Increased Chamber Resting Tone Is a Key Determinant of Left Ventricular Diastolic Dysfunction.
María Tamargo1, Pablo Martínez-Legazpi1,2, M Ángeles Espinosa1
1Department of Cardiology, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Gregorio Marañón, and CIBERCV, Spain (M.T., P.M.-L., M.A.E., I.M., E.G.-I., A.I.F., R.P.-A., A.G.-M., T.M., R.S.-R., J.E., R.Y., F.F.-A., J.B.).
Circulation. Heart Failure
|December 19, 2023
Summary
Twitch-independent tension, termed resting tone (RT), significantly contributes to diastolic dysfunction in heart failure with preserved ejection fraction and hypertrophic cardiomyopathy. This finding suggests antimyosin agents as a potential treatment for heart failure.
Area of Science:
- Cardiology
- Physiology
- Biomedical Engineering
Background:
- Twitch-independent tension in cardiomyocytes is known, but its role in heart failure (HF) remains unclear.
- Diastolic dysfunction in HF is multifactorial, involving impaired relaxation, stiffness, and potentially chamber resting tone (RT).
Purpose of the Study:
- To investigate the role of twitch-independent tension, specifically chamber resting tone (RT), as a cause of diastolic dysfunction in heart failure.
- To differentiate the contribution of RT from impaired relaxation and stiffness in diastolic dysfunction.
Main Methods:
- Invasive pressure-volume data were collected during cardiopulmonary exercise in patients with hypertrophic cardiomyopathy, HF with preserved ejection fraction, and controls.
- A novel method was developed and validated in a computational model to measure RT from continuous pressure-volume measurements.
Main Results:
- Resting tone (RT) was significantly elevated in hypertrophic cardiomyopathy and HF with preserved ejection fraction patients, increasing further with exercise.
- RT accounted for a substantial portion of end-diastolic pressure during peak exercise in hypertrophic cardiomyopathy (64%).
- RT correlated with NT-proBNP and pulmonary wedge pressure, and in silico models showed RT increased with loss of cMyBP-C function.
Conclusions:
- Augmented RT is a primary driver of left ventricular diastolic dysfunction in hypertrophic cardiomyopathy and HF with preserved ejection fraction.
- RT transients have a greater impact on diastolic pressures, pulmonary pressures, and functional capacity than relaxation or stiffness abnormalities.
- These findings support the investigation of antimyosin agents for the treatment of heart failure.
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