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Electrical catheter ablation of arrhythmogenic sites is a new therapy for ventricular tachycardia that is still being investigated. Recent studies have shown, however, that the procedure itself can provoke serious ventricular arrhythmias. The incidence, course and mechanism of these arrhythmias were studied in 10 beagles treated with a single R wave-synchronized cathodal shock delivered to the endocardial ventricular wall (5 dogs left ventricular, 5 dogs right ventricular). Shocks were delivered at 30 (four dogs), 80 (two dogs) or 250 J (four dogs). Each dog underwent programmed electrical stimulation at or near the ablation site before, within 1 hour after and 1 week after the shock. Holter electrocardiographic monitoring (24 hours) was performed during day 1 and 7 after the shock in all the dogs, and extended Holter monitoring was done during the first 5 days in four dogs. All dogs survived for 1 week. Within 10 minutes after the shock, a sustained ventricular tachycardia was recorded in nine dogs; deterioration into ventricular fibrillation occurred in two dogs. In nine dogs, 60 to 169 monomorphic ventricular tachycardia episodes (mean 101) occurred on day 1 and 0 to 11 (mean 3) occurred on day 7; Holter monitoring failed for technical reasons in one dog. Extended Holter monitoring showed a marked decline in the incidence of tachycardia during the first 3 days. Early activation during ventricular tachycardia was always derived at or near the ablation site, and the QRS configuration during pre- and postablation pacing at this site was identical to the tachycardia configuration. Ventricular tachycardia was never inducible with programmed stimulation. These results indicate 1) a high incidence of postablation ventricular tachycardia after a single shock in the 30 to 250 J energy range; 2) arrhythmogenicity markedly declines during the first 3 days; 3) postablation ventricular tachycardia originates in the vicinity of the site where the shock had been delivered; and 4) there is no evidence in favor of reentry or triggered activity as the mechanism of these arrhythmias.

In a previous study patients with bundle branch block complicating acute anteroseptal infarction were found to have a high incidence rate of sudden death and late ventricular fibrillation in the first 6 weeks after infarction. Forty-two such consecutive patients were therefore kept within the monitoring area during those 6 weeks. Eighteen (43 percent) of these 42 patients survived and were then followed up for an average of 13 months to assess long-term prognosis and to evaluate whether the in-hospital monitoring period should be extended over 6 weeks. In most of these 18 patients a bifascicular block developed in the acute stage of infarction and in 3 it progressed to transient high degree atrioventricular (A-V) block. Seven of the 18 survivors had potentially lethal complications during the first 6 weeks. Four of these seven underwent aneurysmectomy between 10 and 20 weeks after infarction, and one of them died of a surgical complication. Major cardiac events occurred in 3 of the 17 survivors. None of these patients died during the follow-up period. In one patient complete A-V block developed after aneurysm resection; this was the only patient treated with permanent pacing. Fifteen of the 17 patients were in functional class I or II. These results indicate that (1) patients with bundle branch block complicating acute anteroseptal infarction who survive the first 6 weeks after infarction have a good prognosis during the 1st year, and (2) extension of the in-hospital monitoring period is not necessary. The results further suggest that prophylactic permanent pacing does not affect prognosis in these patients.

A short refractory period of the accessory pathway is considered a major threat for sudden death in patients with Wolff-Parkinson-White syndrome and atrial fibrillation. RR interval and QRS signal analysis together with signal analysis of a bipolar high right atrial electrogram were obtained in six patients with Wolff-Parkinson-White syndrome and either induced or spontaneous atrial fibrillation. A record of a sufficiently long episode of atrioventricular (AV) conduction by way of the bypass tract that could be used for satisfactory RR interval sequence and QRS analysis was obtained from only one patient. The results were compared with those of a representative patient with atrial fibrillation and normal AV no-dal-His conduction. In a patient with Wolff-Parkinson-White syndrome, atrial fibrillation and AV conduction by way of the bypass tract may exhibit high ventricular rates (median RR intervals of about 300 ms) and long/short RR interval ratios of just over 1 (RR intervals not exceeding 400 ms). The right atrial electrogram showed a noiselike excitation pattern. This study suggests that rather than a short refractory period of the bypass tract, it is lack of concealed conduction, responsible for the presence of long RR intervals, that allows the ventricles to reach very high ventricular rates and at times to fibril-late. The normal AV nodal-His system seems to protect the heart against high ventricular rates and ventricular fibrillation during atrial fibrillation by its relatively long refractory period and capacity to induce long RR intervals by means of concealed conduction.

Abstract —Genetic approaches have succeeded in defining the molecular basis of an increasing array of heart diseases, such as hypertrophic cardiomyopathy and the long-QT syndromes, associated with serious arrhythmias. Importantly, the way in which this new knowledge can be applied to managing patients and to the development of syndrome-specific antiarrhythmic strategies is evolving rapidly because of these recent advances. In addition, the extent to which new knowledge represents a purely research tool versus the extent to which it can be applied clinically is also evolving. The present article represents a consensus report of a meeting of the European Working Group on Arrhythmias. The current state of the art of the molecular and genetic basis of inherited arrhythmias is first reviewed, followed by practical advice on the role of genetic testing in these and other syndromes and the way in which new findings have influenced current understanding of the molecular and biophysical basis of arrhythmogenesis.

In Parts I and II of this article,* we discussed monogenic arrhythmic disorders. These are determined or favored by an inborn alteration and for the most part are characterized by a single genetic alteration. This has allowed the use of “paradigms”; namely, diseases, such as the long-QT syndrome (LQTS), in which it has been possible to trace specific mutations on ion channel genes to their electrophysiological consequences in the patient. Unfortunately for the practicing cardiologist, these “simple” diseases constitute only a small part of the clinical conditions associated with cardiac arrhythmias. The majority of cases affect patients in whom the arrhythmogenic substrate is complex. Indeed, the expression of the molecular systems responsible for normal and abnormal electrical activity vary significantly, depending on a variety of factors, including age, regional factors (type of cells, myocardial perfusion), and such underlying chronic diseases as cardiac hypertrophy, myocardial infarction, and heart failure. The study of this complex system of interacting molecular functions requires an approach somewhat different from that required to consider monogenic disease. Accordingly, in this section we discuss broader themes that are essential to understand the integration of gene expression, ion channel function, and cell coupling in multicellular networks as a first step toward the comprehension of more frequent and more complex arrhythmogenic conditions. ### Diversity of Gene Expression in the Heart Understanding cell-to-cell variability in the cardiac action potential shape and the mechanisms underlying impulse propagation is the key to understanding normal and abnormal cardiac electrophysiology. Much of this variability can be attributed to variability in the characteristics of individual ion currents whose integrated behavior determines the shape and duration of action potentials in individual cardiac cells, as well as to variability in cell-to-cell communications. Ion currents are now recognized to flow through specific pore-forming membrane proteins called ion channels. The first gene encoding an ion channel protein was …