Background— Prior studies have identified key predictors of out-of-hospital cardiac arrest (OHCA), but differences exist in the magnitude of these findings. In this meta-analysis, we evaluated the strength of associations between OHCA and key factors (event witnessed by a bystander or emergency medical services [EMS], provision of bystander cardiopulmonary resuscitation [CPR], initial cardiac rhythm, or the return of spontaneous circulation). We also examined trends in OHCA survival over time.
Methods and Results— An electronic search of PubMed, EMBASE, Web of Science, CINAHL, Cochrane DSR, DARE, ACP Journal Club, and CCTR was conducted (January 1, 1950 to August 21, 2008) for studies reporting OHCA of presumed cardiac etiology in adults. Data were extracted from 79 studies involving 142 740 patients. The pooled survival rate to hospital admission was 23.8% (95% CI, 21.1 to 26.6) and to hospital discharge was 7.6% (95% CI, 6.7 to 8.4). Stratified by baseline rates, survival to hospital discharge was more likely among those: witnessed by a bystander (6.4% to 13.5%), witnessed by EMS (4.9% to 18.2%), who received bystander CPR (3.9% to 16.1%), were found in ventricular fibrillation/ventricular tachycardia (14.8% to 23.0%), or achieved return of spontaneous circulation (15.5% to 33.6%). Although 53% (95% CI, 45.0% to 59.9%) of events were witnessed by a bystander, only 32% (95% CI, 26.7% to 37.8%) received bystander CPR. The number needed to treat to save 1 life ranged from 16 to 23 for EMS-witnessed arrests, 17 to 71 for bystander-witnessed, and 24 to 36 for those receiving bystander CPR, depending on baseline survival rates. The aggregate survival rate of OHCA (7.6%) has not significantly changed in almost 3 decades.
Conclusions— Overall survival from OHCA has been stable for almost 30 years, as have the strong associations between key predictors and survival. Because most OHCA events are witnessed, efforts to improve survival should focus on prompt delivery of interventions of known effectiveness by those who witness the event.
In the United States, more than 166 000 patients experience an out-of-hospital cardiac arrest (OHCA) annually.1 Approximately 60% are treated by emergency medical services.1 Published rates of OHCA survival to hospital discharge range from 0.3% in Detroit2 to 20.4% in Slovenia.3 Among cities reporting data, the median rate of survival to hospital discharge is 6.4%.4
Previous meta-analyses of cardiac arrest research have focused on the use of new or emerging therapies (ie, impedance threshold device,5 active compression-decompression cardiopulmonary resuscitation,6 hypothermia,7 emergency intubation8), new medications (ie, vasopressin,9–11 epinephrine,11,12 time to first medication administration13), and the use of automated external defibrillators by bystanders14–16 and emergency medical technicians.4,17 However, no group has conducted a systematic review to assess, with precision, the associations between key clinical factors and survival, and examine temporal trends in OHCA survival through the decades.
Two resuscitation rules18,19 for emergency medical services (EMS) personnel have recently been shown to accurately predict which OHCA patients warrant rapid transport to the hospital for further care. These rules use 5 clinical criteria to predict survival from OHCA: arrest witnessed by a bystander, arrest witnessed by EMS, provision of bystander CPR, shockable cardiac rhythm, and return of spontaneous circulation (ROSC) in the field. Recently, 3 independent teams of researchers have validated these decision rules with a misclassification rate of 0.1%.20–22 Despite these findings, the variability of survival by each clinical criterion has not been systematically evaluated across populations. Accordingly, we analyzed 30 years of data on OHCA in a systematic review and meta-analysis, taking into account potential sources of variation such as type of EMS system, baseline survival rates in the region, and location. We also analyzed temporal trends in OHCA survival over this time frame to determine whether knowledge of OHCA pathophysiology and treatment is being effectively translated into improvements in outcome.
WHAT IS KNOWN
•
Two resuscitation rules for emergency medical services (EMS) personnel have recently been shown to accurately predict which out-of-hospital cardiac arrest (OHCA) patients warrant rapid transport to the hospital for further care. These rules use 5 clinical criteria to predict survival from OHCA-arrest witnessed by a bystander, arrest witnessed by EMS, provision of bystander cardiopulmonary resuscitation (CPR), shockable cardiac rhythm, and return of spontaneous circulation (ROSC) in the field. Recently, 3 independent teams of researchers validated these decision rules with a misclassification rate of 0.1%.
•
However, no group has conducted a systematic review to assess, with precision, the associations between these 5 key clinical factors and survival, and examine temporal trends in OHCA survival through the decades.
WHAT THE STUDY ADDS
•
This meta-analysis brings together 30 years of research, involving more than 142 000 patients. Our findings conclusively affirm the value of bystander CPR, the critical importance of “shockable” rhythms, and the predictive value of ROSC in the prehospital setting.
•
Forty percent of patients with OHCA are found with ventricular fibrillation/ventricular tachycardia, yet only 22% achieve ROSC. This group may be a priority population for future efforts to improve ROSC and survival to hospital discharge.
•
The magnitude of effect sizes for the 5 clinical factors, such as provision of bystander CPR and an initial rhythm of ventricular fibrillation/ventricular tachycardia, are higher in communities that have low baseline survival rates. This suggests that efforts such as targeted CPR training to increase bystander CPR rates will have their greatest effect in communities with low baseline rates of survival.
•
Survival from OHCA has not significantly improved in almost 3 decades, despite enormous efforts in research spending and the development of novel drugs and devices. The aggregate survival rate, recorded across various populations, is between 6.7% and 8.4%.
Methods
Data Sources and Searches
A systematic review of the literature was conducted to identify studies that evaluated 5 key factors known to be associated with survival: (1) arrest witnessed by a bystander, (2) arrest witnessed by an EMS provider, (3) provision of bystander cardiopulmonary resuscitation (CPR) before EMS arrival, (4) presenting rhythm (determined by EMS personnel to be ventricular fibrillation/ventricular tachycardia [VF/VT] or asystole), and (5) patient response to prehospital emergency cardiac care with ROSC in the field.
All studies published between January 1, 1950 through August 21, 2008 were considered. The following electronic databases were searched with the assistance of an experienced health services librarian, using a Boolean Search Strategy: PubMed, EMBASE, Web of Science, CINAHL, and all EBM Reviews (includes Cochrane DSR, DARE, ACP Journal Club, and CCTR). The root search was “Heart Arrest”[MeSH] AND (“Cardiopulmonary Resuscitation” [MeSH] OR “Resuscitation Orders”[MeSH]) AND (English[lang] AND (“adolescent”[MeSH Terms] OR “adult”[MeSH Terms:noexp] OR (“middle aged”[MeSH Terms] OR “aged”[MeSH Terms]))). We then added the keywords “Witnessed or Bystander” to the root search with “AND ((witness* OR unwitnessed OR bystander* OR observer* OR observed)) AND ((“Survival”[MeSH] OR “Mortality”[MeSH] OR “mortality”[Subheading] OR “Survival Rate”[MeSH]))” or “Defibrillator or ROSC” with “AND ((“Survival”[MeSH] OR “Mortality”[MeSH] OR “mortality”[Subheading] OR “Survival Rate”[MeSH])) AND ((“Electric Countershock”[MeSH] OR ROSC OR defibrillation OR “Arrhythmias, Cardiac”[MeSH])).” The majority of articles we reviewed were retrieved from PubMed (353 of 909 articles). Only reports published in English were included.
In addition to these automated searchers, we conducted a hand search of bibliographies of key articles4,23–26 and abstracts presented at major scientific conferences in 2006 to 2008. We also contacted 2 national cardiac arrest experts to identify any relevant but unpublished studies.
Study Selection
Two reviewers (C.S. and J.D.) evaluated each full text article and determined exclusions based on a priori criteria. This excluded any study which contained greater than 20% pediatric patients (age <18 years), a majority of events caused by a noncardiac etiology (trauma, drowning, electrocution, respiratory), cases of in-hospital arrest, survival through hospital discharge not reported, use of investigational interventions that were outside the standard of care at the time the study was conducted (eg, hypothermia), use of investigational devices (eg, abdominal compression device), and those that did not report any of the 5 variables of interest.
Using these criteria, the kappa for interrater reliability to be included in the study was 0.71. Disagreements were resolved by discussion. Three authors were contacted to clarify the dates of their study to ensure that we did not inadvertently double-count some patients,27,28 to obtain specific data on a sole survivor of OHCA,2 to clarify certain aspects of a field termination protocol,29 and to obtain more information on survivors.30
Data Extraction and Quality Assessment
The 204 studies that met our preliminary selection criteria were further evaluated using the Newcastle Ottawa Scale for cohort studies. The Newcastle Ottawa Scale has been shown to be useful in rating the quality of observational studies in a standardized format.31 Ultimately, 79 of these 204 studies met an a priori aggregate measure of quality, based on clearly defined patient selection, assessment of exposures and outcome, comparability of groups, and adequacy of follow-up to hospital discharge. Reasons for exclusion included: failure to comparably report outcome data for survivors versus nonsurvivors for at least 1 of the 5 clinical factors of interest (n=84); reporting of duplicate cohorts from the same study (n=18), majority of patients with noncardiac etiologies (n=14), and in-hospital cardiac arrests (n=9).
The following variables were extracted from the 79 studies: number of arrests in the study, total survivors followed to hospital discharge, case attributable to a presumed cardiac etiology, mean age, arrest witnessed by bystander or EMS, provision of bystander CPR, initial rhythm (VF/VT or asystole), achievement of ROSC, and outcome to hospital discharge. Bystander CPR was defined as any attempt at CPR initiated by someone other than the EMS/first responder team regardless of whether the event was witnessed or not. The presenting rhythm was based on the paramedic’s assessment on scene. ROSC was recorded in any study that examined it as a predictor variable for survival to hospital discharge. Studies that used ROSC as an intermediate outcome were not included.
Data Synthesis and Analysis
The denominator for calculating rates of survival to hospital discharge in this meta-analysis was the number of adult patients with OHCA of presumed cardiac etiology for whom resuscitation was attempted in the prehospital setting. Crude (ie, unweighted) survival rates to hospital admission and to hospital discharge were calculated, as were pooled (ie, weighted) survival rates using the DerSimonian and Laird random-effects method.32 In addition, pooled odds ratios for survival to discharge were determined for each clinical criterion (eg, witnessed by bystander, witnessed by EMS, etc) using the random-effects model. Studies that were duplicates of the same patient cohort or involved only public-access defibrillation were not included. To evaluate heterogeneity, Cochran’s Q test and I2, the degree of inconsistency among studies, were calculated. Begg’s test and a visual inspection of the funnel plot were conducted to evaluate publication bias. The number needed to treat was calculated for witnessed events and bystander CPR, based on pooled survival rates to hospital discharge. This represents the number of persons with OHCA in whom an intervention (eg, bystander CPR) would have to be used to save 1 life.
Meta-regression was used to explore the heterogeneity in odds ratios (dependent variable) across studies. A random-effects model was used with estimation of the between-study variance by the restricted maximum likelihood method. Independent variables considered for inclusion were type of EMS system, study design (retrospective versus prospective cohort), mean response interval, mean age, time of follow-up, inclusion of <20% pediatric patients, inclusion of any events of noncardiac etiology, dates of patient inclusion, year of publication, physicians as part of the EMS out-of-hospital team, and baseline survival rates calculated as the survival rate of those OHCA patients without the variable of interest (eg, in the VF/VT meta-analysis, the survival rate for the patients in the sample who did not have a VF/VT arrest). Study location (international versus United States) was also evaluated, as many international EMS systems employ physicians in the prehospital setting and centralize operations.33
Temporal trends in OHCA survival were anticipated because of emerging technologies7,34,35 and refinement of clinical guidelines.25,36,37 Therefore, a meta-regression was conducted by regressing time as the independent variable (ie, final year of patient enrollment in the study) on OHCA survival rates (dependent variable) with a random-effects model with adjustment for location (international versus United States), mean age of the patients, mean response time interval (minutes), and type of EMS service.
As a secondary analysis, the association between baseline survival and differences in survival rates were further evaluated. Weighted multivariate linear regression was performed using 2 outcomes: (1) survival difference between bystander witnessed and bystander unwitnessed events; and (2) survival difference between EMS witnessed and EMS unwitnessed events (n=25 studies). In addition, weighted linear regression was conducted using survival difference for patients in VF/VT versus asystole as the dependent variable (n=40 studies). Weights were generated using the DerSimonian and Laird random-effects model. If there were no survivors in a given study, the LaPlace estimate was used to calculate the weights.38,39
All statistical tests were 2-sided, with α set at 0.05. STATA version 10.0 was used to conduct all analyses.
Results
Search Results
There were 909 citations retrieved from the original search, 631 of which were excluded based on a priori exclusion criteria (Figure 1). Of the 278 articles chosen for full text review, 204 articles met inclusion criteria and were evaluated in detail. Studies were included if they had reported at least one of the five variables that are included in this meta-analysis.2,3,19,27–30,40–109 One article by Valenzuela et al67 contrasted OHCA cases that occurred in Washington State from those that occurred in Arizona, so it was analyzed as 2 separate studies. One study did not specify the total number of survivors, so it was only included in the sensitivity analysis of bystander CPR.30
Figure 1. Flowchart of meta-analysis.
Study Characteristics
Tables 1 and 2 display the study characteristics and variables used in the meta-analysis. All 79 articles were cohort studies. All documented the presence of at least 1 of the 5 variables in both survivors and nonsurvivors, with the primary outcome being survival to hospital discharge. The year of publication ranged from 1984 to 2008. Forty-six studies were conducted outside the United States. Twenty studies had less than 20% of their patients who were below the age of 18 years, whereas the remaining studies included adult patients only. Collectively, the 79 studies reported the outcomes of 142 740 patients.
Table 1. Articles Included in the Meta-Analysis
Author
Year
Location
Meta-Analysis Variable Reported
Study Design
EMS System
Age Mean, y
Response Time Mean, min
Wilson
1984
Durham, NC
CPR, VF/VT, Asys
Prospective cohort
BLS
*
6.5
Smith
1985
Sacremento, CA
VF/VT, Asys
Retrospective cohort
BLS+ALS
*
*
Aprahamanian
1986
Milwaukee, WI
CPR, VF/VT, Asys
Retrospective cohort
BLS+ALS
65
6
Bachman
1986
Arrowhead Cty, MN
CPR
Prospective cohort
BLS+BLS-D+ALS
65.2
6.5
Bonnin
1989
Oakland County, MI
ROSC
Retrospective cohort
BLS+ALS
71
4.7
Becker
1991
Chicago, IL
Wit Bys, Wit EMS
Prospective cohort
ALS
67
8
Brison
1992
Canada
Wit Bys, Wit EMS, CPR
Prospective cohort
BLS+BLS-D
68.1
7.7
Bonnin
1993
Houston, TX
CPR, ROSC
Prospective cohort
BLS+ALS
64.7
10.1
Kellermann
1993
Memphis, TN
Wit Bys, VF/VT, CPR, ROSC
Retrospective cohort
BLS+ALS
64
3.4
Pepe
1993
Houston, TX
Wit Bys, Wit EMS, VF/VT, Asys
Prospective cohort
BLS+ALS
65
5
Richless
1993
Allegheny, PA
VF/VT
Retrospective cohort
BLS+ALS
67.3
7.2
Tresch
1993
Milwaukee, WI
VF/VT
Retrospective cohort
BLS+ALS
78.5
*
Van der Hoeven
1993
Leiden, Netherlands
CPR, VF/VT, Asys
Retrospective cohort
BLS+ALS
61.7
4.89
Kass
1994
York/Adams, PA
Wit Bys, Wit EMS, VF/VT, Asys
Retrospective cohort
BLS+ALS
*
*
Lombardi
1994
NYC, NY
Wit Bys, Wit EMS, CPR
Prospective cohort
BLS-D+ALS
70†
9.9
Schneider
1994
Mainz, Germany
VF/VT, Asys
Prospective cohort
BLS+ALS-P
63.2
5†
Crone
1995
Auckland, New Zealand
Wit EMS, CPR, VF/VT, Asys
Prospective cohort
ALS
65
7
Hodgetts
1995
Salford, Australia
ROSC
Retrospective cohort
BLS-D+ALS
63
8†
Rainer
1995
Glasgow/Edinburgh, Scotland
VF/VT, Asys
Prospective cohort
BLS-D+ALS+ALS-P
63.5
6.5†
Giraud
1996
France
Wit Bys, Wit EMS, VF/VT, Asys
Prospective cohort
BLS-D+ALS-P
20% <14
14†
Killien
1996
San Juan Islands, WA
VF/VT, Asys
Retrospective cohort
BLS+ALS
66
4.5
Kuisma
1996
Helsinki, Finland
Wit Bystander
Prospective cohort
BLS-D+ALS+ALS-P
*
7
Adams
1997
Scotland
Wit Bys, Wit EMS
Retrospective cohort
BLS-D
*
*
Fischer
1997
Bonn, Germany
Wit Bys, Wit EMS, VF/VT, Asys
Retrospective cohort
BLS+ALS-P
54% >65
5.5
Kuisma
1997
Helsinki, Finland
VF/VT, Asystole, CPR
Prospective cohort
BLS-D+ALS+ALS-P
56.7
8.4
Mitchell
1997
Edinburgh, Scotland
Wit EMS
Prospective cohort
BLS-D+ALS
67
7.7
Stapczynski
1997
Kentucky
VF/VT, CPR
Retrospective cohort
BLS-D
66
7.38
Valenzuela
1997
King County, WA
VF/VT
Retrospective cohort
BLS+ALS
64
5.1
Valenzuela
1997
Tucson, AZ
VF/VT
Retrospective cohort
BLS+ALS
66
9.5
De Vreede
1998
Maastricht, Netherlands
VF/VT, CPR
Prospective cohort
ALS
60.3
5.9
Joyce
1998
Salt lake City, UT
VF/VT, Asys
Retrospective cohort
BLS-D+ALS
66.9
4.4
Kette
1998
Fruilli, Italy
Wit Bys, Wit EMS
Prospective cohort
BLS+ALS+ALS-P
*
*
Lindholm
1998
Kansas City, MO
