Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development.

Aims: Atrial fibrillation (AF) is associated with tachycardia-induced cellular electrophysiology alterations which promote AF chronification and treatment resistance. Development of novel antiarrhythmic therapies is hampered by the absence of scalable experimental human models that reflect AF-associated electrical remodelling. Therefore, we aimed to assess if AF-associated remodelling of cellular electrophysiology can be simulated in human atrial-like cardiomyocytes derived from induced pluripotent stem cells in the presence of retinoic acid (iPSC-aCM), and atrial-engineered human myocardium (aEHM) under short term (24 h) and chronic (7 days) tachypacing (TP).

Electrophysiological and calcium-handling development during long-term culture of human-induced pluripotent stem cell-derived cardiomyocytes.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used for personalised medicine and preclinical cardiotoxicity testing. Reports on hiPSC-CM commonly describe heterogenous functional readouts and underdeveloped or immature phenotypical properties. Cost-effective, fully defined monolayer culture is approaching mainstream adoption; however, the optimal age at which to utilise hiPSC-CM is unknown.

A Mathematical Model for Electrical Activity in Pig Atrial Tissue.

State of the art mathematical models are currently used to bridge the gap between basic research conducted in the laboratory and preclinical research conducted on large animals, which ultimately paves the way for clinical translation. In this regard, there is a great need for models that can be used alongside experiments for in-depth investigation and validation. One such experimental model is the porcine atrium, which is commonly used to study the mechanisms of onset and control of atrial fibrillation in the context of its surgical management.

Chromatin Accessibility of Human Mitral Valves and Functional Assessment of MVP Risk Loci.

Rationale: Mitral valve prolapse (MVP) is a common valvopathy that leads to mitral insufficiency, heart failure, and sudden death. Functional genomic studies in mitral valves are needed to better characterize MVP-associated variants and target genes.

Objective: To establish the chromatin accessibility profiles and assess functionality of variants and narrow down target genes at MVP loci.