Heart failure syndrome and predicting response to cardiac resynchronisation therapy.

Heart failure results from the heart pumping insufficient quantities of blood to meet the body’s metabolic requirements. This condition affects around 600,000 people in the United Kingdom and carries with it a significant morbidity and mortality. Patients typically complain of reduced exercise capacity and a poor quality of life. Whilst there are various pharmaceutical options available to clinicians, none directly augment cardiac function. Cardiac resynchronisation therapy (CRT) is proven to reverse the progression of left ventricular systolic dysfunction, the most common cause of heart failure. The device resynchronises inefficient cardiac function, reducing symptoms and improving stroke volume and life expectancy. However, only two thirds of patients typically derive benefit from this pacemaker, it being unclear why. Finding a sensitive and specific predictor of response would be invaluable, preventing potential harm to patients, reducing waste and targeting the patient groups who will derive benefit. In this body of work, the heart failure syndrome is delineated; the evidence underpinning CRT discussed and the difficulties in defining response outlined. There are 2 main research themes in this body of work, measuring and predicting response to CRT. In the former, the role of patient specific three-­‐dimensional computational models and biophysical properties are investigated, and, in the latter, the influence of CRT on the heart failure syndrome using biomarkers. It is concluded that CRT response can be predicted using patient specific computational models of the left ventricle, but they are too complex for routine clinical use. Biophysical markers have more merit in the immediate future, being simper and quicker, with measures of endothelial and skeletal muscle function, demonstrating promise in a small cohort of patients. Finally, there exists a significant level of undiagnosed pathology in this patient group, such as hyperuricaemia and hyperparathyroidism, but it remains unclear what impact CRT has on this comorbidity.