\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[greek,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Right ventricular pressure-volume loop produced with simultaneous
application of three-dimensional echocardiography and high-fidelity
micromanometry in a patient with pulmonary arterial hypertension}



\author[1]{Toshitaka Nakaya}%
\author[1]{Ichizo Tsujino}%
\author[1]{Junichi Nakamura}%
\author[1]{Yasuyuki Chiba}%
\author[1]{Hiroyuki Iwano}%
\affil[1]{Hokkaido University Graduate School of Medicine}%


\vspace{-1em}



  
  \date{June 11, 2024}


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





\selectlanguage{english}
\begin{abstract}
Accurate assessment of right ventricular (RV) function is drawing a
growing attention. Pressure-volume (PV) loop analysis is the gold
standard method for evaluating RV function; however, it is not widely
employed due to its invasive nature and complexity. The present report
is the first to have drawn a RV PV loop in a patient with pulmonary
hypertension, with a simultaneous recording of RV pressure and volume
using high fidelity micromanometry and 3D echocardiography. This allows
for less invasive and simple assessment of RV function, potentially
promoting better understanding and management of pulmonary hypertension
and other cardiovascular diseases.%
\end{abstract}%



\sloppy


\textbf{Right ventricular pressure-volume loop produced with
simultaneous application of three-dimensional echocardiography and
high-fidelity micromanometry in a patient with pulmonary arterial
hypertension}

\textbf{Running head:} Right ventricular PV loop produced with 3D echo

\textbf{Authors:}

Toshitaka Nakaya, MD, PhD\textsuperscript{1}; Ichizo Tsujino, MD,
PhD\textsuperscript{1}, Junichi Nakamura, MD\textsuperscript{1},
Yasuyuki Chiba, MD\textsuperscript{2}, Hiroyuki Iwano\textsuperscript{2}

\textsuperscript{1}Department of Respiratory Medicine, Hokkaido
University Graduate School of Medicine

\textsuperscript{2}Department of~Cardiovascular~Medicine,
Hokkaido~University Graduate School of Medicine

\textbf{Disclosures:} Ichizo Tsujino is affiliated to an endowed
department sponsored by Nippon Shinyaku Co., Ltd., Nippon Boehringer
Ingelheim Co., Ltd., and Mochida Pharmaceutical Co., Ltd.

\textbf{IRB approval:} The content of the present report is approved by
the Institutional Review Board of Hokkaido University Hospital for
Clinical Research (No. 016-0461).

\textbf{Corresponding author:}

Ichizo Tsujino

Department of Respiratory Medicine, Hokkaido University Graduate School
of Medicine, N14, W5, Sapporo, Japan. Tel.: 81 11 706 5911, Fax: 81 11
706 7899, Email: itsujino@med.hokudai.ac.jp

\textbf{Funding:}

None

\textbf{Keywords:}

Pulmonary hypertension, Three-dimensional echocardiography, Right
ventricular function



\textbf{Abstract}

Accurate assessment of right ventricular (RV) function is drawing a
growing attention. Pressure-volume (PV) loop analysis is the gold
standard method for evaluating RV function; however, it is not widely
employed due to its invasive nature and complexity. The present report
is the first to have drawn a RV PV loop in a patient with pulmonary
hypertension, with a simultaneous recording of RV pressure and volume
using high fidelity micromanometry and 3D echocardiography. This allows
for less invasive and simple assessment of RV function, potentially
promoting better understanding and management of pulmonary hypertension
and other cardiovascular diseases.

Pressure-volume (PV) loop analysis is the gold standard for evaluating
left/right ventricular (RV) function. Its application has become
increasingly important in pulmonary arterial hypertension (PAH) because
RV function critically affects PAH patients' outcome {[}1{]}. However,
PV loop analysis is not used widely because it is invasive and requires
dedicated catheters and expertise. Recent advances in three-dimensional
(3D) echocardiography have enabled non-invasive RV volume measurements,
potentially replacing conductance catheters required for RV volume
measurements.

