MR spectroscopy in heart failure - clinical and experimental findings

Magnetic resonance spectroscopy (MRS) allows for the non-invasive detection of a wide variety of metabolites in the heart. To study the metabolic changes that occur in heart failure, P-31- and H-1-MRS have been applied in both patients and experimental animal studies. P-31-MRS allows for the detection of phosphocreatine (PCr), ATP, inorganic phosphate (Pi) and intracellular pH, while H-1-MRS allows for the detection of total creatine. All these compounds are involved in the regulation of the available energy from ATP hydrolysis via the creatine kinase (CK) reaction. Using cardiac MRS, it has been found that the PCr/CK system is impaired in the failing heart. In both, patients and experimental models, PCr levels as well as total creatine levels are reduced, and in severe heart failure ATP is also reduced. PCr/ATP ratios correlate with the clinical severity of heart failure and, importantly, are a prognostic indicator of mortality in patients. In addition, the chemical flux through the CK reaction, measured with P-31 saturation transfer MRS, is reduced more than the steady-state levels of high-energy phosphates in failing myocardium in both experimental models and in patients. Experimental studies suggest that these changes can result in increased free ADP levels when the failing heart is stressed. Increased free ADP levels, in turn, result in a reduction in the available free energy of ATP hydrolysis, which may directly contribute to contractile dysfunction. Data from transgenic mouse models also suggest that an intact creatine/CK system is critical for situations of cardiac stress.