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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Assistant Professor Victoria Delgado, Hospital Germans Trias i Pujol, Spain
- Second opponent: Professor Håvard Dalen, NTNU: Norwegian University of Science and Technology,
- Third member and chair of the evaluation committee: Professor II Henrik Schirmer, University of Oslo
Chair of the Defence
Professor Peder L. Myhre, University of Oslo
Principal Supervisor
Professor Alessandro Cataliotti, University of Oslo
Summary
Heart failure is a condition with significant mortality and morbidity worldwide. While sacubitril/valsartan is an established treatment for heart failure with reduced ejection fraction, less is known about the effects of sacubitril/valsartan in cardiac pressure overload and after myocardial infarction.
The aim of the thesis was to understand the effect of sacubitril/valsartan after pressure-overload and myocardial infarction in a rodent model. Furthermore, ways to improve measurement of cardiac stiffness, a known factor in heart failure development, were investigated.
In cardiac pressure overload sacubitril/valsartan resulted in less hypertrophy compared to valsartan treatment alone. Treatment with sacubitril/valsartan furthermore preserved cardiac relaxation as measured by early longitudinal strain rate. After myocardial infarction, treatment with sacubitril/valsartan ameliorated left ventricular dilation and improved contractile function of myocardium in the regions adjacent to the infarct as measured with cardiac magnetic resonance (CMR) strain-imaging. Fibrotic deposition was reduced with sacubitril/valsartan treatment, and indications were found of less apoptosis. Furthermore sacubitril/valsartan was found to have direct effects on cardiomyocyte calcium handling.
Cardiac stiffness was measured with cardiac catheterization to acquire the end-diastolic pressure-volume relationship (EDPVR) in rats that had undergone aortic banding. Imaging markers from echocardiography and CMR were used. Several of the commonly used markers of diastolic dysfunction correlated poorly with EDPVR. For CMR E/Sre(long), left atrial ejection fraction, isovolumic relaxation time and Sre(long) performed well at estimating cardiac stiffness. T1 mapping, a method to measure extracellular volume, also had good characteristics. For echocardiography the parameters E/A, E and left atrial diameter showed the best correlation.
Additional information
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