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MITRAL VALVE DISEASE :
ADVANCES IN CATHETER INTERVENTIONS
MITRAL STENOSIS
Most common cause of Mitral stenosis [MS] is rheumatic heart
disease [RHD].Approximately 25% of all patients with rheumatic
heart disease have pure MS, and an additional 40% have combined
MS and mitral regurgitation [MR] [1-3]. Two thirds of all patients
with MS are female. Pathological process by which rheumatic fever
causes MS includes leaflet thickening and calcification,commissural
fusion, chordal fusion, or a combination of these processes [4, 5].
Normal mitral valve [MV] area is 4.0 - 6.0 cm2.When the orifice is
reduced to 2 cm2, blood flow occurs from left atrium [LA] to left
ventricle [LV] only if propelled by a pressure gradient.This results
in elevation of left atrial pressure, which is reflected back into
the pulmonary venous circulation thereby increasing pulmonary
venous pressure [PVH]. This ultimately leads to pulmonary
arterial hypertension [PAH], right ventricular [RV] dysfunction
and tricuspid regurgitation [TR].
Definite symptoms typically occur only with a substantial
reduction in mitral valve orifice area [MVOA] usually to < 1.0 cm2.
However, functional limitation occurs gradually and many patients
experience exercise limitation at a larger valve area (1 to 2 cm2].
Symptoms: Most common presenting symptoms of MS are
progressive exertional dyspnea and fatigue which may be
accompanied by cough and wheezing. Orthopnea and paroxysmal
nocturnal dyspnea [PND] occur as the disease progresses.
Episodes of acute pulmonary edema may be precipitated by
effort, emotional stress, infection, atrial fibrillation [AF] with fast
ventricular rate [FVR] or pregnancy. Symptoms of right heart
failure may supervene when pulmonary vascular resistance
increases markedly.
Hemoptysis is rare. But it can be sudden and severe, due to
rupture of thin walled, dilated bronchial veins. Milder degrees of
Table 1 : Chest X Ray findings
1. LA enlargement (earliest sign)
2. PVH –prominent upper lobe veins, Kerley lines
3. PAH – dilated pulmonary arteries.
4. RV enlargement, RAE,
5. Calcification of MV
6. Pulmonary hemosiderosis
CN Manjunath, Prabhavathi, Bangalore
hemoptysis may be caused by pulmonary infarction and winter
bronchitis. It may be also seen during episodes of PND and
pulmonary edema.
Chest pain typical of angina is seen in 15% of patients with MS
which may be caused by RV hypertension. Atrial fibrillation is the
most common complication of MS and systemic embolism occurs
in 20% of patients. Infective endocarditis is rare. Compression of
the left recurrent laryngeal nerve by dilated left atrium, pulmonary
artery or enlarged tracheobronchial lymph nodes may cause
hoarseness of voice [Ortner syndrome]
Physical signs: Arterial pulse is usually normal but in patients
with a reduced stroke volume pulse may be low in volume. Pulse is
irregular in patients with AF.A readily palpable, loud S1 and opening
snap [OS] suggest pliable anterior mitral leaflet [AML]. RV lift and
a loud palpable P2 are common in patients with PH. Low pitched
rumbling diastolic murmur, best heard at the apex is the hallmark
of MS. Long diastolic murmur with presystolic accentuation and a
short A2 –OS interval suggest tight MS. Loud S1 and OS indicate
leaflet pliability and do not predict severity.
Murmur of MS may be soft or inaudible in patients with very
severe MS, severe PH, congestive cardiac failure [CCF], extensive
calcification and subvalvar disease and marked RV enlargement.
Intensity may also be reduced in associated diseases like aortic
stenosis [AS], aortic regurgitation [AR] and atrial septal defect
[ASD]. Obesity, thick chest wall and COPD can also attenuate
the murmur of MS.
ECG: Left atrial [LA] enlargement is the earliest finding, seen in
90% of patients with significant MS. Atrial fibrillation occurs in
30 – 40% and the incidence increases with increasing age. RVH,
right axis deviation and right atrial enlargement [RAE] are seen
in patients with PAH and TR.
