Management of Cardiac Sarcoidosis in 2020

Sarcoidosis is an inflammatory granulomatous disease that can affect any organ. Up to one-quarter of patients with systemic sarcoidosis may have evidence of cardiac involvement. The clinical manifestations of cardiac sarcoidosis (CS) include heart block, atrial arrhythmias, ventricular arrhythmias and heart failure. The diagnosis of CS can be challenging given the patchy infiltration of the myocardium but, with the increased availability of advanced cardiac imaging, more cases of CS are being identified. Immunosuppression with corticosteroids remains the standard therapy for the acute inflammatory phase of CS, but there is an evolving role of steroid-sparing agents. In this article, the authors provide an update on the diagnosis of CS, including the role of imaging; review the clinical manifestations of CS, namely heart block, atrial and ventricular arrhythmias and heart failure; discuss updated management strategies, including immunosuppression, electrophysiological and heart failure therapies; and identify the current gaps in knowledge and future directions for cardiac sarcoidosis.

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The prevalence of cardiac sarcoidosis is underestimated: [18F]FDG-PET is the answer

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab111.071 ◽

2021 ◽

Vol 22 (Supplement_3) ◽

Author(s):

J Borges-Rosa ◽

M Oliveira-Santos ◽

R Silva ◽

J Lopes De Almeida ◽

L Goncalves ◽

...

Keyword(s):

Heart Failure ◽

Fdg Pet ◽

Cardiac Involvement ◽

Cardiac Sarcoidosis ◽

Clinical Manifestations ◽

European Population ◽

Response To Therapy ◽

Histological Diagnosis ◽

18F Fdg

Abstract Funding Acknowledgements Type of funding sources: None. Background Overt cardiac involvement is reported in 5% of patients with sarcoidosis, although autopsy and imaging studies suggest higher prevalence, worldwide variation. The role of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) in non-invasive diagnosis and follow-up has increased in the last decade. Purpose Our goal is to describe the prevalence, clinical manifestations and outcomes of cardiac sarcoidosis (CS), diagnosed through [18F]FDG-PET, in a southern European population. Methods We included all patients with histological diagnosis of extracardiac sarcoidosis screened with [18F]FDG-PET between 2009 and 2020. We collected data on clinical manifestations, cardiac magnetic resonance (CMR) results, and mortality outcomes and compared those with and without cardiac involvement. We applied the criteria for the diagnosis of CS from Heart Rhythm Society. Results Of the 400 patients screened with [18F]FDG-PET, 128 had a histological diagnosis of extracardiac sarcoidosis (54.7% females, mean age 51.0 ± 14.2 years). None underwent endomyocardial biopsy. Ten patients had a pattern of [18F]FDG uptake consistent with CS defined as diffuse (n = 5), focal (n = 3), and focal on diffuse (n = 2). Of the 128 patients, 14 also underwent CMR, which identified 2 subjects with positive findings in both modalities and 3 additional patients: focal (n = 1), multifocal mid-wall (n = 2), focal mid-wall (n = 2), and multifocal subepicardial (n = 1) delayed gadolinium enhancement. Overall, 13 patients (10.2%) fulfilled the criteria for probable CS (53.8% female, mean age 56.2 ± 12.6 years), all with multiorgan involvement, mostly lung and lymph nodes (each 92%), followed by skin and central nervous system (each 15%). Median left ventricle ejection fraction was 62% [55-65] and there were cardiac manifestations of CS in 6 patients (46%): sick sinus syndrome (n = 2), complete heart block (n = 1), frequent premature ventricular complexes (n = 1), ventricular tachycardia plus heart failure (n = 1), and bifascicular block plus heart failure (n = 1). Eleven patients (85%) with probable CS were medicated with immunosuppressant drugs: corticosteroids (n = 9), methotrexate (n = 4), and azathioprine (n = 2). Four patients with previous [18F]FDG screening were revaluated after treatment, each showing no cardiac uptake. After a mean follow-up of 4.0 ± 1.0 years, mortality was three-fold higher in patients with cardiac involvement, despite the absence of statistical significance (15% vs. 5%, P = 0.151). Conclusions In a southern European population with histological extracardiac sarcoidosis, the prevalence of cardiac involvement was 10.2%, most asymptomatic. [18F]FDG-PET improves the diagnostic yield and plays an important role in monitoring response to therapy. The higher mortality trend in those with CS needs to be ascertained in longer follow-up.

