Treatment Of Cardiac Sarcoidosis Research Articles

Current Practices and Emerging Therapies to Optimize Heart Failure Management in Cardiac Sarcoidosis: A Systematic Review.

Cardiac sarcoidosis (CS) is a distinctive manifestation of sarcoidosis, a multisystemic inflammatory disorder that is characterized by non-necrotizing granulomas. CS can lead to arrhythmias, heart failure (HF), and sudden cardiac death. The diagnosis of CS involves imaging in the form of a two-dimensional echocardiogram, cardiac magnetic resonance imaging (MRI), an 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan, and an endomyocardial biopsy. Treatment of CS entails corticosteroids, immunosuppressive agents, monoclonal antibodies, and, in advanced cases, heart transplantation (HTx). This systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, focusing on HF in sarcoidosis patients. Eligibility criteria include recent (2019-2024) research papers on sarcoidosis-induced heart failure, excluding other causes. The databases searched were PubMed, Google Scholar, and ScienceDirect. From 36,755 initial articles, 2,060 remained after filtering, and 17 were selected for quality assessment. Based on quality assessment, 11 studies were included in the final review. In CS, a variety of treatment strategies can be implemented. Corticosteroids are the first-line therapeutic options, and in the majority of cases, they are very successful in controlling the disease progression. Immunosuppressive agents like methotrexate and azathioprine are used to avoid long-term steroid use. Both corticosteroids and immunosuppressives act by reducing inflammation and preventing myocardial scarring. Biological agents like infliximab and adalimumab prevent disease progression by targeting specific inflammatory pathways and are used in refractory cases. Regular HF management drugs like angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), sodium-glucose transport protein 2 (SGLT2) inhibitors, beta-blockers, and diuretics help in optimizing cardiac function. In severe cases, a left ventricular assist device (LVAD) may be required. The ultimate treatment for end-stage CS is HTx, which has to be supplemented with a strong, individualized regimen of glucocorticoids and immunosuppressives to avoid graft rejection and to control sarcoidosis. Due to a lack of standard protocols for management and limited knowledge about CS, the ideal treatment of HF is still a matter of debate. Hence, further research and clinical trials need to be performed to optimize patient outcomes.

Abstract 11916: An Elusive and Unusual Diagnosis of Cardiac Sarcoidosis

Introduction: Cardiac sarcoidosis (CS) can present heterogeneously; presentations are often related to conduction system abnormalities in the form of AV block or ventricular arrhythmia, or heart failure. There are not yet widely accepted diagnostic guidelines for CS although diagnostic pathways such as the Japanese Ministry of Health and Welfare and the Heart Rhythm Society criteria exist. Methods: A 65 year old female with a history of hypertension, HFpEF, CAD with remote DES to RCA, CKD3a, Obesity and biopsy proven pulmonary sarcoidosis presented with 3 days of sudden onset dyspnea and hypoxia. Labs included aa pro-BNP of 16,754 pg/mL (0-299) and high-sensitivity troponin of 35 ng/L (0-14). EKG showed sinus rhythm with left axis and QTc of 499 ms. Chest Xray revealed pulmonary edema consistent with heart failure exacerbation Echocardiogram revealed EF 60-64%, normal LV and RV wall motion and thickness, and GLS of-17.2%. Left heart catheterization revealed patent RCA stent and non-obstructive CAD. She was diuresed to euvolemic state. Inpatient cardiac monitoring, repeat EKGs, and an 8 day holter monitor showed no arrhythmia or conduction abnormality. Although clinical suspicion for CS was low due lack of arrhythmia, preserved EF and several independent risk factors for HFpEF. FDG-PET was performed to rule out CS and revealed defects in basal anteroseptal and apical lateral regions consistent with sarcoid related fibrosis (Figure 1). Disseminated disease was seen in mediastinal and splenic regions. The patient was started on prednisone and methotrexate therapy for immunosuppressive treatment of CS. Conclusions: In patients with known sarcoidosis, a high index of suspicion for CS is required due to lack of clear diagnostic guidelines. Although diagnostic criteria frequently highlight systolic heart failure and arrhythmias, CS can present in patients with HFpEF, and the presence of other risk factors for diastolic heart failure should not preclude CS investigation.

