Robinson, Shawn

Three-dimensional (3D) anatomic modeling derived from high-resolution medical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), has been increasingly adopted in preclinical testing and device development. This white paper describes a cardiac-specific workflow that integrates 3D printing and silicone molding for support device development and procedural simulation. Patient-derived computed tomography angiography data were segmented using FDA-cleared medical modeling software to isolate the left ventricular anatomy and were further processed in computer-aided design (CAD) to ensure accurate physiological wall thickness and structural fidelity. Material jetting 3D printing was performed on a Stratasys J750 using material distributions designed to mimic the mechanical properties of myocardium, thereby approximating myocardial compliance. In parallel, stereolithography apparatus molds were designed from the left ventricle CAD model to cast transparent, pliable left ventricular models in Sorta-Clear™ 18 silicone. The 3D-printed models preserved intricate morphological detail and were suitable for mechanical manipulation and device deployment studies, whereas silicone models offered tunable mechanical properties, transparency for visualization, and durability for repeated use. Together, these complementary modalities provided rapid manufacturing capability and application-relevant physical representation. Case-specific parameters, strengths, and limitations of both models in enhancing patient care and device testing are highlighted, with relevance to heart failure applications. Current knowledge gaps, workflow and integration challenges, and future opportunities are identified, positioning this work as a reference framework for continued innovation in anatomic modeling. Within the collaborative framework of Mayo Clinic’s Anatomic Modeling Unit and Simulation Center, this integrated modeling workflow demonstrates the value of multidisciplinary collaboration between engineers and clinicians. Clinically, these patient-specific left ventricular models may enable pre-procedural device sizing and positioning and may support simulation of mechanical circulatory support (MCS) deployment while identifying possible anatomic constraints prior to intervention. This workflow has direct applicability in advanced heart failure patients undergoing MCS support, such as the Impella axillary MCS device or the durable LVAD, with potential to reduce procedural uncertainty while reducing complications and improving peri-procedural outcomes. Additionally, these models also serve as high-accuracy educational tools, enabling trainees and multidisciplinary care teams to visualize and possibly rehearse procedural steps while gaining hands-on experience in a risk-free environment.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator–activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.