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PATIENT CHARACTERISTICS ASSOCIATED WITH VENTRICULAR ARRHYTHMIAS, HEART BLOCK, AND HEART FAILURE IN CARDIAC SARCOIDOSIS PATIENTS

CHEST Journal ◽

10.1016/j.chest.2020.08.152 ◽

2020 ◽

Vol 158 (4) ◽

pp. A131-A132

Author(s):

Matthew Bocchese ◽

David Rosenthal ◽

Abdullah Haddad ◽

Benjamin Rosenfeld ◽

Crystal Chen ◽

...

Keyword(s):

Heart Failure ◽

Heart Block ◽

Ventricular Arrhythmias ◽

Cardiac Sarcoidosis ◽

Patient Characteristics

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Cardiac Sarcoidosis: When and How to Treat Inflammation

Cardiac Failure Review ◽

10.15420/cfr.2021.16 ◽

2021 ◽

Vol 7 ◽

Author(s):

Gerard T Giblin ◽

Laura Murphy ◽

Garrick C Stewart ◽

Akshay S Desai ◽

Marcelo F Di Carli ◽

...

Keyword(s):

Cardiac Involvement ◽

Cardiac Sarcoidosis ◽

Multidisciplinary Treatment ◽

Current Evidence ◽

Myocardial Inflammation ◽

Evidence Based ◽

Future Directions ◽

Evidence Based Treatment ◽

Inflammatory Phase ◽

Treatment Indications

Sarcoidosis is a complex, multisystem inflammatory disease with a heterogeneous clinical spectrum. Approximately 25% of patients with systemic sarcoidosis will have cardiac involvement that portends a poorer outcome. The diagnosis, particularly of isolated cardiac sarcoidosis, can be challenging. A paucity of randomised data exist on who, when and how to treat myocardial inflammation in cardiac sarcoidosis. Despite this, corticosteroids continue to be the mainstay of therapy for the inflammatory phase, with an evolving role for steroid-sparing and biological agents. This review explores the immunopathogenesis of inflammation in sarcoidosis, current evidence-based treatment indications and commonly used immunosuppression agents. It explores a multidisciplinary treatment and monitoring approach to myocardial inflammation and outlines current gaps in our understanding of this condition, emerging research and future directions in this field.

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Clinical phenotypes of cardiac sarcoidosis by latent class analysis

European Heart Journal ◽

10.1093/eurheartj/ehab724.2763 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

Q Dai ◽

B Bose ◽

P Li ◽

B Liu ◽

L Jin ◽

...

Keyword(s):

