Management Of Cardiac Sarcoidosis Research Articles

Correction to: Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.

Correction to: Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.

The role of infliximab in treating refractory cardiac sarcoidosis. Case series and systematic review of literature.

Cardiac sarcoidosis is associated with significant morbidity and mortality. Immunosuppressive treatment focuses on suppressing myocardial inflammation, which can lead to major adverse events especially when progressing to fibrosis. Conventional management usually includes steroids and steroid sparing agents such as methotrexate and azathioprine. Tumour necrosis factor alpha inhibitors are often reserved for those with a worsening clinical status and/or evidence of persistent inflammatory activity despite conventional therapy. Refractory cardiac sarcoidosis (CS) can be defined as the persistence or progression of active disease, evidenced either by lack of clinical response or persistence or progression of imaging abnormalities, despite being on conventional therapy. In the United Kingdom, tumour necrosis factor alpha inhibitors are currently not licensed for cardiac sarcoidosis as there are no randomised controlled trials to assess the efficacy of infliximab in this patient cohort. In this study, we present the outcomes of six patients treated with infliximab for refractory cardiac sarcoidosis at Royal Brompton Hospital and performed a systematic review of the existing literature on use of infliximab in cardiac sarcoidosis. We searched the Cochrane Library, OVID Medline, OVID Embase, Web of Science and Pubmed to identify 7 full-text studies assessing the role of infliximab in the management of cardiac sarcoidosis. Infliximab was found to play a vital role in stabilising refractory cardiac sarcoidosis by stemming clinical deterioration, arrythmia burden and even reducing steroids requirements. Further prospective trial data is necessary to validate these findings.

Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.

Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease, ventricular arrhythmias, and right or left ventricular dysfunction. Over the past several decades, the prevalence of cardiac sarcoidosis has increased. Definitive histological confirmation is often not possible, so clinicians frequently face uncertainty about the accuracy of diagnosis. Hence, the likelihood of cardiac sarcoidosis should be thought of as a continuum (definite, highly probable, probable, possible, low probability, unlikely) rather than in a binary fashion. Treatment should be initiated in individuals with clinical manifestations and active inflammation in a tiered approach, with corticosteroids as first-line treatment. The lack of randomized clinical trials in cardiac sarcoidosis has led to treatment decisions based on cohort studies and consensus opinions, with substantial variation observed across centers. This scientific statement is intended to guide clinical practice and to facilitate management conformity by providing a framework for the diagnosis and management of cardiac sarcoidosis.

