Safety and Clinical Outcomes of Endovascular Treatment of Adult-Onset Pulmonary Artery Stenosis

Pulmonary artery stenosis (PAS), particularly branch stenosis, is one of the most common forms of vascular stenosis associated with congenital heart disease.^1,2 There has been extensive experience with pulmonary artery stenting in children, demonstrating significant improvement in symptoms and improved outcomes.^3-5 In contrast to pediatric PAS, adult-onset PAS is rare and has been associated with a wide variety of clinical conditions including fibrosing mediastinitis, lung parenchymal tumors, primary vascular tumors, and lung transplantation. PAS in these cases results from extrinsic compression or direct vessel involvement from inflammatory or neoplastic process in the adjacent structures. Reported clinical manifestations of PAS are variable and range from dyspnea due to inadequate pulmonary perfusion to right heart failure from chronic pressure overload. Multiple published anecdotal cases and case series have documented efficacy of endovascular stent implantation in the treatment of symptomatic adult-onset PAS. We therefore reviewed the published literature on adult-onset PAS treated with endovascular approach and provide a comprehensive report on the etiology, clinical presentation, diagnostic modalities, procedural details, and outcome of these patients. 

Methods

We performed a retrospective review of all cases of adult PAS published in Pubmed/Medline from 1990 to 2013. We used the MESH words: “pulmonary artery AND stent” in Pubmed and included all case reports and studies reporting PAS in the adult population. To identify further articles, we manually searched the references of papers retrieved. We found a total of 126 case reports of adult PAS, out of which 46 cases reported endovascular intervention. We excluded studies published in languages other than English. We also excluded cases of congenital PAS including isolated peripheral PAS, PAS in pediatric population, and vasculitis-induced PAS. 

 We reviewed the case reports in detail and collected data about the etiology, clinical presentation, patient demographics, diagnostic modalities, angiographic, and procedural details, preprocedure and postprocedure hemodynamic data, adverse events, and clinical outcomes at follow-up. 

Statistics. Continuous variables were reported as values ± standard deviation. The t-test was used to compare preprocedure and postprocedure means and Fischer’s exact test was used to analyze categorical data. 

Results

Etiology and clinical presentation. A total of 126 cases of adult-onset PAS were retrieved in published literature. An endovascular modality was used to treat 46 out of 126 patients (37%) with symptomatic PAS (Table 1). In 17 out of 46 cases, PAS was related to fibrosing mediastinitis (6 infectious causes and 11 non-infectious causes), 12 cases of anastamotic stenosis post lung transplantation, and 16 cases of malignancy/tumors (11 cases of extrinsic compression of the pulmonary artery and 5 cases of intrinsic malignancy of the pulmonary artery). There was 1 case report of radiation-induced PAS treated with stent. The mean age at presentation was 52 ± 14 years for males and 46 ± 14 years for females, with a male to female ratio of 1:1. Shortness of breath at rest (41%) and chest pain (29%) were the most common presenting complaints of adult PAS. Other reported presentations included hemoptysis (11%), cough (11%), peripheral edema (7.4%), pulmonary hypertension (3%), and cardiopulmonary arrest (2%). Among the various diagnostic modalities used to detect PAS, Contrast-enhanced chest computed tomography (24%), pulmonary angiogram (18%), right heart catheterization (8%), and ventilation perfusion scan (8%) were commonly used diagnostic tests to assess location and severity of PAS. 

Angiographic characteristics and endovascular treatment. PAS involved right pulmonary artery (RPA) in 45%, main pulmonary artery (MPA) in 25%, left pulmonary artery (LPA) in 20%, and bilateral involvement was seen in 10% of the cases. Forty-six out of 126 patients (37%) with symptomatic PAS were treated with a total of 62 stents (Table 1). Two stents were required in 8 patients, three stents were required in 1 patient, and one stent was utilized to treat the lesion in the remaining patients. The majority of pulmonary arterial lesions were stenotic (42 out of 46), with complete occlusion reported in 4 cases. The common femoral vein was the most common access site and most cases reported large-bore sheaths (range, 12-16 Fr) for stent delivery. Balloon angioplasty of the stenotic lesions prior to stent placement was performed in 39% of cases (18 out of 46), including 2 cases reporting the use of cutting-balloon angioplasty, while the remaining 61% of cases underwent direct stenting. Post-stent deployment balloon dilation was performed in 72% of cases (33 out of 46). Complete stent information was available for 53 out of 62 stents. Balloon-expandable stents (Palmaz, Express LD) were used in 35 lesions (74%), and self-expanding nitinol stents (E-Luminexx,Wallstent, Self X) were used in 12 lesions (26%) (Table 2). Hand-mounted stents accounted for 7 stent implantation cases (15%). Stent dimensions were available in 35 cases. The average stent diameter was 12 ± 5 mm with a median of 12 mm, while average stent length was 35 ± 13 mm with a median of 40 mm. In 20 patients, larger stents (diameter >10 mm) were used; extremely large stents (16 ± 6 mm) were used to treat stenosis of the main pulmonary artery (Patients #32, #33, #35, #38, #39, and #40). Translesional gradient was reported in 32 out of 46 cases of PAS. Mean translesional gradient at baseline was 47 ± 20 mm Hg, which was reduced to 8 ± 11 mm Hg after stenting (P<.001). Mean preprocedural pulmonary systolic artery pressure was 79 ± 26 mm Hg, which reduced post procedure to 50 ± 20 mm Hg (P=.02) with an average reduction of 36 ± 15% 

