Acute changes in mitral valve insufficiency severity after isolated aortic valve replacement due to aortic stenosis: A literature review.

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Hassan Abdallah

Sixth year, Group 37

Acute changes in mitral valve insufficiency severity after

isolated aortic valve replacement due to aortic stenosis:

A literature review.

Master thesis

Supervisor:

Doc. Vaida Mizariene

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2 LITHUANIAN UNIVERSITY OF HEALTH SCIENCES MEDICAL ACADEMY

FACULTY OF MEDICINE CLINIC OF CARDIOLOGY

Acute changes in mitral valve insufficiency severity after isolated aortic valve replacement due to aortic stenosis:

A literature review.

Master thesis

The thesis was done

by student ……… Supervisor………

(Signature) (signature)

………. ………

(name, surname, year, group) (degree, name, surname)

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ABSTARCT

Aims and objectives: The aim of our study is to analyse the acute changes of mitral valve

insufficiency severity after isolated aortic valve replacement due to aortic stenosis. This review compared the improvement of mitral valve regurgitation according to different degrees, discussed the pathophysiological changes of mitral valve regurgitation after isolated aortic valve replacement and the impact of risk factors on the improvement of mitral valve regurgitation.

Methods: This study is a literature review, the articles used were collected from the PubMed. The

articles were taken within the last 5 years, done on human, in English language and a full text article.

Results: A total of 317 articles were found related to my search on the PubMed. According to

inclusion and exclusion criteria, we exclude 263 articles and we checked the rest if they meet the aim of this article. From the remained 54 articles, 5 articles met the criteria and were chosen to be studied for this review after a careful inspection.

Conclusion: This study showed that mitral valve regurgitation improves after isolated aortic valve

replacement, and the rate of improvement depends on the degree of the mitral valve regurgitation before operation, where moderate or severe regurgitation will improve more than mild regurgitation. Some risk factors can negatively affect the changes in the mitral regurgitation such as diabetes mellitus, dyslipidaemia and male gender.

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ACKNOWLEDGEMENT

I would like to thank everybody who had been involved in gathering all the information necessary, in providing all the useful resources that accumulated in positive results. Special thanks and sincerest respect to Dr. Vaida Mizariene for all the assistance and guidance during the process and completion of this thesis.

CONFLICT OF INTEREST

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1. INTRODUCTION

Mitral valve regurgitation (or insufficiency) and aortic stenosis are the most frequent valvular diseases in both Europe and the united states [1]. Mitral valve regurgitation is a defective process in a mitral valve causing blood to flow back from the left ventricle to the left atrium. It is classified into primary and secondary mitral valve regurgitation.

Primary mitral valve regurgitation, also known as degenerative valve regurgitation, refers to defects in the mitral valve itself and mitral prolapse is the most common among this group [2]. Some other diseases causing mitral regurgitation include rheumatic heart disease and infective endocarditis [2,3]. Secondary mitral valve regurgitation, also known as functional regurgitation, caused by abnormalities in the left ventricle that can change the proper function of the mitral valve [3].

Aortic stenosis is mostly found in old people. It is mostly caused by valve calcification due to ageing, 2-4% of old people above 75, but it can also be congenital or due to rheumatic disease [4]. Patients with aortic stenosis can be asymptomatic until the left ventricle is impaired causing mainly shortness of breath, chest pain and dizziness. Aortic stenosis is an irreversible process that will need aortic valve replacement to be solved [4].

It is shown that most of the patients having severe aortic stenosis also have functional mitral valve regurgitation of various degrees. Patients having aortic stenosis can develop left ventricle dilation due to left ventricle afterload mismatch [7]. This ventricle dilation will lead to mitral valve deformation and leaflet tethering causing functional mitral valve regurgitation.

Combined valvular surgery is not preferable if there is a chance of improvement of mitral valve regurgitation after the isolated aortic valve stenosis, and that’s because the prognosis of combined valvular surgery will be poor as it will extend the operation and increase the risk of mortality [9].

