Journal of Cardiology 68 (2016) 161–167

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Journal of Cardiology
journal homepage: www.elsevier.com/locate/jjcc

Original article

Resistance to conventional cardiopulmonary resuscitation

in witnessed out-of-hospital cardiac arrest patients
with shockable initial cardiac rhythm
Takayuki Otani (MD)*, Hirotaka Sawano (MD, PhD), Keisuke Oyama (MD),
Masaya Morita (MD), Tomoaki Natsukawa (MD), Tatsuro Kai (MD)
Senri Critical Care Medical Center, Osaka Saiseikai Senri Hospital, Osaka, Japan

A R T I C L E I N F O A B S T R A C T

Article history: Background: Shockable initial cardiac rhythm is a key predictor of survival after out-of-hospital cardiac
Received 15 July 2015 arrest (OHCA). However, not all patients with shockable OHCA achieve return of spontaneous circulation
Received in revised form 21 August 2015 (ROSC) via conventional cardiopulmonary resuscitation (CPR). Therefore, we retrospectively analyzed
Accepted 26 August 2015
patients with witnessed OHCA and shockable initial cardiac rhythm to identify the resistance factors for
Available online 2 October 2015
conventional CPR.
Methods: We retrospectively analyzed consecutive patients with witnessed OHCA and shockable initial
Keywords:
cardiac rhythm who were admitted to our hospital between October 2009 and October 2014. We then
Out-of-hospital cardiac arrest
Acute myocardial infarction
compared the baseline characteristics, pre-hospital clinical course, and causes of the cardiopulmonary
Extracorporeal cardiopulmonary arrest among patients who achieved ROSC via conventional CPR and patients who did not achieve ROSC
resuscitation via conventional CPR and underwent extracorporeal CPR (ECPR).
Results: A total of 85 patients achieved ROSC via conventional CPR (non-ECPR group) and 40 patients did
not achieve ROSC via conventional CPR and underwent ECPR (ECPR group). Among these 125 patients,
113 had known causes for their cardiopulmonary arrest, including 66 cases (53%) of acute myocardial
infarction (AMI). There were no significant differences in the causes of arrest between the non-ECPR and
ECPR cases. However, among the 66 cases of AMI (43 non-ECPR and 23 ECPR), the rate of non-
recanalization during the initial coronary angiography was significantly higher among the ECPR cases
(non-ECPR: 58% vs. ECPR: 87%; p = 0.03).
Conclusions: The major cause of witnessed OHCA with shockable initial cardiac rhythm was AMI, and
resistance to conventional CPR was related to continuous myocardial ischemia.
ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Introduction
The prognosis after sudden cardiac death remains poor, and the
survival rate for out-of-hospital cardiac arrest (OHCA) also remains
low [1,2]. However, previous studies have reported improving
survival rates for OHCA [3,4], due to recent improvements in a
public access defibrillation system, revisions to cardiopulmonary
resuscitation (CPR) guidelines, and progress in post-resuscitation
therapies [5]. The key predictors of OHCA survival are: (1)
witnessed arrest, (2) shockable initial cardiac rhythm, (3)
bystander-initiated CPR, and (4) return of spontaneous circulation
* Corresponding author at: 1-1-6, Tsukumodai, Suita-city, Osaka 565-0862,
Japan. Tel.: +81 06 6871 0121; fax: +81 06 6871 0130.
E-mail address: sonnyboy@tempo.ocn.ne.jp (T. Otani).
(ROSC) in the field [6]. Nevertheless, many patients with OHCA die
without ROSC if only above (1)–(3) conditions are satisfied. In this
context, extracorporeal CPR (ECPR) with extracorporeal membrane
oxygenation (ECMO) has recently been reported as effective for
patients in whom ROSC cannot be achieved via conventional CPR
[7,8]. Furthermore, the 2010 American Heart Association guide-
lines recommend ECPR in cases where the time without blood flow
is brief and the condition that led to the cardiac arrest is reversible,
amenable to heart transplantation, or amenable to revasculariza-
tion (Class IIb) [9]. However, there is no consensus regarding which
patients are likely to achieve ROSC via conventional CPR, and the
resistance factors for conventional CPR are poorly understood.
Thus, we hypothesized that resistance to conventional CPR is
affected by the patient’s baseline characteristics, pre-hospital
clinical course, and cause of the cardiopulmonary arrest (CPA).
Therefore, we retrospectively analyzed patients with witnessed

