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Ann Thorac Surg 2005;79:2072-2076
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Obstruction in Modified Blalock Shunts: A Quantitative Analysis With Clinical Correlation

Winfield J. Wells, MD*, R. James Yu, BS, Anjan S. Batra, MD, Hector Monforte, MD, Colleen Sintek, MD, Vaughn A. Starnes, MD

Childrens Hospital Los Angeles, Los Angeles, California

Accepted for publication December 28, 2004.

* Address reprint requests to Dr Wells, The Heart Institute at Childrens Hospital, LA, Division of Cardiothoracic Surgery, Mail Stop 66, 4650 Sunset Blvd, Los Angeles, CA90027 (E-mail: wwells{at}chla.usc.edu).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
BACKGROUND: Despite numerous reports describing the clinical course of patients undergoing a modified Blalock-Taussig shunt (MBTS), there is limited information on shunt obstruction. No studies have quantified MBTS stenosis histopathologically and correlated that with demographic and clinical risk factors.

METHODS: From June 2001 to June 2003, 155 patients had MBTS takedown. The shunt operation (at median age 6 days; shunt size 3.5 mm in 56 [36%]; 4 mm in 84 [54%]; 5 mm in 15 [10%]) was performed on cardiopulmonary bypass (CPB) in 96 patients (62%). At elective takedown (at median 8.1 months), the shunt was excised and histopathologically analyzed for maximal narrowing. Demographics and clinical variables including age, weight, shunt size and duration, diagnosis, use of cardiopulmonary bypass, blood products, anastomosis sites, and concomitant antegrade flow were then tested for correlation with shunt stenosis.

RESULTS: The mean value for maximal narrowing of the shunt lumen was 34% ± 22%, and 32 patients (21%) had greater than 50% stenosis. Myofibroblastic proliferation, often associated with organized thrombus, caused the obstruction. Smaller shunt size (<4 mm) was a statistically significant risk factor for stenosis greater than 50% (odds ratio [OR] = 2.51; p = 0.028). Other variables that showed a clinically important association with obstruction but did not reach statistical significance included age less than 14 days at shunt (OR = 2.08, confidence interval [CI] 0.8 to 5.2), shunt on bypass (OR = 2.07, CI 0.9 to 4.8), and platelet use at shunt operation (OR = 1.96, CI 0.9 to 4.4).

CONCLUSIONS: Most MBTS develop stenosis by the time of takedown, and 21% have greater than 50% obstruction. Shunt size less than 4 mm is a risk factor for high-grade stenosis. Younger age, CPB, and use of platelets are other clinically important factors. Better conduits and suppression of intimal proliferation could potentially improve outcomes.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
Systemic to pulmonary shunts have proven to be highly effective for the palliation of neonates and infants with cyanotic congenital heart disease who are not candidates for early complete repair. They usually allow adequate oxygen saturation and pulmonary artery growth until definitive correction can be performed. However, some patients may become critically cyanotic before the optimal time for staging or definitive repair, and very rarely, interstage sudden death due to shunt occlusion may occur [9].

Several authors have documented the presence of stenosis in modified Blalock-Taussig shunts (MBTS) at the time of takedown [1, 3, 4, 8, 9], but no report has quantified the stenotic process histopathologically. Therefore, the purpose of this study is to quantify and characterize the magnitude of MBTS occlusions from grafts resected at the time of shunt takedown. Further, we hoped to correlate the degree of shunt stenosis with demographic and clinical variables from our patient population.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
In the two-year period between June 2001 and 2003, 155 infants and children had takedown of a MBTS. An Institutional Review Board-approved study of this patient subset was undertaken to determine risk factors for shunt narrowing. Two thirds of the patients (104 of 155) had a single ventricle cardiac morphology. The most common diagnoses were hypoplastic left heart syndrome (HLHS) in 45 (29%), other forms of single ventricle in 51 (33%), pulmonary atresia with ventricular septal defect (VSD) in 23 (15%), pulmonary atresia with intact ventricular septum in 13 (8%), and other forms of severe pulmonary stenosis including tetralogy of Fallot in 23 (15%; Table 1).


