Leveraging AI technology in sarcoidosis.

PURPOSE OF REVIEW: Sarcoidosis is a systemic, granulomatous disease of uncertain cause. Diagnosis may be difficult, prognosis uncertain and response to treatment unpredictable. The application of artificial intelligence to sarcoidosis may provide clinical decision support for these challenges. This review will provide an overview of current and potential future applications of artificial intelligence in sarcoidosis. RECENT FINDINGS: The predominant application of artificial intelligence in sarcoidosis is imaging. Imaging models may differentiate sarcoidosis from other pulmonary disorders. Models, which predict survival and identify key factors relevant to prognosis are also available. The application of cluster analysis to organize sarcoidosis patients into developmental phenotypes is underway. Machine learning algorithms to evaluate the treatment response of sarcoidosis patients do not yet exist but similar models may evaluate patients with other inflammatory disease. The potential applications of artificial intelligence to sarcoidosis is vast, but there are practical limitations that warrant consideration. These include: the accessibility of data, biases in data, cost and privacy. SUMMARY: The application of artificial intelligence in medicine is still in its early stages but models are poised to support the diagnostic and prognostic challenges in sarcoidosis patients. The predictive power of these artificial intelligence is likely to come from combining various models, trained on content-rich datasets from phenotypically heterogeneous sarcoidosis patients.

Big data in sarcoidosis.

PURPOSE OF REVIEW: This review provides an overview of recent advancements in sarcoidosis research, focusing on collaborative networks, phenotype characterization, and molecular studies. It highlights the importance of collaborative efforts, phenotype characterization, and the integration of multilevel molecular data for advancing sarcoidosis research and paving the way toward personalized medicine. RECENT FINDINGS: Sarcoidosis exhibits heterogeneous clinical manifestations influenced by various factors. Efforts to define sarcoidosis endophenotypes show promise, while technological advancements enable extensive molecular data generation. Collaborative networks and biobanks facilitate large-scale studies, enhancing biomarker discovery and therapeutic protocols. SUMMARY: Sarcoidosis presents a complex challenge due to its unknown cause and heterogeneous clinical manifestations. Collaborative networks, comprehensive phenotype delineation, and the utilization of cutting-edge technologies are essential for advancing our understanding of sarcoidosis biology and developing personalized medicine approaches. Leveraging large-scale epidemiological resources and biobanks and integrating multilevel molecular data offer promising avenues for unraveling the disease's heterogeneity and improving patient outcomes.

Progress for all: addressing disparities in sarcoidosis.

PURPOSE OF REVIEW: The impact of healthcare disparities in the treatment, care, and outcomes of patients with sarcoidosis has been described. There is paucity of literature on ways to address these disparities with a goal to improving health outcomes for patients with sarcoidosis. RECENT FINDINGS: Recent findings in other respiratory and systemic diseases suggest that multifaceted interventions directed at improving care at various levels including individual, family, and larger societal levels have been successful in dismantling some of the social and structural barriers to care and consequently have resulted in a reduction in disparate disease outcomes. We explore what some of these interventions would look like in sarcoidosis. SUMMARY: The impact of healthcare disparities in the treatment, care, and outcomes of patients with sarcoidosis has been described. We outline various steps and approaches aimed at addressing these health disparities with a goal to improving outcomes for those most impacted by disease.

Clinical outcomes with cardiac resynchronization therapy in patients with Cardiac Sarcoidosis: A systematic review and proportional meta-analysis.

BACKGROUND: Cardiac sarcoidosis (CS) is an inflammatory condition that can present with heart failure (HF). Cardiac resynchronization therapy (CRT) is known to improve clinical outcomes for patients with left bundle branch block in the general HF population. However, data about the outcomes of CRT in CS is limited. METHODS: A systematic literature search was conducted using PubMed/Medline, Embase, and the Cochrane Library from inception to February 2024 to identify studies that reported clinical outcomes following the use of CRT in patients with CS. Data for outcomes was extracted, pooled, and analyzed. OpenMetaAnalyst was used for pooling untransformed proportions along with the corresponding 95 % confidence intervals (CIs). RESULTS: Five studies with a total of 176 CS patients who received CRT were included. The pooled incidence for all-cause mortality was 7.6 % (95 % CI: -3 % to 18 %), for HF-related hospitalizations 23.2 % (95 % CI: 2 % to 43 %), and for major adverse cerebral and cardiovascular events 27 % (95 % CI: 8 % to 45 %) after a mean follow-up of 60.1 (±48.7) months. The pooled left ventricular ejection fraction (LVEF) was 34.28 % (95 % CI: 29.88 % to 38.68 %) demonstrating an improvement of 3.75 % in LVEF from baseline LVEF of 30.58 % (95 % CI: 24.68 % to 36.48 %). The mean New York Heart Association (NYHA) functional class was 2.16 (95 % CI: 1.47 to 2.84) after CRT as compared to the baseline mean NYHA of 2.58 (95 % CI: 2.29 to 2.86). CONCLUSION: Although improvements were observed in LVEF and mean NYHA, mortality was high in CS patients with CRT.

