Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction

Interleukin (IL)-6 is an emerging therapeutic target in myocardial infarction (MI). IL-6 has 2 distinct signaling pathways: trans-signaling, which mediates inflammation, and classic signaling, which also has anti-inflammatory effects.
The novel recombinant fusion protein sgp130Fc achieves exclusive trans-signaling blockade, whereas anti-IL-6 Bio Med Frontiers antibodies (Abs) result in panantagonism.
In a rat model of reperfused MI, sgp130Fc, but not anti-IL-6-Ab, attenuated neutrophil and macrophage infiltration into the myocardium, reduced infarct size, and preserved cardiac function 28 days after MI.
These data demonstrate the efficacy of exclusive IL-6 trans-signaling blockade and support further investigation of sgp130Fc as a potential novel therapy in MI.
AAR, area at risk; Ab, antibody; CCL, C-C motif chemokine ligand; CMR, cardiac magnetic resonance; CXCL, C-X-C motif ligand; ICAM-1, intercellular adhesion molecule 1; IL, interleukin; IS, infarct size; LGE, late-gadolinium enhancement; LVEF, left ventricular ejection fraction; MHC, major histocompatibility complex; MI, myocardial infarction; NSTEMI, non–ST-segment-elevation MI; RCAEC, rat coronary artery endothelial cell; STEMI, ST-segment-elevation MI; TCZ, tocilizumab; Trop-T, troponin T; c-caspase-3, cleaved caspase-3; inflammation; interleukin-6; myocardial infarction; reperfusion; sIL-6R, soluble IL-6 receptor.

Severe biventricular thrombosis in eosinophilic granulomatosis with polyangiitis: a case report

  •  Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare multisystem disease characterized by asthma, rhinosinusitis, and eosinophilia. Cardiac involvement, present in half the patients, maybe life threatening.
  • A young woman with long-standing asthma and nasal polyposis was admitted with new-onset dyspnoea, sinus tachycardia, and eosinophilia.
  • She had severe biventricular thrombosis and severe tricuspid regurgitation (TR) on echocardiography, with preserved ejection fraction of both ventricles.
  • Cardiac magnetic resonance (CMR) imaging showed diffuse subendocardial late gadolinium enhancement (LGE). She had a positive test for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) confirming the diagnosis of ANCA positive EGPA.
  • She was treated with anticoagulation, high-dose corticosteroids, cyclophosphamide, and rituximab with gradual resolution of her symptoms. Provider Follow-up echocardiography showed significant improvement in ventricular thrombi and TR but could not reliably exclude residual ventricular thrombus. Repeat CMR at 11 months confirmed complete resolution of both ventricular thrombi and near complete resolution of LGE.
  • Cardiac involvement in EGPA, a rare cause of heart failure, can manifest as severe biventricular thrombosis and severe TR, resulting in heart failure with preserved ejection fraction.
  • Combined immunosuppression and anticoagulation can lead to complete remission within a year. CMR is instrumental for both diagnosis and follow-up of EGPA, allowing for safe discontinuation of oral anticoagulation.
  • Phenotyping of myocardial involvement by cardiac magnetic resonance in idiopathic inflammatory myopathies
 Cardiac dysfunction is commonly noted in patients with idiopathic inflammatory myopathies (IIMs). This study aimed to investigate the characteristics of cardiac dysfunction using cardiac magnetic resonance (CMR) in polymyositis (PM), dermatomyositis (DM) and necrotising myositis (NM).
 Fifty-one patients with IIMs and 20 matched healthy controls (HCs) were assessed using CMR examination. The clinical data, cardiac serum markers and autoimmune antibodies were determined for all patients.
Cardiac involvement was identified by myocardial native T1, extracellular volume (ECV), late gadolinium enhancement (LGE) and left ventricular ejection fraction (LVEF).
 Different subtypes of IIMs showed different patterns of LGE and varying degrees of myocardial damage. The PM subgroup showed higher native T1 (p = 0.010) and ECV (p = 0.000) than the HCs.
The prevalence of LGE was comparable between the PM and DM subgroups (40.0% vs. 31.6%, p = 0.741); however, it was higher in the PM subgroup than in the NM subgroup (40% vs. 0.0%, p = 0.014).
Patients with positive LGE in the PM subgroup showed a higher proportion of positive LGE (p = 0.018) and lower LVEF (p = 0.024) than those with positive LGE in the DM subgroup.
In multivariate analysis, the presence of LGE could be predicted by increased NT-proBNP (p = 0.036, OR = 1.001) and anti-MDA-5 antibody positivity (p = 0.011, OR = 12.4).
The risk factors associated with native T1 were NT-proBNP (p = 0.016, β = 0.353) and body mass index (BMI) (p = 0.024, β = – 0.331).
Distinct cardiac involvements in different subtypes of IIMs were identified using CMR. Elevated NT-proBNP and a low BMI were the risk factors associated with LGE and elevated native T1.

