Sarcoidosis-Related Cardiomyopathy: Current Knowledge, Challenges, and Future Perspectives State-of-the-Art Review

Abstract

The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia, and/or heart failure. The diagnosis of cardiac sarcoidosis (CS) can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes, such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of CS. The mainstay of therapy for CS is immunosuppression; however, no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in CS call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.

Keywords: cardiac sarcoidosis; heart transplantation; inflammatory cardiomyopathy; interdisciplinary; myocarditis.

Figure 1.. (Central Figure) Sarcoidosis-Related Cardiomyopathy: Pathobiology to Clinical Manifestations.

Environmental, genetic, and immunologic factors influence the formation and maintenance of granulomas which may manifest in multiple organ systems. Granulomatous infiltration may result in clinically manifest or silent cardiac sarcoidosis and subsequent sarcoidosis cardiomyopathy. Phenotypically, inflammation and infiltration can lead to an active myocarditis stage or patients may develop fibrosis and a resultant restrictive or dilated cardiomyopathy. Immunosuppression is used to reduce myocardial inflammation and resultant clinical endpoints, while use of heart failure guideline directed medical therapies is extrapolated from data in non-sarcoidosis cardiomyopathies to prevent remodeling and improve heart failure outcomes. A subset of patients may progress to advanced, end-stage heart failure or develop refractory ventricular arrhythmia prompting consideration of advanced heart failure therapies. ARNI = angiotensin receptor neprilysin inhibitor; BB = beta-blocker; CM = cardiomyopathy; CRT = cardiac resynchronization therapy; GDMT = guideline directed medical therapy; ICD = implantable cardioverter defibrillator; LVAD = left ventricular assist device; MCS = mechanical circulatory support; MRA = mineralocorticoid receptor agonist; SGLT2i = sodium-glucose cotransporter-2 inhibitor.

Figure 2.. Representative 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images from a patient with cardiac sarcoidosis.

In a patient with cardiac and pulmonary sarcoidosis, baseline cardiac FDG-PET images (Panel A) demonstrate a moderate sized area of abnormal FDG uptake extending to medial and basal segments of the inferior and inferoseptal wall. After treatment with prednisone and mycophenolate mofetil, there is resolution of cardiac FDG uptake (Panel B).

Figure 3.. Pathologic findings from an explanted heart after transplantation.

A: Gross pathology of explanted heart demonstrating extensive granulomatous infiltration of the myocardium. B: Explant heart tissue histopathology (hematoxylin and eosin stain) demonstrating patchy, non-caseating granulomas; C: Microscopic view demonstrating multinucleated giant cell.

Figure 4.. Proposed immunosuppression treatment and monitoring algorithm for patients with cardiac sarcoidosis.

Patients with active cardiac sarcoidosis may be treated with immunosuppression treatment in the form of corticosteroids, with the possible addition of steroid sparing and/or biologic agents. Cardiac imaging and clinical assessment are key to monitoring response to therapy including side effects. There are several considerations for monitoring patients on immunosuppression therapy, as highlighted in panel on right.

Figure 5.. Considerations for Patients with Cardiac Sarcoidosis Undergoing Heart Transplantation and/or Left Ventricular Assist Device Implantation Through Operative Phases of Care.

There are unique clinical considerations for patients with cardiac sarcoidosis related advanced heart failure who are being evaluated for heart transplantation and/or LVAD. Additionally, a confirmed diagnosis of cardiac sarcoidosis on native heart pathology impacts short and long-term post-operative care. Legend: FC = functional capacity; LV = left ventricular; LVAD = left ventricular assist device; QOL = quality of life; RV = right ventricular.

Figure 6.. Bedside to Bench Interdisciplinary Approach to Cardiac Sarcoidosis.

Multidisciplinary care providers and patient connections work together to provide holistic, person-centered care to the individual with sarcoidosis cardiomyopathy. This care produces clinical and patient-reported outcome measures for inclusion in a proposed multi-institution cardiac sarcoidosis registry. These data can then be used by diverse investigators to produce interventions to improve clinical care, outcomes, and patient quality of life.