Series
Out-of-hospital cardiac arrest 1
Lancet 2018; 391: 970–79
This is the first in a Series of
three papers about
out-of-hospital cardiac arrest
Sussex Cardiac Centre, Brighton
and Sussex University
Hospitals NHS Trust, Brighton,
UK (A Myat MD); Division of
Clinical and Experimental
Medicine, Brighton and Sussex
Medical School, Brighton, UK
(A Myat); Department of
Emergency Medicine, Seoul
National University College of
Medicine and Hospital, Seoul,
South Korea (K-J Song PhD);
Laboratory of Emergency
Medical Services, Seoul
National University Hospital
Biomedical Research Institute,
South Korea (K-J Song); and
Division of General Internal
Medicine, Harborview Medical
Centre, University of
Washington, Seattle, WA, USA
(Prof T Rea MD)
Correspondence to:
Dr Aung Myat, Sussex Cardiac
Centre, Brighton and Sussex
University Hospitals NHS Trust,
Brighton BN2 5BE, UK
aung.myat@bsuh.nhs.uk
970 www.thelancet.com Vol 391 March 10, 2018
Out-of-hospital cardiac arrest: current concepts
Aung Myat, Kyoung-Jun Song, Thomas Rea
Out-of-hospital cardiac arrest (OHCA) is a leading cause of global mortality. Regional variations in reporting
frameworks and survival mean the exact burden of OHCA to public health is unknown. Nevertheless, overall prognosis
and neurological outcome are relatively poor following OHCA and have remained almost static for the past three
decades. In this Series paper, we explore the aetiology of OHCA. Coronary artery disease remains the predominant
cause, but there is a diverse range of other potential cardiac and non-cardiac causes to be aware of. Additionally, we
describe how investigators and key stakeholders in resuscitation science have formulated specific Utstein data element
domains in an attempt to standardise the definitions and outcomes reported in OHCA research so that management
pathways can be improved. Finally, we identify the predictors of survival after OHCA and what primary and secondary
prevention strategies can be instigated to mitigate the devastating sequelae of this growing public health issue.
Introduction incidence estimates according to person-years of
Out-of-hospital cardiac arrest (OHCA) is a leading cause EMS-treated OHCA are 34·4 in Europe, 53·1 in North
of mortality worldwide.1,2 It is defined as the loss of America, 59·4 in Asia, and 49·7 in Australia. Of these
functional cardiac mechanical activity in association with estimates, the percentage survival to discharge was
an absence of systemic circulation, occurring outside of a 7·6% in Europe, 6·8% in North America, 3·0% in Asia,
hospital setting. The exact burden of OHCA to public and 9·7% in Australia.2
health is unknown since a considerable number of cases These data not only serve to highlight the extensive
are not attended by emergency medical services (EMS) geographical variation in the incidence of OHCA but also
and regional variations are prevalent in both reporting the very poor outcomes that have remained mostly static
systems and survival.3–5 It is estimated that 275 000 people in the past three decades.1–4 However, some cities have
in Europe have all-rhythm cardiac arrest treated by EMS achieved survival in the region of 20–40%.9,10 This
per year, with only 29 000 of those surviving to hospital difference in survival can partly be attributed to varying
discharge.6 In England, 28 729 EMS-treated OHCA cases definitions of OHCA,2 but it is primarily due to a
were reported in 2014 (ie, 53 cases per 100 000 of the coordinated effort to optimise the effectiveness of the local
resident population) with only 7·9% surviving to hospital chain of survival.11 By identifying and thereafter improving
discharge.7 In the USA, reports from 35 communities weak links in the local chain of survival, positive outcomes
suggested an incidence of 55 per 100  000 person- have been achieved in several locations.9,12–14
years.8 This incidence would equate to approximately In this review, the first of a three-part Series, we look at
155 000 individuals having an EMS-treated all-rhythm the causes of OHCA. Additionally, we look at how
OHCA per year in the USA.8 Globally, the weighted researchers and key stakeholders in resuscitation science
have attempted to standardise the definitions and
outcomes reported in OHCA research at an international
Search strategy and selection criteria level to better delineate how management pathways can
We searched the Cochrane Library, MEDLINE, PubMed, and be enhanced. Finally, we describe the predictors of
Embase for articles published in English only using a survival after OHCA and what primary and secondary
combination of the search terms “out-of-hospital cardiac prevention strategies can be instigated to mitigate the
arrest”, “sudden cardiac death”, “Utstein”, “bystander devastating sequelae of this growing public health issue.
cardiopulmonary resuscitation”, “dispatcher-assisted
cardiopulmonary resuscitation”, “emergency medical Causes of OHCA
services”, “automated external defibrillator”, “ST-segment The causes of OHCA can be broadly categorised into
elevation”, “chain of survival”, “layperson”, “socio-economic cardiac and non-cardiac causes (panel 1).7,15,16 Most people
status”, “Charlson Comorbidity Index”, “shockable rhythm”, reached by an EMS crew, and in whom resuscitation is
and “cardiac resuscitation centre”. We selected publications considered possible, have a cardiac cause.16 On post-
in the past 10 years, but did not exclude commonly mortem examination of 100 patients who died from
referenced and highly regarded older publications. We also sudden cardiac ischaemia, the investigators showed that
searched the reference lists of articles identified by this 74 cases had coronary thrombus.17 In the 26 patients that
search strategy and selected those we judged relevant. did not have evidence of an intraluminal thrombus,
Review articles and online resources are cited to provide 21 had evidence of plaque fissuring. Similarly, Farb and
readers with more details and references. colleagues18 found acute changes in coronary plaque
morphology (thrombus, plaque disruption, or both) in
 Series

