Chronic Dilated Cardiomyopathy Research Articles

Enhancing patient care: a multimodality strategy for dilated cardiomyopathy in Chagas disease

Chagas disease is a systemic illness characterized by acute and chronic phases. If untreated, it can lead to dysfunction of vital organs, notably the heart, ultimately resulting in heart failure. Transmission primarily occurs through the feces of triatomine insects carrying the protozoan parasite Trypanosoma cruzi, either via a bite wound or intact mucous membranes. Diagnosis of Chagas disease involves serological tests, electrocardiographic findings, and imaging studies. A 58-year-old male patient from Peru with chronic dilated cardiomyopathy underwent evaluation at a tertiary care hospital. Given the uncertain etiology, a comprehensive diagnostic approach was adopted, emphasizing the pivotal role of cardiovascular magnetic resonance imaging and computed tomography angiography in managing chronic cardiomyopathy of Chagas disease. Leveraging these imaging modalities together could augment our ability to evaluate myocardial inflammation and tailor therapeutic strategies accordingly.

Comparison of structure and immunogenicity of CVB1-VLP and inactivated CVB1 vaccine candidates.

Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, dilated cardiomyopathy and aseptic meningitis. However, no CVB-vaccines are available for human use. In this study, we investigated the immunogenicity of virus-like particle (VLP) and inactivated whole-virus vaccines for CVB1 when administrated to mice via either subcutaneous or intranasal routes formulated with and without commercial and experimental adjuvants. Here, the potential of utilizing epigallocatechin-3-gallate (EGCG) as a mucosal adjuvant synergistically with its ability to inactivate the virus were investigated. EGCG had promising adjuvant properties for CVB1-VLP when administered via the parenteral route but limited efficacy via intranasal administration. However, intranasal administration of the formalin-inactivated virus induced high CVB1-specific humoral, cellular, and mucosal immune responses. Also, based on CVB1-specific IgG-antibody responses, we conclude that CVB1-VLP can be taken up by immune cells when administrated intranasally and further structural engineering for the VLP may increase the mucosal immunogenicity. The preparations contained mixtures of compact and expanded A particles with 85% expanded in the formalin-inactivated virus, but only 52% in the VLP observed by cryogenic electron microscopy. To correlate the structure to immunogenicity, we solved the structures of the CVB1-VLP and the formalin-inactivated CVB1 virus at resolutions ranging from 2.15 A to 4.1 A for the expanded and compact VLP and virus particles by image reconstruction. These structures can be used in designing mutations increasing the stability and immunogenicity of CVB1-VLP in the future. Overall, our results highlight the potential of using formalin inactivated CVB1 vaccine in mucosal immunization programs and provide important information for future development of VLP-based vaccines against all enteroviruses.

The Role of Rituximab in the Management of Heart Failure

Rituximab is a chimeric monoclonal antibody mice/humans that bind the transmembrane antigen, CD20 specifically. The mechanism of heart failure is mediated by neurohormonal pathways: the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system, and the natriuretic peptide system, thereby triggering activation of the immune system. This literature review will discuss the role of B cell targeted therapy, in this case rituximab in the management of heart failure. Modulation of the immune response holds great promise in the 30% of cases of myocarditis where inflammation does not resolve and progression to chronic inflammatory dilated cardiomyopathy occurs. Pharmacologically, rituximab is a monoclonal immunoglobulin G1 antibody drug that is given intravenously. Rituximab targets the CD20 antigen expressed on the surface of mature B lymphocytes, including memory B cells but not on stem cells or plasma cells. In conclusion, rituximab causes a selective and temporary decrease in the CD20+ B cell subpopulation and represents a more specific and targeted approach to B cell-induced disorders including heart failure.

Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis.