Abstract 15054: Impact of Sarcoidosis-Related Admission in Patients With Heart Failure: A Nationwide Readmissions Database Analysis (2017-2020)

Background: Sarcoidosis is an infiltrative systemic disorder that commonly involves the heart. Despite a higher prevalence of herat failure (HF) among patients with cardiac sarcoidosis (CS), data on these patients’ outcomes remain scarce. Objective: This study aimed to assess the impact of concomitant CS in patients admitted for HF on in-hospital outcomes and 30-day readmission rates. Methods: Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged 18 years or older who were admitted with a primary diagnosis of HF between 2017 and 2020. We stratified the cohort into two groups depending on the presence of sarcoidosis diagnosis. The in-hospital outcomes of both groups were assessed with weighted propensity score matching and multivariable analyses. Results: Our analysis included 1,902,068 patients with a primary diagnosis of HF, whereby 9,343 (0.49%) patients had sarcoidosis. Via multivariable analysis, sarcoidosis was associated with an increased risk of prolonged hospital stays (aOR: 1.15 [95% CI: 1.08 - 1.23], p<0.01), 30-day readmission (aOR: 1.18 [95% CI: 1.11 - 1.25], p=0.01), and higher cumulative cost of hospitalization ($16,179 vs $13,421, p<0.01) among HF cohort. Sarcoidosis was not associated with an increased risk of early mortality. Among HF patients with sarcoidosis, the most common cause of 30-day readmission was cardiovascular causes (59%), where decompensated HF accounted for 50% of the readmission, followed by ischemic heart disease (2%), valvular heart disease (1%), and pulmonary embolism (1%). Conclusion: In conclusion, our study suggests that HF patients with sarcoidosis had poorer in-hospital outcomes with prolonged hospital stays, higher 30-day readmission rates, and increased cumulative hospitalization costs. These findings merit increased effort in the early diagnosis and treatment of CS to improve outcomes in HF patients with sarcoidosis.

An International Survey of Current Clinical Practice in the Treatment of Cardiac Sarcoidosis

Cardiac sarcoidosis (CS) is a potentially serious form of infiltrative cardiomyopathy. Despite scarce evidence, immunosuppressive treatment is generally recommended, but local routines may vary significantly. We sought to survey the clinical practices in the treatment of CS, with the aim that the results may suggest future research priorities. We conducted a web-based survey focused on treatment-naive patients with CS. We subclassified CS according to the presence/absence of overt cardiac presentation (clinically manifest/silent) and to the presence/absence of active inflammation (metabolically active/inactive by fluorodeoxyglucose positron emission tomography). The survey was developed jointly by the authors and administered to expert clinicians (n=79) involved in CS treatment. An agreement threshold was set at 70%. A total of 62 of 79 respondents (78.5%) from 12 countries completed the survey. The agreement threshold was reached for: (1) always treating clinically manifest, metabolically active CS, 57 of 62 (91.9%), (2) never treating clinically silent, metabolically inactive CS, 44 of 62 (71.0%), (3) not requiring histopathologic confirmation of sarcoidosis before treatment initiation, (49 of 62, 79.0%), (4) using fluorodeoxyglucose positron emission tomography for assessing treatment indication (44 of 62, 71.0%) and treatment response (44 of 62, 71.0%), and (5) using prednisone as a first-line agent (100%), although respondents were divided on monotherapy (69.4%) or combination with methotrexate 25.8%. The approach to particular scenarios, tapering, and duration of treatment showed the greatest variation in response. In conclusion, in this survey of clinical practice, important aspects of CS treatment reached the agreement threshold, whereas others showed a great degree of clinical equipoise.

Diagnosis and Treatment of Cardiac Sarcoidosis.

About 5% of sarcoidosis patients develop clinically manifest cardiac features. Cardiac sarcoidosis (CS) typically presents with conduction abnormalities, ventricular arrhythmias and heart failure. Its diagnosis is challenging and requires a substantial degree of clinical suspicion as well as expertise in advanced cardiac imaging. Adverse events, particularly malignant arrhythmias and development of heart failure, are common among CS patients. A timely diagnosis is paramount to ameliorating outcomes for these patients. Despite weak evidence, immunosuppression (primarily with corticosteroids) is generally recommended in the presence of active inflammation in the myocardium. The burden of malignant arrhythmias remains important regardless of treatment, thus leading to the recommended use of an implantable cardioverter defibrillator in most patients with clinically manifest CS.

