Introduction

Because the initial presentation of cardiac sarcoidosis can range from asymptomatic electrocardiographic abnormalities to sudden death, the cardiac electrophysiologist is an integral part of the multidisciplinary team taking care of sarcoidosis patients. Electrophysiologic findings, which often are under-recognized, are more common manifestations of cardiac sarcoidosis than congestive heart failure. However, given the very rare nature of cardiac sarcoidosis, electrophysiologists must rely on small observational studies and correlates with other diseases to guide therapy. It is because of this, that a group of physicians experienced in the management of cardiac sarcoidosis convened to create an expert consensus document for recommendations (based on 75% agreement among the expert writing group) for the management of cardiac sarcoidosis.¹ The purpose and goals of the expert consensus document were as follows: 1) establish working diagnostic criteria for the diagnosis of cardiac sarcoidosis based upon expert opinion and the limited data available; 2) provide guidance and recommendations to physicians treating extra-cardiac sarcoidosis on the appropriate screening to assess for possible cardiac involvement; 3) provide guidance and recommendations to cardiologists and cardiac electrophysiologists on management of specific arrhythmias associated with cardiac sarcoidosis; 4) provide guidance and recommendations to cardiac electrophysiologists on appropriate indications for implantable cardioverter defibrillator (ICD) implantation; 5) identify key areas in which data are lacking to help guide future collaborative research efforts.

Diagnosis of Cardiac Sarcoidosis

The writing group felt that existing guidelines for the clinical diagnosis of cardiac sarcoidosis published by the Japanese Ministry of Health underutilized advanced imaging. In addition, working with the World Association for Sarcoidosis and other Granulomatous Diseases (WASOG), the writing group developed a simplified diagnostic scheme for the clinical diagnosis of cardiac sarcoidosis. If extra cardiac sarcoidosis is histologically proven, cardiac involvement is considered probable if one or more of the following are observed and are not due to a different cause:

1. Steroid/immunosuppressant-responsive cardiomyopathy or heart block
2. Unexplained reduction in left ventricular ejection fraction (LVEF) <40%
3. Unexplained sustained ventricular tachycardia (spontaneous or induced)
4. Second-degree, Mobitz type II heart block
5. Third-degree heart block
6. Patchy uptake on cardiac positron emission tomography (PET) scan
7. Late gadolinium enhancement on cardiac magnetic resonance (CMR)
8. Positive gallium uptake

Screening Asymptomatic Patients

As mentioned above, because the initial presentation of cardiac sarcoidosis can be sudden death, the writing group considered recommendations for screening patients with known extra-cardiac sarcoidosis for cardiac involvement. Several noninvasive studies were considered, and the following achieved consensus recommendation: cardiac focused history and exam, electrocardiogram (ECG), and an echocardiogram. Abnormalities identified with these screening tests would prompt further advanced imaging.

Management of Heart Block

The writing group recommended that all patients under the age of 60 years with newly recognized heart block should be screened for cardiac sarcoidosis as this condition is potentially reversible. Figure 1 shows the algorithmic approach for assessing unexplained heart block (2nd degree Mobitz II or 3rd degree atrioventricular nodal block) that may culminate with voltage guided biopsy to diagnose isolated cardiac sarcoidosis.

Figure 1 AV = atrioventricular; CMR = cardiac magnetic resonance; CT = computed tomography; CS = cardiac sarcoidosis; EMB = endomyocardial biopsy; FDG-PET = fluorodeoxyglucose positron emission tomography

Management of Atrial Arrhythmias

The writing group acknowledged a paucity of clinical studies examining the incidence and response to treatment for atrial arrhythmias related to cardiac sarcoidosis. Based upon this very scarce literature and consensus of the writing group members, the following recommendations can be given for patients with cardiac sarcoidosis: anticoagulation should be initiated if there is sufficiently high risk as determined by CHA₂DS₂-VASc score in patients with AF (Class I); 2. an invasive electrophysiological study may be considered in patients with supraventricular tachycardia other than AF to direct therapy. (Class IIb); Antiarrhythmic drug therapy with class I agents is not recommended for treatment of arrhythmias associated with cardiac sarcoidosis (Class III).

Management of Ventricular Arrhythmias

In the expert consensus statement, the writing group discussed how ventricular arrhythmias related to cardiac sarcoidosis can often be a challenging clinical dilemma. Based on limited evidence in small observational studies, the writing group achieved consensus for the following recommendations regarding treatment of ventricular arrhythmias: immunosuppression can be useful (Class IIa) in all CS patients presenting with any ventricular arrhythmia (premature ventricular contractions [PVCs], nonsustained ventricular tachycardia [NSVT], and ventricular tachycardia/ventricular fibrillation [VT/VF]) and evidence of myocardial inflammation. Antiarrhythmic drug therapy and/or catheter ablation also received a class IIa recommendation for treatment of ventricular arrhythmias refractory to immunosuppression.

Figure 2 CMR = cardiac magnetic resonance; ICD = impantable cardioverter-defibrillator; LVEF = left ventricular ejection fraction; RV = right ventricular; VT = ventricular tachycardia

Management of Sudden Death Risk

Patients with cardiac sarcoidosis are at risk for sudden death because of VT that arises from an arrhythmogenic granulomatous scar. However, there are many patients with evidence of cardiac involvement who have such a small amount of scar, that VT is not possible. In addition, given the expanded diagnostic criteria for "probable" cardiac sarcoidosis, there is a concern for a high number of patients with false positive imaging studies who would then receive an unnecessary ICD. For these reasons, the writing group did not agree to a single recommendation for all patients with evidence of cardiac sarcoidosis. Instead the writing group considered several clinical scenarios using cardiac magnetic resonance imaging (MRI) and electrophysiologic testing results for sudden death risk stratification, based on small observational studies (Figure 2). Importantly, the writing group was able to identify a subgroup of patients who may meet clinical diagnostic criteria who would not meet an indication for ICD implantation. This group may represent false positive imaging results and are felt to be at very low risk of sudden death.

Summary and Future Directions

The opinions described in the Heart Rhythm Society (HRS) expert consensus statement represent an international effort to address the challenges faced by clinicians caring for patients with cardiac sarcoidosis. While the writing group believes that this document will help those with varying levels of experience, it represents only a starting point for understanding this complex disease. The document introduces several unknown questions that should be answered with future research, including the role of immunosuppression regimens and screening techniques.

References

1. Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014;11:1305-23.

Keywords: Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Biopsy, Cardiomyopathies, Catheter Ablation, Cicatrix, Consensus, Death, Sudden, Defibrillators, Implantable, Electrocardiography, Expert Testimony, Gadolinium, Gallium, Goals, Heart Block, Heart Conduction System, Heart Failure, Humans, Immunosuppressive Agents, Incidence, Inflammation, Magnetic Resonance Imaging, Positron-Emission Tomography, Sarcoidosis, Stroke Volume, Tachycardia, Supraventricular, Tachycardia, Ventricular, Ventricular Fibrillation, Ventricular Premature Complexes, Writing, Magnetic Resonance Spectroscopy

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