51 of 90 hearts examined following sudden cardiac death.

In a landmark angiographic study, more than 70% of Panel 1: Recognised causes of out-of-hospital cardiac arrest
84 consecutive survivors of OHCA had clinically Cardiac causes
significant coronary artery disease shown on their • Ischaemic heart disease
immediate coronary angiography.19 Nearly 50% of the • Acute myocardial infarction
cohort was also found to have coronary artery occlusion. • Non-atherosclerotic disease of the coronary arteries
Of note, features such as chest pain or ST-segment • Lethal arrhythmia without ischaemic heart disease
elevation were shown to be poor predictors of coronary • Wolff-Parkinson-White syndrome
occlusion. In patients with no obvious non-cardiac cause • Long QT syndrome
of OHCA, a study showed at least one significant coronary • Brugada syndrome
artery lesion in 70% of patients, 96% with ST-segment • Catecholaminergic polymorphic ventricular tachycardia
elevation on their electrocardiograph and 58% without • Cardiomyopathy
ST-segment elevation.20 A retrospective single-centre • Acute on chronic heart failure
study of 72 consecutive survivors of OHCA also found • Acute heart failure secondary to valvular heart disease
64% of survivors had angiographic evidence of coronary • Myocarditis
artery disease (≥one lesion with >50% stenosis).21 Only • Dilated cardiomyopathy
38%, however, had angiographic and clinical evidence • Left ventricular non-compaction cardiomyopathy
of an acute coronary syndrome due to either an acute • Hypertrophic cardiomyopathy
occlusion (17%) or an irregular lesion suggestive of • Arrhythmogenic right ventricular cardiomyopathy
ruptured plaque or thrombus (25%).21 These findings • Other infiltrative or inflammatory myocardial disease,
emphasise the difficulty in identifying patients with or both
ongoing myocardial ischaemia in the setting of OHCA. • Valvular heart disease
An excess of circulating catecholamines, electrolyte • Congenital heart disease
derangement, hypothermia, and brain injury can all • Presumed cardiac origin (unknown or unobtainable cause)
cause ST-segment deviation, making a definitive
diagnosis of acute myocardial infarction problematic. Non-cardiac causes
The evidence would suggest OHCA of a presumed • Trauma
cardiac origin is usually triggered by coronary plaque • Malignancy
rupture (leading to acute occlusion) or fissuring, • Non-traumatic bleeding
fragmentation, and embolisation of thrombus.18 Up to • Gastrointestinal
80% of individuals who have sudden cardiac death • Gynaecological
have coronary heart disease, the prevalence for both • Cerebrovascular
increasing with age and being more common in men • Acute aortic dissection
than in women.22 In an analysis7 of the OHCA Outcomes • Asphyxia
Project in England (a prospective registry structured and • Submersion (near drowning)
maintained in accordance with the Utstein guideline • Hanging
for resuscitation registries), the investigators reported that • Hypoxia
80% of cases were due to a cardiac cause. The caveat being • Pneumonia
all cases reported as unknown (13%) or unobtainable (5%) • Asthma or chronic obstructive pulmonary disease
were also presumed to have a cardiac origin. • Carbon monoxide poisoning
The consequences of OHCA can be devastating. The • Pulmonary embolism
aftermath of such life-changing events is brought into • Drug overdose
sharper focus if the patient with OHCA was a seemingly • Hypoglycaemia
fit and healthy athlete, young adult, or child. The • Hypothermia
incidence of sudden cardiac death in athletes can range • Epilepsy
from one in 23 000 to one in 200 000 athletes per year, • Septic shock
depending on the methods used to identify cases, • Dehydration and malnutrition
inclusion and exclusion criteria, and what populations are The causes are not listed in order of frequency and the list is not intended to be
being studied.23 In a retrospective analysis of the Rescu exhaustive.
Epistry database of consecutive OHCA attended by EMS
in a specific area of Ontario, Canada, investigators found
the incidence of sudden cardiac death during participation between 35 and 45 years, coronary artery disease was the
in competitive sports to be 0·76 cases per 100 000 athlete- most frequent underlying pathology.24 In a similar but
years.24 The principal causes of sudden cardiac death in prospective study25 of children and young adults aged
this population were stratified by age group. In those 1–35 years, 490 cases of sudden cardiac death were
younger than 35 years, structural heart and primary identified from centres in Australia and New Zealand.
arrhythmic causes were most common. In those aged The cause of death was unexplained in 40% of these cases

