Central airway compression by massively dilated pulmonary artery in a patient with pulmonary arterial hypertension: a rare entity

Abstract

Patients with pulmonary arterial hypertension (PAH) usually die from progressive right ventricular failure. Mechanical complications due to pulmonary artery (PA) enlargement are rare and include tracheobronchial and left main coronary artery compression, and PA dissection. A 62-year-old female with PAH was seen in our office for follow-up. During the evaluation, spirometry was performed, which revealed a severe obstructive ventilatory limitation. Subsequent workup identified compression of bilateral mainstem bronchi from the dilated PA as the aetiology for the abnormal spirometry. Very few cases of this rare complication have been reported in the literature. A significant dilation of the PA is necessary (>4 cm) for the occurrence of these complications. Dilation of PA is an independent risk factor for sudden unexpected death in patients with PAH.

Background

Group 1 pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) causes significant morbidity and mortality. The recent WHO classification has subdivided PAH into multiple subtypes; idiopathic pulmonary hypertension (IPAH) and hereditary PH, among others. Although previously thought to be a disease of the young females, recent data show that IPAH predominantly affects middle-aged women with a female to male ratio of 3.6:1.¹ In comparison to a dismal median survival of 2.4 years following a diagnosis of PAH in the past, the current survival has improved significantly in the era of effective pulmonary vasodilator therapy.^{2 3} Progressive worsening of PH with subsequent right ventricular failure and circulatory collapse is the primary cause of mortality. Mechanical complications of PH are rare, less rigorously studied and are often underappreciated by the clinicians. These are the complications that arise due to the enlargement of the pulmonary artery (PA) and include airway compression, impingement of the left main coronary artery (LMCA) resulting in angina or life-threatening ventricular arrhythmia, and PA dissection. Since overall survival has increased in patients with PAH, physicians are more likely to encounter these entities, and unless awareness is raised, patients might be subjected to unnecessary diagnostic testing or potentially harmful interventions. We present a rare case of severe airway obstruction in a patient with IPAH due to airway compression from massively dilated PA.

Case presentation

A 62-year-old female with a history of severe IPAH was seen in our office for follow-up in August 2018. She was diagnosed with PH in 2007, with a mean pulmonary arterial pressure of 51 mm Hg on right heart catheterisation. Over the past 11 years, her disease had progressed from NYHA class II to IV, and she was receiving triple therapy with intravenous epoprostenol (133.7 ng/kg/min), sildenafil and bosentan since 2012. Other medications were furosemide, digoxin and warfarin. The patient was a never smoker and had no reported family history of PH. Her vital signs were as follows: blood pressure, 133/60 mm Hg; pulse, 92 beats per min; temperature, 98⁰F; respiratory rate, 18 breaths per min; and oxygen saturation of 91% on 6 L pulsed oxygen via nasal cannula. Physical exam revealed minimal lower extremity oedema, left parasternal heave and a pansystolic murmur at the left sternal border.

Investigations

Routine blood work was unremarkable. A 6 min walking distance (6MWD) and spirometry were performed. The results of the spirometry, including the flow–volume loop, are shown in figures 1 and 2. The pulmonary function test (PFT) revealed severe airway obstruction and scooping of the expiratory limb on the flow–volume loop. The 6MWD was reduced to 1040 feet (lower limit of normal 1643 feet) and was associated with severe oxygen desaturation on exertion, and a reduction in blood pressure in response to exercise. An echocardiogram revealed a severely dilated right ventricle with reduced right ventricular fractional shortening. The left ventricular ejection fraction was normal, and there was no wall motion abnormality. The aetiology of this severe obstructive ventilatory limitation was unclear, and a comparison of the previous PFTs is shown in table 1.

Figure 1.

Spirometry showing severe airway obstruction characterised by profoundly reduced FEV₁, and a reduced ratio of FEV₁ to FVC below the lower limit of the normal. DLCO, diffusion capacity for carbon monoxide; FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity.

Figure 2.

Flow–volume loop showing scooping of the expiratory limb consistent with airway obstruction.

Table 1.

Comparison of pulmonary function tests from 2013 to 2018 and echocardiographic measurement of the pulmonary artery

Date	8/2018	3/2017	12/2015	08/2013
FEV1 (Litre) (% predicted)	0.99 (38%)	1.15 (44%)	1.34 (50%)	1.79 (65%)
FVC (Litre) (% predicted)	1.88 (55%)	2.17 (64%)	2.52 (73%)	2.87 (81%)
FEV1/FVC	52%	53%	53%	63%
DLCO	48%	55%	67%	68%
MPA diameter on echocardiography (normal 1.6–2 cm)	8.91	6.39	4.7	3.36
BMI	19.74	18.96	20.45	20.49

BMI, body mass index; DLCO, diffusion capacity for carbon monoxide; FEV₁, forced expiratory volume in the first second; FEV₁/FVC, the ratio of FEV₁; FVC, forced vital capacity; MPA, main pulmonary artery.

