Background Non-ischemic dilated cardiomyopathy (DCM) is a heterogeneous disease with a spectrum of etiological factors. However, subsets of the disease are not well-characterized with respect to these factors. The aim of this study was to evaluate the prevalence of myocardial inflammation and cardiotropic viruses in DCM patients and their impact on clinical outcome. Methods Fifty-seven patients with DCM underwent endomyocardial biopsy between 2010 and 2013. Biopsies were analyzed by polymerase chain reaction (PCR) for the presence of cardiotropic viruses, and inflammatory cell infiltration was assessed by immunohistochemistry. During a 5-year follow-up, 27 (47%) patients reached the composite outcome measure: heart transplantation, left ventricle assist device implantation or cardiovascular-related death. Results Thirty-one (54%) patients had myocardial inflammation and cardiotropic viruses were detected in 29 (52%). The most frequent viruses were parvovirus B19 and human herpesvirus type-6. Four specific sub-groups were distinguished by PCR and immunohistochemistry: virus-positive (chronic) myocarditis, autoreactive inflammatory DCM, viral DCM, non-inflammatory DCM. The presence of a viral genome in myocardium or diagnosis of inflammatory DCM did not predict the outcome of composite outcome measures (p > 0.05). However, univariate Cox regression and survival function estimation revealed an association between inflammation by a high number of T-cells and poor prognosis. Conclusions This study has shown that two markers — cardiotropic viruses and myocardial inflammation — are prevalent among DCM patients. They are also helpful in identifying sub-groups of DCM. An increased number of T-lymphocytes in the myocardium is a predictor of poor mid-term and long-term prognosis.

Clinical interpretation of patients' plasma adiponectin (APN) remains challenging; its value as biomarker in dilated cardiomyopathy (DCM) is equivocal. We evaluated whether circulating APN level is an independent predictor of composite outcome: death, left ventricle assist device (LVAD) implantation, and heart transplantation (HT) in patients with nonischemic DCM. 57 patients with nonischemic DCM (average LV diastolic diameter 6.85 cm, LV ejection fraction 26.63%, and pulmonary capillary wedge pressure 22.06  mmHg) were enrolled. Patients underwent echocardiography, right heart catheterization, and endomyocardial biopsy. During a mean follow-up of 33.42 months, 15 (26%) patients died, 12 (21%) patients underwent HT, and 8 (14%) patients were implanted with LVAD. APN level was significantly higher in patients who experienced study endpoints (23.4 versus 10.9 ug/ml, p = 0.01). APN was associated with worse outcome in univariate Cox proportional hazards model (HR 1.04, CI 1.02–1.07, p = 0.001) but lost significance adjusting for other covariates. Average global strain (AGS) is an independent outcome predictor (HR 1.42, CI 1.081–1.866, p = 0.012). Increased circulating APN level was associated with higher mortality and may be an additive prognostic marker in DCM with advanced HF. Combination of serum (APN, BNP, TNF-α) and echocardiographic (AGS) markers may increase the HF predicting power for the nonischemic DCM patients.

Background Risk stratification in patients with non-ischemic dilated cardiomyopathy (NI-DCM) is essential to treatment planning. Global longitudinal strain (GLS) predicts poor prognosis in various cardiac diseases, but it has not been evaluated in a cohort of exclusively NI-DCM. Although deformation parameters have been shown to reflect diastolic function, their association with other hemodynamic parameters needs further elucidation. We aimed to evaluate the association between GLS and E/GLS and invasive hemodynamic parameters and assess the prognostic value of GLS and E/GLS in a prospective well-defined pure NI-DCM cohort. Methods and results Forty-one patients with NI-DCM were enrolled in the study. They underwent a standard diagnostic workup, including transthoracic echocardiography and right heart catheterization. During a five-year follow-up, 20 (49%) patients reached the composite outcome measure: LV assist device implantation, heart transplantation, or cardiovascular death. Pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure, pulmonary vascular resistance (PVR) correlated with GLS and E/GLS (p < 0.05). ROC analysis revealed that GLS and E/GLS could identify elevated PCWP (≥ 15 mmHg) and PVR (> 3 Wood units). Survival analysis showed GLS and E/GLS to be associated with short- and long-term adverse cardiac events (p < 0.05). GLS values above thresholds of –5.34% and -5.96% indicated 18- and 12-fold higher risk of poor clinical outcomes at one and five years, respectively. Multivariate Cox regression analysis revealed that GLS is an independent long-term outcome predictor. Conclusion GLS and E/GLS correlate with invasive hemodynamics parameters and identify patients with elevated PCWP and high PVR. GLS and E/GLS predict short- and long-term adverse cardiac events in patients with NI-DCM. Worsening GLS is associated with incremental risk of long-term adverse cardiac events and might be used to identify high-risk patients.

Inflammation-related biomarkers are associated with clinical outcomes in mixed-etiology chronic heart failure populations. Inflammation-related markers tend to be higher in ischemic than in non-ischemic dilated cardiomyopathy (NI-DCM) patients, which might impact their prognostic performance in NI-DCM patients. Therefore, we aimed to assess the association of inflammation-related biomarkers with heart failure severity parameters and adverse cardiac events in a pure NI-DCM patient cohort. Fifty-seven patients with NI-DCM underwent endomyocardial biopsy. Biopsies were evaluated by immunohistochemistry for CD3+, CD45ro+, CD68+, CD4+, CD54+, and HLA-DR+ cells. Blood samples were tested for high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-α (TNF-α), soluble urokinase-type plasminogen activator receptor and adiponectin. During a five-year follow-up, twenty-seven patients experienced at least one composite adverse cardiac event: left ventricle assist device implantation, heart transplantation or death. Interleukin-6, TNF-α and adiponectin correlated with heart failure severity parameters. Patients with higher levels of interleukin-6, TNF-α, adiponectin or hs-CRP, or a higher number of CD3+ or CD45ro+ cells, had lower survival rates. Interleukin-6, adiponectin, and CD45ro+ cells were independently associated with poor clinical outcomes. All patients who had interleukin-6, TNF-α and adiponectin concentrations above the threshold experienced an adverse cardiac event. Therefore, a combination of these cytokines can identify high-risk NI-DCM patients.