http://dx.doi.org/10.1016/j.jjcc.2015.08.020
0914-5087/ß 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
162 T. Otani et al. / Journal of Cardiology 68 (2016) 161–167
OHCA and shockable initial cardiac rhythm to identify the
resistance factors for conventional CPR.
Methods
Study design
The Osaka Saiseikai Senri Critical Care Medical Center is a
tertiary care referral center in Japan with a coronary intervention
laboratory that provides treatment 24 h/day, 7 days per week. We
retrospectively analyzed consecutive patients with witnessed
OHCA and shockable initial cardiac rhythm, who were admitted to
our hospital between October 2009 and October 2014. Patients
were excluded if they had a ‘do not attempt resuscitation’ order,
did not provide informed consent, had an existing terminal illness,
or had an implantable cardioverter defibrillator. We compared the
baseline characteristics, pre-hospital clinical course, coronary
angiographic findings, and CPA causes for the non-ECPR (ROSC
was achieved via conventional CPR) and ECPR (ROSC was not
achieved via conventional CPR and ECPR was performed) groups.
Written informed consent for the coronary angiography (CAG) and
ECPR was obtained from the patients’ family members.
All patients received out-of-hospital resuscitation from emer-
gency medical service (EMS) providers, according to the Japanese
CPR guidelines [2]. The EMS providers are allowed to perform
defibrillation for shockable cardiac rhythm, insert tracheal tubes,
insert an intravenous line, and administer intravenous adrenaline
as needed. When medical staff arrived at the patient’s location, the
physician injected any of the following antiarrhythmic drugs (as
needed): lidocaine (1–1.5 mg/kg), amiodarone (100–300 mg), or
nifekalant (0.3 mg/kg). When a patient with OHCA achieved ROSC
in the field, we performed 12-lead electrocardiography (ECG),
Fig. 1. Flowchart of the pre-hospital activities of the doctor car and conventional ambulance.
echocardiography, and computed tomography (CT) after their
hospital admission. If there were no obvious extra-cardiac causes
(e.g. intracranial hemorrhage or aortic dissection), the patient was
admitted to the coronary intervention laboratory, regardless of any
ECG findings, and CAG was performed. In cases where ROSC was
not achieved in the field and CPR was performed for >15 min, the
patient was also admitted directly to the coronary intervention
laboratory and underwent ECPR and CAG.
The doctor car system (pre-hospital physician care)
In January 1993, our hospital established a doctor car system in
cooperation with the nearby Fire -Defense Headquarters. This
system operates 24 h/day, 7 days per week. Fig. 1 shows the
flowchart of pre-hospital activities to OHCA patients by the doctor
car and a conventional ambulance. When the Fire-Defense
Headquarters control room receives an emergency telephone call
that contains keywords that may indicate heart attack or CPA, a
conventional ambulance is dispatched and a doctor car is
simultaneously requested by the Fire-Defense Headquarters. The
doctor car staffs are typically dispatched to the location of the
emergency call and join the EMS staff on-site, although the doctor
car staff may meet the EMS staff at a midpoint if the location is far
from our hospital. Because we only have one doctor car, not all
OHCA cases receive medical treatment from the doctor car staff.
The ECMO system and ECPR management
All ECPR cases underwent ECMO in the coronary intervention
laboratory, using a Capiox emergency bypass system, a Capiox-SX
membrane oxygenator, and a Terumo EBS centrifugal pump
(Terumo Inc., Tokyo, Japan). The femoral artery and vein were
 T. Otani et al. / Journal of Cardiology 68 (2016) 161–167
cannulated with 13.5-Fr and 19.5-Fr catheters, using the percuta-
neous Seldinger technique, while maintaining conventional CPR.
The pump flow was initially set at 2.5–3.0 L/min, and 3000 U of
heparin was administered immediately after ECPR initiation to
maintain an activated clotting time of 160–200 s. An intra-aortic
balloon pump was inserted for all ECPR cases after the CAG or
percutaneous coronary intervention (PCI).
Emergency CAG and the definition of acute myocardial infarction
The CAG was performed using a 5-Fr coronary angiographic
catheter, which was inserted from the femoral artery. In ECPR
cases, CAG was performed from the femoral artery that was
opposite to the ECMO site. The CAG findings were retrospectively
evaluated by at least two coronary interventionists, and acute
myocardial infarction (AMI) was defined as the presence of
coronary occlusions or irregular eccentric coronary lesions with
fresh thrombus and ruptured plaque, regardless of changes in the
post-resuscitation ECG findings [10]. To avoid classifying chronic
total occlusions as AMI, the occlusion had to be easily crossed using
an angiography guide wire. Coronary flow was assessed using the
thrombolysis in myocardial infarction (TIMI) grading. A coronary
artery was considered occluded for TIMI grade 0–1 [11]. All AMI
cases underwent PCI, and a >75% lumen diameter reduction was
considered significant coronary artery disease.
Definitions of the cardiac etiologies
