05Jun 2023
Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure With Pulmonary Hypertension

Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure With Pulmonary Hypertension

This study investigated the right ventricular (RV) myocyte contractile dysfunction in patients with heart failure with reduced ejection fraction and pulmonary hypertension (HFrEF-PH). Permeabilized RV cardiomyocytes were studied in patients undergoing cardiac transplantation and organ donor controls. Unsupervised machine learning identified two HFrEF-PH subgroups corresponding to decompensated or compensated clinical RV function. Reduced calcium-activated tension was observed in decompensated RV function, while other contractile measures were similarly depressed in both groups. X-ray diffraction revealed thick filament defects in decompensated RV function. Altering the proportion of myosin in a crossbridge-ready state affected tension differently in patient groups. Increasing myocyte preload had a reduced effect on myocyte stiffness in HFrEF-PH. Therapeutic strategies targeting these findings may improve outcomes in HFrEF-PH patients.

  • #cardiology

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