Narrow QRS systolic heart failure: is there a target for cardiac resynchronization?

Abstract

Cardiac resynchronization therapy has revolutionized the management of systolic heart failure in patients with prolonged QRS during the past 20 years. Initially, the use of this treatment in patients with shorter QRS durations showed promising results, which have since been opposed by larger randomized controlled trials. Despite this, some questions remain, such as, whether correction of mechanical dyssynchrony is the therapeutic target by which biventricular pacing may confer benefit in this group, or are there other mechanisms that need consideration? In addition, novel techniques of cardiac resynchronization therapy delivery such as endocardial and multisite pacing may reduce potential detrimental effects of biventricular pacing, thereby improving the benefit/harm balance of this therapy in some patients.

Keywords:

• biventricular pacing
• cardiac resynchronization therapy
• dyssynchrony
• heart failure
• narrow QRS

Financial & competing interests disclosure

The authors have received funding from the EU FP7 for research, technological development and demonstration under the grant agreement VP2HF (number 611823). The authors also acknowledge financial support from the Department of Health, via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. T Jackson has received an educational grant from Medtronic and a research grant from EU FP7 (number 611823). S Claridge has received an educational grant from St Jude Medical. J Behar has received an educational grant from Rose Tees Trust. J Webb has received a research grant from EU FP7 (number 611823). R Razavi has received research support from Philips Healthcare. CA Rinaldi has received research support from St. Jude Medical, Medtronic and Boston Scientific. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Key issues

• Initial work in single-armed studies does seem to suggest that there may be a group of patients with narrow QRS who derive some benefit from CRT although the beneficial mechanism is yet to be described.

• There are five RCTs in this group, three of which have a negative result and two of these suggest that there is a possible signal for harm with increased mortality and heart failure hospitalizations in the CRT groups. The largest of these studies is the EchoCRT study, where 809 patients were randomized with 404 having CRT turned on. There was no difference in the primary endpoint of death from any cause and first hospitalization with heart failure; however, there was an increase in total mortality in the CRT-ON group (hazard ratio, 1.81; 95% CI: 1.11–2.93).

• Two of three of the negative RCTs used echocardiographic markers of mechanical dyssynchrony as inclusion criteria. These markers have not been validated as selection criteria for CRT and therefore could be considered a weakness of these trials.

• CRT in narrow QRS is not supported under any guidelines, other than where there is a bradycardia indication for pacing.

• Despite the focus of assessment of mechanical dyssynchrony in patients with narrow QRS, there is little explanation as to the mechanisms responsible and whether these mechanisms might be amenable to correction with CRT.

• There may be other benefits of CRT in this group that have not yet been fully investigated. These include correction of abnormal atrioventricular delays, reduction of external constraint and the ability to titrate up medications following implant.

• If there is a benefit to CRT in a group of patients with narrow QRS, this will need to be balanced against the iatrogenic electropathy and subsequent detrimental effects it induces.

• Novel techniques such as multivein and endocardial pacing have not been tested in this group and may offer strategies for reducing the electropathy caused, thereby improving the risk/benefit ratio of CRT in narrow QRS.

Notes