Management of Cardiac Sarcoidosis in the United States: A Delphi Study

doi:10.1378/chest.11-0263

Chest

Volume 141, Issue 1, January 2012, Pages 154-162

https://doi.org/10.1378/chest.11-0263 Get rights and content

Background

No formal guidelines exist to guide physicians caring for patients with sarcoidosis in their screening for management of patients with cardiac sarcoidosis. We conducted a modified Delphi study to investigate if a consensus could be reached on the best approaches for screening for and management of cardiac sarcoidosis.

Methods

A modified Delphi study design with two rounds of questionnaires was used to investigate if a consensus existed among sarcoid experts in the United States on the best management approaches for cardiac sarcoidosis. Experts were identified based on their national reputation as sarcoid experts and by being actively involved in sarcoidosis clinics at their institutions.

Results

Overall agreement was low to moderate. Agreement was reached on the role of history, physical examination, and 12-lead ECG in screening, echocardiogram, Holter monitor, myocardial fluorodeoxyglucose PET scan, and cardiac MRI in workup, and steroids in treatment. Agreement was not reached on the role of signal-averaged ECG in screening, optimum dose of prednisone, use of steroid-sparing agents, and duration of treatment. Several comments underscore the diverse approaches and uncertainty that exist in managing cardiac sarcoidosis.

Conclusions

Our study highlights the dilemma that sarcoid experts face in their approach to cardiac sarcoidosis. It also highlights the lack of agreement among sarcoid experts on key aspects of diagnosis and management and stresses the importance of collaborative efforts to investigate the best strategies for screening for and management of cardiac sarcoidosis.

Section snippets

Materials and Methods

To learn about current clinical practices and attempt to see if consensus existed regarding these practices, a Delphi study design was used.9, 10 The institutional review board at National Jewish Health approved the study under exempt status (HS#2513). Two rounds of questionnaires were e-mailed to sarcoidosis specialists in the United States. The questions were in the multiple choice format but also included an “other” choice for free-text comments.

The experts were chosen based on their known

Characteristics of the Study Participants

Forty-two sarcoid experts were invited to participate (36 pulmonologists, three cardiologists, three electrophysiologists, one rheumatologist). Thirty-one of the 42 (73.8%) responded to the first round of questions, and 27 of the 31 (87.1%) who responded to the first questionnaire responded to the second round of questions. Characteristics of the experts are shown in Table 1. The majority were pulmonologists and 64.5% have been practicing for > 10 years, and 87.1% (27/31) manage on average >

Discussion

In an editorial titled “Cardiac sarcoidosis: there is no instant replay,” Dr Marc Judson⁸ exemplified the anguish physicians have to deal with when caring for patients with sarcoidosis. Detected clinically in 5% of cases² but most likely present in at least 40%,¹¹ sarcoid physicians struggle to narrow this gap. There is a significant lack of prospective studies that can guide physicians on the best screening, diagnostic, and management strategies. In addition, the lack of a gold standard for

Acknowledgments

Authors contributions: Dr Hamzeh had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Hamzeh: contributed to the study concept, design, and implementation; data analysis and interpretation; and the writing of the manuscript.

Dr Wamboldt: contributed to the study concept and reviewed and critiqued the manuscript.

Dr Weinberger: contributed to the study design and data analysis and reviewed and critiqued the

