Constrictive pericarditis

I. What every physician needs to know.

Constrictive pericarditis represents the end stage of an inflammatory process involving the pericardium, resulting in thickening, dense fibrosis, and adhesions of the pericardium. The scarring forms a non-compliant shell around the heart and prevents it from increasing output in response to peripheral demand. The scarring impairs diastolic filling of the heart, leading to systemic venous congestion, fluid overload, and low cardiac output. The overall clinical features mimic a restrictive cardiomyopathy, and establishing the diagnosis often is challenging and requires extensive testing. If the diagnosis is made early, treatment is effective and consists of surgical removal of the shell of constricting fibrous tissue (pericardiectomy).

II. Diagnostic Confirmation: Are you sure your patient has constrictive pericarditis?

The overall clinical features mimic a restrictive cardiomyopathy, and establishing the diagnosis often is challenging and requires extensive testing.

A. History Part I: Pattern Recognition:

B. History Part 2: Prevalence:

Constrictive pericarditis is a rare disease and accurate data regarding frequency and prevalence is lacking. The frequency of the disease depends on the incidence of the specific causes. A prior history of pericarditis may or may not be present. In the developing world, tuberculosis is an important cause of constrictive pericarditis. In developed countries, pericarditis, cardiac surgeries, and radiation therapy are the most common etiologies. Other causes include malignancy, chronic uremia, trauma, and inflammatory diseases such as systemic lupus erythematosus or sarcoidosis. The majority of cases, however, are idiopathic. Based on some case series, there is suggestion of a male predominance.

C. History Part 3: Competing diagnoses that can mimic constrictive pericarditis

Given the insidious onset and similar presentation, patients with constrictive pericarditis are often misdiagnosed with ascites due to liver cirrhosis. Similar symptoms and findings can also be found in patients with other cardiomyopathies, cardiac tamponade, right ventricular infarction, and pulmonary hypertension. Relatively normal brain natriuretic peptide (BNP) and clear lungs may cause physicians to prematurely exclude a cardiac etiology of volume overload. Echocardiography reliably distinguishes constrictive pericarditis from the above differential diagnoses, except for restrictive cardiomyopathy, which often requires more invasive testing.

D. Physical Examination Findings.

Patients present with findings of right-sided heart failure, including peripheral edema, jugular venous distension, hepatojugular reflux, hepatomegaly, and ascites. Accurate assessment of jugular venous pressure (JVP) is crucial as JVP is elevated in nearly all patients. The contour of the JVP often shows a rapid Y-descent due to rapid but brief early diastolic ventricular filling. Patients may also have Kussmaul’s sign (paradoxical rise in JVP with inspiration), pericardial knock (extra heart sound occurring slightly earlier than an S3), and pulsus paradoxus (exaggerated drop in systemic blood pressure during inspiration).

E. What diagnostic tests should be performed?

A mix of laboratory tests and imaging studies are required (as described in the sections below).

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There is no single diagnostic laboratory test. Passive congestion of the liver can cause abnormal liver function tests. Low cardiac output leading to cardiorenal syndrome can cause impaired renal function. Hyponatremia is seen with fluid overload. Hypoalbuminemia is seen with protein-losing enteropathy from chronic hepatic congestion. BNP is typically only slightly elevated because the constrictive pericardial sac prevents myocardial stretch. A normal BNP level may mislead the clinician early in the course of the disease. Antinuclear antibody, rheumatoid factor, or purified protein derivative (PPD) skin tests may be obtained depending on the level of suspicion for underlying disease.

Once the diagnosis is made, erythrocyte sedimentation rate (ESR) and C-reactive protein may be sent to help identify patients with ongoing pericardial inflammation. Nutritional status markers, such as albumin, prealbumin, and C-reactive protein should be obtained in anticipation of surgery.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Echocardiogram with simultaneous recording of respiration is the test of choice, though no single finding is pathognomonic for constrictive pericarditis. Typical echocardiographic findings include normal systolic function, pericardial thickening, abnormal ventricular septal motion (septal bounce), distended inferior vena cava, hepatic vein expiratory diastolic reversal, and exaggerated transvalvular flow with respiratory cycle. Any concern for constrictive pericarditis should be noted in the imaging requisition so that the cardiac sonographer may perform specific imaging sequences to help confirm or refute the diagnosis.