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  		Table 1. Patient Diagnosis
 
Initial Shunt Procedure
All patients had median sternotomy, and the shunt was performed with cardiopulmonary bypass (CPB) in 62% (96 of 155). In instances where CPB was not used, patients were given heparin (100 U/kg) before vascular clamping for shunt placement. Median age at initial shunt placement was 6 days (range, 1 day to 6 years), and median weight was 3.4 kg (range, 1.7 to 17 kg). An expanded polytetraflorethylene (PTFE) graft was used, with shunt sizes varying from 3.5 mm in 56 patients (36%), 4 mm in 84 (54%), and 5 mm in 15 (10%). The proximal shunt anastomosis came from the innominate artery in 126 (81%), the carotid artery in 4 (3%), the subclavian artery in 8 (5%), and from the ascending aorta in the remaining 17 (11%). Distal anastomosis was to the right, left, or main pulmonary artery in 69%, 10%, and 21%, respectively. In 36% of patients (51 of 155), blood products including fresh frozen plasma and platelets were given after shunt placement to correct a coagulopathy. All patients had been placed on a regimen of aspirin as a platelet inhibitor after their shunt. In most instances, this treatment was continued until the time of the shunt takedown surgery. In some instances, aspirin was stopped 1 week before the reoperation.

Shunt Takedown
The median interval between placement and takedown of the shunt was 8.1 months (range, 0.1 to 126.4). To determine if higher grade stenosis contributed to earlier shunt takedown, we arbitrarily separated the patients into those coming to the second operation at 5 months or less and those operated on at 6 months or more.

Before the takedown procedure, all patients had cardiac catheterization with angiography. Concomitant antegrade pulmonary blood flow in addition to shunt flow was found in 26% (41 of 155). At operation, the shunt was completely exposed and ligated proximally and distally as close to the anastomotic sites as possible. The maximal length of shunt was then excised and placed in 10% buffered formalin.

Histopathological Analysis and Shunt Stenosis Measurement Technique
The shunt segments in formalin were cut in cross sections and embedded in paraffin. Multiple 5-µm sections were taken from the entire length of the shunt, and hematoxylin and eosin/trichrome stained slides were prepared. Slides were examined using an Olympus BH-2 microscope with a 1x SPlan objective, and images of the most high-grade stenosis were sampled and captured with an Olympus DP11 digital camera (Olympus America, Melville, New York). Digital images were then edited of stray marks by using Adobe Photoshop (version 6.0; Adobe Systems, Los Angeles, California), and uploaded onto the Bioquant Image Analysis System-Nova Prime for Windows (version 6.50.10; Bioquant, Nashville, Tennessee).

The Bioquant system is a computer-based software with various image analysis tools, allowing captured digital image components to be either manually or automatically isolated, measured, and quantified by utilizing their structural features or differential contrasting characteristics. This computer system is based on different types of arrays, which are the tools used to collect data. There are primary arrays used to directly measure objects, namely, area arrays that determine the area within a polygonal manual tracing or an automatically generated region defined by color threshold. Other primary arrays include length, individual distance, consecutive distance, object count, density, pixel count, vertex and angle, X/Y coordinates, and topography, the latter used to generate two- or three-dimensional reconstruction. There are also derived arrays generated from any of the primary, namely, perimeter, shape factor, angle of orientation, X/Y projection, center of area, longest dimension, additive count, and calculation array. Calibration was performed using an objective micrometer (Olympus America) using the same 1x objective. Within Bioquant, several arrays were created to automatically outline the synthetic shunt material, delineating and measuring the outer and inner borders of the shunt by thresholding according to their color differential on hematoxylin and eosin stain. The outer border was defined only for reference, while the inner border was delineated to calculate the original luminal area. The percentage of stenosis was automatically calculated by thresholding the residual patent lumen, and inserting a function array with the following formula: (original lumen area - {Sigma} residual lumen areas) / original lumen area. For illustrative purposes, each array was assigned a different color (Fig 1).



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  		Fig 1. Example of the histopathologic appearance of a resected modified Blalock-Taussig shunt. Bioquant array analysis demonstrates (A) 65% occlusion in this cross-sectional image of a modified Blalock-Taussig shunt; and (B) 68% occlusion, demonstrating the ability of the array to detect double-lumen specimens.

 
Demographic and Clinical Variables Tested for Correlation With Greater Than 50% Shunt Stenosis
Demographics and clinical variables including age, weight, shunt size and duration, diagnosis, cardiopulmonary bypass use, blood products such as fresh frozen plasma, platelets, and packed red blood cells, anastomosis sites, and concomitant antegrade flow were then tested for correlation with shunt stenosis.

