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Postoperative Prognostic Nutritional Index and Fibrinogen Could Well Predict Poor Prognosis of Acute Type A Aortic Dissection Patients After Surgery

ABSTRACT

Introduction:

Inflammatory and immunological factors play pivotal roles in the prognosis of acute type A aortic dissection. We aimed to evaluate the prognostic values of immune-inflammatory parameters in acute type A aortic dissection patients after surgery.

Methods:

A total of 127 acute type A aortic dissection patients were included. Perioperative clinical data were collected through the hospital’s information system. The outcomes studied were delayed extubation, reintubation, and 30-day mortality. Multivariate logistic regression analysis and receiver operating characteristic analysis were used to screen the risk factors of poor prognosis.

Results:

Of all participants, 94 were male, and mean age was 51.95±11.89 years. The postoperative prognostic nutritional indexes were lower in delayed extubation patients, reintubation patients, and patients who died within 30 days. After multivariate regression analysis, the postoperative prognostic nutritional index was a protective parameter of poor prognosis. The odds ratios (95% confidence interval) of postoperative prognostic nutritional index were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. Low postoperative fibrinogen could also well predict poor clinical outcomes. The odds ratios (95% confidence interval) of postoperative fibrinogen were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality.

Conclusion:

Postoperative prognostic nutritional index and postoperative fibrinogen could be two promising markers to identify poor prognosis of acute type A aortic dissection patients after surgery.

Keywords:
Airway Extubation; Prognosis; Fibrinogen; Afibrinogenemia; Odds Ratio.

INTRODUCTION

Abbreviations, Acronyms & Symbols AD = Aortic dissection HTN = Hypertension ALI = Advanced lung cancer inflammation index ICU = Intensive care unit ALT = Alanine aminotransferase IDBIL = Indirect bilirubin AST = Aspartate aminotransferase IL-6 = Interleukin-6 ATAAD = Acute type A aortic dissection MHCA = Mild hypothermic circulatory arrest AUC = Area under the curve MV = Mechanical ventilation BMI = Body mass index NLR = Neutrophil-lymphocyte ratio BUN = Blood urea nitrogen OR = Odds ratio CABG = Coronary artery bypass grafting PCT = Procalcitonin CI = Confidence interval PIV = Pan-immune-inflammation value CKD = Chronic kidney disease PLT = Platelet CPB = Cardiopulmonary bypass PNI = Prognostic nutritional index Cre = Creatinine postFIB = Postoperative fibrinogen CRP = C-reactive protein postPNI = Postoperative prognostic nutritional index DBIL = Direct bilirubin RBC = Red blood cell DD = D-dimer ROC = Receiver operating characteristic DM = Diabetes mellitus SII = Systemic immune-inflammation index FDP = Fibrinogen degradation products SIRI = Systemic inflammation response index FIB = Fibrinogen TBIL = Total bilirubin Hb = Hemoglobin WBC = White blood cell

Acute type A aortic dissection (ATAAD) is a life-threatening cardiovascular emergency, which accounts for 58-62% of all aortic dissection (AD) with extremely high mortality and disability rates[11 Gudbjartsson T, Ahlsson A, Geirsson A, Gunn J, Hjortdal V, Jeppsson A, et al. Acute type A aortic dissection - a review. Scand Cardiovasc J. 2020;54(1):1-13. doi:10.1080/14017431.2019.1660401.
https://doi.org/10.1080/14017431.2019.16...
]. According to data from the International Registry of Acute Aortic Dissection, in-hospital surgical mortality rate could be as high as 30%, and the mortality rates after discharge range from 4-48% at the 1st year and 9-63% at the 5th year[22 Gao Y, Li D, Cao Y, Zhu X, Zeng Z, Tang L. Prognostic value of serum albumin for patients with acute aortic dissection: a retrospective cohort study. Medicine (Baltimore). 2019;98(6):e14486. doi:10.1097/MD.0000000000014486.
https://doi.org/10.1097/MD.0000000000014...
]. Therefore, it is important to accurately identify high-risk ATAAD patients by exploring the predictors of poor prognosis.

