- Email: [email protected]
Real clinical management of patients with isolated superior mesenteric artery dissection in Japan
G Model
JJCC-1545; No. of Pages 4 Journal of Cardiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Original article
Real clinical management of patients with isolated superior mesenteric artery dissection in Japan Atsushi Mizuno (MD, FJCC)a,*, Hayato Iguchi b, Yuuka Sawada (RN)b, Hiroshi Nomura b, Nobuyuki Komiyama (MD, PhD, FJCC)a, Sachiko Watanabe (RN)b, Aki Yoshikawa (RN, MHSA, MAE)b a b
St. Luke’s International Hospital, Tokyo, Japan Global Health Consulting Japan Co. Ltd, Tokyo, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 8 May 2017 Received in revised form 28 July 2017 Accepted 22 August 2017 Available online xxx
Background: Due to the rarity of this condition, clinical treatment and outcomes in isolated superior mesenteric artery dissection (ISMAD) patients remain unknown. The primary aim of this retrospective multicenter study was to elucidate the treatment strategies and in-hospital outcomes for ISMAD patients by using administrative data. Methods: We retrospectively analyzed patients that were primarily diagnosed with ISMAD using the Diagnosis Procedure Combination data collected at 141 hospitals in Japan in 2015. Patients with comorbidities that included “aneurysm” were excluded. Results: A total of 221 ISMAD without aneurysm patients (male: 90.5%; mean age: 52.5 10.1 years) were enrolled, and 95 (67.4%) of these encountered just one ISMAD case per year. We found only one (0.5%) in-hospital death and length of stay for ISMAD patients was 13.2 9.1 days. One-third of patients received antiplatelet therapy (32.1%) and anticoagulation therapies, such as heparin (38.9%) and warfarin (10.0%). A total of 146 (66.1%) patients received antihypertensive treatment (either orally or via an intravenous route) during hospitalization. Twelve (5.4%) patients underwent surgical procedures during hospitalization as follows: 4 (33.3%) patients underwent bypass surgery, 3 (25.0%) patients underwent exploratory laparotomies, 2 (16.7%) patients underwent bowel resection, 1 (8.3%) patient underwent a thrombectomy, and 2 (16.7%) patients underwent surgical angioplasties. Conclusions: We found that conservative therapy for ISMAD patients without aneurysm is safe and is also associated with a low rate of surgical intervention in clinical practice. © 2017 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
Keywords: Superior mesenteric artery dissection Operation Ischemia Conservative therapy
Introduction While isolated superior mesenteric artery dissection (ISMAD) is considered a rare condition, recent progress in imaging modalities such as computed tomographic (CT) angiography imaging has improved diagnosis [1]. Despite an increasing number of reports worldwide, the question of how to treat ISMAD largely depends on individual physicians. Although there are many literature reviews and clinical practice reports for ISMAD, many of them describe a sample size of just 20 in each single study [1–3]. Actual clinical treatment strategies and outcomes in ISMAD patients remain unknown. Here we present
* Corresponding author at: Department of Cardiology, St. Luke’s International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo, Japan. E-mail address: [email protected] (A. Mizuno).
a retrospective multicenter study that aimed to show the real clinical practice for ISMAD patients. Methods Study design and data sources This was a retrospective study using Diagnosis Procedure Combination (DPC) data collected between January 2015 and December 2015. These data were collected from 141 Japanese hospitals that had agreed to its secondary usage. The requirement for informed consent was waived as the data were anonymized. The DPC data included the following: patient age and sex; main diagnoses and comorbidities, recorded with both International Classification of Diseases (Tenth Revision) (ICD-10) codes and text data written in Japanese; New York Heart Association (NYHA) functional class at admission; drugs and devices; diagnostic and
http://dx.doi.org/10.1016/j.jjcc.2017.08.006 0914-5087/© 2017 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
Please cite this article in press as: Mizuno A, et al. Real clinical management of patients with isolated superior mesenteric artery dissection in Japan. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.08.006
G Model
JJCC-1545; No. of Pages 4 A. Mizuno et al. / Journal of Cardiology xxx (2017) xxx–xxx
2
