Clinical Observation of Peripartum Cardiomyopathy

Research relevance: the article presents the results after clinical observation of peripartum cardiomyopathy in a patient aged 30 years. Purpose of the study: to analyze the results of a clinical study conducted in the cardiology department of the Osh Medical United Clinical Hospital. Research methods: a differential diagnosis of acute myocarditis, idiopathic dilated cardiomyopathy and peripartum cardiomyopathy was carried out. Research results: taking into account the life history, laboratory and instrumental examination data, the diagnosis was peripartum cardiomyopathy. Conclusion: the treatment carried out gave a satisfactory clinical effect.

Deep Neural Network-Aided Histopathological Analysis of Myocardial Injury

Deep neural networks have become the mainstream approach for analyzing and interpreting histology images. In this study, we established and validated an interpretable DNN model to assess endomyocardial biopsy (EMB) data of patients with myocardial injury. Deep learning models were used to extract features and classify EMB histopathological images of heart failure cases diagnosed with either ischemic cardiomyopathy or idiopathic dilated cardiomyopathy and non-failing cases (organ donors without a history of heart failure). We utilized the gradient-weighted class activation mapping (Grad-CAM) technique to emphasize injured regions, providing an entry point to assess the dominant morphology in the process of a comprehensive evaluation. To visualize clustered regions of interest (ROI), we utilized uniform manifold approximation and projection (UMAP) embedding for dimension reduction. We further implemented a multi-model ensemble mechanism to improve the quantitative metric (area under the receiver operating characteristic curve, AUC) to 0.985 and 0.992 on ROI-level and case-level, respectively, outperforming the achievement of 0.971 ± 0.017 and 0.981 ± 0.020 based on the sub-models. Collectively, this new methodology provides a robust and interpretive framework to explore local histopathological patterns, facilitating the automatic and high-throughput quantification of cardiac EMB analysis.

Matrix metalloproteinase 2 and 9 enzymatic activities are selectively increased in the myocardium of Chronic Chagas Disease cardiomyopathy patients: role of TIMPs

Chronic Chagas disease (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis compared to other cardiomyopathies. We show the expression and activity of Matrix Metalloproteinases (MMP) and of their inhibitors TIMP (tissue inhibitor of metalloproteinases) in myocardial samples of end stage CCC, idiopathic dilated cardiomyopathy (DCM) patients, and from organ donors. Our results showed significantly increased mRNA expression of several MMPs, several TIMPs and EMMPRIN in CCC and DCM samples. MMP-2 and TIMP-2 protein levels were significantly elevated in both sample groups, while MMP-9 protein level was exclusively increased in CCC. MMPs 2 and 9 activities were also exclusively increased in CCC. Results suggest that the balance between proteins that inhibit the MMP-2 and 9 is shifted toward their activation. Inflammation-induced increases in MMP-2 and 9 activity and expression associated with imbalanced TIMP regulation could be related to a more extensive heart remodeling and poorer prognosis in CCC patients.

Idiopathic dilated cardiomyopathy as cor bovinum in infancy: “A foggy road in winter”

Dilated cardiomyopathy, when diagnosed in infancy, poses an array of difficulties from reaching an etiological diagnosis to prognosticating the long-term outcome. Here, we report a case of idiopathic dilated cardiomyopathy in a 6-month-old child who responded well to beta-blocker (Carvedilol) in optimum dosage and revealed favorable cardiac remodeling over 6 months with substantial improvement in ejection fraction (EF) (EF of 22–44%) with significant amelioration of child’s symptoms. Our case has a unique message that while treating idiopathic dilated cardiomyopathy (DCM) in infancy, optimized use of the beta-blockers is most often the only way to clear the foggy road of idiopathic DCM and obtain a favorable outcome.

157 Efficacy and tolerability of sacubitril/valsartan in patients with chronic heart failure and reduced ejection fraction

Aims The PARADIGM-HF study has shown, as is well known, that the association of sacubitril/valsartan (SV) was superior in terms of efficacy compared to enalapril in patients suffering from heart failure chronic cardiac (SC) and reduced systolic function (HFrEF). We have analysed the use of SV in patients with symptomatic HF and HFrEF, andits effect on humoural and functional parameters of easy evaluation. Methods and results From March 2018 to December 2019 we have introduced the SV in 158 patients 135 M and 23 F mean age 40–80 years with fraction of ejection <35% with idiopathic dilated cardiomyopathy (six patients) or post-ischaemic (150 patients), in NYHA III class. Patients were declared eligible according to the ESC 2016 criteria (EF 40%, NT-proBNP> 400 ng/l, target dose of ACE inhibitors/receptor antagonists angiotensin, GFR> 30 ml/min/1.73 m2, serum S-potassium <5.2 mmol/l, treatment with beta-blockers and antialdosteronics). Initially the administration of SV was a cp of 49/51 mg bid up to maximum tolerated dose (one tablet of 97/103 mg bid). All the patients had stopped taking ACE-I or sartans 48 h before and were evaluated at 4-week intervals for two years. In all patients we evaluated: ejection fraction (FE), filtered glomerular, systolic blood pressure, body weight, side effects, hospitalization and mortality. Of the 156 patients, 17 achieved the optimal dose of SV (97/103 mg), 113 achieved SV 49/51 mg bid. In all patients did not experience side effects or alterations of the electrolyte picture and renal function. The SV has determined an improvement NYHA class of at least 1; the echocardiogram showed a significant increase in FE: at follow-up 89 patients reached FE 45%, 44 patients FE 40–44%, and 6 patients about 50%; besides it is an improvement in indexed end-diastolic volume in moles was noted above patients (from 118.4 ± 38.4 to 110.9 ± 30 ml/m2). No case of re-hospitalization. Conclusions Our experience shows that the use of SV is well tolerated, improves functional capacity and ventricular remodelling and that does not modify the parameters of renal function and electrolytic of the patients.