Differential diagnosis

The patient had no exposure to risk factors associated with chronic obstructive pulmonary disease (COPD). There were no previous symptoms suggestive of asthma, chronic bronchitis, bronchiectasis or a destructive lung infection. Obliterative bronchiolitis secondary to an infection or inflammation and tracheobronchomalacia were also considered in the differential diagnosis. A CT scan of the chest was obtained, and representative slides are shown in figures 3 and 4. The CT scan showed massive enlargement of the main PA (MPA) as well as the right and left branches with compression of bilateral main stem bronchi. There was no evidence of emphysema, centrilobular nodule (seen with obliterative bronchiolitis) or bronchiectasis. The profound airway obstruction was determined to be secondary to compression of the large airways by the PA.

Figure 3.

CT chest axial view showing compression of the bilateral mainstem bronchi by the pulmonary artery causing significant narrowing (red arrows). Both the MPA and the RPA are severely dilated. AO, ascending aorta; MPA, main pulmonary artery; RPA, right pulmonary artery.

Figure 4.

Representative coronal sections of the chest CT showing the absence of structural lung disease (lung window, left) and severely dilated pulmonary vasculature (mediastinal window, right).

Treatment

The patient was prescribed an inhaled short-acting beta-agonist as the initial bronchodilator therapy; however, there was no significant benefit. No other inhaled medication was attempted due to a lack of response.

Outcome and follow-up

In January 2019, the patient was admitted to ICU with worsening shortness of breath, hypoxic respiratory failure. The patient was on high flow nasal cannula with a FiO₂ of 100% and a flow of 40 litres to achieve an oxygen saturation of 88% and above. She also required pressor medications to achieve acceptable haemodynamic parameters, including a mean arterial pressure between 60 and 65 mm Hg. New pleural and pericardial effusions were identified. There was no improvement in her condition with antibiotics, diuresis and increased dose of epoprostenol. The patient was deemed to be at extremely high risk of early mortality if an atrial septostomy were to be attempted, given the profound hypoxemia and haemodynamic instability. Given her worsening condition, the patient was eventually made comfortable according to the family’s wishes.

Discussion

We have presented a case of severe obstructive ventilatory limitation in a long-surviving patient with IPAH. The obstructive pattern on the PFTs is due to compression of large central airways by the dilated pulmonary arteries. Our conclusion is based on the following reasoning. First, this patient had never been exposed to any known risk factors for COPD and had no symptoms suggestive of asthma, chronic bronchitis or bronchiectasis, which can result in irreversible airway obstruction. Second, scrutiny of the PFTs presented in table 1 reveals that the obstructive physiology had progressively gotten worse since 2013 and correlated inversely with the progressive enlargement of the PA diameter on serial echocardiograms. Third, the CT chest ruled out any structural lung disease or bronchiolitis as the aetiology and revealed significant compression and narrowing of the bilateral main stem bronchi even without any forced expiratory manoeuvre. And lastly, the absence of any substantial difference between forced (1.88 L) and slow (1.90 L) vital capacity in this patient is inconsistent with severe obstruction of the smaller airways, as the forced manoeuvre accentuates the limitation in case of small airways disease and the slow vital capacity is usually larger in such conditions. Some degree of obstructive physiology on spirometry is seen in 20%–40% of patients with IPAH.⁴ Many of these patients typically have normal lung volumes. The obstruction is due to the enlargement of the PA branches with compression of small airways.

PA dilation is a common finding in PH; in fact, many cases of PH are suspected from the discovery of dilated PA on transverse imaging of the chest, performed for a different reason. However, profound PA dilation resulting in compression and obstruction of central airways is exceedingly rare.^5–7 Most reported cases were seen in patients with a severely dilated PA from PH in the setting of uncorrected congenital heart diseases. To our knowledge, only two cases have been reported in patients with IPAH.^{6 7} These patients had relatively prolonged survival (>6 years) and severely dilated MPA (>9 cm). The airway compression can contribute to worsening of dyspnoea and possibly ventilatory limitation if severe. Massive PA dilation has also been identified as an independent risk factor for sudden death in this patient population (discussed below).

