Characteristics and clinical outcomes of patients with sarcoidosis admitted for ST-elevation myocardial infarction in the United States: a propensity matched analysis from the National Inpatient Sample.

Introduction: Sarcoidosis is a systemic inflammatory disorder characterised by non-caseating granulomas. Cardiac sarcoidosis (CS) normally causes conduction abnormalities, ventricular arrhythmias, and heart failure. Little is known about the characteristics and impact of sarcoidosis in patients admitted with ST-elevation myocardial infarction (STEMI). This study aims to fill this void. Material and methods: Utilising the National Inpatient Sample (NIS) database (2016-2020), individuals with STEMI were identified and categorised based on sarcoidosis presence whilst adjusting for confounders via logistic regression models. Results: Among 851,290 STEMI patients, 1215 had sarcoidosis. Before propensity matching, sarcoidosis patients were notably different in demographics and comorbidities compared to non-sarcoidosis patients. After propensity score matching (PSM), sarcoidosis patients were found to have a higher incidence of supraventricular tachycardia (SVT) (2.5% vs. 1.3%, p = 0.024) and acute kidney injury (AKI) (23.3% vs. 20.8%, aOR = 1.269, 95% CI: 1.02-1.58, p = 0.033) but a lower incidence of undergoing coronary artery bypass graft (CABG) (5.5% vs. 8.5%, aOR = 0.663; 95% CI: 0.472-0.931, p = 0.018), while no significant disparities were noted in PCI, cardiogenic shock, mortality, or mean length of stay (LOS). Conclusions: Using propensity-matched large real-world data of STEMI patients, sarcoidosis was associated with fewer cases of CABG and a greater incidence of AKI and SVT compared to non-sarcoidosis patients.

Comparing outcomes of an 'early' versus 'late' diagnosis of cardiac sarcoidosis following a baseline presentation of high-grade atrioventricular block.

BACKGROUND: There is a paucity of evidence on impact of a delay in Cardiac Sarcoidosis (CS) diagnosis after high-grade atrioventricular-block (AVB) and this study aims to fill this void. METHODS: Consecutive CS patients (n = 77) with high grade AVB referred to one specialist hospital in London between February 2007 to February 2023 were retrospectively reviewed. The median time from AVB to diagnosing CS (112 days) was used to define the Early (n = 38) and Late (n = 39) cohorts. The primary endpoint was a composite of all-cause mortality, cardiac transplantation, ventricular arrhythmic events or heart failure hospitalisation. Secondary endpoints included difference in maintenance prednisolone dose, need for cardiac device upgrade and device complications. RESULTS: The mean age of the cohort was 54.4 (±10.6) years of whom 64 % were male and 81 % Caucasian. After a mean follow up of 54.9 (±45.3) months, the primary endpoint was reached by more patients from the Late cohort (16/39 vs. 6/38, p = 0.02; multivariable HR 6.9; 95 %CI 1.5-32.2, p = 0.01). Early Group were more likely to have received an Implantable Cardioverter Defibrillator or Cardiac Resynchronisation Therapy-defibrillator as index device after AVB (19/38 vs. 6/39; p < 0.01) and had fewer device upgrades (19/38 vs. 30/39, p = 0.01) and a trend towards fewer device complications (1 vs. 5, p = 0.20). The maintenance dose of prednisolone was significantly higher in Late Group [20.7(±9.7) mg vs. 15.3(±7.9) mg, p = 0.02]. CONCLUSION: A late diagnosis of CS was associated with more adverse events, a greater probability of needing a device upgrade and required higher maintenance steroid dose.

Role of serial 18F-fludeoxyglucose positron emission tomography in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis.

