\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[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Analysis of Preoperative and Postoperative Pulmonary Hypertension
Following Mitral Valve Replacement for Rheumatic Mitral Valvular Heart
Disease -- An Institutional study from a Tertiary Care Hospital}



\author[1]{ARUNKUMAR ARASAPPA}%
\author[2]{JAVID RAJA}%
\author[1]{ASHIDA thulaseedharan sarojadevi}%
\author[1]{RIAZ BAZARDEEN}%
\affil[1]{Sri Manakula Vinayagar Medical College and Hospital}%
\affil[2]{Post Graduate Institute of Medical Education and Research}%


\vspace{-1em}



  
  \date{May 21, 2024}


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





\selectlanguage{english}
\begin{abstract}
Background: Pulmonary Hypertension in mitral valvular heart disease
leads to various adverse outcome following surgical treatment of this
condition. In majority of the patients this Pulmonary Hypertension is
reversible following surgery. The objective of this study is to assess
the outcome of changes in Severe Pulmonary Hypertension after Mitral
Valve Replacement during the follow up with postop Echocardiogram.
Patients and methods: In all our 265 patients who underwent Mitral Valve
Replacement Surgery (MVR) for Mitral valvular heart disease with
pulmonary hypertension, females 111/195(56.9\%) outnumbered the males in
this study. 195 among 265 cases had severe PHT. MVR was done with
cardiopulmonary bypass using St Jude's medical valve. Results: Despite
the high operative mortality in most series of MVR in patients with
severe PHT, a striking improvement in survival was noted in the study
with 5.3\% mortality rate.A sudden drop of PHT is not observed in our
study. The fall was found to be gradual and significant over follow up
and the maximum reduction was at 1-3 months post operatively.
Conclusion: It is concluded that MVR reduces PHT in a gradual way and
the mortality rate is also minimum in severe PHT patients. MVR thereby
is an effective invasive procedure for the management of patients with
severe mitral valve disease and PHT. Keywords: Severe Pulmonary
Hypertension, mitral valvular disease, mitral valve replacement,
Pulmonary artery pressure, Rheumatic Heart Disease%
\end{abstract}%



\sloppy


Type of article: ORIGINAL ARTICLE

Title of the article: Analysis of Preoperative and Postoperative
Pulmonary Hypertension Following Mitral Valve Replacement for Rheumatic
Mitral Valvular Heart Disease --An Institutional study from a Tertiary
Care Hospital

Place of study: Sri Manakula Vinayakar medical college and hospital,

Pondicherry, India

\emph{CONTRIBUTORS:}

Arun Kumar Arasappa* MCh.,

Javid Raja\# MCh.,

Ashida MD.,

Riaz bazardeen MCh.,

Department(s) and institution(s)

Associate Professor, Department of Cardiothoracic and vascular surgery,
Sri Manakula Vinayakar Medical College and Hospital, Pondicherry, India

\# Assistant Professor, Department of Cardiothoracic and vascular
surgery, Sri

Manakula Vinayakar Medical College and Hospital, Pondicherry, India

Sri Manakula Vinayakar Medical College and Hospital, Pondicherry, India

\$ Assistant Professor, Department of Cardiathoracic and vascular
surgery,

Sri Manakula Vinayakar Medical College and Hospital, Pondicherry, India

CORRESPONDING AUTHOR:

Dr. ARUNKUMAR ARASAPPA

Associate professor,

Department of CTVS,

Sri Manakula Vinayagar medical college and hospital,

Pondicherry, India

Email:ddkmmc@rediffmail.com

Mobile: 9677048021

\emph{Email address of authors:}

Arun Kumar Arasappa: ddkmmc@rediffmail.com :
drarunkumararasappa414@gmail.com

Javid Raja: javidraj86@gmail.com

Ashida Thulaseedharan sarojadevi: drashidats@gmail.com

Riaz Bazardeen : shahul9505@yahoo.com

Presentation at a meeting: NIL

Conflicting Interest (If present, give more details): None

Informed consent: Obtained from the patients relatives

Ethical approval: Institutional ethical approval obtained

Analysis of Preoperative and Postoperative Pulmonary Hypertension
Following Mitral Valve Replacement for Rheumatic Mitral Valvular Heart
Disease --An Institutional study from a Tertiary Care Hospital

\textbf{Abstract:}

\textbf{Background:} Pulmonary Hypertension in mitral valvular heart
disease leads to various adverse outcome following surgical treatment of
this condition. In majority of the patients this Pulmonary Hypertension
is reversible following surgery. The objective of this study is to
assess the outcome of changes in Severe Pulmonary Hypertension after
Mitral Valve Replacement during the follow up with postop ECHO.

\textbf{Patients and methods:} In all our 265 patients who underwent
Mitral Valve Replacement Surgery (MVR) for Mitral valvular heart disease
with pulmonary hypertension, females 111/195(56.9\%) outnumbered the
males in this study. 195 among 265 cases had severe PHT. MVR was done
with cardiopulmonary bypass using St Jude's medical valve\textbf{.}

\textbf{Results} : Despite the high operative mortality in most series
of MVR in patients with severe PHT, a striking improvement in survival
was noted in the study with 5.3\% mortality rate.A sudden drop of PHT is
not observed in our study. The fall was found to be gradual and
significant over follow up and the maximum reduction was at 1-3 months
post operatively.

\textbf{Conclusion} : It is concluded that MVR reduces PHT in a gradual
way and the mortality rate is also minimum in severe PHT patients. MVR
thereby is an effective invasive procedure for the management of
patients with severe mitral valve disease and PHT.

\textbf{Keywords:} Severe Pulmonary Hypertension, mitral valvular
disease, mitral valve replacement, Pulmonary artery pressure, Rheumatic
Heart Disease

\textbf{INTRODUCTION} :

Pulmonary Hypertension (PHT) is an increase in blood pressure in the
Pulmonary artery, Pulmonary vein, or pulmonary capillaries, together
known as the Lung Vasculature, leading to shortness of breath,
dizziness, fainting, and others Symptoms, all of which are exacerbated
by exertion. Pulmonary Hypertension can be a severe disease with a
markedly decreased exercise tolerance and heart failure{[}1{]}.Patients
with Rheumatic Heart Disease develop Pulmonary Hypertension due to
various reasons and prime cause among them will be the retrograde
transmission of Left atrial hypertension which gets transmitted to the
Pulmonary arteries. Pulmonary venous pressure also is transmitted to
Pulmonary arteries. Pulmonary Arteriolar constriction, morphological
changes in Pulmonary Vasculature and Interstitial Oedema can also lead
to the development of Pulmonary Hypertension {[}1{]}.

PHT was initially classified by World Health Organisation (WHO) as,
Group I - Pulmonary Arterial hypertension (PAH), WHO Group II -
Pulmonary Hypertension associated with left heart disease, WHO Group III
- Pulmonary Hypertension associated with lung diseases and/or Hypoxemia
and WHO Group IV - Pulmonary Hypertension due to chronic thrombotic
and/or embolic disease by the Venice 2003 revised classification system
{[}2{]}.

Heath Edwards grading system classified PH into six grades based on
severity and pathophysiology of the disease. Usually Pulmonary
Hypertension grade 3 and below are reversible and can be taken up for
surgery with better results. Pulmonary Hypertension grade 4 and above
has significant contribution for postoperative morbidity and mortality
{[}3{]}.

Catheterization studies are not done routinely as echocardiogram has
emerged as an effective tool to identify Pulmonary Hypertension and
classify accordingly.

Pulmonary Hypertension in mitral valvular heart disease leads to various
adverse outcomes following surgical treatment of this condition.
Pulmonary Hypertension is said to complicate about 70\% of the patients
affected by this disease. Mitral valvular heart disease includes Mitral
stenosis (MS) which refers to narrowing of the mitral valve orifice and
Mitral valvular Regurgitation (MR) . It is usually caused by rheumatic
heart disease {[}4{]}.

