Acute treatment of atrial fibrillation.

Atrial fibrillation (AFib) is a common clinical entity, responsible for significant morbidity and mortality, but it also accounts for a large percentage of healthcare dollar expenditures. Efforts to treat this arrhythmia in the past have focused on subacute antithrombotic therapy and eventually use of antiarrhythmic drugs for maintenance of sinus rhythm. However, there has been a growing interest in the concept of acute electrical and pharmacologic conversion. This treatment strategy has a number of benefits, including immediate alleviation of patient symptoms, avoidance of antithrombotic therapy, and prevention of electrophysiologic remodeling, which is thought to contribute to the perpetuation of the arrhythmia. There is also increasing evidence that this is a cost-effective strategy in that it may obviate admission to the hospital and the cost of long-term therapy. This article represents a summary of the treatments that may be used acutely to control the ventricular response to AFib, prevent thromboembolic events, and provide for acute conversion either pharmacologically or electrically. It includes information on modalities that are currently available and those that are under active development. We anticipate that an active, acute treatment approach to AFib and atrial flutter will become the therapeutic norm in the next few years, especially as the benefits of these interventions are demonstrated in clinical trials.

The top ten fallacies of nonsustained ventricular tachycardia.

Nonsustained ventricular tachycardia (NSVT) continues to remain a subject of controversy. This is true despite a wealth of epidemiologic and basic/clinical laboratory findings that have accumulated during the past 2 decades. However, these data not only generate the impetus to conduct further research, but also provide compelling arguments against continued adherence to time honored precepts about NSVT that evolved since the inception of the "PVC Hypothesis," although never substantiated by rigorous scientific inquiry. This paper discusses the "top ten" fallacies of NSVT and details the data that support abandonment of them.

Regression of left ventricular hypertrophy with captopril restores normal ventricular action potential duration, dispersion of refractoriness, and vulnerability to inducible ventricular fibrillation.

BACKGROUND: Left ventricular hypertrophy (LVH) is associated with multiple cellular electrophysiological abnormalities, susceptibility to ventricular arrhythmias, and an increased risk of sudden death. Several pharmacological therapies have been shown to produce regression of hypertrophy, but the value of regression is unclear. The present study examines whether pharmacological regression of LVH has effects on the susceptibility to ventricular arrhythmia or the cellular electrophysiological abnormalities of LVH. METHODS AND RESULTS: Rabbits underwent unilateral renal artery banding and contralateral nephrectomy to induce LVH or were placed in the control group. Both groups were studied 3 months later by in vivo and in vitro electrophysiological techniques. Banded rabbits had increased mean arterial pressure, increased left ventricular weight and wall thickness, increased dispersion of refractoriness, and lower ventricular fibrillation thresholds than control rabbits. Action potential duration and cell capacitance were also greater in the banded group. Additional rabbits were treated beginning 3 months after banding with either captopril (5 mg x kg(-1) x d(-1)) or vehicle added to their diet for an additional 3 months. These rabbits and age-matched controls were then studied by in vivo and in vitro electrophysiological techniques. In banded rabbits that received vehicle and were studied 6 months after banding, increased dispersion of refractoriness, a lower ventricular fibrillation threshold, and action potential prolongation persisted and were unchanged from animals studied 3 months after banding. Captopril, started 3 months after banding, caused regression of hypertrophy and normalization of the in vivo and in vitro electrophysiological abnormalities. Addition of captopril to the tissue bath during in vitro electrophysiological study showed no effect on cells from control or banded rabbits. CONCLUSIONS: Pharmacological regression of LVH with captopril normalizes the in vivo and in vitro electrophysiological abnormalities of ventricular hypertrophy and reduces the vulnerability to ventricular fibrillation in a renovascular model of LVH.

Intravenous amiodarone.

Intravenous amiodarone was approved in 1995 for the treatment of malignant and resistant ventricular arrhythmia. Although it is an "old drug," much has been learned recently about this complex drug and its application in a variety of cardiac arrhythmias. The objectives of this review were to summarize what is known about intravenous amiodarone, including its pharmacologic and electrophysiologic effects, to review its efficacy for the treatment of patients with highly malignant ventricular arrhythmia and to provide specific information about its clinical use for this and other indications. The studies that were reviewed were selected on the basis of time published (from 1983 to 1995) and the completeness of information provided regarding patient clinical characteristics, drug dosing and methods of evaluation, efficacy analyses, long-term follow-up and complications. The full data from the three controlled trials that formed the basis of the drug's approval are contained in published reports that were also extensively reviewed. Intravenous amiodarone has demonstrable efficacy for the treatment of frequently recurrent destabilizing ventricular tachycardia and ventricular fibrillation, with suppression rates of 63% to 91% in uncontrolled trials. The three pivotal trials confirmed these findings and demonstrated a dose-response relation, with at least comparable efficacy to bretylium, a drug with a similar indication. The safety profile has also been well described; cardiovascular adverse effects are the most frequent, especially hypotension. Intravenous amiodarone is a useful addition to the drugs available for the treatment of patients with very severe ventricular arrhythmia. Its use in patients with other rhythm disorders appears promising, but final recommendations must await development of definitive data from ongoing clinical trials.

