Plasma Cytokine Profile in Tropical Endomyocardial Fibrosis: Predominance of TNF-a, IL-4 and IL-10

Background: the participation of immune/inflammatory mechanisms in the pathogenesis of tropical endomyocardial fibrosis (EMF) has been suggested by the finding of early blood and myocardial eosinophilia. However, the inflammatory activation status of late-stage EMF patients is still unknown.Methodology/Principal findings: We evaluated pro- and anti-inflammatory cytokine levels in plasma samples from late stage EMF patients. Cytokine levels of Tumor Necrosis Factor (TNF)-alpha, Interferon (IFN)-gamma, Interleukin (IL)-2, IL-4, IL-6, and IL-10 were assayed in plasma samples from 27 EMF patients and compared with those of healthy control subjects. All EMF patients displayed detectable plasma levels of at least one of the cytokines tested. We found that TNF-alpha, IL-6, IL-4, and IL-10 were each detected in at least 74% of tested sera, and plasma levels of IL-10, IL-4, and TNF-alpha were significantly higher than those of controls. Plasma levels of such cytokines positively correlated with each other.Conclusions/Significance: the mixed pro-and anti-inflammatory/Th2circulating cytokine profile in EMF is consistent with the presence of a persistent inflammatory stimulus. On the other hand, the detection of increased levels of TNF-alpha may be secondary to the cardiovascular involvement observed in these patients, whereas IL-4 and IL-10 may have been upregulated as a homeostatic mechanism to buffer both production and deleterious cardiovascular effects of pro-inflammatory cytokines. Further studies might establish whether these findings play a role in disease pathogenesis.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Sch Med, Inst Heart InCor, Immunol Lab, São Paulo, BrazilUniv São Paulo, Sch Med, Div Clin Immunol & Allergy, São Paulo, BrazilUniv São Paulo, Sch Med, Inst Heart InCor, Cardiomyopathy Unit, São Paulo, BrazilProSangue Fdn, São Paulo, BrazilInst Investigat Immunol, INCT, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Div Immunol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Div Immunol, São Paulo, BrazilWeb of Scienc

The association of myocardial strain with cardiac magnetic resonance and clinical outcomes in patients with acute myocarditis

IntroductionThe role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients.Material and methodsThis was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction.ResultsThe mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858–0.982, p = 0.012), LV circumferential strain (HR = 1.177, 95% CI: 1.046–1.325, p = 0.007) and LV longitudinal strain (HR = 1.173, 95% CI: 1.031–1.334, p = 0.015) were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis (HR = 1.282, CI 95%: 1.022–1.524, p = 0.007), even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed.ConclusionMeasurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients

Cytokine plasma levels of endomyocardial fibrosis patients and healthy subjects.

<p>Dot plot represents cytokine levels (interleukin 2, 4, 6, 10, TNF-α and IFN-γ) from endomyocardial fibrosis patients (EMF) and healthy subjects (HS), evaluated by CBA. Horizontal lines indicate the median values. *Differences where <i>P</i>≤0.05 are indicated. (•Healthy Subjects;▪EMF patients).</p

Correlation among cytokine plasma levels of endomyocardial fibrosis patients.

<p>Dot plots represent correlation between cytokine levels (interleukin 2, 4, 6, 10, TNF-α and IFN-γ) from endomyocardial fibrosis patients, evaluated by CBA.</p

Demographic and echocardiographic data from EMF patients and healthy subjects.

<p>NA – Not applicable; AF – Atrial Fibrillation; (Percentage of EMF patients with the conditionregistered in the medical records); Systolic dysfunction: Ejection Fraction <55%; *Valvar regurgitation level: mild, moderate, and severe, respectively; Diastolic dysfunction: grades mild, moderate, and severe ** It was not possible to evaluate diastolic function in 4 patients, due to the presence of pacemaker or bioprosthetic heart valve.</p><p>Demographic and echocardiographic data from EMF patients and healthy subjects.</p