Modern approaches to the diagnosis and treatment of cardiac sarcoidosis: results of a cohort study

Aim. To analyze clinical and paraclinical data in patients with documented cardiac sarcoidosis, outlining the key points of diagnosis and selection of the optimal treatment.Material and methods. For the period from 2016 to 2021, 63 patients (50,4±14,1 years) were included in the cohort study on negotiability. Based on a standard examination, 15 patients (41±13 years old) were selected, who continued the examination to confirm the diagnosis of cardiac sarcoidosis. Contrast-enhanced cardiac magnetic resonance imaging (MRI) was performed in 10 patients, while endomyocardial biopsy in 7 patients. All patients underwent 18F-fluorodeoxyglucose positron emission tomography (PET).Results. The most common (53%) electrocardiographic abnormality was right bundle branch block. Ventricular arrhythmias and high-grade atrioventricular block were recorded mainly in patients with documented activity. Regional contractility disorders were predominantly detected in patients with cardiac fibrosis. Delayed contrast enhancement according to cardiac MRI was recorded mainly intramurally in the interventricular septum and subepicardial area of left ventricular (LV) lateral wall. When analyzing the PET results, we found the predominant radiopharmaceutical accumulation in the interventricular septum (56%), lateral (44%) and anterior (33%) LV walls. There was no significant improvement in global LV contractility against the background of immunosuppressive therapy, especially in patients with reduced ejection fraction: initially 49,2±10,1% vs 46,9±14,9% during therapy (p=0,658).Conclusion. A certain apprehensive attitude of the doctor and adherence to the algorithm for early diagnosis of cardiac sarcoidosis allows minimizing the risks of fatal cardiovascular events. On the contrary, in the case of late diagnosis, even the use of aggressive immunosuppressive therapy does not lead to an improvement in global myocardial contractility, and fibrosis zones can cause life-threatening bradyarrhythmias and ventricular arrhythmias.

Abstract 14466: Recurrent Heart Block Due to Cardiac Sarcoidosis in a Patient With Interrupted Glucocorticoid Therapy

Background: Cardiac involvement is a major cause for mortality in patients with systemic sarcoidosis. Atrioventricular (AV) block caused by inflammation involving the conduction system is one of the major manifestations of cardiac involvement. The mainstay of management is immunosuppressive therapy and device implantation if high degree AV block is present. However, there is lack of evidence regarding the appropriate dose and duration of corticosteroids in the treatment of cardiac sarcoidosis. Case summary: We describe the case of a 62-year-old man who presented with symptoms of dyspnea and bradycardia and was found to be in second degree AV block type II. Computed tomography of the chest showed hilar lymphadenopathy. Echocardiography revealed reduced systolic function (LVEF of 35-40%). A FDG-PET scan showed hypermetabolic activity of the interventricular septum and pericardium consistent with sarcoidosis. Bronchoscopy with BAL and EUS biopsies revealed necrotizing granulomas consistent with pulmonary sarcoidosis. ICD/pacemaker implantation was discussed; however the patient deferred and ultimately underwent Boston Scientific ILR placement to monitor for arrhythmias. He was started on methotrexate and prednisone with improvement in heart rate from 2:1 AV block (rates 30's) to sinus rhythm with rates in the 60's. Subsequent stress testing demonstrated improvement in heart rate with exercise to 113 bpm. His AV block had decreased in frequency per Implantable loop recorder (ILR) monitoring. A month later, the patient stopped taking prednisone and methotrexate and developed a symptomatic recurrence of 2:1 AV block. He then underwent dual chamber pacemaker implantation with ILR explant. Discussion: This case highlights the importance of maintaining and educating patients about long term immunosuppressive treatment in cardiac sarcoidosis to prevent recurrence of conduction abnormalities. The initial dose for those receiving prednisone is typically 40mg daily, while for those patients receiving an additional immunosuppressive agent, the initial dose can be 20mg daily. Based on response to treatment after 1 to 3 months, immunosuppressive therapy should be continued for an additional 9 to 12 months.

