Outcomes after endarterectomy for chronic mesenteric ischemia
Article Outline
Objectives
A retrospective study was performed to identify optimal factors affecting outcomes after open revascularization for chronic mesenteric ischemia.
Methods
All patients who underwent open surgery for chronic mesenteric ischemia from 1987 to 2006 were reviewed. Patients with acute mesenteric ischemia or median arcuate ligament syndrome were excluded. Mortality, recurrent stenosis, and symptomatic recurrence were analyzed using logistic regression, and univariate and multivariate analysis.
Results
We identified 80 patients (69% women, 31% men). Mean age was 64 years (range, 31-86 years). Acute-on-chronic symptoms were present in 26%. Presenting symptoms included postprandial pain (91%), weight loss (69%), and food fear and diarrhea (25%). Preoperative imaging demonstrated severe (>70%) stenosis of the superior mesenteric artery in 75 patients (24 occluded), the celiac axis in 63 (20 occluded), and the inferior mesenteric artery in 53 (20 occluded). Multivessel disease was present in 72 patients (90%), and 40 (50%) underwent multivessel reconstruction. Revascularization was achieved by endarterectomy in 37 patients, mesenteric bypass in 29, and combined procedures in 14. Concurrent aortic reconstruction was required in 13 patients (16%). Three hospital deaths occurred (3.8%). Mean follow-up was 3.8 years (range, 0-17.2 years). One- and 5-year survival was 92.2% and 64.5%. Mortality was associated with age (P = .019) and renal insufficiency (P = .007), but not by clinical presentation. Symptom-free survival was 89.7% and 82.1% at 1 and 5 years, respectively. Symptoms requiring reintervention occurred in nine patients (11%) at a mean of 29 months (range, 5-127 months). Multivariate analysis showed that freedom from recurrent symptoms correlated with endarterectomy for revascularization (5.2% vs 27.6%; hazard ratio, 0.20; 95% confidence interval, 0.04-0.92; P = .02).
Conclusion
For open surgical candidates, endarterectomy appears to provide the most durable long-term symptom relief in patients with chronic mesenteric ischemia.
Chronic mesenteric ischemia (CMI) remains an uncommon yet important cause of chronic abdominal pain. The goal of treatment for CMI is a safe and effective revascularization that provides the patient with immediate and durable relief of symptoms, minimal procedural risk, and protection from morbidity and mortality associated with intestinal ischemia.
Optimal treatment for patients with CMI remains controversial and challenging. Open surgical revascularization is still considered the standard of care, but may be associated with significant morbidity and mortality.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 Percutaneous approaches have been suggested to play an increased role in the treatment of CMI because of high initial technical success and low morbidity13, 14, 15, 16; however, they have been associated with poor long-term patency and a high rate of recurrent symptoms requiring reintervention.
Many different approaches to operative revascularization have been described, including local endarterectomy, transaortic endarterectomy, and surgical bypass. For bypasses, antegrade (supraceliac aorta) and retrograde (distal aorta, iliac artery) inflow sources have been reported, with outflow to one or multiple visceral arteries. Short-term and long-term data demonstrate good results for open surgical bypass but long-term outcomes are limited when comparing endarterectomy with surgical bypass for treatment of CMI.
The goals of this study were to define our institutional experience with open surgical treatment of CMI and to determine if endarterectomy or surgical bypass was associated with improved short-term or long-term outcomes.
Methods
The Institutional Review Board of the University of Wisconsin Hospital and Clinics approved the research protocol. Clinical data were collected from medical records for all patients who underwent visceral revascularization for CMI at the University of Wisconsin Hospital from 1987 to 2006. Inclusion criteria included patients with chronic CMI symptoms and patients who presented with acute or subacute symptoms in the presence of ongoing chronic symptoms. Patients who underwent visceral revascularization in conjunction with aortic reconstruction were included only if they had symptoms of CMI. Patients with acute mesenteric ischemia without a history of CMI were excluded, as were those with median arcuate ligament syndrome and asymptomatic visceral occlusive disease.
