\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Failure of Computed Tomography Angiography to Detect a Large Fistula
Connecting the Left Anterior Descending Artery to the Left Ventricle
Circumflex Artery}



\author[1]{Sam Zeraatian Davani}%
\author[2]{David Pazooki}%
\author[1]{Nazafarin Kamalzadeh}%
\author[1]{Arash Pour Mohammad}%
\author[1]{Milad Gholizadeh Mesgarha}%
\affil[1]{Iran University of Medical Sciences}%
\affil[2]{Sahlgrenska University Hospital}%


\vspace{-1em}



  
  \date{June 14, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
41-year-old male with no significant past medical history presented as
an outpatient with atypical chest pain and had positive nuclear stress
test. The patient subsequently underwent left heart catheterization,
which revealed a fistula between the LAD and LV circumflex artery;
however, CTA failed to show any evidence of a fistula.%
\end{abstract}%



\sloppy


\textbf{Introduction:}

Fistula is defined as an inappropriate connection between two body
parts, such as an organ or blood vessel and another structure. More
specifically, a coronary artery fistula (CAF) is an abnormal connection
between a coronary artery and a major vessel or cardiac chamber.

CAFs are extremely rare, can be asymptomatic, and are often detected
incidentally; thus, the true incidence remains elusive {[}1{]}. CAFs can
either be congenital or acquired.

Congenital CAFs are theorized to be secondary to incomplete embryonic
development, in which the sinusoids that normally communicate the great
vessels and chambers of the heart with the coronary arteries are
incompletely closed. Acquired CAFs can occur as a result of
atherosclerosis, procedure-induced trauma, or collagen vascular disease
{[}2{]}.

Previous literature has demonstrated that CAFs are present in only
0.05-0.25\% of patients who undergo coronary angiography and in 0.9\% of
patients who undergo CTA {[}3{]}.

Fistulas arising from the LAD constitute only 30\% of CAFs, and those
draining into the left side of the heart constitute a mere 10\%, which
was the case illustrated herein {[}4{]}.

The American College of Cardiology recommends closure of all large
fistulas regardless of symptoms due to the vast potential for and
severity of complications, including 'theft' from the adjacent
myocardium, thrombosis and embolism, cardiac failure, atrial
fibrillation, rupture, endocarditis/endarteritis, arrhythmias,
ST-elevation myocardial infarction/non-ST elevation myocardial
infarction, and even sudden cardiac death {[}5{]}.

In this present case study, we describe a 41-year-old male with no
significant past medical, surgical, or family history who presented with
atypical chest pain.

The patient had a positive nuclear stress test and subsequently
underwent installation of a left heart catheter, which revealed a large
fistula between the LAD and the LV circumflex artery; however,
subsequent CTA failed to demonstrate any evidence of a fistula being
present.

We discuss the current imaging modalities and their respective
advantages and limitations, in addition to providing an overview of
disease management.

\textbf{Case Presentation:}

A 41-year-old man with no previous medical history comprising
cardiovascular diseases, hypertension, oral hypoglycemic-treated
diabetes, or dialysis-treated renal failure presented as an outpatient
with atypical chest pain.

The patient had no known family history of heart disease or any personal
history of cardiovascular procedures. Physical examination of the chest
was unremarkable, and no murmurs, rubs, or gallops were detected upon
auscultation. His ECG was normal as well.

The patient was sent for a nuclear myocardial perfusion stress test,
which showed a small reversible perfusion defect in the basal-to-mid
inferior wall, suggestive of inducible ischemia in the right coronary
artery.

There was also a small, mild-intensity, fixed perfusion defect involving
the mid-to-apical anterior segments. According to nuclear imaging
results, the patient was a candidate for an outpatient left heart
catheterization, which revealed no evidence of coronary artery disease
but did show a moderate-sized fistula arising from the LAD to the LV
circumflex artery (Figure-1 ) and luminal irregularity of RCA (Figure-2
).

CTA of the heart was subsequently performed but exhibited no evidence of
coronary artery disease or a fistula from the LAD or OM branches
(Figure-3 ).

The patient was discharged with instructions to follow up as an
outpatient to discuss disease management. Nevertheless, he unfortunately
never returned to the clinic.

Since being diagnosed with coronary AV fistula, the patient has been
following up with the DMC Sinai Grace Primary Care Center and his
private cardiologist on an outpatient basis. He has had three admissions
to the hospital with chest pain and shortness of breath. In 2019, the
patient was admitted with a troponin level of 0.04 and with ECG findings
of T wave inversions in the lateral leads. A transthoracic
echocardiogram (TTE) was obtained, which showed no regional wall motion
abnormalities but did indicate the interval development of moderate
pulmonary hypertension and a small generalized pericardial effusion. As
there was no significant increment in troponin level, no cardiac
intervention was performed. At his last outpatient clinic visit with the
primary care physician, the patient reported having exertional dyspnea
and pedal edema but denied any chest pain, palpitations, diaphoresis, or
vomiting. On physical exam, the patient had bilateral pitting pedal
edema but there were no biochemical abnormalities.

