Sarcoidosis is a multisystem, chronic inflammatory/granulomatous disorder that often affects the heart, causing conduction disturbances, bradyarrhythmias, tachyarrhythmias, and sometimes cardiomyopathy. Diagnosis is suspected in patients with known sarcoidosis or young patients who have otherwise unexplained heart block, arrhythmias, or cardiomyopathy. Treatment is corticosteroids and sometimes an implantable cardioverter-defibrillator (ICD).
(See also Overview of Arrhythmogenic Cardiomyopathies and Overview of Arrhythmias.)
Systemic sarcoidosis is reviewed elsewhere in THE MANUAL. This topic focuses on the cardiac effects of sarcoidosis.
The inflammatory process in sarcoidosis leads to formation of noncaseating granulomas and fibrosis in any tissue. In cardiac sarcoidosis, the conducting system and/or myocardium are typically involved in patients with clinically apparent cardiac sarcoidosis, but valvular, papillary muscle, and pericardial involvement may also occur. Nearly all patients with cardiac sarcoidosis have involvement of other organs (typically the lungs), but cardiac sarcoidosis may rarely occur in isolation. About 25% of patients with systemic sarcoidosis have cardiac involvement identifiable using imaging techniques, but cardiac involvement is symptomatic in only about 20% of these (5% of all patients with sarcoidosis). The disorder shows marked regional variation in incidence being particularly high in people of Northern European and African descent, being particularly high in African-American women.
The predilection of cardiac sarcoid involvement of the interventricular septum causes atrioventricular (AV) conduction system blocks in many patients with cardiac sarcoidosis. Involvement of the conducting system may cause first-, second-, or third-degree AV block, left anterior or left posterior hemiblock, and left or right bundle branch block. Involvement of the sinus node artery may produce the bradyarrhythmias of sinus nodal dysfunction.
Myocardial involvement may produce tachyarrhythmias, predominantly ventricular tachycardia (VT), but atrial tachycardias, atrial flutter, and atrial fibrillation may also occur.
Infiltration of the myocardium may cause an isolated left ventricular, an isolated right ventricular, a biventricular, dilated or restrictive cardiomyopathy. Pericardial involvement may cause pericardial effusion or contribute to restrictive physiology. Multifactorial pulmonary hypertension is also common.
Most patients with cardiac sarcoidosis are asymptomatic, but the associated bradyarrhythmias and tachyarrhythmias may cause palpitations, syncope, and sometimes cardiac arrest or sudden death. In most patients, disease manifests between the ages of 25 to 60 years. A significant number of deaths resulting from systemic sarcoidosis are due to sudden cardiac death, including in many patients who have had no previous indication of cardiac involvement. Cardiomyopathy may cause any heart failure symptom, including exertional dyspnea, fatigue, and peripheral edema.
Diagnosis of Cardiac Sarcoidosis
Clinical suspicion
ECG, echocardiography, and sometimes cardiac MRI with late gadolinium enhancement and/or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan
Biopsy of noncardiac tissue that appears affected by systemic sarcoidosis
Rarely cardiac biopsy
About half of the patients with clinical manifestations suggestive of cardiac sarcoidosis are already known to have systemic sarcoidosis. Patients with known sarcoidosis and no cardiac symptoms should typically have periodic ECGs and echocardiography to screen for cardiac involvement. If cardiac symptoms, signs, or test abnormalities are present, cardiac MRI with gadolinium should also be done, and also ambulatory ECG monitoring if symptoms suggest a rhythm or conduction disturbance. An FDG-PET scan provides additional information regarding active inflammation and is usually also done.
In patients not yet diagnosed with sarcoidosis, diagnosis of cardiac sarcoidosis is frequently difficult. Cardiac sarcoidosis should be suspected in young patients with heart block, ventricular tachyarrhythmias, and/or heart failure who have no obvious cause. All such patients should have an ECG and an echocardiogram. Patients with an unexplained cardiomyopathy should also have a cardiac MRI.
When findings from these examinations suggest cardiac sarcoidosis or when there is a high suspicion thereof (eg, in young patients with unexplained AV block), further testing for cardiac sarcoidosis (ambulatory ECG monitoring, FDG-PET scan) and further testing for extracardiac sarcoidosis, (chest x-ray, chest CT, whole body FDG-PET scan) is needed. With extensive investigation, most patients with cardiac sarcoidosis will be found to also have extracardiac sarcoidosis.
