Zhang, Zhouli

Background/Purpose APS ACTION Registry was created to study the natural course of antiphospholipid syndrome (APS) over 10 years in persistently antiphospholipid antibody (aPL) positive patients with or without systemic autoimmune rheumatic diseases (SARDs). Our primary objective was to compare the characteristics of aPL-positive patients with or without thrombocytopenia (TP) and/or autoimmune hemolytic anemia (AIHA). Methods The registry inclusion criteria are positive aPL based on the Revised Sapporo APS Classification Criteria, tested at least twice within 1 year prior to enrollment. For the primary comparison of demographic, clinical, and serologic characteristics in this retrospective study, we divided patients into two groups: TP/AIHA ever and never. Thrombocytopenia was defined as a platelet count of <100,000 x 10 9 /L tested twice at least 12 weeks apart, and AIHA was defined as anemia with hemolysis and a positive direct antiglobulin test (DAT). For the secondary analysis, we compared patients with TP versus AIHA, and the immunosuppressive use stratified by systemic lupus erythematosus (SLE) classification. Results As of April 2022, of 1,039 patients (primary aPL/APS: 618 [59%]; SLE classification: 334 [31%]) included in the registry, 228 (22%) had baseline (historical or current) TP and/or AIHA (TP only: 176 [17%]; AIHA only: 35 [3%], and both: 17 [2%]). Thrombocytopenia and/or AIHA was significantly associated with Asian race, SLE classification, cardiac valve disease, catastrophic/microvascular APS, triple aPL (lupus anticoagulant, anticardiolipin antibody, and anti-β 2 -glycoprotein-I antibody) positivity, and SLE-related serologic and inflammatory markers. When 101/618 (16%) primary aPL/APS patients and 101/334 (34%) SLE patients with TP and/or AIHA were compared, azathioprine and mycophenolate mofetil were more commonly reported in lupus patients, however corticosteroid, intravenous immunoglobulin, and rituximab use were similar between groups. Conclusion In our large multi-center international cohort of persistently aPL-positive patients, approximately one-fifth had active or historical TP and/or AIHA at registry entry; half of these patients had additional SLE. Cardiac valve disease, catastrophic/microvascular APS, and triple aPL-positivity were aPL-related clinical and laboratory manifestations associated with TP and/or AIHA, suggesting a more severe APS clinical phenotype in aPL-patients with TP and/or AIHA.

BackgroundDoxorubicin and doxorubicin‐trastuzumab combination chemotherapy have been associated with cardiotoxicity that eventually leads to heart failure and may limit dose‐effective cancer treatment. Current diagnostic strategies rely on decreased ejection fraction (EF) to diagnose cardiotoxicity.PurposeThe aim of this study is to explore the potential of cardiac MR (CMR) imaging to identify imaging biomarkers in a mouse model of chemotherapy‐induced cardiotoxicity.MethodsA cumulative dose of 25 mg/kg doxorubicin was administered over three weeks using subcutaneous pellets (n = 9, Dox). Another group (n = 9) received same dose of Dox and a total of 10 mg/kg trastuzumab (DT). Mice were imaged at baseline, 5/6 weeks and 10 weeks post‐treatment on a 7T MRI system. The protocol included short‐axis cine MRI covering the left ventricle (LV) and mid‐ventricular short‐axis tissue phase mapping (TPM), pre‐ and post‐contrast T1 mapping, T2 mapping and Displacement Encoding with Stimulated Echoes (DENSE) strain encoded MRI. EF, peak myocardial velocities, native T1, T2, extracellular volume (ECV), and myocardial strain were quantified. N = 7 mice were sacrificed for histopathologic assessment of apoptosis at 5/6 weeks.ResultsGlobal peak systolic longitudinal velocity was reduced at 5/6 weeks in Dox (0.6 ± 0.3 vs 0.9 ± 0.3, p = 0.02). In the Dox group, native T1 was reduced at 5/6 weeks (1.3 ± 0.2 ms vs 1.6 ± 0.2 ms, p = 0.02), and relatively normalized at week 10 (1.4 ± 0.1 ms vs 1.6 ± 0.2 ms, p > 0.99). There was no change in EF and other MRI parameters and histopathologic results demonstrated minimal apoptosis in all mice (~1–2 apoptotic cell/high power field), suggesting early‐stage cardiotoxicity.ConclusionsIn a mouse model of chemotherapy‐induced cardiotoxicity using doxorubicin and trastuzumab, advanced CMR shows promise in identifying treatment‐related decrease in myocardial velocity and native T1 prior to the onset of cardiomyocyte apoptosis and reduction of EF.