TY - JOUR
AU - Luo,, Jianfang
AB - Abstract View largeDownload slide View largeDownload slide OBJECTIVES The aim of this study was to identify patients who are at high risk of developing postimplantation syndrome (PIS) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection. METHODS This retrospective study included 646 patients who underwent TEVAR for type B aortic dissection between January 2010 and December 2015 at the Guangdong General Hospital. PIS was defined as fever (>38°C) and leucocytosis (>12 000 μl−1) without evidence of infection. The PIS rate was calculated, and a multivariable logistic regression model was used to investigate the factors related to PIS. RESULTS A total of 646 patients (58.8 ± 11.0 years, 87.9% men) were included in the analysis. PIS was diagnosed in 204 (31.6%) patients. Age <60 years [odds ratio (OR) 1.828, 95% confidence interval (CI) 1.277–2.619; P < 0.001), hypertension (OR 12.125, 95% CI 4.310–34.111; P < 0.001), >1 stent graft placed (OR 1.862, 95% CI 1.109–3.124; P = 0.011), arch vessel bypass (OR 2.107, 95% CI 1.397–3.176; P = 0.001) and Ankura stent graft placement (OR 1.951, 95% CI 1.298–2.933; P = 0.001) were positively associated with PIS, whereas statin use (OR 0.659, 95% CI 0.460–0.944; P = 0.023) was negatively associated with PIS in the multivariable logistic regression analysis based on a stepwise regression model. CONCLUSIONS Age <60 years, comorbid hypertension, >1 stent graft placed, arch vessel bypass and Ankura stent graft placement emerged as independent predictors of PIS. Stepwise increases in the prevalence of PIS were found to depend on the number of independent predictors. Type B aortic dissection, Postimplantation syndrome, Thoracic endovascular aortic repair INTRODUCTION The clinical manifestation of a systemic inflammatory response called postimplantation syndrome (PIS) was initially observed in patients treated with endovascular aortic repair (EVAR) for infrarenal abdominal aortic aneurysms [1, 2]. The major clinical features of PIS are postoperative fever despite negative blood cultures and leucocytosis. Thoracic endovascular aortic repair (TEVAR) has emerged as an optimal therapy for type B aortic dissection (TBAD), which is characterized by significant early and late morbidity and mortality [3, 4]. The incidence of PIS and its impact on clinical outcomes after TEVAR have rarely been investigated. Recently, PIS after TEVAR was found to be an independent predictor of major adverse events, together with aortic enlargement, partial thrombosis of the false lumen and stroke [5]. To better understand this inflammatory process in patients with TBAD treated with TEVAR, this study aimed to determine the incidence of PIS and to identify patients who are at higher risk of developing PIS after TEVAR for TBAD. MATERIALS AND METHODS Patients This study was a single-institute, retrospective observational analysis of patients with TBAD treated with TEVAR between November 2010 and December 2015. TEVAR was performed as the following indications were present: persistent or recurrent pain; uncontrolled hypertension despite medical treatment; early aortic expansion; malperfusion of the viscera or limbs; or signs of rupture (haemothorax, increasing periaortic and mediastinal haematoma). Additional factors such as false lumen diameter, location of the primary entry tear and retrograde component of the dissection into the aortic arch were also considered for elective TEVAR. Patients with the following predisposing factors and clinical conditions influencing baseline inflammatory status or precluding the observation of their postimplantation conditions were excluded: (i) patients with proximal landing zone 0 subjected to open-heart surgery; (ii) myocardial infarction or unstable angina treated with dual antiplatelet therapy; (iii) history of a malignant tumour and terminal stage of any disease; (iv) immediate death after the procedure; (v) findings of pulmonary, urinary or skin infection and recent (<7 days) antibiotic therapy or (vi) treatment with anti-inflammatory, immunosuppressant or other immune-modifying agents for any reason. Our institutional ethics board approved this retrospective study, and written informed consent was obtained from the patients before the procedure. The patient flow diagram of this hospital-based cohort study is shown in Fig. 1. Figure 1: View largeDownload slide Patient flow diagram of this hospital-based cohort study. TBAD: type B aortic dissection; TEVAR: thoracic endovascular aortic repair. Figure 1: View largeDownload slide Patient flow diagram of this hospital-based cohort study. TBAD: type B aortic dissection; TEVAR: thoracic endovascular aortic repair. Definition PIS was defined as follows: (i) the presence of fever during hospitalization (persisting body temperature >38°C lasting over 1 day after TEVAR) and (ii) leucocytosis [white blood cell (WBC) count >12 000/ml] with negative blood culture results when infectious complications were excluded. Laboratory examination All TBAD patients admitted to our division underwent the laboratory examinations recommended by the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2010 guidelines [6]. Data on serum levels of haemoglobin (HGB), red blood cells (RBCs), WBCs, neutrophil ratio (N%), platelet (PLT) count, creatinine (Cr), D-dimer (DDI), fibrinogen (FIB), procalcitonin (PCT), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were collected daily after TEVAR. The highest values over 72 h were used for analysis. Triple blood cultures were collected from different venous access points if the patient’s temperature remained >38.0°C. Microbial culture analyses from the throat, urine and stool were performed routinely. Surgical details TEVAR was performed by a multidisciplinary team comprising interventional cardiologists, cardiothoracic surgeons, anaesthesiologists and intensivists. The procedure has been described in detail in a previous study performed at our centre [7]. The following stent grafts were implanted: Valiant (Medtronic Vascular, Santa Rosa, CA, USA), Zenith (Cook Inc., Bloomington, IN, USA), Hercules (Microport, Shanghai, China) and Ankura (Lifetech, Shenzhen, China). All patients received a single intravenous injection of antibiotics (cefazolin, 2 g) at the beginning of the procedure; the use of antibiotics