REVIEW

CURRENT
OPINION The challenge of cardiomyopathies and heart
failure in pregnancy
Giuseppe Limongelli a,b,c,d, Marta Rubino a,b, Augusto Esposito a,b,
Mariagiovanna Russo a, and Giuseppe Pacileo b

Purpose of review
To discuss the risk preexisting or new onset cardiomyopathy/heart failure (CMP/heart failure) in pregnant
woman, and recent insights regarding their management and therapy.
Recent findings
Recent data from the European Registry on Pregnancy and Heart disease of the European Society of
Cardiology (ROPAC) suggest that, after an adequate prepregnancy evaluation in specialized centres, the
vast majority of pregnancies are safe for both mother and foetus. A tailored approach is required
according to cardiac phenotype (i.e. type of cardiomyopathy), clinical and functional status, and new
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potential treatments (i.e. bromocriptine in patients with peripartum cardiomyopathy).

Summary
In clinical practice, prepregnancy cardiac evaluation is mandatory, including evaluation of the clinical
status, standard ECG (and 24–48 h monitoring, whenever required), and imaging, to define the individual
risk profile. In presence of severe symptoms (advanced New York Heart Association class), cardiac
dysfunction (moderate–severe reduced ejection fraction), haemodynamic load (left ventricular outflow tract
obstruction, pulmonary hypertension), pregnancy is contraindicated. A tailored monitoring is warranted in
other cases (mild–moderate risk pregnancies). Likewise, in women who develop PPCM, a risk stratification
and tailored monitoring and therapy should be achieved by an expert, multidisciplinary team, including
cardiologists, gynaecologists, obstetricians, genetic counsellor, and psychologists.
Keywords
arrhythmias, cardiomyopathies, heart failure, pregnancy

INTRODUCTION for both mother and foetus (Fig. 1). Nevertheless,

Haemodynamics during pregnancy, labor and deliv-
ery is characterized by significant changes in fluid
circulation (cardiac and blood volume increase),
haematology (hypercoagulable state, anaemia), pul-
monary function (increased tidal volume), hormone
state (increased cortisol, oestrogen, and Renin Angio-
tensin Aldosterone System) and autonomic nervous
system (increased heart rate) [1,2]. These changes
may favor cardiac complications, especially in pres-
ence of preexisting heart disease. Albeit cardiac
disease is present in a minority of pregnant women
(0.5–1%), cardiac disease is the most common cause
of death among pregnant women in the developed
world [3–5]. Recent data from the European Registry
on Pregnancy and Heart disease of the European
Society of Cardiology (Registry Of Pregnancy And
Cardiac disease, ROPAC) showed that, after an
adequate prepregnancy evaluation in specialized
centres, the vast majority of pregnancies are safe
pregnancy outcomes were markedly worse, in devel-
oping countries, particularly in patients with cardio-
myopathies [6].
In this review, we discuss the risk of preexisting
or new onset cardiomyopathy/heart failure (CMP/
HF) in pregnant woman, and recent insights regard-
ing their management and therapy.
a
Pediatric Cardiology, Department of Translational Medical Sciences,
Luigi Vanvitelli University, bHeart Failure Unit, AORN Colli, Naples, Italy,
c
Institute of Cardiovascular Sciences, University College of London-
London, UK and dMember of the GUARD Heart ERN (European Refer-
ence Network)
Correspondence to Giuseppe Limongelli, Monaldi Hospital, AORN Colli,
Department of Translational Medical Sciences, Luigi Vanvitelli University,
80135 Naples, Italy. Tel: +390817062815;
e-mail: limongelligiuseppe@libero.it
Curr Opin Obstet Gynecol 2018, 30:378–384
DOI:10.1097/GCO.0000000000000496

www.co-obgyn.com Volume 30  Number 6  December 2018

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

 Cardiomyopathies and heart failure in pregnancy Limongelli et al.