The cardiovascular effects of metformin continue to be a subject of debate within the medical community. The Mendelian randomization (MR) study used data from genome-wide association studies (GWAS) to explore the causal association with six diseases that are associated with bimatoprost treatment and myocardial infarction, chronic heart failure, atrial fibrillation, hypertrophic and dilated cardiomyopathy, and valvular disease. Genome-wide significant single nucleotide polymorphisms (SNPs), that are associated with metformin use were selected as the instrumental variables. To determine the causal relationship between metformin use and various cardiovascular diseases, MR analysis was conducted, employing methods such as Instrumental Variable Weighting (IVW). The IVW analysis demonstrated a positive association between metformin treatment and the risk of myocardial infarction (OR = 22.67, 95% CI 3.22-34.01; P = 0.002). Conversely, metformin treatment exhibited a negative association with the risk of developing valvular disease (OR = 0.98, 95% CI 0.95-1.00; P = 0.046) and hypertrophic cardiomyopathy (OR = 0.01, 95% CI 0.00-0.22; P = 0.016). Multiple test correction found that metformin treatment was causally associated with the risk of both hypertrophic cardiomyopathy (PFDR = 0.048) and myocardial infarction (PFDR = 0.012). The analysis revealed limited heterogeneity in the individual results, absence of pleiotropy evidence, and indications of stability in the findings. The MR study discovered from a genetic standpoint that metformin may lower the risk of hypertrophic cardiomyopathy and valvular heart disease, yet it could elevate the risk of myocardial infarction.

Automated assessment of cardiac pathologies on cardiac MRI using T1-mapping and late gadolinium phase sensitive inversion recovery sequences with deep learning

BackgroundA deep learning (DL) model that automatically detects cardiac pathologies on cardiac MRI may help streamline the diagnostic workflow. To develop a DL model to detect cardiac pathologies on cardiac MRI T1-mapping and late gadolinium phase sensitive inversion recovery (PSIR) sequences were used.MethodsSubjects in this study were either diagnosed with cardiac pathology (n = 137) including acute and chronic myocardial infarction, myocarditis, dilated cardiomyopathy, and hypertrophic cardiomyopathy or classified as normal (n = 63). Cardiac MR imaging included T1-mapping and PSIR sequences. Subjects were split 65/15/20% for training, validation, and hold-out testing. The DL models were based on an ImageNet pretrained DenseNet-161 and implemented using PyTorch and fastai. Data augmentation with random rotation and mixup was applied. Categorical cross entropy was used as the loss function with a cyclic learning rate (1e-3). DL models for both sequences were developed separately using similar training parameters. The final model was chosen based on its performance on the validation set. Gradient-weighted class activation maps (Grad-CAMs) visualized the decision-making process of the DL model.ResultsThe DL model achieved a sensitivity, specificity, and accuracy of 100%, 38%, and 88% on PSIR images and 78%, 54%, and 70% on T1-mapping images. Grad-CAMs demonstrated that the DL model focused its attention on myocardium and cardiac pathology when evaluating MR images.ConclusionsThe developed DL models were able to reliably detect cardiac pathologies on cardiac MR images. The diagnostic performance of T1 mapping alone is particularly of note since it does not require a contrast agent and can be acquired quickly.

CD4+TEM cells drive the progression from acute myocarditis to dilated cardiomyopathy in CVB3-induced BALB/c mice

Acute viral myocarditis can progress to chronic myocarditis leading to dilated cardiomyopathy (DCM). Persistent CD4+ T-cell-mediated autoimmunity triggered by infection plays a critical role in this progression. Increasing evidence demonstrates that effector memory CD4+T (CD4+TEM) cells, a subset of memory CD4+ T cells, are crucial pathogenic mediators of many autoimmune diseases. However, the role of CD4+TEM cells during the progression from acute viral myocarditis to DCM remains unknown. In this study, we observed an increase in CD4+TEM cells both in the periphery and the heart, and memory CD4+ T cells were the predominant sources of IL-17A and IFN-γ among inflamed heart-infiltrating CD4+ T cells during the progression from acute myocarditis to chronic myocarditis and DCM in CVB3-induced BALB/c mice. Moreover, splenic CD4+TEM cells sorted from DCM mice induced by CVB3 were found to respond to cardiac self-antigens ex vivo. Additionally, adoptive transfer experiments substantiated their pathogenic impact, inducing sustained myocardial inflammation, tissue fibrosis, cardiac injury, and impairment of cardiac systolic function in vivo. Our findings illustrate that long-lived CD4+TEM cells are important contributors to the progression from acute viral myocarditis into DCM.

