A 47-Year-Old Man With Recurrent Unilateral Pleural Effusion

      Case Presentation

      A 47-year-old man with a medical history of hypertension, diabetes, hyperlipidemia, and OSA presented with a 7- to 10-day history of progressively worsening dyspnea on exertion, with a walking distance of 60 feet. He had bilateral lower-extremity swelling and was prescribed furosemide without clinical improvement. At baseline, he used three pillows for sleeping. The patient was noncompliant with his CPAP treatment. He had no smoking history and was retired from working in technology sales. On review of systems, he denied cough, chest pain, hemoptysis, fevers, chills, or weight loss.

      Physical Examination Findings

      Examination revealed an obese man in no acute distress. Vital signs included a heart rate of 104 beats/min, BP of 128/92, temperature of 97.4°F, and oxygen saturation of 96% on room air. The chest physical examination was notable for decreased breath sounds over the lower three-quarters of the left lung, with associated tactile fremitus. The cardiac examination showed regular rhythm with no murmurs, rubs, or gallops on auscultation, and no jugular venous distention was appreciated, but the patient’s large neck precluded proper assessment of jugular venous distension. Examination of the extremities revealed 2+ pitting edema of the lower extremities bilaterally. The rest of the physical examination was unremarkable.

      Diagnostic Studies

      A suboptimal (due to an obese habitus) echocardiogram was performed and revealed an enlarged right ventricle with right ventricular hypertrophy, concentric left ventricular hypertrophy with a normal ejection fraction, a large left pleural effusion, and no evidence of pericardial disease. Due to an absence of tricuspid regurgitation, an estimate of pulmonary artery systolic pressure was incalculable. A chest radiograph confirmed a large left pleural effusion, and thoracentesis revealed an exudative effusion with negative cytologic features (Fig 1). Furthermore, a CT scan of the thorax demonstrated a small pericardial effusion in addition to the left-sided pleural effusion.
      Figure thumbnail gr1
      Figure 1Chest radiograph showing large left-sided pleural effusion.
      Due to rapid reaccumulation of pleural effusion, the patient underwent two additional thoracenteses, and a chest tube was placed. A video-assisted thoracoscopic pleural biopsy procedure demonstrated chronic pleuritis with fibrosis and calcification. Given that there was evidence of an enlarged right ventricle and left ventricular hypertrophy in combination with peripheral edema, cardiac catheterization was performed to further assess his hemodynamic status (Fig 2). This revealed a dip and plateau of right ventricular pressures, equalization of ventricular diastolic pressures, and ventricular discordance. Cardiac MRI showed impaired diastolic filling, an enlarged thickened pericardium, and marked smooth delayed pericardial enhancement.
      Figure thumbnail gr2
      Figure 2Heart catheterization pressure tracings. Left and right ventricular pressure tracings demonstrating discordance as indicated by the diverging long arrows. The short arrows indicate the classic dip and plateau or “square root” sign in constrictive pericarditis. The figure also shows equalization of the left and right ventricular diastolic pressures, where the two pressure tracings align near the bottom of the graph.
      What is the likely diagnosis?
      Diagnosis: Constrictive pericarditis