An international consensus document (1) indicated that the diagnosis of cardiac sarcoidosis requires a cardiac biopsy showing non-caseating granuloma without alternative explanation or an extracardiac tissue biopsy showing non-caseating granuloma without alternative explanation plus one or more of the following without alternative explanation:
Corticosteroid-responsive cardiomyopathy or heart block
Unexplained reduced left ventricular ejection fraction < 40%
Unexplained spontaneous or induced ventricular tachycardia
Mobitz type II second-degree AV block or third-degree AV block
Cardiac PET scan showing patchy uptake
Cardiac MRI showing late gadolinium enhancement
Positive gallium uptake on a nuclear scan
Most commonly, the diagnosis is established by extracardiac biopsy in conjunction with suggestive cardiac abnormalities on noninvasive testing. Cardiac biopsy has low sensitivity because the disease process is patchy and pathological tissue may not be sampled. However, sensitivity of cardiac biopsy is improved if it is guided by advanced cardiac imaging techniques or by targeting areas of low voltage.
Diagnosis reference
1. Birnie DH, Sauer WH, Gogun F, et al: HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated with Cardiac Sarcoidosis. Heart Rhythm 11:1304–1323, 2014. doi: 10.1016/j.hrthm.2014.03.043
Treatment of Cardiac Sarcoidosis
Corticosteroids
Sometimes other immunosuppressive drugs
Permanent pacemaker and/or implantable cardioverter-defibrillator (ICD)
Sometimes antiarrhythmic drugs (avoiding class I drugs)
Sometimes transcatheter ablation
Heart failure therapy (including transplantation) as required
Standard treatments for sarcoidosis
Cardiac treatment is focused on treatment and prevention of arrhythmias. Recommendations for treatment of bradyarrhythmias or tachyarrhythmias follow that for other arrhythmogenic cardiomyopathies including an ICD for prevention of sudden death (see also table Indications for an ICD). An ICD is recommended for patients with prior sustained VT or resuscitated cardiac arrest or severe right or left ventricular systolic dysfunction. An ICD also may be useful (class IIa indication) for patients with any major risk factor for sudden death, including prior syncope, non-sustained ventricular tachycardia, or moderate right or left ventricular systolic dysfunction.
Specific to cardiac sarcoidosis, a pacemaker is recommended for qualifying AV block even if the AV block reverses spontaneously and, when a permanent pacemaker is indicated (see also table Indications for Permanent Pacemakers), an ICD platform is preferred (each a class IIa recommendation). The Heart Rhythm Society cardiac sarcoid consensus document also suggested an ICD should be considered (class IIb recommendation) in patients with cardiac sarcoidosis with a left ventricular ejection fraction in the 35% to 49% range and/or a right ventricular ejection fraction < 40% despite optimal medical therapy for heart failure and use of immunosuppressants in patients with active inflammation (1).
Heart failure therapy typically includes a beta-blocker (watching for the possibility of worsening AV conduction), an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, and a mineralocorticoid receptor antagonist. Newer pharmacological treatments for dilated cardiomyopathy, including angiotensin receptor neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors have been less well studied in patients with sarcoidosis. The frequent coexistence of left bundle branch block in patients with sarcoidosis dilated cardiomyopathy makes cardiac resynchronization therapy attractive. Heart transplantation may be considered.
Treatment reference
1. Birnie DH, Sauer WH, Gogun F, et al: HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated with Cardiac Sarcoidosis. Heart Rhythm 11:1304–1323, 2014. doi: 10.1016/j.hrthm.2014.03.043
Key Points
About 25% of patients with systemic sarcoidosis have cardiac involvement, but only about 5% have cardiac symptoms.
Cardiac involvement causes a disproportionate percentage of deaths in patients with sarcoidosis.
Diagnosis requires a combination of clinical, electrocardiographic, and imaging findings; cardiac biopsy can be diagnostic but is not usually done.
Cardiac manifestations often require a pacemaker/implantable cardioverter-defibrillator (ICD) and sometimes antiarrhythmic drugs.
Sarcoidosis itself is treated with corticosteroids and sometimes immunosuppressants.
