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Autonomic Dysfunction in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy: Biochemical Evidence of Altered Signaling Pathways
Author(s) -
PAUL MATTHIAS,
MEYBORG MATTHIAS,
BOKNIK PETER,
GERGS ULRICH,
GERSS JOACHIM,
SCHMITZ WILHELM,
BREITHARDT GÜNTER,
WICHTER THOMAS,
NEUMANN JOACHIM
Publication year - 2014
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/pace.12237
Subject(s) - medicine , cardiology , cardiomyopathy , arrhythmogenic right ventricular dysplasia , pathological , sudden cardiac death , ventricular outflow tract , endocrinology , heart failure
Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death especially in times of increased sympathetic tone, for example, during sports, which have been confirmed by nuclear imaging studies. However, the underlying biochemical pathways remain to be delineated. Therefore, we investigated the expression levels of proteins of the signaling cascade in patients with ARVC. Methods During diagnostic work‐up, right ventricular endomyocardial biopsies (EMBs) were sampled from 15 consecutive male ARVC patients (52 ± 14 years). Tissue levels of key proteins of the signaling cascade were analyzed. Results were compared to those obtained from EMBs of 10 patients with idiopathic right ventricular outflow‐tract tachycardia (RVOT; 41 ± 14 years) and of five control subjects without identifiable structural heart disease (42 ± 13 years; P = ns). Results Among the proteins analyzed, only tissue levels of norepinephrine (NE; P < 0.04) and cyclic adenosine‐3´,5´‐monophospate (cAMP; P < 0.01) were significantly lower in ARVC when compared to RVOT patients. When compared to controls, mean cAMP levels were lower in patients with ARVC but did not reach statistical significance. No differences in cAMP were observed between RVOT and controls. Conclusions The current findings confirm and expand the concept of adrenergic dysfunction in ARVC: the reduction of NE in ARVC could lead to an impaired stimulation of β‐adrenoceptor subsequent signaling pathways with potential implication for cardiac fibrosis and arrhythmogenesis.