Next-generation pacemakers: from small devices to biological pacemakers

Abstract

Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator. Modern pacemakers are generally reliable, and their programmability provides options for different pacing modes tailored to specific clinical needs. Advances in device technology will probably include alternative energy sources and dual-chamber leadless pacing in the not-too-distant future. Although effective, current electronic devices have limitations related to lead or generator malfunction, lack of autonomic responsiveness, undesirable interactions with strong magnetic fields, and device-related infections. Biological pacemakers, generated by somatic gene transfer, cell fusion, or cell transplantation, provide an alternative to electronic devices. Somatic reprogramming strategies, which involve transfer of genes encoding transcription factors to transform working myocardium into a surrogate sinoatrial node, are furthest along in the translational pipeline. Even as electronic pacemakers become smaller and less invasive, biological pacemakers might expand the therapeutic armamentarium for conduction system disorders.

Bioresorbable Electronic Implants: History, Materials, Fabrication, Devices, and Clinical Applications

“…Medical implants have been applied for various parts of the human body (Figure a) such as bones, eyes, ears, neurons, blood vessels, and even deeply located key organs (e.g., heart and brain) . A device can be implanted at the target site after surgical incision (Figure b).…”

“…For example, the cochlear implant, which restores hearing capability for patients with auditory disorders (Figure e), senses external sound and converts it into electrical stimulation signals that are transmitted to the auditory nerves through implanted electrodes. Another important electronic implant is the cardiac pacemaker for heart diseases, such as arrhythmia or myocardial infarction (Figure f) . An advanced pacemaker analyzes cardiac signals as well as related health signals (e.g., blood gas concentration, body temperature, and hormone levels), and self‐feedback therapy is achieved via cardiac electrical stimulations based on the sensing results.…”

“…Concurrent with increased human lifespan and technological advances in materials, devices, and fabrication methods, various types of biomedical devices optimized for specific diseases have been developed. In particular, research on medical implants, including those with active electronics, has been highlighted in recent years, as these implantable devices provide effective solutions for critical clinical challenges.…”

Transcriptome analysis of mouse and human sinoatrial node cells reveals a conserved genetic program

“…Ultimately, SAN dysfunction requires implantation of an electronic pacemaker. The generation of bona fide pacemaker cells by programming stem cells or reprogramming endogenous non-pacemaker cells has stimulated much interest, as biological pacemakers may overcome the shortcomings of the currently used electronic devices (Boink et al, 2015;Cingolani et al, 2017;Protze et al, 2017). The ability to create biological pacemakers may be improved by the molecular and developmental characterization of the SAN.…”

Influence and safety of electronic apex locators in patients with cardiovascular implantable electronic devices: a systematic review

“…Cardiovascular implantable electronic devices are small lithium battery-operated electronic devices that are inserted surgically beneath the skin, generally near the left clavicle [1,2]. They have flexible insulated wires (leads) that run through the veins to the heart and monitor heart rate continuously to detect heart rhythm disorders (i.e.…”