Reversal of Idiopathic Pulmonary Arterial        Hypertension and Allograft Pneumonectomy        After Single Lung Transpl...
CHEST                                                                        Original Research                            ...
and left heart valvular disease, normal pulmonary function tests,                           ˙ ˙a ventilation-perfusion (V/...
Figure 2. Posttransplant CT scan revealing a totally atelectatic left lung with bronchiectasis and               fibrosis....
tients might experience regression of their disease.        pneumonectomy to be performed with discontinua-There is one ot...
Reversal of Idiopathic Pulmonary Arterial Hypertension and Allograft         Pneumonectomy After Single Lung Transplantati...
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Reversal of idiopathic pulmonary arterial hypertension and allograft pneumonectomy after single lung transplantation*

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Edward Omron MD, MPH
Pulmonary, Critical Care Medicine
Morgan Hill, CA 95037

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Reversal of idiopathic pulmonary arterial hypertension and allograft pneumonectomy after single lung transplantation*

  1. 1. Reversal of Idiopathic Pulmonary Arterial Hypertension and Allograft Pneumonectomy After Single Lung Transplantation* Subrato Deb, Joon Yun, Nelson Burton, Edward Omron, John Thurber and Steven D. Nathan Chest 2006;130;214-217 DOI 10.1378/chest.130.1.214 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/130/1/214.full.html Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright2006by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692Downloaded from chestjournal.chestpubs.org by guest on May 27, 2011 © 2006 American College of Chest Physicians
  2. 2. CHEST Original Research LUNG TRANSPLANTATION Reversal of Idiopathic Pulmonary Arterial Hypertension and Allograft Pneumonectomy After Single Lung Transplantation* Subrato Deb, MD; Joon Yun, MD; Nelson Burton, MD; Edward Omron, MD; John Thurber, MD; and Steven D. Nathan, MD, FCCP Prior to the advent of effective medical therapies, the only treatment option for patients with idiopathic pulmonary arterial hypertension (IPAH) was lung transplantation. We present the case of a woman who underwent single-lung transplantation for the treatment of IPAH > 10 years ago in whom chronic rejection developed. Despite complete obliteration of the allograft, it was noted that her PA pressure levels had almost normalized. Therefore, an allograft pneumonectomy was performed. To our knowledge, this is the first reported case of the regression of pulmonary vascular disease following lung transplantation with subsequent successful removal of the allograft. (CHEST 2006; 130:214 –217) Key words: graft rejection; hypertension; lung transplantation; pneumonectomy; pulmonary Abbreviations: IPAH idiopathic pulmonary arterial hypertension; PA pulmonary artery; PAH pulmonary ˙ ˙ arterial hypertension; V/Q ventilation-perfusionI is an idiopathic disorder with an estimated inci- diopathic pulmonary arterial hypertension (IPAH) patients with this condition was 2.8 years.2 The only recourse for such patients was lung transplantation.dence of 1 to 2 cases per million people. IPAH is We present the case of a woman who underwentdefined by a mean PA pressure of 25 mm Hg at single-lung transplantation for the treatment ofrest or 30 mm Hg with exercise, with a wedge IPAH 10 years ago in whom chronic rejection ofpressure of 15 mm Hg without any associated the allograft with sustained near normalization of hercause.1 Prior to the advent of effective medical PA pressure levels subsequently developed. Thistherapies, the reported median survival time for allowed for the successful performance of an allo- graft pneumonectomy. To our knowledge, this is the*From the Departments of Cardiothoracic Surgery (Drs. Deb first reported case of the reversal of pulmonaryand Thurber) and Pulmonary and Critical Care Medicine (Drs.Yun and Omron), National Naval Medical Center, Bethesda, vascular disease following lung transplantation thatMD; and Inova Heart and Vascular Institute (Drs. Burton and enabled the allograft and its incumbent immunosup-Nathan), Falls Church, VA. pressive medications to be successfully removed.None of the authors have a conflict of interest to declare.Manuscript