Lay summary
Our heart rate is not fixed. A heart rate of 60 beats per minute does not mean the heart beats every second. Rather, there are time differences between one beat and the next. This naturally-occurring phenomenon is called heart rate variability (HRV). It is widely used as an important indicator of health and wellbeing, and in cardiovascular diagnosis where HRV is often severely reduced. It is surprising that HRV has not been explored for possible therapeutic properties (e.g. restoring HRV to improve heart function in diseases). We propose to study heart muscles to unlock the therapeutic potential of HRV. We will combine muscle experimentation, genomic analysis and computational modelling to compare muscle performance with and without HRV stimulation. Our findings may overturn the conventional fixed-stimulation protocol routinely used in studying heart muscles, and may lead to smarter and more effective clinical pacemakers.