HRS Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated With Cardiac Sarcoidosis
Introduction
This international expert consensus statement was written by experts in the field who were chosen by the Heart Rhythm Society in collaboration with representatives from the American College of Cardiology, American College of Chest Physicians, American Heart Association, Asia Pacific Heart Rhythm Society, European Heart Rhythm Association, and World Association for Sarcoidosis and Other Granulomatous Disorders (WASOG).
The goals of this document are as follows:
- 1.
Establish working criteria for the diagnosis of cardiac sarcoidosis (CS) on the basis of expert opinion and the limited available data.
- 2.
Provide guidance and recommendations to physicians treating extracardiac sarcoidosis on appropriate screening for possible cardiac involvement.
- 3.
Provide guidance and recommendations to cardiologists and cardiac electrophysiologists on the management of specific arrhythmias associated with CS.
- 4.
Provide guidance and recommendations for risk stratification for sudden cardiac death.
- 5.
Provide guidance and recommendations to cardiac electrophysiologists on appropriate indications for implantable cardioverter-defibrillator (ICD) implantation.
- 6.
Identify key areas in which data are lacking to help guide future collaborative research efforts.
Developing consensus recommendations for rare diseases requires adapting the methodology for preparing traditional guidelines for clinical practice. The most obvious difference with rare diseases is that there are no randomized and/or blinded studies in the field. Therefore, the available data are derived from case series and registries that have followed patients and recorded outcome information. Thus, all consensus recommendations are level of evidence C (i.e., based on experts’ opinions) based on the American College of Cardiology (ACC)/American Heart Association’s (AHA) Classification of Recommendation and Level of Evidence grading scheme. The consensus recommendations in this document use ACC/AHA class I, IIa, IIb, and III classifications and the corresponding language: “is recommended” for a class I consensus recommendation; “can be useful” for a class IIa consensus recommendation; “may be considered” to signify a class IIb consensus recommendation; and “should not” or “is not recommended” for a class III consensus recommendation (failure to provide any additional benefit and may be harmful). Patients with CS can develop heart failure; however, the writing group felt that the management of this aspect of CS was beyond the scope of the current document.
It should be noted that although the ACC/AHA classification system was used, we did not otherwise follow their process for guideline development. The recommendations in this document are based on the consensus of the writing group following the Heart Rhythm Society’s process for establishing consensus-based guidance for clinical care. Consensus does not mean unanimous agreement among all writing group members, nor does consensus imply sufficient evidenced-based data to confirm our opinions. We identified the aspects of patient care for which a true consensus could be found. To this end, we carried out surveys of the entire writing group. The authors predefined the threshold for agreement as a vote of more than 75% on all recommendations. When using or considering the guidance given in this document, it is important to remember that there are no absolutes with regard to many clinical situations. The ultimate judgment regarding care of a particular patient must be made by the health care provider and the patient in light of the individual circumstances presented by that patient.
A bibliography was created at the outset of the document with the following search terms of “sarcoidosis” “cardiac sarcoidosis” and “sarcoidosis related arrhythmias.” Members of the writing group screened these relevant manuscripts for inclusion in discussions. All members of the writing group voted on all recommendations. Each section had writing groups (three to five members) who completed the initial drafts. The group assignments were based on individual interests and expertise. The co-chairs contributed equally to directing the writing group. All members of this writing group provided disclosure statements of all relationships that might present real or perceived conflicts of interest. Disclosures for all members of the writing group and peer reviewers are shown in Appendix 1.
Section snippets
Background
Sarcoidosis is a granulomatous disease of unknown etiology. Noncaseating granulomas are the pathological hallmark and are most often associated with pulmonary involvement but may also involve the heart, liver, peripheral lymph node, spleen, skin, eyes, phalangeal bones, parotid gland, or other organs and tissues. Recent studies suggest that the disease may be an immunological response to an unidentified antigenic trigger.1, 2 Sarcoidosis is a worldwide disease, with a prevalence of about 4.7–64
Diagnosis of Cardiac Sarcoidosis
There are no currently accepted international guidelines for the diagnosis of CS. However, there are two proposed diagnostic guidelines. One is the Japanese Ministry of Health and Welfare’s set of criteria. These were originally published in 199334 and then modified in 2007.35 Imaging modalities suggested by the modified criteria include gallium-67 scintigraphy and late gadolinium-enhanced cardiovascular magnetic resonance (LGE-CMR).35 It should be noted that the revised 2006 criteria did not
Role of Endomyocardial Biopsy (EMB) in the Diagnosis of Cardiac Sarcoidosis
In patients with extra-cardiac sarcoidosis, lymph node or lung biopsy is typically targeted first due to the higher diagnostic yield and lower procedural risk. In cases of isolated CS or negative extra-cardiac biopsy, EMB may be required to confirm the diagnosis. However, EMB has low sensitivity due to the focal nature of the disease, revealing non-caseating granulomas in less than 25% of patients with CS.44, 45 To increase the sensitivity of the procedure, electrophysiological (electroanatomic
Screening for Cardiac Involvement in Patients With Biopsy-Proven Extracardiac Sarcoidosis
There are few data comparing the sensitivity and specificity of various screening tests for cardiac involvement in patients with sarcoidosis. Mehta et al25 studied 62 patients with sarcoidosis. Those with symptoms (significant palpitations syncope, or presyncope) or abnormal results (ECG, Holter monitoring, and echocardiography, see Table 4 for definitions of abnormalities) were studied by CMR or FDG-PET scanning. The diagnosis of CS was based on abnormalities detected by PET or CMR. Patients
Management of Conduction Abnormalities
Heart block is a common presentation of clinically manifest CS because of the involvement of the basal septum by scar tissue, granulomas, or the involvement of the nodal artery.16 Furthermore, it can be the first manifestation of sarcoidosis in any organ (see Section B).
