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Inflammatory Infiltrate Drives Myocardial Injury in Human Septic Cardiomyopathy
Session:
Sessão de Comunicações Orais - Doenças do Miocárdio
Speaker:
Francisco Vasques-Nóvoa
Congress:
CPC 2020
Topic:
F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme:
17. Myocardial Disease
Subtheme:
17.1 Myocardial Disease – Pathophysiology and Mechanisms
Session Type:
Comunicações Orais
FP Number:
---
Authors:
Francisco Vasques-Nóvoa; José Miguel Alvarenga; António Gonçalves; João Martinho-Nobrega; Dina Leitão; Perpétua Pinto-do-Ó; Diana S. Nascimento; Fátima Carneiro; Adelino Leite-Moreira; Roncon de Albuquerque
Abstract
<p><strong>Background:</strong> Despite the prognostic impact of myocardial dysfunction in septic shock, the mechanisms of septic cardiomyopathy are still poorly understood. Myocardial infiltration of inflammatory cells has been observed in experimental models of sepsis and anecdotally described in human postmortem observations. However, the pathophysiological role of inflammatory cell myocardial infiltration in human septic cardiomyopathy is still poorly understood.</p> <p><strong>Purpose:</strong> To characterize myocardial inflammatory infiltrate and evaluate its association with myocardial injury in human Septic Cardiomyopathy.</p> <p><strong>Methods:</strong> Post-mortem transmural myocardial specimens from septic shock with positive blood cultures (n=40) and nonseptic control patients (sudden non-cardiac death; n=10) were collected together with antemortem clinical and analytical data. Staining was performed for CD3 (T cells), CD8 (Cytotoxic T cells), CD68 (macrophages), CD163 (M2 macrophages) and myeloperoxidase (MPO, Neutrophills) in an automated IHC system. Slides were scanned and cell density was analyzed with a dedicated image analysis software.</p> <p><strong>Results:</strong> Septic patients presented histologically with severe myocarditis and a significantly higher number of myocardial inflammatory cells for all analyzed cell markers when compared with the control group. Interestingly, higher inflammatory cell infiltration was observed in younger patients. Indeed, a negative association was observed between age and infiltration for most cell types, with the exception of MPO+ cells. Prolonged ICU length of stay was associated with a significant increase in CD8+ T cell myocardial infiltration. Importantly, CD3+ and MPO+ cell infiltration correlated positively with the antemortem troponin plasma levels after adjusting for relevant clinical factors.</p> <p><strong>Conclusions:</strong> Sepsis-induced severe myocarditis was documented in most patients dying with septic shock. Myocardial infiltration of certain inflammatory cell subtypes is positively associated with myocardial injury, unraveling a potentially important role of these cells in human septic cardiomyopathy pathophysiology with therapeutic implications.</p>
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