PhD Scientific Days 2025

Poster Session III. - V: Cardiovascular Medicine and Research

Noninvasive myocardial work correlates with myofilament Ca2+ sensitivity: a translational echocardiographic study

Name of the presenter

Lakatos Bálint Károly

Institute/workplace of the presenter

Semmelweis University Heart and Vascular Center

Authors

Bálint Károly Lakatos¹, Zsuzsanna Ladányi¹, Tímea Turschl¹, Mihály Ruppert¹, Tímea Bálint¹, Dávid Nagy¹, Alexandra Fábián¹, Andrea Ferencz¹, Zoltán Papp², Beáta Bődi², Levente Molnár¹, Endre Zima¹, Attila Kovács¹, Béla Merkely¹

1: Semmelweis University Heart and Vascular Center
2: University of Debrecen

Text of the abstract

In patients with aortic stenosis (AS), left ventricular (LV) afterload is markedly increased. Notably, echocardiographic markers of LV function, such as ejection fraction (EF) or global longitudinal strain (GLS) are substantially influenced by changes in the loading conditions. Myocardial work index (GWI) offers an alternative approach, potentially serving as a load-independent marker of LV contractility. Myofilament Ca2+ sensitivity (pCa50) also reflected alterations of LV contractility in a rat model of pressure overload induced heart failure.
Accordingly, we aimed to investigate the relationship of GWI and pCa50 in rat models of pressure overload-induced heart failure, and to examine AS patients prior to and after Ca-sensitizing therapy (levosimendan loading).
In the experimental arm, we performed speckle-tracking echocardiography and invasive LV pressure measurements on thoracic aortic banded (n=9) and sham-operated (n=8) rats to calculate GWI. pCa50 was determined by myofilament force measurement of permeabilized cardiomyocytes. In our clinical study, we enrolled 25 severe AS patients (76±9 years, 36% female). We conducted echocardiographic measurements before and after a 24-hour intravenous loading dose of levosimendan. GLS and GWI was measured using dedicated echocardiographic softwares.
In our animal study, GWI and pCa50 correlated (r=0.57; p=0.018). In the clinical study, patients with a baseline EF<35% (n=13) had increase in GWI after levosimendan (562±349 vs. 680±408 mmHg%; p=0.004), while those with an initial EF>35% (n=12) did not show any change (1070±341 vs. 1041±290 mmHg%; p= 0.784). The pre-levosimendan GWI correlated with the relative GWI change after the loading dose (r=-0.616; p=0.001).
Based on our findings, GWI and pCa50 correlates in rat model of pressure overload-induced heart failure. In our clinical study, patients with severely reduced baseline EF and GWI experienced greater benefits from levosimendan, while those with better baseline function did not improve. We may hypothesize that patients with initially reduced GWI may possess diminished Ca2+ sensitivity, hinting at a possible correlation between GWI and pCa50 in AS patients.

The study was supported by the EKÖP-2024-208 New National Excellence Program Of The Ministry For Culture And Innovation from the Source of The National Research, Development and Innovation Fund.