Functional Assessment of Decellularized Extracellular Matrix in Patients Undergoing LVAD Implantation

Purpose While changes in the extracellular matrix (ECM) have been demonstrated in the failing heart, changes in mechanical ECM properties are unknown. We aimed to determine the biomechanical properties of ECM obtained from myocardial tissue samples at the time of left ventricular assist device (LVAD) implantation. Methods Myocardial tissue samples obtained at the time of LVAD implantation underwent decellularization and determination of the stress-strain relationship. Storage modulus (G’, an assessment of elastic properties) and loss modulus (G’’, an assessment of viscous properties) were compared against the likelihood of clinical recovery as computed using an established predictive model, the INTERMACS Cardiac Recovery Score (I-CARS). Results 14 myocardial samples were obtained and analyzed at the time of LVAD implantation. Mean age was 48.8 years (range: 17-74). 11 subjects were male (79%) with ischemic etiology in 3 (21%). Mean ejection fraction was 19.2% ± 7.2%. Storage and loss modulus of the ECM samples were grouped into tertiles based on the likelihood of myocardial recovery as predicted by I-CARS score. The group with the lowest recovery likelihood (0.0%, I-CARS score of 0-3) had the highest average value of storage modulus (1312 ±1553 Pa at 1 rad/s). The group with intermediate recovery likelihood (6.3%, I-CARS score of 4-6) had intermediate average value (781 ±517 Pa at 1 rad/s). The group with the highest recovery likelihood (38.9%, I-CARS score of 7-9) had the lowest average value (450 ±308 Pa at 1 rad/s). Similar trends were seen with loss modulus (figure). Conclusion Analysis of ECM in myocardial tissue samples obtained at the time of LVAD implantation showed a trend toward lower storage modulus and loss modulus in those with a higher predicted likelihood of myocardial recovery based on the I-CARS recovery score. The functional properties of decellularized ECM can be assessed ex vivo and may represent an independent parameter for myocardial recoverability.