      Discussion

      Pleural effusions have a wide array of causes and may pose a diagnostic challenge. Thoracentesis is a common initial investigation but establishes a definitive diagnosis only 25% of the time. Hence, combining clinical acumen and a broad differential diagnosis is key in determining the underlying cause. Pleural effusions occur in 44% to 50% of patients with constrictive pericarditis. However, constrictive pericarditis is not commonly in the differential diagnosis for an initial presentation of a pleural effusion. There are a multitude of causes for constrictive pericarditis, including infections (the most common worldwide is tuberculosis), surgery (34% of cases), medications, malignancy, chest trauma, radiation, connective tissue disease, autoimmune disease, and idiopathic causes (18% of cases).
      The pathophysiology of constrictive pericarditis stems from loss of pericardial compliance. This results in dissociation of intrathoracic and intracardiac pressures with respirations. Normally, the change in intrathoracic pressure is transmitted to the pulmonary veins as well as the cardiac chambers, leading to a constant pressure gradient between the two. However, the noncompliant pericardium in constrictive pericarditis isolates the cardiac chambers, nullifying pressure changes. Hence, the pressure gradient decreases between the pulmonary veins and the left ventricle with inspiration, leading to a decrease in left-sided filling. A rigid pericardium also causes left and right ventricular interdependence seen during the respiratory cycle. During inspiration, there is decreased left ventricular filling and associated increased right ventricular filling, shifting the septum leftward. The opposite physiological effect occurs in expiration. This translates to left and right ventricular discordance that could be demonstrated on heart catheterization pressure tracings. Furthermore, a stiff pericardium limits the expansion of the cardiac chambers and, as a result, elevates and equalizes the end-diastolic pressures in all cardiac chambers.
      Constrictive pericarditis impairs diastolic filling of the ventricles, leading to venous congestion and congestive heart failure. Transudative effusions could occur from left ventricular diastolic dysfunction, leading to elevated intravascular hydrostatic pressure and subsequent pleural effusion. One study of 135 patients showed that 67% of patients with constrictive pericarditis present with congestive heart failure, 8% present with chest pain, 6% present with abdominal symptoms, and 5% present with cardiac tamponade, whereas < 5% present with recurrent pleural effusions. A retrospective case series of 30 patients with constrictive pericarditis who reported persistent pleural fluid of unknown origin prompted further investigation with cardiac catheterization. Of these cases, six of 30 patients had unilateral pleural effusion, and analysis in three of four patients with pleural fluid found exudative fluid.
      Despite the expectation that pleural effusions from constrictive pericarditis should be a transudate based on pathophysiological mechanisms and a clinical presentation similar to that of congestive heart failure, the study discussed and other case reports have demonstrated that most cases reveal exudative effusions. This may be because constrictive pericarditis is caused by an underlying inflammatory process. Damage to pericardial mesothelial cells leads to fibrinous inflammation and adhesion formation, which is the proposed mechanism for pericardial fibrosis in constrictive pericarditis.
      Echocardiography is the initial diagnostic imaging method of choice. Findings of pericardial thickening and calcification, indirect signs of constriction, and restrictive filling of both ventricles with respiratory variation suggest constrictive pericarditis. Cardiac MRI is useful for detecting increased pericardial thickness and dilatation of the inferior vena cava. However, up to 20% of patients with constrictive pericarditis may not have pericardial thickening. Although the accuracy of echocardiography has increased with technological advancement, cardiac catheterization remains the gold standard diagnostic tool. Increased atrial pressures, equalization of end-diastolic pressure, and square-root or a dip-and-plateau sign of ventricular diastolic pressure are associated with constrictive pericarditis but may also be present in restrictive cardiomyopathy. Respiratory variation in ventricular filling and ventricular interdependence or discordance are more specific for a diagnosis of constriction.
      Management of well-established constrictive pericarditis, marked by the presence of calcification, is pericardiectomy. Anterior or partial pericardiectomy is often preferred over radical pericardiectomy because it is technically easier. However, incomplete pericardiectomy has been associated with increased mortality compared with complete pericardiectomy, with a survival rate of 74% vs 84%, respectively. Surgical treatment was shown to relieve symptoms in up to 85% of patients in a long-term follow-up study lasting 3.9 ± 3.0 years, with approximately one-third of the patients experiencing recurrent symptoms due to underlying cardiac disease.

      Clinical Course

      The patient in our study had an exudative pleural effusion and evidence of pleuritis with fibrosis and calcification seen on biopsy samples. Pathologic examination of samples from a pericardiectomy revealed chronic fibrosing pericarditis as well. These findings, in addition to the cardiac catheterization findings consistent with constrictive pericarditis, raised suspicion that the patient’s underlying process may have been part of an inflammatory pleuropericarditis that was likely viral in nature. The patient underwent pericardiectomy with resolution of his symptoms.

      Clinical Pearls

      • 1.
        Constrictive pericarditis is an uncommon cause of recurrent unilateral pleural effusions.
      • 2.
        Constrictive pericarditis should be kept in the differential diagnosis despite presentations with exudative pleural effusions, particularly when patients have risk factors for pericarditis. These risk factors include signs and symptoms of congestive heart failure, history of cardiac surgery, or recent infectious symptoms in combination with imaging studies showing pericardial thickening and calcification.
      • 3.
        The diagnosis of constrictive pericarditis remains difficult because patients present with symptoms of congestive heart failure or common symptoms such as chest pain, shortness of breath, and abdominal pain. As such, a high clinical suspicion for constrictive pericarditis is required, particularly when patients are persistently symptomatic and pericardiectomy affords a definitive treatment.

      Acknowledgments

      Financial/nonfinancial disclosures: None declared.
      Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

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