Sinus node disease. Current concepts in diagnosis and therapy.

Sinus node disease (SND) encompasses a number of abnormalities of sinus impulse generation and transmission within the atria and may lead to both bradyarrhythmias and tachycardias. Such abnormalities may be due to primary atrial electrophysiological abnormalities, or be secondary to drugs or abnormal autonomic control. The diagnosis may be readily established from the surface ECG or Holter recordings in many cases, but invasive electrophysiological study or assessment of the effects of autonomic blockade may be required in symptomatic patients in whom the diagnosis is suspected but not confirmed by simple electrocardiographic monitoring. Treatment should be restricted to those patients in whom clear correlation between symptoms and electrocardiographic or electrophysiological abnormalities has been established. Although a number of pharmacological agents have been assessed, the treatment of bradyarrhythmias should be permanent pacing. There is now substantial evidence that physiological (atrial or dual chamber) pacing reduces atrial arrhythmias, systemic embolisation, progression to heart failure and mortality, compared to single chamber ventricular pacing. Antiarrhythmic therapy may be required to control atrial tachyarrhythmias if they persist following pacing. In patients with uncontrolled atrial arrhythmias, especially those with ventricular pacemakers, long term oral anticoagulation should be considered to reduce the risk of systemic embolisation which is a common complication in patients with the bradycardia/tachycardia syndrome.     

Cardiac arrhythmias in childhood. Diagnostic considerations and treatment.

Determining safe and effective antiarrhythmic therapy in paediatric patients requires definition of the mechanism of the arrhythmia, determination of associated risk factors for treatment (such as the presence of congenital cardiac defects, myocarditis or cardiomyopathy), and monitoring for potential drug side effects related to the treatment. A number of modalities for non-invasive evaluation of arrhythmias is available, including ECG, 24-hour ambulatory Holter monitoring, and transtelephonic ECG transmission. Arrhythmias requiring medical treatment in children with normal cardiac anatomy and function include supraventricular tachycardia (SVT), ventricular tachycardia (VT) and primary atrial tachycardias. SVT is treated acutely with vagal manoeuvres or drugs which slow AV conduction [adenosine (adenine riboside), edrophonium, phenylephrine or verapamil]. When medical conversion is not achieved, transoesophageal overdrive pacing or direct current (DC) cardioversion may be required. Long term drug therapy for SVT includes first-line treatment with digoxin, verapamil or propranolol. Ventricular tachycardia is managed acutely with DC cardioversion and intravenous lidocaine (lignocaine). Chronic drug regimens include mexiletine, propranolol or amiodarone. In children with structural congenital heart disease or myocardial dysfunction, hazards of drug therapy for arrhythmias include depression of cardiac function, proarrhythmia (drug-induced worsening of arrhythmias), and conduction abnormalities. Care must be taken to choose medication regimens which are likely to be effective with minimum risk of potentiating abnormal haemodynamics or conduction.     

Electrocardiographic effects of intravenous cocaine: an experimental study in a canine model

Cocaine abuse causes cardiac dysfunction. Acute intravenous administration of cocaine may lead to development of severe arrhythmias, conduction abnormalities, ST-T changes, and sudden death. Understanding arrhythmogenesis due to cocaine may provide a therapeutic approach to reduce morbidity and mortality. We studied the arrhythmogenic activity and other electrocardiographic abnormalities resulting from an intravenous bolus of cocaine. Baseline and postanesthetic electrocardiographic findings were compared with those after administration of intravenous bolus of various doses of cocaine hydrochloride in 20 dogs. The study was done in three phases (phase I: low dose of cocaine [1 mg/kg, 15 experiments]; phase II: medium dose [2 mg/kg, 30 experiments]; and phase III: high dose [5-7 mg/kg, 10 experiments]). Plasma levels of cocaine were estimated. The low dose induced sinus bradycardia, sinus arrhythmia, atrial ectopic, wandering pacemaker, unifocal ventricular premature contractions, and ventricular couplets. The medium dose generated moderately severe arrhythmias that were of supraventricular origin. Atrial flutter and atrial fibrillation were observed in two experiments each. Ventricular arrhythmias were manifested as unifocal, multifocal, interpolated ventricular premature contractions as well as bigeminy, trigeminy, couplets, and salvos. The high dose of 5-7 mg/kg increased electrocardiographic intervals and caused ST-segment elevation as well as serious life-threatening arrhythmias. Three of the dogs developed sustained ventricular tachycardia followed by ventricular flutter-fibrillation and death.     

