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STATE OF THE ART

Surgical Techniques for Repair of PeripheralPulmonary Artery Stenosis

Richard D. Mainwaring, MD, and Frank L. Hanley, MD

An illustration demonstrating key steps in the surgicaltechnique for reconstruction of peripheral pulmonaryartery stenosis.

Central Message

This article provides a detailed description ofthe surgical techniques that have been devel-oped for the surgical reconstruction of periph-eral pulmonary artery stenosis.

Peripheral pulmonary artery stenosis (PPAS) is a rare form of congenital heartdisease that is most frequently associated with Williams and Alagillesyndromes. These patients typically have systemic level right ventricularpressures secondary to obstruction at the lobar, segmental, and subseg-mental branches. The current management of patients with PPAS remainssomewhat controversial. We have pioneered an entirely surgical approach forthe reconstruction of PPAS. This approach initially entailed a surgical patchaugmentation of all major lobar branches and effectively reduced the rightventricular pressures by more than half. This was the first report demonstrat-ing an effective approach to this disease. Over the past 5 years, we havegradually evolved our technique of reconstruction to include segmental andsubsegmental branch stenoses. An important technical aspect of thisapproach entails the division of the main pulmonary and separation of thebranch pulmonary arteries to access the lower lobe branches. Pulmonaryartery homograft patches are used to augment hypoplastic pulmonary arterybranches. In addition, we perform a Heinecke-Miculicz–type ostioplasty forisolated ostial stenoses. The technical details of the surgical approach toPPAS are outlined in this article and can also be used for other complexperipheral pulmonary artery reconstructions.

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Keywords: Congenital heart disease, Pulmonary arteries

INTRODUCTIONPeripheral pulmonary artery stenosis (PPAS) is a rare and

complex form of congenital heart disease that is associatedwith Williams and Alagille syndromes.1-3 The natural historyof PPAS is highly dependent on the degree of obstruction.4-7

Mild cases have a favorable prognosis and may demonstratespontaneous regression of the peripheral stenosis.8 Thesemild cases rarely need any type of intervention. In contrast,severe PPAS is characterized by multiple stenoses of lobar andsegmental branches and tends to progress over time. SeverePPAS results in right ventricular hypertension, right ventric-ular hypertrophy, and eventually right ventricular failure.The severe cases of PPAS almost invariably require interven-tion to alleviate the adverse consequences of high rightventricular pressures.9,10

Division of Pediatric Cardiac Surgery, Lucile Packard Children'sHospital, Stanford University School of Medicine, Stanford, California

Address reprint requests to Richard D. Mainwaring, MD, Division ofPediatric Cardiac Surgery, Lucile Packard Children's Hospital, StanfordUniversity School of Medicine, 300 Pasteur Dr, Falk CVRC, Stanford,CA 94305. E-mail: mainwaring@stanford.edu

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The optimal management of patients with severe PPASremains controversial.11 Many centers have advocated a “multi-modality approach” that includes surgical augmentation of thecentral pulmonary arteries and catheter-based treatment of themore distal stenosis.12,13 However, there is little evidence thatthis multimodality approach has any lasting efficacy for thisdisease. The Achilles heel of catheter-based treatment hasproven to be the ineffectiveness of relieving obstruction at thelobar and segmental level.In 2012, we reported a series of 16 patients who underwent

surgical reconstruction for severe PPAS.14 This was the firstreport in the literature advocating an entirely surgical approachto this disease. The surgical technique for reconstruction ofPPAS is a technically challenging procedure because of the needto access all lobar and segmental branches. This articledescribes our current surgical approach for peripheral pulmo-nary artery reconstruction.

SURGICAL TECHNIQUEA median sternotomy incision is performed, and the

pericardium is opened. The main pulmonary artery as well asthe right and left branch pulmonary arteries is dissected free

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Figure 1. An illustration demonstrating typicalanatomy associated with peripheral pulmonaryartery stenosis (PPAS). There are multiple lobar andsegmental stenoses. (Reproduced with permissionfrom Mainwaring et al.17)

Figure 2. An illustration demonstrating the initial stepin the reconstruction of PPAS. The main pulmonaryartery is divided, as are the right and left branchpulmonary arteries. An incision is made along theinferior aspect of the proximal branch pulmonaryarteries and continuing along the medial border ofthe lower lobe artery. (Reproduced with permissionfrom Mainwaring et al.17)

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from the surrounding structures (Fig. 1). Theintrapericardial portion of this dissection is per-formed in a standard fashion. Before the extraper-icardial portion of the pulmonary artery dissection,both pleural spaces are opened, and the course ofboth phrenic nerves is marked with fine prolenesutures. The lobar and segmental branches aresequentially identified, and the external anatomicalappearance is compared with the preoperativeangiogram.