Heart Failure ◽

Latent Class Analysis ◽

Clinical Outcomes ◽

Ventricular Arrhythmias ◽

Latent Class ◽

Cardiac Sarcoidosis ◽

Information Criterion ◽

Cardiometabolic Syndrome ◽

Study Population ◽

Myocardial Involvement

Abstract Background Sarcoidosis is a systemic granulomatous disease with cardiac involvement reported in 20–27% of patients [1]. Cardiac sarcoidosis (CS) can lead to atrial or ventricular arrhythmias, various conduction system disorders, heart failure or sudden cardiac death, depending on the location of myocardial involvement [2]. Previous studies have investigated the possible types of CS based on the distribution of myocardial involvement on imaging as well as the role of genetic factors [3,4]. However, there are no studies describing the clinical heterogeneity of CS patients. Purpose In order to determine if clinical clusters exist in CS, we carried out a latent class analysis (LCA) to explore potential phenotypes in a large sample of CS patients from the National Inpatient Sample (NIS). Methods We identified 848 patients with a diagnosis of CS from the NIS in 2016–2018. A LCA was performed based on comorbidities. Utilizing the Bayesian information criterion and Akaike's information criterion we divided our study population into 3 cohorts. We subsequently applied the LCA model for our study population to fit each patient into one of the 3 cohorts. Finally, we compared the clinical outcomes among the 3 groups. Results Following LCA, patients in cohort 3 were strongly associated with a cardiometabolic syndrome profile with the highest prevalence of congestive heart failure (CHF, 95.1%), chronic kidney disease (CKD, 69.7%), diabetes mellitus (68.9%), hyperlipidemia (52.5%) and obesity (45.1%). Patients in cohort 2 had an intermediate prevalence of cardiometabolic syndrome with a universal diagnosis of hypertension (100%) but with the lowest number of CHF (32.5%) patients and none with CKD. Finally, patients in cohort 1 had the least comorbidities in comparison to the other groups but there was a higher prevalence of CHF (71.7%). There was no significant difference in mortality among the 3 groups, but acute respiratory failure was the highest in cohort 3. However, ventricular arrhythmias were more prevalent in cohort 1 patients (Table). Conclusion We identified 3 different types of CS based on their clinical phenotype. The clinical outcomes varied among the cohorts with ventricular arrhythmias being the most prevalent in patients with the least cardiometabolic comorbidities. FUNDunding Acknowledgement Type of funding sources: None.

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Heart failure with preserved ejection fraction: controversies, challenges and future directions

Heart ◽

10.1136/heartjnl-2016-310790 ◽

2018 ◽

Vol 104 (5) ◽

pp. 377-384 ◽

Cited By ~ 37

Author(s):

Rosita Zakeri ◽

Martin R Cowie

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Management Strategies ◽

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Protein Kinase G ◽

Preserved Ejection Fraction ◽

Future Directions ◽

Novel Treatments ◽

Inflammatory State

Heart failure with preserved ejection fraction (HFpEF) comprises almost half of the population burden of HF. Because HFpEF likely includes a range of cardiac and non-cardiac abnormalities, typically in elderly patients, obtaining an accurate diagnosis may be challenging, not least due to the existence of multiple HFpEF mimics and a newly identified subset of patients with HFpEF and normal plasma natriuretic peptide concentrations. The lack of effective treatment for these patients represents a major unmet clinical need. Heterogeneity within the patient population has triggered debate over the aetiology and pathophysiology of HFpEF, and the neutrality of randomised clinical trials suggests that we do not fully understand the syndrome(s). Dysregulated nitric oxide–cyclic guanosine monophosphate–protein kinase G signalling, driven by comorbidities and ageing, may be the fundamental abnormality in HFpEF, resulting in a systemic inflammatory state and microvascular endothelial dysfunction. Novel informatics platforms are also being used to classify HFpEF into subphenotypes, based on statistically clustered clinical and biological characteristics: whether such subclassification will lead to more targeted therapies remains to be seen. In this review, we summarise current concepts and controversies, and highlight the diagnostic and therapeutic challenges in clinical practice. Novel treatments and disease management strategies are discussed, and the large gaps in our knowledge identified.

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1173Anti-heart and anti-intercalated disk autoantibodies: possible novel biomarkers of cardiac sarcoidosis

European Heart Journal ◽

10.1093/eurheartj/ehz748.0015 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Caforio ◽

S Gianstefani ◽

A Baritussio ◽

R Marcolongo ◽

M Seguso ◽

...

Keyword(s):

