644 research outputs found

    Dilated Cardiomyopathy. From Genetics to Clinical Management

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    The current definition of dilated cardiomyopathy (DCM) is relatively simple: it is a heart muscle disease characterized by left ventricular (LV) or biventricular dilation and systolic dysfunction in the absence of either pressure or volume overload or coronary artery disease sufficient enough to explain the dysfunction. In the last 30 years, prognosis of patients with DCM has dramatically been improved with few similarities in the history of cardiology and medicine. Typically, in the 1980s, the average survival rate was approximately 50% in a 5-year follow-up. Nowadays, at 10 years of follow-up, the survival/free from heart transplant rate is far beyond 85%, and the projection of this improvement is significantly better for those who have had DCM diagnosed in the late 2010s. This improvement in outcomes is fundamentally due to a better characterization of etiological factors, medical management for heart failure, and device treatment, like the implantable cardioverter defibrillator (ICD), for sudden cardiac death prevention. However, other milestones should be recognized for the improvement in the survival rate, namely, the early diagnosis due to familial and sport-related screening, which allow detection of DCM at a less severe stage, and the uninterrupted, active, and individualized long-term follow-up with continuous reevaluation of the disease and re-stratification of the risk

    Pragmatic electrocardiogram tracings in non-ischaemic dilated cardiomyopathy: diagnostic and prognostic role

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    Dilated cardiomyopathy (DCM) is a primitive heart muscle disease characterized by a great heterogeneous aetiology and prognostic outcome. Dilated cardiomyopathy is an umbrella term encompassing different aetiologies that might require specific treatments. It principally affects young and male adults, with high-risk arrhythmic competitive risk. Unfortunately, the prevention of major ventricular arrhythmic events remains a clinical challenge. In the era of advanced multimodality imaging and widely available genetic testing, electrocardiogram (ECG) continues to represent a reliable diagnostic tool, for specific work up of every single patient. However, approaching DCM patients, only a cardiomyopathy-oriented reading makes the role of ECG central in the management of DCM, both for diagnosis, prognosis, and therapeutic management. In this paper, we present four ECGs of four different DCM patients, in order to guide a cardiomyopathy-oriented ECG reading, emphasizing its impact in an early, cost-effective, and personalized diagnostic and prognostic work up in this specific setting

    Notch1 signaling stimulates proliferation of immature cardiomyocytes

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    The identification of the molecular mechanisms controlling cardiomyocyte proliferation during the embryonic, fetal, and early neonatal life appears of paramount interest in regard to exploiting this information to promote cardiac regeneration. Here, we show that the proliferative potential of neonatal rat cardiomyocytes is powerfully stimulated by the sustained activation of the Notch pathway. We found that Notch1 is expressed in proliferating ventricular immature cardiac myocytes (ICMs) both in vitro and in vivo, and that the number of Notch1-positive cells in the heart declines with age. Notch1 expression in ICMs paralleled the expression of its Jagged1 ligand on non-myocyte supporting cells. The inhibition of Notch signaling in ICMs blocked their proliferation and induced apoptosis; in contrast, its activation by Jagged1 or by the constitutive expression of its activated form using an adeno-associated virus markedly stimulated proliferative signaling and promoted ICM expansion. Maintenance or reactivation of Notch signaling in cardiac myocytes might represent an interesting target for innovative regenerative therapy

    Pianeta Cuore 3.0 istruzioni per conoscerlo e mantenerlo sano

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    Il testo è caratterizzato dall’essenzialità, dalla schematicità e dalla chiarezza e nasce dalle domande più frequenti che i Pazienti e i familiari pongono sulle varie cardiopatie, prefazione all'edizione del 2010, e sugli aspetti diagnostico-terapeutici in Cardiologia. Indugia maggiormente sulla prevenzione cardiovascolare e le cardiopatie coronariche perché, attraverso la prevenzione è possibile ridurre i nuovi casi di malattia e le recidive di malattia, massimizzando i risultati delle procedure e tecnologie terapeutiche avanzate delle quali oggi disponiamo. Include un utilissimo glossario che illustra il significato delle parole più ricorrenti nel gergo cardiologico la cui comprensione non sempre è immediata

