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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP-
dc.contributor.authorHO, Carolyn Y.-
dc.contributor.authorDAY, Sharlene M.-
dc.contributor.authorASHLEY, Euan A.-
dc.contributor.authorMICHELS, Michelle-
dc.contributor.authorPEREIRA, Alexandre C.-
dc.contributor.authorJACOBY, Daniel-
dc.contributor.authorCIRINO, Allison L.-
dc.contributor.authorFOX, Jonathan C.-
dc.contributor.authorLAKDAWALA, Neal K.-
dc.contributor.authorWARE, James S.-
dc.contributor.authorCALESHU, Colleen A.-
dc.contributor.authorHELMS, Adam S.-
dc.contributor.authorCOLAN, Steven D.-
dc.contributor.authorGIROLAMI, Francesca-
dc.contributor.authorCECCHI, Franco-
dc.contributor.authorSEIDMAN, Christine E.-
dc.contributor.authorSAJEEV, Gautam-
dc.contributor.authorSIGNOROVITCH, James-
dc.contributor.authorGREEN, Eric M.-
dc.contributor.authorOLIVOTTO, Iacopo-
dc.identifier.citationCIRCULATION, v.138, n.14, p.1387-1398, 2018-
dc.description.abstractBackground: A better understanding of the factors that contribute to heterogeneous outcomes and lifetime disease burden in hypertrophic cardiomyopathy (HCM) is critically needed to improve patient management and outcomes. The SHaRe registry (Sarcomeric Human Cardiomyopathy Registry) was established to provide the scale of data required to address these issues, aggregating longitudinal data sets curated by 8 international HCM specialty centers. Methods: Data on 4591 patients with HCM (2763 genotyped) followed up for a mean of 5.46.9 years (24791 patient-years; median, 2.9 years; interquartile range, 0.3-7.9 years) were analyzed for cardiac arrest, cardiac transplantation, appropriate implantable cardioverter-defibrillator therapy, all-cause death, atrial fibrillation, stroke, New York Heart Association functional class III/IV symptoms (all making up the overall composite end point), and left ventricular ejection fraction <35%. Outcomes were analyzed individually and as composite end points. Results: Median age at diagnosis was 45.8 (interquartile range, 30.9-58.1) years, and 37% of patients were female. Age at diagnosis and sarcomere mutation status were predictive of outcomes. Patients <40 years old at diagnosis had a 77% (95% CI, 72-80) cumulative incidence of the overall composite outcome by 60 years of age compared with 32% (95% CI, 29-36) by 70 years of age for patients diagnosed at >60 years old. Young patients with HCM (age, 20-29 years) had 4-fold higher mortality than the general US population at a similar age. Patients with pathogenic/likely pathogenic sarcomere mutations had a 2-fold greater risk for adverse outcomes compared with patients without mutations; sarcomere variants of uncertain significance were associated with intermediate risk. Heart failure and atrial fibrillation were the most prevalent adverse events, although typically not emerging for several years after diagnosis. Ventricular arrhythmias occurred in 32% (95% CI, 23-40) of patients <40 years of age at diagnosis but in 1% (95% CI, 1-2) of those >60 years old at diagnosis. Conclusions: The cumulative burden of HCM is substantial and dominated by heart failure and atrial fibrillation occurring many years after diagnosis. Young age at diagnosis and the presence of a sarcomere mutation are powerful predictors of adverse outcomes. These findings highlight the need for close surveillance throughout life and the need to develop disease-modifying therapies.-
dc.description.sponsorshipMyokardia, Inc, a startup company that is developing therapeutics that target the sarcomere-
dc.description.sponsorshipNational Institutes of Health [1P50HL112349, 1U01HL117006, R01 GRANT11572784]-
dc.description.sponsorshipAmerican Heart Association-
dc.description.sponsorshipTaubman Medical Institute (University of Michigan)-
dc.description.sponsorshipItalian Ministry of Health (""Left Ventricular Hypertrophy in Aortic Valve Disease and Hypertrophic Cardiomyopathy: Genetic Basis, Biophysical Correlates and Viral Therapy Models"") [RF-2013-02356787, NET-2011-02347173]-
dc.description.sponsorshipTuscany Registry of Sudden Cardiac Death (ToRSADE) project (FAS-Salute 2014, Regione Toscana)-
dc.description.sponsorshipWellcome Trust [107469/Z/15/Z]-
dc.description.sponsorshipMedical Research Council (United Kingdom)-
dc.description.sponsorshipHoward Hughes Medical Institute-
dc.subjectnatural history-
dc.subject.othercontemporary management strategies-
dc.subject.otherlow cardiovascular mortality-
dc.subject.othersudden cardiac death-
dc.subject.otherphenotype associations-
dc.titleGenotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)-
dc.rights.holderCopyright LIPPINCOTT WILLIAMS & WILKINS-
dc.contributor.groupauthorSHaRe Investigators-
dc.subject.wosCardiac & Cardiovascular Systems-
dc.subject.wosPeripheral Vascular Disease-
dc.type.categoryoriginal article-
dc.type.versionpublishedVersion-, Carolyn Y.:Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA-, Sharlene M.:Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA-, Euan A.:Stanford Ctr Inherited Heart Dis, Stanford, CA USA-, Michelle:Erasmus MC, Dept Cardiol, Thoraxctr, Rotterdam, Netherlands-, Daniel:Yale Univ, New Haven, CT USA-, Allison L.:Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA-, Jonathan C.:MyoKardia Inc, San Francisco, CA USA-, Neal K.:Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA-, James S.:Imperial Coll London, Natl Heart & Lung Inst, London, England; Imperial Coll London, Natl Inst Hlth Res Royal Brompton Cardiovasc Biom, London, England-, Colleen A.:Stanford Ctr Inherited Heart Dis, Stanford, CA USA-, Adam S.:Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA-, Steven D.:Boston Childrens Hosp, Dept Cardiol, Boston, MA USA-, Francesca:Careggi Univ Hosp, Cardiomyopathy Unit, Florence, Italy; Careggi Univ Hosp, Genet Unit, Florence, Italy-, Franco:Careggi Univ Hosp, Cardiomyopathy Unit, Florence, Italy; Careggi Univ Hosp, Genet Unit, Florence, Italy-, Christine E.:Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA; Howard Hughes Med Inst, Chevy Chase, MD USA-, Gautam:Anal Grp Inc, Boston, MA USA-, James:Anal Grp Inc, Boston, MA USA-, Eric M.:MyoKardia Inc, San Francisco, CA USA-, Iacopo:Careggi Univ Hosp, Cardiomyopathy Unit, Florence, Italy; Careggi Univ Hosp, Genet Unit, Florence, Italy-
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Artigos e Materiais de Revistas Científicas - HC/InCor
Instituto do Coração - HC/InCor

Artigos e Materiais de Revistas Científicas - LIM/13
LIM/13 - Laboratório de Genética e Cardiologia Molecular

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar

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