Accumulating evidence has confirmed that inflammatory and immunological factors are intimately involved in the progression and prognosis of ATAAD[33 Wang Q, Chen Z, Peng X, Zheng Z, Le A, Guo J, et al. Neuraminidase 1 exacerbating aortic dissection by governing a pro-inflammatory program in macrophages. Front Cardiovasc Med. 2021;8:788645. doi:10.3389/fcvm.2021.788645.
https://doi.org/10.3389/fcvm.2021.788645...
,44 Wu D, Choi JC, Sameri A, Minard CG, Coselli JS, Shen YH, et al. Inflammatory cell infiltrates in acute and chronic thoracic aortic dissection. Aorta (Stamford, Conn.), 1(6), 259-67. doi:10.12945/j.aorta.2013.13-044.
https://doi.org/10.12945/j.aorta.2013.13...
]. Inflammatory cell infiltration contributes to a sustained injury response, leading to medial degeneration and AD formation[44 Wu D, Choi JC, Sameri A, Minard CG, Coselli JS, Shen YH, et al. Inflammatory cell infiltrates in acute and chronic thoracic aortic dissection. Aorta (Stamford, Conn.), 1(6), 259-67. doi:10.12945/j.aorta.2013.13-044.
https://doi.org/10.12945/j.aorta.2013.13...
]. Several inflammatory factors, such as C-reactive protein, interleukin-6, tumor necrosis factor-α, and pentraxin-3, are increased in ATAAD patients[55 del Porto F, Proietta M, Tritapepe L, Miraldi F, Koverech A, Cardelli P, et al. Inflammation and immune response in acute aortic dissection. Ann Med. 2010;42(8):622-9. doi:10.3109/07853890.2010.518156.
https://doi.org/10.3109/07853890.2010.51...
]. The JAK2 gene, which is involved in the regulation of inflammatory response, was significantly downregulated in aortic specimens of ATAAD patients[66 Kimura N, Futamura K, Arakawa M, Okada N, Emrich F, Okamura H, et al. Gene expression profiling of acute type A aortic dissection combined with in vitro assessment. Eur J Cardiothorac Surg. 2017;52(4):810-7. doi:10.1093/ejcts/ezx095.
https://doi.org/10.1093/ejcts/ezx095....
]. Anti-inflammatory liposome therapy alleviates aortic injury and prolongs survival time in both acute and chronic AD mice[77 Liu J, Yang Y, Liu X, Widjaya AS, Jiang B, Jiang Y. Macrophage-biomimetic anti-inflammatory liposomes for homing and treating of aortic dissection. J Control Release. 2021;337:224-35. doi:10.1016/j.jconrel.2021.07.032.
https://doi.org/10.1016/j.jconrel.2021.0...
]. An Italian study found that T lymphocytes were reduced in the thoracic aortic specimens and peripheral blood of ATAAD patients[55 del Porto F, Proietta M, Tritapepe L, Miraldi F, Koverech A, Cardelli P, et al. Inflammation and immune response in acute aortic dissection. Ann Med. 2010;42(8):622-9. doi:10.3109/07853890.2010.518156.
https://doi.org/10.3109/07853890.2010.51...
]. Innate and cytotoxic cells are upregulated and are involved in the pathogenesis of ATAAD.