received November 30, 2005; revision acceptedJanuary 18, 2006. Case ReportReproduction of this article is prohibited without written permission The patient presented in 1992 at age 28 years with syncope,from the American College of Chest Physicians (www.chestjournal. palpitations, and worsening dyspnea on exertion. Her chestorg/misc/reprints.shtml).Correspondence to: Steven D. Nathan, MD, FCCP, Heart and radiograph revealed cardiomegaly, and echocardiography ruledLung Transplant Center, Inova Heart and Vascular Institute, out an intracardiac shunt but revealed right heart enlargement. A3300 Gallows Rd, Falls Church, VA 22042; e-mail: steven.nathan@ workup was initiated that included ruling out an underlyinginova.com connective tissue disorder with standard serology tests, a left andDOI: 10.1378/Chest.130.1.214 right heart catheterization to rule out congenital heart disease214 Original Research Downloaded from chestjournal.chestpubs.org by guest on May 27, 2011 © 2006 American College of Chest Physicians
  3. 3. and left heart valvular disease, normal pulmonary function tests, ˙ ˙a ventilation-perfusion (V/Q) scan to rule out thromboembolicdisease, and a CT scan of the chest, which demonstrated normallung parenchyma. The patient’s right heart catheterization re-vealed a pulmonary artery (PA) pressure of 82/44 mm Hg with amean of 57 mm Hg, a right atrial pressure of 11 mm Hg, and acardiac index of 2.65 L/min/m2. Primary pulmonary hypertensionwas diagnosed based on these results and the exclusion of otheretiologies. A second cardiac catheterization was performed 5months later and revealed slightly higher pressures with a PApressure of 100/40 mm Hg (mean, 64 mm Hg) with a pulmonarycapillary wedge pressure of 5 mm Hg. Her pulmonary vascularresistance was measured at 14.4 Wood units, and her cardiacindex was 2.5 L/min/m2. She was treated with oral calciumchannel blockers; however, her dyspnea worsened to the point ofNew York Heart Association class 3 symptomatology, and she wastherefore referred for lung transplantation. In March 1994, at age 30 years, the patient underwent a leftsingle-lung transplant without complications. Pathologic exami-nation of the explanted lung showed changes that are consideredto be typical for primary pulmonary hypertension, includingthickened hyperplastic pulmonary arterial intima with narrowedlumina. There was no pathologic evidence of vasculitis or anytype of parenchymal lung disease. The patient underwent a Figure 1. Posttransplant chest radiograph demonstrating severe ˙ ˙quantitative V/Q scan, which revealed 97% perfusion to the volume loss and air bronchograms of the left hemithorax.allograft, early in the postoperative period. Following transplan-tation, the right ventricular dimensions and function returned tonormal levels. The patient’s posttransplant history was significant end-stage chronic rejection with total loss of alveolar architecturefor several episodes of acute rejection and recurrent allograft and the obliteration of bronchioles.infections. Over time, these recurrent allograft problems resulted At 6 months of follow-up, the patient is doing very well. Shein progressive fibrotic changes and bronchiectasis in the allograft. has occasional dyspnea with exertion. She is not receiving oxygenChronic renal insufficiency due to long standing hypertension therapy, and her left shoulder and chest pain have receded. Herand chronic calcineurin therapy also developed. postpneumonectomy chest radiograph is shown in Figure 3. In August 2004, Pseudomonas pneumonia and left mainstem Follow-up transthoracic echocardiography shows normal rightbronchostenosis just distal to the airway anastomosis were diag- ventricular dimensions and a left ventricular ejection fraction ofnosed. An expandable metallic stent was deployed in the left 70%. Repeat cardiac catheterization 6 months following surgerymainstem bronchus. However, the stent migrated into the tra- revealed the following hemodynamic profile: mean right atrialchea and required removal 2 months later. The patient continued pressure, 8 mm Hg; pulmonary capillary wedge pressure, 12 mmto experience dyspnea on exertion, a productive cough, as well as Hg; PA systolic pressure, 47 mm Hg; PA diastolic pressure, 29left shoulder and chest pain. Chest radiography revealed severe mm Hg; mean PA pressure, 35 mm Hg; and