Warning symptoms associated with imminent sudden cardiac arrest: a population-based case-control study with external validation

Abstract

Background: Sudden cardiac arrest is a global public health problem with a mortality rate of more than 90%. Prearrest warning symptoms could be harnessed using digital technology to potentially improve survival outcomes. We aimed to estimate the strength of association between symptoms and imminent sudden cardiac arrest.

Methods: We conducted a case-control study of individuals with sudden cardiac arrest and participants without sudden cardiac arrest who had similar symptoms identified from two US community-based studies of patients with sudden cardiac arrest in California state, USA (discovery population; the Ventura Prediction of Sudden Death in Multi-Ethnic Communities [PRESTO] study), and Oregon state, USA (replication population; the Oregon Sudden Unexpected Death Study [SUDS]). Participant data were obtained from emergency medical services reports for people aged 18-85 years with witnessed sudden cardiac arrest (between Feb 1, 2015, and Jan 31, 2021) and an inclusion symptom. Data were also obtained from corresponding control populations without sudden cardiac arrest who were attended by emergency medical services for similar symptoms (between Jan 1 and Dec 31, 2019). We evaluated the association of symptoms with sudden cardiac arrest in the discovery population and validated our results in the replication population by use of logistic regression models.

Findings: We identified 1672 individuals with sudden cardiac arrest from the PRESTO study, of whom 411 patients (mean age 65·7 [SD 12·4] years; 125 women and 286 men) were included in the analysis for the discovery population. From a total of 76 734 calls to emergency medical services, 1171 patients (mean age 61·8 [SD 17·3] years; 643 women, 514 men, and 14 participants without data for sex) were included in the control group. Patients with sudden cardiac arrest were more likely to have dyspnoea (168 [41%] of 411 vs 262 [22%] of 1171; p<0·0001), chest pain (136 [33%] vs 296 [25%]; p=0·0022), diaphoresis (50 [12%] vs 90 [8%]; p=0·0059), and seizure-like activity (43 [11%] vs 77 [7%], p=0·011). Symptom frequencies and patterns differed significantly by sex. Among men, chest pain (odds ratio [OR] 2·2, 95% CI 1·6-3·0), dyspnoea (2·2, 1·6-3·0), and diaphoresis (1·7, 1·1-2·7) were significantly associated with sudden cardiac arrest, whereas among women, only dyspnoea was significantly associated with sudden cardiac arrest (2·9, 1·9-4·3). 427 patients with sudden cardiac arrest (mean age 62·2 [SD 13·5]; 122 women and 305 men) were included in the analysis for the replication population and 1238 patients (mean age 59·3 [16·5] years; 689 women, 548 men, and one participant missing data for sex) were included in the control group. Findings were mostly consistent in the replication population; however, notable differences included that, among men, diaphoresis was not associated with sudden cardiac arrest and chest pain was associated with sudden cardiac arrest only in the sex-stratified multivariable analysis.

Interpretation: The prevalence of warning symptoms was sex-specific and differed significantly between patients with sudden cardiac arrest and controls. Warning symptoms hold promise for prediction of imminent sudden cardiac arrest but might need to be augmented with additional features to maximise predictive power.

Funding: US National Heart Lung and Blood Institute.

Figure 1:

Participant selection for the discovery population

Figure 2:. Symptom frequency in participants with at least one predefined symptom

Symptom frequency in male participants with sudden cardiac arrest (n=286) and controls (n=514) in the PRESTO discovery population (A), female participants with sudden cardiac arrest (n=125) and controls (n=657) in the PRESTO discovery population (B), male participants with sudden cardiac arrest (n=305) and controls (n=548) in the SUDS replication population (C), and female participants (n=122) and controls (n=690) in the SUDS replication population (D). Data for sex were missing for 14 control participants in the PRESTO discovery population and one control participant in the SUDS replication population.

Figure 3:. UpSet plot of symptoms occurring singly or in sets of symptoms among patients with sudden cardiac arrest in the discovery population

(A) Men with sudden cardiac arrest aged 35–64 years. (B) Men with sudden cardiac arrest aged ≥65 years. (C) Women with sudden cardiac arrest aged 35–64 years. (D) Women with sudden cardiac arrest aged ≥65 years. The five most prevalent symptoms among patients with sudden cardiac arrest are shown, with each bar representing the mutually exclusive frequency of the single symptom or symptom set in each age–sex group. In the legend below each bar, a single dark circle indicates that symptom occurring alone; two or more dark circles connected with a line indicates those symptoms occurring as a group. This graph does not include the smaller proportion of cases with one or more of the five most common symptoms that occurred with less common symptoms (eg, chest pain plus dizziness) or other less common mutually exclusive individual symptoms or sets of symptoms (eg, palpitations or palpitations plus dizziness).