Exacerbation of cardiac energetic impairment during exercise in hypertrophic cardiomyopathy: a potential mechanism for diastolic dysfunction

Eur Heart J. 2015 Jun 21;36(24):1547-54. doi: 10.1093/eurheartj/ehv120. Epub 2015 May 18.


Aims: 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.

Methods and 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).

Conclusion: 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.

Keywords: 31PMRS; Exercise; Hypertrophic Cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adult
  • Blood Pressure / physiology
  • Cardiomyopathy, Hypertrophic / metabolism*
  • Case-Control Studies
  • Diastole
  • Energy Metabolism
  • Exercise / physiology*
  • Female
  • Heart Rate / physiology
  • Humans
  • Magnetic Resonance Angiography
  • Magnetic Resonance Imaging, Cine
  • Magnetic Resonance Spectroscopy
  • Male
  • Phosphocreatine / metabolism
  • Prospective Studies
  • Stroke Volume / physiology
  • Ventricular Dysfunction, Left / etiology*
  • Ventricular Dysfunction, Left / physiopathology


  • Phosphocreatine
  • Adenosine Triphosphate