Browsing by Author "Bhakta, Deepak"

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    Apparent Failure of Automated Threshold Evaluation: What is the Mechanism?
    (Wiley, 2016-08) Kalra, Vikas; Foreman, Lynne; Bhakta, Deepak; Department of Medicine, IU School of Medicine
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    Dysfunction in the βII Spectrin-Dependent Cytoskeleton Underlies Human Arrhythmia.
    (AHA, 2015-02-24) Smith, Sakima A.; Sturm, Amy C.; Curran, Jerry; Kline, Crystal F.; Little, Sean C.; Bonilla, Ingrid M.; Long, Victor P.; Makara, Michael; Polina, Iuliia; Hughes, Langston D.; Webb, Tyler R.; Wei, Zhiyi; Wright, Patrick; Voigt, Niels; Bhakta, Deepak; Spoonamore, Katherine G.; Zhang, Chuansheng; Weiss, Raul; Binkley, Philip F.; Janssen, Paul M.; Kilic, Ahmet; Higgins, Robert S.; Sun, Mingzhai; Ma, Jianjie; Dobrev, Dobromir; Zhang, Mingjie; Carnes, Cynthia A.; Vatta, Matteo; Rasband, Matthew N.; Hund, Thomas J.; Mohler, Peter J.; Department of Medical & Molecular Genetics, IU School of Medicine
    Background: The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked with cardiac pathologies including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction in cardiac electrical activity is not well understood, and often overlooked in the cardiac arrhythmia field. Methods and Results: Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that βII spectrin, an actin-associated molecule, is essential for the post-translational targeting and localization of critical membrane proteins in heart. βII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/βII spectrin interaction leading to severe human arrhythmia phenotypes. Mice lacking cardiac βII spectrin display lethal arrhythmias, aberrant electrical and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, βII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes that include the Na/Ca exchanger, RyR2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in βII spectrin-deficient mice. Conclusions: Our findings identify βII spectrin as critical for normal myocyte electrical activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology.
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    Heart Rate Variability Declines with Increasing Age and CTG Repeat Length in Patients with Myotonic Dystrophy Type 1
    (Wiley, 2003-07) Hardin, Bradley A.; Lowe, Miriam R.; Bhakta, Deepak; Groh, William J.; Medicine, School of Medicine
    Background: Cardiac myopathy manifesting as arrhythmias is common in the neurological disease, myotonic dystrophy type 1 (DM1). The purpose of the present study was to evaluate heart rate variability (HRV) in patients with DM1. Methods: In a multicenter study, history, ECG, and genetic testing were performed in DM1 patients. Results: In 289 patients in whom the diagnosis of DM1 was confirmed by a prolonged cytosine-thymine-guanine (CTG) repeat length the most common ambulatory ECG abnormality was frequent ventricular ectopy (16.3%). The 24-hour time domain parameters of SDNN (SD of the NN interval) and SDANN (SD of the mean NN, 5-minute interval) declined as age and CTG repeat length increased (SDNN: −8.5 ms per decade, 95% confidence intervals [CI]−12.9, −4.2, −8.7 ms per 500 CTG repeats, CI −15.7, −1.8, r = 0.24, P < 0.001; SDANN: −8.1 ms per decade, CI −12.4, −3.8, −8.8 ms per 500 CTG repeats, CI −15.7, −1.9, r = 0.23, P < 0.001). Short-term frequency domain parameters declined with age only (total power: −658 ms2 per decade, CI: −984, −331, r = 0.23, P < 0.001; low frequency (LF) power −287 ms2 per decade, CI: −397, −178, r = 0.30, P < 0.001; high frequency (HF) power: −267 ms2 per decade, CI: −386, −144, r = 0.25, P < 0.001). The LF/HF ratio increased as the patient aged (0.5 per decade, CI: 0.1, 0.9, r = 0.13, P = 0.03). Conclusions: In DM1 patients a decline in HRV is observed as the patient ages and CTG repeat length increases.     
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    Is An Atrial Defibrillator Still An Option In Treating Patients With Atrial Fibrillation?
    (Cardiofront, 2013-02-12) El Khoury, Ziad; Bhakta, Deepak; Medicine, School of Medicine
    Atrial fibrillation (AF) is a common disorder associated with significant morbidities and presents several challenges for the control of symptoms and prevention of long-term implications. Atrial defibrillators (ADs), used for rhythm control in patients with symptoms refractory to medical therapy, can detect recurrences of the arrhythmia, allow prompt patient-directed treatment, and have the potential to reduce hospitalizations and improve quality of life. The efficacy of this form of therapy is highest in patients with paroxysmal AF, and with the use of a coronary sinus shocking lead. While R-wave synchronized shocks are a prerequisite for a safe use, the procedure is well tolerated and usually not associated with long-term psychological side effects. Limitations of ADs include acute and chronic complications related to cardiac rhythm device implantation, the requirement in some cases for more than one shock to terminate AF, the discomfort from shocks, as well as the need for sedation to alleviate pain from the shocks. With the ever-expanding role of catheter-based therapies for AF, it seems that the role of ADs in this regard is rather limited.