Whole-heart ventricular arrhythmia modeling moving forward: Mechanistic insights and translational applications

Abstract Introduction Optogenetics is a low-invasive, flexible and highly selective intervention that enables electrical excitation with light on myocardium overexpressing light-sensitive proteins. Optical illumination can control the simultaneous exciting of the whole myocardium under the spot, which is more conducive to recovery from electrical disturbance to sinus rhythm. Purpose We explored optogenetic defibrillation for different illumination parameters how to affect defibrillation rates and the possible mechanism of continuous illumination defibrillation. Methods Systemic delivery via right jugular vein injection of (AAV9-CAG-hChR2(H134R)-mCherry) were performed in juvenile SD rats to achieve the light sensitive protein Channelrhodopsin-2 (ChR2) transfer throughout the whole heart. We intubated and ventilated rats, opened chest and recorded the ECG. After ligation of the left anterior descending coronary artery, ventricular arrhythmia was induced by electrical burst stimulation (10v, 50Hz, 2s). Cardiac epicardium illumination with 470nm blue laser was performed to investigate the effects of optogenetic defibrillation and its underlying mechanism. Every heart accepted 30 pulses of 20ms duration on 8Hz to test the light intensity threshold for 1:1 capture. Different illumination modes of multiple light intensity (2,4,8,10,20 times threshold intensity), pulse duration (20, 50, 200, 500 and 1000ms) and illumination position (RV apex, RV, RVOT, septum, LV) were applied in each attempt for 4 repetitions with 1 s interval. Results We demonstrated that ventricular arrhythmias could be terminated by illumination of the right ventricle at 20 times threshold intensity in 1s (figure A) with the successful defibrillation rate of 95±2.673% (mean ±SEM; N=7). Herein, the successful optogenetic defibrillation rate was strongly depending on light intensity (N=5, n=50 episodes, p=0.0118) and duration of illumination (N=5, n=50 episodes, p<0.0001) (figure B.C). Notably when there were higher intensity and longer pulse duration, the higher defibrillation rate appeared. There was no significant difference in the defibrillation rate among different illumination positions (N=5, n=25episodes per position, p=0.1177) (figure D). To explore the underlying mechanism of optogenetic defibrillation, we performed the same illumination mode during sinus rhythm in 2 rats (figure E. F. G). We observed that higher light intensity and longer pulse duration were more conducive to induce an episode of higher frequency focal excitement. Views of optogenetic defibrillation Conclusions We demonstrated that optogenetic defibrillation is a highly effective intervention and the possible mechanism is partly attributed to overdrive suppression. We believe that optogenetic approach is potentially to be translated into more efficient and pain-free clinical termination of ventricular arrhythmia. Acknowledgement/Funding The national natural science foundation of China (81772044)

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Effects of a new antiarrhythmic drug KW-3407 on canine ventricular arrhythmia models

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)49157-9 ◽

1992 ◽

Vol 58 ◽

pp. 219

Author(s):

Zhenjiu Wu ◽

Takeo Awaji ◽

Shigeru Motomura ◽

Keitaro Hashimoto

Keyword(s):

Ventricular Arrhythmia ◽

Antiarrhythmic Drug

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Auto Whole Heart Segmentation from CT images Using an Improved Unet-GAN

Journal of Physics Conference Series ◽

10.1088/1742-6596/1769/1/012016 ◽

2021 ◽

Vol 1769 (1) ◽

pp. 012016

Author(s):

Kening Le ◽

Zeyu Lou ◽

Weiliang Huo ◽

Xiaolin Tian

Keyword(s):

Ct Images ◽

Whole Heart

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The Assessment of Ventricular Arrhythmia Indicators Based on Electrocardiography in Patients With Differentiated Thyroid Cancer Followed Up With Levothyroxine Suppression

Angiology ◽

10.1177/0003319721993343 ◽

2021 ◽

pp. 000331972199334

Author(s):

Sema Hepsen ◽

Davut Sakiz ◽

Hilal Erken Pamukcu ◽

Ismail Emre Arslan ◽

Hakan Duger ◽

...

