- Email: [email protected]
Clinical Outcome of Extraanatomic Bypass for Midaortic Syndrome Caused by Takayasu Arteritis
Journal Pre-proof Clinical Outcome of Extra-anatomic Bypass for Midaortic Syndrome Caused by Takayasu Arteritis Young Su Kim, MD, Yang Hyun Cho, MD, PhD, Kiick Sung, MD, PhD, Duk-Kyung Kim, MD, PhD, Suryeun Chung, MD, Taek Kyu Park, MD, Wook Sung Kim, MD, PhD PII:
S0003-4975(19)31420-1
DOI:
https://doi.org/10.1016/j.athoracsur.2019.08.032
Reference:
ATS 33054
To appear in:
The Annals of Thoracic Surgery
Received Date: 14 March 2019 Revised Date:
8 July 2019
Accepted Date: 8 August 2019
Please cite this article as: Kim YS, Cho YH, Sung K, Kim DK, Chung S, Park TK, Kim WS, Clinical Outcome of Extra-anatomic Bypass for Midaortic Syndrome Caused by Takayasu Arteritis, The Annals of Thoracic Surgery (2019), doi: https://doi.org/10.1016/j.athoracsur.2019.08.032. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 by The Society of Thoracic Surgeons
Clinical Outcome of Extra-anatomic Bypass for Midaortic Syndrome Caused by Takayasu Arteritis Running head: Outcome after extra-anatomic bypass
Young Su Kim, MDa*, Yang Hyun Cho, MD, PhDa*, Kiick Sung, MD, PhDa, Duk-Kyung Kim, MD, PhDb, Suryeun Chung, MDa, Taek Kyu Park, MDb, Wook Sung Kim, MD, PhDa
*Drs Kim and Cho contributed equally to this work.
Institution and affiliations: a
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Republic of Korea b
Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Republic of Korea
Corresponding author: Dr. Kiick Sung, MD, PhD Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Email: [email protected]
Word count: 3339
1
Abstract Background. We investigated long-term outcomes and cardiac function after extra-anatomic bypass surgery for Takayasu arteritis and midaortic syndrome. Methods. Between 2007 and 2016, 14 patients underwent extra-anatomic bypass for Takayasu arteritis. Median age was 56.6 years. Median systolic pressure gradient in the stenotic lesion was 79 mmHg. Nine patients underwent bypass surgery from the ascending aorta to the infrarenal aorta, 2 from the ascending aorta to the distal descending thoracic aorta, 1 from the ascending aorta to the supraceliac abdominal aorta, 1 from the descending thoracic aorta to the infrarenal abdominal aorta, and 1 from the descending thoracic aorta to the descending thoracic aorta. Five underwent additional 6 peripheral bypass procedures and 6 underwent concomitant heart surgery. Results. There were no early deaths. Median hospital stay was 10.5 days. Median follow-up duration was 36.3 months, and late death occurred in 2 patients. One died at 1 year postoperatively because of infection due to pancreatic injury and mediastinitis. The other was lost to follow-up, and death was confirmed through the national insurance database. No anastomotic site stenosis or aneurysmal change occurred. The number of antihypertensive medications significantly reduced in all but 1 patient, and organ ischemia symptoms, including dizziness, visual disturbance, and claudication, improved in all patients. Interventricular septal diameter and left ventricular mass index decreased significantly. Serum creatinine level also decreased. Overall estimated 5-year survival was 79±13%. Conclusions. Extra-anatomic bypass for Takayasu arteritis is safe and effective and can be useful for left ventricular unloading and reduction of organ ischemia.
Abstract word count: 250
Keywords: Takayasu arteritis, midaortic syndrome, extra-anatomic bypass, echocardiogram
2
Takayasu arteritis is a form of granulomatous arteritis predominantly affecting the aorta and/or its major branches. It is very rare and mainly affects young women under 50 years [1, 2]. Chronic inflammation of the aorta causes stenotic changes, resulting in uncontrolled hypertension, heart failure, and symptoms of organ hypoperfusion such as renal insufficiency or leg ischemia. In the acute phase, the disease is controlled by medications; however, surgical correction is necessary for chronic progression. Various surgical techniques, including aortic patch angioplasty, anatomic graft interposition, stent graft insertion, and endovascular intervention, are used [3-5]. However, these techniques are difficult to perform because of the presence of diffuse, long-segment lesions, severe calcification with fibrosis, and inflammatory changes. In such cases, extra-anatomic bypass should be performed; however, few cases have been reported worldwide. Several studies have been published on these surgical techniques, but most of these papers have discussed the resolution of stenosis through evaluation of imaging results, graft patency, and clinical outcomes [4, 6, 7]. Therefore, this study aimed to describe our experience on extra-anatomic bypass surgery among patients referred to the Takayasu arteritis clinic of a large tertiary care hospital, with a focus on cardiac unloading and improvement of organ perfusion.
Patients and Methods This study was approved by the institutional review board, and informed consent was waived because this was a retrospective study. We reviewed records of patients who underwent extra-anatomic bypass for Takayasu arteritis between 2007 and 2016. Among the 14 patients enrolled, 2 were men and 12 were women. Patients’ median age was 56.6 (48–62.7) years. Diagnosis was made using computed tomography angiography (CTA). In addition, some patients underwent magnetic resonance angiography or aortography. All patients received immunosuppressant therapy, including steroid administration. However, all of them had disease progression with symptoms such as dyspnea due to heart failure, dizziness, visual disturbances, bilateral leg claudication, and renal failure. The median preoperative erythrocyte 3
sedimentation rate was 30.5 (14.5–46.3) mm/h, and median C-reactive protein level was 0.2 (0.05– 1.32) mg/dL (Table 1). The median systolic blood pressure gradient proximal and distal to the stenotic lesion was 79 (57.5–89) mmHg. Interventricular septal diameter (IVSD), left ventricular mass index (LVMI), systolic (LVIDs) and diastolic (LVIDd) left ventricular internal diameter, and left atrial volume index (LAVI) were measured using echocardiography at 6 months to 1 year postoperatively to confirm cardiac unloading. All personal, clinical, laboratory, and outcome data were collected from patients’ medical records.
