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Editorial
Out-of-Hospital Cardiac Arrest
Getting Beyond the Tip of the Iceberg
Leonard Ilkhanoff, MD, MS; Jeffrey J. Goldberger, MD, MBA
Sudden Cardiac Death: The Scope
Article see p 815
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Sudden cardiac death (SCD), which is responsible for
approximately 300 000 deaths in the United States, refers to
an unexpected death from a cardiovascular cause in a person
with or without preexisting heart disease. Most studies
include cases that are associated with death occurring within
1 hour of an acute change in clinical status or an unexpected
death that occurred within the previous 24 hours,1 but this
definition is not specific for sudden arrhythmic death. The
most common sequence of events leading to arrhythmic SCD
is the degeneration of ventricular tachycardia (VT) into
ventricular fibrillation (VF), often followed by asystole or
pulseless electric activity. The transition of shockable
rhythms (VT/VF) to more ominous rhythms such as asystole
or pulseless electric activity depends on various factors, but is
highly dependent on time; the longer the time interval, the
more likely the VT/VF degenerates to pulseless electric
activity or asystole. Although VF and VT together represent
the initial rhythm in half of all outpatient cardiac arrests, data
suggest that with each passing minute of untreated VF, the
likelihood of survival is reduced by 7% to 10%.2 Preexisting
coronary artery disease and its sequelae (eg, acute myocardial
ischemia, scarring from previous myocardial infarction, heart
failure) are manifest in 80% of SCDs.3 Dilated nonischemic
and hypertrophic cardiomyopathies account for the second
largest number of SCDs, whereas other cardiac disorders such
as congenital heart disease and underlying genetically determined ion channel anomalies account for 5% to 10% of
SCDs.3 Although the cascade of events triggering SCD are
complex and are currently active areas of investigation, the
general goals of reducing SCD are focused on (1) identifying
and preventing sudden death in high-risk individuals by using
efficacious therapies such as medications and implantable cardioverter defibrillators (ICDs), (2) organizing resuscitation services to improve response to and efficiency and effectiveness of
treatments directed to individuals who experience cardiac arrest,
and (3) improving survival rates for individuals who experience
SCD by implementing and organizing specialized services at
hospitals that deliver postresuscitation care.
Multifaceted approaches have been implemented to reduce
the number of SCDs. In this issue of Circulation, Hulleman et
al4 assess the role of ICDs in reducing the incidence of
resuscitation for out-of-hospital cardiac arrest (OHCA)
caused by lethal ventricular arrhythmias, the specific target
for ICD therapy. They found that the incidence of VF-OHCA
decreased during a 10-year period in north Holland from
21.1/100 000 inhabitants per year to 17.4/100 000 inhabitants
per year, and that ICD therapy likely explained approximately
one third of this decrease (1.2/100 000 inhabitants per year).
Interestingly, the incidence of non-VF-OHCA increased during the same time period from 12.2/100 000 inhabitants per
year to 19.4/100 000 inhabitants per year, leading to an
overall increased rate of OHCA.
Although many assumptions are made in this report,
any one of which could affect the results, the sensitivity
analyses as well as concordance with other data5– 8 suggest that these estimates have substantial validity. This
validity enables us to use these important data to provide
a global perspective on the tremendous efforts that have
been put forth during the past several decades on prevention of SCD.
SCD Prevention
Response to OHCA
Hulleman et al4 note that the decline in VF-OHCA is modest
overall, ⬇ 17.5%, which highlights the continued need for
efforts to improve our response to OHCA. Many countries
have identified areas to improve OHCA treatment. Efforts
focus on best practices in resuscitation medicine and
emphasize the need for continuous quality improvement in
processes of care that may translate to improved outcomes
for patients with OHCA. This chain of survival includes
dissemination of knowledge to improve delivery of bystander cardiopulmonary resuscitation, increasing the distribution and early use of automated external defibrillators
in highly trafficked areas such as malls and airports, and
rapid emergency medical services activation and time to
initiation of resuscitation efforts.9
Despite these advances in out-of-hospital cardiopulmonary
resuscitation, survival to hospital discharge after cardiac
arrest in most major metropolitan centers in the United States
remains poor. Survival to hospital discharge was recently
estimated to be 5% to 10% among OHCAs that were treated
by emergency medical services personnel.9,10 In addition, the
majority of SCDs occur at home, often where the event is
unwitnessed. As a result, automated external defibrillators,
which improve resuscitation rates for witnessed arrests,11 may
The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From the Northwestern University Feinberg School of Medicine &
Bluhm Cardiovascular Institute, Chicago, IL.
