Real-Time Closed Loop Diastolic Interval Control Prevents Cardiac Alternans in Isolated Whole Rabbit Hearts

Cardiac alternans, a beat-to-beat alternation in action potential duration (APD), can lead to fatal arrhythmias. During periodic pacing, changes in diastolic interval (DI) depend on subsequent changes in APD, thus enhancing cardiac instabilities through a 'feedback' mechanism. Recently, an anti-arrhythmic Constant DI pacing protocol was proposed and shown to be effective in suppressing alternans in 0D and 1D in silico studies. However, previous experimental validation of Constant DI pacing in the heart has been unsuccessful due to the spatio-temporal complexity of 2D cardiac tissue and the technical challenges in its real-time implementation. Here, we developed a novel closed loop system to detect T-waves from real-time ECG data, enabling successful implementation of Constant DI pacing protocol, and performed high-resolution optical mapping experiments on isolated whole rabbit hearts to validate its anti-arrhythmic effects. The results were compared with: (1) Periodic pacing (feedback inherent) and (2) pacing with heart rate variability (HRV) (feedback modulation) introduced by using either Gaussian or Physiological patterns. We observed that Constant DI pacing significantly suppressed alternans in the heart, while maintaining APD spatial dispersion and flattening the slope of the APD restitution curve, compared to traditional Periodic pacing. In addition, introduction of HRV in Periodic pacing failed to prevent cardiac alternans, and was arrhythmogenic.