The active papillary muscle sign in 18F-FDG PET/CT cardiac sarcoidosis exams and its relationship with myocardial suppression.

OBJECTIVE: Papillary muscle (PM) activity may demonstrate true active cardiac sarcoidosis (CS) or mimic CS in 18FDG-PET/CT if adequate myocardial suppression (MS) is not achieved. We aim to examine whether PM uptake can be used as a marker of failed MS and measure the rate of PM activity presence in active CS with different dietary preparations. MATERIALS AND METHODS: We retrospectively reviewed PET/CTs obtained with three different dietary preparations. Diet-A: 24-h ketogenic diet with overnight fasting (n = 94); Diet-B: 18-h fasting (n = 44); and Diet-C: 72-h daytime ketogenic diet with 3-day overnight fasting (n = 98). Each case was evaluated regarding CS diagnosis (negative, positive, and indeterminant) and presence of PM activity. MaxSUV was measured from bloodpool, liver, and the most suppressed normal myocardium. Linear mixed-effects models were used to compare these factors between those with PM activity and those without. RESULTS: PM activity was markedly lower in the Diet-C group compared with others: Diet-C: 6 (6.1%), Diet-A: 36 (38.3%), and Diet-B: 26 (59.1%) (p < 0.001). MyocardiumMaxSUV was higher, and MyocardiummaxSUV/BloodpoolmaxSUV, MyocardiummaxSUV/LivermaxSUV ratios were significantly higher in the cases with PM activity (p < 0.001). Among cases that used Diet-C and had PM activity, 66.7% were positive and 16.7% were indeterminate. If Diet-A or Diet-B was used, those with PM activity had a higher proportion of indeterminate cases (Diet-A: 61.1%, Diet-B: 61.5%) than positive cases (Diet-A: 36.1%, Diet-B: 38.5%). CONCLUSION: Lack of PM activity can be a sign of appropriate MS. PM activity is less common with a specific dietary preparation (72-h daytime ketogenic diet with 3-day overnight fasting), and if it is present with this particular preparation, the likelihood that the case being true active CS might be higher than the other traditional dietary preparations.

Application of laboratory models for sarcoidosis research.

This manuscript will review the implications and applications of sarcoidosis models towards advancing our understanding of sarcoidosis disease mechanisms, identification of biomarkers, and preclinical testing of novel therapies. Emerging disease models and innovative research tools will also be considered.

Compartment-specific protein interactions in beryllium lung disease.

The study provides insights into proteins that may be relevant in BeS and CBD. It provides a framework to investigate the global changes in lung compartment-specific inflammatory cells to better understand the potential interplay of proteins in CBD. https://bit.ly/3PLNTXC.

Cardiovascular Magnetic Resonance Imaging Phenotypes and Long-term Outcomes in Patients With Suspected Cardiac Sarcoidosis.