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1.1 Aim

The aim of our study is to elaborate the acute changes of mitral valve insufficiency severity after isolated aortic valve replacement due to aortic stenosis. The study will take into consideration the different degrees of mitral valve insufficiency from mild, moderate to severe as well as the risk factors that the patients have that can affect the changes in mitral valve and will focus on how the functional type will change after isolated aortic valve replacement.

1.2 Objectives

The objective in this study was to perform a comprehensive research analysing:

• Changes in the mitral valve regurgitation according to different degrees of regurgitation: mild, moderate and severe.

• Pathophysiological changes affecting mitral valve insufficiency post operation. • Risk factors that affect mitral valve insufficiency post operation.

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ABREVIATION

LVEF: left ventricular ejection fraction

ACE inhibitors: angiotensin converting enzyme inhibitors

SAVR: surgical aortic valve replacement

TAVI: transaortic valve implementation

LVH: left ventricular hypertrophy PE: pulmonary oedema

MRI: magnetic resonance imaging ECG: electrocardiogram

IAVR: isolated aortic valve replacement LV: left ventricle

EF: ejection fraction AS: aortic stenosis PO: post operation

LVEDD: left ventricular end diastolic diameter LVF: left ventricular failure

LA: left atrium AF: atrial fibrillation IE: infective endocarditis

AVMG: aortic valve mean gradient IVSD: interventricular septum diameter LVEDV: left ventricular end diastolic volume

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2. LITERATURE REVIEW

Anatomical structure of mitral valve

The mitral valve is one of the atrioventricular valves that helps in blood circulation. Mitral valve, also called bicuspid valve, is found between the LV and the LA. The main function of the valve is to prevent the backflow of blood from the left ventricle to the left atrium. It is formed of papillary muscles, mitral annulus, leaflet and chorda tendinea.

Mitral annulus is a ring surrounding the mitral opening. During systole, blood must flow from the LV to the aorta, so to prevent the backflow of the blood to the left atrium, the ring will contracts decreasing the area of the mitral valve by closing the leaflet (Figure 1) [25]. Mitral valve has 2 leaflets, anterior and posterior ones. The anterior leaflet has semi-circular shape and is larger than the posterior leaflet [25].

Chorda tendinea are fibrous parts composed of elastin and collagen and originates form papillary muscles. Two kind of chorda tendinea are found, primary and secondary. The primary chorda are thinner and they are attached to the leaflets [25]. Attachment of chorda tendinea to the leaflet prevent the last from being prolapsed. Secondary chorda tendinea are thicker than the primary chorda and they help in relieving the tension of the leaflets [25].

Papillary muscles are the muscular part of the mitral valve that form with the mitral annulus a coordination system. This coordination system can cause contraction of the valve during systole and prevent the leaflet from prolapsing. This can maintain the blood flow and prevent the backflow of blood from the LV to the LA [25].

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Figure 1. Anatomical structure of the mitral valve that is composed of papillary muscles, chorda

tendineae, anterior and posterior leaflets and mitral annulus.

Definition of Mitral valve regurgitation

Mitral valve regurgitation, also known as mitral valve insufficiency, is a very common valvular pathology worldwide affecting 10% of the total population [11]. It is caused by the backflow of blood from the LV to the LA passing by mitral valve, and that will cause systolic murmur that will best be heard above the apex of the heart [10].

Mitral regurgitation can be one of the 2 types, primary or secondary mitral valve regurgitation. Primary mitral regurgitation results from structural deformity of the leaflet and/or papillary muscles causing the valve not to close fully during systole [12]. Secondary mitral regurgitation results from left ventricular deformity where there will be no structural deformity in the valve [10].

Chronic MR mostly goes asymptomatic but it can manifest as dyspnoea and fatigue as an early sign of disease. Treatment of both types of mitral regurgitation differs from patient to another, and it can be pharmacological or surgical depending on the symptoms and left ventricular ejection fraction. So,

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11 if the LVEF is more than 60% with no symptoms then pharmacologic treatment is the best choice. This is achieved by giving beta blockers and ACE inhibitors, whereas if the LVEF is less than 30% and the patient complaining of symptoms such as dyspnoea and exercise intolerance then mitral valve replacement is necessary [2].

