A 70-year-old woman with a history of alcoholic liver disease, peptic ulcer disease, chronic obstructive pulmonary disease (COPD) and hypothyroidism was referred for progressive dyspnea and evaluation of enlarged pulmonary arteries on chest radiograph.  She had smoked approximately one pack of cigarettes daily for 40 years and developed exertional dyspnea 2-3 years earlier.  At that time, she was diagnosed with COPD and inhaled bronchodilators were prescribed.  She continued to smoke and her dyspnea worsened.  Inhaled bronchodilators had little effect. Six months earlier she had been admitted to the hospital with Clostridium difficile colitis, gastrointestinal bleeding and COPD exacerbation. During that admission, she quit smoking and was started on supplemental oxygen therapy. A chest radiograph during the hospital stay showed cardiomegaly and large bilateral pulmonary arteries (Figure 1).  Upon discharge she was referred to a pulmonologist for further evaluation. A computed tomographic pulmonary angiogram (CTPA) confirmed the presence of enlarged pulmonary arteries, but no proximal filling defects were identified (Figure 2).  The lung parenchyma showed mild emphysematous changes, but no large bulla.  Abdominal images revealed hepatomegaly with portal and esophageal varices (Figure 3).  A transthoracic echocardiogram (TTE) found normal cardiac chamber sizes with no evidence of valvular heart disease and normal pulmonary artery pressure.

At the time of presentation to our institution, she was comfortable at rest but reported difficulty walking more than 50 feet.  She was able to ambulate in the house and perform basic housework but avoided stairs. She denied cough, sputum, wheezing, chest pain or exertional lightheadedness, but did notice some lower extremity edema.

Past Medical/Surgical History

The patient had a history of alcoholic cirrhosis but had been sober for many years.  Other medical problems included hypothyroidism and peptic ulcer disease that had been treated with partial gastrectomy. She denied HIV infection, congenital heart disease, thromboembolic disease, connective tissue disease or use of anorexigens.

Medications

Synthroid, Spironolactone, Furosemide, Omeprazole, Zolpidem, Ipatroprium/Albuterol, Fluticasone

PA and lateral chest radiograph: Large dilated pulmonary arteries bilaterally, cardiomegaly, no active pulmonary disease. (Figure 1)

Laboratory tests:

INR 1.1

T. Bili 2.5

Albumin 2.6

HIV negative

ANA 1:40

Childs-Pugh Score8

Pulmonary Function Tests: FEV₁ 1.27 L (64% predicted), FVC 2.12 L (84% predicted), FEV₁/FVC 0.60,  TLC 3.87 L (90% predicted), RV 1.72 L (97% predicted), DL_CO 8.24 (42% predicted) (All values slightly improved from May, 2008).

Ventilation/Perfusion Lung Scan:Heterogeneous perfusion, low probability for pulmonary embolism.

CT chest with contrast:Enlargement of the right and left main pulmonary arteries;  no proximal-filling defects.  No active lung disease, mild emphysematous changes without bullous emphysema.  The liver is cirrhotic with evidence of esophageal and periportal varices (Figure 2).

Transthoracic echocardiogram (TTE):Normal left-ventricular size and systolic function, left-ventricular ejection fraction 60-65% with impaired diastolic relaxation. Normal right-ventricular and right-atrial size.  Normal right-ventricular function.  Minimal tricuspid regurgitation.  Right-ventricular systolic pressure 26 mm Hg assuming a right atrial pressure of 5 mm Hg.  The left atrium was normal in size, normal mitral valve with physiologic mitral regurgitation, normal aortic valve with minimal calcification and trace aortic regurgitation.

Pulmonary hypertension (PH) is not uncommon in patients with portal hypertension or in patients with COPD.  Although dilated pulmonary arteries are an unusual finding in the absence of PH and in this elderly patient with risk factors for pulmonary vascular disease, it is likely that significant PH is present despite the inability to detect it by echocardiography.  The TTE is a useful screening tool for pulmonary vascular disease.  Sensitivity for diagnosing PH in patients with systolic pulmonary arterial pressure above 50 mm Hg is greater than 85% (1).  However, its sensitivity and specificity for diagnosing PH in COPD is more limited (2).  Pulmonary hypertension causes extensive remodeling of the pulmonary vascular bed resulting in increased pulmonary vascular resistance, decreased recruitment of pulmonary vessels and impairment of flow-mediated pulmonary vasodilation. 

COPD is a common cause of dyspnea in adult patients with a history of chronic tobacco use.  This patient’s symptoms, however, appear to be out of proportion to the severity of her lung disease.  The progression of her symptoms despite stable pulmonary function tests (PFTs), tobacco cessation and initiation of bronchodilator therapy argue against COPD as the sole cause of her progressive dyspnea.

Congenital atrial and ventricular septal defects shunt mostly left to right due to lower right-sided filling pressures.  The increase in pulmonary blood flow can lead to pulmonary hypertension in early childhood or adult life depending on the size of the defect and the amount of blood shunted.  Systemic oxygen saturation is not affected because blood from the left atrium or ventricle is fully oxygenated.  As pulmonary hypertension develops, right-sided filling pressures rise, resulting in decreased shunt fraction, bi-directional flow across the defect or reversal of flow to a right-to-left shunt.  The marked enlargement of the main pulmonary arteries in this patient without evidence of PH on TEE makes this diagnosis attractive.  However, the patient’s advanced age and normal cardiac chamber sizes argue against significant intracardiac shunting. Some intracardiac shunts, especially high-atrial septal defects, can be difficult to see on conventional TTE and require further diagnostic testing with TEE or cardiac MRI.

Chronic thromboembolic pulmonary hypertension can cause progressive dyspnea and enlargement of one or both pulmonary arteries.  The low probability V/Q scan and lack of any filling defects in the proximal arteries on CTPA make this diagnosis unlikely.