Percutaneous Pulmonary Artery and Vein Stenting

A Novel Treatment for Mediastinal Fibrosis

THOMAS P. DOYLE, JAMES E. LOYD, AND IVAN M. ROBBINS
Division of Pediatric Cardiology and Center for Lung Research, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee

Mediastinal fibrosis is a rare consequence of infection with the fungus Histoplasma capsulatum that can lead to occlusion of large pulmonary arteries and veins and mainstem bronchi. Medical and surgical treatments for this disorder have been ineffective. We describe successful treatment for central pulmonary arterial and venous obstruction due to mediastinal fibrosis in four patients using percutaneously placed intravascular stents. Patients were severely limited, World Health Organization functional class III or IV. At the time of right and left heart catheterization, stents were placed in pulmonary arteries (n 1), veins (n 2), or both (n 1) to relieve vascular obstruction resulting from mediastinal fibrosis. Immediate hemodynamic and clinical improvement was observed in all patients. Three of the four patients have had sustained improvement in exercise tolerance, from 3.5 mo to 4.5 yr after stent placement. The only complication was a self-limited pulmonary hemorrhage in one patient. Our initial experience suggests that percutaneous stent placement to relieve central pulmonary arterial or venous obstruction due to mediastinal fibrosis is an effective new treatment modality. Keywords: catheterization; stents; pulmonary heart disease; vessels

arteries (1012), which led us to consider this therapeutic technique in patients with MF. Our early experience suggests that stenting is efficacious and safe, and may lead to prolonged improvement in some patients.

METHODS
Informed consent was obtained for all procedures, which were performed in accordance with Vanderbilt University institutional guidelines. Vascular access was obtained from the femoral region and an atrial transseptal puncture was performed if there was evidence or suspicion of pulmonary vein involvement. Right and left heart catheterization with hemodynamic measurements, followed by angiography, was performed to evaluate the pulmonary vascular bed. Pulmonary veins were assessed either by direct injection via transseptal puncture or by pulmonary artery wedge angiography in which a balloon tipped end-hole catheter (Arrow International, Reading, PA) was wedged into a distal branch pulmonary artery with the balloon inflated. Contrast was then hand injected until a capillary blush was seen and then flushed gently through the venous bed with saline. Transesophageal echocardiogram (TEE) during the catheterization was helpful in trying to assess pulmonary vein involvement. Once the extent of vascular obstruction was assessed, pulmonary arterial involvement was always addressed first as there was little benefit to stenting the pulmonary veins if pulmonary arterial flow to the same region could not be restored. The stenosis was crossed with a Glide wire (Medi-tech; Boston Scientific Co, Watertown, MA). An end-hole catheter was positioned beyond the stenosis to allow placement of an Amplatz Super Stiff wire (Medi-tech, Boston Scientific Co). A long (80100 cm), large (812 Fr) sheath (Arrow International, Reading, PA) was passed beyond the stenotic region. P308 Palmaz stents (Johnson and Johnson, Warren, NJ) were mounted on balloons (Braun Medical Inc., Bethlehem, PA) whose diameter was similar to that of adjacent, noninvolved vessels and passed into the region of stenosis. Position was confirmed angiographically. High-pressure balloon dilation (up to 20 atmospheres) was often necessary to achieve optimal stent diameter, which in some vessels allowed us to overexpand the stent to a maximal diameter of 18 mm. Hemodynamics and angiography were then repeated to assess the extent to which the stenosis was alleviated.

Mediastinal fibrosis (MF) is a rare long-term complication of infection with Histoplasma capsulatum occurring years to decades after exposure (13). MF is the result of a fibrotic response to the presence of histoplasma antigens in the mediastinal lymph nodes (3, 4). Progressive fibrosis entraps and occludes pulmonary arteries, pulmonary veins, and mainstem bronchi (4). The structures affected determine the clinical manifestations: Arterial obstruction leads to pulmonary ischemia and infarction, venous obstruction to pulmonary edema, and bronchial obstruction to hypoxemia and hemoptysis (3). Patients most commonly present with cough, dyspnea, hemoptysis, pleuritic chest pain, or pulmonary infections (4). No medical or surgical treatment has been successful for MF affecting central pulmonary arteries and veins. The prognosis in symptomatic patients with bilateral pulmonary vascular involvement is poor with a mortality of 46% in one study (4). There are individual reports of improvement with corticosteroids or with surgical resection, however, in the vast majority of cases, neither of these treatments provides long-term relief (49). Lack of a distinct surgical plane of dissection makes adequate removal of fibrotic material and closure of the incision extremely difficult. Percutaneously implanted vascular stents have been used successfully in other disorders affecting pulmonary veins and