Surgical Indications and Techniquewlr Surgical indications included uncontrolled hypertension, heart failure, and renal ischemia. Additional procedures were performed under specific conditions. Axillary artery bypass was performed when both subclavian arteries were obstructed such that true blood pressure could not be determined in the upper limbs, and carotid artery bypass was performed when stenosis caused cerebral hypoperfusion symptoms. Valve surgery or coronary bypass surgery was performed for significant aortic or mitral valve regurgitation or coronary artery stenosis. Renal artery bypass was performed for significant renal ischemia (Table 1). Nine patients underwent bypass surgery from the ascending to the infrarenal abdominal aorta, 2 from the ascending to the distal descending thoracic aorta, and 1 from the ascending to the supraceliac abdominal aorta. One underwent bypass surgery from the descending thoracic to the infrarenal abdominal aorta and 1 from the descending thoracic to the descending thoracic aorta. Five underwent additional 6 peripheral bypass procedures, including renal artery bypass in 2 cases, axillary bypass in 2, and carotid artery bypass in 2. Six patients underwent a concomitant cardiac procedure (Table 2). Surgery with concomitant cardiac surgery was performed via median sternotomy and midline laparotomy in the supine position. Median sternotomy and midline laparotomy were performed for bypass surgery from the ascending aorta to the abdominal aorta. A patient who underwent bypass surgery from the ascending aorta to the distal descending thoracic aorta only underwent median sternotomy. A case of bypass surgery from the descending aorta to the descending aorta was 4
performed via posterolateral thoracotomy, and a case of bypass surgery from the descending aorta to the infrarenal abdominal aorta was performed via lateral thoracotomy and separate midline abdominal incision. Anastomosis was performed where the intima cleared, and the vessel was expanded past the stenotic lesion. Cardiopulmonary bypass was not needed for patients who underwent only bypass without a cardiac procedure. Graft size was decided according to the surgeon’s judgment during surgery while considering the size of the distal aorta anastomosis site. A 14-mm Dacron vascular graft was used in 9 patients, 16 mm in 3, 12 mm + 14 mm composite graft in 1, and 20 mm in 1.
Statistical Analysis SPSS software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Data were presented as median and interquartile range. The Wilcoxon signed-rank test was used to analyze preoperative and postoperative data. Survival curves were obtained using the Kaplan–Meier method with 95% confidence interval.
Results The median postoperative extubation time was 8.2 (5.6–17.8) hours, median intensive care unit stay was 45.2 (25.3–75.1) hours, and median hospital stay was 10.5 (9–18.8) days. Postoperative complications were observed in 5 patients, including 3 patients with chylothorax, 1 patient with a wound problem, and 1 patient with bleeding due to pancreatic injury and mediastinitis. No early deaths were noted within 30 days. The median follow-up period was 36.3 (9.8–103.5) months. Late deaths occurred in 2 patients. One patient was a 68-year-old woman who underwent bypass surgery from the ascending aorta to the infrarenal abdominal aorta and concomitant Bentall procedure, coronary artery bypass, mitral and tricuspid valve repair, Cox maze procedure, patent foramen ovale primary closure, and bypass surgery aorta to the left axillary. She died due to mediastinitis with pancreatic injury as abovementioned. Infection was unresolved, and she died 1 year later. The other one was a 51-year-old man who was lost to follow-up, and his death was confirmed through the national insurance database 2 years later; the exact cause of death was unknown. During the follow-up 5
period, no cases showed anastomotic site aneurysmal changes or stenosis based on the most recent CTA. One patient was readmitted due to axillary graft infection during follow-up and was treated with graft irrigation and antibiotics. Figure 1 shows that the graft was well-maintained on follow-up CTA. Antihypertensive medications were discontinued or the number was significantly reduced in all except 1 patient at the time of discharge (from 4 [3-6] to 2.5 medications [2-3], p = 0.017) (Table 3). Peripheral symptoms, such as renal impairment and claudication, significantly improved (preoperative, 57% vs. postoperative, 14%, p = 0.014; 50% vs. 0%, p = 0.008). Neurologic symptoms, such as dizziness and visual disturbances, were all resolved. Postoperative creatinine levels were significantly reduced and were within the normal range (1.1 mg/dL [0.93–1.45] vs. 0.8 mg/dL [0.71–1.03], p = 0.028) (Fig 2). One patient required renal replacement therapy postoperatively. Follow-up echocardiography did not show significant increase in ejection fraction, but the IVSD and LVMI significantly decreased (13 mm [10–14] vs. 11.7 mm [9–12], p = 0.016 and 177.7 g/m2 [163.8–205.4] vs. 122.1 g/m2 [101.9–132.2], p = 0.017, respectively). Furthermore, other parameters indicating cardiac unloading, including the LVIDs, LVIDd, and LAVI, significantly decreased (36 mm [26–45.5] vs. 24.5 mm [23.5–34], p = 0.05; 57.5 mm [44.5–64] vs. 43 mm [39.5–52], p = 0.025; and 80.7 mL/m2 [54.8–100.1] vs. 59.3 mL/m2 [42.9–73], p = 0.036, respectively) (Fig 3). The overall 5-year survival rate was 79±13% (95% confidence interval [53.8, 105.2]) (Fig 4).