Importance: In patients with sarcoidosis with suspected cardiac involvement, late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) identifies those with an increased risk of adverse outcomes. However, these outcomes are experienced by only a minority of patients with LGE, and identifying this subgroup may improve treatment and outcomes in these patients. Objective: To assess whether CMR phenotypes based on left ventricular ejection fraction (LVEF) and LGE in patients with suspected cardiac sarcoidosis (CS) are associated with adverse outcomes during follow-up. Design, Setting, and Participants: This cohort study included consecutive patients with histologically proven sarcoidosis who underwent CMR for the evaluation of suspected CS from 2004 to 2020 with a median follow-up of 4.3 years at an academic medical center in Minnesota. Demographic data, medical history, comorbidities, medications, and outcome data were collected blinded to CMR data. Exposures: CMR phenotypes were identified based on LVEF and LGE presence and features. LGE was classified as pathology-frequent or pathology-rare based on the frequency of cardiac damage features on gross pathology assessment of the hearts of patients with CS who had sudden cardiac death or cardiac transplant. Main Outcomes and Measures: Composite of ventricular arrhythmic events and composite of heart failure events. Results: Among 504 patients (mean [SD] age, 54.1 [12.5] years; 242 [48.0%] female and 262 [52.0%] male; 2 [0.4%] American Indian or Alaska Native, 6 [1.2%] Asian, 90 [17.9%] Black or African American, 399 [79.2%] White, 5 [1.0%] of 2 or more races (including the above-mentioned categories and Native Hawaiian or Other Pacific Islander), and 2 [0.4%] of unknown race; 4 [0.8%] Hispanic or Latino, 498 [98.8%] not Hispanic or Latino, and 2 [0.4%] of unknown ethnicity), 4 distinct CMR phenotypes were identified: normal LVEF and no LGE (n = 290; 57.5%), abnormal LVEF and no LGE (n = 53; 10.5%), pathology-frequent LGE (n = 103; 20.4%), and pathology-rare LGE (n = 58; 11.5%). The phenotype with pathology-frequent LGE was associated with a high risk of arrhythmic events (hazard ratio [HR], 12.12; 95% CI, 3.62-40.57; P < .001) independent of LVEF and extent of left ventricular late gadolinium enhancement (LVLGE). It was also associated with a high risk of heart failure events (HR, 2.49; 95% CI, 1.19-5.22; P = .02) independent of age, pulmonary hypertension, LVEF, right ventricular ejection fraction, and LVLGE extent. Risk of arrhythmic events was greater with an increasing number of pathology-frequent LGE features. The absence of the pathology-frequent LGE phenotype was associated with a low risk of arrhythmic events, even in the presence of LGE or abnormal LVEF. Conclusions and Relevance: This cohort study found that a CMR phenotype involving pathology-frequent LGE features was associated with a high risk of arrhythmic and heart failure events in patients with sarcoidosis. The findings indicate that CMR phenotypes could be used to optimize clinical decision-making for treatment options, such as implantable cardioverter-defibrillators.

Multiomic Signatures of Chronic Beryllium Disease Bronchoalveolar Lavage Cells Relate to T-Cell Function and Innate Immunity.

Chronic beryllium disease (CBD) is a Th1 granulomatous lung disease preceded by sensitization to beryllium (BeS). We profiled the methylome, transcriptome, and selected proteins in the lung to identify molecular signatures and networks associated with BeS and CBD. BAL cell DNA and RNA were profiled using microarrays from CBD (n = 30), BeS (n = 30), and control subjects (n = 12). BAL fluid proteins were measured using Olink Immune Response Panel proteins from CBD (n = 22) and BeS (n = 22) subjects. Linear models identified features associated with CBD, adjusting for covariation and batch effects. Multiomic integration methods identified correlated features between datasets. We identified 1,546 differentially expressed genes in CBD versus control subjects and 204 in CBD versus BeS. Of the 101 shared transcripts, 24 have significant cis relationships between gene expression and DNA methylation, assessed using expression quantitative trait methylation analysis, including genes not previously identified in CBD. A multiomic model of top DNA methylation and gene expression features demonstrated that the first component separated CBD from other samples and the second component separated control subjects from remaining samples. The top features on component one were enriched for T-lymphocyte function, and the top features on component two were enriched for innate immune signaling. We identified six differentially abundant proteins in CBD versus BeS, with two (SIT1 and SH2D1A) selected as important RNA features in the multiomic model. Our integrated analysis of DNA methylation, gene expression, and proteins in the lung identified multiomic signatures of CBD that differentiated it from BeS and control subjects.

Novel Human FCGR1A Variants Affect CD64 Functions and Are Risk Factors for Sarcoidosis.

