Sarcoid heart disease: clinical course and treatment

doi:10.1016/j.ijcard.2003.07.024

International Journal of Cardiology

Volume 97, Issue 2, November 2004, Pages 173-182

https://doi.org/10.1016/j.ijcard.2003.07.024 Get rights and content

Abstract

Sarcoidosis is a rare granulomatous disease of unknown etiology that can affect any organ. Cardiac involvement, although uncommon, has a wide spectrum of clinical manifestations and is potentially fatal. Although there is no agreement upon a strategy for the diagnosis (which is difficult to make based on clinical information alone), the introduction of newer technology is promising and may be useful both for the early diagnosis of cardiac involvement and for the evaluation of response to therapy.

Early treatment is crucial in improving symptoms and prognosis. ICD implantation and cardiac transplantation may offer improvements in management, as steroid therapy and pacemaker implantation has led to improved outcomes over the past three decades.

Introduction

Sarcoidosis is a multisystem, granulomatous disease of unknown etiology often seen in young adults. Age-adjusted annual incidence rate in the United States is 35.5 per 100,000 for blacks and 10.9 per 100,000 for whites with an overall prevalence rate of approximately 20 per 100,000 population [1]. Higher prevalence rates have been reported in Japan and some northern European countries such as Sweden.

Three separate clinicians initially described the disease in the 19th century in Europe [2]. In 1899, Boeck first used the word “sarkoid” to describe a cutaneous lesion because of the histological similarity (but favorable course) to sarcoma [3].

Section snippets

Etiology

The current evidence suggest that sarcoidosis results from an exaggerated cellular immune response to a variety of antigens or self-antigens which cause CD4 (helper–inducer) T-cell accumulation, activation and release of inflammatory cytokines eventually leading to granuloma formation [4] Fig. 1, Fig. 2. The disease may affect almost any organ and is characterized classically by the presence of non-caseating granulomas composed mainly of an aggregate of epithelioid cells and Langhans or foreign

Cardiac sarcoidosis

Although the respiratory tract and the lymphatic system are most often affected, the clinical manifestation of sarcoidosis can be widespread and may involve any organ system. The first case of cardiac sarcoidosis was reported in 1929 when Bernstein described sarcoid granulomas involving the pericardium [8]. Since then a wide range of cardiac manifestations of the disease has been described including conduction abnormalities, mitral regurgitation, congestive heart failure (CHF), ventricular

Diagnostic approach

Hugh Fleming, a cardiologist from England who specialized in the study of cardiac sarcoidosis, wrote in 1981 “the recognition of sarcoid heart disease …suggests that many of us have had, and many indeed still have, a blind spot for this diagnosis” [14]. More than 20 years passed since that statement and the diagnosis of cardiac sarcoidosis still a challenge for physicians.

To diagnose sarcoidosis in general, the American Thoracic Society (ATS) recommended the presence of a compatible clinical

Treatment

The treatment strategy of cardiac sarcoidosis should aim at relieving symptoms, controlling the inflammatory process, preventing further deterioration in myocardial function and preventing sudden death. Physicians should not wait until the onset of symptoms to start therapy; the treatment should be started as soon as the diagnosis is made.

Prognosis

The natural history and prognosis of sarcoidosis is difficult to determine due to the variable clinical presentations and severity of the disease, other organ involvement, the waxing and waning nature of the disease, and variable responses to steroid therapy in individual patients.

In the absence of cardiac involvement, the mortality rate of sarcoidosis is about 1–5% per year [73], [87]. Cardiac involvement associated with poorer prognosis and the mortality rate may exceed 40% at 5 years and 55%

Acknowledgements

The authors would like to thank Dr. Sate Hamza of the Department of Pathology, University of Alabama at Birmingham for providing the material of Fig. 1, Fig. 2, and Francine Rampick for technical assistance.

References (88)

W.C. Roberts et al.
Sarcoidosis of the heart. A clinicopathologic study of 35 necropsy patients (group 1) and review of 78 previously described necropsy patients (group 11)
Am. J. Med
(1977)
V. Abeler
Sarcoidosis of the cardiac conducting system
Am. Heart J
(1979)
Y. Yazaki et al.
Comparison of clinical features and prognosis of cardiac sarcoidosis and idiopathic dilated cardiomyopathy
Am. J. Cardiol
(1998)
S.L. Winters et al.
Sustained ventricular tachycardia associated with sarcoidosis: assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device
J. Am. Coll. Cardiol
(1991)
B. Belhassen et al.
Failure of corticosteroid therapy to prevent induction of ventricular tachycardia in sarcoidosis
Chest
(1989)
R.J. Lull et al.
Ventricular aneurysm due to cardiac sarcoidosis with surgical cure of refractory ventricular tachycardia
Am. J. Cardiol
(1972)
S. Bharati et al.
Infiltrative cardiomyopathy with conduction disease and ventricular arrhythmia: electrophysiologic and pathologic correlations
Am. J. Cardiol
(1980)
E.L. Kinney et al.
Thallium-scan myocardial defects and echocardiographic abnormalities in patients with sarcoidosis without clinical cardiac dysfunction. An analysis of 44 patients
Am. J. Med
(1980)
J. Garrett et al.
Constrictive pericarditis associated with sarcoidosis
Am. Heart J
(1984)
S. Zoneraich et al.
Myocardial sarcoidosis presenting as acute mitral insufficiency
Chest
(1974)

E.B. Raftery et al.