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Cardiac sarcoidosis (CS) is a relapsing-remitting disease, and immune suppression (IS) is the mainstay of therapy. Predictors of relapse for patients with CS in remission are not well characterized. We assessed incidence of relapse in consecutive patients with CS treated with high-dose steroids and/or steroid-sparing agents (SSA) in our center from 2000 to 2020. Remission was defined as reaching maintenance therapy (no IS, SSA, and/or prednisone ≤5 mg/d) for ≥1 month. Relapse was defined as recurrence of CS syndrome requiring IS intensification: heart failure, ventricular arrhythmia, decrease in left ventricular ejection fraction, or increased disease burden on imaging. Among 68 patients, the mean age was 50.7±9.0 years; 25 (37%) were women, and 32 (47%) were Black. In total, 59 patients (87%) reached remission. Over a median follow-up of 39.5 months (interquartile range 17.6, 92.5), 28 (48%) relapsed. Greater percentage of late gadolinium enhancement (LGE) on pretreatment magnetic resonance imaging corresponded with increased likelihood of relapse (odds ratio 1.396 per 5% increase [95% confidence interval (CI) 1.04 to 1.88]; p = 0.028). LGE ≥11% predicted elevated risk of relapse (adjusted odds ratio 4.998 [1.34 to 18.64]; p = 0.017). Shorter time to relapse was observed with isolated CS (adjusted hazard ratio 4.084 [1.44,11.56]; p = 0.008) and LGE ≥11% (adjusted hazard ratio 3.007 [1.01, 8.98]; p = 0.049). Approximately 1 in 2 patients with CS in remission experienced relapse. Greater burden of LGE on cardiac magnetic resonance imaging and isolated CS are associated with greater risk of relapse. Future work is needed to refine risk stratification for relapse and to optimize surveillance strategies on the basis of the burden of disease.
An International Survey of Current Clinical Practice in the Treatment of Cardiac Sarcoidosis
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Cardiac sarcoidosis (CS) is a potentially serious form of infiltrative cardiomyopathy. Despite scarce evidence, immunosuppressive treatment is generally recommended, but local routines may vary significantly. We sought to survey the clinical practices in the treatment of CS, with the aim that the results may suggest future research priorities. We conducted a web-based survey focused on treatment-naive patients with CS. We subclassified CS according to the presence/absence of overt cardiac presentation (clinically manifest/silent) and to the presence/absence of active inflammation (metabolically active/inactive by fluorodeoxyglucose positron emission tomography). The survey was developed jointly by the authors and administered to expert clinicians (n = 79) involved in CS treatment. An agreement threshold was set at 70%. A total of 62 of 79 respondents (78.5%) from 12 countries completed the survey. The agreement threshold was reached for: (1) always treating clinically manifest, metabolically active CS, 57 of 62 (91.9%), (2) never treating clinically silent, metabolically inactive CS, 44 of 62 (71.0%), (3) not requiring histopathologic confirmation of sarcoidosis before treatment initiation, (49 of 62, 79.0%), (4) using fluorodeoxyglucose positron emission tomography for assessing treatment indication (44 of 62, 71.0%) and treatment response (44 of 62, 71.0%), and (5) using prednisone as a first-line agent (100%), although respondents were divided on monotherapy (69.4%) or combination with methotrexate 25.8%. The approach to particular scenarios, tapering, and duration of treatment showed the greatest variation in response. In conclusion, in this survey of clinical practice, important aspects of CS treatment reached the agreement threshold, whereas others showed a great degree of clinical equipoise.
The Management of Sarcoidosis in the 2020s by the Primary Care Physician
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Sarcoidosis is an idiopathic granulomatous disease that occurs worldwide and can affect any organ. Because the presenting symptoms of sarcoidosis are not specific for the disease, the primary care physician is usually the first provider to assess these patients. In addition, patients who have previously been diagnosed with sarcoidosis are usually followed longitudinally by primary care physicians. Therefore, these physicians are often the first to address sarcoidosis patient symptoms related to exacerbations of the disease, and first observe complications of sarcoidosis medications. This article outlines the approach to the evaluation, treatment, and monitoring of sarcoidosis patients by the primary care physician.
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Rituximab for the Treatment of Refractory Cardiac Sarcoidosis: A Single-Center Experience
