Cardiology

D-dimer for screening of aortic dissection in patients with ST-elevation myocardial infarction

a b s t r a c t

Background: Acute aortic dissection with concurrent ST-segment elevation myocardial infarction is relatively rare and sometimes overlooked. As D-dimer testing has been reported to have high sensitivity to di- agnose AAD in a clinical scale, Aortic Dissection Detection Risk Score (ADD-RS), a point-of-care D-dimer analyzer capable of measuring in 10 min would be useful to deny AAD with concurrent STEMI. However, an optimal cut- off value of D-dimer in such population remains unclear. Therefore, the aim of this study was to elucidate the op- timal D-dimer threshold in patients clinically diagnosed with STEMI. Methods: This retrospective cohort study was conducted at two Tertiary care centers between 2014 and 2019. Pa- tients clinically diagnosed with STEMI who underwent serum D-dimer measurement on hospital arrival were in- cluded. The primary outcome was the diagnosis of AAD. The area under the receiver operating characteristic curve (AUROC) for D-dimer values to diagnose AAD was evaluated, particularly in patients with low to moderate risks of AAD (1 of ADD-RS). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated with several cut-off values.

Results: A total of 322 patients were included, and 28 were diagnosed with AAD. The AUROC for D-dimer to diag- nose AAD was 0.970 (95% confidence interval: 0.948-0.993) in 262 patients with 1 of ADD-RS. If D-dimer >=750 ng/mL was used as a cut-off value, sensitivity, specificity, PPV and NPV were 100%, 86.4%, 37.7%, and 100%, respec- tively. AAD could be denied in 209 (79.8%) patients using the cut-off value (D-dimer <750 ng/mL).

Conclusions: Serum D-dimer >=750 ng/mL exhibited high sensitivity and NPV to diagnose AAD with concurrent STEMI, while the ADD-RS originally utilized >=500 ng/mL as a cut-off for any suspected AAD. A point-of-care D- dimer measurement with the new cut-off would be useful to rule-out AAD among patients with STEMI.

(C) 2022

  1. Introduction

Acute aortic dissection (AAD) is a life-threatening disease that re- quires emergency treatment including blood pressure management, surgery, and interventional radiology [1]. AAD is usually suspected when patients have acute-onset chest/back pain and is diagnosed with Computed tomography angiography , which has approximately 100% sensitivity and 98-99% specificity [1]. However, the rate of overlooking AAD is still as high as 24-39% [2,3]. Especially when patients are clinically diagnosed with ST-segment elevation myocardial infarction , coronary angiography needs to be conducted imme- diately and CTA, a time-consuming procedure, is often avoided [4].

* Corresponding author.

E-mail address: [email protected] (R. Yamamoto).

AAD with concurrent STEMI often has a devastating prognosis due to delayed surgery for AAD and/or antithrombotic medications adminis- tered for STEMI [2,3]. Although possibilities of coexisting AAD in pa- tients with STEMI is usually estimated with signs/symptoms, chest radiography (CXR), and ultrasound, their accuracy is not sufficient to exclude AAD [5]. Classical symptoms, such as abrupt, severe, ripping, and migrating chest/back pains have only 34-88%, 46-86%, 2-62%, and 39-69% of sensitivity for diagnosis of AAD, respectively [6]. CXR did not show any widened mediastinum in 37.4% of patients with type A-AAD [7]. An accuracy of ultrasound is largely dependent on phy- sicians’ skills, and the sensitivity was reported as 87%, which is not enough to rule-out AAD [8].

Recently, a clinical prediction score for AAD, Aortic Dissection Detec- tion Risk Score (ADD-RS), was developed, in which predisposing condi- tions, pain features, and physical examination findings were used to calculate a 0-3 score with (Table 1) [9]. Moreover, D-dimer testing

https://doi.org/10.1016/j.ajem.2022.07.024

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Table 1

Aortic Dissection Detection Risk Score (ADD-RS).