Chest X Ray findings of MS are summarised in table 1
Echocardiographic findings: Echocardiography plays a central
role in the diagnosis and management of MS [fig 1]. Findings are
summarized in Table 2
Mitral Valve Disease : Advances in Catheter Interventions
Table 2 : Echo findings in MS
1. Thickening of leaflets and subvalvular apparatus
2. Restricted movement of the mitral leaflets
3. Fusion of commissures
4. Diastolic doming of AML
5. MVOA decreases – fish mouth appearance
6. Turbulent high velocity flow with increased gradient
7. LAE, RVH, PH, TR
8. LA Thrombus (Figure 2)
Fig. 2 : LA CLOT
open mitral valvotomy [OMV] / Mitral valve replacement
MVR]
Medical Therapy:
1. Medical management of MS is primarily directed toward
2. Prevention of recurrent rheumatic fever
prophylaxis as per established guidelines
3. Prevention and treatment of complications.
Fig. 1 : ECHO – MS
4.
Natural history of MS:
Mitral stenosis has a slow and stable course in the early years
followed by a progressive acceleration later in life [6-9]. In US
and Western Europe, patients who develop acute rheumatic fever
have an asymptomatic period of approximately 15 to 20 years
before symptoms of MS develop. It then takes approximately 5 to
10 years for most patients to progress from mild disability (NYHA
class II) to severe disability (NYHA class III-IV). In India, critical
MS may be found in children as young as 6 to 12 years of age.
In the asymptomatic or minimally symptomatic patient, survival
is greater than 80% at 10 years, with 60% of patients having no
progression of symptoms [7-9]. However, once significant limiting
symptoms occur, there is a dismal 0% to 15% 10-year survival
rate (7-10). Once there is severe PH, mean survival drops to less
than 3 years [11]. The mortality of untreated patients with MS is
due to progressive pulmonary and systemic congestion in 60%
to 70%, systemic embolism in 20% to 30%, pulmonary embolism
in 10%, and infection in 1% to 5% [4, 9]. Serial hemodynamic and
Doppler-echocardiographic studies have reported annual loss of
MV area ranging from 0.09 to 0.32 cm2 [12, 13].With intervention
9year survival is 90%.
TREATMENT OPTIONS:
1.
with penicillin
Medical Therapy
Monitoring disease progression to allow intervention at the
optimal time point.
In general, all patients with MS should undergo antibiotic
prophylaxis against infective endocarditis for those procedures
known to cause bacteremia. Diuretics are useful for treating
mild symptoms. B blockers attenuate the increases in heart rate
especially during exertion and optimise diastolic filling. Digoxin
has no role in patients with MS and sinus rhythm. Anemia and
infections should be treated promptly and aggressively.
AF commonly accompanies MS and is more related to age
than to stenosis severity. When AF occurs acutely, it is often
associated with a rapid ventricular response. As increased
heart rate primarily reduces time in diastole, it causes further
impairment in left ventricular filling, which leads to abrupt left
atrial hypertension and reduced cardiac output. Immediate rate
control is imperative and can be done by administration of B
blockers or rate-reducing calcium channel blockers [diltiazem &
verapamil]. If these therapies are ineffective in controlling rate and
the patient is unstable, immediate DC cardioversion is indicated.
Patients with MS in chronic AF are at risk of embolic stroke (at
a rate of 7% - 15% per year) [14]. Accordingly, all such patients
require warfarin anticoagulation with a target international
normalized ratio of 2.0 to 3.0. After a first embolic event, the
recurrence rate is increased 2-fold without anticoagulation.
