steps at any treadmill speed decreased. In addition, the height that the paw was lifted during the swing phase decreased, and a smaller range of extension in the hindlimbs occurred during the E3 phase of stance. When three of the spinal cats underwent 1 wk of retraining, stepping ability was regained more rapidly than when trained initially. The finding that stepping ability in trained adult spinal cats can persist for 6 wk without training provides further evidence that training-induced enhancement of stepping is learned in the spinal cats and that a memory of the enhanced stepping is stored in the spinal networks. However, it appears that the spinal cord can forget how to consistently execute stepping if that task is not practiced for 12 wk. The more rapid learning that occurred with retraining is also consistent with a learning phenomenon. These results in conjunction with our earlier findings suggest that the efficacy of the neural pathways that execute a motor task is highly dependent on the periodic activation of those pathways in a sequence compatible with that motor task.     

Thyrotoxicosis. Recognition and management

Thyrotoxicosis is a common endocrine problem encountered in the primary care setting. It can exist in the presence or absence of thyroid disease and is associated with a wide range of causes, including primary hyperthyroidism, thyroid inflammation, and ingestion of exogenous thyroid hormone preparations. presenting complaints and clinical manifestations of this disorder can vary greatly, creating a challenge for the primary care provider. Recognition of clinical signs and symptoms and selection of appropriate laboratory studies can establish the diagnosis promptly. Once the diagnosis is identified, various effective and appropriate treatment options are available. It is important to distinguish between those problems that require subspecialty referral and those that can be treated by primary care providers. Many of the syndromes associated with thyrotoxicosis can be managed in the primary care setting. Interventions include patient counselling, patient education, judicious use of appropriate medications, and careful follow-up.     

Recognition and management of pulmonary hypertension

Pulmonary hypertension (mean pulmonary arterial pressure > 20mm Hg at rest or > 30mm Hg during exercise) occurs (i) as primary pulmonary hypertension (no known underlying cause), (ii) as persistent pulmonary hypertension of the newborn or (iii) secondary to a variety of lung and cardiovascular diseases. In the last 10 to 15 years there have been significant advances in the medical management of this debilitating and life-threatening disorder. The main drugs in current use are anticoagulants (warfarin, heparin) and vasodilators, especially oral calcium antagonists, intravenous prostacyclin (prostaglandin I2; epoprostenol) and inhaled nitric oxide. Calcium antagonists, (e.g. nifedipine, diltiazem) are used chiefly in primary pulmonary hypertension. They are effective in patients who give a pulmonary vasodilator response to an acute challenge with a short acting vasodilator (e.g. prostacyclin, nitric oxide or adenosine), and are used in doses greater than are usual in the treatment of other cardiovascular disorders. Prostacyclin, given by continuous intravenous infusion, is effective in patients even if they do not respond to an acute vasodilator challenge. The long term benefit in these patients is thought to reflect the antiproliferative effects of the drug and/or its ability to inhibit platelet aggregation. It is used either as long term therapy or as a bridge to transplantation. Inhaled nitric oxide, which is used mainly in persistent pulmonary hypertension of the newborn, has the particular benefit of being pulmonary selective, due to its route of administration and rapid inactivation. Anticoagulants have a specific role in the treatment of pulmonary thromboembolic pulmonary hypertension and are also used routinely in patients with primary pulmonary hypertension. Nondrug treatments for pulmonary hypertension include (i) supplemental oxygen (> or = 15 h/day), which is the primary therapy in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease and (ii) heart-lung or lung transplantation, which nowadays is regarded as a last resort. Different types of pulmonary hypertension require different treatment strategies. Future advances in the treatment of pulmonary hypertension may come from the use of drug combinations, the development of new drugs, such as endothelin antagonists, nitric oxide donors and potassium channel openers, or the application of gene therapy.