Characterization of immune response towards modified Coxsackie B virus-like particle vaccine in a murine model

Abstract Coxsackievirus Bs (CVBs) are common human RNA viruses that belong to the enterovirus genus of Picornaviridae. Most commonly, infections with these viruses manifest with mild flu-like symptoms. However, CVBs are also known to cause severe diseases, including aseptic meningitis, myocarditis, and chronic dilated cardiomyopathy (DCM), encephalitis, pancreatitis, and hand-foot-and-mouth disease. In this study, we aimed for a versatile characterization of a modified CVB virus-like particle vaccine in a murine model. The modified CVB-VLP was produced using baculovirus-insect cell production platform. Purified and characterized vaccine was administered to mice via s.c. or i.m. routes, either with or without an adjuvant. Immunological characterization of vaccine response included both humoral and cellular characterization. Antigen-specific IgG levels and neutralizing antibodies in the sera were measured to determine the humoral immune response. To characterize the cellular immunity, activation markers of the lymphocytes were identified using flow cytometry. Additionally, the cytokine secretion of the stimulated splenocytes was determined with FluoroSpot assay. The modified CVB-VLP induced high levels of IgG and neutralizing antibodies in the sera of vaccinated mice. Further, the in vitro stimulation of splenocytes induced activation of mainly CD4+ T-cells, and adjuvanted vaccine induced a significant production level of IFN-γ and IL-2. These results indicate that the virus-like particle combined with an adjuvant is a promising vaccine candidate. In addition, our current challenge study with coxsackie B1 virus will shed us more insight on the protective role of this vaccine. Supported by grants from Finnish Foundations (Instrumentarium Science Foundation, Paulo Foundation and Ida Montini Foundation)

Diagnostic and prognostic role of late gadolinium enhancement in cardiomyopathies.

Late gadolinium enhancement (LGE) is the most relevant tool of cardiac magnetic resonance for tissue characterization, and it plays a pivotal role for diagnostic and prognostic assessment of cardiomyopathies. The pattern of presentation of LGE allows differential diagnosis between ischaemic and non-ischaemic heart disease with high diagnostic accuracy, and among different cardiomyopathies, specific presentation of LGE may help to make a diagnosis. Late gadolinium enhancement may be caused by conditions that significantly increase the interstitial space or, less frequently, that slow down Gd exit, like myocardial fibrosis. In chronic myocardial infarction, hypertrophic cardiomyopathies (HCM), dilated cardiomyopathy, Fabry disease, and other conditions, LGE is a marker of myocardial fibrosis, but also in patients with acute myocarditis where LGE may be also explained by the increase of interstitial space caused by interstitial oedema or by tissue infiltration of inflammatory cells. In cardiac amyloidosis, LGE represents myocardial fibrosis but the interstitial overload of amyloid proteins should also be considered as a potential cause of LGE. The identification of the pattern of presentation of LGE is also very important. In the ischaemic pattern, LGE always involves the subendocardial layer with more or less transmural extent, it is confluent, and every single scar should be located in the territory of one coronary artery. In the non-ischaemic pattern, LGE does not fulfil the previous criteria, being midwall, subepicardial, or mixed, not necessarily confluent or confined to a territory of one coronary artery. For cardiomyopathies, the exact pattern of non-ischaemic LGE is important. Quantitative analysis of LGE is required in some specific conditions as in HCM. Magnetic resonance imaging with LGE technique should be performed in every patient with suspect of cardiomyopathy. The lack of standardization of pulse sequence and mostly of quantification methods is the main limitation of LGE technique.

Prevalence, hematological parameters, and coagulation profiles: Cardiovascular diseases statistics in the Asir region, Saudi Arabia.

