title: Exacerbation of cardiac energetic impairment during exercise in hypertrophic cardiomyopathy: a potential mechanism for diastolic dysfunction.
abstract: OBJECTIVE
  Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden cardiac death in the young, with an excess of exercise-related deaths. The HCM sarcomere mutations increase the energy cost of contraction and impaired resting cardiac energetics has been documented by measurement of phosphocreatine/ATP (PCr/ATP) using (31)Phosphorus MR Spectroscopy ((31)P MRS). We hypothesized that cardiac energetics are further impaired acutely during exercise in HCM and that this would have important functional consequences.
  
  
  RESULTS
  (31)P MRS was performed in 35 HCM patients and 20 age- and gender-matched normal volunteers at rest and during leg exercise with 2.5 kg ankle weights. Peak left-ventricular filling rates (PFRs) and myocardial perfusion reserve (MPRI) were calculated during adenosine stress. Resting PCr/ATP was significantly reduced in HCM (HCM: 1.71 ± 0.35, normal 2.14 ± 0.35 P < 0.0001). During exercise, there was a further reduction in PCr/ATP in HCM (1.56 ± 0.29, P = 0.02 compared with rest) but not in normals (2.16 ± 0.26, P = 0.98 compared with rest). There was no correlation between PCr/ATP reduction and cardiac mass, wall thickness, MPRI, or late-gadolinium enhancement. PFR and PCr/ATP were significantly correlated at rest (r = 0.48, P = 0.02) and stress (r = 0.53, P = 0.01).
  
  
  CONCLUSIONS
  During exercise, the pre-existing energetic deficit in HCM is further exacerbated independent of hypertrophy, perfusion reserve, or degree of fibrosis. This is in keeping with the change at the myofilament level. We offer a potential explanation for exercise-related diastolic dysfunction in HCM.
authors.affiliation: Division of Cardiovascular Medicine, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Sairia
authors.initials: S
authors.lastname: Dass
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Lowri E
authors.initials: LE
authors.lastname: Cochlin
authors.affiliation: Division of Cardiovascular Medicine, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Suttie
authors.affiliation: Division of Cardiovascular Medicine, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Holloway
authors.affiliation: Division of Cardiovascular Medicine, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rider
authors.affiliation: Division of Cardiovascular Medicine, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Leah
authors.initials: L
authors.lastname: Carden
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Tyler
authors.affiliation: Division of Cardiovascular Medicine, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Theodoros D
authors.initials: TD
authors.lastname: Karamitsos
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.affiliation: Division of Cardiovascular Medicine, Anatomy and Genetics, Oxford University, Oxford, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.affiliation: Division of Cardiovascular Medicine, Anatomy and Genetics, Oxford University, Oxford, UK hugh.watkins@cardiov.ox.ac.uk.
authors.forename: Hugh
authors.initials: H
authors.lastname: Watkins
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism*; D016022:Case-Control Studies; D003971:Diastole; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D018810:Magnetic Resonance Angiography; D019028:Magnetic Resonance Imaging, Cine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism; D011446:Prospective Studies; D013318:Stroke Volume / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000503:physiopathology
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate
keywords: 31PMRS; Exercise; Hypertrophic Cardiomyopathy