Rethinking heart rate modulation in heart failure: physiological basis, clinical evidence, and individualized...

Heart rate (HR) is a key determinant of cardiovascular performance and an established prognostic marker in heart failure (HF). While HR reduction improves outcomes in patients with HF with reduced ejection fraction (HFrEF) and sinus rhythm (SR), its role across different HF phenotypes remains uncertain. This review aims to synthesize physiological principles, clinical evidence, and emerging concepts to clarify the role of HR modulation in HF and to explore the potential of individualized HR targets.

We conducted a narrative review of experimental studies, observational analyses, and randomized controlled trials evaluating the physiological and clinical impact of HR and HR modulation strategies across HF phenotypes, including HFrEF, HF with preserved ejection fraction (HFpEF), and atrial fibrillation (AF).

In HFrEF with SR impaired force-frequency and relaxation-frequency relationship render tachycardia maladaptive, and HR reduction with β-blockers or ivabradine is associated with improved outcomes. However, optimal HR targets have not been prospectively defined, and achieved HR thresholds are largely derived from post hoc analyses. In AF, the relationship between HR and prognosis is inconsistent, and HR reduction does not uniformly translate into clinical benefit. In HFpEF, higher resting HR is associated with adverse outcomes, but randomized trials have not demonstrated consistent benefits of pharmacological HR lowering. Emerging evidence suggests that HR modulation in HFpEF may require phenotype-specific approaches, including both HR reduction and HR support, such as pacing-based strategies. Beyond uniform HR thresholds, an individualized target HR (THR), based on diastolic filling dynamics and minimizing E-A overlap, has been proposed for HFrEF with SR. Observational data suggest that achieving HR below the estimated THR is associated with improved outcomes, although this concept remains hypothesis-generating.

HR modulation plays a central role in HF management, particularly in HFrEF with SR. However, uniform HR targets may be suboptimal, and individualized approaches based on patient-specific physiology may be required. While preliminary data support the concept of individualized HR targets, prospective studies are needed to validate their clinical utility and to define phenotype-specific HR strategies across the HF spectrum.