Identification of characteristics of overt myocarditis in adult patients with idiopathic inflammatory myopathies

Myocarditis is a rare complication of idiopathic inflammatory myopathies (IIMs), which is usually underestimated because of limited applications of endomyocardial biopsy and cardiovascular magnetic resonance (CMR) in clinical routines.
 From January 2014 to January 2019, 62 patients with initial untreated IIMs were enrolled, including 31 cases with myocarditis (case group) and 31 cases without cardiac involvement (control group). Myocarditis secondary to IIMs was defined based on definitions of IIMs.
All medical data were retrieved from electrical medical records of PUMCH. The differences between two groups in symptoms, serum levels of cardiac troponin I (cTnI), creatine kinase-isozyme and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analyzed.
The comparisons of arrhythmia, left ventricular ejection fraction (LVEF) and restrictive diastolic dysfunction between two groups were conducted in the analysis of electrocardiogram and electrocardiogram.
Besides, CMR data were analyzed to explore the characteristics of CMR in the identification of myocarditis. Meanwhile, 31 patients with myocarditis were divided into two subgroups based on the activity of anti-mitochondrial antibody M2 (AMA-M2), and the differences between two subgroups in the above tests were also analyzed.
  • Compared with control group, patients with myocarditis exhibited shorter disease durations (defined as the period from onset symptoms of IIM to diagnosis of IIM), more symptoms associated with IIMs, more manifestations of heart failure, and higher frequency of positive AMA-M2 antibody (P<0.05).
  • Patients with myocarditis exhibited elevated levels of cTnI, creatine kinase-isozyme and NT-proBNP compared with control group. In case group, the area under the curve indicating myocarditis for CK-MB, cTnI, and NT-proBNP was 0.654, 0.915 and 0.973, with optimal cut-off values of 24.4 µg/L, 0.1 ng/L and 531 pg/L, respectively.
  • Ventricular arrhythmia, atrial arrhythmia, abnormal Q wave and left anterior fascicular block (LAFB) were showed in 76.7%, 53.3%, 74.2% and 51.6% of patients in case group (P<0.01). Patients of case group were featured as decreased LVEF and restrictive diastolic dysfunction compared with control group (P<0.05).
Analyzing CMR data of patients of case group, the basal segments (74.2%) and mid-cavity segments (71.0%) were the most frequently involved areas of late gadolinium-enhancement (LGE), while intramural LGE (54.8%) and subendocardial LGE (51.6%) were reported more commonly than subepicardial LGE (19.4%).
In patients with myocarditis and positive AMA-M2 antibody, LVEF and right ventricular ejection factor (RVEF) were decreased, and more cases presented diffuse LGE than those with negative AMA-M2 antibody (P<0.05).

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Symptoms of heart failure and arrhythmias, elevated levels of cTnI and NT-proBNP, and positive AMA-M2 antibody play an important role in the identification of myocarditis in IIMs.
Most frequently involved areas of LGE were found in the ventricular septal, basal and mid-cavity segments, as well as in the sub-endocardium and intramural myocardium.
Diffuse LGE is common in the detection, which is correlated with AMA-M2 antibody in patients with myocarditis related to IIMs.
Myocarditis; anti-mitochondrial antibody (AMA); idiopathic inflammatory myopathy (IIM); late gadolinium-enhancement (LGE).



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