MAGIC OF ADVANCED IMAGING AND IMMUNOTHERAPY IN CARDIAC SARCOIDOSIS

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: This case report emphasizes the role of advanced imaging and immunotherapy in the diagnosis and management of cardiac sarcoidosis (CS). CASE PRESENTATION: A 52-year-old healthy male presented with near-syncope for 5 days. He had a blood pressure of 164/67 mmHg and a heart rate of 43 bpm. Electrocardiogram revealed complete-heart-block (CHB) with a ventricular rate of 38/min. Troponin T and electrolytes were normal, and Lyme's serology was negative. Echocardiogram was normal. Cardiac magnetic resonance imaging (CMR) revealed late gadolinium enhancement (LGE) affecting the mid inferior segment at the right ventricle (RV) insertion site (Figure 1). A cardiac and whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed focal areas of increased FDG uptake in the LV involving mid and basal anteroseptal segments, mid inferoseptal segment, basal inferolateral, and basal inferior segments with normal perfusion (Figure 2). The scan also revealed hypermetabolic bilateral hilar and mediastinal lymphadenopathy. A diagnosis of CS was made. An Implantable-Cardioverter-defibrillator (ICD) was placed and the patient was discharged on 40mg of prednisone and 20mg of leflunomide. Within 4 months, he went from 100% RV pacing to 0%. Eventually, the corticosteroid was tapered off. At follow-up after 1.5 years, RV pacing remained 0% on Leflunomide 20mg. DISCUSSION: One should always suspect CS in young patients with high-grade AV block. During the workup of CHB (Figure 3), the 2017 Japanese Circulation Society Working Group Criteria for diagnosing CS was followed (1). The patient had 2 characteristic findings strongly suggestive of sarcoidosis: (a) hilar lymphadenopathy and (b) significant tracer accumulation in the myocardium and hilar lymph nodes on FDG-PET scan. He also met 2 major criteria strongly suggestive of CS: (a) LGE on CMR and (b) abnormal myocardial FDG uptake. These findings, per the criteria, establish the clinical diagnosis of CS. The mainstay of treatment for CS is corticosteroids +/- steroid-sparing agents to decrease intra-cardiac inflammation (1). CHB patients with CS have a high risk of ventricular arrhythmias, hence should receive ICD (2). The addition of antimetabolite adjuvants is more effective than corticosteroids alone (3). They may reduce the total time of glucocorticoid therapy and keep patients in remission. CONCLUSIONS: Clinical diagnosis of CS can be established with FDG-PET imaging and CMR. CS patients with advanced heart block should receive ICD. Corticosteroids are the mainstay of treatment. Immunotherapy is an effective adjunct that can help taper the glucocorticoids and keep patients in remission. Early introduction of these agents should be considered in these patients. REFERENCE #1: 1. Trivieri MG et al. Challenges in Cardiac and Pulmonary Sarcoidosis: JACC State-of-the-Art Review. J Am Coll Cardiol 2020;76:1878-1901 REFERENCE #2: 2. Nordenswan H-K et al. Outcome of Cardiac Sarcoidosis Presenting With High-Grade Atrioventricular Block. Circulation: Arrhythmia and Electrophysiology 2018;11:e006145 REFERENCE #3: 3. Nagai S, Yokomatsu et al. Treatment with methotrexate and low-dose corticosteroids in sarcoidosis patients with cardiac lesions. Intern Med 2014;53:427-33. DISCLOSURES: No relevant relationships by Roy Chung, source=Web Response No relevant relationships by Sachin Kumar, source=Web Response No relevant relationships by Raunak Nair, source=Web Response

Comment on 'Management of Cardiac Sarcoidosis in 2020'.

<p />

Management of Cardiac Sarcoidosis Using Mycophenolate Mofetil as a Steroid-Sparing Agent

BackgroundCardiac sarcoidosis (CS) is a major cause of morbidity and mortality in patients with systemic sarcoidosis. Steroid-sparing agents are increasingly used, despite a lack of randomized trials or published guidelines to direct treatment. Methods and ResultsThis retrospective study included 77 patients with CS treated with prednisone monotherapy (n = 32) or a combination with mycophenolate mofetil (n = 45) between 2003 and 2018. Baseline characteristics and clinical outcomes were evaluated. The mean patient age was 53 ± 11 years at CS diagnosis, 66.2% were male, and 35.1% were Black. The total exposure to maximum prednisone dose (initial prednisone dose × days at dose) was lower in the combination therapy group (1440 mg [interquartile range (IQR), 1200–2760 mg] vs 2710 mg [IQR, 1200–5080 mg]; P = .06). On 18F-fluorodeoxyglucose positron emission tomography scans, both groups demonstrated a significant decrease in the cardiac maximum standardized uptake value after treatment: a median decrease of 3.9 (IQR 2.7–9.0, P = .002) and 2.9 (IQR 0–5.0, P = .001) for prednisone monotherapy and combination therapy, respectively. Most patients experienced improvement or complete resolution in qualitative cardiac 18F-fluorodeoxyglucose uptake (92.3% and 70.4% for the prednisone and combination therapy groups, respectively). Mycophenolate mofetil was well tolerated. ConclusionsMycophenolate mofetil in combination with prednisone for the treatment of CS may minimize corticosteroid exposure and decrease cardiac inflammation without significant adverse effects.

