Living anatomy of the atrioventricular junctions. A guide to electrophysiologic mapping. A Consensus Statement from the Cardiac Nomenclature Study Group, Working Group of Arrhythmias, European Society of Cardiology, and the Task Force on Cardiac Nomenclature from NASPE.

Current nomenclature for the atrioventricular (AV) junctions derives from a surgically distorted view, placing the valvar rings and the triangle of Koch in a single plane with antero-posterior and right-left lateral coordinates. Within this convention, the aorta is considered to occupy an anterior position, although the mouth of the coronary sinus is shown as being posterior. Although this nomenclature has served its purpose for the description and treatment of arrhythmias dependent on accessory pathways and atrioventricular nodal reentry, it is less than satisfactory for the description of atrial and ventricular mapping. To correct these deficiencies, a consensus document has been prepared by experts from the Working Group of Arrhythmias of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. It proposes a new anatomically sound nomenclature that will be applicable to all chambers of the heart. In this report, we discuss its value for description of the AV junctions, establishing the principles of this new nomenclature.

Surgery for ventricular tachycardia associated with right ventricular dysplasia: disarticulation of right ventricle in 9 of 10 cases.

Ten patients (nine men, one woman; mean age 39 years) with arrhythmogenic right ventricular dysplasia underwent surgery to control life-threatening drug refractory ventricular arrhythmias. All had ventricular tachycardia causing syncope and six had a history of cardiac arrest. In all a minimum of three antiarrhythmic drugs (mean five) had been ineffective. At operation, the right ventricle was grossly diseased in all patients. Ventricular tachycardias were induced and mapped intraoperatively in all patients. The surgical plan was to ablate the arrhythmogenic focus if it was less than 4 cm2; one patient was so managed. Of the remaining nine, four underwent partial (approximately 40% of the right ventricular free wall) and five underwent total right ventricular disarticulation. All survived the operation and are alive at a mean follow-up interval of 24 months (range 5 to 67). Two patients developed new sustained ventricular tachycardias. These were well tolerated and, unlike the original arrhythmias, were easily controlled by drug treatment. All patients who underwent right ventricular disarticulation manifested signs of right heart failure in the early postoperative period, but these lessened progressively with the development of systolic septal movement into the right ventricular cavity. All 10 patients are in New York Heart Association class I or II at last review. In selected patients with arrhythmogenic right ventricular dysplasia, surgery offers a curative treatment for ventricular tachycardia and should be considered for patients whose arrhythmias are life-threatening and refractory to drug treatment.

Surgery for control of recurrent life-threatening ventricular tachyarrhythmias within 2 months of myocardial infarction.

Twenty-seven patients (mean age 57 +/- 7 years) underwent surgery for control of recurrent drug-refractory ventricular tachyarrhythmias (uniform ventricular tachycardia alone in 9 patients, ventricular tachycardia and ventricular fibrillation in 15 and ventricular fibrillation alone in 3) within 2 months of acute myocardial infarction. The mean number of major arrhythmic episodes per patient was 15 (range 2 to 200) and of drug failures 4 +/- 2. Left ventricular function was severely impaired in the majority (ejection fraction 29%; range 14% to 47%) and 18 patients (66%) had a left ventricular aneurysm. Endocardial resection guided by a combination of endocardial activation mapping during tachycardia and fragmentation mapping during sinus rhythm was performed in all patients. All electrically abnormal left ventricular endocardium was excised. Eight patients (29.6%) died within 30 days of surgery. Death was not related to age, time of surgery after infarction, ventricular function, bypass time or type of arrhythmia. Patients requiring emergency surgery had a higher early postoperative mortality rate than did those undergoing planned surgery (43% versus 15%). During a follow-up period of 32 +/- 20 months, there have been no arrhythmic deaths and only three patients (16%) have required antiarrhythmic drug therapy. When required in the early weeks after infarction, surgery for ventricular arrhythmias offers a high cure rate at a risk related to the patient's preoperative arrhythmia frequency, which in turn relates to the risk of arrhythmic death.

The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion.

