A continuous-flow total artificial heart (CFTAH) replaces the native heart with rotary blood pumps operating at fixed speed, and its right (venous-side) pump is disproportionately vulnerable to thrombus deposition and embolic obstruction because it must handle unfiltered venous blood. A 2014 Texas Heart Institute eight-year calf experience defined the open problem: define right-pump speed-modulation algorithms with their safety margins and efficacy across physiologic states and device types, and develop dedicated pump designs or larger-area blood paths that trade hydraulic efficiency for reduced embolic obstruction, characterized in long-term implants. Literature since 2014 shows substantive but incomplete progress: right-impeller thrombus was documented in chronic implants (2017), computational redesign reduced thrombus-susceptible flow regions (2022), modulation feasibility was established in awake and chronic calves (2017, 2022), and the BiVACOR magnetically levitated TAH entered a first-in-human early feasibility study (2024, ongoing) with favorable bench hemocompatibility — but no design or algorithm has demonstrated thrombus-free chronic operation on unfiltered venous blood across physiologic states, and optimal modulation remains undefined. The problem is open.

Background

A total artificial heart (TAH) is an implantable machine that replaces the native heart entirely, used to sustain patients with biventricular heart failure while they await transplantation. First-generation TAHs were positive-displacement pumps that mimicked the native pulse; the modern research direction, enabled by the clinical success of continuous-flow left ventricular assist devices (LVADs, rotary pumps that support only the left ventricle), is the continuous-flow total artificial heart (CFTAH): two rotary blood pumps (axial- or centrifugal-flow impeller pumps, in which a rapidly rotating bladed rotor imparts momentum to the blood) or one double-ended rotor that drive the systemic and pulmonary circulations without valves and without a physiological pulse. The Texas Heart Institute program implanted dual rotary-pump CFTAHs (two modified LVADs) in 65 calves for up to 90 days (29 surviving 7 days or more, longest 92 days), with physiological hemodynamics, normal exercise oxygen consumption, and thrombus-free circuits in the 90-day survivors (Cohn et al., 2014, ASAIO J; companion 90-day report Cohn et al., 2014). A parallel Cleveland Clinic design uses a single motor with two impellers, the right one suspended so it passively self-regulates the balance between pulmonary and systemic output (Horvath et al., 2017), and the BiVACOR device uses one magnetically levitated rotor for both circulations.

The source experience nonetheless concluded that important scientific and engineering issues remain unresolved before a fully implantable CFTAH can be considered mature for chronic application. Chief among them is the right (venous-side) pump: unlike a left-sided pump, it receives unfiltered venous return, and in chronic implants the right pump was the site of vulnerability to thrombus (blood clot on impeller or housing surfaces) and to obstruction by entrained particulate material, with consequent embolic risk to the pulmonary circulation. Right-pump rotational-speed modulation (periodic variation of impeller speed to generate pulsatility and improve washout) showed promising initial results, but optimal modulation algorithms, their safety margins, and their efficacy across device types and clinical states were undefined; the pumps otherwise ran at manually set fixed speeds. Dedicated pump designs or larger-area blood paths that deliberately trade hydraulic efficiency for reduced embolic obstruction risk had not been developed or characterized in long-term implants. The same discussion flagged two sibling gaps: the unknown long-term (beyond the 90-day scale) physiologic consequences of completely pulseless perfusion, and the absence of a single integrated closed-loop controller with sensors to maintain right/left atrial pressure (RAP/LAP) balance and matched systemic and pulmonary flows across physiologic conditions.