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We sought to examine the effect of anti–B-cell therapy (rituximab) on cardiac inflammation and function in corticosteroid-refractory cardiac sarcoidosis. Cardiac sarcoidosis (CS) is a rare cause of cardiomyopathy characterized by granulomatous inflammation involving the myocardium. Although typically responsive to corticosteroid treatment, there is a critical need for identifying effective steroid-sparing agents for disease control. Despite increasing evidence on the role of B cells in the pathogenesis of sarcoidosis, there is limited data on the efficacy of anti–B-cell therapy, specifically rituximab, for controlling CS.
We reviewed the clinical experience at a tertiary care referral center of all patients with CS who received rituximab after failing to improve with initial immunosuppression therapy, which included corticosteroids. Fluorodeoxyglucose positron emission tomography (FDG PET/CT) images before and after rituximab treatment were evaluated. All images were interpreted by 2 experienced nuclear medicine trained physicians. We identified 7 patients (5 men, 2 women; mean age at diagnosis, 49.0 ± 7.9 years) with active CS who were treated with rituximab. The median length of follow-up was 5.1 years. All individuals, but 1, had received prior steroid-sparing agents in addition to corticosteroids. Rituximab was administered either as 1000 mg intravenously ×1 or ×2 doses, separated by 2 weeks. Repeat dosing, if appropriate, was considered after 6 months. All tolerated the infusions well. Inflammation as assessed by maximum standardized uptake value on cardiac FDG PET/CT uptake significantly decreased in 6 of 7 patients (median 6.0–4.5, Wilcoxon signed rank z –1.8593, W 3), whereas the left ventricular ejection fraction improved or stabilized in 4 patients but decreased in 3. The mean left ventricular ejection fraction was 40.1% and 43.3% before and after treatment, respectively (P = .28). Three patients reported improved physical capacity, and 5 patients showed improved arrhythmic burden on Holter monitoring or implantable cardioverter-defibrillator interrogation. One patient subsequently developed a fungal catheter-associated infection and sepsis requiring discontinuation.
Rituximab was well-tolerated and seemed to decrease inflammation, as assessed by cardiac FDG PET/CT in all but 1 patient with active CS. These data suggest that rituximab may be a promising therapeutic option for CS, which deserves merits further study.
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Cardiac sarcoidosis (CS) with clinical manifestation occurs in about 5-8% of patients with sarcoidosis. CS may be clinically suspected by the presence of ventricular arrhythmia, conduction abnormalities, and heart failure (HF). However, 20%-25% of patients may present with silent CS, having asymptomatic cardiac involvement. The diagnosis of CS is based on findings from nuclear studies, cardiac magnetic resonance, and extra-cardiac tissue biopsy. Due to the inflammatory nature of the disease, immunosuppressive medications are a cornerstone of therapy. The treatment also includes recommended HF medical therapies. Since CS patients are at risk of sudden cardiac death resulting from progression of cardiac dysfunction or the presence of scar originating from fatal arrhythmias, implantable cardioverter-defibrillators should be considered, with special indication beyond accepted recommendations in HF. In CS, the extent of left ventricular dysfunction is the most important mortality predictor. Heart transplant or mechanical circulatory support may represent life saving strategies in selective CS patients.

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Funding/Support: Supported by NIH/NCATS Colorado CTSI Grant Number UL1 TR000154. Contents are the authors' sole responsibility and do not necessarily represent official NIH views.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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Chest

Original ResearchDiffuse Lung DiseaseManagement of Cardiac Sarcoidosis in the United States: A Delphi Study

Background

Methods

Results

Conclusions

Section snippets

Materials and Methods

Characteristics of the Study Participants

Discussion

Acknowledgments

Chest

Am J Med

Chest

Chest

Chest

Chest

Chest

Rev Med Interne

Chest

J Nucl Cardiol

J Am Coll Cardiol

Am J Cardiol

Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS), and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999

Am J Respir Crit Care Med

Original Research
Diffuse Lung Disease
Management of Cardiac Sarcoidosis in the United States: A Delphi Study