\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{Pulmonary artery aneurysm associated with a non-stenotic bicuspid
pulmonic valve: a role for genetics?}



\author[1]{Sophia Alexis}%
\author[2]{Ismail El-Hamamsy}%
\author[3]{Michael Robbins}%
\affil[1]{Affiliation not available}%
\affil[2]{Mount Sinai School of Medicine}%
\affil[3]{Mount Sinai Doctors Forest Hills}%


\vspace{-1em}



  
  \date{June 13, 2024}


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





\selectlanguage{english}
\begin{abstract}
Background Bicuspid pulmonic valves are quite uncommon, being described
in only 0.1\% of donor hearts, while pulmonary artery aneurysms are even
more rare, having been found in 8 out of 109,571 autopsies. This rarity
makes it difficult to characterize the relationship between them.
Materials \& Methods We describe the case of a 66-year-old female who
was found to have a bicuspid pulmonic valve and pulmonary artery
aneurysm (5.1cm) on imaging by her cardiologist. Discussion \&
Conclusion This case raises the question of whether the association
between bicuspid semilunar valve disease and vascular wall anomalies are
more genetic or hemodynamic. Even on the aortic side, despite the robust
association between bicuspid aortic valves and thoracic aortic
aneurysms, the mechanism still remains unclear. In our patient there was
no significant gradient across the bicuspid pulmonic valve, suggesting
that hemodynamics are not the primum mobile of this association.%
\end{abstract}%



\sloppy


\textbf{Pulmonary artery aneurysm associated with a non-stenotic
bicuspid pulmonic valve: a role for genetics?}

Pulmonary artery aneurysm with bicuspid valve

Sophia L. Alexis, MD\textsuperscript{1}, Ismail El-Hamamsy, MD,
PhD\textsuperscript{1}, Michael J. Robbins, MD\textsuperscript{2}

\textsuperscript{1}Department of Cardiovascular Surgery, Mount Sinai
Health System, New York, NY

\textsuperscript{2}The Cardiovascular Institute, Mount Sinai Medical
Center, New York, NY

Disclosures: The authors have no conflicts of interest to disclose.

Funding: N/A

Word Count: 1307/1500

Address for Correspondence:

Michael J. Robbins, MD

Mount Sinai Doctors Forest Hills

99-01 Queens Boulevard

Rego Park, NY 11374

Tel: 718-520-6100

Email: michael.robbins@mssm.edu

\textbf{Abstract}

\textbf{Background}

Bicuspid pulmonic valves are quite uncommon, being described in only
0.1\% of donor hearts, while pulmonary artery aneurysms are even more
rare, having been found in 8 out of 109,571 autopsies. This rarity makes
it difficult to characterize the relationship between them.

\textbf{Materials \& Methods}

We describe the case of a 66-year-old female who was found to have a
bicuspid pulmonic valve and pulmonary artery aneurysm (5.1cm) on imaging
by her cardiologist.

\textbf{Discussion \& Conclusion}

This case raises the question of whether the association between
bicuspid semilunar valve disease and vascular wall anomalies are more
genetic or hemodynamic. Even on the aortic side, despite the robust
association between bicuspid aortic valves and thoracic aortic
aneurysms, the mechanism still remains unclear. In our patient there was
no significant gradient across the bicuspid pulmonic valve, suggesting
that hemodynamics are not the \emph{primum mobile} of this association.

\textbf{Introduction}

A 66-year-old female (BMI 32.61kg/m\textsuperscript{2}) with a past
medical history of hypertension, hyperlipidemia, type 2 diabetes
mellitus, hypothyroidism, anxiety, obstructive sleep apnea,
osteoarthritis, mechanical falls, paroxysmal atrial fibrillation/flutter
(not on anti-coagulation) status post pulmonary vein isolation (2008)
with repeat ablation/isolation (2014, 2016) and left atrial appendage
(LAA) occlusion (2017) presented to her cardiologist for a routine visit
where she underwent transthoracic echocardiography (TTE) and was found
to have a pulmonary artery aneurysm (PAA). Her PAA measured 5.1cm distal
to the pulmonic valve, and pulmonary artery (PA) systolic pressure was
estimated to be 55mmHg. The aortic valve and root/ascending aorta size
were measured as normal.