Data collected included demographic information, comorbidities (hypertension, cardiac disease, chronic renal insufficiency, chronic obstructive lung disease, diabetes mellitus, hyperlipidemia, smoking, previous vascular surgery), presenting symptoms (postprandial pain, unplanned weight loss, nausea, vomiting, diarrhea), extent of disease, operative revascularization, short-term outcomes, and long-term follow-up data. Cardiac disease was defined as angina, congestive heart failure, or a history of myocardial infarction or coronary revascularization. Renal insufficiency was defined as serum creatinine >1.5 mg/dL. The Social Security Death Index online database was queried to capture all deaths.
The extent of disease was based on radiographic information available for each patient. Accepted imaging modalities included angiography, computed tomography angiography, or magnetic resonance angiography. Occlusive disease was defined as >70% stenosis or occlusion. Data included the number and pattern of vessels involved as well as the extent of disease (stenosis vs occlusion) in each vessel. Operative details included the number of arteries revascularized and type of reconstruction (endarterectomy with or without reimplantation, or bypass). For patients undergoing bypass, type of conduit (autologous, Dacron, polytetrafluoroethylene) and directionality (antegrade or retrograde) was recorded.
Patients were divided into three groups: endarterectomy, bypass, and combined procedures. Combined procedures were those in which revascularization was achieved with endarterectomy of at least one visceral artery, with bypass to one other visceral artery. Endarterectomy of the inflow or outflow vessel as part of a bypass procedure was included in the bypass group. The choice of procedure was determined by the acuity of presentation, presence of necrotic bowel, severity of disease, the number of arteries amenable to revascularization, and surgeon preference.
Perioperative outcome variables included 30-day and inpatient mortality, major morbidity, minor morbidity, and hospital stay. Major morbidity included myocardial infarction, stroke, acute renal failure, respiratory failure, or bowel infarction. Minor morbidity was defined as other complications requiring further treatment or hospitalization.
Long-term outcome variables included 5-year survival, recurrent stenosis, recurrent symptoms, and repeat intervention. Recurrent stenosis was defined as radiographic evidence of >70% stenosis of a treated artery, with or without the presence of symptoms. Recurrent symptoms included all patients whose preoperative symptoms recurred after revascularization. Repeat intervention was defined as any subsequent procedure performed for either recurrent stenosis or symptoms of recurrent CMI.
Statistical analysis was performed on demographic, operative, and outcome variables. Measured values were reported as percentages or mean ± standard deviation. Survival, freedom from recurrent symptoms, freedom from recurrent stenosis, and freedom from reintervention were analyzed using the Kaplan-Meier method. Univariate analysis of demographic and operative variables with respect to outcome measures was performed with χ2, the Fisher exact test, or t tests where appropriate. Multivariate stepwise regression analysis was done of of covariates significantly (P < .05) associated with outcomes. Analyses were performed using SAS 8.2 software (SAS Institute, Cary, NC).
Results
We identified 80 patients (69% women, 31% men). Demographics of patients undergoing endarterectomy, bypass, or combined procedures are noted in Table I. Mean age was 64 ± 13 years (range, 31-86 years). Acute-on-chronic symptoms were present in 26%. Presenting symptoms included postprandial pain (91%), weight loss (69%), and food fear and diarrhea (25%). Intestinal infarction was present in four (5%) patients. Preoperative imaging demonstrated severe (>70%) stenosis of the superior mesenteric artery in 75 patients (24 occluded), the celiac axis in 63 (20 occluded), and the inferior mesenteric artery in 53 (20 occluded). The number of diseased and occluded arteries was similar among the groups (Table I). Multivessel disease was present in 72 patients (90%; Table II).
