Heart failure: is there an energy deficit contributing to contractile dysfunction?

UNLABELLED: Alterations in myocardial energy metabolism have been demonstrated in both animal experiments and clinical observations. Whether these changes contribute to heart failure has been a longstanding and controversial issue. I. The creatine kinase (CK) system and the high energy phosphates under physiological conditions and in acute heart failure: 1. According to in vivo and in vitro experiments the myocardial creatine/creatine phosphate (Cr/CP) system is directly linked to mitochondrial oxidative phosphorylation via the mitochondrial CK. 2. The shift in the mass action ratio of the CK reaction with increasing myocardial oxygen consumption enables marked stimulation of mitochondrial respiratory function via the Cr/CP system with almost maintained free energy of the adenosine triphosphate/adenosine diphosphate (ATP/ADP) system. 3. In acute heart failure the depressed myocardial content mainly of CP can be considered as an adaptive mechanism related to increased oxygen demands. II. The CK system and the high energy phosphates in chronic heart failure: 1. The alterations observed in the CK system in chronic heart failure cannot be interpreted in terms of an "energy deficit" (i.e., the excess of what is spent over what is received on energy). 2. "Energy reserve" (i.e., energy kept back for future use, to fill an emergency) is markedly reduced in heart failure. 3. Under steady state conditions decreased "energy reserve" cannot be expected to contribute to heart failure. Under stress conditions, however, this mechanism is manifest by reducing contractile reserve. 4. The mechanisms by which decreased "energy reserve" induces depression of contractile reserve is not elucidated. III. Heart failure related to alterations in energy metabolism (mitochondrial diseases, stunned, and hibernating myocardium): 1. The phenotype of mitochondrial diseases is predominantly determined by neurological disorders and myopathies. Therefore, the patients are rarely referred to a cardiologist, although the cardiac involvement may ultimately determine the patients' prognosis. 2. Stunned and hibernating myocardium are characterized by prolonged contractile dysfunction in the presence of reversibly damaged myocardium. The underlying mechanisms and its triggers are unknown. INTERPRETATIONS: 1. The reduced energy reserve in heart failure may be considered to contribute to the progression of the disease. 2. As an alternative, however, it can likewise represent a mechanism to protect the endangered myocardium from overload.