Three-dimensional analysis of the tricuspid annular geometry in healthy subjects and in patients with different grades of functional tricuspid regurgitation.

BACKGROUND: Accurate sizing of the tricuspid valve annulus is essential for determining the optimal timing of tricuspid valve (TV) intervention. Two-dimensional (2D) echocardiography has limitations for comprehensive TV analysis. Three-dimensional (3D) imaging of the valve provides a better understanding of its spatial anatomy and enables more accurate measurements of TV structures. OBJECTIVES: The study aimed to analyze tricuspid annulus (TA) parameters in normal heart and in different grades of functional tricuspid regurgitation (TR); to compare TA measurements obtained by 2D and 3D echocardiography. METHODS: One hundred fifty-five patients (median age 65 years, 57% women) with normal TV and different functional TR grades underwent 2D and 3D transthoracic echocardiography. The severity of TR was estimated using multiparametric assessment according to the guidelines. Mid-systolic 3D TA parameters were calculated using TV dedicated software. The conventional 2D systolic TA measurements in a standard four-chamber view were performed. RESULTS: In mid-systole, the normal TA area was 9.2 ± 2.0 cm2 for men and 7.4 ± 1.6 cm2 for women. When indexed to body surface area (BSA), there were no significant differences in the 3D parameters between genders. The 2D TA diameters were smaller than those measured in 3D. The ROC curve analysis identified that all 3D TA parameters can accurately differentiate between different functional TR grades. Additionally, the optimal cut-off values were identified for each TA parameter. CONCLUSIONS: Gender, body size, and age have an impact on the TA parameters in healthy subjects. 2D measurements are smaller than 3D parameters. The reference values for 3D metrics according to TR severity can help in identifying TA dilation and distinguishing between different functional TR grades.

The Early Effects on Tricuspid Annulus and Right Chambers Dimensions in Successful Tricuspid Valve Bicuspidization.

BACKGROUND: It is unclear to what degree of tricuspid annulus (TA) reduction is necessary to achieve good postoperative results in surgical bicuspidization. The study aimed to evaluate TA and right heart chamber's dimensions before and after heart surgery; and to compare TA parameters assessed by different modalities. METHODS: Forty patients underwent mitral valve surgery with or without concomitant tricuspid valve (TV) bicuspidization. Preoperative and postoperative measurements of TA dimensions were performed prospectively using two-dimensional (2D) and three-dimensional (3D) transthoracic echocardiography (TTE). Additionally, preoperative transesophageal echocardiography (TOE) was performed in the operating room prior to surgery. RESULTS: All patients had no or mild TR immediately after surgery. There was a significant reduction in 2D and 3D parameters of the TV and right chambers in the TV bicuspidization group. However, TV leaflets' tethering parameters did not change significantly. Preoperative 3D TTE measurements were smaller than those obtained through 3D TOE in the operation room, before surgery under general anesthesia. The 2D systolic apical 4Ch diameter and the parasternal short axis diameter mainly represent the 3D minor axis of the TA and are smaller than its 3D major axis. CONCLUSIONS: Although bicuspidization results in a one-third reduction of the TV area, tethering of the TV leaflets remains unchanged. Moreover, 3D TOE parameters of the TV under general anesthesia are larger than preoperative 3D TTE measurements. Conventional 2D measurements are insufficient for evaluating the maximum diameter of the TA.

Molecular Mechanisms behind Persistent Presence of Parvovirus B19 in Human Dilated Myocardium.

The role of parvovirus B19 (PVB19) in the pathogenesis of idiopathic dilated cardiomyopathy (DCM) remains poorly understood. Therefore, we have measured the levels of inflammation, fibrosis, apoptosis, and necrosis in endomyocardial biopsies (EMBs) and sera of nonischemic PVB19-positive (n = 14) and PVB19-negative (n = 18) DCM patients. Chronic persistence of PVB19 in myocardium did not induce significant infiltration of T cells (CD3 and CD45Ro) and macrophages (CD68), and did not secrete TNFα, IL-6, and CRB. The fibrosis in PVB19-positive EMBs was also lower compared to the virus-negative ones, while ECM degrading matrix metalloproteinase MMP1 and gelatinase MMP2 were significantly (by twofold) upregulated. In addition, there was no activation of neither apoptotic nor necrotic pathways. However, levels of antiapoptotic mitochondrial Bcl-2 and heat shock protein 60 (Hsp60) in PVB19-positive biopsies were almost threefold lower than in PVB19-negative ones revealing impairment of mitochondria. Altogether, data indicate that persistence of PVB19 in myocardiums of nonischemic DCM patients can cause myocardial ECM remodeling through the MMPs, such as MMP1 and MMP2, and mitochondrial impairment. The correlative analysis of measured biomarkers suggested likely further activation of apoptotic cell death pathways rather than fibrosis. Data also suggest that antiviral therapy could be beneficial for PVB19-positive DCM patients by managing further pathological myocardial remodeling.

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 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.

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.

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 < 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.

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-α 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. Patients were followed-up for 5 years. The study outcome was composite: left ventricular assist device implantation, heart transplantation, or death from cardiovascular causes. Results: T-cad shows an inverse correlation with the mean PCWP (rho = -0.397, p = 0.037). There is a tendency towards a lower T-cad concentration in patients with more severe HF, as indicated by the 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.

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.

Successful application of thrombolysis and angioplasty in case of mechanical aortic valve and coronary graft thrombosis.

Prosthetic valve thrombosis (PVT) is a rare and fatal complication requiring immediate treatment. Optimal management of the left-sided obstructive PVT is still controversial and depends on patient's status, estimated risk of surgery, thrombus location and size, and clinician's experience. We report a case of a 71-year-old woman, presenting with signs of cardiogenic shock. Transesophageal echoscopy was used to diagnose acute obstructive thrombosis of the mechanical aortic valve. Concomitant coronary graft thrombosis was suspected due to signs of acute myocardial infarction. Thrombolysis with alteplase and subsequent stenting of the venous graft lead to successful resolution of the thrombotic lesions and a favourable patient outcome. Fibrinolytic therapy followed by angioplasty is a rational treatment alternative for inoperable or high risk patients in the case of concomitant mechanical valve and graft thrombosis.