therapeutic procedures such as surgical procedures coded using the Japanese claims classification (K-code with Japanese text); admission and discharge dates; discharge status; and unique hospital identifiers. Patient selection and definition We selected patients with a primary diagnosis of superior mesenteric artery dissection between January 2015, and December 2015, as per the Japanese text data. We excluded those patients whose comorbidities including “aneurysm” in the Japanese text, as an aneurysm itself could be an indication for surgery and we were unable to appropriately differentiate between aneurysms with mural thrombosis and dissection with a thrombosed false lumen [4]. Baseline characteristics were compiled based on patient age and sex, the Charlson Comorbidity Index (CCI), and comorbidities (including atrial fibrillation and flutter, cerebrovascular disease, chronic pulmonary disease, chronic liver disease, renal disease, malignancy, diabetes, and hypertension). We defined the patients’ comorbidities by using ICD-10 and CCI definitions (Supplement Table 1) [5,6]. Detailed surgical data during hospitalization were obtained via the K-code with Japanese text. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institutional review board of The St. Luke’s International University. Supplementary Table 1 related to this article can be found, in the online version, at doi:10.1016/j.jjcc.2017.08.006. Statistical analysis Categorical variables are presented as numbers and proportions while continuous variables are presented as the mean standard deviation (SD) or the median with the interquartile range (IQR). All statistical analyses were performed using “R” software (Version 3.2.5, R Foundation, Vienna, Austria). Results Baseline patient characteristics and in-hospital outcomes A total of 221 ISMAD patients were enrolled in this study (Table 1). The majority of patients were male (90.5%) and threefourths were not associated with any comorbidities as calculated by CCI. Of 141 hospitals, the annual number of ISMAD cases per hospital was as follows: 1 case (67.4%), 2 cases (16.3%), 3 cases (11.3%), and 4 cases or more (5.0%) (Table 2). We noted just one (0.5%) in-hospital death and the length of stay of these patients was 13.2 9.1 days. Total cost of hospitalization was 612,854.5 505,399.8 yen (median, 508,546 yen; IQR: 338,080– 745,170). Imaging modality and drug usage CT and Doppler ultrasound were performed on 209 (94.6%) and 71 (32.1%) patients, respectively (Table 3). One-third of these patients received antiplatelet (32.1%) and anticoagulation therapy [such as heparin (38.9%) and warfarin (10.0%)]. Six patients (2.7%) received both antiplatelet and anticoagulation therapy. A total of 146 (66.1%) patients received antihypertensive treatment (either orally or via an intravenous route) during hospitalization. Surgical procedures Twelve (5.4%) patients underwent surgical procedures during hospitalization as follows (Table 4): 4 (33.3%) patients underwent bypass surgery, 3 (25.0%) patients underwent an exploratory
Table 1 Baseline characteristics. Patients Male, n (%) Age, year Height, cm Weight, kg Comorbidities Acute myocardial infarction, n (%) Congestive heart failure, n (%) Peripheral vascular disease, n (%) Cerebral vascular accident, n (%) Dementia, n (%) Pulmonary disease, n (%) Connective tissue disorder, n (%) Peptic ulcer, n (%) Liver disease, n (%) Diabetes, n (%) Diabetes complications, n (%) Paraplegia, n (%) Renal disease, n (%) Cancer, n (%) Metastatic cancer, n (%) Severe liver disease, n (%) HIV, n (%) Atrial fibrillation/Flutter, n (%) Rheumatic disease, n (%) Hypertension, n (%) CCI score, n (%) 0 1 2 3
n = 221 200 (90.5) 52.5 10.1 158.0 41.8 65.2 18.9 0 (0) 11 (5) 2 (0.9) 4 (1.8) 0 (0) 6 (2.7) 0 (0) 29 (13.1) 1 (0.5) 9 (4.1) 0 (0) 0 (0) 2 (0.9) 8 (3.6) 1 (0.5) 0 (0) 0 (0) 3 (1.4) 0 (0) 134 (60.6) 156 (70.6) 51 (23.1) 10 (4.5) 4 (1.8)
HIV, human immunodeficiency virus; CCI, Charlson Comorbidity Index.
Table 2 Annual case volume (n = 141 hospitals). Annual case volume per year
Hospital number
1 2 3 4 5 6
95 (67.4) 23 (16.3) 16 (11.3) 4 (2.8) 2 (1.4) 1 (0.7)
Table 3 Imaging modalities and drug usage during hospitalization. Imaging modalities, n (%) Computed tomography, n (%) Doppler ultrasound, n (%) Prescriptions, n (%) ACE-I/ARB Beta blocker Ca blocker Alpha blocker Nitroglycerin Aldosterone blocker Oral opioid Antiplatelet therapy Anticoagulation therapy Antiplatelet and anticoagulation Intravenous drugs, n (%) Nitroglycerin Beta blocker Ca blocker Thrombolytic therapy Intravenous heparin Opioid
209 (94.6) 71 (32.1) 72 (32.6) 54 (24.4) 4 (1.8) 5 (2.3) 0 (0) 1 (0.5) 1 (0.5) 65 (29.4) 16 (7.2) 6 (2.7) 5 (2.3) 9 (4.1) 115 (52) 3 (1.4) 86 (38.9) 29 (13.1)
ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.
Please cite this article in press as: Mizuno A, et al. Real clinical management of patients with isolated superior mesenteric artery dissection in Japan. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.08.006
G Model
JJCC-1545; No. of Pages 4 A. Mizuno et al. / Journal of Cardiology xxx (2017) xxx–xxx Table 4 Operation during hospitalization. Operation Bypass, n (%) Exploratory laparotomy, n (%) Bowel resection, n (%) Thrombectomy, n (%) Angioplasty, n (%)
n = 12 4 (33.3) 3 (25) 2 (16.7) 1 (8.3) 2 (16.7)
laparotomy, 2 (16.7%) patients underwent bowel resection, one (8.3%) patient underwent a thrombectomy, and 2 (16.7%) patients underwent angioplasty. The differences between operation patients and non-operation patients were shown in Supplement Table 2. Opioid was more frequently used and length of stay was longer in operation patients comparing with others. Supplementary Table 2 material related to this article can be found, in the online version, at doi:10.1016/j.jjcc.2017.08.006.