Tyramine-Induced cardiac arrhythmias

Five out of 12 physically healthy patients with depression undergoing a tyramine pressor test developed cardiac arrhythmias. These arrhythmias occurred in drug-free patients in three out of 12 infusions following as little as 0.03 mg/kg of tyramine and after moclobemide, a reversible inhibitor of monoamine oxidase-A, in four out of 14 tyramine infusions with as little as 0.04 mg/kg of tyramine. The arrhythmias seen were independent of patient's age and occurred both before and after 30 mmHg elevations in systolic blood pressure. Electrocardiographic abnormalities and arrhythmias seen were a loss of p waves, sinus tachycardia, frequent atrial ectopic beats, atrial premature beats, Wenckebach phenomenon, junctional rhythm, ventricular ectopics, varying QRS configurations, and ventricular bigeminy. Tyramine, both oral and intravenous, caused similar reproducible changes in dogs, though not in rats, mice or guinea pigs. Practical implications are that tyramine pressor testing in humans should be performed cautiously and only with adequate cardiac monitoring and resuscitation facilities at hand. These findings suggest that a normal dietary component can induce serious cardiac arrhythmias, and that a low-tyramine diet may be of value for patients who are susceptible to cardiac arrhythmias.     

An update on risk factors for drug-induced arrhythmias

A variety of drugs, either anti-arrhythmics or non-antiarrhythmics, have been associated with drug-induced arrhythmias. Drug-induced arrhythmias are usually observed in the presence of long QT interval or Brugada electrocardiographic pattern. Clinical risk factors, such as female gender, structural heart disease, metabolic and electrolyte abnormalities, bradycardia and conduction disease, increased drug bioavailability, and silent channelopathies act as ‘‘effect amplifiers’’ which can make an otherwise relatively safe drug dangerous with regard to risk for polymorphic ventricular tachycardia in the setting of QT interval prolongation. A drug-induced type 1 electrocardiographic pattern of Brugada syndrome is considered highly proarrhythmic. Specific electrocardiographic markers including the corrected QT interval, QRS duration, T_peak–T_end/QT ratio, and others may predict the risk of arrhythmias in both situations. The present review highlights on the current clinical and electrocardiographic risk factors for prediction of drug-induced arrhythmias.     

Acute ketotifen overdosage. A review of present clinical experience.

Ketotifen (Zaditen) is a widely used prophylactic antiasthmatic drug with pronounced antianaphylactic properties and a specific H1-antihistaminic effect. This article summarises the available information on acute overdosage of this drug, which was reported in 13 adults and 8 children. The symptoms of acute overdosage observed with ketotifen are similar to those described for antihistaminic agents. However, it would appear that the acute toxicity of ketotifen is rather low, since no serious effects have been reported either in children or in adults after the intake of up to 20mg of ketotifen, which is 10 times the recommended dose. No lethal outcome of acute overdosage has been described in association with this drug. Ketotifen seems to be better tolerated in children than in adults. Based on present clinical experience, management of acute overdosage includes gastric lavage within 2 to 4h after ingestion or activated charcoal after this period. Symptomatic treatment is indicated if arrhythmias, hypotension or seizures develop, and the patient should be kept under surveillance for at least 6 to 8h.     

Effects of atrial natriuretic peptide on ischaemia-induced arrhythmias in the rat heart: arrhythmogen or endogenous antiarrhythmic agent?

Myocardial infarction and heart failure are associated with an elevation in plasma levels of atrial natriuretic peptide (ANP). The early stages of myocardial ischaemia and infarction are associated with serious ventricular arrhythmias. We examined the possibility that ANP may function in early ischaemia to alter the susceptibility of the heart to arrhythmias by perfusing rat hearts (n = 12 in each group) with various concentrations of ANP during periods of aerobic perfusion and regional ischaemia. The complications associated with the release of endogenous ANP were precluded by carrying out the experiments with an isolated Langendorff (nonrecirculating) preparation in which the atrial effluent does not gain access to the ventricular coronary arteries. When compared with control hearts, ANP (0.02, 0.2, 0.6, or 2.0 nM) had no significant influence on the ventricular arrhythmias (ventricular premature beats, tachycardia, and fibrillation) elicited by 30-min regional myocardial ischaemia. Heart rate and coronary flow were also unchanged. We conclude that in the isolated rat heart during myocardial ischaemia ANP probably has no significant mediatory or modulatory role in the pathogenesis of serious ventricular arrhythmias.     

