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A major concern in personalised models of heart mechanics is the unknown zero-pressure domain, a prerequisite for accurately predicting cardiac biomechanics. As the reference configuration cannot be captured by clinical data, studies often employ in-vivo frames which are unlikely to correspond to unloaded geometries. Alternatively, zero-pressure domain is approximated through inverse methodologies, which, however, entail assumptions pertaining to boundary conditions and material parameters. Both approaches are likely to introduce biases in estimated biomechanical properties; nevertheless, quantification of these effects is unattainable without ground-truth data. In this work, we assess the unloaded state influence on model-derived biomechanics, by employing an in-silico modelling framework relying on experimental data on porcine hearts. In-vivo images are used for model personalisation, while in-situ experiments provide a reliable approximation of the reference domain, creating a unique opportunity for a validation study. Personalised whole-cycle cardiac models are developed which employ different reference domains (image-derived, inversely estimated) and are compared against ground-truth model outcomes. Simulations are conducted with varying boundary conditions, to investigate the effect of data-derived constraints on model accuracy. Attention is given to modelling the influence of the ribcage on the epicardium, due to its close proximity to the heart in the porcine anatomy. Our results find merit in both approaches for dealing with the unknown reference domain, but also demonstrate differences in estimated biomechanical quantities such as material parameters, strains and stresses. Notably, they highlight the importance of a boundary condition accounting for the constraining influence of the ribcage, in forward and inverse biomechanical models., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Transcatheter aortic valve replacement (TAVR) is being extended to younger patients. However, TAVR-compatible bioprostheses are based on xenogeneic materials with limited durability. Off-the-shelf tissue-engineered heart valves (TEHVs) with remodeling capacity may overcome the shortcomings of current TAVR devices. Here, we develop for the first time a TEHV for TAVR, based on human cell-derived extracellular matrix and integrated into a state-of-the-art stent for TAVR. The TEHVs, characterized by a dense acellular collagenous matrix, demonstrated in vitro functionality under aortic pressure conditions (n = 4). Next, transapical TAVR feasibility and in vivo TEHV functionality were assessed in acute studies (n = 5) in sheep. The valves successfully coped with the aortic environment, showing normal leaflet motion, free coronary flow, and absence of stenosis or paravalvular leak. At explantation, TEHVs presented full structural integrity and initial cell infiltration. Its long-term performance proven, such TEHV could fulfill the need for next-generation lifelong TAVR prostheses.

Heart valve disease is a frequently encountered pathology, related to high morbidity and mortality rates. Animal models are interesting to investigate the causality but also underlying mechanisms and potential treatments of human heart valve diseases. Strongly believing that both in vivo and ex vivo models are fundamental to support research and development of new technologies, we here report some examples of heart valve disease models, which in our experience have been actively used to support the development of new valve therapies.

To investigate the use of computed tomography (CT) to measure the mitral valve annulus size before implantation of a percutaneous mitral valve annuloplasty device in an animal trial. Seven domestic pigs underwent CT before and after implantation of a Cardioband™ (a percutaneously implantable mitral valve annuloplasty device) with a second-generation 128-section dual-source CT machine. Implantation of the Cardioband™ was performed in a standard fashion according to a protocol. Animals were sacrificed afterwards and the hearts explanted. The Cardioband™ was found to be adequately implanted in all animals, with no anchor dehiscence and no damage of the circumflex artery (CX) or the coronary sinus (CS). The correct length of the band as chosen according to the length of the posterior mitral annulus measured in CT before implantation was confirmed in gross examination in all animals. The device did not result in a metal artifact-related degradation of image quality. The closest distance from the closest anchor to the CX was 2.1 ± 0.7 mm in diastole and 1.6 ± 0.5 mm systole. Mitral annulus distance to the CS was 6.4 ± 1.3 mm in diastole and 7.7 ± 1.1 mm in systole. CT visualization and measurement of the mitral valve annulus dimensions is feasible and can become the imaging method of choice for procedure planning of Cardioband™ implantations or other transcatheter mitral annuloplasty devices.