Does a 20% base-rate elevation cause adverse LV remodeling or fibrosis in elderly LBBAP patients with preserved EF?

The clinical question

A recurring question in device programming is whether raising the programmed lower-rate limit — for example from 60 to 72 beats per minute, a roughly 20% elevation — exposes the left ventricle to slow, subclinical harm over the following years. Does chronic base-rate elevation promote adverse remodeling or myocardial fibrosis in elderly patients with preserved ejection fraction who receive left bundle branch area pacing (LBBAP)? Global longitudinal strain (GLS) and cardiac magnetic resonance (CMR) are the tools usually proposed to detect such change before ejection fraction falls.

The intuition — borrowed from the epidemiology of elevated resting heart rate, and from the benefit of heart-rate lowering with beta-blockers and ivabradine in heart failure with reduced ejection fraction — is that slower is safer. In the preserved-EF, conduction-system-paced patient, the best available direct evidence points the other way, or at worst toward neutrality.

What the best evidence shows: the myPACE trial

myPACE is the anchor dataset. It randomized 100 patients with preclinical or overt HFpEF and pre-existing pacemakers that minimize ventricular dyssynchrony — atrial pacing with intrinsic conduction, conduction-system pacing, or biventricular pacing — to a standard 60 bpm backup rate or a personalized accelerated rate averaging about 75 bpm, essentially the elevation in question. The trial reported improved heart-failure-related quality of life, along with better NT-proBNP, greater physical activity, and reduced device-detected atrial fibrillation burden compared with 60 bpm.

The structural substudy: geometry, not fibrosis

The substudy most relevant to remodeling examined paired echocardiograms obtained roughly 3.7 years apart. Sustained moderate acceleration produced a reduced septal wall thickness and a lower LV mass-to-systolic-volume ratio (1.52 versus 1.84) — a shift toward favorable eccentric geometry and improved capacitance, the opposite of the concentric, high-mass-to-volume phenotype that characterizes adverse HFpEF remodeling. A small reduction in ejection fraction (55% versus 60%) remained firmly within the preserved range, and markers of diastolic function and LV performance were unchanged.

The mechanistic rationale is hemodynamic: moderate heart-rate elevation lowers diastolic filling pressure, promotes active filling, and limits exposure to the exponential rise in end-diastolic stiffness. No tachycardia-mediated cardiomyopathy signal appeared — expected, since that phenomenon belongs to much higher, typically incessant rates rather than 72–75 bpm.

Long-term clinical outcomes

A four-year observational extension found, among patients who maintained their assigned setting, a markedly slower accrual of clinical events with accelerated pacing (5 versus 31 events) and longer event-free survival, driven mainly by heart-failure events. The intention-to-treat analysis showed a favorable trend that did not reach statistical significance. The cohort was elderly, with a mean age of 74 years. These findings derive from a single-center study with small imaging numbers and should be regarded as hypothesis-generating.

LBBAP-specific structural and functional data

No study has isolated base rate as a variable within an LBBAP cohort, but the modality-and-burden literature is reassuring. In a prospective LBBAP cohort, no patient in the preserved-EF subgroup met criteria for pacing-induced cardiomyopathy over a median of about two years, and both ejection fraction and GLS remained stable. A mid-to-long-term myocardial-work study of preserved-EF LBBAP patients found preserved global function with only a small GLS decrement and a modest redistribution of myocardial work, consistent with LBBAP being near-physiologic but not perfectly so, given residual transseptal and interventricular delay.

The contrast case remains right ventricular apical pacing, where preserved-EF patients show progressive GLS decline and a 10–20% incidence of pacing-induced cardiomyopathy over two to four years — the rationale for conduction-system pacing, and for using GLS as an early, subclinical readout.

Important caveats and unresolved questions

Two limitations define the current state of knowledge. First, a confound: in a real LBBAP patient, raising the base rate also raises the pacing burden, so rate and cumulative delivered activation move together; no LBBAP study separates the two. Second, a genuine gap in fibrosis data alongside a caveat about strain: every dataset above is echocardiography-based. No study has used CMR tissue characterization to determine whether base-rate elevation drives fibrogenesis in LBBAP recipients, so the fibrosis question is unanswered — no evidence of harm, but no tissue-level evidence excluding it. GLS is itself rate-sensitive, because temporal resolution falls as heart rate rises; any rate-arm comparison using GLS carries a built-in bias favoring the slower arm unless acquisition frame rate is standardized.

Magnitude also matters. Preclinical work shows that LV dilation is proportional to pacing rate, so a modest, physiologic elevation may be adaptive while larger elevations cannot be assumed benign. The myPACE evidence is enriched for HFpEF physiology, where lowering filling pressure is the dominant benefit, rather than representing every preserved-EF patient.

Rate elevation is not universally beneficial

The direction of benefit depends on how and in whom the rate is raised. The RAPID-HF trial, which augmented exertional rate through rate-adaptive pacing in HFpEF patients with chronotropic incompetence, showed no improvement in peak oxygen uptake. The divergence from myPACE — which raised the resting backup rate to offload filling pressure — underscores that resting-rate elevation and exertional-rate augmentation are different interventions with different results.