Acute subvalvar mitral incompetence

Lancet

(1966)

G.J. Fahy et al.

Doppler echocardiographic detection of left ventricular diastolic dysfunction in patients with pulmonary sarcoidosis

Chest

(1996)

Y. Okura et al.

A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis

J. Am. Coll. Cardiol

(2003)

J. Reuhl et al.

Myocardial sarcoidosis as a rare cause of sudden cardiac death

Forensic Sci. Int

(1997)

E. Stein et al.

Asymptomatic electrocardiographic alterations in sarcoidosis

Am. Heart J

(1973)

E.H. Schuster et al.

Systemic sarcoidosis and electrocardiographic conduction abnormalities. Electrophysiologic evaluation of two patients

Chest

(1980)

T. Suzuki et al.

Holter monitoring as a noninvasive indicator of cardiac involvement in sarcoidosis

Chest

(1994)

R.F. Lewin et al.

Echocardiographic evaluation of patients with systemic sarcoidosis

Am. Heart J

(1985)

D.V. Unverferth et al.

Value of endomyocardial biopsy

Am. J. Med

(1986)

S.J. Ratner et al.

Utility of endomyocardial biopsy in the diagnosis of cardiac sarcoidosis

Chest

(1986)

A. Uemura et al.

Histologic diagnostic rate of cardiac sarcoidosis: evaluation of endomyocardial biopsies

Am. Heart J

(1999)

K. Okayama et al.

Diagnostic and prognostic value of myocardial scintigraphy with thallium-201 and gallium-67 in cardiac sarcoidosis

Chest

(1995)

M. Chandra et al.

Diagnosis of cardiac sarcoidosis aided by MRI

Chest

(1996)

T. Shimada et al.

Diagnosis of cardiac sarcoidosis and evaluation of the effects of steroid therapy by gadolinium–DTPA-enhanced magnetic resonance imaging

Am. J. Med

(2001)

P.G. Danias

Gadolinium-enhanced cardiac magnetic resonance imaging: expanding the spectrum of clinical applications

Am. J. Med

(2001)

P. Tellier et al.

Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis

Am. J. Med

(1988)

K. Tawarahara et al.

Thallium-201 and gallium 67 single photon emission computed tomographic imaging in cardiac sarcoidosis

Am. Heart J

(1992)

P.L. Huang et al.

Antiarrhythmic therapy guided by programmed electrical stimulation in cardiac sarcoidosis with ventricular tachycardia

Am. Heart J

(1991)

Y. Yazaki et al.

Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone

Am. J. Cardiol

(2001)

T. Ishikawa et al.

Steroid therapy in cardiac sarcoidosis. Increased left ventricular contractility concomitant with electrocardiographic improvement after prednisolone

Chest

(1984)

R. Lash et al.

Treatment of heart block due to sarcoid heart disease

J. Electrocardiol

(1979)

S.L. Demeter

Myocardial sarcoidosis unresponsive to steroids. Treatment with cyclophosphamide

Chest

(1988)

E.E. Lower et al.

The use of low dose methotrexate in refractory sarcoidosis

Am. J. Med. Sci

(1990)

E.L. York et al.

Cyclosporine and chronic sarcoidosis

Chest

(1990)

H.L. Paz et al.

The automated implantable cardiac defibrillator. Prophylaxis in cardiac sarcoidosis

Chest

(1994)

H.J. Ankersmit et al.

Automated implantable cardiac defibrillator and biventricular thoratec assist device as bridge to transplantation in a patient with sarcoidosis

J. Thorac. Cardiovasc. Surg

(2001)

A.S. Donsky et al.

Heart transplantation for undiagnosed cardiac sarcoidosis

Am. J. Cardiol

(2002)

W.M. Burke et al.

Transmission of sarcoidosis via cardiac transplantation

Lancet

(1990)

N.M. Gideon et al.

Sarcoidosis mortality in the United States 1979–1991: an analysis of multiple-cause mortality data

Am. J. Med

(1996)

B.A. Rybicki et al.

Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization

Am. J. Epidemiol

(1997)

E. Besnier

Lupus pernio de la face: synovites fongueses symetrique des extremites superieures

Ann. Dermatol. Syphilol

(1889)

C. Boeck

Multiple benign sarkoid of the skin

J. Cutaneous Genitourinary Dis

(1899)

P.D. Thomas et al.

Current concepts of the pathogenesis of sarcoidosis

Am. Rev. Respir. Dis

(1987)

D.G. Kern et al.

Investigation of a unique time–space cluster of sarcoidosis in firefighters

Am. Rev. Respir. Dis

(1993)

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A septuagenarian female with cardiac sarcoidosis suffered from drug refractory ventricular tachycardia (VT) requiring multiple implantable cardioverter-defibrillator shocks. The QRS complex during the VT was very similar to that during sinus rhythm although the QRS width during the VT (142 ms) was relatively wider than that during sinus rhythm (107 ms). The VT exit was located on the ventricular septum close to the His-bundle recording region. However, the critical pathway of this VT was detected on the anterior free wall of the left ventricle (LV), and a radiofrequency application at that site could terminate the VT. No Purkinje potentials were recorded there during the VT or sinus rhythm. According to the electrophysiological study, 3-D mapping, and the response to the ablation, the critical circuit of the VT was surrounded by a protected area of scar associated with cardiac sarcoidosis. As a result, the VT circuit was connected to the basal septal area close to the His-Purkinje system as an outer loop of the VT circuit. This unique trajectory of the VT might have caused a similar QRS morphology to that of sinus rhythm, and the relatively narrow QRS complex despite the critical isthmus was located on the anterior free wall of the LV.
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Citation Excerpt :
The proposed mechanism for SVT is atrial dilation or cor pulmonale from pulmonary involvement [9]. Alternatively, focal granulomatous infiltration of atrial myocardium serving as a nidus for ectopy has been proposed as a mechanism for CS-related atrial fibrillation or atrial flutter [8,9,20]. Most patients with CS and SVTs are symptomatic (96%), therefore screening asymptomatic patients for the detection of underlying SVTs is not warranted [9].
Cardiac sarcoidosis (CS) affects less than 5% of patients with pulmonary or systemic sarcoidosis, but when present is often associated with a spectrum of clinically significant conduction abnormalities and arrhythmias. The cardinal manifestations of CS include conduction disturbances, arrhythmias, or congestive heart failure. Less commonly, there is concealed subclinical disease. The electrophysiologic evaluation for CS includes a history and physical exam, ECG, and echocardiogram for all sarcoidosis patients, along with MRI, PET/nuclear scans, and EPS for certain subsets of patients. Despite variable data to support their efficacy, glucocorticoids should still be considered in the treatment plan of CS. Antiarrhythmics in isolation are often ineffective in controlling ventricular arrhythmias. Cardiac pacemakers have provided important therapy for patients with conduction defects and implantable cardioverter defibrillator (ICD) therapy provides the strongest insurance to prevent fatal arrhythmias from CS. A recent consensus statement provides guidance for clinicians on the diagnosis and management of arrhythmias associated with CS including indications for ICDs. The use of pacemakers, ICD implantation and early implementation of corticosteroid therapy have led to an improvement in the overall prognosis and clinical outcomes of CS.

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ReviewSarcoid heart disease: clinical course and treatment

Abstract

Introduction

Section snippets

Etiology

Cardiac sarcoidosis

Diagnostic approach

Treatment

Prognosis

Acknowledgements

Am. J. Med

Am. Heart J

Am. J. Cardiol

J. Am. Coll. Cardiol

Chest

Am. J. Cardiol

Am. J. Cardiol

Am. J. Med

Am. Heart J

Chest

Lancet

Chest

J. Am. Coll. Cardiol

Forensic Sci. Int

Am. Heart J

Chest

Chest

Am. Heart J

Am. J. Med

Chest

Am. Heart J

Chest

Chest

Am. J. Med

Am. J. Med

Am. J. Med

Am. Heart J

Am. Heart J

Am. J. Cardiol

Chest

J. Electrocardiol

Chest

Am. J. Med. Sci

Chest

Chest

J. Thorac. Cardiovasc. Surg

Am. J. Cardiol

Lancet

Am. J. Med

Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization

Am. J. Epidemiol

Lupus pernio de la face: synovites fongueses symetrique des extremites superieures

Ann. Dermatol. Syphilol

Multiple benign sarkoid of the skin

J. Cutaneous Genitourinary Dis

Current concepts of the pathogenesis of sarcoidosis

Am. Rev. Respir. Dis

Investigation of a unique time–space cluster of sarcoidosis in firefighters

Am. Rev. Respir. Dis

Review
Sarcoid heart disease: clinical course and treatment