The Science of Diastole – Inaugural lecture by Honorary Member Sándor Kovács

Honorary Member Sándor Kovács delivered his inaugural academic lecture on 21 June 2023; a summary of the lecture in English, with a picture gallery and video.

2024. január 29.

From the time of Aristotle (4th century BC) to Da Vinci (15th-16th century) to Vesalius (16th century) to Harvey (mid-17th century) to Ugander (2017), our understanding of how the heart works as a pump within a closed circulatory system has continued to evolve. Our current understanding of organ level function awaited the development of invasive (cardiac catheterisation) and non-invasive (echocardiography, cardiac CT, cardiac MRI) technology and the measurement of bioelectric phenomena (ECG), as well as the recording of in vivo pressures, flows and volumes. Despite these advances, the current clinical quantification of diastolic function remains correlative rather than causality-/mechanism-based.

Kovács Sándor
(For more pictures click on the photo)
Photo: / Tamás Szigeti

The realisation that peripheral muscle oscillation requires opposing muscle groups (extensors-flexors) whereas cardiac pumping (oscillation) is achieved by a single muscle (myocardium) that has no opposing muscle group requires further explanation. To appreciate the science of diastole, it is useful to adopt a conceptual framework of the four-chambered heart as primarily a near-perfect ‘constant-volume’ pump that relies on the simultaneous reciprocation of atrial-ventricular volumes during the cardiac cycle. As the ventricles eject, the atria simultaneously fill. Ventricular filling (diastole) requires a rapid drop in ventricular pressure, below atrial pressure, to initiate transmitral flow (Doppler E-wave). Importantly, as the mitral valve opens for a short interval afterward, left ventricular (LV) pressure continues to drop while LV volume rapidly increases (dP/dV<0), meaning that the chamber expands faster than it can fill. It therefore acts as a mechanical suction pump. This process is a cardiohemic inertial oscillation that obeys Newton’s law (equation of motion). The solution (parametrised diastolic filling (PDF) formalism) uses the E-wave contour as input and solves the ‘inverse problem of diastole’ by providing unique values for global chamber stiffness, relaxation and load. Among numerous advances, the PDF framework has solved the ‘load independent index of diastolic function’ (LIIDF) problem, revealed that E-wave asymmetry is due to stiffness-relaxation coupling, and shown that optimal filling is achieved by matching E-wave vortex ring expansion to wall motion. Overall, the science of diastole has advanced our understanding of how the heart works as it fills.

Sándor Kovács was born in Budapest in 1947. He received his PhD in physics from the California Institute of Technology in 1977. He is a Professor of Cell Biology and Physiology in the Department of Internal Medicine at the Washington University School of Medicine in St. Louis. He specialises in cardiology and cell biology. He has made significant contributions to the advances in cardiovascular physiology and clinical cardiology. He has developed new technical procedures in multimodal imaging of the heart, and explained the mechanism of origin of the third (S3) and fourth (S4) heart sounds. He has established a mathematically rigorous model called parameterized diastolic filling (PDF) formalism, which starts from the contour of the clinical E-wave and interprets the inverse problem, the diastolic case. This solved the load-independent diastolic functional (LIIDF) problem. The method was patented. Using multimodal imaging, he created a physical model describing the rapid filling of the left ventricle.