Moderate elevation of arterial pressure caused marked reductions in LVEF and GLS in patients with LBBB. This reflects a cardiodepressive effect of elevated afterload in the dyssynchronous ventricle and was attributed to loss of septal function.

Background: Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function. Objective: To study how LBBB and CRT modify RV free wall function by direct ventricular interaction. Methods: In 24 LBBB patients with non-ischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers. Results: LBBB patients demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, it was demonstrated that this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall which pushed the septum towards the RV. CRT reduced abnormal septal motion and increased RV free wall work as there was less inefficient shortening against low pressure. Conclusions: LBBB reduces workload on the RV free wall due to abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT.

Aims: There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates which contractility indices are best markers of acute CRT response. Methods:In 8 anesthetized dogs with left bundle branch block we measured left ventricular (LV) pressure by micromanometer and end-diastolic (EDV) and end-systolic volumes (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dt max ) and as a gold standard of contractility, LV end-systolic elastance (E es ) and volume axis intercept (V 0 ) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared to inotropic stimulation by dobutamine. Results: Both CRT and dobutamine caused reduction in ESV (P<0.01) and increase in LV dP/dt max (P<0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V 0 (P<0.01), caused no change in E es . Dobutamine markedly increased E es , which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P<0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P=0.02) and caused a more marked increase in LV dP/dt max (P<0.01).Conclusions: Increased contractility by CRT could not be identified by E es which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dt max . These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.

Atrial switch operation in patients with transposition of the great arteries (TGA), leads to leftward shift and changes the geometry of the interventricular septum. By including the implications of regional work and septal curvature, this study investigates if changes in septal function and geometry contribute to reduced function of the systemic right ventricle (RV) in adult TGA patients. Regional myocardial work estimation has been possible by applying a recently developed method for non-invasive work calculation based on echocardiography. In 14 TGA patients (32±6 years, mean±SD) and 14 healthy controls, systemic ventricular systolic strains were measured by speckle tracking echocardiography and regional work was calculated by pressure-strain analysis. In TGA patients septal longitudinal strain was reduced to -14±2% vs -20±2% in controls (p<0.01) and septal work was reduced from 2046±318 to 1146±260 mmHg•% (p<0.01). Septal circumferential strain measured in a subgroup of patients, was reduced to -11±3% vs. -27±3% in controls (p<0.01), and a reduction of septal work (540±273 vs 2663±459 mmHg•%) were seen (p<0.01). These reductions were in part attributed to elevated afterload due to increased radius of curvature of the leftward shifted septum. To conclude, in this mechanistic study we demonstrate that septal dysfunction contributes to failure of the systemic RV after atrial switch in TGA patients. This is potentially a long-term response to increased afterload due to a flatter septum and suggests that medical therapy that counteracts septal flattening may improve function of the systemic RV.