Warning Symptoms Are Associated With Survival From Sudden Cardiac Arrest

Context Because many persons do not survive sudden cardiac arrest (SCA), we need better ways to prevent it. Contribution The researchers collected information about the 4 weeks before SCA from survivors, family members, friends, medical records, and emergency response records. About one half of patients with information had warning symptoms in those 4 weeks that often recurred during the 24 hours before SCA. Most patients ignored their symptoms. Caution Information was not available for about one quarter of patients. Implication Warning symptoms may provide an opportunity to prevent SCA. Sudden cardiac arrest (SCA) is commonly perceived by the lay and medical communities as a sudden unexpected collapse. With more than 550000 U.S. patients having out-of-hospital and in-hospital SCA annually, SCA accounts for more than half of cardiovascular deaths and is a major public health issue (1, 2). Survival after SCA remains very low and stable (approximately 7%), despite major investments by the medical and research communities in SCA over the past decades (3). Further, methods to improve prediction of patients at long-term risk for SCA are lacking; therefore, alternative approaches aimed at preemptive risk stratification and prevention are needed (1, 4, 5). Sentinel events preceding SCA may be of special interest in light of recent advances in communication and remote transmission technologies (6, 7). We hypothesized that warning events in the hours, days, and weeks before SCA might identify a subgroup of patients with SCA in whom timely and early intervention could affect outcomes. Investigation of SCA remains particularly challenging because most patients die in the field, so the information collected by emergency medical services (EMS) is often restricted to data about the resuscitation process. Details of the medical history of patients with SCA (especially those who cannot be resuscitated) are thus usually sparse and very rarely considered systematically. In the Oregon SUDS (Sudden Unexpected Death Study), we collected information on symptoms and clinical history for all patients with SCA, including those who died before reaching the hospital. We therefore conducted a comprehensive assessment of warning symptoms in the 4 weeks before SCA in a large prospective community-based study of deceased and surviving patients with SCA in the Portland, Oregon, metropolitan area. We hypothesized that the presence of and response to warning symptoms may be associated with better survival from SCA. Methods Setting, Definitions, and Survey Methods Oregon SUDS is an ongoing community-based prospective study of out-of-hospital SCA. Detailed methods have been published previously (811). Briefly, since 1 February 2002, cases of SCA in the Portland area were identified using several sources that included a 2-tiered EMS system, the medical examiner's office, and emergency departments of all local hospitals. This study was approved by the relevant institutional review boards of Cedars-Sinai Medical Center, Los Angeles, California, and Oregon Health & Science University, Portland, Oregon. We defined SCA as an unexpected loss of pulse, without obvious extracardiac cause, and rapid collapse with specific resuscitation records available. We excluded SCAs occurring in a patient with a prior terminal condition, such as cancer that was not in remission or end-stage chronic obstructive lung disease. At the time of adjudication, 3 physicians had access to lifetime medical history with all available hospital and outpatient medical records, including information on prior symptoms. Variables considered in the present analysis included demographics, circumstances of occurrence, and resuscitation data according to the revised Utstein style (12). In addition to the data from EMS and the medical examiner, an Oregon SUDS working group collected and assessed the lifetime medical history for deceased patients and survivors, including symptom assessment before SCA, by reviewing records of all inpatient and outpatient visits from the Portland area hospitals. The principal outcome was survival to hospital discharge; such data were available for all decedents and survivors. Assessment of Symptoms Before SCA Symptoms and their frequency were characterized during the 4 weeks before SCA among patients aged 35 to 65 years, and adjudicated from February 2002 to February 2012. The data on symptoms were collected by the Oregon SUDS investigators based on information documented by the EMS team (in the field), intensivists or cardiologists (at 16 hospitals), and physicians (in the community). Symptom assessment recorded on the EMS prehospital care report was derived from several sources, including information provided by family at the scene, witnesses, and survivors of SCA. In addition, available hospital and outpatient medical records for all patients were systematically analyzed for information about