Rick Schreurs

53 Cardiac pacing in first degree AV-block marker of CRT benefit in LBBB patients [26,27]. Yet, the overall hemodynamic benefit of AV-coupling in terms of cardiac output seems at least as large as that of “CRT”. Increases in stroke work, measured in this study using the conductance catheter technique, were on average slightly smaller than those measured during conventional CRT (28 vs. 43%) [28]. However, this difference may be due to very small pressure-volume loop areas in LBBB hearts that may be associated with an artefact of the conductance catheter technique. Another important finding is that the increased LV filling during optimal AV-coupling is achieved by both improved diastolic filling pattern (i.e. larger and better separated E- and A-waves) and less diastolic MR. Finally, an important finding from the animal and simulation studies was that the improved filling was achieved while mean LA pressure was equal to or lower than baseline, indicating that the better forward pump function may even coincide with reduced backward failure. In the past, several studies have shown similar results concerning parts of the parameters investigated in the present study. The importance of proper AV-coupling has already been addressed by animal studies in the 1960s [29,30], reporting that a properly timed effective atrial contraction is necessary for optimal LV systolic function. Similar findings were obtained in a small clinical study where echo-Doppler as well as invasive pressure and flowmeasurements were used. In eight patients with PR-intervals >200ms, AV-optimization using DDD RV pacing increased filling times, LV end-diastolic pressure and cardiac output [31]. Other clinical studies showed echo-Doppler recordings of mitral E- and A-waves with A-wave truncation at too short AV-delays and E-A-wave fusion combined with diastolic MR at too long AV-delays [32,33]. The results from the present study provide the full picture with comprehensive invasive hemodynamic measurements in animals and patients, supplemented by computer simulations that enable control of experimental conditions that cannot be achieved in vivo. Furthermore, the use of the first derivative of the LV volume signal of the conductance catheter provides diastolic ventricular inflow patterns, rather than velocities as is the case in echo-Doppler studies. Therefore, the forward and backward flows, determined in the present study, represent the actual blood volume displaced. The fact that the computer model could replicate all the changes seen in the animals, indicates that the mechanism of hemodynamic improvement by optimizing AV-delay can be explained by the well-established physical and physiological principles that are incorporated in the model, such as conservation of energy, inertia of blood, and length- dependent activation of myocytes (Frank-Starling effect). Effects of ventricular pacing-induced dyssynchrony RV pacing is known to increase ventricular dyssynchrony and thereby to have a negative impact on cardiac pump function [34,35]. Our patient and simulation data show that the benefit of normalizing AV-coupling should be weighed against the detrimental effect 3