Comment Takayasu arteritis, a rare but fatal disease, was first reported by an ophthalmologist Takayasu in 1908. This chronic inflammatory disease mainly involves the large vessels, such as the aorta [8]. Shimizu and Sano called it “pulseless disease” based on the clinical features [9]. The early phase is characterized by nonspecific symptoms such as fever, malaise, weight loss, and myalgia due to systemic inflammation. However, in the chronic phase, progression of stenosis of the aorta or its branches occurs as a result of arterial inflammation, resulting in uncontrolled secondary hypertension, organ hypoperfusion, peripheral obstruction, and symptoms associated with heart failure. The primary treatment is medical therapy, including steroid administration. Additionally, cytotoxic agents such as 6
cyclophosphamide may be used. Good responses to medical treatment are possible when drugs with various treatment spectrums are used [10]. However, in many cases, the disease progresses despite medical treatment, and surgery is necessary for stenosis involving the renal artery, cerebral arteries, and large arteries in the extremities. Surgical treatment is generally performed during the chronic phase to avoid complications such as restenosis, pseudoaneurysm formation, and infection [11]. All except 1 patient in this study also underwent surgery during the chronic phase. Only 1 patient with uncontrolled heart failure underwent surgery in the early phase. Her surgery included ascending aorta to infrarenal abdominal aorta bypass, abdominal aorta to bilateral renal artery bypass, and ascending aorta to right axillary artery bypass. She has been followed-up on an outpatient basis for 10 years. Patients who require surgery are usually in the chronic inactive phase after decades of having Takayasu arteritis. In addition, fibrosis and calcification of the aorta are the main findings, not inflammation. Therefore, there is little need for drugs such as cytotoxic agents or steroids, and hypertensive medications and antiplatelet agents are the mainstay of treatment for Takayasu arteritis. In fact, only 1 patient who underwent surgery used steroids for approximately 1 year at the time of first visit (8 years ago before surgery) and the other patient used cytotoxic drugs for several years at the time of first diagnosis (7 years ago before surgery). Any other patients did not use cytotoxic agents or steroids. Various surgical techniques have been reported, including extra-anatomic bypass, graft interposition, and patch angioplasty. These surgical treatments showed good results, except for aortic aneurysms and especially ruptured aneurysms [12, 13]. Since its introduction in 1980, endovascular treatment has also been used for midaortic syndrome due to Takayasu arteritis [14-16]. Extra-anatomic bypass has shown good results based on previous reports [4, 6, 7], particularly if the involved site includes a long segment. The purpose of surgical treatment is to reduce vital organ ischemia and cardiac loading through optimal blood pressure control. Therefore, we performed follow-up of some indicators to evaluate organ dysfunction and bypass patency through follow-up imaging. Peripheral and neurologic 7
symptoms were almost eliminated, and reduction of renal damage was indirectly confirmed through the reduction of serum creatinine levels. The number of antihypertensive medications was significantly reduced, indicating good blood pressure control. Only in 1 patient, the number of antihypertensive medications was not reduced at the time of discharge. This patient underwent surgery due to progressive heart failure as he was unable to tolerate antihypertensive medications because of dizziness. During follow-up, his antihypertensive medications were not reduced, but his blood pressure improved compared to that preoperatively. Cardiac unloading through afterload reduction is very important. Left ventricular hypertrophy results from pressure overloading caused by systemic hypertension and is a predictor of heart failure and sudden cardiac death. Left ventricular hypertrophy can be measured using the IVSD and LVMI on echocardiography [17-20]. Therefore, cardiac afterload reduction was inferred by confirmation of reduced IVSD and LVMI on the echocardiogram. Moreover, the LVIDs, LVIDd, and LAVI represent LV diastolic functional status resulting from cardiac loading [21]. All of these parameters improved. Several previous reports evaluated the results of extra-anatomic bypass on midaortic syndrome. However, these reports only showed apparently good patency on CTA. In this study, we more clearly confirmed the effect of this surgery on the echocardiogram. Of course, all grafts showed good patency on CTA. This study had a small sample size, which may limit its interpretation and lead to bias. However, Takayasu arteritis is a rare disease, and few patients undergo surgery. Therefore, it is difficult to collect large amount of data. In fact, most previous reports had a small sample size. Hence, the results of this study may be meaningful, despite the small sample size. Another limitation is that a number of concomitant cardiac surgery patients were included, which can act as a confounder to improve echocardiographic finding. However, although statistical interpretation is difficult because of the small number, patients who did not undergo concomitant surgery in this study also had a decrease in LVMI at 1 year postoperatively. In conclusion, extra-anatomic bypass for Takayasu arteritis is safe and effective and can be useful for LV unloading and reduction of organ ischemia. 8
9
References 1.
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013;65:1-11.
2.
Jang SY, Seo SR, Park SW, Kim DK. Prevalence of Takayasu's arteritis in Korea. Clin Exp Rheumatol 2018;36 Suppl 111:163-4.
3.
Stanley JC, Criado E, Eliason JL, Upchurch GR, Jr., Berguer R, Rectenwald JE. Abdominal aortic coarctation: surgical treatment of 53 patients with a thoracoabdominal bypass, patch aortoplasty, or interposition aortoaortic graft. J Vasc Surg 2008;48:1073-82.
4.
Hetzer R, Absi D, Miera O, et al. Extraanatomic bypass technique for the treatment of midaortic syndrome in children. Ann Thorac Surg 2013;96:183-9.
5.
Saadoun D, Lambert M, Mirault T, et al. Retrospective analysis of surgery versus endovascular intervention in Takayasu arteritis: a multicenter experience. Circulation 2012;125:813-9.
6.