Predisposing conditions 1 point

Marfan syndrome, family history of aortic disease, known aortic valve disease recent aortic manipulation, or known thoracic aortic aneurysm

Pain features 1 point

Chest, back, or abdominal pain described as abrupt onset, severe intensity, or ripping/tearing

Physical examination findings 1 point

Perfusion deficit (pulse deficit, differential systolic blood in extremities, or focal neuro deficit), new aortic insufficiency murmur, or hypotension/shock

From the three sections, ADD-RS is calculated to 0-3 points. 0 or 1 of ADD-RS means low- moderate probability and ADD-RS >= 2 means high probability of acute aortic dissection.

has been reported to have high sensitivity (98-99%) to diagnose AAD in patients at low-moderate probability with a cut-off value of 500 ng/ml Fibrinogen Equivalent Units [10,11]. Notably, a point-of-care D- dimer analyzer capable of measuring in 10 min at bedside has been de- veloped and used clinically [12]. Accordingly, an algorithm utilizing both AAD-RS and D-dimer has been analyzed to appropriately diagnose AAD (patients with 0 or 1 of ADD-RS need D-dimer; Fig. 1), and prom- ising results were shown in some studies [13,14].

However, as D-dimer increases in STEMI [15], an optimal cut-off value of D-dimer for screening AAD with concurrent STEMI remains un- clear. AAD with concurrent STEMI usually involves the ascending tho- racic aorta (Stanford type A) [16], the false lumen of which tends to be continuously exposed to the blood without thrombus filling [17], and significant elevation of D-dimer levels has been reported in such pa- tients [18]. Therefore, the aim of this study was to elucidate the optimal D-dimer threshold in patients clinically diagnosed with STEMI. The hy- pothesis was that a D-dimer threshold higher than the current cut-off value (500 ng/mL FEU) would accurately diagnose AAD in patients with STEMI.

ADD-RS >= 2

ADD-RS = 0 or 1

Chest/abdominal/back pain, syncope, perfusion deficit

DD >= 500 ng/mL

DD < 500 ng/mL

D-Dimer (DD)

Acute aortic dissection ruled out

Computed tomography angiography

Fig. 1. Aortic Dissection Detection Risk Score plus D-dimer algorithm in suspected acute aortic dissection.

ADD-RS: Aortic Dissection Detection Risk Score, DD: D-dimer, CTA: computed tomography angiography.

Pre-test probability is calculated using the ADD-RS, which is the total score that considers three factors: predisposing conditions, pain features, and physical examination findings. Patients with 0 or 1 of ADD-RS are considered to have a low to moderate risk of acute aor- tic dissection (AAD), and serum DD level < 500 ng/mL can exclude AAD. Patients with DD level >= 500 ng/mL or ADD-RS >= 2 are considered to have a higher risk of AAD and should undergo CTA.

  1. Material and methods
    1. Study design and setting

This retrospective cohort study was conducted at two tertiary care centers, namely Keio University Hospital, Tokyo, Japan and Saiseikai Utsunomiya Hospital, Tochigi, Japan.

At the study institutions, emergency physicians initially assessed pa- tients who were transported by ambulance. When patients had chest and/or back pain, various tests including Electrocardiography , cardiac enzyme measurements, and CXR were performed in the emer- gency department (ED), while Transthoracic echocardiography and CTA were conducted as needed. When STEMI was suspected ac- cording to the ECG-based definition [19], cardiologists were consulted for Antithrombotic treatment and coronary angiography. Need for CTA was decided via discussions between the emergency physicians and cardiologists, particularly when coexisting AAD was suspected based on clinical information including perfusion deficit (unilateral pulse def- icit, difference in the systolic blood pressure between the extremities, or neurological focal signs), widened mediastinum on CXR, and consider- able signs on ultrasound (intimal flap, dilatation of the thoracic aorta, pericardial effusion, and aortic valve regurgitation). Cardiovascular sur- geons were consulted after AAD was diagnosed using CTA. D-dimer testing was performed almost randomly in patients with chest/back pain for differentiation of AAD or pulmonary embolism at the participat- ing hospitals, based on the preference of the treating physician, rather than clinical features of patients.

This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Keio University School of Medicine Ethics Committee (application number: 20211099). The requirement for informed consent was waived due to the anonymous nature of the data.

    1. Study population

We included patients with chest and/or back pain 1) who were > 20 years old, 2) whose ECG showed ST-segment elevation, and 3) whose serum D-dimer levels were measured upon arrival at the hospital. We excluded patients with cardiac arrest, end-stage malignancy, refusal of medical and surgical interventions, or a lack of diagnosis due to hospital transfer. We defined ST-segment elevation generally based on Fourth Universal Definition of Myocardial Infarction [19] and included cases with clinically suspected STEMI.