arrhythmias and heart failure. Preload, afterload and

KEY POINTS
 Pregnancy may uncover a preexisting heart
muscle disease.
 Prepregnancy clinical status (i.e. NYHA class, signs of
heart failure, moderate–severe systolic/diastolic
function, pulmonary hypertension, arrhythmias) is an
important determinate of outcome in pregnant women
with CMP and heart failure.
 PPCM is a rare cardiomyopathy, with an onset during
the last month of pregnancy or within 5 months of
delivery, and with a high rate of full recovery.
 Bromocriptine, in addition to standard medical therapy for
heart failure, should be considered in patients with PPCM.
 In women with preexisting cardiac disease, individual
counselling, prepregnancy risk assessment and medical
therapy review should be performed by expert teams.
A PREGNANCY WITH CARDIOMYOPATHY
AND/OR HEART FAILURE
Patients with preexisting cardiac disease
Pregnancy may uncover a preexisting heart muscle
disease and/or expose women with cardiomyopa-
thies to an increased risk of complications, including
heart rate variations during gestation determine an
increase in cardiac output of 30–50% and a pro-
longed volume overload, which induces consistent
variations in ventricular geometry (i.e. concentric
remodelling and/or mild eccentric hypertrophy)
[1,2]. These changes are harmless (i.e. adaptive to
pregnancy status) and reversible in healthy woman.
In pregnant women with asymptomatic left ventric-
ular (LV) dysfunction and/or mild LV dilatation and/
or mild LV hypertrophy without LV outflow tract
obstruction, increased hemodynamic stress may
unmask impaired contractile reserve, favour patho-
logical cardiac remodelling, precipitate LV obstruc-
tion, all phenomena that are not apparent ‘at rest’
(i.e. prepregnancy). In these patients, a rapid increase
in heart rate and/or plasma volume can trigger
arrhythmias or precipitate pulmonary oedema [4,5].
The risk of complications can be different for different
cardiomyopathy phenotypes.
In dilated cardiomyopathy (DCM: left ventricu-
lar dilatation, with impaired left ventricular systolic
function) [7], common symptoms, such as dyspnoea
and fatigue, may mimic normal pregnancy-related
symptoms [1,2]. Pregnancy in women with DCM,
moderate-to-severe LV dysfunction or poor func-
tional class, can be associated with adverse outcome
(heart failure and arrhythmias in one of three of

Women with CMP/HF

Women Women without CMP/HF

developing CMP/HF
Pre-Pregnancy Evaluation
(Scores: mWHO - CARPRERG)
Multidisciplinary Team
Management
High Moderate
Low Risk
Risk Risk if other cause
excluded

Contraindication PERIPARTUM
CARDIOMYOPATHY
Multidisciplinary Team
to plan:

to plan:

Tailored Specific Therapy

Risk Stratification
Management (Bromocriptine)
Therapy • Delivery
Periodic Clinical
Evaluation • Breastfeeding
• Postpartum

FIGURE 1. Cardiac management in patients with preexisting and/or new onset cardiomyopathy during pregnancy. CMP,
cardiomyopathy; HF, heart failure.

