Ahead of the pace
Research linking heart rate and breathing cycles is set to revolutionise pacemakers.
Auckland scientists developing a new type of cardiac pacemaker that mimics the heart’s natural rhythm are hailing its potential after animal studies in which it restored muscle function and improved the heart’s ability to pump. It is the first time that a pacemaker has triggered electrical signals as the body normally does, in response to the inflation of the lungs. In a healthy person, the heart rate increases on inhalation and slows on exhalation, but other pacemakers fire in a metronomic rhythm, which lead investigator Professor Julian Paton at the University of Auckland, calls “unphysiological and unnatural”.
He says the dramatic findings in rat and sheep with heart failure showed that after three days with the new pacemaker, the amount of blood the animals’ hearts could pump increased by 20-25%, an unprecedented result for pacemakers, and something that is usually only achieved in a minority of patients with pacemakers who are also taking optimal drug treatment.
The technology uses a novel artificial silicon neuron, which processes information about the animals’ respiration and commands the battery to release a voltage pulse that paces the heart. “Your heart rate is variable and completely synchronous with your breathing cycle normally. This brings back that variability and no one has ever looked at whether or not that is clinically beneficial in heart failure.”
An intriguing finding is that the improvements in heart function kick in three or four days after the device is switched on in the animals, which, Paton says, is a clue to the mechanism by which it’s working. “It’s clearly not through changes in the haemodynamics – the movement of the blood – because that would have happened more quickly. We think potential gene expression is changing – that it is producing an epigenetic effect, which means that the genome within the heart cells is producing new proteins and increasing the availability of calcium. And that is really important for enabling the heart muscle to contract more strongly.”
Paton and his colleagues, cardiovascular physiologist Rohit Ramchandra and interventional cardiologist Nigel Lever, are collaborating with scientists at the universities of Bath and Bristol on the work. Paton and Bath physics researcher Alain Nogaret have co-founded a company, Ceryx Medical, to raise money to take the technology to clinical trial within a few years.
Ramchandra says the next preclinical trials will involve exercise tolerance tests, and adding heart medicines to see if they further improve the condition of patients. “We have a pacemaker now that we believe is going to help heart-failure patients for the very first time by potentially increasing their heart-pumping capabilities. We are keen to understand if this might also reduce their sleep apnoea [a related condition in which patients briefly stop breathing during sleep]. You ask patients with heart failure what they want back and they talk about how they’d just love to be able to get out of their seat, go to the kitchen and put the kettle on without feeling breathless. We hope our pacemaker might help them achieve this.”
The median age of heart-failure patients is 78, but the number of people with the condition is rising as the population ages. Heart failure often occurs after heart attacks, and about half those diagnosed with it die within five years. “There’s no fix for heart failure,” says Paton. But the new device has the potential to change that. “What we are seeing is the reversal of some of this damage, which is remarkable in itself. It’s very exciting – it’s getting me out of bed in the mornings.”
“We have a pacemaker that is going to help heart-failure patients by increasing their heartpumping capabilities.”