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    • The occurrence of RNRVAS first reported as

    2019-04-15

    The occurrence of RNRVAS, first reported as an isolated case in 1985 [16], have since been confirmed in dual-chamber pacemaker recipients undergoing 24-h ambulatory electrocardiograms, who report symptoms similar to those of patients suffering from pacemaker syndrome [17,18].
    Incidence of RNRVAS RNRVAS is not an uncommon observation in dual-chamber pacemaker or ICD recipients [17,19]. We studied 39 patients who had neither histories nor occurrences of ATA before receiving dual-chamber pacemakers that were programmed in the DDD mode with AHRE set at >190 beats per minute (bpm) after order pyrilamine maleate [14]. An atrial overdrive pacing (AOP) algorithm was randomly programmed “ON” in 19 and “OFF” in 20 patients. Of 1528 AHRE, 257 were available for analysis by using intracardiac electrograms (iEGM). Seventy-six episodes occurred with the AOP algorithm “OFF” and 181 occurred with the AOP algorithm “ON”. Surprisingly, 109 of the 257 episodes (42%) were attributable to RNRVAS instead of AF episodes. In the AOP algorithm “OFF” group, 76 of 76 episodes (100%) were true ATA, whereas in the AOP algorithm “ON” group, 109 of 181 episodes (60%) were due to RNRVAS. The specificity of true ATA detection by using AHRE was 40% when the AOP algorithm was activated, versus 100% when it was not used, unequivocally confirming the significantly higher incidence of RNRVAS associated with the AOP activation. Among 2343 pacemaker recipients followed up for a mean of 2.5 years in the ASSERT trial, 50% were randomly assigned to activation of the AOP algorithm, whereas in the other 50%, the algorithm was turned off [20]. The rate of false positive automatic detection of AF was 23.0% in the group assigned to the algorithm “ON”, versus 7.7% in the group assigned to the algorithm “OFF” (relative risk 2.99; 95% CI 2.40–3.74; P<0.001). The cause of false positive automatic ATA detection was mainly due to 226 episodes of RNRVAS occurring in the AOP algorithm “ON” group, compared with 47 episodes in the AOP algorithm “OFF” group (P=0.001).
    Electrophysiological mechanisms of RNRVAS The electrophysiological mechanisms of RNRVAS have been thoroughly studied [17,21,22]. In dual-chamber pacing, it is usually observed in the presence of (1) VA conduction and retrograde P wave sensed within the post-ventricular atrial refractory period (PVARP), (2) additional programming in rate-adaptive mode or use of an AOP algorithm to prevent AF, and (3) programming of a long AV interval to prevent intrinsic AV conduction. The following additional conditions leading to the occurrence of RNRVAS are also notable: (1) setting of a long PVARP, (2) the presence of a long VA conduction time, (3) the presence of a long myocardial atrial refractory period, and (4) programming of a high lower pacing rate limit. Fig. 2 illustrates a common trigger of RNRVAS by a premature ventricular complex (PVC) propagating through the AV node and arriving at the atrium within the PVARP. If the AOP algorithm has been activated, the premature event is recognized as a premature atrial complex within the PVARP, causing early atrial pacing by the algorithm. However, this early pacing attempt might fall in the atrial refractory period, particularly in the presence of prolonged atrial refractoriness, for instance in the case of treatment with antiarrhythmic drugs. Although this ineffective atrial pacing does not activate the atrium, ventricular pacing occurs in programmed AV intervals in DDD or DDI modes. This ventricular-paced event propagates through the AV node retrogradely and activates the atrium. These cyclic atrial and ventricular depolarizations will be repeated continuously. The pacemaker will count 2 atrial (the first from retrograde conduction by a PVC or by ventricular pacing and the second from ineffective atrial pacing) and 1 ventricular paced event. Thus, during RNRVAS, an atrial sensed and a non-captured atrial paced event occurs cyclically with ventricular paced event.