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at autopsy, in whom a structurally normal heart was

Utstein domains • Population served
• System description
• Cardiac arrests attended
• Resuscitation attempted
• Resuscitation not attempted
System
• Resuscitation algorithms followed
• Do not attempt resuscitation legislation
• Termination of resuscitation rules
• Prehospital ECG activity
• Dispatch software
• Data quality activities
Dispatch • Dispatcher-identified cardiac arrest
• Dispatcher CPR instructions
• Age
• Sex
• Cause
• Location
• Witnessed cardiac arrest
• Bystander CPR or use of automated external
defribillator
• First monitored cardiac rhythm
Patient
• Comorbidities
• Independent living
For more on the Cardiac Risk • ST-segment elevation on ECG
in the Young charity see • Implantable cardioverter defibrillator
https://www.c-r-y.org.uk
• Ventricular assist device
found.25 In this study, the annual incidence of sudden
cardiac death was calculated to be 1·3 cases per
100 000 people. When stratified according to age group,
the highest incidence (3·2 cases per 100 000 people per
year) was found in the category of those aged 31–35 years.
Again, coronary artery disease was the most common
cause discovered here. Younger age and sudden cardiac
death occurring at night were independently associated
with unexplained sudden cardiac death. Less common
causes were inherited cardiomyopathies (eg, dilated,
hypertrophic, and arrhythmogenic right ventricular),
myocarditis, and aortic dissection.
Sudden cardiac death in athletes, young adults, and
children can be regarded as relatively uncommon but it
is incumbent on those managing young survivors of
OHCA to be mindful of the causes prevalent in these
particular groups. Indeed, there is widespread consensus,
including recommendations from the American Heart
Association and European Society of Cardiology, that
young athletes should have cardiovascular screening
before participation in competitive sports. A more
detailed synopsis of sudden cardiac death in the young
and non-cardiac causes of OHCA is beyond the scope of
this review; we recommend the work done by the Cardiac
Risk in the Young charity in the UK for further reading.

