Louise L A M Nijenkamp1, Ilse A E Bollen1, Hannah G van Velzen2, Jessica A Regan1, Marjon van Slegtenhorst3, Hans W M Niessen4, Arend F L Schinkel2, Martina Krüger5, Corrado Poggesi6, Carolyn Y Ho7, Diederik W D Kuster1, Michelle Michels2, Jolanda van der Velden8,9. 1. Department of Physiology (L.L.A.M.N., I.A.E.B., J.A.R., D.W.D.K., J.v.d.V.). 2. VU University Medical Center, Amsterdam, The Netherlands. Department of Cardiology (H.G.v.V., A.F.L.S., M.M.). 3. Department of Clinical Genetics (M.v.S.). 4. Department of Pathology and Cardiac Surgery, Amsterdam Cardiovascular Sciences (H.W.M.N.). 5. Erasmus MC, Rotterdam, The Netherlands. Institute of Cardiovascular Physiology, Heinrich Heine University Düsseldorf, Germany (M.K.). 6. Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Italy (C.P.). 7. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.Y.H.). 8. Department of Physiology (L.L.A.M.N., I.A.E.B., J.A.R., D.W.D.K., J.v.d.V.) j.vandervelden@vumc.nl. 9. Netherlands Heart Institute, Utrecht (J.v.d.V.).
Abstract
BACKGROUND: One of the first clinically detectable alterations in heart function in hypertrophic cardiomyopathy (HCM) is a decline in diastolic function. Diastolic dysfunction is caused by changes in intrinsic properties of cardiomyocytes or an increase in fibrosis. We investigated whether clinical and cellular parameters of diastolic function are different between male and female patients with HCM at the time of myectomy. METHODS AND RESULTS: Cardiac tissue from the interventricular septum of patients with HCM (27 women and 44 men) was obtained during myectomy preceded by echocardiography. At myectomy, female patients were 7 years older than male patients and showed more advanced diastolic dysfunction than men evident from significantly higher values for E/e' ratio, left ventricular filling pattern, tricuspid regurgitation velocity, and left atrial diameter indexed for body surface. Whereas most male patients (56%) showed mild (grade I) diastolic dysfunction, 50% of female patients showed grade III diastolic dysfunction. Passive tension in HCM cardiomyocytes was comparable with controls, and myofilament calcium sensitivity was higher in HCM compared with controls, but no sex differences were observed in myofilament function. In female patients with HCM, titin was more compliant, and more fibrosis was present compared with men. Differences between female and male patients with HCM remained significant after correction for age. CONCLUSIONS: Female patients with HCM are older at the time of myectomy and show greater impairment of diastolic function. Furthermore, left ventricular and left atrial remodeling is increased in women when corrected for body surface area. At a cellular level, HCM women showed increased compliant titin and a larger degree of interstitial fibrosis.
BACKGROUND: One of the first clinically detectable alterations in heart function in hypertrophic cardiomyopathy (HCM) is a decline in diastolic function. Diastolic dysfunction is caused by changes in intrinsic properties of cardiomyocytes or an increase in fibrosis. We investigated whether clinical and cellular parameters of diastolic function are different between male and female patients with HCM at the time of myectomy. METHODS AND RESULTS: Cardiac tissue from the interventricular septum of patients with HCM (27 women and 44 men) was obtained during myectomy preceded by echocardiography. At myectomy, female patients were 7 years older than male patients and showed more advanced diastolic dysfunction than men evident from significantly higher values for E/e' ratio, left ventricular filling pattern, tricuspid regurgitation velocity, and left atrial diameter indexed for body surface. Whereas most male patients (56%) showed mild (grade I) diastolic dysfunction, 50% of female patients showed grade III diastolic dysfunction. Passive tension in HCM cardiomyocytes was comparable with controls, and myofilament calcium sensitivity was higher in HCM compared with controls, but no sex differences were observed in myofilament function. In female patients with HCM, titin was more compliant, and more fibrosis was present compared with men. Differences between female and male patients with HCM remained significant after correction for age. CONCLUSIONS: Female patients with HCM are older at the time of myectomy and show greater impairment of diastolic function. Furthermore, left ventricular and left atrial remodeling is increased in women when corrected for body surface area. At a cellular level, HCM women showed increased compliant titin and a larger degree of interstitial fibrosis.
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