Management of cardiac sarcoidosis.

Cardiac sarcoidosis (CS) is a form of inflammatory cardiomyopathy associated with significant clinical complications such as high-degree atrioventricular block, ventricular tachycardia, and heart failure as well as sudden cardiac death. It is therefore important to provide an expert consensus statement summarizing the role of different available diagnostic tools and emphasizing the importance of a multidisciplinary approach. By integrating clinical information and the results of diagnostic tests, an accurate, validated, and timely diagnosis can be made, while alternative diagnoses can be reasonably excluded. This clinical expert consensus statement reviews the evidence on the management of different CS manifestations and provides advice to practicing clinicians in the field on the role of immunosuppression and the treatment of cardiac complications based on limited published data and the experience of international CS experts. The monitoring and risk stratification of patients with CS is also covered, while controversies and future research needs are explored.

[Sarcoid Peripheral Neuropathy and Myopathy: A Diagnostic and Therapeutic Challenge].

Sarcoidosis is an idiopathic granulomatous multi-organ disease, primarily affecting the respiratory system, eyes, and skin, with less involvement in peripheral neurons and muscles. Sarcoid peripheral neuropathy encompasses cranial and spinal nerve impairment. Muscle involvement is often asymptomatic and revealed through imaging. Symptomatic muscle involvement is categorized into three clinical types: nodular myopathy, acute myopathy, and chronic myopathy. The identification of noncaseating granulomas in peripheral nerves or muscles, coupled with the exclusion of other diseases, is essential for establishing a definitive diagnosis of sarcoid peripheral neuropathy and myopathy. Sarcoid neuropathy and myopathy are typically managed with high-dose corticosteroids, immunosuppressants, or a combination of both. In recent times, the use of TNF-alpha inhibitors has notably increased. However, these conditions often exhibit resistance to treatment and may necessitate prolonged therapeutic interventions. Therefore, comprehensive examinations should be conducted before considering immunotherapy. Due to the rarity of these conditions, research on manifestation-specific treatments is lacking, and standard treatments for sarcoid neuropathy and myopathy have not been established. Additional treatment options for sarcoid neuropathy and myopathy are expected to become available in the future.

[Cardiac sarcoidosis: a diagnostic and therapeutic challenge]. / Sarcoïdose cardiaque : un défi diagnostique et thérapeutique.

The diagnosis of cardiac sarcoidosis, particularly in its isolated cardiac form, represents a major challenge due to non-specific symptoms and the limited sensitivity and specificity of basic cardiac investigations. MRI and metabolic PET-CT are important elements in the diagnostic process. Corticosteroids remain the cornerstone for the treatment of the inflammatory phase, in association with biological agents and steroid-sparing therapies. The goal is to limit the progression of fibrosis, which is a source of malignant arrhythmias and heart failure. The indication for implantation of a cardiac defibrillator must be carefully evaluated to reduce the risk of sudden death. Multidisciplinary collaboration is essential for optimal care.

Le diagnostic de sarcoïdose cardiaque, en particulier dans sa forme cardiaque isolée, représente un défi majeur en raison de symptômes aspécifiques et d'une sensibilité et spécificité limitées des explorations cardiologiques de base. L'IRM et le PET-CT métabolique sont devenus des éléments essentiels dans le processus diagnostique. Les corticostéroïdes restent la pierre angulaire du traitement dans la phase inflammatoire, parallèlement aux agents biologiques et aux thérapies d'épargne cortisonique. L'objectif est d'éviter la progression vers la fibrose, source d'arythmies malignes et d'insuffisance cardiaque. L'indication à l'implantation d'un défibrillateur cardiaque doit être soigneusement évaluée afin de réduire le risque de mort subite. Une collaboration multidisciplinaire est essentielle afin d'assurer une prise en charge optimale.

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.