Progress in resuscitation outcomes with the Utstein

• Response time framework
• Defibrillation time
• Pharmacotherapy Although prevention is a key strategy in the drive to
• Targeted temperature management reduce the incidence of OHCA, many events occur among
• Coronary reperfusion attempted
those without clinical heart disease or warning symptoms,
making prevention an incomplete strategy to address this
Process • Airway control growing public health challenge. Therefore, initiatives
• Number of shocks administered aimed at optimising the quality and performance of
• Timing of drugs
• Quality of CPR resuscitation provide a complimentary and necessary
• Manual versus automated CPR pathway to reduce overall mortality.
• Targeted oxygenation and ventilation therapy
• pH, lactate, and glucose
The continual evolution of resuscitation science is
• ECG regularly captured within clinical guidelines through an
• Blood pressure control: ECMO or IABP evidence-based process involving international experts.26
• Hospital type or volume, or both
• Neuro-prognostication The science indicates that a successful resuscitation
attempt requires a coordinated team of rescuers that
include laypeople, emergency dispatchers, first responders,
• A return of spontaneous circulation
• Survival to discharge
EMS, and hospital providers. For the best chances of
• Survival at 30 days survival, the team must deploy a time-sensitive series of
• Cerebral performance category therapies. Derived from scientific understanding, these
therapies are described by the metaphor of “links in the
Outcome
• Cause of death chain of survival”, which highlight the interdependent
• Treatment withdrawal elements of early OHCA recognition and call for
• Transport to hospital
• Organ donation help, early cardiopulmonary resuscitation (CPR), early
• Quality-of-life measures defibrillation, expert advanced cardiac life support, and
• Patient-reported outcome measures expert post-resuscitation care.12,13,27–29
Core elements • Survival at 12 months
Supplemental elements Despite scientific advancement, temporal improvement
in outcome across population-based settings has been
Figure 1: Utstein data element domains for out-of-hospital cardiac arrest
ECG=electrocardiograph. CPR=cardiopulmonary resuscitation.
inconsistent.2 Appreciating the challenges of scientific
ECMO=extracorporeal membrane oxygenation. IABP=intra-aortic balloon pump. discovery and community translation, a multidisciplinary
group of key stakeholders convened at the Utstein Abbey

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in Norway in 1990 to develop and define standard data
elements and definitions that could provide the
framework for resuscitation research and quality
improvement.30 The Utstein data elements include
measures of demographics, prehospital and hospital
care, and outcome organised to feature bystander-
witnessed shockable cardiac arrest. The Utstein data
definitions and presentation template have been refined
over time through expert review and consensus, and
continue to provide the common framework to evaluate
resuscitation process and care (figure 1).31
The Utstein data elements are the foundation for
clinical research. These elements consistently predict
survival and so inform research efforts as important
covariates that can help explain outcome relationships.1
However, the Utstein elements collectively do not fully
predict outcome, indicating that additional measures
influence prognosis.32 The Utstein elements often assess
a binary base category but often do not have the fidelity to
measure quality. For example, bystander CPR is typically
a yes or no variable. The quality of CPR is not routinely
measured. Yet the effectiveness of chest compressions
during CPR incorporates specific characteristics relating
to compression depth, release, rate, and timing.28,29,33
Thus, promising strategies for scientific discovery often
define or evaluate the qualitative and quantitative
components of the categorical Utstein elements.
Equally as important to serving as the platform for
scientific discovery, the Utstein elements also provide
a common framework for emergency systems to
systematically and consistently measure resuscitation
care. The approach has enabled comparison within and
across emergency systems, and in turn highlighted the
marked disparity in OHCA survival. Survival varies up
to ten times across systems as supported by multiple
peer-review investigations, highlighting the opportunity
to improve public health by achieving current best
practices across more communities.3,5,34,35
Indeed, the Utstein forum recognised the reality that
scientific understanding does not uniformly translate to
community success, and so they published a formula for
system survival (figure 2). The formula recognises that
community translation to achieve best practices must pair
medical science with educational efficiency and local
implementation.36 Each of these domains was recognised by
the 2015 Academy of Sciences Report, which endorsed the
need for a multipronged strategy for resuscitation progress
that included scientific discovery and community translation,
the latter built upon programmatic quality improvement to
systematically measure and improve care.37
A prime example is the provision of early CPR by
laypeople before the arrival of professional rescuers.
There is a range of complimentary programme strategies
that collectively enable a community to achieve best
practices in early bystander CPR (figure 3). These
programmes are derived from peer-review evidence and
support efforts to provide community training, telephone
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Medical Educational Local
× × implementation = Survival
science efficiency
Figure 2: The Utstein formula to improve survival after out-of-hospital
cardiac arrest
Targeted training
Social media and technology
School-based training
Dispatcher telephone CPR
Community training programmes
Figure 3: Examples of complimentary bystander CPR programmes
CPR=cardiopulmonary resuscitation.
CPR, school-based training, smart geospatial technology
to activate community rescuers, and focused training
efforts directed at high-risk groups.38–41 Each strategy can
increase knowledge and action for bystander CPR but
requires translation from scientific understanding to
organised action. In communities that effectively use
these strategies, bystander CPR can be provided for more
than three quarters of patients with OHCA.42
Therefore, emergency systems require approaches
that can translate science into actionable and often
pragmatic programmes (table).43 For example, inter­
national experience highlights the potential of effective
quality improvement involving telephone CPR. A series
of studies from around the world reveal a notable
increase in bystander CPR and improvement in survival
with implementation of dispatcher-directed telephone
CPR, whereby dispatchers help identify cardiac arrest
and coach CPR.44–47 The emergency medical dispatcher
is the principal link between the general public and
the EMS system in the prehospital setting. Therefore,
highly trained dispatchers play a pivotal role in guiding
bystanders through what is the most time-critical period
in cardiac arrests. Not only do they attempt to create a
calmer environment more conducive to establishing an
informed diagnosis upon which to act, their skill lies in
the ability to ensure bystander CPR, and defibrillation
if appropriate, is delivered in the most effective way.
Implementation is just the beginning and must be
supported by quality evaluation, incorporating process
measurement with a focus on improvement. This process
can be motivated by performance goals. With the potential
for widespread survival gains through improvements in
education and implementation, resuscitation stakeholders
again convened in 2015 at the Utstein Abbey and in 2016
in Copenhagen, Denmark, to discuss strategies that can
positively affect care and outcome at the community level.
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Stakeholder Programme description