The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion. They cover the design and execution of experiments and the definition, classification, quantification, and analysis of arrhythmias. Investigators are encouraged to adopt the conventions in the hope that this will improve uniformity and interlaboratory comparisons.

Arrhythmogenesis--a European perspective.

Arrhythmogenesis as an effect of antiarrhythmic therapy is a relatively recent concern. Satisfactory definitions are lacking, but 2 categories, clinical and technical, can be recognized. Although arrhythmogenesis is an international problem and multifactorial, its expression depends on variables that differ according to geographic location. In Europe, use of antiarrhythmic therapy is more conservative than it is in the U.S. In the U.S., many antiarrhythmic drugs commonly used in Europe are either recently released, are on limited release or are available only in investigational protocols. Mexiletine, class IC agents and sotalol are agents in routine use in Europe. All have arrhythmogenic potential, although this appears lowest with mexiletine.

Treatment and prophylaxis of ventricular arrhythmias in acute myocardial infarction.

Remarkable advances have been made in the management of cardiac disease in the last 20 years, but antiarrhythmic drug strategy in the acute phase of myocardial infarction remains less than satisfactory. Primary ventricular fibrillation (VF), once considered predictable on the basis of detection of "warning arrhythmias," cannot be anticipated. Management must be either expectant or prophylactic. Restriction of drug use to selected patients and the apparent lack of effect of VF on late prognosis argue for the former approach, yet safe and effective prevention of VF is an attractive therapeutic goal. High-dose intravenous lidocaine probably offers efficacy but the risk-benefit ratio of this regimen is still debated. Adoption of a prophylactic regimen mandates drug administration to a large number of patients who either are not at risk of developing VF (noninfarct patients) or who are destined not to develop VF (70 to 95% of infarct patients). Ventricular arrhythmias other than VF are common in acute infarction and, for emotional rather than scientific reasons, often are aggressively treated. Little evidence exists to support this management. Few ventricular arrhythmias at this time in infarction have either immediate importance or prognostic significance. Reevaluation of antiarrhythmic drug use and arrhythmia treatment in acute myocardial infarction is long overdue. However, there is a paucity of controlled data upon which to base new strategies, and clinical research in this field is hampered by ethical considerations, by rigidly held but unscientifically based beliefs and by a lack of fundamental knowledge of arrhythmia mechanisms and their significance.

Prophylactic antiarrhythmic therapy in acute myocardial infarction.

Safe, effective prophylaxis of arrhythmias in acute myocardial infarction (AMI) is an important clinical goal. Despite rescue squads, out-of-hospital ventricular fibrillation (VF) has a poor prognosis. Even in-hospital VF has an important morbidity and mortality. Successful prophylactic therapy may also prevent infarct size enlargement associated with tachyarrhythmias. Several antiarrhythmic drugs have been investigated. In 3 studies, mortality was significantly reduced, but all of these have serious methodologic flaws and the validity of their conclusions is debatable. More reliance can be placed on 2 other studies which suggested that VF was significantly reduced by prophylactic therapy. However, in one of these studies, which used high-dose intravenous lidocaine, an unusually high incidence of VF was observed in the placebo-treated patients. The second study, reporting the use of metoprolol in AMI, was based on retrospective subset analysis. The reduction in VF was seen from the fourth day onwards and not during the acute phase of infarction. The favorable results with high-dose intravenous lidocaine are the basis for widespread use of prophylactic arrhythmia therapy in AMI. Uncontrolled observations provide some corroboration of the benefit. However, the claimed efficacy for lidocaine remains scientifically poorly substantiated and the safety of the high-dose regimen is controversial. Effective prophylaxis of arrhythmias in AMI could have important clinical benefit. However, the strategy would entail administration of a drug to many patients not at risk of arrhythmias (those without AMI) and to a number of patients in whom the complications of infarction are destined to develop.(ABSTRACT TRUNCATED AT 250 WORDS)

Practical considerations in the use of sotalol for ventricular tachycardia and ventricular fibrillation.