Table I. Patient demographics and disease pattern by repair type
| Variable | Endarterectomy (n = 37) | Bypass (n = 29) | Combined (n = 14) | P |
|---|---|---|---|---|
| Age, mean years | 66 | 62 | 60 | .40 |
| Female gender, No. (%) | 22 (58) | 23(79) | 10(77) | .15 |
| Tobacco history, No. (%) | 26(70) | 20(71) | 7(54) | .57 |
| Diabetes mellitus, No. (%) | 2(5) | 1(4) | 0(0) | .98 |
| Cardiac disease, No. (%) | 16(43) | 6(21) | 7(54) | .08 |
| Hypertension, No. (%) | 30(81) | 18(64) | 11(85) | .23 |
| Hyperlipidemia, No. (%) | 15(41) | 8(29) | 4(31) | .57 |
| Renal insufficiency, No. (%) | 4(11) | 2(7) | 1(8) | .86 |
| Previous surgery, No. (%) | 9(24) | 10(34) | 5(38) | .49 |
| COPD, No. (%) | 8(22) | 10(36) | 4(31) | .44 |
| Diseased arteries, mean | 2.34 | 2.25 | 2.84 | .07 |
| Occluded arteries, mean | 1.34 | 1.17 | 1.38 | .65 |
| Arteries treated, mean | 1.76 | 1.44 | 2.07 | .003 |
Table II. Distribution of visceral disease by patient
| Vessel | No. |
|---|---|
| CA, SMA, IMA | 43 |
| CA, SMA | 19 |
| CA, IMA | 2 |
| SMA, IMA | 8 |
| CA only | 2 |
| SMA only | 6 |
| IMA only | 0 |
Revascularization was achieved by endarterectomy in 37 patients (34 transaortic endarterectomy, 3 local endarterectomy), visceral artery bypass in 29, and combined procedures in 14 (Table III). A total of 134 arteries were treated, with 40 patients (50%) undergoing multivessel reconstruction, and 19 of 72 patients with multivessel disease undergoing single-vessel reconstruction.
Table III. Repair type by vessels revascularized
| Vessel treated | Repair type | ||
|---|---|---|---|
| Endarterectomy | Bypass | Combined | |
| CA, SMA, IMA | 4 | 0 | 3 |
| CA, SMA | 22 | 13 | 7 |
| CA, IMA | 0 | 0 | 1 |
| SMA, IMA | 0 | 0 | 3 |
| CA only | 0 | 5 | 0 |
| SMA only | 11 | 11 | 0 |
| IMA only | 0 | 0 | 0 |
The decision to revascularize diseased visceral arteries was determined by the acuity of presentation, presence of necrotic bowel, extent of disease of each vessel, the suitability of a target vessel, and surgeon preference. Concurrent aortic reconstruction was required in 13 patients (16%). Bypass conduits included Dacron in 14, polytetrafluoroethylene in 13, and autologous tissue in 16. Antegrade bypass was performed in 23 patients, and retrograde in 20.
Mean intensive care unit (ICU) stay was 4.5 ± 4.5 days, and mean hospital stay was 17 ± 15 days. Three deaths occurred ≤30 days or during the index hospitalization, for a perioperative inpatient mortality of 3.8%. One death was secondary to respiratory failure and pneumonia, one was from a myocardial infarction, and one occurred as a consequence of extensive visceral gangrene with a patent antegrade bypass. No clinical or operative factors predicted perioperative mortality.
Overall morbidity was 26.3%, with major events occurring in 11 of 80 (13.8%, Table IV). A logistic regression model showed that age (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.02-1.14; P < .01), the presence of acute-on-chronic symptoms (HR, 5.0; 95% CI, 1.38-17.24; P < .02), and concurrent aortic occlusive disease (HR, 4.8; 95% CI, 1.09-21.74; P < .05), but not aneurysmal disease, were each independent predictors of major morbidity. Symptoms were relieved in 75 patients (93%). Of the 54 patients who presented with weight loss, 52 (96%) regained some or all of the weight.
Table IV. Complications of open repair
| Morbidity | Frequency (%) |
|---|---|
| Cardiac | 2(2.5) |
| Bowel infarction | 2(2.5) |
| Stroke | 1(1.3) |
| Renal failure | 2(2.5) |
| Respiratory failure | 4(5.0) |
| Cholangitis | 1(1.3) |
| Dehiscence | 1(1.3) |
| Deep vein thrombosis | 2(2.5) |
| Arterial occlusion | 1(1.3) |
| Pancreatitis | 1(1.3) |
| Pseudoaneurysm | 1(1.3) |
| Graft thrombosis | 1(1.3) |
| Splenic abscess | 1(1.3) |
| Total | 21(26.3) |
Mean follow-up was 46 months (range, 1-206 months). Clinical follow-up was available for all patients. Estimated overall survival was 92.2%, 72.0%, and 64.5% at 1, 3, and 5 years. Age (P < .01), chronic renal insufficiency (P < .01), and chronic obstructive pulmonary disease (P < .05) were associated with late mortality by univariate analysis; age (HR, 1.05; 95% CI, 1.01-1.09, P < 0.02) and renal insufficiency (HR, 3.87; 95% CI, 1.45-10.31; P < 0.01) remained independent predictors of mortality by multivariate analysis. There was a trend toward improved estimated 5-year survival for patients without acute-on-chronic symptoms, although this did not reach statistical significance (69% vs 50%, P = .07).
