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Contains fulltext : 245658.pdf (Publisher’s version ) (Closed access) PURPOSE: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients. METHODS: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint-echocardiographic reduction of left ventricular end-systolic volume (LVESV)-were evaluated. RESULTS: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT. CONCLUSIONS: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT.

Aims Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational–experimental–clinical study. Methods and results Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction 230 ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure, and cardiac output by 10–15%. In computer simulations of failing hearts and in HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300 ± 61 to 137 ± 30 ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34 ± 40% and 26 ± 31%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation. Conclusion Restoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval.

Left ventricular septal pacing (LVSP) and left bundle branch pacing (LBBP) have been introduced to maintain or correct interventricular and intraventricular (dys)synchrony. LVSP is hypothesised to produce a fairly physiological sequence of activation, since in the left ventricle (LV) the working myocardium is activated first at the LV endocardium in the low septal and anterior free-wall regions. Animal studies as well as patient studies have demonstrated that LV function is maintained during LVSP at levels comparable to sinus rhythm with normal conduction. Left ventricular activation is more synchronous during LBBP than LVSP, but LBBP produces a higher level of intraventricular dyssynchrony compared to LVSP. While LVSP is fairly straightforward to perform, targeting the left bundle branch area may be more challenging. Long-term effects of LVSP and LBBP are yet to be determined. This review focuses on the physiology and practicality of LVSP and provides a guide for permanent LVSP implantation.

Background PR prolongation is associated with poor hemodynamic performance and may contribute to heart failure (HF). There is some evidence that in HF patients, normalization of atrioventricular (AV) coupling can attenuate HF. Purpose To investigate acute hemodynamic effects of restoration of AV coupling by atrio-biventricular (BiV) pacing in patients with HF and PR prolongation, but without evident ventricular dyssynchrony. Methods Nineteen patients underwent BiV pacemaker implantation. An invasive hemodynamic pacing protocol was performed during BiV and right ventricular (RV) pacing with four paced AV delays (100, 75, 50 and 25% of patient's PR interval during baseline AAI pacing). All patients had symptomatic HF, left ventricular ejection fraction (LVEF) 150 ms or left bundle branch block. Acute hemodynamic response was assessed by invasive left ventricular (LV) stroke work measurements (conductance catheter technique). Results At baseline, PR interval was 255±22 ms, QRS duration 122±19 ms and LVEF 29±6%. Reducing AV delay to 50% of patient's intrinsic PR interval by BiV pacing resulted in a median 25% increase (p Conclusion In patients with HF and PR prolongation, BiV pacing can be used to improve AV coupling that leads to hemodynamic improvement. These results suggest that BiV pacing may also be beneficial in this subset of HF patients that are currently not indicated for CRT. ReachPR Trial Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Abbott funded a part of this study.

Contains fulltext : 229186.pdf (Publisher’s version ) (Closed access) The adverse effects of ventricular dyssynchrony induced by right ventricular (RV) pacing has led to alternative pacing strategies, such as biventricular, His bundle (HBP), LV septal (LVSP) and left bundle branch pacing (LBBP). Given the overlap, LVSP and LBBP are also collectively referred to as left bundle branch area pacing (LBBAP). Although among these alternative pacing sites HBP is theoretically the ideal strategy as it maintains a physiological ventricular activation, its application requires more skills and is associated with the most complications. LBBAP, where the ventricular pacing lead is advanced through the interventricular septum to its left side, creates ventricular activation that is only slightly more dyssynchronous. Preliminary studies have shown that LBBAP is feasible, safe and encounters less limitations than HBP. Further studies are needed to differentiate between LVSP and LBBP with regard to acute functional and long-term clinical outcome.

BACKGROUND Cardiac resynchronization therapy (CRT) is usually performed by biventricular (BiV) pacing. Previously, feasibility of transvenous implantation of a lead at the left ventricular (LV) endocardial side of the interventricular septum, referred to as LV septal (LVs) pacing, was demonstrated.OBJECTIVES The authors sought to compare the acute electrophysiological and hemodynamic effects of LVs with BiV and His bundle (HB) pacing in CRT patients.METHODS Temporary LVs pacing (transaortic approach) alone or in combination with right ventricular (RV) (LVs+RV), BiV, and HB pacing was performed in 27 patients undergoing CRT implantation. Electrophysiological changes were assessed using electrocardiography (QRS duration), vectorcardiography (QRS area), and multielectrode body surface mapping (standard deviation of activation times [SDAT]). Hemodynamic changes were assessed as the first derivative of LV pressure (LVdP/dtmax).RESULTS As compared with baseline, LVs pacing resulted in a larger reduction in QRS area (to 73 +/- 22 mu Vs) and SDAT (to 26 +/- 7 ms) than BiV (to 93 +/- 26 mVs and 31 +/- 7 ms; both p CONCLUSIONS LVs pacing provides short-term hemodynamic improvement and electrical resynchronization that is at least as good as during BiV and possibly HB pacing. These results indicate that LVs pacing may serve as a valuable alternative for CRT. (C) 2020 by the American College of Cardiology Foundation.