Chronic rate control is achieved with digoxin, B blocker, a calcium
channel blocker, or some combination of these agents. Adequacy
2. Balloon Mitral Valvotomy (BMV)
3. Surgical Valvotomy – Closed mitral valvotomy[CMV] or
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Medicine Update 2010  Vol. 20
Table 3: Assessment of severity of MS
Severity
NORMAL
MILD MS
MODERATE MS
SEVERE MS
Mean gradient
---
< 5mmHg
5 – 10mmHg
> 10 mmHg
MVOA
4 – 6cm2
1.5 - 2cm2
1.0 – 1.5cm2
< 1.0cm2
Table 4: Expanding indications for PTMC
1. Mitral Restenosis
2. Mitral Stenosis with LA Clot [type Ia, Ib & IIa]
3. Moderate Mitral Regurgitation (Central Jets)
4. Hybrid Therapy - AR, AS, CABG
5. Lutembacher’s syndrome
Table 5: Contraindications for PTMC
1. Left atrial body clot
2. Grade 2 or more MR
3. Bicommissural calcification
4. Lack of expertise
of rate control should be monitored not only at rest but also
during activity, because in many patients, apparently adequate
rate control at rest belies tachycardia with even mild activity.
Such patients are at risk for developing tachycardia-induced
cardiomyopathy.
Fig. 2 : Ballon across MV
BALLOON VALVOTOMY
In the last two decades, BMV has become the treatment of
choice for patients with symptomatic rheumatic MS. Since its
introduction in 1984 by Inoue et al. [15], BMV by Inoue technique
has been widely used in the treatment of mitral stenosis. Several
studies have reported good immediate, short-term and long-term
results [16–24].
Given the excellent hemodynamic and functional results of
percutaneous mitral commissurotomy, especially when the
valve leaflets are thin and mobile, it is reasonable to consider
intervention earlier in the disease course both to prevent
atrial fibrillation and pulmonary hypertension and to preserve
functional status, particularly in young individuals. Patient selection
is based on clinical evaluation and echocardiographic assessment
of disease severity [Table3] and valve morphology.
Fig. 3 : Pre and post PTMC
BMV is also considered in the following subset of patients [Table
4]:
PTMC is contraindicated in following situations [Table 5]:
Technique:Transseptal technique is the most common technique
used to perform BMV. Self positioning Accura or Inoue balloon
is advanced over the wire across the interatrial septum after
transseptal puncture. Ballon is inflated after positioning it across
the mitral valve [fig 2]. Stepwise dilatation with gradual increase of
ballon size is performed which is guided by the echocardiographic
and hemodynamic assessment.
INDICATIONS FOR BMV:
BMV is indicated in patients with moderate to severe MS in the
absence of LA thrombus and not more than mild MR:
1. Symptomatic (NYHA functional class II, - IV) with valve
morphology favorable for PTMC
BMV is considered to be successful if post procedural MVOA
> 1.5cm2 or if there is 50% increase in MVOA compared to pre
procedure valve area and MR not more than mild with adequate
split of one of the commissure [fig 3].
2. Asymptomatic patients who have pulmonary hypertension
[pulmonary artery systolic pressure > 50 mm Hg at rest or
> 60 mm Hg with exercise]
Immediate hemodynamic results:
3. Symptomatic patients who are either not candidates for
surgery or are at high risk for surgery.
MVOA increases from an average of 1cm2 to 2cm2 .Transmitral
pressure gradient reduces from an average of 18 to 6 mm Hg
370
Mitral Valve Disease : Advances in Catheter Interventions
Type Ia
Type Ib
LA appendage clot
confined to apendage.
LA appendage clot
protruding into LA cavity.
Type Ia
Type IIb
LA roof clot limited to a plane LA roof clot extending below
above the plane of fossa ovalis
the plane of fossa ovalis.
patients were in acute pulmonary edema. Single ballon [Inoue or
Acura] was used in all the patients.Average fluoroscopy time was
5.1+2.5mins. Procedure was successful in 95.2% of patients. Mean
left atrial pressure dropped from 32+16 to 14+5 mm Hg and mitral
valve orifice area increased from 0.8+0.4 to 1.85+.03cm2. Mild to
moderate MR was seen in 10.5% of patients and 1.6% had severe
MR. Serious complications like tamponade occurred in 1.8%, CVA
in 0.4% and mortality in 0.7% of patients.