Pathophysiology of Pulmonary Hypertension in Mitral Valvular heart
disease in both Rheumatic Mitral Stenosis and Regurgitation can be
described as follows,

Elevated LA pressureElevated Pulmonary venous pressureTransmitted
pulmonary venous hypertension to arteriesVasoconstriction of Pulmonary
arteriolesPulmonary Artery HypertensionRight ventricular
dilatationTricuspid RegurgitationRight Atrial enlargementCongestive
cardiac failure. Pulmonary Hypertension greatly influences the natural
course of the disease process, treatment response and also the post
intervention prognosis {[}1, 4\&7{]}.

Features indicating severity of disease in mitral valvular lesions
complicated by pulmonary hypertension includes, Severe Subvalvular
Pathology, Small Mitral Valve Area, Higher Transvalvular gradient,
Higher Pulmonary valve resistance, Higher NYHA symptoms, Thickened non
pliable valves, Higher Wilkins score and Higher incidence of Atrial
Fibrillation{[}1,4{]}.

Treatment options can be medical, interventional or surgical. Rate
control drugs like Betablocker and Calcium channel blockers help in
reducing the transmitral gradient and hence the PHT. Digoxin is usually
started for the failing heart and RV dysfunction which has to pump blood
against severe PHT {[}6{]}.

In interventional method for isolated MS and PHT, Balloon Mitral
Valvotomy (BMV) is done in various centres .Balloon Mitral Valvotomy can
be attempted only if the valves are pliable and the Wilkins score is
favorable{[}6{]}.There are many concerns before proceeding to BMV like
the less tolerance to the stress of the procedure, difficulty in
negotiating the septum in large right sided chambers, Tight Mitral
Stenosis and fear of tearing the mitral valve and creating Mitral
Regurgitation{[}6{]}.

Various options are open for surgical management of Mitral Valvular
heart disease like Mitral valve replacement (MVR), Closed Mitral
Commisurotomy and Open Mitral Valvotomy. Mitral Valve Replacement may be
done with either mechanical prosthetic valve or Bioprosthetic Valve ,
Autologous transfer of Pulmonary valve (ROSS II PROCEDURE) has also been
done for this condition{[}6{]} .Pulmonary Hypertension regresses after
the transmitral gradient gets reduced following surgery{[}8{]}.

The objective of this study is to analyze the reduction in Pulmonary
Hypertension following mitral valve replacement during patient follow up
post surgically.An attempt of a prospective study to analyze the facts
is made and the results are tabulated and compared to the national and
international views on the same parameter of this common disease. The
results obtained from the data collection were tabulated and analyzed.

\textbf{PATIENTS AND METHODS:}

A total of 265 patients were taken in this prospective study that came
to the hospital with NYHA Class II-IV symptoms and with Mitral valvular
heart lesions comprising of Mitral stenosis and Mitral Regurgitation
with Pulmonary Hypertension from period of July 2016 --July 2017.

A detailed clinical examination and investigations were done on these
patients and were categorized according to the study. All patients were
prepared and consented before surgery as per the protocol and
institutional ethical clearance was obtained before surgery. All of them
underwent Mitral valve replacement using St Jude's mechanical valve
using cardiopulmonary bypass support (Figure 1).

A detailed clinical findings and preoperative values of the patients
were recorded over a structured proforma for all the patients.All the
patients are classified according to their age, sex, diagnosis,
preoperative and post-operative echo findings and results after surgery.
The results thus obtained are tabulated, analysed and conclusions drawn
thereafter.

Operative procedure:

In all the 265 patients who underwent MVR, 195 of them had severe PHT .
All of them had the classical left atrial approach through Sondergaard's
groove incision except 11 cases which was approached through the septum
after opening the right atrium. All cases were operated through the
standard median sternotomy and were done using cardiopulmonary bypass
utilizing cardioplegic arrest to open the chamber (s) (Figure 2). In
about 195 out of 265 patients (73.58\%), MVR was done with either
partial or complete chordal preservation. All the patients had St Jude's
mechanical prosthetic valve (Figure 2).

