Moderate alcohol consumption and the risk of sudden cardiac death among US male physicians. (49/4675)

BACKGROUND: Individuals who consume high amounts of alcohol (>5 drinks/d) have increased risks of ventricular arrhythmia and sudden cardiac death (SCD). However, the relationship is less clear for drinkers of light-to-moderate amounts. METHODS AND RESULTS: We prospectively assessed whether light-to-moderate alcohol drinkers have a decreased risk of SCD among 21 537 male participants in the Physicians Health Study who were free of self-reported cardiovascular disease and provided complete information on alcohol intake at study entry. Over 12 years of follow-up, 141 SCDs were confirmed. After control for multiple confounders, men who consumed 2 to 4 drinks/wk (RR=0.40; 95% CI, 0.22 to 0.75; P=0.004) or 5 to 6 drinks/wk (RR=0.21; 95% CI, 0.08 to 0.56; P=0.002) at baseline had significantly reduced risks of SCD compared with those who rarely or never consumed alcohol. The relationship for SCD was U-shaped (P=0. 002), with the risk approaching unity at >/=2 drinks/d. In contrast, the relationship of alcohol intake and nonsudden CHD death was L-shaped or linear (P for trend=0.02). CONCLUSIONS: In these prospective data, men who consumed light-to-moderate amounts of alcohol (2 to 6 drinks/wk) had a significantly reduced risk of SCD compared with those who rarely or never consumed alcohol.  (+info)

Effect of Na+/Ca2+ exchange inhibitor, KB-R7943 on ouabain-induced arrhythmias in guinea-pigs. (50/4675)

1. We investigated protective effects of KB-R7943, a Na+/Ca2+ exchange (NCX) inhibitor, on ouabain-induced tonotropy and arrhythmias in isolated whole atria and ouabain-induced changes in electrocardiogram (ECG) in the guinea-pig. 2. KB-R7943 (10 and 30 microM) suppressed the tonotropic effect of ouabain, and prolonged the onset time of extra-systole induced by ouabain in isolated atria. 3. The intravenous injection of KB-R7943 (1 and 3 mg kg-1) significantly increased the doses of ouabain required to induce ventricular premature beats (VPB), ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA) in anaesthetized guinea-pigs. 4. Lidocaine (Na+channel inhibitor) and R56865 (Na+ and Ca2+ overload inhibitor) also suppressed the ouabain-induced tonotropic effect and extra-systole in isolated atria, but Hoe-694 (Na+/H+ exchange inhibitor) or diltiazem (Ca2+ channel inhibitor) did not affect them. 5. Lidocaine also increased the doses of ouabain required to induce VPB, VT, VF and CA in anaesthetized guinea-pigs. 6. From these results, we conclude that KB-R7943 suppresses ouabain-induced arrhythmias through inhibition of the reverse-mode NCX.  (+info)

Management of ventricular arrhythmias: a trial-based approach. (51/4675)

Sudden cardiac death accounts for approximately 300,000 deaths annually in the U.S., and most of these are secondary to ventricular tachycardia (VT) and fibrillation in patients with coronary artery disease. Most patients with cardiac death die before reaching the hospital, which brought about a tremendous amount of research focused at identifying patients at high risk. Several trials were initiated to test the effectiveness of various therapeutic measures in these high-risk patients. A history of myocardial infarction, depressed left ventricular function and nonsustained VT have all been identified as independent risk factors for future arrhythmic death. Similarly, patients with a history of sustained VT or a history of sudden cardiac death are a high-risk group and should be aggressively evaluated and treated. The purpose of this article is to discuss risk stratification and primary prevention of sustained ventricular arrhythmias. We also review the recent secondary prevention trials and discuss the options available in the management of patients with sustained ventricular arrhythmias.  (+info)

EXP3174, the AII antagonist human metabolite of losartan, but not losartan nor the angiotensin-converting enzyme inhibitor captopril, prevents the development of lethal ischemic ventricular arrhythmias in a canine model of recent myocardial infarction. (52/4675)

OBJECTIVES: The antiarrhythmic efficacies of the competitive angiotensin II (AII) antagonist losartan, losartan's more potent noncompetitive AII antagonist human metabolite EXP3174 and the angiotensin-converting enzyme inhibitor captopril were assessed in a canine model of recent myocardial infarction. BACKGROUND: Multiple hemodynamic and electrophysiologic effects of AII may contribute to cardiac electrical instability. In the recent Losartan Heart Failure Study, Evaluation of Losartan in the Elderly (ELITE), a 722-patient trial primarily designed to assess effects on renal function, an unexpected survival benefit was observed with losartan compared with captopril, with the lower mortality using losartan primarily confined to a reduction in sudden cardiac death. METHODS: Intravenous losartan (1 mg/kg + 0.03 mg/kg/min), EXP3174 (0.1 mg/kg + 0.01 mg/kg/min), captopril (1 mg/kg + 0.5 mg/kg/h) or vehicle were infused in anesthetized dogs with recent (8.1 +/- 0.4 days) anterior myocardial infarction. Electrolytic injury of the left circumflex coronary artery to induce thrombotic occlusion and posterolateral ischemia was initiated 1 h after the start of treatment. RESULTS: Losartan, EXP3174 and captopril elevated plasma renin activities and comparably and significantly reduced mean arterial pressure. No significant electrocardiographic or cardiac electrophysiologic effects were noted with any treatment. Incidences of acute posterolateral ischemia-induced lethal arrhythmias were: vehicle, 7/9 (77%); losartan, 6/8 (75%); EXP3174, 2/8 (25%; p < 0.05 vs. vehicle control); captopril, 7/10 (70%). There were no among-group differences in time to onset of acute posterolateral ischemia or underlying anterior infarct size. CONCLUSIONS: EXP3174, but not losartan nor captopril, reduced the incidence of lethal ischemic ventricular arrhythmia in this preparation. The antiarrhythmic efficacy of EXP3174 may be due to an attenuation of deleterious effects of local cardiac AII formed during acute myocardial ischemia or, alternatively, a non-AII-related activity specific to EXP3174. These findings suggest that in humans, metabolic conversion of losartan to EXP3174 may afford antiarrhythmic protection.  (+info)