CD64 (or FcγRIA) is the sole functional high affinity IgG Fc receptor coded by FCGR1A gene in humans. The FCGR1A genetics has not been comprehensively investigated and effects of human FCGR1A variants on immune functions remain unknown. In the current study, we identified three novel FCGR1A variants including the single nucleotide variant (SNV) rs1848781 (c.-131) in the proximal FCGR1A gene promoter region, the rs587598788 indel variant within the FCGR1A intron 5, and the non-synonymous SNV rs1050204 (c.970G>A or FcγRIA-p.D324N) in the FCGR1A coding region. Genotype-phenotype analyses revealed that SNV rs1848781 genotypes were significantly associated with CD64 expression levels. Promoter reporter assays show that rs1848781G allele had significantly higher promoter activity than the rs1848781C, confirming that the rs1848781 is a functional FCGR1A SNV affecting promoter activity and gene expression. The rs587598788 indel genotypes were also significantly associated with levels of CD64 expression. Moreover, the non-synonymous SNV rs1050204 (FcγRIA-p.D324N) alleles significantly affected CD64-mediated phagocytosis, degranulation, and pro-inflammatory cytokine productions. Genetic analyses revealed that FCGR1A genotypes were significantly associated with sarcoidosis susceptibility and severity. Our data suggest that FCGR1A genetic variants may affect immune responses and play a role in sarcoidosis.

The landscape of transcriptomic and proteomic studies in sarcoidosis.

Multiple overlapping pathways are identified in tissue, BAL cells, PBMCs and a sarcoidosis in vitro granuloma model. Inferences from omic studies are constrained by small sample sizes. Studies comparing differences between sarcoidosis phenotypes are needed. https://bit.ly/30NaHz4.

Granulomatous-Lymphocytic Interstitial Lung Disease Mimicking Sarcoidosis.

Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiency disorders characterized by hypogammaglobulinemia and inadequate antibody response to immunizations. The impaired antibody response occurs due to the failure of B cells to differentiate into plasma cells resulting in low immunoglobulins levels and increased frequency of infections. Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) is a non-infectious complication of CVID that is seen in 10-30% of cases. GLILD is a multisystem inflammatory disease involving the lungs, lymph node, liver, spleen and gastrointestinal tract that mimics sarcoidosis. This report describes a series of cases who presented with dyspnea, recurrent respiratory infections or autoimmunity and on further evaluation revealed features suggestive of GLILD. There is very limited understanding of GLILD in terms of clinical presentation, the histo-pathological logical findings, and the diagnostic criteria by itself are limited. A diagnosis of GLILD is established in cases of CVID when there is evidence of lymphoproliferation, cytopenia, autoimmune processes and a lung biopsy demonstrating lymphocytic interstitial pneumonia, follicular bronchiolitis, lymphoid hyperplasia, and/or non-necrotizing granulomas. We review the treatment strategies, including replacement of immunoglobulin and agents targeting B and T lymphocytes. Systematic characterization of GLILD cases and long term follow up studies are sorely needed to understand the natural history of GLILD.

Clinical Presentation and Treatment of High-Risk Sarcoidosis.

Sarcoidosis is a multisystem disease of unknown cause with heterogeneous clinical manifestations and variable course. Spontaneous remissions occur in some patients, whereas others have progressive disease impacting survival, organ function, and quality of life. Four high-risk sarcoidosis phenotypes associated with chronic inflammation have recently been identified as high-priority areas for research. These include treatment-refractory pulmonary disease, cardiac sarcoidosis, neurosarcoidosis, and multiorgan sarcoidosis. Significant gaps currently exist in the understanding of these high-risk manifestations of sarcoidosis, including their natural history, diagnostic criteria, biomarkers, and the treatment strategy, such as the ideal agent, optimal dose, and treatment duration. The use of registries with well-phenotyped patients is a critical first step to study high-risk sarcoidosis manifestations systematically. We review the diagnostic and treatment approach to high-risk sarcoidosis manifestations. Appropriately identifying these disease subgroups will help enroll well-phenotyped patients in sarcoidosis registries and clinical trials, a necessary step to narrow existing gaps in understanding of this enigmatic disease.

Sex Differences in Patients With Suspected Cardiac Sarcoidosis Assessed by Cardiovascular Magnetic Resonance Imaging.