Due to this association, multiple systemic inflammatory and immune biomarkers have been studied in AD to predict its prognosis, including neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI). Higher NLR and SII were associated with adverse events in the hospital or during follow-up in AD patients[88 Zhang H, Guo J, Zhang Q, Yuan N, Chen Q, Guo Z, et al. The potential value of the neutrophil to lymphocyte ratio for early differential diagnosis and prognosis assessment in patients with aortic dissection. Clin Biochem. 2021;97:41-7. doi:10.1016/j.clinbiochem.2021.08.002.
https://doi.org/10.1016/j.clinbiochem.20...
,99 Su S, Liu J, Chen L, Xie E, Geng Q, Zeng H, et al. Systemic immune-inflammation index predicted the clinical outcome in patients with type-B aortic dissection undergoing thoracic endovascular repair. Eur J Clin Invest. 2022;52(2):e13692. doi:10.1111/eci.13692.
https://doi.org/10.1111/eci.13692....
]. Patients with a lower preoperative PNI showed significantly higher in-hospital mortality, a higher proportion of prolonged mechanical ventilation (MV), and longer intensive care unit (ICU) stay after surgery for ATAAD[1010 Keskin HA, Kurtul A, Esenboğa K, Çiçek MC, Katırcıoğlu SF. Prognostic nutritional index predicts in-hospital mortality in patients with acute Stanford type A aortic dissection. Perfusion. 2021;36(7):710-6. doi:10.1177/0267659120961937.
https://doi.org/10.1177/0267659120961937...
,1111 Lin Y, Chen Q, Peng Y, Chen Y, Huang X, Lin L, et al. Prognostic nutritional index predicts in-hospital mortality in patients with acute type A aortic dissection. Heart Lung. 2021;50(1):159-64. doi:10.1016/j.hrtlng.2020.06.004.
https://doi.org/10.1016/j.hrtlng.2020.06...
]. In addition, several new biomarkers derived from NLR were correlated with systemic inflammation and immune status and were good prognostic indicators of malignant tumors and cardiovascular diseases, including systemic inflammation response index (SIRI), advanced lung cancer inflammation index (ALI), and pan-immune-inflammation value (PIV)[1212 Fucà G, Guarini V, Antoniotti C, Morano F, Moretto R, Corallo S, et al. The pan-immune-inflammation value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the valentino and TRIBE first-line trials. Br J Cancer. 2020;123(3):403-9. doi:10.1038/s41416-020-0894-7.
https://doi.org/10.1038/s41416-020-0894-...
,1313 Fan W, Zhang Y, Liu Y, Ding Z, Si Y, Shi F, et al. Nomograms based on the advanced lung cancer inflammation index for the prediction of coronary artery disease and calcification. Clin Appl Thromb Hemost. 2021;27:10760296211060455. doi:10.1177/10760296211060455.
https://doi.org/10.1177/1076029621106045...
]. These indices outperformed other well-known peripheral blood parameters. However, it remains to be clarified whether these indices can act as prognostic biomarkers of ATAAD, and which one is optimal.

Therefore, the present study explored the predictive value of SIRI, SII, ALI, PNI, and PIV on delayed extubation, reintubation, and 30-day mortality. We further compared the sensitivity and specificity of these indices in the prediction of adverse outcomes. We aimed to identify the optimal indicator to guide risk stratification and treatment of ATAAD patients.

METHODS

Study Subjects

Patients diagnosed with ATAAD from September 2020 to September 2021 were enrolled in this study. The diagnosis of ATAAD was confirmed by computed tomographic angiography. Patients who underwent no surgical treatment or who died during the operation were excluded. There were 142 ATAAD patients at first. Of these patients, seven were excluded because they did not receive surgical therapy due to aortic rupture or economic factors or died during the operation, three were excluded because some clinical data were missing, and another five patients who were lost to follow-up at the 1st month after surgery were also excluded (Figure 1). The study was conducted in accordance with the Declaration of Helsinki and was approved by the Medical Science Research Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University (No.2021-621), and individual consent for this retrospective analysis was waived.

Fig. 1
Flow chart of screening. ATAAD=acute type A aortic dissection.