RESULTS
Case 1

(Received in original form December 27, 2000 and in revised form April 25, 2001) Sources of support: NIH Grant HL48164 (Dr. Loyd) and NIH Grant K23 RR1553401 (Dr. Robbins). Correspondence and requests for reprints should be addressed to Ivan M. Robbins, M.D., Vanderbilt University School of Medicine, Room T-1219, MCN, Nashville, TN 37232. E-mail: Ivan.Robbins@mcmail.vanderbilt.edu Am J Respir Crit Care Med Vol 164. pp 657660, 2001 Internet address: www.atsjournals.org

A 27-year-old man with a history of dyspnea on exertion and massive hemoptysis was diagnosed with MF by thoracotomy. Quantitative perfusion scan demonstrated only 10% of pulmonary blood flow to the right lung. When initially seen, the patient was bed-bound, World Health Organization (WHO) functional class IV. Cardiac catheterization demonstrated a mean pulmonary artery (PA) pressure of 52 mm Hg, and mean pulmonary vein (PV) pressure of 31 mm Hg on the right and 23 mm Hg on the left. The left PVs were obstructed by a 5-mm luminal stenosis at the junction with the left atrium (Figure 1A). There was a 3-cm-long stenotic lesion of the right upper PV. A stent was placed in the left PV stenosis with complete resolution of obstruction (Figure 1B). Two additional stents were placed in series in the right upper PV without significant improvement in flow. Mild pulmonary hemorrhage, which did

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Figure 1. Contrast injection of the left lower pulmonary vein is seen in A. Note the large distended vein that tapers to 5 mm as it converges with the left atrium (arrow). A marker pigtail catheter is in the descending aorta for calibration purposes (2 cm between marker bands). The left upper pulmonary vein enters the same region, but is not seen in this injection. (B) The same injection following stent placement. Note the complete relief of obstruction. A second wire can be seen positioned in the left upper lobe vein.

not require treatment, occurred during wire manipulation in the right pulmonary vein. Stenting resulted in a decrease in mean PA pressure to 39 mm Hg and a dramatic improvement in the patients symptoms and activity level. At the time of discharge from the hospital, he was WHO class I and remains so 4.5 yr after the procedure.
Case 2

A 50-year-old gentleman was diagnosed with MF after presenting with a 6-mo history of dyspnea, chest pain, and a rightsided pleural effusion. At the time of evaluation, he was functionally WHO class III. Perfusion scan demonstrated no flow to the right lung and magnetic resonance imaging (MRI) of the chest revealed external compression and occlusion of the right main PA. Right heart catheterization demonstrated normal left PA pressure and flow but complete occlusion of the right PA (Figure 2A). Two overlapping stents were placed in the right PA. Repeat angiography demonstrated good blood flow primarily to the right lower lobe (Figure 2B). Distal left and right pulmonary artery pressures following stent placement were normal and equal. Follow-up perfusion scan demonstrated 23% of blood flow to the right lower lung zone. The patients dyspnea and chest pain resolved, and his exercise tolerance returned to normal. Follow-up chest X-ray demonstrated resolution of the right-sided effusion. Three years following the procedure the patient remains asymptomatic, WHO class I.
Case 3

flow to the right lung and computed tomography (CT) of the chest demonstrated significant compression of the right PA by a mediastinal mass. Cardiac catheterization demonstrated occlusion of the right lower PA with mild stenosis of the right middle and upper lobe PAs as well as stenosis of the right lower PV. Mean PA pressure was mildly elevated at 28 mm Hg. Stents were placed in two separate branches of the right lower lobe PA and in the right lower PV. Repeat angiography demonstrated all stented vessels to be patent, however flow through the distal right lower pulmonary bed was sluggish. In addition, there was further narrowing of the right middle lobe PA. Despite only mild angiographic improvement, the patients dyspnea and chest pain resolved. One month later symptoms returned, although not as severe as initially reported. Repeat catheterization demonstrated complete occlusion of the right lower PA stents despite chronic anticoagulation. No further intervention was attempted. Thirty-two months later, the patient remains WHO class III.
Case 4

