Age, sex, and survival following ventricular fibrillation cardiac arrest: a mechanistic evaluation of the ECG waveform

Abstract

Background: Sex-based outcome comparisons in out-of-hospital cardiac arrest (OHCA) have produced mixed results. Sex-based outcomes may depend in part on age, as menopause produces a range of biological effects that may influence resuscitation. We used quantitative measures of the ventricular fibrillation (VF) waveform – a surrogate of the myocardium’s acute physiology – to assess whether outcome differences according to sex and age group may be mediated via a biologic mechanism. Methods: We conducted a retrospective cohort study of adult non-traumatic VF-OHCA patients in King County, Washington between 2008-2020. We used multivariable logistic regression to assess the relationship of outcome (survival to hospital discharge, favorable neurological outcome (Cerebral Performance Category (CPC) 1 or 2), according to sex and age group (<55, 55). We determined the proportion of the outcome difference mediated by the waveform measure by incorporating the VF waveform measures - probability of survival, amplitude spectrum area, frequency, and median peak amplitude individually - into the multivariable model. Results: Of 1526 VF-OHCA, average age was 62 years, and 29% were female. Overall, we observed that younger women were more likely to survive than younger men (survival 67% vs 54% and favorable neurologic outcome 61% vs 51%), while older women and older men fared more similarly (survival 44% vs 40% and favorable neurologic survival 39% vs 37%). After adjusting for Utstein characteristics, women < 55 compared to men <55 was associated with greater odds of survival to hospital discharge (OR 1.93, 95% CI 1.23-3.09, p=0.005) and favorable neurological survival (OR 1.72, 95% CI 1.10-2.71, p=0.018). In contrast, women 55 compared to men 55 was not associated with a difference in the odds of survival to hospital discharge (1.19, 95% CI 0.87-1.62, p=0.283) and favorable neurological survival (1.07, 95% CI 0.78-1.46, p=0.683). The added waveform measures mediated some the beneficial association between survival and female sex among those <55: 47% for probability of survival, 25% for amplitude spectrum area, 19% for frequency, and 17% for median peak amplitude. Conclusions: In this observational cohort study of VF-OHCA, we observed that women <55 years were more likely to survive to hospital discharge and survive with favorable neurological status compared to men <55 years; a sex-based outcome difference not observed among the older age group. VF waveform measures as a surrogate for acute physiologic status of the heart– mediated some, though not all, of the outcome difference.