cardiac output asvolume loss and air bronchograms of the left hemithorax (Fig 1). measured by thermodilution, 4.7 L/min. Despite stability in herA CT scan revealed a totally atelectatic left lung with bronchiec- symptoms, the patient has been started on oral therapy withtasis and fibrosis (Fig 2). Echocardiography showed normal bosentan (Actelion; Allschwil, Switzerland) for treatment of hercardiac dimensions, and an ejection fraction of 65% with mild IPAH. The patient consented to having her case submitted as adiastolic dysfunction. Cardiac catheterization revealed a mean PA report.pressure of 32 mm Hg at rest. The pulmonary vascular resistance ˙ ˙was measured at 3.3 Wood units. V/Q scanning showed almost noventilation or perfusion to the allograft. Discussion Based on these findings, the decision was made to perform a We have reported the case of a patient whopneumonectomy of the allograft. The patient was tapered off all underwent successful single-lung transplantation forof her immunosuppressive agents prior to undergoing the sur-gery, which was successfully performed without complications 10 the treatment of IPAH in 1994 and 10 years lateryears and 10 months posttransplant. The findings at surgery underwent a successful allograft pneumonectomy.included a dense fibrothorax with complete destruction of the This was predicated by the total destruction of theallograft and severe left mediastinal rotation. An extrapleural allograft and apparent reversal of the IPAH in thedissection was necessary to remove the transplanted lung due to patient’s residual native lung.the severity of the fibrous reaction around the allograft. The leftmain bronchus was divided flush with the carina, ensuring that In 1990, approximately 10% of all lung transplantsthe division line was across the native bronchus to minimize the were performed for the treatment of IPAH, whereasrisk of postoperative bronchial breakdown. The bronchial stump in 2002 only about 3% of transplants were performedwas also reinforced with transposed intrathoracic intercostal for treatment of this condition.3 This is an attestationmuscle. Intraoperative transesophageal echocardiography re- to the efficacy of the medical therapies that havevealed no changes in right ventricular function when the leftmain PA was clamped prior to division. The patient had an been made available for this otherwise lethal condi-unremarkable hospital course and was released to home 7 days tion. There are now five such agents that are ap-following surgery. Pathology of the explanted allograft revealed proved by the Food and Drug Administration for thewww.chestjournal.org CHEST / 130 / 1 / JULY, 2006 215 Downloaded from chestjournal.chestpubs.org by guest on May 27, 2011 © 2006 American College of Chest Physicians
  4. 4. Figure 2. Posttransplant CT scan revealing a totally atelectatic left lung with bronchiectasis and fibrosis. Left, A: lung window. Right, B: mediastinal window.treatment of IPAH, and therefore the need for lung controversial as to whether a single or bilateral lungtransplantation continues to diminish. Of the cur- transplant should be performed. Most programsrently available therapies, IV epoprostenol was the prefer the bilateral procedure due to issues of V/Q ˙ ˙first to be approved, but was only made available mismatching with single lungs. 9 Despite this, pa-subsequent to our patient undergoing lung trans- tients who undergo single-lung transplants can doplantation.4 Since our patient was not one of the quite well, with reports of survival statistics similar tosmall group of patients who respond to therapy with those seen in patients undergoing the bilateral pro-calcium channel blockers, the only recourse available cedure.3,10 –12 An advantage of single-lung transplan-at the time was lung transplantation.5 It is contro- tation is that it lends to greater allograft availabilityversial as to which form of transplantation is best for and a simpler operative procedure.the treatment of IPAH. Initially, heart/lung trans- Our report underscores another potential advan-plants were performed for these patients, until the tage of the single-lung procedure. Unexpectedly,realization of the remarkable recuperative properties there was sufficient regression of the disease in theof the right ventricle.6 – 8 Since then, it has remained remaining native lung that, despite