during follow-up was at the discretion of the attending ward physician. For patients with proximal landing zones 1 and 2 or an aberrant right subclavian artery, carotid-to-carotid bypass and/or carotid-to-subclavian bypass was performed under general anaesthesia and cerebral flow monitoring using cerebral oximetry in a hybrid operating room. The procedure has been described in detail elsewhere [8]. Treatment algorithm according to proximal landing zone is reported in Supplementary Figure 1. Statistical analyses All analyses were performed using the SPSS software version 24.0 (IBM Corp., Armonk, NY, USA). For continuous variables, the normal distribution was confirmed using the Shapiro–Wilk test and presented as the mean ± standard deviation. For skewed continuous variables, the median (interquartile range) was used to describe distributions. The Student’s t-test or the Mann-Whitney U-test was used to analyse the difference in distribution of continuous variables. Categorical variables are presented as proportions (%) and analysed with the Pearson χ2 test or the the Fisher’s exact test (if the expected count was <5). A multivariable logistic regression analysis was used to elucidate the independent predictors of PIS, and a 2-sided P-value <0.05 was considered statistically significant. RESULTS Clinical characteristics of the study population A total of 646 patients (58.8 ± 11.0 years, 87.9% men) were included in the study. PIS was diagnosed in 204 (31.6%) patients. Baseline and preoperative characteristics in patients with and without PIS are provided in Table 1. Patients with PIS were significantly younger than those without PIS (51.9 ± 10.3 vs 55.4 ± 11.2, P < 0.001). Interestingly, patients treated with angiotensin-converting enzyme inhibitors or statins were less likely to develop PIS (15.7 vs 23.3%, P = 0.027; 39.2 vs 49.5%, P = 0.014). Table 1: Baseline characteristics of the study population divided according to the presence of PIS Variables Total (N = 646) PIS (N = 204) Non-PIS (N = 442) P-value Demographic characteristics  Age (years), mean ± SD 58.8 ± 11.0 51.9 ± 10.3 55.4 ± 11.2 <0.001  Age <60 years, n (%) 328 (50.8) 236 (53.4) 82 (40.2) 0.002  Male gender, n (%) 568 (87.9) 181 (88.7) 387 (87.6) 0.672 Comorbidities, n (%)  Hypertension 563 (87.2) 200 (98.0) 363 (82.1) <0.001  CAD 64 (9.9) 21 (10.3) 43 (9.7) 0.887  COPD 7 (1.1) 4 (3.1) 3 (0.7) 0.215a  Diabetes mellitus 46 (7.1) 12 (5.9) 34 (7.7) 0.511  Stroke 11 (1.7) 2 (1.0) 9 (2.0) 0.516a  Smoking 321 (49.7) 100 (49.0) 221 (50.0) 0.817 Medication treatment, n (%)  β-blockers 602 (93.2) 189 (92.6) 413 (93.6) 0.710  ɑ-blockers 139 (21.5) 43 (21.1) 96 (21.7) 0.854  ACEIs 135 (20.9) 32 (15.7) 103 (23.3) 0.027  ARBs 273 (42.3) 54 (41.9) 173 (42.3) 0.892  CCBs 486 (75.2) 147 (72.1) 339 (76.7) 0.204  Statins 299 (46.3) 80 (39.2) 219 (49.5) 0.014 Hospitalization post-TEVAR (days), mean ± SD 9.1 ± 6.4 11.5 ± 8.0 8.1 ± 5.4 <0.001 Temperature >38°C within 120 h, n (%) 315 (48.8) 196 (96.1) 119 (27.0) <0.001 All-cause mortality, n (%) 11 (1.7) 5 (2.5) 6 (1.4) 0.336a Specific complications, n (%)  Stroke 18 (2.8) 4 (2.0) 14 (3.2) 0.386  Acute renal failure 15 (2.3) 4 (2.0) 11 (3.2) 0.785a  Acute heart failure 6 (0.9) 1 (0.5) 5 (2.5) 0.671a  Reinterventionb 3 (0.5) 1 (0.5) 2 (0.5) 1.000a Variables Total (N = 646) PIS (N = 204) Non-PIS (N = 442) P-value Demographic characteristics  Age (years), mean ± SD 58.8 ± 11.0 51.9 ± 10.3 55.4 ± 11.2 <0.001  Age <60 years, n (%) 328 (50.8) 236 (53.4) 82 (40.2) 0.002  Male gender, n (%) 568 (87.9) 181 (88.7) 387 (87.6) 0.672 Comorbidities, n (%)  Hypertension 563 (87.2) 200 (98.0) 363 (82.1) <0.001  CAD 64 (9.9) 21 (10.3) 43 (9.7) 0.887  COPD 7 (1.1) 4 (3.1) 3 (0.7) 0.215a  Diabetes mellitus 46 (7.1) 12 (5.9) 34 (7.7) 0.511  Stroke 11 (1.7) 2 (1.0) 9 (2.0) 0.516a  Smoking 321 (49.7) 100 (49.0) 221 (50.0) 0.817 Medication treatment, n (%)  β-blockers 602 (93.2) 189 (92.6) 413 (93.6) 0.710  ɑ-blockers 139 (21.5) 43 (21.1) 96 (21.7) 0.854  ACEIs 135 (20.9) 32 (15.7) 103 (23.3) 0.027  ARBs 273 (42.3) 54 (41.9) 173 (42.3) 0.892  CCBs 486 (75.2) 147 (72.1) 339 (76.7) 0.204  Statins 299 (46.3) 80 (39.2) 219 (49.5) 0.014 Hospitalization post-TEVAR (days), mean ± SD 9.1 ± 6.4 11.5 ± 8.0 8.1 ± 5.4 <0.001 Temperature >38°C within 120 h, n (%) 315 (48.8) 196 (96.1) 119 (27.0) <0.001 All-cause mortality, n (%) 11 (1.7) 5 (2.5) 6 (1.4) 0.336a Specific complications, n (%)  Stroke 18 (2.8) 4 (2.0) 14 (3.2) 0.386  Acute renal failure 15 (2.3) 4 (2.0) 11 (3.2) 0.785a  Acute heart failure 6 (0.9) 1 (0.5) 5 (2.5) 0.671a  Reinterventionb 3 (0.5) 1 (0.5) 2 (0.5) 1.000a a P-value was calculated using the Fisher’s exact test. b Indications for reintervention include aortic rupture (n = 2) and acute coronary syndrome (n = 1). ACEIs: angiotensin-converting enzyme inhibitors; ARB: angiotensin receptor antagonist; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; CCB: calcium channel blocker; PIS: postimplantation syndrome; SD: standard deviation; TEVAR: thoracic endovascular aortic repair. View Large Table 1: Baseline characteristics of the study population divided according to the presence of PIS Variables Total (N = 646) PIS (N = 204) Non-PIS (N = 442) P-value Demographic characteristics  Age (years), mean ± SD 58.8 ± 11.0 51.9 ± 10.3 55.4 ± 11.2 <0.001  Age <60 years, n (%) 328 (50.8) 236 (53.4) 82 (40.2) 0.002  Male gender, n (%) 568 (87.9) 181 (88.7) 387 (87.6) 0.672 Comorbidities, n (%)  Hypertension 563 (87.2) 200 (98.0) 363 (82.1) <0.001  CAD 64 (9.9) 21 (10.3) 43 (9.7) 0.887  COPD 7 (1.1) 4 (3.1) 3 (0.7) 0.215a  Diabetes mellitus 46 (7.1) 12 (5.9) 34 (7.7) 0.511  Stroke 11 (1.7) 2 (1.0) 9 (2.0) 0.516a  Smoking 321 (49.7) 100 (49.0) 221 (50.0) 0.817 Medication treatment, n (%)  β-blockers 602 (93.2) 189 (92.6) 413 (93.6) 0.710  ɑ-blockers 139 (21.5) 43 (21.1) 96 (21.7) 0.854  ACEIs 135 (20.9) 32 (15.7) 103 (23.3) 0.027  ARBs 273 (42.3) 54 (41.9) 173 (42.3) 0.892  CCBs 486 (75.2) 147 (72.1) 339 (76.7) 0.204  Statins 299 (46.3) 80 (39.2) 219 (49.5) 0.014 Hospitalization post-TEVAR (days), mean ± SD 9.1 ± 6.4 11.5 ± 8.0 8.1 ± 5.4 <0.001 Temperature >38°C within 120 h, n (%) 315 (48.8) 196 (96.1) 119 (27.0) <0.001 All-cause mortality, n (%) 11 (1.7) 5 (2.5) 6 (1.4) 0.336a Specific complications, n (%)  Stroke 18 (2.8) 4 (2.0) 14 (3.2) 0.386  Acute renal failure 15 (2.3) 4 (2.0) 11 (3.2) 