3
[13]. Furthermore, they found that 43.9% of dissections showed complete remodeling. Aneurysmal formation on initial CT was one of the most important findings. According to these data, the use of conservative therapy in ISMAD cases without aneurysmal formation is a safe option. Progress in imaging modalities has enabled us to analyze the morphology of ISMAD, especially using the Sakamoto or Yun classifications [14,15]. Unfortunately, these classifications do not include aneurysm formation. Further studies are required in order to optimize the algorithm used for current imaging modalities. Anticoagulation and antiplatelet therapy
This report is the first of its type and the largest multicenter retrospective study on clinical practice for ISMAD patients. Our results suggest that conservative therapy for ISMAD without aneurysm is both safe and comparable to findings from previous studies [7].
Although appropriate conservative therapy has not yet been fully evaluated, anticoagulation and antiplatelet therapies are considered the mainstay for conservative treatment of ISMAD and are associated with better results [16]. In our study, just one-third of patients received antiplatelet or anticoagulation therapy, a finding that is lower than that previously reported. This could be attributed to a negative image of anticoagulation therapy as an area of uncertainty [17]. In addition to the uncertain effect of anticoagulation and antiplatelet therapy, these drugs might induce bleeding. We should be careful to use these types of drugs. Although we observed fairly good clinical outcomes in our study, the usage of antiplatelet or anticoagulation therapies requires further investigation.
Diagnosis
Future global studies
We used several imaging modalities to diagnose ISMAD, including CT, Doppler ultrasound, and conventional angiography. Many clinicians are primarily dependent on contrast-enhanced CT due to its high diagnostic value. Luan et al. reported that CT was performed on 95.2% of ISMAD patients in a review of the literature, similar to the results obtained in this study (94.6%) [3]. In addition, we performed abdominal ultrasound in one-third of ISMAD patients in the present study. Doppler ultrasound is an inexpensive and noninvasive technique that can be performed repeatedly. While CT does offer more precise images, Doppler ultrasound can be useful for patients requiring serial assessment of superior mesenteric artery (SMA) blood flow [8]. However, the added value of these imaging modalities for ISMAD patients is not yet clear.
A large number of previous studies have been limited to Asian countries such as Korea, China, and Japan [2]. Due to the rarity of this disease, many are case reports or retrospective literature reviews. Recent serial reports from China support revascularization strategies such as surgery and endovascular stenting. Indeed, such strategies may be useful considering the pathophysiology of the disease. A major factor contributing to this uncertainty is the relative inexperience of treating ISMAD within a single institution, as our study found that the majority of institutions saw just one case annually. The relationship between hospital case volume and quality of care has previously been demonstrated in many areas, including surgery and process of care [18–20]. In the case of such rare diseases, a global registry may be useful [21]. Now is the time to collaborate and create a new, large worldwide registry that could elucidate real clinical practice and improve clinical outcomes.
Discussion
Surgical intervention Although several management protocols and algorithms have previously been advocated for the treatment of ISMAD, most have concluded that conservative therapy is a preferable primary course of management [7,9,10]. However, as symptom relief is achieved in just 60–80% of cases with conservative therapy, and considering certain patients may develop morphological progression, alternative therapy options such as surgical or endovascular approaches are imperative [7,10,11]. In our study, 5.4% of cases treated with surgical intervention and after excluding 3 exploratory laparotomy cases, just 4.0% eventually needed surgical intervention. This is lower than that previously described in literature reviews of several case series (more than 20%). The overall in-hospital mortality in this study was 0.4%, compatible with the literature review by Luan et al., but somewhat lower than other publications [1,3]. Several reports have advocated the following indications for surgical repair: increasing aneurysmal dilation, thrombosis of the SMA true lumen, persistent symptoms despite anticoagulation, arterial rupture, or bowel infarction [12]. Our exclusion about aneurysmal formation could be related with the lower mortality. Tomita et al. revealed exacerbation of SMA dissection after 2 years to be just 4.9% due to enlargement of the existing aneurysm
Limitations Although we were successful in describing clinical practice and outcomes in ISMAD patients, it should be mentioned that this study had several limitations. First, we were unable to evaluate the patients’ symptoms, which are an important indication for surgery, as previously discussed. As a result, indications for surgery could not be identified in this study. Symptoms necessitating surgical intervention have been previously discussed in numerous reports. Instead, we focused on the frequency of surgical intervention, which was the most important numerical value of this study. Second, this study included patients with a chief diagnosis of superior mesenteric artery dissection, and excluded those with an associated diagnosis of “aneurysm”. As discussed, even if CT data were collected, we would not be able to differentiate an aneurysm with mural thrombosis from dissection with a thrombosed false lumen, which is a wholly different category [4]. Our primary aim in this study was to elucidate the clinical practice and outcomes of ISMAD patients, therefore, only “isolated” superior mesenteric artery dissection cases were included in the analysis.
