In a large prospective multi-center observational study of out-of-hospital cardiac in regions dispersed throughout North America, 8.0% of treated arrests and 21.0% of ventricular fibrillation arrests survived to discharge. A minority of treated arrests received bystander CPR. Incidence, mortality, case fatality rate and survival to discharge of EMS-assessed, EMS-treated and ventricular fibrillation arrests differed significantly across geographic regions. Part of the regional differences in incidence could be attributable to differences in the completeness of case ascertainment and potential for undetected cases. However each site had or implemented approaches to ascertain arrests from all EMS agencies within their geographic area. This prospective approach in conjunction with statistical methods to account for missing cases provide the most robust resource to date for determining the public health magnitude of cardiac arrest. Thus the observed differences in incidence reflect differences in the underlying risk of OHCA as well as the local approach to organized emergency response and post-resuscitation care in hospital.
Others have reported regional variation in the incidence of out-of-hospital cardiac arrest.(10
) Such gradients are associated with socioeconomic and racial disparities in health. As a consequence of these gradients, cardiovascular disease is the leading cause of income-related differences in premature mortality in the United States,(12
) and Canada.(13
It is plausible that use of secondary prevention in patients with established cardiovascular disease is more common in some regions compared to others.(14
) This would reduce the occurrence of out-of-hospital cardiac arrest if secondary prevention attenuated arrhythmic risk. Randomized trials of statin therapy,(15
) and secondary analyses of statin use in a trial of implantable defibrillators demonstrate that use of such medication reduces the risk of subsequent arrest.(17
) Other studies demonstrate that beta-antagonists reduce the risk of death due to arrest in patients with heart failure.(18
) But the magnitude of regional variation in medication use is much less than the magnitude of variation in cardiac arrest observed in the present study. Therefore differences in prevention do not fully explain our findings.
Also it is plausible that patients with symptoms of acute myocardial infarction have less delay in seeking care in some geographic regions compared to others.(19
) This would reduce the occurrence of infarct-related ventricular fibrillation or shift it to the in hospital setting. If such differences in delay in care exist, it seems unlikely that they are due to differences in patient delay in reacting to symptoms of infarction since interventions to modify this delay have had limited success.(20
) Instead such differences could reflect regional differences in care and outcome for patients with acute cardiovascular events.(14
) Such differences could be reduced by implementation of systems of care for such patients.(22
) But we observed large regional variation in survival of all EMS-treated arrests as well as in the minority of arrests that were due to ventricular fibrillation and potentially associated with acute infarction. Therefore regional variation in care for acute cardiovascular events does not fully explain our findings.
Others have reported survival from 0%(23) to 21%(4) after treatment of out-of-hospital cardiac arrest. EMS agencies in large cities have special challenges in achieving good outcomes after cardiac arrest.(24
) Our analysis suggests that such differences do not reflect inter-study differences in inclusion criteria or outcome definition, as each site in the present study implemented uniform definitions of cardiac arrest and survival.
Instead, it seems likely that these differences reflect in part regional differences in the availability of emergency cardiac care.(26
) These differences include: bystander CPR, lay responder defibrillation programs,(27
) EMS factors such as experience of providers,(28
) and types of interventions provided by EMS providers(29
) or treatments available at receiving hospitals.(31
) Some of these factors have been associated with differences in survival or quality of life after resuscitation,(3
) although no analysis has had adequate power to detect the independent effect of all of these factors.
Morbidity and mortality from most cardiovascular diseases has declined over the last 30 years.(36
) The majority of this reduction has been attributed to risk factor modification.(37
) Unfortunately, there has been little improvement in the incidence of OHCA survival over this same period of time.(38
) Experts have proposed that OHCA be designated a reportable event to facilitate monitoring and improvement of cardiovascular health.(40
) The present study demonstrates that large regional differences in OHCA epidemiology exist, and are a prelude to further analysis to understand the causes of these variations as well as implementation of targeted interventions to reduce them. The discordance between case fatality rate and survival to discharge re-emphasize the importance of complete ascertainment of vital status as national, public reports of OHCA incidence and outcome become available.