0.785a  Acute heart failure 6 (0.9) 1 (0.5) 5 (2.5) 0.671a  Reinterventionb 3 (0.5) 1 (0.5) 2 (0.5) 1.000a Variables Total (N = 646) PIS (N = 204) Non-PIS (N = 442) P-value Demographic characteristics  Age (years), mean ± SD 58.8 ± 11.0 51.9 ± 10.3 55.4 ± 11.2 <0.001  Age <60 years, n (%) 328 (50.8) 236 (53.4) 82 (40.2) 0.002  Male gender, n (%) 568 (87.9) 181 (88.7) 387 (87.6) 0.672 Comorbidities, n (%)  Hypertension 563 (87.2) 200 (98.0) 363 (82.1) <0.001  CAD 64 (9.9) 21 (10.3) 43 (9.7) 0.887  COPD 7 (1.1) 4 (3.1) 3 (0.7) 0.215a  Diabetes mellitus 46 (7.1) 12 (5.9) 34 (7.7) 0.511  Stroke 11 (1.7) 2 (1.0) 9 (2.0) 0.516a  Smoking 321 (49.7) 100 (49.0) 221 (50.0) 0.817 Medication treatment, n (%)  β-blockers 602 (93.2) 189 (92.6) 413 (93.6) 0.710  ɑ-blockers 139 (21.5) 43 (21.1) 96 (21.7) 0.854  ACEIs 135 (20.9) 32 (15.7) 103 (23.3) 0.027  ARBs 273 (42.3) 54 (41.9) 173 (42.3) 0.892  CCBs 486 (75.2) 147 (72.1) 339 (76.7) 0.204  Statins 299 (46.3) 80 (39.2) 219 (49.5) 0.014 Hospitalization post-TEVAR (days), mean ± SD 9.1 ± 6.4 11.5 ± 8.0 8.1 ± 5.4 <0.001 Temperature >38°C within 120 h, n (%) 315 (48.8) 196 (96.1) 119 (27.0) <0.001 All-cause mortality, n (%) 11 (1.7) 5 (2.5) 6 (1.4) 0.336a Specific complications, n (%)  Stroke 18 (2.8) 4 (2.0) 14 (3.2) 0.386  Acute renal failure 15 (2.3) 4 (2.0) 11 (3.2) 0.785a  Acute heart failure 6 (0.9) 1 (0.5) 5 (2.5) 0.671a  Reinterventionb 3 (0.5) 1 (0.5) 2 (0.5) 1.000a a P-value was calculated using the Fisher’s exact test. b Indications for reintervention include aortic rupture (n = 2) and acute coronary syndrome (n = 1). ACEIs: angiotensin-converting enzyme inhibitors; ARB: angiotensin receptor antagonist; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; CCB: calcium channel blocker; PIS: postimplantation syndrome; SD: standard deviation; TEVAR: thoracic endovascular aortic repair. View Large After TEVAR, prolonged hospitalization and a notable systemic inflammatory response were observed in patients with PIS, but no significant differences were found in postoperative outcomes during hospitalization (Tables 1 and 2). In total, 196 of 204 (96.1%) PIS patients presented with body temperature of >38°C within 120 h in our study. The other 8 patients in the PIS group presented with body temperature of >38°C at 6, 6, 6, 7, 7, 8, 12 and 13 days during hospitalization. There was a significant increase in the WBC, DDI, ESR and CRP levels post-TEVAR in the PIS group, whereas there were no significant differences in HGB, PLT, Cr or PCT levels. Characteristics of the study population divided according to the acute, subacute and chronic phase are reported in Supplementary Table 1 and Supplementary Figure 2. Table 2: Laboratory parameters of the study population Variables Total (N = 646) (N = 204) (N = 442) P-value Baseline  Haemoglobin (g/l), mean ± SD 128.7 ± 17.0 128.4 ± 16.7 128.1 ± 17.1 0.687  WBC (×109/l), median (IQR) 10.1 (8.0–12.4) 10.6 (8.7–12.7) 9.9 (7.9–12.3) 0.077  Platelet (×106/l), median (IQR) 204.0 (159.0–269.8) 213.0 (168.4–296.4) 200.5 (156.9–262.3) 0.131  Creatinine (μmol/l), median (IQR) 87.1 (72.0–117.5) 89.5 (70.9–114.5) 87.0 (72.9–118.8) 0.588  Fibrinogen (mg/ml), median (IQR) 5.6 (4.8–6.8) 5.7 (4.9–6.7) 5.8 (4.9–6.9) 0.516  D-dimer (mg/l), median (IQR) 1225.0 (430.5–2770) 1340.0 (478.5–2615.0) 1110.0 (430.0–2840.0) 0.807 Peak value within 72 h post-TEVAR  Haemoglobin (g/l), mean ± SD 115.7 ± 17.4 113.6 ± 17.7 116.4 ± 17.2 0.168  WBC (×109/l), median (IQR) 12.9 (10.9–15.8) 14.8 (12.9–17.0) 12.0 (10.3–15.3) <0.001  Platelet (×106/l), median (IQR) 224.9 (170.7–293.3) 233.0 (175.0–305.0) 222.3 (162.9–288.5) 0.103  Creatinine (μmol/l), median (IQR) 94.0 (74.7–129.0) 99.9 (75.0–132.0) 93.0 (74.2–127.4) 0.511  Fibrinogen (mg/ml), median (IQR) 5.7 (4.5–7.4) 5.4 (4.4–6.6) 6.1 (4.8–7.5) 0.371  D-dimer (mg/l), median (IQR) 2580.0 (837.5–6205.0) 3140.0 (874.0–9640.0) 2511.5 (830.0–5199.8) 0.097  ESR (mm), median (IQR) 46.0 (17.0–84.75) 54.0 (17.0–98.0) 44.0 (17.0–82.0) 0.002  CRP (mg/l), median (IQR) 77.5 (19–143.0) 88.8 (21.0–168.5) 74.2 (18.0–133.0) <0.001  PCT (μg/l), median (IQR) 0.5 (0.2–0.6) 0.4 (0.2–0.7) 0.5 (0.2–0.6) 0.727 Variables Total (N = 646) (N = 204) (N = 442) P-value Baseline  Haemoglobin (g/l), mean ± SD 128.7 ± 17.0 128.4 ± 16.7 128.1 ± 17.1 0.687  WBC (×109/l), median (IQR) 10.1 (8.0–12.4) 10.6 (8.7–12.7) 9.9 (7.9–12.3) 0.077  Platelet (×106/l), median (IQR) 204.0 (159.0–269.8) 213.0 (168.4–296.4) 200.5 (156.9–262.3) 0.131  Creatinine (μmol/l), median (IQR) 87.1 (72.0–117.5) 89.5 (70.9–114.5) 87.0 (72.9–118.8) 0.588  Fibrinogen (mg/ml), median (IQR) 5.6 (4.8–6.8) 5.7 (4.9–6.7) 5.8 (4.9–6.9) 0.516  D-dimer (mg/l), median (IQR) 1225.0 (430.5–2770) 1340.0 (478.5–2615.0) 1110.0 (430.0–2840.0) 0.807 Peak value within 72 h post-TEVAR  Haemoglobin (g/l), mean ± SD 115.7 ± 17.4 113.6 ± 17.7 116.4 ± 17.2 0.168  WBC (×109/l), median (IQR) 12.9 (10.9–15.8) 14.8 (12.9–17.0) 12.0 (10.3–15.3) <0.001  Platelet (×106/l), median (IQR) 224.9 (170.7–293.3) 233.0 (175.0–305.0) 222.3 (162.9–288.5) 0.103  Creatinine (μmol/l), median (IQR) 94.0 (74.7–129.0) 99.9 (75.0–132.0) 93.0 (74.2–127.4) 0.511  Fibrinogen (mg/ml), median (IQR) 5.7 (4.5–7.4) 5.4 (4.4–6.6) 6.1 (4.8–7.5) 0.371  D-dimer (mg/l), median (IQR) 2580.0 (837.5–6205.0) 3140.0 (874.0–9640.0) 2511.5 (830.0–5199.8) 0.097  ESR (mm), median (IQR) 46.0 (17.0–84.75) 54.0 (17.0–98.0) 44.0 (17.0–82.0) 0.002  CRP (mg/l), median (IQR) 77.5 (19–143.0) 88.8 (21.0–168.5) 74.2 (18.0–133.0) <0.001  PCT (μg/l), median (IQR) 0.5 (0.2–0.6) 0.4 (0.2–0.7) 0.5 (0.2–0.6) 0.727 CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; IQR: interquartile range; PCT: procalcitonin; SD: standard deviation; TEVAR: thoracic endovascular aortic repair; WBC: white blood cell. View Large Table 2: Laboratory parameters of the study population Variables Total (N = 646) (N = 204) (N = 442) P-value Baseline  Haemoglobin (g/l), mean ± SD 128.7 ± 17.0 128.4 ± 16.7 128.1 ± 17.1 0.687  WBC (×109/l), median (IQR) 10.1 (8.0–12.4) 10.6 (8.7–12.7) 9.9 (7.9–12.3) 0.077  Platelet (×106/l), median (IQR) 204.0 (159.0–269.8) 213.0 (168.4–296.4) 200.5 (156.9–262.3) 0.131  Creatinine (μmol/l), median (IQR) 87.1 (72.0–117.5) 89.5 (70.9–114.5) 87.0 (72.9–118.8) 0.588  Fibrinogen (mg/ml), median (IQR) 5.6 (4.8–6.8) 5.7 (4.9–6.7) 5.8 (4.9–6.9) 0.516  D-dimer (mg/l), median (IQR) 1225.0 (430.5–2770) 