Cardiac involvement in sarcoidosis: evolving concepts in diagnosis and treatment

Abstract

Clinically evident sarcoidosis involving the heart has been noted in at least 2 to 7% of patients with sarcoidosis, but occult involvement is much higher (> 20%). Cardiac sarcoidosis is often not recognized antemortem, as sudden death may be the presenting feature. Cardiac involvement may occur at any point during the course of sarcoidosis and may occur in the absence of pulmonary or systemic involvement. Sarcoidosis can involve any part of the heart, with protean manifestations. Prognosis of cardiac sarcoidosis is related to extent and site(s) of involvement. Most deaths due to cardiac sarcoidosis are due to arrhythmias or conduction defects, but granulomatous infiltration of the myocardium may be lethal. The definitive diagnosis of isolated cardiac sarcoidosis is difficult. The yield of endomyocardial biopsies is low; treatment of cardiac sarcoidosis is often warranted even in the absence of histologic proof. Radionuclide scans are integral to the diagnosis. Currently, 18F-fluorodeoxyglucose positron emission tomography/computed tomography and gadolinium-enhanced magnetic resonance imaging scans are the key imaging modalities to diagnose cardiac sarcoidosis. The prognosis of cardiac sarcoidosis is variable, but mortality rates of untreated cardiac sarcoidosis are high. Although randomized therapeutic trials have not been done, corticosteroids (alone or combined with additional immunosuppressive medications) remain the mainstay of treatment. Because of the potential for sudden cardiac death, implantable cardioverter-defibrillators should be placed in any patient with cardiac sarcoidosis and serious ventricular arrhythmias or heart block, and should be considered for cardiomyopathy. Cardiac transplantation is a viable option for patients with end-stage cardiac sarcoidosis refractory to medical therapy.

Fig. 1

(A–E) Photomicrographs. (A and B): Gross photographs of heart from young man dying suddenly while playing basketball. (A) Cross-section of ventricles showing scars in papillary muscles (PM) and subepicardium (SE) with normal coronary artery characteristic of sarcoid lesions as opposed to ischemic injury. (B) Right ventricular outflow tract from same patient showing scarring below the pulmonary valve (S) and a granuloma in the pulmonary artery (arrow). (C) Histologic section of left ventricular lesion showing typical discrete, well-circumscribed nonnecrotizing granulomas (G) typical of sarcoidosis (hematoxylin and eosin [H&E] stain, ×40). (D) High magnification showing typical giant cells with numerous nuclei (H&E stain, ×400). (E) Endomyocardial biopsy from patient resuscitated from sudden cardiac death, showing nonnecrotizing granuloma (NNG) typical of sarcoidosis (H&E stain, ×200).

Fig. 2

Patterns of myocardial ¹⁸FDG uptake on PET scan (reproduced with permission from Ishimaru et al). ¹⁸FDG, 18F-fluorodeoxyglucose; PET, positron emission tomography.

Fig. 3

Patient with nonischemic cardiomyopathy and VT with mismatch. Perfusion shows normal septal uptake with decreased lateral uptake by NH3. On ¹⁸FDG-PET, the myocardial uptake is increased on the lateral wall, which indicates inflammation. ¹⁸FDG, 18F-fluorodeoxyglucose; PET, positron emission tomography; VT, ventricular tachycardia.

Fig. 4

Patient with VT referred for ablation with presumed arrhythmogenic right ventricular dysplasia with right precordial T wave inversion. PET/ CT demonstrated extracardiac ¹⁸FDG uptake in right hilar lymph node and patchy focal uptake throughout both ventricles. Biopsy of the right hilar node confirmed NNG consistent with sarcoidosis. ¹⁸FDG, 18F-fluorodeoxyglucose; NNG, nonnecrotizing granuloma; PET, positron emission tomography; VT, ventricular tachycardia.

Fig. 5

Multiphase inflammation in a 49-year-old female with a history of heart block requiring a pacemaker. Nonsustained VT was documented on pacer interrogation. PET/CT revealed decreased anteroseptal perfusion with focal uptake of ¹⁸FDG in the septum and inferolateral wall. The mismatch in the septum suggests chronic scarring. ¹⁸FDG, 18F-fluorodeoxyglucose; NNG, nonnecrotizing granuloma; PET, positron emission tomography; VT, ventricular tachycardia.

Fig. 6

Typical bilateral hilar update and patchy myocardial uptake in the septum with progressive heart block in a patient presenting with intermittent lightheadedness.

Fig. 7

MRI scan showing delayed enhancement throughout RV in a 48-year-old male with recurrent VT of RV origin and suspected ARVC. An ICD was placed and he subsequently had recurrent ICD shocks. He was referred for VT ablation. MRI showed diffuse hyperenhancement of the RV extending into the IVS. The RV was dilated and hypokinetic. PET/CT showed intense ¹⁸FDG uptake in the interior wall and most of the RV free wall, with diffuse lymph node uptake (arrows). Lymph node biopsy revealed NNG consistent with sarcoidosis. With treatment of his sarcoidosis, VT has not recurred. CT, computed tomography; ¹⁸FDG, 18F-fluorodeoxyglucose; ICD, implantable cardioverter-defibrillators; MRI, magnetic resonance imaging; NNG, nonnecrotizing granuloma; PET, positron emission tomography; RV, right ventricle; VT, ventricular tachycardia