Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy

Iacopo Olivotto, Francesca Girolami, Michael J. Ackerman, Stefano Nistri, J. Martijn Bos, Elisabetta Zachara, Steve R. Ommen, Jeanne L. Theis, Rachael A. Vaubel, Federica Re, Corinna Armentano, Corrado Poggesi, Francesca Torricelli, Franco Cecchi

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275 Scopus citations


OBJECTIVE: To determine the influence of a positive genetic test for hypertrophic cardiomyopathy (HCM) on clinical outcome. PATIENTS AND METHODS: A cohort of 203 unrelated patients with HCM (mean ± SD age, 50±18 years) was enrolled from January 1, 2002, through December 31, 2003. They were followed up for a mean ± SD time of 4.0±1.7 years after genetic testing of the 8 HCM-susceptibility genes that encode key sarcomeric/myofilament proteins. The clinical phenotype of those with a positive genetic test (myofilament-positive HCM) was compared with those with a negative genetic test (myofilament-negative HCM). RESULTS: In this cohort of 203 patients, 87 mutations were identified in 126 patients (myofilament-positive HCM, 62%); the remaining 77 patients (38%) were myofilament-negative. Despite similar baseline features, patients with myofilament-positive HCM showed increased risk of the combined end points of cardiovascular death, nonfatal stroke, or progression to New York Heart Association class III or IV compared with the patients with myofilament-negative HCM (25% vs 7%, respectively; independent hazard ratio, 4.27; P=.008). These end points occurred at any age among patients with myofilament-positive HCM (range, 14-86 years), but only in those aged 65 years and older among patients with myofilament-negative HCM. Moreover, patients with myofilament-positive HCM showed greater probability of severe left ventricular systolic and diastolic dysfunction, defined as an ejection fraction of less than 50% and a restrictive filling pattern (P=.02 and P<.02, respectively, vs myofilament-negative HCM). CONCLUSION: Screening for sarcomere protein gene mutations in HCM identifies a broad subgroup of patients with increased propensity toward long-term impairment of left ventricular function and adverse outcome, irrespective of the myofilament (thick, intermediate, or thin) involved.

Original languageEnglish (US)
Pages (from-to)630-638
Number of pages9
JournalMayo Clinic proceedings
Issue number6
StatePublished - Jun 2008

ASJC Scopus subject areas

  • Medicine(all)


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