Author + information
- Published online March 29, 2017.
- Section of Cardiac Electrophysiology, Edith and Benson Ford Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan
- ↵∗Address for correspondence:
Dr. Claudio D. Schuger, Cardiac Electrophysiology Section, Edith and Benson Ford Heart and Vascular Institute, Henry Ford Health System, 2799 West Grand Boulevard, M322, Detroit, Michigan 48202.
- ↵∗∗Dr. Gurjit Singh, Cardiac Electrophysiology Section, Edith and Benson Ford Heart and Vascular Institute, Henry Ford Health System, 2799 West Grand Boulevard, M322, Detroit, Michigan 48202.
Sinus node dysfunction (SND) or “sick sinus syndrome” is an umbrella definition that includes sinus bradycardia, sinus arrest or pause, and bradycardia−tachycardia syndrome. Permanent pacemaker therapy is the gold standard treatment for symptomatic SND, with the goal of alleviating patient symptoms and improving quality of life. Although the annual incidence of development of atrioventricular (AV) block in SND is estimated to be approximately 0.6% to 1.7%, dual-chamber pacing has become the standard of care throughout the world because of the need for ventricular pacing in the event of development of symptomatic AV block (1,2).
Single-chamber AAI(R) pacing was compared with DDD(R) pacing in the DANPACE (Danish Multicenter Randomized Trial on Single Lead Atrial Pacing versus Dual Chamber Pacing in Sick Sinus Syndrome) trial with no difference in long-term mortality, but there was a higher incidence of paroxysmal atrial fibrillation (AF) with single-chamber atrial pacing (3). In contrast, long-term detrimental effects of right ventricular (RV) apical pacing has gained significant attention since the publication of the DAVID (Dual Chamber and VVI Implantable Defibrillator Trial) and MOST (Mode Selection Trial In Sinus Node Dysfunction Trial) studies, and a subanalysis of the MADIT II (Multicenter Automatic Defibrillator Implantation Trial) trial, all of which showed increased risk of AF, heart failure (HF), and death with >40% RV pacing. A recent publication in a permanent pacemaker cohort with AV block showed a significant 2.3% incidence of pacing-induced cardiomyopathy with chronic RV pacing with as low as 20% RV pacing burden (4).
Because of these previous findings, multiple algorithms were developed to minimize ventricular pacing in pacemaker and defibrillator recipients without complete AV block. Two basic ways of reducing RV pacing in dual-chamber devices were developed to promote intrinsic AV nodal conduction, either by allowing extended AV delays (AV hysteresis) or by operating in AAI(R) mode, with a rapid mode switch to ventricular pacing mode DDD(R) in case of loss of AV conduction. All device manufacturers have different types of these algorithms, and there have been multiple studies in patients with SND and AV conduction disease comparing one modality to the other in their ability to reduce the percent of RV pacing. The Managed Ventricular Pacing (MVP) (Medtronic, Minneapolis, Minnesota) algorithm has been studied the most and has shown a consistent reduction in cumulative ventricular pacing compared with other search AV hysteresis algorithms in patients without a high-degree AV block (5–7).
