1. D . B A S E M E L S A I D E N A N Y
L E C T U R E R O F C A R D I O L O G Y
A I N S H A M S U N I V E R S I T Y
Mitral regurge

3. ETIOLOGY
--Primary MR:
-Mitral valve prolapse is the most common in developed countries and is also called "degenerative"
or myxomatous mitral valve disease. (valve prolapse of 2 mm or more above the mitral annulus, as
seen in the parasternal long-axis view).
The most common cause of chronic primary MR in developed countries is mitral
valve prolapse, which has a wide spectrum of etiology and presentation. Younger populations
present with
severe myxomatous degeneration with gross redundancy of both anterior and posterior leaflets and
the chordal
apparatus (Barlow’s valve). Alternatively, older populations present with fibroelastic deficiency
disease, in
which lack of connective tissue leads to chordal rupture. The differentiation between these 2
etiologies has
important implications for operative intervention.
-Infective endocarditis.
-Trauma, which can cause ruptured chordae and acute MR.
-Rheumatic heart disease is uncommon in developed countries but continues to constitute a
significant burden in the rest of the world. Although rheumatic valve disease often results in MR in
the first two decades of life, mitral stenosis (MS) and mixed MS/MR are more often seen in adults.

4. -Anorectic drug combinations that are no longer available and
prolonged use of certain other drugs, such as
ergotamine, pergolide, and cabergoline, which may induce MR by a
mechanism similar to that with anorectic drugs {Serotonin stimulates
fibroblast growth and fibrogenesis}
-Congenital due, for example, to a valve cleft.
-Mitral annular calcification is a common finding in older adults that
is often associated with mild to moderate MR
-Rupture of a papillary muscle in the setting of an acute myocardial
infarction
--Secondary (functional) MR:
-Ischemic heart disease.
-Left ventricular systolic dysfunction.
-Hypertrophic cardiomyopathy.

5. Because MR is only 1 component of the disease (severe LV
dysfunction, coronary disease, or idiopathic myocardial disease are the
others), restoration of mitral valve competence is not by itself curative;
thus, the best therapy for chronic secondary MR is much less clear than it is
for chronic primary MR.
The data are limited, and there is greater difficulty in defining the severity of
MR in patients with secondary MR than in those with primary MR. In
patients with secondary MR, adverse outcomes are associated with a
smaller calculated effective regurgitant orifice compared to primary MR due
to multiple reasons.
The MR will likely progress due to the associated progressive LV systolic
dysfunction and adverse remodeling. In addition, there is an underestimation
of effective regurgitant orifice area by the 2-dimensional echocardiography
derived flow convergence method due to the crescentic shape of the
regurgitant orifice.
There are the additional clinical effects of a smaller amount of regurgitation in
the presence of compromised LV systolic function and baseline elevated filling
pressures.

6. AHA 2014

9. CLINICAL MANIFESTATIONS
--Patients with isolated mild to moderate MR are
asymptomatic, since there is little volume overload
--Even with severe MR, most patients remain
asymptomatic until there is left ventricular
failure, pulmonary hypertension, or the onset of atrial
fibrillation
--Exertional dyspnea and fatigue, palpitation
symptomatic heart failure with pulmonary congestion and
edema.{often irreversible due to the long standing MR}
--Thromboembolism, hemoptysis, and right-sided heart
failure do occur, but are less common than with mitral
stenosis
--IEC

10. PHYSICAL EXAMINATION
--Bounding pulse, However, the pulse pressure is
normal
--Leftward displacement of the apical impulse; it is
usually brisk or hyperdynamic
--Thrill and an S3 may be palpable

11. CARDIAC AUSCULTATION
--Heart sounds:
-S1 is diminished, reflecting failure of the mitral leaflets to
close properly.
-Wide splitting of S2 is common because the decrease in
left ventricular ejection time results in an early A2.
Furthermore, if pulmonary artery hypertension is
present, P2 will be increased and delayed, further widening
the splitting of S2.
-The augmented flow rate across the mitral valve orifice
into a dilated left ventricle produces an S3 gallop, which
becomes particularly prominent if left ventricular failure
occurs.

12. --Murmurs:
-Most cases, the murmur is holosystolic, commencing
immediately after S1 and continuing up to and sometime
beyond and obscuring A2, a result of the persistent pressure
gradient between the left ventricle and atrium after aortic valve
closure.
-Best over the apex, radiating to the axilla and when very loud
may often radiate to the back. It is most often blowing and high
pitched in quality.
-Loudness of the murmur correlates even less well with severity
in secondary (functional) MR
-Moderate to severe acute MR is often silent or associated with
only a soft murmur due to equalization of left ventricular and
left atrial pressures

13. -Isometric hand grip is carried out by asking the
patient to lock the cupped fingers of both hands
into a grip and then trying to pull them apart. The
resulting increase in peripheral vascular
resistance intensifies MR (and ventricular septal
defect) while softening instead AS (and aortic
sclerosis). Hence, a positive hand grip argues strongly
in favor of MR.