A 45-year-old woman, functional class III, with a history of dyspnea and chest pain, was diagnosed with MF at the time of thoracotomy. Perfusion scan demonstrated decreased blood

A 31-year-old woman was diagnosed with MF after presenting with a 9-mo history of worsening dyspnea on exertion, hemoptysis, and chest pain. MRI demonstrated obstruction of the right main pulmonary artery and left pulmonary veins and narrowing of the left upper lobe bronchus. Perfusion scan demonstrated no flow to the entire right lung. At the time of evaluation, the patient was limited to ambulating across the room, functional class IV. Bronchoscopic evaluation of the airways showed a patent but narrowed left upper lobe with submucosal vascular hypertrophy. Cardiac catheterization demonstrated pulmonary arterial and venous hypertension. Mean PA pressure was 62 mm Hg. Mean left upper PV pressure was 40 mm Hg and left lower PV pressure

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Figure 2. Right pulmonary arteriogram (A) demonstrates complete occlusion of the proximal right pulmonary artery. Note the tapered appearance of the distal right pulmonary artery. A marker pigtail catheter is in the descending aorta for calibration purposes. Following placement of two stents across the obstruction (B) there is restoration of flow to the right lower lobe.

was 21 mm Hg. There was severe stenosis of the left upper PV to 1.5 mm as it entered the LA (Figure 3A) and mild narrowing of both left lower PVs. In addition, there was complete absence of flow to the right lung and functional atresia of the right PVs. A stent was placed in the left upper PV with an increase in the diameter of the vein to 10 mm (Figure 3B) leading to a significant reduction in left upper PV pressure to 11 mm Hg and in PA pressure to 37 mm Hg. A stent was also placed in the left lower PV without any significant change in pressure or diameter. The pa-

tients hemoptysis resolved following the procedure and her dyspnea has improved although she continues to have significant exercise limitation and remains WHO class III 3.5 mo after stenting.

DISCUSSION
Percutaneous intravascular stent placement has been reported for the treatment of superior vena caval and pulmonary arterial obstruction secondary to MF (1315). We now report ex-

Figure 3. Contrast injection of the right upper pulmonary vein in A. Note the distended vein that tapers to 1.5 mm as it enters to the left atrium (arrow) and the sluggish flow of contrast remaining in smaller branches of the vein. A second catheter is seen in the left lower pulmonary vein. (B) The same injection following stent placement with expansion of the vein to a diameter of 11 mm. Note the lack of contrast in branches of the vein.

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tended experience with four patients who received stents for central pulmonary arterial and venous obstruction due to MF. Intravascular stents are effective for the treatment of a variety of stenotic vascular lesions in patients with congenital heart disease and are particularly effective in branch pulmonary arteries (1012). Stents have also been used for the treatment of congenital and acquired pulmonary vein stenosis (16, 17). However, the results with pulmonary vein stenosis have been less impressive, probably due to the presence of disease in both large and small vessels, the latter of which are not amenable to stenting. We employed Palmaz stents because of proven results in the treatment of congenital vascular stenosis. They also can be overexpanded and have excellent radial hoop strength. This small series demonstrates that percutaneously placed stents can improve pulmonary arterial and venous hypertension and alleviate symptoms due to MF. Despite achieving patency, we were unable to establish flow in all stented vessels. Chronic vascular obstruction may lead to irreversible changes that preclude reestablishment of effective flow despite stent placement. We have found that airway stents placed to alleviate bronchial obstruction from MF have been associated with recurrent occlusion by proliferative granulation tissue (unpublished observations), and this may yet occur in our patients with vascular stents. Prior to the consideration of intervention, an evaluation is needed to rule out other diagnoses and to identify the major areas of obstruction. Diagnoses that can be confused with MF included chronic pulmonary thromboembolic disease, tumor emboli, tumor compression of mediastinal structures, and superior vena cava syndrome. The diagnosis of mediastinal fibrosis can often be made on the basis of noninvasive testing. Chest CT (and more recently MRI) and V/Q scans are important studies to obtain in cases of suspected MF. Assessment of the distribution of ventilation is important in planning a treatment approach, as there is a potential danger of worsening V/Q matching by reestablishing blood flow to unventilated regions of the lung. Because of this, we stented only vessels in areas in which there was evidence of ventilation. Bronchoscopy, as in Case 4, may be necessary to better define airway involvement. It also needs to be strongly emphasized that vascular stenting in MF requires a highly skilled cardiac interventionalist with extensive experience in the management of pulmonary arterial and venous stenosis. Although our experience is small, we are encouraged by the ability to successfully stent severely stenotic and even occluded pulmonary arteries and veins. The complete resolution of symptoms in our first patient who was bed bound indicates that this technique can be life saving. Our experience with the third and fourth cases, however, demonstrates that simply opening the pul-

