Heart rate fragmentation: using cardiac pacemaker dynamics to probe the pace of biological aging

This perspectives article discusses the use of a novel set of dynamical biomarkers in the assessment of biological versus chronological age. The basis for this development is a recently delineated property of altered sinoatrial pacemaker-neuroautonomic function, termed heart rate fragmentation (HRF). Fragmented rhythms manifest as an increase in the density of changes in heart rate acceleration sign, not mechanistically explicable by physiological cardiac vagal tone modulation. We reported that HRF increased monotonically with cross-sectional age and that HRF measures, but not conventional heart rate variability metrics, were significantly associated with major incident cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA). Furthermore, HRF measures added value to both Framingham and MESA cardiovascular risk indices. Here, we propose that interventions that fundamentally slow or reverse the pace of biological aging, via system-wide effects, should be associated with a decrease in the degree of HRF and possibly with a reemergence of the nonfragmented (“fluent”) patterns associated with more youthful heart rate dynamics.