Statistical Analysis
Statistical analysis was performed using the Pearson {chi}2 test or the two-sided Fisher exact test. Statistical significance of potential outcome variables was defined at the 95% confidence level (p < 0.05).


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Shunt Stenosis
The mean value for maximal narrowing of the shunt lumen was 34% ± 22%. Fewer than one quarter of the shunts (23%) had important stenosis of greater than 50%. There were 56 patients (36%) with less than 25% narrowing, and 63 (41%) with 25% to 50% narrowing (Fig 2). As shown in Figure 3 there was no difference in the degree of shunt stenosis between patients coming for earlier takedown (5 months or less) and patients reoperated on at 6 months or later. The problem of relative desaturation, which influenced early operation, may have been more impacted by sources of pulmonary flow other than the shunt. Patients with aortopulmonary collaterals may not become significantly cyanotic even if their shunt has a higher grade stenosis.



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  		Fig 2. Distribution of percent of obstruction.

 


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  		Fig 3. Time of shunt takedown versus shunt obstruction. (mo = months).

 
Histopathology of Shunt Obstruction
The obstruction of the shunt consisted of variably concentric fibrous or myofibroblastic tissue, or both. In some specimens, there was also a partially reendothelialized lumen. Evidence of thrombi, endothelial cell growth, and myofibroblastic proliferation were recorded. In 1 patient, there was evidence of infection that was associated with an acute thrombosis.

Variables Associated With Important Shunt Stenosis
Smaller shunt size (<4 mm) was the only statistically significantly risk factor for stenosis greater than 50% (odds ratio [OR] = 2.5, p = 0.028). Other variables showed an important association with high-grade obstruction but did not reach statistical significance. Age less than 14 days at the initial shunt operation was associated with increased shunt obstruction (OR = 2.08, confidence interval [CI]: 0.8 to 5.2, p < 0.144) with 27 of 103 patients (26%) aged less than 14 days showing more than 50% obstruction versus 7 of 48 (14%) aged more than 14 days. Shunts that were done on CPB were also more likely to have stenosis greater than 50% (OR = 2.07, CI: 0.9 to 4.8, p < 0.112). Additionally, the use of platelets at the shunt procedure was associated with higher-grade stenosis (OR = 1.96, CI: 0.9 to 4.4, p < 0.128; Table 2). Variables that did not correlate with a higher grade of stenosis included patient weight, the length of time the shunt was in place, the type of cardiac anomaly, the site of proximal and distal anastomosis, and the presence of concomitant antegrade flow.


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  		Table 2. Univariate Analysis of Factors Potentially Influencing Important >(50%) BT Shunt Obstruction
 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
Although palliation with a modified Blalock shunt is usually effective, complications may occur. Distortion of the native pulmonary artery at the distal shunt anastomosis has been documented and historically has been the most common shunt-related problem [6]. In the current era, this complication appears to be less prevalent, probably because smaller shunts are usually placed anticipating that the interval to takedown and complete repair will be short (6 to 12 months). Shunts that are relatively oversized may also be problematic, leading to excessive pulmonary flow and heart failure as well as low diastolic pressure that can negatively affect coronary flow [9]. Additionally, there is a very low incidence of shunt-related infection, which can lead to rapid and catastrophic thrombosis.

Shunt stenosis is a well-recognized and widely reported problem after MBTS placement [2, 6, 9, 10]. Gladman and colleagues [7] analyzed shunt obstruction angiographically, finding a mean narrowing of 26%, which is similar to the 34% mean stenosis we found by histological analysis.

A number of studies have investigated possible risk factors associated with shunt stenosis and failure. In several reports [3, 6, 9], smaller shunt size was found to correlate with higher grade stenosis, similar to the findings in this study. That has led some authors [3, 5] to recommend placing as large a shunt as possible. However, this recommendation ignores the potential problems of volume overload and low systemic diastolic pressures.

Whereas our study showed only a trend toward an association between shunt narrowing and younger age and lower weight, other investigators established statistical significance between these factors and shunt failure [2–4, 10]. We believe that it is the smaller diameter graft that predisposes to important stenosis while lower weight and younger age probably represent surrogates for this factor in other series.

