A new dosing regimen for esmolol to treat supraventricular tachyarrhythmia in Chinese patients

Objective. The purpose of this study was to find a safe dosing regimen for esmoiol infusion to rapidly control supraventricular tachyarrhymia after cardiac surgery to Chinese patients.Background. Tachycardia increase cardiac work but reduces myocardial perfusion. Thus, in the critical period immediately after cardiac surgery, tachycardia itself warrants urgent intervention. Esmolol an ultrashort-acting beta-adrenergic blocking agent, has been reported In western published reports to have good remits and few side effects In the treatment of supraventricular tachyarrhythmia. However, its clinical application in Chinese patients has not yet been reported.Methods. When supraventricular tachyarrhymia with a rapid ventricular response (>110/min) was found early after surgery esmolol infusion with a different dosing regimen was used to control the tachyarrhythmia.Results. With the dosing regimen recommended in western published reports (repeated loading infusion with stepwise increment), acute hypotension with systolic pressure <80 mm Hg occurred in all ste patients after 1 min of loading infusion of esmolol (500 μg/kg body weight per min). To avoid the aforementioned complications, a new dosing regimen was constructed. The initial infusion rate of esmolol was set at 150 or 100 μg/kg per min, depending on the patient's age and blood pressure. When the desired heart rate was achieved, the initial infusion rate was reduced to the maintenance infusion rate to maintain the therapeutic effect [Maintenance infusion rate = Initial infusion rate x (1 − e^−0.077t), where t is the time period in minutes required by the initial infusion of esmolol to achieve the therapeutic effect]. With this new dosing regimen, tachycardia in most patients (9 of 11) could be controlled within 10 mm, and no one experienced the side effect of hypotension. The maintenance infusion rate of esmolol needed to control supraventricular tachyarrhythmia in our patients was only 73 ± 42 μg/kg per min (mean ± SD), much less than that noted hi western reports.Conclusions. The dosing reghnen for esmolol infusion recommended in western studies is not suitable for Chinese patients. In this report we propose a new dosing regimen for esmolol infusion that is both safe and rapid in the treatment of supraventricular tachyarrhythmia in Chinese patients.     

Intravenous esmolol for the treatment of supraventricular tachyarrhythmia: Results of a multicenter,baseline-controlled safety and efficacy study in 160 patients

Efficacy and safety of esmolol in the treatment of supraventricular tachyarrhythmias (SVT) was evaluated in this open-label, baseline-controlled, multicenter study. One hundred sixty patients with SVT received an intravenous infusion of esmolol in doses ranging from 25 to 300 μg/kg/min for up to 24 hours. All of the 160 patients were evaluated for safety, and 147 of them were eligible for evaluation of therapeutic response. Therapeutic response was defined as ≥ 15% reduction in the average baseline heart rate or conversion to normal sinus rhythm. Seventy-nine percent (116 of 147) of the patients exhibited a therapeutic response. The cumulative percentage response increased significantly with increasing esmolol doses up to 200 μg/kg/min. The mean (±SEM) dose of esmolol producing a therapeutic response was 97.2 ± 5.5 μg/kg/min. Among all patients (n = 160), 39% exhibited hypotension. In 58% of these patients, hypotension resolved with or without adjustment of the esmolol dose while the infusion continued; among almost all of the remaining patients, hypotension resolved within 30 minutes after esmolol was discontinued. Most patients at risk for adverse effects during beta blockade (i.e., those with diabetes mellitus, congestive heart failure, asthma, etc.) tolerated esmolol therapy, and there were no clinically important trends among the reported changes in laboratory variables. The results of the study indicate that esmolol is effective and well tolerated for the treatment of SVT.     

Combined verapamil and propranolol for supraventricular tachycardia

The electrophysiologic effects of intravenous verapamil and propranolol were compared alone and in combination in 14 patients (aged 21 to 69 years) with paroxysmal Supraventricular tachycardia (SVT). Ten patients had atrioventricular (AV) reentry utilizing a manifest (7 patients) or concealed (3 patients) accessory pathway. Four patients had AV nodal reentry. Electrophysiology studies were performed using standard techniques in the control state and after verapamil (0.15 mg/kg intravenous bolus and 0.005 mg/kg/min). The next day, studies were repeated after propranolol (0.1 mg/kg) and a combination of verapamil and propranolol. No adverse effects occurred with the drug combination. Each drug intervention prolonged anterograde functional refractory period of the AV node (control, 370 ± 50 ms; verapamil, 446 ± 90 ms; propranolol, 436 ± 92, p < 0.05), with the greatest increase occurring after the drug combination (502 ± 103 ms, p < 0.001). In 2 patients prolonged sinus node recovery time developed after the drug combination. Verapamil or propranolol prevented SVT induction in 7 patients (50%). However, only the drug combination prevented reinduction of sustained SVT in 6 patients. These 6 patients were treated chronically with verapamil and propranolol, with no recurrence of SVT in any patient after 2 to 26 months.     

Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachyarrhythmias: a multicenter double-blind clinical trial

The efficacy and safety of intravenous esmolol infusion was compared to that of intravenous propranolol injection in patients with supraventricular tachyarrhythmias (SVT) in a multicenter double-blind parallel study. A total of 127 patients were randomized to either the esmolol (n = 64) or propranolol (n = 63) group. Therapeutic response was achieved in 72% of esmolol and 69% of propranolol patients (p = NS). The average dose of esmolol in responders was 115 +/- 11 micrograms/kg/min. Therapeutic response was sustained in the 4-hour maintenance period in 67% of esmolol and 58% of propranolol patients (p = NS). Rate of conversion to normal sinus rhythm was similar in the two treatment groups. After discontinuation, rapid recovery from beta blockade (decrease in heart rate reduction) was observed in esmolol patients (within 10 minutes) compared to propranolol patients (no change in heart rate up to 4.3 hours). The principal adverse effect was hypotension, reported in 23 esmolol (asymptomatic in 19) and four propranolol (asymptomatic in three) patients. In the majority of esmolol patients, hypotension resolved quickly (within 30 minutes) after esmolol was discontinued. It was concluded that esmolol was comparable in efficacy and safety to propranolol in the treatment of patients with SVT. Unlike propranolol, because of the short half-life of esmolol, rapid control of beta blockade is possible with esmolol in clinical conditions when required.     

Time of onset of supraventricular tachyarrhythmia in relation to alcohol consumption

It is widely believed but has never been proved that idiopathic supraventricular tachyarrhythmias beginning during or after weekends or winter holidays are frequently alcohol-related ("holiday heart" syndrome). The time of arrhythmia onset was therefore studied in relation to self-reported ethanol consumption and results of a screening test for alcoholism (CAGE questionnaire) in 289 patients aged less than 65 years admitted for supraventricular tachyarrhythmias. There were 102 patients having an etiologically idiopathic arrhythmia with a known time of onset. Among them, but not among those with disease-related arrhythmias, patients with arrhythmic episodes beginning on Saturdays or on Sundays were more often chronic alcohol abusers (9 of 19, 47%) than either patients with episodes beginning from Mondays through Fridays (18 of 83, 22%; p = 0.040) or control subjects from the out-of-hospital population (8 of 66, 12%; p = 0.002). In multivariate analysis, the time of arrhythmia onset was related to the CAGE response (G2 = 6.0, p = 0.014) but not to the most recent ethanol use. However, the increased frequency of problem drinkers among patients with weekend-onset idiopathic arrhythmias was only relative, and resulted from a decreased number of abstainers and non-problem drinkers. No conspicuous clustering of alcohol-related arrhythmias was seen after New Year's or May Day. Thus, although the present study confirms an association between heavy drinking and idiopathic arrhythmias beginning during weekends, it shows that the question may be of a relative rather than an absolute overrepresentation. The term holiday heart may also be somewhat misleading since no postholiday accumulation of alcohol-related arrhythmias was found.     

Characterization of impact-induced tachyarrhythmia utilizing propranolol, quinidine and pacing

Direct impact of the heart on the right ventricle induces transient ventricular tachycardia. Preconditioning the heart with a moderate dose of propranolol (0.4 mg/Kg, IV) did not affect impact-induced tachyarrhthmia although effective beta adrenergic blockage was evident. A high dose of propranolol (1.6 mg/Kg, IV) or a moderate dose of quinidine (3 mg/Kg, IV) prevented impact-induced ventricular tachycardia. High-dose propranolol and quinidine, an agent with no beta blockade properties, share similar local effects on the myocardial cell membrane which was sufficient to prevent the tachyarrhythmia. Pacing of the right ventricular free wall at the impact site resulted in an ECG similar to that observed following impact. Pacing of the subjacent septem, the other possible arrhythmogenic site affected by the impact, resulted in a large aberrant S wave (Lead II) different from the QRS complex during impact-induced tachyarrhythmia. Therefore, impact-induced ventricular tachycardia originates from the impact site by a direct ventricular mechanism.     