To determine the prevalence of cardiovascular disease (CVD) types in the Asir region of Saudi Arabia and the importance of hematological testing for CVD patients in the context of disease management. This retrospective study comprised 416 CVD patients, and samples were divided based the type of CVD. The Mann Whitney U test was used to compare patients' hematological markers and coagulation profiles to those of healthy controls. The rate of ischemic heart disease (IHD) was 80.7% that of other CVDs, and the rate of ST-elevation myocardial infarction (STEMI) was 37.3% the rate of CVD. Significant differences were observed in the hematological and coagulation parameters of CVD patients compared to the control group. White blood cells (WBC) were significantly higher in STEMI, non-ST-elevation myocardial infarction (NSTEMI), unstable angina (UA), and heart failure (HF) groups. Red blood cells (RBC) were significantly lower in STEMI, NSTEMI, UA, chronic coronary syndrome (CCS), HF, dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). Red distribution width (RDW) was significantly greater in the HF, DCM, and ICM groups. Prothrombin time (PT) was significantly higher in the STEMI, HF, and DCM groups. ST-elevation myocardial infarction has a higher prevalence rate among CVD patients in the Asir region. Both coagulation and hematological indicators have high potential utility as CVD diagnostic and prognostic markers.

Right ventricular peak systolic free wall longitudinal strain as a practical tool to detect right ventricular dysfunction in acute myocarditis.

Acute myocarditis is one of the etiologies of acute heart failure, chronic dilated cardiomyopathy, and cardiac mortality. The extent of right ventricular (RV) involvement and its impact on the course of the disease have been scarcely studied. This study aimed to evaluate both the prevalence of RV dysfunction in acute myocarditis and echocardiographic measures as a diagnostic tool for RV dysfunction compared with cardiac magnetic resonance imaging (CMR) findings. This retrospective study enrolled patients with a definite or probable acute myocarditis diagnosis based on the Lake Louise criteria in CMR and evaluated the diagnostic accuracy of echocardiographic measures in predicting RV dysfunction in CMR. The study population consisted of 71 patients, including 54 men (76%), at a median (Q1-Q3) age of 33 (26-46) years. CMR detected RV dysfunction in 53.5% of the patients. The RV free wall peak systolic longitudinal strain showed the highest correlation (r=-.786, p<.001) and area under the curve (.919) with the RV ejection fraction in CMR, followed by the RV global peak systolic longitudinal strain and the RV fractional area change. The RV-free wall peak systolic longitudinal strain had a sensitivity of 92% and a specificity of 73% for the diagnosis of RV dysfunction in myocarditis. A cutoff value of -17.9% was 100% specific for RV systolic dysfunction. Echocardiography, as a readily available tool, was predictive of and had acceptable accuracy for RV dysfunction in acute myocarditis compared with CMR.

Poisoning with atropine-based eye drops: An almost perfect murder?

A 56-year-old man was found unresponsive in his bathroom by his daughter, and declared dead by the mobile emergency and resuscitation service (SMUR). There were no signs of tampering or an intervention by a third party. However, in the absence of the deceased's wallet and identification documents, the emergency doctor cannot certify the death as natural. Thus, the Public Prosecutor's Office launched an investigation and a forensic doctor was required at the scene. The man was known to be an alcohol addict and numerous licit drugs were prescribed. The deceased had a new friend since 6 months. An external examination and an autopsy were done by a forensic pathologist. A systematic toxicological analysis (STA) was performed on blood, urine and gastric content. In addition, other investigations such as financial data, mobile phone transcripts, etc. were initiated. A rectal temperature of 41.2 °C, bilateral mydriasis and the absence of traumatic lesions was observed during the external examination of the body. The autopsy revealed hepatic steatosis, chronic dilated cardiomyopathy, acute pulmonary edema and a vesical globe. STA was positive for alcohol, alprazolam, venlafaxine, bisoprolol and atropine. Despite a therapeutic atropine blood concentration (23 ng/mL), this compound turns out to be the main element of this case. With its short half-life, atropine intoxication cannot be excluded, certainly in the event that a significant period of time has elapsed between the intake of atropine and death. Dose estimates of consumed atropine were made on the basis of the STA urinary concentration and the volume of urine in the bladder noted during the autopsy. Depending on the route of administration, the dose of atropine consumed would be at least 20 times higher than in a therapeutic setting. Research concerning the new friend of the deceased revealed some interesting findings: (a) a search of medical prescriptions of the friend revealed two prescriptions for Isopto-Atropine®, the day before or the day of death, delivered in two different pharmacies, (b) a third prescription was dispensed four months earlier, (c) the mobile phone transcripts raised suspicion of another poisoning. This person was hospitalized but fully recovered. The urine sample collected at the hospital of this third person was sent for STA. This sample revealed the presence of four drugs identical to those identified in the deceased, namely alprazolam, venlafaxine, bisoprolol and atropine. After a consistent denial of committing a crime on the second day of the trial, the accused admitted having emptied two bottles of Isopto-Atropine® into the beer of the deceased victim. This confirmed what we had calculated as dose.

