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J Am Soc Hypertens. 2009 Mar-Apr;3(2):133-40. doi: 10.1016/j.jash.2008.10.004. Epub 2009 Jan 20.

Development of cardiomyopathy and atrial tachyarrhythmias associated with activating autoantibodies to beta-adrenergic and muscarinic receptors.

Journal of the American Society of Hypertension : JASH

Xichun Yu, Eugene Patterson, Stavros Stavrakis, Shijun Huang, Isabel De Aos, Sean Hamlett, Madeleine W Cunningham, Ralph Lazarra, David C Kem


  1. Heart Rhythm Institute, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, Oklahoma, USA; Endocrinology, Department of Medicine, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma City, Oklahoma, USA.

PMID: 20409953 PMCID: PMC3116651 DOI: 10.1016/j.jash.2008.10.004


A 71-year-old male with well-controlled hypertension developed atrial tachyarrhythmias in 2002 and a restrictive cardiomyopathy in 2006 to 2007. Sera from 1992, 2001, and 2006 to 2008 demonstrated activating autoantibodies against beta-adrenergic (AAbetaAR) and M2 muscarinic receptors (AAM2R). These sera have been characterized for bioactivity using in vitro assays of cardiac contractility and automaticity using a canine cardiac Purkinje fiber assay as well as protein kinase assay activation in H9c2 cells. These assays demonstrated concurrent positive betaAR and inhibitory M2R effects that were blocked by nadolol and atropine, respectively. In a canine pulmonary vein atrial sleeve preparation, sera diluted 1:100 produced atrial hyperpolarization that was blocked by atropine. Atrial tachyarrhythmias developed in 2002 in the presence of a persistent bradycardia. Serial echocardiograms demonstrated progressive diastolic dysfunction in the absence of cardiac hypertrophy between 2006 and 2007. A dual-chamber pacemaker was installed with combined betaAR (nadolol) and M2<3R (oxybutynin) blockade, resulting in marked suppression of atrial ectopy and improved diastolic function. The estimated pulmonary artery pressure decreased and exercise tolerance returned. Blood pressure has remained normal with beta-blockade. AAbetaAR and AAM2R prospectively influenced atrial and ventricular function in this patient, and specific receptor blockade was associated with improved cardiac function.


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