Activation of the Anrep Effect in Aortic Stenosis Pre-TAVR and Post-TAVR

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BACKGROUND: In aortic stenosis (AS), chronic pressure overload of the left ventricle (LV) may sustain an intrinsic, afterload-dependent adaptive response known as the Anrep effect, characterized by increased myocardial contractility and prolonged systolic duration. Whether this response resolves following transcatheter aortic valve replacement (TAVR) remains unknown. OBJECTIVES: The objective of the study was to determine whether the Anrep is chronically activated in severe AS and acutely reverses after TAVR. METHODS: We studied 119 patients with high-gradient AS undergoing TAVR. Pressure-volume (PV) loops were analyzed by echocardiography before and 24-hours after intervention. The "Anrep triad", defined as elevated afterload (LV end-systolic pressure, effective arterial elastance), enhanced contractility (end-systolic elastance, end-systolic volume at 150 mm Hg), and prolonged systolic ejection time, was assessed. Stroke work (SW), potential energy, PV area (PVA), and mechanical efficiency (SW/PVA) quantified LV energetics. RESULTS: TAVR reduced afterload (LV end-systolic pressure: 220 vs 143 mm Hg; effective arterial elastance: 2.8 vs 2.0 mm Hg/mL) and contractility (end-systolic elastance: 4.5 vs 2.6 mm Hg/mL; end-systolic volume at 150 mm Hg: 39 vs 53 mL), while shortening systolic duration (systolic ejection time: 390 vs 321 ms) (all P < 0.0001). LV ejection fraction was unchanged (56% vs 56%, P = 0.44). Mechanical workload decreased (SW: 9,017 vs 6,257 mm Hg mL; PVA: 14,261 vs 10,017 mm Hg mL, P < 0.0001), while efficiency was preserved (64% vs 63%, P = 0.101). CONCLUSIONS: In severe AS, the Anrep effect supports output at high energetic cost. TAVR reverses this state, unloading the heart and reducing mechanical demand without altering ejection fraction. This identifies the Anrep as a clinically relevant load-dependent mechanism in AS and highlights its reversibility post-TAVR.

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