On exam, our patient lacked pathologic features of a connective tissue
disorder, and she noted no family history of such. Her auscultatory exam
did not reveal any murmurs/gallops that would suggest valvular disease.
She denied angina, dyspnea, orthopnea, paroxysmal nocturnal dyspnea,
syncope, and change in exercise tolerance, but endorsed occasional
episodes of palpitations and right-sided chest pain (attributed to acid
reflux).

\textbf{Materials and Methods}

The PAA was diagnosed by TTE, but it was unclear what the growth pattern
and etiology were. We were able to retrospectively follow the growth of
the aneurysm because she had multiple computed tomography scans for
electrophysiologic procedure planning. International Review Board,
consent statement, and clinical trial registration were not applicable
to deidentified report of her case.

\textbf{Results \& Discussion}

In 2014, the PA was 4.2 cm, in 2016 it was 4.6 cm, and in 2018 it was
4.7 cm, despite the absence of any hemodynamically significant pulmonary
stenosis. Transesophageal echocardiogram from 2018 obtained for LAA
occlusion device monitoring noted EF 65\% with normal biventricular
function, a trileaflet aortic valve, and normal Sinus of Valsalva
(2.9cm)/ascending aorta (3.1cm). It did not have descriptors of PA
pressures/size. Follow-up computed tomography angiography (CTA) reported
a bicuspid pulmonic valve without stenosis and PA dilation to 4.7cm
(Figures 1, 2).

While the risk of rupture and dissection with PAAs is less than that of
aortic aneurysms, it has been reported. Therefore, care should be taken
to monitor those with a \textgreater{}2mm increase in size/year, a PA
pressure \textgreater{}50mmHg, and a diameter
\textgreater{}7.5cm.\textsuperscript{1} PAAs that become large enough
undetected are eventually found due to sequelae of compression of nearby
structures.\textsuperscript{2} Indications to intervene on a bicuspid
valve if stenotic include a PA systolic pressure gradient
\textgreater{}64mmHg and right ventricular
dysfunction.\textsuperscript{1}

Although our patient presented without symptoms that could be directly
attributed to a bicuspid pulmonic valve and PAA, symptomatic patients
can exhibit exertional dyspnea, weakness, cough, and
hemoptysis.\textsuperscript{2,3} In their case series of 7 patients with
isolated bicuspid disease and PAA, Izumida et al found that over half
were asymptomatic with diagnosis made on investigation of other
diseases.\textsuperscript{1}

Because the patient did not meet size criteria for operative
intervention and because symptomatology was not thought to be direct
sequelae of physiologic/mass effect of the PAA, the decision was made to
continue surveillance with imaging.

\textbf{Conclusions}

Causes of PAAs have been divided into those associated with
Eisenmenger's physiology, pulmonic valve abnormalities, and connective
tissue disorders.\textsuperscript{4} Gupta et al also included
infectious causes such as tuberculosis (Rasmussen's aneurysm),
vasculitis, and endocarditis.\textsuperscript{4} This rare entity has
been associated with congenital defects in almost half of
cases.\textsuperscript{2} The pathophysiology of PAAs remains poorly
understood, especially in the absence of connective tissue
disorders.\textsuperscript{2} This case report describes the rare
incidence of a normally functioning, non-stenotic bicuspid pulmonic
valve and a PAA, suggesting a developmental association versus a
hemodynamic one.

