Comparative electromechanical and hemodynamic effects of left ventricular and biventricular pacing in dyssynchronous heart failure: electrical resynchronization versus left-right ventricular interaction

Abstract

Objectives: The purpose of this study was to enhance understanding of the working mechanism of cardiac resynchronization therapy by comparing animal experimental, clinical, and computational data on the hemodynamic and electromechanical consequences of left ventricular pacing (LVP) and biventricular pacing (BiVP).

Background: It is unclear why LVP and BiVP have comparative positive effects on hemodynamic function of patients with dyssynchronous heart failure.

Methods: Hemodynamic response to LVP and BiVP (% change in maximal rate of left ventricular pressure rise [LVdP/dtmax]) was measured in 6 dogs and 24 patients with heart failure and left bundle branch block followed by computer simulations of local myofiber mechanics during LVP and BiVP in the failing heart with left bundle branch block. Pacing-induced changes of electrical activation were measured in dogs using contact mapping and in patients using a noninvasive multielectrode electrocardiographic mapping technique.

Results: LVP and BiVP similarly increased LVdP/dtmax in dogs and in patients, but only BiVP significantly decreased electrical dyssynchrony. In the simulations, LVP and BiVP increased total ventricular myofiber work to the same extent. While the LVP-induced increase was entirely due to enhanced right ventricular (RV) myofiber work, the BiVP-induced increase was due to enhanced myofiber work of both the left ventricle (LV) and RV. Overall, LVdP/dtmax correlated better with total ventricular myofiber work than with LV or RV myofiber work alone.

Conclusions: Animal experimental, clinical, and computational data support the similarity of hemodynamic response to LVP and BiVP, despite differences in electrical dyssynchrony. The simulations provide the novel insight that, through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by cardiac resynchronization therapy.

Keywords: % change in maximal rate of left ventricular pressure rise; % change in maximal rate of right ventricular pressure rise; ANOVA; AT(TOT); AV; BiVP; CRT; ECM; HF; LBBB; LV; LVP; LVdP/dt(max); RV; RVdP/dt(max); analysis of variance; atrioventricular; biventricular pacing; cardiac resynchronization therapy; dyssynchrony; electrocardiographic mapping; electrophysiology mapping; heart failure; left bundle branch block; left ventricle/ventricular; left ventricular pacing; myocardial work; right ventricle/ventricular; total ventricular activation time; ventricular interaction.

Figure 1. Electrocardiographic mapping in a dog and a patient with nonischemic heart failure and LBBB

Isochronal maps show timing of electrical activation during baseline, LVP, and BiVP. Black arrows indicate the left anterior descending coronary artery (LAD). The gray patch in the PA view represents the segmentation of the mitral orifice. Red asterisks indicate pacing sites. AP = anterior-posterior, LAO = left anterior oblique, and PA = posterior-anterior.

Figure 2. Pacing-induced changes of electrical dyssynchrony in dogs and patients

A) Change of total ventricular activation time (LV+RV free walls+septum in dogs; LV+RV free walls in patients). B) Change of LV activation time (LV free wall+septum in dogs; only LV free wall in patients). * p<0.05 versus baseline.

Figure 3. Simulated local myofiber mechanics in a failing heart during LBBB and pacing

Time courses of natural myofiber strain are plotted in black. Red asterisks indicate pacing sites. Vertical dashed lines indicate moment of mitral valve closure and LV ejection is highlighted in grey. Black circles indicate onset of systolic shortening. Relations between myofiber stress and myofiber strain are plotted in blue. Black arrows indicate segments with a clockwise stress-strain relation, indicating negative myofiber work. Color maps indicate myofiber work per ventricular wall segment.

Figure 4. Distribution of ventricular myofiber work during LBBB and pacing

Total ventricular myofiber work generated per cardiac cycle; percentages indicate the relative contributions of the LV and RV myocardium. LV myocardium includes the interventricular septum and the LV free wall.

Figure 5. Relationship between ventricular myofiber work and LV systolic function during pacing

Total ventricular myofiber work (left), LV myofiber work (middle), and RV myofiber work (right) per cardiac cycle versus LVdP/dt_max in 25 LVP simulations (circles) and 25 BiVP simulations (squares). The left panel indicates that total ventricular myofiber work increased linearly with LVdP/dt_max and that this linear relationship was virtually independent of the pacing mode. The middle and right panel show that LVP and BiVP behaved differently when considering LV and RV myofiber work separately. For both pacing modes, five clusters of simulations can be discriminated by their color, indicating total ventricular activation time (AT_TOT) that ranged from 54 to 162 ms for LVP and from 24 to 72 ms for BiVP. Each cluster (e.g. dashed circle) consists of five simulations with the same AT_TOT, but with different AV delays (60/80/100/120/140 ms).