Background: There are few data on sex differences in suspected cardiac sarcoidosis. Methods: Consecutive patients with histologically proven sarcoidosis and suspected cardiac involvement were studied. We investigated sex differences in presenting features, cardiac involvement, and the long-term incidence of a primary composite end point of all-cause death or significant ventricular arrhythmia and secondary end points of all-cause death and significant ventricular arrhythmia. Results: Among 324 patients, 163 (50.3%) were female and 161 (49.7%) were male patients. Female patients had a greater prevalence of chest pain (37.4% versus 23.6%; P=0.010) and palpitations (39.3% versus 26.1%; P=0.016) than male patients but not dyspnea, presyncope, syncope, or arrhythmias at presentation. Female patients had a lower prevalence of late gadolinium enhancement on cardiovascular magnetic resonance imaging (20.2% versus 35.4%; P=0.003) and less often met criteria for a clinical diagnosis of cardiac sarcoidosis (Heart Rhythm Society consensus criteria, 22.7% versus 36.0%; P=0.012 and 2016 Japanese Circulation Society guideline criteria, 8.0% versus 19.3%; P=0.005), indicating lesser cardiac involvement. However, the long-term incidence of all-cause death or significant ventricular arrhythmia was not different between female and male patients (23.2% versus 23.2%; P=0.46). Among the secondary end points, the incidence of all-cause death was not different between female and male patients (20.7% versus 14.3%; P=0.51), while female patients had a lower incidence of significant ventricular arrhythmia compared with male patients (4.3% versus 13.0%; P=0.022). On multivariable analyses, sex was not associated with the primary end point (hazard ratio for female patients, 1.36 [95% CI, 0.77­2.43]; P=0.29). Conclusions: We observed distinct sex differences in patients with suspected cardiac sarcoidosis. A paradox was identified wherein female patients had a greater prevalence of chest pain and palpitations than male patients, but lesser cardiac involvement, and a similar long-term incidence of all-cause death or significant ventricular arrhythmia.

COMPARISON OF THE EFFECT OF THREE DIFFERENT DIETARY MODIFICATIONS ON MYOCARDIAL SUPPRESSION IN 18F-FDG PET/CT EVALUATION OF PATIENTS FOR SUSPECTED CARDIAC SARCOIDOSIS.

Rationale: A definitive dietary preparation recommendation is not possible based on literature in achievement of myocardial suppression for diagnosis of cardiac sarcoidosis (CS) with 18F-FDG PET/CT. Our goal is to compare three different dietary preparations in achievement of the best myocardial suppression and CS diagnosis. Methods: We retrospectively reviewed and compared three dietary preparations used at our institution. Three different diets were applied from 03/2014 to 12/2019. 24-h ketogenic diet with overnight fasting (n = 94); 18h-fasting (n = 44); 72-h daytime ketogenic diet with 3-day overnight fasting (n = 98). The interpretation of initial reports was recorded, and an independent radiologist (observer) retrospectively re-evaluated each case regarding CS diagnosis (Negative, Positive, Indeterminant) and myocardial suppression (Complete, Failed, Partial). Interobserver agreement was analyzed. We measured MaxSUV from bloodpool, liver, and the most suppressed normal myocardium. Results: We identified superior myocardial suppression with the 72-h preparation indicated by a higher bloodpool/myocardium and liver/myocardium ratios (P<0.001). Myocardial suppression rates for 72-h ketogenic diet, 24-h ketogenic diet and 18-h fasting preparations are as follows; Complete myocardial suppression: 96.9%/68.1%/52.3%, Failed myocardial suppression: 0%/23.4%/25%, Partial myocardial suppression: 3.1%/8.5%/22.7%) (P<0.001). The 72-hour preparation had significantly fewer "indeterminant" and "positive" exams. CS diagnosis rates for 72-h ketogenic diet, 24-h ketogenic diet and 18-h fasting preparations are as follows; Negative: 82.7%/52.1%/27.3%, Indeterminant: 2.0%/24.5%/40.9%, Positive: 15.3%/23.4%/31.8% (P<0.001). High agreement was present with the observer and the report (κ=0.88) Conclusion: A 72-h daytime ketogenic diet with 3-day overnight fasting, achieved substantially superior myocardial suppression versus 24-h ketogenic diet with overnight fasting and 18h-fasting using 18F-FDG PET/CT. This 72-h preparation results in significantly fewer "indeterminant" and potentially "false positive" CS results.

