Fig. 1

The evolution of cardiac pacing from electronic devices to biological pacemakers. In 1958, the medical world witnessed a breakthrough when the first fully implantable pacemaker was introduced. This used an epicardial lead fixed at the epicardial site of the ventricle. The pacemaker lead was connected to the generator within the generator pocket, which has been formed in the abdominal wall within the rectus abdominus muscle sheath, typically at the level of the umbilicus. Placing epicardial leads and the generator pocket led to lead failure or device infection. Since 1989, the transvenous approach, which inserted the leads through the subclavian veins (SV), replaced epicardial lead implantation as the mainstream procedure. The generator was typically inserted into a pocket just above the pectoral fascia (subcutaneously in the chest wall). Furthermore, the transvenous leads could be fixed through the endocardial site over the right atrium (RA) and ventricle (RV). This made synchronized electrical pacing on atrial and ventricular chambers possible, providing a more physiological way similar to normal atrioventricular conduction. Fast forward to 2016, the Food and Drug Administration approved the marketing of a leadless cardiac pacemaker. This is a one-piece device including a generator and electrodes, implanted into RV septum through a vein. There was neither a separate battery under the skin nor leads that go to the heart. Looking ahead, the dawn of the era of biological pacemakers is on the horizon. The biological pacemaker has been developed as a device-free therapy which injects a biological product (blue dots) through the catheter, e.g., viral vector, to generate a biological pacemaker in situ (orange dots). The biological pacemakers generate a natural and efficient heart rhythm from PCs similar to a de novo sinoatrial node, and might provide physiological pacing compatible with normal cardiac conduction. This further avoids the complications from the electrical pacing of the electronic device, e.g., heart failure. BV, brachiocephalic vein; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; SV, subclavian vein; SVC, superior vena cava