In this study, maximum SV was obtained during RV pacing with optimal AV delay rather than during intrinsic AV conduction in patients with pacemakers and first-degree AV block. However, even though the pacemaker was programmed to the optimal setting based on echocardiographic assessment, seven (41%) patients developed HF, suggesting that some patients may have better hemodynamics in a pacing mode that preserves intrinsic ventricular contraction with very long PR intervals than with RV pacing in the DDD pacing mode with an optimal AV delay, which is believed to be more physiological. This is the first study that compared the incidence of HF between a pacing mode-preserving intrinsic ventricular contraction with prolonged PR intervals and RV pacing with the optimal AV delay in patients with pacemakers.
Sweeney et al. reported that RV pacing induces HF and atrial fibrillation in the Mode Selection Trial (MOST) [
9]. The development of HF in seven patients in the present study supports this report. On the other hand, Riahi et al. reported that RV pacing in the DDD pacing mode is not associated with the development of HF [
19]. Ten patients in the present study did not develop HF, similar to the results from Riahi et al.
There are many studies indicating that RV pacing is harmful [
5‐
7]. Therefore, pacemaker manufacturers have developed pacemakers with new algorithms that preserve intrinsic conduction. These algorithms include Managed Ventricular Pacing (MVP
™; Medtronic, Minneapolis, USA) and Ventricular Intrinsic Preference (VIP
™; Abbott Laboratories, Illinois, USA). In our clinical practice, there have been questions about what is the maximum acceptable prolongation of the PR interval and whether intrinsic AV conduction should be preserved even if the PR interval is ≥ 300 ms when these algorithms are applied. In the present study, RV pacing did not lead to adverse events in approximately 60% of patients. However, RV pacing led to HF in approximately 40% of patients. These findings cannot completely suggest that RV pacing is harmful. In this study, some patients developed HF even though all patients had LVEF > 50% at baseline and their pacemakers were programed with the optimal AV delay to provide the maximum SV, suggesting that the development of HF might not always be associated with impaired systolic function. In contrast, some studies reported that worsening of HF is associated with impaired systolic function [
20,
21]. E/E′ ratio has commonly been used as an index of diastolic function in clinical practice and research studies [
22,
23]. The present study compared changes in E/E′ ratio before and after RV pacing between the HF and non-HF groups. Compared with the non-HF group, E/E′ ratio worsened to > 15 or increased from baseline in the HF group. Therefore, patients with impaired diastolic function or who develop left heart strain during RV pacing might be at risk of developing HF associated with RV pacing. Although it is difficult to fully explain why the optimal AV delay sometimes leads to HF, we speculate that RV pacing can lead to systolic dyssynchrony despite AV delay optimization, resulting in diastolic dysfunction. In this study, optimal AV delay was determined based on echocardiographic assessment. Echocardiography was performed in the resting state and this programming might not be the best in situations when heart rate increases. Intrinsic AV conduction might differ as heart rate increases. Therefore, it is possible that the optimal AV delay was no longer optimal when the patient is active or in an emotional state. We believe that this is a limitation of AV optimization based on echocardiography, unless the echocardiographic assessment was performed during exercise (e.g., with an ergometer).
Clinical implications
The results of this study suggested that E/E′ ratio might be useful for predicting an increase in heart strain and the development of heart failure in association with RV pacing. Previous studies have found RV pacing unfavorable and recommended intrinsic conduction [
5‐
7]. However, it is unknown whether a very long AV conduction time is acceptable. In this study, the DDD pacing mode with optimal AV delay resulted in greater SV than very long intrinsic AV conduction based on echocardiographic assessment. Approximately 60% of the study patients did not develop HF during RV pacing, suggesting that the DDD pacing mode with the optimal AV delay, which is believed to be physiological, might be better than intrinsic conduction if the intrinsic AV conduction time is too long. On the other hand, the remaining 40% patients developed HF during RV pacing, indicating that intrinsic conduction should be preferred over RV pacing in such patients even if their intrinsic AV conduction time is substantially longer than the optimal AV delay. These findings might be consistent with findings from the Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial [
24], which showed that CRT should be selected for patients with low cardiac function (LVEF < 50%). This study might help determine whether the current pacemaker should be replaced with CRT-P to enhance treatment. E/E′ ratios before and after RV pacing may be useful information for determining whether intrinsic AV conduction should be preferred or the current pacemaker should be replaced with CRT-P early in patients with first-degree AV block who will inevitably require pacing.
Limitations
This study has some limitations. First, the sample size was small, with only 17 patients. We originally planned to include more patients, but had to discontinue patient enrollment, because some patients developed HF associated with RV pacing and there was a possible risk of causing a disadvantage to patients. Second, follow-up duration was too short to determine the effect of RV pacing on HF, due to the same reason as for the first limitation. However, despite this short follow-up duration, a relatively high number of patients developed HF unexpectedly. This result demonstrated that undesirable effects are possible with RV pacing in certain patients. Third, the AV delay that provided the maximum SV was selected as the optimal AV delay based only on echocardiography. We are not sure whether relying only on echocardiographic assessment is the gold standard. However, we selected this strategy because previous studies also set AV delay based on echocardiographic findings [
8‐
13].