Biomechanics and Mechanobiology of Heart Failure

The heart failure (HF) subgroup was established in 2018, with a focus on understanding myocardial adaptation to hemodynamic stress (such as in valvular heart disease) at the organ, tissue, cell and sub-cellular levels. We seek to translate this knowledge to clinical application, by developing biomechanical markers of early cardiac dysfunction, and develop technologies that restore physiological biomechanics as a therapeutic target.

Recent publications

Project 1) Mechanobiology of cardiac remodeling in valvular heart disease

Heart valve disease imposes a hemodynamic stress on the left atrial and left ventricular chambers, either in the form of pressure or volume overload. The chambers respond to such a stress in unique ways, structurally, functionally and biologically remodeling the chambers towards dysfunction. Longitudinal changes in the left sided cardiac chambers in response to such hemodynamic stress and not well defined, which we seek to establish. Building upon this work, we are investigating if structural changes in the cardiac chambers parallel changes in myocardial mechanical properties, and if such changes can be detected with non-invasive imaging, providing a powerful diagnostic tool to assess myocardial state in valve disease patients.
Recent publications:
Corporan D, Onohara D, Amedi A, Saadeh M, Guyton RA, Kumar S, Padala M. Hemodynamic and Transcriptomic Studies Suggest Early Left Ventricular Dysfunction in a Preclinical Model of Severe Mitral Regurgitation. Journal of Thoracic and Cardiovascular Surgery. E-pub ahead of print (PMID: 33277035).

Project 2) Non-invasive biomechanical markers of cardiac dysfunction in valve disease

Structural changes in the myocardium manifest as changes in the myocardial mechanics, i.e. strain, twist and torsion. In valvular heart disease, the myocardium undergoes progressive changes which can alter the mechanics. We are interested in delineating in a quantitative way, the progressive changes that occur in myocardial mechanics and shape in preclinical models with valvular heart disease. We use 2D/3D echocardiography and cardiac MRI for these investigations.

Project 3) Response of the failing left ventricle to valvular interventions

Correcting valvular lesions removes the excessive hemodynamic forces that act on the ventricular and atrial chambers, enabling a halt in their further remodeling to failure, and sometimes reversing the damage that has already occurred. Clinically, both halting and reversal in remodeling are vaguely used terms that lack any physiological basis. We are using preclinical models to investigate the effect of different valvular lesions and their correction on cardiac chamber reverse remodeling. Our translational goal is to use these studies to identify if imaging based markers can be useful in determining the optimal timing of valvular interventions.

Project 4) Biomechanical reshaping and de-stressing as a heart failure therapy

One of the hallmarks of progressive and worsening heart failure is the increase in chamber volume and thinning of the myocardial walls, which work in tandem to elevate the chamber wall stress. Timely reduction of wall stress and unloading the heart has been shown to reverse these structural changes and make the heart reform its t-tubules and increase contractility. We have developed a device for percutaneous reshaping of the chamber in heart failure, and are now interested in understanding its effects at multiple scales (gene, cell, tissue, organ function).
Recent publications:

Onohara D, Corporan D, Kono T, Kumar S, Guyton RA, Padala M. Restoring physiological conical shape with a beating heart transcatheter implant improves left ventricular function in heart failure. Journal of Thoracic and Cardiovascular Surgery, 2020, E-pub ahead of print. (PMID:  33046233)