Novel protein pathways in development and progression of pulmonary sarcoidosis.

Pulmonary involvement occurs in up to 95% of sarcoidosis cases. In this pilot study, we examine lung compartment-specific protein expression to identify pathways linked to development and progression of pulmonary sarcoidosis. We characterized bronchoalveolar lavage (BAL) cells and fluid (BALF) proteins in recently diagnosed sarcoidosis cases. We identified 4,306 proteins in BAL cells, of which 272 proteins were differentially expressed in sarcoidosis compared to controls. These proteins map to novel pathways such as integrin-linked kinase and IL-8 signaling and previously implicated pathways in sarcoidosis, including phagosome maturation, clathrin-mediated endocytic signaling and redox balance. In the BALF, the differentially expressed proteins map to several pathways identified in the BAL cells. The differentially expressed BALF proteins also map to aryl hydrocarbon signaling, communication between innate and adaptive immune response, integrin, PTEN and phospholipase C signaling, serotonin and tryptophan metabolism, autophagy, and B cell receptor signaling. Additional pathways that were different between progressive and non-progressive sarcoidosis in the BALF included CD28 signaling and PFKFB4 signaling. Our studies demonstrate the power of contemporary proteomics to reveal novel mechanisms operational in sarcoidosis. Application of our workflows in well-phenotyped large cohorts maybe beneficial to identify biomarkers for diagnosis and prognosis and therapeutically tenable molecular mechanisms.

Application of Proteomics in Sarcoidosis.

Sarcoidosis is a multisystem disease with heterogeneity in manifestations and outcomes. System-level studies leveraging "omics" technologies are expected to define mechanisms contributing to sarcoidosis heterogeneous manifestations and course. With improvements in mass spectrometry (MS) and bioinformatics, it is possible to study protein abundance for a large number of proteins simultaneously. Contemporary fast-scanning MS enables the acquisition of spectral data for deep coverage of the proteins with data-dependent or data-independent acquisition MS modes. Studies leveraging MS-based proteomics in sarcoidosis have characterized BAL fluid (BALF), alveolar macrophages, plasma, and exosomes. These studies identified several differentially expressed proteins, including protocadherin-2 precursor, annexin A2, pulmonary surfactant A2, complement factors C3, vitamin-D-binding protein, cystatin B, and amyloid P, comparing subjects with sarcoidosis with control subjects. Other studies identified ceruloplasmin, complement factors B, C3, and 1, and others with differential abundance in sarcoidosis compared with other interstitial lung diseases. Using quantitative proteomics, most recent studies found differences in PI3K/Akt/mTOR, MAP kinase, pluripotency-associated transcriptional factor, and hypoxia response pathways. Other studies identified increased clathrin-mediated endocytosis and Fcγ receptor-mediated phagocytosis pathways in sarcoidosis alveolar macrophages. Although studies in mixed BAL and blood cells or plasma are limited, some of the changes in lung compartment are detected in the blood cells and plasma. We review proteomics for sarcoidosis with a focus on the existing MS data acquisition strategies, bioinformatics for spectral data analysis to infer protein identity and quantity, unique aspects about biospecimen collection and processing for lung-related proteomics, and proteomics studies conducted to date in sarcoidosis.

Does vitamin D deficiency increase the severity of COVID-19?

The severity of coronavirus 2019 infection (COVID-19) is determined by the presence of pneumonia, severe acute respiratory distress syndrome (SARS-CoV-2), myocarditis, microvascular thrombosis and/or cytokine storms, all of which involve underlying inflammation. A principal defence against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs). Treg levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation. Low vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections. Vitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19. Vitamin D deficiency has been found to occur more frequently in patients with obesity and diabetes. These conditions are reported to carry a higher mortality in COVID-19. If vitamin D does in fact reduce the severity of COVID-19 in regard to pneumonia/ARDS, inflammation, inflammatory cytokines and thrombosis, it is our opinion that supplements would offer a relatively easy option to decrease the impact of the pandemic.

Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical cohort studies of different populations are important to understand the high variability in clinical presentation and disease course of sarcoidosis. The aim of the study is to evaluate clinical characteristics, including organ involvement, pulmonary function tests, and laboratory parameters, in a sarcoidosis cohort at the University of Minnesota. We compare the organ system involvement of this cohort with other available cohorts. METHODS: We conducted a retrospective data collection and analysis of 187 subjects with biopsy-proven sarcoidosis seen at a tertiary center. Organ system involvement was determined using the WASOG sarcoidosis organ assessment instrument. Clinical phenotype groups were classified using the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis criteria. RESULTS: Mean subject age at diagnosis was 45.8 ± 12.4, with a higher proportion of males (55.1%), and a higher proportion of blacks (17.1%) compared to the racial distribution of Minnesota residents (5.95%). The majority (71.1%) of subjects required anti-inflammatory therapy for at least 1 month. Compared to the A Case Control Etiologic Study of Sarcoidosis cohort, there was a higher frequency of extra-thoracic lymph node (34.2% vs. 15.2%), eye (20.9% vs. 11.8%), liver (17.6% vs. 11.5%), spleen (20.9% vs. 6.7%), musculoskeletal (9.6% vs. 0.5%), and cardiac (10.7% vs. 2.3%) involvement in our cohort. A multisystem disease with at least five different organs involved was identified in 13.4% of subjects. A restrictive physiological pattern was observed in 21.6% of subjects, followed by an obstructive pattern in 17.3% and mixed obstructive and restrictive pattern in 2.2%. Almost half (49.2%) were Scadding stages II/III. Commonly employed disease activity markers, including soluble interleukin-2 receptor and angiotensin-converting enzyme, did not differ between treated and untreated groups. CONCLUSIONS: This cohort features a relatively high frequency of high-risk sarcoidosis phenotypes including cardiac and multiorgan disease. Commonly-utilized serum biomarkers do not identify subpopulations that require or do better with treatment. Findings from this study further highlight the high-variability nature of sarcoidosis and the need for a more reliable biomarker to predict and measure disease severity and outcomes for better clinical management of sarcoidosis patients.

Right Ventricular Abnormalities on Cardiovascular Magnetic Resonance Imaging in Patients With Sarcoidosis.

OBJECTIVES: This study aimed to determine the prevalence on cardiac magnetic resonance (CMR) of right ventricular (RV) systolic dysfunction and RV late gadolinium enhancement (LGE), their determinants, and their influences on long-term adverse outcomes in patients with sarcoidosis. BACKGROUND: In patients with sarcoidosis, RV abnormalities have been described on many imaging modalities. On CMR, RV abnormalities include RV systolic dysfunction quantified as an abnormal right ventricular ejection fraction (RVEF), and RV LGE. METHODS: Consecutive patients with biopsy-proven sarcoidosis who underwent CMR for suspected cardiac involvement were studied. They were followed for 2 endpoints: all-cause death, and a composite arrhythmic endpoint of sudden cardiac death or significant ventricular arrhythmia. RESULTS: Among 290 patients, RV systolic dysfunction (RVEF <40% in men and <45% in women) and RV LGE were present in 35 (12.1%) and 16 (5.5%), respectively. The median follow-up time was 3.2 years (interquartile range [IQR]: 1.6 to 5.7 years) for all-cause death and 3.0 years (IQR: 1.4 to 5.5 years) for the arrhythmic endpoint. On Cox proportional hazards regression multivariable analyses, only RVEF was independently associated with all-cause death (hazard ratio [HR]: 1.05 for every 1% decrease; 95% confidence interval [CI]: 1.01 to 1.09; p = 0.022) after adjustment for left ventricular EF, left ventricular LGE extent, and the presence of RV LGE. RVEF was not associated with the arrhythmic endpoint (HR: 1.01; 95% CI: 0.96 to 1.06; p = 0.67). Conversely, RV LGE was not associated with all-cause death (HR: 2.78; 95% CI: 0.36 to 21.66; p = 0.33), while it was independently associated with the arrhythmic endpoint (HR: 5.43; 95% CI: 1.25 to 23.47; p = 0.024). CONCLUSIONS: In this study of patients with sarcoidosis, RV systolic dysfunction and RV LGE had distinct prognostic associations; RV systolic dysfunction but not RV LGE was independently associated with all-cause death, whereas RV LGE but not RV systolic dysfunction was independently associated with sudden cardiac death or significant ventricular arrhythmia. These findings may indicate distinct implications for the management of RV abnormalities in sarcoidosis.

