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 immunosuppression 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 patients with clinically apparent cardiac sarcoidosis, the conducting system and/or myocardium are typically involved, 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) (1). Systemic sarcoidosis shows marked regional variation in incidence, being higher in patients of Northern European or African descent, particularly African American females. Nevertheless, in patients with systemic sarcoidosis men are more likely to manifest cardiac sarcoidosis and no racial difference in cardiac sarcoidosis is apparent in North American studies (2).
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 node 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.
General references
1. Birnie D, Ha AC, Gula LJ, et al: Cardiac Sarcoidosis. Clin Chest Med 2015;36(4):657-668. doi:10.1016/j.ccm.2015.08.008
2. Duvall C, Pavlovic N, Rosen NS, et al: Sex and Race Differences in Cardiac Sarcoidosis Presentation, Treatment and Outcomes. J Card Fail 29(8):1135–1145, 2023. doi:10.1016/j.cardfail.2023.03.022
Symptoms and Signs of Cardiac Sarcoidosis
Most patients with cardiac sarcoidosis are asymptomatic, but the associated bradyarrhythmias and tachyarrhythmias may cause palpitations, syncope, and sometimes cardiac arrest or sudden death.
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.
In most patients, disease manifests between the ages of 25 to 60 years.
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 35% of the patients with cardiac sarcoidosis are already known to have systemic sarcoidosis or have clinical evidence of extracardiac sarcoidosis at presentation (1). 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. Ambulatory ECG monitoring should be done 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 systemic sarcoidosis, diagnosis of isolated 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 ECG and echocardiography. Patients with an unexplained cardiomyopathy should also have 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 scanning) and testing for extracardiac sarcoidosis, (chest x-ray, chest CT, whole body FDG-PET scan) is needed. With extensive investigation, > 80% of patients with apparent isolated cardiac sarcoidosis are found to also have extracardiac sarcoidosis.
An international consensus document (2) 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 ≥ 1 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.
Similar, but not identical, criteria for the diagnosis of cardiac sarcoidosis have been published by the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) (3) and the Japanese Circulation Society (JCS) (4).
Diagnosis references
1. Kandolin R, Lehtonen J, Airaksinen J, et al: Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study. Circulation 131(7):624–632, 2015. doi: 10.1161/CIRCULATIONAHA.114.011522
2. 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
3. Judson MA, Costabel U, Drent M, et al: The WASOG sarcoidosis organ assessment instrument: An update of a previous clinical tool. Sarcoidosis Vasc Diffuse Lung Dis 31:19‒27, 2014.
4. Terasaki F, Azuma A, Anzai T, et al: JCS 2016 guideline on diagnosis and treatment of cardiac sarcoidosis‒digest version. Circ J 83:2329‒2388, 2019. doi 10.1253/circj.CJ-19-0508
Treatment of Cardiac Sarcoidosis
Corticosteroids
Sometimes other immunosuppressive medications
Sometimes permanent pacemaker and/or implantable cardioverter-defibrillator (ICD)
Sometimes antiarrhythmic medications (avoiding class I medications)
Sometimes transcatheter ablation
Heart failure therapy (including transplantation) as required
Standard treatments for sarcoidosis1).
Cardiac treatment is focused on treatment and prevention of arrhythmias. Recommendations for treatment of bradyarrhythmias or tachyarrhythmias follow those for other arrhythmogenic cardiomyopathies. In cardiac sarcoidosis specifically, a pacemaker is recommended (class of recommendation IIa) for qualifying AV block even if the AV block reverses spontaneously (2).
When a permanent pacemaker is indicated (see table Indications for Permanent Pacemakers), an ICD is preferred (class IIa recommendation). The Heart Rhythm Society cardiac sarcoid consensus document recommends an ICD for patients with prior sustained VT, resuscitated cardiac arrest, or left ventricular ejection fraction of ≤ 35% despite optimal medical therapy (including a period of immunosuppression in patients with active inflammation) (each a class I recommendation)(2) (see table Indications for an ICD). The Heart Rhythm Society cardiac sarcoid consensus document also suggests an ICD can be useful (class IIa recommendation) for patients with cardiac sarcoidosis with unexplained syncope or near-syncope thought to be arrhythmic in etiology and for those with inducible sustained VT/VF at a programmed stimulation electrophysiologic study (each a class IIa recommendation) (2). The document further suggests that an ICD may 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 (2). Similar, but not identical, recommendations for ICD therapy have been proposed by the Japanese Circulation Society (3), the American Heart Association/American College of Cardiology/Heart Rhythm Society (4), and the European Society of Cardiology (5). Because ventricular late gadolinium enhancement (LGE) on cardiac MRI (a marker of ventricular scarring) predicts life-threatening ventricular arrhythmias, ICD placement is recommended (class IIa recommendations) for patients with significant LGE despite an LVEF > 35% (4, 5).
Heart failure therapy typically includes a beta-blocker (watching for the possibility of worsening AV conduction), an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, and a mineralocorticoid receptor antagonist. Pharmacological treatments for dilated cardiomyopathy, including angiotensin receptor/neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors, have been less well studied in patients with cardiac sarcoidosis. The frequent coexistence of left bundle branch block in patients with sarcoidosis-related dilated cardiomyopathy makes cardiac resynchronization therapy attractive. Heart transplantation may be considered.
Treatment references
1. Ribeiro Neto ML, Jellis CL, Cremer PC, et al: Cardiac Sarcoidosis. Clin Chest Med 45(1):105–118, 2024. doi: 10.1016/j.ccm.2023.08.006.
2. 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
3. Terasaki F, Azuma A, Anzai T, et al: JCS 2016 guideline on diagnosis and treatment of cardiac sarcoidosis‒digest version. Circ J 83:2329‒2388, 2019. doi 10.1253/circj.CJ-19-0508
4. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al: 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 138(13):e272–e391, 2018. doi: 10.1161/CIR.0000000000000549
5. Zeppenfeld K, Tfelt-Hansen J, De Riva M, et al: 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J 43(40):3997–4126, 2022. doi.org/10.1093/eurheartj/ehac262
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 medications.
Sarcoidosis itself is treated with corticosteroids and sometimes other immunosuppressants.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Malhi JK, Ibecheozor C, Chrispin J, et al: Diagnostic and management strategies in cardiac sarcoidosis. Int J Cardiol 403:131853, 2024. doi: 10.1016/j.ijcard.2024.131853
Ribeiro Neto ML, Jellis CL, Cremer PC, et al: Cardiac Sarcoidosis. Clin Chest Med 45(1):105–118, 2024. doi: 10.1016/j.ccm.2023.08.006.
