Effect of KCNQ1 G229D mutation on cardiac pumping efficacy and reentrant dynamics in ventricles: Computational study. (11th April 2018)

• Record Type: Journal Article
• Authors: Yuniarti, Ana Rahma; Setianto, Febrian; Marcellinus, Aroli; Hwang, Han Jeong; Choi, Seong Wook; Trayanova, Natalia; Lim, Ki Moo
• Is Part Of: International journal for numerical methods in biomedical engineering. Volume 34:Number 6(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-04-11
• Subjects: arrhythmia -- computational model -- KCNQ1 G229D -- mutation; Biomedical engineering -- Periodicals; Imaging systems in medicine -- Periodicals; Numerical analysis -- Periodicals; Engineering mathematics -- Periodicals; 610.28
• DOI: 10.1002/cnm.2970
• Languages: English
• ISSNs: 2040-7939

Abstract

Abstract: There is growing interest in genetic arrhythmia since mutations in gene which encodes the ion channel underlie numerous arrhythmias. Hasegawa et al reported that G229D mutation in KCNQ1 underlies atrial fibrillation due to significant shortening of action potential duration (APD) in atrial cells. Here, we predicted whether K CNQ1 G229D mutation affects ventricular fibrillation generation, although it shortens APD slightly compared with the atrial cell. We analyzed the effects of G229D mutation on electrical and mechanical ventricle behaviors (not considered in previous studies). We compared action potential shapes under wild‐type and mutant conditions. Electrical wave propagations through ventricles were analyzed during sinus rhythm and reentrant conditions. I Ks enhancement due to G229D mutation shortened the APD in the ventricular cells (6%, 0.3%, and 8% for endo, M, and epi‐cells, respectively). The shortened APD contributed to 7% shortening of QT intervals, 29% shortening of wavelengths, 20% decrease in intraventricular pressure, and increase in end‐systolic volume 17%, end‐diastolic volume 7%, and end‐diastolic pressure 11%, which further resulted in reduction in stroke volume as well as cardiac output (28%), ejection fraction 33% stroke work 44%, and ATP consumption 28%. In short, using computational model of the ventricle, we predicted that G229D mutation decreased cardiac pumping efficacy and increased the vulnerability of ventricular fibrillation. Abstract : We have expanded the preliminary study on G229D mutation, which only considered the electrophysiological responses, up to mechanical contraction, particularly regarding ventricular hemodynamics and energy. The mechanical contraction was normal under sinus rhythm simulation but worsened under reentrant dynamic simulation.