Pacemakers help regulate slow or skipping heartbeats through electrical currents that run via leads to the heart. Since the first artificial one was implanted into Arne Larsson in 1958, modern pacemakers have become a bit smaller than the size of a matchbox, weighing around 20-50g. While current pacemakers run to a set pattern, we’re working on a smaller intelligent device that adjusts heartbeats to match breathing. This will improve the pumping efficiency of the heart and could, over time, help heart failure to recede.
The beat rate of a healthy heart is normally modulated by a respiratory cycle that causes a naturally occurring arrhythmia – something called respiratory sinus arrhythmia (RSA). This means the heart beats a little faster when you breathe in than when you breathe out. This is most prominent at birth and in trained athletes but it is lost with ageing and cardiovascular disease. RSA is normally brought about by sensory signals from the lungs and heart that tell the brain to alter heart rate, as well as cross-talk between the brain cells that specifically control heart rate and breathing.
RSA is highly preserved during evolution (it is still present in cartilaginous fish, amphibians, reptiles) so it must be important for life, but its functional significance in humans is still not completely understood. It has been suggested that the reason for RSA is to optimise oxygen uptake into the blood at the lungs.
Heart rate variability is known to be reduced in animals and humans with heart failure and can increase susceptibility to lethal arrhythmias and sudden cardiac death. It is therefore used as an indicator for potential problems. We wondered whether re-introducing this variability to a failing heart would have therapeutic benefit, so we set about designing a micro-stimulator capable of being triggered by inhalation.
A smart way forward
In invertebrates, heart pacing is performed by a small group of brain cells that generate electrical signals at precise times, called natural a central pattern generator (CPG). The simplest CPG is something called a half-centred oscillator, which consists of a pair or group of brain cells that compete to generate an alternating pattern of activity. The CPG technology we are developing is based on artificial brain cells made from silicon that would provide a more natural way to pace the heart dependent on the degree of physical exertion. This would allow proportional increases in heart rate based on the level of exercise.
Pacing using our artificial brain cells has advantages over electronics found in conventional pacemakers because our CPG will naturally synchronise the heart beat physiological signals, such as respiration and heart rate, and give appropriate timed outputs. Early trials of the technology have demonstrated its efficacy of slowing down heart rate at different points of the breathing cycle in rats, and in particular we saw increases in cardiac pumping ability. Our plan now is to optimise the device and then conduct trials on human patients with heart failure.
Worldwide, there are 22m patients with heart failure and 2m are diagnosed each year. In the UK, there are more than 750,000 patients with heart failure and despite the best medical therapy available, the prognosis remains poor. There is a significant unmet clinical need. While pacemakers are fitted for numerous heart-related diseases, our novel device could provide improved benefit to heart failure patients.
Current devices ensure the heart beats robustly, but metronomically. Our pacemaker would not only ensure the heart beats, but by altering the timing of the beat in a naturalistic way with breathing we believe we can improve the pumping efficiency of a failing heart. This would reverse some of the pathology within the heart and over time we hope the heart failure will recede.
The pacing device we’re developing, then, could provide some light at the end of the tunnel – it could lead not only to increased longevity for heart failure patients, but also greater mobility, independence and a better quality of life.