A middle-aged man with progressive fatigue

CARDIAC SARCOIDOSIS

2. What percentage of patients with sarcoidosis have cardiac involvement?

• 10%–20%
• 20%–30%
• 50%
• 80%

Cardiac involvement is seen in 20% to 30% of patients with sarcoidosis.^5–7 However, most cases are subclinical, and symptomatic cardiac involvement is present in only about 5% of patients with systemic sarcoidosis.⁸ Isolated cardiac sarcoidosis has been described in case reports but is rare.⁹

The clinical manifestations of cardiac sarcoidosis depend on the location and extent of granulomatous inflammation. In a necropsy study of 113 patients with cardiac sarcoidosis, the left ventricular free wall was the most common location, followed by the interventricular septum.¹⁰

3. How does cardiac sarcoidosis most commonly present?

• Conduction abnormalities
• Ventricular tachycardia
• Cardiomyopathy
• Sudden death
• None of the above

Common presentations of cardiac sarcoidosis include conduction system disease and arrhythmias (which can sometimes result in sudden death), and heart failure.

Conduction abnormalities due to granulomas (in the active phase of sarcoidosis) and fibrosis (in the fibrotic phase) in the atrioventricular node or bundle of His are the most common presentation of cardiac sarcoidosis.⁹ These lesions may result in relatively benign first-degree heart block or may be as potentially devastating as complete heart block.

In almost all patients with conduction abnormalities, the basal interventricular septum is involved.¹¹ Patients who develop complete heart block from sarcoidosis tend to be younger than those with idiopathic heart block. Therefore, complete heart block in a young patient should raise the possibility of this diagnosis. ¹²

Ventricular tachycardia (sustained or nonsustained) and ventricular premature beats are the second most common presentation. Up to 22% of patients with sarcoidosis have electrocardiographic evidence of ventricular arrythmias. ¹³ The cause is believed to be myocardial scar tissue resulting from the sarcoid granulomas, leading to electrical reentry.¹⁴ Sudden death due to ventricular tachyarrhythmias or conduction blocks accounts for 25% to 65% of deaths from cardiac sarcoidosis.^9,15,16

Heart failure may result from sarcoidosis when there is extensive granulomatous disease in the myocardium. Depending on the location of the granulomas, both systolic and diastolic dysfunction can occur. In severe cases, extensive granulomas can cause left ventricular aneurysms.

The diagnosis of cardiac sarcoidosis as the cause of heart failure can be difficult to establish, especially in patients without evidence of sarcoidosis elsewhere. Such patients are often given a diagnosis of idiopathic dilated cardiomyopathy. However, compared with patients with idiopathic dilated cardiomyopathy, those with cardiac sarcoidosis have a greater incidence of advanced atrioventricular block, abnormal wall thickness, focal wall motion abnormalities, and perfusion defects of the anteroseptal and apical regions.¹⁷

Progressive heart failure is the second most frequent cause of death (after sudden death) and accounts for 25% to 75% of sarcoid-related cardiac deaths.^9,18,19

DIAGNOSING CARDIAC SARCOIDOSIS

4. How is cardiac sarcoidosis diagnosed?

• Electrocardiography
• Echocardiography
• Computed tomography
• Endomyocardial biopsy
• There are no guidelines for diagnosis

Given the variable extent and location of granulomas in sarcoidosis, the diagnosis of cardiac sarcoidosis is often challenging.

To make the diagnosis of sarcoidosis in general, the American Thoracic Society² says that the clinical picture should be compatible with this diagnosis, noncaseating granulomas should be histologically confirmed, and other diseases capable of producing a similar clinical or histologic picture should be excluded.

A newer diagnostic tool, the Sarcoidosis Three-Dimensional Assessment Instrument,²⁰ incorporates two earlier tools.^20,21 It assesses three axes: organ involvement, sarcoidosis severity, and sarcoidosis activity and categorizes the diagnosis of sarcoidosis as “definite,” “probable,” or “possible.”²⁰

In Japan, where sarcoidosis is more common, the Ministry of Health and Welfare²² says that cardiac sarcoidosis can be diagnosed histologically if operative or endomyocardial biopsy specimens contain noncaseating granuloma. In addition, the diagnosis can be suspected in patients who have a histologic diagnosis of extracardiac sarcoidosis if the first item in the list below and one or more of the rest are present:

• Complete right bundle branch block, left axis deviation, atrioventricular block, ventricular tachycardia, premature ventricular contractions (> grade 2 of the Lown classification), or Q or ST-T wave abnormalities
• Abnormal wall motion, regional wall thinning, or dilation of the left ventricle on echocardiography
• Perfusion defects on thallium 201 myocardial scintigraphy or abnormal accumulation of gallium citrate Ga 67 or technetium 99m on myocardial scintigraphy
• Abnormal intracardiac pressure, low cardiac output, or abnormal wall motion or depressed left ventricular ejection fraction on cardiac catheterization
• Nonspecific interstitial fibrosis or cellular infiltration on myocardial biopsy.

The current diagnostic guidelines from the American Thoracic Society² and the Japanese Ministry of Health and Welfare²² and the Sarcoidosis Three-Dimensional Assessment Instrument,²⁰ however, do not incorporate newer imaging studies as part of their criteria.