The definition of the cardiac etiologies is described in Table 1
[12–14]. If no significant coronary lesions were found during the
initial CAG assessment, total or subtotal lesions that were induced
by the acetylcholine provocation test (at a later date) were also
diagnosed as coronary vasospasm [12]. We defined AMI and
coronary vasospasm as acute ischemic heart disease (IHD). The
‘non-ischemic cardiomyopathy’ group included hypertrophic
cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), while
the ‘primary arrhythmia’ group included Brugada syndrome,
primary and secondary long-QT syndrome, idiopathic ventricular
fibrillation, and J-wave syndrome. These conditions were diag-
nosed at a later date via post-resuscitation ECG or electrophysio-
logical examination, in the absence of coronary and
echocardiography abnormalities [14].
Acute IHD classifications according to TIMI grade
We classified acute IHD into two groups using their TIMI grade.
‘Acute IHD with TIMI grade 0–10 included AMI and coronary
vasospasm with TIMI grade 0–1 during the initial shot CAG, which
is ‘continuous myocardium ischemia’ in this study. ‘Acute IHD with
TIMI grade 2–30 was defined as AMI and coronary vasospasm with
TIMI grade 2–3 during the initial shot CAG, which involved
myocardium ischemia that had recanalized before the CAG.
Table 1
Definitions of the cardiac etiologies.
Coronary vasospasm
A total or subtotal coronary artery lesion that exhibited recanalization after
intracoronary administration of nitroglycerine (0.05–0.2 mg).
Ischemic cardiomyopathy
Significantly impaired left ventricular function due to chronic coronary artery
disease.
Hypertrophic cardiomyopathy
Left ventricular wall thickness during echocardiography in the absence of
another systemic or cardiac disease.
Dilated cardiomyopathy
Left ventricular chamber enlargement and systolic dysfunction during
echocardiography, without coronary artery disease.
163
Statistical analysis
The data are presented as median (interquartile range) for
continuous variables, and as number and percentage for categori-
cal variables. Continuous variables were compared using the
Mann–Whitney U-test, and categorical variables were compared
using the chi-square or Fisher’s exact test. All statistical analyses
were performed using SPSS software (version 21.0; SPSS Inc.,
Chicago, IL, USA). A p-value of <0.05 was considered statistically
significant.
Results
Patient characteristics
The patient selection flow chart is shown in Fig. 2, and the
patients’ baseline characteristics are shown in Table 2. Of
85 patients in the non-ECPR group, 7 (8%) achieved ROSC after
hospital admission. The median patient age was 65 years (range:
16–88 years). Most patients (111, 89%) were men, 20 (16%)
patients’ OHCAs were witnessed by EMS providers, 65 patients
(52%) received bystander-initiated CPR, and 31 patients (25%)
received bystander-delivered shocks. The median times for ‘call (or
EMS witnessed) to first shock’ and ‘to hospital arrival’ were 7 min
and 38 min, respectively. However, there were no significant
differences in the patients’ characteristics or medical histories
when we compared the ECPR and non-ECPR groups. The median
time for ‘call (or EMS witnessed) to ROSC’ was 15 min in the non-
ECPR group. The median time for ‘call (or EMS witnessed) to ECMO
initiation’ was 52 min in the ECPR group. The doctor car was
dispatched in 99 cases (79%), and the number of shocks and
frequency of adrenaline and antiarrhythmic drugs use in the field
were significantly higher in the ECPR group (p < 0.001).
Causes of CPA
Among the 125 included cases, 113 patients (90%) had known
causes for their CPA. Sixty-six patients (53%) had AMI, 8 patients
(6%) had coronary vasospasm, 12 patients (10%) had ischemic
cardiomyopathy, 4 patients (3%) had non-ischemic cardiomyopa-
thy, and 14 patients (11%) had primary arrhythmia (Table 3). None
of the patients had intracranial hemorrhage. The non-ECPR cases
with ‘other’ causes included valvular disease (2 patients), complete
atrioventricular block (1 patient), and intoxication (1 patient). The
ECPR cases with ‘other’ causes included valvular disease (1 patient),
aortic dissection (2 patients), and accidental hypothermia
(2 patients). There were no significant differences in the causes
of the CPAs for the two groups.
Coronary angiographic findings in AMI
We compared the CAG findings in the 66 patients with AMI
(non-ECPR: 43 patients; ECPR: 23 patients) (Table 4). This analysis
revealed that there were no significant differences in the location
of the causative lesion and the number of significant coronary
artery diseases. However, patients with no recanalization during
the initial shot CAG (TIMI grade 0–1) were significantly more
common in the ECPR group (ECPR: 87% vs. non-ECPR: 58%;
p = 0.03).
Comparing the TIMI grades in patients with acute IHD
The TIMI grades in patients with acute IHD are shown in
Table 5. Because all 8 patients with coronary vasospasm were TIMI
grade 2–3 during the initial shot CAG, they were included in the
‘acute IHD with TIMI grade 2–30 group. The ‘acute IHD with TIMI
164 T. Otani et al. / Journal of Cardiology 68 (2016) 161–167