Sotalol is a unique antiarrhythmic drug that combines beta-blocking effects with actions to prolong action potential duration. The net effect is a drug that is efficacious in the management of ventricular tachyarrhythmias. Although sotalol has effects on both heart rate and QT interval, these effects do not help predict the antiarrhythmic efficacy of the agent. Changes in QT dispersion may, however, prove to be relevant to both the antiarrhythmic effects and the arrhythmogenic effects of sotalol. Thus, although sotalol may occasionally cause torsades de pointes, this complication may be predictable and clinically controllable. Sotalol is well tolerated, and it may be used, with caution, in some patients with impaired myocardial contractile performance, despite its beta-blocking action. Sotalol has an important indication for the management of ventricular tachyarrhythmias.

Risk-benefit profiles of antiarrhythmic therapy.

Whereas much has been learned of the mechanisms and pathophysiology of cardiac arrhythmias, treatment remains controversial and is largely empiric. Cardiac arrhythmias range in severity from innocuous to fatal; antiarrhythmic agents offer differing degrees of efficacy, inefficacy or toxicity. For an arrhythmia that needs treatment, there is no reliable or easy method for selecting the most appropriate antiarrhythmic drug. Antiarrhythmic treatment is justified for arrhythmias that are symptomatic or hemodynamically significant, the risk of lethality dictating the degree of drug toxicity that might be tolerated. The treatment of prognostically important arrhythmias is indicated if their suppression is rewarded by an improved prognosis. However, these arrhythmias are often merely indicators of a bad prognosis rather than the cause of death. Assessment of the risk-benefit ratio of antiarrhythmic treatment principally depends on the perceived risk and symptomatology of the arrhythmia and the efficacy and toxicity of the antiarrhythmic drug. Beta-adrenoceptor blocking drugs offer optimal risk-benefits for the prevention of ventricular fibrillation (infarct survivors and long QT syndrome); disopyramide and the class IC agents offer acceptable risk-benefit ratios for the treatment of ventricular tachycardia, whereas no antiarrhythmic drug offers an acceptable risk-benefit for the suppression of asymptomatic "cosmetic" atrial or ventricular ectopic beats.

Atrial fibrillation in the preexcitation syndrome.

One hundred patients with proved accessory pathways of the Kent bundle type were studied with multiple intracardiac catheters. During the procedure 16 had atrial fibrillation. Two patterns of induction of atrial fibrillation were noted. In most patients an earlier than expected atrial deflection appeared in one of the atrial recordings and was followed by atrial flutter (cycle length less than 220 msec) or atrial fibrillation either immediately or after a brief period of acceleration of atrial rate. In a few patients, intraatrial conduction delay, manifested as 2:1 block or Wenckebach block from the right to the left atrium or vice versa, occurred before the onset of atrial fibrillation. The incidence of atrial fibrillation was not statistically related to any associated cardiac abnormalities. A significantly large incidence of ventricular fibrillation was recorded in patients who had documented atrial fibrillation either before admission or during the catheter study.

Effects of surgery for postinfarction ventricular tachycardia on parameters of left ventricular function.

Heart failure is the leading cause of death in patients after surgery for ventricular tachycardia. This study examines the effects of antiarrhythmic surgery on 4 parameters of left ventricular (LV) function. Global ejection fraction, segmental wall motion score, homogeneity of contraction, and diastolic function were measured in 32 patients by technetium-99m radionuclide ventriculography. Ejection fraction was measured from the left anterior oblique image. Wall motion score was assessed semiquantitatively for 11 LV segments from 3 projections. Homogeneity of contraction was expressed as the SD of the LV phase analysis curve during systole from the left anterior oblique image. Diastolic function was expressed in terms of peak and mean first time derivative of the action potential (dV/dt) of the LV function curve. Subgroup analyses were performed to distinguish the effects of aneurysmectomy, coronary artery bypass grafting, and changes in angiotensin converting enzyme inhibitor therapy. Mean systolic function improved after surgery (ejection fraction 22% vs 32%, p <0001; wall motion score 20 vs 13, p <0.0001; phase analysis 18 vs 12, p <0.03). Mean diastolic function also improved (peak dV/dt 0.83 +/- 0.32 vs 1.49 +/- 0.39, p = 0.006; mean dV/dt 0.41 +/- 0.15 vs 0.76 +/- 0.27, p = 0.006). Improvements were not confined to those who had aneurysmectomy or coronary bypass grafting and were not explained by changes in vasodilator therapy. Thus, antiarrhythmic surgery does not inherently damage LV function. Significant improvements were observed in most patients. Failure to improve indicated a poor longer term prognosis.

