Abstract 16924: Multimodality Imaging Reveals Decreased Creatine-Kinase Flux and Systolic Strain in Patients with Hypertrophic Cardiomyopathy and Preserved LVEF
Background/Objectives: We investigated in vivo cardiac creatine kinase (CK) ATP supply and function in a family with HCM who carry an extensively characterized point mutation (R403Q) in the cardiac β-myosin heavy chain gene.
Methods: Quantitative phosphorus (31P) saturation transfer MRS was used to noninvasively measure cardiac CK energy transfer-the forward CK flux and the CK rate constant, kf-and CK metabolite concentrations (phosphocreatine, [PCr], and [ATP]) in patients with HCM (n=10), and in age-matched healthy controls (n=15). Systolic strain, LV ejection fraction (EF), diastolic function and cardiac morphology were assessed by echocardiography in HCM patients (n=11) and a second group of healthy controls (n=10).
Results: LV mass was higher in HCM patients than controls (307.21 ± 12.37 vs 167.63 ± 42.53; p=0.0037). [PCr] was significantly decreased by 22% in HCM patients (7.36 ± 2.29µmol/g wet weight) as compared to controls (9.41 ± 1.2µmol/g; p=0.005), but PCr/ATP ratio was not significantly altered (1.54 ± 0.4 in HCM vs. 1.69 ± 0.29, p=0.26). The pseudo-first-order rate-constant for the CK reaction, kf was reduced by 26% (0.266 ± 0.14 vs. 0.36 ± 0.08, p<0.04) and the forward CK flux was reduced by 43% (1.94 ± 1.27 vs 3.39 ± 0.96, p<0.003) in HCM patients when compared to controls. Diastolic function (E/A) was impaired (0.90 ± 0.31 in HCM vs 1.48 ± 0.27 controls; p=0.0003) and peak systolic strain (longitudinal; εL) was significantly decreased in HCM patients (-13.40 ± 5.32 vs -18.93 ± 2.46; p=0.0076). Peak longitudinal strain and diastolic function (E/A) correlated with NYHA class (R²=0.50; p=0.0007); E/A <1 correlated with NYHA class progression over 5 years of follow up (R2=0.6, p=0.024).
Conclusions: PCr, kfor and CK flux are significantly reduced in patients compared to age-matched healthy control subjects, indicating impaired CK ATP energy supply even at rest, consistent with prior work on a HCM (R403Q) mouse model. However, only systolic strain and diastolic function were correlated with NYHA class and progression respectively, suggesting that while bioenergetic alterations are associated with the underlying mutation, other downstream molecular effects contribute to the severity of dysfunction and clinical status of these patients.
- © 2011 by American Heart Association, Inc.