10.5826/dpc.1203a150
&nbsp;
BACKGROUND:&nbsp;Some studies have assessed the incidence of heart defects in children suffering from Infantile Hemangioma to be treated with propranolol, showing a possible higher prevalence of cardiac abnormalities in this group of patients.
METHODS: We retrospectively reviewed clinical charts of children with infantile haemangiomas referred to our Dermatologic division from 2016 to 2021, who underwent our pediatric cardiology protocol screening before starting propranolol therapy.
RESULTS:&nbsp;A total of 60 infants were enrolled. Electrocardiograms were available for all the patients and echocardiograpy for 50/60 (83.3%) children. Electrocardiogram didn’t reveal any alterations in the large majority of cases (pathologic in 2/60, 3.3%) while echocardiograms revealed findings in 31/50 (51.7%) patients. Of these, persistent foramen ovale, which was found in 14/50 patients (28%), was considered as non-pathologic. Interatrial septal defects were the main pathological finding in 15/50 patients (30%), as single defect or in association with other abnormalities.&nbsp;&nbsp;&nbsp;
CONCLUSION:&nbsp;Our study confirms the presence of a higher rate of cardiologic findings in patients with infantile hemangioma evaluated before starting oral propranolol, compared to the known rate of those defects in healthy newborns. We also confirm that interatrial septal defects are the most frequent pathologic finding with a higher prevalence compared to published studies. Large prospective studies are needed to clarify a possible association of pathological cardiac findings in all patients with infantile hemangiomas and thereafter to evaluated the possible effect of propranolol therapy on these defects during time.
&nbsp;
&nbsp;
text/xml
2160-9381
2211
en
Carlo Mazzatenta
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
Infantile hemangioma and cardiac defects: a puzzling association. A single center experience : hemangioma and cardiac defects
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-07-28
2021-12-01
2022-07-28
2022-09-13
e2022150
Dermatol Pract Concept
&nbsp;
BACKGROUND:&nbsp;Some studies have assessed the incidence of heart defects in children suffering from Infantile Hemangioma to be treated with propranolol, showing a possible higher prevalence of cardiac abnormalities in this group of patients.
METHODS: We retrospectively reviewed clinical charts of children with infantile haemangiomas referred to our Dermatologic division from 2016 to 2021, who underwent our pediatric cardiology protocol screening before starting propranolol therapy.
RESULTS:&nbsp;A total of 60 infants were enrolled. Electrocardiograms were available for all the patients and echocardiograpy for 50/60 (83.3%) children. Electrocardiogram didn’t reveal any alterations in the large majority of cases (pathologic in 2/60, 3.3%) while echocardiograms revealed findings in 31/50 (51.7%) patients. Of these, persistent foramen ovale, which was found in 14/50 patients (28%), was considered as non-pathologic. Interatrial septal defects were the main pathological finding in 15/50 patients (30%), as single defect or in association with other abnormalities.&nbsp;&nbsp;&nbsp;
CONCLUSION:&nbsp;Our study confirms the presence of a higher rate of cardiologic findings in patients with infantile hemangioma evaluated before starting oral propranolol, compared to the known rate of those defects in healthy newborns. We also confirm that interatrial septal defects are the most frequent pathologic finding with a higher prevalence compared to published studies. Large prospective studies are needed to clarify a possible association of pathological cardiac findings in all patients with infantile hemangiomas and thereafter to evaluated the possible effect of propranolol therapy on these defects during time.
&nbsp;
&nbsp;
Carlo Mazzatenta
2022/07/28
10.5826/dpc.1203a150
e2022150
Dermatology Unit , Azienda Toscana Nord Ovest, Lucca, Italy
2160-9381
en
e2022150
Infantile hemangioma and cardiac defects: a puzzling association. A single center experience : hemangioma and cardiac defects
https://dpcj.org/index.php/dpc/article/download/2211/1703
                    Dermatology Practical & Conceptual


     Infantile Hemangioma and Cardiac Defects: a
    Puzzling Association. A Single-center Experience
                 Andrea Bassi1, Andrea Azzarelli2, Angelina Vaccaro3, Carlo Mazzatenta1


1. Dermatology Unit , Azienda Toscana Nord Ovest, Lucca, Italy
2. Pediatric Cardiology, Azienda Toscana Nord Ovest, Lucca, Italy
3. Pediatric and Neonatology Unit, Azienda Toscana Nord Ovest, Lucca, Italy



