Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay
Background Mortality for infants undergoing complex cardiac surgery is >10% with a 30% to 40% risk of complications. Early identification and treatment of high‐risk infants remains challenging. Metabolites are small molecules that determine the minute‐to‐minute cellular phenotype, making them ide...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-12-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.118.010711 |
| _version_ | 1818288155320647680 |
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| author | Jesse A. Davidson Zachary Pfeifer Benjamin Frank Suhong Tong Tracy T. Urban Paul A. Wischmeyer Peter Mourani Bruce Landeck Uwe Christians Jelena Klawitter |
| author_facet | Jesse A. Davidson Zachary Pfeifer Benjamin Frank Suhong Tong Tracy T. Urban Paul A. Wischmeyer Peter Mourani Bruce Landeck Uwe Christians Jelena Klawitter |
| author_sort | Jesse A. Davidson |
| collection | DOAJ |
| description | Background Mortality for infants undergoing complex cardiac surgery is >10% with a 30% to 40% risk of complications. Early identification and treatment of high‐risk infants remains challenging. Metabolites are small molecules that determine the minute‐to‐minute cellular phenotype, making them ideal biomarkers for postsurgical monitoring and potential targets for intervention. Methods and Results We measured 165 serum metabolites by tandem mass spectroscopy in infants ≤120 days old undergoing cardiopulmonary bypass. Samples were collected prebypass, during rewarming, and 24 hours after surgery. Partial least squares–discriminant analysis, pathway analysis, and receiver operator characteristic curve analysis were used to evaluate changes in the metabolome, assess altered metabolic pathways, and discriminate between survivors/nonsurvivors as well as upper/lower 50% intensive care unit length of stay. Eighty‐two infants had preoperative samples for analysis; 57 also had rewarming and 24‐hour samples. Preoperation, the metabolic fingerprint of neonates differed from older infants (R2=0.89, Q2=0.77; P<0.001). Cardiopulmonary bypass resulted in progressive, age‐independent metabolic disturbance (R2=0.92, Q2=0.83; P<0.001). Multiple pathways demonstrated changes, with arginine/proline (P=1.2×10−35), glutathione (P=3.3×10−39), and alanine/aspartate/glutamate (P=1.4×10−26) metabolism most affected. Six subjects died. Nonsurvivors demonstrated altered aspartate (P=0.007) and nicotinate/nicotinamide metabolism (P=0.005). The combination of 24‐hour aspartate and methylnicotinamide identified nonsurvivors versus survivors (area under the curve, 0.86; P<0.01), as well as upper/lower 50% intensive care unit length of stay (area under the curve, 0.89; P<0.01). Conclusions The preoperative metabolic fingerprint of neonates differed from older infants. Large metabolic shifts occurred after cardiopulmonary bypass, independent of age. Nonsurvivors and subjects requiring longer intensive care unit length of stay showed distinct changes in metabolism. Specific metabolites, including aspartate and methylnicotinamide, may differentiate sicker patients from those experiencing a more benign course. |
| first_indexed | 2024-12-13T01:51:53Z |
| format | Article |
| id | doaj.art-2c3acf35a5b94b8ba69fba5f616eb5df |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-13T01:51:53Z |
| publishDate | 2018-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-2c3acf35a5b94b8ba69fba5f616eb5df2022-12-22T00:03:30ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802018-12-0172410.1161/JAHA.118.010711Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of StayJesse A. Davidson0Zachary Pfeifer1Benjamin Frank2Suhong Tong3Tracy T. Urban4Paul A. Wischmeyer5Peter Mourani6Bruce Landeck7Uwe Christians8Jelena Klawitter9Department of Pediatrics University of Colorado/Children's Hospital Colorado Aurora COSchool of Medicine University of Colorado Aurora CODepartment of Pediatrics University of Colorado/Children's Hospital Colorado Aurora CODepartment of Biostatistics University of Colorado/Children's Hospital Colorado Aurora CODepartment of Research Institute Children's Hospital Colorado Aurora CODepartment of Anesthesiology Duke University Durham NCDepartment of Pediatrics University of Colorado/Children's Hospital Colorado Aurora CODepartment of Pediatrics University of Colorado/Children's Hospital Colorado Aurora CODepartment of Anesthesiology University of Colorado Aurora CODepartment of Anesthesiology University of Colorado Aurora COBackground Mortality for infants undergoing complex cardiac surgery is >10% with a 30% to 40% risk of complications. Early identification and treatment of high‐risk infants remains challenging. Metabolites are small molecules that determine the minute‐to‐minute cellular phenotype, making them ideal biomarkers for postsurgical monitoring and potential targets for intervention. Methods and Results We measured 165 serum metabolites by tandem mass spectroscopy in infants ≤120 days old undergoing cardiopulmonary bypass. Samples were collected prebypass, during rewarming, and 24 hours after surgery. Partial least squares–discriminant analysis, pathway analysis, and receiver operator characteristic curve analysis were used to evaluate changes in the metabolome, assess altered metabolic pathways, and discriminate between survivors/nonsurvivors as well as upper/lower 50% intensive care unit length of stay. Eighty‐two infants had preoperative samples for analysis; 57 also had rewarming and 24‐hour samples. Preoperation, the metabolic fingerprint of neonates differed from older infants (R2=0.89, Q2=0.77; P<0.001). Cardiopulmonary bypass resulted in progressive, age‐independent metabolic disturbance (R2=0.92, Q2=0.83; P<0.001). Multiple pathways demonstrated changes, with arginine/proline (P=1.2×10−35), glutathione (P=3.3×10−39), and alanine/aspartate/glutamate (P=1.4×10−26) metabolism most affected. Six subjects died. Nonsurvivors demonstrated altered aspartate (P=0.007) and nicotinate/nicotinamide metabolism (P=0.005). The combination of 24‐hour aspartate and methylnicotinamide identified nonsurvivors versus survivors (area under the curve, 0.86; P<0.01), as well as upper/lower 50% intensive care unit length of stay (area under the curve, 0.89; P<0.01). Conclusions The preoperative metabolic fingerprint of neonates differed from older infants. Large metabolic shifts occurred after cardiopulmonary bypass, independent of age. Nonsurvivors and subjects requiring longer intensive care unit length of stay showed distinct changes in metabolism. Specific metabolites, including aspartate and methylnicotinamide, may differentiate sicker patients from those experiencing a more benign course.https://www.ahajournals.org/doi/10.1161/JAHA.118.010711congenital heart diseasecritical carekynurenic acidmetabolitemetabolomemethylnicotinamide |
| spellingShingle | Jesse A. Davidson Zachary Pfeifer Benjamin Frank Suhong Tong Tracy T. Urban Paul A. Wischmeyer Peter Mourani Bruce Landeck Uwe Christians Jelena Klawitter Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease congenital heart disease critical care kynurenic acid metabolite metabolome methylnicotinamide |
| title | Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay |
| title_full | Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay |
| title_fullStr | Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay |
| title_full_unstemmed | Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay |
| title_short | Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay |
| title_sort | metabolomic fingerprinting of infants undergoing cardiopulmonary bypass changes in metabolic pathways and association with mortality and cardiac intensive care unit length of stay |
| topic | congenital heart disease critical care kynurenic acid metabolite metabolome methylnicotinamide |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.118.010711 |
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