Type III
Layered Clot over the IAS.
BMV in patients with Left Atrial Thrombus:
Type IV
Type V
Mobile clot which is attached
to LA free wall or roof or IAS.
Ball valve thrombus (Free Floating)
Fig. 5 : Classification of LA clot
and the pulmonary vascular resistance declines rapidly. MV
morphology is found to be a strong predictor of successful BMV.
LA thrombus occurs in 3–13% of patients with MS and its
presence is generally considered as a contraindication for BMV
[27]. Systemic embolization occurs in 0.3–0.8% of patients during
or shortly after the procedure and represents a potentially
devastating complication.
Mild to moderate MR – 15%.
Our center has performed more than 12,000 BMVs in the last
15 years. On many occasions we were compelled to perform
BMV in the presence of LA/LA appendage thrombus as a bail
out procedure in emergency situations. In all these situations,
to minimize the risk of embolic complications, we adopted a
modification of over the wire technique described earlier [28].
Encouraged by this we conducted a prospective study of BMV
in 108 patients with LA thrombus between January 2005 and
December 2007[29].
Nearly 20% of patients are left with a small residual atrial septal
defect, which closes or decreases in size in most patients.
We classified LA thrombus based on their location, extension,
and mobility as assessed by TTE/TEE as follows: [Fig 5]
COMPLICATIONS of BMV: In general, BMV is a safe
procedure with high success rate in patients with optimal valve
morphology. Reported rates of complications are: Mortality - 0
- 0.5%, Cerebral embolism – 0.5 – 1%,
Cardiac perforation and tamponade - 0.7 - 1%,
Severe MR requiring emergency surgery - 2%,
Type Ia: LA appendage clot confined to appendage.
BMV IN SPECIAL CIRCUMSTANCES
Type Ib: LA appendage clot protruding into LA cavity.
BMV IN PREGNANCY:
Type IIa: LA roof clot limited to a plane above the plane of
fossa ovalis.
Majority of patients with moderate to severe MS worsen during
pregnancy due to increased intravascular volume and increase in
heart rate. Symptoms occur in 25% of patients, become apparent
by 20th week and aggravate at the time of labor and delivery.
Type IIb: LA roof clot extending below the plane of fossa ovalis.
Type III: Layered clot over the interatrial septum (IAS).
Without intervention maternal mortality is significantly higher
[6.8%] for those in NYHA classes III and IV, particularly during
labor and delivery. Compared to surgical commissurotomy, BMV
has been shown to yield similar immediate and long term results
with lower maternal and fetal mortality.
Type IV: Mobile clot which is attached to LA free wall or roof
or IAS.
Type V: Ball valve thrombus (Free Floating).
Now we have more than 15 year experience of BMV either
with very limited fluoroscopy [2-5 minutes of exposure] or
echocardiographic guidance. The reported results of BMV have
been excellent, with few maternal or fetal complications [25].
Optimal timing of BMV is end of 2nd trimester or beginning of
third trimester during which radiation risk to the fetus is negligible.
During BMV average amount of radiation received by the fetus is
0.5 rad, far below the established limit of 5 rads. Risk of radiation
is reduced by abdominal & pelvic shielding, avoiding the procedure
before 20 weeks of pregnancy, using single ballon [Inoue or Accura]
rather than double ballon and minimizing fluoroscopy time [26].
Out of 12,555 patients who underwent BMV in our hospital,
605 were pregnant. Majority were in NYHA class III and IV. 47
371
Patients were included in the study if they had type Ia (n - 69),
type Ib (n -35) and type IIa (n - 4) LA clots. All these patients
were adequately anticoagulated (INR 2.0–3.0) for 8–12 weeks.
All patients underwent BMV by modified over the wire technique.
