A Case Report of Pulmonary Vein Stenosis Within the Labyrinth of Fibrosing Mediastinitis

Abstract

This case centers on a 76-year-old male experiencing exertional dyspnea and hemoptysis, with a medical history marked by recurrent pulmonary embolism and chronic obstructive pulmonary disease (COPD). Notably, he resides in a histoplasmosis-endemic area. A computed tomography (CT) pulmonary embolism scan revealed notable findings, including an enlarged right lower pulmonary artery, vascular congestion, atelectasis, and a mass exerting pressure on the right lower pulmonary vein. Biopsy results identified the mass as fibrosing mediastinitis, likely attributed to histoplasmosis. A transthoracic echocardiogram indicated right ventricular dilatation, impaired function, and a right ventricular systolic pressure of 63 mm Hg. During right heart catheterization, the patient displayed disparate pulmonary artery wedge pressures (PAWPs) between the right and left sides. This discrepancy was linked to a blunted back wave from the left atrium to the catheter, induced by pulmonary vein compression. Although an infrequent phenomenon, the recorded asymmetry in PAWPs played a crucial role in guiding accurate patient management. The absence of subsequent evaluation of PAWP on the left side could have altered the treatment plan, potentially delaying appropriate patient care. This case emphasizes the necessity of thorough exploration with right heart catheterization when clinical symptoms warrant, highlighting the importance of standardized practices in such procedures.

Introduction

Pulmonary vein stenosis (PVS) is a rare condition, with an estimated incidence of about 2 to 3 cases per year in large medical centers, and its morbidity and mortality rates are notably high, particularly in advanced stages of the disease. ¹ Pulmonary vein stenosis has bimodal age distribution with fibrosing mediastinitis (FM) being one of the causes in adults.^1,2 Fibrosing mediastinitis is a rare disorder characterized by the excessive growth of fibrous tissue in the mediastinum, which envelops and compresses mediastinal structures resulting in potentially lethal outcomes such as pulmonary hypertension (PH). ³

In this case report, we discuss a rare situation where PH caused by FM resulted in 2 distinct pulmonary artery wedge pressures (PAWPs). This difference was due to the unilateral compression of the pulmonary vein (PV) by FM. This emphasizes the importance of early recognition and understanding of such complications for effective management and improved outcomes in FM patients.

Case Presentation

A 76-year-old male patient was admitted with exertional dyspnea and hemoptysis. His past medical history is significant for recurrent pulmonary embolism (PE) on Apixaban and chronic obstructive pulmonary disease (COPD) with chronic hypoxic respiratory failure on 2 L oxygen at baseline. Social history is significant for previous tobacco smoking and residence in an endemic area of Histoplasmosis.

On presentation, the vitals included a blood pressure (BP) of 148/90, heart rate of 110 beats/minute sinus rhythm, respiratory rate of 28 cycles/min, and oxygen saturation was 90% on 4 L by nasal cannula. Cardiac examination showed sinus tachycardia without any murmurs. Chest examination showed decreased air entry bilateral, basal rales, and scattered expiratory rhonchi. Otherwise, the physical examination reveals no significant findings.

The chest X-ray indicated increased lung volumes, an enlarged right lower pulmonary artery, vascular congestion, and right lower lobe (RLL) atelectasis. A transthoracic echocardiogram (TTE) identified normal left ventricular systolic function and indeterminate diastolic dysfunction. It also noted right ventricular dilatation, impaired right ventricular function (Tricuspid annular plane systolic excursion) (TAPSE) = 1.6 cm, Fractional Area Change (FAC) = 15.2%), and a right ventricular systolic pressure of 63 mm Hg and no evidence of atrial septal defect (Figure 1). H2FPEF score, a validated algorithm for the diagnosis of heart failure with preserved ejection fraction, showed a 92% probability of heart failure with preserved ejection fraction (HFpEF). The patient was treated as a case of acute decompensated heart failure, initiating intravenous diuretics that resulted in clinical improvement, leading to a safe discharge.

Figure 1.

Transthoracic echocardiography, top right: M-Mode shows impaired right ventricular function with TAPSE of 1.6 cm, top left: continuous wave Doppler shows right ventricular systolic pressure of 63 mm Hg, bottom: dilated right ventricular dimension. TAPSE:Tricuspid annular plane systolic excursion

Following discharge, a PH work-up was initiated. Computed tomography (CT) chest with and without intravenous (IV) contrast (Figure 2) revealed RLL atelectasis with possible endobronchial lesion and RLL mass, a mass distal to the bronchus basalis of RLL, and right lower PV compression. It also showed dilatation of the central pulmonary artery up to 4.6 cm and the main pulmonary arteries with no evidence of pulmonary artery filling defects. Large noncalcific right paratracheal lymph nodes measuring up to 2.6 cm with calcific bilateral hilar and subcarinal lymph nodes indicative of chronic granulomatous process identified. Granulomatous calcifications were also observed within the liver and spleen. A ventilation/perfusion (V/Q) scan showed a defect involving the RLL with no mismatch along with positive perfusion showing 52% perfusion to the right lung and 48% perfusion to the left lung.