    1. Data collection and definition

We used data from April 2014 to March 2019. Data were extracted from electronic medical records. Available data included demographics; details of chest and/or back pain; comorbidities; vital signs at the time of admission; physical examination; ADD-RS (on a scale of 0-3) calculated as 1 point each for predisposing conditions, pain features, and examina- tion findings (Fig. 1); serum D-dimer level; CXR, TTE, and CTA findings; diagnosis at discharge from the ED; and Door-to-balloon time if coro- nary reperfusion therapy was performed. AAD was confirmed by CTA or aortography during coronary angiography. All CTA images were eval- uated by board-certified radiologists.

Blood samples were sent to the local laboratory and D-dimer was measured using latex-enhanced immunoassay (Nanopia D-dimer, Sekisui Medical, Japan) at Saiseikai Utsunomiya Hospital and latex pho- tometric immunoassay (LPIA-ACE D-dimer II or LPIA-GENESIS D-dimer, LSI Medience Corporation, Japan) at Keio University Hospital. In both the assays, results were obtained in D-dimer units, which can be con- verted to fibrinogen equivalent units (FEU) that are used globally [20]. Therefore, all D-dimer values were converted to FEU before the analy- ses. D-dimer level >= 500 ng/mL FEU was currently validated as an initial screening test for diagnosis of AAD [13,14].

379 met all inclusion criteria

57 patients were excluded: 49 cardiac arrest

1 end-stage malignancy 4 refusal of interventions 3 hospital transfer

322 were eligible to this study

19 ADD-RS = 0

0 AAD

262 ADD-RS = 1

20 AAD

41 ADD-RS > 1

8 AAD

Fig. 2. Patient flow diagram.

ECG: electrocardiogram, ADD-RS: Aortic Dissection Detection Risk Score, AAD: acute aortic dissection.

Among 4405 patients with chest and/or back pain, 379 met the following inclusion criteria: 1) > 20 years old, 2) ST-segment elevation on ECG, and 3) D-dimer testing imme- diately after arrival at the hospital. After 57 patients were excluded due to cardiac arrest, end-stage malignancy, refusal of medical and surgical interventions, or hospital transfer, 322 patients were eligible for the study. Primary analysis was performed for 262 patients (81.4%) who had 1 of ADD-RS.

    1. Outcome measures

The primary outcome was the diagnosis of AAD. The secondary out- comes were in-hospital mortality and the length of hospital stay.

    1. Statistical analysis

Descriptive statistics are presented as means and standard devia- tions, medians with interquartile ranges, or numbers with percentages. To analyze the discrimination and classification power of D-dimer, the included patients were divided based on the ADD-RS. Primary analysis included patients with 1 of ADD-RS, since ADD-RS >= 2 was validated to have high enough possibility of AAD to conduct CT with contrast and 0 of AAD-RS was expected to be rare in patients with STEMI (1 point is assigned to abrupt or severe chest pain). A receiver operating characteristic (ROC) curve for D-dimer values according to AAD diagno- sis was obtained and the area under the ROC curve (AUROC) was eval- uated. To obtain the most clinically feasible cut-offs for ruling out the possibility of coexisting AAD; the sensitivity, specificity, positive predic- tive value (PPV), and negative predictive value (NPV) were calculated based on several cut-off values of D-dimer, including 500 ng/ml, a cut- off value in the current algorithm [13]. Patients with indeterminate or missing results of D-dimer test and CTA or coronary angiography were not included in the analysis.

The discrimination of secondary outcomes according to D-dimer values was evaluated using the same cut-off values as those utilized for the primary outcome. Sensitivity analysis was also performed including patients with ADD-RS >= 1. In this analysis, discrimination and classifica- tion power was calculated using the same method described previously. Subgroup analyses were performed by dividing the patients accord- ing to age (>=65 vs. <65 years), mediastinum diameter on CXR (>=8.65 vs.

<8.65 cm) [21], and existence of D-dimer modifiers such as chronic kid- ney disease, thoracic and Abdominal aortic aneurysm, liver cirrhosis, and neoplastic diseases [22].

Exploratory analyses were also conducted on patients with STEMI, to elucidate differences in door-to-balloon time and in-hospital mortality between those with and without CTA. Statistical analyses were performed using IBM SPSS Statistics, version 27.0 (IBM Corp., Armonk, NY, USA).