The PV loop in \textbf{Figure 1} was created using data obtained from
simultaneous 3D echocardiography for RV volume (\textbf{Movie 1} ) and
high-fidelity micromanometry for RV pressure (\textbf{Figure 2} ) in a
PAH patient. Using PV data along with the single-beat method,
end-systolic elastance (Ees) (1.22 mmHg/mL) and Ees/{[}arterial
elastance{]} (1.27), representative indices of RV systolic function and
RV-pulmonary arterial coupling, respectively, were calculated. The
representative index of RV relaxation, tau, was calculated as 36.3 ms.
The RV stiffness/compliance index, \selectlanguage{greek}β, \selectlanguage{english}was 0.0412, calculated using Rain
et al.'s formula {[}2{]}.

To the best of our knowledge, the PV loop image presented in this report
is the first to have been created with a simultaneously obtained RV
pressure and 3D echocardiography-derived volume. This method waives the
conductance catheter use, thereby significantly lessening examination
time, cost, and dedicated expertise needed. With better temporal
resolution of 3D echocardiography and by modifying the RV's
pre/after-load, such as by Valsalva maneuver, a more detailed and less
invasive RV function assessment will become possible.

\textbf{Acknowledgments:} We thank Ms. Azusa Nakasato, Mamiko Inoue MT,
Mr. Hajime Hatanaka, and Dr. Hiroshi Ohira PhD for their assistance in
data collection and analysis.

\textbf{Author contributions:}

Toshitaka Nakaya created the PV loop shown in Figure 1. Junichi Nakamura
recorded the RV pressure during the catheterization using a
micromanometry. Yasuyuki Chiba and Hiroyuki Iwano recorded the 3D image,
analyzed the data, and created the 3D movie clip. Ichizo Tsujino
conceptualized the study and reviewed the manuscript.



\textbf{References}

1. Vonk Noordegraaf A, Chin KM, Haddad F, et al: Pathophysiology of the
right ventricle and of the pulmonary circulation in pulmonary
hypertension: an update. Eur Respir J 2019;53:1801900.

2. Rain S, Handoko MP, Trip P, et al.: Right ventricular diastolic
impairment in patients with pulmonary arterial hypertension. Circulation
2013;128: 2016--2025, 1--10.



\textbf{Figure 1. RV pressure-volume curve of a patient with pulmonary
arterial hypertension}

The image was created based on a dataset of RV pressure and volume,
simultaneously recorded using high-fidelity micromanometry and 3D
echocardiography.

RV, right ventricular; 3D, 3-dimensional

\textbf{Figure 2. RV pressure curves recorded with a high fidelity
micromanometer}

RV pressure was recorded using a high-fidelity micromanometer
(Mikro-Cath Pressure Cather, Millar Inc., TX, USA). The pressure
catheter was connected to an AV converter (PowerLab\selectlanguage{ngerman}\textsuperscript{®},
ADInstruments, Dunedin, New Zealand) and to a personal computer in which
dedicated software (LabChart Pro\textsuperscript{®}, ADInstruments,
Dunedin, New Zealand) was installed. This software allowed for a
pressure recording with 1,000 Hz and for an export of the data as a csv
file. Zero level was determined while the tip of the catheter was placed
just below the surface of warmed water put in a cup. The RV pressure was
recorded at the natural end-expiration, and the dataset of the first
cardiac cycle was used for drawing the PV loop of Figure 1.

RV, right ventricular

\textbf{Supplementary material:} The following supplementary material is
available online (Codec ID: avc1)

\textbf{- Movie Clip 1: Three-dimensional movie image of the right
ventricle}

RV images were recorded with a 3D echo (Aplio i800, Cannon Medical
Systems, Tokyo) while the patient was asked to hold her breath at the
natural end-expiration. Six consecutive beats were recorded to create a
dataset of the RV volume of one cardiac cycle. The numerical data was
exported afterward as a csv file and then used, along with the pressure
data, to draw an RV pressure-volume loop shown in the Figure 1.

RV, right ventricular; 3D, 3-dimensional\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1-Nakaya-et-al/Figure-1-Nakaya-et-al}

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

\end{center}
\end{figure}

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