[Therapeutic Pathways in Sarcoidosis. A Position Paper of the German Society of Respiratory Medicine (DGP)]. / Therapie der Sarkoidose. Ein Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

The present recommendations on the therapy of sarcoidosis of the German Respiratory Society (DGP) was written in 2023 as a German-language supplement and update of the international guidelines of the European Respiratory Society (ERS) from 2021. It contains 5 PICO questions (Patients, Intervention, Comparison, Outcomes) agreed in the consensus process, which are explained in the background text of the four articles: Confirmation of diagnosis and monitoring of the disease under therapy, general therapy recommendations, therapy of cutaneous sarcoidosis, therapy of cardiac sarcoidosis.

Hybrid Magnetic Resonance Positron Emission Tomography Is Associated With Cardiac-Related Outcomes in Cardiac Sarcoidosis.

BACKGROUND: Imaging with late gadolinium enhancement (LGE) magnetic resonance (MR) and 18F-fluorodeoxyglucose (18F-FDG) PET allows complementary assessment of myocardial injury and disease activity and has shown promise for improved characterization of active cardiac sarcoidosis (CS) based on the combined positive imaging outcome, MR(+)PET(+). OBJECTIVES: This study aims to evaluate qualitative and quantitative assessments of hybrid MR/PET imaging in CS and to evaluate its association with cardiac-related outcomes. METHODS: A total of 148 patients with suspected CS underwent hybrid MR/PET imaging. Patients were classified based on the presence/absence of LGE (MR+/MR-), presence/absence of 18F-FDG (PET+/PET-), and pattern of 18F-FDG uptake (focal/diffuse) into the following categories: MR(+)PET(+)FOCAL, MR(+)PET(+)DIFFUSE, MR(+)PET(-), MR(-)PET(+)FOCAL, MR(-)PET(+)DIFFUSE, MR(-)PET(-). Further analysis classified MR positivity based on %LGE exceeding 5.7% as MR(+/-)5.7%. Quantitative values of standard uptake value, target-to-background ratio, target-to-normal-myocardium ratio (TNMRmax), and T2 were measured. The primary clinical endpoint was met by the occurrence of cardiac arrest, ventricular tachycardia, or secondary prevention implantable cardioverter-defibrillator (ICD) before the end of the study. The secondary endpoint was met by any of the primary endpoint criteria plus heart failure or heart block. MR/PET imaging results were compared between those meeting or not meeting the clinical endpoints. RESULTS: Patients designated MR(+)5.7%PET(+)FOCAL had increased odds of meeting the primary clinical endpoint compared to those with all other imaging classifications (unadjusted OR: 9.2 [95% CI: 3.0-28.7]; P = 0.0001), which was higher than the odds based on MR or PET alone. TNMRmax achieved an area under the receiver-operating characteristic curve of 0.90 for separating MR(+)PET(+)FOCAL from non-MR(+)PET(+)FOCAL, and 0.77 for separating those reaching the clinical endpoint from those not reaching the clinical endpoint. CONCLUSIONS: Hybrid MR/PET image-based classification of CS was statistically associated with clinical outcomes in CS. TNMRmax had modest sensitivity and specificity for quantifying the imaging-based classification MR(+)PET(+)FOCAL and was associated with outcomes. Use of combined MR and PET image-based classification may have use in prognostication and treatment management in CS.

The role of ICDs in patients with sarcoidosis-A comprehensive review.

BACKGROUND: Implantable cardioverter defibrillator (ICD) use in cardiac sarcoidosis (CS) to prevent sudden cardiac death (SCD) is a potentially life-saving intervention. However, the factors that determine outcome in this cohort remains largely unknown. This review analyses CS patients with an ICD and highlights determinants of poor outcome. OUTCOMES: Analysis of studies which used the 2014 HRS Consensus, 2017 AHA/ACC/HRS Guideline and 2022 ESC Guidelines showed that those with class I recommendations have higher incidences of ventricular arrhythmia (VA) than those with class II recommendations. Additionally, even those with normal left ventricular ejection fraction (LVEF) and CS are at high risk of VA and SCD. SUMMARY: Compounding research emphasises the importance of cardiac imaging in those with sarcoidosis, with evidence to suggest a possible need for revision of the guidelines. Other variables such as demographics and ventricular characteristics may prove useful in predicting those to benefit most from ICD insertion.

Diagnostic and management strategies in cardiac sarcoidosis.

Cardiac sarcoidosis (CS) is increasingly recognized in the context of with otherwise unexplained electrical or structural heart disease due to improved diagnostic tools and awareness. Therefore, clinicians require improved understanding of this rare but fatal disease to care for these patients. The cardinal features of CS, include arrhythmias, atrio-ventricular conduction delay and cardiomyopathy. In addition to treatments tailored to these cardiac manifestations, immunosuppression plays a key role in active CS management. However, clinical trial and consensus guidelines are limited to guide the use of immunosuppression in these patients. This review aims to provide a practical overview to the current diagnostic challenges, treatment approach, and future opportunities in the field of CS.

