Neurohormonal Activation and the Chronic Heart Failure Syndrome in Adults With Congenital Heart Disease

Abstract

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.

Treatment of Terminal Heart Failure in Grown Up Congenital Heart Disease.

“…Lovrić D ispravljenim TGA-om koji imaju simptome 14 te a 79 % pacijenata sa složenim prirođenim srčanim bolestima koji imaju ograničenja funkcijskog kapaciteta u klasi II ili više prema NYHA klasifikaciji 4 . S druge strane, odrasli pacijenti s prirođenim srčanim bolestima često su asimptomatični ili tvrde da nemaju simptome zato što cijelog života žive s njima, pa se ne obaziru na manje promjene u podnošenju tjelesnog napora 15 .…”

“…ing symptomatic 14 , and 79% of patients with complex congenital heart disease having NYHA Class II or higher limitation in functional capacity 4 . On the other hand, GUCH patients are often asymptomatic or claim no symptoms due to the fact that living with symptoms has been a lifetime constant so little attention is attributed to minor variations in exercise tolerance 15 .…”

“…There is sufficient data showing that patients with complex congenital heart disease, even if surgically repaired, often have elevated B-type natriuretic peptide (BNP) levels that correlate both with NYHA Class and mortality 5-7. Not only that, but neurohormonal activation in GUCH bears the hallmarks of chronic heart failure, increasing in relation to the symptom severity and ventricular dysfunction and not necessarily connected to the anatomic substrate 4 .…”

“…Kod ovih pacijenata popuštanje srca vjerojatnije je posljedica višegodišnjih ustrajnih nepravilnosti u arterijskom tlaku i/ili volumenu, a ne posljedica gubitka miocita zbog infarkta miokarda ili naslijeđe-nih intrinzičnih abnormalnosti stanica miokarda 3 . Premda je dugo nedostajalo literature o ovoj temi, u tom je području u međuvremenu došlo do znatnog napretka te se pokazalo kako je neurohormonalna aktivacija prisutna u prirođenim srča-nim bolestima odraslih (PSBO), kako u simptomatskim, tako i u asimptomatskim bolestima 4 . Dosta podataka pokazuje da pacijenti sa složenim prirođenim srčanim bolestima, čak i nakon kirurškog zahvata, često imaju povišene razine mož-danoga natriuretskog peptida (BNP) koje koreliraju s klasifikacijom udruge New York Heart Association (NYHA) i smrtnošću 5-7 .…”

“…Rather than due to the loss of myocites due to myocardial infarction or by inherited intrinsic abnormalities in myocardial cells, HF in these patients is most probably sculpted over many years by persistent abnormalities in cardiac pressure and/or volume 3 . Literature, quite silent on the topic for a long while, has now shown a significant progress in the field showing that neurohormonal activation is present in grown up congenital heart disease (GUCH), both in symptomatic and asymptomatic patients 4 . There is sufficient data showing that patients with complex congenital heart disease, even if surgically repaired, often have elevated B-type natriuretic peptide (BNP) levels that correlate both with NYHA Class and mortality 5-7.…”