N-terminal pro-brain-type natriuretic peptide: a biochemical surrogate of cardiac function in the potential heart donor.
OBJECTIVE
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is elevated in subarachnoid haemorrhage, brainstem death (BSD) and heart failure. We examined the relationship between NT-proBNP and cardiac functional status after BSD and left ventricular (LV) BNP precursor gene expression.


METHODS
We assayed NT-proBNP in the serum of potential heart donors investigated with pulmonary artery flotation catheters, transthoracic echocardiography and cardiac troponin (cTn) I and T. After 6.9 h of optimisation, haemodynamic studies were repeated to determine haemodynamic functional suitability for transplantation. Median (interquartile range (IQR)) NT-proBNP levels are reported according to initially measured dichotomised pulmonary capillary wedge pressure (PCWP), cardiac index (CI), indexed cardiac power output (CPOi), left ventricular ejection fraction (LVEF), wall motion score (WMS), extravascular lung water index (EVLWI), cTnT and cTnI and end-management functional suitability. LV biopsies were snap-frozen, mRNA extracted and reverse-transcribed, allowing performance of Taqman real-time polymerase chain reaction assays of mRNA-BNP precursor.


RESULTS
There were 79 subjects. Median NT-proBNP was 121 pg ml(-1) (range 5-4139) and levels correlated with time from coning (p<0.01, r=-0.379). Higher NT-proBNP was found in donors with PCWP >14 mmHg; 504 (120-1544) versus 101 (38-285); p=0.01; CI <2.4 l min(-1) m(-2) 410 (123-1511) versus 95 (37-264); p=0.001; CPOi <0.5 Wm(-2) 256 (78-694) versus 105 (37-315); p=0.02; LVEF <50% 231 (75-499) versus 72 (36-177); p=0.04; WMS >2; 343 (80-673) versus 99 (37-236); p=0.01; cTnT >0.1 microg ml(-1) 499 (127-967) versus 80 (36-173); p<0.001 and cTnI >1 mg ml(-1) 410 (97-684) versus 88 (36-190); p<0.01 and in hearts functionally unsuitable at end-optimisation; 189 (74-522) versus 85 (39-243); p=0.02. Hearts functionally suitable for transplantation expressed significantly less mRNA encoding for BNP precursor (0.19-fold; p=0.01).


CONCLUSIONS
During or after BSD, NT-proBNP is released and the heart is a likely source. Higher NT-proBNP levels are associated with donor heart dysfunction and a failure to achieve haemodynamic functional suitability criteria. This supports the hypothesis that biomarkers, including NT-proBNP, may be useful in donor heart assessment.
Dronavalli
Vamsidhar B
VB
Heart & Lung Transplant Unit, Department of Cardiothoracic Surgery, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
Ranasinghe
Aaron M
AM
Venkateswaran
Rajamiyer J
RJ
James
Sally R
SR
McCabe
Christopher J
CJ
Wilson
Ian C
IC
Mascaro
Jorge G
JG
Bonser
Robert S
RS
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001926:Brain Death / Q000097:blood; D002302:Cardiac Output; D002423:Cause of Death; D046148:Donor Selection; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000235:genetics; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013318:Stroke Volume; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting; D055815:Young Adult
D015415:Biomarkers; D010446:Peptide Fragments; D012333:RNA, Messenger; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain