Abstract: Background. Recent studies suggest that primary percutaneous coronary intervention (PCI) and targeted temperature management (TTM) improve outcome in ST-segment elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA). The objective of this study was to evaluate a contemporary series of patients with STEMI and OHCA to characterize treatment approaches and predictors of neurologic outcome. Methods. From January 2009 through November 2012, a total of 239 patients who underwent emergent coronary angiography at 10 medical centers across the United States were enrolled. All patients suffered OHCA with STEMI on either the prehospital or post-resuscitation electrocardiogram. Neurologic outcome was assessed using the cerebral performance category (CPC) score. Predictors of neurologic outcome were determined using multivariate logistic regression analysis. The primary endpoint was in-hospital survival with good neurologic function (CPC score 1 or 2). Results. Mean age was 60 ± 13 years, 72% were male, and the majority of patients had a history of cardiovascular event. Initial rhythm was ventricular fibrillation in 72%. At hospital presentation, 76% of patients were intubated, 37% were in cardiogenic shock, and 33% were receiving vasopressors. Primary PCI was performed in 74%, with an average door-to-balloon time of 95 ± 77 minutes, and TTM was used in 51%. Forty-four percent of patients had full neurologic recovery (CPC score 1) and 55% had good neurologic function. Overall in-hospital survival rate was 66%. Independent predictors of in-hospital survival with good neurologic function were: receiving bystander cardiopulmonary resuscitation, location of arrest, receiving drug-eluting stents, and not experiencing a recurrent cardiac arrest. Conclusions. Short-term survival for patients with STEMI and OHCA undergoing emergent coronary angiography and revascularization with TTM in this contemporary, multicenter registry was high and neurologic outcome was good in more than half of patients.
J INVASIVE CARDIOL 2020 January 15 (Epub Ahead of Print).
Key words: out-of-hospital cardiac arrest, primary PCI, STEMI, targeted temperature management
Current treatment for patients with ST-segment elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA) includes emergent coronary angiography and targeted temperature management (TTM).1 Observational studies suggest that this aggressive approach is associated with improved neurologic outcome and survival.2-8 Although randomized clinical studies in this area are lacking, a recent position paper from the American College of Cardiology supports this approach in select patients.9
Treatment times and mortality remain performance metrics for STEMI care for which physicians and hospital systems are often compared and held accountable.10 Given the critical nature of patients with STEMI and OHCA, treatment times for primary PCI are longer, and this increase in time is frequently not adjusted for within current reporting systems.11,12 In addition to prolonged treatment times, mortality for this unique subgroup of STEMI patients remains high. A recent analysis of the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry-GWTG) found an in-hospital mortality rate of 29% despite the use of primary PCI in 77% of patients.13 High mortality rates and concerns about risk adjustment in public reporting may influence the adoption of widespread use of primary PCI in STEMI complicated by OHCA.14
In this study, we sought to evaluate patients with STEMI and OHCA treated at various medical centers across the United States to characterize the use of primary PCI and TTM and determine predictors of in-hospital survival with good neurologic outcome.
Patient population. The ST elevation And myocaRdial infarcTion (START) registry is a retrospective, multicenter registry within the United States that was designed to investigate real-world outcomes of patients with STEMI and OHCA. Both academic and community-based clinical sites were chosen based upon established experience with primary PCI for STEMI and use of TTM for OHCA. All centers had established TTM protocols for OHCA and the ability to provide primary PCI by a skilled cardiac catheterization laboratory team. Patients were enrolled from 10 clinical sites throughout the United States from January 2009 to November 2012. Inclusion criteria included age ≥18 years, OHCA with return of spontaneous circulation, STEMI on either the prehospital (PH) or initial post-resuscitation electrocardiogram (ECG), and survival to the completion of emergent coronary angiography. ECG criteria for STEMI were ≥2 mm of ST-segment elevation in 2 contiguous precordial leads or ≥1 mm of ST-segment elevation in 2 contiguous limb leads. Exclusion criteria were those with termination of resuscitation in the field, those who died prior to the completion of emergent coronary angiography, and those who did not meet the ECG criteria for STEMI. A waiver of informed consent was granted by the investigational review board and the study was approved by the local investigational review board at each clinical site. The study was coordinated by University of Southern California and was conducted in accordance with the Declaration of Helsinki.
Procedures and treatment received. Anticoagulant (heparin or bivalirudin), antiplatelet therapy, glycoprotein IIb/IIIa inhibitor, type of coronary stent (bare-metal or drug-eluting), and additional treatment devices including thrombectomy were at the discretion of the treating physician. Use of a specific device for TTM, duration of cooling, target temperature, methods of rewarming, and use of paralytic agents during cooling were at the discretion of the treating physician and established institutional hypothermia protocols.
Study variables. At each clinical site, trained clinical research assistants recorded data onto standardized data collection forms using the Utstein style.15 Completed data collection forms were reviewed by two authors (MZ and DMS) and entered into a dedicated study database. Demographic variables, treatment time intervals, procedural variables, and angiographic variables were collected. Ejection fraction was assessed by transthoracic echocardiography. Culprit lesion was determined using angiographic and ECG findings. Thrombus was defined according to the definition established by Ellis et al.16 In-hospital clinical events including refractory cardiogenic shock, recurrent cardiac arrest, repeat revascularization, stroke, infection, blood transfusion, placement of implantable cardiac defibrillator, and neurologic status at discharge were collected. Refractory cardiogenic shock was defined as systolic blood pressure <90 mm Hg for >30 minutes or the use of vasopressors to maintain systolic blood pressure >90 mm Hg. Recurrent cardiac arrest was defined as an episode of pulseless ventricular tachycardia, ventricular fibrillation, asystole, or pulseless electrical activity requiring treatment that occurred following the initial episode. Repeat revascularization was defined as recurrent ischemic symptoms lasting 30 minutes with either new ECG charges of re-elevation of troponin or creatinine phosphokinase MB. Stroke was defined as a focal neurologic deficit lasting 72 hours and resulting in irreversible brain damage or body impairment, and was confirmed by an imaging study. Infection was defined as clinical evidence of an infection requiring treatment with intravenous antibiotics. Neurologic status was assessed with the 5-point cerebral performance category (CPC) scale (1 = no major disability; 2 = moderate disability; 3 = severe disability; 4 = coma or vegetative state; and 5 = death).17 Discharge destination was classified as home, acute-care facility, or long-term care facility. Clinical follow-up was obtained in all survivors at a mean time of 24 months.
Statistical analyses. The primary endpoint of the study was in-hospital survival with good neurologic function (CPC scale 1 or 2). We also determined predictors of survival with good neurologic outcome (CPC scale 1 and 2). Categorical variables are presented as number and percentage. Continuous variable are presented as mean ± standard deviation or median and 25th to 75th percentile. Student’s t-test was used to compare categorical variables, and Chi-square or Fisher’s exact test were used to compare continuous variables. Candidate predictors of good neurologic outcome (CPC scale 0 and 1) were initially assessed by means of the univariate analysis of demographic, clinical, angiographic, and procedural variables. Variables with a P-value of <.10 were included in a multivariate logistic regression model to identify independent predictors of in-hospital survival with good neurologic outcome. The risk estimates of each variable are reported as odds ratio (OR) and 95% confidence interval (CI). A P-value <.05 was considered statistically significant. All analyses were performed using SAS software, version 9.4 (SAS Institute).
Baseline characteristics. Demographics of the study population are shown in Table 1. The majority of patients had a history of cardiovascular event (21% with prior myocardial infarction, 31% with established coronary artery disease, 6% with coronary artery bypass surgery, and 16% with prior PCI). At hospital presentation, the cohort was critically ill, with 37% in cardiogenic shock, 76% intubated, and 15% receiving two or more pressor agents. Initial arrest rhythm was ventricular fibrillation in 72%, ventricular tachycardia in 7% and non-shockable (asystole and pulseless electrical activity) in 16%. Forty-six percent of patients suffered the arrest in a public place and 50% had ECG evidence of an anterior-wall myocardial infarction.
