SCMR 22nd Annual Scientific Sessions
Creatine kinase (CK) regenerates ATP from phosphocreatine (PCr) (according to PCr2-+ MgADP- + H+ ⇌Cr + MgATP2-, where kf is the pseudo-first order forward rate constant), and is the prime temporal energy reserve in muscle. CK flux may be estimated by 31P-magnetic resonance spectroscopy (MRS) magnetisation saturation transfer as kf × [PCr]. We studied human severe primary mitral regurgitation as a model of metabolic adaptation to chronic volume overload, asking whether the left ventricle (LV) is metabolically compromised.
19 patients (age 67 ± 10) with severe primary mitral regurgitation awaiting surgical repair and 25 healthy volunteers (age 44±19) were recruited. Exclusion criteria included previous myocardial infarction, flow-limiting coronary disease, and LVEF <55%. All underwent cardiac magnetic resonance imaging (3T Siemens) for LV volumes, function and mass and 31P-MRS for (1) PCr/ATP ratio and (2) CK kf by Triple Repetition time magnetisation Saturation Transfer (TRiST).
Patients had severe mitral regurgitant volume (LV stroke volume minus RV stroke volume 67±31 vs 0±7 mL, p<.001). Compared with controls, subjects had increased LVEDV (220 ± 64 vs 158 ± 41 mL, p<.001) and LVEF (68 ± 7 vs 64 ± 4%, p=.01). Severe mitral regurgitation was associated with reduced PCr/ATP ratios (1.56 vs 2.04, p=.001) and unaltered CK kf (0.15 ± 0.08 vs 0.18 ± 0.08 s-1, p=.29). Estimated CK flux i.e. kf × PCr/ATP was reduced in the MR group (0.25 ± 0.16 vs 0.36 ± 0.17, p=.03) (Figure A). A negative correlation was observed between estimated mitral regurgitant volume and PCr/ATP (r = -0.62, p<0.001) (Figure B).
In this first study (to our knowledge) of CK kf in symptomatic patients with severe primary MR and preserved LVEF who are referred for mitral valve surgery, PCr/ATP and estimated ATP delivery rates, but not CK kf, are significantly reduced. PCr/ATP correlated negatively with markers of mitral regurgitant volume. This finding of energetic compromise will inform the current debate about early intervention in asymptomatic primary MR, as it indicates the ‘supra-normal LVEF’ ventricle is metabolically abnormal.