Whole Body FDG PET-CT in the Evaluation and Management of Cardiac Sarcoidosis and Isolated Cardiac Sarcoidosis

Introduction Sarcoidosis is a multisystem inflammatory disease defined histologically by the formation of non-caseating granulomas. Cardiac involvement can be seen in up to 5% of cases [1]. These patients are at a high risk for major cardiac events [1]. Diagnosing and monitoring Cardiac Sarcoidosis (CS) is not trivial but can be currently accomplished by a combination of cardiac MRI and cardiac FDG PET-CT scanning [2]. With appropriate patient preparation, cardiac FDG PET has a high sensitivity for detecting cardiac lesions but also extra-cardiac lesions and for monitoring the efficacy of treatment. Discussion Current standard clinical practice consists of acquiring dedicated, limited field of view cardiac FDG PET scans. This would cover the heart and immediately adjacent thoracic structures. Although this is of great value and used with great success to diagnose and monitor cardiac sarcoidosis, it fails to assess the patient’s disease in a holistic manner. Still with this limited field of view, several reports including ours have described a high rate of extra-cardiac findings. We reviewed a series of sixty-five PET-CT scans of 54 patients referred for CS evaluation. These were performed between September 2010 and April 2013 at Yale New Haven Hospital and we found extra-cardiac findings were present in 92.3% of scans (n=60). Overall disease distribution is summarized in (Table 1). Highlight some of these extra-cardiac findings (Figures 1-4). 52.3% of these patients were asymptomatic at the time of the scan. CS was diagnosed in 50.8% of patients (n=33). All the patients (100%) with CS had extra-cardiac findings. Additionally, extra-cardiac findings were present in 48.3% of the scans when there was no cardiac involvement. In our cohort, we had no cases of Isolated Cardiac Sarcoidosis (ICS).

Utility of FDG PET and Cardiac MRI in Diagnosis and Monitoring of Immunosuppressive Treatment in Cardiac Sarcoidosis.

To compare the contributions of cardiac MRI and PET in the diagnosis and management of cardiac sarcoidosis (CS), with particular reference to quantitative measures. This is a retrospective, observational study of 31 patients (mean age, 45.7 years) with proven extracardiac sarcoidosis and possible CS who were investigated with fluorine 18 fluorodeoxyglucose (FDG) PET/CT and cardiac MRI. Patients were treated at physicians' discretion with repeat combined imaging after an interval of 102-770 days (median, 228 days). Significant myocardial FDG uptake was shown on visit 1 (myocardial maximum standardized uptake value [SUVmax] > 3.6) in 17 of 22 patients who were subsequently treated. Myocardial SUVmax decreased at follow-up (6.5 to 4.0; P < .01) and was matched by significant decreases in FDG-avid lung and mediastinal node disease. A volumetric measure of myocardium above a threshold SUV (cardiac metabolic volume) decreased from a mean of 42.5 to a mean of 4.1 (P < .001). This was associated with significant improvement in the left ventricular ejection fraction (LVEF) (45.8 increasing to 50.9; P < .031). There was no change in volume of late gadolinium enhancement at treatment. Patients who were untreated showed no change in any FDG PET or cardiac MRI parameter. Myocardial FDG uptake in patients suspected of having CS is presumed to represent active inflammation. When treated with corticosteroids, this resolved or regressed at follow-up, with an improvement in LVEF and FDG-avid thoracic disease. Patients who were untreated showed no change in any parameter. Quantification of FDG-avid myocardium using cardiac metabolic volume is proposed as a useful objective measure for assessing response to therapy.© RSNA, 2020See also commentary by Gutberlet in this issue.

