Faculty Bibliography

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.