Changes In Ventricular Refractory Periods Research Articles

Arrhythmic Mitral Valve Prolapse and Mitral Annular Disjunction: Clinical Features, Pathophysiology, Risk Stratification, and Management

Mitral valve prolapse (MVP) is a common cause of valvular heart disease. Although many patients with MVP have a benign course, there is increasing recognition of an arrhythmic phenotype associated with ventricular arrhythmias and sudden cardiac death (SCD). Pathophysiologic mechanisms associated with arrhythmias include cardiac fibrosis, mechanical stress induced changes in ventricular refractory periods, as well as electrophysiologic changes in Purkinje fibers. Clinically, a variety of risk factors including demographic, electrocardiographic, and imaging characteristics help to identify patients with MVP at the highest at risk of SCD and arrhythmias. Once identified, recent advances in treatment including device therapy, catheter ablation, and surgical interventions show promising outcomes. In this review, we will summarize the incidence of ventricular arrhythmias and SCD in patients with MVP, the association with mitral annular disjunction, mechanisms of arrhythmogenesis, methods for arrhythmic and SCD risk stratification including findings with multimodality imaging, and treatments for the primary and secondary prevention of SCD.

Differential Effects of Changes in Local Myocardial Refractoriness on Atrialand Ventricular Latency

Assessment of myocardial refractoriness and conduction properties, critical to development and propagation of reentrant arrhythmias, is an integral part of the investigation of atrial and ventricular tachycardias through the use of programmed electrical stimulation. Local conduction itself, however, may be affected by myocardial refractoriness. We studied the effects of changes in myocardial refractoriness on local conduction in right atrial and ventricular myocardium in 19 patients. Changes in effective, functional, and relative refractoriness were accomplished with the use of four pacing protocols, including drive train pacing cycle lengths (PCLs) of 600 and 400 milliseconds (ms) and drive train durations (DTDs) of 8 and 50 stimuli. Unipolar cathodal stimulation was performed from the distal electrode, and unipolar electrograms were recorded from the proximal three poles of quadripolar catheters with 5-mm interelectrode spaces. Atrial and ventricular effective and relative refractory periods (ERPs and RRPs) were significantly shortened by both the reduction in PCL and the increase in DTD. The reduction in the PCL shortened atrial and ventricular refractory periods significantly more than did the increase in the DTD. Changes in ventricular refractory periods were significantly greater compared with atrial refractory periods. The ratio of RRP to ERP was reduced in the atrium but significantly increased in the ventricle with reduction in PCL and increase in DTD. For all premature intervals, the conduction interval from stimulus to the first recording electrode pole was significantly greater than conduction intervals measured between subsequent electrode poles. The greatest increase in conduction interval with closely coupled premature complexes occurred between the stimulus artifact and the first recording electrode pole. Reduction in ventricular but not atrial ERP was associated with significantly increased local conduction interval. First, most of the conduction delay after the stimulus artifact occurs within 5 mm from the pacing site. Second, closely coupled premature complexes delay conduction primarily by prolonging latency in the first 5 mm from the pacing site. Third, fundamental differences occur between the atrium and ventricle regarding changes in local conduction as a function of changes in ERP, suggesting that factors involved in sudden changes in refractoriness (eg, heart rate acceleration) could produce divergent effects on atrial and ventricular arrhythmogenesis.

Antifibrillatory and Profibrillatory Actions of Selected Class I Antiarrhythmic Agents

We wished to examine selected class I antiarrhythmic agents for their potential to exhibit proarrhythmic or antifibrillatory actions. Quinidine, lidocaine, aprindine, and flecainide were evaluated in an experimental model that made use of rabbit isolated perfused heart. Hearts were stabilized with oxygenated buffer (95% O2/5% CO2) with or without pinacidil (1.25 microM) and then were subjected to hypoxia (95% N2/5% CO2) for 12 min, followed by 40-min normoxic perfusion (95% O2/5% CO2). Test drugs were added to the perfusion medium 5 min before hypoxia was induced. Prevention of spontaneous ventricular fibrillation (VF) was determined. To characterize the electrophysiologic effects of the selected antiarrhythmic agents, we determined the changes in threshold current and effective refractory period (ERP) before and after drug treatment. Addition of the potassium channel agonist, pinacidil, to the perfusion medium invariably resulted in VF during the hypoxic interval or shortly after reoxygenation. Pretreatment of the heart with glibenclamide prevented pinacidil-induced VF. Quinidine, aprindine, lidocaine, and flecainide each were studied at a single concentration. The respective drug concentrations were selected to produce comparable changes in ventricular refractory period. Of the class I agents selected for study, only quinidine prolonged the ventricular ERP and provided significant protection against pinacidil-induced VF. In contrast, aprindine and lidocaine decreased ventricular ERP and did not prevent VF induced by the combination of pinacidil and hypoxia. Quinidine, aprindine, and lidocaine did not exhibit proarrhythmic effects in the presence of hypoxia when pinacidil was not added to the perfusion medium. Flecainide, when added to the perfusion medium without pinacidil elicited proarrhythmic activity leading to VF when the hearts were made hypoxic. Flecainide-induced VF was antagonized by glibenclamide. The data suggest that VF can be provoked by the potassium channel agonist pinacidil or by flecainide under conditions that reduce intracellular ATP concentration. Glibenclamide, a selective antagonist of the KATP channel prevented the profibrillatory actions of pinacidil and flecainide. Quinidine, but not lidocaine and aprindine, prevented VF induced by pinacidil and hypoxia.

Electrophysiologic and antiarrhythmic effects of magnesium in patients with inducible ventricular tachyarrhythmia.

