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\begin{document}

\title{Anomalous origin of the right coronary artery from the pulmonary artery
(ARCAPA): echocardiographic diagnosis in a critically ill newborn.}



\author[1]{Cosimo Marco Campanale}%
\author[1]{Patrizio Moras}%
\author[1]{Marco Masci}%
\author[1]{Flavia Cobianchi Bellisari}%
\author[1]{Maria Carolina Colucci}%
\author[2]{Luciano Pasquini}%
\author[1]{Alesssandra Toscano}%
\affil[1]{Ospedale Pediatrico Bambino Gesu}%
\affil[2]{Policlinico Universitario Agostino Gemelli Dipartimento Scienze della Salute della Donna e del Bambino}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
Anomalous origin of the right coronary artery from the pulmonary artery
(ARCAPA) is a very rare disease. Echocardiographic diagnosis can be very
challenging, especially in both asymptomatic children with no history of
cardiac disease or critically ill newborns in the setting of intensive
care unit. We report a case of ARCAPA in a neonate with congenital
pulmonary airway malformation (CPAM), whose echocardiographic diagnosis
was particularly challenging due to the critical status at presentation.%
\end{abstract}%



\sloppy


\textbf{Anomalous origin of the right coronary artery from the pulmonary
artery (ARCAPA): echocardiographic diagnosis in a critically ill
newborn.}

Authors:

Cosimo Marco Campanale\textsuperscript{1}, Patrizio
Moras\textsuperscript{1}, Marco Masci\textsuperscript{1}, Flavia
Cobianchi Bellisari\textsuperscript{2}, Maria Carolina
Colucci\textsuperscript{1}, Luciano Pasquini\textsuperscript{3},
Alessandra Toscano\textsuperscript{1}.

Affiliations:

1: Perinatal Cardiology Unit; Department of Fetal, Neonatal and
Cardiovascular Sciences, Bambino Ges\selectlanguage{ngerman}ù Children's Hospital, IRCCS, Rome,
Italy.

2: Department of Imaging; Advanced Cardiovascular Imaging Unit, Bambino
Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165, Rome,
Italy.

3: Department of Maternal-Fetal Medicine, Catholic University of the
Sacred Heart, Rome, Italy.

\textbf{Abstract}

Anomalous origin of the right coronary artery from the pulmonary artery
(ARCAPA) is a very rare disease. Echocardiographic diagnosis can be very
challenging, especially in both asymptomatic children with no history of
cardiac disease or critically ill newborns in the setting of intensive
care unit. We report a case of ARCAPA in a neonate with congenital
pulmonary airway malformation (CPAM), whose echocardiographic diagnosis
was particularly challenging due to the critical status at presentation.

\textbf{Case report}

A neonate with prenatal diagnosis of CPAM, born from cesarean section at
35 weeks of gestation and 2.5 kg, was led in neonatal intensive care for
respiratory failure at birth. He was intubated and mechanically assisted
with high-frequency oscillatory ventilation (HFOV). At that time, first
urgent cardiac ultrasound (CUS), with poor acoustic window, showed
normal origin and course of the coronary branches and systemic right
ventricular pressures (Fig 1a, b). At day2 for worsening clinical
conditions he was put on veno-arterial extracorporeal membrane
oxygenation (VA-ECMO). At day7 he underwent right upper and medium
lobectomy for removal of CPAM III and at day 16 he was weaned-off ECMO.
Serial CUS showed progressive reduction of pulmonary arterial pressure
(PAP). At day52 CUS showed the presence of a small network of multiple
coronary vessels in the field of the right coronary artery (RCA), a
systo-diastolic jet of flow into the main pulmonary artery (MPA) at
color-mapping and an inverted retrograde flow into the RCA (Fig 2a, b --
video 1, 2 and 3). A more detailed examination showed a suspected
abnormal origin of the RCA from the main pulmonary artery (ARCAPA) (Fig
2c -- video 4). At day59 CT scan confirmed the echocardiographic
diagnosis of ARCAPA origination from the medial wall of the MPA (Fig 2d
and 3) and dilation of the main epicardial coronary network due to the
presence of a multiple coronary collateral connections. After recovery
from thoracic surgery and multidisciplinary review of the case, the
patient was discharged at home with strict follow-up and future
evaluation for elective coronary surgery.