It is imperative to perform the entire surgicaldissection before the administration of heparin toachieve complete hemostasis. In addition, we havenoted a significant incidence of intraparenchymalhemorrhage, if the dissection is performed after thepatient is anticoagulated.

Cardiopulmonary bypass is instituted, and thepatient is cooled to 251C. This degree of hypo-thermia results in a significant reduction in metabolicrate, permitting the safe reduction in pump flow withan important physiological effect of a commensuratedecrease in collateral flow to the lung. A vent catheteris inserted through the right superior pulmonaryvein into the left ventricle. The main pulmonaryartery is divided distally, and the right and leftbranch pulmonary arteries are separated. Neuroclipsare placed on each of the lobar branches to preventbackbleeding.

The right and left branch pulmonary arteries areincised starting along the inferior aspect of the artery.This incision is continued distally following themedial border of the artery and extended into themedial basal segment of each lower lobe. Stay suturesare placed at the upper edges of the branchpulmonary arteries to facilitate exposure (Fig. 2).The orientation of this incision is critical as it resultsin the opening in each artery facing into the freespace away from the superior pulmonary veins andbronchi. Other potential orientations of this incisionuniformly result in a “competition for space” withadjoining structures. Specifically, an anterior incisionwould result in competing for space with the upperlobe pulmonary veins. A superior incision wouldresult in competition with the distal bronchi as wellas the origin of the lobar branches, whereas aposterior incision would compete with the proximalbronchus.

Each of the peripheral stenoses is then addressedsequentially. Segmental and subsegmental stenosesare often amenable to surgical ostioplasty using aHeineke-Miculicz technique (Fig. 3A), particularlyin the presence of ostial stenosis with a normaldistal vessel (Fig. 3B). The vessel is probed with ametal dilator to get a “feel” for the severity andextent of the stenosis (Fig. 3C). The carina of the

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vessel is then incised with fine scissors to a pointbeyond the limits of the stenosis (Fig. 3D). Theincision is then closed in a transverse direction (901to the direction of the incision) with 8-0 prolenesutures (Fig. 3E).There are circumstances when the anatomy of a

peripheral pulmonary artery would not be ame-nable to ostioplasty. Specifically, in the settingof a longer stenosis, an ostioplasty would notadequately address the full extent of the narrowingleading to the 2 distal branches (Fig. 4A). This

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Figure 3. (A) Anatomy of a segmental branch pulmonary artery with severe stenosis, located at the ostia. (B) The branchpulmonary artery is opened to reveal the ostia of the segmental branch. (C) The ostia is probed to assess the severity andextent of the stenosis. (D) The carina is incised to a point beyond the level of stenosis. (E) The incision is repaired in atransverse direction with 8-0 prolene suture.

PERIPHERAL PA RECONSTRUCTION

disparity in size can be discerned visually andconfirmed by probing the proximal and distalvessels. In this circumstance, the main artery isopened (Fig. 4B), and the side branch is incisedbeyond the bifurcation (Fig. 4C). The side branchis augmented with a patch of pulmonary arteryhomograft (Fig. 4D).

The primary longitudinal incisions in the branchpulmonary arteries are then augmented with longpulmonary homograft patches, as shown inFigure 5. The reconstructed branch pulmonaryarteries are then sewn together end to end. Themain pulmonary artery is augmented with a patch ofpulmonary artery homograft. The main pulmonaryartery is then anastomosed to the reconstructedbranch pulmonary arteries to complete the oper-ation (Fig. 6).

There are specific instances in which we recon-struct the central pulmonary artery confluenceanterior to the aorta using a LeCompte maneuver.The primary indication for a LeCompte is theabsence of adequate space for the branch pulmonaryarteries to traverse through the aortopulmonarywindow. This situation may arise when the nativebranch pulmonary arteries are hypoplastic and thisspace is usurped by other adjoining structuresincluding the ascending aorta, descending aorta,and tracheobronchial tree. There may also be limitedspace in the aortopulmonary window after

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reconstruction of the ascending aorta or aortic archin patients with Williams syndrome. This optionshould be entertained in all patients undergoingPPAS repair and was used in one-quarter of thepatients in our series.The patients are rewarmed during the finishing

stages of the reconstruction. Virtually all of thepatients have an extremely hypertrophied rightventricle because of the systemic level pressures thatwere present preoperatively. In view of this, wespecifically avoid the administration of epinephrineand use only low-dose dopamine and milrinone.The administration of catecholamines may exacer-bate the gradient across the right ventricular outflowtract, which invariably is present to a modest extent.Two transthoracic pressure lines are placed tomonitor left atrial and right ventricular pressures.The patient is weaned from cardiopulmonarybypass, and transesophageal echocardiography isperformed to assess ventricular function and pres-ence or absence of gradient across the right ven-tricular outflow tract.