Abstract 10946: Myocardial Inflammatory Activity and Oxidative Stress Immunosuppressive Therapy Are Associated With Prognosis in Patients With Cardiac Sarcoidosis

Background: P atients with cardiac sarcoidosis (CS) have been shown to be at an increased risk of major adverse cardiovascular events (MACE). Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of MACE. Immunosuppressive therapy is recommended for the treatment of active CS. After immunosuppressive therapy, however, there is no predictable markers for prognosis. We hypothesized that the inflammation and oxidative stress in heart were associated with MACE. Aim: We identified prognostic markers for MACE in patients with CS after steroid therapy. Methods: This prospective cohort study enrolled 103 consecutive patients with CS diagnosed according to the Japanese guideline; Of 103 CS patients, 39 patients underwent 18F-FDG PET/CT 6 months after steroid therapy, and levels of urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG) as a marker of oxidative DNA damage, other biomarkers, indices of cardiac function, and renal function were measured. Then they were followed up for a median of 42 months. The primary endpoint was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and worsening CS with increased accumulation of FDG in heart and exacerbation of clinical manifestation. Results: During the follow-up period, 7 of 30 patients showed sVT/SCD (N= 9), hospitalization (N= 2) and worsening CS (N= 4). A Cox proportional-hazard model showed that U-8-OHdG concentration and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis showed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 14.2 ng/mg·Cr and 4.6 respectively. Patients with a U-8-OHdG ≥ 14.2 ng/mg·Cr or SUV max ≥4.6 had a significantly higher MACE risk (Figure A and B). Conclusions: U-8-OHdG and SUV max after steroid therapy were powerful predictors of MACE in CS, suggesting that CS patients with high U-8OHdG and/or high SUV max might be resistant to steroid therapy.

Cardiac involvement in sarcoidosis: Evolving concepts in diagnosis and treatment

Clinically evident cardiac involvement has been noted in at least 2 to 7% of patients with sarcoidosis, but occult involvement is much higher (> 20%). Cardiac Sarcoidosis (CS) is often not recognized as an 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. The prognosis of CS is related to the extent and site(s) of involvement. Most deaths due to CS are due to arrhythmias or conduction defects, but granulomatous infiltration of the myocardium may cause progressive and ultimately lethal cardiomyopathy. The definitive diagnosis of isolated CS is difficult and the yield of Endomyocardial Biopsies (EMB) is low. Treatment of CS is often warranted even in the absence of histologic proof. Radionuclide scans are integral to the diagnosis. Gadolinium-enhanced cardiac magnetic imaging scans and 18Fluorodeoxyglucose (18FDG)-Positron Emission Tomography (PET) are the key imaging modalities to diagnose CS. The prognosis of CS is variable, but mortality rates of untreated CS are high. Randomized therapeutic trials have not been done, but corticosteroids (alone or combined with additional immunosuppressive agents) are the mainstay of therapy. Additionally, anti-arrhythmic agents and therapy for heart failure are often required. Because of the potential for sudden cardiac death, an Implantable Cardioverter-Defibrillator (ICD) should be placed in any patient with CS and serious ventricular arrhythmias or heart block and should be considered for cardiomyopathy. Cardiac transplantation is a viable option for patients with end-stage CS refractory to medical therapy.

Cardiac sarcoidosis: from diagnosis to treatment.

Sarcoidosis is a systemic granulomatous disease of unknown cause. Its clinical presentations are heterogeneous and virtually any organ system can be affected, most commonly lungs. The manifestations of cardiac sarcoidosis (CS) are heterogenous depending on the extent and location of the disease and range from asymptomatic forms to life-threatening arrhythmias as well as to progressive heart failure. Cardiac involvement is associated with a worse prognosis. The diagnosis of CS is often challenging and requires a multimodality approach based on current international recommendations. Pharmacological treatment of CS is based on administration of anti-inflammatory therapy (mainly corticosteroids), which is often combined with heart failure medication and/or antiarrhythmics. Nonpharmacological therapeutic approaches in CS cover pacemaker or defibrillator implantation, catheter ablations and heart transplantation. This review aims to summarize the current understanding of CS including its epidemiology, etiopathogenesis, clinical presentations, diagnostic approaches, and therapeutic possibilities.

