How to differentiate from restrictive cardiomyopathy Recognizing constrictive pericarditis as a cause of shortness of breath key words: Constrictive pericarditis, Pericardial calcification

Constrictive pericarditis (CP) is a rare condition characterized by nonspecificsymptoms, including dyspnea, abdominal distention, and generalized edema. It frequently is misdiagnosed as chronic liver or renal disease or is confused with restrictive cardiomyopathy.^1,2 Correct diagnosis is vital, since pericardiectomy can dramatically improve patients' symptoms. CP should be suspected in any patient who has signs and symptoms of right-sided heart failure that are disproportionate to pulmonary disease or right-sided heart disease.³

The underlying pathology of CP is chronic inflammation of the pericardial sac, leading to variable thickening, fibrosis, and pericardial calcification. This eventually leads to impaired filling of the cardiac chambers.⁴ Pericardium thickness exceeds normal in 80% of cases, and pericardial calcifications are observed in 25% of patients who have chronic CP. The symptoms of CP arise as the thickened and fibrotic pericardium interferes with normal diastolic cardiac filling.

Traditionally, increased pericardial thickness and calcification were considered important in the diagnosis of CP; many patients had significant calcifications of the entire pericardium, secondary to tuberculosis.⁵ Today, other causes of CP predominate and a calcified pericardium is uncommon. Recent reports have indicated that patients with calcifications have longer duration of symptoms, larger atria, and more atrial arrhythmias, suggesting calcification is a nonspecific response to inflammation. Calcifications are a marker of poor postoperative outcome in some studies.^6,7 Pericardial calcification can occur in the absence of CP, but it is usually patchy and less dense.

In this article, we discuss the pathophysiology, diagnosis, and treatment of CP.

Epidemiology

Today, CP is rare. It is seen in 25% to 44% of patients with a surgically resected pericardium in developed countries and in up to 79%of patients undergoing pericardiectomyin countries in which tuberculosis is prevalent.^8-12 It primarily affects adults and has a male preponderance of 2:1 to 3:1.

The rate of calcification among patients with CP has declined. In a 1959 study, calcification was present in 90% of patients with CP, usually after tuberculous pericarditis.¹³ A Mayo Clinic study of 231 patients followed for 40 years found only a 40% incidence of calcific disease.¹⁴ Because CP is now less likely to be caused by tuberculosis, the incidence of calcific disease in patients with CP in the United States has been less than 5% in one report¹⁵ and 25% to 28% in other reports.^16-19

Physiology

CP is secondary to chronic inflammation of the pericardial sac, which leads to scarring and inelasticity. The upper limits of cardiac vol- ume are constricted by the inelas- tic pericardium. As cardiac volume increases, compression occurs in mid-to-late diastole. Because the total cardiac volume does not change, ventricular interdependence is enhanced.

Venous return to the right side of the heart does not increase during inspiration. Pulmonary venous pressure decreases during inspiration, while left ventricular (LV) pressure does not. Decreased pressure gradient reduces LV volume and increases right ventricular (RV) volume by shifting the interventricu- lar septum. Equal elevation of central venous, pulmonary venous, and ventricular diastolic pressure is observed. Pulmonary hypertension in the range of 35 to 50 mm Hg may be seen.²⁰

Etiology

Historically, the most common cause of CP was tuberculosis. Today, 42% to 49% of CP cases are idiopathic.^21-23 Among cases with known causes, CP is often secondary to multiple chronic diseases. CP is frequently preceded by injury or trauma; infection; systemic diseases, such as systemic lupus erythematosus (SLE); uremia; or previous cardiac surgery. About 11% to 37% of patients with CP have a history of cardiac surgery,^24,25 and 9% to 13% had CP after undergoing mediastinal radiation therapy for Hodgkin disease or breast cancer.^13,16,18

Connective-tissue disorders, usually SLE, rheumatoid arthritis, or Dressler syndrome, are responsible for 3% to 7% of cases of CP.¹⁸ Another 3% to 6% of cases are postinfectious, usually viral. Other infectious causes include bacteria, fungi, and parasites.²²