Cardiac arrest registry
Telephone CPR
High-performance EMS CPR
Rapid dispatch
Measurement of professional EMS and hospital
rescuer cardiac arrest care
AED programme for first
responders
Smart technologies for CPR
and AED
Mandatory CPR and AED
training
Hospital care
Culture of excellence
Community, telecommunication
centre, EMS, and hospital
Community, telecommunication
centre, and EMS
EMS
Telecommunication centre and EMS
Community, telecommunication
centre, and EMS
Community, telecommunication
centre, and EMS
Community and EMS
Hospital
Telecommunication centre, EMS,
and hospital
A registry acts as measurement tool that enables data-driven assessment of the emergency system so that
implementation and improvement efforts can be benchmarked, directed, and refined
Telecommunicators facilitate cardiac arrest identification and coach layperson CPR using a directed approach that
prioritises cardiac arrest identification and care; quality improvement with use of audio review enables case-specific
feedback and evaluation of performance metrics
High-quality CPR metrics can be achieved by combining individual CPR skills and coordinated team choreography that
incorporates local EMS operations, staffing, equipment, and logistics
Telecommunicators immediately dispatch EMS for certain initial descriptions such as unconscious, difficulty breathing,
chest pain, and seizure, which might represent or develop into cardiac arrest, and then complete caller interview and action
Programmes that provide case-specific review provide the basis to review and improve individual and team performance;
review can include team debriefing or objective review of CPR performance generated through real-time recording of care;
this review includes measurement of guideline-directed CPR metrics for benchmarking
Programmes of public access and law enforcement defibrillation can achieve early defibrillation, but must incorporate
local understanding of the geographical distribution of risk and the logistics of public service response
Interconnected technology provides the potential for real-time arrest geolocation, proximal layperson notification,
nearby AED locations, and just-in-time CPR instruction; collectively, a well integrated system with community
participation can mobilise community responders
Mandated and volunteer programmes of CPR and AED training involve a variety of settings such as schools, work places,
community organisations, and targeted populations; training approaches use a range of formats and mediums to achieve
competency
Hospital programmes of targeted temperature management, coronary revascularisation, and supportive critical care
with deferred prognostication provide a composite to assess best practices; successful hospitals often use as standard
practice this composite as part of a standing programmatic strategy that might establish best practice; performance
review and feedback provides for benchmarking and improvement
System measurement and reporting that engages all stakeholders, informs ongoing quality improvement, and establishes
accountability; the framework produces commitment to professional excellence and an expectation of success

EMS=Emergency medical services. CPR=cardiopulmonary resuscitation. AED=automated external defibrillator.

