The main hemodynamic interactions that may impact on the diagnosis of multiple and mixed Multiple and Mixed Valvular Heart Diseases:HOW TO USE IMAGINGThe interplay of multiple valve pathology.The clinical challenge of concomitant aortic and mitral valve stenosis . .

1. Challenges in
Multivalvular
Disease
Magdy El-Masry
Prof. of Cardiology
Tanta University

2. The relative positions of the aortic, mitral, pulmonary, and tricuspid valves are shown in the diagram of
the heart at the center of the figure. The aortic valve has three cusps: the left coronary cusp (LCC), the
right coronary cusp (RCC), and the non-coronary cusp (NCC). The mitral valve has an alphanumeric
nomenclature that numbers from the anterior to the posterior, with respect to the heart, and attaches an
A or a P in front of the anterior or posterior leaflets, respectively (A1-A3, P1-P3). The pulmonary valve
has three cusps: the anterior cusp (AC), the left cusp (LC), and the right cusp (RC). The tricuspid valve has
three leaflets named the anterior (A), septal (S), and posterior (P).

3. Multiple and mixed valvular heart disease

4. Multiple valvular disease and mixed valvular disease are highly prevalent conditions

5. EPIDEMIOLOGY
EUROHEART SURVEY
Patients undergoing valvular surgery - 14.6%
SOCIETY OF THORACIC SURGEONS (STS) database
Multiple-valve surgery accounted for 10.9% of
the 623,039 patients undergoing valve surgery.
a) 57.8% on the aortic and mitral valves,
b) 31.0% on the mitral and tricuspid,
c) 3.3% on the aortic and tricuspid,
d) 7.9% underwent triple-valve surgery.

6. Etiology
Primary:
• Rheumatic Heart Disease
• Degenerative Valve Disease >90%
Other Causes:
• Endocarditis
• Radiation
• Drugs : fenfluramine/phentermine (i.e. fen-phen)
• Connective tissue disease
• Genetic syndromes
Secondary:
• Malcoaptation

7. Aortic Stenosis
Aortic Regurgitation
Mitral Stenosis
Mitral Regurgitation
Tricuspid Regurgitation
Tricuspid Stenosis
 Data on multivalve disease is scarce because of a large number of possible combinations
 Many areas are not covered by the guidelines

8. What is the net clinical effect of multiple valve lesions?
How do we grade severity of each lesion?
What is the optimal treatment strategy?
Multiple valve disease:
Challenges in diagnosis, assessment and treatment

9. Multivalvular disease –
1+1 may not be 2
Double
Trouble
Triple
Trouble

10. Single Valve Disease
Mild Moderate Severe
 Symptoms
 Cavity enlargement
 LV dysfunction

11. Multivalvular Disease
Moderate Severe
 Symptoms
 Cavity enlargement
 LV dysfunction
Moderate + =

16. • Very Poorly tolerated
• Post-operatively:
- High incidence of LV Dysfunction
- Reduced survival
- Often persistent symptoms

18. In this example of severe MR, SVMV was 183 mL (d = 3.5 cm, VTI = 19 cm) and SVLVOT was
58 mL (d = 2.3 cm, VTI = 14 cm). This yielded an RVol of 125 mL and an RF of 125/183 or
68%. d, Diameter of the annulus; PW, pulsed wave Doppler.
Echo-Doppler calculations of SV at the LVOT and MV annulus sites.

19. 𝑅𝑒𝑔 𝑉𝑜𝑙 𝑀𝑅 = 𝑆𝑉 𝑀𝑉 − 𝑆𝑉 𝐿𝑉𝑂𝑇 𝑅𝑒𝑔 𝑉𝑜𝑙 𝐴𝑅 = 𝑆𝑉 𝐿𝑉𝑂𝑇 − 𝑆𝑉 𝑀𝑉
• 𝑺𝑽 𝑹𝑽𝑶𝑻 ?
• Direct measurement of forward and reverse flow by CMR
AR and MR
Reference Stroke Volume:
→Volumetric Methods

20. MR and TR
 Secondary TR is highly prevalent in patients with left-sided valvular disease

21. MR and TR
How does MR affect TR?
1. Increased Regurgitant Volume for given ROA
2. Increased Color Jet Area
(out of proportion to increased Regurgitant Volume)
3. Increased ROA due to TV annular dilation

22. Myocardial
dysfunction
assessment
Interaction
between
different
valve lesions
Separate
assessment of
each valve
lesion
Multivalve disease – evaluation tips

24. The main hemodynamic interactions that may impact on
the diagnosis of multiple and mixed VHDs are :
Low-flow, low-gradient stenosis is frequent
Mixed valve disease may be associated with increased
anterograde flow and gradient
The continuity equation is inapplicable when transvalvular
flows are unequal
Any severe valvular lesion may induce or increase
upstream secondary MR or TR
Pressure half-time–derived methods may be invalid in the
presence of altered LV compliance/relaxation or abnormal
LV filling in the presence of mixed VHD
Doppler Echo → Diagnostic Caveats

25. Grading severity:
Does the addition of a second lesion:
 Modify the actual severity of the primary lesion?
 Affect the quantification and grading of the
primary lesion?

