Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 59 min ago
Peer-reviewedCC BY 4.0Advanced Science

Human Engineered Heart Tissues Reproduce Trigger‐ and Substrate‐Driven Mechanisms of Ventricular Tachycardia

  • Matthew Fiedler1,2
  • Alejandra Vasquez Limeta1
  • Ernesto Reyes Sanchez1
  • Leah Carter1
  • Francisco Altamirano1,2,3
  1. 1Department of Cardiovascular Sciences Houston Methodist Research Institute Houston Methodist Hospital Houston Texas USA
  2. 2Program in Physiology Biophysics & Systems Biology Weill Cornell Medicine New York USA
  3. 3Department of Cardiothoracic Surgery Weill Cornell Medicine New York USA
Read full textPDFDOICite

Abstract

Human iPSC‑derived engineered heart tissues (EHTs) are used to model cardiac physiology and drug responses, yet whether they reproduce tissue‑scale ventricular arrhythmia mechanisms remains unclear. We combined modified milliPillar EHT fabrication with high‐resolution dual‐channel voltage/Ca2+ optical mapping. Baseline electrophysiology showed action potential durations (APD) within the range reported for human ventricles and conduction velocities approximately half of human longitudinal values, with rate‑dependent restitution of APD and Ca2+ transient duration, conduction slowing, and physiologic AP‐Ca2+ latency. To interrogate a trigger arm of ventricular tachycardia (VT), we modeled acquired long‐QT syndrome (aLQTS; hERG blockade with hypokalemia/hypomagnesemia) in EHTs from two hiPSC lines. aLQTS EHTs developed VT‐like episodes with beat‑to‑beat instability. Early afterdepolarizations propagated heterogeneously, generating triggered activity, tissue acceleration, APD dispersion, wavebreak, and rotor formation. These were short and self‐terminating (median 0.4 s) and clustered at head/neck region curvatures. To test whether a fixed spatial substrate supports prolonged reentry, we developed a reproducible focal cryoinjury model. After injury, all tissues developed VT‐like episodes, and 70% anatomically anchored rotors at the border; three persisted beyond 10 s, a recording‐limited lower bound. Dual voltage/Ca2+ mapping at this resolution establishes EHTs as a non‐animal platform for mechanistic study of both trigger‐ and substrate‐driven ventricular arrhythmias.

Related

  1. Thirty years of percutaneous epicardial access: reflections on the evolution of ventricular tachycardia substrate mapping and ablation
    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of CardiologyPeer-reviewedCC BYFull textCardiovascular medicineEurope PMC
  2. Persistence of atrioventricular nodal re-entrant tachycardia during ventricular fibrillation.
    Laura Simon, Thomas Rosseel, Tomas Robyns +1
    HeartRhythm case reportsPeer-reviewedCC BY-NC-NDFull textCardiovascular medicineEurope PMC
  3. Fifty Shades of Calpain: Couplon Breakdown in Catecholaminergic Polymorphic Ventricular Tachycardia and Beyond
    Tri Q. Do, Björn C Knollmann
    Circulation researchPeer-reviewedLicence not statedFull textCardiovascular medicinePMC
  4. Global Advances in Ventricular Tachycardia Ablation
    Fahd Mohamed, Amar Ghaleb, Abimbola Kolawole +1
    The Journal of innovations in cardiac rhythm managementPeer-reviewedCC BYFull textCardiovascular medicineEurope PMC
  5. NKX2-5 mutation in a family with ventricular tachycardia and aborted sudden cardiac death.
    Abinash Pandey, Burt Bromberg, Dipika Menon
    HeartRhythm case reportsPeer-reviewedCC BY-NC-NDFull textCardiovascular medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{fiedler2026human,
  title = {{Human Engineered Heart Tissues Reproduce Trigger‐ and Substrate‐Driven Mechanisms of Ventricular Tachycardia}},
  author = {Matthew Fiedler and Alejandra Vasquez Limeta and Ernesto Reyes Sanchez and Leah Carter and Francisco Altamirano},
  journal = {Advanced Science},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78429},
  url = {https://doi.org/10.1002/advs.78429},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Human Engineered Heart Tissues Reproduce Trigger‐ and Substrate‐Driven Mechanisms of Ventricular Tachycardia
AU  - Matthew Fiedler
AU  - Alejandra Vasquez Limeta
AU  - Ernesto Reyes Sanchez
AU  - Leah Carter
AU  - Francisco Altamirano
PY  - 2026
DA  - 2026/10/26
JO  - Advanced Science
DO  - 10.1002/advs.78429
UR  - https://doi.org/10.1002/advs.78429
AB  - Human iPSC‑derived engineered heart tissues (EHTs) are used to model cardiac physiology and drug responses, yet whether they reproduce tissue‑scale ventricular arrhythmia mechanisms remains unclear. We combined modified milliPillar EHT fabrication with high‐resolution dual‐channel voltage/Ca2+ optical mapping. Baseline electrophysiology showed action potential durations (APD) within the range reported for human ventricles and conduction velocities approximately half of human longitudinal values, with rate‑dependent restitution of APD and Ca2+ transient duration, conduction slowing, and physiologic AP‐Ca2+ latency. To interrogate a trigger arm of ventricular tachycardia (VT), we modeled acquired long‐QT syndrome (aLQTS; hERG blockade with hypokalemia/hypomagnesemia) in EHTs from two hiPSC lines. aLQTS EHTs developed VT‐like episodes with beat‑to‑beat instability. Early afterdepolarizations propagated heterogeneously, generating triggered activity, tissue acceleration, APD dispersion, wavebreak, and rotor formation. These were short and self‐terminating (median 0.4 s) and clustered at head/neck region curvatures. To test whether a fixed spatial substrate supports prolonged reentry, we developed a reproducible focal cryoinjury model. After injury, all tissues developed VT‐like episodes, and 70% anatomically anchored rotors at the border; three persisted beyond 10 s, a recording‐limited lower bound. Dual voltage/Ca2+ mapping at this resolution establishes EHTs as a non‐animal platform for mechanistic study of both trigger‐ and substrate‐driven ventricular arrhythmias.
SN  - 2198-3844
ER  -