Please cite this article in press as: Mizuno A, et al. Real clinical management of patients with isolated superior mesenteric artery dissection in Japan. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.08.006
G Model
JJCC-1545; No. of Pages 4 A. Mizuno et al. / Journal of Cardiology xxx (2017) xxx–xxx
4
Finally, patient selection bias could not be denied. Although our database included many ISMAD patients, this dataset might not cover all patients. According to our previous experiences of heart failure analysis, it might only account for about one-fourth of the total patients in Japan [22]. Furthermore, previous data revealed the limitations of using administrative data [23]. Therefore, we should wait for the results by using real-clinical dataset such as registry data to conclude what is the preferable therapeutic option because our data did not include any patients treated by endovascular treatment. Conclusion We showed that conservative therapy for ISMAD patients without aneurysm is not only safe, but is associated with low rates of surgical intervention. Further large-scale studies are required to support these findings and to characterize any country-specific differences. Conflicts of interest The authors have no conflicts of interest to declare. References [1] Garrett HE. Options for treatment of spontaneous mesenteric artery dissection. J Vasc Surg 2014;59. 1433–9.e1432. [2] Luan JY, Li X, Li TR, Zhai GJ, Han JT. Vasodilator and endovascular therapy for isolated superior mesenteric artery dissection. J Vasc Surg 2013;57:1612–20. [3] Luan JY, Guan X, Li X, Wang CM, Li TR, Zhang L, et al. Isolated superior mesenteric artery dissection in China. J Vasc Surg 2016;63:530–6. [4] Willoteaux S, Lions C, Gaxotte V, Negaiwi Z, Beregi J. Imaging of aortic dissection by helical computed tomography (CT). Eur Radiol 2004;14:1999–2008. [5] Isogai T, Yasunaga H, Matsui H, Tanaka H, Hisagi M, Fushimi K. Clinical practice patterns in constrictive pericarditis patients with heart failure: a retrospective cohort study using a national inpatient database in Japan. Clin Cardiol 2015;38:740–6. [6] Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 2011;173:676–82.
[7] Satokawa H, Takase S, Seto Y, Yokoyama H, Gotoh M, Kogure M, et al. Management strategy of isolated spontaneous dissection of the superior mesenteric artery. Ann Vasc Dis 2014;7:232–8. [8] Dushnitsky T, Peer A, Katzenelson L, Strauss S. Dissecting aneurysm of the superior mesenteric artery: flow dynamics by color Doppler sonography. J Ultrasound Med 1998;17:781–3. [9] Subhas G, Gupta A, Nawalany M, Oppat WF. Spontaneous isolated superior mesenteric artery dissection: a case report and literature review with management algorithm. Ann Vasc Surg 2009;23:788–98. [10] Li DL, He YY, Alkalei AM, Chen XD, Jin W, Li M, et al. Management strategy for spontaneous isolated dissection of the superior mesenteric artery based on morphologic classification. J Vasc Surg 2014;59:165–72. [11] Sun J, Li DL, Wu ZH, He YY, Zhu QQ, Zhang HK. Morphologic findings and management strategy of spontaneous isolated dissection of the celiac artery. J Vasc Surg 2016;64:389–94. [12] Morris JT, Guerriero J, Sage JG, Mansour MA. Three isolated superior mesenteric artery dissections: update of previous case reports, diagnostics, and treatment options. J Vasc Surg 2008;47. 649–53.e642. [13] Tomita K, Obara H, Sekimoto Y, Matsubara K, Watada S, Fujimura N, et al. Evolution of computed tomographic characteristics of spontaneous isolated superior mesenteric artery dissection during conservative management. Circ J 2016;80:1452–9. [14] Sakamoto I, Ogawa Y, Sueyoshi E, Fukui K, Murakami T, Uetani M. Imaging appearances and management of isolated spontaneous dissection of the superior mesenteric artery. Eur J Radiol 2007;64:103–10. [15] Yun WS, Kim YW, Park KB, Cho SK, Do YS, Lee KB, et al. Clinical and angiographic follow-up of spontaneous isolated superior mesenteric artery dissection. Eur J Vasc Endovasc Surg 2009;37:572–7. [16] Gobble RM, Brill ER, Rockman CB, Hecht EM, Lamparello PJ, Jacobowitz GR, et al. Endovascular treatment of spontaneous dissections of the superior mesenteric artery. J Vasc Surg 2009;50:1326–32. [17] Maeda K, Sakai T, Hira K, Sato TS, Bito S, Asai A, et al. Physicians’ attitudes toward anticoagulant therapy in patients with chronic atrial fibrillation. Intern Med 2004;43:553–60. [18] Finks JF, Osborne NH, Birkmeyer JD. Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med 2011;364:2128–37. [19] Gammie JS, O’Brien SM, Griffith BP, Ferguson TB, Peterson ED. Influence of hospital procedural volume on care process and mortality for patients undergoing elective surgery for mitral regurgitation. Circulation 2007;115:881–7. [20] Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative mortality for major cancer surgery. JAMA 1998;280:1747–51. [21] Forrest CB, Bartek RJ, Rubinstein Y, Groft SC. The case for a global rare-diseases registry. Lancet 2011;377:1057–9. [22] Mizuno A, Iguchi H, Sawada Y, Hurley M, Nomura H, Hayashi K, et al. The impact of carperitide usage on the cost of hospitalization and outcome in patients with acute heart failure: high value care vs. low value care campaign in Japan. Int J Cardiol 2017;241:243–8. [23] Nathan H, Pawlik TM. Limitations of claims and registry data in surgical oncology research. Ann Surg Oncol 2008;15:415–23.
