title: Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations.
abstract: BACKGROUND
  Mild hypertrophy but increased arrhythmic risk characterizes the stereotypic phenotype proposed for hypertrophic cardiomyopathy (HCM) caused by thin-filament mutations. However, whether such clinical profile is different from more prevalent thick-filament-associated disease is unresolved.
  
  
  OBJECTIVE
  This study aimed to assess clinical features and outcomes in a large cohort of patients with HCM associated with thin-filament mutations compared with thick-filament HCM.
  
  
  METHODS
  Adult HCM patients (age >18 years), 80 with thin-filament and 150 with thick-filament mutations, were followed for an average of 4.5 years.
  
  
  RESULTS
  Compared with thick-filament HCM, patients with thin-filament mutations showed: 1) milder and atypically distributed left ventricular (LV) hypertrophy (maximal wall thickness 18 ± 5 mm vs. 24 ± 6 mm; p < 0.001) and less prevalent outflow tract obstruction (19% vs. 34%; p = 0.015); 2) higher rate of progression to New York Heart Association functional class III or IV (15% vs. 5%; p = 0.013); 3) higher prevalence of systolic dysfunction or restrictive LV filling at last evaluation (20% vs. 9%; p = 0.038); 4) 2.4-fold increase in prevalence of triphasic LV filling pattern (26% vs. 11%; p = 0.002); and 5) similar rates of malignant ventricular arrhythmias and sudden cardiac death (p = 0.593).
  
  
  CONCLUSIONS
  In adult HCM patients, thin-filament mutations are associated with increased likelihood of advanced LV dysfunction and heart failure compared with thick-filament disease, whereas arrhythmic risk in both subsets is comparable. Triphasic LV filling is particularly common in thin-filament HCM, reflecting profound diastolic dysfunction.
authors.affiliation: Center of Molecular Medicine (CIMMBA), University of Florence, Florence, Italy. Electronic address: raffaele.coppini@unifi.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Coppini
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Carolyn Y
authors.initials: CY
authors.lastname: Ho
authors.affiliation: Cardiovascular Medicine, Stanford Medical Center, Stanford, California.
authors.forename: Euan
authors.initials: E
authors.lastname: Ashley
authors.affiliation: University of Michigan Medical Center, Ann Arbor, Michigan.
authors.forename: Sharlene
authors.initials: S
authors.lastname: Day
authors.affiliation: Center of Molecular Medicine (CIMMBA), University of Florence, Florence, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ferrantini
authors.affiliation: Genetics Unit; Careggi University Hospital, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Girolami
authors.affiliation: Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Tomberli
authors.affiliation: Genetics Unit; Careggi University Hospital, Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Bardi
authors.affiliation: Genetics Unit; Careggi University Hospital, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Torricelli
authors.affiliation: Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Cecchi
authors.affiliation: Center of Molecular Medicine (CIMMBA), University of Florence, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.affiliation: Center of Molecular Medicine (CIMMBA), University of Florence, Florence, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Poggesi
authors.affiliation: Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona.
authors.forename: Jil
authors.initials: J
authors.lastname: Tardiff
authors.affiliation: Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Olivotto
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics; D000199:Actins / Q000235:genetics*; D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006334:Heart Function Tests; D006801:Humans; D007558:Italy; D020930:MAP Kinase Kinase Kinases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063868:Patient Outcome Assessment; D017346:Protein Serine-Threonine Kinases; D012720:Severity of Illness Index; D020107:Troponin T / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000235:genetics; D014693:Ventricular Fibrillation / Q000209:etiology / Q000235:genetics; D014694:Ventricular Outflow Obstruction / Q000209:etiology / Q000235:genetics
chemical_list: C526913:ACTC1 protein, human; D000199:Actins; C545568:TNNT2 protein, human; D020107:Troponin T; D017346:Protein Serine-Threonine Kinases; C481078:TNNI3K protein, human; D020930:MAP Kinase Kinase Kinases
keywords: diastolic function; end-stage; genotype to phenotype correlation; triphasic filling; troponin