Figure 2.

Axial IV contrast-enhanced CT image through the chest shows a dilated central pulmonary artery, right and left main pulmonary arteries (right image), and right calcific mass (circle) obliterating the right lower pulmonary vein (left image).

For further evaluation of PH, he underwent Right hearth catheterization (RHC), which showed a mean pulmonary artery pressure of 30 mm Hg. Although evaluating the PAWP, the catheter was initially directed to the right lower pulmonary artery, where it measured a PAWP of 8 mm Hg, inconsistent with the clinical presentation. As a result, the catheter was redirected to the left side, revealing a PAWP of 20 mm Hg (Figure 3), corresponding to a pulmonary vascular resistance (PVR) of 1.8 Wood units (WU). This raises a concern about PVS likely attributed to possible external compression by the mediastinal mass.

Figure 3.

Right heart catheterization tracings of pulmonary artery wedge pressure (PAWP). Right figure: PAWP on the right side of 8 mm Hg. Left figure: PAWP on the left side of 20 mm Hg.

Bronchoscopy was performed to evaluate the mass which revealed a partially occluded right middle lobe (RML) bronchus and almost near complete narrowing of RLL bronchus with mucosal swelling and extrinsic compression. Submucosal friable soft tissue swelling compromising the opening of RML/RLL bronchus, and extensive dilated tortuous veins in the RLL, with atelectatic lung, extensive vascularity, and lithiasis.

The biopsy of the mass revealed findings consistent with necrotizing granuloma, no evidence of malignancy and negative acid-fast bacilli and fungus stains, whereas serology results indicated a prior Histoplasma capsulatum infection. Thus, the radiological findings, coupled with positive histoplasmosis antibody results and negative biopsy findings for tuberculosis or malignancy, collectively provide strong support for the diagnosis of FM likely secondary to histoplasmosis. The patient was offered stenting for the occluded bronchus and PV angioplasty but declined the procedures.

Discussion

This is a case involving a patient who exhibited 2 different PAWP readings during the evaluation for PH. He had a PAWP of 8 mm Hg on the right side, which did not parallel his clinical presentation, so professional judgment prompted further exploration with the passage of the catheter to the left side and resulted in a pressure reading of 20 mm Hg, which confirmed the diagnosis of a postcapillary PH. The discrepancy between the wedge pressures can be explained by damping the flow from the left atrium to the catheter caused by PV compression, causing the pressure wave to be reduced. This can be explained by the fact that PVS causes obstruction between the blocked balloon in the distal pulmonary artery branch and the left atrium, leading to different PAWPs. This PAWP can serve as a diagnostic tool to assess and classify the severity of PVS. ⁴

Although this is an infrequent finding, it was crucial to record the asymmetric PAWPs for the appropriate guidance in the management of our patient. Had no further exploration of the left side been taken, the treatment plan would have been altered, delaying the proper management of our patient. The findings from our patient should encourage the standard use of extensive exploration with RHC when clinical symptoms lead to so.

If we had relied on the initial RHC values compatible with groups 3 and/or 5 PH and did not pursue the true PAWP on the left side that was not affected by external compression, we could have mismanaged the patient. The improvement of the patient with diuresis confirmed our working diagnosis.

Pulmonary Artery Wedge Pressure

Pulmonary hypertension is characterized by a resting mean pulmonary arterial pressure of 20 mm Hg or higher and classified into 5 main groups based on PAWP and PVR measured during RHC. ⁵

The PAWP may represent either an approximation of left ventricular end-diastolic pressure (LVEDP), the average pressure sensed by the pulmonary vasculature when intrathoracic pressure nears atmospheric levels, or the cumulative passive pressures affecting the pulmonary vasculature. Traditionally, it is defined as a stand-in for LVEDP. Normal PAWP is 6 to 12 mm Hg. For an accurate measurement of LVEDP using PAWP, specific conditions must be met: an uninterrupted fluid connection between the catheter tip and the left atrium during the end of diastole and expiration, along with positioning the catheter in West’s lung zone 3, where alveolar pressure is lower than pulmonary arterial and venous pressure, ensuring direct pressure transmission. This zone typically aligns with the catheter tip placement in most of the lung when a patient is in the supine position. Elevated LVEDP leads to increased PAWP pressure. Conditions such as mitral stenosis, left ventricular systolic or diastolic dysfunction, volume overload, and myocardial infarction resulting in reduced left ventricular compliance are the examples that can raise PAWP. ⁶

Normally, PAWP should closely match the pressure in the left atrium (LA). However, in cases of PH caused by FM, it typically presents as precapillary PH due to PVS because this condition involves an obstruction between the occluded balloon in the distal pulmonary arterial branch and the left atrium. ⁴ This means a PAWP measured can be deceptively diminished or elevated.