There was significant and comparable improvement in the
mitral valve area, mitral valve gradient, LA mean and pulmonary
artery systolic pressure following the procedure. There were no
thromboembolic episodes during the procedure. However, there
was one case of transient ischemic attack which occurred 6 hr
after a successful BMV.
Hence in selected patients of mitral stenosis with LA thrombus
(type Ia, Ib, and IIa), BMV can be performed safely with the modified
Medicine Update 2010  Vol. 20
2. PTMC is contraindicated [Table 5] because of left atrial
thrombus despite anticoagulation [OMV if valve morphology is suitable] or because of concomitant moderate to severe MR [MVR]
over the wire technique. Systemic thromboembolism, technical
failures and other complications are very rare when performed
by experienced operators.
BMV in Juvenile MS
3. Mitral valve morphology is not favorable for PTMC, in a
patient with acceptable operative risk [MVR].
Special features of Mitral Stenosis in children are fibrotic, rubbery
valve with severe sub-valvular disease. Calcification is rare and
atrial fibrillation is less common. Significant pulmonary arterial
hypertension is seen in majority of children.
MITRAL REGURGITATION
Proper functioning of the mitral valvular complex depends on the
structural and functional integrity of its individual components
- mitral annulus, leaflets, chordae tendineae, papillary muscles,
left atrial and left ventricular walls in continuity with the leaflets,
and papillary muscles. MR can be classified as primary, due to
abnormality of the mitral valve apparatus (e.g., rheumatic or
degenerative mitral valve disease), or secondary (or functional),
as a result of an ischemic or nonischemic dilated cardiomyopathy
in the setting of anatomically normal mitral valvular leaflets and
chords.
In our series of 12,550 cases, 4% were less than 10 years [youngest
was 7year old] and 14% were in the age range of 10–20 years.
BMV in children appears to be safe and effective similar to adult
patients. In the long term follow up there was no significant
difference in the incidence of restenosis and event free survival.
BMV in patients with moderate MR:
BMV may be successful in a small subset of patients with moderate
MR when the jet is central with minimal non coaptation of the
leaflets and noncalcified commissures.
Despite the superior long-term outcomes associated with mitral
valve repair rather than mitral valve replacement, mitral valve
repair is performed in only one-third of patients undergoing
mitral valve surgery.
BMV in Mitral restenosis
Definition of mitral restenosis is return of symptoms with >
50% loss of post valvotomy MVOA or MVOA at follow up
<
1.5cm2. Restenosis rate for BMV is 5 - 8% Over 8 Years [OMV - 7
to 11%, CMV - 10 - 20%].
BMV is safe and provides good immediate results in patients with
restenosis. Long term results are satisfactory [though inferior
to de novo MS] with more than half of the patients remaining
minimally symptomatic at 10 years enabling the reoperation to
be deferred.
BMV in Lutembacher’s Syndrome:
Ideal strategy is surgical closure of ASD with OMV/MVR. But in
critically ill patients surgery carries a higher risk. In such patients
BMV restores hemodynamics and improves metabolic parameters.
After a few weeks ASD closure can be done electively.
Hybrid Therapy – BMV in patients with AR, AS:
In patients with combined MS and significant aortic valve disease
balloon mitral valvotomy followed by AVR may be performed
[27].This obviates the need for double-valve replacement, which
has a higher risk of perioperative mortality and postoperative
complications than single-valve replacement (30). In most cases,
it is advisable to perform ballon mitral valvotomy first and then
monitor the patient for symptomatic improvement. If symptoms
disappear, AVR can be delayed.
Indications for mitral valve surgery in patients with
MS: [closed/open mitral valvotomy or mitral valve
Annuloplasty is the cornerstone of mitral valve repair and is
essential for the surgical correction of functional MR. For repair of
degenerative mitral valve disease; failure to perform a concomitant
annuloplasty procedure adversely affects the long term durability
of the repair.Annuloplasty may be used concomitantly with leaflet
repair (resection, sliding annuloplasty) or chordal reconstruction
(transposition, artificial chords). The Alfieri procedure involves
suturing the free edges of the middle anterior (A2) and posterior
(P2) leaflets of the mitral valve. This produces a double orifice
mitral valve. This procedure can be used to treat degenerative
or functional MR. Same principle is used in transcatheter edgeto-edge repair technique [31].
