The 2013 (with updates in 2016 and 2017) American College of Cardiology/American Heart Association and 2016 European Society of Cardiology guidelines provide practical evidence-based clinical ...guidelines for the diagnosis and treatment of both acute and chronic heart failure (HF). Both guidelines address noninvasive and invasive testing to establish the diagnosis of HF with reduced ejection fraction and HF with preserved ejection fraction. Extensive trial evidence supports the use of guideline-directed medical therapy and device-based therapies for the optimal management of patients with HF with reduced ejection fraction. Specific recommendations are also provided for HF with preserved ejection fraction although the evidence is substantially weaker. Management of medical comorbidities is now addressed in both guidelines. Acute HF and end-stage disease requiring advanced therapies are also discussed. This review compares specific recommendations across the spectrum of HF phenotypes and disease severity, highlights areas where differences exist, and lists consequential studies published since the latest guidelines.
Myocarditis--a frequent cause of dilated cardiomyopathy and sudden cardiac death--typically results from cardiotropic viral infection followed by active inflammatory destruction of the myocardium. ...Characterization of this disease has been hampered by its heterogeneous clinical presentations and diverse aetiologies. Advances in cardiac MRI and molecular detection of viruses by endomyocardial biopsy have improved our ability to diagnose and understand the pathophysiological mechanisms of this elusive disease. However, therapeutic options are currently limited for both the acute and chronic phases of myocarditis. Several randomized, controlled trials have demonstrated potential benefit with immunosuppressive and immunomodulatory therapies, but further investigations are warranted. In this Review, we explore the pathophysiology, natural history, and modes of diagnosis of myocarditis, as well as evidence-based treatment strategies. As novel imaging techniques and human in vitro models of the disease emerge, the landscape of therapies for myocarditis is poised to improve.
Restrictive cardiomyopathies are the least common form of heart muscle disease. They are characterized as infiltrative and noninfiltrative, storage diseases, and endomyocardial disorders. Genetic ...diseases commonly present during childhood or adolescence. However, a growing percentage of elderly patients with heart failure with preserved ejection fraction are being recognized as having forms of restrictive cardiomyopathy, particularly cardiac amyloidosis. Noninvasive evaluation has replaced endomyocardial biopsy in the diagnostic evaluation of most suspected etiologies. The detection of infiltrative cardiomyopathies, including lysosomal and glycogen storage disorders, iron overload, and amyloidosis (both light chain amyloidosis and transthyretin amyloidosis variants), as well as inflammatory diseases such as sarcoidosis has slowly led to improved outcomes via disease-specific therapies.
A substantial increase in the knowledge of the genetic basis of cardiomyopathy has occurred, and noninvasive phenotypic characterization has become significantly more sophisticated. ...the American ...Heart Association (AHA) (7) and the European Society of Cardiology (ESC) (8) in the last decade have proposed revisions to the classification of cardiomyopathic disorders. In the ESC 2008 classification, the cardiomyopathy was defined as familial when present in more than 1 member of the family.\n Disease MIM# Phenotype Inheritance Age of Onset Disease Gene Cardiac Phenotype Extracardiac Markers/Involvement of Other Organs Treatment Multiple acyl-CoA dehydrogenase deficiency Glutaric acidemia IIA 231680 AR Neonatal ETFA DCM, neonatal Nervous, skeletal, muscle, liver, kidney (often polycystic), metabolic acidosis, hypoglycemia  Glutaric acidemia IIB 231680 AR Neonatal, childhood ETFB Sudden neonatal death Nervous, skeletal, muscle, liver  Glutaric acidemia IIC 231680 AR Childhood to adult ETFDH DCM Nervous, skeletal, muscle, liver, kidney (often polycystic), lung, metabolic acidosis, hypoglycemia  Primary, systemic, carnitine transporter deficiency 212140 AR Childhood to adult SLC22A5 DCM, HCM < Total plasma carnitine, hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia in infants; skeletal myopathy, > creatine kinase, in childhood; cardiomyopathy, arrhythmias, or fatigability in adulthood Carnitine supplementation Chanarin-Dorfman syndrome (NLSD-I) 275630 AR Childhood to adult ABHD5 DCM Skin (ichthyosiform erythroderma), liver, muscle, nervous (with possible MR), ocular Suggested: diet low in long-chain fatty acids; retinoids for skin in patients w/o liver dysfunction Neutral lipid storage disease with myopathy (NLSD-M) 610717 AR Childhood to adult PNPLA2low * DCM Myopathy  Table 5 Major Lipid Storage Disorders With Possible Myocardial Involvement MR = mental retardation; other abbreviations as in Table 1.
Restrictive cardiomyopathies are the least common form of heart muscle disease. They are characterized as infiltrative and noninfiltrative, storage diseases, and endomyocardial disorders. Genetic ...diseases commonly present during childhood or adolescence. However, a growing percentage of elderly patients with heart failure with preserved ejection fraction are being recognized as having forms of restrictive cardiomyopathy, particularly cardiac amyloidosis. Noninvasive evaluation has replaced endomyocardial biopsy in the diagnostic evaluation of most suspected etiologies. The detection of infiltrative cardiomyopathies, particularly primary and secondary forms of iron overload, as well as inflammatory diseases such as sarcoidosis has slowly led to improved outcomes via disease-specific therapies.
Alternative splicing has a major role in cardiac adaptive responses, as exemplified by the isoform switch of the sarcomeric protein titin, which adjusts ventricular filling. By positional cloning ...using a previously characterized rat strain with altered titin mRNA splicing, we identified a loss-of-function mutation in the gene encoding RNA binding motif protein 20 (Rbm20) as the underlying cause of pathological titin isoform expression. The phenotype of Rbm20-deficient rats resembled the pathology seen in individuals with dilated cardiomyopathy caused by RBM20 mutations. Deep sequencing of the human and rat cardiac transcriptome revealed an RBM20-dependent regulation of alternative splicing. In addition to titin (TTN), we identified a set of 30 genes with conserved splicing regulation between humans and rats. This network is enriched for genes that have previously been linked to cardiomyopathy, ion homeostasis and sarcomere biology. Our studies emphasize the key role of post-transcriptional regulation in cardiac function and provide mechanistic insights into the pathogenesis of human heart failure.
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