Cardiac Digital Twin — cell-up depolarization

Cell-up cardiac digital twin

Sources

Anatomy

Doste R, et al. InSilicoHeartGen: a pipeline for generating synthetic biventricular and four-chamber heart meshes. Comput Methods Programs Biomed, 109290, 2026. Dataset Zenodo 10.5281/zenodo.19369570, CC BY. Biventricular volume mesh, per-node fibre directions and cobiveco universal ventricular coordinates. The mesh is SYNTHETIC — generated by a VAE trained on UK Biobank healthy-adult CMR, not a single named patient.

Streeter DD Jr, Spotnitz HM, Patel DP, Ross J Jr, Sonnenblick EH. Fiber orientation in the canine left ventricle during diastole and systole. Circ Res 24:339–347, 1969. Helical fibre architecture, +60° endocardium to −60° epicardium.

Cellular electrophysiology

ten Tusscher KHWJ, Noble D, Noble PJ, Panfilov AV. A model for human ventricular tissue. Am J Physiol Heart Circ Physiol 286:H1573–H1589, 2004. doi:10.1152/ajpheart.00794.2003 Base ionic model — I_Na and the fast/slow inactivation gates.

ten Tusscher KHWJ, Panfilov AV. Alternans and spiral breakup in a human ventricular tissue model. Am J Physiol Heart Circ Physiol 291:H1088–H1100, 2006. doi:10.1152/ajpheart.00109.2006 The TT06 model used throughout: transmembrane potential, transmural endo/mid/epi strand composition and APD₉₀. For the rotor, additionally the 25×25 cm domain, diffusivity, restitution parameter settings and cross-field S1–S2 protocol.

Clerx M, Barral Y, Agrawal A, Mirams GR. TNNP unit fixes. 2020. Unit corrections applied to the published TT06 formulation.

Antzelevitch C, et al. Electrical heterogeneity within the ventricular wall. 2001. Three-layer endo / M-cell / epi wall structure and the M-cell APD₉₀.

Activation sequence — sinus and LBBB

Durrer D, van Dam RT, Freud GE, Janse MJ, Meijler FL, Arzbaecher RC. Total excitation of the isolated human heart. Circulation 41:899–912, 1970. doi:10.1161/01.CIR.41.6.899 Human endocardial breakthrough sites and the ~30 ms Purkinje–myocardial junction span that set the sinus activation sequence.

Cardone-Noott L, Bueno-Orovio A, Minyé A, Rodriguez B. Human ventricular activation sequence and the simulation of the electrocardiographic QRS complex. Europace 18(suppl 4):iv4, 2016. Activation-sequence parameterisation.

Goldberger AL. Clinical Electrocardiography: A Simplified Approach, Ch. 4. Left bundle branch block activation pattern.

Numerics & verification

Rush S, Larsen H. A practical algorithm for solving dynamic membrane equations. IEEE Trans Biomed Eng 25(4):389–392, 1978. Integration of the Hodgkin–Huxley gating variables.

Niederer SA, Kerfoot E, Benson AP, Bernabeu MO, Bernus O, Bradley C, et al. Verification of cardiac tissue electrophysiology simulators using an N-version benchmark. Philos Trans R Soc A 369(1954):4331–4351, 2011. doi:10.1098/rsta.2011.0139 Monodomain conductivities along / transverse to fibre, χ and C_m; cross-simulator verification of this solver.

Potse M, Dubé B, Richer J, Vinet A, Gulrajani RM. A comparison of monodomain and bidomain reaction-diffusion models for action potential propagation in the human heart. IEEE Trans Biomed Eng 53(12):2425–2435, 2006. Harmonic-mean reduction of the bidomain conductivities to a monodomain tensor.

Qu Z, Garfinkel A. An advanced algorithm for solving partial differential equation in cardiac conduction. IEEE Trans Biomed Eng 46(9):1166–1168, 1999. doi:10.1109/10.784149 Operator splitting of the reaction–diffusion step.

Pezzuto S, Hake J, Sundnes J. Space-discretization error analysis and stabilization schemes for conduction velocity in cardiac electrophysiology. Int J Numer Method Biomed Eng 32:e02762, 2016. doi:10.1002/cnm.2762 Mesh-dependent conduction-velocity error and apparent-conductivity correction.

VT substrate — constructed circuit only

de Bakker JMT, van Capelle FJL, Janse MJ, Tasseron S, Vermeulen JT, de Jonge N, Lahpor JR. Slow conduction in the infarcted human heart. ‘Zigzag’ course of activation. Circulation 88:915–926, 1993. PMID 8353918. Tortuous isthmus: activation weaves along surviving myocyte bundles at normal local velocity over a lengthened path.

Measured vs constructed. The Rotor view is a solved monodomain simulation — its 247 ms period was measured over 14 rotations, not prescribed. The VT view is a constructed circuit with an imposed activation sequence, shown to illustrate the substrate geometry; it is not a solved reentry and its timing is not a measurement.

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Time after onset

0ms

Myocardium activated

Total activation

78ms

Transmembrane potential

−86−20+40 mV

0 / 460 ms

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