Correspondence to Jeffrey J. Goldberger, MD, Northwestern University Feinberg School of Medicine, Division of Cardiology, 251 East
Huron, Feinberg Pavilion 8-503, Chicago, IL 60611. E-mail
[email protected]
(Circulation. 2012;126:793-796.)
© 2012 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.112.123588
793
794
Circulation
August 14, 2012
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have limited effectiveness in reducing overall mortality from
SCD. Delays in emergency medical services (personnel
reaching a witnessed SCD individual, not having an automated external defibrillators readily available, and not initiating immediate cardiopulmonary resuscitation) may contribute to rapid deterioration of a life-threatening ventricular
tachyarrhythmia to asystole. More important, unwitnessed
SCD carries a grave prognosis, largely because the time to
resuscitative efforts is delayed and resuscitative efforts may not
even be initiated in one third of cases.10 –12 It is important to note
that improvement in postarrest therapies and approaches are not
likely to influence the number of OHCAs, only the outcome.
Although there are significant limitations in delivering
optimal services to individuals with OHCA, some metropolitan areas that have adopted organized approaches to resuscitative medicine have shown that overall rates of survival
from OHCA—in particular, witnessed VF— can improve
over time.9,10 Time to first shock has averaged 6 minutes in
Rochester, MN, and between 2006 and 2008, survival to
hospital discharge for bystander-witnessed events in which
individuals presented with VF exceeded 50%.9
Prevention of OHCA
These coordinated efforts to provide rapid response to SCD
individuals are complemented by approaches to prevent SCD.
Prevention requires a synergy of efforts, including proper
medical therapy and ICD placement in appropriate high-risk
individuals. The work by Hulleman et al4 is important
because it, specifically, places into context the role of ICDs in
reducing VF-OHCA in light of important changes in the
epidemiology of disease and other factors in north Holland.
Because ICD use explained only 33% of the reduced incidence of VF-OHCA in this study, the implication is that
additional factors are significant contributors to the decline in
VF-OHCA incidence.
Medication Use
Improved use of medical therapies such as ␤-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, and polyunsaturated fatty acids
that may affect SCD likely have had an impact on the declining
incidence of VF-OHCA. These therapies most likely confer their
antiarrhythmic potential indirectly by inhibiting or delaying
adverse structural remodeling in a diseased heart, and by
modulating upstream inflammatory and neurohormonal pathways, thereby contributing to electrophysiological stability.13
Specifically, Hulleman et al4 point out that ␤-blocker use,
which has been reported to decrease sudden death by as much
as 50%, may have reduced the incidence of VF. Yet, there are
potentially important ramifications of these therapies, particularly in light of the reported increase in non-VF-OHCA.
Individuals taking ␤-blockers who experienced OHCA were
5 times more likely to present with non-VF than VF as the
first documented rhythm. A recent trial using implantable
loop recorders in myocardial infarction patients with left
ventricular dysfunction reported that VF and bradyarrhythmias accounted for equal proportions of recordings at the
time of death. Even though VT/VF was the terminal rhythm
and was associated primarily with SCD, intermittent high-
degree atrioventricular block was also a strong predictor of
cardiac death.14 It is conceivable that ␤-blockers not only
reduce the incidence of VT/VF, but also may alter the
electrophysiological milieu in such a manner as to convert
VF-OHCA events to non-VF events. Further efforts to ensure
proper medical therapy and to understand the interactions of
medical therapy with the diverse mechanisms of SCD are
necessary.
Declines in Coronary Heart Disease Rates
A second potential reason for reduction in VF-OHCA incidence is a concomitant decline in coronary heart disease
(CHD) burden over time. This decline can likely be explained
by improvements in diagnosis and treatment of comorbidities
associated with CHD, such as diabetes mellitus, hypertension,
and dyslipidemia, and improved targeted therapies and interventions for CHD. Because CHD is the leading cause of SCD
in the world, a decline in CHD rates should parallel the
reduction in VF-OHCA rates to some degree. As Hulleman et
al4 note, the decline in VF-OHCA may also be attributed to
other changing biological mechanisms in the population at
risk for VF.