26.  This case highlights the inaccuracy of the pressure half-time method to assess mitral valve
effective area in the presence of severe aortic valve disease.
 Moreover, this patient exemplifies the frequent and challenging situation of low-flow,
low-gradient stenosis, present here at both the aortic and the mitral valve.
 This situation can lead to underestimation of the severity of aortic and mitral stenoses.
NYHA III
EF 60%
MS & AS
VTI LVOT
CSA LVOT
VTI AV
MPG 21 AVA = 0.62 cm2
C/W
LF-LG AS
Mean PG 8
MVA PHT =1.65 Cm2
MVA Planimetry 1.2Cm2

27. Subtypes of low-gradient aortic stenosis

28. Secondary modality →? Solutions
Primary modality →Diagnostic caveats
Multiple and Mixed Valvular Heart Diseases:
HOW TO USE IMAGING

29. The interplay of multiple valve pathology
The presence of AS → Impacts the diagnosis of:
Mitral RegurgitationMitral StenosisAortic Regurgitation
 Increased mitral regurgitant
volume
 Increased area of MR jet
 Mitral ROA less affected than
MR volume
 Unreliable PHT due to
impaired ventricular relaxation
 Low flow-low gradient MS can
occur
*Unreliable PHT
The presence of AR → Impacts the diagnosis of:
Mitral RegurgitationMitral StenosisAortic Stenosis
 Doppler volumetric
method invalid
 PISA method remains
accurate for the
assessment of MR
 AR jet can be mistaken
for MS jet
 Continuity equation
unreliable ( for MVA )
 Unreliable PHT(MS) due
to overestimation of the
MVA
 Increased LVOT velocity in
AR may affect AS gradient if
using Simplified Bernoulli
formula
 Continuity equation is
applicable to assess AVA
 Peak Vmax reflects the
severity of both AS and AR
3D echo to
measure mitral valve
anatomic area and confirm
MS severity
CMR may be used to
quantify MR volume and
fraction and
corroborate MR severity
3D echocardiography to
measure mitral valve
anatomic
area and confirm MS
severity

30. The interplay of multiple valve pathology
The presence of MS → Impacts the diagnosis of:
Mitral RegurgitationAortic RegurgitationAortic Stenosis
 Not affected MS can blunt the increase in
pulse pressure and the LV
dilatation associated with AR
 Low flow-low
gradient AS common
The presence of MR → Impacts the diagnosis of:
Mitral StenosisAortic RegurgitationAortic Stenosis
 Continuity equation
unreliable due to
underestimation of MVA due
to increased antegrade
mitral flow
 Unreliable PHT
 Doppler volumetric
method inapplicable
 Unreliable PHT
 Low flow-low gradient AS
common
 MR jet can be mistaken for
AS jet on CW doppler
DSE or AV calcium
scoring by MDCT to
confirm AS severity
DSE or aortic valve calcium
scoring by MDCT can be
used to to confirm AS
severity
CMR may be used
to quantify AR and MR
volumes and fractions
and corroborate both
AR and MR
severity

31. Clinical scenarios and proposed decision-
making process in the management of
patients with multiple valvular heart disease.
Circ Cardiovasc Imaging. 2018
*Because of the large number of possible
combinations of valve lesions, a standardized
approach cannot be proposed.
*Nevertheless, the clinician may face one of the
following 3 clinical scenarios

36. Two or more
severe lesions
One severe
lesion plus at
least one non-
severe lesion
Two or more
non-severe
lesions
Three Clinical Scenarios
Severe AS + Severe MS
Severe MS + NonSevere AS
Severe AS + NonSevere MS
NonSevere AS + NonSevere MS
Let me give you an example
The clinical challenge of concomitant aortic and mitral valve stenosis.

37. The clinical challenge of concomitant aortic and mitral valve stenosis. 2017 ESC/EACTS GUIDELINES

39. Combined and multiple-
valve diseases
 There is a lack of data on
combined or multiple-
valve diseases.
 This does not allow for
evidence-based
recommendations.

