| Summary: | Background The mechanism by which bystander cardiopulmonary resuscitation (CPR) improves survival following out‐of‐hospital cardiac arrest is unclear. We hypothesized that ventricular fibrillation (VF) waveform measures, as surrogates of myocardial physiology, mediate the relationship between bystander CPR and survival. Methods and Results We performed a retrospective cohort study of adult, bystander‐witnessed patients with out‐of‐hospital cardiac arrest with an initial rhythm of VF who were treated by a metropolitan emergency medical services system from 2005 to 2018. Patient, resuscitation, and outcome variables were extracted from emergency medical services and hospital records. A total of 3 VF waveform measures (amplitude spectrum area, peak frequency, and median peak amplitude) were computed from a 3‐second ECG segment before the initial shock. Multivariable logistic regression estimated the association between bystander CPR and survival to hospital discharge adjusted for Utstein elements. Causal mediation analysis quantified the proportion of survival benefit that was mediated by each VF waveform measure. Of 1069 patients, survival to hospital discharge was significantly higher among the 814 patients who received bystander CPR than those who did not (0.52 versus 0.43, respectively; P<0.01). The multivariable‐adjusted odds ratio for bystander CPR and survival was 1.6 (95% CI, 1.2, 2.1), and each VF waveform measure attenuated this association. Depending on the specific waveform measure, the proportion of mediation varied: 53% for amplitude spectrum area, 31% for peak frequency, and 29% for median peak amplitude. Conclusions Bystander CPR correlated with more robust initial VF waveform measures, which in turn mediated up to one‐half of the survival benefit associated with bystander CPR. These results provide insight into the biological mechanism of bystander CPR in VF out‐of‐hospital cardiac arrest.
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