The road to biological pacing.

The field of biological pacing is entering its second decade of active investigation. The inception of this area of study was serendipitous, deriving largely from observations made by several teams of investigators, whose common interest was to understand the mechanisms governing cardiac impulse initiation. Research directions taken have fallen under the broad headings of gene therapy and cell therapy, and biomaterials research has also begun to enter the field. In this Review, we revisit certain milestones achieved through the construction of a 'roadmap' in biological pacing. Whether the end result will be a clinically applicable biological pacemaker is still uncertain. However, promising constructs that achieve physiologically relevant heart rates and good autonomic responsiveness are now available, and proof of principle studies are giving way to translation to large-animal models in long-term studies. Provided that interest in the field continues, the next decade should see either biological pacemakers become a clinical reality or the improvement of electronic pacemakers to a point where the biological approach is no longer a viable alternative.