Key words: infantile haemangiomas, hearth, septal defects, propranolol
Citation: Bassi A, Azzarelli A, Vaccaro A, Mazzatenta C. Infantile hemangioma and cardiac defects: a puzzling association. A single center
experience. Dermatol Pract Concept. 2022;12(3):e2022150. DOI: https://doi.org/10.5826/dpc.1203a150
Accepted: December 28, 2021; Published: July 2022
Copyright: ©2022 Bassi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Andrea Bassi, MD, Dermatology Unit, Azienda Toscana Nord Ovest, Lucca, Italy, Telephone number:
+39-3389340371, E-mail address: andrea.bassi@uslnordovest.toscana.it




  ABSTRACT             Objectives: to evaluate clinical chart of patients with IH who had cardiologic evaluation before pro-
                       pranolol therapy and to compare our findings with literature data.
                       Introduction: Some studies have assessed the incidence of heart defects in children suffering from
                       infantile hemangioma (IH) treated with propranolol, showing a possible higher prevalence of cardiac
                       abnormalities in this group of patients.
                       Methods: We retrospectively reviewed clinical charts of children with infantile hemangiomas referred
                       to our dermatologic division from 2016 to 2021, who underwent our pediatric cardiology protocol
                       screening before starting propranolol therapy.
                       Results: A total of 60 infants were enrolled. Electrocardiograms were available for all the patients and
                       echocardiography for 50/60 (83.3%) children. Electrocardiogram didn’t reveal any alterations in most
                       cases (pathologic in 2/60 ones, 3.3%) while echocardiograms revealed findings in 31/50 (51.7%) pa-
                       tients. Of these, persistent foramenovale, which was found in 14/50 patients (28%), was considered as
                       non-pathologic. Interatrial septal defects were the main pathological finding in 15/50 patients (30%),
                       as single defect or in association with other abnormalities.
                       Conclusions: Our study confirms the presence of a higher rate of cardiologic findings in patients
                       with infantile hemangioma evaluated before starting oral propranolol, compared to the known rate
                       of those defects in healthy newborns. We also confirm that interatrial septal defects are the most fre-
                       quent pathologic finding with a higher prevalence compared to published studies. Large prospective
                       studies are needed to clarify a possible association of pathological cardiac findings in all patients with
                       infantile hemangiomas and thereafter to evaluate the possible effect of propranolol therapy on these
                       defects during time.