Potential Role ◽

Cardiac Involvement ◽

Cardiac Sarcoidosis ◽

Cross Sectional Study ◽

Cross Sectional ◽

Non Invasive ◽

Immune Mediated ◽

Novel Biomarkers ◽

Intercalated Disk

Abstract Background Sarcoidosis is an immune-mediated disease; cardiac involvement, a granulomatous form of myocarditis, is under-recognised and prognostically relevant, as it can present with significant morbidity and mortality. Anti-heart autoantibodies (AHA) and anti-intercalated disk autoantibodies (AIDA) are reliable autoimmune markers in non-sarcoidosis myocarditis forms. Purpose The aim of this study was to assess the potential role of serum AHA and AIDA in cardiac sarcoidosis. Methods This is a cross-sectional study on a series of 29 patients with biopsy proven extra-cardiac sarcoidosis and with biopsy-proven or clinically suspected cardiac involvement, who were tested for AHA and AIDA. Patients were recruited in two recruiting tertiary centres, in USA and Italy. AHA and AIDA were detected by indirect immunofluorescence on human myocardium and skeletal muscle. Controls included sera from patients with non-inflammatory cardiac disease (NICD) (n=160), with ischemic heart failure (IHF) (n=141) and normal blood donors (NBD) (n=270). Results The frequencies of AHA and of AIDA were higher in sarcoidosis (86%; 62%) than in NICD (8%; 4%), IHF (7%; 2%), NBD (9%; 0%) (p=0.0001; p=0.0001 respectively). Sensitivity and specificity were: 86% and 92% for positive AHA and 62% and 98% for positive AIDA, respectively (see figure). Figure 1 Conclusions The detection of serum AHA and AIDA in biopsy-proven or clinically suspected cardiac sarcoidosis supports the involvement of heart-specific autoimmunity in the majority of our cases and may provide a novel non invasive diagnostic marker.

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Cardiac Sarcoidosis

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0040-1712535 ◽

2020 ◽

Vol 41 (05) ◽

pp. 626-640 ◽

Cited By ~ 1

Author(s):

David H. Birnie

Keyword(s):

Heart Failure ◽

Cardiac Involvement ◽

Cardiac Sarcoidosis ◽

Positron Emission Tomography Imaging ◽

Left Ventricular ◽

Implantable Cardioverter Defibrillators ◽

Heart Failure Treatment ◽

Positron Emission ◽

Minimal Data ◽

Cardioverter Defibrillators

AbstractApproximately 5% of patients with sarcoidosis will have clinically manifest cardiac involvement presenting with one or more of ventricular arrhythmias, conduction abnormalities, and heart failure. It is estimated that another 20 to 25% of pulmonary/systemic sarcoidosis patients have asymptomatic cardiac involvement (clinically silent disease). Cardiac presentations can be the first (and/or an unrecognized) manifestation of sarcoidosis in a variety of circumstances. Immunosuppression therapy (usually with corticosteroids) has been suggested for the treatment of clinically manifest cardiac sarcoidosis (CS) despite minimal data supporting it. Positron emission tomography imaging is often used to detect active disease and guide immunosuppression. Patients with clinically manifest disease often need device therapy, typically with implantable cardioverter defibrillators (ICDs). The extent of left ventricular dysfunction seems to be the most important predictor of prognosis among patients with clinically manifest CS. In the current era of earlier diagnosis, modern heart failure treatment, and use of ICD therapy, the prognosis from CS is much improved. In a recent Finnish nationwide study, 10-year cardiac survival was 92.5% in 102 patients.

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Electrocardiographic markers for the prediction of ventricular arrhythmias in patients with systemic sclerosis

Rheumatology ◽

10.1093/rheumatology/kez644 ◽

2020 ◽

Vol 59 (3) ◽

pp. 478-486 ◽

Cited By ~ 1

Author(s):

Veronika Sebestyén ◽

Gabriella Szűcs ◽

Dénes Páll ◽

Dóra Ujvárosy ◽

Tamás Ötvös ◽

...

Keyword(s):

Ventricular Arrhythmias ◽

Cardiac Involvement ◽

Internal Organs ◽

Exact Role ◽

Microvascular Damage ◽

Increased Risk ◽

Major Organ ◽

Electrocardiographic Markers ◽

Cardiac Manifestation

Abstract SSc is an autoimmune disease characterized by microvascular damage, endothelial dysfunction and fibrosis of the skin and the internal organs. Cardiac manifestation in patients with SSc is one of the major organ involvements. Approximately 20% of SSc patients suffer from primary cardiovascular disease and another 20% may have secondary cardiac involvement. Although cardiac arrhythmias are mostly linked to myocardial fibrosis, atrioventricular conduction abnormalities are secondary to the fibrosis of the pulse conduction system. Despite the severe consequences of ventricular rhythm disturbances in patients with SSc, the exact role of electrocardiographic markers in the prediction of these arrhythmias has not yet been clearly elucidated. Therefore, the question is whether certain ECG parameters reflecting ventricular repolarization may help to recognize scleroderma patients with increased risk for ventricular arrhythmias and sudden cardiac death.