Except for the 14 deaths which occurred due to low cardiac output
failures, all other cases were weaned of the ventilator by day 1 and
from the inotropic supports by day 2 or day 3.Those patients who had
severe Pulmonary Hypertension who underwent MVR were followed up using
echo at day 0, 3 months and 6 months.

\textbf{Results:}

Quantitative variables were expressed as mean, standard deviation.
Qualitative variables were expressed as proportions.

Data analysis was done using SPSS version 16.0

According to the age group distribution of the disease (severe PHT) , we
can see from the \textbf{fig 3} ,that the age group affected is mostly
from 20 yrs to 50 yrs (90.1 \%) .This is a productive age group and
needs to be addressed carefully

While considering the sex of the population affected its seen that
females are slightly more affected (54.7\%) compared to males (45.3\%)
as evident from the \textbf{fig 4.}

On comparing the tables 1 and 2, we could decipher that most of the
patients in the preoperative period were in class III NYHA (67.5 \%) and
were symptomatically improved to NYHA class II (68.7\%). On performing
the chi square test it was statistically found to be significant p
\textless{}0.001

On statistically analyzing the results for the regression in Pulmonary
Hypertension following Mitral valve Replacement in our study, we could
definitely appreciate that the regression starts from the first month of
post surgical period and continues till 3 months post surgical period (p
0.026; p0.095) \textbf{Table 3} which is quite significant statistically
.It's quite interesting to note that the regression is not appreciable
after 3 months as is evident from the \textbf{fig. 3}

The Kaplan Meir curve depicts the drastic regression at 1 month of
surgery and gradual regression thereafter in the following months.

As far as the age groups are compared it's not statistically seen that
significant regression occurs following Mitral Valvular Replacement due
to severe pulmonary Hypertension .In other words Age doesn't influence
much in the regression of PHT after Mitral valve replacement in patients
with severe PHT preoperatively{[}\textbf{Table 5} {]} .

\textbf{DISCUSSION} :

Normal Pulmonary arterial pressure in a person living at sea level has a
mean value of 12--16 mm Hg (1600--2100 Pa). Pulmonary Hypertension is
present when mean Pulmonary artery pressure exceeds 25 mm Hg (3300 Pa)
at rest or 30 mm Hg (4000Pa) with exercise {[}9{]}.

PHT can be idiopathic or familial with various underlying causes and
classifications. PHT classifications were modified regularly for better
understanding of the disease .the latest modification was done in Nice,
France 2013. {[}Table 1{]} The reduction of PHT following MVR is not
well understood and relies on various factors{[}10,11{]}. This is a
follow up study providing information on the agenda.

In all our 265 patients who underwent MVR, 195 had severe Pulmonary
Hypertension females 111/195(56.9\%) outnumbered the males in this
diagnosis. The immediate reduction of Pulmonary Hypertension happened in
only approximately 21 \% of the patients and the remaining had
persistent PHT which showed a fall progressively following a 1-3 months
period suggesting the various factors which might be responsible for the
Pulmonary Hypertension.

Yang and colleagues found the long term survival was inversely related
to the degree of PHT and had an early (30 day) mortality of 9\% in
patients with severe PHT, However in our study it was found to be only
5.3\% .But it needs further follow up of these patients in the long run.
{[}12{]}.

Cesjnvar et al has reported higher early mortality among his series of
382 patients who underwent MVR for Mitral Valvular disease with
Pulmonary Hypertension. But the late mortality was no different among
patients with or without Pulmonary Hypertension {[}13{]}.In our study
the mortality was 5.3\%, which was less compared to the previous
studies. The difference might be because of the earlier decision to
operate upon this severe group before irreversible factors sets in and
also due to the better intraoperative and postoperative care using
latest agents so far approved for this purpose.

Most studies have demonstrated an immediate reduction in PAP and PVR,
signifying a sudden drop in left atrial pressure and reversal of the
severe spastic pulmonary vasoconstriction that accompanies left atrial
hypertension in some patients {[}10\& 14{]}. Others have shown slow
regression of elevated PAP and PVR several months postoperatively
{[}14{]}. These reports point toward the involvement of multiple factors
in the development of PAH in mitral valve disease {[}14{]}. In our study
the mean PAP and PVR did not fall significantly immediately following
MVR. The mean fall in PAP was about 46.1mmHg in
1\textsuperscript{st}month and 38.9 mmHg in the 3\textsuperscript{rd}
month follow up after surgery, which was against the previous views.