Original Article | Dermatol Pract Concept. 2022;12(3):e2022150                                                                               1
Introduction                                                      Methods
Infantile hemangiomas (IH) are the most common benign             Study Population
tumor in infancy with an incidence between 5% and 10%             We retrospectively evaluated clinical charts of all children
in different population [1]. Usually, they undergo a natural      with IH requiring propranolol therapy at our countryside
regression and do not require any treatment, therefore a          hospital between January 2016 and January 2021. Accord-
“wait and see” approach is considered the best option for         ing to our protocol patients referred to our outpatient service
most affected newborns. However, in a subset of patients,         for IH undergo a complete pediatric and cardiology evalua-
IH can be worrisome for the risk of functional or aesthetic       tion including ECG and ECHOcardiogram before starting
consequences. In 2008, following a serendipitous clinical         therapy. Children with segmental IH are also investigated
observation, oral propranolol has been shown to be highly         with magnetic resonance imaging (MRI) to exclude the as-
effective in the treatment of IH since then this drug has been    sociation with other congenital vascular malformations.
widely used as galenic formulation. In 2014 an oral formu-        Two-dimensional, M-mode, continuous Doppler and color
lation has been licensed in Europe and oral propranolol is        Doppler echocardiography is performed using iE33 Philips
now considered the gold standard for the therapy of compli-       Medical Ultrasound System equipped with a high-frequency
cated hemangioma. In our hospital patients starts treatment       phased-array sector scan probe (S8) and second-harmonic
with oral propranolol at 1 mg/kg in 2 divided doses under         technology. All the evaluations are performed by the same
pediatric observation for 2 hours. The dose is then gradually     senior cardiologist (AA) and comprise a complete sequen-
increased over the subsequent weeks following the standard        tial segmental analysis for each child. Atrial septal defect
protocol of stepping the dose up to 2 mg/kg daily the second      is diagnosed when a shunt through the interatrial septum
week of treatment and up to 3 mg/kg daily the third week.         can be documented by color flow mapping in subcostal
Another possibility is to follow an “at home” dose escalation     four-chambers and sagittals views. We do not record as atrial
strategy with telemedicine follow-up [2]. We developed and        septal defect (ASD) the interatrial communications less than
applied this protocol during the lock-down phase related to       4 mm in length detected in infants less than 3 months of age.
the SARS-CoV-2 pandemic, but we now offer this possibility        According to the local ethical board, informed consent was
to all families aiming to reduce the number of hospital visits.   not required, since it was retrospective study with anony-
The therapy is usually continued until the 12th month of life     mous data.
with rare exceptions, such as rapid improvement of the le-
sion or extensive/recurrent IH in which therapy length could
                                                                  Statistical Analysis
be respectively reduced or prolonged.
                                                                  Data were analyzed by SPSS Statistics, 24.0 statistics soft-
    Potential side effects of propranolol include bradycardia,
                                                                  ware. Categorical variables and frequencies were compared
hypotension, hypoglycemia, bronchospasm and sleep distur-
                                                                  by means of the χ2 test or Fisher test, as appropriate. Quan-
bances. All these are rare and usually not lead to discontinue
                                                                  titative variables were reported as median and interquartile
the treatment [3]. Nevertheless in order to exclude congenital
                                                                  range (IQR) and compared by means of nonparametric tests
hidden heart disease which would contraindicate proprano-
                                                                  (Mann–Whitney U). A P value of 0.05 was considered to
lol administration and to identify children in whom the drug
                                                                  indicate statistical significance.
may potentially induce side effects before starting therapy a
general evaluation it is usually performed by a pediatrician.
However, in our hospital, while not specifically requested in
                                                                  Results
routine practice patients with IH who need propranolol ther-
apy are also evaluated by a pediatric cardiologist [4]. Our       During this study period 950 children with IH presented
cardiology unit offers a care package in which next to car-       in our clinic. Of these, 60 (6.3%) patients with IH were
diologic examination also an electrocardiogram (ECG) and          treated with oral propranolol in the study frame time and
echocardiography (ECHO) are performed in all children.            all clinical charts were reviewed to retrieve relevant data.
                                                                  The median corrected age at first evaluation was 3 months
                                                                  (IQR: 2-5). Seventy percent of cases were female (42/60),
Objectives
                                                                  and the median gestational age at delivery was of 40 weeks
Few published studies have shown a raised incidence of car-       (IQR: 36-40). In our population, 18/60 (30%) infants were
diac defects in patients with IH [5,6]. We then decided to ret-   born preterm. Regarding the localization of IH, in 40/60
rospectively evaluate clinical chart of patients with IH who      (66.7%) children was on the head and among these in 7/40
had cardiologic evaluation before propranolol therapy and         (17.5%) were “Cyrano” IH. 12/40 (30%) were on the scalp,
to compare our findings with literature data.                     5/40 (12.5%) on the cheek (2 of these were diagnosed as



2                                                                     Original Article | Dermatol Pract Concept. 2022;12(3):e2022150
PHACE syndrome after MRI imaging), 4/40 (10%) on the               2-4); 9 out of these were observed at ≥ 3 months of age
ears and 12/40 (30%) on the forehead. In 9/60 (15%) IH             (18% of all patients) and 6 at < 3month (12% of all pa-
were localized on the lower and upper arms including shoul-        tients). Of the 9 patients observed at ≥ 3months, 8 presented
der, 7/60 (11.7%) on the trunk, 1/60 (1.7%) on the diaper          an interatrial defect > 3mm.
area and 3/60 (5%) presented with multiple IH. All data are           The median defects diameter was 4 mm (IQR: 3-6) with
summarized in Table 1.                                             an ostium secundum type and left to right shunt in all pa-
    Data about cardiologic screening in particular for ECG         tients. The 2 patients with abnormal ECG didn’t present any
examination were available for all the patients and almost         ultrasound alterations.
all (58/60, 96.7%) presented a regular ECG for age. Only 2            A possible association of abnormal cardiac findings with
patients presented a right ventricular overload.                   demographic or clinical variables was evaluated. However,
    Ultrasound examination was available for 83.3% (50/60)         no statistically significant association was found with age
of the patients. Among these, 19/50 (38%) didn’t reveal any        (p = 0.354), sex (P = 0.757), gestational age (P = 0.480),
alterations and 14/50 (28%) had a persistent foramen ovale,        prematurity (p = 0.329) or hemangioma localization
a common finding considered to be non-pathological. Pool-          (P = 0.494).
ing together these two groups 33/50 patients (66%) had a              None of the ECG and ECHO findings were considered
normal ultrasound, while the remaining 17/50 (34%) showed          contraindications for systemic propranolol treatment.
significant cardiac alterations. The most frequent cardiac
defect was an isolated interatrial septal defect observed in
                                                                   Conclusions
13/17 (26% of all patients). Moreover, one patient had an in-
teratrial septal defect associated with persistent left superior   Since systemic propranolol therapy was introduced for the
vena cava and another one associated with pulmonary steno-         treatment of IH several protocols of administration and mon-
sis. Finally, one patient had a patent ductus arteriosus and in    itoring have been proposed in order to reduce the potential
another one a flow acceleration in the aortic arch was seen.       risks related to the therapy [1,6]. Pretreatment evaluation is
The median age (corrected for gestational age) at which the        warranted both to exclude congenital hidden heart disease
interatrial septal defect was observed was 3 months (IQR:          which would contraindicate propranolol administration and