Please cite this article in press as: Mizuno A, et al. Real clinical management of patients with isolated superior mesenteric artery dissection in Japan. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.08.006
JJCC-1545; No. of Pages 4 Journal of Cardiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Cardiology journal homepage: www.elsevier.com/locate/jjcc
Original article
Real clinical management of patients with isolated superior mesenteric artery dissection in Japan Atsushi Mizuno (MD, FJCC)a,*, Hayato Iguchi b, Yuuka Sawada (RN)b, Hiroshi Nomura b, Nobuyuki Komiyama (MD, PhD, FJCC)a, Sachiko Watanabe (RN)b, Aki Yoshikawa (RN, MHSA, MAE)b a b
St. Luke’s International Hospital, Tokyo, Japan Global Health Consulting Japan Co. Ltd, Tokyo, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 8 May 2017 Received in revised form 28 July 2017 Accepted 22 August 2017 Available online xxx
Background: Due to the rarity of this condition, clinical treatment and outcomes in isolated superior mesenteric artery dissection (ISMAD) patients remain unknown. The primary aim of this retrospective multicenter study was to elucidate the treatment strategies and in-hospital outcomes for ISMAD patients by using administrative data. Methods: We retrospectively analyzed patients that were primarily diagnosed with ISMAD using the Diagnosis Procedure Combination data collected at 141 hospitals in Japan in 2015. Patients with comorbidities that included “aneurysm” were excluded. Results: A total of 221 ISMAD without aneurysm patients (male: 90.5%; mean age: 52.5 10.1 years) were enrolled, and 95 (67.4%) of these encountered just one ISMAD case per year. We found only one (0.5%) in-hospital death and length of stay for ISMAD patients was 13.2 9.1 days. One-third of patients received antiplatelet therapy (32.1%) and anticoagulation therapies, such as heparin (38.9%) and warfarin (10.0%). A total of 146 (66.1%) patients received antihypertensive treatment (either orally or via an intravenous route) during hospitalization. Twelve (5.4%) patients underwent surgical procedures during hospitalization as follows: 4 (33.3%) patients underwent bypass surgery, 3 (25.0%) patients underwent exploratory laparotomies, 2 (16.7%) patients underwent bowel resection, 1 (8.3%) patient underwent a thrombectomy, and 2 (16.7%) patients underwent surgical angioplasties. Conclusions: We found that conservative therapy for ISMAD patients without aneurysm is safe and is also associated with a low rate of surgical intervention in clinical practice. © 2017 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
Keywords: Superior mesenteric artery dissection Operation Ischemia Conservative therapy
Introduction While isolated superior mesenteric artery dissection (ISMAD) is considered a rare condition, recent progress in imaging modalities such as computed tomographic (CT) angiography imaging has improved diagnosis [1]. Despite an increasing number of reports worldwide, the question of how to treat ISMAD largely depends on individual physicians. Although there are many literature reviews and clinical practice reports for ISMAD, many of them describe a sample size of just 20 in each single study [1–3]. Actual clinical treatment strategies and outcomes in ISMAD patients remain unknown. Here we present
* Corresponding author at: Department of Cardiology, St. Luke’s International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo, Japan. E-mail address: [email protected] (A. Mizuno).
a retrospective multicenter study that aimed to show the real clinical practice for ISMAD patients. Methods Study design and data sources This was a retrospective study using Diagnosis Procedure Combination (DPC) data collected between January 2015 and December 2015. These data were collected from 141 Japanese hospitals that had agreed to its secondary usage. The requirement for informed consent was waived as the data were anonymized. The DPC data included the following: patient age and sex; main diagnoses and comorbidities, recorded with both International Classification of Diseases (Tenth Revision) (ICD-10) codes and text data written in Japanese; New York Heart Association (NYHA) functional class at admission; drugs and devices; diagnostic and
http://dx.doi.org/10.1016/j.jjcc.2017.08.006 0914-5087/© 2017 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
Please cite this article in press as: Mizuno A, et al. Real clinical management of patients with isolated superior mesenteric artery dissection in Japan. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.08.006
G Model
JJCC-1545; No. of Pages 4 A. Mizuno et al. / Journal of Cardiology xxx (2017) xxx–xxx
2