CPR, VF/VT, Asys, ROSC
Retrospective cohort
ALS
67
6.5
Tadel
1998
Slovenia
Wit Bys, Wit EMS, VF/VT, Asys
Retrospective cohort
BLS+ALS-P
*
10†
Waalewijn
1998
Amsterdam, Netherlands
Wit Bys, Wit EMS, CPR, VF/VT, Asys
Prospective cohort
ALS
64
10†
Absalom
1999
Norfolk, United Kingdom
Wit EMS, CPR, ROSC
Retrospective cohort
ALS
68
*
Bottinger
1999
Heidelberg, Germany
Wit Bys, Wit EMS, CPR, VF/VT, Asys
Prospective cohort
BLS+ALS+ALS-P
67
8
(Continued)
Table 1. Continued
Author
Year
Location
Meta-Analysis Variable Reported
Study Design
EMS System
Age Mean, y
Response Time Mean, min
Kuilman
1999
Rotterdam, Netherlands
VF/VT, Asys
Retrospective cohort
ALS-P
64.8
*
Lui
1999
Hong Kong
Wit Bys, Wit EMS, CPR, VF/VT, Asys
Retrospective cohort
BLS-D
68.7
6.42
Stiell
1999
Canada-OPALS 1
CPR, VF/VT, Asys
Prospective cohort
BLS-D
68
6.7
Sunde
1999
Oslo, Norway
Wit Bys, Wit EMS
Prospective cohort
ALS+ALS-P
69.5
7†
Swor
2000
Oakland County, MI
Wit EMS, VF/VT, CPR
Prospective cohort
BLS+ALS
66.5
6.1
Valenzuela
2000
casinos
VF/VT, Asys
Prospective cohort
D at public sites
64
9.8
Finn
2001
Perth, Australia
Wit Bys, Wit EMS
Prospective cohort
BLS-D+ALS
65.1
*
Groh
2001
Indiana
VF/VT, CPR
Prospective cohort
BLS-D+ALS
65.9
6.3
Jennings
2001
Victoria, Australia
VF/VT, Asys
Retrospective cohort
BLS+ALS
68.2
8
Rea
2001
Kings County, WA
CPR
Prospective cohort
BLS-D+ALS
68.7
5.2
Citerio
2002
Lombardia, Italy
VF/VT, Asys
Prospective cohort
BLS+ALS+ALS-P
70.1
8.5
Fan
2002
Hong Kong
VF/VT
Prospective cohort
BLS-D
73†
9†
Lim
2002
Singapore
VF/VT, Asys, ROSC
Retrospective cohort
BLS-D
65.1
11.9
Myerberg
2002
Miami, FL
Wit Bys, VF/VT
Prospective cohort
BLS-D+ALS
68.5
4.88
Smith
2002
Melbourne, Australia
Wit Bys, Wit EMS
Prospective cohort
BLS+BLS-D+ALS
*
8.75
Goto
2003
Akita, Japan
Wit Bys, Wit EMS, VF/VT, Asys
Prospective cohort
BLS-D
63.7
*
Grmec
2003
Slovenia
Wit Bys, VF/VT, Asys
Prospective cohort
BLS-D+ALS
63.9
10.6
Haukoos
2003
Los Angeles, CA
VF/VT, Asys
Retrospective cohort
BLS-D+ALS
70†
*
Nishiuchi
2003
Osaka, Japan
VF/VT
Prospective cohort
BLS-D
67.5
5.9
Ong
2003
Singapore
Wit Bys, Wit EMS, CPR
Prospective cohort
BLS-D
62.2
10.2
Horsted
2004
Copenhagen, Denmark
Wit Bys, Wit EMS, VF/VT, Asys
Prospective cohort
BLS-D+ALS-P
68
5
Rudner
2004
Katowice, Poland
Wit Bys, Wit EMS, CPR, VF/VT, Asys
Prospective cohort
BLS+ALS
63
7
Davies
2005
London, England
VF/VT, Asys
Prospective cohort
D at public sites
63.1
9.1
Handel
2005
Reading, OH
CPR, VF/VT, Asys, ROSC
Retrospective cohort
BLS+ALS
65.3
*
Hayashi
2005
Okayama, Japan
Wit Bys, Wit EMS, VF/VT, Asys
Prospective cohort
BLS-D
67.1
11
White
2005
Rochester, MN
Wit Bys, VF/VT
Prospective cohort
BLS-D+ALS
64.3
6.2
Drezner
2006
Multicenter
VF/VT
Retrospective cohort
D at public sites
21
*
Kellum
2006
Wisconsin
Wit Bys, VF/VT
Prospective cohort
BLS-D+ALS
*
6
Pleskot
2006
East Bohemia, Czech Republic
Wit Bys, CPR, VF/VT, Asys
Prospective cohort
BLS+ALS-P
67
7.4
Davis
2007
San Diego, CA
VF/VT, Asys, ROSC
Prospective cohort
BLS+ALS
66.3
7
Daya
2007
Resuscitation Outcomes Consortium
ROSC
Prospective cohort
BLS-D+ALS
*
*
Dunne
2007
Detroit, MI
Wit Bys, Wit EMS, VF/VT, Asys, ROSC
Retrospective cohort
ALS
63.3
8.36
Estner
2007
Dachau, Germany
Wit Bys, Wit EMS, CPR, VF/VT, Asys
Prospective cohort
BLS+ALS-P
63.9
7.74
Fairbanks
2007
Rochester, NY
Wit Bys, CPR, VF/VT, Asys
Retrospective cohort
BLS-D+ALS
67
5
Herlitz
2007
Sweden
Wit Bys, Wit EMS, VF/VT, CPR
Prospective cohort
BLS-D+ALS
67
6
Hostler
2007
Resuscitation Outcomes Consortium
Wit Bys, Wit EMS, CPR
Prospective cohort
BLS-D+ALS
*
*
(Continued)
Table 1. Continued
Author
Year
Location
Meta-Analysis Variable Reported
Study Design
EMS System
Age Mean, y
Response Time Mean, min
BLS indicates basic life support; ALS, advanced life support; D, defibrillator capable; D at public sites, publicly available defibrillator studies; P, physicians onboard EMS; Wit Bys, witnessed by bystander; Wit EMS, witnessed by EMS; CPR, cardiopulmonary resuscitation; VF/VT, ventricular fibrillation/ventricular tachycardia; Asys, asystole; ROSC, return of spontaneous circulation.
*Not reported in study.
†Median value (age or response time).