Reduction of PHT is not random after MVR and is found to be reducing
gradually at 1 and 3 months in our study. This analysis showed that the
reduction in PHT had a gradual course. This gives us a clue that the
reduction in Pulmonary Hypertension is a gradual one and needed change
in organic level as well as in the dynamic level which takes some time
to achieve {[}15-20{]}.

However, the long-term follow up of these patients are needed to
conclude firmly regarding reduction of PHT postoperatively.

\textbf{CONCLUSION:}

We conclude that MVR is safe and effective even in the presence of
severe PHT as long as the pulmonary arterial pressures are below
systemic pressures. With suprasystemic PHT, MVR carries a high risk of
mortality, and the patient continues to have persistent PHT in the
postoperative period. Significant reduction in PHT following MVR takes
place only gradually and in this study about 1 to 3 months period showed
a decline in PHT as compared to the previous belief of immediate
reduction in PHT in majority of the patients. This explains the
multifactorial causes of PHT in patients with Rheumatic mitral valvular
heart disease and severe PHT.

\textbf{LIMITATIONS} :

Lack of follow-up of Pulmonary vascular dynamics by catheterization
constitutes a limitation of this study and was related primarily to
economic factors. A postoperative lung biopsy might have added to the
information, but this was not undertaken as most of the patients refused
consent for it.

\textbf{References:}

1. Magne J, Pibarot P, Sengupta PP, Donal E, Rosenhek R, Lancellotti
P.~Pulmonary hypertension in valvular disease: a comprehensive review on
pathophysiology to therapy from the HAVEC Group.~JACC Cardiovasc
Imaging~(2015)~8(1):83--99. 10.1016/j.jcmg.2014.12.003 {[}PubMed{]}
{[}CrossRef{]}~{[}Google Scholar

2 .Rich~S,~Rubin~LJ,~Abenhail~L,~et al.~Executive Summary From the World
Symposium on Primary Pulmonary Hypertension (Evian, France; September
6--10, 1998).~\emph{Geneva, Switzerland: World Health Organization;}
1998:1--27.Google Scholar

3. Heath~D,~Edwards~JE.~The pathology of hypertensive pulmonary vascular
disease; a description of six grades of structural changes in the
pulmonary arteries with special reference to congenital cardiac septal
defect.~\emph{Circulation} .~1958;18(4, pt 1):533--547

4. Weitsman T, Weisz G, Farkash R, Klutstein M, Butnaru A, Rosenmann D,
et al.~Pulmonary hypertension with left heart disease: prevalence,
temporal shifts in etiologies and~outcome.~Am J
Med~(2017)~130(11):1272--9. 10.1016/j.amjmed.2017.05.003 {[}PubMed{]}
{[}CrossRef{]}~{[}Google Scholar{]}

5. Simonneau~G,~Gatzoulis~MA,~Adatia~I,~et al.~Updated clinical
classification of pulmonary hypertension published correction appears
in\emph{J Am Coll Cardiol} .~2014; 63(7):746{]}. J Am Coll Cardiol.
2013;62(25)(suppl):D34--D41.

6\textbf{.} N.~Galie,~M.~Humbert,~J.L.~Vachiery,~\emph{et al\textbf{.}}
2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary
hypertension: The Joint Task Force for the Diagnosis and Treatment of
Pulmonary Hypertension of the European Society of Cardiology (ESC) and
the European Respiratory Society (ERS): Endorsed by: Association for
European Paediatric and Congenital Cardiology (AEPC). International
Society for Heart and Lung Transplantation (ISHLT) Eur Heart
J,~37~(2016), pp.~67-119

\textbf{{[}CrossRef{]}{[}View Record in Scopus{]}{[}Google Scholar{]}}

\textbf{7.}Simonneau G, Montani D, Celermajer DS, et al. Hemodynamic
definitions and updated clinical classification of pulmonary
hypertension. Euro Respir J 2019; 53.