Role of 24-hour ambulatory electrocardiographic monitoring in a general hospital

During 1976, 24-hour ambulatory electrocardiographic (ECG) monitoring was available to all physicians at this hospital, and 281 patients were investigated by 322 recordings. Cardiac arrhythmias requiring treatment were detected in 100 patients (36%). Some presented after symptoms such as faintness, giddiness, palpitations, collapse, or fits, but ominous arrhythmias were also found in asymptomatic patients. A demand pacemaker was implanted for episodic sinoatrial or atrioventricular conduction disorder in 30, while 70 patients (25%) required antiarrhythmic drug treatment for ventricular or atrial tachyarrhythmias. Facilities for ambulatory 24-hour ECG monitoring are necessary in any large hospital, and precise diagnosis in most of our patients studied could not have been achieved by any other investigation.     

Properties of acebutolol in twenty patients with cardiac arrhythmias

Summary Acebutolol (M & B 17,803 A), a new cardioselective beta-adrenergic blocking agent, was given intravenously to 20 selected patients with various cardiac arrhythmias. Cumulative doses ranging from 12.5 to 50 mg were moderately or highly effective in 4 out of 4 patients with sinus tachycardia, 2 out of 3 patients with premature atrial beats, 3 out of 4 patients with premature ventricular beats, 3 out of 5 patients with atrial fibrillation (one was converted to sinus rhythm) and in 2 out of 3 patients with atrial flutter. The drug was ineffective in one patient with atrial tachycardia. Mild systolic hypotension occured in two patients with recent myocardial infarction and there was some aggravation of a preexisting bronchospasm in a patient with congestive heart failure secondary to hyperthyroidism. It was concluded that acebutolol is a cardioselective beta-blocker which by intravenous route may be useful in the treatment of selected cardiac arrhythmias.     

射频消融治疗快速性心律失常102例分析

目的探讨射频导管消融(RFCA)在治疗快速性心律失常中的临床价值。方法采用RFCA治疗快速心律失常102例。除特发性室性心动过速(IVT)1例,阵发性心房扑动2例,其余均为房室折返性心动过速(AVRT)和房室结折返性心动过速(AVNRT)。结果室上性心动过速(SVT)消融成功率为100%,右侧旁道消融所用时间多于左侧旁道及房室结慢径路消融的时间。随访(21±8)个月,无一例复发。IVT首次消融成功,心房扑动消融成功,全组无并发症发生。结论RFCA治疗快速性心律失常是有效的、安全的。     

Propafenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias

Propafenone is a Class I antiarrhythmic agent with weak beta-adrenoceptor antagonist activity which can be given both intravenously and orally. Dosage must be individualised because of dose-dependent pharmacokinetics, a wide range of clinically effective plasma concentrations (64 to 3271 micrograms/L) after comparable doses, the presence of an active metabolite (5-hydroxy-propafenone) and genetically determined metabolic oxidation. In non-comparative studies propafenone 450 and 900 mg/day orally significantly suppressed premature ventricular complexes and couplets in 96% and 75% of patients, respectively, and abolished ventricular tachycardia in 75% of patients. Efficacy was confirmed in placebo-controlled studies in which propafenone 300 to 900mg daily suppressed premature ventricular complexes (greater than 80%) in 77% of patients; 87% of patients had significant reductions in couplets and abolition of ventricular tachycardia. In patients with ventricular arrhythmias refractory to other antiarrhythmic agents, propafenone 450 to 1200 mg/day suppressed arrhythmias in 63% of patients (in long term therapy 66%). Electrically induced arrhythmias were prevented by intravenously administered propafenone in 12 to 23% of patients. However, long term oral therapy was effective in 77% of patients selected using programmed electrical stimulation. Propafenone was also effective in suppressing atrial and AV nodal/junctional re-entrant tachycardias and Wolff-Parkinson-White tachycardias involving accessory pathways. A limited number of comparisons with other antiarrhythmic drugs indicate that the antiarrhythmic efficacy of propafenone is superior or similar to that of quinidine, disopyramide and tocainide, and comparable to that of lignocaine (lidocaine), flecainide and metoprolol against ventricular arrhythmias and a smaller number of atrial arrhythmias. Cardiovascular side effects indicate a proarrhythmic effect similar to that with other Class I drugs, occasional precipitation of congestive heart failure and conduction abnormalities; the latter two occur more often in patients with underlying ventricular dysfunction. Non-cardiovascular side effects (neurological, gastrointestinal) are well tolerated and generally resolve with continued therapy or dosage reduction. Thus, propafenone is an effective antiarrhythmic agent, and is a useful addition to currently available drugs, although further studies will be required to determine clearly its place in therapy compared with more established antiarrhythmic drugs.     