Pathophysiology of mitral regurgitation

Mitral regurgitation increases the blood volume within the LA after the backflow of blood from the left ventricle, and this will increase the preload of the left ventricle in diastolic phase. The increase in the preload will cause increase in the stroke volume as well as left ventricular volume overload [12]. In case of chronic mitral regurgitation, ventricular dilatation will take place as well as decreased contractility causing a decrease in the ejection fraction that will result in worsening of mitral regurgitation [10].

Decreasing contractility of the LV as well as mitral regurgitation will cause the heart to pump less blood, so cardiac output will decrease and because of increased regurgitant volume left atrial size will be increased and that will cause atrial dilatation after worsening of the mitral regurgitation. The dilatation of the left atrium can be a cause many complications including atrial arrhythmias, right heart failure and thrombus reactive pulmonary hypertension [10].

Also having decreased cardiac output and lower contractility will cause left ventricle to be volume overloaded that will be the cause of concentric LVH and then then leading to LVD [12]. This dilatation with time will cause LV to lose adaptation and cause LVF that can lead to many other complications causing PE and systemic hypotension [10].

Diagnosis and treatment of Mitral regurgitation

Echocardiography is considered the gold standard for diagnosing mitral regurgitation. Both transthoracic and transoesophageal echocardiography can provide quantitative and qualitative analysis for patients with mitral regurgitation [10]. For a good evaluation of mitral regurgitation and to take the appropriate choice of treatment, echocardiography must be repeated every 6 to 12 months for patients having severe mitral regurgitation. In case of moderate mitral regurgitation, echocardiography must be repeated every 1 to 2 years to follow the changes in severity. For mild mitral regurgitation, it is enough to repeat echocardiography every 2 to 5 years as a follow up [13].

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12 In case electrocardiography did not show the severity of mitral regurgitation, cardiac MRI can be done and can provide quantitave measures describing the regurgitant volume and the relation between mitral regurgitation and left ventricle remodelling [14]. Many other tests can help in diagnosing mitral regurgitation but they are not as specific as echocardiography such as electrocardiogram, exercise stress test and biomarkers as B-type natriuretic peptide [10].

Treatment depends on the severity and the chronicity of mitral valve regurgitation. In some studies, pharmacological treatment is not considered as a solution that can treat or help in case of mitral regurgitation because there is no evidence that supports that [13].

Other studies showed that angiotensin-converting enzyme inhibitors as well as angiotensin II receptor blocker can help in slowing the progression of mitral regurgitation according to severity, and that can occur by decreasing the regurgitant volume and the size of LV [15]. Studies also showed that beta blockers can increase the survival rate in secondary mitral regurgitation but has no effect on the primary mitral regurgitation [10].

Mitral valve surgery has certain indications that can differ according to the aetiology of the mitral valve regurgitation whether it is primary or secondary. In case of primary mitral regurgitation, surgery is indicated when the patient is symptomatic with LVEF is more than 30% or in asymptomatic patients with left ventricular dysfunction or having AF caused by the mitral valve regurgitation [26].

In case of secondary mitral valve regurgitation, surgery is indicated when the patient is symptomatic having severe regurgitation with LVEF lower than 30% and the medical treatment did not show any improvement [26].

Mitral valve repair or replacement is needed in patients having acute severe Mitral regurgitation or if complications are occurring such as ischemia and endocarditis [16]. Mitral valve replacement is preferred over repair in case there is sever tissue destruction such as IE [10].

Treatment of mitral regurgitation in patients with severe aortic stenosis

As we said before that AS is a very common valvular disease worldwide. For asymptomatic patients, no medical treatment is needed to stop the progression of AS, but it must be always monitored by serial doppler echocardiography [5]. Asymptomatic patients with severe AS need to do echocardiography every six months, those with moderate AS need to do it every 2 years and others with mild stenosis need echocardiography every 5 years [5].