Table 2

Patient characteristics of all eligible patients (n = 322)

36 not > 20 years old

3971 no ST-elevation on ECG

19 serum D-dimer not assayed

4405 arrived with chest/back pain

Age, years, median (IQR) 66 (55-75)

Sex, male, n (%) 251 (78.0%)

Comorbidity, n (%)

Hypertension 188 (58.4%)

Diabetes mellitus 117 (36.3%)

Ever smoker 219 (68.0%)

Coronary artery disease 28 (8.7%)

Details of pain

Time from onset to arrival, h, median (IQR) 1.7 (0.9-3.9)

Chest pain, n (%) 299 (95.8%)

Back pain, n (%) 53 (17.0%)

Vital signs on presentation

Systolic blood pressure, mmHg 142 +- 35

Heart rate, /min 75 +- 19

Hypotension, n (%) 45 (14.0%)

ADD-RS

ADD-RS = 0, n (%) 19 (5.9%)

ADD-RS = 1, n (%) 262 (81.4%)

ADD-RS > 1, n (%) 41 (12.7%)

D-dimer (DD) ng/mL FEU

DD < 500, n (%) 221 (68.6%)

500 <= DD <1000, n (%) 45 (14.0%)

1000 <= DD < 10,000, n (%) 43 (13.4%)

10,000 <= DD, n (%) 13 (4.0%)

DD in AAD, median (IQR) 5900 (1288-36,462)

DD in STEMI, median (IQR) 350 (300-500)

Time from hospital arrival to D-dimer test, min (IQR) 7 (4-13)

Computed tomography angiography (CTA), n (%) 71 (22.0%) Coronary angiography, n (%) 301 (93.5%)

Diagnosis, n (%)

Aortic dissection 28 (8.7%)

Stanford type A 17 (5.3%)

Stanford type B 11 (3.4%)

STEMI 268 (83.2%)

Others 28 (8.7%)

VSA 11 (3.4%)

Takotsubo cardiomyopathy 5 (1.6%)

acute pericarditis 1 (0.3%)

Treatment

Anti-thrombotic medication to AAD, n (%) 8 (28.6%)

Door-to-balloon time for STEMI

without CTA, min, median (IQR) 73 (57-88)

with CTA, min, median (IQR) 81 (66-113)

In-hospital death, n (%) 13 (4.0%)

Aortic dissection 6 (21.4%)

Aortic dissection with AT? 3 (37.5%)

STEMI 8 (3.0%)

Hospital length of stay, d, median (IQR) 9 (6-12)

Data are presented as number (%), mean +- standard deviation, or median (interquartile range).

IQR: interquartile range, ADD-RS: aortic dissection detection risk score, FEU: fibrinogen equivalent units, AAD: acute aortic dissection, STEMI: ST-segment elevation myocardial infarction, VSA: vasospastic angina, CTA: computed tomography angiography, AT: anti- thrombotic medication.

* Patients with aortic dissection who received anti-thrombotic medication in emergency

department.

  1. Results
    1. Patient characteristics

Altogether, 4405 patients with chest and/or back pain were identi- fied. Among these, 379 met all the inclusion criteria. Fifty-seven patients were excluded due to cardiac arrest, end-stage malignancy, refusal of medical and surgical interventions, or hospital transfer. Thus, 322 pa- tients were eligible for this study (Fig. 2).

Patient characteristics are presented in Table 2. The median age was 66 years. The ADD-RS was 0 in 19 (5.9%) patients, 1 in 262 (81.4%)

ADD-RS = 1 (n = 262) ALL (n = 322)

AUROC = 0.970

(95% CI: 0.948-0.993)

AUROC = 0.951

(95% CI: 0.918-0.984)

Fig. 3. Receiver operating characteristic curves for D-dimer levels according to the diagnosis of acute aortic dissection in patients with 1 of Aortic Dissection Detection Risk Score (A) and all eligible patients (B).

AUROC: area under the receiver operating characteristic curve, ROC: receiver operating characteristic, ADD-RS: Aortic Dissection Detection Risk Score, CI: confidence interval. The AUROC for D-dimer to diagnose acute aortic dissection was 0.970 (95% CI: 0.948-0.993) in 262 patients with 1 of ADD-RS. For all eligible patients (n = 322), the AUROC was 0.951 (95% CI: 0.918-0.984).

patients, and >= 2 in 41 (12.7%) patients. Furthermore, 221 (68.6%) pa- tients had D-dimer level < 500 ng/mL FEU; 45 (14.0%) had D-dimer level of >=500 and <1000 ng/mL; 43 (13.4%) had D-dimer level of

>=1000 and <10,000 ng/mL; and 13 (4.0%) had D-dimer level >= 10,000 ng/mL. Aortic dissection was diagnosed in 28 patients (17 [5.3%] with Stanford type A and 11 [3.4%] with Stanford type B). Definitive diagnosis of STEMI was established in 268 patients (83.2%). In patients with STEMI, door-to-balloon time was significantly shorter when CTA was not performed (73 min without CTA vs. 81 min with CTA; Table 2 and Table S1 [Supplemental material]).

