Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is a well-established therapy in patients with reduced left ventricular ejection fraction (LVEF) and bundle branch block or indication for pacing.^1,2 However, BVP achieves CRT through non-physiological fusion of paced wave fronts from the right ventricular endocardium and left ventricular epicardium. Up to one third of patients treated with BVP may not derive clinical or echocardiographic benefit, and some may worsen.³ Conduction system pacing (CSP) utilizing His bundle pacing (HBP), or left bundle branch area pacing (LBBAP) has been shown to be a feasible and more physiologic alternative to BVP.^4-8 Whether CRT through CSP results in better patient outcomes than conventional BVP was the scope of Vijayaraman et al.'s publication in Heart Rhythm.⁹

In their multi-center observational study, the investigators published the findings from 477 consecutive patients with LVEF ≤35% and Class I or II indications for CRT. Patients underwent BVP (n = 219) or CSP (n = 258, which included HBP, n = 91, and LBBAP, n = 167) based on operator's preference and/or institutional practice. Both groups' baseline characteristics were similar. Procedural characteristics were slightly different. More patients received defibrillators in BVP group (93% vs. 85% respectively, P = 0.06), whereas longer procedural duration with similar fluoroscopy times were required for CSP group. LVEF improved in both groups during a mean follow-up duration of 27±12 months but significantly greater in the CSP group (39.7% vs. 33.1%, P<0.001). The primary outcome of death or heart failure hospitalization (HFH) was significantly lower in CSP versus BVP (28.3% vs. 38.4%; hazard ratio [HR] 1.52; confidence interval [CI] 1.082-2.087; P=0.013). Within the CSP group, no significant differences in the primary endpoint of death or HFH were observed among HBP versus LBBAP (33% vs. 27%; HR 1.095, 95% CI 0.677-1.769, p=0.712). Paced QRS duration was significantly narrower in the CSP group than in the BVP group (133±21ms vs. 152±24 ms, respectively; p<0.001).

BVP to improve electrical resynchronization is very effective in reducing death and HFH¹⁰ but the non-physiological fusion of paced wavefronts does not always result in complete electrical resynchronization. Previous studies have well demonstrated the higher success rates of electrical resynchronization with HBP or LBBAP.^6,11 For the first time, the long-term clinical outcomes of death or HFH among the CRT population undergoing BVP versus CSP was addressed and was shown to achieve better outcomes with CSP.

As acknowledged by the study investigators, this is an observational study leaving room for selection bias. Patients underwent CSP or BVP based on operator/institutional preference and were not randomized to either strategy. Echocardiographic evaluations were not blinded or performed in a core-lab. Furthermore, although the baseline characteristics were similar due to its non-randomized nature, this study does not ensure homogeneity between the study groups.

In conclusion, this study establishes a major constituent in the literature of CRT in heart failure patients and inspires researchers to look meticulously into the use of CSP to achieve CRT. Moreover, it also illustrates the previously demonstrated success rate of greater electrical synchronization with CSP. Large, prospective, randomized trials with a longer-term follow-up, comparing BVP and CSP are needed to confirm the clinical outcomes superiority of CSP as noted in this study.

References

1. Cleland JGF, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-49.
2. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-50.
3. Varma N, Boehmer J, Bhargava K, et al. Evaluation, management, and outcomes of patients poorly responsive to cardiac resynchronization device therapy. J Am Coll Cardiol 2019;74:2588-2603.
4. Sharma PS, Dandamudi G, Herweg B, et al. Permanent His-bundle pacing as an alternative to biventricular pacing for cardiac resynchronization therapy: a multicenter experience. Heart Rhythm 2018;15:413-20.
5. Huang W, Su L, Wu S, et al. Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block. Heart 2019;105:137-43.
6. Vijayaraman P, Ponnusamy S, Cano Ó, et al. Left bundle branch area pacing for cardiac resynchronization therapy: results from the International LBBAP Collaborative Study Group. JACC Clin Electrophysiol 2021;7:135-47.
7. Lustgarten DL, Crespo EM, Arkhipova-Jenkins I, et al. His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: a crossover design comparison. Heart Rhythm 2015;12:1548-57.
8. Upadhyay GA, Vijayaraman P, Nayak HM, et al. His corrective pacing or biventricular Pacing for Cardiac Resynchronization in Heart Failure. J Am Coll Cardiol 2019;74:157-59.
9. Vijayaraman P, Zalavadia D, Haseeb A, et al. Clinical outcomes of conduction system pacing compared to biventricular pacing in patients requiring cardiac resynchronization therapy. Heart Rhythm 2022;19:1263-71.
10. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:1810–52.
11. Arnold AD, Shun-Shin MJ, Keene D, et al. His resynchronization versus biventricular pacing in patients with heart failure and left bundle branch block. J Am Coll Cardiol 2018;72:3112-22.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Cardiac Resynchronization Therapy, Bundle-Branch Block, Stroke Volume, Bundle of His, Ventricular Function, Left, Endocardium, Confidence Intervals, Follow-Up Studies, Institutional Practice, Echocardiography, Heart Failure, Pericardium, Hospitalization, Fluoroscopy, Defibrillators, Selection Bias, Prospective Studies

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