Cardiac Autonomic Function score: a novel risk stratification tool in the cardiac intensive care unit based on periodic repolarization dynamics and deceleration capacity of heart rate (LMU-eICU study)

Mathias Klemm (München)1, L. von Stülpnagel (München)1, V. Ostermaier (München)1, C. Theurer (München)1, L. Villegas Sierra (München)1, F. N. Wenner (München)1, L. Freyer (München)1, S. Massberg (München)1, A. Bauer (Innsbruck)2, K. Rizas (München)1

1LMU Klinikum der Universität München Medizinische Klinik und Poliklinik I München, Deutschland; 2Tirol Kliniken GmbH Kardiologie und Angiologie Innsbruck, Österreich



Treatment capacities in intensive care units (ICU) are a critical resource in modern medicine. Current concepts of risk stratification are primarily based on evaluation of clinical and vital signs, as well as laboratory values. Here, we propose a novel ECG-based cardiac autonomic risk stratification score (CAFICU) based on periodic repolarization capacity (PRD), a repolarization biomarker of sympathetic overactivity and deceleration capacity of heart rate (DC), a parameter showing vagal imbalance.


CAFICU was developed in a retrospective cohort of 355 patients, consecutively admitted to the cardiac ICU at the LMU-university hospital between February 1st 2018 and November 30th 2018. CAFICU was subsequently validated in a cohort of 702 patients admitted between December 1st 2018 to April 30th 2020 to the same cardiac ICU. All patients in both cohorts were in sinus rhythm.  PRD and DC were calculated using the ECG-signals acquired within the first night of the ICU-stay between 2:00 am and 2:30 am. The primary endpoint of the study was intrahospital mortality within 30 days after ICU admission. We used Cox-regression analysis to calculate the continuous hazard ratios for PRD and DC in the training cohort and we subsequently defined CAFICU for each patient, as the cumulative risk derived from both PRD and DC. Survival curves were generated using the Kaplan-Maier method and were dichotomized at the median value of CAFICU. The incremental prognostic value of CAFICU on top of the established Simplified Acute Physiology score 3 (SAPS3) score was tested using integrated discrimination improvement index (IDI), continuous net reclassification index (NRI) and AI-based decision trees. 


Thirty (8.5%) and 100 (14.2 %) patients reached the primary endpoint in the training and validation cohorts, respectively. CAFICU was significantly higher in non-survivors than survivors in both the training (2.58 ± 1.34 vs. 1.76 ± 0.97 units, p = 0.003) and validation cohorts (2.20 ± 1.05  vs. 1.70 ± 0.83 units, p < 0.001). Moreover, CAFICU was a strong predictor of the primary outcome in both the training (HR 12.94; 95% CI 3.08 – 54.32; p < 0.001; Figure 1A) and validation cohorts (HR 3.65; 95% CI 2.26 – 5.91; p < 0.001; Figure 1B). In the pooled cohort CAFICU significantly improved risk stratification based on SAPS3-score (increase in IDI 0.032; 95% CI 0.014 – 0.064; p < 0.001, and continuous NRI 0.332; 95% CI 0.243-0.403; p < 0.001). Figure 2 illustrates decision-tree based classification of patients into risk-groups based on SAPS3 and CAFICU scores. 



ECG-based automatic cardiac autonomic risk stratification by means of PRD and DC is highly predictive of short-term mortality in the ICU and can be combined with the SAPS3-score to identify patients with increased risk for intrahospital mortality. 

Figure 1 Cumulative 30-days mortality rates in the training (A) and validation (B) cohorts stratified by cardiac autonomic function score (CAFICU) ≥ 1.5 units (red line) and < 1.5 units (blue line).

Figure 2 Decision-tree based classification of patients into risk-groups based on the Simplified Acute Physiology score 3 (SAPS3) and cardiac autonomic function score (CAFICU) scores. Risk 0: SAPS3-Score < 56; Risk 1 SAPS3-Score ≥ 56 and < 69 or SAPS3-Score ≥ 69 and CAFICU < 1.5; Risk 2: SAPS3-Score ≥ 69 and < 86 and CAFICU ≥ 1.5 and Risk 3: SAPS3-Score ≥ 86 and CAFICU ≥ 1.5. 



Diese Seite teilen