Effectiveness of digitalis with or without acebutolol in preventing atrial arrhythmias after coronary artery surgery.

In this study, a beta-adrenergic blocker in combination with digoxin provided marginal protection against atrial fibrillation/flutter after coronary artery surgery. The economic comparison of patients who did and did not develop atrial fibrillation/flutter indicates that prevention of these arrhythmias can have a significant impact on length of hospital stay and cost of this common surgical procedure.

Management of atrial fibrillation in patients with hypertension.

Atrial fibrillation (AF) is a common arrhythmia in patients with hypertensive heart disease. In addition, the presence of hypertension in patients with AF constitutes an important risk factor for the development of thromboembolic events and probably also selects out those individuals who may be resistant to drug therapy. AF in patients with hypertensive heart disease may lead to a number of serious clinical sequelae including stroke, left atrial myopathy, left ventricular dysfunction, and congestive heart failure. This needs to be treated aggressively since many patients may become quite symptomatic when AF develops in the setting of diastolic and systolic dysfunction, regular features of hypertensive heart disease. There are several treatment approaches that may be considered in such patients ranging from interventions to prevent thromboembolic events, drugs and procedures for control of the ventricular response, and drug and non-pharmacologic therapy specifically designed to prevent AF or to restore normal sinus rhythm. This review article will cover each of these components of therapy of AF and will attempt to focus on those therapies that might be best suited for patients with hypertensive heart disease.

Parenteral antiarrhythmics for life-threatening ventricular arrhythmias.

The acute management of life-threatening ventricular tachyarrhythmias often includes the use of parenteral antiarrhythmics. There are a number of agents currently available for this purpose. They are used to suppress inducible monomorphic ventricular tachycardia during programmed electrical stimulation, they terminate spontaneous sustained ventricular tachycardia, and prevent ventricular fibrillation in the setting of an acute myocardial infarction. Serious adverse reactions include proarrhythmia, hypotension, severe bradyarrhythmias, and precipitation of congestive heart failure. A comparative evaluation of intravenous antiarrhythmics is difficult due to inherent differences in the choice of agents for study, protocol design, patient population, defined endpoint, and serum drug levels. Likewise, the reported adverse reaction rates vary from 0.4% to 75%. To understand the difficulties in clinical decision-making in this problem area, particularly drug selection, we present here a review of pertinent clinical trials evaluating parenteral drug efficacy and adverse effects.

Destruction of noradrenergic innervation to the paraventricular nucleus: deficits in food intake, macronutrient selection, and compensatory eating after food deprivation.

Norepinephrine (NE) injected into the paraventricular nucleus (PVN) has a stimulatory effect on feeding behavior and is found to selectively enhance preference for carbohydrate in the rat. The present experiments were conducted to assess the impact of chronic depletion of NE within the PVN on food intake and appetite regulation. The catecholamine (CA) neurotoxin, 6-hydroxydopamine (6-OHDA), when administered into the PVN, produced a significant depletion of PVN NE in association with a variety of behavioral changes. The immediate consequence of the neurotoxin lesion was a dramatic increase in 24-hr food intake, attributed predominantly to a preferential increase in carbohydrate and fat consumption. The long-term effects related to CA depletion were a deficit in daily food consumption, particularly of carbohydrate (-42%). Although animals with diminished PVN NE maintained a normal diurnal feeding pattern, they failed to exhibit the increased ingestion of an energy-rich carbohydrate diet which rats normally show during the dark period of the diurnal cycle. Rats injected with 6-OHDA directly into the PVN exhibited a normal response to glucoprivic challenge, but demonstrated a deficit in their ability to produce compensatory feeding, particularly of carbohydrate and fat, in response to food deprivation. These findings suggest a specific function for PVN noradrenergic mechanisms in normal energy repletion when body energy stores are reduced.

Morphine-stimulated feeding: analysis of macronutrient selection and paraventricular nucleus lesions.

The hypothalamic paraventricular nucleus (PVN) has been found to be sensitive to the feeding stimulatory effects of opiates. The present experiments investigated the effect of systemic morphine (2 mg/kg) on macronutrient selection in freely-feeding and food-restricted rats and assessed the impact of PVN electrolytic and 6-hydroxydopamine lesions on the rats' ability to respond to peripheral morphine injection. In satiated rats, maintained ad lib on pure macronutrient diets, morphine increased food intake. This effect was associated with a preferential increase in protein ingestion; carbohydrate consumption, compared with fat and protein intake, was least affected. In food-restricted rats, permitted to eat for 6 hr, morphine instead produced a particular preference for fat, with no significant enhancement of total calorie intake. While PVN 6-hydroxydopamine lesions, which depleted PVN catecholamine levels by 70%, failed to alter morphine-stimulated feeding, electrolytic lesions of the PVN significantly attenuated this response, particularly protein and fat ingestion. This suggests that opiate-induced feeding may, in part, be mediated through the PVN, which is known to have an important function in the control of food ingestion.