Table: Programmes designed to operationalise scientific understanding

The consequence was the call for a Global
Alliance. The mission of the alliance is
community implementation of effective
programmes designed to be synergistic
scientific guideline groups.
Predictors of survival after OHCA
Several studies report substantial regional variation in
morbidity and mortality after OHCA and point to factors
that affect the chances of survival with a favourable
neurological outcome.3,5,6,8,31,35,48 Although some predictors
are intuitively obvious, the effects of many remain
unclear. In the main, predictors of survival after OHCA
can be categorised into patient factors, event factors,
system factors, and therapeutic factors (panel 2).
Associated comorbid conditions are not always a direct
cause of cardiac arrest, but refer collectively to chronic or
acute disease states that a patient had prior to having an
event. A comorbidity index based on the existence of heart
failure, myocardial infarction, use of heart medications,
diabetes, hypertension, chest pain, chronic pulmonary
disease, gastrointestinal disorders, cancer, and other
chronic conditions in conjunction with the development
of recent symptoms 2 days before out-of-hospital
ventricular fibrillation has been used to determine
whether such factors would affect survival.49 Despite using
this index relative to a comprehensive set of predictors of
survival, the investigators could only account for 25% of
Resuscitation what might be expected from an ideal model. Nevertheless,
to accelerate comorbidity was shown to be the most powerful predictor
resuscitation of survival from OHCA due to ventricular fibrillation.49 In
with current addition to a larger number of pre-existing conditions
being inversely associated with odds of survival to hospital
discharge, the deleterious effect of the chronic condition–
outcome association is further exacerbated by the response
time of EMS. Investigators found that the odds ratio (OR)
of survival was 0·72 (95% CI 0·59–0·88) for each
additional comorbidity when response time was 8 min
compared with an OR of 0·95 (0·79–1·14) after a 3-min
EMS response, suggesting that the relationship between
chronic condition count and survival might be modified
by response interval.50 It is both intuitive and appropriate,
therefore, to appreciate that baseline comorbidity (espec­
ially cardiac disease) is likely to influence survival, and
recognition of this factor might assist with prognostication
decisions for patients with OHCA.51–53
Taken together, there is an assumption that increasing
age and comorbid conditions act in tandem to attenuate
the chances of a positive outcome after OHCA. Some, but
not all, studies have observed independent and distinct
associations between the burden of comorbidity, age, and
outcome.54 A retrospective observational cohort study of
non-traumatic OHCA admissions to the University of
Michigan Emergency Department found age, but not the
Charlson Comorbidity Index, to be significantly associated
with less favourable neurological outcomes after adjusting

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Panel 2: Factors associated with survival following OHCA

Factors that can affect survival outcomes • Community CPR training
Patient related • Public access defibrillation
• Age Therapeutic related
• Sex • Pharmacotherapy
• Ethnicity • Impedance threshold device for CPR
• Comorbidity • CPR adjuncts
• Diet • Compression only CPR
• Obesity • Airway management
• Medications • Targeted temperature control
• Socioeconomic status • Quality of in-hospital care
• Genetic determinants • Distance to invasive heart centre
Event related • Immediate coronary angiography for all patients with
• Symptoms before collapse OHCAs on admission to hospital
• Location at time of event
Factors shown to have a strong relationship with survival
• Time of the day
outcomes
• Witness status (bystander, EMS, no witness, or unknown)
Patient related
• Decision to begin resuscitation
• Age
• Bystander CPR
• Ethnicity
• Cause of cardiac arrest
• Comorbidity
• Type of heart rhythm
• Socioeconomic status
• Use of on-scene AED
Event related
System related
• Type of heart rhythm
• Time to CPR
• Witness status
• Quality of CPR
• Bystander CPR
• Time to defibrillation
• Agonal breathing
• Interaction of CPR and defibrillation
• Type of EMS system System related
• System size • Time to CPR
• Number of responders • Time to defibrillation
• Ratio of paramedics to population • Interaction of CPR and defibrillation
• Dispatcher-assisted telephone CPR • Dispatcher-assisted telephone CPR
• Quality of EMS care Therapeutic related
• Ongoing medical quality improvement • No therapeutic-related factors have shown a clear association
• Organisational structure and culture with positive outcome after OHCA
• Administrative support
• Quality of training EMS=emergency medical service. CPR=cardiopulmonary resuscitation. AED=automated
external defibrillator. OHCA=out-of-hospital cardiac arrest.

