Heart failure – HOPE-HF

The clinical question

Heart failure happens when the heart becomes less effective at pumping blood around the body. In some people with heart failure, the left and right sides of the heart don’t beat in time with each other. This is called left bundle branch block (LBBB), and happens when there is a problem with the heart's electrical conduction system. This can make symptoms – such as fatigue or shortness of breath - worse. Many people experiencing this receive a type of pacemaker therapy called cardiac resynchronisation therapy (CRT).

CRT works in the same way as a normal pacemaker in controlling the heartbeat, but also sends small electrical impulses to the left and right sides of the heart to help them beat together properly. CRT has been found to be a very effective treatment, but it has only been shown to be beneficial in people who have LBBB. Problems with the heart's conduction system can also cause an an abnormally long delay between activation of the top and bottom chambers of the heart with each heart beat. This is called PR interval prolongation, which can be seen using a electrocardiogram (ECG) and also leads to less efficient heart function. However, it's not clear whether pacing therapy could also help this group of patients.

Usually when a pacemaker is fitted, a lead is implanted into the lower right chamber of the heart (right ventricle), where it delivers electrical pulses to the heart muscle to tell it to contract. But this doesn’t activate the heart through its normal conduction system, so long-term pacing in this way can impair heart function and lead to further symptoms of heart failure. An alternative way of pacing the heart involves implanting a lead that delivers electrical signals directly to the heart’s own conduction system, called His-bundle pacing. It’s thought that this could be a better way of pacing the heart in people with heart failure and PR prolongation. 

Led by Dr Zachary Whinnett at Imperial College London, the BHF-funded His Optimised Pacing Evaluated for Heart Failure trial (HOPE-HF) trial aimed to find out whether this alternative pacing technique, alongside a method for identifying the best pacemaker settings, could help improve symptoms for people with heart failure and PR prolongation.

What did the study involve?

HOPE-HF recruited participants with heart failure and PR prolongation from 28 UK hospitals, who underwent a procedure to implant a CRT pacemaker (with one lead placed on the His bundle). For the first two months after the procedure, this lead was programmed to be ‘off’ (but with other leads ‘on’ to provide pacing as needed). Participants then attended the hospital to have tests to assess:

• How much they were able to exercise.
• How well their heart was working (including an echocardiogram of their heart and a blood test for B-type natriuretic peptide).
• Their quality of life (using questionnaires).
• What the best settings were for their pacemaker, based on measuring their blood pressure using a sensor attached to a finger.

167 participants were then randomly assigned to have the ‘His lead’ either on or off for the next 6 months. After 6 months they attended another hospital visit to have the same tests again, before having their treatment assignment ‘swapped’ for the next 6 months – e.g., those who had been assigned to have the His lead ‘on’ initially had the lead turned ‘off’. The tests were repeated at a final study visit 6 months later, so that researchers could compare everyone’s individual readings and symptoms between having the His pacing on and off.

What did the study show?

• His bundle pacing did not improve participants ability to exercise.
• His pacing did not negatively affect how the heart was working.
• However, His pacing was linked to better quality of life and improved symptoms, measured using the ‘Minnesota Living with Heart Failure Questionnaire’.
• 76% of participants reported that they preferred having His pacing turned on.

Why is the study important?

The symptoms of heart failure can be debilitating. So while the study did not show an improvement in the participants’ ability to exercise, the finding that His pacing was linked to improved symptoms is important both for people living with this condition, and providing a clear basis for further research in this area.

HOPE-HF also provided vital evidence that His pacing is feasible and safe to do in people with heart failure and PR prolongation. Other forms of pacing (right ventricular or biventricular pacing) have been shown to be harmful in this patient group, so the study could help to pave the way for CRT – which we know can greatly help to improve symptoms for people living with heart failure - being used more widely in the future.

Dr Whinnett summarised the trial’s findings: “HOPE-HF is the first substantial trial targeting isolated PR prolongation in patients with heart failure, and we wouldn’t have been able to do it without BHF support. We initially approached manufacturers, but they decided not to fund this trial. I hope that our findings will reawaken interest in PR prolongation as a treatment target for pacing therapy. "

The participant voice

HOPE-HF was featured in BHF's Heart Matters magazine in 2019. John Hughes, a retired publican from London, was one of the people who took part in the trial and shared his thoughts: “I was getting tired, breathless and dizzy. It crept up on me, a bit like old age, so at first I didn’t see a doctor about it. After I had the pacing in the trial, it took about a week to make a difference and I felt 500 times better."

Study details

“AV optimisation delivered with direct His bundle pacing, in patients with heart failure, long PR without left bundle branch block: randomised multi-centre clinical outcome study 'The His Optimised Pacing Evaluated for Heart Failure trial (HOPE-HF)”
Award reference: CS/15/3/31405
Principal investigator: Dr Zachary Whinnett
Trial registration number: NCT02671903

Publication details

Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial. Eur J Heart Fail. 2023 Feb;25(2):274-283.