Role of QRS amplitude, fractionation and duration in predicting clinical response to anti-inflammatory treatment in cardiac sarcoidosis

Abstract Background Low QRS amplitude (QRSa), QRS fractionation (QRSf) and longer QRS duration (QRSd) are markers of myocardial fibrosis and inflammation in non-ischemic cardiomyopathy (NICM). Objective To determine if reduction of inflammation with treatment of cardiac sarcoidosis (CS) may reverse these 12 lead ECG parameter changes. Methods 21 patients (pts) with CS and VT ablation with a positive baseline positron emission tomographic (PET 1) scan were studied. All pts received prednisone ≥40 mg for 4 to 8 weeks followed by a taper and maintenance with methotrexate ± low-dose prednisone, <10 mg/day, until clinically stable and resolution of inflammation on PET 2 one year after initial. In addition, pts with low LV ejection fraction (13/21) received guideline directed medical therapy for heart failure. Pts at 1yr with positive PET2 (9) were compared to those with negative PET2 (12). Baseline and 1yr 12-lead ECGs were analyzed for QRSd, ≥2QRSf contiguous leads and QRSa in the limb leads. Results Pts in PET2(+) vs PET2(−) groups has similar gender (men 89% vs 100%, p=0.42), age (57±8 vs 56±10 years, p=0.8) and LV ejection fraction (41±11 vs 46±11, p=0.31). Baseline 12-lead ECGs showed similar QRSd, ≥2QRSf contiguous leads and QRSa for PET2(+) vs PET2(−); P all >0.15 (Table 1). At 1 yr there was a lower prevalence of ≥2QRSf contiguous leads and strong trend for shorter QRS duration and larger QRSa in lead DI if PET2(−) vs PET2(+). 4 pts demonstrated loss of QRSf 2 contiguous leads and/or increase in QRSa in DI by at least 0.15 mV from baseline if PET2(−) and none if PET2(+). Conclusions In pts with CS and VT, reversal of inflammation may result in a greater QRSa and reduction in QRSf. An increase in QRSa in lead 1 by >0.15mV and/or loss of QRSf identifies a clear positive response to treatment and negative PET at 1 year. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Richard T and Angela Clark Innovation Fund in Cardiovascular Medicine, the Mark S Marchlinski EP Research and Education Fund and the Winkelman Family Fund in Cardiovascular Innovation. Table 1

Sarcoid Heart Disease: an Update on Diagnosis and Management.

The purpose of this review is to provide an update on cardiac sarcoidosis (CS) and to discuss the current recommendations and progress in diagnosis and management of this disease. Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Cardiac involvement is seen in at least 25% and is associated with poor prognosis. Manifestations of cardiac sarcoidosis (CS) can vary from presence of silent myocardial granulomas, which may lead to sudden death, to symptomatic conduction abnormalities, ventricular arrhythmias, and heart failure. We discuss newer imaging modalities such as cardiac magnetic resonance imaging and positron emission tomography in conjunction with clinical criteria increasingly used for diagnosing and prognosticating patients with CS. Immunosuppression (primarily corticosteroids) is recommended for treatment of CS; however, its efficacy has never been proven in prospective randomized studies. The role of imaging to guide the use of immunotherapy is unknown. Cardiac sarcoidosis continues to challenge clinicians due to its protean presentations, lack of diagnostic standards, and data for risk stratification and treatment. There is a need for prospective, randomized controlled trials to understand how best to diagnose and treat cardiac sarcoidosis.