Assessment of the 2017 AHA/ACC/HRS Guideline Recommendations for Implantable Cardioverter-Defibrillator Implantation in Cardiac Sarcoidosis.

BACKGROUND: Implantable cardioverter-defibrillators are used to prevent sudden cardiac death in patients with cardiac sarcoidosis. The most recent recommendations for implantable cardioverter-defibrillator implantation in these patients are in the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. These recommendations, based on observational studies or expert opinion, have not been assessed. We aimed to assess them. METHODS: We performed a large retrospective cohort study of patients with biopsy-proven sarcoidosis and known or suspected cardiac sarcoidosis that underwent cardiovascular magnetic resonance imaging. Patients were followed for a composite end point of significant ventricular arrhythmia or sudden cardiac death. The discriminatory performance of the Guideline recommendations was tested using time-dependent receiver operating characteristic analyses. The optimal cutoff for the extent of late gadolinium enhancement predictive of the composite end point was determined using the Youden index. RESULTS: In 290 patients, the class I and IIa recommendations identified all patients who experienced the composite end point during a median follow-up of 3.0 years. Patients meeting class I recommendations had a significantly higher incidence of the composite end point than those meeting class IIa recommendations. Left ventricular ejection fraction (LVEF) >35% with >5.7% late gadolinium enhancement on cardiovascular magnetic resonance imaging was as sensitive as and significantly more specific than LVEF >35% with any late gadolinium enhancement. Patients meeting 2 class IIa recommendations, LVEF >35% with the need for a permanent pacemaker and LVEF >35% with late gadolinium enhancement >5.7%, had high annualized event rates. Excluding 2 class IIa recommendations, LVEF >35% with syncope and LVEF >35% with inducible ventricular arrhythmia, resulted in improved discrimination for the composite end point. CONCLUSIONS: We assessed the Guideline recommendations for implantable cardioverter-defibrillator implantation in patients with known or suspected cardiac sarcoidosis and identified topics for future research.

Acute exacerbation of interstitial lung disease after procedures.

Interstitial lung disease (ILD) is a category of diffuse parenchymal lung diseases characterized by inflammation and/or fibrosis. The best characterized ILD is idiopathic pulmonary fibrosis (IPF). Acute exacerbation of IPF is a dreaded occurrence with grim prognosis and suboptimal treatment options. There have been recent reports that acute exacerbation can occur in other ILDs (AE-ILD). Of note, some of these acute exacerbations follow lung procedures. This review summarizes the available information on AE-ILD and discusses the procedures reported to cause AE-ILD. We also discuss proposed mechanisms, risk factors, treatment and prognosis. This review should help to inform decision-making about risks versus benefits of procedures that are commonly recommended to diagnose ILD.

Simultaneous treatment of ischaemic bowel and ischaemic stroke with intravenous thrombolysis therapy.

Novel treatment of simultaneous mesenteric and cerebral ischaemia with systemic thrombolysis. A 75-year-old man presented to the acute stroke team with aphasia, right-sided weakness and distressed with a pain he was unable to localise. He was treated with intravenous thrombolysis with tissue plasminogen activator for a left middle cerebral artery stroke. Decompensation on the ward during thrombolysis with worsening abdominal distension and pain, hypotension and tachycardia prompted a CT angiogram scan, which displayed proximal inferior mesenteric artery occlusion. Thrombolysis treatment resulted in excellent improvement of both his dysphasia and weakness from the left cerebral ischaemic stroke and reperfusion of the ischaemic bowel, without surgical intervention.