Bolger Aidan P, Sharma Rakesh, Li Wei, Leenarts Marjolein, Kalra Paul R, Kemp Michael, Coats Andrew J S, Anker Stefan D, Gatzoulis Michael A
Department of Clinical Cardiology, National Heart & Lung Institute, Imperial College of Science, Technology and Medicine, London, UK.
Circulation. 2002 Jul 2;106(1):92-9. doi: 10.1161/01.cir.0000020009.30736.3f.
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.
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.
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.
神经激素激活是慢性心力衰竭的特征，与预后相关，是一个治疗靶点。目前尚不清楚先天性心脏病成人中是否存在类似的神经激素激活模式，如果存在，它是否与疾病严重程度的常用指标相关，或者心脏解剖结构是否是更好的判别因素。
测定了53例先天性心脏病成人（包括4个不同的解剖亚组，29例女性，年龄33.5±1.5岁，纽约心脏协会心功能分级2.0±0.1，均值±标准误）和15名健康对照者（8例女性，年龄32.3±1.3岁）的心房利钠肽（ANP）、脑利钠肽（BNP）、内皮素-1（ET-1）、肾素、醛固酮、去甲肾上腺素和肾上腺素浓度。由一位不知情的超声心动图检查者将全心室功能分级为正常、轻度、中度或重度受损。先天性心脏病成人的ANP（56.6对3.1 pmol/L）、BNP（35.8对5.7 pmol/L）、ET-1（2.5对0.7 pmol/L，均P<0.0001）、肾素（147对16.3 pmol/L）、去甲肾上腺素（2.2对1.6 pmol/L，均P<0.01）和醛固酮（546对337 pmol/L，P<0.05）水平升高。根据纽约心脏协会心功能分级和全心室功能，ANP、BNP、ET-1和去甲肾上腺素呈高度显著的逐步升高，即使无症状患者也有明显的神经激素激活证据。相比之下，4个解剖亚组与所研究的任何神经激素之间均无直接关系。
成人先天性心脏病中的神经激素激活具有慢性心力衰竭的特征，与症状严重程度和心室功能障碍相关，而不一定与解剖学基础相关。应考虑在这一庞大且解剖结构多样的人群中应用神经激素拮抗剂。