Subsequent literature documents the problem as real and persistent: thrombotic depositions were found on the right impeller (never the left) of the Cleveland Clinic CFTAH at explant even in animals that met their planned 14- to 90-day endpoints (Karimov et al., 2017), motivating computational fluid dynamics (CFD, numerical simulation of blood flow fields) studies that identified right-impeller blade-tip flow separation and low-wall-shear regions as the thrombogenic culprit and produced a redesigned right impeller (Goodin et al., 2022; Kuroda et al., 2024). Sinusoidal speed-modulation protocols were shown feasible in awake calves (±15% and ±25% at 80 beats/min; Fukamachi et al., 2017) and in a 30-day chronic calf (0 to ±35% at 80 bpm; Kuroda et al., 2022), and six different modulation speed profiles were compared in vitro on the BiVACOR TAH, revealing trade-offs between pulsatility measures and power with no single accepted metric for hemodynamic pulsatility (Kleinheyer et al., 2016). On the control side, passive self-regulation (Horvath et al., 2017), an adaptive Starling-like controller (a control law that, like the native heart's Frank-Starling mechanism, raises pump output as cardiac filling pressure rises) evaluated on a mock circulation loop (Ng et al., 2017), and a closed-loop circulatory-equilibrium controller validated acutely in anesthetized dogs (Yokota et al., 2024) each address part of the flow-balance problem, but none constitutes the integrated sensor-based closed-loop controller validated across physiologic states in chronic implants. Clinically, the BiVACOR TAH was first implanted in a human in July 2024 as an 8-day bridge to transplantation (Shah, 2024), and a five-patient early feasibility study is recruiting (NCT06174103); its published hemocompatibility data are in vitro, showing performance comparable to an approved clinical pump in both continuous and pulsatile modes (McNamee et al., 2026a, 2026b). Field reviews in 2015, 2022, and 2026 continue to list biocompatibility, thromboembolism, and the unresolved role of pulsatility among the principal reasons no TAH yet qualifies as chronic destination therapy (Cohn, Timms and Frazier, 2015; Vis et al., 2022; Nair et al., 2026). On the long-term pulseless-perfusion gap, the largest subsequent total heart-replacement experience in calves remained within (or barely at) the 90-day scale, with preserved end-organ function and histology (Baldwin et al., 2022), and a 14-day microvascular permeability study found no peripheral endothelial injury (Feng et al., 2015); no months- to years-scale data on totally pulseless circulation exist.

Problem Statement

For a continuous-flow total artificial heart (CFTAH), in which rotary blood pumps replace the native heart and the right (venous-side) pump must pass unfiltered venous blood, establish chronic thromboembolic safety of the venous-side pump. Specifically, as posed by the eight-year Texas Heart Institute calf experience (Cohn et al., 2014): (1) define, by systematic experimentation, right-pump speed-modulation algorithms together with their safety margins and their efficacy across physiologic states and device types; and (2) develop and characterize in long-term implants dedicated pump designs or larger-area blood paths that deliberately trade hydraulic efficiency for reduced risk of thrombus deposition and embolic obstruction by venous particulate material — the two directions the source identifies as required before a fully implantable CFTAH system can be considered mature for chronic application. A complete answer must demonstrate, in chronic implants (beyond the 90-day scale of the source experience, or with an explicit rationale for the chosen duration), that the venous-side pump operates without thrombus accumulation or embolic events while maintaining adequate hemodynamic performance (systemic and pulmonary flows, atrial-pressure balance), with the efficiency-versus-embolic-risk trade-off quantified and the modulation operating envelope (speed, amplitude, frequency, profile) and its safety margins stated. Completion boundary: the demonstration above is required on at least one device architecture, with the answer stating how the modulation algorithm and blood-path design are expected to apply to the other architectures the Background introduces (the Texas Heart dual-pump, Cleveland Clinic self-regulating two-impeller, and BiVACOR magnetically levitated designs), so testing every architecture is not required; it must also cover at least a resting state and one stressed state (for example exercise or volume loading), with states beyond these not required; and a chronic-implant duration that exceeds the 90-day source scale is required unless an explicit rationale establishes that a shorter duration suffices for the chronic-safety claim, so a shorter demonstration without that rationale is partial progress rather than a resolution.