In this issue of JACC: Clinical Electrophysiology, Calvi et al. (8) described the comparative performance of 2 ventricular pacing minimizing algorithms in a manufacturer-sponsored (Biotronik SE & Co. KG, Woermannkehre, Berlin, Germany) randomized, multicenter study of 230 patients with SND. Patients with advanced AV block were excluded. Patients were randomized to intrinsic rhythm support (IRS plus), a form of search AV hysteresis, versus ventricular pace suppression (VpS), a DDD(R)–ADI(R) mode switch algorithm, in a crossover design study after 6 month follow-up. The primary objective of the trial was the efficacy of each algorithm in reducing the percent of RV pacing. The IRS plus algorithm included both scan hysteresis (after 180 ventricular paced events, the AV delay was extended to 400 ms for 5 cycles to check for intrinsic conduction, and if no sensed ventricular event was recorded in those 5 cycles, the AV delay was reprogrammed to its nominal value), and repetitive hysteresis (if a V paced event was noted at a maximum AV delay of 400 ms, the AV delay continued in extended mode for the next 5 cycles searching for intrinsic conduction). The VpS algorithm was initiated in DDD(R) mode, and a ventricular sense (Vs) event search began with a spontaneous Vs event or after continuous V pacing starting at 30 s, with doubling of unsuccessful searching intervals up to 128 min. In each of these searching intervals, the AV delay was extended up to 450 ms for the next 8 cycles, and if 6 of these 8 cycles revealed a Vs event, the mode was switched to ADI(R). DDD(R) function was restored if 1 of 4 independent conditions were met, all of them based on either lack of Vs over time or recording of frequent mode switches.
The results basically confirmed what was already known, that is, patients implanted with dual-chamber pacemakers for SND that is programmed with any V pacing minimizing algorithms do not require much V pacing; in this study the median V pacing was ≤3%. However, as opposed to previous trials in which pacing mode switch strategies were mostly superior to AV hysteresis in reducing RV pacing, this trial showed a surprising statistically significant difference of reduced V pacing with the IRS plus algorithm (median percentage of V pacing: 1%) compared with the VpS mode switching algorithm (median percentage of V pacing: 3%), with no significant clinical difference in terms of AF, change in ejection fraction, or left ventricular volumes.
Although no direct comparisons are possible across algorithms from different manufacturers because of the absence of head-to-head comparison trials, a possible explanation could be that the IRS plus algorithm is initiated easily and performs more frequent checks of Vs events, which, in turn, may promote more intrinsic conduction than other types of AV search hysteresis algorithms. In contrast, the VpS algorithm requires more stringent and additional checks for AV conduction to avoid frequent mode switches. As a comparison, the situation may be the exact opposite with Medtronic pacing reduction algorithms, that is, the MVP algorithm checks for AV conduction more frequently (after 1 minute of DDD pacing), whereas the SAV+ algorithm checks for AV conduction only after 15 minutes, which may lead to overestimating the incremental benefit of the MVP algorithm over their own search hysteresis.
Regardless of the specifics and complexities of these algorithms, we can conclude that patients with SND and overall intact AV conduction require infrequent RV pacing and choosing one algorithm versus the other does not seem to have much clinical impact. No study has ever shown a clinical benefit in terms of cardiovascular hospitalization or mortality by using RV pacing minimizing algorithms compared with straight DDD pacing. In the PreFER MVP (Prefer for Elective Replacement MVP) trial, which involved 605 patients with >40% RV pacing who underwent pacemaker or implantable cardioverter-defibrillator generator replacement, programming MVP mode did not reduce cardiovascular hospitalization or persistent AF despite marked reduction in the percent of RV pacing (9). Although infrequent, programming pacing reduction algorithms may result in significant side effects. There have been multiple case reports of ventricular arrhythmias precipitated by short−long−short sequences seen with MVP programming, in addition to pacemaker syndrome, due to a failure to switch from AAI to DDD mode in patients with intermittent second-degree AV block because of long dynamic atrial refractory periods (10–12). Long intrinsic AV intervals have been associated with increased risk of AF and all-cause mortality, and the potential adverse effects of long AV delays allowed by current pacing reduction algorithms cannot always be justified only on the basis of reducing the putative damage of modest RV pacing (13).
Because of all the nuances of these different algorithms, which all have excellent efficacy in minimizing unnecessary RV pacing, but do not have any effect on hard clinical endpoints in SND populations, it seems prudent to continuously assess AV conduction in patients and change the programming to best suit individual patients without getting entangled in the knots.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Drs. Schuger and Singh have reported that they have received research grants from Boston Scientific, Biotronik, and St. Jude Medical. Dr. Singh has received honorarium from Zoll.
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