Adverse events and clinical outcomes. Immediate periprocedural adverse events were reported in 3 out of 46 patients (7%) in the form of lung reperfusion injury,¹⁸ stent migration,⁴⁰ and hemothorax.²⁴ Reperfusion injury was treated with mechanical ventilation and steroids with successful outcome. The case of stent migration occurred in a hand-mounted stent system and required surgical cutdown for removal of stent from the femoral vein. The patient who developed hemothorax required surgical drainage. Three cases reported jailing and occlusion of sub-segmental branches; however, these were deemed clinically insignificant.^12,13 

Follow-up was reported in 29 of the 46 cases of PAS treated with stents, with an average duration of 19 ± 5 months. The majority of these patients (22 out of 29; 76%) were asymptomatic at follow-up. Besides clinical follow-up, multiple imaging modalities were used to assess the patency of the stents, including chest computed tomography (11; 23%), pulmonary angiogram (7; 17%), and V/Q scan (8; 19%). On follow-up, in-stent restenosis (ISR) was seen in 7 patients (24%) at 9 ± 4.7 months of follow-up. The majority of ISR was seen in patients with fibrosing mediastinitis (5 out of 7 cases; 72%). Treatment for ISR included repeat intervention with stenting (4 cases), balloon angioplasty (1 case), surgical bypass (1 case), and conservative management (1 case). Of those treated with stents, 7 patients (15%) died during the follow-up period. This included 4 patients with malignancy-related PAS and 2 patients with anastomotic stenosis. 

The results of this review are summarized in Table 2.

Discussion

Based on our review, endovascular treatment appears to be an effective therapeutic option in patients with symptomatic adult-onset PAS. Immediate postprocedure symptomatic improvement was reported in 98% of the patients and 76% of cases were reported to be asymptomatic on follow-up. Proximal location and treatment of hemodynamically significant lesions in this vascular bed may be reasons for improved symptoms with endovascular therapy. This is in contrast to congenital PAS, where segmental lesions are often encountered in addition to proximal vessel disease.⁶ 

Endovascular stenting in adult-onset PAS also appears safe and has similar immediate and long-term outcomes as compared with the pediatric population. In adult PAS, an immediate complication rate of 7% was noted. This event rate appears similar to the 12% rate of immediate adverse events reported after pulmonary artery stenting in pediatric patients.⁸ In contrast to congenital PAS, reperfusion injury was not common in adults after stent deployment. Only 1 case reported reperfusion injury post stenting.¹⁸ This may be explained by the presence of a predominantly proximal PA disease in adult-onset PAS, the treatment of which effectively relieves PA hypertension. However, in congenital PAS, there are additional distal branch diseases, which after the treatment of proximal PA stenosis results in persistent distal vessel hypertension and eventually leads to reperfusion injury.

Despite use of larger stents and higher blood flow in these central vessels, an ISR rate of 24% (7 out of 29 cases) was reported on follow-up. This appears similar to a restenosis rate of 24% reported in pediatric patients. ⁹ ISR was commonly seen in patients with fibrosing mediastinitis-related PAS (71%). This is likely due to the persistent inflammation seen in patients with fibrosing mediastinitis, which can result in aggressive neointimal hyperplasia. ISR was also associated with recurrence of symptoms, with a repeat intervention rate of 10.8% (5 out of 46 cases). In some cases, adjunctive medical therapy including antifungals and steroids was used to treat the underlying inflammation and possibly prevent ISR.^13,19,21

Among the stent types, balloon-expandable stents were more commonly used to treat stenotic lesions compared with self-expanding stents (74% vs 26%). The advantage of balloon-expandable over self-expanding stents in the PA is not fully known. Precise deployment and better radial strength with balloon-expandable stents could have influenced the decision in these patients; however, better deliverability of self-expanding stents may be of value in treating lesions in highly angulated vessels.

Mortality was seen on follow-up in 4 out of 16 cases of malignancy-related PAS (25%) as compared with 0% mortality reported in patients with benign etiology of PAS. In patients with malignancy, PAS represents advanced disease stage and the prognosis remains worse despite symptom relief with successful stenting. However, in carefully selected patients with malignancy-related PAS, stenting might be considered as a potential palliative option.

Study limitations. Although our study has the inherent limitations of a retrospective analysis, it may be the only available evidence for this rare clinical entity. The follow-up period was variable, ranging from 6 months to 1.5 years, and was not available in some reports. Lesion length and angiographic severity of the stenotic segments were missing in a few case reports. Other potential complications of the endovascular procedure, including access-site bleeding, perforation and/or dissection of the PA, migration of stents, and stent fractures were not reported, and hence their incidence remains unknown. In patients with benign etiology of PAS, although the treatment was successful, the lack of longer duration of follow-up might have underestimated the true incidence of ISR. Moreover, it is possible that only successful cases of PAS were reported in the literature and the true incidence of this disease process, and therefore its treatment outcomes, may be underappreciated.

Conclusion

Endovascular treatment approach in patients with adult-onset of PAS is feasible, safe, and leads to improved symptomatology in the majority of the patients. Our review of published cases provides important procedural and outcome data for adult-onset PAS and could help with the decision making for this clinical condition.

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