A 1992 retrospective study of 378 total artificial heart (TAH) implantations in animals at the Utah artificial-heart program found that 39% developed 'thrombus with infection' (T&I) — intradevice thrombus accompanied by positive blood culture — with Pseudomonas species predominant and sepsis a leading cause of termination. The authors explicitly identified as needing further investigation: the mechanisms of bacterial interaction with thrombus and biomaterial surfaces (bacterial adhesion, biofilm formation, and whether bacteria initiate thrombogenesis or passively colonize preformed thrombi), the role of post-implant host immunomodulation, the contribution of gut barrier dysfunction and bacterial translocation to prosthetic infection, and design improvements and surface modifications to reduce thrombosis together with elimination of the route of entry of pathogenic microorganisms. A related question, documented by the subsequent literature rather than stated by the 1992 authors, is whether established intrathrombotic (biofilm-protected) infection can be eradicated. As of 2026, all five facets remain open at the translational level: bench studies established that thrombus components enhance bacterial adhesion to device polymers and that bacteria can promote coagulation, but causality in vivo under device-relevant flow is unsettled; human data on the gut–device infection route are small-cohort and correlational; no device surface or design durably prevents both thrombosis and infection; and eradication of established device biofilm infection remains unsolved, with recent phage-therapy series failing.

Background

A total artificial heart (TAH) is a mechanically implanted pump that replaces both ventricles of the failing heart; a ventricular assist device (VAD) is a related implantable pump that supports one or both ventricles while the native heart remains in place. Most durable VADs in clinical use have a percutaneous driveline — a cable crossing the skin to power the pump — which is the dominant site of infection in modern devices. Thrombogenesis here means the formation of blood clots (thrombi) on the foreign surfaces of the device, typically at flow-disturbing features such as valve junctions and connectors. Biofilm is a structured community of bacteria encased in an extracellular matrix (historically called 'slime') that adheres to surfaces and confers protection against antibiotics and host immune defenses; bacterial translocation is the passage of bacteria or their products from the intestinal lumen through a damaged gut barrier into the bloodstream. In January 1980–December 1990 the Utah artificial-heart program implanted various TAH types in 378 animals; a retrospective analysis (Chiang et al. 1992) found 147 (39%) with thrombus plus a positive blood culture ('T&I'), most commonly Pseudomonas species, with portals of entry suspected to be skin lesions and pressure-line contamination, and intestinal bacterial translocation proposed as a further possible route. Necropsy showed sepsis, infected thrombus, thromboembolism, and multiple organ infarctions, with thrombi originating mainly at valve junctions and connectors. On this basis the authors proposed a pathogenesis scheme in which thrombus and infection reinforce one another on device surfaces, and stated that bacterial interaction with thrombus, device-related bacterial colonization, host immunomodulation (altered immune function induced by implantation surgery and chronic contact with device biomaterials), and gut barrier function after artificial heart implantation need further investigation, together with design improvements and surface modifications to reduce thrombosis and elimination of the microorganism entry route. Subsequent decades moved the field from pneumatic TAHs with externalized drivelines to transcutaneously powered prototypes, the clinical SynCardia/CardioWest-type TAH, the bioprosthetic-surface Carmat Aeson TAH, and modern continuous-flow VADs, yet the twin biocompatibility problems named in 1992 — thrombosis and infection, and their coupling — remain the central obstacles: a 2019 Annual Review of Biomedical Engineering assessment of TAH evolution concludes that low hemocompatibility, calcification, and susceptibility to infection 'seriously affect the success of TAHs', and 2020s clinical reviews report device-specific infections at roughly 10–20% per year with frequently unsatisfactory treatment outcomes.

Problem Statement

For blood-contacting circulatory-support devices, the interlinked 1992 open questions remain. (The 1992 source studied total artificial hearts implanted in animals; the questions below also cover ventricular assist devices and human clinical use.) (1) By what mechanisms do bacteria and thrombus interact on biomaterial surfaces — quantitatively, what are the adhesion and biofilm-formation kinetics of pathogens such as Pseudomonas and Staphylococcus species on device polymers under physiological intradevice flow and shear, and do bacteria actively induce thrombogenesis on these surfaces or predominantly colonize preformed thrombi? (2) To what extent does post-implantation host immunomodulation permit systemic device-related infection or prevent clearance of organisms sequestered within thrombus? (3) Does gut barrier dysfunction with bacterial translocation contribute materially to device infection, and under which hemodynamic or ischemic conditions? (4) Can design improvements and surface modifications to reduce thrombosis (including endothelialization, i.e., lining the device's blood-contacting surfaces with endothelial cells, the cells that form the inner wall of natural blood vessels), together with elimination of the route of entry of pathogenic microorganisms, prevent thrombus initiation and subsequent bacterial colonization in actual use? (5) As a related contemporary open question, documented by later literature (for example, the failed phage-therapy series) rather than by the 1992 agenda itself: can established intrathrombotic, biofilm-protected device infection be eradicated?

Questions (1)–(5) are distinct parts of the same interlinked problem.

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