Safety and efficacy of esmolol for unstable angina pectoris

Esmolol is a rapidly metabolized cardioselective beta-adrenergic blocker that provides steady state beta-adrenergic blockade when administered by continuous intravenous infusion. To determine the efficacy of esmolol in the management of unstable angina, 23 patients with known coronary artery disease, who averaged 3.7 +/- 2.7 daily episodes of chest pain at rest, were randomized to receive either a continuous infusion of esmolol (n = 12) or oral propranolol (n = 11), as an adjunct to concomitant antianginal therapy. Patients with systolic blood pressure less than 110 mm Hg, heart rate less than 60 beats/min or known contraindications to beta blockade were excluded. Esmolol was titrated in a step-wise fashion from 2 to 24 mg/min at 5-minute intervals up to a 30% reduction in heart rate and systolic blood pressure double-product. The propranolol dose was increased every 6 hours by 50 to 100% to achieve a similar reduction in heart rate and blood pressure. When compared with their 24-hour baseline periods, both groups achieved a significant reduction in episodes of chest pain, from 4.6 +/- 3.3 to 1.4 +/- 1.5 in the esmolol group (p less than 0.02) and 2.6 +/- 1.4 to 1.0 +/- 1.5 in the propranolol group (p less than 0.02) during the subsequent study period. The cardiac event rate and incidence of drug side effects were similar between the 2 groups; however, side effects seen with esmolol did not require treatment after drug discontinuation. Thus, maximally tolerated beta blockade is an effective therapy for unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)     

射频消融治疗快速心律失常的疗效及安全性

目的：评价射频消融术治疗快速心律失常的临床疗效及安全性。方法：381例快速心律失常的患者接受射频消融术,术后随访1～120个月,平均（24±18）个月,分析手术成功率、复发率及并发症。结果：381例快速心律失常中,房室结折返性心动过速（AVNRT）111例;房室折返性心动过速（AVRT）208例,其中左侧旁道109例,右侧旁道99例;显性预激（WPW）45例,其中A型预激16例,B型预激29例;频发特发性右室流出道室早（RVOT-VPC）17例。射频消融总成功率97．6％,术中及术后并发症3：67％,复发率2．37％。结论：经导管射频消融治疗快速心律失常成功率高,并发症少,复发率低,安全、可靠,是目前治疗快速心律失常的首选方法。     

艾司洛尔和普罗帕酮治疗阵发性室上性心动过速的临床疗效

目的观察艾司洛尔和普罗帕酮治疗阵发室上性心动过速（PSVT）的临床疗效,分析比较两种药物的差异。方法纳入PSVT患者120例,随机分为艾司洛尔组（n=60）和普罗帕酮（n=60）。两组在积极治疗原发病及纠正电解质紊乱、低氧血症,调整盐酸平衡的基础上,艾司洛尔组通过输液泵注射艾司洛尔,初始按负荷量0.5mg/kg,每次增加0.05mg/kg,直至显效,最大剂量≤0.25mg/kg。普罗帕酮组采用注射用水20mL＋普罗帕酮70mg缓慢注射（10min～15min）。结果两组治疗有效率无统计学差异（85.0%vs.83.3%,P〉0.05）,且减慢心率和降低血压的疗效接近（P〉0.05）。结论艾司洛尔注射液治疗PSVT与普罗帕酮同等有效。     

Comparative efficacy of amiodarone and propranolol on ventricular arrhythmia in the post-infarction period