SURGICAL EXPERIENCE AND RESULTSOverall, 38 patients have undergone surgical

reconstruction of PPAS at our center between 2002and 2016. Furthermore, 20 patients had Williamssyndrome and 12 had Alagille syndrome, accountingfor the preponderance (86%) of patients. For the

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Figure 4. (A) Anatomy of a long-segment stenosis of a branch pulmonary artery. The proximal vessel is thesame size as the 2 distal vessels, indicative of a relative narrowing. (B) The main artery is openedlongitudinally to reveal the ostium of the side branch. This vessel can be probed to evaluate theextent and severity of the narrowing. (C) The side branch is incised beyond the bifurcation. (D) The sidebranch is augmented with a patch of pulmonary artery homograft. This is sutured in place with 8-0prolene suture.

Figure 5. An illustration demonstrating surgicalreconstruction of PPAS. An ostioplasty has beenperformed to the basilar segment of the right lowerlobe. Separate homograft patches are performed toaugment the segmental and lobar branch stenoses.A long homograft patch is then sutured in place toaugment the branch pulmonary arteries.(Reproduced with permission from Mainwaringet al.17)

Figure 6. An illustration demonstrating re-establishment of continuity between the right and theleft branch pulmonary arteries and reanastamosis tothe reconstructed main pulmonary artery.(Reproduced with permission from Mainwaringet al.17)

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Figure 7. Depiction of the right ventricle to aortic peaksystolic pressure ratios before surgery, immediatelyafter surgery, and at mid-term follow-up for the 38patients in this series.

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remaining 6 patients, 1 had pulmonary calcinosissyndrome, 1 had arterial tortuosity syndrome, 1 hadNoonan syndrome, and 3 had no identifiable geneticsyndrome.

The average preoperative right ventricular orleft ventricular peak systolic pressure ratio was0.94 � 0.07 (range: 0.72-1.30). The median age atsurgery was 14 months, ranging from 2 months to13 years.

The patients underwent an average of 12 � 8homograft patch augmentations or Heineke-Miculiczostioplasties (range: 5-32). The average cardiopul-monary bypass time was 285 � 164 minutes(range: 78-669 minutes). Of the 19 patients, 13with Williams syndrome underwent concomitant

Figure 8. (A) Bar graph demonstrating the number of perithe first portion of the surgical series compared with patsegmental disease. (B) Bar graph demonstrating the righof the series compared with patients who underwent anIllustrations drawn by Erin Anne Mainwaring.

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reconstruction of the ascending aorta for supravalvaraortic stenosis, and of these 13 patients, 5 had patchaugmentation of the left main coronary ostium.Postoperatively, the average right ventricle to

aortic peak systolic pressure ratio was 0.36 � 0.07(range: 0.19-0.54). This represents a 62% decreasein right ventricle to left ventricle pressure ratiocompared with the preoperative values (Fig. 7).There was no discernible difference in either thepreoperative or postoperative right ventricle to aorticpressure ratios among the various syndromes.There was 1 operative mortality (2.5%) in a

patient with Williams syndrome, severe PPAS, andsupravalvar aortic stenosis with a 70-mm Hg gra-dient. This patient underwent repair of both thePPAS and ascending aorta but postoperatively haddepressed left ventricular function, developed multi-system organ dysfunction, and eventually did notsurvive.One patient in our series developed a severe

lung reperfusion injury and required institution ofextracorporeal membrane oxygenation supportfor lungs for 4 days. This patient was successfullyweaned from extracorporeal membrane oxygen-ation and demonstrated gradual resolution of thelung reperfusion injury. This patient was dis-charged from the hospital on the 22nd post-operative day.Of the 38 patients, 35 underwent a single-stage

repair, whereas 3 patients had a staged approach.The decision to pursue a staged approach was relatedto specific circumstances for each patient. One

pheral pulmonary artery reconstructions performed inients who have undergone an extended approach tot ventricle to aortic pressure ratios in the first portionextended approach to segmental disease.

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patient with Alagille syndrome had a marked dis-parity in blood flow to the right (85%) vs left (15%)lungs owing to a tight ostial stenosis of the leftbranch pulmonary artery. This patient underwentrepair of the left side first followed by the right side ayear later.