It seems logical that the use of clotting factors and platelets at the time of the MBTS procedure would predispose to early layering of thrombus within the shunt lumen. That might then lead to cellular ingrowth and a higher propensity toward shunt stenosis. Although we could not make this association, we still try to avoid the use of these blood products in procedures that include a shunt. In those instances where the shunt is performed without cardiopulmonary bypass, we often will not reverse the heparin if hemostasis is adequate, again hoping to minimize the chance of early clot formation. Also, early in the postoperative period, patients have been started on aspirin in the hope of reducing platelet aggregation. Whether the newer generation of platelet inhibitors such as clopidogrel might reduce the likelihood of clot and neointimal formation is unknown, but is of interest as a topic for further investigation.

Understanding the histopathology of the intimal tissue that leads to shunt stenosis may help in developing therapies to avoid this problem. The only other report that addressed intimal ingrowth in MBTS [1] had findings that were strikingly similar to ours, with myofibroblastic proliferation and endothelial cell ingrowth associated with organic thrombus. Strategies that locally inhibit this cellular ingrowth, such as those used in drug-eluting endovascular stents, might be considered.

Limitations of this study include the following: (1) no consistent measurement of preshunt pulmonary artery diameters was available to be included as a variable that might influence shunt patency; (2) the lengths of resected shunts were variable, and the submitted specimens might not have included a more highly stenotic area at the proximal or distal anastomotic site, which were often left in place at takedown; and (3) correlations between shunt stenosis and oxygen saturation could not be consistently analyzed because saturation data were frequently incomplete from clinical records in the interval between shunt placement and takedown. In addition, saturations obtained at catheterization were often taken with the patient on oxygen supplementation, further skewing the data. Finally, many patients had aortopulmonary collaterals, which could influence saturations, and a quantitative analysis of such collaterals is not possible.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Tomizawa Y, Takanashi Y, Noishiki Y, et al. Evaluation of small caliber vascular prostheses implanted in small childrenactivated angiogenesis and accelerated calcification. ASAIO J 1998;44:M496-M500.[Medline]
  2. Alkhulaifi AM, Lacour-Gayet F, Serraf A, Belli E, Planche C. Systemic pulmonary shunts in neonatesearly clinical outcome and choice of surgical approach. Ann Thorac Surg 2000;69:1499-1504.[Abstract/Free Full Text]
  3. Tsai KT, Chang CH, Lin PJ. Modified Blalock-Taussig shuntstatistical analysis of potential factors influencing shunt outcome. J Thorac Cardiovasc Surg 1996;37:149-152.
  4. Bove EL, Kohman L, Sereika S, et al. The modified Blalock-Taussig shuntanalysis of adequacy and duration of palliation. Circulation 1997;76(Suppl 3):19-23.
  5. McKay R, de Leval MR, Rees P, Taylor JFN, Macartney FJ, Stark J. Postoperative angiographic assessment of modified Blalock-Taussig shunts using expanded polytetrafluoroethylene (Gore-Tex) Ann Thorac Surg 1980;30:137-143.[Abstract]
  6. Karpawich PP, Bush CP, Antillon JR, Amato JJ, Marbey ML, Agarwal KC. Modified Blalock-Taussig shunt in infants and young children J Thorac Cardiovasc Surg 1985;89:275-279.[Abstract]
  7. Gladman G, McCrindle BW, Williams WG, Freedom RM, Benson LN. The modified Blalock-Taussig shuntclinical impact and morbidity in Fallot’s tetralogy in the current era. J Thorac Cardiovasc Surg 1997;114:25-30.[Abstract/Free Full Text]
  8. Malm TK, Holmqvist C, Olsson CG, et al. Successful thrombolysis of an occluded modified Blalock-Taussig shunt three days after operation Ann Thorac Surg 1998;65:1453-1455.[Abstract/Free Full Text]
  9. Fenton KN, Siewers RD, Rebovich B, Pigula FA. Interim mortality in infants with systemic to pulmonary artery shunts Ann Thorac Surg 2003;76:152-157.[Abstract/Free Full Text]
  10. Al Jubair KA, Al Fagih MR, Al Jarallah AS, et al. Results of 546 Blalock-Taussig shunts performed in 478 patients Cardiol Young 1998;8:486-490.[Medline]



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