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      Impact of D-dimer on in-hospital mortality following aortic dissection: A systematic review and meta-analysis

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          Abstract

          BACKGROUND

          The utility of D-dimer (DD) as a biomarker for acute aortic dissection (AD) is recognized. Yet, its predictive value for in-hospital mortality remains uncertain and subject to conflicting evidence.

          AIM

          To conduct a meta-analysis of AD-related in-hospital mortality (ADIM) with elevated DD levels.

          METHODS

          We searched PubMed, Scopus, Embase, and Google Scholar for AD and ADIM literature through May 2022. Heterogeneity was assessed using I 2 statistics and effect size (hazard or odds ratio) analysis with random-effects models. Sample size, study type, and patients’ mean age were used for subgroup analysis. The significance threshold was P < 0.05.

          RESULTS

          Thirteen studies (3628 patients) were included in our study. The pooled prevalence of ADIM was 20% (95%CI: 15%-25%). Despite comparable demographic characteristics and comorbidities, elevated DD values were associated with higher ADIM risk (unadjusted effect size: 1.94, 95%CI: 1.34-2.8; adjusted effect size: 1.12, 95%CI: 1.05-1.19, P < 0.01). Studies involving patients with a mean age of < 60 years exhibited an increased mortality risk (effect size: 1.43, 95%CI: 1.23-1.67, P < 0.01), whereas no significant difference was observed in studies with a mean age > 60 years. Prospective and larger sample size studies ( n > 250) demonstrated a heightened likelihood of ADIM associated with elevated DD levels (effect size: 2.57, 95%CI: 1.30-5.08, P < 0.01 vs effect size: 1.05, 95%CI: 1.00-1.11, P = 0.05, respectively).

          CONCLUSION

          Our meta-analysis shows elevated DD increases in-hospital mortality risk in AD patients, highlighting the need for larger, prospective studies to improve risk prediction models.

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          Most cited references20

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          Insights From the International Registry of Acute Aortic Dissection: A 20-Year Experience of Collaborative Clinical Research.

          Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality rates, and it remains a challenge to diagnose and treat. The International Registry of Acute Aortic Dissection was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment. Since then, >7300 cases have been included from >51 sites in 12 countries. Although presenting symptoms and physical findings have not changed significantly over this period, the use of computed tomography in the diagnosis has increased, and more patients are managed with interventional procedures: surgery in type A AAD and endovascular therapy in type B AAD; with these changes in care, there has been a significant decrease in overall in-hospital mortality in type A AAD but not in type B AAD. Herein, we summarized the key lessons learned from this international registry of patients with AAD over the past 20 years.
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            A Test in Context: D-Dimer

            D-dimer is a soluble fibrin degradation product that results from ordered breakdown of thrombi by the fibrinolytic system. Numerous studies have shown that D-dimer serves as a valuable marker of activation of coagulation and fibrinolysis. Consequently, D-dimer has been extensively investigated for the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D-dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and as an aid in the identification of medical patients at high risk for VTE. Thus, quantification of D-dimer levels serves an important role in guiding therapy. This review: 1) describes how D-dimer is generated; 2) reviews the assays used for its detection; and 3) discusses the role of D-dimer determination in these various conditions.
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              Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study.

              D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients. To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE. A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013. All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period. The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result. Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings. Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism. clinicaltrials.gov Identifier: NCT01134068.
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                Author and article information

                Contributors
                Journal
                World J Cardiol
                WJC
                World Journal of Cardiology
                Baishideng Publishing Group Inc
                1949-8462
                26 June 2024
                26 June 2024
                : 16
                : 6
                : 355-362
                Affiliations
                Department of Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
                Department of Research, Independent Outcomes Research, Los Angeles, CA 90036, United States
                Department of Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
                Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, United States
                Department of Vascular Medicine, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
                Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77079, United States
                Department of Cardiology, Heart and Vascular Clinic, Newark, DE 19713, United States
                Department of Cardiology, Heart and Vascular Clinic, Newark, DE 19713, United States. sguruparan@ 123456yahoo.com
                Independent Researcher, Atlanta, GA 30079, United States
                Author notes

                Author contributions: Srikanth S was responsible for conceptualization, methodology, investigation, writing-original draft, writing-review and editing, visualization; Mahadevaiah A was responsible for methodology, investigation, resources, data curation, writing-original draft, visualization; Abrishami S and Subramanian L were responsible for methodology, data curation, writing-original draft, writing-review and editing; Vyas A and Jain A were responsible for conceptualization, methodology, writing-original draft, writing-review and editing, project administration; Nathaniel S and Gnanaguruparan S were responsible for writing-review and editing; Desai R was responsible for conceptualization, methodology, software, formal analysis, resources, data curation, writing-original draft, writing-review and editing, project administration, supervision.

                Corresponding author: Subramanian Gnanaguruparan, MBBS, Doctor, Department of Cardiology, Heart and Vascular Clinic, 620 Stanton Christiana Road, Suite 203 Newark, Newark, DE 19713, United States. sguruparan@ 123456yahoo.com

                Article
                jWJC.v16.i6.pg355 94521
                10.4330/wjc.v16.i6.355
                11235203
                38993588
                ffe0ac26-f441-43fd-a84d-e0d1dcf56965
                ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 19 March 2024
                : 7 May 2024
                : 27 May 2024
                Categories
                Meta-Analysis

                d-dimer,aortic dissection,mortality,biomarker,systematic review,meta-analysis

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