https://doi.org/10.1007/s00392-025-02625-4
1Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland; 2Herz- und Diabeteszentrum NRW Klinik für Elektrophysiologie/ Rhythmologie Bad Oeynhausen, Deutschland; 3Klinikum Oldenburg Universitätsklinik für Innere Medizin I, Kardiologie Oldenburg, Deutschland; 4Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz Würzburg, Deutschland; 5Herz- und Diabeteszentrum NRW Klinik für Kardiologie Bad Oeynhausen, Deutschland
Introduction: The Anrep effect describes acute, afterload-dependent increases in contractility. However, recent evidence in obstructive hypertrophic cardiomyopathy (HOCM) suggests a chronic role for the Anrep effect in sustaining myocardial function, with reversal upon relief of the obstruction. This study investigated whether a similar chronic Anrep effect operates in severe (high-grade) aortic valve stenosis and whether it reverses following transcatheter aortic valve implantation (TAVI), which provides marked afterload reduction.
Methods: Using non-invasive, echocardiography-supported volume measurements and (non-invasive) blood pressure measurements via an arm cuff, a pressure-volume (PV) diagram was reconstructed in 30 patients with high-grade aortic stenosis and preserved ejection fraction (EF), before TAVI and two days post-TAVI. End-systolic elastance served as a contractility marker, and effective arterial elastance (Ea) as an afterload parameter. Stroke work (SW), potential energy (PE), and total PV area (PVA) quantified mechanical work and efficiency (SW/PVA). Systolic ejection time (SET) was determined using PW Doppler signals, with frequency correction applied using the Fridericia formula for QT interval correction (QTc=QT/(RR1/3)), and values presented as SETc.
Results: After TAVI, a significant reduction in afterload was documented (max Gradient. 75±16 vs. 16±8 mmHg; p<0.0001; R stroke work. Rrsyst: 215±27 vs. 139±22 mmHg; p<0.0001; Ea: 2.7±0.5 vs. 2.0±0.5 mmHg/ml; p<0.0001), accompanied by a reduction in contractility (Ees: 3.9±0.9 vs. 2.6±0.8 mmHg/ml; p<0.0001). Ejection fraction remained unchanged (EF: 53±7% vs. 53±6%; p=0.61). Systolic duration also decreased significantly, even when frequency-corrected (SETc 385±26 vs. 330±22 ms; p< 0.0001). This triadic pattern of reduced afterload, contractility, and SET is characteristic for the reversal of the chronic Anrep effect. The observed afterload and contractility changes were accompanied by economized. stroke work, as SW, PE and total PVA decreased significantly, while mechanical efficiency remained unchanged (SW/PVA: 62±5% vs 63±7%; p=0.87). Other explanations for the reduced contractility, such as decreased adrenergic drive, were ruled out, as this would have likely prolonged systolic duration or changed heart rate after afterload reduction. The nearly unchanged heart rate also excludes the involvement of the Bowditch effect. The Frank-Starling mechanism was also deemed unlikely, as preload does not influence Ees, a specific marker of contractility. Lastly, the Gregg effect, which suggests a change in contractility due to coronary flow, is unlikely in the blood-perfused heart.
Conclusion: This study demonstrates that the afterload reductions associated with TAVI in aortic stenosis can be attributed to a persistent activation of the Anrep effect, mirroring its chronic presence in obstructive hypertrophic cardiomyopathy. These findings highlight the important role of the Anrep effect in myocardial contractility regulation, suggesting broader clinical implications for conditions marked by chronic afterload changes.