Browsing by Subject "Heart Conduction System"

Now showing 1 - 5 of 5
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    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 Medicine
    Objectives 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.
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    Loss of function of hNav1.5 by a ZASP1 mutation associated with intraventricular conduction disturbances in left ventricular noncompaction
    (Ovid Technologies Wolters Kluwer -American Heart Association, 2012-10) Xi, Yutao; Ai, Tomohiko; De Lange, Enno; Li, Zhaohui; Wu, Geru; Brunelli, Luca; Kyle, W. Buck; Turker, Isik; Cheng, Jie; Ackerman, Michael J.; Kimura, Akinori; Weiss, James N.; Qu, Zhilin; Kim, Jeffrey J.; Faulkner, Georgine; Vatta, Matteo; Department of Medicine, IU School of Medicine
    BACKGROUND: Defects of cytoarchitectural proteins can cause left ventricular noncompaction, which is often associated with conduction system diseases. We have previously identified a p.D117N mutation in the LIM domain-binding protein 3-encoding Z-band alternatively spliced PDZ motif gene (ZASP) in a patient with left ventricular noncompaction and conduction disturbances. We sought to investigate the role of p.D117N mutation in the LBD3 NM_001080114.1 isoform (ZASP1-D117N) for the regulation of cardiac sodium channel (Na(v)1.5) that plays an important role in the cardiac conduction system. METHODS AND RESULTS: Effects of ZASP1-wild-type and ZASP1-D117N on Na(v)1.5 were studied in human embryonic kidney-293 cells and neonatal rat cardiomyocytes. Patch-clamp study demonstrated that ZASP1-D117N significantly attenuated I(Na) by 27% in human embryonic kidney-293 cells and by 32% in neonatal rat cardiomyocytes. In addition, ZASP1-D117N rightward shifted the voltage-dependent activation and inactivation in both systems. In silico simulation using Luo-Rudy phase 1 model demonstrated that altered Na(v)1.5 function can reduce cardiac conduction velocity by 28% compared with control. Pull-down assays showed that both wild-type and ZASP1-D117N can complex with Na(v)1.5 and telethonin/T-Cap, which required intact PDZ domains. Immunohistochemical staining in neonatal rat cardiomyocytes demonstrates that ZASP1-D117N did not significantly disturb the Z-line structure. Disruption of cytoskeletal networks with 5-iodonaphthalene-1-sulfonyl homopiperazine and cytochalasin D abolished the effects of ZASP1-D117N on Na(v)1.5. CONCLUSIONS: ZASP1 can form protein complex with telethonin/T-Cap and Na(v)1.5. The left ventricular noncompaction-specific ZASP1 mutation can cause loss of function of Na(v)1.5, without significant alteration of the cytoskeletal protein complex. Our study suggests that electric remodeling can occur in left ventricular noncompaction subject because of a direct effect of mutant ZASP on Na(v)1.5.
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    Origin, development, and differentiation of cardiac fibroblasts
    (Elsevier, 2014-05) Lajiness, Jacquelyn D.; Conway, Simon J.; Department of Pediatrics, IU School of Medicine
    Cardiac fibroblasts are the most abundant cell in the mammalian heart. While they have been historically underappreciated in terms of their functional contributions to cardiac development and physiology, they and their activated form, myofibroblasts, are now known to play key roles in both development and disease through structural, paracrine, and electrical interactions with cardiomyocytes. The lack of specific markers for fibroblasts currently convolutes the study of this dynamic cell lineage, but advances in marker analysis and lineage mapping technologies are continuously being made. Understanding how to best utilize these tools, both individually and in combination, will help to elucidate the functional significance of fibroblast-cardiomyocyte interactions in vivo. Here we review what is currently known about the diverse roles played by cardiac fibroblasts and myofibroblasts throughout development and periods of injury with the intent of emphasizing the duality of their nature.
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