Category Archives: What’s New

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.

Maria Inês Francisco Gândara

Maria Inês Francisco Gândarra

Maria Inês Francisco Gândara.

Inês joined our lab as an international graduate student from NOVA school of science & technology, Lisbon, Portugal to pursue her M.S. thesis. I had the good fortune of being her thesis advisor. I am excited and happy to report that Inês successfully defended her dissertation and is now a proud graduate of NOVA University.

THESIS TITLE

Effects of spatial resolution on arrhythmia driver detection and localization

ABSTRACT

Arrhythmia is a cardiac rhythm disorder that can be fatal. Its treatment includes ab- lation of the cardiac tissue and/or defibrillation. Advances are being made for both treatment options to localize the culprit region and apply therapy directly where it is needed. However, success rates have been inconsistent, with frequent arrhythmia recurrence. A likely reason is the limited current resolution of mapping devices, that averages 4 mm. Higher resolution may improve localization of arrhythmia drivers, termed rotors, and consequently improve efficacy of treatment.

This study evaluates the effects of spa- tial resolution on arrhythmia dynamics, rotor tracking, and rotor localization. Optical data from ex vivo human hearts was used, being clinically relevant and with ultra-high spatial resolution. To simulate different resolutions, original data was downsampled by multiple factors and upsampled back to full resolution. Rotors were tracked for each sub-resolution and compared to the rotors in the original data. Further comparisons were made according to arrhythmia type, sex, anatomical region, and mapped surface. Accuracy profiles were created for both rotor detection and localization, describing how accuracy changed with spatial resolution and spatial accuracy.

Rotor detection accuracy for currently used mapping devices was found to be 57±4%. Localization accuracy is 61±7%. Detection accuracy was above 80% only for a resolution of 1.4 mm. Moreover, the detection and localization accuracies were affected by arrhythmia type, and rotor incidence was found to be higher in the endocardium. Therefore, current clinical rotor detection and localization accuracies can be expected to fall within a confidence interl,gttval of 47-67% and 46-75%, respectively. This means that a higher spatial resolution is needed in cardiac mapping devices than what is currently available.

For high accuracy, a resolution of at least 1.4 mm is required. The accuracy profiles provided in this thesis may serve as a guideline for future mapping device development.

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.