for important covariates. Each decade of life was shown to
reduce the odds of a positive outcome by 21%.55 Analysis
of the Amsterdam Resuscitation Study, a prospective
registry of all-cause OHCA, also observed no significant
association between the Charlson Comorbidity Index and
cardiac arrest outcomes in people older than 70 years.56 In
effect, resuscitation-related factors and not the extent of
comorbidity were shown to determine outcome after
OHCA in older patients. Age, therefore, should be
regarded as an independent predictor of prognosis
rather than simply seen as a surrogate marker for an
accumulation of comorbidity.55
Socioeconomic status is an important predictor of
survival. A secondary analysis of the Ontario Prehospital
Advanced Life Support study looked at OHCA of cardiac
origin occurring in a single residential dwelling, not
witnessed by EMS. The investigators found that for every
CAN$100 000 increment in the value of the property in
which the event took place, the chances of receiving
bystander CPR increased (OR 1·07, 95% CI 1·01–1·14;
p=0·03).57 Similarly, in Taiwan a study of non-traumatic
OHCA found the OR of receiving bystander CPR in low-
socioeconomic status areas was 0·72 (95% CI 0·60–0·88)
after adjusting for multiple confounders.58 Real estate
value was again used as the surrogate of socioeconomic
status. There was a significant difference in the proportion
of bystander CPR in administrative districts of low
socioeconomic status versus high socioeconomic status
(14·5% vs 19·6%; p<0·01).58 The racial composition of a
neighbourhood in which an OHCA event occurs, the
educational background of the individual succumbing to
OHCA, the median household income, and level of social

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deprivation have all been shown to predict outcome
after OHCA.59–63 These analyses also serve to emphasise
the importance of early and effective bystander CPR
(regardless of witness status), along with early de­
fibrillation, in the context of OHCA survival.10,14,42 Areas of
low socioeconomic status consistently have the lowest
rates of bystander CPR and defibrillation compared with
those of high socioeconomic status.60,61 These findings
have wide-ranging implications on where to concentrate
public health resources, none more so than when
decisions regarding the optimal deployment of automated
external defibrillators have to be made. These issues are
further amplified when basic life support training is
considered in the context of low-income and middle-
income countries.64
It is well established that a shockable rhythm, such
as ventricular fibrillation or ventricular tachycardia, is
a strong predictor of survival.1 The strength of the
association is greatest in locations where early bystander
defibrillation is viable. Conversely, non-shockable
rhythms, such as asystole and pulseless electrical activity,
are associated with the lowest survival.1 Furthermore,
shockable rhythm conversion from initially non-
shockable rhythms, especially asystole, is associated with
an increased rate of prehospital return of spontaneous
circulation, survival to hospital discharge, 1 month
survival, and 1 month favourable neurological outcome.65
Younger age, male gender, witnessed cardiac arrest, short
response time, and underlying cardiac disease increase
the likelihood of conversion to a shockable rhythm.66
Early and effective CPR also delays the degradation of
tachyarrhythmias to asystole.1
There are few studies on the relationship between
population density and survival after OHCA. However, it
would appear intuitive to assume that lower bystander
CPR and longer EMS response times would be a factor in
larger geographical regions where the population is more
widely distributed. In a study of the Swedish Cardiac
Arrest Register, ambulance response time was indeed
more protracted in less-populated areas (p<0·0001).
There was, however, no significant association between
population density and survival to 1 month after OHCA.67
Conversely, a study of the Victorian Ambulance Cardiac
Arrest Registry of all OHCA of presumed cardiac cause
found population density to be independently associated
with survival.68 Indeed, when compared with very
low-density populations, the odds of survival increased
to 1·88 (95% CI 1·15–3·07) in low-density areas, 2·49
(1·55–4·02) in medium-density areas, 3·47 (2·20–5·48)
in high-density areas, and 4·32 (2·67–6·99) in very high-
density areas.68
Patients presenting with OHCA are a heterogeneous
group that requires a multifaceted approach to care.
Effective post-resuscitation care cannot readily be
provided by all hospitals because of a paucity of
appropriate facilities and expertise. Because this fifth
link in the chain of survival contributes profoundly to
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survival, it has been proposed that regional systems of
care should be established to allow concentration of
best practice in managing patients with OHCA.48,69
Similar successful programmes have improved pro­
vider experience and patient outcomes following life-
threatening traumatic injury.70
However, the establishment of a robust cardiac
resuscitation centre infrastructure will require extensive
interhospital cooperation, which might be a challenge in
some health-care systems. Additionally, in remote
areas, the potential delays in transport might not allow
direct transfer to a cardiac resuscitation centre. Recent
data have suggested this increase in transport time does
not detract from the net gain in survival achieved
after admission to an invasive heart centre and regional
performance of acute coronary angiography where
indicated.71
Primary and secondary prevention of sudden
cardiac arrest
Both the European Society of Cardiology and the American
Heart Association/American College of Cardiology/Heart
Rhythm Society have published extensive guideline
recommendations for the manage­ment of patients with
ventricular arrhythmias and the prevention of sudden
cardiac death.72,73 In the US guideline recommendations,
sudden cardiac arrest is defined as the sudden cessation
of cardiac activity such that the patient becomes un­
responsive, with either persisting gasping respirations or
absence of any respiratory movements, and no signs of
circulation. The most common consequence of sudden
cardiac arrest is sudden cardiac death. In this context,
primary prevention constitutes therapies to reduce the
risk of sudden cardiac death in individuals who are at risk
but have not yet had a cardiac arrest or life-threatening
arrhythmia.72 Secondary prevention constitutes therapies
to reduce the risk of sudden cardiac death in patients
who have already had a cardiac arrest or life-threatening
arrhythmia.72 An implantable cardioverter defibrillator is
the mainstay of treatment for both primary and secondary
prevention of sudden cardiac death in patients with
either ischaemic or non-ischaemic cardiomyopathy. The
key determinant for intervention common to all those
potentially eligible for a device is a life expectancy greater
than 1 year.73 Supplementary pharmacotherapy and the
increasing importance of radiofrequency catheter ablation
of sympto­ matic premature contractions or ventricular
tachycardia, refractory to medical therapy, also underscore
these current guidelines. The value of screening of family
members of patients with sudden cardiac death and risk
stratification for those with structural heart disease or
inherited primary arrhythmia syndromes have also been
emphasised.72,73 Education on warning symptoms such as
chest pain and dyspnoea, typically ignored by patients
and relatives, should also be noted as a potential short-
term prevention strategy in those at risk of sudden
cardiac arrest.74,75 We recommend the European and US