经食道心房调搏诊治快速型室上性心律失常的临床分析

目的讨论快速型室上性心律失常经食道心房调搏术（TEAP）进行诊断的临床价值。方法采用经食道心房调搏术对快速型心律失常患者共139例进行诊断。结果 78例患者为阵发性室上性心动过速（PSVT）、7例室性心动过速、32例心房扑动、22例心房颤动。PSVT患者中,46例AVRT,17例AVNRT,15例PAT。采用TEAP对PSVT发作进行诱发及终止,72例成功,6例失败,终止成功率为92.3%。采用TEAP对心房扑动进行终止,28例成功,4例失败,终止成功率为87.5%。采用药物终止心律失常,能够对患者心脏生理相关参数造成影响,而电刺激治疗不会对心脏造成影响。结论快速型室上性心律失常采用经食道心房调搏术进行诊断,操作简便、准确性高、安全可靠,值得推广应用。     

Drug-induced torsade de pointes

Three patients who developed torsade de pointes associated with antiarrhythmic or psychotropic drugs are described, and the electrocardiographic characteristics, clinical presentation, predisposing factors, and management of this form of ventricular tachycardia are reviewed. The first patient was a 56-year-old schizophrenic man receiving thioridazine hydrochloride, trifluoperazine hydrochloride, and benztropine mesylate who was admitted to a hospital after a syncopal episode. Subsequently, the patient experienced several episodes of ventricular tachycardia combined with multifocal premature ventricular contractions (PVCs) and torsade de pointes; the arrhythmias were attributed to antipsychotic therapy. The second patient was a 69-year-old man who experienced ventricular tachycardia that progressed to ventricular fibrillation 41 days after surgery. Quinidine sulfate probably induced the ventricular tachycardia, which was identified as torsade de pointes. The third patient was a 71-year-old man admitted to the hospital for treatment of refractory ventricular arrhythmias. Previous drug therapy with quinidine sulfate and procainamide hydrochloride had been associated with torsade de pointes. Despite unsuccessful treatment of ventricular ectopy, the patient was discharged on maintenance therapy with pindolol, topical nitrates, and phenytoin. No additional episodes of torsade de pointes have been observed. Torsade de pointes is characterized by polymorphous electrocardiographic appearance and delayed repolarization (prolonged QT interval). It may occur in association with a number of disease states and also as a complication of treatment with therapeutic doses of drugs that affect repolarization (quinidine, disopyramide, procainamide, and phenothiazines). Clinical outcomes range from asymptomatic, self-terminating arrhythmias to ventricular fibrillation resulting in cardiac arrest. The definitive emergency therapy for torsade de pointes is overdrive pacing; cautious isoproterenol administration can also be used. Lidocaine and bretylium are often ineffective in treating this form of ventricular tachycardia. Potassium and magnesium repletion appear to be essential in abolishing drug-induced torsade de pointes. Drug-induced torsade de pointes is best prevented by avoiding agents known to induce arrhythmias in patients with a pre-existing prolonged QT interval. Periodic serum electrolyte assessment is warranted, and new drugs that prolong the QT interval should be considered potential causative agents of torsade de pointes.     

Efficacy and tolerance of tocainide during acute and long-term treatment of chronic ventricular arrhythmias

Summary The acute efficacy of tocainide and procainamide was studied in 10 patients with chronic, reproducible ventricular arrhythmia. The drugs were administered in random order, by intravenous infusion, during repeated standardized, submaximal exercise tests. The proposed peak therapeutic plasma concentrations of both drugs were achieved. Both agents had an equal and statistically significant anti-arrhythmic effect; thus, a reduction in ventricular ectopic beat frequency by 70% or more was seen 9 patients after procainamide, and in 7 patients after tocainide. A fall in blood pressure was seen in two patients after procainamide and in one patient after tocainide. No other adverse reaction was observed. The long-term efficacy of tocainide was studied in 19 patients with chronic ventricular arrhythmias. All patients were monitored by 6–8-h electrocardiographic recordings, and 9 of them also during exercise tests. Tocainide 400 mg every 8 h resulted in a mean peak plasma tocainide concentration of 31.6 µmol/l, and caused suppression of ventricular extrasystolic beats by 70% or more in 11 patients. Adverse reactions to tocainide were seen in 14 patients. Gastro-intestinal and central nervous system side effects were most common, which often disappeared after a reduction in dose. In 5 patients adverse effects were more serious (one patient had syncope and 4 patients had skin rashes) and withdrawal of tocainide was required. Eight patients were treated with tocainide for more than 6 months, of whom 7 were restudied after withdrawal of tocainide; arrhythmias reappeared in 5.The studies demonstrate that tocainide is an effective antiarrhythmic drug in selected patients, but the high frequency of adverse effects may limit its long-term use.     

