on June 17, 2002
Circulation. 2002
Published online before print June 17, 2002, doi: 10.1161/01.CIR.0000020009.30736.3F
Published online before print June 17, 2002, doi: 10.1161/01.CIR.0000020009.30736.3F
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Submitted on February 15, 2002
From the Department of Clinical Cardiology (A.P.B., R.S., P.R.K., A.J.S.C., S.D.A.), National Heart & Lung Institute, Imperial College of Science, Technology and Medicine, London, UK; Adult Congenital Heart Program (W.L., M.L., M.A.G.) and Department of Clinical Biochemistry (M.K.), Royal Brompton Hospital, London, UK; and Franz-Volhard-Klinik (Charité, Campus Berlin-Buch) at Max-Delbrück-Centrum for Molecular Medicine (S.D.A.), Berlin, Germany. * To whom correspondence should be addressed. E-mail: a.bolger{at}ic.ac.uk.
Background—Neurohormonal activation characterizes chronic heart failure, relates to outcome, and is a therapeutic target. It is not known whether a similar pattern of neurohormonal activation exists in adults with congenital heart disease and, if so, whether it relates to common measures of disease severity or whether cardiac anatomy is a better discriminant. Methods and Results—Concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin-1 (ET-1), renin, aldosterone, norepinephrine, and epinephrine were determined in 53 adults with congenital heart disease, comprising 4 distinct anatomic subgroups (29 female; 33.5±1.5 years of age; New York Heart Association class 2.0±0.1, mean±SEM) and 15 healthy control subjects (8 female; 32.3±1.3 years of age). Systemic ventricular function was graded by a blinded echocardiographer as normal or mildly, moderately, or severely impaired. Adults with congenital heart disease had elevated levels of ANP (56.6 versus 3.1 pmol/L), BNP (35.8 versus 5.7 pmol/L), ET-1 (2.5 versus 0.7 pmol/L, all P<0.0001), renin (147 versus 16.3 pmol/L), norepinephrine (2.2 versus 1.6 pmol/L, both P<0.01) and aldosterone (546 versus 337 pmol/L, P<0.05). There was a highly significant stepwise increase in ANP, BNP, ET-1, and norepinephrine according to New York Heart Association class and systemic ventricular function, with even asymptomatic patients having evidence of significant neurohormonal activation. In contrast, there was no direct relationship between the 4 anatomic subgroups and any of the neurohormones studied. Conclusions—Neurohormonal activation in adult congenital heart disease bears the hallmarks of chronic heart failure, relating to symptom severity and ventricular dysfunction and not necessarily to anatomic substrate. Neurohormonal antagonism across this large and anatomically diverse population should be considered.
Revised on April 15, 2002
Accepted on April 15, 2002
Neurohormonal Activation and the Chronic Heart Failure Syndrome in Adults With Congenital Heart Disease
Aidan P. Bolger BSc, MRCP*,
Key words: heart diseases • heart failure • heart defects, congenital
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|
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|
|
|
|
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|
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|
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