Data Collection and Definition

Perioperative clinical data of all patients, including demographic characteristics, laboratory parameters, surgical information, and detailed data of MV and reintubation, were retrospectively collected through the hospital’s information system. The prognostic indices included delayed extubation, reintubation, and 30-day mortality. Delayed extubation was defined as MV for > 48 hours. Patients were followed up at the 1st month after surgery through re-examination in the outpatient clinic or telephone consultation. Body mass index (BMI) was calculated as weight/height2 (kg/m2). The immune-inflammation parameters were obtained according to the following formulas:

  • ► NLR: peripheral blood levels of neutrophil count/lymphocyte count.

  • ► SIRI: monocyte count × NLR.

  • ► SII: platelet count × NLR.

  • ► PNI: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count.

  • ► ALI: BMI × blood albumin (g/dL)/NLR.

  • ► PIV: platelet count × monocyte count × NLR.

Surgical Technique

The operation was performed by a surgical team with the patient under general anesthesia. Cardiopulmonary bypass (CPB) was established at different sites according to the status of the patient (right axillary artery, femoral artery, innominate artery, and double arterial cannulation). Left radial artery and left dorsalis pedis artery catheterization for pressure measurement were performed. The patient was cooled to 28°C (nasopharyngeal temperature). The ascending aorta was clamped, and cold blood cardioplegia was infused through the coronary ostia to accomplish cardiac arrest. Antegrade cerebral perfusion for brain protection was established by axillary perfusion with a clamped brachiocephalic artery and direct cannulation of the left common carotid and subclavian arteries. The detailed operation procedure depended on the specific pathological changes of each patient, including Bentall procedure, David procedure, ascending aorta replacement + semiarch or total arch replacement, or Sun’s procedure (total arch replacement using a tetrafurcate graft with stented elephant trunk implantation). Some patients also concomitantly underwent coronary artery bypass grafting (CABG) and ascending-femoral bypass.

Statistical Analysis

Statistical analyses were performed using IBM Corp. Released 2013, IBM SPSS Statistics for Windows, version 22.0, Armonk, NY: IBM Corp., MedCalc 18.2 (MedCalc statistical software, Inc., San Diego, California, United States of America), and GraphPad Prism 8.0 (GraphPad Software, Inc., San Diego, California, United States of America). Variable distribution was examined using the Kolmogorov-Smirnov test. Continuous variables are presented as means ± standard deviation for normal distributions and as medians (interquartile range) for skewed distributions. Percentages are given for categorical data. Differences of variables between groups were examined using Student’s t-test, Mann-Whitney U test, χ2 test, or Fisher’s exact test, as appropriate. Univariate and multivariate logistic regression analyses were used to screen the risk factors for poor prognosis. Receiver operating characteristic (ROC) analysis was used to assess the predictive performance of selected risk factors. Statistical significance was defined as P<0.05, and all results were two-tailed.

RESULTS

Baseline Characteristics of Participants by Clinical Outcomes

A total of 127 patients were included in this study. Ninety-four of them were male, and the mean age was 51.95±11.89 years. A total of 49.6% were hypertensive. The rates of delayed extubation, reintubation, and 30-day mortality were 43.7%, 16.8%, and 13.6%, respectively, in the present study. Eighty-six patients underwent ascending aorta replacement + Sun’s procedure, 24 underwent Bentall procedure + Sun’s procedure, six underwent David procedure + Sun’s procedure, five underwent Bentall procedure, three underwent Bentall procedure + semiarch replacement, two underwent ascending aorta + semiarch replacement, and one underwent ascending aorta replacement. In addition, seven patients underwent ascending-femoral bypass, and two underwent CABG. Eight patients who died or were discharged within 48 hours after surgery for personal reasons were excluded from the analysis of delayed extubation. Fourteen patients who had never been weaned from MV were excluded from the reintubation analysis.

