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Purpose of Review: In recent years new recommendations have been published about organ assessment in the diagnosis of sarcoidosis., Recent Findings: Screening for pulmonary, cardiac, ocular, neurologic and renal involvement and hypercalcemia is recommended in the work-up for sarcoidosis, additionally, screening for hypercalciuria at the time of the diagnosis might be beneficial., Summary: One of the goals in the work-up of sarcoidosis is to assess the extent and severity of organ involvement. Timely and accurate assessment leads to determination of treatment indication. Screening for pulmonary involvement should include pulmonary imaging and pulmonary function tests. Screening for cardiac involvement should include a clear history including palpitations and collapse and a baseline electrocardiogram or 24-h Holter monitoring. At diagnosis, ophthalmological assessment is recommended. Furthermore, serum calcium level and serum creatinine level should be obtained. Although routine 24-h urinary calcium excretion is not included in the guidelines, performing this test routinely can be considered. On indication, neurologic, rheumatologic or dermatologic assessment can be performed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients., Methods and Results: In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups., Conclusions: Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Cardiac sarcoidosis (CS) is associated with an increased risk for sudden cardiac death. An implantable cardiac defibrillator (ICD) is recommended in a subgroup of CS patients. However, the recommendations for primary prevention differ between guidelines. The purpose of the study was to evaluate the efficacy and safety of ICDs in CS and to identify predictors of appropriate therapy., Methods: A retrospective cohort study was performed in CS patients with an ICD implantation between 2010 and 2019. Primary outcome was appropriate ICD therapy. Independent predictors were calculated using Cox proportional hazard analysis., Results: 105 patients were included. An ICD was implanted for primary prevention in 79%. During a median follow-up of 2.8 years, 34 patients (32.4%) received appropriate ICD therapy of whom 24 (22.9%) received an appropriate shock. Three patients (2.9%) received an inappropriate shock due to atrial fibrillation. Independent predictors of appropriate therapy included prior ventricular arrhythmias (hazard ratio [HR]: 10.5 [95% confidence interval (CI): 5.0-21.9]) and right ventricular late gadolinium enhancement (LGE) (HR: 3.6 [95% CI: 1.7-7.6]). Within the primary prevention group, right ventricular LGE (HR: 5.7 [95% CI: 1.6-20.7]) was the only independent predictor of appropriate therapy. Left ventricular ejection fraction did not differ between patients with and without appropriate therapy (44.4% vs. 45.6%, p = .70)., Conclusion: In CS patients with an ICD, a high rate of appropriate therapy was observed and a low rate of inappropriate shocks. Prior ventricular arrhythmias and right ventricular LGE were independent predictors of appropriate therapy., (© 2022 Wiley Periodicals LLC.)

Sarcoidosis-associated pulmonary hypertension (SAPH) is an important complication of advanced sarcoidosis. Over the past few years, there have been several studies dealing with screening, diagnosis and treatment of SAPH. This includes the results of two large SAPH-specific registries. A task force was established by the World Association of Sarcoidosis and Other Granulomatous disease (WASOG) to summarise the current level of knowledge in the area and provide guidance for the management of patients. A group of sarcoidosis and pulmonary hypertension experts participated in this task force. The committee developed a consensus regarding initial screening including who should undergo more specific testing with echocardiogram. Based on the results, the committee agreed upon who should undergo right-heart catheterisation and how to interpret the results. The committee felt there was no specific phenotype of a SAPH patient in whom pulmonary hypertension-specific therapy could be definitively recommended. They recommended that treatment decisions be made jointly with a sarcoidosis and pulmonary hypertension expert. The committee recognised that there were significant defects in the current knowledge regarding SAPH, but felt the statement would be useful in directing future studies., Competing Interests: Conflict of interest: L. Savale reports support for the present manuscript from Janssen and Janssen, and MSD. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from Janssen and Janssen, and MSD, outside the submitted work. Support for attending meetings and/or travel received from Janssen and Janssen, and MSD, outside the submitted work. Conflict of interest: O. Shlobin reports participation on a Data Safety Monitoring Board or Advisory Board for Bayer, United Therapeutics, Johnson and Johnson, and Altavant, outside the submitted work. Conflict of interest: V. Kouranos reports receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, and Roche, outside the submitted work. Conflict of interest: S.D. Nathan reports receiving consulting fees from United Therapeutics, Bellerophon, Merck, Bayer, Roche, and Boehringer Ingelheim, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from United Therapeutics, Bayer, Roche, and Boehringer Ingelheim, outside the submitted work. Payment for expert testimony received from Roche. Conflict of interest: H. Nunes reports receiving consulting fees from Actelion (now Janssen), outside the submitted work. Conflict of interest: R. Gupta reports receiving grants of contracts from Bayer, outside the submitted work. Conflict of interest: J.C. Grutters reports receiving grants or contracts from SPHINX trial (Actelion) outside the submitted work. J.C. Grutters also reports to be member of the SPHINX trial steering committee. Conflict of interest: D.A. Culver reports participation on a Data Safety Monitoring Board or Advisory Board for Actelion (Janssen), and United Therapeutics, outside the submitted work. Conflict of interest: D. Ouellette reports receiving grants or contracts from US Federal Government/PICORI, and Sanofi, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sunrise 2019, India, outside the submitted work. Payment for expert testimony received from Adam & McGrevey Law Firm, and Spangenberg, Shibley & Liber, outside the submitted work. Unpaid Incoming chair Critical Care Network; CHEST. Conflict of interest: E.E. Lower reports receiving grants or contracts from Bayer, Bellephron, Actelion, Genentech, Mallinckrodt, aTyr, Novartis, and Gilead, outside the submitted work. Conflict of interest: T. Al-Hakim reports support for the present manuscript from Foundation for Sarcoidosis Research, and Bayer Pharmaceuticals. Conflict of interest: A.U. Wells reports participation on a Data Safety Monitoring Board or Advisory Board for Roche, outside the submitted work. A.U. Wells also reports to be President Elect of the World Association of Sarcoidosis and Other Granulomatous Diseases. Conflict of interest: M. Humbert reports receiving grants or contracts from Acceleron, Janssen, and Merck, outside the submitted work. Consulting fees received from Acceleron, Janssen, and Merck, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from AOP, Janssen, and Merck, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for Acceleron, Janssen, and Merck. Conflict of interest: R.P. Baughman reports support for the present manuscript from Foundation for Sarcoidosis Research. Grants or contracts received from Bayer, Bellephron, Actelion, Genentech, Mallinckrodt, aTyr, Novartis, and Gilead, outside the submitted work. Consulting fees received from Mallinckrodt. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from Mallinckrodt, Boehringer Ingelheim, and United Therapeutics. Participation on a Data Safety Monitoring Board or Advisory Board for Bellephron, United Therapeutics, Mallinckrodt, and Actelion. Conflict of interest: M. Huitema and M.C. Post have nothing to disclose., (Copyright ©The authors 2022.)