Beta-blockers are known to be effective against post-infarction ventricular arrhythmias and amiodarone has recently been shown to have this property. The purpose of this prospective randomized study was to compare the effects of beta-blockers and amiodarone during the first 6 months following infarction. Nine days after the onset of myocardial infarction, 97 patients were put on either amiodarone (48) or propranolol (49). Holter monitoring was performed on four occasions: on the 7th post-infarction day (baseline), then on the 21st, 90th and 180th days (under treatment). On D7 the two groups were similar in age, sex, risk factors, medical history, characteristics of the infarction and type of arrhythmia. For result analysis purposes the patients were divided into two categories depending on whether their arrhythmia was "moderate" (less than 10 monomorphous and isolated ventricular extrasystoles per hour) or "severe" (at least 10 ventricular extrasystoles per hour, or polymorphous or repetitive ventricular extrasystoles). Concerning the frequency of "severe" arrhythmia, there was no statistical difference between the two treatment groups on D7 (p = 0.53), but differences in favour of amiodarone became increasingly important during the study (p = 0.08 on D21; p = 0.07 on D90; p = 0.04 on D180).(ABSTRACT TRUNCATED AT 250 WORDS)     

Interatrial conduction block and retrograde activation of the left atrium and paroxysmal supraventricular tachyarrhythmia

We studied 16 patients with electrocardiographic evidence ofadvanced interatrial block and retrograde activation of theleft atrium (P0.12 s, and diphasic (±) P waves in leadsII, III, and VF). Eight patients had valvular heart disease,four had dilated cardiomyopathy and four had other forms ofheart disease. Patients with valvular heart disease and cardiomyopathywere compared with a control group of 22 patients with similarclinical and echocardiographic characteristics, but withoutthis type of interatrial block. Patients with advanced interatrial block and retrograde activationof the left atrium had a much higher incidence of paroxysmalsupraventricular tachyarrhythmias (93.7%) during follow-up thandid the control group, (27.7%) (P>0.001). Eleven of 16 patients(68.7%) with advanced interatrial block and retrograde activationof left atrium had atrial flutter (atypical in seven cases,typical in two cases, and with two or more morphologies in twocases). Six patients from the control group (27.7%) had sustainedatrial tachyarrhythmias (five atrial fibrillation and one typicalatrial flutter). The atrial tachyarrhythmias were due more toadvanced interatrial block and retrograde activation of leftatrium and frequent atrial extrasystoles than to left atrialenlargement, because the control group with a left atrium ofthe same size, but without advanced interatrial block and retrogradeactivation of left atrium and with less incidence of atrialextrasystoles, had a much lower incidence of paroxysmal tachycardia.     

Summary of efficacy and safety of flecainide for supraventricular arrhythmias

This report provides an overview of the safety and efficacy of flecainide for supraventricular tachyarrhythmias (SVT) based on a review of the world literature. This review provided 107 entries, but 5 were review articles and 22 were articles not translated into English. The remaining 80 articles or published abstracts form the basis for this report. A total of 1,371 courses of therapy with intravenous or oral flecainide, or both, were represented. Efficacy was defined by each investigator. Intravenous flecainide was successful in terminating ongoing tachycardias in 81% of reported cases of atrioventricular (AV) nodal reentrant tachycardias, 88% of AV reentrant tachycardias and 100% of atrial tachycardias. Atrial fibrillation or flutter was terminated by intravenous flecainide in 62% of cases and arrhythmias associated with Wolff-Parkinson-White syndrome in 73%. Oral flecainide was successful in longer-term management of arrhythmia in 74 and 81% of patients with AV nodal and AV reentrant tachycardia, respectively, and in 83% with atrial tachycardia. Atrial flutter or fibrillation responded to oral drug in 61% of cases and arrhythmias related to Wolff-Parkinson-White syndrome in 61%. Adverse experiences were reported in studies totaling 695 patients (designated "at-risk patients"). They were not commented on in studies with the remaining 594 patients. Overall, a total of 6.9% of at-risk patients (3.7% of total patients) reported cardiac adverse experiences; 19% of at-risk patients (10% of total patients) reported at least 1 noncardiac adverse effect. Cardiac adverse events included worsened arrhythmias in 28, conduction disturbances in 15 and congestive heart failure in 5. The most frequent noncardiac adverse experiences were paresthesia and visual disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term efficacy of antitachycardia pacing for supraventricular and ventricular tachycardias

