Impact of Acute Kidney Injury on Early to Long-Term Outcomes in Patients Who Underwent Surgery for Type A Acute Aortic Dissection Toshiyuki Ko, MDa, Michiaki Higashitani, MD, PhDb,*, Akihiko Sato, MDc, Yukari Uemura, PhDd, Togo Norimatsu, MDe, Keitaro Mahara, MD, PhDb, Itaru Takamisawa, MDb, Atsushi Seki, MD, PhDb, Jun Shimizu, MD, PhDf, Tetsuya Tobaru, MD, PhDb, Haruo Aramoto, MD, PhDe, Nobuo Iguchi, MD, PhDb, Toshihiro Fukui, MD, PhDe, Masafumi Watanabe, MD, PhDa, Masatoshi Nagayama, MD, PhDb, Morimasa Takayama, MD, PhDb, Shuichiro Takanashi, MD, PhDe, Tetsuya Sumiyoshi, MD, PhDb, Issei Komuro, MD, PhDa, and Hitonobu Tomoike, MD, PhDb Acute kidney injury (AKI) is relatively common after cardiothoracic surgery for type A acute aortic dissection (TA-AAD) and increases mortality. We investigated the incidence and risk factors for AKI in patients with TA-AAD and its impact on their outcomes. The records of 375 consecutive patients who underwent surgical treatment for TA-AAD from October 2007 to March 2013 were analyzed retrospectively. We defined AKI using the Kidney Disease Improving Global Outcomes criteria, which are based on serum creatinine concentration or glomerular filtration rate. We used Kaplan-Meier methods and multivariate Cox proportional hazards regression to assess the impact of AKI on both mortality and major adverse cardiovascular and cerebrovascular events. We also examined the association between risk factors and AKI using logistic regression modeling. Postoperative AKI was observed in 165 patients (44.0%). The overall 30-day and mid- to long-term mortality was 1.6% and 8.8%, respectively. Mortality and major adverse cardiovascular and cerebrovascular events correlated significantly with the severity of AKI, and multivariate analysis showed that AKI stage 3 (the most sever stage) was an independent risk factor for mortality (hazard ratio 6.83, 95% confidence interval 2.52 to 18.52) after adjustment for important confounding factors. Extracorporeal circulation time, body mass index, perioperative peak serum C-reactive protein concentration, renal malperfusion, and perioperative sepsis were found to be risk factors for AKI. In conclusion, AKI was common in patients who underwent surgery for type A acute aortic dissection. The severity of AKI strongly influences patient outcomes, so it should be recognized promptly and treated aggressively when possible. Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;-:-e-) Despite recent advances in medical management and surgical techniques, type A acute aortic dissection (TA-AAD) still carries a high burden of morbidity and mortality.1e3 In addition to many predictors previously reported,4e7 acute kidney injury (AKI) has received recent attention as an important risk factor for mortality after TA-AAD8e10; however, the diagnostic criteria and classification systems used to define AKI in previous studies have not been consistent. Furthermore, patient populations have been relatively small and the length of follow-up relatively short, raising the a Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan; Departments of bCardiology, eCardiovascular Surgery, and f Anesthesia, Sakakibara Heart Institute, Tokyo, Japan; cDepartment of Cardiology, Fukushima Medical University, Fukushima, Japan; and d Biostatistics Division, Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan. Manuscript received February 27, 2015; revised manuscript received and accepted April 30, 2015. See page 5 for disclosure information. *Corresponding author: Tel: (þ81) 042-314-3141; fax: (þ81) 042-3143199. E-mail address: [email protected] (M. Higashitani).

0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.04.043

possibility that previous studies lacked sufficient statistical power. The primary aims of this study were to clarify the incidence of AKI in a large population of patients who received surgical treatment for TA-AAD and to investigate its impact on both short- and mid- to long-term outcomes. Methods We reviewed the medical records and the results of laboratory investigations of 418 consecutive patients admitted to the Sakakibara Heart Institute (a 320-bed cardiac center in Tokyo, Japan) diagnosed with TA-AAD according to the Stanford classification from October 2007 to March 2013. Previous approval was obtained from the institutional research ethics committee (approval number: 13-31), which waived the need for individual informed consent. Aortic dissection was diagnosed by computed tomography angiography at either our institution or the referring hospital. None of the patients was in cardiopulmonary arrest at the time of admission; 16 patients who did not undergo surgery were excluded from the analysis: in 5, surgery was considered to be contraindicated because of advanced age or www.ajconline.org

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Table 1 Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury Stage 1 2 3

serum Creatinine (sCr) Increase 1.5 w 1.9 times baseline or 0.3 mg/dl increase 2.0 w 2.9 times baseline 3.0 times baseline or increase in sCr to 4.0 mg/dl or initiation of renal replacement therapy

a history of end-stage cancer and 11 did not meet the criteria for surgery. We selected these patients for medical management according to the guidelines of the Japanese Circulation Society, which identifies those with noncommunicating TA-AAD with an ascending aortic diameter 70 years. The most common symptoms on presentation included chest pain (70%), back pain (56%), and syncope (12%). Emergent surgery was performed on the ascending aorta (62%), aortic arch (37%), or aortic valve (12%); 26 patients (7%) underwent re-thoracotomy because of either infection or hemorrhage. AKI was observed in 165 patients within 7 days of surgery (44%): 89 patients (24%) fulfilled the KDIGO criteria for stage 1 AKI, 23 patients (6%) for stage 2, and 53 patients (14%) for stage 3. Postoperative outcomes and major complications are summarized in Table 3. In total, 33 patients (9%) required temporary renal replacement therapy (dialysis) after operation and 11 (3%) progressed to dialysisdependent end-stage renal disease. The mean length of hospital stay and intensive care unit stay was significantly longer in those who developed AKI. The overall 30-day and long-term mortality was 2.6% and 8.8%, respectively. Figure 1 shows Kaplan-Meier survival curves of both 30-day/long-term mortality and 30-day/ long-term occurrences of MACCE. Both mortality and MACCE correlated significantly with the severity of AKI defined by the KDIGO criteria. Multivariate Cox analysis for mortality (Table 4) and MACCE (Table 5) revealed that AKI stage 3 was a significant and independent risk factor after adjustment for other major clinical factors, including those known to increase postoperative AKI, eliminating the possibility that AKI itself was a confounding factor. There was no significant association between the earlier stages of AKI and mortality or MACCE. Other major risk factors

Miscellaneous/AKI-Type A Aortic Dissection Study

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Table 2 Patient characteristics Variables

Overall(n¼375)

Age, mean  SD (years) Male BMI, mean  SD (kg/m2) Smoker Hypertension Diabetes mellitus Obesity Peripheral vascular disease Coronary artery disease Cerebrovascular disease Previous cardiac surgery Shock or tamponade (Systolic BP