Risk stratification for arrhythmic death in an emergency department cohort: a new method of nonlinear PD2i analysis of the ECG

Abstract

Heart rate variability (HRV) reflects both cardiac autonomic function and risk of sudden arrhythmic death (AD). Indices of HRV based on linear stochastic models are independent risk factors for AD in postmyocardial infarction (MI) cohorts. Indices based on nonlinear deterministic models have a higher sensitivity and specificity for predicting AD in retrospective data. A new nonlinear deterministic model, the automated Point Correlation Dimension (PD2i), was prospectively evaluated for prediction of AD. Patients were enrolled (N = 918) in 6 emergency departments (EDs) upon presentation with chest pain and being determined to be at risk of acute MI (AMI) >7%. Brief digital ECGs (>1000 heartbeats, approximately 15 min) were recorded and automated PD2i results obtained. Out-of-hospital AD was determined by modified Hinkle-Thaler criteria. All-cause mortality at 1 year was 6.2%, with 3.5% being ADs. Of the AD fatalities, 34% were without previous history of MI or diagnosis of AMI. The PD2i prediction of AD had sensitivity = 96%, specificity = 85%, negative predictive value = 99%, and relative risk >24.2 (p ≤ 0.001). HRV analysis by the time-dependent nonlinear PD2i algorithm can accurately predict risk of AD in an ED cohort and may have both life-saving and resource-saving implications for individual risk assessment.

Keywords: chaos; heart rate variability; non-linear; sudden death; ventricular arrhythmias.

Figure 1

Receiver-operator curve (ROC) for all data with a positive or negative PD2i Test. The ROC determines the criterion cut-point for the PD2i Test that maximizes the sensitivity and specificity. At a cut-point of PD2i ≤ 1.4, the maximum sensitivity and specificity are found with the area under the ROC being high (0.92).

Figure 2

RR intervals and associated PD2is from two types of patients. Upper panel shows RR data and corresponding PD2i results from a patient who experienced documented arrhythmic death (AD) within 24 hours; note the two patterns of either a sustained low-dimension (line) or the systematic low-dimensional excursion (arrow). The lower panel shows data and results from a normal patient discharged after diagnosis of gastro-esophageal reflux disorder (CONTROL).

Figure 3

All-cause death vs time of occurrence after the brief ECG recording. Large squares indicate cardiac arrhythmic death (AD), as adjudicated by the Events Committee. All non-AD deaths are indicated by small unfilled squares, and include deaths due to cancer, sepsis, stroke, etc. AD patients admitted to low-level telemetry observation at admission are indicated by dots.

Figure 4

Composite RR and PD2i results for the first 18 arrhythmic death (AD) cases with all clinical data and no a priori exclusions for noise contamination. NCA = cases in which a single bit (noise-bit) was removed from each data point thus forcing the background noise level below ± 5 integers. In the acute myocardial infarction (AMI) controls all PD2i >3.0 are pushed down to the 3.0 line for display.