1340.0 (478.5–2615.0) 1110.0 (430.0–2840.0) 0.807 Peak value within 72 h post-TEVAR  Haemoglobin (g/l), mean ± SD 115.7 ± 17.4 113.6 ± 17.7 116.4 ± 17.2 0.168  WBC (×109/l), median (IQR) 12.9 (10.9–15.8) 14.8 (12.9–17.0) 12.0 (10.3–15.3) <0.001  Platelet (×106/l), median (IQR) 224.9 (170.7–293.3) 233.0 (175.0–305.0) 222.3 (162.9–288.5) 0.103  Creatinine (μmol/l), median (IQR) 94.0 (74.7–129.0) 99.9 (75.0–132.0) 93.0 (74.2–127.4) 0.511  Fibrinogen (mg/ml), median (IQR) 5.7 (4.5–7.4) 5.4 (4.4–6.6) 6.1 (4.8–7.5) 0.371  D-dimer (mg/l), median (IQR) 2580.0 (837.5–6205.0) 3140.0 (874.0–9640.0) 2511.5 (830.0–5199.8) 0.097  ESR (mm), median (IQR) 46.0 (17.0–84.75) 54.0 (17.0–98.0) 44.0 (17.0–82.0) 0.002  CRP (mg/l), median (IQR) 77.5 (19–143.0) 88.8 (21.0–168.5) 74.2 (18.0–133.0) <0.001  PCT (μg/l), median (IQR) 0.5 (0.2–0.6) 0.4 (0.2–0.7) 0.5 (0.2–0.6) 0.727 Variables Total (N = 646) (N = 204) (N = 442) P-value Baseline  Haemoglobin (g/l), mean ± SD 128.7 ± 17.0 128.4 ± 16.7 128.1 ± 17.1 0.687  WBC (×109/l), median (IQR) 10.1 (8.0–12.4) 10.6 (8.7–12.7) 9.9 (7.9–12.3) 0.077  Platelet (×106/l), median (IQR) 204.0 (159.0–269.8) 213.0 (168.4–296.4) 200.5 (156.9–262.3) 0.131  Creatinine (μmol/l), median (IQR) 87.1 (72.0–117.5) 89.5 (70.9–114.5) 87.0 (72.9–118.8) 0.588  Fibrinogen (mg/ml), median (IQR) 5.6 (4.8–6.8) 5.7 (4.9–6.7) 5.8 (4.9–6.9) 0.516  D-dimer (mg/l), median (IQR) 1225.0 (430.5–2770) 1340.0 (478.5–2615.0) 1110.0 (430.0–2840.0) 0.807 Peak value within 72 h post-TEVAR  Haemoglobin (g/l), mean ± SD 115.7 ± 17.4 113.6 ± 17.7 116.4 ± 17.2 0.168  WBC (×109/l), median (IQR) 12.9 (10.9–15.8) 14.8 (12.9–17.0) 12.0 (10.3–15.3) <0.001  Platelet (×106/l), median (IQR) 224.9 (170.7–293.3) 233.0 (175.0–305.0) 222.3 (162.9–288.5) 0.103  Creatinine (μmol/l), median (IQR) 94.0 (74.7–129.0) 99.9 (75.0–132.0) 93.0 (74.2–127.4) 0.511  Fibrinogen (mg/ml), median (IQR) 5.7 (4.5–7.4) 5.4 (4.4–6.6) 6.1 (4.8–7.5) 0.371  D-dimer (mg/l), median (IQR) 2580.0 (837.5–6205.0) 3140.0 (874.0–9640.0) 2511.5 (830.0–5199.8) 0.097  ESR (mm), median (IQR) 46.0 (17.0–84.75) 54.0 (17.0–98.0) 44.0 (17.0–82.0) 0.002  CRP (mg/l), median (IQR) 77.5 (19–143.0) 88.8 (21.0–168.5) 74.2 (18.0–133.0) <0.001  PCT (μg/l), median (IQR) 0.5 (0.2–0.6) 0.4 (0.2–0.7) 0.5 (0.2–0.6) 0.727 CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; IQR: interquartile range; PCT: procalcitonin; SD: standard deviation; TEVAR: thoracic endovascular aortic repair; WBC: white blood cell. View Large Surgical details Three hundred and ninety-five (61.1%), 209 (32.4%) and 42 (6.5%) patients underwent TEVAR in acute, subacute and chronic settings, respectively, and the timing of TEVAR was not significantly different between the 2 groups (Table 3). Patients who had more than 1 aortic stent graft placed developed PIS slightly more frequently than those who had only 1 stent graft placed, but the difference was not significant [34 (16.7%) vs 50 (11.3%), P = 0.077]. General anaesthesia, left subclavian artery stenting, deployment of an uncovered aortic stent, rapid artificial cardiac pacing and type Ia endoleak were not significantly different between the 2 groups, whereas aortic arch vessel bypass was more frequently performed in the PIS group than in the non-PIS group [64 (31.4%) vs 75 (17.0%), P < 0.001]. The types of aortic stent grafts used were significantly different between the 2 groups [polyester, P = 0.023; expanded polytetrafluoroethylene (ePTFE), P < 0.001]. The prevalence of PIS in patients with different types of stent grafts is shown in Fig. 2. Figure 2: View largeDownload slide Prevalence of PIS in patients with different types of stent grafts. PIS: postimplantation syndrome. Figure 2: View largeDownload slide Prevalence of PIS in patients with different types of stent grafts. PIS: postimplantation syndrome. Table 3: Surgical details of patients with and without PIS Variables Overall (N = 646) PIS (N = 204) Non-PIS (N = 442) P-value Timing of TEVAR, n (%) 0.603  Acute (<14 days) 395 (61.1) 121 (59.3) 274 (62.0)  Subacute (15–90 days) 209 (32.4) 67 (32.8) 142 (32.1)  Chronic (>90 days) 42 (6.5) 16 (7.8) 26 (5.9) General anaesthesia, n (%) 91 (14.1) 32 (15.7) 59 (13.3) 0.466 >1 stent graft placed, n (%) 84 (13.0) 34 (16.7) 50 (11.3) 0.077 Arch vessel bypass, n (%) 139 (21.5) 64 (31.4) 75 (17.0) <0.001  LCCA-LSA 21 (3.3) 7 (3.4) 14 (3.2) 0.860  RCCA-LCCA-LSA 19 (2.9) 11 (5.4) 8 (1.8) 0.012  RSA-LCCA-LSA 81 (12.5) 39 (19.1) 42 (9.5) 0.001  Othera 18 (2.8) 7 (3.4) 11 (2.5) 0.499 LSA stent, n (%) 54 (8.4) 21 (10.3) 33 (7.5) 0.224 Uncovered aortic stent, n (%) 48 (7.4) 12 (5.9) 26 (5.9) 0.749 Type Ia endoleak, n (%) 49 (7.6) 18 (8.8) 31 (7.0) 0.425 RACP, n (%) 611 (94.6) 194 (95.1) 417 (94.3) 0.694 Material of the covered stent graft, n (%)  Polyester 571 (88.4) 170 (83.3) 401 (90.7) 0.028   Medtronic, Valiant® 295 (45.7) 75 (36.3) 220 (45.5) 0.017   Cook, Zenith® 120 (18.6) 44 (16.7) 76 (14.9) 0.324   Microport, Hercules® 156 (24.1) 51 (20.1) 105 (21.5) 0.385  ePTFE   Lifetech, Ankura® 164 (25.4) 63 (30.9) 111 (25.1) <0.001 Variables Overall (N = 646) PIS (N = 204) Non-PIS (N = 442) P-value Timing of TEVAR, n (%) 0.603  Acute (<14 days) 395 (61.1) 121 (59.3) 274 (62.0)  Subacute (15–90 days) 209 (32.4) 67 (32.8) 142 (32.1)  Chronic (>90 days) 42 (6.5) 16 (7.8) 26 (5.9) General anaesthesia, n (%) 91 (14.1) 32 (15.7) 59 (13.3) 0.466 >1 stent graft placed, n (%) 84 (13.0) 34 (16.7) 50 (11.3) 0.077 Arch vessel bypass, n (%) 139 (21.5) 64 (31.4) 75 (17.0) <0.001  LCCA-LSA 21 (3.3) 7 (3.4) 14 (3.2) 0.860  RCCA-LCCA-LSA 19 (2.9) 11 (5.4) 8 (1.8) 0.012  RSA-LCCA-LSA 81 (12.5) 39 (19.1) 42 (9.5) 0.001  Othera 18 (2.8) 7 (3.4) 11 (2.5) 0.499 LSA stent, n (%) 54 (8.4) 21 (10.3) 33 (7.5) 0.224 Uncovered aortic stent, n (%) 48 (7.4) 12 (5.9) 26 (5.9) 0.749 Type Ia endoleak, n (%) 49 (7.6) 18 (8.8) 31 (7.0) 0.425 RACP, n (%) 611 (94.6) 194 (95.1) 417 (94.3) 0.694 Material of the covered stent graft, n (%)  Polyester 571 (88.4) 170 (83.3) 401 (90.7) 0.028   Medtronic, Valiant® 295 (45.7) 75 (36.3) 220 (45.5) 0.017   Cook, Zenith® 120 (18.6) 44 (16.7) 76 (14.9) 0.324   Microport, Hercules® 156 (24.1) 51 (20.1) 105 (21.5) 0.385  ePTFE   Lifetech, Ankura® 164 (25.4) 63 (30.9) 111 (25.1) <0.001 a Other forms of arch vessel bypass include RSA-LCCA, RCCA-ARSA and RCCA-LCCA bypass. ARSA: aberrant right subclavian artery; ePTFE: expanded