Sarcoidosis is a multisystem, chronic granulomatous inflammatory disorder that often affects the heart, causing conduction disturbances, bradyarrhythmias, tachyarrhythmias, and sometimes cardiomyopathy. Diagnosis is suspected in patients with known sarcoidosis or young (< 60 years) patients who have otherwise unexplained heart block, arrhythmias, or cardiomyopathy. Treatment is immunosuppression and sometimes an implantable cardioverter-defibrillator (ICD).
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. Clinically apparent cardiac sarcoidosis typically involves the conducting system and/or myocardium, 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. Approximately 20 to 30% of patients with systemic sarcoidosis have cardiac involvement identifiable using imaging techniques or on autopsy, but cardiac involvement is symptomatic in only approximately 5% of all patients with sarcoidosis (1). In a United States-based study, patients with cardiac sarcoidosis, females patients, and Black patients are more likely than male patients and White patients to have heart failure at presentation, while male patients are more likely to have ventricular arrhythmias. (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, or left or right bundle branch block. In patients with cardiac sarcoidosis, AV blocks occur in approximately 35 to 50% (3). 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. (See also Overview of Arrhythmogenic Cardiomyopathies and Overview of Arrhythmias.)
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 (4).
General references
1. Lehtonen J, Uusitalo V, Pöyhönen P, Mäyränpää MI, Kupari M. Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis. Eur Heart J. 2023;44(17):1495-1510. doi:10.1093/eurheartj/ehad067
2. Duvall C, Pavlovic N, Rosen NS, et al. Sex and Race Differences in Cardiac Sarcoidosis Presentation, Treatment and Outcomes. J Card Fail. 2023;29(8):1135-1145. doi:10.1016/j.cardfail.2023.03.022
3. Arunachalam Karikalan S, Yusuf A, El Masry H. Arrhythmias in Cardiac Sarcoidosis: Management and Prognostic Implications. J Clin Med. 2024;13(11):3165. doi:10.3390/jcm13113165
4. Huitema MP, Mathijssen H, Mager JJ, Snijder RJ, Grutters JC, Post MC. Sarcoidosis-Associated Pulmonary Hypertension. Semin Respir Crit Care Med. 2020;41(5):659-672. doi:10.1055/s-0040-1713615
Symptoms and Signs of Cardiac Sarcoidosis
Many, if not most, patients with cardiac sarcoidosis are asymptomatic, but the associated bradyarrhythmias and tachyarrhythmias may cause palpitations, syncope, and sometimes cardiac arrest or sudden death (1).
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 (2).
Cardiomyopathy may cause any heart failure symptom, including exertional dyspnea, fatigue, and peripheral edema (1).
In most patients, disease manifests between the ages of 25 to 60 years (3).
Symptoms and signs references
1. Lehtonen J, Uusitalo V, Pöyhönen P, Mäyränpää MI, Kupari M. Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis. Eur Heart J. 2023;44(17):1495-1510. doi:10.1093/eurheartj/ehad067
2. Ekström K, Lehtonen J, Nordenswan HK, et al. Sudden death in cardiac sarcoidosis: an analysis of nationwide clinical and cause-of-death registries. Eur Heart J. 2019;40(37):3121-3128. doi:10.1093/eurheartj/ehz428
3. Weber BN, Paik JJ, Aghayev A, et al. Novel Imaging Approaches to Cardiac Manifestations of Systemic Inflammatory Diseases: JACC Scientific Statement. J Am Coll Cardiol. 2023;82(22):2128-2151. doi:10.1016/j.jacc.2023.09.819
Diagnosis of Cardiac Sarcoidosis
Clinical suspicion
ECG, echocardiography, cardiac MRI with late gadolinium enhancement, and fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan
Biopsy of noncardiac tissue that appears affected by systemic sarcoidosis
Rarely cardiac biopsy
Patients with known sarcoidosis and no cardiac symptoms may undergo periodic ECGs to screen for cardiac involvement; some clinicians suggest a baseline echocardiogram but recommendations are inconsistent (1, 2). If cardiac symptoms, signs, or test abnormalities are present, cardiac MRI with gadolinium should also be performed (2). Ambulatory ECG monitoring should be performed if symptoms suggest a rhythm or conduction disturbance. An FDG-PET scan provides additional information regarding active inflammation and is often also performed.
In patients not yet diagnosed with systemic sarcoidosis, diagnosis of isolated cardiac sarcoidosis is frequently difficult. Cardiac sarcoidosis should be suspected in young (< 60 years) 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.
This MRI shows granulomas in the right ventricular free wall and ventricular septum.
JAMES CAVALLINI / SCIENCE PHOTO LIBRARY
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 radiograph, chest CT, whole body FDG-PET scan) is needed. With extensive investigation, the majority of patients with apparent isolated cardiac sarcoidosis are found to also have extracardiac sarcoidosis (1).
This histologic image of cardiac sarcoidosis shows non-necrotizing epithelioid granulomas with multinucleated giant cells and areas of interstitial fibrosis.
WEBPATHOLOGY / SCIENCE PHOTO LIBRARY
An international consensus document (3) 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:
Glucocorticoid-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 (4). However, sensitivity of cardiac biopsy is improved if it is guided by advanced cardiac imaging techniques or by targeting areas of low voltage (5).
Similar, but not identical, criteria for the diagnosis of cardiac sarcoidosis have been published by other organizations (6, 7).
