328 Targetting sudden cardiac death: improving prediction
identified in the pre-hospital setting, easy to obtain by a non physician phone
dispatcher. The identification of those SCD predictors could allow a quicker inter-
vention and a faster resuscitation on high risk patients.
1741 | BENCH
Nationwide study on sudden cardiac death in Danes aged 1-49
years
B. Risgaard
1
,B.G.Winkel
1
, R. Jab bari
1
, O. Ingemann-Hansen
2
, J.L. Thomsen
3
,
G.L. Ottesen
4
, H. Bundgaard
1
, S. Hausoe
1
,A.G.Holst
1
, J. Tfelt-Hansen
1
.
1
Rigshospitalet, Laboratory of Molecular Cardiology, Department of Cardiology,
The Heart Centre, 2142, Copenhagen, Denmark;
2
Department of Forensic
Medicine, Aarhus University, Aarhus, Denmark;
3
Institute of Forensic Medicine,
University of Southern Denmark, Odense, Denmark;
4
Department of Forensic
Medicine, University of Copenhagen, Copenhagen, Denmark
Purpose: Incidence rates and causes of sudden cardiac death (SCD) in the
young have varied markedly in previous studies. The aim of this first nationwide
study was to identify the causes of SCD in persons aged 1-49 years and to esti-
mate the incidence rate using both autopsied and non-autopsied cases.
Methods: All deaths in persons aged 1-49 years in 2007-2009 were included
(population 3.4 million). Death certificates were reviewed independently and SCD
cases were identified. We defined SCD in autopsied cases as the sudden, nat-
ural unexpected death of cardiac or unknown cause; in unwitnessed cases as a
person last seen alive and functioning normally <24 h and in witnessed cases
as an acute change in cardiovascular status with time to death being <1h.In
non-autopsied cases the same criteria were used in cases presumed to be of
cardiac cause. The highest possible incidence of SCD was calculated using both
autopsied and non-autopsied cases.
Results: In the 3-year study-period there were 7,849 deaths of which we identi-
fied 1,039 (13%) presumed SCDs, of which 585 (56%) were autopsied. Autopsies
showed that death was non-cardiac in 146 cases. Hence, we identified 439 au-
topsied SCDs and 454 non-autopsied SCDs. The most common cardiac cause
of death was ischaemic heart disease (IHD) (n=158, 36%). In 136 cases (31%)
death was unexplained (SUD) after autopsy with fatal arrhythmia being the pre-
sumed cause of death. The SCD incidence was 8.6 per 100,000 person-years
using both autopsied and non-autopsied cases. For age distribution, see figure.
Distribution of 893 SCDs aged 1-49
Conclusion: This is the first nationwide study describing the highest possible
incidence of SCD in persons aged 1-49 years. We report a incidence of SCD of
8.6 per 100,000 person-years with IHD and SUD being the most common causes
of SCD
1742 | BEDSIDE
Systematic assesment of patients with unexplained cardiac arrest:
results from the FIVI-Gen study
J. Jimenez Jaimez
1
, R. Peinado
2
, E. Zorio Grima
3
,J.R.Gimeno
4
, F. Segura
5
,
F. Mazuelos
6
, P. Morinas
7
, M. Alvarez
1
, L. Montserrat
8
, L. Tercedor
1
on behalf
of FIVI-Gen Study Group.
1
University Hospital Virgen de las Niev es, Granada,
2
University Hospital La Paz, Madrid,
3
Hospital La Fe, Valencia,
4
University
Hospital Virgen de la Arrixaca, Murcia,
5
Insular Hospital, Las Palmas De Gran
Canaria,
6
University Hospital Reina Sofia, Cordoba,
7
Hospital Juan Ramon
Jimenez, Huelva,
8
Health in Code SL, La Coruna, Spain
Background and objectives: Idiopathic Ventricular Fibrillation (IVF) is a rare
entity that might be due to subclinical underlying cardiomyopathies and chan-
nelopathies of genetic origin. We aim to assess the diagnostic yield of a novel
systematic protocol in patients with IVF.