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Women’s health
total pregnancies), low birth weight and preterm
delivery [8].
Adverse events are more likely to happen in the
later stages of pregnancy, because of the progressively
increased hemodynamic load, and to the fact that
pregnant women discontinue heart failure medica-
tions, because of their known foetal toxicity. Thus,
clinical [New York Heart Association (NYHA) class] and
echocardiographic (systolic and diastolic function)
surveillance should be provided in pregnant women
who were advised to stop Angiotensin Converting
Enzyme (ACE)-inhibitors/angiotensin receptor inhib-
itors (ARBs)/combined angiotensin receptor-neprily-
sin inhibitors (ARNI)[9]. On the other hand, women
with mild LV dysfunction, good functional status, and
no history of cardiac events are more likely to have
successful pregnancy, free from major events [8].
Most pregnant women with hypertrophic car-
diomyopathy (HCM: increased left ventricular
hypertrophy, not solely explained by haemody-
namic load) have mutations in sarcomere protein-
encoding genes that are responsible for the disease
[10]. Pregnancy is generally well tolerated, exclud-
ing a subset of woman with a complicated prepreg-
nancy clinical status, including those with a history
of arrhythmias, significant left ventricular outflow
tract (LVOT) obstruction, or reduced left ventricular
systolic function [11]. Recent data from the Euro-
pean Society of Cardiology initiated Registry of
Pregnancy and Cardiac disease (ROPAC) confirmed
that most women with HCM tolerated pregnancy
well, even though cardiovascular complications
were not uncommon (23% of the overall cohort
of 60 HCM pregnant women; including heart failure
and arrhythmias, particularly in the third trimester
and postpartum period; 5% of emergency caesarean
delivery and 5% of foetal loss; no maternal deaths)
and predicted by prepregnancy status (NYHA >II
&
and prepregnancy signs of heart failure) [12 ].
In AVC, as in other cardiomyopathy phenotypes
(i.e. noncompaction, restrictive cardiomyopathy),
the prepregnancy clinical status (NYHA class, signs
of heart failure, moderate–severe systolic/diastolic
function, pulmonary hypertension, arrhythmias)
are likely to represent the main determinants of
& &
outcome [13,14 ,15,16].
Prevalence and clinical outcome of heart failure
in pregnant women was evaluated by ROPAC inves-
tigators [17]. This observational study, including
60 hospitals in 28 countries, enrolled 1321 women
with different cardiac disease (congenital heart dis-
ease, cardiomyopathies, valvular heart disease,
ischemic heart disease) between 2007 and 2011.
One hundred and seventy-three (13.1%) of the
1321 patients developed heart failure at a median
time of 31 weeks gestation [interquartile range (IQR)
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23–40] with the highest incidence at the end of the
second trimester (34%) or peripartum (31%). Women
with heart failure showed higher maternal mortality
(4.8% in patients with heart failure and 0.5% in those
without heart failure P < 0.001), foetal death and the
incidence of preterm birth (4.6 vs. 1.2%, P ¼ 0.001;
and 30 vs. 13%, P ¼ 0.001) [17]. Risk factors for heart
failure were: New York Heart Association class at least
3, signs of heart failure, WHO category at least 3, CMP
or pulmonary hypertension. Maternal mortality was
higher in patients with heart failure. Preeclampsia
was also strongly related to heart failure [odds ratio
(OR) 7.1, 95% CI 3.9–13.2, P < 0.001] [17].
A more recent study of the ROPAC investigators
evaluated the prevalence and clinical impact of
ventricular arrhythmias in pregnant women. The
study enrolled 2966 woman with different cardiac
disease, and it was conducted from 2007 and 2013,
with 99 participating hospitals in 39 countries. Ven-
tricular arrhythmias occurred in 1.4% of total preg-
nancy, mainly in the third trimester, and they were
often associated with prepregnancy symptomatic
heart disease (NYHA class >1) and heart failure
during pregnancy [18].
Peripartum cardiomyopathy
Peripartum cardiomyopathy (PPCM) is a rare condi-
tion diagnosed in presence of: signs and symptoms
of heart failure during the last month of pregnancy
or within 5 months of delivery; absence of other
causes of heart failure; previous healthy heart and
LV systolic dysfunction (i.e. ejection fraction <45%)
[19]. Incidence of PPCM is regionally different rang-
ing between 1 per 100 in Nigeria, 1 in 299 in Haiti to
1 in 1149–3189 live births in the USA [19–22].
The pathogenesis of PPCM is still a matter of
debate, but genetic predisposition has been recently