symptoms. Symptoms were categorized as absent, present, or not evaluable based on the extent of information available and the agreement of investigators. Symptoms were considered absent when there was no record of any medical consultation during the 4 weeks preceding SCA, at least 1 of the other sources specifically ascertained the absence of any symptoms, and none of the other sources reported any symptoms. Symptoms were considered present if they were documented by at least 1 of the sources. Of note, symptoms starting immediately before SCA (symptoms with instantaneous collapse) were considered no symptoms because they would have been unlikely to lead to any early intervention. Symptoms were classified as chest pain (subclassified as typical and atypical), dyspnea, palpitations, syncope, and other (including abdominal pain, nausea or vomiting, back pain, and miscellaneous symptoms). Finally, the presence of ongoing typical influenza-like symptoms was also evaluated. In cases of multiple symptoms (combined symptoms), chest pain was designated as the principal symptom when present. Time intervals from the onset of a symptom to SCA were categorized into 4 groups where possible (98%): within the first hour, 24 hours or less, 7 days or less, and 4 weeks or less before SCA. Symptoms were considered not acted on if patients, relatives, or witnesses did not attempt to contact EMS (911) in response to symptoms that occurred before SCA. Statistical Analysis This report was prepared in compliance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for observational studies (13, 14). The characteristics of SCA were reported as means (SDs), proportions, medians, and interquartile ranges as appropriate. Comparisons between groups used the chi-square test for categorical variables and the t test for continuous variables. A logistic regression model was used to compare survival to hospital discharge by 911 call in patients with symptoms. Covariates included age, sex, and meaningful independent variables according to Utstein guidelines (12). Missing values for covariates were accounted for using multiple imputations (mi impute command in Stata, version 11.0 [StataCorp]) by chained equations. Imputation models included terms for age, sex, location, witnessed and cardiopulmonary resuscitation status, initial rhythm, timing, onset, diabetes, dyslipidemia, body mass index, hypertension, current smoking, coronary artery disease, time to intervention, and the outcome. We used 10 imputations and Rubin rules to combine the results (15, 16). The results were similar to those from a complete-case analysis, so only results using multiply imputed data are presented as primary results. Sensitivity analyses were done to assess the relationship between survival and a 911 call, with additional adjustment for possible confounding due to the hospital or period (before and after 2005). Differences were assumed to be statistically significant for a 2-tailed probability (P 0.05). We calculated 95% CIs when appropriate. All data were analyzed using STATA software. Role of Funding Source The National Heart, Lung, and Blood Institute provided funding for the study. The funding source had no role in the design, conduct, and analysis of the study or in the decision to submit the manuscript for publication. Results Frequency of Warning Signs and Associated Characteristics Sixteen hospitals in the Portland area were included, with the median number of patients per hospital of 71 (IQR, 56 to 81). Overall, symptom data were not available for analysis in 260 patients (24%) because of insufficient or conflicting documentation (Figure 1 and Appendix Table 1). Reasons for not having symptom data included the absence of witnesses and relatives before and at the time of SCA and no medical report recorded in the area during the previous 4 weeks (166 patients); witnesses or relatives could not provide clear information in the absence of a specific medical record (69 patients); information on symptoms provided by patients, witnesses, or relatives considered as being too nonspecific to make definite conclusions (23 patients); and brain injury with significant cognitive dysfunction (2 patients). Patients without symptom assessment were more likely to not have a witness (65.4% vs. 43.3%) (Appendix Table 2). The most common source for symptom information was the Oregon EMS personnel, in 766 patients (91%) overall (Appendix Table 1), who were trained to gather important information in the field. Figure 1. Study flow diagram. Appendix Table 1. Primary Sources for SCA Symptom Information* Appendix Table 2. Patient Characteristics and Circumstances of SCA, by Symptom Assessment* Of the 839 patients with symptom assessment, 430 patients (51%) presented with at least 1 symptom within the 4 weeks before SCA (Figure 1), with similar frequency in men and women (50% vs. 53%; P= 0.59). Of the 430 patients with symptoms, 51 had consulted a family or specialist physician during the 4 weeks be