Therapies currently approved to treat heart failure with reduced ejection fraction
(HFrEF) have generally shown significant benefit on morbidity and mortality, resulting in
strong recommendations in treatment guidelines. Four standard drugs classes, composed of
beta-blockers, angiotensin-converting enzyme-inhibitor/angiotensin receptor
blocker/angiotensin receptor-neprilysin inhibitor (ACE-I/ARB/ARNI), mineralocorticoid
receptor antagonist (MRA) and sodium-glucose co-transporter 2 inhibitor (SGLT2i), have
already been standard background therapy in HFrEF. Cardiac resynchronization therapy with
pacemaker/Cardiac resynchronization therapy with defibrillation (CRT-P/CRT-D) is an
established treatment to HF patients, especially in LVEF ≤35%, sinus rhythm, CLBBB with a
QRS duration (QRSd) ≥150 ms, and symptoms on 3-6 months of GDMT. Both the 2021 ESC and
the 2022 AHA/ACC/HFSA guidelines for HF included LVEF≤35% after 3-6 months of GDMT as a
strong indication for ICD implantation in non-ischemic heart disease.
The traditional biventricular pacing (BiVP) could correct the cardiac dyssynchrony to
improve clinical symptoms and reduce all-cause mortality in HF. However, almost 30%-40%
of patients with successful implantation show no response and BiVP just corrects the
mechanical dyssynchrony caused by LBBB not corrects the LBBB. His Purkinje conduction
system pacing (HPCSP) technology has made significant progress in recent five years. His
bundle pacing (HBP) and left bundle branch pacing(LBBP) can correct LBBB and achieve
physiological cardiac resynchronization only by ordinary single-chamber or dual-chamber
pacemaker. LBBP has been reported to produce stable pacing thresholds, adequately sensed
R-wave amplitude, and higher likelihood to correct LBBB by pacing more distal to the site
of conduction block compared with HBP. The feasibility and efficacy of LBBP for CRT in HF
patients with LBBB was demonstrated by previous observational studies showing that
LBBP-CRT achieves a narrower QRSd, higher percentage of super responders, and lower
pacing thresholds than BiVP-CRT. The LBBP-RESYNC study showed that LBBP-CRT demonstrated
greater LVEF improvement than BiVP-CRT in HF patients with NICM and LBBB.
It remains unclear as to the following questions: 1. After 3-6 months of GDMT, what is
the percentage of patients with LVEFs improvement from ≤35% to >35% in HFrEF patients
with NICM and CLBBB, and what are the absolute values of the increase in LVEFs; 2. How is
the long-term prognosis of those patients with LVEF increased to >35% after GDMT. Whether
these patients still need an ICD/CRT-D since they do not fall within the recommendations
for primary prevention of sudden cardiac death (SCD); 3. What are the differences of
LVEFs changes if LBBP is added to the medical treatment at the beginning.
There are to date no randomized studies comparing GDMT and LBBP combined with GDMT
(LBBP+GDMT) as the initial therapy in HFrEF patients with NICM and CLBBB. The purpose of
this study is to compare the therapeutic effects of LBBP+GDMT and GDMT on LV function and
clinical endpoints in such patients. The present study will randomize about 50 patients
in multiple centres to LBBP+GDMT group or GDMT group.
The study is divided into two phases:
Phase I (0-6 months) : Patients are randomly assigned to either the drug therapy group
(GDMT group) or the experimental group (LBBP+GDMT group). In GDMT group at 3-month
follow-up, CRT-P/CRT-D will be implanted if LVEF is still ≤35% with absolute increase <5%
from baseline or ventricular tachycardia/ventricular fibrillation (VT/VF) events are
recorded; otherwise, GDMT will be continued when LVEF >35% or LVEF≤35% but absolute
increase >5% from baseline and no VT/VF event is observed. Patients in LBBP+GDMT group
are directly treated with LBBP and GDMT after enrollment. The proportions of patients
with LVEF ≤35% or VT/VF events in LBBP+GDMT group are assessed at 3-month and 6-month.
The percentages of patients with LVEF ≤35% or VT/VF events in GDMT group are also
assessed after 3 and 6 months as well.
Phase II (7-18 months): Patients in each group are followed up regularly (every 3-6
months, with mandatory at 12 and 18 months, with additional as appropriate) to assess the
need for CRT-P/CRT-D/ICD when EF decreasing to ≤35%, syncope, or VT/VF events occurred.