Intravenous magnesium is reported to be effective in the treatment of ventricular arrhythmias associated with hypomagnesemia, digitalis toxicity, or prolongation of the QT interval. In most previous reports, magnesium was added to conventional antiarrhythmic drugs that had failed. There are few data on the antiarrhythmic efficacy of magnesium as monotherapy in patients without these associated abnormalities. Ten patients with life-threatening ventricular arrhythmia and inducible ventricular tachyarrhythmia by programmed electrophysiologic testing were treated with intravenous magnesium. Following magnesium infusion, all patients still had inducible ventricular tachyarrhythmia. Moreover, magnesium therapy was not associated with significant changes in ventricular refractory period or in the morphology, cycle length, or hemodynamic response to induced ventricular tachycardia. These data suggest that intravenous magnesium has no significant electrophysiologic or antiarrhythmic effects in patients with life-threatening ventricular arrhythmia and inducible ventricular tachyarrhythmia.

Refractoriness as a determinant of tachycardia inducibility in the right ventricle

The use of more than one right ventricular site for programmed electrical stimulation has been reported to increase the number of patients in whom ventricular tachycardia can be provoked. To determine a possible reason for these observations, programmed ventricular tachycardia studies were evaluated in 316 patients (185 men and 131 women) with a mean age of 63 ± 7 years who presented with ventricular tachycardia or cardiac arrest. The underlying cardiac disease was atherosclerosis (81%), cardiomyopathy (15%), valvular heart disease (3%), and miscellaneous conditions (1%). Programmed electrical stimulation studies employed a six-beat pacing train, at a cycle length of 500 msec with the introduction of one to three premature stimuli at twice diastolic threshold at the right ventricular apex. If ventricular tachycardia at the right ventricular apex could not be provoked in a patient, the study was repeated at the right ventricular outflow tract. A total of 36 patients were studied at the right ventricular outflow tract. Eleven (31%) were provoked into ventricular tachycardia, while 25 (69%) were not. No difference existed between the QRS, QT, and QT c intervals between those having ventricular tachycardia provoked at the outflow tract compared to those without inducible tachycardia at the right ventricular outflow tract. The effective refractory period was 280 ± 5 msec at the right ventricular outflow tract in those patients not inducible, and 226 ± 4 msec in those inducible ( p < 0.05). We defined the change in ventricular refractory period as the difference in the effective refractory period at the right ventricular outflow tract minus the effective refractory period at the right ventricular apex. The change in effective refractory period was −16 ± 2 msec for the 11 inducible patients and 8 ± 3 msec for the noninducible group ( p < 0.01). Thus, patients who are inducible for ventricular tachycardia at programmed ventricular stimulation at the right ventricular outflow tract have a shorter effective refractory period, and the difference in effective refractory period compared to the apex in the inducible group is also shorter. The earlier introduction of premature stimuli at the right ventricular outflow tract may permit a critically timed stimulus to initiate ventricular tachycardia.

The effects of verapamil on the electrophysiology of the intact immature mammalian heart.

The electrophysiologic effects of intravenous verapamil were compared in six intact neonatal puppies ages 3-15 days and in adult dogs. Utilizing standard intracardiac recording and programmed stimulation techniques, sinus and AV nodal function and atrial and ventricular refractory periods were determined following incremental intravenous doses of 0.075 mg/kg, 0.15 mg/kg, and 0.30 mg/kg of verapamil. In the neonate, intravenous verapamil resulted in a significant increase of the sinus cycle length (37 +/- 6%) but no changes occurred in either the percent sinus node recovery time or the corrected sinus node recovery time. The atrial effective refractory period was prolonged by verapamil (32 +/- 12%). Concerning atrioventricular (AV) nodal function, verapamil produced a small but significant prolongation of resting AH interval (50.5 +/- 2.4 ms (control) versus 57.3 +/- 4.7 ms post 0.30 mg/kg) and a dose-related prolongation of the paced cycle length resulting in AV nodal Wenckebach (170 +/- 12.8 ms control, 190 +/- 10.3 ms post 0.075 mg/kg, 215.8 +/- 13.0 ms post 0.15 mg/kg and 246.7 +/- 22.8 ms post 0.30 mg/kg). The effective refractory period (ERP) and functional refractory period (FRP) of the atrioventricular node (AVN) were prolonged in a dose-dependent fashion (ERP-AVN: 75 +/- 19% increase, FRP-AVN: 42 +/- 14% increase). Retrograde conduction, present in all six neonates, was completely abolished in four of six subjects and significantly prolonged in one other puppy by verapamil. No changes in ventricular refractory periods were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional distribution of right and left stellate innervation to the ventricles. Production of neurogenic electrocardiographic changes by unilateral alteration of sympathetic tone.

Changes of the electrocardiogram and of ventricular refractory period were measured following either unilateral stellate ganglion stimulation or ablation in the open chest dog preparation. Right stellate ganglionectomy or left stellate stimulation produces prolonged Q-T intervals and increased T-wave amplitude. Left stellate ganglionectomy or right stellate stimulation produces increased T-wave negativity without measurable change in the Q-T interval. The differing patterns of electrocardiographic wave form resulting from changes in sympathetic tone mediated by right and left stellate innervation could be correlated with changes in ventricular refractory period. Following right stellate ganglionectomy, refractory period prolongations were most marked over the anterior ventricular surface; left stellate ganglionectomy produced the greatest prolongation on the posterior surface. Although the right and left stellate innervations of the ventricles overlap, the left stellate influence is predominant over the posterior wall of the ventricles, while right stellate influence dominates the anterior ventricular walls. The electrocardiographic form changes observed following unilateral alteration of sympathetic tone paralleled those electrocardiographic abnormalities seen in patients with lesions of the central nervous system, suggesting a possible functional explanation for these clinical findings.