Methods: IVF was defined as sustained VF episode which required external de-
fibrillation, and with no pathological findings in basal electrocardiogram (EKG),
echocardiogram, and coronary angiography. The diagnostic protocol consisted of
three sequential steps: 1.- pharmacological tests with epinephrine and flecainide;
2.- first and second-degree relatives assesment with EKG and echocardiogram
and 3.- genetic testing with ne xt-generation sequencing method including 126
genes for cardiomyopathies and channelopathies.
Results: Twenty three probands (69,6% males, mean age 40,5±14,5 years) and
87 first and second degree relatives from 7 spanish centres were assesed. Final
diagnosis was obtained in 17 probands/families (73,9%). The most prevalent un-
derlying etiology was Brugada Syndrome (30,4%), followed by Cathecolaminergic
P olymorphic Ventricular Tachycardia (17,3%) and Long QT syndrome (13%). The
way to reach the diagnosis and cumulative diagnostic rate of each sequential step
of the protocol is summarized in table 1.
Table 1. Diagnostic yield of each sequential step of the protocol
First step Second step Third step Total
(Ph tests) (Familial screening) (Gene test)
Brugada S 4 2 1 7
Long QT 1 0 2 3
Short QT 0 1 0 1
CPVT 1 0 3 4
HCM 0 0 1 1
AC 0 0 1 1
Cumulative diagnosis (%) 6/23 (26,1%) 3/23 (13,0%) 8/23 (34,8%) 17/23 (73,9%)
CPVT, Cathecolaminergic P olymorphic Ventricular Tachycardia; HCM, Hypertrophic Cardiomy-
opathy; AC, Arrhythmogenic Cardiomyopathy.
Conclusions: In patients with IVF the systematic application of a protocol that
included next-generation sequencing rendered a definitive diagnosis in almost
three-fourths of the cases. As expected, cardiac channelopathies were the main
hidden etiology, but there were also cardiomyopathies with no e xpression in the
EKG and imaging tests.
1743 | BEDSIDE
Incidence, characteristics and outcome of sudden cardiac death in
France
W. Bougouin
1
, L. Lamhaut
2
, E. Marijon
1
,D.Jost
1
, E. Chazelle
1
,H.Mustafic
1
,
F. D u m a s
3
,N.Deye
4
, X. Jouven
1
,A.Cariou
1
on behalf of CEMS investigators.
1
Inserm U970 - Paris Cardiovascular Research Center (PARCC), Cardiovascular
Epidemiology-Sudden Death, Paris, France;
2
AP-HP - Hospital Necker, SAMU
75, Paris, France;
3
AP-HP - Hospital Cochin, Department of Emergency, P aris,
France;
4
AP-HP - Hospital Lariboisiere, Paris, France
Purpose: Sudden Cardiac Death (SCD) is a major public health concern, but the
actual epidemiology of SCD in Western European countries remains unclear. This
study reports the results of a large registry to assess the incidence, prognostic
factors, and outcomes of SCD in F rance.
Methods: A population-based registry was established in Ma y 2011 using mul-
tiple sources to collect every case of SCD in Paris and its suburbs, a population
of 6.6 million. Both pre-hospital and in-hospital courses were considered, and the
main outcome was survival at hospital discharge. Neurologic status at discharge
was established.
Results: Over one year, 1,903 cases of SCD were included. The annual inci-
dence was 44/100,000 persons per year. Most cases occurred at home (72%)
with bystanders in 81% of cases, performing CPR in 42% of cases. Initial rhythm
was shockable in 23% of cases. 635 patients (33%) were admitted alive to hos-
pital. Among hospitalized patients, 58% had coronary angiogram, and 58% had
therapeutic hypothermia. Finally, 129 patients (6.8%) were discharged alive, of
whom 94% had favorable neurological outcome. Prognostic factors were initial
shockable rhythm (OR=15.7, 95%IC 9.0–27.3), age (OR=0.96, 95%IC 0.95–
0.98), occurrence at home (OR=0.5, 95%IC 0.3–0.8), and epinephrine dose
greater than 3 mg (OR=0.07, 95%IC 0.04–0.1). Among hospitalized patients, pa-
tients who received both therapeutic hypothermia and coronary angiogram had
better survival (32% vs. 13%, P<0.001).