Diagnosis references
1. Cheng RK, Kittleson MM, Beavers CJ, et al. Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association. Circulation. 2024;149(21):e1197-e1216. doi:10.1161/CIR.0000000000001240
2. Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;201(8):e26-e51. doi:10.1164/rccm.202002-0251ST
3. 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. 2014;11(7):1304-1323. doi: 10.1016/j.hrthm.2014.03.043
4. Kandolin R, Lehtonen J, Graner M, et al. Diagnosing isolated cardiac sarcoidosis. J Intern Med. 2011;270(5):461-468. doi:10.1111/j.1365-2796.2011.02396.x
5. Liang JJ, Hebl VB, DeSimone CV, et al. Electrogram guidance: a method to increase the precision and diagnostic yield of endomyocardial biopsy for suspected cardiac sarcoidosis and myocarditis. JACC Heart Fail. 2014;2(5):466-473. doi:10.1016/j.jchf.2014.03.015
6. 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. 2014;31(1):19-27.
7. Terasaki F, Azuma A, Anzai T, et al. JCS 2016 guideline on diagnosis and treatment of cardiac sarcoidosis‒digest version. Circ J. 2019;83(11):2329-2388. doi 10.1253/circj.CJ-19-0508
Treatment of Cardiac Sarcoidosis
Glucocorticoids
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
Treatment for cardiac sarcoidosis, similar to treatment for extracardiac sarcoidosis, includes glucocorticoids and sometimes other immunosuppressants (eg, methotrexate, mycophenolate, azathioprine, leflunomide). Biologic agents including tumor necrosis factor alpha inhibitors (eg, infliximab, adalimumab) or others (eg, rituximab) may be used for refractory cases (1, 2).
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 reasonable for qualifying AV block even if the AV block reverses spontaneously (1, 3). When a permanent pacemaker is indicated (see table ), an ICD is preferred.
ICD placement is recommended for patients with cardiac sarcoidosis and any of the following (see table ):
Prior sustained ventricular tachycardia
Resuscitated cardiac arrest
Left ventricular ejection fraction of ≤ 35% despite optimal medical therapy, including a period of immunosuppression in patients with active inflammation
ICD placement is also reasonable for patients with cardiac sarcoidosis and any of the following:
Unexplained syncope or near-syncope thought to be arrhythmic in etiology
Inducible sustained VT/VF during a programmed stimulation electrophysiologic study
ICD placement may be considered for patients with cardiac sarcoidosis and any of the following:
Left ventricular ejection fraction in the 35% to 49% range
Right ventricular ejection fraction < 40% despite optimal medical therapy for heart failure, including immunosuppressants in patients with active inflammation
Similar, but not identical, recommendations for ICD therapy have also been proposed (4, 5, 6). Because ventricular late gadolinium enhancement (LGE) on cardiac MRI (a marker of ventricular scarring) predicts life-threatening ventricular arrhythmias, ICD placement is considered reasonable by some (5, 6) for patients with:
Significant LGE despite an left ventricular ejection fraction > 35%
Antiarrhythmic medications such as amiodarone and sotalol may be given as necessary to control frequently recurrent ventricular tachycardias and/or other tachyarrhythmias. If medications (and adequate anti-inflammatory therapy) do not control VT, electrophysiologic studies may be performed to identify the origin of the arrhythmia (often a reentrant site) that can then be treated using transcatheter ablation.
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. Pharmacologic 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 (7). The frequent coexistence of left bundle branch block in patients with sarcoidosis-related dilated cardiomyopathy makes cardiac resynchronization therapy attractive although results are mixed (8). Heart transplantation may be considered.
Treatment references
1. Cheng RK, Kittleson MM, Beavers CJ, et al. Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association. Circulation. 2024;149(21):e1197-e1216. doi:10.1161/CIR.0000000000001240
2. Ribeiro Neto ML, Jellis CL, Cremer PC, et al. Cardiac Sarcoidosis. Clin Chest Med. 2024;45(1):105-118. doi: 10.1016/j.ccm.2023.08.006.
3. 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. 2014;11(7):1304-1323. doi: 10.1016/j.hrthm.2014.03.043
4. Terasaki F, Azuma A, Anzai T, et al. JCS 2016 guideline on diagnosis and treatment of cardiac sarcoidosis‒digest version. Circ J. 2019;83(11):2329-2388. doi 10.1253/circj.CJ-19-0508
5. 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. 2018;138(13):e272-e391. doi: 10.1161/CIR.0000000000000549
6. 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. 2022;43(40):3997-4126. doi.org/10.1093/eurheartj/ehac262
7. Nagai T, Tamura T, Anzai T. The Diagnosis and Management of Cardiac Sarcoidosis. Intern Med. Published online March 24, 2026. doi:10.2169/internalmedicine.7161-26
8. Lehtonen J, Uusitalo V, Pöyhönen P, Mäyränpää MI, Kupari M. Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis. Eur Heart J. 2023;44(17):1495-1510. doi:10.1093/eurheartj/ehad067
Prognosis
Prognosis is quite good for cardiac sarcoidosis, with 5-year survival of 90 to 96% and 10-year survival from 80 to 90% (1).
Prognosis reference
1. Lehtonen J, Uusitalo V, Pöyhönen P, Mäyränpää MI, Kupari M. Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis. Eur Heart J. 2023;44(17):1495-1510. doi:10.1093/eurheartj/ehad067
Key Points
Of patients with systemic sarcoidosis, 20 to 35% have cardiac involvement, but only approximately 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 performed.
Cardiac manifestations often require a pacemaker/implantable cardioverter-defibrillator (ICD) and sometimes antiarrhythmic medications or medications for heart failure.
Sarcoidosis itself is treated with glucocorticoids and sometimes other immunosuppressants.
Drug Information for the Topic