Respiratory limitation on spirometry is divided into two categories: obstructive and restrictive. An obstructive defect is characterised by a reduced ratio of FEV₁ to FVC below the lower limit of normal for the individual and a low FEV₁. The FVC is usually normal, at least with mild-to-moderate obstruction. However, with severe obstruction, the FVC might be reduced due to air trapping. The flow–volume loop demonstrates characteristic scooping of the expiratory limb. The restrictive defect is shown by a low FEV₁ and FVC with a preserved ratio of FEV₁ to FVC. Sometimes, patients show evidence of a mixed obstructive and restrictive physiology on spirometry, and assessment of lung volumes provides more insight into these situations. An increased total lung capacity (TLC) and residual volume (RV) are consistent with obstructive lung disease, whereas reduced TLC and RV are the norms for restrictive limitation. Patients with PH usually have normal or restrictive physiology on PFT, which includes both spirometry and measurement of lung volumes.^{8 9} The restriction is thought to be secondary to the enlargement of pulmonary blood vessels and the heart.¹⁰ Since the lung volumes were not measured in our patient, a component of restriction, in addition to the significant airway obstruction can not be completely ruled out.

The role of a dilated PA in the diagnosis and prognosis of PH is of recent interest. Studies have shown that the ratio of PA over ascending aortic diameter is significantly higher in patients with PH.¹¹ Our patient suffered from gradual and massive dilatation of her pulmonary arteries over the years (figure 3). Her PA diameter was reported to be 9.1 cm on the CT scan. Based on the Framingham study, the mean PA diameter has been proposed to be 2.9 cm in men and 2.7 cm in women.¹² Research has shown that a PA diameter greater than 4.5 cm is associated with mechanical complications.¹³ A PA diameter greater than 4.8 cm has been identified as an independent risk factor for right ventricular failure and sudden death.¹⁴ More pronounced dilation was noted in patients with unrepaired cardiac defects in comparison to IPAH, and chronic thromboembolic PH.¹⁴ The sudden death appears to be secondary to LMCA compression leading to cardiac arrhythmia and rupture of the PA with cardiac tamponade.

The incidence of coronary artery compression is more common than tracheobronchial compression from PA dilation.¹³ Due to its close proximity to LMCA, progressive enlargement of the pulmonary trunk is associated with downward displacement and extrinsic compression of the coronary artery. This can lead to episodes of angina, and in unfortunate patients, the sudden onset of arrhythmia and death—the risk increases in a linear fashion with the increasing diameter of the MPA. A diameter of less than 4 cm does not increase the incidence significantly.¹⁵ Chest pain is a common symptom in patients with PH, and a potential diagnosis of angina might be missed if such events are mistakenly attributed to non-angina etiologies. The duration of PH concordantly correlates with the size of the MPA.¹⁴ Our patient did not clinically suffer from angina, and multiple EKGs obtained during the course of her illness did not reveal any changes suggestive of coronary ischaemia.

PA dissection and cardiac tamponade is a relatively less known mechanical complication of PH. Due to rapid fatality, most patients remain undiagnosed unless they undergo an autopsy. The risk factors include severe dilation of the MPA, higher than 7 cm and mean pulmonary arterial pressure greater than 50 mm Hg.¹⁶ Other factors associated with a higher risk of dissection are a rapid evolution of the aneurysm (>2 mm/year) and weakness of the arterial wall due to an infection or pregnancy.¹⁶ Our patient showed rapid enlargement of the PA diameter (table 1). We believe that our patient died from progressive right ventricular failure, and the severe airway obstruction possibly also played a role in her worsening symptomatology.

With a better understanding of underlying pathophysiology and the invention of effective treatment, the prognosis has gotten significantly better for patients with IPAH. As these patients continue to survive longer, mechanical complications due to pulmonary arterial enlargement are more likely to be identified in the future. Since the significant PA dilation is independently associated with an increased risk of an unexpected death from ventricular arrhythmia due to coronary ischemia from LMCA compression and worsening dyspnoea from airway compression, physicians should be aware of these entities. More research is necessary for early recognition of risk factors to devise intervention in this patient population.

Learning points.

• Tracheobronchial compression causing severe obstructive ventilatory limitation is a rare mechanical complication of pulmonary hypertension (PH). The extrinsic compression is caused by the massive enlargement of the pulmonary artery (PA).

• Other mechanical complications include left main coronary artery impingement by the pulmonary trunk with resultant angina, cardiac arrhythmia and even sudden death. A PA diameter greater than 4.8 cm is independently associated with an unexpected death.

• A PA size less than 4 cm is unlikely to be associated with any mechanical complication.

• PH associated with uncorrected congenital heart disease is more likely to be associated with a mechanical complication than idiopathic pulmonary hypertension.