Heart rate modulation in heart failure with preserved ejection fraction: lessons from nature

In heart failure with preserved ejection fraction (HFpEF), the left ventricle (LV) often functions as a small, stiff pump. Once stroke-volume (SV) reserve is exhausted, heart rate (HR) becomes the primary lever to sustain cardiac output. Yet we often suppress it. Perhaps it is time to learn from nature’s own solutions. Heart failure with preserved ejection fraction is not a failure of contraction but of reserve. Concentric hypertrophy and fibrosis create a noncompliant, small LV that operates near its diastolic limit even at rest (Figure 1).1 Under stress, SV augmentation is minimal; filling pressures rise sharply with small increases in preload, further constrained by the pericardium and limited pulmonary venous capacitance. In this setting, the Frank–Starling mechanism is preserved in principle but rapidly exhausted in practice: modest increases in preload translate into disproportionate rises in filling pressure.2 Similarly, force–frequency and lusitropic responses—while fundamental to normal cardiovascular reserve—may be attenuated or uncoupled in patients with HFpEF. Experimental work in hypertensive and hypertrophied models demonstrates downregulation of the sarco/endoplasmic reticulum calcium ATPase, slowed cytosolic calcium clearance and an often blunted or even negative force–frequency relationship.3,4 Once these SV-based reserve mechanisms are saturated, heart rate does not replace impaired preload or contractile reserve but increasingly becomes the dominant relative determinant of cardiac output.