© 2013 Wiley Periodicals, Inc.
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REVIEW ARTICLE _______________________________________________________________
Cardiac Sarcoidosis Pavel Zacek, M.D., Ph.D.,* Nedal Omran, M.D.,* James L. Chek, M.D.,* Lukas Krbal, M.D.,y Jan Vojacek, M.D., Ph.D.,* and Jan Harrer, M.D., Ph.D.* *Faculty of Medicine and Faculty Hospital, Department of Cardiac Surgery, Charles University in Prague, Hradec Kralove, Czech Republic; and yFaculty of Medicine and Faculty Hospital, The Fingerland’s Department of Pathology, Charles University in Prague, Hradec Kralove, Czech Republic ABSTRACT Cardiac sarcoidosis is a rare entity and may be difficult to diagnose prior to cardiac surgery. We review the imaging and diagnostic studies necessary to make the diagnosis and discuss therapeutic algorithms to manage this disease. doi: 10.1111/jocs.12163 (J Card Surg 2013;XX:1–4)
Sarcoidosis is a granulomatous disease of unknown etiology involving multiple organs.1 Isolated cardiac sarcoidosis, that is, with no detectable evidence of sarcoidosis in other organs, is rare. The clinical manifestations of cardiac sarcoidosis include conduction disorders, arrhythmias, congestive heart failure, valvular pathology, pericardial effusions,2 and sudden cardiac death.3 While a correct and timely diagnosis can be relatively easily made in the case of extracardiac sarcoidosis, isolated cardiac involvement is difficult to diagnose.4 We review the diagnosis and management of patients presenting with isolated cardiac sarcoidosis. PATIENT PROFILE A 73-year-old female was admitted for recent onset dyspnea on exertion (NYHA class III). The ECG revealed first-degree atrioventricular block, right bundle branch block, and left anterior hemiblock. Chest X-ray revealed cardiomegaly. Echocardiography showed enlargement of the left atrium, and systolic dysfunction of an undilated left ventricle with dyskinesis of the interventricular septum. The left ventricular ejection fraction was 40%. The systolic function of the right ventricle was preserved. Moderate to significant mitral and tricuspid valve regurgitation were present due to dilation of the atrioventricular annuli. The systolic pressure in the pulmonary circulation, assessed echocardiographically, was about 40 mmHg. Coronary angiography showed normal arteries. Conflict of interest: The authors acknowledge no conflict of interest in the submission. Funding: This work was supported by the program PRVOUK P37/03. Address for correspondence: Nedal Omran, M.D., Department of Cardiac Surgery, Charles University Hospital, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. Fax: þ420-495-833-026; e-mail:
[email protected]
During hospitalization the patient had atrial fibrillation, which was converted to sinus rhythm by amiodarone. Later, the patient experienced sustained ventricular tachycardia resulting in hemodynamic instability, which was terminated by cardioversion. Electrophysiological investigation showed symptomatic sustained ventricular tachycardia arising from the myocardium of the interventricular septum, which was then terminated by antitachycardic pacing. On magnetic resonance imaging (MRI), subendocardial fibrotic lesions were found in the myocardium of the interventricular part of the right ventricle leading to suspicion of an arrhythmogenic right ventricular cardiomyopathy (Fig. 1a and b). Repair of these valvular lesions was recommended to improve her dyspnea. Following a mediansternotomy and after the initiation of the cardiopulmonary bypass, the mitral and tricuspid valves were approached via a biatrial transeptal hockey-stick incision.5 Both valves appeared morphologically normal with slightly dilated annuli. Effective repair of the mitral and tricuspid valves was achieved by implantation of Carpentier-Edwards Classic annuloplasty rings (Edwards Lifesciences, Irvine, CA, USA), sizes 26 and 32, respectively. Biatrial cryomaze procedure was performed and a direct myocardial biopsy from the right side of the interventricular septum was obtained via the tricuspid orifice. The operation and early postoperative course were uneventful; however, during postoperative day (POD) 1 the patient gradually developed signs of low cardiac output with increased need for catecholamines. Cardiac tamponade was excluded. Echocardiography confirmed good competency of both repaired mitral and tricuspid valves, left ventricular ejection fraction was approximately 35%, and there was normal systolic function of the right ventricle. Increased inotropic support with levosimendan and dobutamine was required. Intra-aortic balloon counterpulsation was initiated. Repeated attacks of sustained monomorphic ventricular tachycardia,
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ZACEK, ET AL. ISOLATED CARDIAC SARCOIDOSIS
Figure 1. (a and b) Subendocardial fibrotic changes in the septal part of the right ventricle.
resistant to amiodarone, had to be terminated by cardioversion. Despite aggressive pharmacologic therapy, the patient later developed refractory cardiogenic shock with multiorgan failure and expired on POD 6. Histopathology findings from the operative specimen revealed massive myocardial infiltration of the interventricular septum by noncaseating granulomas with gross postinflammatory fibrotic changes of the myocardium (Fig. 2a and b). This finding was consistent with fulminant cardiac sarcoidosis. DISCUSSION Despite the recent advanced progress in imaging modalities cardiac sarcoidosis remains a diagnosis that is more frequently made during post-mortem studies.
Figure 2. (a) Transverse section of the ventricles. Scarring affects the interventricular septum and the left ventricular posterior wall. (b) Epithelioid and Langhans giant cells without caseous necrosis on histopathology finding (hematoxylin-andeosin stain, magnification 400).
