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Elevated plasma phenylalanine predicts mortality in critical patients with heart failure.
ESC Heart Fail. 2020 Jul 02 [Online ahead of print]EH

Abstract

AIMS

Previous studies found a relationship between elevated phenylalanine levels and poor cardiovascular outcomes. Potential strategies are available to manipulate phenylalanine metabolism. This study investigated whether increased phenylalanine predicted mortality in critical patients with either acute heart failure (HF) or acute on chronic HF, and its correlation with inflammation and immune cytokines.

METHODS AND RESULTS

This study recruited 152 subjects, including 115 patients with HF admitted for critical conditions and 37 normal controls. We measured left ventricular ejection fraction (LVEF), plasma concentrations of phenylalanine, C-reactive protein, albumin, pre-albumin, transferrin, and pro-inflammatory and immune cytokines. Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and maximal vasoactive-inotropic scores (VISmax) were calculated. Patients were followed up until death or a maximum of 1 year. The primary endpoint was all-cause death. Of the 115 patients, 37 (32.2%) were admitted owing to acute HF, and 78 (67.8%) were admitted owing to acute on chronic HF; 64 (55.7%) had ST elevation/non-ST elevation myocardial infarction. An LVEF measured during the hospitalization of <40%, 40-50%, and ≥50% was noted in 51 (44.3%), 15 (13.1%), and 49 (42.6%) patients, respectively. During 1 year follow-up, 51 (44.3%) patients died. Death was associated with higher APACHE II, SOFA, and VISmax scores; higher levels of C-reactive protein and phenylalanine; higher incidence of atrial fibrillation and use of inotropic agents; lower cholesterol, albumin, pre-albumin, and transferrin levels; and significant changes in pro-inflammatory and immune cytokines. Phenylalanine levels demonstrated an area under the receiver operating characteristic curve of 0.80 for mortality, with an optimal cut-off value set at 112 μM. Phenylalanine ≥ 112 μM was associated with a higher mortality rate than was phenylalanine < 112 μM (80.5% vs. 24.3%, P < 0.001) [hazard ratio = 5.07 (2.83-9.05), P < 0.001]. The Kaplan-Meier curves revealed that phenylalanine ≥ 112 μM was associated with a lower accumulative survival rate (log rank = 36.9, P < 0.001). Higher phenylalanine levels were correlated with higher APACHE II and SOFA scores, higher C-reactive protein levels and incidence of using inotropic agents, and changes in cytokines suggestive of immunosuppression, but lower levels of pre-albumin and transferrin. Further multivariable analysis showed that phenylalanine ≥ 112 μM predicted death over 1 year independently of age, APACHE II and SOFA scores, atrial fibrillation, C-reactive protein, cholesterol, pre-albumin, transferrin, and interleukin-8 and interleukin-10.

CONCLUSIONS

Elevated phenylalanine levels predicted mortality in critical patients, phenotypically predominantly presenting with HF, independently of traditional prognostic factors and cytokines associated with inflammation and immunity.

Authors+Show Affiliations

Intensive Care Unit, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan. Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taoyuan, Taiwan. Chang Gung University College of Medicine, Taoyuan, Taiwan.Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taoyuan, Taiwan. Chang Gung University College of Medicine, Taoyuan, Taiwan.Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taoyuan, Taiwan. Chang Gung University College of Medicine, Taoyuan, Taiwan.Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taoyuan, Taiwan. Chang Gung University College of Medicine, Taoyuan, Taiwan.Division of Pulmonary, Critical Care and Sleep Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.Division of Pulmonary, Critical Care and Sleep Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.Nutrition Department, Chang Gung Memorial Hospital, Keelung, Taiwan.Nutrition Department, Chang Gung Memorial Hospital, Keelung, Taiwan.Intensive Care Unit, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan. Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taoyuan, Taiwan. Chang Gung University College of Medicine, Taoyuan, Taiwan.Intensive Care Unit, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan. Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taoyuan, Taiwan. Chang Gung University College of Medicine, Taoyuan, Taiwan.Department of Nursing, Chang Gung Memorial Hospital, Keelung, Taiwan.Department of Nursing, Chang Gung Memorial Hospital, Keelung, Taiwan.Intensive Care Unit, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan. Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taoyuan, Taiwan. Chang Gung University College of Medicine, Taoyuan, Taiwan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32618142