14. Other types of murmurs
--Posterior leaflet involved (due to prolapse or chordal rupture), the murmur may radiate
anteriorly toward the sternum and is heard well at the base. This type of murmur is often confused
with aortic stenosis but does not radiate to the carotid arteries.
--Mid to late systolic murmur, harsh in quality, is often heard when the MR is due to prolapse or
papillary muscle displacement (previously known as papillary muscle dysfunction)==mitral
valve prolapse (MVP) murmur?
It is an MR murmur—hence, loudest at the apex, mid to late systolic in onset (immediately
following the click), and usually extending all the way into the second sound (A2). In fact, it often
has a crescendo shape that peaks at S2. It is usually not too loud (never greater than 3/6), with
some musical features that have been variously described as whoops or honks (as in the honking of
a goose). Indeed, musical murmurs of this kind are almost always due to MVP.
--Infrequently, the large diastolic volume across the mitral valve produces an early diastolic
murmur
--Mitral valve prolapse, a mid systolic click (correlating with the maximal prolapse and tension on
the chordae) may be heard and the murmur may start in mid to late systole
--MR due to dilatation of the valvular annulus, the murmur often diminishes in intensity or
disappears as the heart failure is treated and left ventricular function improves
-- Maneuvers that decrease venous return and reduce the left ventricular volume cause the systolic
click to occur earlier (move toward S1) and the murmur to be of longer duration (although it is
often fainter). On the other hand, those maneuvers that increase venous return or afterload cause
the click to occur later (move toward S2) and the murmur to be abbreviated

16. Electrocardiogram
--Left atrial enlargement
--Left ventricular hypertrophy
--Pulmonary artery hypertension right ventricular
hypertrophy, which includes a tall R wave in V1 or V2
with R/S ratio >1

17. Chest radiograph
--Cardiomegaly, resulting from enlargement of the left
ventricle {cardiac silhouette to be displaced towards
the left chest wall and the chamber becomes globular}
and left atrium {straightening of the left heart border
with the appearance of a double density and elevation
of the left main stem bronchus}
--Right ventricle is usually normal in size, unless there
is pulmonary hypertension.
--Lung fields are usually clear unless congestive heart
failure is present.
--Calcification of the mitral valve annulus may be seen.

19. Echocardiogram
--If image quality is suboptimal, transesophageal
imaging is recommended
--Severity of MR:
-Severe chronic MR does NOT exist (with rare
exceptions) without clear evidence of left atrial or left
ventricular enlargement

20. AHA 2014

22. Mitral:EROA= regurg V/VTI mr jet
Regurge V=vol transmitral (CSA mitral annulusX VTI mitral annulus)- vol
transaortic (CSA lvotX VTI lvot)
Regurg fraction=rgeurge V/vol transmitral

25. --Cause of MR:
Intraoperative TEE is indicated to establish the anatomic basis for chronic primary
MR (stages C and D) and to guide repair . (Level of Evidence: B)
TEE is indicated for evaluation of patients with chronic primary MR (stages B to D)
in whom noninvasive imaging provides nondiagnostic information about severity of
MR, mechanism of MR, and/or status of LV function. (Level of Evidence: C)
-Mitral valve prolapse, there is posterior movement of the leaflets (hammocking) into the left
atrium during systole. Either one or both leaflets may prolapse to variable degrees. In addition, the
leaflets are thickened and redundant
-Rheumatic heart disease, there is significant thickening of the leaflets and some evidence of
commissural fusion or chordal shortening
-Endocarditis, vegetations are present, typically on the atrial side of the mitral valve leaflets
-Perforated mitral valve leaflet is present, an MR jet can be seen passing through the leaflet
-Chordal or papillary muscle rupture is present, the movement of the leaflets is markedly
exaggerated and the ruptured chord or papillary muscle is seen in the left atrium in systole
-Ischemic MR restricted leaflet motion, particularly of the posterior leaflet, resulting in
inadequate apposition of the leaflets, often called "tenting" or "tethering"