the development of severe bronchiolitis obliterans syndrome resulting in the total destruction of the allograft, the patient had sufficient native lung recovery to sustain her. Ultimately, a transplant pneumonectomy could suc- cessfully be accomplished nearly 11 years later. In a sense, the transplant functioned as a “bridge to recovery.” The allograft pneumonectomy has also allowed the discontinuation of her immunosuppres- sive medications and the amelioration of the inher- ent side effects associated with these. Although inflammation and some of the cytokines invoked in the pathogenesis of IPAH might have been affected by the patient’s immunosuppression, it is unlikely that they had any role in the regression of the patients’ primary disease. Prior to 1994, there were not many lung trans- plants performed, and a small minority were for the treatment of IPAH. The 10-year survival rate post- lung transplant is also quite low at 25%; and therefore it is likely that there are not many patients with IPAH who received single-lung transplants who could have survived for 10 years.3 Therefore, it is Figure 3. Chest radiograph postpneumonectomy. impossible to predict what proportion of such pa-216 Original Research Downloaded from chestjournal.chestpubs.org by guest on May 27, 2011 © 2006 American College of Chest Physicians
  5. 5. tients might experience regression of their disease. pneumonectomy to be performed with discontinua-There is one other case report13 of a patient with tion of immunosuppressive therapy. Our case hasIPAH who received a single-lung transplant but possible implications with regard to the pathogenesisultimately died from bronchiolitis obliterans syn- of IPAH, the potential for regression, and the opti-drome. At autopsy, the apparent resolution of the mal transplant procedure for those patients whoseIPAH was noted.13 Regression of pulmonary arterial disease progresses despite medical therapy.hypertension (PAH) has been described in somepatients receiving long-term epoprostenol therapy, Referenceswith successful discontinuation of therapy. This only 1 Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonaryoccurs in a very small percentage of such patients hypertension: a national prospective study. Ann Intern Medand has generally been attributed to “remodeling” of 1987; 107:216 –223the pulmonary vasculature.14 Whether this is a direct 2 D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patientsaction of the drug or is perhaps a flow-mediated with primary pulmonary hypertension. Ann Intern Med 1991;phenomenon is uncertain. Our case lends credence 115:343–349 3 The International Society for Heart and Lung Transplanta-to the latter concept, in that the likely cause of tion. Heart/Lung Transplant Registry. Available at: http://regression of the disease was related to the low flow www.ishlt.org/registries/slides.asp. Accessed January 15, 2005and reduced shear stress to the native lung.13 Sup- 4 Barst RJ, Rubin LJ, Long WA, et al. A comparison ofportive of this is the early postoperative quantitative continuous intravenous epoprostenol (prostacyclin) with con-perfusion scan, which showed only 3% of the flow to ventional therapy for primary pulmonary hypertension: thethe native lung. This is a common accompaniment of Primary Pulmonary Hypertension Study Group. N Engl J Med 1996; 334:296 –302single-lung transplants in patients with high native 5 Rich S, Kaufmann E, Levy PS. The effect of high doses oflung pulmonary vascular resistance.8 This might calcium-channel blockers on survival in primary pulmonaryrepresent the reverse phenomenon that results in the hypertension. N Engl J Med 1992; 327:76 – 81genesis of PAH in patients with Eisenmenger phys- 6 Moser KM, Daily PO, Peterson K, et al. Thromboendarter-iology. This same phenomenon of “resting” a dis- ectomy of chronic, major vessel thromboembolic pulmonary hypertension: immediate and long-term results in 42 patients.eased organ has been shown to result in regression of Ann Intern Med 1987; 107:560 –565the disease in certain patients with cardiomyopa- 7 Kramer MR, Valantine HA, Marshall SE, et al. Recovery ofthies.15,16 the right ventricle after single-lung transplantation in pulmo- It is commonly held that IPAH occurs in individ- nary hypertension. Am J Cardiol 1994; 73:494 –500uals who are so predisposed, with precipitating