monary arteries and veins may not result in hemodynamic or clinical improvement in all patients. Clearly, however, percutaneous stent placement represents a new therapeutic modality for selected patients with MF who have previously had no effective treatment options.

References
1. Goodwin RA, Des Prez RM. Histoplasmosis. Am Rev Respir Dis 1978; 117:929956. 2. Goodwin RA Jr, Loyd JE, Des Prez RM. Histoplasmosis in normal hosts. Medicine 1981;60:231266. 3. Goodwin RA Jr. Histoplasmosis with symptomatic lymphadenopathy. Chest 1981;77:213215. 4. Loyd JE, Tillman BR, Atkinson JB, Des Prez RM. Mediastinal fibrosis complicating histoplasmosis. Medicine 1988;67:295309. 5. Berry DF, Buccigrossi D, Peabody J, Peterson KL, Moser KM. Pulmonary vascular occlusion and fibrosing mediastinitis. Chest 1986;89: 296301. 6. Mitchell IM. Saunders NR. Maher O. Lennox SC. Walker DR. Surgical treatment of idiopathic mediastinal fibrosis: report of five cases. Thorax 1986;41:210214. 7. Nassar WK, Feigenbaum H, Fisch C. Clinical and hemodynamic diagnosis of pulmonary venous obstruction due to sclerosing mediastinitis. Am J Cardiol 1967;20:725792. 8. Hewlett TH, Steer A, Thomas DE. Progressive fibrosing mediastinitis. Ann Thorac Surg 1966;3:345356. 9. Cameron DG, Ing ST, Boyle M, Mathews WH. Idiopathic mediastinal fibrosis and retroperitoneal fibrosis. Can Med Assoc J 1961;85:227232. 10. OLaughlin MP, Perry SB, Lock JE, Mullins CE. Use of endovascular stents in congenital heart disease. Circulation 1991;83:19231939. 11. OLaughlin MP, Slack MC, Grifka RG, Perry SB, Lock JE, Mullins CE. Implantation and intermediate-term follow-up of stents in congenital heart disease. Circulation 1993;88:605614. 12. Shaffer KM, Mullins CE, Grifka RG, OLaughlin MP, McMahon W, Ing FF, Nihill MR. Intravascular stents in congenital heart disease: shortand long-term results from a large single-center experience. J Am Coll Cardiol 1998;31:661667. 13. Dodds GA3rd, Harrison JK, OLaughlin MP, Wilson JS, Kisslo KB, Bashore TM. Relief of superior vena cava syndrome due to fibrosing mediastinitis using the Palmaz stent. Chest 1994;106:315318. 14. Kandzari DE, Warner JJ, OLoughlin MP, Harrison JK. Percutaneous stenting of right pulmonary artery stenosis in fibrosing mediastinitis. Cardiovasc Intervent 2000;49:321324. 15. Guerrero A, Hoffer EK, Hudson L, Schuler P, Karmy-Jones R. Treatment of pulmonary artery compression due to fibrous mediastinitis with endovascular stent placement. Chest 2001;119:966968. 16. Coles JG, Yemets I, Najm HK, Lukanich JM, Perron J, Wilson GJ, Rabinovitch M, Nykanen DG, Benson LN, Rebeyka IM, et al. Experience with repair of congenital heart defects using adjunctive endovascular devices. J Thorac Cardiovasc Surg 1995;110:15131519. 17. Mendelsohn AM, Bove EL, Lupinetti FM, Crowley DC, Lloyd TR, Fedderly RT, Beekman RH 3rd. Intraoperative and percutaneous stenting of congenital pulmonary artery and vein stenosis. Circulation 1993; 88:210217.