\textbf{Discussion:}

When a fistula drains into the right side of the heart, the volume
overload is occurring there, as well as in the pulmonary vascular bed,
left atrium, and left ventricle. When the fistula drains into the left
atrium or ventricle, volume overloading takes place in these chambers,
but pulmonary blood flow does not dramatically increase. The size of the
shunt is determined by the size of the fistula and the pressure
difference between the coronary artery and the chamber into which the
fistula drains. Most patients display no symptoms, especially during the
first two decades of life, and are referred for testing due to an
asymptomatic murmur; however, older patients may experience dyspnea or
angina and occasionally arrhythmias. Complications that may arise
include `theft' from the adjacent myocardium, which can lead to
myocardial infarction (MI), thrombosis and embolism, heart failure,
atrial fibrillation, rupture, endocarditis/endarteritis, and even sudden
death {[}4,5{]}. When diagnosing an AV shunt, CXR and EKG do not
generally have significant value {[}6{]}. When the initial EKG is
normal, treadmill or nuclear stress tests often reveal ischemic changes.
2D Doppler echocardiography and TEE may also show the site of drainage,
but it is difficult to understand the detailed anatomy using these
techniques. {[}4,5,6{]} Cardiac MRA is limited because the information
regarding the origin and drainage site of the fistula are less clear in
comparison with those observed with CTA and conventional angiography
{[}7{]}. Previously, cardiac catheterization was the first-line modality
for diagnosing CAFs and was thought to have the highest efficiency for
detailing the anatomy, size, origin, course, and presence of any
stenosis and/or drainage; however, more recent studies have shown that
CTA actually produces the best results. It has been demonstrated that
the exact 3D course of the artery is difficult to obtain by conventional
angiography, the drainage sites may not be as well visualized, and the
invasive nature yields a higher mortality rate than CTA {[}7{]}. CTA is
a relatively new imaging tool that was introduced 20 years ago for
non-invasive cardiac imaging, and with the introduction of
multi-detector computed tomography (MDCT), many problems related to
image quality have been resolved {[}8{]}. CTA can produce high quality
images that clearly delineate the cardiac chambers and coronary arteries
and veins {[}5{]}, in addition to having a shorter acquisition time and
higher spatiotemporal resolution. The multiplanar reformation clearly
demonstrates the sites of origin and termination of abnormal blood
vessels, and 3D data provide a more precise overview of the heart, its
vascular anatomy, and information pertaining to the diagnosis of
coexistent abnormalities as compared with left heart catheterization
{[}7{]}. However, limitations include less hemodynamic information,
which we speculate to be the rationale for its failure to detect the
fistula in our case.

According to the 2008 ACC/AHA guidelines, all large fistulas and
small-to-moderate fistulas associated with myocardial ischemia,
systolic/diastolic dysfunction, or ventricular dilation should undergo
closure irrespective of the symptoms of lack thereof {[}9{]}. Patients
diagnosed with CAFs should be educated prior to treatment. In contrast
to patients with acquired heart disease, those with CAFs or adult
congenital heart disease (ACHD) may have never experienced ''normal''
function. Cardiopulmonary exercise testing provides an objective
assessment and has been shown to possess prognostic value for a wide
variety of congenital conditions. There exist conflicting arguments
regarding physical activity in these patients, with some suggesting
restricted exercise, which will inevitably lead to a greater prevalence
of obesity and other forms of heart disease. The most recent guidelines
recommend safe exercise in patients across the spectrum of CAF severity,
being individualized depending on patient clinical status. Self-directed
activity is usually at 40-60\% of the maximal exercise capacity, whereas
fitness training occurs at 60-80\% {[}9{]}. The treatment options for
CAFs include surgery or catheter closure {[}5{]}. The main surgical
options are epicardial fistula mobilization with ligation or division,
arteriotomy of the dilated proximal coronary artery with suturing close
to the fistula origin, and exposure of the fistulous connection and
closure by direct suture or autologous pericardial patch. However,
surgery is associated with a morbidity and mortality rate ranging from
0-6\%, and there is a risk of MI and recurrence of the fistula {[}10{]}.
Catheter closure is considered an effective and safe alternative, with
the aim of occluding the fistula artery as distally and close to its
termination point as possible to avoid occlusion of the branches
supplying the normal myocardium {[}10{]}. There are many tools available
for closure, including occlusion coils, detachable balloons, and
deployable stents and balloons. The techniques and tools used for
catheter closure are influenced by several different factors such as the
morphology of the feeding arteries, patient age, and location of the
fistula {[}10{]}. With catheter closure techniques, complete occlusion
of the fistula may be achieved in \textgreater{}95\% of patients. In the
remaining patients, either further procedures are required to close the
fistulas or conservative management can be undertaken if the residual
fistulas are small {[}11{]}. Selection of percutaneous or surgical
management is influenced by the anatomy and physiology of the CAF.
Indications for surgical management are large, symptomatic, and/or
tortuous fistulas with or without multiple communications and drainage;
whereas, percutaneous transcatheter closure is considered when the
origin of the fistula is in the proximal portion of the feeding coronary
artery, is non-tortuous, or is in an older patient with high
preoperative risk {[}7{]}. After closure, these patients should be
placed on Coumadin, with a goal therapeutic INR of 2.5 for 6-12 months;
and should be on anti-platelet drugs indefinitely.