Strategies for transcatheter mitral valve repair:
1. Creation of a double orifice mitral valve using percutaneous edge-to-edge techniques with a clip device [MitraClip] or stitch [ Mobius]
2. Remodeling of the annulus of the mitral valve by suturebased
techniques (e.g., Percutaneous Suture Annuloplasty), or application of radiofrequency energy
3. Remodeling of the mitral valvular complex by transventricular (e.g., iCoapsys) or transatrial (e.g., Percutaneous
Septal Sinus shortening) devices.
4.
Remodeling of the annulus of the mitral valve by devices implanted in the coronary sinus (e.g., Percutaneous
Mitral Annuloplasty device).
replacement]
Symptomatic patients with moderate or severe MS when
A number of transcatheter mitral valve therapies are currently
under various phases of clinical trials.
1. PTMC is not available [closed mitral valvotomy]
372
Mitral Valve Disease : Advances in Catheter Interventions
1960;52:741-49.
8. Olesen KH. The natural history of 271 patients with mitral stenosis
under medical treatment. Br Heart J 1962;24:349-57.
9. Selzer A, Cohn KE. Natural history of mitral stenosis a review. Circulation 1972;45:878-90.
10. Munoz S, Gallardo J, Diaz-Gorrin JR, Medina O. Influence of surgery on
the natural history of rheumatic mitral and aortic valve disease. Am J
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11. Ward C, Hancock BW. Extreme pulmonary hypertension caused by
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Fig. 6 : Mitra clip and double orifice MV with Mitra clip
Edge-to-Edge Technique - MitraClip: The MitraClip uses a
tri-axial catheter system with a clip device at its distal tip (Fig: 6).
The goal of the procedure is to create a double orifice mitral valve
similar to the Alfieri surgical technique The guide catheter is 24-F
at its proximal end, tapering to 22-F at its distal end.The system is
delivered via a standard transseptal approach into the left atrium.
The 2-armed clip is a polyester-covered device. Each clip arm
opposes against a multipronged friction element that allows up to
8 mm of mitral valve leaflet to be grasped securely on each side.
Once clip placement and real-time echocardiography confirm
adequate reduction of MR (grade < 2+), the clip device is detached
from the delivery catheter. Use of standardized echocardiographic
protocols can greatly improve procedural times and ease of clip
placement.The EVEREST (EndovascularValve Edge-to-Edge Repair
Study) phase I clinical study is completed and EVEREST phase II is
currently enrolling patients with degenerative or functional MR.
12. Dubin AA, March HW, Cohn K, Selzer A. Longitudinal hemodynamic
and clinical study of mitral stenosis. Circulation 1971;44:381-9.
Conclusion: BMV is the procedure of choice in the treatment
of rheumatic mitral stenosis, with excellent immediate and long
term results. It is safe and effective across wide spectrum of clinical
subset of patients with MS. Echocardiography before and during
the procedure optimizes the outcome. Over the wire technique is
useful in difficult entry situations & in patients with LA thrombus
(Type Ia, Ib & IIa).
18. Manjunath CN, Srinivas KH, Dattatreya PV, Nakul Sinha, Achyut Sarkar,
Milan Chag, Mantri RR, Srinivas Kumar A. The 7th report of the noncoronary cardiac interventions. Registry of India—The Cardiological
Society of India. Indian Heart J 2008; 60:73–78.
A number of transcatheter mitral valve therapies for MR are
currently evolving. It may obviate the need for surgeries in future.
20. Fawzy ME, Stefadouros MA, Hegazy H, El Shaer F, Chaudhary MA, Al
Fadley F. Long term clinical and echocardiographic results of mitral balloon valvotomy in children and adolescents. Heart 2005;91:743–748.
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