Outcome of sudden cardiac death
Conclusion: In F rance, incidence of SCD is lower than previously described, but
prognosis remains poor. Prognostic factors are initial rhythm, age, occurrence at
home, and epinephrine dose. Therapeutic hypothermia and early coronary an-
giogram are significantly associated with survival, but applied in only half of pa-
tients.
1744 | BEDSIDE
Prehospital factors associated with favorable neurological
outcomes in out-of-hospital cardiac arrest patients without a
prehospital return of spontaneous circulation
Y. G o t o
1
, T. Maeda
1
,Y.Goto
2
.
1
Kanazawa University Hospital, Section of
Emergency Medicine, Kanazawa, Japan;
2
Yawata Medical Center, Department
of Cardiology, Komatsu, Japan
Purpose: Obtaining fa vorable neurological outcomes is extremely difficult in Out-
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Targetting sudden cardiac death: improving prediction / Role of the nucleus and mitochondria in heart failure 329
of-Hospital Cardiac Arrest (OHCA) patients transported to hospitals without a pre-
hospital return of spontaneous circulation (ROSC). The crucial prehospital factors
for long-term survival with meaningful outcomes in this unique cohort remain elu-
sive. This study aimed to determine prehospital factors with significant impacts on
long-term survival and favorable neurological outcomes (cerebral performance
category scale, category 1 or 2 [CPC 1–2]) in patients transported to hospitals
without a prehospital ROSC after OHCA.
Methods: Of 461,633 OHCA patients, 398,121 adults (age, > or = 18 years;
86.2% of total) in whom resuscitation was attempted, but without a prehospi-
tal ROSC, were eligible for enrolment into the present study. These patients
were analyzed using a prospectively recorded nationwide Utstein-style Japanese
database for 4 years (2007–2010). The endpoints were survival and CPC 1–2 at
1 month after the cardiac arrest. As Emergency Medical Services (EMS) person-
nel in Japan are legally prohibited from terminating resuscitation in the field, most
OHCA patients receive resuscitation from EMS providers and are transported to
hospitals.
Results: The over all rates of 1-month survival and CPC 1–2 were 1.89% (n =
7532) and 0.49% (n = 1957), respectively. Multivariate logistic regression analysis
for 21 variables revealed that the following independent factors had significant
impacts on the probability of 1-month survival: initial ventricular fibrillation (VF)
rhythm (adjusted odds ratio [OR], 5.50; 95% confidence interval (CI), 4.96–6.10),
witnessed arrest (OR, 2.15; 95% CI, 2.04–2.28), call-to-hospital arrival time <
24 min (OR, 3.19; 95% CI, 2.93–3.46), and age < 65 years (OR, 2.12; 95% CI,
1.97–2.30). The multivariate logistic regression analysis also indicated that the
independent variables significantly associated with 1-month CPC 1–2 were as
follows: initial VF rhythm (OR, 9.37; 95% CI, 7.71–11.4), age < 65 years (OR,
3.90; 95% CI, 3.28–4.67), EMS-witnessed arrest (OR, 2.82; 95% CI, 2.48–3.19),
and call-to-hospital arrival time < 24 min (OR, 2.58; 95% CI, 2.22–3.01).
Conclusions: The crucial prehospital factors for survival at 1 month after cardiac
arrest were initial VF rhythm followed by witnessed arrest, call-to-hospital arrival
time < 24 min, and age < 65 years in patients transported to hospitals without
a prehospital ROSC after OHCA. These survivors, especially patients with EMS-
witnessed arrest, could obtain long-term meaningful outcomes.
ROLE OF THE NUCLEUS AND MITOCHONDRIA IN
HEART FAILURE
1752 | BENCH
MicroRNA-208a increases myocardial fibrosis via endoglin in
volume overload heart
K.G. Shyu, B.W. Wang.
Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
Aim: MicroRNA-208a (mir-208a) is essential for cardiac h ypertrophy and fibrosis.
Endoglin, a co-receptor of transforming growth factor-b is also essential for car-
diac fibrosis. Endoglin has been shown to be a target of mir-208a in the in vitro
mechanical stress model. V olume overload can lead to heart failure and cardiac
fibrosis. The role of mir-208a and endoglin in volume overload heart failure is not
well known. W e sought to investigate the mechanism of regulation of mir-208a
and endoglin in volume overload-induced heart failure.