References

  1. Cohn WE, Handy KM, Parnis SM, Conger JL, Winkler JA, Frazier OH. Eight-Year Experience with a Continuous-Flow Total Artificial Heart in Calves. ASAIO Journal 2014;60(1):25-30. DOI: 10.1097/MAT.0000000000000027. https://doi.org/10.1097/MAT.0000000000000027
  2. Cohn WE, Winkler JA, Parnis S, Costas GG, Beathard S, Conger J, Frazier OH. Ninety-day survival of a calf implanted with a continuous-flow total artificial heart. ASAIO Journal 2014;60(1):15-18. DOI: 10.1097/MAT.0000000000000026. https://doi.org/10.1097/MAT.0000000000000026
  3. Horvath D, Byram N, Karimov JH, Kuban B, Sunagawa G, Golding LAR, Moazami N, Fukamachi K. Mechanism of Self-Regulation and In Vivo Performance of the Cleveland Clinic Continuous-Flow Total Artificial Heart. Artificial Organs 2017;41(5):411-417. DOI: 10.1111/aor.12780. https://doi.org/10.1111/aor.12780
  4. Karimov JH, Horvath DJ, Okano S, Goodin M, Sunagawa G, Byram N, Moazami N, Golding LAR, Fukamachi K. Thrombotic Depositions on Right Impeller of Double-Ended Centrifugal Total Artificial Heart In Vivo. Artificial Organs 2017;41(5):476-481. DOI: 10.1111/aor.12778. https://doi.org/10.1111/aor.12778
  5. Karimov JH, Moazami N, Kobayashi M, Sale S, Such K, Byram N, Sunagawa G, Horvath D, Gao S, Kuban B, Golding LA, Fukamachi K. First report of 90-day support of 2 calves with a continuous-flow total artificial heart. Journal of Thoracic and Cardiovascular Surgery 2015;150(3):687-693. DOI: 10.1016/j.jtcvs.2015.06.023. https://doi.org/10.1016/j.jtcvs.2015.06.023
  6. Goodin MS, Horvath DJ, Kuban BD, Polakowski AR, Fukamachi K, Flick CR, Karimov JH. Computational Fluid Dynamics Model of Continuous-Flow Total Artificial Heart: Right Pump Impeller Design Changes to Improve Biocompatibility. ASAIO Journal 2022;68(6):829-838. DOI: 10.1097/MAT.0000000000001581. https://doi.org/10.1097/MAT.0000000000001581
  7. Kuroda T, Miyagi C, Polakowski AR, Flick CR, Kuban BD, Fukamachi K, Karimov JH. Cleveland Clinic Continuous-Flow Total Artificial Heart: Progress Report and Technology Update. ASAIO Journal 2024;70(2):116-123. DOI: 10.1097/MAT.0000000000002076. https://doi.org/10.1097/MAT.0000000000002076
  8. Fukamachi K, Karimov JH, Sunagawa G, Horvath DJ, Byram N, Kuban BD, Dessoffy R, Sale S, Golding LAR, Moazami N. Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in awake calves. Journal of Artificial Organs 2017;20(4):381-385. DOI: 10.1007/s10047-017-0958-5. https://doi.org/10.1007/s10047-017-0958-5
  9. Kuroda T, Miyamoto T, Miyagi C, Polakowski AR, Flick CR, Kuban BD, Voros GB, Such K, Fukamachi K, Karimov JH. Pulsatility hemodynamics during speed modulation of continuous-flow total artificial heart in a chronic in vivo model. Artificial Organs 2022;46(8):1555-1563. DOI: 10.1111/aor.14237. https://doi.org/10.1111/aor.14237
  10. Kleinheyer M, Timms DL, Tansley GD, Nestler F, Greatrex NA, Frazier OH, Cohn WE. Rapid Speed Modulation of a Rotary Total Artificial Heart Impeller. Artificial Organs 2016;40(9):824-833. DOI: 10.1111/aor.12827. https://doi.org/10.1111/aor.12827