Iwami
2007
Osaka, Japan
Wit Bys
Prospective cohort
BLS+BLS-D
69.5
9.2
Jasinskas
2007
Lithuania
VF/VT, Asys
Prospective cohort
ALS-P
67
6
Ma
2007
Taipei, Taiwan
CPR, VF/VT, Asys
Prospective cohort
BLS-D+ALS
68.6
4†
Morrison
2007
Canada-OPALS 3
Wit Bys, Wit EMS, VF/VT, CPR
Prospective cohort
BLS-D+ALS
*
*
Vadeboncoeur
2007
Arizona
CPR
Prospective cohort
BLS+BLS-D+ALS
*
*
Fleischhackl
2008
Austria
VF/VT
Prospective cohort
D at public sites
62.5
*
Table 2. Determination of Study Survival Rates
Author
Year
Total Adult Cardiac Arrests With Resuscitation Attempted
Resuscitation Not Attempted (Includes DNR, Obvious Death)
Survive to Admission
Survive to Discharge
Survival Rate to Hospital Discharge, %
Wilson
1984
126
0
28
11
8.7
Smith
1985
893
0
79
29
3.2
Aprahamanian
1986
319
126
94
42
13.2
Bachman
1986
512
*
24
14
2.7
Bonnin
1989
232
7
56
22
9.5
Becker
1991
3221
*
241
55
1.7
Brison
1992
1510
*
143
38
2.5
Bonnin
1993
1461
0
*
92
6.3†
Kellermann
1993
1068
0
267
85
8.0
Pepe
1993
2404
0
*
193
8.0
Richless
1993
96
0
14
3
3.1
Tresch
1993
196
0
37
10
5.1
Van der Hoeven
1993
257
0
39
6
2.3
Kass
1994
599
0
113
24
4.0§
Lombardi
1994
2329
*
*
52
2.2
Schneider
1994
211
125
50
19
9.0
Crone
1995
1069
0
240
135
12.6
Hodgetts
1995
100
82
*
2
2.0
Rainer
1995
455
0
105
52
11.4
Giraud
1996
113
146
22
8
7.1
Killien
1996
78
2
31
17
21.8
Kuisma
1996
255
68
98
44
17.3
Adams
1997
8651
*
*
612
7.1
Fischer
1997
464
82
185
74
15.9
Kuisma
1997
162
43
45
8
4.9
Mitchell
1997
275
*
*
27
9.8
Stapczynski
1997
311
0
46
19
6.1
Valenzuela
1997
7635
0
*
1086
14.2
Valenzuela
1997
665
0
*
46
6.9
De Vreede
1998
288
350
*
47
16.3
Joyce
1998
322
0
83
26
8.1
Kette
1998
344
*
60
23
6.7
Lindholm
1998
832
0
*
67
8.1
Tadel
1998
337
511
78
19
5.6
Waalewijn
1998
1046
400
165
134
12.8
Absalom
1999
260
0
59
26
10.0
Bottinger
1999
338
243
129
48
14.2
Kuilman
1999
898
0
441
276
30.7
Lui
1999
744
0
89
12
1.6
Stiell
1999
5335
0
366
197
3.7
Sunde
1999
326
573
96
30
9.2
Swor
2000
2608
108
538
189
7.2
Valenzuela
2000
148
0
71
56
37.8†
Finn
2001
1293
*
*
85
6.6‡
Groh
2001
388
0
61
21
5.4
Jennings
2001
115
96
22
6
5.2
Rea
2001
7265
*
*
1112
15.3
(Continued)
Table 2. Continued
Author
Year
Total Adult Cardiac Arrests With Resuscitation Attempted
Resuscitation Not Attempted (Includes DNR, Obvious Death)
Survive to Admission
Survive to Discharge
Survival Rate to Hospital Discharge, %
Survival Rate to hospital admission and discharge is for all presenting rhythms.
*Not reported in study.
†Not included in overall survival rate.
‡Survival at 1-month reported.
§Survival at 1-year reported.
Citerio
2002
178
0
*
10
5.6‡
Fan
2002
320
82
*
4
1.3
Lim
2002
93
0
15
1
1.1
Myerberg
2002
738
0
*
51
6.9
Smith
2002
436
778
82
35
8.0
Goto
2003
203
227
*
20
9.9
Grmec
2003
216
*
128
44
20.4
Haukoos
2003
575
0
*
25
4.3
Nishiuchi
2003
974
176
236
50
5.1‡
Ong
2003
351
*
30
7
2.0
Horsted
2004
219
233
82
25
11.4
Rudner
2004
147
150
43
15
10.2
Davies
2005
172
4
*
39
22.7
Handel
2005
84
79
26
12
14.3‡
Hayashi
2005
179
0
*
2
1.1
White
2005
326
0
158
85
26.1
Drezner
2006
9
0
*
1
11.1†
Kellum
2006
358
169
*
39
10.9
Pleskot
2006
560
144
149
53
9.5
Davis
2007
1095
46
197
47
4.3
Daya
2007
7478
6052
*
568
7.6†
Dunne
2007
471
51
28
1
0.2‡
Estner
2007
412
277
180
47
11.4
Fairbanks
2007
539
277
*
27
5.0§
Herlitz
2007
38 413
*
*
2114
5.5‡
Hostler
2007
9886
*
*
727
7.4
Iwami
2007
12 437
*
*
433
3.5§
Jasinskas
2007
62
10
11
*
*
Ma
2007
1423
86
242
80
5.6
Morrison
2007
4673
40
671
239
5.1
Vadeboncoeur
2007
1097
*
*
*
*
Fleischhackl
2008
62
*
*
17
27†
The overall crude survival rate to hospital discharge in all the studies was 7.1% (10 017 survivors of 141 581 cases of OHCA). One study was not included because the total number of survivors was not reported.30 The pooled rate of survival to hospital discharge in these studies was 7.6% (95% CI, 6.7 to 8.4). Of those studies that reported survival to hospital admission (n=49), the overall crude rate was 17.6%. The pooled survival to hospital admission rate was 23.4% (95% CI, 20.7 to 26.1).
Survival rates to hospital discharge, over 5-year time periods, are illustrated in Figure 2. There was no significant difference in survival rates over time (P=0.152) after adjustment for location (international versus United States), mean age of the patients, mean response interval, and type of EMS.
Figure 2. OHCA survival to hospital discharge by 5-year time periods (based upon final year of patient enrollment into study).
The results for each of the 5 clinical criteria are presented in the same manner (Figures 3 through 8). The studies were stratified into quintiles (tertiles for ROSC) based on the baseline survival rate. The vertical line marks the aggregate measure of the odds ratios across all studies.
Figure 3. Forest plot of studies reporting witnessed by bystander stratified by baseline survival.
