Cardiac Resynchronisation Therapy and its effects on systolic heart failure

Abstract

Cardiac Resynchronisation Therapy (CRT) is now an established therapeutic option for patients with symptomatic left ventricular systolic dysfunction, broad QRS duration (>120 milliseconds on surface electrocardiogram) and on optimal tolerated medical therapy. The numbers of implants are rising throughout the Westernised world. The United Kingdom has also had a rapid increase in CRT implantation.

Despite the large randomised trials which prove clinical effectiveness, there is a realisation that a significant minority of patients who undergo CRT implantation do not derive the anticipated clinical benefit. This has been labelled as non-response with up to 40 percent of patients being affected depending on diagnostic criteria.

However potential solutions to a lack of clinical benefit do exist. These include medical optimisation of the patient’s heart failure pharmacotherapy following CRT implantation, and device based optimisation adjusting atrioventricular and ventriculo-ventricular (AV and VV) intervals. Other reasons for a lack of clinical improvement may be explained on pathophysiology which is currently not accounted for in the guidelines and selection criteria.

The thesis is therefore dedicated to the exploration of these issues using the dataset from the specialist heart failure pacing clinic at the Royal Brompton Hospital.

The study of medical optimisation following CRT implantation observed increased rates of neurohormonal antagonists and anticoagulants when a systematic structured clinical approach was adopted.

One potential method of evaluating device based optimisation is impedance cardiography and within chapter V, a cohort of 44 patients underwent device based optimisation with either conventional echocardiographic techniques or impedance cardiography. Though underpowered and a pilot study, the impedance cardiographic method within this cohort performed adequately.

Heart failure remains a complex syndrome with complex pathophysiology. One of the potential reasons for non-response is the lack of acknowledgement of other physiological criteria in the selection criteria. The study performed using cardiac magnetic resonance (CMR) imaging to evaluate right ventricular function on cardiovascular outcomes in patients following CRT implantation. Here it was demonstrated that right ventricular dysfunction as assessed by CMR is a powerful predictor of adverse outcomes and of a failure to undergo left ventricular remodelling.

The last study chapter was a small pilot study which compared impedance cardiographic performance to echocardiography within an intensive care setting. Whilst the numbers of patients recruited were small (n=6), the adjustment of atrioventricular and ventriculo-ventricular delays did induce a change in haemodynamics.

In conclusion the thesis represents studies and work focussed on the problem of lack of clinical benefit experienced by patients following CRT implantation. It has covered a prognosticator and two potential methods for improving the rate of clinical response following CRT implantation.