Background and Objective: Pulmonary hypertension (PH) is a known complication of pulmonary sarcoidosis and its aetiology is unclear. Different pathophysiological mechanisms in sarcoidosis-associated pulmonary hypertension (SAPH) are known. Clinical phenotyping can aid clinicians in choosing the optimal treatment strategy. This study aimed to describe clinical phenotypes of SAPH and their characteristics., Methods: A retrospective cohort study was performed on all SAPH patients at a tertiary referral centre. All patients were extensively analysed and discussed case by case in a multidisciplinary expert team to determine the most likely pathophysiological mechanism of PH. Patients were then classified into conceptual clinical phenotypes., Results: Forty (40) patients with SAPH were identified between 2010 and 2019. Three (3) patients were classified as the postcapillary phenotype. Of the remaining 37 patients with precapillary PH, six were classified as 'compression of pulmonary vasculature', 29 as 'parenchymal', one as 'suspected vasculopathy', and one as 'chronic pulmonary emboli' phenotypes. Of the patients with compression of pulmonary vasculature, four showed compression by fibrotic disease and two by active sarcoidosis-based disease. Within the parenchymal phenotype, 20 patients (69%) showed pulmonary vascular resistance >3.0 Wood Units (WU) and had significantly lower diffusing capacity of the lung for carbon monoxide compared with the nine patients (31%) with pulmonary vascular resistance ≤3.0 WU., Conclusion: SAPH had multiple pathophysiological mechanisms and clinical phenotypes in this retrospective study. Further studies are necessary to examine how these phenotypes can affect appropriate treatment and prognosis., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Pulmonary hypertension (PH) is a severe complication of sarcoidosis in a minority of patients. Several genetic defects are known to cause hereditary or sporadic PH, but whether variants in PH-associated genes are also involved in sarcoidosis-associated PH (SAPH) is unknown. Methods: 40 patients with SAPH were individually matched to 40 sarcoidosis patients without PH (SA). Whole exome sequencing was performed to identify rare genetic variants in a diagnostic PH gene panel of 13 genes. Additionally, an exploratory analysis was performed to search for other genes of interest. From 572 genes biologically involved in PH pathways, genes were selected in which at least 15% of the SAPH patients and no more than 5% of patients without PH carried a rare variant. Results: In the diagnostic PH gene panel, 20 different rare variants, of which 18 cause an amino-acid substitution, were detected in 23 patients: 14 SAPH patients carried a variant, as compared to 5 SA patients without PH (p = 0.018). Most variants were of yet unknown significance. The exploratory approach yielded five genes of interest. First, the NOTCH3 gene that was previously linked to PH, and furthermore PDE6B, GUCY2F, COL5A1, and MMP21. Conclusions: The increased frequency of variants in PH genes in SAPH suggests a mechanism whereby the presence of such a genetic variant in a patient may increase risk for the development of PH in the context of pulmonary sarcoidosis. Replication and studies into the functionality of the variants are required for further understanding the pathogenesis of SAPH. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a well-known complication of sarcoidosis, defined by a mean pulmonary artery pressure of ≥25 mm Hg. Since both PH and sarcoidosis are rare diseases, data on sarcoidosis-associated PH (SAPH) is retrieved mostly from small retrospective studies. Estimated prevalence of SAPH ranges from 3% in patients referred to a tertiary center up to 79% in patients awaiting lung transplant. Most patients with SAPH show advanced parenchymal disease as the underlying mechanism. However, some patients have disproportional elevated pulmonary artery pressure, and PH can occur in sarcoidosis patients without parenchymal disease. Other mechanisms such as vascular disease, pulmonary embolisms, postcapillary PH, extrinsic compression, and other sarcoidosis-related comorbidities might contribute to SAPH. The diagnosis of PH in sarcoidosis is challenging since symptoms and signs overlap. Suspicion can be raised based on symptoms or tests, such as pulmonary function tests, laboratory findings, electrocardiography, or chest CT. PH screening mainly relies on transthoracic echocardiography. Right heart catheterization should be considered on a case-by-case basis in patients with clinical suspicion of PH, taking into account clinical consequences. Treatment options are considered on patient level in a PH expert center, and might include oxygen therapy, immunosuppressive, or PH-specific therapy. However, qualitative evidence is scarce. Furthermore, in a subset of patients, interventional therapy or eventually lung transplant can be considered. SAPH is associated with high morbidity. Mortality is higher in sarcoidosis patients with PH compared with those without PH, and increases in patients with more advanced stages of sarcoidosis and/or PH. [ABSTRACT FROM AUTHOR]