Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations

Raffaele Coppini, Carolyn Y. Ho, Euan Ashley, Sharlene Day, Cecilia Ferrantini, Francesca Girolami, Benedetta Tomberli, Sara Bardi, Francesca Torricelli, Franco Cecchi, Alessandro Mugelli, Corrado Poggesi, Jil Tardiff, Iacopo Olivotto

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


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.

Objectives 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.

Original languageEnglish (US)
Pages (from-to)2589-2600
Number of pages12
JournalJournal of the American College of Cardiology
Issue number24
StatePublished - Dec 23 2014


  • correlation triphasic filling troponin
  • diastolic function end-stage
  • genotype to phenotype

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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