In-hospital mortality was 21.4% in patients with AAD (37.5% in pa- tients with AAD receiving anti-thrombotic medication) and 3.0% in pa- tients with STEMI.

    1. D-dimer and the diagnosis of acute aortic dissection

The ROC curves for D-dimer values according to the diagnosis of AAD are depicted in Fig. 3. The AUROC was 0.970 (95% confidence interval [CI]: 0.948-0.993) in patients with 1 of ADD-RS. The classification power for each cut-off value is presented in Table 3. With D-dimer

and NPV were 100%, 86.4%, 37.7%, and 100%, respectively. In addition, AAD could be denied in 209 (79.8%) patients using the cut-off value (D-dimer <750 ng/mL). Conversely, a cut-off value of 10,000 ng/mL ex- hibited high specificity and PPV (99.6% and 88.9%, respectively).

In the sensitivity analyses (Table S2 [Supplemental material]), pa-

tients with ADD-RS > 1 were included along with those having 1 of ADD-RS. The AUROC for D-dimer values was 0.952 (95% CI: 0.919-0.985). D-dimer level >= 750 ng/mL exhibited a high NPV (99.2%), while D-dimer level >= 10,000 ng/mL exhibited a high PPV (92.3%).

Subgroup analyses revealed that the sensitivity and NPV of the cut-off value of 750 ng/mL remained at 100%, and specificity and PPV decreased in patients aged >=65 years and patients with any D-dimer modifier (Table 4). In patients with widened mediastinum on CXR, specificity decreased to 81% but PPV increased from 32.3% to 45.5% (Table 4).

Table 4

Subgroup analyses with D-dimer >=750 ng/mL as cut-off value in patients with 1 of ADD-RS.

>=500 ng/mL, the current cut-off value, sensitivity, specificity, PPV, and NPV were 100%, 76.5%, 26.0%, and 100%, respectively, while >=750 ng/mL had similar classification abilities; sensitivity, specificity, PPV,

Subgroup analysis in

ADD-RS = 1

Age

AUROC Sensitivity Specificity PPV NPV

>=65 years

0.883 (0.813-0.953)

100%

79.7%

17.6%

100%

<65 years

0.994 (0.982-1.000)

100%

95.2%

73.7%

100%

Table 3

Serum D-dimer levels associated with aortic dissection in the group of ADD-RS = 1 (n = 262).

D-dimer modifier? with any modifiers

0.787 (0.478-1.000) 100% 57.5% 10.5% 100%

no modifiers 0.994 (0.982-1.000) 100% 92.1% 52.9% 100%

Cutoff value of D-dimer (ng/mL)

>=500

>=750

>=1000

>=2000

>=5000

>=10,000

Sensitivity (%)

100

100

90.0

70.0

60.0

40.0

Specificity (%)

76.5

86.4

89.3

97.5

99.2

99.6

Positive predictive value

(%)

26.0

37.7

40.9

70.0

85.7

88.9

Negative predictive value

(%)

100

100

99.1

97.5

96.8

95.3

Patients with D-dimer <

185

209

218

242

248

253

cut-off value, n (%)

(70.6)

(79.8)

(83.2)

(92.4)

(94.7)

(96.6)

Chest X ray

widened 0.959 (0.912-1.000) 100% 81.0% 45.5% 96.5%

mediastinum

no widened mediastinum

0.977 (0.953-1.000) 100% 88.3% 32.3% 100%

ADD-RS: Aortic Dissection Detection Risk Score, AUROC: area under the receiver operating characteristic curve, CI: confidence interval, PPV: positive predictive value, NPV: negative predictive value.

* D-dimer modifiers included chronic kidney disease, thoracic and abdominal aortic an- eurysm, liver cirrhosis, or neoplastic diseases.

    1. D-dimer and secondary outcomes

In-hospital mortality increased linearly with D-dimer values, and the length of hospital stay also increased with D-dimer values (Table S3 [Supplemental material]). In patients with D-dimer level >= 750 ng/mL, in-hospital mortality was 9.4% and the length of hospital stay was 13 days.

  1. Discussion

The present study revealed that D-dimer level >= 750 ng/mL exhib- ited high sensitivity and NPV and this level could be feasible as a new screening cut-off value to rule-out coexisting AAD in patients with chest/back pain and ST-segment elevation on ECG. We also observed that D-dimer level >= 10,000 ng/mL exhibited high specificity and PPV in the diagnosis of AAD.