Witnessed by Bystander
Thirty-six studies contained sufficient data to assess the association of an OHCA witnessed by a bystander (Figure 3). Collectively, these studies reported the outcomes of 95 539 cases. In these studies, the crude rate of survival to hospital discharge was 7.6% (7214 survivors). The pooled odds ratio for surviving to hospital discharge if a bystander witnessed the arrest (compared to unwitnessed events) ranged from 0.34 (95% CI, 0.07 to 1.66) among those with the highest baseline survival rates to 4.42 (95% CI, 1.81 to 10.80) in studies with the lowest baseline rates.
Witnessed by EMS
Thirty articles reported sufficient data to assess the association between OHCA being witnessed by EMS personnel and survival (Figure 4). In total, these studies reported on the outcomes of 83 229 cases, with a crude overall survival rate to hospital discharge rate of 6.1% (5056 survivors). The pooled odds ratio for survival among OHCA patients witnessed by EMS compared to all other arrests, ranged from 1.65 (95% CI, 0.63 to 4.34) in those with the highest baseline rates to 6.04 (95% CI, 4.12 to 8.85) in the studies with the lowest baseline rates of survival.
Figure 4. Forest plot of studies reporting witnessed by EMS stratified by baseline survival.
Bystander CPR
Odds ratios for the association between bystander CPR and survival are given in Figure 5 (n=32 studies). Collectively, these studies reported on the outcomes of 76 485 cases. In studies reporting overall rates of survival to hospital discharge, the crude rate was 6.7% (5094 survivors out of 75 388 patients). The pooled odds ratio for survival among patients receiving bystander CPR compared with those who did not ranged from 1.23 (95% CI, 0.71 to 2.11) in the studies with the highest baseline survival rates to 5.01 (95% CI, 2.57 to 9.78) in the studies with the lowest baseline rates. One study30 was not included in the overall pooled odds ratio for bystander CPR because no information was provided on the community’s baseline survival percentage.
Figure 5. Forest plot of studies reporting bystander CPR stratified by baseline survival.
The reporting of bystander CPR differed among studies. Because a patient who arrested in the presence of EMS personnel was never “eligible” to receive bystander CPR, we stratified studies by whether the arrest was witnessed by EMS. For the 19 studies that did not include EMS witnessed arrests in the total, the odds ratio for bystander CPR was 2.44 (95% CI, 1.69 to 3.19). This compared with an odds ratio of 1.69 (95% CI, 1.10 to 2.28) for studies in which all arrests, including EMS witnessed arrests, were included.
Ventricular Fibrillation/Ventricular Tachycardia
Fifty-eight studies contained sufficient data to assess the association between VF/VT as the presenting cardiac rhythm and OHCA survival (Figure 6). Outcomes were reported in 82 854 cases, with an overall crude survival rate to hospital discharge in these studies of 7.2% (5972 survivors). The pooled odds ratio for survival to hospital discharge among patients found in VF/VT compared to those found in all other rhythms ranged from 2.91 (95% CI, 1.10 to 7.66) in the studies with the highest baseline rates of survival to 20.62 (95% CI, 12.61 to 33.72) in the studies with the lowest baseline survival.
Figure 6. Forest plot of studies reporting ventricular fibrillation/tachycardia stratified by baseline survival.
Asystole
Odds ratios for the relationship between asystole as the presenting cardiac rhythm and OHCA survival are shown in Figure 7 (n=40 studies). In total, outcomes were reported on 23 202 cases, with an overall crude survival rate in these studies of 8.1% (1870 survivors). The pooled odds ratio for survival to hospital discharge among those patients found in asystole compared with those patients found in all other cardiac rhythms ranged from 0.10 (95% CI, 0.03 to 0.31) in the studies with the lowest baseline rates of survival to 0.15 (95% CI, 0.09 to 0.25) in studies with the highest baseline rates.
Figure 7. Forest plot of studies reporting asystole stratified by baseline survival.
Return of Spontaneous Circulation
Twelve studies reported data on the relationship between achieving prehospital ROSC and survival to hospital discharge (Figure 8). These studies reported the outcomes of 17 697 patients. Overall, the crude rate of survival to hospital discharge in these studies was 6.6% (1,162 survivors). The pooled odds ratio for survival to hospital discharge among patients who achieved ROSC in the field (compared to those who did not) ranged from 20.96 (95% CI, 7.43 to 59.13) in those with the highest baseline survival rates to 99.84 (95% CI, 14.30 to 696.89) in the studies with the lowest baseline rates of survival.
Figure 8. Forest plot of studies reporting return of spontaneous circulation stratified by baseline survival.
Study-specific odds ratios for ROSC were considerably elevated above the null in all strata; no point estimate was less than 8.49. Three of the 12 studies required ROSC to be “sustained” (patient had a pulse on leaving the scene of the OHCA). The other 9 considered any restoration of a palpable pulse, no matter how transient, to represent ROSC. One study did not document whether ROSC occurred in the prehospital setting versus in the emergency department.20 The others defined ROSC as occurring before transport from the scene.
Excluding the one study20 that did not limit ROSC to the prehospital setting reduced the subgroup OR (lowest baseline survival) from 99.84 (95% CI 14.30 to 696.89) to 35.29 (95% CI, 5.54 to 224.94). The overall pooled survival rate (absolute risk) of all subjects included in this analysis decreased from 15.5% (95% CI 0.0 to 33.3) to 5.1% (95% CI, 0.0 to 12.9) following exclusion of this study.
Number Needed to Treat to Save One Life
Survival rates to hospital discharge are listed by each of the 5 main clinical criteria in Table 3. The results indicate that 53% of all OHCA cases were witnessed by a bystander, 10% were witnessed by EMS, and 36% were unwitnessed. In addition, 32% of patients received bystander CPR, 40% were found in VF/VT arrest, 42% were found in asystole, and 22% achieved ROSC in the prehospital setting. Reported rates of survival to hospital discharge ranged from 0.1% to 33.6% across these groups, depending on the baseline survival rate (Table 3). The strongest predictor of survival to hospital discharge was ROSC in the field. In this group as many as 1 in 3 survived.
Table 3. Survival Rates and Number Needed to Treat by Clinical Criteria
Variable
Pooled Percentage of Cardiac Arrests With Attribute
Low Baseline Survival
High Baseline Survival
Pooled Survival Rate, %
NNT
Pooled Survival Rate, %
NNT
NNT indicates number needed to treat to save 1 life.
