Does circulating BNP normalize after heart transplantation in patients with normal hemodynamic and right and left heart functions?
BACKGROUND
Increased brain natriuretic peptide (BNP) in cardiovascular disease is thought to be a compensatory protective mechanism allowing to delay the occurrence of terminal heart failure. Heart transplantation should normalize the neuroendocrine balance but BNP remains elevated in stable heart-transplant recipients (Htx). Such increase has been related to persistent endothelial and cardiac dysfunctions. The purpose of this study was to determine whether selected Htx, presenting with normal hemodynamic and cardiac systolic and diastolic functions on both side of the heart, show a normalization of their BNP plasma values.


METHODS
Of a cohort of well-being 26 Htx, we selected 12 patients with normal hemodynamics and left and right heart systolic and diastolic functions and compared their circulating BNP, cyclic guanosine monophosphate (cGMP) (the BNP second messenger) and endothelin-1 (ET) values with that of 12 age-, body mass index- and mean arterial pressure-matched controls. Cardiac function determination by echodoppler included cardiac filling pressures assessment using tissue Doppler imaging. Blood samples for biological and hormonal determinations were drawn at rest, within 15 min before echocardiography.


RESULTS
As selected, hemodynamic and left and right heart systolic and diastolic functions were located in the normal range in Htx. Plasma ET value was also similar in Htx and controls (20.7 +/- 0.9 vs. 19.6 +/- 0.9 fmol/mL). However, circulating BNP, like cGMP, was still significantly increased after heart transplantation, when compared with controls (33.8 +/- 8.5 vs. 4.0 +/- 0.9 pg/mL, p = 0.002 and 8.2 +/- 1.1 vs. 4.4 +/- 0.3 nmol/L, p = 0.003) for BNP and cGMP, respectively, in Htx and controls. Interestingly, the sole correlation observed was between BNP and cGMP (r = 0.85, p < 0.0001) after heart transplantation.


CONCLUSIONS
After heart transplantation, BNP remained increased despite the normalization of hemodynamic and cardiac systolic and diastolic functions. This suggests that such endocrine heart stimulation should not be viewed only as a hemodynamic marker in Htx. Further studies will be useful to investigate the role of pro-inflammatory cytokines and whether elevated BNP still possesses antifibrotic properties, further supporting the interest of enhancing its activity after heart transplantation.
Talha
S
S
Service de Physiologie et d'Explorations Fonctionnelles and EA 3072, Hôpitaux Universitaires de Strasbourg, Strasbourg cedex, France. samy.talha@chru-strasbourg.fr
Di Marco
P
P
Doutreleau
S
S
Rouyer
O
O
Piquard
F
F
Geny
B
B
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006152:Cyclic GMP / Q000097:blood; D015150:Echocardiography, Doppler; D019332:Endothelin-1 / Q000097:blood; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology; D016027:Heart Transplantation / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D013318:Stroke Volume; D016277:Ventricular Function, Left / Q000502:physiology; D016278:Ventricular Function, Right / Q000502:physiology
D015415:Biomarkers; D019332:Endothelin-1; D020097:Natriuretic Peptide, Brain; D006152:Cyclic GMP