                   Table 1. clinical and cardiological screening results of the study population
                          Characteristics                                              Patients (N = 60)
 Age starting propranolol and cardiac screening                                       3 months (IQR: 2-5)
 Sex (female)                                                                                  42
 Preterm                                                                                       18
 Gestational age                                                                     40 weeks (IQR: 36-40)
 IH localization
   • face                                                                                      40
   • trunk                                                                                        7
   • arms                                                                                         9
   • diaper                                                                                       1
   • multiple IH                                                                                  3
 Cardiological findings
 Electrocardiogram (60/60available)                                               58/60 no pathologic findings
 Echocardiogram (50/60available)
   • no findings                                                                              19/50
   • persistent foramen ovale                                                                 14/50
   • interatrial septal defect                                                                13/50
   • interatrial septal defect+ patent doctus arteriosus                                      1/50
   • interatrial septal defect + pulmunary stenosis                                           1/50
   • flow acceleration in aortic arch                                                         1/50
   • persistent left superior vena cava                                                       1/50
IH = infantile hemangiomas; IQR = interquartile range.



Original Article | Dermatol Pract Concept. 2022;12(3):e2022150                                                                 3
to identify children in whom the drug may potentially in-         children older than 3 months (thus excluding children less
duce side effects including bradycardia, hypotension, bron-       than 3 months), the prevalence of ASD is anyway clearly
chospasm or hypoglycemia. Whether to perform ultrasound,          greater than data reported in literature for general popula-
ECG or simply a clinical examination is however controver-        tion (18% versus 0.8%-1%) [12-13].
sial. The most recent literature underlines the lack of addi-        The limited number of patients and the intrinsic limita-
tional value of performing instrumental evaluations such as       tions of retrospective studies does not allow us to draw a
ECG as a pretreatment screening tool [7-11]. In our hospital      definitive conclusion however our study along with liter-
a clinical protocol in which a complete pediatric and cardi-      ature data seems to confirm that patients with IH have a
ologic screening, including ECG and ultrasound, is usually        substantially higher prevalence of congenital heart disease in
performed in all patients as part of a specific care package.     respect to general population. Indeed, these data needs con-
In line with previous studies, in our population we didn’t        firmation in larger prospective, multicenter, studies which
find any cardiac contraindications to start propranolol treat-    should include all patients with IH to be evaluated at spe-
ment. In particular ECG was performed in all the patients,        cific time points irrespectively of therapy with propranolol.
but no significant findings were found thus confirming the        Such a study will also be of interest to reveal a possible effect
low informative value of this exam. On the contrary some          of propranolol therapy on the closure of ASD and also the
interesting data were derived from ultrasound heart exam-         significance and the possible value of IH as a clue to sus-
ination. ECHO was available for 83.3% patients and in             pect the presence of a cardiac defect. In particular it would
38% of patients was normal. A persistent foramen ovale            be of great importance to understand whether along with
was found in 28% of patients and considered as a normal           well-known syndromes such as PHACE a particular com-
variant. The most frequent pathological abnormality was an        bination of characteristics such as dimension, number and
interatrial septal defect that was present in 15/50 of patients   or localization could indicate a raised risk of cardiac dis-
(30%) either as an isolated finding (13/50 - 26%) with a pre-     ease [19].
sentation as ostium secundum type with left to right shunt
or associated with a persistent left superior vena cava or pul-
monary stenosis.
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Original Article | Dermatol Pract Concept. 2022;12(3):e2022150                                                                                5
