Remodeling of Ion Channel Expression in Patients with Chronic Atrial Fibrillation and Mitral Valvular Heart Disease

BACKGROUND/AIMS: Underlying cardiac pathology and atrial fibrillation (AF) affect the molecular remodeling of ion channels in the atria. Changes in the expression of these molecules have not been demonstrated in Korean patients with mitral valvular heart disease. Thus, the purpose of this study was to analyze ion channel expression in patients with chronic AF and mitral valvular heart disease. METHODS: A total of 17 patients (eight males and nine females; mean age, 57 +/- 14 years [range, 19 to 77]) undergoing open-heart surgery were included in the study. Twelve patients (seven with coronary artery disease and five with aortic valvular disease) had sinus rhythm, and five patients (all with mitral valvular disease) had chronic, permanent AF. A piece of right atrial appendage tissue (0.5 g) was obtained during surgery. RT-PCR was used to evaluate the expression of L-type Ca2+ channels, ryanodine receptor (RyR2), sarcoplasmic reticular Ca2+-ATPase (SERCA2), gene encoding the rapid component of the delayed rectifier Ikr (HERG), gene encoding calcium-independent transient outward current I(to1) (Kv4.3), gene encoding the ultrarapid component of the delayed rectifier Iku (Kv1.5), K+ channel-interacting protein 2 (KChIP2), hyperpolarization-activated cation channel 2 associated with the pacemaker current If (HCN2), and gene encoding Na+ channel (SCN5A). RESULTS: Reduced L-type Ca2+ channel, RyR2, SERCA2, Kv1.5, and KChIP2 expression and borderline increased HCN2 expression were observed in the patients with AF and mitral valvular heart disease. Left atrial diameter was negatively correlated with RyR2 and KChIP2 expression. Fractional area shortening of the left atrium was positively correlated with RyR2 and KChIP2 expression. CONCLUSIONS: Alterations in ion channel expression and the anatomical substrate may favor the initiation and maintenance of AF in patients with mitral valvular heart disease.

Immunohistochemical characterization of Aschoff nodules and endomyocardial inflammatory infiltrates in resected left atrial appendages.

Presence of Aschoff nodules and other chronic inflammatory cells in the left atrial appendage even in the absence of rheumatic activity has been reported in a high percentage of patients with chronic rheumatic valvular heart disease. This study was conducted on 37 left atrial appendages resected at the time of closed mitral valvotomy. Aschoff nodules were present in 61.2 percent of resected appendages, positivity being 71.4 percent in the age group of 20 years of less and 53.3 percent in patients more than 20 years of age. The histological findings did not change significantly in the presence of activity. The frequency of Aschoff nodules and chronic inflammatory cells and their subtypes also did not show any correlation with age, sex, duration of symptoms or severity of mitral stenosis.