A second patient (also with Alagille) presentedwith PPAS and severe liver dysfunction. This patientwas in need of a liver transplant, and there wasconcern that the patient might not tolerate thelengthy bypass time that would be required for acomplete repair. This patient underwent repair of theleft lung to reduce right ventricular pressures. Thepatient subsequently underwent a successful liver

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transplant followed by repair of the right lung. Athird patient had undergone a thoracotomy proce-dure at an outside institution. This patient under-went a staged approach at our institution with re-repair of the previously operated side followed byrepair of the contralateral lung.The average duration of follow-up is 4 � 3 years.

There has been no delayed mortality in the 37operative survivors. None of the patients haverequired reoperation. One patient subsequentlyhad balloon angioplasty of a residual proximalbranch pulmonary artery stenosis. The right ventricleto aortic pressure ratios have remained stable overtime, with an average ratio of 0.35 � 0.04.

1. Williams JC, Barratt-Boyes BG, Lowe JB:Supravalvular aortic stenosis. Circulation 24:1311-1318, 1961

2. Beuren AJ, Schulze C, Eberle P, et al: Thesyndrome of supravalvular aortic stenosis,peripheral pulmonary stenosis, mental retarda-tion and similar facial appearance. Am JCardiol 13:471-483, 1964

3. McElhinney DB, Krantz ID, Bason L, et al:Analysis of cardiovascular phenotype andgenotype-phenotype correlation in individualswith a JAG1 mutation and/or Alagille syn-drome. Circulation 106:2567-2574, 2002

4. Giddins NG, Finley JP, Nanton MA, et al: Thenatural course of supravalvar aortic stenosisand peripheral pulmonary artery stenosis inWilliam's syndrome. Br Heart J 62:315-319,1989

5. Wren C, Oslizlok P, Bull C: Natural history ofsupravalvular aortic stenosis and pulmonaryartery stenosis. J Am Coll Cardiol 15:1625-1630, 1990

6. Wessel A, Pankau R, Kececioglu D, et al: Threedecades of follow-up of aortic and pulmonaryvascular lesions in the Williams-Beuren syn-drome. Am J Med Genet 52:297-301, 1994

7. Kim YM, Yoo SJ, Choi JY, et al: Natural courseof supravalvar aortic stenosis and peripheralpulmonary arterial stenosis in Williams' syn-drome. Cardiol Young 9:37-41, 1999

8. Miyamura H, Watanabe H, Tatebe S, et al:Spontaneous regression of peripheral pulmonary

artery stenosis in Williams syndrome. Jpn Circ J60:311-314, 1996

9. Katz NM, Blackstone EH, Kirklin JW, et al: Latesurvival and symptoms after repair of tetralogyof Fallot. Circulation 62:403-410, 1982

10. Kirklin JW, Blackstone EH, Jonas RA, et al:Morphologic and surgical determinants ofoutcome events after repair of tetralogy ofFallot and pulmonary stenosis. A two-institution study. J Thorac Cardiovasc Surg103:706-723, 1992

11. Gandy KL, Tweddell JS, Petech AN: How weapproach peripheral pulmonary stenosis inWilliams-Beuren syndrome. Semin ThoracCardiovasc Surg Pediatr Card Surg Ann 12:118-121, 2009

12. Trivedi KR, Benson LN: Interventional strat-egies in the management of peripheral pulmo-nary artery stenosis. J Interven Cardiol 16:171-188, 2003

13. Geggel RL, Gauvreau K, Lock JE: Balloondilation angioplasty of peripheral pulmonarystenosis associated with Williams syndrome.Circulation 103:2165-2170, 2001

14. Monge M, Mainwaring RD, Sheikh AY, et al:Surgical reconstruction of peripheral pulmo-nary artery stenosis in Williams and Alagillesyndromes. J Thorac Cardiovasc Surg 145:476-481, 2013

15. Mainwaring RD, Sheikh AY, Punn R, et al:Surgical outcomes for patients with pulmonaryatresia/major aortopulmonary collaterals and

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y January 20, 27. Elsevier Inc

Alagille syndrome. Eur J Cardiothorac Surg 42(2):235-241, 2012

16. Mainwaring RD, Reddy VM, Peng L, et al:Hemodynamic assessment after complete re-pair of pulmonary atresia/major aortopulmo-nary collaterals. Ann Thorac Surg 95(4):1397-1402, 2013

17. Mainwaring RD, Ibrahimiye AN, Hanley FL:Surgical techniques for repair of peripheralpulmonary artery stenosis and other complexperipheral reconstructions. Ann Thorac Surg102:e181-e183, 2016

18. Stamm C, Friehs I, Moran AM, et al: Surgeryfor bilateral outflow tract obstruction in elastinarteriopathy. J Thorac Cardiovasc Surg 120:755-763, 2000