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13 In symptomatic patients, treatment for AS can be done by surgical aortic valve replacement (SAVR) for low and moderate risk patients, while for high risk patient Transcatheter aortic valve implantation (TAVI) is preferred. The advantage of TAVI is that it is showing the same good results as SAVR in high risk patients and reducing the mortality rate for these patients [6].

It is very common for patients that are candidates for aortic valve replacement due to severe AS to have mitral regurgitation as well [17]. Combined aortic and mitral valve surgery is associated with high mortality rate, so because of that it is very important to decide whether it is necessary to do combined aortic valve and mitral valve replacement or it is enough to do only aortic valve replacement that can improve mitral regurgitation as well [18].

Some studies showed that in case the patient is having mild or mild-moderate mitral regurgitation with severe AS, isolated aortic valve replacement is done without mitral valve repair or replacement, and in this case treatment of functional mitral regurgitation is done by conservative treatment [19]. On the other hand, if the patient is having moderate-severe to severe mitral regurgitation then it is necessary to do combined aortic and mitral valve replacement [19].

Mechanism of acute changes in mitral valve regurgitation after isolated aortic valve replacement

Many studies were concerned to study the improvement or worsening of mitral valve regurgitation after isolated aortic valve replacement. Some studies showed that the mechanism that can lead to improvement of mitral regurgitation post operation was that the intraventricular pressure will be reduced after treatment of AS, and that can help in improving the functional mitral regurgitation [21].

Some studies observed that the reason that mitral valve regurgitation is improving after isolated aortic valve replacement was because of changes in the mitral annulus. Between the anterior mitral annulus and the aortic valve there is aortic mitral curtain, and some studies showed that after the aortic valve replacement, changes in this annulus is causing the regurgitant volume to be reduced and thus improving the mitral valve regurgitation [24].

On the other hand, a study showed that the cause of the improvement of mitral valve regurgitation after the isolated aortic valve replacement was the left ventricular remodelling [21]. The reason is after the operation, the volume afterload in the left ventricle will be reduced and the stress on its wall will be reduced as well. This will cause left ventricle size to be decreased causing the tethering forces of the mitral valve, resulting in improvement in mitral regurgitation severity [21].

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Echocardiographic changes of mitral regurgitation after isolated aortic valve replacement

To determine whether there are acute changes in the mitral valve regurgitation after isolated aortic valve replacement, echocardiographic images were needed to evaluate these changes and to compare the degree of mitral valve regurgitation preoperatively and postoperatively.

According to some studies, mitral valve regurgitation showed an improvement in around 45% in patients having mild mitral regurgitation and in around 95% of patients having moderate mitral regurgitation [19]. The changes of mitral regurgitation was evaluated according to some echocardiographic parameters that showed that after isolated aortic valve replacement, left ventricular ejection fraction as well as left ventricle end diastolic diameter and left ventricle end systolic diameter showed a decrease after the isolated aortic valve replacement and that caused a reduction in the mitral regurgitation [19].

Another indicator for mitral regurgitation changes after isolated aortic valve replacement is the pulmonary artery systolic pressure that can be considered as an indicator of unchanging of moderate to severe mitral regurgitation post operation [8].

Risk factors affecting improvement of mitral regurgitation after isolated aortic valve replacement

The improvement of mitral valve regurgitation after isolated aortic valve replacement can be associated by risk factors that can reduce this improvement or even prevent the improvement from occurring. Some studies showed a relation between gender of the patient and the improvement of the mitral valve regurgitation. These studies showed that women are more capable of having improvement in mitral valve regurgitation after isolated aortic valve replacement than men, and that can be caused by the reason that women have less body weight, left ventricular volume is lower and the ejection fraction in higher [8].

Also, diabetes and dyslipidaemia showed to be associated with reduction in the improvement of mitral valve regurgitation [8]. In some studies, it was shown that age is not related to improvement or worsening in the mitral valve regurgitation after isolated aortic valve replacement and is not considered a parameter that can affect the improvement [8].