Future Approaches to OHCA
The impact of the ICD in reducing the population-based
problem of SCD is clearly significant, but is far from
enough. Certainly one of the factors limiting the population impact of ICDs is the consistent finding that most
individuals who experience SCD fall outside the current
guidelines for consideration of an ICD. Substantial impact
on VF-OHCA can be achieved by improving our ability to
identify individuals at risk for SCD prior to them experiencing a life-threatening event. More important, enhancing
our risk stratification armamentarium of tools, genetic
markers, and other techniques to provide adequate discriminatory power to manage individuals requires rigorous and
ongoing research.15
Although the field of risk stratification for the prevention
of SCD is currently focused on using certain approaches to
identify appropriate ICD candidates, the importance of this
research endeavor transcends this specific treatment. Individuals found to be at significant risk for SCD could be treated
with a host of therapies, including lifestyle modifications (ie,
exercise, diet), more aggressive medical therapy, and newer
medical or other novel therapies. Examples of the latter could
include vagus nerve stimulators or spinal cord stimulators
meant to modulate the autonomic nervous system effects on
the heart.
The final challenge in addressing the vast public health
problem of SCD is that, in a sizable percentage of individuals,
SCD is the first manifestation of cardiac disease.16 Improved
public education and screening for cardiovascular disease are
modalities that may impact SCD in this subpopulation.
Because of the number of susceptible individuals who would
not be identified as candidates for an ICD using current
guideline approaches, it remains important to continue to
focus on rapid identification and efficient response systems to
OHCA, and successful restoration of spontaneous circulation.
Continued improvements in this field, such as greater dissem-
Ilkhanoff and Goldberger
Out-of-Hospital Cardiac Arrest
795
Figure. The universe of out-of-hospital cardiac arrest (OHCA) is divided into those with
ventricular fibrillation (VF) and non-VF arrest,
with slightly higher prevalence of the latter
based on Hulleman et al.4 Within each major
mode of OHCA, there are opportunities for
improved prevention (the middle slices) and
improved response (the top 2 slices), with
some of the potential approaches listed. In
some cases (the bottom 2 slices), OHCA is
a terminal event for which no preventive or
response measures could be effective (Zone
of futility). The size of the slices are meant to
be relative, not absolute. For example, more
non-VF-OHCAs are likely terminal events
than VF-OHCAs, and there is greater opportunity for prevention of VF-OHCA than nonVF-OHCA. EMS indicates emergency medical services; AED, automated external
defibrillator; CPR, cardiopulmonary resuscitation; and ACLS, advanced cardiac life
support.
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ination of automated external defibrillators, rapid and early
cardiopulmonary resuscitation, the development and implementation of hypothermia protocols, and other systems of
care will also further impact SCD outcomes and lead to
improved survival rates in OHCA.9,10 In Philadelphia, for
example, a comprehensive multidisciplinary treatment protocol for patients resuscitated from OHCA and its implementation led to survival rates that improved from 22% to
⬎50%.9
The future clearly holds significant opportunity to reduce
the population burden of OHCA (Figure). Our greatest
opportunity appears to stem from unlocking the mechanisms
and triggering events leading to VF in at-risk individuals and
disseminating appropriate therapies to limit this risk. Our
greatest challenge may be in preventing and treating
non-VF-OHCA, for which the triggering events for SCD
remain elusive. Because non-VF-OHCA represents a sizable portion of all OHCAs, a better understanding of this
mode of SCD and its precursors is required to have a
tangible impact. The future, as suggested by Hulleman et al,4
may bring further shifts in OHCA from VF to non-VF cases.
Improvements in risk stratification and identification
of individuals as appropriate candidates for medical and
device therapy, advancements in medical therapy to limit
progression of cardiac disease, and enhancements in resuscitative services collectively will lead to incremental and
continued declines in the incidence of VF-OHCA and overall
SCD rates. Further studies are necessary to continue to track
the epidemiological impact of all these efforts on OHCA.
Disclosures
Dr Goldberger is director of the Path to Improved Risk Stratification,
a not-for-profit think tank on risk stratification for prevention of
sudden cardiac death, which has received unrestricted educational
grants from Medtronic, Boston Scientific, and St. Jude Medical. Dr
Goldberger has received past honoraria from Medtronic, Biotronik
and St. Jude Medical. Dr Ilkhanoff has received past honoraria from
Biotronik and St. Jude Medical.
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KEY WORDS: Editorials 䡲 death
䡲 ventricular tachycardia
䡲
sudden
䡲
ventricular fibrillation
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Out-of-Hospital Cardiac Arrest: Getting Beyond the Tip of the Iceberg
Leonard Ilkhanoff and Jeffrey J. Goldberger
Circulation. 2012;126:793-796; originally published online August 6, 2012;
doi: 10.1161/CIRCULATIONAHA.112.123588
Downloaded from http://circ.ahajournals.org/ by guest on June 15, 2017
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