Cardiac Resynchronisation Therapy and Myocardial Metabolism: Acute and Chronic Effects in Heart Failure

Cardiac resynchronisation therapy (CRT) improves morbidity and mortality in severe systolic heart failure with a broad left bundle branch block, although comorbidities such as Diabetes Mellitus are associated with worse outcome. CRT improves cardiac performance beyond electrical correction of the QRS duration on the electrocardiogram, with reverse remodelling occurring in up to two thirds of patients. How reverse remodelling changes the heart from an "engine out of fuel" to one performing more efficiently at a higher stroke work is yet to be established. We aim to use simultaneous novel measurements of cardiac work, coronary arterial venous blood sampling and flow measurements to assess whether CRT acutely improves and rebalances substrate uptake in patients with dilated cardiomyopathy, and compare those with and without Diabetes Mellitus. We will also use state of the art cardiac magnetic resonance spectroscopy to assess the metabolic flexibility of the heart to improve glucose oxidation, ATP delivery and assess the size of the phosphocreatine pool at rest and during stress, as potential predictors of those who are able to successfully reverse remodel left ventricular function with CRT.

If our method of measuring cardiac efficiency at the time of implant during biventricular pacing proves to be a good way to predict reverse remodelling and long term CRT response, it may help identify those patients who would best benefit from implantation of cardiac resynchronisation devices and also help guide LV lead placement and device programming in future. Our findings may also shed light on the underlying mechanisms behind the reverse remodelling process, and help identify potential therapeutic targets for the treatment of heart failure.