Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status

Abstract

Background: Early prognosis in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is unreliable, especially in patients undergoing mild hypothermia. We aimed at developing a reliable risk-score to enable early prediction of cerebral performance and survival.

Methods: Sixty-one out of 239 consecutive patients undergoing mild hypothermia after cardiac arrest, with eventual return of spontaneous circulation (ROSC), and comatose status on admission fulfilled the inclusion criteria. Background clinical variables, VF time and frequency domain fundamental variables were considered. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (n = 32; September 2006-September 2011, 48.5 ± 10.5 months of follow-up) and further validated in a prospective cohort (n = 29; October 2011-July 2013, 5 ± 1.8 months of follow-up).

Results: FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p < 0.001). Retrospective multivariate analysis provided a prediction model (sensitivity = 0.94, specificity = 1) that included spectral dominant frequency, derived power density and peak ratios between high and low frequency bands, and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity = 0.88 and specificity = 0.91. A model-derived risk-score properly predicted 93% of FNP. Testing the model on follow-up showed a c-statistic ≥ 0.89.

Conclusions: A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors undergoing mild hypothermia after cardiac arrest.

Keywords: Cardiac arrest; Cerebral injury; Dominant frequency; Early prognosis; Ventricular fibrillation.

Fig. 1

Digitization and signal processing of a representative VF trace. A. Upper panel, single lead VF trace from paper ECG prior to the first DC shock. Lower panel, 5-s VF epoch after digitization, segmentation and codification. B. Representative spectra of the VF trace shown in A. DF, MF, 1-Hz DF spectral concentration and PSD80%, are shown. The univariate cut-off at 3.9 Hz was used to define low and high PSD bands. DF = dominant frequency. MF =median frequency. NSC = normalized spectral concentration. PSD = power spectral density.

Fig. 2

Workflow of patients included in group 1 and group 2.

Fig. 3

A. Power spectral density (PSD) of all patients with in-hospital favorable (A1) and non-favorable (A2) neurological performance. The patients are sorted based on their DF values. DF peaks are pointed out for each individual (black vertical dashed-line). The cut-off threshold of 3.9 Hz was chosen for color-coding above (red) and below (blue) the PSD. B. Boxplot representation of DF comparing patients from both groups for primary and secondary endpoints. Boxes depict median and interquartile range (25–75%). Red dots are outliers at least twice the interquartile range from the median. Green dots represent outliers to hospital discharge who improved neurological performance during follow-up.

Fig. 4

Risk score based on the predictive performance of the model. A. Observed (triangles) and predicted (circles) probability of FNP for the entire population. Blue and red represent FNP and non-FNP, respectively (dark fill, retrospective; light fill, prospective).We defined four risk groups of non-FNP performance according to their risk scores as follows: expected FNP; very low (VL) and low risk (L) and expected non-FNP; high (H) and very high risk (VH). B. Percentage of patients (predicted, dark gray and observed, light gray) who belong to each of the risk score groups in both the retrospective (B1) and prospective cohorts (B2). (α) and (β) represent false negative and false positive individuals, respectively. FNP= favorable neurological performance.