Fig. 2. Flowchart of the patients with out-of-hospital resuscitation. OHCA, out-of-hospital resuscitation; ICD, implantable cardioverter defibrillator; ECMO, extracorporeal
membrane oxygenation; ECPR, extracorporeal cardiopulmonary resuscitation; ROSC, return of spontaneous circulation.

grade 0–10 classification was significantly more common in the except for the number of shocks and use of adrenaline and
ECPR group (ECPR: 87% vs. non-ECPR: 49%; p = 0.002). antiarrhythmic drugs in the field.

Comparing non-ECPR and ECPR groups with acute IHD and TIMI grade
0–1
A comparison of the non-ECPR and ECPR groups with acute IHD
and TIMI grade 0–1 is shown in Table 6. There were no significant
differences in the patients’ characteristics or medical histories,
Discussion
The major findings of this study are: (1) 113 (79%) of the
143 consecutive patients with witnessed OHCA and shockable
initial cardiac rhythm had known causes for their CPA; (2) among
66 patients with AMI, the frequency of TIMI grade 0–1 was

Table 2
Baseline clinical characteristics of the patients in this study.

All Non-ECPR ECPR p-Value

(n = 125) (n = 85) (n = 40)

Age, years 65 (53–72) 66 (58–72) 58 (49–72) 0.41

Male 111 (89) 72 (85) 39 (98) 0.06
Arrest witnessed by EMS 20 (16) 13 (15) 7 (18) 0.75
Bystander-initiated CPR 65 (52) 44 (52) 21 (53) 0.94
Shocks by bystander 31 (25) 22 (26) 9 (23) 0.68
Call (or EMS witnessed) to first shock, min 7 (5–10) 7 (5–10) 6 (5–9) 0.72
Call (or EMS witnessed) to hospital arrival, min 38 (32–48) 38 (31–47) 39 (34–49) 0.73
Call (or EMS witnessed) to ROSC, min 15 (11–25)
Call (or EMS witnessed) to initiation of ECMO, min 52 (47–63)
Doctor car 99 (79) 66 (78) 33 (83) 0.53
Shocks in the field, n 2 (1–5) 2 (1–3) 5 (4–5) <0.001
Use of adrenaline in the field, mg 1 (0–3) 0 (0–2) 3 (2–4) <0.001
Use of antiarrhythmic drugs in the field 41 (33) 16 (19) 25 (63) <0.001
Hypertension 74 (59) 54 (64) 20 (50) 0.15
Dyslipidemia 47 (38) 34 (40) 13 (33) 0.42
Diabetes mellitus 51 (41) 37 (44) 14 (35) 0.37
Current smoking 41 (33) 26 (31) 15 (38) 0.44
History of coronary artery disease 20 (16) 15 (18) 5 (13) 0.6

Data are presented as the number (%) of patients or median (interquartile range).
ECPR, extracorporeal cardiopulmonary resuscitation; EMS, emergency medical services; CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation;
ECMO, extracorporeal membrane oxygenation.
 T. Otani et al. / Journal of Cardiology 68 (2016) 161–167 165

Table 3 Table 6
Causes of out-of-hospital resuscitation in the conventional and extracorporeal Comparing the non-ECPR and ECPR patients with acute ischemic heart disease and
cardiopulmonary resuscitation groups. TIMI grade 0–1.