Keyword(s):

Regression Analysis ◽

Thyroid Cancer ◽

Ventricular Arrhythmia ◽

Differentiated Thyroid Cancer ◽

Linear Regression Analysis ◽

Male Gender ◽

Qtc Interval ◽

Inclusion Criteria ◽

Raising Awareness ◽

Number Of Patients

Levothyroxine suppression therapy (LST) can cause some unfavorable effects on the cardiovascular system in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate ventricular arrhythmia predictors based on electrocardiography (ECG) in patients with DTC with LST. The ECG parameters including QT, corrected QT (QTc), Tp-e intervals, Tp-e/QT, and Tp-e/QTC ratios of 265 patients with DTC who met the inclusion criteria were compared with 100 controls. No difference was observed in the number of patients with DTC and controls with prolonged and borderline QTc interval ( P = .273). Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly higher in patients ( P = .002, P = .02, P = .003; respectively). Linear regression analysis suggested that male gender was a predictor of higher Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios (β = 4.322, R 2 = 0.024, P = .042; β = 0.016, R 2 = 0.048, P = .005; β = 0.015, R 2 = 0.044, P = .006, respectively). A higher serum fT4 level was found to be associated with a higher Tp-e/QT ratio (β = 0.018, R 2 = 0.089, P = .007). Ventricular arrhythmia indicators were found to be higher in patients with DTC with LST. Defining ventricular arrhythmia predictors through ECG, an easily accessible cardiac diagnostic tool, can be potentially useful in raising awareness of the possible cardiac harm of LST.

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Self-navigated 3D whole-heart MRA for non-enhanced surveillance of thoracic aortic dilation: a comparison to CTA

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.318 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

P Poskaite ◽

M Pamminger ◽

C Kranewitter ◽

C Kremser ◽

M Reindl ◽

...

Keyword(s):

Computed Tomography ◽

Image Quality ◽

Aortic Aneurysm ◽

Thoracic Aortic Aneurysm ◽

Aortic Dilation ◽

Subjective Image Quality ◽

Contrast Enhanced ◽

Whole Heart ◽

Enhanced Computed Tomography ◽

Contrast Enhanced Computed Tomography

Abstract Funding Acknowledgements Type of funding sources: None. Background The natural history of thoracic aortic aneurysm (TAA) is one of progressive expansion. Asymptomatic patients who do not meet criteria for repair require conservative management including ongoing aneurysm surveillance, mostly carried out by contrast-enhanced computed tomography angiography (CTA). Purpose To prospectively compare image quality and reliability of a prototype non-contrast, self-navigated 3D whole-heart magnetic resonance angiography (MRA) with contrast-enhanced computed tomography angiography (CTA) for sizing of thoracic aortic aneurysm (TAA). Methods Self-navigated 3D whole-heart 1.5 T MRA was performed in 20 patients (aged 67 ± 8.6 years, 75% male) for sizing of TAA; a subgroup of 18 (90%) patients underwent additional contrast-enhanced CTA on the same day. Subjective image quality was scored according to a 4-point Likert scale and ratings between observers were compared by Cohen’s Kappa statistics. Continuous MRA and CTA measurements were analyzed with regression and Bland-Altman analysis. Results Overall subjective image quality as rated by two observers was 1 [interquartile range (IQR) 1-2] for self-navigated MRA and 1.5 [IQR 1-2] for CTA (p = 0.717). For MRA a perfect inter-observer agreement was found for presence of artefacts and subjective image sharpness (κ=1). Subjective signal inhomogeneity correlated highly with objectively quantified inhomogeneity of the blood pool signal (r = 0.78-0.824, all p <0.0001). Maximum diameters of TAA as measured by self-navigated MRA and CTA showed excellent correlation (r = 0.997, p < 0.0001) without significant inter-method bias (bias -0.0278, lower and upper limit of agreement -0.74 and 0.68, p = 0.749). Inter- and intraobserver correlation of aortic aneurysm as measured by MRA was excellent (r = 0.963 and 0.967, respectively) without significant bias (all p ≤ 0.05). Conclusion Self-navigated 3D whole-heart MRA enables reliable contrast- and radiation free aortic dilation surveillance without significant difference to standardized CTA while providing predictable acquisition time and by offering excellent image quality. Abstract Figure.

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