40. Treatment for Multiple Valve Lesions
If you’re already going to the OR,
what is the indication to treat:

41. Indications for
concomitant valve
surgery in patients
undergoing surgery on
another valve

44. •No clear positionMitral
regurgitation
Surgery is preferable to PMC in patients with
severe mitral stenosis combined with severe
aortic valve disease
In patients with severe mitral stenosis and moderate aortic
valve disease, PMC can be performed to postpone the
surgical treatment of both valves
Severe concomitant aortic valve
disease is a contraindication to PMC
Mitral stenosis

45. Severe
1° TR

46. Moderate
1° TR
Severe
2° TR
Mild/
Moderate
2° TR

47. Moderate TR
MVA 1.2 cm2
MPG 12 mmHg
Tricuspid annulus
(late diastole) 41 mm
MS & TR →Concomitant tricuspid annuloplasty, class IIaC

48. Mild/
Moderate
2° TR

49. Management of multiple valve disease
Medical Surgical Percutaneous
 Is it possible to treat multiple valve disease
with medications alone ?
 Surgical and interventional management :
options and considerations

50. The new paradigm for the management of valvular heart disease:
The Multidisplinary Heart Team

51. Treatment
Surgical Risk
EuroHeart Survey:
 6.5% in hospital mortality for multi-valve surgery
compared with 0.9%-3.9% for single valve surgery
STS Database:
 10.7% in hospital mortality for multi-valve surgery
compared with 5.7% for single valve surgery
• 10.7% for combined AV and MV surgery
• 4.9% for isolated AV surgery
• 6.9% for isolated MV surgery
Good long-term survival and clinical improvement at experienced centers
- Preferred treatment strategy
What if surgery is not an option?
 Percutaneous Options?
 Staged Approach vs. Simultaneous Treatment

52. Percutaneous treatment of multiple valve disease
Is it a reality?
Continuing the paradigm shift in valve heart disease therapy

53. With the disruptive advancement of catheter-based technologies and minimally invasive
techniques in structural heart disease, surgeons must obtain necessary skills to continue to
serve this large patient population. We believe that surgeons are uniquely positioned to
offer the full spectrum of therapy in structural heart disease (transcatheter, minimally
invasive, and complex redo interventions), making them comprehensive valve specialists.
Given the variability in structural heart training, we urgently recommend the establishment
of a standardized curriculum and pathways for surgical trainees to gain proficiency in
transcatheter technologies.

54. MitraClipTAVR

56. Local socio-economic implications
Egyptian professionals cannot ignore our
responsibility to analyze and individualize the
benefit/cost balance of our actions.

57. Percutaneous intervention is feasible
for multivalvular disease –
a tailored Imaging guided approach for
individual patient is essential
Key message today

58. August 2018

60. Case
Scenario

61. Case Scenario 1: AS + MR
91M in CHF w/ CAD, CKD, AS, MR,& AF-RVR
Normal LV EF,
Myxomatous MV,
Sclerotic AV

62. Flail posterior leaflet
 PISA radius = 1.1 cm @ ~40 cm/s
 EROA = 0.49 cm2
 Regurgitant Volume 78 mL
 Systolic flow reversal noted in
pulmonary veins
 Severe MR

63. Perform quantitative methods whenever possible
Journal of the American Society of Echocardiography .April 2017
Chronic Mitral Regurgitation by Doppler Echocardiography

64. AS
Planimetry: 0.7 cm2
 Vmax 3.6 m/s
 Mean grad 29 mmHg
 AVA = 0.6 cm2
 DI = 0.17
 SVI = 28 mL/m2
Paradoxical
low-flow/low-gradient AS

65. Subtypes of low-gradient aortic stenosis

66. Pathophysiology of combined aortic stenosis and mitral regurgitation
Clinical Impact for Each is Compounded by the Other
Mitral valve deformation and tethering, as well as an increase in transmitral pressure gradient
caused by aortic stenosis, all contribute to mitral regurgitation.
Increased LV afterload related to aortic stenosis, combined with mitral regurgitation, result in a
decrease in forward LV stroke volume and, therefore, often to a low-flow, low-gradient pattern.
Both aortic stenosis and mitral regurgitation can, in the long-term, induce LV myocardial
fibrosis and dysfunction. However, the extent of LV systolic dysfunction in such cases is
underestimated by LV ejection fraction owing to the LV concentric remodelling related to aortic
stenosis and the retrograde flow (mitral regurgitant volume) related to mitral regurgitation.

71. By this Valvular
Lesion
• Aortic stenosis
Impact on this
Regurgitant Lesion
• Mitral
regurgitation
For constant ROA , RVol
increases in proportion
to square root of excess
pressure; jet area
exaggerated beyond
this.
ROA may increase if LV dilates.