All Non-ECPR ECPR p-Value All Non-ECPR ECPR p-Value

(n = 125) (n = 85) (n = 40) (n = 45) (n = 25) (n = 20)

Acute myocardial infarction 66 (53) 43 (51) 23 (58) 0.12 Age, years 61 (53–70) 63 (58–71) 59 (53–67) 0.38
Coronary vasospasm 8 (6) 8 (9) 0 (0) Male 44 (98) 24 (96) 20 (100) 1
Ischemic cardiomyopathy 12 (10) 10 (12) 2 (5) Arrest witnessed by EMS 9 (20) 6 (24) 3 (15) 0.71
Non-ischemic cardiomyopathy 4 (3) 3 (4) 1 (3) Bystander-initiated CPR 26 (58) 16 (64) 10 (50) 0.34
Primary arrhythmia 14 (11) 11 (13) 3 (8) Shocks by bystander 14 (31) 10 (40) 4 (20) 0.2
Others 9 (7) 4 (5) 5 (13) Call or (EMS witnessed) 6 (4–8) 7 (3–8) 6 (5–8) 1
Unknown origin 12 (10) 6 (7) 6 (15) to first shock, min
Call or (EMS witnessed) 39 (31–49) 41 (30–49) 38 (32–46) 0.91
Data are presented as the number (%) of patients. ECPR, extracorporeal
to hospital arrival, min
cardiopulmonary resuscitation.
Doctor car 34 (76) 18 (72) 16 (80) 0.73
Shocks in the field, n 3 (1–5) 2 (1–3) 5 (4–5) <0.001
Use of adrenaline in 1 (0–3) 0 (0–2) 3 (2–4) <0.001
the field, mg
Table 4 Use of antiarrhythmic 15 (33) 4 (16) 11 (55) 0.01
Angiographic findings from the patients with acute myocardial infarction.
drugs in the field
Non-ECPR ECPR p-Value Data are presented as the number (%) of patients or median (interquartile
(n = 43) (n = 23) range). ECPR, extracorporeal cardiopulmonary resuscitation; TIMI, thromboly-
Location of causative lesion sis in myocardial infarction; EMS, emergency medical services; CPR,
Left anterior descending 26 (60) 14 (61) 0.78 cardiopulmonary resuscitation.
Left circumflex 4 (9) 1 (4)
Right 10 (23) 5 (22)
Left main 3 (7) 3 (13) OHCA [15–20], and troponin levels can be elevated in patients with
Number of significant coronary artery diseases
OHCA (even those without AMI) [21]. Interestingly, epidemiologic
One 16 (37) 12 (52) 0.47
Two 19 (44) 7 (30)
data indicate that DCM and HCM are the second most common
Three 8 (19) 4 (17) causes of sudden cardiac death (10–15%), and other cardiac
TIMI grade disorders (e.g. primary arrhythmia) are much less common [22]. In
Grades 0–1 25 (58) 20 (87) 0.03 contrast, primary arrhythmia and non-ischemic cardiomyopathy
Grades 2–3 18 (42) 3 (13)
were observed in 11% and 3% of our cases, respectively. Therefore,
Data are presented as the number (%) of patients. ECPR, extracorporeal country- or ethnicity-specific differences may explain the different
cardiopulmonary resuscitation; TIMI, thrombolysis in myocardial infarction. causes of sudden cardiac death.

