RESUMEN

BACKGROUND: Adult-onset Still's disease (AOSD) should be considered in the differential diagnosis of patients with endocarditis, with or without a cardiac decompensation. CASE PRESENTATION: We report the case of a 68-year-old Caucasian male diagnosed with AOSD after an initial acute manifestation of endocarditis with severe aortic acute manifestation of endocarditis with severe aortic insufficiency. The histological findings revealed Libman-Sacks endocarditis. He was treated with the IL-1 receptor inhibitor anakinra. Two years later the patient developed a symptomatic dilated cardiomyopathy with reduced ejection fraction (23.5%) and functional anti-beta-1-adrenergic receptor antibodies, which was initially treated with plasmapheresis; anakinra was maintained. While his AOSD symptoms responded well, our patient presented with recurrent arthritis in multiple joints, dual-energy CT showed urate deposition compatible with a gouty arthropathy. Over 7 years, he presented with recurrent episodes of arthritis and the adjustment of dosages of colchicine and febuxostat was needed. In 2018, our patient died due to a deterioration of his underlying cardiac disease. CONCLUSIONS: Only two cases with initial endocarditis prior to AOSD diagnosis have been published, and we are not aware of any other cases reporting -ß1AR-Ab development with DCM and gout in the setting of AOSD treated with anakinra.

Asunto(s)

RESUMEN

AIMS: Aptamer BC 007, a 15-mer single-strand DNA oligonucleotide (5'-GGTTGGTGTGGTTGG-3'), was developed to neutralize functional autoantibodies that bind to the extracellular domains of G protein-coupled receptors (GPCR-AAB), leading to the modulation of receptor-mediated signalling cascades that induce pathophysiological states. Among the GPCR-AAB, there are those directed against the ß1-adrenergic receptor (ß1-AAB) that are highly present in patients with dilated cardiomyopathy (DCM) and are increasingly accepted as disease drivers. Using Doberman Pinschers (DP) with DCM, which possess similarities with human DCM among these ß1-AAB positivity for that the disease-driving role in DP DCM was demonstrated, the safety of BC 007, efficacy for neutralizing ß1-AAB, and the DP's outcome were investigated. METHODS AND RESULTS: Fourteen client-owned ß1-AAB-positive DP with electrocardiographically and echocardiographically indicated DCM were treated with BC 007. For controlling, two groups were created: 14 ß1-AAB-positive DP with DCM not treated with BC 007 (Control 1) and 14 DP with DCM closely matched to the BC 007-treated DP (Control 2), retrospectively selected from the institutional database of DP. After treatment, DP were monitored both echocardiographically, and for ß1-AAB, and survival curves were calculated. Based on clinical and laboratory examination, no adverse effects associated with BC 007 treatment were observed during the study. Forty-eight hours after treatment, the DP's blood was free of ß1-AAB, which led to a reduction or stabilization of left ventricular end-systolic volume (ESVI) during ß1-AAB free time in 10 of the treated DP. In one DP, where ß1-AAB returned after 3 months and ESVI worsened again, a second BC 007 treatment after 9 months again cleared the blood from ß1-AAB and improved the ESVI. Compared with the controls, DP treated with BC 007 showed a significantly longer survival time [572 days, interquartile range (IQR) 442-840 days] vs. Control group 1 (266 days, IQR 97-438 days; logrank: P = 0.009) and Control group 2 (229 days, IQR 174-319 days; logrank: P = 0.012). CONCLUSIONS: Treatment with BC 007 for ß1-AAB neutralization was safe, resulted in a long-lasting reduction of ß1-AAB combined with improved cardiac function and prolonged the survival of DP with DCM. Using a natural large animal model of DCM considered superior to small animal models of immunization-induced cardiomyopathy, combined with a study design comparable with clinical trials, we believe that our results provide the basis for optimism that treatment with BC 007 might also be effective in human patients with DCM.

Asunto(s)

RESUMEN

Background: Anti-beta-1-adrenergic receptor antibodies (anti-ß1AR Ab) are associated with ischemic cardiomyopathies (ICM). Evidence continues to emerge supporting an autoimmune component to various cardiac diseases. This study compares anti-ß1AR Ab concentrations in patients with different entities of acute coronary syndromes (ACS) to asymptomatic non-ACS patients with positron-emission computed tomography (PET/CT)-proven atherosclerosis, and healthy controls. Methods: Serum anti-ß1AR Ab IgG concentrations were measured in 212 ACS patients, 100 atherosclerosis patients, and 62 controls using ELISA. All ACS patients underwent coronary angiography. All 374 patients participating completed a structured questionnaire regarding traditional cardiovascular risk factors. ACS patients were followed up for 6 months. Results: Patients with ACS exhibited lower anti-ß1AR Ab levels compared to patients with atherosclerosis or healthy controls (both p < 0.001). No differences in the ab levels were evident between healthy controls and patients with atherosclerosis. In the ACS groups, lower concentrations were found in patients with ST-elevation myocardial infarction (STEMI) (0.67 µg/ml) compared to patients with angina pectoris (AP) and non-ST elevation myocardial infarction (NSTEMI) (both 0.76 µg/ml, p = 0.008). Anti-ß1AR Ab levels ≤ 0.772 µg/ml were predictive for death and reinfarction (AUC 0.77, p = 0.006). No significant correlations between anti-ß1AR Ab levels and atherosclerotic burden or traditional cardiovascular risk factors were identified. Conclusions: Lower anti-ß1AR Ab concentrations appear to characterize ACS phenotypes and could serve as diagnostic and prognostic markers independent from traditional risk factors for atheroscle. The prognostic predictive value of anti-ß1AR Ab in ACS remains to be confirmed in larger studies.