72. Choice of TAVR Versus Surgical AVR in the Patient With Severe Symptomatic AS

73. Case 1: What is the optimal treatment strategy?
Surgical? Percutaneous?
Fix AS? Fix MR? Fix Both?
Surgical Risk Prohibitive
 2 elements of frailty
 STS Scores:
• SAVR: 7.6%
• Mitral Valve Repair: 10.0%
• Mitral Valve Replacement: 14.1%
• No way to score double valve but certainly greater than 20%
Plan for Percutaneous Approach
 Simultaneous or staged?
 Which order?

74. Staged vs. Simultaneous
• Always fix AS first
- May result in cardiac decompensation after MV repair in the presence of
elevated afterload due to AS
 MR reduction in 60% of patients with moderate functional MR after
isolated SAVR
 MR reduction in 30% of patients after TAVR
• LV Dysfunction, Afib, MV annular calcification, LA enlargement
associated with MR progression
• Therefore, TAVR + maximal medical therapy
- Reassess and consider MitraClip if still severe, symptomatic MR
• No increased risk or technical complexity of MitraClip in the presence of
prior TAVR (assuming no distortion of the MV annulus)
• Simultaneous treatment has been described – consider in primary MR
unlikely to recover significantly (may be tough to get paid for both!)

75. What Happens to MR after TAVR?
JACC: CARDIOVASCULAR INTERVENTIONS
Cortés et al. 2016
CONCLUSIONS
Significant MR is not uncommon in TAVR recipients and associates with
greater mortality.
In more than one-half of patients, the degree of MR improves after
TAVR, which can be predicted by characterizing the mitral apparatus
with multidetector computed tomography.
According to standardized imaging criteria, at least 1 in 10 patients whose MR
persists after TAVR could benefit from percutaneous mitral procedures, and
even more could be treated with MitraClip after dedicated pre-imaging
evaluation.

76. Sannino A, Grayburn PA. Heart 2018 (modified)

77. Case 1 Treatment : TAVR first with #34 Evolut

78. Post TAVR
AV

79. 2 Month Follow Up
Improved but still persistent Class 2 sx
Continued severe
organic MR
 MR EROA = 0.4 cm2
 Mitral Regurgitant Volume = 61 mL
 Mitral Mean Grad = 3 mmHg (HR 72)

80. TEE
A2-P2 A1-P1
Flail P2 with severe MR Small central leak laterally

81. MitraClip : 2 clips on A2-P2
Final Result:
Trivial MR
Mean MV gradient = 4 mmHg
(HR 50)

82. 1 Month Follow Up
Vmax = 2.1 m/s
Mean AV gradient = 9 mmHg
AVA = 1.23 cm2
Trivial to mild MR
Mean MV gradient = 4 mmHg (HR 61)
Climbed Kilimanjaro last summer!
OK, that’s a lie, but he’s Class 1
FC, riding a stationary bike daily

83. Case 2
• 84 year old female presents as an external transfer for
MitraClip evaluation during an admission for a heart failure
exacerbation, chest pain and tachycardia.
• Past Medical History
- PE s/p IVC filter
- HTN
- HL
- Breast Ca s/p Right mastectomy
- GERD

84. Case 2
• Normal LV Systolic Function
• Severely Dilated LA and LV

85. MR
Severely prolapsed vs. flail posterior leaflet

86. AR
𝑃 1/2t = 249 ms

87. AR and MR
• Very Poorly tolerated
• Post-operatively:
- High incidence of LV Dysfunction
- Reduced survival
- Often persistent symptoms

88. AR and MR

89. 𝑅𝑒𝑔 𝑉𝑜𝑙 𝑀𝑅 = 𝑆𝑉 𝑀𝑉 − 𝑆𝑉 𝐿𝑉𝑂𝑇 𝑅𝑒𝑔 𝑉𝑜𝑙 𝐴𝑅 = 𝑆𝑉 𝐿𝑉𝑂𝑇 − 𝑆𝑉 𝑀𝑉
• 𝑺𝑽 𝑹𝑽𝑶𝑻 ?
• Direct measurement of forward and reverse flow by CMR
AR and MR
Reference Stroke Volume:
Volumetric Methods

90. By this Valvular
Lesion
• Aortic regurge
Impact on this
Regurgitant Lesion
• Mitral regurge
 LV dilation may increase ROA
(especially in secondary MR).
 Mixed regurgitant lesions
render volumetric methods challenging,
as one must find some location reflective
of net forward flow (e.g., RVOT).