Kim SM, Jung IM, Han A, et al. Surgical treatment of middle aortic syndrome with Takayasu arteritis or midaortic dysplastic syndrome. Eur J Vasc Endovasc Surg 2015;50:206-12.
7.
Taketani T, Miyata T, Morota T, Takamoto S. Surgical treatment of atypical aortic coarctation complicating Takayasu's arteritis--experience with 33 cases over 44 years. J Vasc Surg 2005;41:597-601.
8.
Takayasu M. A case with peculiar changes of the central retinal vessels. Acta Societatis Ophthalmologicae Japonicae 1908;12:554-5.
9.
Shimizu K, Sano K. Pulseless disease. J Neuropathol Clin Neurol 1951;1:37-47.
10.
Seyahi E. Takayasu arteritis: an update. Curr Opin Rheumatol 2017;29:51-6.
11.
Johnston SL, Lock RJ, Gompels MM. Takayasu arteritis: a review. J Clin Pathol 2002;55:481-6.
12.
Fields CE, Bower TC, Cooper LT, et al. Takayasu's arteritis: operative results and influence of disease activity. J Vasc Surg 2006;43:64-71.
13.
Robbs JV, Abdool-Carrim AT, Kadwa AM. Arterial reconstruction for non-specific arteritis (Takayasu's disease): medium to long term results. Eur J Vasc Surg 1994;8:401-7.
14.
Martin EC, Diamond NG, Casarella WJ. Percutaneous Transluminal Angioplasty in Non10
Atheroscklerotic Disease. Radiology 1980;135:27-33. 15.
Tyagi S, Kaul UA, Nair M, Sethi KK, Arora R, Khalilullah M. Balloon angioplasty of the aorta in Takayasu's arteritis: initial and long-term results. Am Heart J 1992;124:876-82.
16.
Sharma S, Thatai D, Saxena A, Kothari SS, Guleria S, Rajani M. Renovascular hypertension resulting from nonspecific aortoarteritis in children: midterm results of percutaneous transluminal renal angioplasty and predictors of restenosis. AJR Am J Roentgenol 1996;166:157-62.
17.
Jaafar MS, Hamid O, Khor CS, Yuvaraj RM. Preliminary studies of left ventricular wall thickness and mass of normotensive and hypertensive subjects using m-mode echocardiography. Malays J Med Sci 2002;9:28-33.
18.
Cramariuc D, Gerdts E. Epidemiology of left ventricular hypertrophy in hypertension: implications for the clinic. Expert Rev Cardiovasc Ther 2016;14:915-26.
19.
Lazzeroni D, Rimoldi O, Camici PG. From Left Ventricular Hypertrophy to Dysfunction and Failure. Circ J 2016;80:555-64.
20.
Levy D. Left ventricular hypertrophy. Epidemiological insights from the Framingham Heart Study. Drugs 1988;35 Suppl 5:1-5.
21.
Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am J Cardiol 2002;90:1284-9.
11
Table 1. Preoperative Clinical Status and Operative Indications preoperative Age (years)
56.6 (48-62.7)
Female (%)
12 (86)
Inflammatory status ESR
30.5 (14.5-46.3)
CRP
0.2 (0.05-1.32)
Peripheral symptoms (%) renal impairment
8 (57)
claudication
7 (50)
Neurologic symptoms (%)
4 (29)
Operative indication Uncontrolled hypertension
2 (14)
Heart failure
10 (71)
Renal ischemia
2 (14)
CRP = C-reactive protein; ESR = erythrocyte sedimentation rate
12
Table 2. Combined Operative Data Both renal + axillary (1) Both renal (1)
Peripheral bypass (n = 5)
Axillary (1) Carotid (2) Ascending aorta replacement + AVP (2) Ascending aorta replacement + AVR + Maze (1)
Cardiac procedure (n = 6)
Bentall + MVP + TAP + Maze + CABG + PFO (1) MVP (1) MVP + TAP + Maze + CABG (1)
AVP = aortic valvuloplasty; AVR = aortic valve replacement; CABG = coronary artery bypass graft; MVP = mitral valvuloplasty; PFO = patent foramen ovale; TAP = tricuspid valve annuloplasty
13
Table 3. Medical Management During Preoperative and Postoperative Status Preoperative
Postoperative
p-value
Median number of drug
4 [3-6]
2.5 [2-3]
0.017
Beta-blockers (%)
12 (85.7)
9 (64.3)
ACE inhibitor or ARB (%)
12 (85.7)
5 (35.7)
Calcium channel blocker (%)
9 (64.3)
7 (50)
Diuretics (%)
12 (85.7)
8 (57.1)
Others (%)
2 (14.3)
1 (7.1)
None
None
N/A
11 (78.6)
12 (85.7)
N/A
2
2
N/A
Antihypertensive drug
Cytotoxic agent/steroid (%) Anti-platelet agent (%) Warfarin (%)
ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker
14
Figure Legends Fig. 1. Postoperative 3D CT showing good graft status. White arrow indicates bypass graft. ASC, ascending aorta; DDTA, distal descending thoracic aorta; DTA, descending thoracic aorta; IRABD, infrarenal abdominal aorta; SCABD, supraceliac abdominal aorta; 3D CT, 3-dimensional computed tomography.
Fig. 2. Perioperative creatinine changes: creatinine levels markedly improved.
Fig. 3. Perioperative echocardiogram data: preoperative, immediate postoperative, and follow-up at 1 year. (A) EF change: EF shows a tendency toward normalization in patients with heart failure. (B) IVSD change: At 1-year follow-up, IVSD is significantly decreased. (C) LVMI: LVMI is significantly decreased. (D), (E) systolic and diastolic LV internal diameters are also significantly decreased. (F) LAVI is significantly decreased at 1 year. EF, ejection fraction; IVSD, interventricular septal diameter; LAVI, left atrial volume index LVMI, left ventricular mass index
Fig. 4. Kaplan–Meier survival analysis: overall 5-year survival rate.