Witnessed by bystander
53% (45.0–59.9)
6.4 (3.5–9.3)
17
13.5 (5.6–21.5)
71
Witnessed by EMS
10% (8.0–11.3)
4.9 (1.3–8.4)
23
18.2 (3.7–32.8)
16
Not witnessed
36% (30.4–40.8)
0.5 (0.2–0.9)
12.1 (7.5–16.7)
Bystander CPR
32% (26.7–37.8)
3.9 (1.8–6.0)
36
16.1 (11.5–20.7)
24
No bystander CPR
68% (62.6–74.8)
1.1 (0.5–1.8)
12.0 (10.0–14.0)
Ventricular fibrillation/tachycardia
40% (36.6–43.3)
14.8 (9.4–20.2)
23.0 (13.8–32.2)
No ventricular fibrillation/tachycardia
60% (56.2–62.9)
0.4 (0.2–0.6)
7.4 (6.1–8.7)
Asystole
42% (36.0–46.8)
0.2 (0–0.3)
4.7 (1.0–8.4)
No asystole
58% (52.9–63.8)
4.4 (2.1–6.6)
30.1 (23.8–36.4)
Return of spontaneous circulation
22% (17.7–25.5)
15.5 (0.0–33.3)
33.6 (24.9–42.2)
No return of spontaneous circulation
78% (74.5–82.3)
0.1 (0.0–0.2)
1.8 (1.5–2.1)
The number needed to treat (NNT) to save one life is also shown in Table 3. The data indicate that 17 persons experiencing OHCA would need to be witnessed by a bystander to save the life of one person in those areas where baseline survival rates were low. The corresponding NNT for areas with high baseline survival was 71. For regions in which baseline survival rates were high, 16 persons with OHCA would need to be witnessed by EMS to save the life of one person and in locations where baseline survival rates are low, 23 persons with OHCA would require an EMS witnessed event to save the life of one person. For bystander CPR, the NNT was 24 in areas with high baseline survival rates and 36 in areas with low rates.
Regression Analyses
Meta-regression analyses were conducted to assess predictors of heterogeneity among odds ratios. The only factor that significantly explained the heterogeneity in odds ratios for all 5 clinical criteria was baseline survival rate and therefore, analyses were stratified by this variable. In addition, the results of the weighted multivariate linear regression indicated that baseline survival significantly explained differences in survival rates. For example, as the baseline survival rate increased, the difference in survival between bystander-witnessed and unwitnessed arrests decreased (β coefficient=−0.7617; P=0.023).
The type of EMS system significantly explained heterogeneity in the odds ratio for VF/VT (P<0.05); the largest pooled OR was evident at those locations in which a defibrillator was available at public sites (OR=12.5) and the smallest pooled OR was at sites in which both basic and advanced life support were available (OR=5.1). The type of EMS system also significantly explained the heterogeneity in odds ratio for asystole; locations with basic life support only and locations with public access defibrillation yielded the greatest reduction in the odds ratios (P<0.05). Variation in the odds ratios could also be significantly explained by differences in case mix (ie, some studies included arrests of all etiologies) and length of follow-up (ie, some studies reported survival 1 month postevent). Mean response interval was a significant predictor of heterogeneity for arrests that were witnessed by EMS (P<0.05); for those locations in which the mean response time interval was less than 8 minutes, the pooled OR was 5.9, it was 2.4 in locations with a mean response time interval of 8 minutes or longer.
Sensitivity Analyses
We limited our analyses to adult cardiac arrest patients for whom resuscitation was attempted in the prehospital setting. Because having a consistent denominator (ie, total number of resuscitations attempted in the prehospital setting) was important, we conducted a sensitivity analysis that excluded four studies that described patients who sustained OHCA but failed to include information on patients who were treated but not transported to the emergency department.29,51,57,86 Excluding these articles did not appreciably change our results. For example, the pooled odds ratio for VF/VT changed from 20.62 (95% CI, 12.61 to 33.72) to 22.69 (95% CI, 13.54 to 38.87) in the lowest baseline survival group, and from 2.91 (95% CI, 1.10 to 7.66) to 2.91 (95% CI, 1.10 to 7.67) in the highest baseline survival group.
In further sensitivity analyses, studies that contained elements which deviated from other studies were excluded. Four studies limited their analysis to OHCA cases that were not witnessed by EMS providers78,97,99,103; 6 studies reported survival at 1 month rather than at hospital discharge2,81,85,90,95,108; 3 studies reported survival 1 year post OHCA52,103,105; and 2 studies grouped pulseless electric activity and asystole together.55,95 Excluding these studies did not appreciably alter our final pooled results.
Publication Bias
The Begg’s test for publication bias was conducted. For all 5 criteria of interest, the Begg test was not significant (P>0.05). Visual inspection of funnel plots did not suggest publication bias.
Discussion
Survival from OHCA has not significantly improved in almost 30 years. The aggregate survival rate, recorded across various populations, is between 6.7% and 8.4%. This lack of progress, despite enormous efforts in research spending, the introduction of novel drugs and devices, and periodic evidence-based revisions to clinical guidelines may be attributable, in part, to the offsetting influence of declining incidence of ventricular fibrillation arrests,110–112 increasing age of the population,113 and longer EMS response time intervals attributable to urbanization and population growth.114 Breaking this barrier to achieve decisive improvements in OHCA survival represents a challenging and worthwhile goal for emergency cardiac care.
Recognizing the importance of several clinical predictors of OHCA survival may help communities and research scientists focus their efforts to achieve this goal. We found that OHCA victims who receive CPR from a bystander or an EMS provider, and those who are found in VF or VT, are much more likely to survive than those who do not. Moreover, we found that the strength of association between VF/VT and survival was greatest in locations in which a defibrillator is available at public sites. To put these observations in context, approximately 1 of every 4 to 7 patients with a presenting rhythm of VF/VT survive to hospital discharge, compared to only 1 of every 21 to 500 patients found in asystole. Because prompt provision of CPR delays the degradation of tachyarrythmias to asystole, this may explain why bystander CPR and prehospital defibrillation have such a positive impact on survival.115
By far the most powerful criterion associated with survival from OHCA is ROSC in the field. The odds of survival ranged from 50% in communities where baseline survival rates are high to 20% (1 in 5) in areas were baseline survival is low. Failure to restore a pulse on scene indicates that the patient will not likely survive to hospital discharge, irrespective of the subsequent sophistication of in-hospital care. This finding strongly suggests that future efforts to boost OHCA survival should focus on optimizing provision of prehospital emergency cardiac care.116,117 It is noteworthy that 40% of patients with OHCA were found with VF/VT, yet only 22% achieved ROSC. This group may be a priority population for future efforts to improve ROSC and survival to hospital discharge.