Importance of lead selection in QT interval measurement.

The influence of lead selection on QT estimation in the 12-lead electrocardiogram was assessed in 63 patients (21 control subjects, 21 with anterior myocardial infarction, 21 with inferior myocardial infarction). QT estimates varied between leads. The variation was greater in patients with myocardial infarction than in control subjects (mean dispersion of QT: control subjects, 48 +/- 18 ms [+/- standard deviation]; anterior myocardial infarction, 70 +/- 30 ms; inferior myocardial infarction, 73 +/-32 ms). The maximum QT in any lead (QTmax) was determined and the deviation of each lead from this maximum value calculated. In all 3 groups, anteroseptal leads (V2 or V3) provided the closest approximation to QTmax. Interlead variability was found to be mainly due to variation in timing of the end of the T wave, rather than the onset of the QRS complex. The variability due to leads was considerably greater than the variability due to cycles, observers or measurement error. Implementation of a variety of current lead selection practices resulted in widely divergent estimates of QT interval. It is concluded that there is a need for standardization of lead selection practice for QT measurement. If measurements are confined to one or a few leads, anteroseptal leads provide the closest approximation to QTmax.

Electrocardiographic features of septal location of right ventricular outflow tract tachycardia.

A consistent 12-lead electrocardiogram (ECG) morphology and characteristic frontal plane axis shift from sinus rhythm to ventricular tachycardia (VT) was demonstrated in 10 consecutive patients with idiopathic right ventricular outflow tract (RVOT) VT. All arrhythmias were successfully ablated on the septal side of the RVOT.

Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia. Dofetilide Arrhythmia Study Group.

There is increasing evidence that class III antiarrhythmic agents may be superior to class I agents for the long-term treatment of life-threatening ventricular tachyarrhythmias. This open study evaluated the acute electrophysiologic effects, antiarrhythmic efficacy, and safety of different doses of intravenous dofetilide, a new class III drug, in 50 patients with sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation who had previously been unsuccessfully treated with 0 to 7 (median 3) other drugs. Intravenous dofetilide was administered over 60 minutes at the following dose levels: 1.5, 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Significant class III activity was apparent at doses of 3.0 to 15.0 micrograms/kg, as evidenced by dose-related prolongation of the QTc interval by 13.4% to 14.2%, ventricular effective refractory period by 7.9% to 20.6%, and ventricular functional refractory period by 7.3% to 25.0%. The corresponding mean +/- SD plasma dofetilide concentrations ranged from 1.45 +/- 0.52 to 6.48 +/- 1.31 ng/ml. There was no evidence of reverse use-dependence. At these electrophysiologically active dose levels, intravenous dofetilide suppressed (complete response) or slowed (partial response) inducible ventricular tachycardia in 17 of 41 patients (41%) compared with 0 of 9 patients receiving only 1.5 micrograms/kg. The response rate was fairly uniform among the groups receiving 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Intravenous dofetilide was hemodynamically well tolerated. Torsades de pointes (which was self-limiting) developed in only 1 patient, who was allocated to receive 15.0 micrograms/kg. There were no other proarrhythmic episodes or serious adverse effects. Further evaluation of the therapeutic potential of dofetilide in the management of life-threatening ventricular arrhythmias is justified.

Assessment of the risk-benefit ratio for antiarrhythmic drug use.