\textbf{Conclusions:} The present case illustrated a rare CAF, in which
the drainage is into the left circulation. CAFs are only detected in
0.05-0.25\% of patients who undergo coronary angiography and left-sided
drainage is seen in a mere 10\% of these cases. Although current
literature states that CTA is the first-line modality for the detection
of CAFs and provides a more precise overview of the heart, its vascular
anatomy and information pertaining to coexisting abnormalities via 3D
data, we found that conventional angiography was able to detect the
fistula when CTA was not. Further research should be elicited to
directly compare the sensitivity and specificity of coronary angiography
with that of CTA for the detection of CAFs.

\textbf{Declaration of Interest:}

There was no identifiable harm or risk to the patient during the
formation of this report, this was a retrospective case report and
medical testing performed was strictly for diagnostic purposes. No PHI
information was included in this manuscript. None of the authors had any
conflicts of interest or financial incentives in the writing in this
paper.

\textbf{Ethics approval and consent to participate}

Approved by the Institutional ethics committee. Published with written
consent of the patient.

\textbf{Financial support}

This research received no specific grant from any funding agency,
commercial, or not-for-profit sectors.

\textbf{Author Contributions:}

SZND was responsible for conceptualization of data. DP and NK gathered
data and wrote the initial draft. APM revised the manuscript and
prepared figures. MGM revised and prepared the final draft.

\textbf{References:}

{[}1{]} P, Yelisetti R: Multiple Left Anterior Descending Coronary
Artery to Left Ventricular Fistula - A Case Series and Literature
Review. J. Community Hosp. Intern. Med. Perspect. 2017, 7:258-261.
10.1080/20009666.2017.1369380

{[}2{]} Abe T, Kamata K, Nakanishi K, et al.: Successful Repair of
Coronary Artery-Coronary Sinus Fistula with Aneurysm in an Adult.. Ann.
Cardiothorac. Surg. 1996, 61:1520-1523.

{[}3{]} Lim JJ, Jung JI, Lee BY, et al.: Prevalence and types of
coronary artery fistulas detected with coronary CT angiography. AJR Am.
J. Roentgenol. 2014, 203:237-43.

{[}4{]} Al-Douri A, Cedars A, Tran D, et al.: Coronary Artery Fistula
between the Left Anterior Descending Artery and Pulmonary Artery.. Proc
(Bayl Univ Med Cent). 2018, 31:64-66. 10.1080/08998280.2017.1401380

{[}5{]} Qureshi SA: Coronary Arterial Fistulas.. Orphanet J Rare Dis.
2006, 1:51-1764722. 10.1186/1750-1172-1-51

{[}6{]} Early SA, Meany TB, Fenlon HM, et al.: Coronary Artery Fistula;
Coronary Computed Topography-The Diagnostic Modality of Choice. J.
Cardiothorac. Surg. 2008, 3:41-2491619. 10.1186/1749-8090-3-41

{[}7{]} Yun G, Nam T, Chun E, et al.: Coronary Artery Fistulas:
Pathophysiology, Imaging Findings, and Management.. RadioGraphics. 2008,
38:688-703. 10.1118/1.597705

{[}8{]} Liang Y, Kruger RA: Dual-Slice Spiral versus Single-Slice Spiral
Scanning: Comparison of the Physical Performance of Two Computed
Tomography Scanners.. Medical Physics. 1996, 23:205-220.
10.1118/1.597705

{[}9{]} 2008 AHA/ACC Guideline for the Management of Adults With
Congenital Heart Disease: A Report of the American College of
Cardiology/American Heart Association Task Force on Clinical Practice
Guidelines.. (2008). Accessed: 02/01/2021:
http://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.108.190690.

{[}10{]} Mavroudis C, Backer CL, Rocchini AP, et al.: Coronary Artery
Fistulas in Infants and Children: A Surgical Review and Discussion of
Coil Embolization.. Ann. Cardiothorac. Surg. 1997, 63:1235-1242.
10.1016/s0003-4975(97)00251-8

{[}11{]} Qureshi SA, Reidy JF, Alwi MB, et al.: Use of interlocking
detachable coils in embolization of coronary arteriovenous fistulas.. Am
J Cardiol. 1996, 78:110-113. 10.1016/s0002-9149(96)00239-1



\textbf{Figure Legends:}

\textbf{Fig. 1} The coronary angiogram demonstrates LAD
collateralization to OM branches of the LCFX finally fistulizes to the
left atrium

\textbf{Fig. 2} The coronary angiogram demonstrates mild luminal
irregularity of RCA

\textbf{Fig. 3} CTA shows no evidence of a fistula from the LAD or OM
branches\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

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

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

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