    Gene Therapy for the Heart Lessons Learned and Future Perspectives

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    While clinical gene therapy celebrates its first successes, with several products already approved for clinical use and several hundreds in the final stages of the clinical approval pipeline, there is not a single gene therapy approach that has worked for the heart. Here, we review the past experience gained in the several cardiac gene therapy clinical trials that had the goal of inducing therapeutic angiogenesis in the ischemic heart and in the attempts at modulating cardiac function in heart failure. Critical assessment of the results so far achieved indicates that the efficiency of cardiac gene delivery remains a major hurdle preventing success but also that improvements need to be sought in establishing more reliable large animal models, choosing more effective therapeutic genes, better designing clinical trials, and more deeply understanding cardiac biology. We also emphasize a few areas of cardiac gene therapy development that hold great promise for the future. In particular, the transition from gene addition studies using protein-coding cDNAs to the modulation of gene expression using small RNA therapeutics and the improvement of precise gene editing now pave the way to applications such as cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies that were unapproachable until a decade ago

    A note on prognostic accuracy evaluation of regression models applied to longitudinal autocorrelated binary data

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    Background: Focus of this work was on evaluating the prognostic accuracy of two approaches for modelling binary longitudinal outcomes, a Generalized Estimating Equation (GEE) and a likelihood based method, Marginalized Transition Model (MTM), in which a transition model is combined with a marginal generalized linear model describing the average response as a function of measured predictors. Methods: A retrospective study on cardiovascular patients and a prospective study on sciatic pain were used to evaluate discrimination by computing the Area Under the Receiver-Operating-Characteristics curve, (AUC ), the Integrated Discrimination Improvement (IDI) and the Net Reclassification Improvement (NRI) at different time occasions. Calibration was also evaluated. A simulation study was run in order to compare model’s performance in a context of a perfect knowledge of the data generating mechanism. Results: Similar regression coefficients estimates and comparable calibration were obtained; an higher discrimination level for MTM was observed. No significant differences in calibration and MSE (Mean Square Error) emerged in the simulation study; MTM higher discrimination level was confirmed. ConclusionS: The choice of the regression approach should depend on the scientific question being addressed: whether the overall population-average and calibration are the objectives of interest, or the subject-specific patterns and discrimination. Moreover, some recently proposed discrimination indices are useful in evaluating predictive accuracy also in a context of longitudinal studies

    A note on prognostic accuracy evaluation of regression models applied to longitudinal autocorrelated binary data

    Get PDF
    Background: Focus of this work was on evaluating the prognostic accuracy of two approaches for modelling binary longitudinal outcomes, a Generalized Estimating Equation (GEE) and a likelihood based method, Marginalized Transition Model (MTM), in which a transition model is combined with a marginal generalized linear model describing the average response as a function of measured predictors. Methods: A retrospective study on cardiovascular patients and a prospective study on sciatic pain were used to evaluate discrimination by computing the Area Under the Receiver-Operating-Characteristics curve, (AUC), the Integrated Discrimination Improvement (IDI) and the Net Reclassification Improvement (NRI) at different time occasions. Calibration was also evaluated. A simulation study was run in order to compare model’s performance in a context of a perfect knowledge of the data generating mechanism. Results: Similar regression coefficients estimates and comparable calibration were obtained; an higher discrimination level for MTM was observed. No significant differences in calibration and MSE (Mean Square Error) emerged in the simulation study, that instead confirmed the MTM higher discrimination level. Conclusions: The choice of the regression approach should depend on the scientific question being addressed, i.e. if the overall population-average and calibration or the subject-specific patterns and discrimination are the objectives of interest, and some recently proposed discrimination indices are useful in evaluating predictive accuracy also in a context of longitudinal studie
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