The groups with different clinical outcomes (Table 1) had comparable baseline characteristics, except for a higher malperfusion rate in the delayed extubation group. Surgery time was longer in reintubated patients and patients who died within 30 days. The rate of ascending-femoral bypass was higher in patients who died within 30 days. Delayed extubation patients had a longer CPB time and a higher rate of David procedure. D-dimer and fibrinogen (FIB) degradation products at admission were significantly higher in patients who died within 30 days but lower in delayed extubation patients. We also found that postoperative FIB (postFIB) was significantly lower in delayed extubation patients, reintubation patients, and patients who died within 30 days (P-values 0.001, 0.001, and 0.003, respectively). Among all immune-inflammatory parameters (Table 2), preoperative SIRI and PIV were higher and PNI was lower in delayed extubation patients. The postoperative PNIs (postPNI) were significantly lower in longer MV patients, reintubation patients, and patients who died within 30 days (P-values 0.003, 0.027, and 0.009, respectively). Pre and postoperative ALI did not show significant differences between groups. These results indicated that postFIB and postPNI were intimately correlated with poor clinical outcomes.

Table 1
Baseline characteristics of acute type A aortic dissection patients by different clinical outcomes.
Table 2
Perioperative immune-inflammatory parameters by different clinical outcomes.

Risk Factors for Poor Clinical Outcomes

By multivariate logistic regression analysis adjusted for age, sex, BMI, history of diseases, smoking, drinking, and preoperative malperfusion, postPNI and postFIB were the two protective parameters of poor clinical outcomes. The odds ratios (ORs) (95% confidence interval [CI]) of postPNI were 0.898 (0.815, 0.989) for delayed extubation and 0.792 (0.696, 0.901) for 30-day mortality. The ORs (95% CI) of postFIB were 0.487 (0.291, 0.813) for delayed extubation, 0.292 (0.124, 0.687) for reintubation, and 0.249 (0.093, 0.669) for 30-day mortality. CPB time was the only risk factor of delayed extubation in the multivariate logistic regression analysis (Table 3). Other immune-inflammatory parameters did not reach statistical significance even during univariate regression analysis.

Table 3
Prognostic parameters screened by univariate and multivariate logistic regression analysis.

Discriminating Performances of PostPNI and PostFIB in Predicting Poor Clinical Outcomes

To determine the prognostic predictive abilities of postPNI and postFIB for a poor clinical prognosis of ATAAD after surgery, we conducted ROC analysis. The areas under the curve (AUCs) for postPNI were 0.659 (0.567, 0.743) for delayed extubation, 0.603 (0.507, 0.693) for reintubation, and 0.746 (0.661, 0.820) for 30-day mortality, and the cutoff values were 42.1, 40.3, and 38.55, respectively. The AUCs for postFIB were 0.678 (0.584, 0.762) for delayed extubation, 0.751 (0.659, 0.828) for reintubation, and 0.745 (0.656, 0.821) for 30-day mortality, and the cutoff values were 2.87, 2.54, and 2.08, respectively (Figure 2, Table 4). The predicted values of the two parameters for different clinical outcomes did not show significant differences. The combination of two parameters did not further enhance the predictive values.

Table 4
ROC analysis of postPNI and postFIB by different clinical outcomes.

Fig. 2
Receiver operating characteristic curves by different clinical outcomes. postFIB=postoperative fibrinogen; postPNI=postoperative prognostic nutritional index.

DISCUSSION

This study explored the prognostic predictive and discriminative abilities of different immune-inflammatory parameters, including SIRI, SII, PNI, ALI, and PIV, in ATAAD patients after surgery. The prognostic indices included delayed extubation, reintubation, and 30-day mortality. The rates of delayed extubation, reintubation, and 30-day mortality were 43.7%, 16.8%, and 13.6%, respectively. The 30-day mortality was similar to those in previous multicenter studies, which uniformly approximately 17%. We found that only low postPNI was intimately associated with delayed extubation and 30-day mortality. Other perioperative immune-inflammatory indices did not present any predictive value of poor clinical outcomes after ATAAD surgery. In addition, low postFIB could well predict poor clinical outcomes.