J CARD SURG 2013;XX:1–4
Symptomatic cardiac impairment can be evident in about 5% of patients with sarcoidosis, whereas features of noncaseating granulomatous myocardial infiltration can be seen in up to 50% of patients with sarcoidosis in autopsy studies.6 The clinical presentation of cardiac sarcoidosis can range from an asymptomatic course to sudden cardiac death.3 No ideal noninvasive screening for cardiac sarcoidosis exists. Elevated serum levels of angiotensin-converting enzyme, caused by its increased secretion from the epithelioid cells,7 and hypercalcemia and hypercalciuria due to its increased absorption in the intestine,8 may support the diagnosis. These tests, however, are not specific. Biomarkers of cardiomyocyte damage caused by the inflammatory process, such as troponin, can also be used although their specificity is low. In addition, the troponin level can be a helpful tool in the assessment of the response to steroid therapy in patients with cardiac sarcoidosis.9 Cardiac MRI has 100% sensitivity and 78% specificity for cardiac sarcoidosis.10 Sarcoidotic lesions which are detected on late gadolinium enhancement are localized predominantly subepicardially.11 The high uptake during fasting positron emission tomography using 18-fluorodeoxyglucose (FDG PET) can be more specific for lesions with hypermetabolic activity, such as those caused by sarcoidotic inflammatory lesions.12 According to Langah et al.13 FDG PET scan has 85% sensitivity and 95% specificity for cardiac sarcoidosis. Furthermore, FDG PET scan can be advantageous in patients with implantable cardioverter-defibrillators, pacemakers, patients with renal failure, and for the assessment of disease activity in patients treated with corticosteroids.14 Distinguishing between active inflammatory lesions and postinflammatory myocardial scars is a difficult task during cardiac imaging. In the literature, several reports of cardiac sarcoidosis presumed to be arrhythmogenic right ventricular cardiomyopathy were reported.15–17 This misdiagnosis may be partially explained by the fact that regions showing delayed contrast enhancement on MRI represent myocardial fibrosis18 and thus, in the case of right ventricular involvement, can lead the radiologist to diagnose arrhythmogenic right ventricular cardiomyopathy as a cause of fibrous myocardial replacement instead of diagnosing postinflammatory fibrous scar formation. Subendocardial fibrotic lesions localized in the interventricular part of the right ventricle were also found on the MRI in our patient. A simultaneous use of PET/MRI allows the acquisition of data that clearly detect the intramyocardial distribution of the inflammation, fibrotic changes, and the disease activity in cardiac sarcoidosis.19 Cardiac sarcoidosis has no pathognomonic histopathologic finding. The histopathologic finding of noncaseating granulomas, after ruling out infective diseases, especially tuberculosis, and idiopathic giant cell myocarditis remains the only hallmark for sarcoidosis. Endomyocardial biopsy (EMB) remains the gold standard in confirming the diagnosis. Nevertheless, even a negative histopathology from the samples acquired by
J CARD SURG 2013;XX:1–4
transvenous EMB does not rule out cardiac sarcoidosis.20 This can be explained by the patchy character of the myocardial involvement in patients with cardiac sarcoidosis or by the fibrotic replacement of the myocardium that was previously infiltrated by granulomas.21 Imaging-guided endomyocardial biopsy can increase the sensitivity of this diagnostic procedure.22 The treatment of cardiac sarcoidosis is aimed at suppression of the inflammation and prevention of the structural and functional myocardial deterioration. Corticosteroids present first line treatment for sarcoidosis. The early initiation of steroid therapy, before the impairment of the left ventricular systolic function, can increase the efficacy of the treatment.23,24 Corticosteroids administration can even lead to resolution of atrioventricular conduction disturbances25 and may suppress the recurrence of ventricular tachycardia in the group of responder patients in early stages of cardiac sarcoidosis.26 The appropriate dose of prednisone has not been determined and can be up to 1 mg/kg daily with tapering to a maintenance dose of 10 to 15 mg daily over a variable period of time after a careful assessment of the disease activity using imaging modalities or/and laboratory markers. The use of alternative immunosuppressive agents such as cyclophosphamide, methotrexate, cyclosporine, and infliximab may be considered in case of no response or intolerance to corticosteroid therapy; however, data supporting their administration are extremely limited.27 Additional therapeutic modalities for the management of sarcoidosis-related heart disorders, such as permanent pacemaker implantation for conduction disturbance or cardioverter-defibrillator implantation in case of ventricular arrhythmias, are indicated. Patients with refractory heart failure unresponsive to medical therapy should be considered for heart transplantation. According to Zaidi et al., patients undergoing orthotopic heart transplantation due to cardiac sarcoidosis had better short- and intermediateterm survival than the majority of heart transplant recipients. Therefore, the diagnosis of sarcoidosis should not disqualify potential candidates for cardiac transplantation.28 However, cases of cardiac sarcoidosis in allografted hearts were also reported.29,30 The prognosis of patients with cardiac sarcoidosis is not well established. Several reports demonstrate a five-year survival rate exceeding 70%.23,24 According to Yazaki et al., patients treated with corticosteroids with left ventricular ejection fraction (LVEF) 50% had a tenyear survival rate of 89% compared with 27% for the same patients with LVEF