proposed by the IPAC investigators [23]. Interest-
ingly, the distribution of truncating variants in a large
series of women with peripartum cardiomyopathy
was similar to that found in patients with idiopathic
dilated cardiomyopathy. Moreover, increased oxida-
tive stress, angiogenesis imbalance, and inflamma-
tory reactions have also been proposed as key features
of the disease [24 ,25–28]. In particular, the antian-
giogenic 16-kDa N-terminal prolactin fragment
(16KDa-PRL), produced by cleavage of the full-length
nursing hormone, prolactin (PRL), by cathepsin D,
has been identified as a potential factor initiating the
disease, and this has been supported by the use of
prolactine blocker, bromocriptine, as a potential
therapy in PPCM [27–28] (Fig. 1).
Risk factors for developing PPCM are age,
history of hypertension (both preexisting and
pregnancy-induced), preeclampsia, multiparity,
Volume 30  Number 6  December 2018
 Cardiomyopathies and heart failure in pregnancy Limongelli et al.
and twin pregnancies [20,29,30]. Recently, a clinical
and genetic overlap between preeclampsia and
&
PPCM has been proposed [31,32 ]. Cardiomyopathy
is present with similar characteristics in both dis-
eases (though diastolic dysfunction vs. systolic dys-
function is predominant in preeclampsia vs. PPCM)
[31]. In addition, an antiangiogenic milieu and a
genetic predisposition have also been proposed in
&
preeclampsia [32 ]. In a study on 181 women with
preeclampsia, 10 rare loss-of-function variants and
228 rare damaging missense variants were found in
43 cardiomyopathy genes considered. Loss-of-func-
tion variants were significantly more frequent in
preeclampsia vs. controls (5.5 vs. 2.5%; P ¼ 0.014).
Sixty-eight percent of women with preeclampsia
carried at least one loss-of-function or damaging
missense variant (mean of 1.94 mutations). As for
PPCM, most mutations (55%) were found in the
titin (TTN) gene (73% of preeclampsia women vs.
48% in controls).
Early diagnosis of PPCM is mandatory to avoid
serious complications. Goland et al. [31] showed
that major cardiac adverse events occur in pregnant
women with a more delayed diagnosis of PPCM. In
addition, African American race, LVEF and right
ventricular function at the time of diagnosis have
been suggested as predictors of outcome in PPCM
&& &
[33,34 ,35 ].
According to the IPAC Study (Investigations of
Pregnancy-Associated Cardiomyopathy), who pro-
spectively enrolled and followed 100 women with
PPCM through 1-year postpartum, PPCM has a very
high rate of full recovery (72% of the patients
achieved an LVEF 0.50 by 1 year after delivery)
[33]. However, 13% of the patients experienced
major events or had persistent severe cardiomyopa-
thy with an LVEF less than 0.35. A baseline LVEF less
than 0.30 (P ¼ 0.001), an LVEDD at least 6.0 cm
(P < 0.001), black race (P ¼ 0.001), and presentation
after 6 weeks postpartum (P ¼ 0.02) were associated
with a lower LVEF at 12 months.
In a recent single-centre, retrospective study
&&
[34 ], LV ejection fraction less than 30% and mod-
erate-to-severe right ventricular dysfunction were
associated with a worse outcome [composite of left
ventricular assist device implantation, cardiac trans-
plantation, or death; hazard ratios (95% confidence
intervals) of 4.85 (1.11–21.3) and 4.26 (1.47–11.6),
respectively]. After multivariate model, only base-
line right ventricular dysfunction [hazard ratio (95%
confidence interval) 3.21 (1.13–9.10)] was indepen-
dently associated with a more advanced cardiomy-
opathy phenotype and increased risk of adverse
outcomes in PPCM, within and beyond the first year
of diagnosis, prompting earlier consideration of
advanced heart replacement therapies.
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Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
A large, retrospective study on a cohort of 220
&
women with PPCM [35 ], showed a different clinical
profile in in African American vs. non-African Amer-
ican women: African American women were: diag-
nosed with PPCM at a younger age (27.6 vs. 31.7
years, P < 0.001) more likely to present with a LVEF
less than 30% [48 (56.5%) vs. 30 (39.5%), P ¼ 0.03];
more likely to worsen after initial diagnosis [30
(35.3%) vs. 14 (18.4%), P ¼ 0.02]; more likely to fail
to recover [52 (43.0%) vs. 24 (24.2%), P ¼ 0.004],
and, when they did recover, recovery took at least
twice as long (median, 265 vs. 125.5 days; P ¼ 0.02)
despite apparent adequate treatment.
An important issue is the outcome of subsequent
pregnancies in patients with PPCM. Patients with
persistent LV systolic dysfunction are at higher risk
of major events compared with those who had a full