Aberrant activation of the immune-inflammatory system plays a pivotal role in the progression of AD, contributing to vascular remodeling and dissection formation[1414 Lian G, Li X, Zhang L, Zhang Y, Sun L, Zhang X, et al. Macrophage metabolic reprogramming aggravates aortic dissection through the HIF1α-ADAM17 pathway✰. EBioMedicine. 2019;49:291-304. doi:10.1016/j.ebiom.2019.09.041.
https://doi.org/10.1016/j.ebiom.2019.09....
]. In ATAAD patients, neutrophils usually secrete cytokines in response to inflammatory stimuli, and cellular immunity is weakened, which is indicated by a decrease in lymphocytes. Therefore, NLR and NLR-derived parameters could reflect the general immune-inflammatory status. In this study, preNLR and postNLR were 14.93±14.57 and 27.06±19.13, respectively, indicating the activation of inflammation. Studies have reported that NLR can distinguish AD from other acute chest pain diseases, and patients with a higher NLR tend to have higher in-hospital mortality[88 Zhang H, Guo J, Zhang Q, Yuan N, Chen Q, Guo Z, et al. The potential value of the neutrophil to lymphocyte ratio for early differential diagnosis and prognosis assessment in patients with aortic dissection. Clin Biochem. 2021;97:41-7. doi:10.1016/j.clinbiochem.2021.08.002.
https://doi.org/10.1016/j.clinbiochem.20...
,1515 Oz K, Iyigun T, Karaman Z, Çelik Ö, Akbay E, Akınc O, et al. Prognostic value of neutrophil to lymphocyte ratio and risk factors for mortality in patients with stanford type A aortic dissection. Heart Surg Forum. 2017;20(3):E119-23. doi:10.1532/hsf.1736.
https://doi.org/10.1532/hsf.1736....
]. There are few data on the relationship of SIRI, SII, ALI, and PIV with the prognosis of ATAAD after surgery. In this study, we did not find any significant differences between different groups divided by delayed extubation, reintubation, or 30-day mortality.

Previous studies have proposed albumin as an indicator of protein status in non-inflamed patients, but it is not nutritionally informative in an ICU setting. The distribution between the intravascular and extravascular compartments, the rates of synthesis, and the metabolism of albumin are all significantly altered during inflammation and stress. It was reported that the normal transcapillary escape rate for albumin increases by 100% after cardiac surgery. In addition, the transcription rate of albumin messenger ribonucleic acid is decreased in response to inflammation[1616 Ruan GT, Yang M, Zhang XW, Song MM, Hu CL, Ge YZ, et al. Association of systemic inflammation and overall survival in elderly patients with cancer cachexia - results from a multicenter study. J Inflamm Res. 2021;14:5527-5540. doi:10.2147/JIR.S332408.
https://doi.org/10.2147/JIR.S332408....

