Single-lead pacing systems for the delivery of cardiac resynchronization therapy (CRT) match or even surpass three-track systems? Perhaps suggest several new comparative studies, including a small randomized trial.
Together, the studies make a strong case for conduction system pacing (CSP) as an alternative, at least, to conventional biventricular (BiV) pacing for CRT in appropriate patients with cardiac arrest and reduced ejection fraction.
They also appear to validate expectations that CSP would be superior to BiV pacing in improving electrocardiographic (ECG) dyssynchrony, left ventricular (LV) function, and possibly clinical risk in these patients.
Unlike BiV pacing, CSP as performed in studies relies on a lead positioned on either the left bundle branch (LBB) or the His bundle to directly stimulate the heart’s native conduction network. It is considered more physiological and, in a major advantage, does not directly stimulate the right ventricle.
Two of the new studies – the 40-patient randomized trial and a 10-fold larger prospective registry study – were reported separately at the Heart Rhythm Society (HRS) 2022 Scientific Sessions, held virtually and live in San Francisco. Another registry-based study with 100 patients recently appeared in the literature.
According to observers, they are setting the stage for larger and more definitive random competitions between the two pacing strategies that could determine whether CRT is ready for its next big evolutionary step.
CSP “has the potential to replace all the pacing we do, both standard brady pacing, but also resynchronization,” said Jeffrey Healey, MD, MSc, Hamilton Health Sciences and McMaster University, Ontario, Canada. lecoeur.org | Medscape Cardiology.
“Large clinical trials are going to be key to this,” Healey said, given the extensive history of randomized trials supporting BiV pacing to reverse ventricular dyssynchrony and improve survival in patients who meet appropriate criteria. EKG and LV functional criteria. This exceptionally well-established evidence base dates back over 2 decades to the MIRACLE and COMPANION trials.
“All predictions have come true”
The new randomized efficacy comparison, conducted at two centers in China, represents “the first step” in advancing LBB stimulation as a viable CRT alternative to BiV stimulation in suitable patients with HF, said said Fengwei Zou, MD, Montefiore Medical Center, Bronx, New York, when presenting these findings April 30 at HRS Sessions. The trial, called LBBP-RESYNCHonly enrolled patients with nonischemic disease and LBB block.
Left ventricular ejection fraction (LVEF) at 6 months, the primary endpoint, increased significantly from baseline in both CRT groups, but increased an average of an additional 5.7 points (P = 0.039) with LBB stimulation, with most of the difference evident within the first 3 months.
The trial suggests that LBB stimulation has the potential to become a first-line CRT strategy “alongside BiV stimulation” in non-ischemic HF with LBB block, Zou said, provided it is small and the follow-up is short compared to the decade or more some patients can live with CRT devices.
Baseline LVEF averaged 29.7 and mean QRS duration was 174.6 ms in the 20 men and 20 women randomly assigned to CRT with LBB stimulation or BiV stimulation. Two patients in the LBB stimulation group crossed over to BiV stimulation, and reverse crossover was required for four assigned to BiV stimulation.
However, the analysis was by intention to treat, reported Zou, who is not a co-author of the study but who, as presenter, replaced his father, co-lead investigator Jiangang Zou, MD, PhD, First Affiliated Hospital of Nanjing Medical University, China.
|Change of LVEF, LBB stimulation vs BiV stimulation for CRT in LBBP-RESYNCH|
|LVEF Parameter||LBB stimulation group||BiV stimulation group|
|6 months (%)||49.4||46.5|
|Increase (% points)||21.1*||15.4|
|*P = 0.039 vs. BiV pacing|
The limited pilot study showed significant “surprising trends” in favor of LBB-CRT that warrant larger and more definitive randomized comparisons with BiV-CRT, agreed Kenneth Ellenbogen, MD, Virginia Commonwealth University Medical Center, Richmond, as a guest discussant for Zou’s presentation.
“All the predictions one could have made based on physiology came true; i.e. better ejection fraction, decreased left ventricular volume, N-terminal proBNP levels lower values, a trend towards shorter QRS duration and increased response rate,” said Ellenbogen, who was the lead author of perhaps the first published experience of LBB stimulation in HF.
Less risk of hospitalization for HF
Elsewhere during HRS sessions, CRT by CSP – either at the LBB or His beam – outperformed BiV-CRT for the primary endpoint of death at 1 year or hospitalization for HF in a patient registry study with indications of CRT with or without LBB block at four centers in two major US healthcare systems.
The benefit of LBB stimulation appeared to be driven by a strong reduction in the risk of hospitalization for HF, reported Pugazhendhi Vijayaraman, MD, Geisinger Heart Institute, Danville, PA, April 29 during HRS sessions. Vijayaraman was also the lead author of the study on the day publication in Heartbeat.