recovery, and a subsequent pregnancy should be dis-
couraged; patients who recover LV function are likely
to experience a transient minor decrease in LV ejection
&
fraction during future pregnancies [36,37,38 ].
HOW TO EVALUATE THE RISK OF
PREGNANCY IN PATIENTS WITH
CARDIOMYOPATHIES AND HEART
FAILURE?
In women with preexisting cardiac disease, individ-
ual counselling and risk assessment by expert teams
should be performed prior to pregnancy, and medi-
cal therapy reviewed. The risk of pregnancy depends
on the specific heart disease, its severity, and clinical
status of the patient. Different scores has been pro-
posed [9,39,40] (Fig. 1), including: modified World
Health Organization (WHO) classification, with an
increasing pregnancy risk from classes I–IV; hyper-
trophic cardiomyopathy is considered in classes II
and III; any cardiomyopathy with end stage evolu-
tion, presenting severe ventricular dysfunction
(LVEF <30%, NYHA III and IV), and/or pulmonary
arterial hypertension is considered in class IV (preg-
nancy cpntroindicated); Cardiac Disease in Preg-
nancy (CARPREG) risk score: including four
clinical features [prior cardiac event (heart failure,
transient ischaemic attack, stroke before pregnancy
or arrhythmia; baseline NYHA functional class >II
or cyanosis; left heart obstruction; LVEF <40%], and
with an increasing risk of cardiac events during
pregnancy from 0 point (5% risk), 1 point (27%),
at least two points (75%). Other scores, as ZAHARA
(Zwangerschap bij vrouwen met een Aangeboren
HARtAfwijking-II), are specifically dedicated to pop-
ulation with congenital heart disease [9,41].
According to the European Society of Cardiol-
ogy (ESC) guidelines for the management of cardio-
vascular diseases during pregnancy, women with
www.co-obgyn.com 381
Women’s health
cardiomyopathies who are in WHO class II should be
reviewed by a cardiologist with clinical examination
and echo assessment each trimester [9]. For women in
WHO class III, a more strict follow-up (i.e. monthly or
bimonthly), is warranted. These women should be
managed in a tertiary care centre by expert teams [9].
Follow-up during pregnancy should focus on
the development of new symptoms, arrhythmias,
increased left ventricular outflow tract obstruction,
diastolic and systolic ventricular function. An early,
multidisciplinary approach from a high experienced
team is warranted, including cardiologists, gynaecol-
ogists, obstetricians, genetic counsellor, psycholo-
gists. In the series by Billebeau et al. [42], a major
cardiovascular event was observed during 15 preg-
nancies (35%), including three cardiac deaths. The
highest risks were observed in women who do not
benefit from early multidisciplinary team manage-
ment, and in patients with DCM.
Neonatal outcome is strictly related to maternal
outcome [43]. Adverse events occur in up to 30% of
patients with heart disease with a neonatal mortality
between 1 and 4% [9,39,41,43]. Maternal predictors of
neonatal events in women with heart disease
[9,39,41,43] are: baseline NYHA class greater than II
or cyanosis; maternal left heart obstruction; smoking
during pregnancy; multiple gestation; use of oral anti-
coagulants during pregnancy; mechanical valve pros-
thesis.
WHICH MEDICATION SHOULD BE USED,
STOPPED OR CHANGED DURING
PREGNANCY?
The ROPAC study reported a rate of 32% of cardiac
medications used during pregnancy [44]. Out of
1321 women, 424 used medications at some point
during pregnancy: 22% used beta-blockers, 8% anti-
platelet agents, 7% diuretics, 2.8% ACE inhibitors
and 0.5% statins. Birth weight was significantly
lower in children of patients taking beta-blockers
(3140 vs. 3240 g, P ¼ 0.002), whereas foetal malfor-
mations were found more commonly in patients
taking ACE inhibitors (8%).
Systolic/diastolic dysfunction
Women already taking beta-blockers prior to preg-
nancy should go on during pregnancy. Neverthe-
less, any woman who becomes symptomatic during
pregnancy should start a beta-blocker and be pre-
scribed with diuretics, in presence of signs and
symptoms of congestion [9]. According to the ESC
guidelines, a beta-blocker should be considered if
there is more than mild LVOT obstruction or a septal
thickness of more than 15 mm, in order to reduce
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the risk of pulmonary congestion [9]. Metoprolol is
the preferred beta-blocker as there is wide experi-
ence with its use in pregnant women; however,
bisoprolol may also be used.
Arrhythmias
Beta-blockers are also helpful to control atrial fibril-
lation and to reduce the risk of ventricular arrhyth-
mias. Verapamil can be used during pregnancy, but
caution is necessary because of the risk of foetal