Angiographic findings. PCI was performed in 74% of patients, with an average door-to-balloon time of 95 ± 77 minutes (Table 2). Normal coronary arteries were present in 12% and probable cardiomyopathy was present in 6%. Of patients receiving PCI, stent placement was performed in 85% and thrombectomy was performed in 56%, with 88% of patients achieving final TIMI 3 flow grade. TTM was used in 51% of patients (79% with shockable and 15% with non-shockable rhythms). The method for TTM was cold saline and an external cooling system in the majority of patients.
Clinical events. Refractory cardiogenic shock occurred in 26% and recurrent cardiac arrest occurred in 18% (Table 3). A total of 158 patients (66%) survived to hospital discharge. At hospital discharge, 44% had CPC scale 1 and 55% had CPC scale 1 or 2. Most patients were discharged to an acute-care facility. Survival rate at 1 year was 35%.
Predictors of neurologic outcome. Univariate predictors of in-hospital survival with good neurologic function (CPC scale 1 or 2) are shown in Supplemental Table S1. Independent predictors of in-hospital survival with good neurologic function (CPC scale 1 or 2) were receiving bystander cardiopulmonary resuscitation (CPR), location of arrest (any location other than home or public place), receiving drug-eluting stents, and not experiencing a recurrent cardiac arrest (Figure 1).
In the current study, we evaluated a large series of patients with STEMI complicated by OHCA treated at various medical centers throughout the United States. These centers were included in this registry based upon established institutional protocols mandating emergent coronary angiography with consideration of primary PCI and early initiation of TTM. We found that the use of primary PCI and TTM was high, with rapid treatment times (average door-to-balloon time, 95 ± 77 minutes). Using these contemporary treatment approaches, in-hospital survival rate was 66%, with good neurologic outcome in 55%.
Several prior observational studies have evaluated the use of emergent coronary angiography and revascularization with PCI combined with TTM for STEMI complicated by OHCA.4,7,13,18 Garot et al described the experience of five high-volume centers in France in 2007 detailing the benefits of coordinated prehospital care, emergent coronary angiography, and early revascularization in 186 patients with cardiac arrest (both OHCA and in-hospital cardiac arrest) complicating acute myocardial infarction.7 Prehospital thrombolytics were used in 12% and PCI was successful in 87%. In-hospital and 6-month survival rates were 55% and 54%, respectively. Lettieri et al evaluated 2617 STEMI patients undergoing primary PCI and described the outcomes of 99 patients with OHCA.4 Primary PCI was performed in 80% and TTM in 12%. In-hospital and 6-month survival rates were 78% and 75%, respectively. Kontos et al evaluated over 49,000 STEMI patients enrolled in the NCDR ACTION Registry-GWTG and identified 3716 patients with STEMI complicated by OHCA.13 Despite the use of primary PCI in 77%, with 79% of patients achieving a door-to-balloon time of ≤90 minutes, in-hospital survival rate was only 71%. Iqbal et al reported 174 patients treated in England within a regional-care system of eight acute-care hospitals.18 Survival at 1 year was 62% and independent predictors of survival were cardiogenic shock, advanced airway use, increased duration of resuscitation, and the absence of TTM.
An important consideration in the current series and other reports of primary PCI for STEMI complicated by OHCA is the affected patient population. Despite a relatively high frequency of prior coronary artery disease, subjects are generally healthy and relatively young at the time of the catastrophic event. The average age of 61 years in the current series is similar to other reports.3,4,12 This observation provides additional rationale for the liberal use of health-care resources including early coronary angiography and consideration of primary PCI. In addition, multivessel disease was common in the current series (41%) and similar to the series by Garot et al and Kontos et al (48% and 60%, respectively). The optimal revascularization strategy and timing of non-culprit PCI in this population remains unknown and is a topic for ongoing research.
