Objective: Chronic heart failure is associated with neurohormonal activation that is not only related to outcome but is also a therapeutic target. We have attempted to demonstrate whether a similar pattern of neurohormonal activation exists in adult congenital heart disease (ACHD) and, if so, whether it relates to disease severity determined by cardiopulmonary exercise testing.
Methods and results: Concentrations of N-terminal pro-atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin (ET)-1, renin, aldosterone, adrenalin, and noradrenalin were determined in 50 adults (mean age, 27.8 +/- 1.7 years [+/- SEM]; 26 women) with tetralogy of Fallot (TOF) after surgical repair (New York Heart Association functional class 1.1 +/- 0.1). One hundred age- and sex-matched healthy blood donors served as a control group for NT-proBNP determination. Dimensions of ventricles, left ventricular pump function, and estimated right ventricular (RV) systolic pressure were determined by echocardiography. Maximum oxygen uptake (V(O2max) was measured in all patients using spiroergometry. TOF patients had elevated levels of NT-proBNP compared with healthy individuals: NT-proBNP (women: 180 pg/mL vs 43 pg/mL, and men: 147 pg/mL vs 32 pg/mL; p < 0.0001) and ET-1 (2.5 fmol/L vs 0.7 fmol/L). There was a significant correlation of NT-proBNP to dimension and estimated peak systolic pressure of the RV as well as impairment of V(O2max).
Conclusions: RV dysfunction detected by echocardiography and plasma NT-proBNP determination in asymptomatic or minimally symptomatic TOF patients correlates well with their cardiopulmonary exercise capacity. Thus, these simple and noninvasive screening methods can be used additionally to stratify ACHD patients with impaired cardiac function before they become clinically symptomatic.