Arrhythmia treatment has always been difficult, particularly as there are no good indicators of the optimal management strategy. The introduction of new antiarrhythmic agents has forced reappraisal of how these drugs are used. Dynamic electrocardiography and invasive electrophysiological studies are important tools for classifying and characterizing arrhythmias and for assessing the efficacy of therapy. There is still an enormous gulf between present day treatment and a scientific basis for drug selection, but risk-benefit analysis is possible, at least for patient populations and for some specific arrhythmias. Individual risk-benefit analysis, much needed by clinicians, is still a long way from reality. This article examines the concept of risk-benefit analysis and indicates those areas where progress can be made.

Strategy for the detection and management of coronary artery disease. "Physiology before anatomy".

A strategy for the diagnosis of ischemic heart disease should be based on knowledge of the prevalence of the disease in population subgroups. Asymptomatic patients should not be routinely screened. Asymptomatic patients or patients with nonanginal chest pain should have both a positive exercise electrocardiogram and stress nuclear scan before a diagnosis of ischemic heart disease is justified or arteriography is recommended. Patients with atypical angina should be evaluated with exercise radionuclide ventriculography. Coronary arteriography is rarely needed for diagnosis and is most properly used as a preoperative evaluation of a patient who has symptoms uncontrolled by medical management, or in whom a significant amount of myocardium is at risk as determined by physiologic testing with exercise electrocardiography or stress nuclear techniques.

High-performance liquid chromatographic measurement of amiodarone and desethylamiodarone in small tissue samples after enzymatic digestion.

A method is described for the measurement of amiodarone and desethylamiodarone in small tissue samples. With the exception of fat, for which lipase is used, the tissues are digested with a proteolytic enzyme. After the addition of an internal standard the analytes are extracted from the homogeneous digest into an organic solvent and measured by high-performance liquid chromatography (HPLC) with UV detection at 240 nm. The method shows good reproducibility using tissue samples as small as 20 mg and suggests extensive accumulation of both compounds in some tissues, with particularly high concentrations in tissues associated with adverse effects of the drug.

Identifying patients at low risk of death from cardiac failure after operation for postinfarct ventricular tachycardia.

BACKGROUND: In unselected patients, cardiac failure accounted for most deaths after antiarrhythmic operation (ER) for postinfarction ventricular tachycardia (VT). This study aimed to determine whether patients at low risk of this outcome could be predicted from a retrospective analysis of variables from 100 consecutive ER patients. METHODS: Thirteen variables suggested by other researchers as predictive of outcome were analyzed. At the time of study, ER was the only therapy available for drug refractory VT. RESULTS: Only emergency ER, wall motion score less than 3 and Killip classification were significantly related to death from cardiac failure. The lack of correlation between emergency ER and variables of ER timing, VT less than 24 hours of ER or VT type implies that the need for emergency ER is also related to ventricular dysfunction. Multivariate analysis identified a group at particularly low risk of death with a specificity of 95%. CONCLUSIONS: Patients at low risk of death after ER can be identified prospectively. In the implantable cardioverter defibrillator era, elective ER is best reserved for such patients. Emergency ER may still be justified in younger patients without comorbidity who will die of VT without it.

Absorption and antiarrhythmic efficacy of sustained-release mexiletine.

Absorption of the antiarrhythmic agent mexiletine from conventional capsules (200 mg) and two sustained-release formulations (360 and 432 mg) was studied in four healthy volunteer subjects, and use of the 360-mg preparation was studied in nine patients who had been using conventional capsules. In the four volunteers, acute dosage with the 432-mg preparation produced a markedly lower peak mexiletine concentration and fewer side effects than did two 200-mg capsules. Chronic dosing in two volunteers, which indicated that the 360-mg preparation produced fewer side effects and lower predose and peak plasma mexiletine concentrations than did the 432-mg preparation, suggested the use of equivalent doses of the 360-mg preparation in the nine patients who had been using 100-, 200-, or 250-mg preparations. The arrhythmia control produced by the slow-release preparation, as measured by 24-hour ECGs, was comparable to that produced by the conventional forms of mexiletine; gastrointestinal side effects were less marked when patients took the slow-release preparation, despite higher mean predose plasma mexiletine concentrations associated with use of the 360-mg preparation. Reduced frequency of daily dosage as well as patient acceptance are clinical advantages of the slow-release preparation.