Browsing by Author "Homsi, Mohamed"
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Item Atrial fibrillation and electrophysiology in transgenic mice with cardiac-restricted overexpression of FKBP12(American Physiological Society, 2019-02-01) Pan, Zhenwei; Ai, Tomohiko; Chang, Po-Cheng; Liu, Ying; Liu, Jijia; Maruyama, Mitsunori; Homsi, Mohamed; Fishbein, Michael C.; Rubart, Michael; Lin, Shien-Fong; Xiao, Deyong; Chen, Hanying; Chen, Peng-Sheng; Shou, Weinian; Li, Bai-Yan; Medicine, School of MedicineCardiomyocyte-restricted overexpression of FK506-binding protein 12 transgenic (αMyHC-FKBP12) mice develop spontaneous atrial fibrillation (AF). The aim of the present study is to explore the mechanisms underlying the occurrence of AF in αMyHC-FKBP12 mice. Spontaneous AF was documented by telemetry in vivo and Langendorff-perfused hearts of αMyHC-FKBP12 and littermate control mice in vitro. Atrial conduction velocity was evaluated by optical mapping. The patch-clamp technique was applied to determine the potentially altered electrophysiology in atrial myocytes. Channel protein expression levels were evaluated by Western blot analyses. Spontaneous AF was recorded in four of seven αMyHC-FKBP12 mice but in none of eight nontransgenic (NTG) controls. Atrial conduction velocity was significantly reduced in αMyHC-FKBP12 hearts compared with NTG hearts. Interestingly, the mean action potential duration at 50% but not 90% was significantly prolonged in αMyHC-FKBP12 atrial myocytes compared with their NTG counterparts. Consistent with decreased conduction velocity, average peak Na+ current ( INa) density was dramatically reduced and the INa inactivation curve was shifted by approximately +7 mV in αMyHC-FKBP12 atrial myocytes, whereas the activation and recovery curves were unaltered. The Nav1.5 expression level was significantly reduced in αMyHC-FKBP12 atria. Furthermore, we found increases in atrial Cav1.2 protein levels and peak L-type Ca2+ current density and increased levels of fibrosis in αMyHC-FKBP12 atria. In summary, cardiomyocyte-restricted overexpression of FKBP12 reduces the atrial Nav1.5 expression level and mean peak INa, which is associated with increased peak L-type Ca2+ current and interstitial fibrosis in atria. The combined electrophysiological and structural changes facilitated the development of local conduction block and altered action potential duration and spontaneous AF. NEW & NOTEWORTHY This study addresses a long-standing riddle regarding the role of FK506-binding protein 12 in cardiac physiology. The work provides further evidence that FK506-binding protein 12 is a critical component for regulating voltage-gated sodium current and in so doing has an important role in arrhythmogenic physiology, such as atrial fibrillation.Item Coupling Interval Variability Differentiates Ventricular Ectopic Complexes Arising in the Aortic Sinus of Valsalva and Great Cardiac Vein From Other Sources(Elsevier, 2014-05-27) Bradfield, Jason S.; Homsi, Mohamed; Shivkumar, Kalyanam; Miller, John M.; Department of Medicine, IU School of MedicineObjectives The objective of this study was to determine whether premature ventricular contractions (PVCs) arising from the aortic sinuses of Valsalva (SOV) and great cardiac vein (GCV) have coupling interval (CI) characteristics that differentiate them from other ectopic foci. Background PVCs occur at relatively fixed CI from the preceding normal QRS complex in most patients. However, we observed patients with PVCs originating in unusual areas (SOV and GCV) in whom the PVC CI was highly variable. We hypothesized that PVCs from these areas occur seemingly randomly because of the lack of electrotonic effects of the surrounding myocardium. Methods Seventy-three consecutive patients referred for PVC ablation were assessed. Twelve consecutive PVC CIs were recorded. The ΔCI (maximum – minimum CI) was measured. Results We studied 73 patients (age 50 ± 16 years, 47% male). The PVC origin was right ventricular (RV) in 29 (40%), left ventricular (LV) in 17 (23%), SOV in 21 (29%), and GCV in 6 (8%). There was a significant difference between the mean ΔCI of RV/LV PVCs compared with SOV/GCV PVCs (33 ± 15 ms vs. 116 ± 52 ms, p < 0.0001). A ΔCI of >60 ms demonstrated a sensitivity of 89%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 94%. Cardiac events were more common in the SOV/GCV group versus the RV/LV group (7 of 27 [26%] vs. 2 of 46 [4%], p < 0.02). Conclusions ΔCI is more pronounced in PVCs originating from the SOV or GCV. A ΔCI of 60 ms helps discriminate the origin of PVCs before diagnostic electrophysiological study and may be associated with increased frequency of cardiac events.Item Fragmented QRS Complexes on 12‐Lead ECG: A Marker of Cardiac Sarcoidosis as Detected by Gadolinium Cardiac Magnetic Resonance Imaging(Wiley, 2009-10) Homsi, Mohamed; Alsayed, Lamaan; Safadi, Bilal; Mahenthiran, Jo; Das, Mithilesh K.; Medicine, School of MedicineBackground: Fragmented QRS complexes (fQRS) on a 12‐lead ECG are a marker of myocardial scar in patients with coronary artery disease. Cardiac sarcoidosis is also associated with myocardial granuloma formation and scarring. We evaluated the significance of fQRS on a 12‐lead ECG compared to Gadolinium‐delayed enhancement images (GDE) in cardiac magnetic resonance imaging (CMR). Method and results: The ECGs of patients (n = 17, mean age: 52 ± 11 years, male: 53%) with established diagnosis of sarcoidosis who underwent a CMR for evaluation of cardiac involvement were studied. ECG abnormalities included bundle branch block, Q wave, and fQRS. fQRS, Q wave, and bundle branch block were present in 9 (53%), 1 (6%), and 4 (24%) patients, respectively. The sensitivity and specificity of fQRS for detecting abnormal GDE were 100% and 80%, respectively. Sensitivity and specificity of Q waves were 11% and 100%, respectively. Conclusions: fQRS on a 12‐lead ECG in patients with suspected cardiac sarcoidosis are associated with cardiac involvement as detected by GDE on CMR.