Power-law properties of nocturnal arrhythmia avalanches: a novel marker for incident cardiovascular events

Background: Bursting nonsustained cardiac arrhythmia events are a common observation during sleep. Objectives: The purpose of this study was to investigate the hypothesis that nocturnal arrhythmia episode durations could follow a power law, whose exponent could predict long-term clinical outcomes. Methods: We defined “nocturnal arrhythmia avalanche” (NAA) as any instance of a drop in electrocardiographic (ECG) template-matched R-R intervals ≥30% of R-R baseline, followed by a return to 90% of baseline. We studied NAA in ECG recordings obtained from the Sleep Heart Health Study (SHHS), Osteoporotic Fractures in Men Study (MrOS) Study, and Multi-Ethnic Study of Atherosclerosis (MESA). The association of nocturnal arrhythmia durations with a power-law distribution was evaluated and the association of derived power-law exponents (α) with major adverse cardiovascular (CV) events and mortality assessed with multivariable Cox regression. Results: A total of 9176 participants were studied. NAA episodes distribution was consistent with power-law vs comparator distributions in all datasets studied (positive log likelihood ratio of power-law vs exponential in MESA: 83%; SHHS: 69%; MrOS: 81%; power-law vs log-normal in MESA: 95%; SHHS: 35%; MrOS: 64%). The NAA power-law exponent (α) showed a significant association of with adverse CV outcomes (association with CV mortality: SHHS hazard ratio 1.39 [1.07–1.79], P = .012; MrOS hazard ratio 1.42 [1.02–1.94], P = .039; association with CV events: MESA HR 3.46 [1.46–8.21], P = .005) in multivariable Cox regression, after adjusting for conventional CV risk factors and nocturnal ectopic rate. Conclusion: The NAA power-law exponent is a reproducible, predictive marker for incident CV events and mortality.