\textbf{Discussion}

ARCAPA is an extremely rare congenital heart disease (CHD) firstly
described by the Irish anatomist John Brooks in 1885 . Its incidence,
based on coronary angiographic procedures, is estimated around 0.002\%,
but, given the usually asymptomatic behavior of this anomaly, its real
prevalence in general population might be higher . Compared to the more
common anomalous origin of the left coronary artery from the pulmonary
artery (ALCAPA), ARCAPA is associated with lower mortality rate in
infancy and childhood and has a bimodal age presentation with peaks near
after birth or in the middle 40-60s . ARCAPA is often diagnosed
incidentally and usually is an isolated lesion. Sometimes it is
associated with other malformations : more often CHD (23.8\%), less
frequently extracardiac and genetic syndromes . As described, the most
frequent associated CHDs are aorto-pulmonary window and ventricular
septal defect , in rare cases aortic arch hypoplasia or patent ductus
arteriosus with coronary fistulae . In 4\% of cases ARCAPA has been
found in patients with extracardiac lesions such as anal atresia,
tracheoesophageal fistula, limb anomalies or other . Our case is the
first described in a patient with CPAM. Historically, embryological
origin of coronary anomalies is thought to be linked to defects in
arterial septation, the same process that, around the 12th day of life,
leads to the formation of aorta and pulmonary trunk from the common
truncus arteriosus . Another theory advocates abnormal signaling in
pathways that regulate implantation of the primary coronary plexus to
the aorta or pulmonary trunk . Embryologic causes of CPAM, which results
from the cessation of lung development during various stages of
embryogenesis , seems to be different and not linked to those of
coronary anomalies.

Pathology reports described the anomalous coronary artery made different
for the normal coronaries: thin walled, dilated and/or vein-like .
Precise origin of the abnormal vessel is not always described in
literature reports but it can originate from any site off the pulmonary
trunk wall: the anterior or posterior sinus of Valsalva, the anterior
aspect of trunk, or more frequently distal to the pulmonary valve . In
our case ARCAPA took-off from the medial wall of the pulmonary trunk,
distal to the anterior Valsalva sinus. A web of small vessels
(collaterals) nearby the ostium (as in our case) or stenosis of the
origin of ARCAPA have been reported .

\emph{Diagnosis and pathophysiology.}

Various tools are available for diagnosis of ARCPA. Conventionally,
coronary angiography is the gold standard for its ability to visualize
the retrograde flow through the RCA, extensive collateralization between
RCA and LCA, dilation and increased flow into the epicardial coronary
system and direct flow between RCA and MPA . Recently, echocardiography
and computed tomography/magnetic resonance (CT/MR) can be fundamental
for diagnosis of ARCPA, thanks to the improvements of these
technologies. Echocardiography plays a crucial role as a screening,
low-cost and diffusely used tool. It can provide first and immediate
suspicion, and definitive diagnosis, in about 25\% of cases of
ARCAPA/ALCAPA , thus improving survival of asymptomatic patients.
However, echocardiographic diagnosis of coronary anomaly is not simple.
In our case and in other reports , it is very easy to confuse the origin
of the RCA. As our figure 1 shows, also in the presence of ARCAPA the
sonographer can often visualize an ``apparently normal'' RCA-origin for
the right aortic sinus of Valsalva: this ultrasound artifact may be due
to the contact of the aortic wall with the proximal part of the RCA
usually coursing strictly nearby and leading to erroneous evidence of
the vessel originating from the aorta. If not highly suspected, for
example during a pediatric routine screening ultrasound, the operator
would never search for a coronary origin from the MPA, thus leading to
misdiagnosis. The evidence of retrograde (commonly ``blue'', away from
the probe) systo-diastolic flow into the RCA, is the key diagnostic sign
and should mandatorily induce the sonographer to search for ARCAPA. To
be noted that, as opposed to the normal pulsatile coronary blood flow
which is visible at color-doppler during diastole , the blood flow in
the abnormal vessel is present both during systole and diastole because
the pressure into the coronary system (derived from the left coronary
artery and from the wall stress into the myocardium) is higher than the
pulmonary pressure. Sometimes a proper jet of blood flow draining into
the MPA (fig 2b - the amount of blood shunting from the left to the
right system and increasing the Qp/Qs) can be identified at the
color-doppler mapping (commonly ``blue'', away from the probe) and
should ``ring-the-bell'' about the presence of ARCAPA to the
sonographer. Multiple small tortuous vessels, resembling coronary
fistulae (i.e. collateralizations), with low-velocity and retrograde
flow in the area of the proximal RCA course are also key signs of ARCPA.
However, as in this case, collateralizations do not develop soon after
birth, as sometimes they may only slowly develop during infancy.
Moreover, retrograde inverted (left-to-right) flow in RCA appears only
after PAP declines, but this may take days, weeks or months, especially
in critically ill patients, ECMO patients or newborn with persistently
high PAP for several reasons. Our case is a peculiar example since
several obstacles to the prompt diagnosis were faced: the neonate was on
HFOV for several days, thus preventing a good acoustic window, and he
was put on ECMO at day 2 and this might have delayed the PAP decrease.
As showed , ECMO circuit alters the coronary flow which can become, in
some cases, continuous instead of normally pulsatile . This may
complicate the color-doppler analysis of the coronary flow pattern.

