Atrioventricular dromotropathy: an important substrate for complete resynchronization therapy-Authors' reply.

Mežnar et al. commented on our publication on the effect of biventricular pacing in patients with long PR interval and no Class I indication for cardiac resynchronization therapy. They mention that in their clinical experience a long PR interval is not always related to left-sided atrioventricular (AV) uncoupling. Of course, this is possible if inter-atrial conduction is slow. However, in the present cohort, we found only three patients not responding haemodynamically to biventricular pacing (i.e. 85% of the cohort showed haemodynamic improvement). Interestingly, the three non-responders did not show fusion of the transmitral E- and A-waves at baseline and had a longer baseline E–A interval compared to responders (253 ± 81ms vs. 83 ± 119ms, respectively), indeed suggesting a role for actual mechanical AV delay. Therefore, the left ventricular (LV) filling pattern at baseline may be important for selection of patients with long PR for pacemaker therapy. Of course, a larger study is needed to support this hypothesis.

The point the authors raise about left atrial (LA) pressure is highly relevant. Indeed, elevated LA pressure has important clinical implications, such as higher risk for development of atrial fibrillation as well as lung oedema and congestion. We addressed LA pressure in several ways: in the animal studies we observed that at optimal AV delay of BiV pacing LV end diastolic volume (LVEDV) was larger while mean LA pressure was similar to baseline, due to the optimal timing of LA vs. LV contraction: larger forward flow and less mitral regurgitation. The latter two improvements were also observed in the patients, but in patients we did not measure LA pressure due to unacceptable invasiveness of that procedure.

The best control of mechanical AV delay was present in the computer simulations. In the simulations performed in the present study default right atrial (RA)–LA delay was 30 ms, so that actual LA–LV mechanical delay was effectively 30 ms shorter than the programmed A–LV ‘stimulation’ delay. The effect of larger RA–LA delay and, hence, smaller mechanical LA–LV delay has been studied in a recent, yet unpublished study from our group. It was shown that an increase in RA–LA conduction time indeed resulted in a shorter optimal AV delay. However, the shift towards shorter optimal AV delay was consistently smaller than the increase in inter-atrial conduction delay (i.e. a 28 ms decrease of optimal AV delay at a 40 ms increase of inter-atrial conduction delay). Therefore, we think that inter-atrial conduction delay has only a limited modulating effect on the optimal AV delay and haemodynamic effect. A yet unstudied factor that may be of importance is the role of myocardial stiffness on the response to AV delay optimization in those patients. Theoretically, larger stiffness leads to smaller volume effects at similar changes of diastolic pressures. As a result, haemodynamic response to AV optimization may be reduced in stiffer hearts, but further studies are required.

Conflict of interest: J.L. has received research grants from Medtronic. F.W.P. has received research grants from Medtronic, Abbott, Microport CRM, and Biotronik. K.V. has received research grants from Medtronic, Abbott and has a consultancy agreement with Medtronic and Abbott. The remaining authors have nothing to disclose.