Is Conduction System Pacing Going to Be the New Gold Standard for Cardiac Resynchronization Therapy?

Abstract

The current gold standard in device therapy for advanced heart failure (HF), which has been firmly established in HF management for more than 25 years, is classical biventricular pacing (BiV-CRT). In the last decade, a new pacing modality called conduction system pacing (CSP) has emerged as a variant for advanced cardiac device therapy. It provides pacing with preserved intrinsic cardiac activation by direct stimulation of the specific cardiac conduction system. The term CSP integrates the modalities of HIS bundle pacing (HBP) and left bundle branch area pacing (LBBAP), both of which have provided convincing data in smaller randomized and big non-randomized studies for the prevention of pacemaker-induced cardiomyopathy and for providing effective cardiac resynchronization therapy in patients with classical CRT-indication (primary approach or after failed CRT). Recent American guidelines proposed the term "cardiac physiological pacing" (CPP), which summarizes CSP including left ventricular septal pacing (LVSP), a technical variant of LBBAP together with classical BiV-CRT. The terms HOT-CRT (HIS-optimized CRT) and LOT-CRT (LBBP-optimized CRT) describe hybrid technologies that combine CSP with an additional coronary-sinus electrode, which is sometimes useful in patients with advanced HF and diffuse interventricular conduction delay. If CSP continues providing promising data that can be confirmed in big, randomized trials, it is likely to become the new gold standard for patients with an expected high percentage of pacing (>20%), possibly also for cardiac resynchronization therapy. CSP is a sophisticated new treatment option that has the potential to raise the term "cardiac resynchronization therapy" to a new level. The aim of this review is to provide basic technical, anatomical, and functional knowledge of these new pacemaker techniques in order to facilitate the understanding of the different modalities, as well as to provide an up-to-date overview of the existing randomized and non-randomized evidence, particularly in direct comparison to right ventricular and classical biventricular pacing.

Keywords: BiV-CRT; CRT; CSP; HBP; HIS bundle pacing; LBBAP; conduction system pacing; left bundle branch area pacing.

Figure 1

HIS bundle pacing (HBP). (A) shows nonselective HBP with both stimulation of the specific conduction system (red arrow) and the adjacent septal myocardium (blue arrows). The resulting QRS-complex is slim but appears somewhat broadened in the beginning by additional myocardial capture (compare preexcitation/pseudo delta wave in WPW, blue segment). (B) shows selective HBP, where the electrode is perfectly anchored to the HIS-bundle, exclusively capturing the HIS without excitation of the surrounding tissue. The stimulus then travels over the conduction system until myocardial excitation occurs (intrinsic 35–55 ms; stimulated up to approx. 80 ms), recognizable by a short isoelectric line (red segment) between stimulus and QRS; LA: left atrium; RA: right atrium; RV: right ventricle; HIS: Bundle of HIS; V4: chest lead V4 from a patient’s ECG.

Figure 2

Left bundle branch (area) pacing (LBBAP). Figure 2 shows possible variants of left bundle branch pacing (LBBP), which can usually be differentiated using electrophysiological and ECG criteria. If there is a threshold-dependent change in QRS-morphology from nsLBBP to LVSP, we call it left bundle branch area pacing (LBBAP). Solid red arrows show antegrade capture of the conduction system; blue arrows indicate myocardial capture (A) shows selective LBBP/LFP, where the electrode is perfectly anchored to the left bundle branch (or one of its fascicles) exclusively capturing the LBB or left fascicle without excitation of the surrounding tissue (at usually very low output). Excitation therefore initially travels via the conduction system (intrinsic < 35) until myocardial excitation occurs. The isoelectric line, if detectable at all, is much more discrete than during HBP. (B) shows nonselective LBBP, where the electrode excites the left bundle branch and the surrounding septal myocardium. (C) shows left ventricular septal pacing (LVSP), where the electrode is anchored deep in the interventricular septum but does not directly stimulate the conduction system. Here the stimulation connects to the left subendocardial HIS-Purkinje network (red dotted line) with rapid and very synchronous activation of both ventricles. (D) shows anodal nonselective left bundle branch pacing (anodal nsLBBP), with a hybrid activation of the left bundle branch together with anodal ring-capture (through hyperpolarization; bipolar configuration); LA: left atrium; RA: right atrium; RV: right ventricle; LV: left ventricle; LBBP: left bundle branch pacing.

Figure 3

Anatomical and fluoroscopic orientation for CSP procedures. (A) shows the positional relationship of the cardiac conduction system in an anatomical specimen (light yellow: right bundle branch, dark yellow/transparent: projection of the left bundle branch on the opposite side of the interventricular septum) and relevant anatomical structures (right atrium/ventricle, RVOT, septal leaflet of the tricuspid valve), as well as the approximate target regions for HBP (small blue shaded oval) and LBBAP (large blue shaded oval). LAF: left anterior fascicle, LSF: left septal fascicle, LPF: left posterior fascicle. Figure 3A is modified from doi: 10.1155/2015/547364. Epub 2015 Nov 19. Copyright © 2015 Damián Sánchez-Quintana et al. (B) shows, analogous to (A), a fluoroscopic orientation aid in a right anterior oblique 20° projection (RAO) for an approximative estimation of the HIS bundle or the LBBAP target region after contrast administration; OF: foramen ovale; STV: septal leaflet of the tricuspid valve; RVOT: right outflow tract; RVA: right ventricular apex; LAF: left-anterior fascicle; LSF: left-septal fascicle; LPF: left-posterior fascicle; HIS: suggested position of the HIS-bundle; LBBAP: left bundle branch area pacing; CSO: coronary sinus ostium.

Figure 4

Principle of longitudinal dissociation of the cardiac conduction system, which assumes that the conduction fibrils already have a fixed arrangement proximally in the HIS bundle and are thus predetermined to form the left or right fascicle. Accordingly, it should be possible in many cases to correct a bundle branch block already proximally at the HIS bundle or left bundle branch; AVN: AV node; RA: right atrium; LA: left atrium; RV: right ventricle; LV: left ventricle; LBB: left bundle branch; dark green arrows: fibers forming the left anterior fascicle (LAF); light green arrows: fibers forming the left posterior fascicle (LPF); light blue arrows: fibers forming the right bundle branch (RBB).

Figure 5

PubMed-listed publications on the topics of BiV-CRT or CSP over time. Figure 5 shows the combined PubMed-listed publications on the topics of BiV-CRT vs. CSP and the rising scientific interest in the new variants of physiological pacing, winning the publication race in 2023 for the first time. BiV-CRT: classical biventricular cardiac resynchronization therapy; CSP: conduction system pacing; HBP: HIS bundle pacing; LBBAP: left bundle branch area pacing.

Figure 6

Visualization of CSP—and BiV-CRT—considerations using cardiac 3D reconstructions. (A) RAO view of a patient’s heart, showing a vast area of scar (light blue) and dense scar (dark blue) in the mid-myocardial and subendocardial tissue (pink/light pink) of the interventricular septum, possibly making this patient unsuitable for a pacing lead in the LBBAP region (yellow dotted area) (B) Left (postero-)lateral view of a patient’s heart, showing a big posterolateral scar with extensive wall thinning (dark red: 1 mm, red: 2 mm, orange: 3 mm, yellow: 4 mm of wall thickness) after a previous myocardial infarction, possibly making the posterolateral veins (yellow dotted areas) unsuitable for a standard BiV-CRT system. CSP: conduction system pacing; LBBAP: left bundle branch area pacing; BiV-CRT: classical biventricular cardiac resynchronisation therapy; RAO: right anterior oblique.