Recent Heart Rhythm Society device guideline documents generally apply to patients who have CS and advanced heart block.61, 62 In addition, the writing group reached consensus on three CS-specific recommendations (all class IIa)
Incidence and Mechanism
The true frequency of atrial arrhythmias in CS is unknown. Atrial involvement is common in CS, but it tends to involve the atria less extensively than the ventricles.16 It is likely that atrial arrhythmias associated with CS are due to inflammation and/or scarring. AF can be the presenting manifestation of CS.68 Recent observational studies have reported a substantial prevalence of atrial arrhythmias in CS. Viles-Gonzalez et al70 investigated 100 patients with biopsy-proven systemic sarcoidosis
Mechanisms of Ventricular Arrhythmias
Triggered activity and abnormal automaticity have been described secondary to myocardial inflammation in myocarditis.81, 82 These non-reentrant ventricular arrhythmias are also observed clinically in patients with CS presenting with frequent ventricular ectopy, and some of these patients have a reduction in arrhythmia burden after taking corticosteroids.66, 83 However, the most common mechanism is likely to be macroreentrant arrhythmias around areas of granulomatous scar.55, 80, 83 Active
Risk Stratification for Sudden Cardiac Death
Patients with CS are at risk of suuden death, and there are few data to help with risk stratification. The writing group agreed, however, that data from the major primary and secondary prevention ICD trials were relevant. Hence, it follows that the recommendations from the general device guideline documents apply to this population.60, 61 Therefore, this section of the consensus document mainly focuses on patients who do not have a clear indication for ICD implantation, that is, those with
LV Function
CS, perhaps because of its element of active granulomatous inflammation and perhaps because of the variable involvement of the LV and/or RV, may not behave in the same fashion as other types of nonischemic cardiomyopathy with regard to ventricular arrhythmias, LVEF, and sudden death risk. For example, CS patient cohorts appear to have more frequent ICD therapies than do other populations. In the three large published series, annualized appropriate therapy rates were 8.6%, 13.2%, and 14.5%,
Indications for ICD Implantation
There are few data specific to ICD use in the CS population. There is a class IIa recommendation in the general device guidelines with the following wording: “ICD implantation is reasonable for patients with CS, giant cell myocarditis, or Chagas disease.”60, 61 The writing group felt that there were sufficient data to provide more detailed recommendations for ICD implantation in CS. The writing group agreed that data from the major primary and secondary prevention ICD trials were relevant.
Conclusions and Future Directions
Much remains to be learned about how to best diagnose and manage patients with CS. Key unresolved questions include, but are not limited to, the following:
- 1.
What is the effect of corticosteroid treatment on the clinical course of the various manifestations of CS?
- 2.
What is the effect of other immunotherapy on the clinical course of the various manifestations of CS?
- 3.
What is the best, most cost-effective method to screen for CS? How frequently should patients be screened?
- 4.
Should we treat clinically
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Developed in collaboration with and endorsed by the World Association for Sarcoidosis and Other Granulomatous Disorders (WASOG), the American College of Cardiology (ACC), the American College of Chest Physicians (ACCP), the American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the European Heart Rhythm Association (EHRA).
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Representative for the World Association for Sarcoidosis and Other Granulomatous Disorders (WASOG)
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Representative for the American College of Cardiology (ACC)
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Representative for the American College of Chest Physicians (ACCP)
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Representative for the American Heart Association (AHA)
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Representative for the Asia Pacific Heart Rhythm Society (APHRS)
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Representative for the European Heart Rhythm Association (EHRA)