BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a disease characterized by substantial genetic, morphologic, and prognostic heterogeneity. Recently, sex-related differences in HCM were reported, with women being older at diagnosis and exhibiting greater left ventricular outflow tract obstruction than men. We sought to evaluate the influence of sex on the HCM phenotype in a large cohort of unrelated patients with genetically and morphologically classified HCM. METHODS: Comprehensive genotyping of 13 HCM-susceptibility genes encoding myofilament and Z-disc proteins of the cardiac sarcomere was performed previously on 382 unrelated patients with HCM. Blinded to the genotype, the septal morphology was graded as reverse-curvature, sigmoidal, apical, or neutral-contour HCM by echocardiography. RESULTS: Overall, women (a) were significantly older at diagnosis (45.1 +/- 20 vs 35.8 +/- 17 years, P < .001), (b) had greater left ventricular outflow tract obstruction (53.5 +/- 45 vs 41.7 +/- 42 mm Hg, P = .009), (c) were more likely to have concomitant hypertension (19% vs 11%, P = .02), and (d) had a higher rate of surgical myectomy (49% vs 36%, P = .01) than men. Interestingly, these sex-based differences were apparent only among patients with sigmoidal HCM (P < .001). CONCLUSIONS: In this largest cohort of comprehensively genotyped and morphologically classified patients with clinically diagnosed HCM, we observed that the striking sex-related differences in the clinical phenotype are confined largely to the subset of mutation-negative sigmoidal HCM. Whereas mutations within the sarcomere appear to dominate the disease process, in their absence, sex has a significant modifying effect, specifically noted in cases of sigmoidal HCM.
BACKGROUND:Hypertrophic cardiomyopathy (HCM) is a disease characterized by substantial genetic, morphologic, and prognostic heterogeneity. Recently, sex-related differences in HCM were reported, with women being older at diagnosis and exhibiting greater left ventricular outflow tract obstruction than men. We sought to evaluate the influence of sex on the HCM phenotype in a large cohort of unrelated patients with genetically and morphologically classified HCM. METHODS: Comprehensive genotyping of 13 HCM-susceptibility genes encoding myofilament and Z-disc proteins of the cardiac sarcomere was performed previously on 382 unrelated patients with HCM. Blinded to the genotype, the septal morphology was graded as reverse-curvature, sigmoidal, apical, or neutral-contour HCM by echocardiography. RESULTS: Overall, women (a) were significantly older at diagnosis (45.1 +/- 20 vs 35.8 +/- 17 years, P < .001), (b) had greater left ventricular outflow tract obstruction (53.5 +/- 45 vs 41.7 +/- 42 mm Hg, P = .009), (c) were more likely to have concomitant hypertension (19% vs 11%, P = .02), and (d) had a higher rate of surgical myectomy (49% vs 36%, P = .01) than men. Interestingly, these sex-based differences were apparent only among patients with sigmoidal HCM (P < .001). CONCLUSIONS: In this largest cohort of comprehensively genotyped and morphologically classified patients with clinically diagnosed HCM, we observed that the striking sex-related differences in the clinical phenotype are confined largely to the subset of mutation-negative sigmoidal HCM. Whereas mutations within the sarcomere appear to dominate the disease process, in their absence, sex has a significant modifying effect, specifically noted in cases of sigmoidal HCM.
Authors: Mohit Jain; Ronglih Liao; Bruno K Podesser; Soeun Ngoy; Carl S Apstein; Franz R Eberli Journal: Am J Physiol Heart Circ Physiol Date: 2002-08-01 Impact factor: 4.733
Authors: Martin S Maron; Iacopo Olivotto; Andrey G Zenovich; Mark S Link; Natesa G Pandian; Jeffery T Kuvin; Stefano Nistri; Franco Cecchi; James E Udelson; Barry J Maron Journal: Circulation Date: 2006-11-06 Impact factor: 29.690
Authors: Jeanne L Theis; J Martijn Bos; Virginia B Bartleson; Melissa L Will; Josepha Binder; Matteo Vatta; Jeffrey A Towbin; Bernard J Gersh; Steve R Ommen; Michael J Ackerman Journal: Biochem Biophys Res Commun Date: 2006-11-09 Impact factor: 3.575
Authors: J S Shah; M T T Esteban; R Thaman; R Sharma; B Mist; A Pantazis; D Ward; S K Kohli; S P Page; C Demetrescu; E Sevdalis; A Keren; D Pellerin; W J McKenna; P M Elliott Journal: Heart Date: 2007-11-21 Impact factor: 5.994
Authors: Sinead L Murphy; Jason H Anderson; Jamie D Kapplinger; Teresa M Kruisselbrink; Bernard J Gersh; Steve R Ommen; Michael J Ackerman; J Martijn Bos Journal: J Cardiovasc Transl Res Date: 2016-02-25 Impact factor: 4.132
Authors: Zahara Meghji; Anita Nguyen; Benish Fatima; Jeffrey B Geske; Rick A Nishimura; Steve R Ommen; Brian D Lahr; Joseph A Dearani; Hartzell V Schaff Journal: JAMA Cardiol Date: 2019-03-01 Impact factor: 14.676
Authors: J Martijn Bos; Melissa L Will; Bernard J Gersh; Teresa M Kruisselbrink; Steve R Ommen; Michael J Ackerman Journal: Mayo Clin Proc Date: 2014-05-01 Impact factor: 7.616
Authors: I A W van Rijsingen; J F Hermans-van Ast; Y H J M Arens; S M Schalla; C E M de Die-Smulders; A van den Wijngaard; Y M Pinto Journal: Neth Heart J Date: 2009-12 Impact factor: 2.380
Authors: Jeffrey B Geske; Kevin C Ong; Konstantinos C Siontis; Virginia B Hebl; Michael J Ackerman; David O Hodge; Virginia M Miller; Rick A Nishimura; Jae K Oh; Hartzell V Schaff; Bernard J Gersh; Steve R Ommen Journal: Eur Heart J Date: 2017-12-07 Impact factor: 29.983
Authors: Sherif M Helmy; Gomaa F Maauof; Ahmed A Shaaban; Ahmed M Elmaghraby; Smitha Anilkumar; Abdel Halim H Shawky; Rachel Hajar Journal: Heart Views Date: 2011-10
Authors: Patricia Reant; Gabriella Captur; Mariana Mirabel; Arthur Nasis; Daniel M Sado; Viviana Maestrini; Silvia Castelletti; Charlotte Manisty; Anna S Herrey; Petros Syrris; Maite Tome-Esteban; Sharon Jenkins; Perry M Elliott; William J McKenna; James C Moon Journal: J Cardiovasc Magn Reson Date: 2015-07-30 Impact factor: 5.364
Authors: Ethan J Rowin; Martin S Maron; Sophie Wells; Parth P Patel; Benjamin C Koethe; Barry J Maron Journal: J Am Heart Assoc Date: 2019-10-30 Impact factor: 5.501