Association of Left Atrial Endothelin-1 With Atrial Rhythm, Size, and Fibrosis in Patients With Structural Heart Disease

Abstract

Background-Atrial fibrillation (AF) promotes atrial remodeling and can develop secondary to heart failure or mitral valve disease. Cardiac endothelin-1 (ET-1) expression responds to wall stress and can promote myocyte hypertrophy and interstitial fibrosis. We tested the hypothesis that atrial ET-1 is elevated in AF and is associated with AF persistence. Methods and Results-Left atrial appendage tissue was studied from coronary artery bypass graft, valve repair, and/or Maze procedure in patients in sinus rhythm with no history of AF (SR, nϭ21), with history of AF but in SR at surgery (AF/SR, nϭ23), and in AF at surgery (AF/AF, nϭ32). The correlation of LA size with atrial protein and mRNA expression of ET-1 and ET-1 receptors (ETAR and ETBR)was evaluated. LA appendage ET-1 content was higher in AF/AF than in SR, but receptor levels were similar. Immunostaining revealed that ET-1 and its receptors were present both in atrial myocytes and in fibroblasts. ET-1 content was positively correlated with LA size, heart failure, AF persistence, and severity of mitral regurgitation. Multivariate analysis confirmed associations of ET-1 with AF, hypertension, and LA size. LA size was associated with ET-1 and MR severity. ET-1 mRNA levels were correlated with genes involved in cardiac dilatation, hypertrophy, and fibrosis. Conclusions-Elevated atrial ET-1 content is associated with increased LA size, AF rhythm, hypertension, and heart failure. ET-1 is associated with atrial dilatation, fibrosis, and hypertrophy and probably contributes to AF persistence.Interventions that reduce atrial ET-1 expression and/or block its receptors may slow AF progression. (Circ Arrhythm Electrophysiol. 2010;3:369-379.)

EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication

“…Angiotensin II and endothelin-1 are linked to inflammatory and proarrhythmogenic atrial remodelling. 2,[264][265][266] This evidence suggests that inflammatory cell infiltration has an important role in promoting the creation of a substrate for AF, as a result of conduction heterogeneity and slowing, both in the setting of cardiac surgery and beyond.…”

Mitral Regurgitation and Atrial Fibrillation: The Contribution of Impaired Left Atrial Appendage Function to Atrial Thrombogenesis

“…However, expression of cardiac alpha-actin isotypes 1 and 2, tropomyosin alpha-and beta-chains, and myosin light chain embryonic muscle/atrial isoform in LAA from AF patients was found increased when compared to those from SR patients [24]. Another potential contributor to atrial remodelling, cardiac endothelin-1 (ET-1), is expressed as a response to wall stress and can promote myocyte hypertrophy and interstitial fibrosis [25]. Elevated atrial ET-1 level is been found associated with increased LA size, AF prevalence, hypertension, and heart failure [25].…”

“…Another potential contributor to atrial remodelling, cardiac endothelin-1 (ET-1), is expressed as a response to wall stress and can promote myocyte hypertrophy and interstitial fibrosis [25]. Elevated atrial ET-1 level is been found associated with increased LA size, AF prevalence, hypertension, and heart failure [25]. An association between ET-1 and atrial dilatation, fibrosis, and hypertrophy is been reported.…”

“…An association between ET-1 and atrial dilatation, fibrosis, and hypertrophy is been reported. Endothelin-1 is suggested as a contributing factor to AF persistence [25]. Although both mitral stenosis and MR are strongly associated with AF, the prevalence of AF in mitral stenosis patients is much higher than MR patients.…”

Endothelines and Cardiovascular Pathology

“…В последующих работах была показана активация эндотелиновой системы у больных с тяжелой ХСН, маркером чего явилось повыше-ние плазменного уровня ЭТ и его предшествен-ника (Big-ET) [24,25]. При этом не было отмечено статистически достоверной связи между уровнем ЭТ-1 и Big-ET с этиологией сердечной недоста-точности [26]. Следует подчеркнуть, что достовер-ное повышение ЭТ и его предше ственника у здо-ровых людей, пациентов с бессимптомной дис-функцией ЛЖ и начальными стадиями сердечной недостаточности выявлено не было [6].…”