Fragmentation Of The Heartbeat: Probing The Breakdown Of Biologic Time With Aging And Disease

heartbeat

The trace of the human heartbeat, a dynamical signature of life itself, is regulated by an exquisitely complex “clock” called the sino-atrial (SA) node. The cells comprising this cardiac timekeeper, like those in all biologic pacemakers, are nonlinear oscillators. It is widely assumed that the SA node beats with metronomic regularity.

However, even under resting conditions and during sleep, the time period between beats shows subtle, non-random fluctuations. These correlation properties give the healthy heartbeat a kind of swaying or “fluent” appearance in time series graphs.

While the variations in heart rate have been of interest for decades or longer, this signal continues to reveal surprising properties that may provide useful information about health status, as well as about how the body’s oscillators break down with senescence and pathology.

From basic and translational perspectives, tracking the behavior of the heart’s intrinsic pacemaker is uniquely valuable. Heartbeat recordings are among the most accessible biologic signals, requiring only continuous recordings of the electrocardiogram (ECG). Furthermore, the variations in heartbeat dynamics under healthy conditions are self-regulated by an orchestral ensemble, including neurohormonal, respiratory, and cardiac components. Thus, the heartbeat cadence may provide a portal through which to unlock key aspects of our systems biology in physiologic and pathologic settings.

Our recent work on heartbeat dynamics has uncovered an intriguing class of abnormalities, grouped under the rubric of heart rate fragmentation, which appears to provide biomarkers of electrophysiologic instability. The basic mechanisms of heart rate fragmentation remain to be delineated but likely relate to electrophysiologic, inflammatory and mechanical perturbations, singly or in combination.

Electrocardiogram recordings (Holter monitor lead) from a healthy subject (top) and a patient with coronary artery disease (CAD) (middle) are virtually indistinguishable by clinical criteria, both showing apparently normal sinus rhythm.  However, time series of interbeat intervals from the healthy subject (bottom, left) and the patient with CAD (bottom, right) highlight dynamical differences. The former has the more fluent, pattern of variations; the latter shows a fragmented profile.  The voltage of the ECG is given in arbitrary units (a.u.). From Costa MD, Davis, RB, Goldberger AL. Front Physiol. 2017.

Of note, clinicians are very unlikely to diagnose fragmentation patterns from clinical ECG displays, which are only 10-sec in duration, or even from visual inspection of longer cardiac monitors recordings obtained in critical care units. But the jagged profiles of fragmentation, reflecting abrupt changes in heart rate acceleration not attributable physiologic control mechanisms, are clearly evident in heart rate time series.

Follow-up studies are now aimed at validating these findings and seeing if proposed new measures of heart rate fragmentation can be used to enhance the prediction of adverse outcomes due to cardiovascular and other systemic diseases, as well as to assess the aging process.

These two studies, Heart Rate Fragmentation: A New Approach to the Analysis of Cardiac Interbeat Interval Dynamics and Heart Rate Fragmentation: A Symbolic Dynamical Approach were recently published in the journal Frontiers in Physiology.

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