Methods: Aorto-Caval (AV) shunt was performed in adult Sprague-Dawley rats
to induce volume ov erload. Echocardiography was used to measure heart size.
TaqMan
®
MicroRNA real-time quantitative assay was used to quantitate mir-208a.
Myocardial fibrosis was detected by immunohistochemistry.
Results: Heart weight and heart weight/body weight ratio significantly increased
in AV shunt animals. AV shunt significantly increased left ventricular end-diastolic
dimension as compared to sham group. Mir-208a was significantly induced by
AV shunt from 3 to 14 days. Endoglin, myosin heavy chain-b and brain natriuretic
peptide were significantly induced by AV shunt from 3 to 14 days . Overexpression
of mir-208a in the sham group without AV shunt significantly increased endoglin
expression similar to the AV shunt group. Antomir-208a attenuated the endoglin
expression induced by AV shunt. Pretreatment with atorvastatin also attenuated
the endoglin expression induced by AV shunt. AV shunt significantly increased
myocardial fibrosis as compared to sham group. Overexpression of mir-208a
in the sham group significantly increased my ocardial fibrosis. Antagomir-208a
and atorvastatin significantly attenuated the myocardial fibrosis induced by AV
shunt.
Conclusions: Mir-208a increased endoglin e xpression to induce myocardial fi-
brosis in volume overloaded heart failure. Treatment with atorvastatin can atten-
uate the myocardial fibrosis induced by volume overload through inhibition of en-
doglin expression.
1753 | BENCH
Galectin-3 signaling pathway is modulated by mineralocorticoid
receptor antagonists in chronic heart failure
M.C. Asensio-Lopez
1
,A.Lax
1
, D.A. Pascual-Figal
1
, M.J. Fernandez-Del
Palacio
2
, G. Santarelli
2
, S. Abenza
1
,L.Caballero
1
, M.T. Perez-Martinez
1
,
M. Valdes-Chavarri
1
, J. Sanchez-Mas
1
.
1
University Hospital Virgen De La
Arrixaca, Murcia, Spain;
2
Department of Animal Medicine and Surgery, Murcia,
Spain
Purpose: Galectin-3 (Gal-3) plays an active role in the dev elopment of cardiac
fibrosis, inflammation and remodeling in heart failure (HF). Higher concentration
of Gal-3 is associated with worse prognosis, increased risk for incident HF and
mortality. Although the anti-inflammatory and anti-fibrotic properties of mineralo-
corticoid receptor antagonists (MRAs) are documented in heart failure context,
the involved mechanisms have not been well elucidated. Thi study aimed to ana-
lyze whether MRAs modulate the Gal-3 signaling in an experimental model of HF
and their association with cardiac remodeling.
Methods: Myocardial infarction (MI) was induced by ligation of the left anterior
descending coronary in 56 male Wistar rats (200-270 g). Animals were randomly
assigned to not receive treatment (MI group, n=12) or to receive a MRA from the
day of surgery and for 4 weeks, either eplerenone (Eple, n=18) or spironolactone
(Spiro, n=18) at the dose of 100 mg/kg/day. A sham group was used as control
(n=8). The modulation of Gal-3 expression and the involvement of TGF-β/Smad3
signaling pathway were e valuated by quantitative RT-PCR in the infarcted area
of the left ventricle. Markers of cardiac fibrosis (collagen I, collagen III, TIMP1)
and inflammation (IL-6, TNFα) were also analyzed by RT-PCR. Each value is
expressed as fold of control.
Results: Compared to sham group, Gal-3 expression was induced in the in-
farcted area of MI rats (53.7, p<.001). The expression levels of TGF-β and
Smad3, molecules involved in Gal-3 signaling, were also higher in the MI group
(7.8, p<.001 and 6.7, p=.012, respectively) and correlated with Gal-3 (p<0.001
for both). In addition, Gal-3 correlated with markers of fibrosis as collagen I
(p<0.001), collagen III (p=0.41) and TIMP1 (p<0.001); and markers of inflamma-
tion as IL-6 (p<0.001) and TNFα (p<0.001). Gal-3 expression was reduced by
the treatment with either Eple (10.9, p=.04) or Spiro (12.4, p=.047); but only Eple
was able to reduce TGF-β (2.9, p=.012) and Smad3 (1.1, p=.017). The treatment
with either Eple or Spiro significantly reduced the expression level of collagen I
(12.9, p=.016 and 8.5, p=.008; respectively), collagen III (6.4, p=.003 and 2.8,
p=.019) and TIMP1 (17.5, p=.003 and 22.5, p=.02). Eple, but no Spiro, reduced
expression level of TNFα (2.5, p=.01), whereas IL-6 was not affected.
Conclusions: This study shows for the first time the modulating role of MRAs
on Gal-3 cardiac expression and suggests that the inhibition of Gal-3 expression
may be an important mechanism involved in the anti-fibrotic effect of MRAs in the
context of postinfarction HF.
1754 | BENCH
Cardiac overexpression of Translationally Controlled Tumor
Protein (TCTP) prevents the development of doxorubicin-induced
heart failure
T. Fujita, W. Cai, Y. Hidaka, H. Jin, M. Jin, K. Suita, Y. Ishikawa.
Yokohama City
University, Yokohama, Japan
Objectives: Do xorubicin (DOX) is one of the widely used chemotherapeutic
agents for cancer therapy. However, its clinical usage has been limited by its
serious cardiotoxicity. p53 induced apoptosis and production of reactive o xygen
species (ROS) have been reported to contribute to the cardiotoxicity. Recent re-
ports rev ealed that translationally controlled tumor protein (TCTP), one of the
anti-apoptotic proteins, binds to p53 and inhibits its function. In addition, TCTP is
reported to protect cells from oxidative stress induced cell death. On the basis of
these findings, we hypothesize that cardiac overexpression of TCTP prev ents the
development of DOX-induced heart failure.
Methods and results: We generated TCTP transgenic (TG) mice in which a car-
diac specific alpha-myosin heavy chain (MHC) promoter drives TCTP expression.
After intraperitoneal injections of DOX (24 mg/kg cumulative dose), we assessed
cardiac function by echocardiography and cardiac catheterization. The baseline
cardiac function indices including left ventricular ejection fraction (LVEF), LV dP/dt
max and LV dP/dt min were similar in wild type (WT) and TG mice. However,
DOX-induced cardiac dysfunction was significantly attenuated in TCTP TG mice
compared with WT mice. (LVEF: 62.0±1.7% in WT, 66.9±1.5% in TG, P<0.05, LV
dP/dt max: 7646±606 mmHg/sec in WT, 10303±1644 mmHg/sec in TG, P<0.05)
In rat neonatal cardiomyocytes, down-regulation of TCTP by siRNA resulted in in-
creased production of ROS (∼1.6 fold higher than control siRNA-treated cells,
P<0.05) and lower cell viability (∼20% lower than control siRNA-treated cells,
P<0.05) after treatment of DOX. In addition, the increase of ROS production was
not observed in the presence of p53 inhibitor (pifithrin-alpha).
Conclusions: These findings indicate that cardiac overexpression of TCTP pro-
tects against DOX-induced cardiotoxicity. Inhibitory effect of TCTP on p53 depen-
dent ROS production ma y be involved in the mechanism.
1755 | BENCH
The GLP-1 analogue liraglutide decreases the pro-inflammatory
status of the heart in diabetes
R.W. Emmens
1
,U.Baylan
1
, B. Naaijkens
1
, C.G. Schalkwijk
2
, H.W.M. Niessen
1
,
P.A.J. Kr ijnen
1
,S.Simsek
3
.
1
VUmc, Amsterdam, Netherlands;
2
Maastricht
University, CARIM, Department of Internal Medicine, Maastricht, Netherlands;
3
Medical Center Alkmaar , Alkmaar, Netherlands
Background: Diabetes mellitus (DM) induces cardiac complications in which ad-
vanced glycation endproducts (AGE) play an important role. Previously, we have
found that the AGE product N-epsilon-carboxymethyl lysine (CML) forms deposi-
tions in intramyocardial arteries both in advance of and subsequent to myocardial
infarction. It has been h ypothesized that CML can be formed by reactive oxygen
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