All the previous discussions highlight the importance of an
echocardiographic revision in patients with critical acuteness, poor
acoustic windows, and transient hemodynamic conditions for diagnosis of
anomalies that might have been missed at first CUS. In our center our
clinical practice includes a second complete screening CUS for
critically ill newborns after resolution of the acute event and before
discharge.

The pathophysiology of myocardial ischemia in ARCAPA is dependent from
the PAP and the collateralizations. High PAP after birth drives
antegrade flow of deoxygenated blood from MPA to RCA . As PAP decreases,
inverted systo-diastolic retrograde flow runs from the myocardium to the
MPA and causes a ``steal phenomenon'', the reason for progressive
chronic myocardial ischemia in children. If collateralization between
RCA and LCA is not sufficient symptoms and signs of myocardial ischemia
occur earlier in infancy, while, if collateralization is wide enough and
PAP remain low, oxygenated blood from LCA would perfuse the myocardium
and the patient would reach adulthood asymptomatic (about 48\% of cases
). Vessel diameter, pulmonary resistances and coronary dominance also
influence the amount of coronary steal and the subsequent ischemia. It
has been estimated to be up to 1/1.4 L/min (20-25\% of the cardiac
output, increasing the Qp/Qs).

\emph{Treatment.}

Ligation or percutaneous occlusion of the ARCAPA have been performed in
the past with relief of the left-to-right shunt but with concerns about
myocardial ischemia . The most common surgical strategy nowadays is
coronary reimplantation. With good results and low risk profile in
experienced centers, it guarantees antegrade and oxygenated blood flow
to the myocardium, establishing dual coronary artery system and
preventing the steal phenomenon .

Indications for surgery of ARCAPA are based on general consensus, since
for the rarity of the disease randomized trials and observational
studies are lacking. In adults, according to the 2020 ESC guidelines,
surgical intervention due to ARCAPA is needed when symptoms or
ventricular dysfunction or other signs of myocardial ischemia are
present as a consequence of the malformation . Since ARCAPA can lead to
increased risk of myocardial infarction and sudden cardiac death even in
asymptomatic patients, surgical correction is recommended in all cases
also in infancy and adulthood. Symptomatic patients should receive
surgical correction (RCA reimplantation onto the aorta) as soon as
possible to relief myocardial damage, unless, especially older patients,
deemed inoperable and good candidates for ligation or occlusion of
ARCAPA . Asymptomatic patients should receive elective surgical
reimplantation : this approach is practically applied in 90\% of
asymptomatic patients and in our center accordingly. In neonates,
usually asymptomatic, elective repair should be planned when they reach
a good weight in the first months of life. Our patient is planned to
receive surgery in few months (around 6 kg).

\textbf{Conclusion}

ARCAPA diagnosis is often challenging especially in neonates, usually
asymptomatic, and in critically ill patients with ventilatory mechanic
assistance or poor acoustic windows. Given its peculiar pathophysiology,
hemodynamic conditions (such as ECMO, high pulmonary pressure, etc
\ldots{}) can make its recognition very difficult. Echocardiography is a
precious tool in expert hands and subtle pitfalls, depending on
hemodynamic conditions, should always be taken into consideration.
Although less aggressive than ALCAPA, ARCAPA leads to myocardial
ischemia and also in asymptomatic neonates or children elective surgical
repair is recommended.

\textbf{Figures}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Fig 1. a. The \selectlanguage{ngerman}«apparently normal» origin (*) of the RCA from the
anterior aortic rightward sinus of Valsalva, a common pitfall in
echocardiographic screening of coronary arteries; b. RV dilation and
D-shaped LV due to the leftward shift of the interventricular septum for
the high pulmonary pressures of the newborn at arrival.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Fig 2. a. A network of small multiple coronary vessels (*) around aorta
(AO), being the small initial collaterals between the left and right
coronary artery; b. a systo-diastolic jet of flow into the MPA which
represents the left-to-right shunt through the abnormal coronary vessel;
c. the origin (*) of the RCA from the MPA (ARCAPA) with retrograde
inverted \selectlanguage{ngerman}«blue» flow inside, running anterior to the aorta. d. CT-scan
image showing RCA arising (*) from MPA.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Fig 3. a, b. ARCAPA arising (*) from MPA in the echocardiographic
parasternal short-axis view (a) and in the similarly oriented
multiplanar reformat CT plane (b), running anterior to the aorta; c. 3D
view from CT scan of the ARCAPA.



\textbf{Bibliography}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/ARCAPA-image-1/ARCAPA-image-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/ARCAPA-image-2-2/ARCAPA-image-2-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/ARCAPA-image-3/ARCAPA-image-3}

\end{center}
\end{figure}

\selectlanguage{english}
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