Over a 14-year period, 53 patients received implanted pacemakers to assist in the control of recurrent tachycardias. Indications were: prevention of tachycardia in 2 patients with supraventricular tachycardia (SVT), and 4 with ventricular tachycardia (VT); termination of tachycardia (15 SVT, 20 VT); and long-term periodic programmed electrical stimulation with potential for tachycardia termination (12 VT). Pacemakers for prevention of VT were implanted in 3 patients with prolonged QT interval syndromes and 1 in whom Holter monitoring showed a significant reduction in ectopic activity during pacing. Pacers were implanted for tachycardia termination only after patients underwent a rigorous protocol aimed at achieving 100 trials of the proposed modality. Patients with tachycardia also requiring antibradycardia pacemakers received pacemakers capable of noninvasive programmed stimulation for use during follow-up. There were no tachycardia recurrences among those patients in whom pacemakers were implanted for prevention. Pacers capable of outpatient programmed stimulation were useful, and it may be desirable to expand their use. The 15 patients with pacers designed for termination of SVT were followed for a mean of 68 months. Among these, actuarial continuation of pacing efficacy was 93% at 1 year, and 78% at 5 years. The 20 patients with pacers for termination of VT were followed for a mean of 37 months. Actuarial efficacy was 78% at 1 year, and 55% at 5 years. Sudden death occurred in 4 of these patients, none clearly pacer related. Pacemakers can play a major therapeutic role in some patients with recurrent tachycardias. The role of such pacemakers in patients with VT may be expanded with the advent of combined pacer-defibrillators.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactions of esmolol and adenosine in atrioventricular nodal-dependent supraventricular tachycardia: implication for the cellular mechanisms of adenosine

INTRODUCTION: Cellular mechanisms of adenosine include a direct effect on the activation of the adenosine-sensitive potassium current (I(K,Ado)) and an indirect effect on antagonism of catecholamine-stimulated adenylate cyclase activity. However, previous studies evaluating the influence of catecholamine activity on the electrophysiologic effects of adenosine have yielded conflicting results. We tested the hypotheses that if adenosine exerts its atrioventricular (AV) nodal blocking effects directly by activating the I(K,Ado) potassium current, rather than indirectly by reversing the catecholamine effects, then pretreatment with beta-adrenergic blockade would not potentiate the effects of adenosine in terminating AV nodal-dependent supraventricular tachycardia (SVT). METHODS AND RESULTS: During sustained AV nodal reentrant tachycardia (AVNRT) or AV reentrant tachycardia (AVRT) in 28 patients, adenosine was rapidly injected in incremental doses of 1.5, 3, 6, 9, 12 and 18 mg to determine the lowest effective dose required for tachycardia termination before and immediately after the end of esmolol infusion. Esmolol infusion was started with loading doses of 500 /kg/min for 1 min and 150 microg/kg/min for 4 min, followed by a maintenance infusion of 50-100 microg/kg/min. Esmolol infusion was continued until the tachycardia was terminated or the maximal dose of 100 mg was reached. Adenosine was effective in terminating SVT in all 28 patients with a mean lowest effective dose of 96 +/- 54 microg/kg before esmolol. During esmolol infusion, tachycardia was reproducibly terminated in 8 patients (6 with AVNRT, 2 with AVRT) with a mean dose of 67 +/- 23 mg. In the other 20 patients with persistent tachycardia after 100 mg of esmolol infusion, the lowest effective dose of adenosine could be determined in 19 patients. In the remaining patient with AVRT, the maximal dose of adenosine (18 mg) was unable to terminate the tachycardia immediately after the end of esmolol infusion. In these 19 patients, esmolol infusion caused significant lengthening of the tachycardia cycle length from 338 +/- 36 to 372 +/- 51 ms (p < 0.0001) and reduction of the mean arterial blood pressure from 96 +/- 15 to 88 +/- 18 mm Hg (p = 0.034). Compared to the dosage that was determined before esmolol infusion, the lowest effective dose of adenosine remained the same in 13 patients after the end of esmolol infusion, whereas the dose increased in 5 and decreased in 1 patient. The mean lowest effective dose of adenosine was not significantly different before (98 +/- 54 microg/kg) and immediately after (115 +/- 56 microg/kg) the end of esmolol infusion (p = 0.054). CONCLUSIONS: Intravenous esmolol infusion (up to 100 mg total dose) usually fails to terminate AV nodal-dependent SVT. In the esmolol-resistant tachycardia, esmolol pretreatment does not produce a positive synergistic effect on the efficacy of adenosine-induced termination of SVT. Therefore, in this tachycardia adenosine may exert its effects on AV nodal conduction directly by activation of the I(K,Ado) potassium current, rather than by antagonizing the beta-adrenergic system.