Cardiac Electrophysiology · Conduction System Pacing

Can long-term remodeling from LBBAP improve LV chamber compliance, diastolic filling, and stroke volume in elderly preserved-EF bradycardia?

The clinical question

Can long-term reverse electrical and structural remodeling induced by left bundle branch area pacing (LBBAP) improve global left ventricular chamber compliance and diastolic filling, leading to a sustained increase in stroke volume in elderly patients with bradycardia and preserved ejection fraction?

The question bundles several claims that the evidence supports very unevenly. They have to be unbundled, because the construct merges prevention of pacing-induced harm with active improvement of intrinsic diastolic properties, and these are mechanistically distinct.

Electrical remodeling

In a preserved-EF bradycardia patient, LBBAP does not so much reverse electrical remodeling as prevent the dyssynchronous remodeling that right ventricular (RV) pacing would otherwise impose. Documented reverse electrical remodeling — QRS narrowing predicting complete reverse remodeling, T-wave memory normalization — comes almost entirely from true left bundle branch block (LBBB) / heart failure with reduced ejection fraction (HFrEF) and pacing-induced cardiomyopathy (PICM) cohorts, where there was pathological activation to correct in the first place. In His-Purkinje conduction system pacing for true LBBB and HFrEF, QRS has shortened from roughly 170 ms to about 114 ms with left ventricular end-systolic volume (LVESV) falling from approximately 168 mL to 86 mL. None of that maps onto a patient with sinus node disease, a narrow native QRS, and an EF of 60%, where there is no abnormal activation sequence to reverse.

Structural remodeling

The same problem applies. The robust reverse-remodeling signal (LVESV reduction, EF recovery) is a HFrEF / PICM / cardiac resynchronization therapy (CRT) non-responder phenomenon. In the preserved-EF bradycardia population, what the data show is prevention of deterioration, not active reverse remodeling of a normal chamber. At six-month follow-up, left atrial (LA) size has increased significantly with RV pacing versus LBBAP and non-selective His-bundle pacing (46 vs 39 vs 38 mm), while LV end-diastolic and end-systolic volumes and EF did not differ across groups. In larger cohorts, RV-paced patients lose EF over a year while LBBAP patients do not, and new-onset atrial fibrillation (AF) is markedly lower with LBBAP (around 3% vs 12%). That is a story about averting LA stretch, AF, and PICM — preserving an existing substrate — not about improving compliance beyond baseline.

Chamber compliance — the load-bearing claim

This is where the hypothesis is weakest. Global passive compliance — the slope and position of the end-diastolic pressure-volume relationship (EDPVR) — is governed by titin isoform shift and phosphorylation state, interstitial collagen content and cross-linking, advanced glycation end-product (AGE) accumulation, and microvascular-inflammatory remodeling. None of those is a plausible target of pacing site. There is no mechanism by which depolarizing the septum via the left conduction system instead of the RV apex alters the passive stiffness constant of the myocardium.

So a sustained increase in global LV chamber compliance attributable to LBBAP is, on current understanding, mechanistically unsupported. What pacing legitimately influences are the functional / dynamic determinants of filling that sit on top of passive stiffness: uniformity and rate of active relaxation, diastolic untwisting and restoring-force-driven early suction, the operative filling pressures, and atrioventricular (AV) coupling. Synchronous activation preserves a normal relaxation sequence and avoids the regional tethering and prolonged segmental relaxation that RV pacing imposes — which shifts the operating point and lowers filling pressures without moving the passive EDPVR.

Diastolic filling and left atrial mechanics

Here there is a real but modest and mostly relative signal. A controlled trial found LBBAP produced lower seven-day B-type natriuretic peptide (BNP) than RV outflow pacing (65 vs 130 pg/mL) along with better early diastolic (e′) indices, and a separate randomized study found LBBAP improved LA reservoir, conduit, and contractile strain-rate components at six months versus RV outflow septal pacing in pace-dependent patients. But note the ceiling: in a myocardial-work study, mean E/e′ did not differ among LBBAP, non-selective His pacing, and RV pacing groups at implant or at six months. So the diastolic advantage is consistent for LA function and filling-pressure surrogates, less consistent for E/e′, and almost always framed as superiority over RV pacing rather than improvement over the patient's own pre-pacing diastole.

Stroke volume

In preserved EF, resting stroke volume (SV) is by definition near-normal, so the room for a sustained increase is small and the dominant levers are not compliance. The realistic contributors to any SV gain are: restoration of AV synchrony and the timed atrial kick — critical when the ventricle is stiff, and an AV-optimization effect rather than an LBBAP-specific one; chronotropic competence via rate-response; and avoidance of dyssynchrony-mediated SV loss. A Frank-Starling nudge from marginally better filling is possible but small and load- and rate-dependent. Attributing a durable SV increase specifically to remodeling-mediated compliance change is not demonstrated in this phenotype.

The confounder that cannot be ignored

In a bradycardia patient, a large fraction of any diastolic or SV benefit may come from correcting the rate itself, independent of pacing site — the bradycardiomyopathy mechanism, in which prolonged diastole and chronic volume overload produce a reversible preserved-EF picture that improves once an adequate rate is restored. Any single-arm before-and-after improvement in this population will be heavily contaminated by this rate effect, making it difficult to credit LBBAP physiology specifically.

Measurement and attribution problems

Diastolic indices are load-dependent; AV-optimization effects are hard to separate from pacing-site effects; rate effects overlay both; and there are no invasive pressure-volume loop or validated single-beat non-invasive EDPVR data in this specific phenotype. The clean test would be invasive (or validated non-invasive) EDPVR estimation before and after implant with AV delay and rate held constant. Absent that, the compliance claim stays hypothetical.

Effect-size evidence

Both supporting studies are small, single-center, and use a right ventricular septal / outflow comparator rather than the apex, so they are hypothesis-supporting rather than definitive. The numbers are usable with appropriate framing.

Interpretive caution on E/e′: the LBBP improvement is a within-group pre-to-post change at seven days, when the contrast is intrinsic conduction versus acute pacing — so it partly reflects the acute hemodynamic penalty of RV pacing rather than a durable compliance gain.

The consistent signal is at the atrial level — size, strain, LAEF, BNP. The chamber-level E/e′ and volumes often do not move, which is exactly consistent with "preserved dynamic filling and averted LA remodeling" rather than "improved passive LV compliance."

Synthesis

The honest synthesis is narrower than the original question. Versus RV septal / outflow pacing, LBBAP yields better LA reservoir and contractile strain, smaller LA size, higher LAEF, lower BNP, and better early LV diastolic indices (E/e′, e′, peak E) — with the LV-level diastolic advantage most visible acutely and partly attributable to avoiding the acute penalty of RV pacing. None of these studies measured the EDPVR or passive stiffness, none enrolled the specific elderly preserved-EF phenotype as such, follow-up is six months or less, and the comparator is septal RV pacing (so the contrast understates the gap versus apical pacing). That is the appropriate envelope for any claim about LBBAP and diastole.

The stronger claim — that long-term LBBAP actively augments intrinsic global chamber compliance and drives a sustained stroke-volume increase in elderly preserved-EF bradycardia — outruns the data and, for the passive-compliance component, outruns the mechanism.

References