Mortality risk of untreated myosin-binding protein C-related hypertrophic cardiomyopathy: insight into the natural history.

Abstract

OBJECTIVES:

The goal of this study was to assess the mortality of hypertrophic cardiomyopathy (HCM), partly in times when the disease was not elucidated and patients were untreated.

BACKGROUND:

HCM is feared for the risk of sudden cardiac death (SCD). Insight in the natural history of the disorder is needed to design proper screening strategies for families with HCM.

METHODS:

In 6 large, 200-year multigenerational pedigrees (identified by using genealogical searches) and in 140 small (contemporary) pedigrees (first-degree relatives of the proband) with HCM caused by a truncating mutation in the myosin-binding protein C gene (n = 1,118), we determined all-cause mortality using the family tree mortality ratio method. The study's main outcome measure was the standardized mortality ratio (SMR).

RESULTS:

In the large pedigrees, overall mortality was not increased (SMR 0.86 [95% confidence interval (CI): 0.72 to 1.03]), but significant excess mortality occurred between 10 and 19 years (SMR 2.7 [95% CI: 1.2 to 5.2]). In the small families, the SMR was increased (SMR 1.5 [95% CI: 1.3 to 1.6]) [corrected] and excess mortality was observed between 10 and 39 years (SMR 3.2 [95% CI: 2.3 to 4.3]) and 50 and 59 years (SMR 1.9 [95% CI: 1.4 to 2.5]).

CONCLUSIONS:

We identified specific age categories with increased mortality risks in HCM families. The small, referred pedigrees had higher mortality risks than the large 200-year multigenerational pedigrees. Our findings support the strategy of starting cardiological and genetic screening in the first-degree relatives of a proband from 10 years onward and including persons in the screening at least until the age of 60 years. Screening of more distant relatives is probably most efficient between 10 and 19 years.

• Authors: Eline A Nannenberg, Michelle Michels, Imke Christiaans, Danielle Majoor-Krakauer, Yvonne M Hoedemaekers, J Peter van Tintelen, M Paola Lombardi, Folkert J ten Cate, Arend F L Schinkel, Jan G P Tijssen, Irene M van Langen, Arthur A M Wilde, Eric J G Sijbrands
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 58 Issue 23 Pg. 2406-14 (Nov 29 2011) ISSN: 1558-3597 [Electronic] United States
• PMID: 22115648 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Carrier Proteins
• myosin-binding protein C
• Myosins

Topics

• Adolescent
• Adult
• Age Distribution
• Aged
• Aged, 80 and over
• Cardiomyopathy, Hypertrophic (blood, genetics, mortality)
• Carrier Proteins (blood)
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Humans
• Infant
• Male
• Middle Aged
• Myosins
• Pedigree
• Prognosis
• Retrospective Studies
• Risk Assessment (methods)
• Survival Rate (trends)
• Time Factors
• Young Adult