17 Nicholson JP, Wolmarans MR, Park GR. The role of albumin in critical illness. Br J Anaesth. 2000;85(4):599-610. doi:10.1093/bja/85.4.599.
https://doi.org/10.1093/bja/85.4.599....
-1818 Rashedi S, Keykhaei M, Pazoki M, Ashraf H, Najafi A, Kafan S, et al. Clinical significance of prognostic nutrition index in hospitalized patients with COVID-19: results from single-center experience with systematic review and meta-analysis. Nutr Clin Pract. 2021;36(5):970-83. Erratum in: Nutr Clin Pract. 2023;: doi:10.1002/ncp.10750.
https://doi.org/10.1002/ncp.10750....
]. Anti-inflammation and immune regulation are also two important physiological roles of albumin[1818 Rashedi S, Keykhaei M, Pazoki M, Ashraf H, Najafi A, Kafan S, et al. Clinical significance of prognostic nutrition index in hospitalized patients with COVID-19: results from single-center experience with systematic review and meta-analysis. Nutr Clin Pract. 2021;36(5):970-83. Erratum in: Nutr Clin Pract. 2023;: doi:10.1002/ncp.10750.
https://doi.org/10.1002/ncp.10750....
]. Therefore, hypoalbuminemia could reflect a systemic immune-inflammatory state and further enhance the inflammatory response. A lower albumin level has predicted higher in-hospital mortality in both ATAAD and type B AD[1919 Sun L, Yin H, Liu M, Xu G, Zhou X, Ge P, et al. Impaired albumin function: a novel potential indicator for liver function damage? Ann Med. 2019;51(7-8):333-44. doi:10.1080/07853890.2019.1693056.
https://doi.org/10.1080/07853890.2019.16...
]. PNI is an effective index that integrates two inflammatory markers - serum albumin and lymphocytes. Previous studies reported that PNI was independently associated with all-cause and cardiovascular mortality in patients hospitalized for acute heart failure, coronary artery disease, or infective endocarditis[2121 Cheng YL, Sung SH, Cheng HM, Hsu PF, Guo CY, Yu WC, et al. Prognostic nutritional index and the risk of mortality in patients with acute heart failure. J Am Heart Assoc. 2017;6(6):e004876. doi:10.1161/JAHA.116.004876.
https://doi.org/10.1161/JAHA.116.004876....
,2222 Mas-Peiro S, Hoffmann J, Seppelt PC, De Rosa R, Murray MI, Walther T, et al. Value of prognostic nutritional index for survival prediction in trans-catheter aortic valve replacement compared to other common nutritional indexes. Acta Cardiol. 2021;76(6):615-22. doi:10.1080/00015385.2020.1757854.
https://doi.org/10.1080/00015385.2020.17...
]. Similar prognostic predictive values have been observed for PNI in patients after cardiac surgery, including CABG or aortic valve replacement[2222 Mas-Peiro S, Hoffmann J, Seppelt PC, De Rosa R, Murray MI, Walther T, et al. Value of prognostic nutritional index for survival prediction in trans-catheter aortic valve replacement compared to other common nutritional indexes. Acta Cardiol. 2021;76(6):615-22. doi:10.1080/00015385.2020.1757854.
https://doi.org/10.1080/00015385.2020.17...

23 Keskin M, İpek G, Aldağ M, Altay S, Hayıroğlu Mİ, Börklü EB, et al. Effect of nutritional status on mortality in patients undergoing coronary artery bypass grafting. Nutrition. 2018;48:82-6. doi:10.1016/j.nut.2017.10.024.
https://doi.org/10.1016/j.nut.2017.10.02...
-2424 Gürbak İ, Güner A, Güler A, Şahin AA, Çelik Ö, Uzun F, et al. Prognostic influence of objective nutritional indexes on mortality after surgical aortic valve replacement in elderly patients with severe aortic stenosis (from the nutrition-SAVR trial). J Card Surg. 2021;36(6):1872-81. doi:10.1111/jocs.15434.
https://doi.org/10.1111/jocs.15434....
]. Recently, several studies revealed its intimate association with ATAAD. Low PNI at admission has been strongly correlated with in-hospital mortality in patients after surgery, especially in hypertensive patients, even after adjusting for other risk factors[1010 Keskin HA, Kurtul A, Esenboğa K, Çiçek MC, Katırcıoğlu SF. Prognostic nutritional index predicts in-hospital mortality in patients with acute Stanford type A aortic dissection. Perfusion. 2021;36(7):710-6. doi:10.1177/0267659120961937.
https://doi.org/10.1177/0267659120961937...
,1111 Lin Y, Chen Q, Peng Y, Chen Y, Huang X, Lin L, et al. Prognostic nutritional index predicts in-hospital mortality in patients with acute type A aortic dissection. Heart Lung. 2021;50(1):159-64. doi:10.1016/j.hrtlng.2020.06.004.
https://doi.org/10.1016/j.hrtlng.2020.06...
]. Though we found that prePNI was lower in patients with delayed extubation, it was not an independent risk factor after multivariate analysis. This discrepancy might be attributed to the different populations, statistical methods, and surgical processes. Furthermore, those studies did not assess the influence of postPNI on prognosis. In this study, we found that low postPNI well predicted poor clinical outcomes after multivariate logistic regression analysis. PostPNI was significantly lower in the groups with the poor clinical outcomes of delayed extubation or 30-day mortality.