In a previously studied rare case of PVS, the right lung’s PAWP mirrored the pressure on the left side of the heart, whereas PAWP in the left lung indicated elevated pulmonary venous pressure. This scenario is analogous to the situation observed in our case. ⁷

Pulmonary Vein Stenosis

Pulmonary vein stenosis is a rare condition in 2 distinct age groups. In children, it is most likely congenital, whereas in adults, causes like FM, sarcoidosis, iatrogenicity following atrial fibrillation ablation, and tumors are more prevalent. Other causes may include bronchogenic cysts, aneurysmal dilatation of the aorta and pulmonary artery, postsurgical compression from a left atrial appendage occlude, and pectus excavatum.^8-10 Although there is not a universally agreed-upon definition, a 2017 consensus statement on atrial fibrillation ablation characterizes PVS as a decrease in PV diameter, categorized as mild (<50%), moderate (50%-70%), or severe (>70%) based on the extent of luminal constriction. ⁹

The severity of symptoms related to PVS is influenced by the extent of constriction and the extent of affected PVs. Some studies indicated that stenoses exceeding 60% to 70% tended to cause symptoms, particularly when multiple PVs were involved, whereas milder stenoses were generally asymptomatic. Symptoms of PVS include dyspnea, hemoptysis, chest discomfort, and cough due to elevated PV pressure or infarction. These symptoms may overlap with other diseases such as pneumonia, malignancy, or PE and represent a diagnostic challenge that may lead to delayed diagnosis, improper treatment, and worsened outcomes.^8,9

Indirect signs of PVS include asymmetrical pulmonary edema. When pulmonary edema affects only the area drained by the blocked PV, it leads to progressive interstitial thickening and airspace disease. Computed tomography scans may display disrupted PV drainage, resulting in pulmonary venous congestion, and reduced pulmonary blood flow, mimicking PE, which can advance to pulmonary infarction. ¹⁰

Di Biase et al’s study involving 16 patients with complete PV occlusion revealed an association between CT lung findings and symptom severity. Patients with mild symptoms displayed mild CT findings such as subsegmental atelectasis or mild consolidation. Moderate symptoms revealed more pronounced CT abnormalities like pulmonary congestion and significant pleural effusion. Severe symptoms were associated with severe CT-detected lung conditions including pulmonary infarction, severe pneumonia, pleural effusion, pulmonary edema, and alveolar hemorrhage. Misdiagnoses occurred, mistaking pulmonary infarction for embolism and bronchospasm for asthma. Unnecessary interventions included filter placement for suspected embolism and lung resection for misdiagnosed cancer. ¹¹

Fibrosing Mediastinitis

Historically, adult PVS was linked to mediastinal conditions like FM, characterized by excessive fibrous tissue encasing mediastinal lymph nodes. In the United States, FM commonly stems from an immune reaction triggered by prior H capsulatum infection. Tuberculosis or immunoglobulin G4-related disease is other causes. This fibro-inflammatory mass can externally compress and narrow PVs, often leading to a grim prognosis.

The effectiveness of prolonged steroid or antifungal therapy for H capsulatum-related FM remains unclear, especially with calcified masses. Studies suggest limited benefit from itraconazole/prednisone, with interventions often necessary for significant vessel involvement. Rituximab shows promise in cases with active uptake, but its precise role and timing in FM treatment need further clarification. ⁹

The primary treatment for PVS, balloon angioplasty, yields favorable short-term outcomes, but nearly 50% of patients experience restenosis within a year. Stenting provides better medium-term results; however, regular imaging follow-ups are necessary to monitor intrastent restenosis, often requiring further interventions for sustained vessel openness. In a significant series involving 40 patients with 77 stents, 87% experienced primary success with symptomatic relief. Reintervention was required in 28% of cases, mainly in superior vena caval (SVC) stenting and sooner than in other sites. Major complications, affecting 7 patients, included vessel injury, pulmonary edema, thrombosis needing anticoagulation, and 1 fatal stroke. Another study on 8 patients treated with PV angioplasty reported immediate symptom relief but encountered 50% restenosis within 9 months. Notably, 3 patients experienced mortality, including 2 procedural deaths due to thrombotic ST-elevation myocardial infarction (STEMI), stroke, and severe intra-procedural hemoptysis.^4,7,11,12

Conclusions

Pulmonary vein stenosis secondary to FM is a progressive and fatal disease if not well managed. Combining the clinical scenario with the RHC results cannot be emphasized enough to reach the right conclusion, avoiding mismanagement of the patient. In our patient, the history of COPD, HFpEF, PE, and FM required a detailed and comprehensive evaluation with RHC and PAWP of both the right and left side plus a deep understanding of the pathophysiology and proper clinical judgment to reach the correct diagnosis.