Recurrent symptoms developed in 11 patients (13.8%), consisting of eight (28%) after surgical bypass, three (8%) after endarterectomy, and one (7%) after a combined procedure. For these patients, mean time to symptom recurrence was 28 months (range, 1-127 months). Estimated symptom-free survival was 89.7%, 85.6%, and 82.1% at 1, 3, and 5 years, respectively. Both univariate and multivariate analysis demonstrated endarterectomy (HR, 0.20; 95% CI, 0.04-0.92; P = .04) to be inversely associated with recurrent symptoms (Table V). Extent of disease, number of occluded vessels, and number of vessels treated were not associated with symptom recurrence. By life-table analysis, freedom from recurrence at 2 years was estimated at 79% for the bypass group vs 95% for those undergoing endarterectomy and 92% for combined procedures (P = .03; Fig 1).
Table V. Analysis of factors associated with recurrent symptoms
| Variable | HR (95% CI) | P |
|---|---|---|
| Univariate analysis | ||
| Age | .002 | |
| Smoking | .22 | |
| Diabetes mellitus | .99 | |
| Renal failure | .99 | |
| Hyperlipidemia | .77 | |
| Cardiac history | .54 | |
| Hypertension | .06 | |
| Acute symptoms | .14 | |
| Endarterectomy | .003 | |
| Number of diseased vessels | .14 | |
| Occluded vessels | .09 | |
| Number of vessels repaired | .94 | |
| Aortic reconstruction | .99 | |
| Directionality of bypass | .47 | |
| Type of conduit | .10 | |
| Multivariate analysis | ||
| Age | 0.94(0.90-0.99) | .01 |
| Endarterectomy | 0.20(0.04-0.92) | .04 |
Fig 1.
Kaplan-Meier estimates of freedom from recurrent symptoms after open repair for mesenteric ischemia with endarterectomy (blue line), bypass (red line), and combined procedures (green line).
Follow-up radiographic data were available for 56 of 80 patients (70%), of whom 14 had documented >70% recurrent stenosis or occlusion and 11 were symptomatic. Recurrent stenosis occurred in three patients after endarterectomy, 10 patients after surgical bypass, and one patient after a combined procedure. Freedom from recurrent stenosis was estimated at 91%, 80%, and 75% at 1, 3, and 5 years. No factors were independently associated with recurrent stenosis but there was a trend toward decreased recurrent stenosis for patients undergoing endarterectomy. Two-year estimates of recurrent stenosis were 79% for the bypass group and 88% for the endarterectomy and combined treatment groups (P = .13; Fig 2).
Fig 2.
Kaplan-Meier estimates of freedom from recurrent stenosis after open repair for mesenteric ischemia with endarterectomy (blue line), bypass (red line), and combined procedures (green line).
Nine patients with recurrent symptoms and documented recurrent disease had reintervention at a mean of 29 months (range, 5-127 months). Two patients with recurrent symptoms did not undergo repeat intervention. One patient had mild symptoms with a recurrent stenosis after surgical bypass; symptoms resolved with observation. The other patient refused treatment.
Estimated freedom from repeat intervention was 96%, 88%, and 85% at 1, 3 and 5 years; no statistical difference was identified when comparing endarterectomy, surgical bypass, and combined procedures (P = .22; Fig 3). Increasing age (P < .01), acute symptoms (P < .05), and total occlusion of visceral arteries (P < .05) were associated with repeat intervention by univariate analysis; only age was an independent factor by multivariate analysis (HR 0.94, 95% CI 0.88-0.99; P = .036; Table VI).
Fig 3.
Kaplan-Meier estimates of freedom from repeat intervention after open repair for mesenteric ischemia with endarterectomy (blue line), bypass (red line), and combined procedures (green line).