34. --contrast angiography of the left ventricle is generally avoided at the
time of catheterization in patients with acute MR because of the
contrast load in an already compromised patient
--Fup / 6-12 m according to severity
AHA2014:
Class IIa
1. Exercise hemodynamics with either Doppler
echocardiography or cardiac catheterization is reasonable in
symptomatic patients with chronic primary MR where there
is a discrepancy between symptoms and the severity of MR
at rest (stages B and C) . (Level of Evidence: B)
2. Exercise treadmill testing can be useful in patients with
chronic primary MR to establish symptom status and
exercise tolerance (stages B and C). (Level of Evidence: C)

36. PHYSICAL ACTIVITY AND EXERCISE
--2006 ACC/AHA guidelines concluded that there are no
exercise restrictions in asymptomatic patients who are in
sinus rhythm and have normal left ventricular and left
atrial dimensions and a normal pulmonary artery pressure
--Mild left ventricular enlargement can participate in low
and moderate static and all dynamic competitive sports
--Severe MR and definite left ventricular
enlargement, pulmonary hypertension, or any reduction in
left ventricular systolic function at rest should not
participate in any competitive sports
-- AF who are treated with long-term anticoagulation
therapy should not engage in sports with any for bodily
contact or risk of trauma

37. Medical treatment
--USE OF VASODILATORS:
-Asymptomatic patients:
There are no published studies that support the hypothesis
that vasodilator therapy is beneficial in asymptomatic
patients with chronic MR.
In addition, the administration of vasodilators in patients
with normal LV function might limit the development of
symptoms due to increasing LV dysfunction, thereby
masking an indication for surgery.
Thus, with some exceptions (eg, the hypertensive
patient), vasodilators are not recommended for use in
asymptomatic patients with chronic MR due to primary
valve disease

38. -Symptomatic patients:
--In primary MR (eg, myxomatous or rheumatic), the
therapeutic goal should be a reduction in systolic pressure.
Thus, a beta blocker, diuretic, hydralazine, or calcium channel
blocker should be used. {medical therapy is not a substitute for
surgical intervention in patients with chronic symptomatic MR}.
--Chronic vasodilator therapy is indicated in symptomatic
patients who are not candidates for surgery. The evidence of
benefit is best in patients with secondary (functional) MR due to
left ventricular dysfunction
--Several studies confirm a beneficial effect of acute vasodilator
therapy in patients with chronic MR. Intravenous
nitroprusside, for example, decreases left ventricular end-
diastolic pressure and volume while increasing forward stroke
volume and cardiac index. Also Hydralazine.

39. --ANTICOAGULATION:
-Mitral annular calcification, which is often associated with MR,
increases the risk of embolism, even in the absence of atrial
fibrillation.
-2008 ACCP guidelines that anticoagulation with warfarin (target INR
2.5, range 2.0 to 3.0) is indicated in patients with rheumatic mitral
valve disease who have a history of systemic embolism, left atrial
thrombus, or paroxysmal or chronic atrial fibrillation, left atrial
diameter >55 mm and rheumatic mitral valve disease
-Recurrent systemic embolism despite adequate anticoagulation, the
addition of aspirin (75 to 100 mg/day) is suggested or higher target
INR (target INR 3.0, range 2.5 to 3.5
-Data are lacking to support the use of direct thrombin inhibitors in
patients with valve disease and atrial fibrillation.

40. --ENDOCARDITIS PROPHYLAXIS:
-No longer recommended when patients with mitral
valve disease (in the absence of prosthetic repair or
replacement)

41. AHA 2014
The patient and family should be sufficiently
educated by the Heart Valve Team about all
alternatives for treatment so that their expectations
can be met as fully as possible using a shared decision-
making approach.

42. Heart Valve Centers of Excellence
1) are composed of experienced healthcare providers with
expertise from multiple disciplines;
2) offer all available options for diagnosis and
management, including complex valve repair, aortic
surgery, and transcatheter therapies;
3) participate in regional or national outcome
registries;
4) demonstrate adherence to national guidelines;
5) participate in continued evaluation and quality
improvement processes to enhance patient outcomes; and
6) publicly report their available mortality and success
rates.

48. Mechanical or bioprosthetic
--Mechanical valves have the disadvantage of requiring lifelong warfarin
therapy, while bioprosthetic valves have the disadvantage of limited durability
due to valve degeneration, particularly in patients under age 65
--2006 ACC/AHA guidelines when valve replacement:
-Bioprosthetic valves are recommended in patients who cannot or will not
take warfarin or have a clear contraindication to warfarin therapy.
-Among patients who can take warfarin, the weight of evidence supports the
following approach:
--A mechanical valve in patients under age 65 who have long-standing AF.
--A bioprosthetic valve in patients ≥65 years of age.
--Among patients under age 65 who are in sinus rhythm, patient preference
plays a central role in the choice of valve. The guidelines suggested that a
bioprosthetic valve should only be considered after a detailed discussion with
the patient of the risks of warfarin therapy compared to the likelihood of
repeat valve replacement in the future