19. Burch TM, McGowan FX, Kussman BD, et al:Congenital supravalvular aortic stenosis andsudden death associated with anesthesia: What'sthe mystery? Anesthesia 107:1848-1854, 2008

20. Formigari R, Michielon G, Digillio MC, et al:Genetic syndromes and congenital heartdefects: How is surgical management affected?Eur J Cardiothorac Surg 35:606-614, 2009

21. Michielon G, Marino B, Formigari R, et al:Genetic syndromes and outcome after surgicalcorrection of tetralogy of Fallot. Ann ThoracSurg 81:968-975, 2006

22. Blue GM, Mah JM, Cole AD, et al: The negativeimpact of Alagille syndrome on survival ofinfants with pulmonary atresia. J ThoracCardiovasc Surg 133:1094-1096, 2007

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DISCUSSIONReconstruction of PPAS is technically quite chal-lenging because of the need to address theextrapericardial stenoses to the middle and lowerlobes. Our center has acquired an extensiveexperience with extrapericardial pulmonary arterysurgery in patients with pulmonary atresia withventricular septal defect and major aortopulmonarycollateral arteries.15,16 It was this broad experiencewith peripheral pulmonary artery reconstructionthat was subsequently applied to PPAS.

The surgical approach that we use for PPASreconstruction has evolved considerably over thepast 5 years. Our initial experience concentrated onrepairing the lobar branch pulmonary artery sten-oses along with augmentation of the central andmain pulmonary arteries as needed.14 This approachentailed a median of 7 peripheral pulmonary arterypatch augmentations and resulted in a 57%reduction in right ventricle to aortic pressure ratios.However, we also recognized that there weresignificant stenoses at the segmental and subseg-mental levels that were not able to be addressedwith this original approach. Therefore, we sought toexpand our surgical armamentarium to be able toaccess and address the more distal disease.

Our current surgical technique includes theseparation of the right and left branch pulmonaryarteries to access the distal branches and underside ofthe arteries.17 Homograft patches are then used to“anchor” the pathway to the lower lobe branches.Each segmental branch is sequentially assessedvisually and by passing probes through the ostia intothe distal vessel. It is not uncommon to find nearlyevery segmental branch affected by this disease and torequire reconstruction. The 2 principal methods forreconstruction include homograft patch augmenta-tion in the circumstance of long-segment stenosis andsurgical ostioplasty for localized ostial disease. TheHeinecke-Miculicz ostioplasty technique can also beapplied to subsegmental ostial disease and haseffectively extended our approach to address moredistal abnormalities.

The current approach to PPAS has beenimplemented over the past 5 years to addressdisease at the segmental and subsegmental branches.

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The patients who have undergone this extendedapproach underwent a median of 18 peripheralpulmonary artery reconstructions or two and a halftimes the number performed in the earlier part ofour series (Fig. 8). The extended surgical approachresulted in a 72% reduction in right ventricle toaortic pressure ratios compared with 55% in ouroriginal approach. We believe that the physiologicalbenefits of the extended surgical approach provide avindication of this method and justify the additionaltime that it takes to perform this procedure.

Despite the fact that the name “PPAS” presentsthe appearance of a single anatomical entity, it isevident that there is considerable diversity frompatient to patient. Most patients with Williamssyndrome and PPAS have associated supravalvaraortic stenosis,18 with a subset of these demonstrat-ing left main coronary artery ostial disease.19 Incontrast, patients with Alagille syndrome do nothave aortic or coronary abnormalities but frequentlyhave complex, multisystem organ problems (mostnotably liver dysfunction) that increase the risk ofsurgical procedures.20-22 Most patients with PPAShave small, thickened main and central branchpulmonary arteries. However, more distally, somepatients have predominantly ostial disease (amena-ble to ostioplasty), whereas others have longersegment tubular stenoses (amenable to homograftpatch augmentation). Our experience would suggestthat there is no discernible difference in peripheralpulmonary artery phenotype when comparingpatients with Williams syndrome, Alagille syn-drome, and the smaller group of patients with noidentifiable syndrome. The data would also indicatethat there is no significant difference in eitherpreoperative or postoperative right ventricle to leftventricle pressure ratios comparing Williams orAlagille syndromes.

In summary, this report provides a description ofour technical approach to the surgical reconstruc-tion of PPAS. This technique is also applicable toother complex reoperative peripheral pulmonaryartery surgeries including patients with pulmonaryatresia or ventricular septal defect or major aorto-pulmonary collateral arteries and residual peripheralarchitectural stenosis.

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