Other imaging modalities can offer important clues, however they can often be inconclusive. Chest X-ray may show calcification of the pericardium, but is neither sensitive nor specific in diagnosing constrictive pericarditis. Volumetric and high-resolution computed tomography (CT) scans are more sensitive at detecting small amounts of calcification and may detect pericardial thickening. Testing characteristic of cardiac magnetic resonance imaging (MRI) is similar to CT, and in addition MRI may demonstrate abnormal septal motion and ongoing pericardial inflammation. However, even CT and MRI miss pericardial thickening in up to 28% of patients with surgically proven constrictive pericarditis.

Unlike acute pericarditis, no specific electrocardiogram (ECG) pattern is associated with chronic constrictive pericarditis. Nonspecific T wave flattening and inversion as well as atrial arrhythmia may be seen. Low voltage is not commonly present.

Despite extensive noninvasive workup, right heart catheterization is still considered the “gold standard” to confirm the diagnosis and differentiate constrictive pericarditis from restrictive cardiomyopathy. Both constrictive and restrictive pericarditis cause elevated and equalized diastolic pressures on cardiac catheterization. Additionally in both conditions, early ventricular filling is rapid and blunted late by the pericardial sac, leading to the characteristic square root sign on ventricular pressure tracings. Features distinguishing constrictive pericarditis are ventricular interdependence and discordant changes in left ventricular (LV) and right ventricular (RV) pressure during respiration. This is caused by increased blood flow to the right ventricle during inspiration causing the interventricular septum to compress the left ventricle.

If the diagnosis is still unclear despite right heart catheterization, direct inspection and pericardial biopsy may be required, but this is a more invasive procedure. Pathologic findings of the pericardium include fibrosis, chronic inflammation, granulomas, and calcification.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Unfortunately, confirming a diagnosis of constrictive pericarditis is challenging and often requires extensive workup.

III. Default Management.

A. Immediate management.

Loop diuretics can be used for volume overload, however they must be used with caution as patients with constrictive pericarditis can be very dependent on preload, and dehydration can cause a marked reduction in cardiac output.

In patients with evidence of ongoing pericardial inflammation, a short course anti-inflammatory (nonsteroidal anti-inflammatory drugs, colchicine, or corticosteroids) may be considered.

B. Physical Examination Tips to Guide Management.

Weight, JVP, and degree of peripheral edema should be closely monitored. Note that early on the course, JVP may be so elevated that it can only be seen with the patient sitting at a 90° angle.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Renal function should be closely monitored for overdiuresis. Liver function test often improves significantly with resolution of hepatic congestion.

In patients receiving anti-inflammatory therapy, serial ESR and C-reactive protein may help monitor response to therapy.

D. Long-term management.

Constrictive pericarditis is a progressive disease with poor overall prognosis. Although a small number of cases may resolve with anti-inflammatory treatment (transient constrictive pericarditis), most patients will eventually require surgical pericardiectomy for definitive treatment. Removal of densely adherent pericardium is usually successful but can be extremely challenging and recovery can be prolonged. Operative mortality is as high as 20%, but if they survive patients can have dramatic relief of symptoms and good long-term prognosis. Given the limitation of medical management, early referral to cardiothoracic surgery is recommended.

E. Common Pitfalls and Side-Effects of Management

Though patients with constrictive pericarditis can be markedly volume overloaded on presentation, care must be taken to avoid overdiuresis as they are very dependent on preload. Additionally, afterload-reducing agents can result in precipitous and dangerous drops in blood pressure as patients cannot augment cardiac output. Finally, nodal-blocking agents should be avoided as these prevent the compensatory tachycardia required to maintain adequate cardiac output.

IV. Management with Co-Morbidities

Patients often present late in the course of disease. Chronic hepatic congestion can lead to cirrhosis. Chronic low-output state can lead to chronic kidney disease and anemia of chronic disease. Other sequelae include severe deconditioning and malnutrition (cardiac cachexia). The severity of these factors can make patients very high-risk operative candidates. Unfortunately, patients with advanced disease (abnormal ventricular function, severely reduced cardiac output, cachexia, or end-organ dysfunction) derive the least benefit from surgical pericardiectomy.

A. Renal Insufficiency.

Patients with underlying chronic kidney disease are even more prone to overdiuresis, and great care must be taken in titrating diuretic doses.