therapeutic procedures such as surgical procedures coded using the Japanese claims classification (K-code with Japanese text); admission and discharge dates; discharge status; and unique hospital identifiers. Patient selection and definition We selected patients with a primary diagnosis of superior mesenteric artery dissection between January 2015, and December 2015, as per the Japanese text data. We excluded those patients whose comorbidities including “aneurysm” in the Japanese text, as an aneurysm itself could be an indication for surgery and we were unable to appropriately differentiate between aneurysms with mural thrombosis and dissection with a thrombosed false lumen [4]. Baseline characteristics were compiled based on patient age and sex, the Charlson Comorbidity Index (CCI), and comorbidities (including atrial fibrillation and flutter, cerebrovascular disease, chronic pulmonary disease, chronic liver disease, renal disease, malignancy, diabetes, and hypertension). We defined the patients’ comorbidities by using ICD-10 and CCI definitions (Supplement Table 1) [5,6]. Detailed surgical data during hospitalization were obtained via the K-code with Japanese text. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institutional review board of The St. Luke’s International University. Supplementary Table 1 related to this article can be found, in the online version, at doi:10.1016/j.jjcc.2017.08.006. Statistical analysis Categorical variables are presented as numbers and proportions while continuous variables are presented as the mean standard deviation (SD) or the median with the interquartile range (IQR). All statistical analyses were performed using “R” software (Version 3.2.5, R Foundation, Vienna, Austria). Results Baseline patient characteristics and in-hospital outcomes A total of 221 ISMAD patients were enrolled in this study (Table 1). The majority of patients were male (90.5%) and threefourths were not associated with any comorbidities as calculated by CCI. Of 141 hospitals, the annual number of ISMAD cases per hospital was as follows: 1 case (67.4%), 2 cases (16.3%), 3 cases (11.3%), and 4 cases or more (5.0%) (Table 2). We noted just one (0.5%) in-hospital death and the length of stay of these patients was 13.2 9.1 days. Total cost of hospitalization was 612,854.5 505,399.8 yen (median, 508,546 yen; IQR: 338,080– 745,170). Imaging modality and drug usage CT and Doppler ultrasound were performed on 209 (94.6%) and 71 (32.1%) patients, respectively (Table 3). One-third of these patients received antiplatelet (32.1%) and anticoagulation therapy [such as heparin (38.9%) and warfarin (10.0%)]. Six patients (2.7%) received both antiplatelet and anticoagulation therapy. A total of 146 (66.1%) patients received antihypertensive treatment (either orally or via an intravenous route) during hospitalization. Surgical procedures Twelve (5.4%) patients underwent surgical procedures during hospitalization as follows (Table 4): 4 (33.3%) patients underwent bypass surgery, 3 (25.0%) patients underwent an exploratory
Table 1 Baseline characteristics. Patients Male, n (%) Age, year Height, cm Weight, kg Comorbidities Acute myocardial infarction, n (%) Congestive heart failure, n (%) Peripheral vascular disease, n (%) Cerebral vascular accident, n (%) Dementia, n (%) Pulmonary disease, n (%) Connective tissue disorder, n (%) Peptic ulcer, n (%) Liver disease, n (%) Diabetes, n (%) Diabetes complications, n (%) Paraplegia, n (%) Renal disease, n (%) Cancer, n (%) Metastatic cancer, n (%) Severe liver disease, n (%) HIV, n (%) Atrial fibrillation/Flutter, n (%) Rheumatic disease, n (%) Hypertension, n (%) CCI score, n (%) 0 1 2 3
n = 221 200 (90.5) 52.5 10.1 158.0 41.8 65.2 18.9 0 (0) 11 (5) 2 (0.9) 4 (1.8) 0 (0) 6 (2.7) 0 (0) 29 (13.1) 1 (0.5) 9 (4.1) 0 (0) 0 (0) 2 (0.9) 8 (3.6) 1 (0.5) 0 (0) 0 (0) 3 (1.4) 0 (0) 134 (60.6) 156 (70.6) 51 (23.1) 10 (4.5) 4 (1.8)
HIV, human immunodeficiency virus; CCI, Charlson Comorbidity Index.
Table 2 Annual case volume (n = 141 hospitals). Annual case volume per year
Hospital number
1 2 3 4 5 6
95 (67.4) 23 (16.3) 16 (11.3) 4 (2.8) 2 (1.4) 1 (0.7)
Table 3 Imaging modalities and drug usage during hospitalization. Imaging modalities, n (%) Computed tomography, n (%) Doppler ultrasound, n (%) Prescriptions, n (%) ACE-I/ARB Beta blocker Ca blocker Alpha blocker Nitroglycerin Aldosterone blocker Oral opioid Antiplatelet therapy Anticoagulation therapy Antiplatelet and anticoagulation Intravenous drugs, n (%) Nitroglycerin Beta blocker Ca blocker Thrombolytic therapy Intravenous heparin Opioid
209 (94.6) 71 (32.1) 72 (32.6) 54 (24.4) 4 (1.8) 5 (2.3) 0 (0) 1 (0.5) 1 (0.5) 65 (29.4) 16 (7.2) 6 (2.7) 5 (2.3) 9 (4.1) 115 (52) 3 (1.4) 86 (38.9) 29 (13.1)
ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.
Please cite this article in press as: Mizuno A, et al. Real clinical management of patients with isolated superior mesenteric artery dissection in Japan. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.08.006
G Model
JJCC-1545; No. of Pages 4 A. Mizuno et al. / Journal of Cardiology xxx (2017) xxx–xxx Table 4 Operation during hospitalization. Operation Bypass, n (%) Exploratory laparotomy, n (%) Bowel resection, n (%) Thrombectomy, n (%) Angioplasty, n (%)
n = 12 4 (33.3) 3 (25) 2 (16.7) 1 (8.3) 2 (16.7)
laparotomy, 2 (16.7%) patients underwent bowel resection, one (8.3%) patient underwent a thrombectomy, and 2 (16.7%) patients underwent angioplasty. The differences between operation patients and non-operation patients were shown in Supplement Table 2. Opioid was more frequently used and length of stay was longer in operation patients comparing with others. Supplementary Table 2 material related to this article can be found, in the online version, at doi:10.1016/j.jjcc.2017.08.006.
