title: Defining phenotypes and disease progression in sarcomeric cardiomyopathies: contemporary role of clinical investigations.
abstract: Mutations in cardiac sarcomere protein genes are associated with a variety of clinical phenotypes, including hypertrophic (HCM), dilated (DCM), and restrictive (RCM) cardiomyopathy as well as left ventricular non-compaction, with the overlap of morpho-functional manifestations in individual patients and families. Over time, initial phenotypes may undergo profound changes which determine clinical course and disease progression. Although genetic defects causing HCM and DCM have opposite effects at the myofilament level, a number of downstream maladaptive mechanisms, ranging from microvascular dysfunction and ischaemia to myocardial fibrosis and from diastolic dysfunction to abnormal sympathetic activation and arrhythmogenesis, seem to recur in sarcomeric cardiomyopathies, independent of the presenting phenotype. The extent and rate at which each of these features occur and evolve may be radically different in each form of cardiomyopathy, determining a clinical heterogeneity that is not only cross-sectional, but also longitudinal, i.e. time-related. Timely and sensitive detection of these long-term modifications in the clinical setting is a key to preventing advanced disease and identifying novel therapeutic targets. The present review evaluates the contribution of contemporary technology to pre-clinical diagnosis, characterization of phenotypes, and assessment of disease progression in sarcomere cardiomyopathies, including echocardiography, positron emission tomography, magnetic resonance, pathology, and circulating biomarkers.
authors: Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy olivottoi@aou-careggi.toscana.it.
authors: Iacopo
authors: I
authors: Olivotto
authors: Department of Radiology, Oncology and Pathology, Sapienza, University of Rome, Rome.
authors: Giulia
authors: G
authors: d'Amati
authors: Division of Cardiology, Department of Cardiological Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
authors: Cristina
authors: C
authors: Basso
authors: VU University Medical Center, Amsterdam, The Netherlands.
authors: Albert
authors: A
authors: Van Rossum
authors: Clinic of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
authors: Monica
authors: M
authors: Patten
authors: Fondazione Toscana Gabriele Monasterio, Pisa, Italy Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors: Michele
authors: M
authors: Emdin
authors: Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands.
authors: Yigal
authors: Y
authors: Pinto
authors: Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy.
authors: Benedetta
authors: B
authors: Tomberli
authors: Vita Salute University and Scientific Institute San Raffaele, Milan, Italy.
authors: Paolo G
authors: PG
authors: Camici
authors: Thoraxcenter, Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
authors: Michelle
authors: M
authors: Michels
mesh_terms: D000818:Animals; D001706:Biopsy; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D003952:Diagnostic Imaging / Q000379:methods; D018450:Disease Progression; D004562:Electrocardiography; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012518:Sarcomeres / Q000378:metabolism / Q000473:pathology*
chemical_list: D005819:Genetic Markers
keywords: Cardiomyopathies; MRI; PET; Sarcomere