Clinical and Imaging Response to Tumor Necrosis Factor Alpha Inhibitors in Treatment of Cardiac Sarcoidosis: A Multicenter Experience

BackgroundCardiac sarcoidosis (CS) is an increasingly recognized cause of cardiomyopathy; however, data on immunosuppressive strategies are limited. Treatment with tumor necrosis factor (TNF) alpha inhibitors is not well described; moreover, there may be heart failure–related safety concerns. MethodsRetrospective multicenter study of patients with CS treated with TNF alpha inhibitors. Baseline characteristics, treatments, and outcomes were adjudicated. ResultsThirty-eight patients with CS (mean age 49.9 years, 42% women, 53% African American) were treated with TNF alpha inhibitor (30 infliximab, 8 adalimumab). Prednisone dose decreased from time of TNF alpha inhibitor initiation (21.7 ± 17.5 mg) to 6 months (10.4 ± 6.1 mg, P = .001) and 12 months (7.3 ± 7.3 mg, P = .002) after treatment. On pre-TNF alpha inhibitor treatment positron emission tomography with 18-flourodoxyglucose (FDG-PET), 84% of patients had cardiac FDG uptake. After treatment, there was a significant decrease in number of segments involved (3.5 ± 3.8 to 1.0 ± 2.5, P = .008) and maximum standardized uptake value (3.59 ± 3.70 to 0.57 ± 1.60, P = .0005), with 73% of patients demonstrating complete resolution or improvement of cardiac FDG uptake. The left ventricular ejection fraction remained stable (45.0 ± 16.5% to 47.0 ± 15.0%, P = .10). Four patients required inpatient heart failure treatment, and 8 had infections; 2 required treatment cessation. ConclusionsTNF alpha inhibitor treatment guided by FDG-PET imaging may minimize corticosteroid use and effectively reduce cardiac inflammation without significant adverse effect on cardiac function. However, infections were common, some of which were serious, and therefore patients require close monitoring for both infection and cardiac symptoms.

Comparing and Contrasting Guidelines for the Management of Cardiac Sarcoidosis.

Introduction: The Japanese Circulation Society (JCS) recently published new guidelines for the diagnosis and treatment of Cardiac Sarcoidosis (CS). There are two other guideline documents, the World Association of Sarcoidosis and Other Granulomatous Disorders Sarcoidosis Organ (WASOG) Assessment Instrument created in 1999 and updated in 2014. Also, in 2014, the Heart Rhythm Society (HRS) published their international guideline document. As co-chair of the HRS document I have been invited to compare and contrast the management aspects of the HRS guidelines with the new JCS document. Comments: (i) The HRS document recommended a stepwise approach to VT management and the JCS document is somewhat similar; but with some key differences. (ii) The HRS statement suggested that an ICD for CS patients with an indication for a pacemaker "can be useful". The JCS document take a similar position although with some additional criteria related to National Health Institute Coverage guidelines. (iii) Both HRS and the JCS documents agree that ICDs are recommended in patients with general guideline indications for primary prevention (i.e. LVEF less than 35%). However which additional patients should be considered for ICDs is controversial. The 2016 JCS document is broadly similar, with the major exception that it is recommended that all patients with LVEF 35-50% should have an EP study. Conclusion: The Japanese have been leaders in many aspects of CS including in guideline development. It is clear that the future of CS management is bright, with increasing international collaborations and also multiple efforts underway to obtain higher quality data to inform future guidelines.

P1806Diagnosis of isolated cardiac sarcoidosis using FDG-PET/CT on the basis of new guidelines

Abstract Introduction Sarcoidosis is a systemic inflammatory disease which can involve any organs. The reported prevalence of isolated cardiac sarcoidosis (CS) varies widely because of the lack of an agreed definition of isolated CS (iCS). ICS was newly defined in the new guidelines for CS by Japanese Circulation Society. Purpose We aimed to examine the diagnostic accuracy of 18F-FDG PET/CT and the ratio of iCS in the whole CS by reviewing the patients with suspected CS undergoing the whole-body and cardiac FDG PET/CT scans. Methods We retrospectively reviewed 74 consecutive patients undergoing 18F-FDG PET/CT from 2013 to 2018 (mean age 60±14 years, 37 male) without the initiation of corticosteroid. Myocardial FDG uptake in CS was defined as a “focal” or “focal on diffuse” pattern. Systemic sarcoidosis (sCS) and iCS were diagnosed according to guidelines for the diagnosis and treatment of CS by Japanese Circulation Society. In short, iCS was diagnosed clinically when no clinical findings of sarcoidosis in any other organs and FDG uptake in heart were shown in addition to the following three of four criteria: high-grade atrioventricular block or fatal ventricular arrhythmia, structural abnormality, left ventricular contractile dysfunction, and delayed Gadolinium enhancement of myocardium on MRI. Results Of 31 patients with extra-cardiac sarcoidosis, 10 already met the diagnostic criteria of sCS before undergoing 18F-FDG PET/CT and 11 was newly diagnosed as sCS after FDG PET/CT. Of the remaining 43 without extra-cardiac sarcoidosis, 18 had FDG uptake in heart. Of 18 with FDG uptake in heart, iCS was diagnosed in 7, and sCS in 3 with extra-cardiac uptake of FDG as well as myocardium. Finally, 24 and 7 patients met the criteria of sCS and iCS based on the guideline, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG PET/CT for CS including sCS and iCS were 90, 87, 88, 85, and 92%, respectively. Conclusion The ratio of iCS on the basis of new guidelines for diagnosis and treatment of CS was 22% of the whole CS.