3
[13]. Furthermore, they found that 43.9% of dissections showed complete remodeling. Aneurysmal formation on initial CT was one of the most important findings. According to these data, the use of conservative therapy in ISMAD cases without aneurysmal formation is a safe option. Progress in imaging modalities has enabled us to analyze the morphology of ISMAD, especially using the Sakamoto or Yun classifications [14,15]. Unfortunately, these classifications do not include aneurysm formation. Further studies are required in order to optimize the algorithm used for current imaging modalities. Anticoagulation and antiplatelet therapy
This report is the first of its type and the largest multicenter retrospective study on clinical practice for ISMAD patients. Our results suggest that conservative therapy for ISMAD without aneurysm is both safe and comparable to findings from previous studies [7].
Although appropriate conservative therapy has not yet been fully evaluated, anticoagulation and antiplatelet therapies are considered the mainstay for conservative treatment of ISMAD and are associated with better results [16]. In our study, just one-third of patients received antiplatelet or anticoagulation therapy, a finding that is lower than that previously reported. This could be attributed to a negative image of anticoagulation therapy as an area of uncertainty [17]. In addition to the uncertain effect of anticoagulation and antiplatelet therapy, these drugs might induce bleeding. We should be careful to use these types of drugs. Although we observed fairly good clinical outcomes in our study, the usage of antiplatelet or anticoagulation therapies requires further investigation.
Diagnosis
Future global studies
We used several imaging modalities to diagnose ISMAD, including CT, Doppler ultrasound, and conventional angiography. Many clinicians are primarily dependent on contrast-enhanced CT due to its high diagnostic value. Luan et al. reported that CT was performed on 95.2% of ISMAD patients in a review of the literature, similar to the results obtained in this study (94.6%) [3]. In addition, we performed abdominal ultrasound in one-third of ISMAD patients in the present study. Doppler ultrasound is an inexpensive and noninvasive technique that can be performed repeatedly. While CT does offer more precise images, Doppler ultrasound can be useful for patients requiring serial assessment of superior mesenteric artery (SMA) blood flow [8]. However, the added value of these imaging modalities for ISMAD patients is not yet clear.
A large number of previous studies have been limited to Asian countries such as Korea, China, and Japan [2]. Due to the rarity of this disease, many are case reports or retrospective literature reviews. Recent serial reports from China support revascularization strategies such as surgery and endovascular stenting. Indeed, such strategies may be useful considering the pathophysiology of the disease. A major factor contributing to this uncertainty is the relative inexperience of treating ISMAD within a single institution, as our study found that the majority of institutions saw just one case annually. The relationship between hospital case volume and quality of care has previously been demonstrated in many areas, including surgery and process of care [18–20]. In the case of such rare diseases, a global registry may be useful [21]. Now is the time to collaborate and create a new, large worldwide registry that could elucidate real clinical practice and improve clinical outcomes.
Discussion
Surgical intervention Although several management protocols and algorithms have previously been advocated for the treatment of ISMAD, most have concluded that conservative therapy is a preferable primary course of management [7,9,10]. However, as symptom relief is achieved in just 60–80% of cases with conservative therapy, and considering certain patients may develop morphological progression, alternative therapy options such as surgical or endovascular approaches are imperative [7,10,11]. In our study, 5.4% of cases treated with surgical intervention and after excluding 3 exploratory laparotomy cases, just 4.0% eventually needed surgical intervention. This is lower than that previously described in literature reviews of several case series (more than 20%). The overall in-hospital mortality in this study was 0.4%, compatible with the literature review by Luan et al., but somewhat lower than other publications [1,3]. Several reports have advocated the following indications for surgical repair: increasing aneurysmal dilation, thrombosis of the SMA true lumen, persistent symptoms despite anticoagulation, arterial rupture, or bowel infarction [12]. Our exclusion about aneurysmal formation could be related with the lower mortality. Tomita et al. revealed exacerbation of SMA dissection after 2 years to be just 4.9% due to enlargement of the existing aneurysm
Limitations Although we were successful in describing clinical practice and outcomes in ISMAD patients, it should be mentioned that this study had several limitations. First, we were unable to evaluate the patients’ symptoms, which are an important indication for surgery, as previously discussed. As a result, indications for surgery could not be identified in this study. Symptoms necessitating surgical intervention have been previously discussed in numerous reports. Instead, we focused on the frequency of surgical intervention, which was the most important numerical value of this study. Second, this study included patients with a chief diagnosis of superior mesenteric artery dissection, and excluded those with an associated diagnosis of “aneurysm”. As discussed, even if CT data were collected, we would not be able to differentiate an aneurysm with mural thrombosis from dissection with a thrombosed false lumen, which is a wholly different category [4]. Our primary aim in this study was to elucidate the clinical practice and outcomes of ISMAD patients, therefore, only “isolated” superior mesenteric artery dissection cases were included in the analysis.