Table VI. Analysis of factors associated with repeat intervention
| Variable | HR (95% CI) | P |
|---|---|---|
| Univariate analysis | ||
| Age | .005 | |
| Smoking | .35 | |
| Diabetes mellitus | .99 | |
| Renal failure | .99 | |
| Hyperlipidemia | .77 | |
| Cardiac history | .97 | |
| Hypertension | .42 | |
| Acute symptoms | .03 | |
| Endarterectomy | .15 | |
| Number of diseased vessels | .13 | |
| Occluded vessels | .04 | |
| Number of vessels repaired | .94 | |
| Aortic reconstruction | .99 | |
| Directionality of bypass | .51 | |
| Type of conduit | .47 | |
| Multivariate analysis | ||
| Age | 0.94(0.88-0.99) | .04 |
| Acute symptoms | 3.27(0.00-0.00) | .11 |
| Occluded vessels | 2.68(0.00-0.00) | .14 |
Discussion
Although asymptomatic visceral arterial stenosis is a common occurrence,1 CMI is a rare clinical entity. The exact incidence is unknown, but treatment for CMI has been estimated to comprise <1% of vascular procedures performed.2 Vague symptoms can delay diagnosis, although postprandial pain and weight loss are common and may be present in up to 90% of patients.3 Undiagnosed CMI results in severe nutritional depletion, and may progress to acute mesenteric ischemia and intestinal infarction. Emergency operation for acute mesenteric ischemia is associated with a mortality of up to 60%.4, 5
Open surgical repair has remained the standard of therapy for CMI. Because of its uncommon and varied presentation, no consensus exists about the optimal surgical approach. Discussion has centered on the type of repair (endarterectomy vs bypass), the number of arteries revascularized, the directionality of bypass (antegrade vs retrograde), and the type of conduit (synthetic vs autologous). All approaches have shown good overall perioperative outcomes, with mortality of 2% to 11%, symptom improvement in 90% to 100%, and complication rates of 33% to 66%.2, 6, 7, 8, 9, 10, 11 In these studies long-term graft patency was 63% to 90% and symptomatic recurrence occurred in 9% to 41% of patients, depending on the length of follow-up. The type of bypass did not affect survival, symptom-free survival, or graft patency.
Reports of the use of endarterectomy have declined in the past two decades (Table VII), with most studies focusing on outcomes after surgical bypass. An early study by Rapp et al12 reported a 7% recurrence of symptoms in a cohort of 67 CMI patients who received endarterectomy (n = 47) or antegrade bypass (n = 20), with a mean follow-up of 4.4 years. No comparison was made between the two groups. Cho et al8 noted a gradual decline in the use of endarterectomy in favor of bypass. Contrary to our findings, that study did not demonstrate that the type of revascularization predicted late survival, graft patency, or freedom from symptom recurrence. Failure to show any difference related to these factors is likely because this and other small series with good outcomes were under-powered to detect differences from treatment approaches.
Table VII. Outcomes after open surgical revascularization for chronic mesenteric ischemia
| First author | Patients, No. | Vessels treated, No. | Endarterectomy, % | Complications, % | Operative mortality, % | Follow-up, months | Symptom recurrence, % |
|---|---|---|---|---|---|---|---|
| Present seriesa | 80 | 134 | 46 | 29 | 4 | 46 | 14 |
| Kruger,3 2007 | 39 | 67 | 0 | 12 | 3 | 39 | 8 |
| Atkins,6 2007 | 49 | 88 | 37 | 35 | 2 | 42 | 35 |
| English,7 2004a | 58 | 80 | 9 | 62 | 29 | 42 | 6 |
| Cho,8 2002 | 25 | 41 | 41 | 60 | 11 | 60 | 41 |
| Park,4 2002 | 98 | 179 | 5 | NA | 5 | 24 | 9 |
| Jimenez,9 2002 | 47 | 92 | 0 | 35 | 11 | 31 | 9 |
| Mateo,10 1999 | 85 | 130 | 22 | 33 | 8 | 36 | 24 |
| McAfee,11 1992 | 58 | 119 | 8 | 36 | 10 | 40 | 12 |
| Rapp,12 1986 | 67 | 111 | 70 | 21 | 8 | 50 | 8 |
aIncludes patients with acute-on-chronic symptoms. |
Some studies have shown higher morbidity and mortality when mesenteric revascularization was combined with aortic reconstruction.5, 10 A recent report by Atkins et al6 demonstrated no increased morbidity or mortality for combined procedures. In our series, reconstruction for aortic occlusive disease was associated with increased morbidity but did not translate into increased perioperative mortality or inferior long-term outcomes. We therefore continue to offer combined procedures when clinically warranted.