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Improvement of mitral regurgitation after isolated aortic valve replacement according to its Degree

In addition to all the risk factors that can affect the improvement of mitral regurgitation after isolated aortic valve replacement, also the degree of mitral regurgitation before operation plays a role in determining the rate and level of improvement of mitral regurgitation post operation.

Some studies showed that all degrees of mitral regurgitation can show an improvement, but it is 24 times greater to have improvement in patients with mitral regurgitation higher than mild than those patients with only mild regurgitation [19]. Even some studies stated that whenever the mitral regurgitation is of higher degree, then it is more likely that this patient will have improvement of mitral regurgitation after isolated aortic valve replacement, and that was confirmed in a study that showed in its statistics that out of 14 patients having severe mitral regurgitation before operation, 8 out of these 14 showed improvement at least 1-degree post operation [20].

Prognosis in patients after aortic valve replacement with functional mitral valve regurgitation

It is important to determine the long-term survival for patients undergoing isolated aortic valve replacement having mitral valve regurgitation of various degrees. First by comparing patients without mitral regurgitation undergoing isolated aortic valve replacement and those with mitral regurgitation, studies showed that patients without preoperative mitral regurgitation have better prognosis post operation than that of having mitral regurgitation of various degrees [22].

Studies have shown that patient having moderate or severe mitral valve regurgitation as well as severe AS have lower long-term survival than those who have mild or no mitral valve regurgitation (Fig 2) [22]. The reason behind this lower prognosis was because moderate or severe mitral regurgitation will be improved after isolated aortic valve replacement but after one year it was shown that the severity will start to increase according to echocardiography [22].

These results were shown in the figure below showing the difference between survival rate for patients without preoperative mitral regurgitation and between those with preoperative mitral regurgitation, and it is clear that those without mitral regurgitation has a better survival rate than patients undergoing isolated aortic valve replacement having preoperative mitral valve regurgitation.

Some studies also showed that patients with mitral valve regurgitation that worsens after 1- or 2-years post operation will have a poor survival rate as well these studies showed that mild mitral valve regurgitation will not worsens in a 5-years interval and will have a good prognosis [23].

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Figure 2. Survival rate comparison between patients with or without mitral regurgitation. This figure

shows that patient having no mitral regurgitation before isolated aortic valve replacement has a better prognosis than those with mitral valve regurgitation pre operation.

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3. MATERIALS AND METHODS

3.1 Literature search and screening

This study is a literature review that is done according to the PRISMA guidelines. The articles was taken from the PubMed and the search strategy was as following: (("mitral valve insufficiency"[MeSH Terms] OR ("mitral"[All Fields] AND "valve"[All Fields] AND "insufficiency"[All Fields]) OR "mitral valve insufficiency"[All Fields] OR ("mitral"[All Fields] AND "valve"[All Fields] AND "regurgitation"[All Fields]) OR "mitral valve regurgitation"[All Fields]) AND (("aortic valve"[MeSH Terms] OR ("aortic"[All Fields] AND "valve"[All Fields]) OR "aortic valve"[All Fields]) AND ("replantation"[MeSH Terms] OR "replantation"[All Fields] OR "replacement"[All Fields]))) AND ("aortic valve stenosis"[MeSH Terms] OR ("aortic"[All Fields] AND "valve"[All Fields] AND "stenosis"[All Fields]) OR "aortic valve stenosis"[All Fields] OR ("aortic"[All Fields] AND "stenosis"[All Fields]) OR "aortic stenosis"[All Fields]).

To choose the appropriate articles, some criteria were taken to collect enough and necessary articles that can be used in our study. To do so, inclusions and exclusions were used to determine which articles are the best in our study.

3.2 Selection of studies

Last electronic search was done on 20th February, 2020. I found 317 articles related to my search including the criteria of human and 5-year publication date. No duplicated were found so nothing were removed. 54 articles were having a good topic but after reading the abstract, 11 articles were nominated for this study. These 11 articles were read and 5 articles met the criteria and were necessary for this study. Figure 3 elaborate the searching process.