49. Mitral valve replacement versus repair
--In most patients, mitral valve repair at experienced surgical centers
is the preferred approach because of both functional and survival
benefits compared to valve replacement {It preserves the patient's
native valve, avoids the risk of chronic anticoagulation or prosthetic
valve failure ,,, Preservation of the mitral chordal apparatus  better
postoperative left ventricular function ---chordal preservation can also
be attained during mitral valve replacement---}
--Patients should not participate in sports that are associated with a
risk of bodily contact or trauma that might disrupt the repair
--Rate of late recurrent MR following mitral valve repair is as high as
28 percent redo only 3%
*Degree of MR may have limited importance compared with the
underlying cardiovascular disease
*Almost one-half of patients died within five years
*Surgeons may be reluctant to perform a repeat operation in this
older, high-risk population

50. --Unlike the aortic valve, the mitral valve serves to do
more than just direct forward cardiac flow. The mitral
valve is also an integral part of the LV, coordinating LV
contraction and maintaining LV shape. When the valve
is destroyed at the time of surgery, there is a
precipitous fall in LV function postoperatively, which
does not occur when the valve apparatus is conserved
--The use of the maze procedure or radiofrequency or
cryoablation as an adjunct to mitral valve repair or
replacement is an effective approach to reduce the
incidence of postoperative AF

54. --The 2005 ACC/AHA heart failure guidelines note that the
effectiveness of mitral valve repair or replacement for severe
secondary mitral regurgitation in refractory end-stage HF is not
established.
--The 2006 Heart Failure Society of America (HFSA) practice
guidelines note that isolated mitral valve repair or replacement
for severe mitral regurgitation secondary to ventricular
dilatation in the presence of severe LV systolic dysfunction is
not generally recommended.
--The 2006 International Society for Heart and Lung
Transplantation (ISHLT) guidelines for cardiac transplant
candidates note that isolated mitral valve repair (not associated
with revascularization or ventricular restoration) should not be
routinely performed in patients with advanced LV dysfunction
and HF

55. PERCUTANEOUS REPAIR
--Under investigation
--Techniques include direct and indirect annuloplasty approaches and
an implantable clip.
--The MitraClip provides a noninvasive means of mitral valve
repair, superior safety and similar improvements in clinical
outcomes, but its efficacy in reducing mitral regurgitation is somewhat
limited {EVEREST II trial}
--European 2012:
The percutaneous mitral clip procedure may be considered in
patients with symptomatic severe secondary MR despite optimal
medical therapy (including CRT if indicated), who fulfil the echo
criteria of eligibility, are judged inoperable or at high surgical risk
by a team of cardiologists and cardiac surgeons, and who have a
life expectancy greater than 1 year (recommendation class IIb)
-- Despite the lack of evidence, a combination of low-dose aspirin and
a thienopyridine is used early after TAVI and percutaneous edge-to-
edge repair, followed by aspirin or a thienopyridine alone

56. AHA 2014
I
Concomitant mitral valve repair or MVR is indicated in patients
with chronic severe (or moderate IIb)primary MR undergoing
cardiac surgery for other indications. (Level of Evidence: B)
IIb
Transcatheter mitral valve repair may be considered for severely
symptomatic patients (NYHA class III to IV) with chronic severe
primary MR (stage D) who have favorable anatomy for the
repair procedure and a reasonable life expectancy but who have
a prohibitive surgical risk because of severe comorbidities and
remain severely symptomatic despite optimal GDMT for HF.
(Level of Evidence: B)

57. Other valvular lesions
--When either stenosis or regurgitation is
predominant, management follows the recommendations
concerning the predominant VHD
--Interaction between the different valve lesions ex. associated
MR may lead to underestimation of the severity of AS
--Indications for intervention are based on global assessment of
the consequences of the different valve lesions, i.e. symptoms
or presence of LV dilatation or dysfunction
--The decision to intervene on multiple valves should take into
account the extra surgical risk
--The choice of surgical technique should take into account the
presence of the other VHD.

58. Noncardiac surgery
--Asymptomatic patients with severe MR or AR and
preserved LV function, non-cardiac surgery can be
performed safely.
--The presence of symptoms or LV dysfunction should lead
to consideration of valvular surgery, but this is seldom
needed before non-cardiac surgery.
--If LV dysfunction is severe (EF <30%), non-cardiac
surgery should only be performed if strictly necessary, after
optimization of medical therapy for HF.
----Control heart rate (particularly in MS), to avoid fluid
overload as well as volume depletion and hypotension
(particularly in AS)

59. Thank you