The resistance factors for conventional CPR in OHCA

Table 5
Comparing the non-ECPR and ECPR groups with acute ischemic heart disease,
To our best knowledge, this is the first study to report the
according to their TIMI grade.
baseline characteristics, pre-hospital records, and causes of CPA in
All Non-ECPR ECPR p-Value patients with witnessed OHCA and shockable initial cardiac
(n = 74) (n = 51) (n = 23)
rhythm, and to evaluate their relationship with conventional
Acute IHD with TIMI grade 0–1 45 (61) 25 (49) 20 (87) 0.002 CPR resistance. Because the ROSC rate from ventricular fibrillation
Acute IHD with TIMI grade 2–3 29 (39) 26 (51) 3 (13) decreases with increasing collapse-to-shock time [23], we only
Data are presented as the number (%) of patients. ECPR, extracorporeal included cases with witnessed OHCA and shockable initial cardiac
cardiopulmonary resuscitation; IHD, ischemic heart disease; TIMI, thromboly- rhythm. Nevertheless, 33% of our patients received antiarrhythmic
sis in myocardial infarction.
drugs in the field and our observed ROSC rate with conventional
CPR was 67%; these findings are similar to those of previous reports
[24,25]. However, in the non-ECPR group, most patients (92%)
significantly higher in the ECPR group (p = 0.03), and (3) achieved ROSC in the field and there is a possibility that the use of
continuous myocardium ischemia was related to conventional antiarrhythmic drugs in the field is useful for achieving ROSC in the
CPR resistance. field. Although patients with and without bystander-initiated CPR
were included, this factor was not set as an inclusion criterion, as
Causes of CPA the quality of CPR cannot be retrospectively assessed. In addition,
we did not set any age restrictions, as we perform CAG and ECPR for
In this study, 125 of the 143 patients (87%) underwent CAG, patients of all ages if they were in good condition before the CPA.
which revealed the cause of the CPA in 113 patients (79%). Among When we compared the ECPR and non-ECPR groups, the only
the 125 included cases, the causes of CPA were cardiac-related in significant differences were in the number of shocks and the rate of
109 patients [87%, including 66 (53%) AMI cases]; the exceptions adrenaline and antiarrhythmic drug use in the field. In the ECPR
were aortic dissection (2 patients), accidental hypothermia cases, the median time from first shock to hospital arrival was
(2 patients), and unknown etiologies (12 patients). However, the approximately 30 min and the median number of shocks was
results of this study cannot be easily compared to those of previous 5. This number of shocks was relatively low, compared to the
reports, because the previous studies had patient populations that duration of CPA, because there were cases that developed non-
were limited to patients with refractory shockable cardiac rhythm shockable rhythm after defibrillation. Although bystander-initiat-
[8] or not exclusively limited to patients with shockable initial ed CPR is a predictor of ROSC [26], we did not observe a significant
cardiac rhythm [15–19]. Nevertheless, the reported incidences of intergroup difference; this discrepancy may be related to our small
AMI are 36–61% [8,15–19], which is similar to our finding. In this sample size. Among the patients with AMI, TIMI grade 0–1 was
study, we diagnosed AMI exclusively based on CAG findings, significantly more common during the initial shot CAG in the ECPR
because clinical and ECG findings are poor predictors of AMI in group (p = 0.03), which indicated that ROSC and coronary
166 T. Otani et al. / Journal of Cardiology 68 (2016) 161–167
recanalization were related. Therefore, we divided patients with
acute IHD (AMI and coronary vasospasm) into two groups using
their TIMI grade, and compared the patients with and without
ECPR. Interestingly, acute IHD with TIMI grade 0–1 was
significantly more common in the ECPR group (p = 0.002).
Ventricular fibrillation can be complicated with acute IHD after
coronary artery occlusion and after recanalization [27]. Therefore,
our findings may explain that ventricular fibrillation after
recanalization is easier to achieve ROSC than ventricular fibrilla-
tion after coronary artery occlusion. However, the results of
previous similar studies are not consistent. For example, Kagawa
et al. reported a frequency of 80% (65/81 cases) for AMI with TIMI
grade 0–1 in ECPR cases [7]. In contrast, Spaulding et al. and Garcia-
Tejada et al. reported frequencies of 67% (40/67 cases) and 90% (44/
49 cases), respectively, for AMI with TIMI grade 0–1 in non-ECPR
cases [15,16]. Nevertheless, these studies are difficult to compare,
given the differences in study population (e.g. not exclusively
limited to patients with shockable initial cardiac rhythm) and the
small sample sizes.
We observed a relationship between ROSC and recanalization,
