Fig 1.

Representative heart rate recordings in health and disease, presented as four unknowns. One record is normal; the other three represent severe pathologies. Can you identify which is normal? Answers: A and C are from patients in sinus rhythm with severe congestive heart failure. D is from a subject with a cardiac arrhythmia, atrial fibrillation, which produces an erratic heart rate. The healthy record, B, far from a homeostatic constant state, is notable for its visually apparent nonstationarity and “patchiness.” These features are related to fractal and nonlinear properties. Their breakdown in disease may be associated with the emergence of excessive regularity (A) and (C), or uncorrelated randomness (D). Of note in C is the presence of strongly periodic oscillations (≈1/min), which are associated with Cheyne-Stokes breathing, a pathologic type of cyclic respiratory pattern. Quantifying and modeling the complexity of healthy variability, and detecting more subtle alterations with disease and aging, present major challenges in contemporary biomedicine.