Sudden death in cardiac sarcoidosis: an analysis of nationwide clinical and cause-of-death registries.

The present study was done to assess the role of sudden cardiac death (SCD) among the presenting manifestations of and fatalities from cardiac sarcoidosis (CS). We analysed altogether 351 cases of CS presenting from year 1998 through 2015 in Finland. There were 262 patients with a clinical diagnosis and treatment of CS, 27 patients with an initial lifetime diagnosis of giant cell myocarditis that was later converted to CS, and 62 cases detected at autopsy and identified by screening >820000 death certificates from the national cause-of-death registry. The total case series comprised 253 females and 98 males aged on average 52 years at presentation. High-grade atrioventricular block was the most common first sign of CS (n = 147, 42%) followed by heart failure (n = 58, 17%), unexpected fatal (n = 38) or aborted (n = 12) SCD (14%), and sustained ventricular tachycardia (n = 48, 14%). Severe coronary artery disease was found at autopsy concomitant with CS in four of the 38 cases presenting with fatal SCD. Of all deaths recorded till the end of 2015, 64% (n = 54/84) were unexpected SCDs from CS that had either been silent during life or defied all attempts at diagnosis. The Kaplan-Meier estimate (95% CI) of survival from symptom onset was 85% (80-90%) at 5 years and 76% (68-84%) at 10 years. Together fatal and aborted SCD constitute 14% of the presenting manifestations of CS. Nearly two-thirds of all fatalities from CS are caused by undiagnosed granulomas in the heart.

Treatment of cardiac sarcoidosis: A comparative study of steroids and steroids plus immunosuppressive drugs

BackgroundWe aimed to compare the efficacy of steroids alone or associated with immunosuppressive drugs for the prevention of relapse in cardiac sarcoidosis (CS). MethodsIn this monocentric multidisciplinary retrospective single center study, all consecutive patients with histologically proven sarcoidosis hospitalized from January 2012 to December 2016 were considered. All patients with symptomatic CS were studied. Patients received steroids or steroids plus immunosuppressive drugs (IS) for CS treatment at diagnosis. The efficacy of each treatment strategy (steroids vs steroids + IS) was assessed by the cardiac relapse rate over follow up. Results326 consecutive patients with histologically proven sarcoidosis were screened. Among them, 36 (11%) had symptomatic CS (20 (55.5%) men, median age at diagnosis 48.5 [22.8–76]). Twenty-four patients received steroids and 12 received steroids + IS (azathioprine n = 5, methotrexate n = 5, cyclophosphamide n = 2) at CS diagnosis. Over a median follow up of 3.6 [1–15.2] years, 13 (36.1%) patients suffered a cardiac relapse including reduced left ventricular ejection fraction (LVEF, n = 4), third degree heart block (n = 2), atrio-ventricular (n = 1) or ventricular (n = 1) tachycardia and sudden cardiac death (n = 1). Except for a higher frequency of black patients in patients receiving IS, CS features at diagnosis and median time to relapse did not significantly differ between patients who did or did not receive IS. Relapse rate was 45.8% in the steroids group versus 16.7% in the steroids + IS group (p = 0.048). ConclusionsIn cardiac sarcoidosis, the combination of steroids with immunosuppressive drugs might reduce the risk of cardiac relapse, as compared to steroids alone.

