The mechanisms and consequences of haemodialysis induced acute cardiac injury

Patients on dialysis are subject to a hugely elevated risk of cardiovascular mortality. Incidence and prevalence of, and mortality and morbidity from heart failure is significantly higher in the haemodialysis population than the general population as a whole. This thesis describes research work focusing on the large scale haemodynamic changes that occur during haemodialysis and how they may negatively impact on the cardiovascular system. Our results show that the haemodynamic disturbances which occur during haemodialysis are capable of causing a reduction in myocardial blood flow sufficient in magnitude to induce myocardial ischaemia. This is associated with a matched reduction in regional left ventricular (LV) function and is entirely in keeping with other published work describing haemodialysis induced myocardial stunning reflecting subclinical myocardial ischaemia (myocardial stunning). In addition, we now know that this phenomenon of haemodialysis induced myocardial ischaemia and stunning is common and associated with both short and long term complications including ventricular arrhythmias, left ventricular dysfunction, an increased hazard of death and time to first cardiovascular event. This is pertinent as in non-dialysis patients repeated episodes of myocardial stunning lead to chronic heart failure, and in dialysis patients the presence of LV dysfunction dramatically increases the risk of death. We also identified a number of factors associated with the presence of myocardial stunning including age, raised biochemical markers of cardiac damage (troponin-T), higher ultrafiltration volumes and lower intradialytic blood pressure. This is of crucial importance as ultrafiltration volumes and intradialytic haemodynamics are potentially modifiable risk factors that could provide targets for dialysis based interventions aimed at improving cardiovascular outcomes in the haemodialysis population