54-Year-Old Man With Acute Dyspnea on Exertion

54-Year-Old Man With Acute Dyspnea on Exertion

The role of cardiovascular magnetic resonance in the evaluation of acute myocarditis and inflammatory cardiomyopathies in clinical practice - a comprehensive review.

Inflammatory cardiomyopathy (I-CMP) is defined as myocarditis in association with cardiac dysfunction and/or ventricular remodelling. It is characterized by inflammatory cell infiltration into the myocardium and has heterogeneous infectious and non-infectious aetiologies. A complex interplay of genetic, autoimmune, and environmental factors contributes to the substantial risk of deteriorating cardiac function, acute heart failure, and arrhythmia as well as chronic dilated cardiomyopathy and its sequelae. Multi-parametric cardiovascular magnetic resonance (CMR) imaging is sensitive to many tissue changes that occur during myocardial inflammation, regardless of its aetiology. In this review, we summarize the various aetiologies of I-CMP and illustrate how CMR contributes to non-invasive diagnosis.

Myocarditis and pericarditis: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data

Myocarditis and/or pericarditis (also known as myopericarditis) are inflammatory diseases involving the myocardium (with non-ischemic myocyte necrosis) and/or the pericardial sac. Myocarditis/pericarditis (MPC) may present with variable clinical signs, symptoms, etiologies and outcomes, including acute heart failure, sudden death, and chronic dilated cardiomyopathy. Possible undiagnosed and/or subclinical acute myocarditis, with undefined potential for delayed manifestations, presents further challenges for diagnosing an acute disease and may go undetected in the setting of infection as well as adverse drug/vaccine reactions.The most common causes of MPC are viral, with non-infectious, drug/vaccine associated hypersensitivity and/or autoimmune causes being less well defined and with potentially different inflammatory mechanisms and treatment responses. Potential cardiac adverse events following immunization (AEFIs) encompass a larger scope of diagnoses such as triggering or exacerbating ischemic cardiac events, cardiomyopathy with potential heart failure, arrhythmias and sudden death. The current published experience does not support a potential causal association with vaccines based on epidemiologic evidence of relative risk increases compared with background unvaccinated incidence. The only evidence supporting a possible causal association of MPC with a vaccine comes from case reports.Hypersensitivity MPC as a drug/vaccine induced cardiac adverse event has long been a concern for post-licensure safety surveillance, as well as safety data submission for licensure. Other cardiac adverse events, such as dilated cardiomyopathy, were also defined in the CDC definitions for adverse events after smallpox vaccination in 2006. In addition, several groups have attempted to develop and improve the definition and adjudication of post-vaccination cardiovascular events. We developed the current case definitions for myocarditis and pericarditis as an AEFI building on experience and lessons learnt, as well as a comprehensive literature review. Considerations of other etiologies and causal relationships are outside the scope of this document.