Bicuspid pulmonic valves are quite uncommon, being described in only
0.1\% of donor hearts, while PAAs are even more rare, having been found
in 8 out of 109,571 autopsies.\textsuperscript{1,5-7} This rarity makes
it difficult to characterize relationships. Even on the aortic side,
despite the robust association between bicuspid aortic valves and
thoracic aortic aneurysms, the mechanism still remains unclear. It has
been postulated that with a bicuspid valve, there is an increase in
matrix metalloproteinase 2 activity and a decrease in fibrillin-1 that
leads to dilation.\textsuperscript{8} Fedak et al found this decrease in
fibrillin-1 to also be present in PAs of patients with bicuspid aortic
valves independent of valvular function.\textsuperscript{8} Abnormal
neural crest cell migration could also be a culprit since neural crest
cells are involved in both semilunar valve and vascular wall
formation.\textsuperscript{1}

Previously noted relationships between bicuspid valves and PAAs has been
attributed to post-stenotic dilation.\textsuperscript{3} However, in our
patient there was no significant gradient across the bicuspid pulmonic
valve, suggesting that hemodynamics are not the \emph{primum mobile} of
this association and that progression can occur in the absence of
significant pulmonic stenosis. Furthermore, the association between PAAs
and bicuspid \emph{aortic} valves adds additional weight to a common
developmental abnormality, along with the more recognized relationship
between bicuspid aortic valves and
aortopathies.\textsuperscript{1,9}Further studies are needed to
determine if the incidental finding of a bicuspid pulmonic valve
warrants routine imaging for the development of a PAA, but given the
continued enlargement of the PAA in our patient, we will perform
surveillance imaging.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Izumida S, Kawano H, Tsuneto A, Doi Y, Maemura K. Pulmonary Artery
  Aneurysm Associated with Bicuspid Pulmonary Valve. Intern Med
  2020;59:1867-1871.
\item
  Deb SB, Zehr KJ, Shields RC. Idiopathic Pulmonary Artery Aneurysm. Ann
  Thorac Surg 2005;80:1500-1502.
\item
  Vistarini N, Aubert S, Gandjbakhch I, Pavie A. Surgical treatment of a
  pulmonary artery aneurysm. Eur J Cardiothorac Surg 2007;31:1139-1141.
\item
  Gupta M, Agrawal A, Iakovou A, Cohen S, Shah R, Talwar A. Pulmonary
  artery aneurysm: a review. Pulm Circ 2020;10:1-10.
\item
  Jamis-Dow CA, Barbier GH, Watkins MP, Lanza GM, Caruthers SD, Wickline
  SA. Bicuspid Pulmonic Valve and Pulmonary Artery Aneurysm. Cardiol Res
  2014;5:83-84.
\item
  Jashari R. Bicuspidy and quadricuspidy of semilunar valves: a cause of
  fragility of heart valves. Kosova J Surg 2008;2:10-19.
\item
  Bartter T, Irwin RS, Nash G. Aneurysms of the pulmonary arteries.
  Chest 1988;94:1065-1075.
\item
  Fedak PWM, de Sa MPL, Verma S, Nili N, Kazemian P, Butany J, et al.
  Vascular matric remodeling in patients with bicuspid aortic valve
  malformations: implications for aortic dilatation. J Thorac Cardiovasc
  Surg 2003;126:797-805.
\item
  Di Nora C, Pecoraro R, Evangelista A, Antonine-Canterin F. Giant
  Pulmonary Artery Aneurysm in Bicuspid Pulmonary Valve. J Am Coll Case
  Rep 2020;2:1720-1722.
\end{enumerate}

\textbf{Figures}

\textbf{Figure 1.} \textbf{Axial CTA}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Axial CTA demonstrating the main pulmonary artery aneurysm (PAA) at
4.7cm, which is 0.5cm growth from 4 years prior.

\textbf{Figure 2.} \textbf{Pulmonary Artery Reconstruction}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Reconstruction demonstrating the bicuspid pulmonic valve and main
pulmonary artery aneurysm (PAA).

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