polytetrafluoroethylene; LCCA: left common carotid artery; LSA: left subclavian artery; PIS: postimplantation syndrome; RACP: rapid artificial cardiac pacing; RCCA: right common carotid artery, RSA: right subclavian artery; TEVAR: thoracic endovascular aortic repair. View Large Table 3: Surgical details of patients with and without PIS Variables Overall (N = 646) PIS (N = 204) Non-PIS (N = 442) P-value Timing of TEVAR, n (%) 0.603  Acute (<14 days) 395 (61.1) 121 (59.3) 274 (62.0)  Subacute (15–90 days) 209 (32.4) 67 (32.8) 142 (32.1)  Chronic (>90 days) 42 (6.5) 16 (7.8) 26 (5.9) General anaesthesia, n (%) 91 (14.1) 32 (15.7) 59 (13.3) 0.466 >1 stent graft placed, n (%) 84 (13.0) 34 (16.7) 50 (11.3) 0.077 Arch vessel bypass, n (%) 139 (21.5) 64 (31.4) 75 (17.0) <0.001  LCCA-LSA 21 (3.3) 7 (3.4) 14 (3.2) 0.860  RCCA-LCCA-LSA 19 (2.9) 11 (5.4) 8 (1.8) 0.012  RSA-LCCA-LSA 81 (12.5) 39 (19.1) 42 (9.5) 0.001  Othera 18 (2.8) 7 (3.4) 11 (2.5) 0.499 LSA stent, n (%) 54 (8.4) 21 (10.3) 33 (7.5) 0.224 Uncovered aortic stent, n (%) 48 (7.4) 12 (5.9) 26 (5.9) 0.749 Type Ia endoleak, n (%) 49 (7.6) 18 (8.8) 31 (7.0) 0.425 RACP, n (%) 611 (94.6) 194 (95.1) 417 (94.3) 0.694 Material of the covered stent graft, n (%)  Polyester 571 (88.4) 170 (83.3) 401 (90.7) 0.028   Medtronic, Valiant® 295 (45.7) 75 (36.3) 220 (45.5) 0.017   Cook, Zenith® 120 (18.6) 44 (16.7) 76 (14.9) 0.324   Microport, Hercules® 156 (24.1) 51 (20.1) 105 (21.5) 0.385  ePTFE   Lifetech, Ankura® 164 (25.4) 63 (30.9) 111 (25.1) <0.001 Variables Overall (N = 646) PIS (N = 204) Non-PIS (N = 442) P-value Timing of TEVAR, n (%) 0.603  Acute (<14 days) 395 (61.1) 121 (59.3) 274 (62.0)  Subacute (15–90 days) 209 (32.4) 67 (32.8) 142 (32.1)  Chronic (>90 days) 42 (6.5) 16 (7.8) 26 (5.9) General anaesthesia, n (%) 91 (14.1) 32 (15.7) 59 (13.3) 0.466 >1 stent graft placed, n (%) 84 (13.0) 34 (16.7) 50 (11.3) 0.077 Arch vessel bypass, n (%) 139 (21.5) 64 (31.4) 75 (17.0) <0.001  LCCA-LSA 21 (3.3) 7 (3.4) 14 (3.2) 0.860  RCCA-LCCA-LSA 19 (2.9) 11 (5.4) 8 (1.8) 0.012  RSA-LCCA-LSA 81 (12.5) 39 (19.1) 42 (9.5) 0.001  Othera 18 (2.8) 7 (3.4) 11 (2.5) 0.499 LSA stent, n (%) 54 (8.4) 21 (10.3) 33 (7.5) 0.224 Uncovered aortic stent, n (%) 48 (7.4) 12 (5.9) 26 (5.9) 0.749 Type Ia endoleak, n (%) 49 (7.6) 18 (8.8) 31 (7.0) 0.425 RACP, n (%) 611 (94.6) 194 (95.1) 417 (94.3) 0.694 Material of the covered stent graft, n (%)  Polyester 571 (88.4) 170 (83.3) 401 (90.7) 0.028   Medtronic, Valiant® 295 (45.7) 75 (36.3) 220 (45.5) 0.017   Cook, Zenith® 120 (18.6) 44 (16.7) 76 (14.9) 0.324   Microport, Hercules® 156 (24.1) 51 (20.1) 105 (21.5) 0.385  ePTFE   Lifetech, Ankura® 164 (25.4) 63 (30.9) 111 (25.1) <0.001 a Other forms of arch vessel bypass include RSA-LCCA, RCCA-ARSA and RCCA-LCCA bypass. ARSA: aberrant right subclavian artery; ePTFE: expanded polytetrafluoroethylene; LCCA: left common carotid artery; LSA: left subclavian artery; PIS: postimplantation syndrome; RACP: rapid artificial cardiac pacing; RCCA: right common carotid artery, RSA: right subclavian artery; TEVAR: thoracic endovascular aortic repair. View Large Factors associated with the presence of postimplantation syndrome Patients who were younger than 60 years more frequently developed PIS than those who were older than 60 years [109 (53.4%), P = 0.002, Table 1]. Moreover, multivariable logistic regression analysis showed that age less than 60 years was positively associated with PIS [odds ratio (OR) 1.828, 95% confidence interval (CI) 1.277–2.619; P < 0.001). Clinical features, including hypertension (OR 12.125, 95% CI 4.310–34.111; P < 0.001), >1 stent graft placed (OR 1.862, 95% CI 1.109–3.124; P = 0.011), arch vessel bypass (OR 2.107, 95% CI 1.397–3.176; P < 0.001) and Ankura stent graft placement (OR 1.951, 95% CI 1.298–2.933; P = 0.001) were positively associated with PIS, whereas statin use (OR 0.659, 95% CI 0.460–0.944; P = 0.023) was negatively associated with PIS in the multivariable logistic regression analysis based on a stepwise regression model (Table 4). Table 4: Identified independent predictors of PIS Variables Univariable analysis Multivariable logistic analysis (full model) Multivariable logistic analysis (stepwise regression model) OR 95% CI P-value OR 95% CI P-value OR 95% CI P-value Age <60 years 1.704 1.217–2.386 0.002 1.992 1.310–2.713 0.001 1.828 1.277–2.619 0.001 Male gender 1.118 0.666–1.877 0.672 0.942 0.578–1.763 0.975 Hypertension 10.882 3.927–30.153 <0.001 11.336 4.288–34.104 <0.001 12.125 4.310–34.111 <0.001 Medical treatment  ACEIs 0.612 0.396–0.948 0.028 0.749 0.470–1.193 0.224  Statins 0.657 0.469–0.920 0.015 0.633 0.440–0.912 0.014 0.659 0.460–0.944 0.023 >1 stent graft placed 1.568 0.979–2.512 0.061 1.973 1.095–3.090 0.021 1.862 1.109–3.124 0.019 Arch vessel bypass 2.237 1.520–3.291 <0.001 2.065 1.366–3.121 0.001 2.107 1.397–3.176 <0.001 Stent graft type  Valiant® 0.683 0.485–0.960 0.028 1.443 0.478–1.085 0.117  Ankura® 1.962 1.339–2.873 0.001 2.178 1.024–2.552 0.039 1.951 1.298–2.933 0.001 Variables Univariable analysis Multivariable logistic analysis (full model) Multivariable logistic analysis (stepwise regression model) OR 95% CI P-value OR 95% CI P-value OR 95% CI P-value Age <60 years 1.704 1.217–2.386 0.002 1.992 1.310–2.713 0.001 1.828 1.277–2.619 0.001 Male gender 1.118 0.666–1.877 0.672 0.942 0.578–1.763 0.975 Hypertension 10.882 3.927–30.153 <0.001 11.336 4.288–34.104 <0.001 12.125 4.310–34.111 <0.001 Medical treatment  ACEIs 0.612 0.396–0.948 0.028 0.749 0.470–1.193 0.224  Statins 0.657 0.469–0.920 0.015 0.633 0.440–0.912 0.014 0.659 0.460–0.944 0.023 >1 stent graft placed 1.568 0.979–2.512 0.061 1.973 1.095–3.090 0.021 1.862 1.109–3.124 0.019 Arch vessel bypass 2.237 1.520–3.291 <0.001 2.065 1.366–3.121 0.001 2.107 1.397–3.176 <0.001 Stent graft type  Valiant® 0.683 0.485–0.960 0.028 1.443 0.478–1.085 0.117  Ankura® 1.962 1.339–2.873 0.001 2.178 1.024–2.552 0.039 1.951 1.298–2.933 0.001 ACEIs: angiotensin-converting enzyme inhibitors; CI: confidence interval; OR: odds ratio; PIS: postimplantation syndrome. View Large Table 4: Identified independent predictors of PIS Variables Univariable analysis Multivariable logistic analysis (full model) Multivariable logistic analysis (stepwise regression model) OR 95% CI P-value OR 95% CI P-value OR 95% CI P-value Age <60 years 1.704 1.217–2.386 0.002 1.992 1.310–2.713 