Potencial arrítmico de cardiopatias em cães

ABSTRACT: Presently, pet life expectancy is becoming longer and several diseases inherent to age have been diagnosed, with heart disease being a frequent finding. Although various heart diseases have different pathophysiologies, many morphological and hemodynamic changes can predispose patients to arrhythmias. The presence of arrhythmias can worsen the underlying heart disease and predispose patients to develop new alterations, making arrhythmia detection important for establishing adequate therapeutic protocols and a better prognosis. The present study aimed to determine the arrhythmias most frequently found in dogs treated at the Cardiology and Respiratory Diseases Service (SCDR) of the Small Animals Sector of the Veterinary Hospital of the Federal Rural University of Rio de Janeiro (UFRRJ), during the period from January to 2014 to December 2017, relating them to sex, age group, size, and the presence or absence of heart disease. A total of 586 medical records of dogs treated with SCDR-UFRRJ were retrospectively evaluated. Of these, 15.4% had arrhythmias, 95.6% had diagnoses of heart disease, 61.1% (55/90) were diagnosed with mitral valve disease, and 27.8% (25/90) had dilated cardiomyopathies. The most frequent rhythm disturbances were premature ventricular complexes associated with chronic degenerative mitral valve disease or dilated cardiomyopathy. Statistical analysis confirmed the risk of a cardiac patient developing rhythm or conduction alterations (OR, 4.46; p = 0.0003). In conclusion, the pathophysiology of heart failure can lead to the development of rhythm and conduction disorders.

Drug Repurposing Patent Applications April–June 2021

Drug Repurposing Patent Applications April–June 2021

Cushing Syndrome in the Setting of Chronic Dilated Cardiomyopathy: Can Treatment Improve Chronic Dilated Cardiomyopathy?

Background: Cushing syndrome (CS) is well known to be associated with metabolic syndrome, venous thromboembolism, hypertension, left ventricular hypertrophy, and rarely dilated cardiomyopathy. The pathophysiological effects of hypercortisolism on the myocardium results in cardiomyocyte hypertrophy, myofibrillolysis, myocardial fibrosis, global longitudinal and circumferential strain. Our patient presents an example of CS in the setting of chronic heart failure with reduced ejection fraction, multiple thromboembolic events, and diabetes mellitus in a young adult.Clinical Case: A 34-year male with a past medical history of dilated cardiomyopathy with biventricular failure and left ventricle ejection fraction of 10%, pulmonary embolism, diabetes mellitus, and gout presented with shortness of breath. On physical exam he presented with symptoms of CS: moon facies, supraclavicular fat pads, dorsal fat pads, purple striae of abdominal skin, truncal obesity, ecchymosis, and skin atrophy. Labs showed elevated morning cortisol after overnight 1 mg dexamethasone suppression test (cortisol 8.6 mcg/dl, n< 5 mcg/dl), repeat morning cortisol after overnight 1 mg dexamethasone suppression test (cortisol 5.7 mcg/dl, n< 5 mcg/dl), and ACTH-concentrations <5 pg/ml. CT-scan was insignificant for adrenal hyperplasia. He was admitted and treated for acute congestive heart failure exacerbation with plans for definitive treatment of CS outpatient with further imaging studies.Conclusion: The occurrence of CS induced heart failure results in increased mortality. There have been numerous accounts of resolution of cardiomyopathy after surgical treatment for CS secondary to adrenal adenoma. Our patient had a 10-year history of chronic dilated cardiomyopathy prior to cushingoid symptoms and confirmatory endocrinological data. The definitive treatment for CS syndrome in our patient would eventually be surgery targeting the source of hypercortisolism, however his cardiovascular risk factors would make him a poor surgical candidate. Severely reduced ejection fraction is a contraindication for generalized anesthesia needed for surgery. When surgery is contraindicated in CS medical management is recommended according to guidelines that target pituitary-directed medical treatments for Cushing’s disease and targeted therapies to treat ectopic ACTH syndrome. To our knowledge there have been few studies that demonstrate the effects of CS treatment on chronic conditions such as dilated cardiomyopathy. Studies have shown that surgical treatment for CS have reversed cardiomyopathy caused by CS but it still remains to be answered whether this same effect is achieved to some degree in chronic dilated cardiomyopathy.

Relationships between circulating galectin-3, extracellular matrix fibrosis and outcomes in dilated cardiomyopathy.