fac- 8 Pasque MK, Trulock EP, Cooper JD, et al. Single lung transplantation for pulmonary hypertension: single institutiontors perhaps fueling or precipitating the process. Our experience in 34 patients. Circulation 1995; 92:2252–2258report lends support to the role of the mechanical 9 Levine SM. A survey of clinical practice of lung transplanta-effects of flow as part of this process in some of these tion in North America. Chest 2004; 125:1224 –1238patients. While it is encouraging that our patient has 10 Gammie JS, Keenan RJ, Pham SM, et al. Single-versusexperienced a sustained regression of her PAH, the double lung transplantation for primary pulmonary hyperten- sion. J Thorac Cardiovasc Surg 1998; 115:397– 403same predisposition for the subsequent progression 11 Conte JV, Borja MJ, Patel CB, et al. Lung transplantation forof PAH likely exists. Therefore, with the high flow to primary and secondary pulmonary hypertension. Ann Thoracher residual lung, it is likely that her IPAH will Surg 2001; 72:1673–1679progress in the future; indeed, there is early evi- 12 Mendeloff EN, Meyers BF, Sundt TM, et al. Lung transplan-dence of such with her recently recorded pressures. tation for pulmonary vascular disease. Ann Thorac Surg 2002; 73:209 –217Although she remains classified in World Health 13 Levy NT, Liapis H, Eisenberg PR, et al. Pathologic regressionOrganization class II, her mild PAH and propensity of primary pulmonary hypertension in left native lung follow-for progression has factored into the decision to start ing right single-lung transplantation. J Heart Lung Transplanther on bosentan therapy. One of the limitations 2001; 20:381–384of our case report is that we only have 6 months of 14 Kim NH, Channick RN, Rubin LJ. Successful withdrawal of long-term epoprostenol therapy for pulmonary arterial hyper-follow-up. It is possible that future progression of tension. Chest 2003; 124:1612–1615her disease might necessitate more aggressive ther- 15 Heerdt PH, Schlame M, Jehle R, et al. Disease-specificapies or even require consideration of the patient for remodeling of cardiac mitochondria after a left ventricularretransplantation. assist device. Ann Thorac Surg 2002; 73:1216 –1221 In summary, we have described the case of a 16 Barbone A, Holmes JW, Heerdt PM, et al. Comparison of right and left ventricular responses to left ventricular assistpatient with regression of PAH in a patient with device support in patients with severe heart failure: a primaryIPAH who previously had undergone single-lung role of mechanical unloading underlying reverse remodeling.transplantation. This allowed a successful allograft Circulation 2001; 104:670 – 675www.chestjournal.org CHEST / 130 / 1 / JULY, 2006 217 Downloaded from chestjournal.chestpubs.org by guest on May 27, 2011 © 2006 American College of Chest Physicians
  6. 6. Reversal of Idiopathic Pulmonary Arterial Hypertension and Allograft Pneumonectomy After Single Lung Transplantation * Subrato Deb, Joon Yun, Nelson Burton, Edward Omron, John Thurber and Steven D. Nathan Chest 2006;130; 214-217 DOI 10.1378/chest.130.1.214 This information is current as of May 27, 2011Updated Information & ServicesUpdated Information and services can be found at:http://chestjournal.chestpubs.org/content/130/1/214.full.htmlReferencesThis article cites 15 articles, 10 of which can be accessed free at:http://chestjournal.chestpubs.org/content/130/1/214.full.html#ref-list-1Cited BysThis article has been cited by 2 HighWire-hosted articles:http://chestjournal.chestpubs.org/content/130/1/214.full.html#related-urlsPermissions & LicensingInformation about reproducing this article in parts (figures, tables) or in its entirety can befound online at:http://www.chestpubs.org/site/misc/reprints.xhtmlReprintsInformation about ordering reprints can be found online:http://www.chestpubs.org/site/misc/reprints.xhtmlCitation AlertsReceive free e-mail alerts when new articles cite this article. To sign up, select the"Services" link to the right of the online article.Images in PowerPoint formatFigures that appear in CHEST articles can be downloaded for teaching purposes inPowerPoint slide format. See any online figure for directions. Downloaded from chestjournal.chestpubs.org by guest on May 27, 2011 © 2006 American College of Chest Physicians

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