Distinct Microbial Communities in Dilated Cardiomyopathy Explanted Hearts Are Associated With Different Myocardial Rejection Outcomes

BackgroundIdiopathic dilated cardiomyopathy (IDCM) myocardial inflammation may be associated with external triggering factors such as infectious agents. Here, we searched if moderate/severe heart transplantation rejection is related to the presence of myocardial inflammation in IDCM explanted hearts, associated with microbial communities.MethodReceptor myocardial samples from 18 explanted hearts were separated into groups according to post-transplant outcome: persistent moderate rejection (PMR; n = 6), moderate rejection (MR; n = 7) that regressed after pulse therapy, and no rejection (NR; n = 5)/light intensity rejection. Inflammation was quantified through immunohistochemistry (IHC), and infectious agents were evaluated by IHC, molecular biology, in situ hybridization technique, and transmission electron microscopy (TEM).ResultsNR presented lower numbers of macrophages, as well as B cells (p = 0.0001), and higher HLA class II expression (p ≤ 0.0001). PMR and MR showed higher levels of Mycoplasma pneumoniae (p = 0.003) and hepatitis B core (p = 0.0009) antigens. NR presented higher levels of parvovirus B19 (PVB19) and human herpes virus 6 (HHV6) and a positive correlation between Borrelia burgdorferi (Bb) and enterovirus genes. Molecular biology demonstrated the presence of M. pneumoniae, Bb, HHV6, and PVB19 genes in all studied groups. TEM revealed structures compatible with the cited microorganisms.ConclusionsThis initial study investigating on infectious agents and inflammation in the IDCM explanted hearts showed that the association between M. pneumoniae and hepatitis B core was associated with a worse outcome after HT, represented by MR and PMR, suggesting that different IDCM microbial communities may be contributing to post-transplant myocardial rejection.

Computational and biochemical analyses reveal that cofilin-2 self assembles into amyloid-like structures and promotes the aggregation of other proteinaceous species: Pathogenic relevance to myopathies

Cofilin-2 is a member of the ADF/cofilin family, expressed extensively in adult muscle cells and involved in muscle maintenance and regeneration. Phosphorylated cofilin-2 is found in pre-fibrillar aggregates formed during idiopathic dilated cardiomyopathy. A recent study shows that phosphorylated cofilin-2, under oxidative distress, forms fibrillar aggregates. However, it remains unknown if cofilin-2 holds an innate propensity to form amyloid-like structures. In the present study, we employed various computational and biochemical techniques to explore the amyloid-forming potential of cofilin-2. We report that cofilin-2 possesses aggregation-prone regions (APRs), and these APRs get exposed to the surface, become solvent-accessible, and are involved in the intermolecular interactions during dimerization, an early stage of aggregation. Furthermore, the cofilin-2 amyloids, formed under physiological conditions, are capable of cross-seeding other monomeric globular proteins and amino acids, thus promoting their aggregation. We further show that Cys-39 and Cys-80 are critical in maintaining the thermodynamic stability of cofilin-2. The destabilizing effect of oxidation at Cys-39 but not that at Cys-80 is mitigated by Ser-3 phosphorylation. Cysteine oxidation leads to partial unfolding and loss of structure, suggesting that cysteine oxidation further induces early events of cofilin-2 aggregation. Overall, our results pose a possibility that cofilin-2 amyloidogenesis might be involved in the pathophysiology of diseases, such as myopathies. We propose that the exposure of APRs to the surface could provide mechanistic insight into the higher-order aggregation and amyloidogenesis of cofilin-2. Moreover, the cross-seeding activity of cofilin-2 amyloids hints towards its involvement in the hetero-aggregation in various amyloid-linked diseases.

Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients’ myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.

Assessment of Right Ventricular Function and Structure in Children with Idiopathic Dilated Cardiomyopathy

Background: Dilated cardiomyopathy (DCM) refers to dilating the ventricles and dysfunction of their systolic functions (predominantly the left ventricle) with or without congestive heart failure. In children, it is the most common form of heart muscle disease. We aimed to evaluate the right ventricular functions and structure using speckling tracking echocardiography in children with dilated cardiomyopathy and correlate this parameter with other echocardiographic findings. Methods: This observational Case-Control Study was carried out on 75 subjects. They were subdivided into two groups: Group 1: 50 patients with dilated cardiomyopathy Group 2: 25 healthy children matched for age and sex. Patients were evaluated by M-mode echocardiography, Transthoracic 2DE Examination (TTE), Tissue Doppler Examination (TDE) and Speckling Tracking Technique. Results: Left ventricle (LV) and right ventricle (RV) systolic dysfunction was evidenced by a significant decrease of mitral and tricuspid annular systolic velocities and a significant decrease of LV and RV global systolic strain and a significant decrease of LV and RV Ejection fraction (EF). LV and RV diastolic dysfunction were evidenced by a significant decrease of mitral and tricuspid annular diastolic velocities (E’/A’) and a significant increase of LV and RV Myocardial Perfusion Imaging (MPI). LV and RV global strains were significantly reduced in comparison to controls, suggesting that the dilated cardiomyopathy is a diffuse disease. Conclusion: In DCM patients, RV had significant systolic and diastolic dysfunction mainly elicited by the Tissue Doppler imaging (TDI) beside LV affection secondary to the interventricular interaction. TDI and 2D-STE add value to interpreting the findings and the dependency of RV systolic and diastolic functions on each other in DCM patients.