Galectin-3 is an emerging biomarker in cardiovascular disease. Myocardial galectin-3 is involved in the pathology of cardiac fibrosis; however, the role of circulating galectin-3 is not yet established. To assess the relationships between circulating galectin-3, fibrosis and outcomes in dilated cardiomyopathy (DCM). We included 70 patients (age: 48 ±12.1 years, ejection fraction (EF) 24.4 ±7.4%) with new-onset DCM (n = 35, ≤6 months). Galectin-3 and procollagen type I and III (PICP, PINP, PIIICP, and PIIINP), transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), osteopontin (OPN), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitor (TIMP-1) were determined in serum at baseline and after 3 and 12 months. Patients underwent endomyocardial biopsy. The endpoint was a combination of death and urgent hospitalization at 12 months. Galectin-3 did not correlate with biopsy-determined fibrosis. Baseline galectin-3 correlated with OPN,, TIMP-1, PIIICP, and MMP-2. In new-onset DCM, galectin-3 levels at baseline were higher than at 3 and 12 months, whereas in chronic DCM there was no difference. Galectin-3 was a predictor of the endpoint (hazard ratio (HR) = 1.115; 95% confidence interval (95% CI) = 1.009-1.231; p < 0.05). The best cut-off value was 14.54 ng/mL (area under the curve (AUC) = 0.67). Patients with galectin-3 ≥14.54 ng/mL had an increased risk of events (HR = 2.569; 95% CI = 1.098-6.009; p < 0.05). Circulating galectin-3 is unrelated to fibrosis. Serial measurements of galectin-3 correlated with markers of fibrosis, including markers of collagen synthesis and OPN. Circulating galectin-3 was independently associated with cardiovascular (CV) outcomes in DCM.

Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial.

AimsPrevious uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)‐related dilated cardiomyopathy (DCM). This randomized, double‐blind, placebo‐controlled, single‐centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.Methods and resultsFifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6‐min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end‐diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (−7;5) vs. placebo −2 (−6;6), P = 0.904] and LVEDV (IVIg −16 ± 49 mL/m2 vs. placebo −29 ± 40 mL/m2; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups.ConclusionIntravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence.Clinical Trial Registration: ClinicalTrials.gov ID NCT00892112.

Tropism of Coxsackie virus A9 depends on the +1 position of the RGD (arginine- glycine- aspartic acid) motif found at the C’ terminus of its VP1 capsid protein

An understanding of how viruses interact with their receptors is vital as this step is a major determinant of host susceptibility and disease. The enterovirus coxsackievirus A9 (CVA9) is an important pathogen responsible for respiratory infections, myocarditis, infections of the central nervous system, chronic dilated cardiomyopathy and possibly type I diabetes. CVA9 harbours an integrin- recognition motif, RGD (Arg-Gly-Asp), in the capsid protein VP1 and this motif is believed to be primarily responsible for binding to integrins αvβ6 and/or αvβ3 during cell entry. Despite the consistent conservation of RGD-flanking amino acids in multiple RGD-containing picornaviruses, the significance of these amino acids to cell tropism has not been thoroughly investigated. In this study we used 10 CVA9 mutants and a panel of cells to analyse cell tropism. We showed that CVA9 infection proceeds by either an RGD- dependent or an apparently RGD- independent pathway. Differences in the amino acid found at the +1 position of the RGD motif affect the cell tropism of CVA9 when an RGD- dependent pathway is used. Naturally occurring CVA9 isolates have either the sequence RGDM and RGDL and we found that the corresponding viruses in our panel infected cells most efficiently. There was also a strong selection pressure for RGDL in adaptation experiments. However, there was also an unexpected selection of an RGDL variant in an apparently RGD- independent cell line. There was also no simple relationship between infection of cells and expression of integrins αvβ3 and αvβ6. The results obtained have greatly improved our understanding of how CVA9 infects cells. This will be useful in the design of antivirus drugs and also gives a framework for the modification of CVA9 or other RGD containing picornaviruses for specific targeting of cancer cells for oncolytic therapy.