Cardiac Sarcoidosis

doi:10.1016/j.ccm.2008.03.005

Clinics in Chest Medicine

Volume 29, Issue 3, September 2008, Pages 493-508

https://doi.org/10.1016/j.ccm.2008.03.005 Get rights and content

Sarcoidosis is a systemic disease with a favorable prognosis, high remission rate, and low mortality. Cardiac involvement alters this prognosis. Clinical manifestations most commonly include arrhythmias, conduction abnormalities, and congestive heart failure. Treatment includes immunosuppressant therapy, permanent pacemakers in the setting of conduction abnormalities, and implantable cardioverter-defibrillators in patients at risk for sudden cardiac death. Risk stratification for sudden cardiac death is essential in otherwise asymptomatic patients who have suspected cardiac sarcoidosis.

Section snippets

Epidemiology

Myocardial involvement of sarcoidosis was described as early as 1929 by Bernstein and Sidlick [1]. The first large autopsy series reviewing cardiac sarcoidosis was published in 1952. Twenty percent of 92 autopsies in patients with sarcoidosis demonstrated noncaseating granulomas of the heart [2]. Although other clinicopathologic studies have shown a similar incidence of myocardial involvement on autopsy, clinical disease is present only in a minority of patients. There is geographic variation

Pathologic findings

Any structure of the heart can be involved by sarcoidosis, but the myocardium is the most common site. Granulomatous inflammation, fibrosis, hypertrophy, or thinning of cardiac structures can be seen on pathologic examination. The hallmark of sarcoidosis is the presence of noncaseating granulomas surrounded by lymphocytes and Langerhans giant cells that may contain Schaumann's or asteroid bodies (Fig. 1). These granulomas can heal leaving scarring, fibrosis, and thinning of ventricular walls.

Pathogenesis of cardiac sarcoidosis

The precise etiology of sarcoidosis remains unknown; the principal inciting event leads to granuloma formation, which can then either resolve or progress to fibrosis. Activated CD4⁺ cells differentiate into type 1 helper T cells inducing secretion of interleukin (IL)-2 and interferon-γ leading to recruitment and activation of macrophages. In turn, macrophages secrete cytokines including IL-1, IL-6, and tumor necrosis factor-α (TNF-α), further augmenting the type 1 helper inflammatory cascade.

Genetics of cardiac sarcoidosis

Both HLA and non-HLA genes have been associated with various forms of sarcoidosis. A significant overrepresentation of DQB1.0601 has been demonstrated in patients with cardiac involvement [19]. Recent phenotypic analysis of a large genome scan of black Americans with sarcoidosis found a linkage between cardiac and renal features of sarcoidosis and genes at the chromosome 18q22.20 locus [20]. Both genes for TNF-α and TNF-β have been studied for association with sarcoidosis; the less common TNF-a

Clinical manifestations

Clinical manifestations of cardiac sarcoidosis are dependent on the location, extent, and activity of disease. Cardiac signs and symptoms may be the first presentation of sarcoidosis [22]. Cardiac involvement can be unpredictable, ranging from clinically silent disease to the most feared consequence, sudden cardiac death from ventricular arrhythmia. The three principal sequelae of cardiac sarcoidosis are (1) conduction abnormalities, (2) arrhythmias, and (3) heart failure.

In addition to classic

Methods of diagnosing cardiac sarcoidosis

The definition of cardiac sarcoidosis varies. The American Thoracic Society and World Association for Sarcoidosis and Other Granulomatous Disorders consider cardiac dysfunction, ECG abnormalities, and thallium-201 imaging defects with or without endomyocardial biopsy in sarcoidosis patients as evidence of cardiac involvement [42]. ACCESS panel investigators defined criteria for “definite” cardiac involvement as treatment-responsive cardiomyopathy, ECGs with conduction defects, and positive

Ventricular arrhythmias and methods of risk assessment

Once the diagnosis of cardiac sarcoidosis has been established, risk stratification for sudden cardiac death is mandated. The use of programmed ventricular stimulation in the risk stratification of patients with cardiac sarcoidosis was assessed in a study of 32 consecutive patients with cardiac sarcoidosis [88]. All patients underwent programmed ventricular stimulation, and those patients with spontaneous or inducible sustained ventricular arrhythmias subsequently had placement of ICDs. Over a

Immunosuppressive therapy

CS is the cornerstone of treatment for cardiac sarcoidosis despite the lack of confirmatory randomized trials to confirm this treatment. It is known that early initiation of CS therapy can improve and possibly reverse cardiac disease secondary to sarcoidosis. Anecdotal accounts of response to CS have been reported as evaluated by imaging studies, clinical symptoms, and histopathologic improvement [61], [68], [76], [81], [92], [93], [94], [95]. In one large retrospective study of 95 patients

Prognosis

The mortality from sarcoidosis is low at 1% to 5% per year, usually secondary to progressive lung disease. With the addition of cardiac involvement, the prognosis is adversely impacted. In an early autopsy study of 113 patients, the median survival was less than 2 years following development of cardiac signs and symptoms [10]. A decade later, a United Kingdom study observed a 5-year survival rate in a cohort of patients with cardiac sarcoidosis of 40% [106]. With the increased recognition of

Summary

Sarcoidosis is a disease with grave consequences when there is cardiac involvement. This article reviews the protean manifestations of cardiac involvement in patients known to have sarcoidosis. Also reviewed is the initial manifestations in patients whose sarcoidosis was detected only after first presentation with a cardiac event. A high degree of suspicion and systematic evaluation to uncover the involvement is warranted to improve outcome of patients with sarcoidosis and cardiac involvement (

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