Please cite this article in press as: Mizuno A, et al. Real clinical management of patients with isolated superior mesenteric artery dissection in Japan. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.08.006
G Model
JJCC-1545; No. of Pages 4 A. Mizuno et al. / Journal of Cardiology xxx (2017) xxx–xxx
4
Finally, patient selection bias could not be denied. Although our database included many ISMAD patients, this dataset might not cover all patients. According to our previous experiences of heart failure analysis, it might only account for about one-fourth of the total patients in Japan [22]. Furthermore, previous data revealed the limitations of using administrative data [23]. Therefore, we should wait for the results by using real-clinical dataset such as registry data to conclude what is the preferable therapeutic option because our data did not include any patients treated by endovascular treatment. Conclusion We showed that conservative therapy for ISMAD patients without aneurysm is not only safe, but is associated with low rates of surgical intervention. Further large-scale studies are required to support these findings and to characterize any country-specific differences. Conflicts of interest The authors have no conflicts of interest to declare. References [1] Garrett HE. Options for treatment of spontaneous mesenteric artery dissection. J Vasc Surg 2014;59. 1433–9.e1432. [2] Luan JY, Li X, Li TR, Zhai GJ, Han JT. Vasodilator and endovascular therapy for isolated superior mesenteric artery dissection. J Vasc Surg 2013;57:1612–20. [3] Luan JY, Guan X, Li X, Wang CM, Li TR, Zhang L, et al. Isolated superior mesenteric artery dissection in China. J Vasc Surg 2016;63:530–6. [4] Willoteaux S, Lions C, Gaxotte V, Negaiwi Z, Beregi J. Imaging of aortic dissection by helical computed tomography (CT). Eur Radiol 2004;14:1999–2008. [5] Isogai T, Yasunaga H, Matsui H, Tanaka H, Hisagi M, Fushimi K. Clinical practice patterns in constrictive pericarditis patients with heart failure: a retrospective cohort study using a national inpatient database in Japan. Clin Cardiol 2015;38:740–6. [6] Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 2011;173:676–82.
[7] Satokawa H, Takase S, Seto Y, Yokoyama H, Gotoh M, Kogure M, et al. Management strategy of isolated spontaneous dissection of the superior mesenteric artery. Ann Vasc Dis 2014;7:232–8. [8] Dushnitsky T, Peer A, Katzenelson L, Strauss S. Dissecting aneurysm of the superior mesenteric artery: flow dynamics by color Doppler sonography. J Ultrasound Med 1998;17:781–3. [9] Subhas G, Gupta A, Nawalany M, Oppat WF. Spontaneous isolated superior mesenteric artery dissection: a case report and literature review with management algorithm. Ann Vasc Surg 2009;23:788–98. [10] Li DL, He YY, Alkalei AM, Chen XD, Jin W, Li M, et al. Management strategy for spontaneous isolated dissection of the superior mesenteric artery based on morphologic classification. J Vasc Surg 2014;59:165–72. [11] Sun J, Li DL, Wu ZH, He YY, Zhu QQ, Zhang HK. Morphologic findings and management strategy of spontaneous isolated dissection of the celiac artery. J Vasc Surg 2016;64:389–94. [12] Morris JT, Guerriero J, Sage JG, Mansour MA. Three isolated superior mesenteric artery dissections: update of previous case reports, diagnostics, and treatment options. J Vasc Surg 2008;47. 649–53.e642. [13] Tomita K, Obara H, Sekimoto Y, Matsubara K, Watada S, Fujimura N, et al. Evolution of computed tomographic characteristics of spontaneous isolated superior mesenteric artery dissection during conservative management. Circ J 2016;80:1452–9. [14] Sakamoto I, Ogawa Y, Sueyoshi E, Fukui K, Murakami T, Uetani M. Imaging appearances and management of isolated spontaneous dissection of the superior mesenteric artery. Eur J Radiol 2007;64:103–10. [15] Yun WS, Kim YW, Park KB, Cho SK, Do YS, Lee KB, et al. Clinical and angiographic follow-up of spontaneous isolated superior mesenteric artery dissection. Eur J Vasc Endovasc Surg 2009;37:572–7. [16] Gobble RM, Brill ER, Rockman CB, Hecht EM, Lamparello PJ, Jacobowitz GR, et al. Endovascular treatment of spontaneous dissections of the superior mesenteric artery. J Vasc Surg 2009;50:1326–32. [17] Maeda K, Sakai T, Hira K, Sato TS, Bito S, Asai A, et al. Physicians’ attitudes toward anticoagulant therapy in patients with chronic atrial fibrillation. Intern Med 2004;43:553–60. [18] Finks JF, Osborne NH, Birkmeyer JD. Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med 2011;364:2128–37. [19] Gammie JS, O’Brien SM, Griffith BP, Ferguson TB, Peterson ED. Influence of hospital procedural volume on care process and mortality for patients undergoing elective surgery for mitral regurgitation. Circulation 2007;115:881–7. [20] Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative mortality for major cancer surgery. JAMA 1998;280:1747–51. [21] Forrest CB, Bartek RJ, Rubinstein Y, Groft SC. The case for a global rare-diseases registry. Lancet 2011;377:1057–9. [22] Mizuno A, Iguchi H, Sawada Y, Hurley M, Nomura H, Hayashi K, et al. The impact of carperitide usage on the cost of hospitalization and outcome in patients with acute heart failure: high value care vs. low value care campaign in Japan. Int J Cardiol 2017;241:243–8. [23] Nathan H, Pawlik TM. Limitations of claims and registry data in surgical oncology research. Ann Surg Oncol 2008;15:415–23.
Please cite this article in press as: Mizuno A, et al. Real clinical management of patients with isolated superior mesenteric artery dissection in Japan. J Cardiol (2017), http://dx.doi.org/10.1016/j.jjcc.2017.08.006