Changes in electrical delay is associated with the hemodynamic response to cardiac pacing

Landmark studies on heart failure patients with prolonged QRS duration on the electrocardiogram (ECG) demonstrated that biventricular pacing (BIVP) was superior to right ventricular pacing (RVP).1Kass D.A. Chen C.-H. Curry C. et al.Improved left ventricular mechanics from acute vdd pacing in patients with dilated cardiomyopathy and ventricular conduction delay.Circulation. 1999; 99: 1567-1573Crossref PubMed Google Scholar Detrimental long-term effects and unpredictable acute hemodynamic effect to RVP led to the existing RVP skepticism, and BIVP was favored as the standard of care implementing cardiac resynchronization therapy (CRT).2Wilkoff B.L. Cook J.R. Epstein A.E. et al.Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator -The dual chamber and VVI implantable defibrillator (DAVID) trial.JAMA. 2002; 288: 3115-3123Crossref PubMed Scopus (0) Google Scholar However, despite reduction in mortality and morbidity, one third of eligible patients do not benefit from BIVP demonstrating the shortcoming of QRS duration and morphology to predict CRT response. Patients with left bundle branch block (LBBB) typically have deep S-waves in ECG electrode V1 and large R-waves in V5 representing a septal-to-lateral activation sequence. Plesinger et al. reported that ventricular electrical delay may be assessed as the dispersion of peak septal and lateral ECG amplitudes, and that a high ventricular electrical delay at sinus rhythm was associated with greater CRT benefit.3Plesinger J.F. Jurak J.P. Halamek J.J. et al.Ventricular electrical delay measured from body surface ECGs is associated with cardiac resynchronization therapy response in left bundle branch block patients from the MADIT-CRT trial (Multicenter automatic defibrillator implantation-cardiac resynchronization therapy).Circ Arrhythm Electrophysiol. 2018; 11e005719PubMed Google Scholar Conduction system pacing (CSP) have recently gained great interest and specifically left bundle branch area pacing (LBBAP) appears to be an attractive pacing option. Rapid activation is the overall aim of cardiac pacing and is measured continuously during the LBBAP procedure. Jastrzebski et al recently showed that the V6-V1 interpeak interval is a novel criterion for LBB capture confirmation.4Jastrzebski M. Burri H. Kielbasa G. et al.The V6-V1 interpeak interval: a novel criterion for the diagnosis of left bundle branch capture.Europace. 2022; 24: 40-47Crossref PubMed Scopus (86) Google Scholar The intrinsic conduction system is not utilized with RVP and BIVP. Still, we hypothesized that measurements of cardiac activation times would provide valuable information also in conventional pacing. In the present acute experimental study, we aimed to investigate the association between the electrical and hemodynamic changes induced by cardiac pacing and hypothesized that modification of the ventricular electrical delay caused by RVP and BIVP would influence on the acute hemodynamic response in patients undergoing CRT implantation. The Regional Ethical Committee for Medical Research (REK South East, Oslo, Norway) approved the research protocol and the study complied with the Declaration of Helsinki. All patients gave written informed consent. Statistical analysis was performed by linear mixed model regression (STATA SE 15.1) Values are reported as mean with 95% confidence interval. Thirty-eight patients (63±10 years, 31% women, 40% ischemic) with LBBB and a mean ejection fraction of 29±5% were included. Atrial pacing was followed by sequential RVP and BIVP with a patient specific paced AV delay (142±30 ms). Acute hemodynamic response was defined as the maximum rate of invasive LV pressure change (LV dP/dtmax). ECG analyses were performed using digital software (LabChart Pro 8.0, ADInstruments Ltd, Oxford, UK) and averaged over three consecutive heart beats. Ventricular electrical delay was assessed using ECG electrode V1 and V5. We measured time from intrinsic QRS onset or pacing spike to the point of steepest deflection at or after the peak amplitude of the S-wave or R-wave (Figure, left panel). Ventricular electrical delay was defined as the absolute time difference between these two points. We observed improved LV dP/dtmax with decreasing ventricular electrical delay independent of pacing site (10 [4,16] mmHg/s increase in LV dP/dtmax per 10 ms reduction of ventricular electrical delay, p=0.002). Compared to baseline, the increase in LV dP/dtmax during RVP was 32 (10,54) mmHg/s (p=0.004) but this effect was confounded by a reduction of ventricular electrical delay (Adjusted beta LV dP/dtmax 17 [-5,39], p=0.14). LV dP/dtmax increased 74 (46,101) mmHg/s with BIVP (p<0.001), plus an additional 10 mmHg/s per 10 ms reduction in ventricular electrical delay. Our results were independent of paced QRS duration. (Figure). This indicate that alignment of V1 and V5 reflect reduced LV electrical dyssynchrony regardless of paced QRS duration and translates into beneficial hemodynamics. In line with previous data, we found a great variation in acute hemodynamic response to RVP ranging from -21% to +20% change in LV dP/dtmax when compared to atrial pacing. Ventricular electrical delay identified the patients with LV dP/dtmax increase during RVP (AUC=0.78, p=0.009). However, whether a reduction in ventricular electrical delay is indicative of ability to withstand pacing induced heart failure remains to be explored. Time to onset of the steepest deflection measured in two precordial ECG electrodes is a simple method for assessment of LV electrical dyssynchrony in heart failure patients with LBBB. Reduction of ventricular electrical delay was a marker of favorable hemodynamic response to both RVP and BIVP and should be validated in a larger cohort including long-term response and clinical outcome.