Angermann Christiane E, Ertl Georg
Medizinische Poliklinik der Universität Würzburg, Würzburg.
Herz. 2004 Sep;29(6):609-17. doi: 10.1007/s00059-004-2619-8.
In patients with heart failure, increased wall stretch due to volume and pressure overload leads to an increase in circulating natriuretic peptides (ANP and BNP and their N-terminal fragments NT-proANP and NT-proBNP). Plasma BNP levels commonly considered normal (< 20 pg/ml) are influenced by age, sex, and also by genetic factors. ANP and BNP are synthesized and released by atrial and ventricular myocytes (Figure 1). In subjects with acute dyspnea, a BNP plasma concentration of 100 pg/ml has been established as a cutoff value for the diagnosis of heart failure yielding a very high negative predictive value coupled with an acceptable positive predictive value (Figure 3). However, recent evidence suggests that much more subtle elevations of plasma BNP may also indicate an increased long-term risk of cardiovascular events and death (Figure 2). In acute heart failure, natriuretic peptides correlate with ventricular pressure and volume overload, as well as with NYHA functional class. They can, however, not reliably discriminate between heart failure due to reduced ejection fraction and heart failure with preserved systolic function (Figure 4). Thus, elevated BNP or NT-proBNP levels always demand further clarification of heart failure etiology using echocardiography as the method of choice. As indicated by the algorithm for a BNP-based differential diagnosis of acute heart failure symptoms (Figure 5), a variety of noncardiac causes may also lead to moderate elevations of the markers (BNP plasma concentrations of 100-400 pg/ml). In addition, normal marker levels may be observed in > 20% of patients with long-term stable heart failure. Thus, increased plasma concentrations of natriuretic peptides are not strictly specific for heart diseases and also lack sensitivity in the chronic compensated state. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, and spironolactone have been shown to decrease BNP and NT-proBNP in parallel with clinical and hemodynamic improvement. In patients hospitalized for decompensated heart failure, predischarge plasma BNP levels reflect the risk of future death and rehospitalization (Figure 6). Although adjusting heart failure treatment to reduce plasma NT-proBNP levels may improve outcome, a general recommendation for monitoring drug therapy using this marker should not be derived from this observation. General practitioners may, in the future, use BNP or NT-proBNP as a rule-out test for heart failure and preselect patients for further diagnostic work-up on the basis of an elevated plasma level. Within the framework of the German network for heart failure the multicentric "Handheld-BNP Study" will clarify, whether echocardiography using low-price simple handcarried devices could be used as an alternative or, more likely, as a complementary diagnostic tool to further improve heart failure diagnosis in primary care.
在心力衰竭患者中，由于容量和压力超负荷导致的室壁伸展增加会使循环利钠肽（心房钠尿肽和脑钠肽及其N端片段N末端前心房钠尿肽和N末端前脑钠肽）增加。通常认为正常的血浆脑钠肽水平（<20 pg/ml）受年龄、性别以及遗传因素影响。心房钠尿肽和脑钠肽由心房和心室肌细胞合成并释放（图1）。在急性呼吸困难患者中，已确定血浆脑钠肽浓度100 pg/ml为心力衰竭诊断的临界值，其具有非常高的阴性预测值以及可接受的阳性预测值（图3）。然而，最近的证据表明，血浆脑钠肽更为细微的升高也可能表明心血管事件和死亡的长期风险增加（图2）。在急性心力衰竭中，利钠肽与心室压力和容量超负荷以及纽约心脏协会（NYHA）心功能分级相关。然而，它们无法可靠地区分射血分数降低所致的心力衰竭和收缩功能保留的心力衰竭（图4）。因此，脑钠肽或N末端前脑钠肽水平升高总是需要使用超声心动图作为首选方法进一步明确心力衰竭的病因。如基于脑钠肽的急性心力衰竭症状鉴别诊断算法所示（图5），多种非心脏原因也可能导致这些标志物中度升高（血浆脑钠肽浓度为100 - 400 pg/ml）。此外，在超过20%的长期稳定心力衰竭患者中可能观察到标志物水平正常。因此，利钠肽血浆浓度升高并非严格特异性地针对心脏病，在慢性代偿状态下也缺乏敏感性。利尿剂、血管紧张素转换酶（ACE）抑制剂、血管紧张素受体拮抗剂和螺内酯已被证明可使脑钠肽和N末端前脑钠肽水平随着临床和血流动力学改善而降低。在因失代偿性心力衰竭住院的患者中，出院前血浆脑钠肽水平反映未来死亡和再次住院的风险（图6）。尽管调整心力衰竭治疗以降低血浆N末端前脑钠肽水平可能改善预后，但不应基于这一观察结果得出使用该标志物监测药物治疗的一般建议。未来，全科医生可能会将脑钠肽或N末端前脑钠肽用作心力衰竭的排除试验，并根据血浆水平升高预先选择患者进行进一步的诊断检查。在德国心力衰竭网络框架内，多中心“手持式脑钠肽研究”将阐明，使用低价简单手持式设备进行超声心动图检查是否可作为一种替代方法，或者更有可能作为一种补充诊断工具，以进一步改善基层医疗中的心力衰竭诊断。