Viewpoints in the diagnosis and treatment of cardiac sarcoidosis: Proposed modification of current guidelines.

Isolated cardiac sarcoidosis is a generally accepted disease condition, and the low yield of endomyocardial biopsy because of patchy involvement is also well known. However, current guidelines still require histologic confirmation of granuloma for the diagnosis of cardiac sarcoidosis, either in myocardial or extra-cardiac tissues. Therefore, only a presumptive diagnosis of chronic multifocal myocarditis of unknown origin can be made in a large number of patients in whom the only considerable diagnosis is cardiac sarcoidosis based on current knowledge. Even if these patients are treated with the same treatment scheme as that for cardiac sarcoidosis, which may not cause harm in the absence of a definite diagnosis, the true spectrum of cardiac sarcoidosis could not be determined for deciding the optimal treatment strategy. In addition, the current recommendations for dose, duration of initial steroid therapy, and treatment in patients who did not respond to initial steroid therapy are not easy to follow in real-world practice. We would like to propose a scoring system for the diagnosis of cardiac sarcoidosis and suggest our adoption or modification of the diverse current recommendations.

O28-3 - A Case of Amyloid Cardiomyopathy Proved by Myocardial Biopsy but Diagnosed as Isolated Cardiac Sarcoidosis with Clinical Manifestations

A 74-year-old man with dyspnea on exertion was referred to our hospital for treatment of heart failure and evaluation of the cause. The symptom was immediately improved by medical therapy including oxygenation and diuretics. Electrocardiography showed frequent premature ventricular contraction with non-sustained ventricular tachycardia. Echocardiography revealed left ventricular (LV) dilatation (LV end-diastolic diameter/end-systolic diameter = 64/56 mm), thinning of the basal interventricular septum with severe hypokinesis of the region and LV systolic dysfunction (LVEF = 25%). Coronary angiography showed patent coronary artery. Late gadolinium enhancement in cardiac MR imaging was observed in septal to anterior wall. Furthermore, his lysozyme value was high (13.6 µg/mL). Cardiac sarcoidosis was strongly suspected, and 18F-fluorodeoxy glucose-positron emission tomography imaging showed lightly increased uptake in interventricular septum. Although he did not have the clinical findings other than heart, based on current guidelines for diagnosis and treatment of cardiac sarcoidosis (JCS 2016), a diagnosis of isolated cardiac sarcoidosis was finally made and we decided to start corticosteroid therapy with the initial dose of 30 mg/day of prednisolone. However, the specimens of myocardial biopsy revealed significant amount of transthyretin amyloid deposit. In addition 99mTc-pyrophosphate scintigraphy showed increased uptake by interventricular septum. In this case, there are two possibilities: first, all clinical manifestations due to transthyretin cardiac amyloidosis, and second, a chance complication with cardiac sarcoidosis and amyloid cardiomyopathy.

Cardiac sarcoidosis: challenges in clinical practice.

To address the current recommendations for screening, diagnosis, and treatment of cardiac sarcoidosis and the difficulties to put these recommendations into clinical practice. The incidence of cardiac sarcoidosis appears to be higher than earlier reported, probably because of improved imaging techniques. Late gadolinium enhancement with cardiac MRI (LGE-CMR) and fluorodeoxyglucose positron emission tomography obtained a central role in the diagnostic algorithm and monitoring of disease activity. New techniques are being investigated: T1 and T2 mapping for early detection in CMR, a sarcoid-specific tracer in PET, integrated positron emission tomography/MRI scanners, and assessment of scar with LGE in cardiac computed tomography. Isolated cardiac sarcoidosis is an increasingly recognized phenotype, but still an enormous challenge in clinical practice. The prognostic value of (and extent of) LGE-CMR should be taken into account for risk assessment and internal cardiac defbrillator therapy, even in patients with preserved left ventricular function. Unfortunately, randomized controlled trials to guide immunosuppressive therapy are still lacking. A multidisciplinary approach to diagnose and treat cardiac sarcoidosis patients in specialized centers is strongly recommendable. Cardiac sarcoidosis is increasingly recognized because of improved imaging techniques; however, treatment of cardiac sarcoidosis is still mainly based on expert opinion.