BACKGROUND: Myocardial inflammation and perfusion defects detected by 18F-fludeoxyglucose (FDG) and Rubidium-82 positron emission tomography (PET) may be associated with ventricular arrhythmias (VAs) in cardiac sarcoidosis (CS). The role of serial quantitative PET in determining the effect of treatment on myocardial inflammation and clinical outcomes is yet to be defined. METHODS: Newly diagnosed CS patients with active myocardial inflammation (maximum standardised uptake value (SUVmax) ≥ 2.5) were treated with immunosuppression, then underwent repeat FDG-PET, Rubidium-82, and echocardiographic imaging 6-12 months later. Serial changes in SUVmax, SUVmean, inflammatory extent, perfusion defect (PD) extent, metabolism/perfusion mismatch extent, global cardiac metabolic activity, and left ventricular ejection fraction (LVEF) were assessed. The primary endpoint was a composite of all-cause mortality, serious VA and heart-failure (HF) hospitalisation. Event data were recorded from the date of the second FDG-PET. RESULTS: The study population consisted of 113 patients (66% male, age: 55 ± 11 years, LVEF: 54 ± 13%). SUVmax reduced from 4.5 (interquartile range: 3.3-7.1) to 2.7 (2.2-3.6). Overall, 94 (83%) patients saw serial reduction in SUVmax, with 42 (37%) demonstrating complete response (SUVmax <2.5). Following a median of 46 (25-57) months, 28 (25%) patients reached the endpoint (8 deaths, 17 VAs, and 3 HF hospitalisations). PD extent (Hazard ratio 1.03, 95% confidence interval: 1.01-1.05; p = 0.035) was a significant predictor of outcome following treatment, even after accounting for LVEF and change in SUVmean. The risk of adverse events was the greatest in those with a pre-treatment or post-treatment PD extent of >10%. CONCLUSION: In our cohort with active CS, following a treatment-induced reduction in myocardial inflammation, PD extent was the main predictor of adverse events.

Racial disparities among patients with cardiac sarcoidosis and arrhythmias in the United States: A propensity matched-analysis from the national inpatient sample database 2016-2020.

BACKGROUND: Cardiac sarcoidosis (CS) is frequently associated with conduction abnormalities and arrhythmias. In this study, we aim to evaluate racial disparities in the frequency of arrhythmias, and associated co-morbidities, among patients with CS. METHODS: White and African American (AA) patients diagnosed with CS were identified and compared from the 2016-2020 National Inpatient Sample (NIS) database whilst adjusting for confounders via logistic regression models. RESULTS: A total of 7,935 patients with CS were included in the study. The propensity-matched sample comprised of 5,570 patients, of whom 2,785 were White and 2,785 were AA. AA patients had a longer mean length of hospital stay (LOS) (7.84 vs. 6.94, p<0.01), a higher mean Charlson Comorbidity Index (CCI) score (3.10 vs. 2.84, p<0.01), and significantly higher incidences of cardiogenic shock [(9.2% vs 6.3%, p<0.01), aOR 1.45 (95% CI 1.17-1.78), p<0.01] and acute kidney injury (AKI) [(34.3% vs. 26.9%, p<0.01), aOR 1.41 (95% CI 1.24-1.61), p<0.01]. From an arrhythmia perspective, AA CS patients were shown to have a lower frequency of: (1) ventricular tachycardia (32.5% vs. 37.9%, p<0.01), (2) ventricular fibrillation (5.4% vs.7.2%, p<0.01), (3) first-degree AV block (1.8% vs. 4.1%, p<0.01), (4) complete AV block (6.3% vs. 14.2%, p<0.01), and (5) atrial fibrillation (31.8% vs. 34.8%, p=0.016) when compared to Whites with CS. Mortality remained higher for AAs (3.8% vs. 2.7%, p=0.024). CONCLUSION: Our study demonstrates a higher incidence of cardiac arrhythmias among White patients but a higher incidence of cardiogenic shock, AKI, mean LOS, and mortality among AA patients with cardiac sarcoidosis.

Overnight desaturation in interstitial lung diseases: links to pulmonary vasculopathy and mortality.