Relation between activation sequence fluctuation and arrhythmogenicity in sodium-channel blockades. (53/4675)

To examine the correlation between activation sequence fluctuation and arrhythmogenicity, we investigated temporal changes in the activation sequence by measuring activation times [negative first derivative of voltage over time (-dV/dt) in QRS] from the entire heart in 18 dogs. The heart was paced by constant atrial stimulation. The character of the activation sequence fluctuation was established by a principal component analysis, in which the first principal component was defined as a stable component of the sequence and the second or third component as a fluctuated component. Steady state contained 2.2 +/- 0.6% (percent total principal component, mean +/- SD) of fluctuated components, which appeared in a beat-by-beat manner (activation sequence alternans). Activation sequence alternans was observed only during flecainide administration and not during lidocaine or disopyramide administration. Fluctuated components at a high dose of flecainide significantly increased (3.3 +/- 0.8%). Ventricular fibrillation ensued in all dogs (n = 6) exposed to flecainide after an increase in activation sequence alternans. In conclusion, flecainide evoked local activation sequence alternans. This phenomenon correlated with the occurrence of ventricular fibrillation.  (+info)

Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction. (54/4675)

Background-Treatment with diuretics has been reported to increase the risk of arrhythmic death in patients with hypertension. The effect of diuretic therapy on arrhythmic death in patients with left ventricular dysfunction is unknown. Methods and Results-We conducted a retrospective analysis of 6797 patients with an ejection fraction <0.36 enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to assess the relation between diuretic use at baseline and the subsequent risk of arrhythmic death. Participants receiving a diuretic at baseline were more likely to have an arrhythmic death than those not receiving a diuretic (3.1 vs 1.7 arrhythmic deaths per 100 person-years, P=0.001). On univariate analysis, diuretic use was associated with an increased risk of arrhythmic death (relative risk [RR] 1.85, P=0.0001). After controlling for important covariates, diuretic use remained significantly associated with an increased risk of arrhythmic death (RR 1.37, P=0.009). Only non-potassium-sparing diuretic use was independently associated with arrhythmic death (RR 1.33, P=0.02). Use of a potassium-sparing diuretic, alone or in combination with a non-potassium-sparing diuretic, was not independently associated with an increased risk of arrhythmic death (RR 0.90, P=0.6). Conclusions-In SOLVD, baseline use of a non-potassium-sparing diuretic was associated with an increased risk of arrhythmic death, whereas baseline use of a potassium-sparing diuretic was not. These data suggest that diuretic-induced electrolyte disturbances may result in fatal arrhythmias in patients with systolic left ventricular dysfunction.  (+info)

Protective effect of FR168888, a new Na+/H+ exchange inhibitor, on ischemia and reperfusion-induced arrhythmia and myocardial infarction in rats: in comparison with other cardioprotective compounds. (55/4675)

We have studied the effects of FR168888 (5-hydroxymethyl-3-(pyrrol-1-yl)benzoylguanidine methanesulfonate), a new Na+/H+ exchange inhibitor, on ischemia and reperfusion-induced arrhythmia and myocardial infarction in anesthetized rats and compared them with those of other cardioprotective compounds. FR168888 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes acidified with Na+-propionate with a Ki value of 6.4 nM. Pretreatment with FR168888 (0.032-0.32 mg/kg, i.v.) reduced or completely abolished the ventricular fibrillation (VF) induced by reperfusion after 5 min of regional ischemia, while lidocaine, a class I antiarrhythmic agent, showed less effect against VF as compared with FR168888. The size of myocardial infarction induced by 60-min ischemia and 60-min reperfusion was attenuated by FR168888 dose-dependently (1.0-10 mg/kg, i.v.), and ventricular tachycardia and VF were significantly reduced during the ischemic period. In contrast, propranolol and diltiazem did not show such protective effects on myocardial infarct size. In addition, FR168888 did not change hemodynamic parameters in rats. These results indicate that FR168888 has a strong inhibitory effect on Na+/H+ exchange and that treatment with FR168888 can protect the heart from arrhythmia and myocardial cell death in ischemic and reperfused situations.  (+info)

An overview of contemporary approaches to antiarrhythmic therapy. (56/4675)

This review discusses the evolution in the approach to the therapy of cardiac arrhythmias that has occurred during the past 2 decades. The major changes have been driven by advances in understanding arrhythmia mechanisms, in bioengineering, and in clinical trials. It seems likely that progress in understanding the cellular and molecular basis of arrhythmias and their response to drug therapy may allow further identification of patient subsets in which specific therapies are indicated or contraindicated.  (+info)