Device therapies, including cardiac resynchronisation therapy (CRT) pacemakers and implantable cardioverter defibrillators (ICD), are established treatment options for patients with symptomatic heart failure due to reduced left ventricular ejection fraction (HeFREF) despite optimal medical therapy. Other novel treatments such as ultrafiltration and gene therapy may have a role in future. This module reviews these other treatment options.
Cardiac resynchronisation therapy
Cardiac resynchronisation therapy (CRT) is a useful adjunct to optimal medical therapy in patients with left ventricular systolic dysfunction (LVSD) and an ejection fraction (EF) ≤35%. In clinical trials, CRT is proven to reduce both mortality and heart failure hospitalisation rates. CRT also improves symptoms, functional state and quality of life (QoL) (see section on ‘Clinical evidence base for CRT’ below).
What is CRT?
Many patients with LVSD have a delay in the electrical conduction through the heart. The electrical conduction delay is identified on a 12-lead electrocardiogram (ECG) by a widened QRS complex, often meeting criteria for bundle branch block. Over 30% of patients with LVSD have left bundle branch block (LBBB) in comparison to <1% of the general population (figure 1). Around 10% of patients with normal conduction develop new LBBB each year. Atrioventricular nodal disease, particularly first degree heart block, is also common in LVSD.
Despite the success of CRT in clinical practice, it is not clear how CRT mediates its benefits. Much discussion has centred around the mechanical consequences of a prolonged QRS duration, particularly:
- late LV contraction relative to right ventricular contraction – inter-ventricular dyssynchrony
- unco-ordinated LV systolic contraction – intra-ventricular dyssynchrony.
The hypothesis is then that CRT, which paces the right ventricular (RV) apex (or septum) and LV free wall simultaneously, corrects inter-ventricular dyssynchrony (and shortens the QRS duration). It is commonly assumed that this translates to more co-ordinate LV systolic contraction.
There are two types of CRT device:
- CRT-pacemakers (CRT-P)
- CRT-defibrillators (CRT-D)
Some patients with LVSD are also at high risk of ventricular arrhythmias and CRT can be combined with defibrillation therapy (CRT-D). (Implantable cardioverter defibrillators are covered below). CRT-P is the pacing element of the device alone and is used in patients for whom defibrillation therapy is not appropriate.
CRT has numerous benefits in appropriately selected patients:
- reduced mortality rate
- reduced heart failure hospitalisation rate
- improved New York Heart Association (NYHA) class
- improved six-minute walk test distance
- improved cardiopulmonary exercise testing
- improved quality of life (QoL) questionnaire scores in over two-thirds of the patients undergoing the procedure
- increased systolic arterial pressure
- improved myocardial efficiency – improved LV function without increased LV oxygen consumption
- reduced LV size and mass, and reduction in severity of mitral regurgitation
- in some patients, ‘super-responders’, LV systolic function may ‘normalise’.
However, around 20–30% of patients treated with CRT do not appear to benefit in terms of either symptomatic improvement or improvement in LV size or function. There is no universally agreed definition of ‘response’. It’s not at all clear whether a ‘non-responder’ might actually have deteriorated without the CRT (and hence ‘response’ might be failure to deteriorate), and it’s not clear if lack of clinical response translates into lack of mortality benefit from CRT.
The best predictors of response to CRT are:
- QRS complex ≥150 ms
- LBBB morphology
- non-ischaemic cardiomyopathy
- female sex.
Despite the established benefits of CRT therapy, the UK implant rates for the devices remain amongst the lowest in Europe.
A brief note about mechanical dyssynchrony
The mechanisms underlying the benefit of CRT are not clear. There is no convincing evidence that any one of several measures of mechanical dyssynchrony is associated with the beneficial effects of CRT, and the latest (2014) NICE guidance on CRT has removed any reference to measuring mechanical dyssynchrony on echocardiography as part of patient selection.1
QRS morphology, rather than duration, may the important factor for predicting response and survival following CRT implantation; LBBB is associated with improved survival following CRT implantation compared to patients with non-LBBB QRS morphology. In the same study, QRS duration was not associated with survival.2
However, it may be that a major part of the benefit of CRT is simply to shorten the atria-ventricular delay. Old studies in patients with heart failure and a long PR interval showed that AV sequential pacing reduced mitral regurgitation and could improve some aspects of myocardial function. It may be that CRT (by pacing the left ventricle as well as the right) shortens the AV delay whilst avoiding the potentially harmful effects of RV apical pacing alone.