15
S0003-4975(19)31420-1
DOI:
https://doi.org/10.1016/j.athoracsur.2019.08.032
Reference:
ATS 33054
To appear in:
The Annals of Thoracic Surgery
Received Date: 14 March 2019 Revised Date:
8 July 2019
Accepted Date: 8 August 2019
Please cite this article as: Kim YS, Cho YH, Sung K, Kim DK, Chung S, Park TK, Kim WS, Clinical Outcome of Extra-anatomic Bypass for Midaortic Syndrome Caused by Takayasu Arteritis, The Annals of Thoracic Surgery (2019), doi: https://doi.org/10.1016/j.athoracsur.2019.08.032. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 by The Society of Thoracic Surgeons
Clinical Outcome of Extra-anatomic Bypass for Midaortic Syndrome Caused by Takayasu Arteritis Running head: Outcome after extra-anatomic bypass
Young Su Kim, MDa*, Yang Hyun Cho, MD, PhDa*, Kiick Sung, MD, PhDa, Duk-Kyung Kim, MD, PhDb, Suryeun Chung, MDa, Taek Kyu Park, MDb, Wook Sung Kim, MD, PhDa
*Drs Kim and Cho contributed equally to this work.
Institution and affiliations: a
Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Republic of Korea b
Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Republic of Korea
Corresponding author: Dr. Kiick Sung, MD, PhD Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea Email: [email protected]
Word count: 3339
1
Abstract Background. We investigated long-term outcomes and cardiac function after extra-anatomic bypass surgery for Takayasu arteritis and midaortic syndrome. Methods. Between 2007 and 2016, 14 patients underwent extra-anatomic bypass for Takayasu arteritis. Median age was 56.6 years. Median systolic pressure gradient in the stenotic lesion was 79 mmHg. Nine patients underwent bypass surgery from the ascending aorta to the infrarenal aorta, 2 from the ascending aorta to the distal descending thoracic aorta, 1 from the ascending aorta to the supraceliac abdominal aorta, 1 from the descending thoracic aorta to the infrarenal abdominal aorta, and 1 from the descending thoracic aorta to the descending thoracic aorta. Five underwent additional 6 peripheral bypass procedures and 6 underwent concomitant heart surgery. Results. There were no early deaths. Median hospital stay was 10.5 days. Median follow-up duration was 36.3 months, and late death occurred in 2 patients. One died at 1 year postoperatively because of infection due to pancreatic injury and mediastinitis. The other was lost to follow-up, and death was confirmed through the national insurance database. No anastomotic site stenosis or aneurysmal change occurred. The number of antihypertensive medications significantly reduced in all but 1 patient, and organ ischemia symptoms, including dizziness, visual disturbance, and claudication, improved in all patients. Interventricular septal diameter and left ventricular mass index decreased significantly. Serum creatinine level also decreased. Overall estimated 5-year survival was 79±13%. Conclusions. Extra-anatomic bypass for Takayasu arteritis is safe and effective and can be useful for left ventricular unloading and reduction of organ ischemia.
Abstract word count: 250
Keywords: Takayasu arteritis, midaortic syndrome, extra-anatomic bypass, echocardiogram
2
Takayasu arteritis is a form of granulomatous arteritis predominantly affecting the aorta and/or its major branches. It is very rare and mainly affects young women under 50 years [1, 2]. Chronic inflammation of the aorta causes stenotic changes, resulting in uncontrolled hypertension, heart failure, and symptoms of organ hypoperfusion such as renal insufficiency or leg ischemia. In the acute phase, the disease is controlled by medications; however, surgical correction is necessary for chronic progression. Various surgical techniques, including aortic patch angioplasty, anatomic graft interposition, stent graft insertion, and endovascular intervention, are used [3-5]. However, these techniques are difficult to perform because of the presence of diffuse, long-segment lesions, severe calcification with fibrosis, and inflammatory changes. In such cases, extra-anatomic bypass should be performed; however, few cases have been reported worldwide. Several studies have been published on these surgical techniques, but most of these papers have discussed the resolution of stenosis through evaluation of imaging results, graft patency, and clinical outcomes [4, 6, 7]. Therefore, this study aimed to describe our experience on extra-anatomic bypass surgery among patients referred to the Takayasu arteritis clinic of a large tertiary care hospital, with a focus on cardiac unloading and improvement of organ perfusion.
Patients and Methods This study was approved by the institutional review board, and informed consent was waived because this was a retrospective study. We reviewed records of patients who underwent extra-anatomic bypass for Takayasu arteritis between 2007 and 2016. Among the 14 patients enrolled, 2 were men and 12 were women. Patients’ median age was 56.6 (48–62.7) years. Diagnosis was made using computed tomography angiography (CTA). In addition, some patients underwent magnetic resonance angiography or aortography. All patients received immunosuppressant therapy, including steroid administration. However, all of them had disease progression with symptoms such as dyspnea due to heart failure, dizziness, visual disturbances, bilateral leg claudication, and renal failure. The median preoperative erythrocyte 3
sedimentation rate was 30.5 (14.5–46.3) mm/h, and median C-reactive protein level was 0.2 (0.05– 1.32) mg/dL (Table 1). The median systolic blood pressure gradient proximal and distal to the stenotic lesion was 79 (57.5–89) mmHg. Interventricular septal diameter (IVSD), left ventricular mass index (LVMI), systolic (LVIDs) and diastolic (LVIDd) left ventricular internal diameter, and left atrial volume index (LAVI) were measured using echocardiography at 6 months to 1 year postoperatively to confirm cardiac unloading. All personal, clinical, laboratory, and outcome data were collected from patients’ medical records.
