Abstract Introduction In patients with left bundle branch block (LBBB) cardiac function has been found to be particularly sensitive to alterations in left ventricular (LV) afterload. Nevertheless, whether the detrimental hemodynamic effect of right ventricular pacing (RVP)-induced electromechanical dyssynchrony on LV function is also associated with afterload dependency, has not been investigated yet. Purpose Hence, in the current study we sought to examine the acute effect of RVP on LV function in patients with aortic stenosis (AS) before (with elevated afterload) and after (without elevated afterload) transcatheter aortic valve implantation (TAVI). Methods Patients with a previously implanted permanent pacemaker (PM) and significant AS referred for TAVI at our heart and vascular center university were screened for this observational study. Only those patients who had an intrinsic, regular, narrow QRS or right bundle branch block (RBBB) morphology rhythm were included. From 2022 March to 2023 February, nine patients with a DDD PM (with sick sinus syndrome and maintained AV conduction) and four patients with a VVI PM (with atrial fibrillation and complete AV block but stable junctional escape rhythm) were enrolled. Following TAVI, four patients were excluded due to the development of new-onset persistent LBBB. Transthoracic conventional and advanced echocardiography and non-invasive blood pressure monitoring were performed immediately before TAVI and on the second postoperative day. The measurements were carried out during intrinsic QRS rhythm and during frequency-matched RVP as well. Global longitudinal strain was determined by speckle-tracking echocardiography, then using LV pressure curves estimated from systolic blood pressure and mean aortic gradient, global myocardial work index (GMWI) was calculated to assess LV contractility. Results Mean aortic gradient was decreased after TAVI (40.2±3.6 vs. 6.7±1.3mmHg before vs. after TAVI, P<0.001) indicating successful reduction of LV afterload. Compared to the intrinsic QRS rhythm, RVP decreased GMWI before TAVI (GMWI: 1967±206 vs. 1240±174mmHg% intrinsic QRS vs. RVP, P<0.001) and after TAVI (GMWI: 1399±149 vs. 1020±121mmHg% intrinsic QRS vs. RVP, P=0.019) as well. Nevertheless, the extent of RVP-induced LV contractility impairment (expressed as ΔGMWI) was significantly alleviated after pressure unloading therapy (ΔGMWI: -37.1±6.6 vs. -24.5±7.8% before TAVI vs. after TAVI, P=0.024). Conclusion Our preliminary results indicate that RVP-induced LV dysfunction is afterload dependent. Hence, in patients with AS and a high percentage of RVP, TAVI might entail substantial functional improvement.