1,721,102 research outputs found
Trattamento dello scompenso cardiaco con terapia genica: i risultati inattesi del trial CUPID 2
Full text linkLo scompenso cardiaco è ancora oggi un’importante causa di morbilità e mortalità in tutto il mondo. La terapia genica dei meccanismi implicati nello scompenso cardiaco è emersa sin dagli anni ’90 come potenziale target terapeutico incoraggiando studi preclinici su piccoli e poi più grandi modelli animali. Le prime esperienze in letteratura hanno documentato una ridotta espressione del reticolo sarcoplasmatico/endoplasmatico Ca2+-ATPasi2a (SERCA2a) nello scompenso cardiaco. Questi risultati hanno portato allo sviluppo di trial clinici sul trasferimento genico di SERCA2a. I primi risultati positivi in termini di fattibilità, sicurezza ed endpoint clinici hanno aperto la strada al primo grande trial randomizzato, il CUPID, su pazienti con scompenso cardiaco e frazione di eiezione ridotta in cui sono stati arruolati 250 pazienti a infusione intracoronarica di virus adeno-associati di tipo 1 (AAV1)/SERCA2a o placebo. Le grandi aspettative riposte sono state disattese e non si è osservato alcun miglioramento in termini di outcome nei pazienti trattati. In questa revisione abbiamo rivisitato i precedenti lavori che hanno portato al disegno di questo trial, analizzato le sue principali caratteristiche e risultati, fornendo infine alcune ipotesi sul motivo di un fallimento parzialmente inatteso in modo da comprendere quali possano essere le future prospettive per la terapia genica nello scompenso cardiaco
Valutazione dell’ereditarietà e analisi molecolare alla luce delle nuove linee guida europee sulla cardiomiopatia ipertrofica
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Arrhythmogenic right ventricular cardiomyopathy: From genetics to diagnostic and therapeutic challenges
No full textArrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular (RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involvement. The identification of ARVC can be often challenging, because of the heterogeneous clinical presentation, highly variable intra- and inter-family expressivity and incomplete penetrance. This genotype-phenotype "plasticity" is largely unexplained. A familial history of ARVC is present in 30% to 50% of cases, and the disease is considered a genetic cardiomyopathy, usually inherited in an autosomal dominant pattern with variable penetrance and expressivity; in addition, autosomal recessive forms have been reported (Naxos disease and Carvajal syndrome). Diagnosis of ARVC relays on a scoring system, with major or minor criteria on the Revised Task Force Criteria. Implantable cardioverter defibrillators (ICDs) are increasingly utilized in patients with ARVC who have survived sudden death (SD) (secondary prevention). However, there are few data available to help identifying ARVC patients in whom the prophylactic implantation of an ICD is truly warranted. Prevention of SD is the primary goal of management. Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and ICD are the mainstay of treatment of ARVC
The role of clinical observation: Red flag 7-syndromic and multi-system cardiomyopathies
No full textPathophysiology of dilated cardiomyopathy: from mechanisms to precision medicine
No full textDilated cardiomyopathy (DCM) is a complex disease with multiple causes and various pathogenic mechanisms. Despite improvements in the prognosis of patients with DCM in the past decade, this condition remains a leading cause of heart failure and premature death. Conventional treatment for DCM is based on the foundational therapies for heart failure with reduced ejection fraction. However, increasingly, attention is being directed towards individualized treatments and precision medicine. The ability to confirm genetic causality is gradually being complemented by an increased understanding of genotype-phenotype correlations. Non-genetic factors also influence the onset of DCM, and growing evidence links genetic background with concomitant non-genetic triggers or precipitating factors, increasing the extreme complexity of the pathophysiology of DCM. This Review covers the spectrum of pathophysiological mechanisms in DCM, from monogenic causes to the coexistence of genetic abnormalities and triggering environmental factors (the 'two-hit' hypothesis). The roles of common genetic variants in the general population and of gene modifiers in disease onset and progression are also discussed. Finally, areas for future research are highlighted, particularly novel therapies, such as small molecules, RNA and gene therapy, and measures for the prevention of arrhythmic death
Genetic causes of dilated cardiomyopathy
No full textDilated cardiomyopathy is a disease of the myocardium characterized by left ventricular dilatation and/or dysfunction, affecting both adult and pediatric populations. Almost half of cases are genetically determined with an autosomal pattern of inheritance. Up to 40 genes have been identified affecting proteins of a wide variety of cellular structures such as the sarcomere, the nuclear envelope, the cytoskeleton, the sarcolemma and the intercellular junction. Novel gene mutations have been recently identified thanks to advances in next-generation sequencing technologies. Genetic screening is an essential tool for early diagnosis, risk assessment, prognostic stratification and, possibly, adoption of primary preventive measures in affected patients and their asymptomatic relatives. The purpose of this article is to review the genetic basis of DCM, the known genotype-phenotype correlations, the role of current genetic sequencing techniques in the discovery of novel pathogenic gene mutations and new therapeutic perspectives
Correlation between histomorphometric findings and endomyocardial biopsy and clinical findings in idiopathic dilated cardiomyopathy
No full textMultivariate analysis was used to analyze the morphometric data of endomyocardial biopsies (area, perimeter and minor diameter) of myocardial cells obtained at light microscopy by a computerized approach with 16 clinical parameters and prognosis in 52 patients with idiopathic dilated cardiomyopathy. The best morphometric parameter was "area" (R2 = 0.47). A positive correlation was found with age (p less than 0.02), interval between first symptoms and diagnosis (p less than 0.02), left ventricular end-diastolic volume (p less than 0.02), cardiac index (p less than 0.05) and echocardiographic end-diastolic diameter (p less than 0.1). A negative correlation was found with prognosis (p less than 0.02), ejection fraction (p less than 0.02), shortening fraction (p less than 0.05), echocardiographic end-systolic diameter (p less than 0.06) and mitral regurgitation presence (p less than 0.1). The parameters that provided no correlation were New York Heart Association class, left ventricular end-diastolic pressure, right atrial pressure, cardiothoracic ratio, presence or absence of heart failure, fever or alcohol intake. These findings suggest that endomyocardial biopsy may provide prognostic information and confirm clinical diagnosis
Historical Terminology, Classifications, and Present Definition of DCM.
No full textDilated cardiomyopathy (DCM) is defined by the presence of left ventricular (LV) dilation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause the LV systolic impairment. In the last years, advances in pathophysiology, pathology, biomarkers, genetics and molecular medicine, echocardiography, and cardiac magnetic resonance have allowed an evolution from an etiological to a morphological and then to a morphofunctional classification of the disease. Familial forms account for the 40% of cases, and thanks to the recent discoveries in the genetic field, clinicians have the opportunity but also the responsibility to provide an etiological diagnosis, stratify the risk, and treat patients with the best strategy available. Nowadays the etiologic characterization has dramatically improved so that it is possible to understand the etiologic basis of many so-called idiopathic heart muscle disease. A step toward a comprehensive DCM classification and an attempt to reconcile clinic with genetic in the complexity of the disease is genotype-phenotype correlation, with its prognostic implication in clinical practice. In this chapter will be discussed the historical evolution of DCM classification, and an overview of the main issues discussed in the next sections will be given
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