8. Guidelines on the management of valvular heart disease: The Task
Force on the

Management of Valvular Heart Disease of the European Society of
Cardiology. Eur

Heart J. 28: 2007; 230-268.

9. Kaul TK,Bain WH, Jones Jr, Lorimer AR, Thomsen RM, Turner MA et al :

Mitral Valve Replacement in the presence of severe Pulmonary
Hypertension.

THORAX 1976; 31: 332

10. Reeve R, Selzer, A., and Popper R. w., Leeds R F., and Gerbode .F.
1966:

Reversibility of Pulmonary Hypertension following Cardiac Surgery.
Circulation, 33,

Supplement 1, 107.

11. Vachi\selectlanguage{ngerman}éry JL, Tedford RJ, Rosenkranz S, et al. Pulmonary hypertension
due to left heart disease.~\emph{Eur Respir J} ~2019;53:1801897.

12. Yang B, Debenedictus C, Watt T, Farley S, Salita A, Hornsby W, et
al.~The impact of concomitant pulmonary hypertension on early and late
outcomes following surgery for mitral stenosis.~J Thorac Cardiovasc
Surg~(2016)~152(2):394--400. 10.1016/j.jtcvs.2016.02.038 {[}PubMed{]}
{[}CrossRef{]}~{[}Google Scholar{]}

13. Cesnjevar ra, Feyrer R, Walther F,Mahmoud FO,Lindemann Y,von der
Emde

J.High risk Mitral valve replacement in severe Pulmonary
Hypertension.-30 years

Experience. European J cardiothoracic surg1998; 13:344-51

14. Walls MC, Cimino N, Bolling SF, Bach DS.Persistent Pulmonary
Hypertension after

Mitral valve surgery. Does surgical procedure affects the outcome? J
Heart Valve

Disease. 2008; 17:1-9.

15. Vachiéry JL, Adir Y, Barberà JA, Champion H, Coghlan JG, Cottin V,
De Marco T, Galiè N, Ghio S, Gibbs JS,~et al..~Pulmonary hypertension
due to left heart diseases.\textbf{J Am Coll Cardiol} .~2013; 62(25
suppl):D100--D108. doi: 10.1016/j.jacc.2013.10.033
{[}Crossref{]}{[}Medline{]}{[}Google Scholar{]}

16. Mentias A, Patel K, Patel H, Gillinov AM, Sabik JF, Mihaljevic T, et
al.~Effect of pulmonary vascular pressures on~long-term outcome in
patients with primary mitral regurgitation.~J Am Coll
Cardiol~(2016)~67(25):2952--61. 10.1016/j.jacc.2016.03.589 {[}PubMed{]}
{[}CrossRef{]}~{[}Google Scholar{]}

17. Pourafkari L, Ghaffari S, Ahmadi M, Tajlil A, Aslanabadi N, Nader
ND.~Pulmonary hypertension in rheumatic mitral stenosis
revisited.~Herz~(2017)~42(8):746--51. 10.1007/s00059-016-4509-2
{[}PubMed{]} {[}CrossRef{]}~{[}Google Scholar{]}

18. . Braunwald E, Braunwald .s, Ross J Jr, Morrow AG. Effects of Mitral
Valve

Replacement on the pulmonary vascular Dynamics of patients with
Pulmonary

Hypertension. N.ENGL J MED 1965; 273; 509.

19. M.~Guazzi,~B.A.~Borlaug. Pulmonary hypertension due to left heart
disease. Circulation,~126~(2012), pp.~975-990

20. Dalen JF, Matloff JM , Evans GL, Hoppin FG Jr, Bhardwaj P, Harken DE
et al

: Early Reduction of Pulmonary vascular Resistance after Mitral Valve
Replacement.

N. ENGL.J.Med 1967; 277; 387.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/fig1/fig1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/fig2/fig2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/fig3/fig3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/fig4/fig4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/fig5/fig5}

\end{center}
\end{figure}

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