Surgical Indications and Techniquewlr Surgical indications included uncontrolled hypertension, heart failure, and renal ischemia. Additional procedures were performed under specific conditions. Axillary artery bypass was performed when both subclavian arteries were obstructed such that true blood pressure could not be determined in the upper limbs, and carotid artery bypass was performed when stenosis caused cerebral hypoperfusion symptoms. Valve surgery or coronary bypass surgery was performed for significant aortic or mitral valve regurgitation or coronary artery stenosis. Renal artery bypass was performed for significant renal ischemia (Table 1). Nine patients underwent bypass surgery from the ascending to the infrarenal abdominal aorta, 2 from the ascending to the distal descending thoracic aorta, and 1 from the ascending to the supraceliac abdominal aorta. One underwent bypass surgery from the descending thoracic to the infrarenal abdominal aorta and 1 from the descending thoracic to the descending thoracic aorta. Five underwent additional 6 peripheral bypass procedures, including renal artery bypass in 2 cases, axillary bypass in 2, and carotid artery bypass in 2. Six patients underwent a concomitant cardiac procedure (Table 2). Surgery with concomitant cardiac surgery was performed via median sternotomy and midline laparotomy in the supine position. Median sternotomy and midline laparotomy were performed for bypass surgery from the ascending aorta to the abdominal aorta. A patient who underwent bypass surgery from the ascending aorta to the distal descending thoracic aorta only underwent median sternotomy. A case of bypass surgery from the descending aorta to the descending aorta was 4
performed via posterolateral thoracotomy, and a case of bypass surgery from the descending aorta to the infrarenal abdominal aorta was performed via lateral thoracotomy and separate midline abdominal incision. Anastomosis was performed where the intima cleared, and the vessel was expanded past the stenotic lesion. Cardiopulmonary bypass was not needed for patients who underwent only bypass without a cardiac procedure. Graft size was decided according to the surgeon’s judgment during surgery while considering the size of the distal aorta anastomosis site. A 14-mm Dacron vascular graft was used in 9 patients, 16 mm in 3, 12 mm + 14 mm composite graft in 1, and 20 mm in 1.
Statistical Analysis SPSS software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Data were presented as median and interquartile range. The Wilcoxon signed-rank test was used to analyze preoperative and postoperative data. Survival curves were obtained using the Kaplan–Meier method with 95% confidence interval.
Results The median postoperative extubation time was 8.2 (5.6–17.8) hours, median intensive care unit stay was 45.2 (25.3–75.1) hours, and median hospital stay was 10.5 (9–18.8) days. Postoperative complications were observed in 5 patients, including 3 patients with chylothorax, 1 patient with a wound problem, and 1 patient with bleeding due to pancreatic injury and mediastinitis. No early deaths were noted within 30 days. The median follow-up period was 36.3 (9.8–103.5) months. Late deaths occurred in 2 patients. One patient was a 68-year-old woman who underwent bypass surgery from the ascending aorta to the infrarenal abdominal aorta and concomitant Bentall procedure, coronary artery bypass, mitral and tricuspid valve repair, Cox maze procedure, patent foramen ovale primary closure, and bypass surgery aorta to the left axillary. She died due to mediastinitis with pancreatic injury as abovementioned. Infection was unresolved, and she died 1 year later. The other one was a 51-year-old man who was lost to follow-up, and his death was confirmed through the national insurance database 2 years later; the exact cause of death was unknown. During the follow-up 5
period, no cases showed anastomotic site aneurysmal changes or stenosis based on the most recent CTA. One patient was readmitted due to axillary graft infection during follow-up and was treated with graft irrigation and antibiotics. Figure 1 shows that the graft was well-maintained on follow-up CTA. Antihypertensive medications were discontinued or the number was significantly reduced in all except 1 patient at the time of discharge (from 4 [3-6] to 2.5 medications [2-3], p = 0.017) (Table 3). Peripheral symptoms, such as renal impairment and claudication, significantly improved (preoperative, 57% vs. postoperative, 14%, p = 0.014; 50% vs. 0%, p = 0.008). Neurologic symptoms, such as dizziness and visual disturbances, were all resolved. Postoperative creatinine levels were significantly reduced and were within the normal range (1.1 mg/dL [0.93–1.45] vs. 0.8 mg/dL [0.71–1.03], p = 0.028) (Fig 2). One patient required renal replacement therapy postoperatively. Follow-up echocardiography did not show significant increase in ejection fraction, but the IVSD and LVMI significantly decreased (13 mm [10–14] vs. 11.7 mm [9–12], p = 0.016 and 177.7 g/m2 [163.8–205.4] vs. 122.1 g/m2 [101.9–132.2], p = 0.017, respectively). Furthermore, other parameters indicating cardiac unloading, including the LVIDs, LVIDd, and LAVI, significantly decreased (36 mm [26–45.5] vs. 24.5 mm [23.5–34], p = 0.05; 57.5 mm [44.5–64] vs. 43 mm [39.5–52], p = 0.025; and 80.7 mL/m2 [54.8–100.1] vs. 59.3 mL/m2 [42.9–73], p = 0.036, respectively) (Fig 3). The overall 5-year survival rate was 79±13% (95% confidence interval [53.8, 105.2]) (Fig 4).
