The effect of apnea length on vital parameters in apnea of prematurity - Hybrid observations from clinical data and simulation in a mathematical model.

Apnea of prematurity (AOP) is a critical condition for preterm infants which can lead to several adverse outcomes. Despite its relevance, mechanisms underlying AOP are still unclear. In this work we aimed at improving the understanding of AOP and its physiologic responses by analyzing and comparing characteristics of real infant data and model-based simulations of AOP. We implemented an existing algorithm to extract apnea events originating from the central nervous system from a population of 26 premature infants (1248 h of data in total) and investigated oxygen saturation (SpO2) and heart rate (HR) of the infants around these events. We then extended a previously developed cardio-vascular model to include the lung mechanics and gas exchange. After simulating the steady state of a preterm infant, which successfully replicated results described in previous literature studies, the extended model was used to simulate apneas with different lengths caused by a stop in respiratory muscles. Apneas identified by the algorithm and simulated by the model showed several similarities, including a far deeper decrease in SpO2, with the minimum reached later in time, in case of longer apneas. Results also showed some differences, either due to how measures are performed in clinical practice in our neonatal intensive care unit (e.g. delayed detection of decline in SpO2 after apnea onset due to signal averaging) or to the limited number of very long apneas (≥80 s) identified in our dataset.

Heart rate fragmentation gives novel insights into non-autonomic mechanisms governing beat-to-beat control of the heart's rhythm.

To demonstrate how heart rate fragmentation gives novel insights into non-autonomic mechanisms of beat-to-beat variability in cycle length, and predicts survival of cardiology clinic patients, over and above traditional clinical risk factors and measures of heart rate variability. Approach: We studied 2893 patients seen by cardiologists with clinical data including 24-hour Holter monitoring. Novel measures of heart rate fragmentation alongside canonical time and frequency domain measures of heart rate variability, as well as an existing local dynamics score were calculated. A proportional hazards model was utilized to relate the results to survival. Main results: The novel heart rate fragmentation measures were validated and characterized with respect to the effects of age, ectopy and atrial fibrillation. Correlations between parameters were determined. Critically, heart rate fragmentation results could not be accounted for by undersampling respiratory sinus arrhythmia. Increased heart rate fragmentation was associated with poorer survival (p ≪ 0.01 in the univariate model). In multivariable analyses, increased heart rate fragmentation and more abnormal local dynamics (p 0.045), along with increased clinical risk factors (age (p ≪ 0.01), tobacco use (p ≪ 0.01) and history of heart failure (p 0.019)) and lower low- to high-frequency ratio (p 0.022) were all independent predictors of 2-year mortality. Significance: Analysis of continuous ECG data with heart rate fragmentation indices yields information regarding non-autonomic control of beat-to-beat variability in cycle length that is independent of and additive to established parameters for investigating heart rate variability, and predicts mortality in concert with measures of local dynamics, frequency content of heart rate, and clinical risk factors.