Category Archives: Publications

The Secretome of Atrial Epicardial Adipose Tissue Facilitates Reentrant Arrhythmias by Myocardial Remodeling

Atrial EAT promotes arrhythmias
Atrial EAT promotes arrhythmias

WHAT IS KNOWN?

  1. Obesity is an independent risk factor for sudden cardiac death and atrial fibrillation.
  2. The molecular mechanisms underlying how atrial epicardial adipose tissue (EAT) can induce arrhythmias is not well understood.

WHAT THIS STUDY ADDS

  1. Atrial EAT induces electrophysiological remodeling of myocardium by decreasing electrical coupling, reducing IK1 and depolarizing the maximum diastolic potential.
  2. This results in slowed conduction and increased conduction heterogeneity, depolarized resting potential, which in turn, can facilitate reentrant arrhythmias.

LINK TO THE ARTICLE

Ernault AC, Verkerk AO, Bayer JD, Aras K, Agudo PM, Mohan RA, Veldkamp M, Kawasaki M, van Amersfoorth SCM, Driessen AHG, Efimov IR, de Groot J, Coronel R. The Secretome of Epicardial Adipose Tissue Facilitates Reentrant Arrhythmias by Myocardial RemodelingHeart Rhythm, 2022.

Electrophysiology and Arrhythmogenesis in the Human RVOT

Human RVOT susceptibility to arrhythmias

WHAT IS KNOWN?

  1. Right ventricular outflow tract (RVOT) is a common source of idiopathic ventricular arrhythmias (IVAs). 
  2. However, the mechanisms underlying the RVOT’s unique arrhythmia susceptibility remains not well elucidated due to lack of detailed electrophysiological and molecular studies of human RVOT.

WHAT THE STUDY ADDS

  1. Human RVOT electrophysiology is characterized by shorter APD relative to the right ventricular apical region and drives the transmural dispersion of repolarization and transmural APD dispersion under normal physiological conditions.
  2. Cholinergic stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of PVCs and shortening of wavelength.
  3. Arrhythmia in the RV is associated with weak positive spatiotemporal autocorrelation between the epicardial-endocardial arrhythmic wavefronts and reentrant rotors that are relatively more organized in the endocardium.

LINK TO THE ARTICLE

Aras KK, Gams A, Faye NR, Brennan JB, Goldrick K, Li J, Zhong Y, Chiang C, Smith EH, Poston MD, Chivers J, Hanna P, Mori S, Ajijola O, Shivkumar K, Hoover DB, Viventi J, Rogers JA, Bernus O, Efimov IR. Electrophysiology and Arrhythmogenesis of the human right ventricle outflow tract. Circ Arrhythm Electrophysiol. 2022. (Editor’s pick)

Photocurable bioresorbable adhesives as functional intefaces between flexible bioelectronic devices and soft biological tissues

Soft interface materials for joining bioelectronic devices with biological tissues

WHAT IS KNOWN?

  1. Flexible electronic/optoelectronic systems that can physically interface with soft biological tissue surfaces offer revolutionary diagnostic and therapeutic capabilities for various diseases.
  2. However, current approaches to coupling the tissue-device interfaces either through surgical sutures, staples, cuffs, etc., damage the tissue and the devices and often result in adverse immune responses and mechanical instabilities.

WHAT DOES THIS STUDY ADD?

  1. We introduce a functional adhesive bioelectronic-tissue interface material (BTIM), which is mechanically compliant, electrically conductive, and optically transparent. The material can bond to the surface of tissue and the device and provide stable adhesion for several days to months.
  2. We demonstrate the capabilities of this material in live animal models that includes device applications ranging from battery-free optoelectronic systems for deep-brain optogenetics to wireless millimeter-scale pacemakers and flexible multi electrode epicardial arrays.

LINK TO THE ARTICLE

Yang Q, Wei T, Yin RT, Wu M, Xu Y, Koo J, Choi YS, Xie Z, Chen SW, Kandela I, Yao S, Deng Y, Avila R, Liu TL, Bai W, Yang Y, Han M, Zhang Q, Haney CR, Benjamin Lee K, Aras K, Wang T, Seo MH, Luan H, Lee SM, Brikha A, Ghoreishi-Haack N, Tran L, Stepien I, Aird F, Waters EA, Yu X, Banks A, Trachiotis GD, Torkelson JM, Huang Y, Kozorovitskiy Y, Efimov IR, Rogers JA. Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues. Nat Mater. 2021 Jul 29;. doi: 10.1038/s41563-021-01051-x. [Epub ahead of print] PubMed PMID: 34326506.

Book chapter: conformal electronics therapy for defibrillation

Book

Cardiac Bioelectric Therapy: Mechanisms and Practical Applications

Chapter 38

Conformal Electronics Therapy for Defibrillation

Authors

Kedar K. Aras, John A. Rogers, Igor R. Efimov

Abstract

Defibrillation remains the only effective therapy against sudden cardiac death. However, the current coil-based lead ICD devices are limited by high defibrillation threshold (DFT) and low arrhythmia sensing resolution, which can result in inappropriate and painful shocks adversely affecting the quality of life. Emerging classes of materials and mechanics concepts in the field of flexible and stretchable electronics have created new opportunities for integrating high-performance electronics with the human body and its organs and various tissues. These conformal electronics devices offer a platform for high-definition arrhythmia sensing to minimize inappropriate shocks and improve therapy and high-definition therapy delivery circuit to reduce DFT.

Chromatin Accessibility of human mitral valves and functional assessment of MVP Risk Loci

rs6723013 is a potential causal variant at IGFBP5/TNS1 MVP-associated locus

WHAT IS KNOWN?

  1. Mitral valve prolapse (MVP) is a common valvopathy that can lead to heart failure and sudden death. However, the causes of MVP development are still poorly understood.
  2. Functional genomic studies are needed to better characterize MVP associated variants and target genes

WHAT DOES THIS STUDY ADD?

  1. We used ATAC-Seq (assay for transposes-accessible chromatin using sequencing) genomic annotation technique in combination with 4C-Seq (circular chromosome conformation capture, coupled to high-throughput sequencing), to describe unprecedented genome-wide chromatin profiles from human pathogenic and non-pathogenic mitral valves.
  2. The experiments also provided evidence for plausible causal variants for rs2641440 at SMG6/SRR locus and rs6723013 at IGFBP2/IGFBP5/TNS1 locus. In addition, we also identified several target genes including SRR, HIC1, and DPH1 at SMG6/SRR locus.

LINK TO THE ARTICLE

Kyryachenko S, Georges A, Yu M, Berrandou T, Guo L, Bruneval P, Rubio T, Gronwald J, Baraki H, Kutschka I, Aras K, Efimov IR, Norris RA, Voigt N, Bouatia-Naji N. Chromatin Accessibility of Human Mitral Valves and Functional Assessment of MVP Risk Loci. Circ Res. 2021 Jan 28;. doi: 10.1161/CIRCRESAHA.120.317581. [Epub ahead of print] PubMed PMID: 33508947.