Some members of the electrophysiology community have explored CSP in practice as a first-line CRT approach, despite the long and successful experience of BiV-CRT because it is more physiological, but no one knows for sure if this mechanistic rationale translates into better functionality. and clinical outcomes, Vijayaraman observed at a press conference about the study.
Still, he said, the “signal is quite strong.” The current study “gives us confidence that we are only making things worse with established therapy and that we are able to improve outcomes beyond what can be achieved with BiV stimulation.”
Indeed, electrophysiologists “should learn bundle of His and left bundle pacing skills” as additional tools to achieve the best results from CRT. They wouldn’t necessarily be a first approach, he said, but should be available for “patients who don’t get the best biventricular pacing at the time of implantation,” perhaps due to anatomical limitations or myocardial scars. In such cases, “we can quickly move on to stimulation of the conduction system.”
Baseline LVEF averaged 26% in the 477 patients in the registry study, of whom 219 received BiV-CRT at one center and 258 in whom CRT was performed either by His-bundle or LBB stimulation in three other centers of the same health system; about a third of the participants were women.
The rates of death or hospitalization for HF were 28.3% and 38.4% for CSP and BiV pacing, respectively, for an adjusted relative risk (HR) of 1.52 (95% CI, 1. 08 – 2.09; P = 0.013) for the absence of the primary endpoint. There were no significant differences in all-cause mortality per se, but the RR for no hospitalization for HF was 3.15 (95% CI, 2.07, 4.79; P
The results were similar and possibly more pronounced in favor of PSC among the 227 patients with LBB block: RR 2.1 (95% CI, 1.24, 3.52; P = 0.006) for the absence of the primary outcome and an RR of 3.48 (95% CI, 1.73, 6.98; P
|Echocardiographic responses to CSP vs. BiV pacing for CRT|
|Response by group||PCS (%)||BiV stimulation (%)||P Value|
|All patients (n=442)|
|Patients in LBB block (n = 227)|
|Echo response, ≥ 5% increase in LVEF; super echo response, increase in LVEF to >50% or at least 15 percentage points absolute.|
Broadly consistent echo results emerged from a recently published registry study of 100 patients successfully implanted with CRT systems, 49 with LBB stimulation, and 51 with BiV stimulation. Stimulation thresholds and QRS responses also significantly favored the LBB stimulation group in the experiment. published in the May issue of Europace EPwith lead author Xueying Chen, MD, PhD, Zhongshan Hospital of Fudan University, Shanghai, and Ellenbogen as co-author.
CRT response rates did not differ significantly between the LBB and BiV stimulation groups; a response was defined as an absolute increase of more than 5% in LVEF at 6 months or 1 year. But superresponse rates—defined here as an absolute increase from greater than 20% in LVEF to greater than 50%—were 53.1% and 36.6% for LBB and BiV stimulation, respectively, at 6 month (P = 0.016) and 61.2% and 39.2%, respectively, at 1 year (P = 0.028).
Following Zou’s LBBP-RESYNCH presentation, Ellenbogen proposed that any future trial pitting CSP-CRT versus BiV-CRT enroll “somewhere between 800 and 2,000 patients” and seek “long-term improvement in indisputably important outcomes.” : cardiovascular mortality, hospitalization for heart failure, cardiovascular death and death, then secondarily examine LV remodeling and ejection fraction.”
Such trials, added Mina Chung, MD, Cleveland Clinic, as a guest commentator for Vijayaraman’s presentation, should include not only patients with a current guideline-recommended LVEF of 35% or less, “but let’s look at those LVEFs intermediate from 36% to 50%.”
Healey discloses receiving honoraria or fees to speak or consult from Cypher Pharma, Servier, Boston Scientific, Myokardia and Bayer Healthcare; speaker’s bureau member for Bristol-Myers Squibb; and receiving research grants from Boston Scientific, Medtronic, Bristol-Myers Squibb, Pfizer, and Servier. Zou reports no relevant disclosures. Ellenbogen discloses receiving fees or honoraria to speak or consult from Boston Scientific, Medtronic, Kestra, Hylomorph, Biotronik, MediLynx, Milestone Pharmaceuticals, Impulse Dynamics, Abbott, Biosense Webster, Sanofi, and Medpace; and Elsevier royalties. Vijayaraman Discloses He Received Fees or Fees to Speak or Consult from Abbott, Boston Scientific, Medtronic, Biotronik, and Eaglepoint; and receive research grants from Medtronic. Chen and his co-authors declare no conflict of interest. Chung reveals that he received royalties from Elsevier.
Heartbeat. Published online April 29, 2022. Abstract
Europace. 2022;24:807-816. Full Text