Inflammation is an important regulator of coagulation and fibrinolytic system activity. Acute inflammation is known to shift the hemostatic balance toward a prothrombotic and antifibrinolytic state, and FIB could also be a driver of local inflammation[2525 Luyendyk JP, Schoenecker JG, Flick MJ. The multifaceted role of fibrinogen in tissue injury and inflammation. Blood. 2019;133(6):511-20. doi:10.1182/blood-2018-07-818211.
https://doi.org/10.1182/blood-2018-07-81...
]. An animal study showed that FIB was oxidized at first and proteolyzed three hours later in response to leukocyte-associated inflammation[2626 Han CY, Pichon TJ, Wang X, Ringgold KM, St John AE, Stern SA, et al. Leukocyte activation primes fibrinogen for proteolysis by mitochondrial oxidative stress. Redox Biol. 2022;51:102263. doi:10.1016/j.redox.2022.102263.
https://doi.org/10.1016/j.redox.2022.102...
]. Changes in coagulation and fibrinolysis are prominent in ATAAD patients due to acute inflammatory response, endothelial injury, formation of false lumen, and thrombosis. A Swedish study described that FIB levels at admission were significantly lower in ATAAD patients than in patients undergoing surgery of the ascending aorta or the aortic root in mild-tomoderate hypothermia[2727 Zindovic I, Sjögren J, Bjursten H, Ingemansson R, Ingimarsson J, Larsson M, et al. The coagulopathy of acute type A aortic dissection: a prospective, observational study. J Cardiothorac Vasc Anesth. 2019;33(10):2746-54. doi:10.1053/j.jvca.2019.02.013.
https://doi.org/10.1053/j.jvca.2019.02.0...
]. The levels of FIB further decreased after CPB. Low FIB (< 2.17 g/L) at admission was reported to be an independent predictor of in-hospital mortality in patients undergoing ATAAD surgery, especially in patients > 65 years[2828 Liu J, Sun LL, Wang J, Ji G. The relationship between fibrinogen and in-hospital mortality in patients with type A acute aortic dissection. Am J Emerg Med. 2018;36(5):741-4. doi:10.1016/j.ajem.2017.10.001.
https://doi.org/10.1016/j.ajem.2017.10.0...
]. However, few studies have discussed the influence of postFIB. We found that low postFIB was strongly associated with delayed extubation, reintubation, and 30-day mortality after adjusting for confounders in this study. These results indicate that low postFIB could well predict poor clinical outcomes and might be a promising prognostic marker of ATAAD after surgery.

Limitations

Several limitations of this study should be stressed. It was a small, single-center retrospective study. There were few events, and local surgical skills might have influenced the clinical outcomes. Therefore, larger, multicenter, and prospective studies are required to verify our results.

CONCLUSION

Prognostic estimation is crucial for the management of ATAAD. We found that low postPNI, rather than other perioperative immune-inflammatory indices, was intimately associated with delayed extubation and 30-day mortality. Low postFIB was strongly associated with delayed extubation, reintubation, and 30-day mortality after adjusting for confounders in this study. Overall, postPNI and postFIB might be two easily accessible and effective prognostic markers to guide the risk stratification and treatment of ATAAD patients.

  • No financial support.

REFERENCES

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Publication Dates

  • Publication in this collection
    23 Feb 2024
  • Date of issue
    2024

History

  • Received
    24 Apr 2022
  • Accepted
    01 Oct 2022
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