Cardiovascular disease is the leading cause of death in the United States.(1
) The Institute of Medicine has identified the need to improve funding for EMS operations.(41
) Extrapolation of the mortality rate observed in the study regions to the total population of the United States suggests that there are 294,851 (quasi confidence intervals 236,063, 325,007) EMS-assessed OHCA cases annually in the United States.a
Extrapolation of this study to the total population of Canada suggests that there are 32,160 (quasi confidence intervals 25,748, 35,450) EMS-assessed OHCA cases annually in Canada.b
Collectively these estimates of burden imply that allocation of increased resources to EMS operations is necessary to achieve an important impact on cardiovascular health in either country.
If survival after OHCA treated by EMS could be increased from the study average of 7.9% to the maximum of 16.2% throughout North American, then the premature deaths of 15,500 individuals would be prevented each year.c
Ongoing funding for fundamental, translational and clinical research related to emergency cardiovascular care is necessary to ensure that we are able to achieve such improvements in public health.
This study has several strengths compared to previous studies. Clinical trials often exclude patients at higher risk of poor outcomes so estimation of the burden of illness based only on those enrolled in trials is subject to bias. Existing OHCA registries do not contain the necessary information to determine which interventions are effective in the out-of-hospital setting. Several large regional registries have evaluated the effectiveness of out-of-hospital interventions upon outcomes after OHCA.(42
) However these underestimated the incidence of OHCA because they excluded individuals who are assessed but not treated by EMS personnel.
This study has some limitations. First, ROC sites were selected by a competitive process emphasizing regional sites with well organized EMS systems and associated investigators, so results observed in participating ROC sites may not be representative of the community at large. However the catchment population of participating communities includes approximately 10% of the North American population and has diverse geographic and socioeconomic characteristics. To the best of our knowledge, this population is larger than that of any other ongoing out-of-hospital cardiac arrest registry. Second, it is plausible that incidence, structure, process and outcome data reported by each site are subject to ascertainment bias since not all responses are audited. However all sites agreed to the data elements before study initiation, trained data collection personnel, and altered existing paper or electronic data capture to increase the likelihood of data capture. As well, our use of timely episode reporting by sites facilitates quick feedback from the coordinating center to sites and to responders to reduce incomplete data. Another limitation is that the expected number of OHCA cases was not observed for some agencies during specific time intervals within the sampling period. Multiple imputation was used to account for such missing data. This approach allows us to better estimate variability of the data, and ensure appropriately proportionate weight for each agency. This method assumes that the cases we randomly impute, which in our case were from the same agency in a
different time period, have the same patient, EMS process and outcome characteristics as the missing data. Registry data have not shown any significant time trends that would bias this imputation process.(44
) Furthermore only a small proportion of the total cases were imputed in this study, so it seems unlikely that this imputation would reduce its validity.
We were unable to assess the effect of hospital-based post-resuscitation care on outcomes after out-of-hospital cardiac arrest due to our lack of patient-specific data about processes of care delivered in hospital. In-hospital therapeutic hypothermia improves outcomes after out-of-hospital cardiac arrest.(31
) A small trial suggested that hemofiltration to reduce inflammation after out-of-cardiac arrest offers additional benefit.(45
) Observational studies suggest that early percutaneous coronary intervention improves outcomes as well.(46
) Therefore, future assessments of regional variation in outcome after out-of-hospital cardiac arrest should assess the relative impact of out-of-hospital and hospital-based care.
Also we were unable to describe neurologic outcome at discharge. Assessment of Cerebral Performance Category (CPC) at discharge is a recommended part of resuscitation outcome studies.(48
) However CPC has limited discrimination between mild and moderate brain injury. A small study with incomplete follow-up of survivors demonstrated only moderate correlation with other measures of health-related quality of life.(49
) Although a larger study demonstrated a better correlation between CPC and a generic measures of health-related quality of life, CPC should not be considered a substitute for reliable and valid measures of the latter.(50
) Nonetheless previous studies demonstrate that resuscitation interventions that are associated with better survival are also associated with better quality of life.(34
These findings have implications for prehospital emergency care. The four-fold variation in survival after EMS-treated cardiac arrest and seven-fold variation in survival after ventricular fibrillation demonstrate that cardiac arrest is a treatable condition. But only 31.4% of treated arrests (84.8% of bystander witnessed) received bystander CPR. Therefore ongoing efforts are necessary to encourage lay people to be ready, willing and able to provide CPR when necessary. Further improvements in outcome could be achieved by reducing the time to ALS arrival by improving early detection of cardiac arrest, dispatch protocols, deployment of existing vehicles, the number of vehicles available to respond, the quality of CPR, and real-time or post-event quality assurance.