although only 59% of our patients had acute IHD and 56% of
patients with acute IHD and TIMI grade 0–1 achieved ROSC via
conventional CPR. In addition, there were no significant differences
in the characteristics or medical histories of patients with and
without ECPR, except for their number of shocks and use of
adrenaline and antiarrhythmic drugs in the field. Therefore, it is
likely that continuous myocardium ischemia was not the only
factor that affected conventional CPR resistance, and further
studies are needed to identify the additional factor(s).
Comparing our findings to previous Japanese reports of OHCA
Compared to previous Japanese reports of OHCA [3,28], the
frequency of patients with a shockable initial cardiac rhythm was
about the same (15.4–16.2%). We observed a shorter ‘call to first
shock’ time, although this may be related to our institution’s inner
city location and good traffic access. However, our ‘call to arrival’
time was longer than that in previous studies [3,8]. This difference
is likely because of our use of the doctor car system to provide
advanced resuscitation treatment (e.g. administer antiarrhythmic
drugs). Nevertheless, the early medical staff involvement allowed
us to gather more detailed pre-hospital information, which
resulted in our ‘call to initiation of ECMO’ time being the same
as that in previous reports [7].
Limitations
There are several limitations in this study. First, this study used
a retrospective design with a relatively small sample size. Second,
although all of our patients had witnessed OHCA and the ‘collapse
to call’ time was short, the witnesses generally did not remember
the exact time of the collapse, which prevented us from reporting
the ‘collapse to call’ time. Third, we calculated the time courses as
from the ‘‘call’’ for patients who collapsed before the EMS arrival,
compared to from the ‘‘collapse’’ for patients who collapsed after
the EMS arrival. Fourth, selection bias is possible, as the type and
dose of the antiarrhythmic drugs were not the same in all cases.
Finally, not all of the patients with witnessed OHCA and shockable
initial cardiac rhythm underwent CAG, and 12 patients in our
analysis were undiagnosed.
Conclusions
The major cause of witnessed OHCA with shockable initial
cardiac rhythm was AMI, and resistance to conventional CPR
appears to be related to continuous myocardium ischemia.
Funding
This research received no grant from any funding agency in the
public, commercial, or not-for-profit sectors.
Conflicts of interest
The authors declare that there is no conflict of interest.
Acknowledgment
We thank Editage (www.editage.jp) for English language
editing.
References
[1] Nichol G, Thomas E, Callaway CW, Hedges J, Powell JL, Aufderheide TP, Lowe R,
Brown T, Rea T, Dreyer J, Davis D, Idris A, Stiell I. Regional variation in out-of-
hospital cardiac arrest incidence and outcome. JAMA 2008;300:1423–31.
[2] Japan Resuscitation Council. Japan Resuscitation Council guidelines 2010. 1st
ed. Tokyo: Health Shuppansha; 2010 [In Japanese].
[3] Kitamura T, Iwami T, Kawamura T, Nitta M, Nagao K, Nonogi H, Yonemoto N,
Kimura T. Nationwide improvements in survival from out-of-hospital cardiac
arrest in Japan. Circulation 2012;126:2834–43.
[4] Iwami T, Nichol G, Hiraide A, Hayashi Y, Nishiuchi T, Kajino K, Morita H, Yukioka
H, Ikeuchi H, Sugimoto H, Nonogi H, Kawamura T. Continuous improvements in
chain of survival increased survival after out-of-hospital cardiac arrests: a large-
scale population-based study. Circulation 2009;119:728–34.
[5] Shinada T, Hata N, Yokoyama S, Kobayashi N, Tomita K, Shirakabe A, Tsurumi M,
Okazaki H, Yamamoto Y. Usefulness of a surface cooling device (Arctic Sun1) for
therapeutic hypothermia following cardiac arrest. J Cardiol 2014;63:46–52.
[6] Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out-of-
hospital cardiac arrest: a systematic review and mete-analysis. Circ Cardiovasc
Qual Outcomes 2010;3:63–81.
[7] Kagawa E, Dote K, Kato M, Sasaki S, Nakano Y, Kajikawa M, Higashi A, Itakura K,
Sera A, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Kurisu S. Should we
emergently revascularize occluded coronaries for cardiac arrest?: rapid-re-
sponse extracorporeal membrane oxygenation and intra-arrest percutaneous
coronary intervention. Circulation 2012;126:1605–13.
[8] Sakamoto T, Morimura N, Nagao K, Asai Y, Yokota H, Nara S, Hase M, Tahara Y,
Atsumi T. Extracorporeal cardiopulmonary resuscitation versus conventional
cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: a
prospective observation study. Resuscitation 2014;85:762–8.
[9] Cave DM, Gazmuri RJ, Otto CW, Nadkarni VM, Cheng A, Brooks SC, Daya M, Sutton
RM, Branson R, Hazinski MF. Part 7: CPR techniques and devices: 2010 American
Heart Association guidelines for cardiopulmonary resuscitation and emergency