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A Clinical Review of Ventricular Arrhythmias in Patients with Congestive Heart Failure

EMJ Cardiology ◽

10.33590/emjcardiol/18-00058r1 ◽

2019 ◽

Author(s):

Noel Boyle

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Ventricular Arrhythmias ◽

Beta Blockers ◽

Management Strategies ◽

Significant Risk ◽

Holter Monitoring ◽

Current Evidence ◽

Compensatory Mechanisms ◽

Ventricular Ejection Fraction

Heart failure is an increasingly prevalent condition, which is associated with ventricular arrhythmias. The reduction in cardiac pumping efficiency leads to the activation of several compensatory mechanisms. These mechanisms eventually lead to cardiac remodelling and a decline in haemodynamic status, contributing to the formation of a substrate conducive to arrhythmias, including increased automaticity, triggered activity, and, most commonly, re-entry circuits. In turn, ventricular arrhythmias can lead to the worsening of heart failure. A diagnosis of heart failure and ventricular arrhythmias is obtained using the patient’s history, examination findings, and investigation results. A key tool in this is echocardiogram imaging, which visualises the cardiac chambers, determines ventricular ejection fraction, and identifies structural abnormalities. A reduction in ejection fraction is a significant risk factor for the development of ventricular arrhythmias. Arrhythmias are diagnosed by ECG, Holter monitoring, and telemetry or event monitoring, and should initially be treated by optimising the medical management of heart failure. Anti-arrhythmic drugs, including beta-blockers, are usually the first-line therapy. Sudden cardiac death is a significant cause of mortality in heart failure patients, and implantable cardioverter defibrillator devices are used in both primary and secondary prevention. Anti-arrhythmic drugs and catheter ablation are important adjunctives for minimising shock therapy. In addition, autonomic modulation may offer a novel method of controlling ventricular arrhythmias. The objective of this review is to provide a practical overview of this rapidly developing field in relation to current evidence regarding the underlying pathophysiology, burden of disease, and management strategies available.

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Review of Atypical and Anaplastic Meningiomas: Classification, Molecular Biology, and Management

Frontiers in Oncology ◽

10.3389/fonc.2020.565582 ◽

2020 ◽

Vol 10 ◽

Author(s):

Taylor Anne Wilson ◽

Lei Huang ◽

Dinesh Ramanathan ◽

Miguel Lopez-Gonzalez ◽

Promod Pillai ◽

...

Keyword(s):

Molecular Biology ◽

Surgical Resection ◽

Management Strategies ◽

Standard Of Care ◽

Adjuvant Radiation ◽

Therapeutic Approaches ◽

Future Directions ◽

Atypical Meningiomas ◽

Slow Growing

Although the majority of meningiomas are slow-growing and benign, atypical and anaplastic meningiomas behave aggressively with a penchant for recurrence. Standard of care includes surgical resection followed by adjuvant radiation in anaplastic and partially resected atypical meningiomas; however, the role of adjuvant radiation for incompletely resected atypical meningiomas remains debated. Despite maximum treatment, atypical, and anaplastic meningiomas have a strong proclivity for recurrence. Accumulating mutations over time, recurrent tumors behave more aggressively and often become refractory or no longer amenable to further surgical resection or radiation. Chemotherapy and other medical therapies are available as salvage treatment once standard options are exhausted; however, efficacy of these agents remains limited. This review discusses the risk factors, classification, and molecular biology of meningiomas as well as the current management strategies, novel therapeutic approaches, and future directions for managing atypical and anaplastic meningiomas.

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