Citation

Chen, Wei-Siang, et al. "Elevated Plasma Phenylalanine Predicts Mortality in Critical Patients With Heart Failure." ESC Heart Failure, 2020.
Chen WS, Wang CH, Cheng CW, et al. Elevated plasma phenylalanine predicts mortality in critical patients with heart failure. ESC Heart Fail. 2020.
Chen, W. S., Wang, C. H., Cheng, C. W., Liu, M. H., Chu, C. M., Wu, H. P., Huang, P. C., Lin, Y. T., Ko, T., Chen, W. H., Wang, H. J., Lee, S. C., & Liang, C. Y. (2020). Elevated plasma phenylalanine predicts mortality in critical patients with heart failure. ESC Heart Failure. https://doi.org/10.1002/ehf2.12896
Chen WS, et al. Elevated Plasma Phenylalanine Predicts Mortality in Critical Patients With Heart Failure. ESC Heart Fail. 2020 Jul 2; PubMed PMID: 32618142.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated plasma phenylalanine predicts mortality in critical patients with heart failure. AU - Chen,Wei-Siang, AU - Wang,Chao-Hung, AU - Cheng,Chi-Wen, AU - Liu,Ming-Hui, AU - Chu,Chien-Ming, AU - Wu,Huang-Ping, AU - Huang,Pao-Chin, AU - Lin,Yi-Tsen, AU - Ko,Ta, AU - Chen,Wen-Hsin, AU - Wang,Huei-Jen, AU - Lee,Shu-Chiu, AU - Liang,Chung-Yu, Y1 - 2020/07/02/ PY - 2020/03/17/received PY - 2020/06/21/revised PY - 2020/06/24/accepted PY - 2020/7/4/entrez KW - Biomarkers KW - Heart failure KW - Phenylalanine KW - Prognosis JF - ESC heart failure JO - ESC Heart Fail N2 - AIMS: Previous studies found a relationship between elevated phenylalanine levels and poor cardiovascular outcomes. Potential strategies are available to manipulate phenylalanine metabolism. This study investigated whether increased phenylalanine predicted mortality in critical patients with either acute heart failure (HF) or acute on chronic HF, and its correlation with inflammation and immune cytokines. METHODS AND RESULTS: This study recruited 152 subjects, including 115 patients with HF admitted for critical conditions and 37 normal controls. We measured left ventricular ejection fraction (LVEF), plasma concentrations of phenylalanine, C-reactive protein, albumin, pre-albumin, transferrin, and pro-inflammatory and immune cytokines. Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and maximal vasoactive-inotropic scores (VISmax) were calculated. Patients were followed up until death or a maximum of 1 year. The primary endpoint was all-cause death. Of the 115 patients, 37 (32.2%) were admitted owing to acute HF, and 78 (67.8%) were admitted owing to acute on chronic HF; 64 (55.7%) had ST elevation/non-ST elevation myocardial infarction. An LVEF measured during the hospitalization of <40%, 40-50%, and ≥50% was noted in 51 (44.3%), 15 (13.1%), and 49 (42.6%) patients, respectively. During 1 year follow-up, 51 (44.3%) patients died. Death was associated with higher APACHE II, SOFA, and VISmax scores; higher levels of C-reactive protein and phenylalanine; higher incidence of atrial fibrillation and use of inotropic agents; lower cholesterol, albumin, pre-albumin, and transferrin levels; and significant changes in pro-inflammatory and immune cytokines. Phenylalanine levels demonstrated an area under the receiver operating characteristic curve of 0.80 for mortality, with an optimal cut-off value set at 112 μM. Phenylalanine ≥ 112 μM was associated with a higher mortality rate than was phenylalanine < 112 μM (80.5% vs. 24.3%, P < 0.001) [hazard ratio = 5.07 (2.83-9.05), P < 0.001]. The Kaplan-Meier curves revealed that phenylalanine ≥ 112 μM was associated with a lower accumulative survival rate (log rank = 36.9, P < 0.001). Higher phenylalanine levels were correlated with higher APACHE II and SOFA scores, higher C-reactive protein levels and incidence of using inotropic agents, and changes in cytokines suggestive of immunosuppression, but lower levels of pre-albumin and transferrin. Further multivariable analysis showed that phenylalanine ≥ 112 μM predicted death over 1 year independently of age, APACHE II and SOFA scores, atrial fibrillation, C-reactive protein, cholesterol, pre-albumin, transferrin, and interleukin-8 and interleukin-10. CONCLUSIONS: Elevated phenylalanine levels predicted mortality in critical patients, phenotypically predominantly presenting with HF, independently of traditional prognostic factors and cytokines associated with inflammation and immunity. SN - 2055-5822 UR - https://www.unboundmedicine.com/medline/citation/32618142/Elevated_plasma_phenylalanine_predicts_mortality_in_critical_patients_with_heart_failure L2 - https://doi.org/10.1002/ehf2.12896 DB - PRIME DP - Unbound Medicine ER -
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