Notably, a point-of-care D-dimer analyzer has been developed, en- abling the measurement of D-dimer in 10 min at bedside [12], although usual D-dimer immunoassays generate results within 30-60 min. Adopting the new D-dimer cut-off value in the current algorithm would allow adequate screening for AAD with 100% sensitivity and NPV, and avoid unnecessary CTA in 79.8% of patients clinically diag- nosed with STEMI.

The idea of utilizing D-dimer to diagnose or rule-out AAD is based on the pathophysiological mechanism of aortic dissection. An intimal tear of the aortic vessel causes blood contact with subcutaneous collagen, leading to activation of the coagulation cascade [23]. In addition, a large amount of tissue factor is released, which leads to hypercoagula- tion and secondary hyperfibrinolysis [24]. Therefore, D-dimer is rapidly elevated at the beginning of AAD. D-dimer has been studied as a diag- nostic and Prognostic biomarker for AAD [10-14,25]. In this study, AUROC for D-dimer to diagnose AAD exhibited significantly high accu- racy as 0.970 (95% CI: 0.948-0.993) in patients with 1 of ADD-RS. How- ever, AUROC in all patients was 0.951 (95% CI: 0.918-0.984) and tended to be lower than AUROC in patients with 1 of ADD-RS.

One of the pathophysiological reasons behind the higher cut-off value of D-dimer is elevation of D-dimer in STEMI even without AAD, since ruptured plaque induces coronary thrombus [15,26]. Moreover, AAD with concurrent STEMI usually involves the ascending thoracic aorta (Stanford type A) [16], the false lumen of which tends to be con- tinuously exposed to the blood without thrombus filling [17], and sig- nificant elevation of D-dimer levels has been reported in such patients [18]. Notably, increasing the D-dimer cut-off level from 500 ng/mL to 750 ng/mL could increase the percentage of patients who would not re- quire CTA to 79.8%. Considering that door-to-balloon time was pro- longed by 8 min by CTA in patients with STEMI in this study, avoiding unnecessary CTA would be clinically important.

The sensitivity and NPV of the cut-off value of 750 ng/mL remained at 100% in the all the subgroup analyses (Table S3 [Supplementary ma- terial]). Conversely, patients with aged >=65 years and D-dimer- modifiers such as chronic kidney disease, thoracic and abdominal aortic aneurysm, liver cirrhosis, or neoplastic diseases exhibited a lower spec- ificity and PPV. This might be from the fact that D-dimer levels in such patients increased even without AAD [12,22]. Therefore, physicians should need to take account of false positives in this population. More- over, PPV at 750 ng/ml of cut-off was increased from 32.3% to 45.5% in patients with widen mediastinum, while specificity decreased from 88.3% to 81%.

The present study has several limitations. Due to the limited sample size, generalizability of the D-dimer cut-off value is a concern. D-dimer measurement was performed immediately after arrival at the hospital. However, the duration from the onset of symptoms to D-dimer mea- surement was not analyzed in this study. A previous study suggested that D-dimer might effectively rule-out AAD when it is measured within 24 h of symptom onset [27]. Further studies are needed to validate the new cut-off value, especially with consideration to the duration

between the symptom onset and D-dimer measurement. Although D- dimer was measured almost randomly in most of the patients with chest pain, the indications for D-dimer measurement were not recorded in the medical charts. Therefore, an unmeasured bias in the indications for D-dimer testing might have influenced the outcomes.

  1. Conclusions

Serum D-dimer >=750 ng/mL exhibited high sensitivity and NPV to diagnose AAD with concurrent STEMI, while the ADD-RS originally uti- lized >=500 ng/mL as a cut-off for any suspected AAD. A point-of-care D- dimer measurement with the new cut-off would be useful to rule-out AAD among patients with STEMI. D-Dimer test might prevent overlooking AAD with concurrent STEMI, and the new cutoff value would reduce unnecessary CTA.

Funding

No funding was received for this study.

Prior presentations

None.

Declaration of Competing Interest

The authors declare no conflicts of interest.

Acknowledgements

Dai Kujirai, Manabu Izumi (Saiseikai Utsunomiya Hospital), and Masaki Ano (Haga Red Cross Hospital) advised for concept and analysis of the article. Chiho Oshima (Keio University School of Medicine) sup- ported data collection. Editage (www.editage.com) edited the article for English language.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2022.07.024.

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