Myocardial structural alteration and systolic dysfunction in preclinical hypertrophic cardiomyopathy mutation carriers

• Published in: PloS one Vol. 7; no. 5; p. e36115
• Main Authors: Yiu, Kai Hang, Atsma, Douwe E, Delgado, Victoria, Ng, Arnold C T, Witkowski, Tomasz G, Ewe, See Hooi, Auger, Dominique, Holman, Eduard R, van Mil, Anneke M, Breuning, Martijn H, Tse, Hung Fat, Bax, Jeroen J, Schalij, Martin J, Marsan, Nina Ajmone
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.05.2012; Public Library of Science (PLoS)
• Subjects: Adult; Alterations; Backscatter; Backscattering; Biology; Cardiology; Cardiomyopathy; Cardiomyopathy, Hypertrophic - diagnostic imaging; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - pathology; Cardiomyopathy, Hypertrophic - physiopathology; Carriers; Echocardiography; Electrocardiography; Eutrophication; Female; Genetic aspects; Genotype & phenotype; Heart; Heterozygote; Humans; Hypertrophic cardiomyopathy; Male; Medical research; Medicine; Middle Aged; Mutation; Myocardium - pathology; NMR; Nuclear magnetic resonance; Patients; Phenotype; Prognosis; Reproducibility of Results; Screening; Systole - physiology; Ventricle; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036115

To evaluate the presence of myocardial structural alterations and subtle myocardial dysfunction during familial screening in asymptomatic mutation carriers without hypertrophic cardiomyopathy (HCM) phenotype. Sixteen HCM families with pathogenic mutation were studied and 46 patients with phenotype expression (Mut+/Phen+) and 47 patients without phenotype expression (Mut+/Phen-) were observed. Twenty-five control subjects, matched with the Mut+/Phen- group, were recruited for comparison. Echocardiography was performed to evaluate conventional parameters, myocardial structural alteration by calibrated integrated backscatter (cIBS) and global and segmental longitudinal strain by speckle tracking analysis. All 3 groups had similar left ventricular dimensions and ejection fraction. Basal anteroseptal cIBS was the highest in Mut+/Phen+ patients (-14.0±4.6 dB, p<0.01) and was higher in Mut+/Phen- patients as compared to controls (-17.0±2.3 vs. -22.6±2.9 dB, p<0.01) suggesting significant myocardial structural alterations. Global and basal anteroseptal longitudinal strains (-8.4±4.0%, p<0.01) were the most impaired in Mut+/Phen+ patients as compared to the other 2 groups. Although global longitudinal strain was similar between Mut+/Phen- group and controls, basal anteroseptal strain was lower in Mut+/Phen- patients (-14.1±3.8%, p<0.01) as compared to controls (-19.9±2.9%, p<0.01), suggesting a subclinical segmental systolic dysfunction. A combination of >-19.0 dB basal anteroseptal cIBS or >-18.0% basal anteroseptal longitudinal strain had a sensitivity of 98% and a specificity of 72% in differentiating Mut+/Phen- group from controls. The use of cIBS and segmental longitudinal strain can differentiate HCM Mut+/Phen- patients from controls with important clinical implications for the family screening and follow-up of these patients.