About 6% to 20% of patients with CP have a history of pericarditis,²⁶ and 14% have pericardial effusions. Miscellaneous causes that account for fewer than 10% of cases include malignancy (0% to 3%), trauma, drugs, asbestosis, sarcoidosis, and uremia (0% to 3%).^13,16,18 CP is an uncommon and late consequence of dialysis and is seen in 5% of patients with chronic renal disease.⁴ CP is secondary to chronic disease in 96% of cases with known causes.¹⁹

Diagnosis

About 67% of patients with CP present with symptoms of heart failure, such as dyspnea, peripheral edema (52% to 63%), and abdominal fullness (46%). Others have chest pain (8% to 20%), palpitations (4% to 28%), signs of cardiac tamponade (5% to 8%), and frank liver disease (4%).^1,16,26 Some patients may also present with postoperative low cardiac output, recurrent pleural effusions, transient ischemic attack, and syncope.¹⁶

The median duration of symptoms before pericardiectomy was 11.7 months (range, 3 days to 29.1 years) in one study.²⁶ About 50% of patients with CP who have chest pain are New York Heart Association (NYHA) class I or II, and 46% to 69% are class III or IV at the time of diagnosis.¹

Physical examination typically reveals elevated jugular venous pressures. More than half of patients with severe CP demonstrate peripheral edema, ascites, pulsatile hepatomegaly, pleural effusion, and pericardial knock.⁵ Pulsus paradoxus occurs in 19% of patients¹⁶ and is uncommon in the absence of pericardial fluid or pulmonary disease.²⁷ Kussmaul sign is present in 13% to 21% of patients,^16,23 and 16% of patients have a pericardial friction rub.¹⁶ Profound cachexia occurs with late-stage CP.

The diagnostic evaluation of patients with suspected CP should include electrocardiography; chest radiography; echocardiography; and thoracic imaging, such as chest CT and MRI. In uncertain cases, pericardial biopsy may be necessary. Electrocardiography typically exhibits nonspecific ST-segment and T-wave changes and generalized T-wave inversion or flattening. It demonstrates low-voltage criteria in more than 25% of cases and atrial fibrillation in 12% to 28%.¹⁵ CP is more prevalent in patients who have atrial arrhythmias, and in one study, it occurred in 64% of such patients, compared with 17% of patients in sinus rhythm.¹⁶

Chest radiography shows pericardial calcification in 27% to 31% of patients with CP.^5,6 Echocardiography often shows increased pericardial thickness and calcification.^5,20,25,28 Thickness greater than 4 mm suggests pericardial constriction; thickness greater than 6 mm is highly specific.^29,30 Of interest, pericardial thickness on echocardiography was not increased in 18% of patients with surgically proven CP.^14-16 Pericardial thickness is not different in patients with and without pericardial calcification.²⁰

Echocardiography reveals diastolic "septal bounce" with inspiration and abrupt checking of LV posterior wall diastolic movement by rigid pericardium, coinciding with pericardial knock. Another suggestive sign is early opening of the pulmonary valve in late diastole because of elevated RV end-diastolic pressure (RVEDP).³¹

CT scans show increased pericardial thickness and calcification in 72% of patients; other findings may include dilatation of the inferior vena cava, deformed ventricular contours, and angulation of ventricular septum (Figure).³² MRI scans also show pericardial thickening and dilatation of the inferior vena cava.³³

Invasive hemodynamic evaluation shows increased right atrial pressures (mean right atrial pressure of 21 mm Hg), prominent x and y descents of venous and atrial pressure tracings, increased RVEDP, square root sign in the right ventricle and LV diastolic pressure tracings, inspiratory fall in the pulmonary capillary wedge pressure compared with LV diastolic pressure, equalization of LV and RV diastolic plateau pressure changes to within 5 mm Hg,⁵ and discordance between RV and peak LV systolic pressure during inspiration.³⁴