91. By this Valvular
Lesion
• Mitral regurge
Impact on this
Regurgitant Lesion
• Aortic regurge
 Little direct impact,
 but mixed regurgitant lesions
render volumetric methods
challenging, as one must find
some location reflective of net
forward flow (e.g.,RVOT).
 Rapid early filling may
decrease AR pressure half-
time

92. Echo Evaluation : Grading MR
• PISA Radius = 2 cm
• ERO = 1.6 cm2
• Regurgitant Volume = 167 ml
• Systolic flow reversal noted in pulmonary veins
Severe MR

93. AR and MR
AR Pressure Half-Time
𝑃 1 /2 t = 249 ms
May overestimate severity of AR

94. TEE Flail P2

95. TEE
Mild to moderate AR

96. Case 2
Treatment
• Surgical Risk Prohibitive
- 2 elements of frailty
- STS Scores:
• Mitral Valve Repair: 6.1%
• Mitral Valve Replacement: 10.5%
• Treat MR with MitraClip

98. MitraClip
Positioning First Clip –Mid A2-P2

99. MitraClip
Second Clip at lateral aspect of A2-P2

100. Final Result
Mild residual MR (central and lateral jets)
Mean MV gradient = 6 mmHg
(HR 113)

101. 1 Month Follow Up
Mild Aortic Regurgitation Mild-mod MR (eccentric, anteriorly directed)
Mean MV gradient = 9 mmHg (HR 82)

102. Trans catheter Heart Valves
for Pure Aortic Regurgitation
(A) CoreValve Evolut R
(Medtronic).
(B) Acurate (Symetis SA).
(C) Lotus (Boston Scientific).
(D) Direct Flow (Direct Flow
Medical Inc.).
(E) Engager (Medtronic).
(F) JenaValve (JenaValve
Technology).
(G) J-Valve (JieCheng Medical
Technology).
(H) Helio dock (left) and SAPIEN
XT valve (right) (Edwards
Lifesciences).
Percutaneous Options for Aortic Regurgitation

103. Chronic Aortic Regurgitation by Doppler Echocardiography
Perform quantitative methods whenever possible to refine assessment
Journal of the American Society of Echocardiography .April 2017

104. TAVI for pure severe NAVR
Conclusions
This registry analysis demonstrates the feasibility and potential
procedure difficulties when using TAVI for severe NAVR.
Acceptable results may be achieved in carefully selected patients
who are deemed too high risk for conventional surgery, but the
possibility of requiring 2 valves and leaving residual aortic
regurgitation remain important considerations.

105. Case 3
• 88 year old male presents was referred to hospital for
consideration for percutaneous options for severe MR and TR.
He was very active until about 6 months prior to presentation.
Now with severe fatigue, LE edema, and dyspnea on exertion.
• Past Medical History
- CAD s/p LIMA-LAD bypass
- Atrial Fibrillation
- Prostate Ca

106. Echo
Severe TR,
severely dilated RV and RA

107. Echo
Severe MR – 2 Jets (A1-P1, A3-P3), EROA 0.5 cm2

108. MR and TR
 Secondary TR is highly prevalent in patients with left-sided valvular disease

109. MR and TR
How does MR affect TR?
1. Increased Regurgitant Volume for given ROA
2. Increased Color Jet Area
(out of proportion to increased Regurgitant Volume)
3. Increased ROA due to TV annular dilation

110. By this Valvular
Lesion
• Mitral regurge
Impact on this
Regurgitant Lesion
• Tricuspid regurge
 Likely to increase PAP
and thus worsen RVol
and jet area.
 If RV dysfunction
occurs, may increase
ROA

111. By this Valvular
Lesion
• Tricuspid regurge
Impact on this
Regurgitant Lesion
• Mitral regurge
Little direct impact

112. Case 3
Treatment
• Surgical Risk Prohibitive
- 2 elements of frailty
- STS Scores:
• Mitral Valve Repair: 5%
• Mitral Valve Replacement: 8%
• MR – MitraClip
• TR - MitraClip at the same time vs. return at a later date for
percutaneous TV repair

113. MitraClip
Final Result:
 2 Clips (A1-P1, A3-P3)
 Mild residual MR
 MV mean gradient = 2 mmHg (HR 87)

114. Transcatheter
options
(heterotopic
caval valve
implantation,
coaptation
devices,
annuloplasty
devices)
Challenges for
treating
tricuspid
regurgitation
JACC VOL. 67, NO. 15, 2016

115. Take Home Points
• Multivalvular Disease is common
• Complex inter-relationship resulting in overall
clinical picture
• Grading severity can be a challenge
- Actual severity and echo appearance affected
• Many new transcatheter options are in
development