P1483 Noninvasive multimodality imaging in diagnosis and management of cardiac sarcoidosis (CS)

Abstract Introduction The clinical presentation of cardiac sarcoidosis (CS) ranges from an incidentally discovered condition to heart failure with risk of sudden cardiac death (SCD). As there is no single reliable test for detecting CS, noninvasive multimodality imaging plays a crucial role in establishing the diagnosis and SCD risk-stratification. We present a case of a young patient diagnosed with CS in whom, on the basis of multiple imaging results, dual-chamber ICD for primary prevention was implanted outside practice guidelines. Case A 37-year-old woman was admitted to our hospital due to occasional palpitations and incidentally recorded nonsustained monomorphic ventricular tachycardia (VT). One year ago she was diagnosed with pulmonary sarcoidosis and was put on methylprednisolone; ECG, 24-h Holter monitoring and echocardiogram were normal. In the present admission control echocardiogram, with the exception of decreased longitudinal deformation of the basal and mid segments of the infero- and anterolateral left ventricle (LV) wall, was unremarkable. However, cardiac magnetic resonance (CMR) showed sub-epicardial late gadolinium enhancement (LGE) along the lower third of the antero- and inferolateral LV free wall and in the apical lateral segment of LV. Apart from some focal metabolically active lesions in the lungs and liver, fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) displayed increased metabolic activity in the apical half of the antero- and infero-lateral segments of the LV. On the basis of this results CS was confirmed. Given the age, reduced longitudinal strain, notable LV LGE presence and increased cardiac metabolic activity, dual-chamber ICD to prevent SCD and possible bradycardia risk was implanted. The patient continued with immunosupressive therapy; 8 mg of methylprednisolone every other day. Conclusion In our case, integrated multimodality imaging played a crucial role in establishing CS diagnosis and SCD risk stratification. A comprehensive evaluation of patients with CS is vital for making the best clinical decisions.

Cardiac sarcoidosis: diagnosis and management.

Sarcoidosis is a chronic inflammatory disease of unknown etiology characterized by multi-organ involvement. End-organ disease consists of granulomatous inflammation, which if left untreated or not resolved spontaneously, leads to permanent fibrosis and end-organ dysfunction. Cardiac involvement and fibrosis in sarcoidosis occur in 5-10% of cases and is becoming increasingly diagnosed. This is due to increased clinical awareness among clinicians and new diagnostic modalities, since magnetic resonance imaging and positron-emission tomography are emerging as "gold standard" tools replacing endomyocardial biopsy. Despite this progress, isolated cardiac sarcoidosis is difficult to differentiate from other causes of arrhythmogenic cardiomyopathy. Cardiac fibrosis leads to congestive heart failure, arrhythmias and sudden cardiac death. Immunosuppressives (mostly corticosteroids) are used for the treatment of cardiac sarcoidosis. Implantable devices like a cardioverter-defibrillator may be warranted in order to prevent sudden cardiac death. In this article current trends in the pathophysiology, diagnosis and management of cardiac sarcoidosis will be reviewed focusing on published research and latest guidelines. Lastly, a management algorithm is proposed.

A new era of imaging for diagnosis and management of cardiac sarcoidosis: Hybrid cardiac magnetic resonance imaging and positron emission tomography

A new era of imaging for diagnosis and management of cardiac sarcoidosis: Hybrid cardiac magnetic resonance imaging and positron emission tomography

Cardiac Sarcoidosis.

In this state-of-the-art review, we highlight our current understanding of diagnosis, assessment, and management of cardiac sarcoidosis (CS), focusing on recently published data and expert consensus statement guidelines. Academic interest in cardiac sarcoidosis research has increased over the past decade along with increased clinical awareness among clinicians. In 2014, the Heart Rhythm Society published the first expert consensus statement on diagnosing and managing arrhythmias associated with CS. Cardiac magnetic resonance has emerged as a valuable tool both for diagnosing CS and predicting risk of life-threatening ventricular arrhythmias based on burden of late gadolinium enhancement. Cardiac fluorodeoxyglucose-positron emission tomography now plays a role in diagnosis, risk stratification, and assessing response to immunosuppressive therapy. Collaborative, multidisciplinary research efforts are needed to further our understanding of this rare, complex disease. Two large multicenter prospective registries-the international Cardiac Sarcoidosis Consortium and the Canadian Cardiac Sarcoidosis Research Group-are enrolling patients to help provide insights into the natural history of the disease and current treatment strategies. Future research should focus on randomized controlled trials comparing different treatment strategies and identifying and testing novel therapeutic agents.

