Faculty Bibliography

BACKGROUND:The landscape of sarcoidosis in the United States is unclear, which makes it difficult to optimize the allocation of health care resources, clinical care programs, and research activities for sites that specialize in sarcoidosis. RESEARCH QUESTION/OBJECTIVE:Can the features of sarcoidosis be defined in patients requiring specialty care in the United States to inform the design of clinical management and research programs? STUDY DESIGN AND METHODS/METHODS:Adult patients were enrolled in this multicenter, longitudinal cohort study. Demographic and clinical characteristics, including lung function and imaging features, were recorded at baseline. Patients were followed up for a median of 21 months (interquartile range, 9-27 months). RESULTS:The cohort comprised 2,034 patients from 39 states. Even when excluding lymph node involvement, 51.8% of patients had multi-organ disease, and sarcoidosis was chronic (≥ 3 years) for 66.5% of patients. Pulmonary fibrosis was present in 35.9% of those with lung involvement and was associated with worse lung function, an effect most pronounced when bronchiectasis was present. Slightly more than one-half (53.4%) of the cohort required treatment at the time of study entry; of those, 24.8% were on a steroidal regimen alone, 39.7% were on a nonsteroidal regimen alone, and 35.5% were on a combination regimen. During follow-up, there were 120 new organ events, resulting in a new organ rate of 5.5 per 100 patient-years (95% CI, 4.60-6.64). Cardiac sarcoidosis was present in 16.2% of patients at baseline, and emergent cardiac involvement was the most common new organ phenotype during follow-up. INTERPRETATION/CONCLUSIONS:Sarcoidosis is frequently chronic and dynamic. These data support the need for programs for the prevention and treatment of pulmonary fibrosis and cardiac sarcoidosis, as well as the development of long-term, multidisciplinary management strategies.

Sarcoidosis is a systemic disease with heterogenous clinical phenotypes characterized by non-necrotizing granuloma formation in affected organs. Most disease either remits spontaneously or responds to corticosteroids and second-line disease-modifying therapies. These medications are associated with numerous toxicities that can significantly impact patient quality-of-life and often limit their long-term use. Additionally, a minority of patients experience chronic, progressive disease that proves refractory to standard treatments. To date, there are limited data to guide the selection of alternative third-line medications for these patients. This review will outline the pathobiological rationale behind current and emerging therapeutic agents for refractory or drug-intolerant sarcoidosis and summarize the existing clinical evidence in support of their use.

Heart failure with preserved ejection fraction is a heterogeneous clinical syndrome that includes distinct subtypes with different pathophysiologies, genetics, and treatment. Distinguishing heart failure with preserved ejection fraction caused by transthyretin cardiac amyloidosis (ATTR-CA) is critical given its specific treatment. We analyzed a single-center retrospective cohort to determine the association of body mass index (BMI) with a composite of either ATTR-CA or the valine-to-isoleucine substitution (Val122Ile) variant genotype (ATTR-CA+Val122Ile). These BMI differences were prospectively evaluated in the multicenter Screening for Cardiac Amyloidosis using nuclear imaging for Minority Populations (SCAN-MP) study of Black and Hispanic patients with heart failure. The association of BMI with ATTR-CA+Val122Ile was compared by Wilcoxon rank sum analysis and combined with age, gender, and maximum left ventricle wall thickness in multivariable logistic regression. In the retrospective analysis (n = 469), ATTR-CA+Val122Ile was identified in n = 198 (40%), who had a lower median BMI (25.8 kg/m², interquartile range [IQR] 23.4 to 28.9) than other patients (27.1 kg/m², IQR 23.9 to 32.0) (p <0.001). In multivariable logistic regression, BMI <30 kg/m² (odds ratio 2.6, 95% confidence interval 1.5 to 4.5) remained independently associated with ATTR-CA+Val122Ile with a greater association in Black and Hispanic patients (odds ratio 5.8, 95% confidence interval 1.7 to 19.6). In SCAN-MP (n = 201), 17 (8%) had either ATTR-CA (n = 10) or were Val122Ile carriers (n = 7) with negative pyrophosphate scans. BMI was lower (25.4 kg/m² [IQR 24.3 to 28.2]) in ATTR-CA+Val122Ile patients than in non-amyloid patients (32.7 kg/m² [28.3 to 38.6]) (p <0.001), a finding that persisted in multivariable analysis (p = 0.002). In conclusion, lower BMI is associated with ATTR-CA+Val122Ile in heart failure with increased left ventricle wall thickness, particularly in Black and Hispanic patients, and may aid in the identification of those benefiting from ATTR-CA evaluation.

BACKGROUND:Atrial fibrillation (AF) is common in patients with transthyretin cardiac amyloidosis (ATTR-CA). The optimal strategy to prevent strokes in patients with ATTR-CA and AF is unknown. OBJECTIVES/OBJECTIVE:To compare outcomes in patients with ATTR-CA and AF treated with warfarin versus novel oral anticoagulants (NOACs). METHODS:This study was a retrospective analysis of patients with ATTR-CA stratified by presence or absence of AF and anticoagulation therapy. The primary outcome included a time to event analysis for the combined outcomes of stroke, transient ischaemic attack (TIA), major bleed, or death. RESULTS: = .35). CONCLUSION/CONCLUSIONS:Patient with ATTR-CA and AF are at increased risk for stroke compared to patients with ATTR-CA and without AF. Thrombotic events and major bleeds did not differ between those who received warfarin and NOACs.