0.001 1.828 1.277–2.619 0.001 Male gender 1.118 0.666–1.877 0.672 0.942 0.578–1.763 0.975 Hypertension 10.882 3.927–30.153 <0.001 11.336 4.288–34.104 <0.001 12.125 4.310–34.111 <0.001 Medical treatment  ACEIs 0.612 0.396–0.948 0.028 0.749 0.470–1.193 0.224  Statins 0.657 0.469–0.920 0.015 0.633 0.440–0.912 0.014 0.659 0.460–0.944 0.023 >1 stent graft placed 1.568 0.979–2.512 0.061 1.973 1.095–3.090 0.021 1.862 1.109–3.124 0.019 Arch vessel bypass 2.237 1.520–3.291 <0.001 2.065 1.366–3.121 0.001 2.107 1.397–3.176 <0.001 Stent graft type  Valiant® 0.683 0.485–0.960 0.028 1.443 0.478–1.085 0.117  Ankura® 1.962 1.339–2.873 0.001 2.178 1.024–2.552 0.039 1.951 1.298–2.933 0.001 Variables Univariable analysis Multivariable logistic analysis (full model) Multivariable logistic analysis (stepwise regression model) OR 95% CI P-value OR 95% CI P-value OR 95% CI P-value Age <60 years 1.704 1.217–2.386 0.002 1.992 1.310–2.713 0.001 1.828 1.277–2.619 0.001 Male gender 1.118 0.666–1.877 0.672 0.942 0.578–1.763 0.975 Hypertension 10.882 3.927–30.153 <0.001 11.336 4.288–34.104 <0.001 12.125 4.310–34.111 <0.001 Medical treatment  ACEIs 0.612 0.396–0.948 0.028 0.749 0.470–1.193 0.224  Statins 0.657 0.469–0.920 0.015 0.633 0.440–0.912 0.014 0.659 0.460–0.944 0.023 >1 stent graft placed 1.568 0.979–2.512 0.061 1.973 1.095–3.090 0.021 1.862 1.109–3.124 0.019 Arch vessel bypass 2.237 1.520–3.291 <0.001 2.065 1.366–3.121 0.001 2.107 1.397–3.176 <0.001 Stent graft type  Valiant® 0.683 0.485–0.960 0.028 1.443 0.478–1.085 0.117  Ankura® 1.962 1.339–2.873 0.001 2.178 1.024–2.552 0.039 1.951 1.298–2.933 0.001 ACEIs: angiotensin-converting enzyme inhibitors; CI: confidence interval; OR: odds ratio; PIS: postimplantation syndrome. View Large Prevalence of postimplantation syndrome in patients with different risk factors In the present study, the incidence of PIS was 31.6% (204/646) in patients treated with TEVAR for TBAD. As age <60 years, hypertension, >1 stent graft placed and arch vessel bypass were independent predictors of PIS, stepwise increases in the prevalence of PIS were found to depend on the number of independent predictors (P < 0.001). The prevalence of PIS was 0% (0/642) in patients without any independent predictors, 17.7% (34/192) in patients with 1 predictor, 31.2% (84/269) in patients with 2 predictors, 49.3% (68/138) in patients with 3 predictors and up to 66.7% (18/27) in patients with 4 predictors. The prevalence of PIS in patients with different predictors is shown in Fig. 3. Figure 3: View largeDownload slide Prevalence of PIS in patients with different predictors. PIS: postimplantation syndrome. Figure 3: View largeDownload slide Prevalence of PIS in patients with different predictors. PIS: postimplantation syndrome. DISCUSSION In the present study, we found a significant incidence of PIS (31.6%) in patients undergoing TEVAR. In the published literature, PIS incidence varies from 15.8% to 34% [5, 9–11] when different diagnostic criteria are used. In this study, PIS was defined as the development of fever (>38.0°C) and leucocytosis (>12 000/μl) for the following reasons. First, to the best of our knowledge, fever and leucocytosis are the most important features of PIS. Other characteristics that have been used to define PIS, such as CRP, were increased in only 20.6% of patients in the present study using a cut-off value of 10 mg/dl [5]. Thus, numerous patients who present with fever and leucocytosis would not be diagnosed with PIS because their CRP levels were not sufficiently high. However, close surveillance and a longer recovery time, which are typical consequences of PIS, were also observed in these patients. Several inflammatory biomarkers appeared to increase in all patients after TEVAR: CRP, WBC and ESR. In a recent prospective study involving 214 patients who underwent EVAR for abdominal aortic aneurysms, Arnaoutoglou et al. [9] observed that a cut-off value of 125 mg/l for postoperative high-sensitivity CRP appeared to correlate with the presence of a cardiovascular adverse event during the first 30 days. However, current reports clarifying the association between PIS and outcomes in patients with TBAD are scarce. Gorla et al. [12] reported that PIS is associated with increased rates in major adverse events (defined as aortic rupture, all-cause death and the need for reintervention) after TEVAR for acute aortic syndrome (including TBAD, intramural haematoma and penetrating aortic ulcer) with a mean follow-up time of 4.0 ± 2.9 years. The present study showed no significant differences in postoperative outcomes during the hospitalization of patients with or without PIS. Further studies are needed to investigate the prognosis of PIS in patients who underwent TEVAR or EVAR. The potential mechanisms of PIS are still unknown. Multiple factors have been considered causes of the inflammatory response after EVAR, such as manipulation of the aneurysm, injury to the endothelium and the use of iodide-containing contrast agents [13–15]. In the present study, an interesting finding was that ePTFE stent graft placement was an independent predictor of PIS, which is contrary to published results reporting that the use of polyester stent grafts is associated with a higher incidence of PIS than other types of grafts [9, 16, 17]. Furthermore, the only ePTFE stent graft used in this study was the Ankura stent graft. Thus, it is not unlikely that the development of PIS was related to other components of the endograft, such as the nitinol or bare metal material, which have previously been linked to allergic reactions [18]. Similarly, nickel allergy was reported to correlate with neurological complications in cerebral aneurysm treatments [19]. Thus, a hypothesis that PIS may be related to a nitinol or metal allergy was proposed; several implications for this hypothesis are as follows: first, fever and leucocytosis with negative blood cultures, as the major characteristics of PIS, may also be present in anaphylaxis [20]. Second, biomarkers of PIS, such as high-sensitivity CRP and cytokines, are also surrogate markers for histamine or tryptase released by mast cells or basophils in allergic reactions [21]. Finally, a faster recovery and a reduced incidence of PIS were observed after the perioperative administration of glucocorticoids in EVAR or TEVAR patients [10, 11]. However, it