3.3 Inclusion and exclusion criteria

Inclusion criteria:

• The publication dates must be 5 years • Human sample

• Full text article

• articles in English language

• Acute changes in mitral regurgitation • Functional mitral regurgitation

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18 • Clinical studies

Exclusion criteria:

• More than 5 years publication period

• Systematic or literature review

• Animal sample

• Patients with other cardiological problems (coronary disease)

• Structural mitral regurgitation

• Prior mitral surgery

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Figure 3. Prisma flow chart

Records identified through database searching

(n = 317)

Additional records identified through other sources

(n = 0)

Records after duplicates removed (n = 317) Records screened (n = 54) Records excluded (n = 263) Full-text articles assessed for eligibility

(n = 11)

Full-text articles excluded, with reasons

(n =6) Studies included in qualitative synthesis (n = 5) Ide nti fic ati on S cre ening Eligi bil it y Inc luded

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4. RESULTS

The 5 articles were collected from the PubMed and were analysed to compare and discuss the results, to have a good conclusion about the acute changes of mitral valve insufficiency severity after isolated aortic valve replacement (IAVR) due to AS. The results of these articles were summarized in the table below and organized for a good comparison and discussion (Table 1).

All the articles collected were retrospective studies collected from the last 5 years and all discuss different aspects of changes in the mitral insufficiency, covering by that the points of objectives that we are aiming to discuss.

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Table 1. Results

Title Study type Publish

ing year Country Number of patients Age Type of mitral insufficiency Degree of mitral insufficiency Result Khosravi , Arezoo et al. [19] Retrospect ive study March 2015 Iran, Tahran 85 patients (27 were female) 56 ±6.1 years old (youngest 16 years old, oldest 79 years old) Functional mitral insufficiency 64 Mild and 21 moderate mitral insufficiency patients

95% of patients having preoperatively moderate mitral insufficiency had at least 1-degree improvement, while 45% of those having preoperatively mild mitral insufficiency had improvement.

Sehovic, Sejla et al. [8] Retrospect ive study 25 May 2015 Bosnia and Herzego vina 45 patients (17 females ) 55 - 65 years old Functional mitral insufficiency Moderate and severe mitral insufficiency

This study showed that 46.7% of patients having moderate to severe mitral

insufficiency showed improvement in the mitral insufficiency, while 53.3% did not show any improvement, and the cause of that was these patients were having concomitant diseases such as diabetes mellitus and dyslipidemia.

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22 Fojt, Richard, et al. [20] Retrospect ive study June 2016 Czech Republic 101 patients (60 males) 76.1 ± 8.2 years old Functional mitral insufficiency Mild to moderate, moderate, moderate to severe and severe mitral insufficiency

This study showed that 59% of patients showed improvement of mitral

insufficiency after aortic valve replacement, while 24% showed no change in mitral insufficiency, 12% showed worsening in the mitral

insufficiency post operation and 5% died before even postoperative

echocardiography. Also, it showed that the prognosis of patients with unchanged mitral regurgitation is poor compared to that of improved mitral insufficiency.

Wang, Weitie et al. [21] Retrospect ive study Novem ber 2019 China 49 patients 52.6 ± 12.2 years old Functional mitral insufficiency Moderate mitral insufficiency

This study showed that mitral

insufficiency was improved after isolated aortic valve replacement by showing a decrease in the annular area by 17.7%. Left ventricular end diastolic volume, left ventricular size and left atrial size had shown an improvement as well after operation.

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23 Schubert , Sarah A, et al. [23] Retrospect ive study April 2016 Canada 172 patients (41 females ) 73 ± 13 years old Functional mitral insufficiency Mild and moderate mitral valve insufficiency

This study had showed that patients with moderate mitral insufficiency had more improvement than that having mild mitral valve insufficiency. This study also showed that moderate mitral

insufficiency worsens after 2-years post operation while in case of patients having mild mitral valve insufficiency, it shows no worsening after this year.