Background Cardiac resynchronization therapy (CRT) is usually performed with a right (RV) and left ventricular (LV) lead. In a previous patient study, pacing the interventricular septum permanently on the LV endocardial side (LV septum) proved feasible in patients with sinus node dysfunction. Objective To investigate the effects of LV septal pacing as compared to conventional biventricular (BiV) pacing with respect to acute hemodynamic and electrophysiological effects in CRT indicated heart failure patients. Methods Temporary LV septal pacing (transarterial approach) and pacing in the conventional BiV mode using the implanted leads was performed in 26 patients (QRS duration 163±17 ms, 23 left bundle branch block patients) undergoing CRT implantation. Acute hemodynamic response (relative to baseline AAI pacing) was assessed by LVdP/dtmax. Multi-electrode body-surface mapping, what has been used previously to characterize electrical dyssynchrony in CRT patients, was evaluated using the standard deviation of activation times (SDAT) (figure, right panel). Results LV septal pacing resulted in a significant LV dP/dtmax increase, that was comparable to conventional BiV pacing (figure, left panel). Combined RV and LV septal pacing did not provide an additional increase. LV septal pacing resulted in a significantly larger reduction in SDAT than RV plus LV septal pacing and conventional BiV pacing (figure, middle panel). Conclusions LV septal pacing results in acute hemodynamic improvement and electrical resynchronization that is at least as good as conventional BiV pacing. These results suggest that LV septal pacing with a single ventricular lead may serve as an alternative to conventional BiV pacing for cardiac resynchronization. Acknowledgement/Funding Medtronic is a subsidising party.

Background The effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited, compared to those with LBBB. Still, a substantial part of these patients can benefit from therapy and additional selection criteria are needed to identify these patients. Purpose To evaluate the association of additional baseline 12-lead ECG features; with clinical and echocardiographic outcomes in CRT-treated non-LBBB patients. Methods Pre-implantation 12-lead ECGs from 790 consecutive non-LBBB CRT patients from 3 implanting centres in the Netherlands were evaluated for the presence of predefined ECG parameters. QRS morphology (right bundle branch block and intraventricular conduction delay), QRS duration (≥/ Results There was a significantly lower occurrence of the primary endpoint in non-LBBB patients with QRS area ≥109 μVs (p Figure 1 Conclusion A large QRS area and the absence of fQRS are positively associated to event free survival in non-LBBB patients treated with CRT. Whereas currently used patient selection cut-off QRS duration is not associated to outcome in these patients. These data may provide additional value for the non-LBBB patient selection for CRT and warrant prospective evaluation of these ECG features. Acknowledgement/Funding None

Background Patients without left bundle branch block (non-LBBB) generally derive little benefit from CRT. Recently, CRT has been suggested to be beneficial in patients with prolonged PR interval. However in the general HF population, the presence of prolonged PR interval is associated with worse outcome. Purpose To evaluate the association of a prolonged PR interval with clinical outcome in CRT-treated LBBB and non-LBBB patients. Methods Pre-implantation 12-lead ECGs from 1.245 consecutive CRT patients without atrial fibrillation from 3 implanting centres in the Netherlands were evaluated for the presence of LBBB QRS morphology and PR interval prolongation (≥230ms). The primary endpoint was the combination of left ventricular assist device implantation, cardiac transplantation and all-cause mortality. Results Patients with LBBB (n=620) showed a significantly shorter mean PR interval than non-LBBB patients (n=625) (187ms vs 198ms, p Figure 1 Conclusion In HF patients treated with CRT, PR prolongation is negatively associated with long term clinical outcome. The association seems to be stronger in non-LBBB patients than in LBBB patients. Acknowledgement/Funding None

Background Cardiac resynchronization therapy (CRT) is usually performed with a right (RV) and left ventricular (LV) lead. Previous observational studies showed promising results with His bundle pacing (HBP) in patients with left bundle branch block (LBBB) by capturing and recruiting the native His-Purkinje system as an alternative to provide ventricular resynchronization. Objective To investigate the effects of HBP as compared to conventional biventricular (BiV) pacing with respect to acute hemodynamic and electrophysiological effects in heart failure patients with LBBB. Methods RV apical and BiV pacing, using the implanted leads, and temporary HBP, using an electrophysiology catheter, was performed in 13 patients (QRS duration 168±16 ms) undergoing CRT implantation. Hemodynamic response (relative to baseline AAI pacing) was assessed as change in LVdP/dtmax. Multi-electrode body-surface mapping, what has been used previously to characterize electrical dyssynchrony in CRT patients, was evaluated using the standard deviation of activation times (SDAT) (figure, right panel). Results HBP resulted in a significant LV dP/dtmax increase, that was comparable to the increase during BiV pacing and significantly larger than RV pacing (figure, left panel). HBP resulted in a more homogenized electrical activation and larger reduction in SDAT than both conventional BiV pacing and RV pacing (figure, middle panel). Conclusions Acute HBP results in hemodynamic improvement and electrical resynchronization that is as good as conventional BiV pacing. These results suggest that HBP may serve as an alternative for conventional BiV pacing in LBBB patients, however prospective studies are needed to prove chronic clinical outcomes. Acknowledgement/Funding Medtronic is a subsidising party.

Item does not contain fulltext Heart failure (HF) is often accompanied by atrioventricular (AV) conduction disturbance, represented by prolongation of the PR interval on the electrocardiogram. Studies suggest that PR prolongation exists in at least 10% of HF patients, and it seems more prevalent in the presence of prolonged QRS duration. A prolonged PR interval may result in elevated left ventricular (LV) end-diastolic pressure, diastolic mitral regurgitation, and reduced LV pump function. This seems especially the case in patients with heart disease, in whom it is associated with an increased risk for atrial fibrillation, advanced AV heart block, HF, and death. These findings point towards the importance of proper AV coupling in HF patients. A few studies, strongly differing in design, suggest that restoration of AV coupling in patients with PR prolongation by pacing improves cardiac function and clinical outcomes. These observations argue for AV-dromotropathy as a potential target for pacing therapy, but other studies show inconsistent results. Given its potential clinical implications, restoration of AV coupling by pacing warrants further investigation. Additional possible future research goals include assessing different techniques to measure compromised AV coupling, determine the best site(s) of ventricular pacing, and assess a potential influence of diastolic mitral regurgitation in the efficacy of such therapy.