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Published on: October 31, 2012
Circulating growth differentiation factor-15 as a novel biomarker in heart transplant
Nithi Tokavanich1, Supanee Sinphurmsukskul2, Narisorn Kongruttanachok3
1Division of Cardiovascular Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, 1873 Rama IV Rd, Pathumwan, Bangkok, 10330, Thailand.
Insights
Growth Differentiation Factor-15 (GDF-15) levels are elevated in heart failure patients and decrease post-transplant. While not a marker for acute cellular rejection, GDF-15 predicts severe primary graft dysfunction and mortality in heart transplant recipients.
Area of Science:
- Cardiology
- Transplantation Immunology
- Biomarker Discovery
Background:
- Growth Differentiation Factor-15 (GDF-15) is implicated in various cardiovascular conditions.
- Understanding its role in heart transplantation is crucial for patient outcomes.
Purpose of the Study:
- To investigate the association between GDF-15 and acute cellular rejection (ACR) post-heart transplantation.
- To analyze the longitudinal trend of GDF-15 after heart transplantation.
- To evaluate GDF-15's prognostic value for severe primary graft dysfunction (PGD) and 30-day mortality.
Main Methods:
- Serum GDF-15 levels were measured pre- and post-heart transplantation in 60 patients.
- Samples were correlated with endomyocardial biopsies (EMBs) to assess ACR.
- GDF-15 levels were analyzed longitudinally and in relation to post-transplant outcomes.
Main Results:
- No significant difference in GDF-15 levels was found between patients with and without ACR.
- GDF-15 concentrations decreased from pre-transplant levels to 4 weeks post-transplant.
- Elevated post-operative GDF-15 was significantly associated with severe PGD and 30-day mortality.
Conclusions:
- GDF-15 is not a reliable biomarker for detecting ACR in heart transplant recipients.
- GDF-15 shows potential as a prognostic marker for identifying patients at high risk of severe PGD and mortality.
- GDF-15 may aid in risk stratification and guide timely interventions in the early post-transplant period.
Aims:
This study aimed to examine (i) whether circulating growth differentiation factor-15 (GDF-15) is associated with acute cellular cardiac allograft rejection (ACR); (ii) a longitudinal trend of GDF-15 after heart transplantation; and (iii) the prognostic value of GDF-15 in predicting a composite outcome of severe primary graft dysfunction (PGD) and 30 day mortality post-transplant.
Methods And Results:
Serum samples were collected before heart transplantation and at every endomyocardial biopsy (EMB) post-heart transplantation in de novo transplant patients. A total of 60 post-transplant serum samples were matched to the corresponding EMBs. Seven (12%) were considered International Society for Heart Lung Transplantation Grade 1R ACR, and one (2%) was identified as Grade 2R ACR. GDF-15 levels in patients with ACR were not different from those in the non-rejection group (6230 vs. 6125 pg/mL, P = 0.27). GDF-15 concentration gradually decreased from 8757 pg/mL pre-transplant to 5203 pg/mL at 4 weeks post-transplant. The composite adverse outcome of PGD and 30 day mortality was significantly associated with increased post-operative GDF-15 (odds ratio: 40; 95% confidence interval: 2.01-794.27; P = 0.005) and high inotrope score post-transplant (odds ratio: 18; 95% confidence interval: 1.22-250.35; P = 0.01).
Conclusions:
Circulating GDF-15 concentration was markedly elevated in patients with end-stage heart failure and decreased after heart transplantation. GDF-15 was significantly associated with post-transplant PGD and mortality. A lack of association between ACR and GDF-15 did not support routine use of GDF-15 as a biomarker to detect ACR. However, GDF-15 may be potentially useful to determine heart transplant recipients at high risk for adverse post-transplant outcomes. We suggest that GDF-15 levels in recipient serum can provide risk stratification for severe PGD including death during post-operative period. This novel biomarker may serve to inform and guide timely interventions against severe PGD and adverse outcomes during the first 4 weeks after transplantation. Further studies to support the utility of GDF-15 in heart transplantation are required.