atrioventricular block. Amiodarone should not be
used unless absolutely necessary, as it can induce
foetal thyroid disorders, whereas sotalol can be used
during pregnancy [9]. Electrical cardioversion is
considered to be safe during pregnancy, and it is
mandatory when atrial fibrillation/flutter is poorly
tolerated, but continuous foetal heart rate monitor-
ing and possible emergency caesarean section
should be provided if required [9]. In selected cases,
prophylactic AICD implantation may also be con-
sidered to prevent adverse events during pregnancy
in patients at high risk (i.e. arrhythmogenic or
hypertrophic cardiomyopathy; patients with very
low ejection fraction; patients with frequent pre-
pregnancy arrhythmic events). In case of life-threat-
ening events (sustained ventricular arrhythmias,
cardiac arrest), antiarrhythmic drugs and electrical
therapy (shocks) are indicated.
Thromboembolism
Women with cardiomyopathy/heart failure are
vulnerable to thrombotic (intracardiac thrombi)
and/or thromboembolic complications (pulmonary
embolism) because of pregnancy-induced hyperco-
agulability, which persists up to several months post-
partum. Anticoagulation should be considered in
patients with a severe systolic dysfunction (LVEF
<35%) and/or patients at high risk for venous throm-
boembolic embolism. An usual prophylactic dose of
0.5 IU /kg body weight of low-molecular weight
heparin, LMWH (enoxaparin) twice daily is recom-
mended [9]. No enough data have been reported on
new anticoagulants (such as direct factor Xa inhib-
itors and direct thrombin inhibitors) [45].
Inhibition of prolactin (bromocriptine)
Recommended treatment for PPCM is similar to that
of heart failure from other causes [9]. However, based
on experimental and clinical registry and trials data,
bromocriptine (a prolactine inhibitor used for many
years to stop lactation in postpartum women) therapy
has been suggested as a well tolerated and efficacious
&&
treatment in women with PPCM [27,28,46 ]. A recent
Volume 30  Number 6  December 2018
 Cardiomyopathies and heart failure in pregnancy Limongelli et al.
&&
randomized multicentre trial [46 ] showed that inhi-
bition of prolactin release with long-term or short-
term bromocriptine, in addition to standard medical
therapy for heart failure, is associated with a high
recovery rate and very low rate of adverse outcome.
DELIVERY AND POSTPARTUM
Delivery
Vaginal delivery is usually the preferred approach, as
planned caesarean section does not confer any
advantage over planned vaginal delivery [7,9,47].
Epidural and spinal anaesthesia must be adminis-
tered cautiously in women with obstructive HCM, as
vasodilatation and hypotension may worsen LVOT
obstruction [7,9].
Postpartum
The postpartum period is highly vulnerable for left
ventricular systolic function deterioration, especially
in patients with DCM or risk factors for developing
PPCM. Usual heart failure medications (including
ACE-inhibitors, ARBs and ARNI) represent the main-
stays of therapy. Other therapeutic measures (includ-
ing antiarrhythmic and/or device-based therapy)
should be taken into considerations according to
current guidelines [7,9]. Breast-feeding should be
encouraged, even in women with cardiomyopathies
who are taking heart failure medication [7,9].
CONCLUSION
Pregnancy is always a challenge in women with preex-
isting cardiomyopathy, and/or who develop a peripar-
tum heart muscle disease. Prepregnancy cardiac
evaluation is mandatory, including evaluation of the
clinical status, standard ECG (and 24–48 h monitoring,
when required), and imaging, to define the individual
risk profile (Fig. 1). In presence of severe symptoms
(advanced NYHA class), cardiac dysfunction (moder-
ate–severe reduced ejection fraction), haemodynamic
load (LVOT obstruction, pulmonary hypertension),
pregnancy is contraindicated. A tailored monitoring
is warranted in other cases (mild–moderate risk preg-
nancies). Likewise, in women who develop PPCM, a risk
stratification and tailored monitoring and therapy
should be achieved by an expert, multidisciplinary
team, including cardiologists, gynaecologists, obstetri-
cians, genetic counsellor, and psychologists.
Acknowledgements
We would like to thank our nurses, Mrs Giuseppina
Cacciuottolo, Giuseppina Tabasco, Carmela Pica, and
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Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Margherita Chianese for their continuous support, both
in clinical and research settings.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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Volume 30  Number 6  December 2018