guidelines, which are exhaustive in their content, as
further reading.
Of note, the Improve Sudden Cardiac Arrest study
(NCT02099721) is currently enrolling a sample size target
of 4800 patients eligible for an implantable cardioverter
defibrillator from countries where device therapy for
primary prevention is underused, including Asia, Latin
America, eastern Europe, the Middle East, and Africa.76
The study aims to show that individuals who require
primary prevention for sudden cardiac arrest, who also
have one or more additional risk factors (syncope or pre-
syncope, left ventricular ejection fraction <25%, non-
sustained ventricular tachycardia, or ≥ten premature
ventricular contractions per hour) have a similar risk of
sudden cardiac death when compared with secondary
prevention patients. The results are eagerly awaited.
Conclusion
Although programmatic implementation of established
science can improve survival and in turn achieve public
health gains, effective implementation can be challen­ging
and must overcome a broad range of barriers that
involve training, equipment, adminis­trative and political
obstacles, and medical considerations.77 Successful com­
munity implementation often requires leadership, team­
work, and accountability to overcome organisation inertia
and to introduce lasting change.78 Population-based efforts
aimed at implementation have had mixed success.79 Taken
together, population-based systems committed to quality
measures and improved philosophy can on average
achieve an all-rhythm survival of 12% and a witnessed
shockable rhythm survival of 35%, which are substantially
greater than historical figures of 6% for all-rhythm survival
and 16% for witnessed shockable rhythm survival.1,79
And yet, there is still substantial disparity across sys­
tems, highlighting the opportunity to improve survival
after resuscitation further through efforts aimed at
scientific discovery and a transition away from an
onus on the patient of sudden cardiac arrest to a
community-centred approach. Adoption of a Haddon
Matrix, for example, would shift emphasis to more
passive measures in public health policy such as the
incorporation of wide-ranging legislation, which would in
turn apply to the whole community rather than the
individual, by contrast with active measures such as
public education.80
Contributors
AM, K-JS, and TR were all involved in the conception and content of this
Series paper. All authors wrote prespecified sections of the manuscript,
and AM then combined these sections to produce a single manuscript. All
authors reviewed the manuscript for intellectual content and have seen
and approved the final submitted version.
Declaration of interests
AM and K-JS declare no competing interests. TR has received
research grants from the American Heart Association, the Laerdal
Foundation, the Life Sciences Foundation, Medtronic Philanthropy,
National Institutes of Health, Philips Healthcare, and PhysioControl,
which were administered by the University of Washington (Seattle,
WA, USA).
www.thelancet.com Vol 391 March 10, 2018 977
Series
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