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CARDIOKIN1: Computational Assessment of Myocardial Metabolic Capability in Healthy Controls and Patients With Valve
Nikolaus Berndt1, Johannes Eckstein1,2, Iwona Wallach1,2
1Institute of Computer-Assisted Cardiovascular Medicine (N.B., J.E., I.W., S.N., M. Kelm, L.G., M.S., A.H., T.K.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, and Humboldt-Universität zu Berlin, Germany.
Circulation
|November 11, 2021
Summary
Heart disease can impair the heart
Area of Science:
- Cardiology
- Biochemistry
- Computational Biology
Background:
- Heart diseases often reduce the heart muscle's pumping capacity.
- Mismatches in cardiomyocyte ATP production and demand contribute to heart dysfunction.
- Assessing myocardial ATP production (MVATP) relative to workload is crucial for understanding disease and guiding treatment.
Purpose of the Study:
- To develop and utilize a kinetic model of cardiac energy metabolism (CARDIOKIN1).
- To assess the energy status of the left ventricle in healthy individuals and patients with valvular heart disease.
- To investigate the relationship between myocardial ATP production, workload, and cardiac function.
Main Methods:
- Developed CARDIOKIN1, a comprehensive kinetic model of cardiac energy metabolism.
- Scaled maximal enzyme activities using protein abundance data from left ventricle tissue.
- Quantified left ventricular energy status, including ATP consumption at rest (MVATP[rest]) and maximal workload (MVATP[max]).
Main Results:
- Patients with aortic stenosis or mitral valve insufficiency showed increased MVATP[rest] and decreased MVATP[max] compared to controls.
- A reduced myocardial ATP production reserve was observed in patients, despite preserved ejection fraction.
- Energetic status correlated with mechanical energy demand and cardiac output, indicating coupled cardiac functionality and energetic performance.
Conclusions:
- Left ventricular ATP-producing capacity is diminished in patients with valvular dysfunction.
- Diminished ATP production capacity positively correlates with mechanical energy demand and cardiac output.
- Significant variability exists in myocardial energetic status among patients with similar clinical markers.
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