Although our analysis focused on 5 key variables, we examined several potentially confounding factors (eg, type of EMS system, United States versus international study, mean response time interval) to determine whether they introduced an unacceptable degree of heterogeneity to the main estimates of effect. The only external factor that was consistently significant across the 5 clinical factors was the baseline performance of the community’s EMS system. In systems with lower baseline survival rates, the magnitude of effect sizes for the 5 clinical factors such as provision of bystander CPR and an initial rhythm of VF/VT, were higher than in communities that had high baseline survival rates. This suggests that efforts such as targeted CPR training to increase bystander CPR rates will have their greatest effect in communities with low baseline rates of survival. A corollary hypothesis is that the return on investment for focusing on these characteristics may diminish as the overall performance of a community’s EMS system improves. It is important to note, however, that certain factors, most notably VF/VT arrest and ROSC, were significantly associated with OHCA survival in even the highest-performing EMS systems.
Some of the remaining heterogeneity between studies may be attributable to the highly variable nature of EMS systems in the United States and worldwide.118 For example, many EMS agencies use locally-created protocols to determine whether and when to cease efforts if an OHCA patient does not respond to prehospital advanced cardiac life support.119 Some communities provide their first responders with Basic Life Support training and an automated external defibrillator, whereas others rely on paramedics trained to provide Advanced Life Support. A few U.S. systems and many foreign countries routinely employ nurses or physicians in prehospital settings.120 It is not clear whether different approaches to provider training affect survival rates from OHCA.4,121
Our study is limited in certain respects. Because individual-level patient data were not reported for each study, we could not adequately assess all patient characteristics and potential confounding factors which may influence survival. The studies in our meta-analysis did not contain enough data to simultaneously evaluate the effect of all 5 key criterion, so combined effects could not be assessed.
Despite our effort to apply quality criteria, it is possible that the reporting of predictor and outcome variables was inconsistent in some studies. The Utstein guidelines, designed by EMS leaders in 1991 and subsequently revised in 1996 and 2002, created a standardized approach to data collection.120,122,123 Research has shown that even in the era of Utstein-guided reporting of OHCA care and outcomes, marked variations in survival from one community to the next persist.124 This variability probably reflects persistent differences in approach. For example, although 57 of the 79 studies included in our meta-analysis were published after 1996, some articles did not consistently report the length of prehospital resuscitation intervals (ie, call to ambulance response time and first defibrillation), the range of pharmaceutical interventions, the training level of EMS providers, the duration of resuscitation efforts, or policies permitting termination of unsuccessful resuscitations in the field. We chose not to report our findings using the Utstein definition of survival (witnessed VF arrest surviving to hospital discharge), as this has been summarized in previous studies.72,124,125
We did not include studies that assessed investigational devices or emerging therapies that were outside the standard of care at the time these studies were conducted. Pulseless electric activity (or idioventricular rhythm) was not included in the meta-analysis, because the definitions applied to this type of rhythm were highly nonuniform across studies. And, although the articles included in our meta-analysis were limited to English publications, the information was gathered from 26 countries and represents a variety of populations and EMS systems. Finally, our analysis was restricted to studies with primarily adult patients. Cardiac arrest in pediatric populations differs in fundamental ways from OHCA in adults.
Although the overall rate of OHCA survival has not improved, the field of cardiac and cerebral resuscitation is rapidly evolving. Most of the studies incorporated in our meta-analysis were conducted before the advent of therapeutic hypothermia. This treatment has been shown to benefit resuscitated patients.7,34,35 Patients treated under the recently revised AHA guidelines for CPR, which emphasize rapid compressions and deemphasize ventilation, could not be distinguished from earlier studies included in the meta-analysis.36 However, there is hope that these recent changes in technique and emphasis will improve outcomes.126–129 Future studies will need to take such changes into account to assess their impact on survival.
This meta-analysis brings together almost 30 years of research, involving more than 142 000 patients. Our findings conclusively affirm the value of bystander CPR, the critical importance of “shockable” rhythms, and the predictive value of ROSC in the field. Focused strategies designed to boost rates of bystander CPR, deliver earlier defibrillation, and achieve ROSC before transport are likely to do more to improve aggregate rates of OHCA survival than interventions applied later in a patient’s treatment. Currently, 92% of individuals who experience OHCA each year do not survive to hospital discharge. This dismal statistic can be improved.
Acknowledgments
Dr Sasson is primary author of the manuscript and had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We thank Dr Bryan McNally and Dr Robert Swor for their assistance with the expert review, and the Robert Wood Johnson Clinical Scholars Program, Dr Sandeep Vijan, Dr Rodney Hayward, Dr Sanjay Saint, Preet Rana, and Dr Catherine Marco for their assistance.
Disclosures
None.
Footnote
Presented at the Society of Academic Emergency Medicine Meeting, May 2008, and the American College of Emergency Physicians Meeting, October 2008.
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Received June 25, 2009; accepted September 1, 2009.
Authors
Affiliations
ComillaSasson, MD, MS
From the Departments of Emergency Medicine (C.S.) and Internal Medicine (M.A.M.R.), University of Michigan, Ann Arbor; the University of Rochester (J.D.), NY; and the Department of Emergency Medicine (A.L.K.), Emory University, Atlanta, Ga.
From the Departments of Emergency Medicine (C.S.) and Internal Medicine (M.A.M.R.), University of Michigan, Ann Arbor; the University of Rochester (J.D.), NY; and the Department of Emergency Medicine (A.L.K.), Emory University, Atlanta, Ga.
From the Departments of Emergency Medicine (C.S.) and Internal Medicine (M.A.M.R.), University of Michigan, Ann Arbor; the University of Rochester (J.D.), NY; and the Department of Emergency Medicine (A.L.K.), Emory University, Atlanta, Ga.
From the Departments of Emergency Medicine (C.S.) and Internal Medicine (M.A.M.R.), University of Michigan, Ann Arbor; the University of Rochester (J.D.), NY; and the Department of Emergency Medicine (A.L.K.), Emory University, Atlanta, Ga.
Correspondence to Comilla Sasson, MD, MS, Robert Wood Johnson Clinical Scholars Program, 1150 W Medical Center Dr, 6312 Medical Science Building 1, Campus Box 5604. Ann Arbor, MI 48109. E-mail [email protected]
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eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.
Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.