Update of diagnosis and management of cardiac sarcoidosis

心脏结节病是指结节病患者的心肌肉芽肿性病变，是结节病的少见临床表型，但因为对心脏结节病的认识不够、治疗不及时，心脏结节病患者的死亡率很高，是影响结节病患者预后的重要因素。近几年来，随着心脏增强核磁、正电子体层扫描-CT（positron emission tomography-CT，PET-CT）以及心内膜下心肌活检的应用，对心脏结节病认识有很大的进展。现就近年来心脏结节病的诊断措施、治疗方法等方面的进展进行综述，以期提高临床诊治水平，改善此类患者的预后。.

MYOCARDIAL INFLAMMATION/FIBROSIS DETECTION BY PULSE-CANCELLATION ECHOCARDIOGRAPHY IN PATIENTS WITH CARDIAC SARCOIDOSIS-CORRELATION WITH FDG-PET

Fluorodeoxyglucose positron emission tomography (FDG-PET) is used for diagnosis and management of cardiac sarcoidosis (CS). Pulse cancellation echocardiography (eSCAR) allows detection of fibrosis in post MI patients. We sought to correlate abnormal areas of myocardial enhancement by eSCAR with FDG-

Combination Therapy with Prednisone and Mycophenolate Mofetil in the Management of Cardiac Sarcoidosis

Introduction Cardiac sarcoidosis (CS) is characterized histologically by the presence of noncaseating granulomas and manifests as conduction abnormality, ventricular arrhythmia and progressive heart failure. With advances in imaging techniques, CS is being increasingly recognized as an underlying cause of cardiomyopathy. To date, there are no randomized trials or published guidelines to direct treatment strategies in CS, specifically in regards to optimal immunosuppressive therapy. We sought to describe our experience using a combination of prednisone and mycophenolate mofetil (MMF) in the treatment of patients (pts) with CS. Methods We retrospectively identified pts with CS who received either prednisone monotherapy or combination therapy with MMF. Outcomes assessed were response to immunosuppression based on occurrence of post-treatment ventricular arrhythmias, change in left ventricular ejection fraction (LVEF) on echocardiogram (recovery defined as LVEF ≥ 50%, improvement defined as any increase in LVEF) and change in inflammation on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Results Thirty-seven pts with CS were identified, 9 of whom were classified as having isolated CS. A total of 25 pts (51.5 ± 11.4 yrs old, 40% female, 40% African American (AA)) were treated with combination therapy: 16 were initiated on MMF within 60 days of prednisone and 9 greater than 60 days after prednisone. Twelve pts (57.2 ± 8.8 yrs old, 50% female, 42% AA) were treated with prednisone only. The combination therapy group, when compared to the prednisone only group, were sicker at presentation and more commonly presented with ventricular tachycardia (VT) (8/25, 32% vs 1/12, 8% respectively), advanced AV block (7/25, 28% vs 2/12, 16.7%) and EF Conclusion We found that patients with severe CS appear to respond well to combination therapy with prednisone and MMF, with more than half having improvement in LV function and two-thirds showing improvement in FDG uptake. Those with severe LV dysfunction at treatment initiation however, are less likely to recover LV function. Our experience suggests that MMF is an effective steroid-sparing therapy in patients with CS.

Radiological and nuclear medicine imaging of sarcoidosis.

