PhD Scientific Days 2024

Poster Session N - Cardiovascular Medicine and Research 2.

Myocardial Work and Calcium Sensitivity: Hand-in-Hand Markers of Contractility in Aortic Valve Stenosis - A Translational Study

Text of the abstract

Left ventricular (LV) contractility assessment is challenging in aortic stenosis (AS) due to the influence of increased afterload on conventional echocardiographic parameters, such as ejection fraction (EF). 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.
We hypothesized that GWI and pCa50 may correlate, both being reliable measures of contractility in elevated LV afterload.
In our animal study, we conducted speckle-tracking echocardiography and invasive LV pressure measurements on thoracic aortic banded (n=2) and sham-operated (n=3) 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) receiving levosimendan therapy. We conducted echocardiographic measurements before and after a 24-hour intravenous loading dose. Global longitudinal strain was assessed via speckle-tracking, and GWI was quantified utilizing estimated LV pressure curves.
In our animal study, GWI and pCa50 correlated (r=0.942; p=0.017). In the clinical study, patients with a baseline EF<35% (n=13) had increase in GWI after levosimendan therapy (562±349 vs. 680±408 mmHg%; p=0.004), while those with an initial EF>35% (n=12) did not manifest 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).
Our findings suggest a correlation between GWI and pCa50 in a rat model of pressure overload induced heart failure. In the clinical setting, patients with severely reduced baseline EF and GWI experienced greater benefits from Ca2+ sensitization, while those with better baseline function did not show improvement. These observations imply that patients with initially reduced GWI may possess diminished Ca2+ sensitivity, hinting at a possible correlation between GWI and pCa50 in AS patients.
The research was supported by ÚNKP-23-3-I-SE-64 New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development, and Innovation Fund. The research was supported by SE250+ Grant of Semmelweis University.