Patients presenting with acute symptoms superimposed on CMI were associated with a higher morbidity, a higher incidence of reintervention, and a trend toward decreased long-term survival. Progression of mesenteric stenosis to occlusion has been estimated to account for 20% to 50% of acute mesenteric ischemia.17, 18 English et al7 demonstrated significantly higher perioperative mortality for patients who presented with acute-on-chronic symptoms. Multivariate analysis identified intestinal gangrene and age as independent predictors of early death.
Increased morbidity in some subsets of patients with CMI paired with recent advances in endovascular technology has focused much of the recent attention on the potential role of percutaneous approaches to treatment. No prospective randomized trials have been reported. Many studies have demonstrated high technical success, low procedural morbidity.6, 13, 14, 15, 16 Kasirajan et al19 compared 28 patients undergoing percutaneous angioplasty and stent (PTA/stent) with 85 historical controls. Morbidity and recurrent stenosis were not different, but patients undergoing PTA/stent had a higher incidence of symptom recurrence, prompting recommendation of operative revascularization for those medically fit. Atkins et al6 reported equivalent morbidity and mortality when comparing PTA/stent with open repair. PTA/stent was associated with lower primary and clinical patency compared with open repair. Both approaches were associated with a 20% recurrence of symptoms, which occurred sooner with PTA/stent repair. Although they recognized that operative repair offers superior results for open surgical candidates, they acknowledged that patient preference and more rapid recovery has driven their practice to offering PTA/stent as the initial treatment to patients with suitable anatomy, providing it does not preclude later operative repair.
Brown et al20 noted during a mean follow-up of 13 months that their stent cohort was seven times more likely to develop restenosis, four times more likely to develop recurrent symptoms, and 15 times more likely to require reintervention. They concluded that percutaneous revascularization may be best reserved for patients with severe nutritional depletion or other morbidity resulting in preclusive surgical risk, and may serve as a temporizing bridge to definitive operative repair. Nearly two-thirds of our patient cohort was alive at 5 years, suggesting that prolonged survival can be expected in a significant percentage of patients with CMI and therefore providing a durable revascularization is a relevant and desirable goal.
This study has certain limitations. It is a retrospective, nonrandomized study reviewing two decades, a small number of patients, and multiple surgeons; therefore, it is subject to selection bias and interpretation bias. Changes in medical, surgical, and anesthetic care may have affected outcomes. Differences in outcomes may be influenced by important unmeasured or uncontrolled variables between different groups. As a single-center study, results may not be generally applicable or reproducible.
Symptom recurrence may be difficult to measure as a subjective measure. Incomplete radiographic follow-up may have reflected bias toward patients with recurrent symptoms; patients doing well during follow-up were less likely to undergo routine imaging. Although anatomic data are not complete, valid conclusions can be made with respect to protection from recurrent symptomatic visceral ischemia. Of note, because recurrent stenosis or graft occlusion may not necessarily lead to recurrent mesenteric ischemia, symptom recurrence may be a better outcome measure than patency.21
Conclusions
Our study shows that open mesenteric revascularization can be performed with effective symptom relief, low perioperative mortality, acceptable morbidity, and results in excellent long-term survival. For open surgical candidates, endarterectomy appears to provide the most durable outcomes for graft patency and long-term symptom relief. Because of the uncertain long-term outcomes of endovascular treatment of CMI, we believe that patients without significant comorbid conditions or limited life expectancy should be offered open surgical repair as initial therapy for CMI.
Author contributions
We acknowledge the contributions of Glen Leverson, PhD, for his help with statistical analysis of the data.
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Competition of interest: none.
PII: S0741-5214(08)01025-2
doi:10.1016/j.jvs.2008.06.033
© 2008 The Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
