Prevalence and prognostic relevance of myocardial inflammation and cardiotropic viruses in non-ischemic dilated cardiomyopathy

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 primary composite outcome measure: heart transplantation, left ventricle assist device implantation or cardiovascular-related death. Results: rvovirus 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

Adiponektino reikšmė širdies nepakankamumo dėl neišeminės kardiomiopatijos progresavimui

Non-ischemic dilated cardiomyopathy (NI-DCM) remains a substantial cause of chronic heart failure, eventually leading to heart transplantation. The course of the disease is not easily predictable: some of the patients remain stable while others deteriorate quickly. There are no reliable tools to differentiate early between these two disease courses. The accurate assessment of prognosis in patients with NI-DCM and advanced heart failure is also critical because of the limited number of hearts available for transplantation. Novel biomarkers or a combination of new biomarkers with the well-established ones would aid in patient counseling and transplantation list prioritization. Adiponectin is an adipocyte-derived cytokine, possessing cardioprotective properties. Adiponectin seems to protect the heart from stress-induced pathological remodeling through its association with its myocardial receptor T-cadherin. However, clinical studies of patients with chronic heart failure have revealed that adiponectin levels correlate with disease severity and portend increased risk of recurrent cardiovascular events and mortality. The aim of the present investigation, was to assess the impact of circulating adiponectin and cardiac T-cadherin levels on a five-year outcome of patients with NI-DCM and chronic heart failure. In the prospective cohort investigation, we have shown that higher serum adiponectin levels predict increased risk of composite outcome (death from cardiovascular causes, left ventricular assist device implantation, or heart transplantation) in patients with chronic NI-DCM. Higher T-cadherin concentration was linked to lower myocardial inflammation but failed to be a prognostic biomarker

The role of adiponectin in patients with non-ischemic dilated cardiomyopathy and chronic heart failure

Non-ischemic dilated cardiomyopathy (NI-DCM) remains a substantial cause of chronic heart failure, eventually leading to heart transplantation. The course of the disease is not easily predictable: some of the patients remain stable while others deteriorate quickly. There are no reliable tools to differentiate early between these two disease courses. The accurate assessment of prognosis in patients with NI-DCM and advanced heart failure is also critical because of the limited number of hearts available for transplantation. Novel biomarkers or a combination of new biomarkers with the well-established ones would aid in patient counseling and transplantation list prioritization. Adiponectin is an adipocyte-derived cytokine, possessing cardioprotective properties. Adiponectin seems to protect the heart from stress-induced pathological remodeling through its association with its myocardial receptor T-cadherin. However, clinical studies of patients with chronic heart failure have revealed that adiponectin levels correlate with disease severity and portend increased risk of recurrent cardiovascular events and mortality. The aim of the present investigation, was to assess the impact of circulating adiponectin and cardiac T-cadherin levels on a five-year outcome of patients with NI-DCM and chronic heart failure. In the prospective cohort investigation, we have shown that higher serum adiponectin levels predict increased risk of composite outcome (death from cardiovascular causes, left ventricular assist device implantation, or heart transplantation) in patients with chronic NI-DCM. Higher T-cadherin concentration was linked to lower myocardial inflammation but failed to be a prognostic biomarker

Oxygen Saturation Increase in Ischemic Wound Tissues after Direct and Indirect Revascularization

Background: The primary approach for treating ischemic wounds is restoring oxygen supply to the ischemic region. While direct angiosomal revascularization is often associated with better post-operative wound healing and limb salvage, its superiority over non-angiosomal revascularization remains controversial. This study aimed to compare intraoperative tissue oxygen saturation changes in ischemic zones following either direct or indirect revascularization in below-the-knee arteries. Methods: This prospective observational study included patients undergoing direct and indirect below-the-knee endovascular revascularizations. Assignment to the groups was not randomized. Near-infrared spectroscopy was used to monitor rSO2 changes near the ischemic wounds intraoperatively. The changes were compared between the groups. Results: 15 patients (50%) underwent direct angiosomal revascularization, while an equal number of patients underwent indirect revascularization. Overall, a statistically significant increase in regional oxygen saturation was observed after revascularization (p = 0.001). No statistically significant difference was found between the direct and indirect revascularization groups (p = 0.619). Conclusions: This study revealed a minor difference in the oxygen saturation increase between the angiosomal and non-angiosomal revascularization groups. Such a finding indicates that the clinical significance of angiosomal revascularization is negligible and might be concealed by confounding factors, such as the vessel diameter and outflow impact on the restenosis rate

Inflammation-Related Biomarkers Are Associated with Heart Failure Severity and Poor Clinical Outcomes in Patients with Non-Ischemic Dilated Cardiomyopathy

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

The Role of Serum Adiponectin for Outcome Prediction in Patients with Dilated Cardiomyopathy and Advanced Heart Failure

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

Left ventricular global longitudinal strain predicts elevated cardiac pressures and poor clinical outcomes in patients with non-ischemic dilated cardiomyopathy

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  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

The role of cardiac T-cadherin in the indicating heart failure severity of patients with non-ischemic dilated cardiomyopathy

Background and objectives: T-cadherin (T-cad) is one of the adiponectin receptors abundantly expressed in the heart and blood vessels. Experimental studies show that T-cad sequesters adiponectin in cardiovascular tissues and is critical for adiponectin-mediated cardio-protection. However, there are no data connecting cardiac T-cad levels with human chronic heart failure (HF). The aim of this study was to assess whether myocardial T-cad concentration is associated with chronic HF severity and whether the T-cad levels in human heart tissue might predict outcomes in patients with non-ischemic dilated cardiomyopathy (NI-DCM). Materials and Methods: 29 patients with chronic NI-DCM and advanced HF were enrolled. Patients underwent regular laboratory investigations, echocardiography, coronary angiography, and right heart catheterization. TNF- and IL6 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, endomyocardial biopsies were obtained, and the levels of T-cad were assessed by ELISA and CD3, CD45Ro, CD68, and CD4- immunohistochemically. Mean pulmonary capillary wedge pressure (PCWP) was used as a marker of HF severity, subdividing patients into two groups: mean PCWP > 19 mmHg vs. mean PCWP 19 mmHg compared to those with mean PCWP 19 mmHg (p = 0.058). Cardiac T-cad levels correlate negatively with myocardial CD3 cell count (rho = 0.423, p = 0.028). Conclusions: Univariate Cox regression analysis did not prove T-cad to be an outcome predictor (HR = 1, p = 0.349). However, decreased T-cad levels in human myocardium can be an additional indicator of HF severity. T-cad in human myocardium has an anti-inflammatory role. More studies are needed to extend the role of T-cad in the outcome prediction of patients with NI-DCM