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5. DISCUSSION

Mitral regurgitation in patients with AS is very common worldwide, and multiple valvular surgeries such as aortic valve replacement with mitral valve replacement or repair can lower the survival rate for patients especially those with high risk and old patients. It is important to check whether the patient needs multiple valve surgeries or mitral regurgitation severity can improve after isolated aortic valve replacement.

The results that our study collected showed that there is an improvement in the mitral valve regurgitation after isolated aortic valve replacement, and this improvement depends on certain factors including the degree of mitral valve regurgitation preoperatively as well as the risk factors and the concomitant chronic diseases the patient might have that can influence the severity and the rate of this improvement.

Khosravi, Arezoo et al. [19] in his study showed that the degree of mitral valve regurgitation plays an important role in determining the rate of improvement of the regurgitation post isolated valve replacement. In his study, 85 patients were collected to check the acute changes of mitral valve regurgitation after isolated aortic valve replacement and it showed that patients having more than mild regurgitation had 24 times more improvement than those with mild or lower regurgitation [19].

To prove these results echocardiography was done before and after aortic valve replacement, and the results showed that there was a significant improvement in the left ventricular ejection fraction (LVEF) as well as left ventricular end diastolic diameter (LVEDD) [19]. These results can confirm the improvement of mitral regurgitation through reducing mitral annulus size that is caused by reducing the LVEDD.

In addition, also this study showed a reduction in the aortic valve mean gradient (AVMG) and the inter-ventricular septum diameter (IVSD) that can help in decreasing the severity of mitral regurgitation by reducing the stress on the left ventricular wall [19].

The study of Khosravi, Arezoo et al. was done over a short period after aortic valve replacement, and that was considered a limitation because the results might be influenced by the surgery itself as in case of LVEF that can be reduced due to anaesthetic drugs. The point of strength in this article was that it excluded all patients undergone mitral valve surgery before or coronary artery bypass grafting, so that they are focusing on the acute changes of the mitral regurgitation post isolated aortic valve replacement only [19].

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25 Fojt, Richard, et al. [20] in his study had shown that 59% of the patients that had mitral regurgitation with severe AS had improvement in the severity of the mitral regurgitation, 24% of the patients showed no changes in their mitral regurgitation, 12% had worsening in the mitral regurgitation post operation and 5% died before doing the echocardiography post operation [20].

Fojt, Richard, et al. also proved in his study as the study before of Khosravi, Arezoo et al. that having mitral regurgitation more than mild can show higher rate improvement than having mild mitral regurgitation before operation. The results showed that before operation 45.6% of patients had moderate or higher mitral regurgitation with severe AS, and this percentage was decreased to 27% after the isolated aortic valve replacement [20].

The study of Fojt, Richard, et al. didn't exclude the vessel diseases with the severe AS and the TAVI procedure as Khosravi, Arezoo et al. in his study did, and it showed that the severity of mitral regurgitation post operation in patients having three vessel disease or undergoing TAVI procedure will have less changes and will improve less [20]. Also in his study, he showed that changes of mitral regurgitation severity after isolated aortic valve replacement is associated with the morbidity after operation, so whenever there is less changes in mitral regurgitation severity, morbidity post operation will increase [20].

In another study, Sehovic, Sejla et al. [8] in his study proved that some risk factors can influence the improvement of mitral valve insufficiency severity after isolated aortic valve replacement. 45 patients, 28 males and 17 females, in this study were included with mitral regurgitation from moderate to severe, and these patients had some risk factors such as diabetes mellitus ( 9 patients), dyslipidaemia (30) and hypertension (34) [8].

Sehovic, Sejla et al. showed in his study that 46.7% of the patients had improvement in the mitral regurgitation severity post operation while 53.3% didn't show any improvement [8]. This percentage that didn't show any improvement were associated with the patients having certain risk factors such as being male, having diabetes mellitus or dyslipidaemia and having atrial fibrillation [8].

