Pacing with Digital Twins of Brainstem Neuronal Circuits as an Effective Therapy for Chronic Cardiac Disease

Informazioni relative al progetto

CResPulse

ID dell’accordo di sovvenzione: 101214165

DOI

10.3030/101214165

Data della firma CE 14 Aprile 2025

Data di avvio 1 Giugno 2025

Data di completamento 31 Maggio 2028

Finanziato da

• The European Innovation Council (EIC)

Costo totale

Nessun dato

Contributo UE

€ 2 469 280,71

Coordinato da

UNIVERSITY OF BATH
United Kingdom

Periodic Reporting for period 1 - CResPulse (Pacing with Digital Twins of Brainstem Neuronal Circuits as an Effective Therapy for Chronic Cardiac Disease)

Periodo di rendicontazione: 2025-06-01 al 2026-05-31

Sintesi del contesto e degli obiettivi generali del progetto

Small neural networks known as central pattern generators (CPG) are now proven to be a prospective cure to chronic cardiorespiratory disease for which no long-term therapy exists. The present project develops adaptive neuromorphic circuits and the nonlinear programming methods to train more advanced CPGs to produce accurate beat-to-beat cardiac stimulation. The devices integrates multiple physiological feedback in real time, such as lung inflation signals and oxygen partial pressure to compute the timing of electrical impulses to three heart chambers. By restoring heart rate variability, cardiorespiratory synchronization and adaptation of cardiac dynamics to physiological feedback, the CResPulse pacemaker is expected to improve patient outcomes in a variety of unmet conditions such as paroxysmal atrial fibrillation, heart failure, left bundle branch block unresponsive to conventional treatment; and to save costs by freeing healthcare provider resources.

This EIC transition project translates our 3-lead adaptive pacing (PM) and cardiac biventricular resynchronization (CRT) technology from its successful proof-of-concept in acute trials and chronic small animal models of heart failure (TRL4) to a miniaturized solution which is compliant with the ISO13485 medical device standard and EMA requirements for Phase 1 human trials (TRL6). In the process, the technology will be matured, integrated and its safety improved under strict quality control. Large animal trials will be conducted over a period of 3 months follow-up with the CResPulse pacemaker to demonstrate reversal of adverse cardiac remodelling by new top-on-care treatment for heart failure. Animal trials will be extended to acute and chronic arrhythmias, caused by atrial fibrillation, to demonstrate new therapeutic option for diverse cardiac arrhythmias, validate medical hypotheses and broaden impact.

Project outcomes will be incorporated in a spin-off venture that will manage clinical trials and commercialize the CResPulse pacemaker. Investment readiness will be achieved through the delivery of a business plan incorporating market feedback, mapping the reimbursement landscape by healthcare providers, delivery of an IP strategy, quality control leading to ISO13485 compliance, entrepreneurship, dissemination, and human trial plans.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Technical work:
- UBAH has designed, manufactured and tested the miniaturized board of the pacemaker incorporating the optical sensor, the chest impedance sensor, the central pattern generator, I/Os, and the telemetry module.
- ICRC has tested the chest impedance module in animal models under a variety of scenarios to minimize power consumption and maximize signal to noise ratios. Optimal settings have been shared with UBAH for incorporation in the integrated board.
- UBAH has designed and manufactured an ISO13485 compliant pacemaker enclosure with optical window for hosting the miniaturized board.

- MUW have secured National ethical approval for trials in March 2026.
- MUW, UBAH and ICRC have conducted a first set of in-vivo acute trials to resynchronize 3 heart chambers and adding heart rate variability. They verified the ability of the pacemaker to restore rate control after atrial rhythm disturbance had been induced.

- UBAH have developed an advanced CPG model providing enhanced dynamic range and stability. The model was designed to be implemented in VLSI for both optimal scaling and low power consumption, and as a digital twin running on the pacemaker microcontroller, for flexibility. This design has been filed as one of the two patents planned for this project.

-UBAH have completed simulations of the cardiorespiratory system proving, from first principles calculations and a simple argument, that respiratory-induced heart rate variability minimizes viscoelastic dissipation in the pulmonary vascular impedance. These simulation predicted that neuronal pacing with the CResPulse pacemaker increases human cardiac efficiency by 10% relative to monotonic pacing with a conventional pacemaker. This corroborate earlier trials showing an increase in cardiac output by ~19% under neuronal pacing.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

At month 12, we have filed 1 patent on describing the pacemaker architecture and training of its digital twin training on biological data using RPDA optimization.

We have published 4 journal articles (Adv.Sci. Sci.Rep.,Front. Comp. Sci, BioPhysics Reviews).

We have presented project results or have accepted abstract at 10 international conferences (Canada, Germany, France, China…) including 5 invited talks (ICMNS2026 Montreal, European Society of Cardiology Congress, N.I.C.E International RendezVous 2025, Shandong Univ., Austrian Soc Cardiol Annual Meeting 2026, Salzburg).

We have interviewed about 20 medical device industry participants and consultants including at the MedTech UK trade event at the Coventry Arena in March 2026. However some of this effort were embargoed by out TTO pending the filing of the patent.

We have completed approximately 50% of the IS013485 compliance Quality Control and Risk and Assessment documentation of the pacemaker.


In parallel with these actions, future key needs will be file the second patent and to pitching our business value proposition at international pitching events (Techtour UK, Biovaria Germany) and to investors some of whom have already contacted us.