Pathologically, signs of chronic inflammation are seen in 80% of patients, granulomas in 3%, acute inflammation in 5%, fibrotic thickening in 90%, fibrin deposition in 37%, hemosiderin pigment in 34%, and granulation tissue in 14%; mesothelial hyperplasia is seen in 3% of tissue samples.^8,15,17

The main consideration in the differential diagnosis of CP is restrictive cardiomyopathy. Vaitkus and Kussmaul³⁵ have identified 3 hemodynamic criteria that have excellent positive predictive value in differentiating CP from restrictive cardiomyopathy: a difference between RVEDP and LV end-diastolic pressure of 5 mm Hg, an RV systolic pressure of 50 mm Hg, and a ratio of RVEDP to RV systolic pressure of 1:3. These hemodynamic criteria all favor constriction.³⁵ Interventricular interdependence on cardiac catheterization is generally more sensitive and specific and is demonstrated by the discordance of LV and RV systolic pressures during inspiration. Nuclear ventriculography and angiocardiography illustrate more rapid ventricular filling in CP than in restrictive cardiomyopathy.

Treatment and outcome

In about 20% of patients, CP resolves at intervals ranging from 2 months to 2 years.²⁶ The 5-year survival rate among patients with transient CP was 100% in one study.²⁶ Therefore, patients with newly diagnosed CP who are hemodynamically stable and have no evidence of chronic disease may be given a trial of conservative management for up to 3 months. Treatment includes NSAIDs, corticosteroids, antibiotics, angiotensin-converting enzyme inhibitors, and diuretics.

For chronic CP, surgery is the accepted standard of treatment.^5,18 There are no definite guidelines for selecting patients for surgery. Patients with long-standing CP, extensive pericardial calcifications, atrial fibrillation, liver failure, cachexia, severe renal insufficiency, myocardial dysfunction, and CP caused by radiation have greater risk of operative mortality and poor outcomes, so surgery should be considered carefully in these patients. However, most authors agree that once the diagnosis of CP has been made, pericardiectomy should be considered because without surgery, the disease progresses relentlessly.^4,16,18,36

Short-term mortality was 6% in patients who underwent pericardiectomy between 1977 and 2001.^1,4,18 The 7-year survival rates after surgery were 88% for patients with idiopathic CP, 66% for postsurgical CP, and 27% for radiation-induced CP.¹⁸ Overall survival at 5 and 10 years was 78% and 57%, respectively.⁴ On follow-up in all studies, mortality among patients who did not undergo pericardiectomy was significantly higher than mortality among patients who underwent pericardiectomy.^14,18,19

NYHA functional class improves markedly after pericardiectomy. In a Mayo Clinic study of 135 patients, functional class could be determined in 90 late survivors; 83% of them were free of symptoms.¹⁶ Functional status usually improved by 1 class. In a study evaluating 58 patients with CP who underwent pericardiectomy, 41% had normal diastolic function at 3 months postprocedure. At 4 years, 76% of patients were asymptomatic.³⁶

The poorest outcomes were observed in patients with radiation- induced CP and patients with previous complicated cardiac surgery. Late deaths were attributed to cardiac causes, including progressive congestive heart failure and sudden cardiac death. The cumulative incidence of cardiovascular deaths was 14 ± 4% and 35 ± 9% at 5 and 10 years, respectively. Independent predictors of adverse long-term outcome include advanced age, higher NYHA class, renal dysfunction, pulmonary hypertension, LV dysfunction, and hyponatremia.^{4,9-12,18,19,37}

In conclusion, CP is a rare, curable cardiac disease. Pericardiectomy gives excellent results, including long-term survival. Therefore, early diagnosis and differentiation from other conditions that mimic CP is vital. In the presence of other cardiac comorbidities, the loss in function resulting from CP should be estimated to determine the need for pericardiectomy.

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PRACTICE GUIDELINES

•Maisch B, Seferovic PM, Ristic AD, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary: the task force on the diagnosis and management of pericardial diseases of the European society of cardiology.

Eur Heart J

. 2004;25:587-610.