Sehovic, Sejla et al. showed in his study that women had more improvement in the mitral regurgitation severity post operation than men. This can be explained because women usually have lower body weight, lower left ventricular volume and higher ejection fraction, and these parameters can influence positively the improvement of mitral valve regurgitation after isolated aortic valve replacement [8].

In another study, Wang, Weitie et al. [21] also had some results in his study concerning the improvement of mitral regurgitation severity after isolated aortic valve replacement. 49 patients were involved in this study, and all of them did the isolated aortic valve replacement. This study showed

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26 that functional mitral regurgitation is improving at least one degree in patients with moderate mitral regurgitation post operation without the need of mitral valve operation [21].

Wang, Weitie et al. in his study has proved that during operation, there was no direct change in the left ventricle size, left ventricle atrium or left ventricle end diastolic volume (LVEDV) [21]. But also, in the same study, changes in the size of LA and LV were observed 10 days after the operation and a decrease in the LVEDV was also observed [21].

Wang, Weitie et al. agreed in his study with Khosravi, Arezoo et al. that the cause of the acute changes in the mitral valve regurgitation after isolated aortic valve replacement is the decrease in the pressure on the left ventricular wall post operation as well as the decrease in the trans mitral pressure [21]. These two improvements after operation are the main cause of changes in the mitral valve regurgitation severity post operation.

Wang, Weitie et al. had limitations in his study that can influence the results, such as using only one centre with a limited number of patients. Also, in this study, the patients were not excluded from having ischemic heart disease and coronary angiography were not done to check whether they have a concomitant disease or not [21].

All studies mentioned before have included only changes in the mitral valve regurgitation severity during or directly after isolated aortic valve replacement (IAVR). Schubert, Sarah A, et al. [23] in his study compared the changes in mitral valve regurgitation severity of patients undergoing IAVR directly post operation and after some years. In this study, 423 patients were involved 53% of them are women. Most of these patients had functional mitral regurgitation and only 3% were presented with rheumatic mitral regurgitation [23].

As what previous studies confirmed, Schubert, Sarah A, et al. had results that the improvement in moderate mitral valve regurgitation (0.53 degrees) is more than that in patients with mild mitral valve regurgitation preoperatively (0.13 degrees) [23].

This study also did a follow up for the patients after 5 years, and this follow up showed that patients with moderate mitral valve regurgitation preoperatively had worsening in the mitral regurgitation severity after 5 years while those with mild mitral regurgitation preoperatively maintained their improvement after 5 years [23].

Also, Schubert, Sarah A, et al. had results that the survival rate for patients having mild mitral regurgitation before operation is higher than that in patients with moderate mitral valve regurgitation, and this can be related to the worsening of the moderate mitral valve regurgitation after 5 years post

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27 operation [23]. This study had strength point by excluding patients that undergone concomitant operations such as CABG, but it had a limitation that it was done in a single institution so there was no large enough sample for generalizability.

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6. CONCLUSION

Patients having mitral valve regurgitation as well as AS will have improvement in this regurgitation after isolated aortic valve replacement, without the need of interventions to fix the mitral valve. The reason behind this improvement was decreasing the pressure on the left ventricle that will reduce the trans mitral pressure as well and by that mitral valve regurgitation will improve post operation.

Also, according to the different degrees of mitral valve regurgitation, moderate and more mitral valve regurgitation will have acute changes in severity of regurgitation more than that in mild mitral valve regurgitation severity. Patients having moderate or more mitral valve regurgitation will have a significant improvement after the aortic valve replacement, but with time the regurgitation will worsen and can be more severe than that before the IAVR and because of that the prognosis of patients having moderate or severe mitral valve regurgitation is worse than that with mild mitral valve regurgitation.

Some risk factors can influence the improvement of mitral valve regurgitation severity after IAVR. Diabetes mellitus, dyslipidaemia and male gender are risk factors that affects negatively the improvement of mitral valve regurgitation after IAVR where most of the patients with these risk factors showed no improvement in the regurgitation after IAVR.

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7. REFERENCES

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