This study applies a previously developed imaging-modelling approach to investigate the subject-specific effects of dobutamine on left ventricular contraction and relaxation patterns in healthy subjects. We created personalized models for nine subjects at rest and under dobutamine stress. The personalized parameter values were in agreement with the effects of inotropy and lusitropy reported in previous studies, and demostrated the anticipated variability in individual responses to dobutamine. With further validation, the given approach has the potential to generate advanced metrics of cardiovascular physiology and pathophysiology that could extend beyond conventional techniques for both diagnosis and optimization of a personalized medical regimen.
Non-invasive measurements were acquired in nine subjects without a known heart condition (mean age: 29±11 years, range 20-56 years, 2 men) at rest and during continuous dobutamine infusion (mean peak dose: 20±7 μg/kg/min, range 10-30 μg/kg/min). Two personalized models, both based on a reduced version of our previous model5, were created for each subject, using the datasets acquired at rest and during dobutamine stress, respectively. Under each physiological condition, morphological cine balanced steady-state free precession (bSSFP) images and 4D Flow MRI data were acquired using a clinical 3T Philips Ingenia scanner (Philips Healthcare, Best, the Netherlands). The acquisition settings are described in Casas et al.5 Heart rate and cuff-based pressure measurements were monitored during the infusion protocol.
The generic model where parameters are fitted comprises the pulmonary venous system, the left side of the heart, the ascending aorta and a Windkessel model representing the systemic vessels (Figure 1B). The pumping function of the cardiac chambers is described using time-varying elastances6, which relate chamber volume and pressure along the cardiac cycle for the left atrium and the left ventricle, respectively (Figure 1C). Elastance parameters are load independent and well-accepted indexes of cardiac function7,8. Model parameters were personalized based on subject-specific inputs including measurements characterizing the morphology and function of the left ventricle and the aortic valve, as well as 4D Flow MRI-derived volumetric flow waveforms at the mitral valve (MV), the aortic valve (AV) and the ascending aorta (AA) (Figure 1A). The resulting subject-specific parameters based on data at rest and dobutamine stress were compared using a Wilcoxon signed-rank test. A p-value<0.05 was considered significant.
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