is worth noting that this study is a clinical observation and was not designed to provide insights into the molecular and pathophysiological mechanisms that might explain the link between anaphylaxis and PIS. We hope that these clinical observations may prompt detailed pathophysiological investigations into potential shared pathways. There is no consensus regarding the treatment for PIS. Some authors have suggested the use of non-steroidal anti-inflammatory drugs as a valuable therapeutic option to limit the inflammatory response. However, prolonged antibiotic prophylaxis beyond the usual period showed no benefits in a previous study [22]. Recently, the ability of the preoperative use of methylprednisolone to reduce the incidence of PIS without increasing adverse events was evaluated in a randomized, double-blinded, placebo-controlled clinical trial [11]. A single preoperative dose of 30 mg/kg methylprednisolone before surgery was shown to improve recovery and was associated with a shorter hospitalization without increasing the use of antibiotics or the prevalence of adverse events at a 3-month follow-up. Similar benefits were also observed in patients who received postoperative glucocorticoids after TEVAR for TBAD [10]. It appears that corticosteroids can be a therapeutic agent to improve the prognosis of patients with PIS, but further studies are needed to confirm the validity of this strategy in long-term results. In the present study, age <60 years was an independent predictor of PIS. Other predictors, such as hypertension, >1 stent graft placed and arch vessel bypass were positively associated with PIS. These results are consistent with those of Ker et al. [23] and agree with the concept of PIS as a host immune response. As younger patients have stronger immune reactions, more invasive strategies and a longer aortic conversion can trigger a more extensive host immune response in these patients. Stepwise increases in the prevalence of PIS were found to depend on the number of independent predictors, supporting the potential for administration of preoperative glucocorticoids in high-risk patients. Hence, the side effects of glucocorticoids could be reduced, and patients who are likely to develop PIS would have a better recovery. Interestingly, statin use is correlated with the presence of PIS (OR 0.659, 95% CI 0.460–0.944; P = 0.023). The anti-inflammatory and immunomodulatory effects of statins have been well documented previously [24]. In an experimental study, statins have been shown to decrease leucocyte recruitment and oedema formation in animal models of acute inflammation [12]. In a clinical study, the use of statins reduced the rates of graft rejection in statin-treated patients after heart transplantation [25], and anti-inflammatory effects have been demonstrated in several rheumatic conditions, such as rheumatoid arthritis [26], systemic sclerosis [27] and lupus [28]. Based on the hypothesis that PIS is a systemic inflammatory response trigged by a host-versus-graft reaction, statins appeared to decrease the prevalence of PIS due to their anti-inflammatory and immunomodulatory benefits and should be investigated in randomized studies. Limitations There were several limitations in this study. First, as polyester stent grafts have been identified as a risk factor for PIS in several previous studies, the incidence of PIS may have been overestimated by the predominant use (88.4%) of polyester stent grafts (Valiant, Zenith and Hercules) in this study. A total of 21.5% of the patients underwent additional bypass surgery; although patients with proximal landing zone 0 who underwent open-heart surgery were excluded, the occurrence of PIS may be overestimated due to the pronounced inflammatory reaction following surgical trauma. Second, the only ePTFE stent graft used in this study was an Ankura stent graft (Lifetech, Shenzhen, China); thus, a larger proportion of PIS cases may be attributed to the metal material or other characteristics of the product. Finally, although we profiled the biochemical changes and several clinical risk factors for PIS after TEVAR, we are not yet able to elucidate the pathogenetic mechanisms or their impact on the clinical outcomes of this process. CONCLUSIONS In summary, one-third of the patients who underwent TEVAR for TBAD developed PIS. Age <60 years, comorbid hypertension, >1 stent graft placed, arch vessel bypass and Ankura stent graft placement emerged as independent predictors of PIS. Stepwise increases in the prevalence of PIS were found to depend on the number of independent predictors. Funding This study was supported by the Guangdong Provincial Public Research and Capacity Building Foundation, China [2014A020215023], and Guangzhou Science and Technology Project, China [1561000356]. Conflict of interest: none declared. Footnotes Presented at the 32nd Annual Meeting of the European Society for Vascular Surgery, Valencia, Spain, 25–28 September 2018. REFERENCES 1 Velazquez OC , Carpenter JP , Baum RA , Barker CF , Golden M , Criado F et al. Perigraft air, fever, and leukocytosis after endovascular repair of abdominal aortic aneurysms . Am J Surg 1999 ; 178 : 185 – 9 . Google Scholar Crossref Search ADS PubMed 2 Sweeney KJ , Evoy D , Sultan S , Coates C , Moore DJ , Shanik DG et al. Endovascular approach to abdominal aortic aneurysms limits the postoperative systemic immune response . Eur J Vasc Endovasc Surg 2002 ; 23 : 303 – 8 . Google Scholar Crossref Search ADS PubMed 3 Eggebrecht H , Nienaber CA , Neuhauser M , Baumgart D , Kische S , Schmermund A et al. Endovascular stent-graft placement in aortic dissection: a meta-analysis . Eur Heart J 2006 ; 27 : 489 – 98 . Google Scholar Crossref Search ADS PubMed 4 Nienaber CA , Kische S , Rousseau H , Eggebrecht H , Rehders TC , Kundt G et al. Endovascular repair of type B aortic dissection: long-term results of the randomized investigation of stent grafts in aortic dissection trial . Circ Cardiovasc Interv 2013 ; 6 : 407 – 16 . Google Scholar Crossref Search ADS PubMed 5 Gorla R , Erbel R , Kahlert P , Tsagakis K , Jakob H , Mahabadi AA et al. Clinical features and prognostic value of stent-graft-induced post-implantation syndrome after thoracic endovascular aortic repair in patients with type B acute aortic syndromes . Eur J Cardiothorac Surg 2016 ; 49 : 