Partnering With Patients With Sarcoidosis to Implement a Community Advisory Board.

BACKGROUND: Community advisory boards (CABs) are increasingly recognized as a means of incorporating patient experience into clinical practice and research. The power of CABs is derived from engaging with community members as equals throughout the research process. Despite this, little is known of community member experience and views on best practices for running a CAB in a rare pulmonary disease. RESEARCH QUESTION: What are CAB members' views on the best practices for CAB formation and maintenance in a rare pulmonary disease? STUDY DESIGN AND METHODS: In August 2021, we formed the Cleveland Clinic Sarcoidosis Health Partners (CC-HP) as a CAB to direct research and clinic improvement initiatives at a quaternary sarcoidosis center. We collaboratively evaluated our process for formation and maintenance of the CC-HP with the patient members of the group. Through the series of reflection/debriefing discussions, CAB patient members developed a consensus account of salient obstacles and facilitators of forming and maintaining a CAB in a rare pulmonary disease. RESULTS: Clinician and community members of the CC-HP found published guidelines to be an effective tool for structuring formation of a CAB in a rare pulmonary disease. Facilitators included a dedicated coordinator, collaborative development of projects, and a focus on improving clinical care. Obstacles to CAB functioning were formal structure, focus on projects with academic merit but no immediate impact to patients, and overreliance on digital resources. INTERPRETATION: By centering our evaluation of our CAB on community member experience, we were able to both identify facilitators and impediments to CAB as well as improve our own processes.

Health-Related Quality of Life Assessment in Sarcoidosis.

Health-related quality of life (HRQoL) is of major concern to patients with sarcoidosis. HRQoL impairment is the most common reason to treat the disease. Advances in patient-reported outcome (PRO) methodology offer the promise to use these instruments to follow quality of life in individual patients with sarcoidosis over time. Several HRQoL issues will be highlighted including their clinical importance, common causes in patients with sarcoidosis, the construction and use of PROs in clinical sarcoidosis trials, methods to adapt PROs to monitor HRQoL in individual patients with sarcoidosis, and the approach to improving HRQoL in this disease.

Cardiac Sarcoidosis.

Cardiac involvement is a major cause of morbidity and mortality in patients with sarcoidosis. It is important to distinguish between clinical manifest diseases from clinically silent diseases. Advanced cardiac imaging studies are crucial in the diagnostic pathway. In suspected isolated cardiac sarcoidosis, it's key to rule out alternative diagnoses. Therapeutic options can be divided into immunosuppressive agents, guideline-directed medical therapy, antiarrhythmic medications, device/ablation therapy, and heart transplantation.

Hematologic and Oncologic Aspects of Sarcoidosis: Some of the Least Studied but Most Common Dilemmas.

The hematologic system is frequently involved in sarcoidosis. Lymphopenia is the most common hematologic manifestation noted, although anemia and thrombocytopenia also occur. The etiology of these common manifestations can be direct granulomatous infiltration of bone marrow, lymph nodes, or spleen or related to immunologic dysfunction. Although not life threatening, these problems can lead to cytopenias requiring close monitoring in patients receiving a variety of disease treatments. The relationship between sarcoidosis and malignancy remains complex. However, some sarcoidosis patients are at increased risk for the development of malignancies, particularly lymphomas and gastrointestinal cancers. Conversely, cancer patients can experience an increase in the likelihood for the development of breast cancer and lymphomas.

Ocular Sarcoidosis.

Sarcoidosis frequently affects the eye and can do so in many different ways. Sarcoidosis causing uveitis can have distinctive features that facilitate identifying sarcoidosis as the cause of the uveitis. Progress is being made in elucidating ocular sarcoidosis, as for example, by transcriptomics, genetics, therapy, and imaging.

Biomarkers in Sarcoidosis: Beginning of a New Era?

At present, no biomarker exists which is truly specific for sarcoidosis and the ones available have modest sensitivity and specificity. The clinical context should dictate the choice of biomarker(s) used to address different clinical questions such as diagnosis, monitoring disease activity or monitoring response to treatment. In the future, in addition to known serum biomarkers, it seems fruitful to further explore a possible role of imaging, exhaled air and even biopsy-related biomarkers in sarcoidosis to guide clinical management.