Autoimmune markers are undetectable in end stage idiopathic dilated cardiomyopathy.

BACKGROUND: Autoreactive humoral and cellular immune responses may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Certain human leucocyte antigens (HLA) could also be linked to the development of IDC. AIM: To determine whether various markers of autoimmunity are present in the final phase of the disease, to substantiate the role of an autoimmune process in IDC. METHODS: 37 patients with end stage IDC were studied, together with 39 patients with end stage heart disease of known aetiology who were included for comparison. Multiple myocardial tissue samples from the explanted heart of each patient were evaluated (immuno)histologically. An indirect immunofluorescence assay was used to screen patient serum samples for the presence of heart specific autoantibodies. HLA class I and II frequencies were determined in each group and compared with HLA frequencies from healthy blood donors. RESULTS: Only scanty small mononuclear cell infiltrates were present in myocardial tissue of seven patients with IDC and of 11 patients with heart disease of known cause. The majority of these inflammatory cells were negative for T cell markers. All blood specimens were negative for heart specific autoantibodies and there was no apparent association of IDC with particular HLA phenotypes. CONCLUSIONS: These findings suggest that an active autoimmune process is not involved in the end stage of IDC

Predictors of adverse prognosis in COVID-19: A systematic review and meta-analysis

Background: Identification of reliable outcome predictors in coronavirus disease 2019 (COVID-19) is of paramount importance for improving patient's management. Methods: A systematic review of literature was conducted until 24 April 2020. From 6843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587 790 and 602 234 cases. Two endpoints were defined: (a) a composite outcome including death, severe presentation, hospitalization in the intensive care unit (ICU) and/or mechanical ventilation; and (b) in-hospital mortality. We extracted numeric data on patients’ characteristics and cases with adverse outcomes and employed inverse variance random-effects models to derive pooled estimates. Results: We identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR) = 3.15, 95% confidence intervals (CIs) 2.26-4.41), acute cardiac (OR = 10.58, 5.00-22.40) or kidney (OR = 5.13, 1.78-14.83) injury, increased procalcitonin (OR = 4.8, 2.034-11.31) or D-dimer (OR = 3.7, 1.74-7.89), and thrombocytopenia (OR = 6.23, 1.031-37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D-dimer conferred an increased risk of in-hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR = 3.61, 95% CI 1.934-6.73), but not with mortality. Conclusions: Advanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in-hospital mortality. © 2020 Stichting European Society for Clinical Investigation Journal Foundatio

Recurrent pericarditis : still idiopathic? The pros and cons of a well-honoured term

In developed countries, more than 80% of cases of acute pericarditis remain without an established diagnosis after a conventional and standard diagnostic approach. These cases are generally labelled as \u2018idiopathic\u2019, i.e. without a known cause. This lack of information is a matter of concern for both patients and clinicians. Some years ago, this term reflected the state of the art of scientific knowledge on the topic. Advances have changed this point of view, in light of available molecular techniques like polymerase chain reaction able to identify viral cardiotropic agents in pericardial fluid and biopsies. Furthermore, the remarkable efficacy of interleukin-1 antagonists, a therapy targeting the innate immune response, suggests clinical and pathogenic similarity between a proportion of patients with idiopathic recurrent pericarditis and classical autoinflammatory diseases. So, it seems useful to discuss the pros and cons of using the term \u201cidiopathic\u201d in light of the new knowledge

Recurrent pericarditis: Autoimmune or autoinflammatory?

Idiopathic recurrent acute pericarditis (IRAP) represents the most troublesome complication of acute pericarditis and occurs in up to 20-50% of patients. It is generally idiopathic or postcardiac injury. IRAP is a disease of suspected immune-mediated pathogenesis. On the other hand, it has been suggested that some of these patients might have an atypical or subclinical form of an autoinflammatory disease, e.g. genetic disorders characterized by primary dysfunction of the innate immune system and caused by mutations of genes involved in the inflammatory response. We found that IRAP patients were negative for mutations associated with familial Mediterranean fever, but 6% (8/131 patients) carry a mutation in the TNFRSF1A gene, encoding the receptor for tumor necrosis factor-alfa. C-reactive protein (CRP) may be useful to follow the disease activity and guide the appropriate length of therapy, with continuation of the attack doses of the drugs until CRP normalization, at which time tapering may be considered. IRAP often needs a multidrug therapy: NSAIDs or aspirin at high dosages every 6-8 h, corticosteroids only rarely, at low dosages and with a very gradual tapering (months) and colchicine at low dosages if tolerated. Anakinra could be a solution for patients who do not tolerate other therapies