Sarcoidosis is a multisystem chronic inflammatory disease of unknown etiology characterized by widespread growth of non-caseating granulomas. The diagnosis of sarcoidosis is based on clinical and imaging presentation, histologic confirmation and the absence of alternative diseases. Radiology and Nuclear Medicine play an essential role in the diagnostic work-up of patients with sarcoidosis to assess disease extent and activity. In addition, imaging modalities have shown their potential in managing these patients in terms of treatment response and prognostic assessment. Sarcoidosis has a predilection for chest involvement, showing typical and atypical manifestations in the lungs, airways and hilar/mediastinal lymph nodes. Chest radiography (X-ray) still plays an important role in suggesting diagnosis for cases with typical presentation of sarcoidosis, while computed tomography (CT) has higher accuracy in detecting early stage disease and in narrowing differential diagnosis, particularly in atypical manifestations. For extrathoracic involvement, both CT and MR (magnetic resonance) have comparable performance even though MR is the modality of choice for assessing neurosarcoidosis and cardiac sarcoidosis. In the last decades positron emission tomography/CT (PET/CT) has demonstrated an increasing and relevant value in assessing disease extent and activity, treatment planning and therapy response, with a crucial role in the management of cardiac sarcoidosis. In this article, an overview of the possible imaging manifestations of thoracic and extrathoracic sarcoidosis and current concepts on staging, response assessment and prognosis is provided. Finally, the potential applications of non-FDG radiotracers is briefly discussed.

A joint procedural position statement on imaging in cardiac sarcoidosis: from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology.

This joint position paper illustrates the role and the correct use of echocardiography, radionuclide imaging with 18F-fluorodeoxyglucose positron emission tomography, radionuclide myocardial perfusion imaging and cardiovascular magnetic resonance imaging for the evaluation and management of patients with known or suspected cardiac sarcoidosis. This position paper will aid in standardizing imaging for cardiac sarcoidosis and may facilitate clinical trials and pooling of multi-centre data on cardiac sarcoidosis. Proposed flow charts for the work up and management of cardiac sarcoidosis are included.

Update on the diagnosis and management of cardiac sarcoidosis

Update on the diagnosis and management of cardiac sarcoidosis

SY15-4 - Current Status and Future Perspectives in the Diagnosis and Management of Cardiac Sarcoidosis

A new guideline for cardiac sarcoidosis (CS) is published. This guideline highlights new imaging modalities such as cardiac magnetic resonance imaging (CMR) and 18F-fluorodeoxy glucose (18F-FDG) PET, and isolated cardiac sarcoidosis (iCS). Late gadolinium enhancement (LGE) of CMR and abnormal 18F-FDG uptake in the myocardium are adopted as major criteria. Clinical diagnosis of iCS is defined for the first time, although the definition of iCS is controversial. However, 18F-FDG PET still has a problem regarding myocardial accumulation without inflammation in spite of long fasting time and dietary modification. T2 weighed images of CMR are rarely available in limited cases. Since histologic confirmation of sarcoidosis is essential for the diagnosis in the Western countries, but not in Japan, it is urgently required to improve reliability in those imaging modalities. The aim of medical treatment for CS is to control the inflammatory process by immunosuppressant to prevent further deterioration and sudden cardiac death. However, optimal treatment protocol and reliable markers for evaluating inflammatory activity still remains to be established. Although implantable cardioverter defibrillator is needed in selected patients to prevent sudden death, the indication remains controversial. Cardiac resynchronization therapy and mitral surgical treatment have been introduced in CS patients with refractory heart failure. Future perspectives in the diagnosis and management of CS are discussed in this presentation.

Role of Imaging in Evaluating Infiltrative Heart Disease.

Infiltrative heart disease is caused by the deposition of abnormal substances in the heart and can lead to abnormalities in cardiac function and electrical conduction. Advances in non-invasive cardiovascular imaging have allowed for improved diagnosis of infiltrative heart disease, as well as ways to track disease progression or regression, thus enabling a mechanism to follow response to therapy. In this review, we provide an overview of the role of imaging in the diagnosis and management of cardiac sarcoidosis (CS) and cardiac amyloidosis (CA), as well as outline a proposed algorithm for using non-invasive cardiovascular imaging for evaluating these conditions.