title: ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study).
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence of another cardiac or systemic disease. At present it lacks specific treatment to prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and HCM patients. Previous studies have indicated that sarcomere mutations increase energetic costs of cardiac contraction and cause myocardial dysfunction and hypertrophy. By using a translational approach, we aim to determine to what extent disturbances of myocardial energy metabolism underlie disease progression in HCM.
  
  
  METHODS
  Hypertrophic obstructive cardiomyopathy (HOCM) patients and aortic valve stenosis (AVS) patients will undergo a positron emission tomography (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with tissue tagging before and 4 months after myectomy surgery or aortic valve replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to determine efficiency of sarcomere contraction in-vitro, and results will be compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic HCM mutation carriers will serve as a control group.
  
  
  METHODS
  Our study will reveal whether perturbations in cardiac energetics deteriorate during disease progression in HCM and whether these changes are attributed to cardiac remodelling or the presence of a sarcomere mutation per se. In-vitro studies in hypertrophied cardiac muscle from HOCM and AVS patients will establish whether sarcomere mutations increase ATP consumption of sarcomeres in human myocardium. Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired cardiac energetics are restored by cardiac surgery.
authors.affiliation: Department of Cardiology, Institute for Cardiovascular Research (ICaR-VU, VU University Medical Center, ZH 5F-13, PO Box 7057, 1007MB, Amsterdam, the Netherlands, a.guclu@vumc.nl.
authors.forename: A
authors.initials: A
authors.lastname: Güçlü
authors.forename: T
authors.initials: T
authors.lastname: Germans
authors.forename: E R
authors.initials: ER
authors.lastname: Witjas-Paalberends
authors.forename: G J M
authors.initials: GJ
authors.lastname: Stienen
authors.forename: W P
authors.initials: WP
authors.lastname: Brouwer
authors.forename: H J
authors.initials: HJ
authors.lastname: Harms
authors.forename: J T
authors.initials: JT
authors.lastname: Marcus
authors.forename: A B A
authors.initials: AB
authors.lastname: Vonk
authors.forename: W
authors.initials: W
authors.lastname: Stooker
authors.forename: A
authors.initials: A
authors.lastname: Yilmaz
authors.forename: P
authors.initials: P
authors.lastname: Klein
authors.forename: J M
authors.initials: JM
authors.lastname: Ten Berg
authors.forename: J
authors.initials: J
authors.lastname: Kluin
authors.forename: F W
authors.initials: FW
authors.lastname: Asselbergs
authors.forename: A A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: P
authors.initials: P
authors.lastname: Knaapen
authors.forename: A C
authors.initials: AC
authors.lastname: van Rossum
authors.forename: J
authors.initials: J
authors.lastname: van der Velden