The START registry represents a high-risk and contemporary cohort of patients undergoing primary PCI for STEMI and OHCA. Cardiogenic shock, respiratory failure requiring endotracheal intubation, use of vasopressors, anterior STEMI in 50%, and a high prevalence of co-morbid medical conditions (diabetes mellitus, chronic kidney disease) characterize this patient cohort. The START registry represents one of the largest multicenter experiences in the United States describing contemporary treatment for STEMI and OHCA. Primary PCI was applied in the majority of patients and TTM was used in approximately 50%. The decision to proceed with primary PCI in patients following OHCA is often complex and multifactorial and may not be solely based upon medical evidence nor driven by guideline-based recommendations.11,14,19 Given issues with public reporting of data and the worse outcomes of patients with STEMI complicated by OHCA, many institutions have yet to adopt the widespread practice of emergent coronary angiography for all patients with OHCA and STEMI.9
Bystander CPR, location of arrest, and receiving drug-eluting stents were independent predictors of in-hospital survival with good neurologic outcome. Prior studies of patients with OHCA have also found bystander CPR and location of arrest to be associated with improved outcome.20,21 In the current study, we characterized location of arrest as home, public place, or other. Prior studies have shown that experiencing an arrest in a public place is associated with a higher rate of bystander CPR, use of automated external defibrillator, and improved outcome.22 Interestingly, in the current study, an “other” location had a favorable effect on outcome. The reasons for this remain unclear, but may include that our study population comprised those with OHCA complicated by STEMI, as opposed to the broader group of patients with OHCA. Location of arrest may have been associated with time to defibrillation; unfortunately, we did not collect time to defibrillation. We also found that receiving drug-eluting stents was associated with improved outcome. Prior studies have found that drug-eluting stents are more frequently used in clinically stable STEMI patients, those with private insurance, and those without known contraindications to prolonged dual-antiplatelet therapy.23 Not surprisingly, suffering a recurrent cardiac arrest was an independent predictor of poor outcome.
Study limitations. There are several limitations for the present analysis. We were unable to account for confounders not available within the study database. The current analysis represents a subgroup of all STEMI patients experiencing OHCA with return of spontaneous circulation. We intentionally included only patients who survived to the completion of emergent coronary angiography; all patients dying in transport to the hospital and those dying while in the emergency department (prior to receiving emergent coronary angiography) were not included. We chose to identify patients following cardiac arrest based upon the presence of ST-segment elevation on the post-resuscitation or first hospital ECG. The diagnostic accuracy of the ECG in the postresuscitation setting is limited; in the absence of ST-segment elevation, up to 15% of patients may have a culprit coronary lesion.24 In addition, the presence of ST-segment elevation does not exclusively identify patients with an acute coronary syndrome, as evidenced by the 12% of the study cohort who met the ECG inclusion criteria and had normal coronary arteries. Time to initiation of TTM, duration of cooling, target temperature, the specific device used for TTM, and rewarming protocols were not standardized across clinical sites. There was a high rate of survival with good neurologic outcome in this report. Selection or referral bias in the population undergoing early angiography and PCI in the current series cannot be excluded. Nonetheless, outcomes in STEMI with OHCA are known to be distinctly superior to those of the overall OHCA population and both PCI and TTM appear to be associated with improved survival.
In this contemporary series of patients with STEMI complicated by OHCA treated at various medical centers throughout the United States, we found that emergent coronary angiography and revascularization combined with TTM was associated with high survival rates and good neurologic outcome.
Acknowledgments. Please refer to Supplemental Table S2 for a list of study coordinators who assisted with this study.
From the 1Division of Cardiovascular Medicine, University of Southern California, Los Angeles, California; 2Division of Cardiology, University of Massachusetts, Worcester, Massachusetts; 3Division of Cardiology, Harbor UCLA Medical Center, Torrance, California; 4Division of Cardiology, University of Chicago, Chicago, Illinois; 5Department of Cardiology, Torrance Memorial Medical Center, Torrance, California; 6Division of Cardiology, University of Washington, Seattle, Washington; 7Department of Emergency Medicine, Sharp Memorial Medical Center, San Diego, California; 8Department of Emergency Medicine, University of Maryland, Baltimore, Maryland; 9Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas; 10Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina; 11Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California; 12Department of Emergency Medicine, University of Southern California, Los Angeles, California.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted August 6, 2019, provisional acceptance given August 14, 2019, final version accepted September 5, 2019.
Address for correspondence: David M. Shavelle, MD, Division of Cardiovascular Medicine, University of Southern California, 1510 San Pablo Street, Suite 322, Los Angeles, CA 90033. Email: email@example.com
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