Comment Takayasu arteritis, a rare but fatal disease, was first reported by an ophthalmologist Takayasu in 1908. This chronic inflammatory disease mainly involves the large vessels, such as the aorta [8]. Shimizu and Sano called it “pulseless disease” based on the clinical features [9]. The early phase is characterized by nonspecific symptoms such as fever, malaise, weight loss, and myalgia due to systemic inflammation. However, in the chronic phase, progression of stenosis of the aorta or its branches occurs as a result of arterial inflammation, resulting in uncontrolled secondary hypertension, organ hypoperfusion, peripheral obstruction, and symptoms associated with heart failure. The primary treatment is medical therapy, including steroid administration. Additionally, cytotoxic agents such as 6
cyclophosphamide may be used. Good responses to medical treatment are possible when drugs with various treatment spectrums are used [10]. However, in many cases, the disease progresses despite medical treatment, and surgery is necessary for stenosis involving the renal artery, cerebral arteries, and large arteries in the extremities. Surgical treatment is generally performed during the chronic phase to avoid complications such as restenosis, pseudoaneurysm formation, and infection [11]. All except 1 patient in this study also underwent surgery during the chronic phase. Only 1 patient with uncontrolled heart failure underwent surgery in the early phase. Her surgery included ascending aorta to infrarenal abdominal aorta bypass, abdominal aorta to bilateral renal artery bypass, and ascending aorta to right axillary artery bypass. She has been followed-up on an outpatient basis for 10 years. Patients who require surgery are usually in the chronic inactive phase after decades of having Takayasu arteritis. In addition, fibrosis and calcification of the aorta are the main findings, not inflammation. Therefore, there is little need for drugs such as cytotoxic agents or steroids, and hypertensive medications and antiplatelet agents are the mainstay of treatment for Takayasu arteritis. In fact, only 1 patient who underwent surgery used steroids for approximately 1 year at the time of first visit (8 years ago before surgery) and the other patient used cytotoxic drugs for several years at the time of first diagnosis (7 years ago before surgery). Any other patients did not use cytotoxic agents or steroids. Various surgical techniques have been reported, including extra-anatomic bypass, graft interposition, and patch angioplasty. These surgical treatments showed good results, except for aortic aneurysms and especially ruptured aneurysms [12, 13]. Since its introduction in 1980, endovascular treatment has also been used for midaortic syndrome due to Takayasu arteritis [14-16]. Extra-anatomic bypass has shown good results based on previous reports [4, 6, 7], particularly if the involved site includes a long segment. The purpose of surgical treatment is to reduce vital organ ischemia and cardiac loading through optimal blood pressure control. Therefore, we performed follow-up of some indicators to evaluate organ dysfunction and bypass patency through follow-up imaging. Peripheral and neurologic 7
symptoms were almost eliminated, and reduction of renal damage was indirectly confirmed through the reduction of serum creatinine levels. The number of antihypertensive medications was significantly reduced, indicating good blood pressure control. Only in 1 patient, the number of antihypertensive medications was not reduced at the time of discharge. This patient underwent surgery due to progressive heart failure as he was unable to tolerate antihypertensive medications because of dizziness. During follow-up, his antihypertensive medications were not reduced, but his blood pressure improved compared to that preoperatively. Cardiac unloading through afterload reduction is very important. Left ventricular hypertrophy results from pressure overloading caused by systemic hypertension and is a predictor of heart failure and sudden cardiac death. Left ventricular hypertrophy can be measured using the IVSD and LVMI on echocardiography [17-20]. Therefore, cardiac afterload reduction was inferred by confirmation of reduced IVSD and LVMI on the echocardiogram. Moreover, the LVIDs, LVIDd, and LAVI represent LV diastolic functional status resulting from cardiac loading [21]. All of these parameters improved. Several previous reports evaluated the results of extra-anatomic bypass on midaortic syndrome. However, these reports only showed apparently good patency on CTA. In this study, we more clearly confirmed the effect of this surgery on the echocardiogram. Of course, all grafts showed good patency on CTA. This study had a small sample size, which may limit its interpretation and lead to bias. However, Takayasu arteritis is a rare disease, and few patients undergo surgery. Therefore, it is difficult to collect large amount of data. In fact, most previous reports had a small sample size. Hence, the results of this study may be meaningful, despite the small sample size. Another limitation is that a number of concomitant cardiac surgery patients were included, which can act as a confounder to improve echocardiographic finding. However, although statistical interpretation is difficult because of the small number, patients who did not undergo concomitant surgery in this study also had a decrease in LVMI at 1 year postoperatively. In conclusion, extra-anatomic bypass for Takayasu arteritis is safe and effective and can be useful for LV unloading and reduction of organ ischemia. 8
9
References 1.
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013;65:1-11.
2.
Jang SY, Seo SR, Park SW, Kim DK. Prevalence of Takayasu's arteritis in Korea. Clin Exp Rheumatol 2018;36 Suppl 111:163-4.
3.
Stanley JC, Criado E, Eliason JL, Upchurch GR, Jr., Berguer R, Rectenwald JE. Abdominal aortic coarctation: surgical treatment of 53 patients with a thoracoabdominal bypass, patch aortoplasty, or interposition aortoaortic graft. J Vasc Surg 2008;48:1073-82.
4.
Hetzer R, Absi D, Miera O, et al. Extraanatomic bypass technique for the treatment of midaortic syndrome in children. Ann Thorac Surg 2013;96:183-9.
5.
Saadoun D, Lambert M, Mirault T, et al. Retrospective analysis of surgery versus endovascular intervention in Takayasu arteritis: a multicenter experience. Circulation 2012;125:813-9.
6.
Kim SM, Jung IM, Han A, et al. Surgical treatment of middle aortic syndrome with Takayasu arteritis or midaortic dysplastic syndrome. Eur J Vasc Endovasc Surg 2015;50:206-12.
7.
