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Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy
K K Kalsi1, R T Smolenski, R D Pritchard
1Heart Science Centre, National Heart and Lung Institute at Harefield Hospital, Harefield, UK.
Insights
Heart failure significantly reduces creatine levels and citrate synthase activity, indicating impaired energy reserves and oxidative capacity in both dilated and hypertrophic cardiomyopathy. These metabolic changes are similar despite differing cardiac failure mechanisms.
Area of Science:
- Cardiology
- Biochemistry
- Metabolic Research
Background:
- Impaired myocardial energy metabolism is a key factor in heart failure progression.
- Understanding these metabolic changes is crucial for addressing functional deterioration in the failing human heart.
Purpose of the Study:
- To investigate alterations in myocardial energy metabolism in end-stage human heart failure.
- To compare metabolic changes in dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM).
Main Methods:
- Analyzed left ventricular myocardium from heart transplant patients (DCM, n=14; HCM, n=5) and healthy donors (n=4).
- Assessed citrate synthase (CS) activity, glycolytic enzymes, and concentrations of phosphocreatine (PCr), creatine (Cr), adenine, and guanine nucleotides.
Main Results:
- Total creatine levels were significantly decreased in both DCM and HCM compared to controls.
- Citrate synthase activity was markedly reduced in failing hearts (DCM and HCM).
- Glycolytic enzyme activity decreased, with a more pronounced reduction in DCM.
Conclusions:
- Metabolic changes in hypertrophic and dilated cardiomyopathy are similar, despite differences in cardiac failure mechanisms and contractility.
- Depletion of the creatine pool suggests impaired intracellular energy reserves and transfer.
- Reduced citrate synthase activity indicates diminished oxidative capacity in both types of cardiomyopathy.
Background:
Impaired energy metabolism in the failing human heart could be an important mechanism of functional deterioration. The purpose of this study was to assess the changes of myocardial energy metabolism in the human heart at end-stage heart failure.
Materials And Methods:
The left ventricular myocardium of patients undergoing heart transplantation due to dilated (DCM, n = 14) or hypertrophic cardiomyopathy (HCM, n = 5) and non-diseased donor heart samples (n = 4) were analysed for citrate synthase (CS), enzymes of the glycolytic pathway as well as concentrations of phosphocreatine (PCr), creatine (Cr), adenine and guanine nucleotides.
Results:
Total creatine levels (phosphocreatine + creatine) were significantly decreased (P < 0.05) in both groups of diseased hearts (3.87 +/- 0.57 in DCM, 5.09 +/- 1.23 in HCM compared with control 10. 7 +/- 3.5 micromol g-1 wet weight). There was a trend for higher guanine nucleotide content in failing hearts, but no significant differences were observed in total adenine nucleotides and total NAD content. CS was markedly reduced (P < 0.05) in both groups of diseased hearts: in the DCM to 13.8 +/- 1.3 micromol min-1 g-1 wet weight, and in HCM to 11.9 +/- 2.4 compared with the control 29.2 +/- 2.2. Glycolytic enzymes were decreased compared with the control, and this decrease was greater in DCM than in HCM. Echocardiographic indices of contractility were considerably better in hypertrophic cardiomyopathy.
Conclusion:
Despite the different mechanisms of cardiac failure and the differences in contractility of the heart we have observed, metabolic changes are very similar in hypertrophic and dilated cardiomyopathy. Depletion of the creatine pool suggests an alteration in the intracellular energy reserves and transfer, whereas the decrease in citrate synthase activity suggests reduced oxidative capacity in both dilated and hypertrophic cardiomyopathy.