1239 – 47 . Google Scholar Crossref Search ADS PubMed 6 Hiratzka LF , Bakris GL , Beckman JA , Bersin RM , Carr VF , Casey DE Jr. et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine . Catheter Cardiovasc Interv 2010 ; 76 : E43 – 86 . Google Scholar Crossref Search ADS PubMed 7 Huang W , Yang F , Luo J , Xie N , He P , Luo S et al. Outcomes and morphologic changes of immediate type Ia endoleak following endovascular repair of acute type B aortic dissection . Ann Vasc Surg 2015 ; 29 : 174 – 82 . Google Scholar Crossref Search ADS PubMed 8 Ding H , Luo S , Liu Y , Huang W , Jiang M , Li J et al. Outcomes of hybrid procedure for type B aortic dissection with an aberrant right subclavian artery . J Vasc Surg 2018 ; 67 : 704 – 11 . Google Scholar Crossref Search ADS PubMed 9 Arnaoutoglou E , Kouvelos G , Papa N , Kallinteri A , Milionis H , Koulouras V et al. Prospective evaluation of post-implantation inflammatory response after EVAR for AAA: influence on patients’ 30 day outcome . Eur J Vasc Endovasc Surg 2015 ; 49 : 175 – 83 . Google Scholar Crossref Search ADS PubMed 10 Wu M , Zhang L , Bao J , Zhao Z , Lu Q , Feng R et al. Postoperative glucocorticoid enhances recovery after endovascular aortic repair for chronic type B aortic dissection: a single-center experience . BMC Cardiovasc Disord 2016 ; 16 : 59 . Google Scholar Crossref Search ADS PubMed 11 de la Motte L , Kehlet H , Vogt K , Nielsen CH , Groenvall JB , Nielsen HB et al. Preoperative methylprednisolone enhances recovery after endovascular aortic repair: a randomized, double-blind, placebo-controlled clinical trial . Ann Surg 2014 ; 260 : 540 – 8 ; discussion 548–9. Google Scholar Crossref Search ADS PubMed 12 Sparrow CP , Burton CA , Hernandez M , Mundt S , Hassing H , Patel S et al. Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering . Arterioscler Thromb Vasc Biol 2001 ; 21 : 115 – 21 . Google Scholar Crossref Search ADS PubMed 13 Swartbol P , Truedsson L , Norgren L. Adverse reactions during endovascular treatment of aortic aneurysms may be triggered by interleukin 6 release from the thrombotic content . J Vasc Surg 1998 ; 28 : 664 – 8 . Google Scholar Crossref Search ADS PubMed 14 Gerasimidis T , Sfyroeras G , Trellopoulos G , Skoura L , Papazoglou K , Konstantinidis K et al. Impact of endograft material on the inflammatory response after elective endovascular abdominal aortic aneurysm repair . Angiology 2005 ; 56 : 743 – 53 . Google Scholar Crossref Search ADS PubMed 15 Videm V , Odegard A , Myhre HO. Iohexol-induced neutrophil myeloperoxidase release and activation upon contact with vascular stent-graft material: a mechanism contributing to the postimplantation syndrome? J Endovasc Ther 2003 ; 10 : 958 – 67 . Google Scholar Crossref Search ADS PubMed 16 Ferreira V , Machado R , Martins J , Loureiro L , Loureiro T , Borges L et al. Post-implantation syndrome—retrospective analysis of 52 patients . Angiologia e Cirurgia Vascular 2015 ; 11 : 204 – 8 . Google Scholar Crossref Search ADS 17 Arnaoutoglou E , Kouvelos G , Koutsoumpelis A , Patelis N , Lazaris A , Matsagkas M. An update on the inflammatory response after endovascular repair for abdominal aortic aneurysm . Mediators Inflamm 2015 ; 2015 : 945035. Google Scholar Crossref Search ADS PubMed 18 Spanos K , Drakou A , Giannoukas AD. Should we consider nickel allergy a potential factor associated with peripheral stent patency? Vascular 2015 ; 23 : 220. Google Scholar Crossref Search ADS PubMed 19 Tsang ACO , Nicholson P , Pereira VM. Nickel-related adverse reactions in the treatment of cerebral aneurysms: a literature review . World Neurosurg 2018 ; 115 : 147 – 53 . Google Scholar Crossref Search ADS PubMed 20 Schneider G , Kachroo S , Jones N , Crean S , Rotella P , Avetisyan R et al. A systematic review of validated methods for identifying hypersensitivity reactions other than anaphylaxis (fever, rash, and lymphadenopathy), using administrative and claims data . Pharmacoepidemiol Drug Saf 2012 ; 21 : 248 – 55 . Google Scholar Crossref Search ADS PubMed 21 Stone SF , Cotterell C , Isbister GK , Holdgate A , Brown SG ; Emergency Department Anaphylaxis Investigators. Serum cytokines during human anaphylaxis: identification of potential mediators of acute allergic reactions . J Allergy Clin Immunol 2009 ; 124 : 786 – 92.e4 . Google Scholar Crossref Search ADS PubMed 22 Akin I , Nienaber CA , Kische S , Rehders TC , Ortak J , Chatterjee T et al. Effect of antibiotic treatment in patients with postimplantation syndrome after aortic stent placement . Rev Esp Cardiol 2009 ; 62 : 1365 – 72 . Google Scholar Crossref Search ADS PubMed 23 Ker CR , Ho MC , Huang JW , Hsieh CC , Chen HM. Pyrexia of postimplantation syndrome for patients undergoing (thoracic) endovascular aortic repair . Thorac Cardiovasc Surg 2014 ; 63 : 126 – 33 . Google Scholar Crossref Search ADS PubMed 24 Youssef S , Stuve O , Patarroyo JC , Ruiz PJ , Radosevich JL , Hur EM et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease . Nature 2002 ; 420 : 78 – 84 . Google Scholar Crossref Search ADS PubMed 25 Kobashigawa JA , Katznelson S , Laks H , Johnson JA , Yeatman L , Wang XM et al. Effect of pravastatin on outcomes after cardiac transplantation . N Engl J Med 1995 ; 333 : 621 – 7 . Google Scholar Crossref Search ADS PubMed 26 McCarey DW , McInnes IB , Madhok R , Hampson R , Scherbakov O , Ford I et al. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial . Lancet 2004 ; 363 : 2015 – 21 . Google Scholar Crossref Search ADS PubMed 27 Abou-Raya A , Abou-Raya S , Helmii M. Statins as immunomodulators in systemic sclerosis . Ann N Y Acad Sci 2007 ; 1110 : 670 – 80 . Google Scholar Crossref Search ADS PubMed 28 Ferreira GA , Navarro TP , Telles RW , Andrade LE , Sato EI. Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial . Rheumatology (Oxford) 2007 ; 46 : 1560 – 5 . Google Scholar Crossref Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Predictors associated with an increased prevalence of postimplantation syndrome after thoracic endovascular aortic repair for type B aortic dissection
JF - European Journal of Cardio-Thoracic Surgery
DO - 10.1093/ejcts/ezy379
DA - 2019-05-01
UR - https://www.deepdyve.com/lp/oxford-university-press/predictors-associated-with-an-increased-prevalence-of-postimplantation-MmvaHk30d0
SP - 998
VL - 55
IS - 5
DP - DeepDyve
ER -