  11. Ng BC, Smith PA, Nestler F, Timms D, Cohn WE, Lim E. Application of Adaptive Starling-Like Controller to Total Artificial Heart Using Dual Rotary Blood Pumps. Annals of Biomedical Engineering 2017;45(3):567-579. DOI: 10.1007/s10439-016-1706-3. https://doi.org/10.1007/s10439-016-1706-3
  12. Yokota S, Uemura K, Unoki T, Matsushita H, Kakuuchi M, Yoshida Y, Sasaki K, Kawada T, Nishikawa T, Kataoka Y, Peterson J, Sunagawa K, Alexander J, Saku K. Novel Closed-Loop Control System of Dual Rotary Blood Pumps in Total Artificial Heart Based on the Circulatory Equilibrium Framework: A Proof-of-Concept In Vivo Study. IEEE Transactions on Biomedical Engineering 2024;71(12):3358-3369. DOI: 10.1109/TBME.2024.3420907. https://doi.org/10.1109/TBME.2024.3420907
  13. Shah AM. First successful implant of BiVACOR's Total Artificial Heart. Artificial Organs 2024;48(10):1075-1076. DOI: 10.1111/aor.14844. https://doi.org/10.1111/aor.14844
  14. McNamee AP, Timms D, Nestler F, Bartnikowski N, Smith A, Tansley GD, Simmonds MJ. In Vitro Hemocompatibility of the BiVACOR Total Artificial Heart in Continuous and Pulsatile Flow. Artificial Organs 2026;50(1):84-93. DOI: 10.1111/aor.70009. https://doi.org/10.1111/aor.70009
  15. McNamee AP, Timms D, Nestler F, Bartnikowski N, Tansley GD, Wu E, Simmonds MJ. In Vitro Hemocompatibility of the BiVACOR Total Artificial Heart Near the Boundaries of Clinical Operation. ASAIO Journal 2026;72(8):643-650. DOI: 10.1097/MAT.0000000000002536. https://doi.org/10.1097/MAT.0000000000002536
  16. Baldwin AC, Gemmato CJ, Cohn WE, Frazier OH. Feasibility of long-term continuous flow total heart replacement in calves. International Journal of Artificial Organs 2022;45(1):44-51. DOI: 10.1177/0391398820987851. https://doi.org/10.1177/0391398820987851
  17. Feng J, Cohn WE, Parnis SM, Sodha NR, Clements RT, Sellke N, Frazier OH, Sellke FW. New continuous-flow total artificial heart and vascular permeability. Journal of Surgical Research 2015;199(2):296-305. DOI: 10.1016/j.jss.2015.06.035. https://doi.org/10.1016/j.jss.2015.06.035
  18. Cohn WE, Timms DL, Frazier OH. Total artificial hearts: past, present, and future. Nature Reviews Cardiology 2015;12(10):609-617. DOI: 10.1038/nrcardio.2015.79. https://doi.org/10.1038/nrcardio.2015.79
  19. Vis A, Arfaee M, Khambati H, Slaughter MS, Gummert JF, Overvelde JTB, Kluin J. The ongoing quest for the first total artificial heart as destination therapy. Nature Reviews Cardiology 2022;19(12):813-828. DOI: 10.1038/s41569-022-00723-8. https://doi.org/10.1038/s41569-022-00723-8
  20. Nair A, van der Kaaij NP, Kluin J, Rogers J. Total artificial hearts: an evolution on the horizon. European Heart Journal 2026;47(32):4396-4409. DOI: 10.1093/eurheartj/ehag395. https://doi.org/10.1093/eurheartj/ehag395
  21. BiVACOR Total Artificial Heart Early Feasibility Study, protocol record NCT06174103, ClinicalTrials.gov (study start 2024-06-26, 5 planned subjects, bridge-to-transplant). https://clinicaltrials.gov/study/NCT06174103