Taketani T, Miyata T, Morota T, Takamoto S. Surgical treatment of atypical aortic coarctation complicating Takayasu's arteritis--experience with 33 cases over 44 years. J Vasc Surg 2005;41:597-601.
8.
Takayasu M. A case with peculiar changes of the central retinal vessels. Acta Societatis Ophthalmologicae Japonicae 1908;12:554-5.
9.
Shimizu K, Sano K. Pulseless disease. J Neuropathol Clin Neurol 1951;1:37-47.
10.
Seyahi E. Takayasu arteritis: an update. Curr Opin Rheumatol 2017;29:51-6.
11.
Johnston SL, Lock RJ, Gompels MM. Takayasu arteritis: a review. J Clin Pathol 2002;55:481-6.
12.
Fields CE, Bower TC, Cooper LT, et al. Takayasu's arteritis: operative results and influence of disease activity. J Vasc Surg 2006;43:64-71.
13.
Robbs JV, Abdool-Carrim AT, Kadwa AM. Arterial reconstruction for non-specific arteritis (Takayasu's disease): medium to long term results. Eur J Vasc Surg 1994;8:401-7.
14.
Martin EC, Diamond NG, Casarella WJ. Percutaneous Transluminal Angioplasty in Non10
Atheroscklerotic Disease. Radiology 1980;135:27-33. 15.
Tyagi S, Kaul UA, Nair M, Sethi KK, Arora R, Khalilullah M. Balloon angioplasty of the aorta in Takayasu's arteritis: initial and long-term results. Am Heart J 1992;124:876-82.
16.
Sharma S, Thatai D, Saxena A, Kothari SS, Guleria S, Rajani M. Renovascular hypertension resulting from nonspecific aortoarteritis in children: midterm results of percutaneous transluminal renal angioplasty and predictors of restenosis. AJR Am J Roentgenol 1996;166:157-62.
17.
Jaafar MS, Hamid O, Khor CS, Yuvaraj RM. Preliminary studies of left ventricular wall thickness and mass of normotensive and hypertensive subjects using m-mode echocardiography. Malays J Med Sci 2002;9:28-33.
18.
Cramariuc D, Gerdts E. Epidemiology of left ventricular hypertrophy in hypertension: implications for the clinic. Expert Rev Cardiovasc Ther 2016;14:915-26.
19.
Lazzeroni D, Rimoldi O, Camici PG. From Left Ventricular Hypertrophy to Dysfunction and Failure. Circ J 2016;80:555-64.
20.
Levy D. Left ventricular hypertrophy. Epidemiological insights from the Framingham Heart Study. Drugs 1988;35 Suppl 5:1-5.
21.
Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am J Cardiol 2002;90:1284-9.
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Table 1. Preoperative Clinical Status and Operative Indications preoperative Age (years)
56.6 (48-62.7)
Female (%)
12 (86)
Inflammatory status ESR
30.5 (14.5-46.3)
CRP
0.2 (0.05-1.32)
Peripheral symptoms (%) renal impairment
8 (57)
claudication
7 (50)
Neurologic symptoms (%)
4 (29)
Operative indication Uncontrolled hypertension
2 (14)
Heart failure
10 (71)
Renal ischemia
2 (14)
CRP = C-reactive protein; ESR = erythrocyte sedimentation rate
12
Table 2. Combined Operative Data Both renal + axillary (1) Both renal (1)
Peripheral bypass (n = 5)
Axillary (1) Carotid (2) Ascending aorta replacement + AVP (2) Ascending aorta replacement + AVR + Maze (1)
Cardiac procedure (n = 6)
Bentall + MVP + TAP + Maze + CABG + PFO (1) MVP (1) MVP + TAP + Maze + CABG (1)
AVP = aortic valvuloplasty; AVR = aortic valve replacement; CABG = coronary artery bypass graft; MVP = mitral valvuloplasty; PFO = patent foramen ovale; TAP = tricuspid valve annuloplasty
13
Table 3. Medical Management During Preoperative and Postoperative Status Preoperative
Postoperative
p-value
Median number of drug
4 [3-6]
2.5 [2-3]
0.017
Beta-blockers (%)
12 (85.7)
9 (64.3)
ACE inhibitor or ARB (%)
12 (85.7)
5 (35.7)
Calcium channel blocker (%)
9 (64.3)
7 (50)
Diuretics (%)
12 (85.7)
8 (57.1)
Others (%)
2 (14.3)
1 (7.1)
None
None
N/A
11 (78.6)
12 (85.7)
N/A
2
2
N/A
Antihypertensive drug
Cytotoxic agent/steroid (%) Anti-platelet agent (%) Warfarin (%)
ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker
14
Figure Legends Fig. 1. Postoperative 3D CT showing good graft status. White arrow indicates bypass graft. ASC, ascending aorta; DDTA, distal descending thoracic aorta; DTA, descending thoracic aorta; IRABD, infrarenal abdominal aorta; SCABD, supraceliac abdominal aorta; 3D CT, 3-dimensional computed tomography.
Fig. 2. Perioperative creatinine changes: creatinine levels markedly improved.
Fig. 3. Perioperative echocardiogram data: preoperative, immediate postoperative, and follow-up at 1 year. (A) EF change: EF shows a tendency toward normalization in patients with heart failure. (B) IVSD change: At 1-year follow-up, IVSD is significantly decreased. (C) LVMI: LVMI is significantly decreased. (D), (E) systolic and diastolic LV internal diameters are also significantly decreased. (F) LAVI is significantly decreased at 1 year. EF, ejection fraction; IVSD, interventricular septal diameter; LAVI, left atrial volume index LVMI, left ventricular mass index
Fig. 4. Kaplan–Meier survival analysis: overall 5-year survival rate.
15