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.

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.

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.

Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation.

AIMS: Cardiac sarcoidosis (CS) is a potentially fatal condition that varies in its clinical presentation. Here, we describe baseline characteristics at presentation along with prognosis and predictors of outcome in a sizable and deeply phenotyped contemporary cohort of CS patients. METHODS AND RESULTS: Consecutive CS patients seen at one institution were retrospectively enrolled after undergoing laboratory testing, electrocardiogram, echocardiography, cardiac magnetic resonance (CMR) imaging and 18 F-flourodeoxyglucose positron emission tomography (FDG-PET) at baseline. The composite endpoint consisted of all-cause mortality, aborted sudden cardiac death, major ventricular arrhythmic events, heart failure hospitalization and heart transplantation. A total of 319 CS patients were studied (67% male, 55.4 ± 12 years). During a median follow-up of 2.2 years (range: 1 month-11 years), 8% of patients died, while 33% reached the composite endpoint. The annualized mortality rate was 2.7% and the 5- and 10-year mortality rates were 6.2% and 7.5%, respectively. Multivariate analysis showed serum brain natriuretic peptide (BNP) levels (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.34-4.31, p = 0.003), CMR left ventricular ejection fraction (LVEF) (HR 0.96, 95% CI 0.94-0.98, p < 0.0001) and maximum standardized uptake value of FDG-PET (HR 1.11, 95% CI 1.04-1.19, p = 0.001) to be independent predictors of outcome. These findings remained robust for different patient subgroups. CONCLUSION: Cardiac sarcoidosis is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP levels, lower LVEF and more active myocardial inflammation were independent predictors of outcomes.

An update on current and emerging drug treatments for idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic Pulmonary Fibrosis (IPF) is a progressive and devastating lung disease, characterized by progressive lung scarring. AREAS COVERED: Prior to antifibrotic therapy (pirfenidone and nintedanib), there was no validated pharmaceutical therapy for IPF. Both antifibrotics can slow disease progression; however, IPF remains a detrimental disease with poor prognosis and treatment survival rates of less than 7 years from diagnosis. Despite their effect the disease remains non-reversible and progressing whilst their side effect profile is often challenging. Treatment of comorbidities is also crucial. In this review, we discuss the current pharmacological management as well as management of comorbidities and symptoms. We also reviewed clinicaltrials.gov and summarized all the mid- to late-stage clinical trials (phase II and III) registered in IPF over the last 7 years and discuss the most promising drugs in clinical development. EXPERT OPINION: Future for IPF management will need to focus on current unresolved issues. First a primary pathogenetic pathway has not been clearly identified. Future management may involve a combination of the brushstroke approach with antifibrotics with targeted treatments for specific pathways in patient subsets following an 'oncological' approach. Another unmet need is the management of exacerbations, which are deadly in most cases, as well as either treating or preventing lung cancer.

Diagnosis of cardiac sarcoidosis in patients presenting with cardiac arrest or life-threatening arrhythmias.

OBJECTIVE: Cardiac sarcoidosis (CS) may present with cardiac arrest or life-threatening arrhythmias. There are limited data on this subgroup of patients with CS. Advanced imaging including cardiovascular magnetic resonance (CMR) and cardiac 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) are used for diagnosis. This study aimed to describe advanced imaging patterns suggestive of CS among patients presenting with cardiac arrest or life-threatening arrhythmias. METHODS: An imaging database of a CS referral centre (Royal Brompton Hospital, London) was screened for patients presenting with cardiac arrest or life-threatening arrhythmias and having imaging features of suspected CS. Patients diagnosed with definite or probable/possible CS were included. RESULTS: Study population included 60 patients (median age 49 years) with male predominance (76.7%). The left ventricle was usually non-dilated with mildly reduced ejection fraction (53.4±14.8%). CMR studies showed extensive late gadolinium enhancement (LGE) with 5 (4-8) myocardial segments per patient affected; the right ventricular (RV) side of the septum (28/45) and basal anteroseptum (28/45) were most frequently involved. Myocardial inflammation by FDG-PET was detected in 45 out of 58 patients vs 11 out of 33 patients with oedema imaging available on CMR. When PET was treated as reference to detect myocardial inflammation, CMR oedema imaging was 33.3% sensitive and 77% specific. CONCLUSIONS: In patients with CS presenting with cardiac arrest or life-threatening arrhythmias, LGE was located in areas where the cardiac conduction system travels (basal anteroseptal wall and RV side of the septum). While CMR was the imaging technique that raised possibility of cardiac scarring, oedema imaging had low sensitivity to detect myocardial inflammation compared with FDG-PET.

Diffuse alveolar haemorrhage associated with subsequent development of ANCA positivity and emphysema in three young adults.

BACKGROUND: Diffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement. CASE PRESENTATION: Patient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis. CONCLUSIONS: We believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as "idiopathic". Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.