Background: Overnight desaturation predicts poor prognosis across interstitial lung diseases (ILDs). The aim of the present study was to investigate whether nocturnal desaturation is associated with pulmonary vasculopathy and mortality. Methods: A retrospective single centre study of 397 new ILD patients was carried out including patients with idiopathic pulmonary fibrosis (IPF) (n=107) and patients with non-IPF fibrotic ILD (n=290). This is the largest study to date of the effect of significant nocturnal desaturation (SND) (≥10% of total sleep time with oxygen saturation ≤90% measured by pulse oximetry). Results: The prevalence of SND was 28/107 (26.2%) in IPF and 80/290 (27.6%) in non-IPF ILD. The prevalence of SND was higher in non-IPF ILDs than in IPF (p=0.025) in multivariate analysis. SND was associated with noninvasive markers of pulmonary hypertension (PH): tricuspid regurgitation velocity (TRV) (p<0.0001), brain natriuretic peptide (p<0.007), carbon monoxide transfer coefficient (p<0.0001), A-a gradient (p<0.0001), desaturation >4% in 6-min walking test (p<0.03) and pulmonary artery diameter (p<0.005). SND was independently associated with high echocardiographic PH probability in the entire cohort (OR 2.865, 95% CI 1.486-5.522, p<0.002) and in non-IPF fibrotic ILD (OR 3.492, 95% CI 1.597-7.636, p<0.002) in multivariate analysis. In multivariate analysis, SND was associated with mortality in the entire cohort (OR 1.734, 95% CI 1.202-2.499, p=0.003) and in IPF (OR 1.908, 95% CI 1.120-3.251, p=0.017) and non-IPF fibrotic ILD (OR 1.663, 95% CI 1.000-2.819, p=0.041). Separate models with exclusion of each one of the diagnostic subgroups showed that no subgroup was responsible for this finding in non-IPF ILDs. SND was a stronger marker of 5-year mortality than markers of PH. Conclusion: SND was associated with high echocardiographic probability and mortality and was a stronger predictor of mortality in IPF and non-IPF ILDs grouped together to power the study.

Low bleeding rates following transbronchial lung cryobiopsy in unclassifiable interstitial lung disease.

BACKGROUND AND OBJECTIVE: Bronchoscopic transbronchial lung cryobiopsy (TBLC) is a guideline-endorsed alternative to surgical lung biopsy for tissue diagnosis in unclassifiable interstitial lung disease (ILD). The reported incidence of post-procedural bleeding has varied widely. We aimed to characterize the incidence, severity and risk factors for clinically significant bleeding following TBLC using an expert-consensus airway bleeding scale, in addition to other complications and diagnostic yield. METHODS: A retrospective cohort study of consecutive adult outpatients with unclassifiable ILD who underwent TBLC following multidisciplinary discussion at a single centre in the UK between July 2016 and December 2021. TBLC was performed under general anaesthesia with fluoroscopic guidance and a prophylactic endobronchial balloon. RESULTS: One hundred twenty-six patients underwent TBLC (68.3% male; mean age 62.7 years; FVC 86.2%; DLCO 54.5%). Significant bleeding requiring balloon blocker reinflation for >20 min, admission to ICU, packed red blood cell transfusion, bronchial artery embolization, resuscitation or procedural abandonment, occurred in 10 cases (7.9%). Significant bleeding was associated with traction bronchiectasis on HRCT (OR 7.1, CI 1.1-59.1, p = 0.042), a TBLC histological pattern of UIP (OR 4.0, CI 1.1-14, p = 0.046) and the presence of medium-large vessels on histology (OR 37.3, CI 6.5-212, p < 0.001). BMI ≥30 (p = 0.017) and traction bronchiectasis on HRCT (p = 0.025) were significant multivariate predictors of longer total bleeding time (p = 0.017). Pneumothorax occurred in nine cases (7.1%) and the 30-day mortality was 0%. Diagnostic yield was 80.6%. CONCLUSION: TBLC has an acceptable safety profile in experienced hands. Radiological traction bronchiectasis and obesity increase the risk of significant bleeding following TBLC.

Imaging of Pulmonary Sarcoidosis-A Review.

Sarcoidosis is the classic multisystem granulomatous disease. First reported as a disorder of the skin, it is now clear that, in the overwhelming majority of patients with sarcoidosis, the lungs will bear the brunt of the disease. This review explores some of the key concepts in the imaging of pulmonary sarcoidosis: the wide array of typical (and some of the less common) findings on high-resolution computed tomography (HRCT) are reviewed and, with this, the concept of morphologic/HRCT phenotypes is discussed. The pathophysiologic insights provided by HRCT through studies where morphologic abnormalities and pulmonary function tests are compared are evaluated. Finally, this review outlines the important contribution of HRCT to disease monitoring and prognostication.