海洛因依赖者并发急性支气管哮喘28例

目的··:总结海洛因依赖者在戒断过程中并发急性支气管哮喘的临床特点及治疗经验。方法··:对我院收治的500例戒毒者的资料进行回顾性分析。结果·· :有28例海洛因依赖者并发急性支气管哮喘 ,发生率为5.6%。其中轻度发作16例 (57% ) ;中度发作8例 (29 % ) ;重度发作3例 (11 % ) ;危重度发作1例 (3 % )。在有效脱毒的基础上行抗炎平喘治疗 ,轻度发作者多在6h之内哮喘缓解 ,中、重度发作者多在48h之内缓解 ,1例危重度发作者经常规治疗无效时im海洛因0.2g后哮喘症状迅速缓解。结论··:此类病人临床表现复杂多样 ,在积级有效的综合脱毒基础上行抗炎平喘治疗 ,控制症状较好     

Adult domiciliary oxygen therapy: position statement of the Thoracic Society of Australia and New Zealand

Evidence shows that patients with chronic obstructive pulmonary disease and a stable daytime PaO2 of 55 mm Hg or less will have longer life expectancy if given supplemental oxygen to keep the PaO2 above 60 mm Hg, preferably for longer than 15 hours a day, including sleep. There is some evidence for improved quality of life. It is reasonable to offer this therapy for other lung diseases which cause chronic hypoxaemia, and there are also less well defined indications for supplemental oxygen during exercise, sleep and air travel.     

Effect of tiapamil in the Wolff-Parkinson-White syndrome

The effect of tiapamil was studied in 9 patients with the Wolff-Parkinson-White syndrome using programmed stimulation of the heart. Before the drug, sustained orthodromic tachycardias could be initiated in 7 patients and antidromic tachycardia in 2 by premature atrial and/or ventricular stimulation. An intravenous bolus of tiapamil, 2 mg/kg, terminated the tachycardia in 7 out of 8 cases by a block in the atrioventricular (AV) node. Tiapamil lengthened the effective refractory period of the AV node in the only patient in whom it could be measured and the atrial effective refractory period in 1 out of 9 cases, but the drug had no influence on antegrade or retrograde refractory periods of the accessory pathway or on that of the ventricle. The AV nodal conduction time (A-H interval) was prolonged. Following tiapamil, it was not possible to initiate the tachycardia in 4 cases, in 2 patients the tachycardia zone widened, and in 3 it was unaltered. In the latter cases, the cycle length of the tachycardia was increased. Tiapamil appears to be useful for the termination of tachycardia and also for its prevention in some cases. In others, it may facilitate the inhibition of tachycardia. The delayed AV nodal conduction during sinus rhythm augments the area of ventricular preexcitation, which may facilitate the electrocardiographic localization of the accessory pathway.     

Cardiac arrhythmias after phenylpropanolamine ingestion

Physicians and pharmacists should be alerted to the potential adverse effects of phenylpropanolamine-containing products, which may include exaggerated hypertensive effects, arrhythmias (premature ventricular and atrial contractions together with paroxysmal ventricular or atrial tachycardia), psychotic reactions, and neurologic effects (grand mal seizures and intracerebral hemorrhage). A case of paroxysmal atrial tachycardia in a woman, after the ingestion of diet pills containing phenylpropanolamine and caffeine is reported.     

A trial of intravenous and oral mexiletine in acute myocardial infarction

Summary Intravenous and oral mexiletine prophylaxis was compared with lignocaine supplemented placebo in a single blind trial in 240 high-risk patients with acute myocardial infarction. Although atrial fibrillation, supraventricular tachycardia and ventricular extrasystoles occurred less frequently in the mexiletine treated patients, ventricular tachycardia and primary ventricular fibrillation were not prevented. Mortality at 6 weeks was less in the mexiletine group (19%) than placebo (27%) but not significantly so (0.2>p>0.1). An 80% chance of showing a significant difference would require 860 high-risk patients. Low plasma mexiletine levels after 3 h treatment were due to diamorphine and may explain failure to prevent major arrhythmias. Pretreatment with intravenous metoclopramide tended to reverse this effect of diamorphine.