cardiovascular care. Circulation 2010;122(18 Suppl. 3):S720–8.
[10] Thygesen K, Alpert JS, White HD, Jaffe AS, Apple FS, Galvani M, Katus HA,
Newby LK, Ravkilde J, Chaitman B, Clemmensen PM, Dellborg M, Hod H, Porela
P, Underwood R, et al. Universal definition of myocardial infarction. Circula-
tion 2007;116:2634–53.
[11] TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial.
Phase I findings. N Engl J Med 1985;312:932–6.
[12] JCS Joint Working Group. Guidelines for diagnosis and treatment of patients
with vasospastic angina (coronary spastic angina) (JCS 2013). Circ J 2014;78:
2779–801.
[13] Felker GM, Shaw K, O’Connor CM. A standardized definition of ischemic cardio-
myopathy for use in clinical research. J Am Coll Cardiol 2002;39:210–8.
[14] Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnettt D, Moss AJ,
Seidman CE, Young JB. Contemporary definitions and classification of the
cardiomyopathies: an American Heart Association scientific statement from
the council on clinical cardiology, heart failure and transplantation commit-
tee; quality of care and outcomes research and functional genomics and
translational biology interdisciplinary working groups; and council on epide-
miology and prevention. Circulation 2006;113:1807–16.
[15] Spaulding CM, Joly LM, Rosenberg A, Monchi M, Weber SN, Dhainaut JF, Carli P.
Immediate coronary angiography in survivors of out-of-hospital cardiac ar-
rest. N Engl J Med 1997;336:1629–33.
[16] Garcia-Tejada J, Jurado-Román A, Rodrı́guez J, Velázquez M, Hernández F,
Albarrán A, Martı́n-Asenjo R, Granada-Nistal C, Coma R, Tascón J. Post-resus-
citation electrocardiograms, acute coronary findings and in-hospital prognosis
of survivors of out of hospital cardiac arrest. Resuscitation 2014;85:1245–50.
[17] Dumas F, Cariou A, Manzo-Silberman S, Grimaldi D, Vivien B, Rosencher J,
Empana JP, Carli P, Mira JP, Jouven X, Spaulding C. Immediate percutaneous
coronary intervention is associated with better survival after out-of-hospital
cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital
Cardiac ArresT) registry. Circ Cardiovasc Interv 2010;3:200–7.
[18] Zanuttini D, Armellini I, Nucifora G, Grillo MT, Morocutti G, Carchietti E, Trilló
G, Spedicato L, Bernardi G, Proclemer A. Predictive value of electrocardiogram
in diagnosing acute coronary lesions among patients with out-of-hospital-
cardiac-arrest. Resuscitation 2013;84:1250–4.
 T. Otani et al. / Journal of Cardiology 68 (2016) 161–167
[19] Sideris G, Voicu S, Dillinger JG, Stratiev V, Logeart D, Broche C, Vivien B, Brun
PY, Deye N, Capan D, Aout M, Megarbane B, Baud FJ, Henry P. Value of
post-resuscitation electrocardiogram in the diagnosis of acute myocardial
infarction in out-of-hospital cardiac arrest patients. Resuscitation 2011;82:
1148–53.
[20] Yamashina Y, Yagi T, Ishida A, Mibiki Y, Sato H, Nakagawa T, Sato E, Komatsu J.
Differentiating between comatose patients resuscitated from acute coronary
syndrome-associated and subarachnoid hemorrhage-associated out-of-hos-
pital cardiac arrest. J Cardiol 2015;65:508–13.
[21] Røsjø H, Vaahersalo J, Hagve TA, Pettilä V, Kurola J, Omland T. Prognostic value
of high-sensitivity troponin T levels in patients with ventricular arrhythmias
and out-of-hospital cardiac arrest: data from the prospective FINNRESUSCI
study. Crit Care 2014;18:605.
[22] Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhyth-
mias. N Engl J Med 2001;345:1473–82.
[23] Larsen MP, Eisenberg MS, Cummins RO, Hallstorm AP. Predicting survival from
out-of-hospital cardiac arrest: a graphic model. Ann Emerg Med 1993;22:
1652–8.
167
[24] Cobb LA, Fahrenbruch CE, Walsh TR, Copass MK, Olsufka M, Breskin M,
Hallstrom AP. Influence of cardiopulmonary resuscitation prior to defibrilla-
tion in patients with out-of-hospital ventricular fibrillation. JAMA 1999;281:
1182–8.
[25] Wik L, Hansen TB, Fylling F, Steen T, Vaagenes P, Auestad BH, Steen PA.
Delaying defibrillation to give basic cardiopulmonary resuscitation to patients
with out-of-hospital ventricular fibrillation: a randomized trial. JAMA
2003;289:1389–95.
[26] Hollenberg J, Herlitz J, Lindqvist J, Riva G, Bohm K, Rosenqvist M, Svensson L.
Improved survival after out-of-hospital cardiac arrest is associated with an
increase in proportion of emergency crew-witnessed cases and bystander
cardiopulmonary resuscitation. Circulation 2008;118:389–96.
[27] Kaplinsky E, Ogawa S, Michelson EL, Dreifus LS. Instantaneous and delayed
ventricular arrhythmias after reperfusion of acutely ischemic myocardium:
evidence for multiple mechanisms. Circulation 1981;63:333–40.
[28] SOS-KANTO Committee. Incidence of ventricular fibrillation in patients with
out-of-hospital cardiac arrest in Japan: survey of survivors after out-of-hos-
pital cardiac arrest in Kanto area (SOS-KANTO). Circ J 2005;69:1157–62.