Monitoring of Sarcoidosis.

This article focuses on the monitoring of pulmonary sarcoidosis. The monitoring of sarcoidosis is, in part, focused on serial change in major organ involvement but also includes diagnostic re-evaluation and review of change in quality of life. Recent criteria for progression of fibrotic interstitial lung disease are adapted to pulmonary sarcoidosis. The frequency and nature of monitoring are discussed, integrating baseline risk stratification and strategic treatment goals. Individual variables used to identify changes in pulmonary disease severity are discussed with a focus on their flaws and the need for a multidimensional approach. Other key monitoring issues are covered briefly.

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK.

Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.

Sarcoidosis Associated Pulmonary Hypertension.

In patients with sarcoidosis, the development of pulmonary hypertension is associated with significant morbidity and mortality. The global prevalence of sarcoidosis-associated pulmonary hypertension (SAPH) reportedly ranges between 2.9% and 20% of sarcoidosis patients. Multiple factors may contribute to the development of SAPH, including advanced parenchymal lung disease, severe systolic and/or diastolic left ventricular dysfunction, veno-occlusive or thromboembolic disease, as well as extrinsic factors such as pulmonary vascular compression from enlarged lymph nodes, anemia, and liver disease. Early diagnosis of SAPH is important but rarely achieved primarily due to insufficiently accurate screening strategies, which rely entirely on non-invasive tests and clinical assessment. The definitive diagnosis of SAPH requires right heart catheterization (RHC), with transthoracic echocardiography as the recommended gatekeeper to RHC according to current guidelines. A 6-min walk test (6MWT) had the greatest prognostic value in SAPH patients based on recent registry outcomes, while advanced lung disease determined using a reduced DLCO (<35% predicted) was associated with reduced transplant-free survival in pre-capillary SAPH. Clinical management involves the identification and treatment of the underlying mechanism. Pulmonary vasodilators are useful in several scenarios, especially when a pulmonary vascular phenotype predominates. End-stage SAPH may warrant consideration for lung transplantation, which remains a high-risk option. Multi-centered randomized controlled trials are required to develop existing therapies further and improve the prognosis of SAPH patients.

A formula for predicting emphysema extent in combined idiopathic pulmonary fibrosis and emphysema.

BACKGROUND: No single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are needed to determine emphysema extent. Here, we report the development and validation of a formula to predict emphysema extent in patients with IPF and emphysema. METHODS: The development cohort included 76 patients with combined IPF and emphysema at the Royal Brompton Hospital, London, United Kingdom. The formula was derived using stepwise regression to generate the weighted combination of pulmonary function data that fitted best with emphysema extent on high-resolution computed tomography. Test cohorts included patients from two clinical trials (n = 455 [n = 174 with emphysema]; NCT00047645, NCT00075998) and a real-world cohort from the Royal Brompton Hospital (n = 191 [n = 110 with emphysema]). The formula is only applicable for patients with IPF and concomitant emphysema and accordingly was not used to detect the presence or absence of emphysema. RESULTS: The formula was: predicted emphysema extent = 12.67 + (0.92 x percent predicted forced vital capacity) - (0.65 x percent predicted forced expiratory volume in 1 second) - (0.52 x percent predicted carbon monoxide diffusing capacity). A significant relationship between the formula and observed emphysema extent was found in both cohorts (R2 = 0.25, P < 0.0001; R2 = 0.47, P < 0.0001, respectively). In both, the formula better predicted observed emphysema extent versus individual pulmonary function tests. A 15% emphysema extent threshold, calculated using the formula, identified a significant difference in absolute changes from baseline in forced vital capacity at Week 48 in patients with baseline-predicted emphysema extent < 15% versus ≥ 15% (P = 0.0105). CONCLUSION: The formula, designed for use in patients with IPF and emphysema, demonstrated enhanced ability to predict emphysema extent versus individual pulmonary function tests. TRIAL REGISTRATION: NCT00047645; NCT00075998.

Mortality surrogates in combined pulmonary fibrosis and emphysema.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. METHODS: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (D LCO) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. RESULTS: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. CONCLUSION: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.