Rick Schreurs

42 Chapter 3 hemodynamic data of this study showed significant improvement. Patients were excluded when they already had a CRT device, in the presence of a class I CRT indication (LBBB or QRS duration >150ms). Also, a resting heart rate >90bpm, chronic renal failure requiring dialysis, moderate to severe aortic stenosis, frequent premature ventricular complexes (≥two complexes on a standard ECG), significant peripheral vascular disease, an age below 18 years or recent (<3 months) myocardial infarction, coronary artery bypass grafting or valve surgery were exclusion criteria. All participants underwent CRT device implantation according to routine clinical practice. The atrial lead was positioned in the right atrial appendage, the RV lead in the RV apical septum, and a quadripolar LV lead in a suitable vein on the posterolateral LV wall. A 7Fr pressure-volume loop conductance catheter (CD Leycom, Zoetermeer, The Netherlands) was introduced into the LV cavity via the femoral artery. ECG and LV pressure and volume were recorded during BiV and RV pacing at four paced AV-delays. The paced AV-delay was set to approximate 100, 75, 50 and 25% of patient’s PR-interval during baseline AAI pacing minus 30ms to ensure capture at the longest AV- delay. The pacing protocol (in DDD mode) was performed at ±10bpm above intrinsic sinus rate. Interventricular pacing delay was set to -40ms (LV first). Baseline measurements were performed during atrial pacing (AAI mode) at the same pacing rate before and after each mode of ventricular pacing. Pressure-volume loops were recorded for 60 seconds during the ventricular pacing protocol and 30 seconds before and after each setting in AAI mode. The latter were averaged and are referred to as baseline [22]. Data analysis The acute hemodynamic effect of pacing at the different AV-delays in animals and patients was evaluated by invasive measurement of LV stroke volume and stroke work (area of the pressure-volume loop) as well as the diastolic flow pattern, derived from the first derivative of the LV volume signal (flow; right panel of figure 1 ) using a combination of the Conduct NT software (CD Leycom, Zoetermeer, The Netherlands) and customized software programmed in MATLAB R2019b (MathWorks, Natick, Massachusetts, USA). Diastolic MR volume was quantified as the area below zero of the flow curve during diastole. Forward flow over the mitral valve was quantified as the combined area under the E- and A-waves (see also figure 1 and 2 ). The diastolic MR fraction was defined as diastolic MR as a percentage of forward flow. In the animals stroke volume was derived from the aortic flow probe. To account for spontaneous changes in baseline hemodynamic outcome parameters, each ventricular pacing setting was compared to the corresponding baseline. Ectopic ventricular beats and the two subsequent heart beats were excluded from the analysis. Conductance catheter measurements were volume calibrated by adjusting baseline stroke volume to stroke volume measured using Swan Ganz thermodilution catheters in animals and to preprocedural echocardiography in patients.