Impact of myocardial phenotype on optimal atrioventricular delay settings during biventricular and left bundle branch pacing at rest and during exercise: insights from a virtual patient study

Figures

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  Figure 1. Overview of the simulation protocol used in this study. The first box shows the simulation of different HF phenotypes. Starting from the default reference with prolonged AVD, an LBBB-like ventricular activation pattern was imposed, followed by the simulation of dilatation (EF < 35%) with maintained, reduced contractility. We imposed an increase in myocardial stiffness until an mLAP exceeded 15 mmHg. The top and bottom boxes represent the simulation of cardiac pacing (i.e. BiVP and nsLBBP) and AVD optimization at rest and during exercise. The optimal paced AVD at rest was assessed using SV and mLAP which is used as a measure of LV filling pressure. AVD, atrio-ventricular delay, CO, cardiac output; EF, ejection fraction; HF, heart failure; HR, heart rate; LBBB, left bundle branch block; LV, left ventricular; mLAP, mean left atrial pressure; nsLBBP, non-selective LBB pacing; SBP, systolic blood pressure; SV, stroke volume.

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  Figure 2. Exercise protocol divided into six zones, each calculated as a percentage of the maximum heart rate (HRmax), which is determined using the fox formula (HRmax = 220–age). The calculation is based on a virtual patient aged 65 years. CO, cardiac output.

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  Figure 3. Effect of shortening AVD on SV and dPdtmax, representing the acute response, and mLAP representing the chronic response, starting from LBBB baseline at an AVD of 220 ms and applying BiVP (pink squared line) and nsLBBP (blue triangle line). The left panel shows the results in the presence of LBBB with dilatation and mantained contractility, while the right panel presents the results in the presence of LBBB with dilatation and decreased contractility. The green arrow and green square indicate the increase (for SV and dPdtmax) and decrease (for mLAP) due to pacing, while the orange arrow and orange square represent the increase (for SV and dPdtmax) and decrease (for mLAP) due to AVD optimization. AVD, atrio-ventricular delay; BiVP, biventricular pacing; dPdtmax, maximum rate of pressure change; LBBB, left bundle branch block; LV, left ventricle; mLAP, mean left atrial pressure; nsLBBP, non-selective left bundle branch pacing; SV, stroke volume.

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  Figure 4. Effect of shortening AVD on pressure and flow signals in the presence of LBBB with LV dilatation and maintained contractility (virtual patient A). The upper panel illustrates AVD optimization during BiVP , while the lower and right panels show results from AVD optimization during nsLBBP (blue lines). In both panels, mitral flow velocity and pressures are presented, with LA pressure shown by the solid line and LV pressure shown by the dotted line. These measurements are shown from the unpaced LBBB baseline at an AVD of 220 ms to pacing with a short AVD of 60 ms. The figure also presents mitral flow velocity and pressures before and after pacing at long (220 ms), medium (140 ms), and short (60 ms) AVDs. At long AVD, mitral flow is characterized by MR, while at short AVD LA pressure is characterized by a prominent canon A-wave. AVD, atrio-ventricular delay; BiVP, biventricular pacing; CRT, cardiac resynchronization therapy; EF, ejection fraction; LA, left atrium; LBBB, left bundle branch block; LV, left ventricle; mLAP, mean left atrial pressure; MR, diastolic mitral regurgitation; SV, stroke volume.

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  Figure 5. Haemodynamic effects of improving AV coupling during BiVP pacing (pink) and nsLBBP (blue). The figure shows the relative changes in haemodynamic function by shortening AVD, compared to baseline values for BiVP and nsLBBP at 220 ms (white dot). Virtual patient A shows LBBB with dilatation and preserved contractility (green); Virtual patient B represents LBBB with dilatation and reduced contractility (yellow); Virtual patient C demonstrates LBBB with dilatation, reduced contractility, and severe increase in passive stiffness (yellow + orange); Virtual patient D shows LBBB with severe reduction in contractility (red). The optimal AVD corresponds to the maximum SV, maximum dPdtmax, and minimum mLAP. AVD, atrio-ventricular delay; BiVP, biventricular pacing; mLAP, mean left atrial pressure; LBBB, left bundle branch block; nsLBBP, non-selective LBB pacing; SV, stroke volume.

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  Figure 6. Simulation-based assessment of the relative importance of AV delay optimization BiVP, across six exercise intensity zones: zone 0 (rest), zone 1 (50–60% HRmax), zone 2 (60–70% HRmax), zone 3 (70–80% HRmax), zone 4 (80–90% HRmax), and zone 5 (90–100% HRmax). The white dot marks the value of mLAP at an AVD of 220 ms during paced baseline. The vertical black line represents the optimal AVD at rest, while the black dot indicates the corresponding mLAP at this resting optimum. The red dot shows the mLAP at the optimal AVD for each level of exercise intensity. Starting from the resting condition with BiVP (depicted by the black parabolic line), the optimal AVD shifts to shorter values across all six substrates during exercise, as indicated by the black arrow. AVD, atrio-ventricular delay; BiVP, biventricular pacing; CO, cardiac output; HR, heart rate; HRmax, maximum heart rate; mLAP, mean left atrial pressure; Opt, optimal.

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  Figure 7. Mean left atrial pressure (mLAP) as a function of exercise intensity and the considered optimal AVD. The black line represents the mLAP values when the optimal AVD identified at baseline is maintained across all exercise stages. The gradient black-to-red line illustrates the mLAP values when the AVD is optimized for each individual exercise stage. The definition of the exercise intensity zones can be found in the caption of Figure 6. AVD, atrio-ventricular delay; LV, left ventricle.