Floppy Mitral Valve (FMV)/Mitral Valve Prolapse (MVP) and...
Transcript of Floppy Mitral Valve (FMV)/Mitral Valve Prolapse (MVP) and...
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Floppy Mitral Valve (FMV)/Mitral Valve
Prolapse (MVP) and the FMV/MVP Syndrome:
Pathophysiologic Mechanisms, Diagnostic and
Therapeutic Considerations
Haris Boudoulas, MD, Dr., Dr. Hon.Professor of Medicine/Cardiovascular Medicine and Pharmacy (emeritus)
The Ohio State University, Columbus, Ohio, USA
Honorary Professor, Academician (an. mem.)
Council Member Aristotelian University of Thessaloniki, Greece
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Morphology – Pathology
Robert H. Anderson
Noby Baba
Peter Baker
Anton E. Becker
Michael J. Davies
Heritable Aspects
Julie Johnson
Hervé Le Marec
Reed E. Pyeritz
Clinical Manifestations
John B. Barlow
Thomas Bashore
Blase Carabello
Mary E. Fontana
Tsuguya Sakamoto
James Shaver
Charles F. WooleySurgical Approach
Lawrence K. Cohn
Delos M. Cosgrove, III
Robert E. Michler
Physiology/Pathophysiology
F. Andrew Gaffney
Derek Gibson
Robert C. Little
William C. Little
Ernest Mazzaferri
Imaging
J. Michael Criley
Jos Roelandt
Subha Raman
Pravin P. Shah
VALVE DISEASE Editor
Richard P. Lewis, MD
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Editorial
Floppy Mitral Valve and Mitral Valve Prolapse: Lack of
Precise Definition (The Tower of Babel Syndrome)Boudoulas KD, Boudoulas H. Cardiology 2011;118:93-96
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Mitral Valve
Floppy mitral valve (partial to complete involvement) is the central
issue in the mitral valve prolapse, mitral valvular regurgitation story.
Normal FMV/MVP
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Floppy Mitral Valve (FMV) Genetics
• Gene map loci:
– 16p12.1 – p11.2
– 11p15.4
– 13q31.3 – q32.1
– xq28
• Clinical trials.gov
(2012-2020)
Four generations pedigree of a family with
floppy mitral valve/mitral valve prolapse/mitral
regurgitation
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FMV/MVP/Mitral Valvular Regurgitation: Diagnostic Considerations
Imaging: (echo, angio, MRI)
Thick redundant valve with
prolapse
3rd chamber
Skeletal abnormalities
Thinner than normal
Height/weight > normal
Arm span > height
Auscultation:
Click-murmur
Hemodynamic:
(angio/Doppler,
MRI, mitral
regurgitation)
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ECG
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Courtesy Jos Roelandt, Thorax Center, Rotterdam
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Courtesy Subha Raman, MD, The Ohio State University
LV
LA
LV
LA
ALPL
RVRV
Ao
PM
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FMV/MVP: Ventriculogram
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Floppy Mitral Valve/Mitral Valve Prolapse
Association with Other Disorders/Diseases
• Heritable connective tissue disorders
Marfan
Ehlers-Danlos
Adult polycystic kidney diseases
Multi valve prolapse
MASS (mitral, aorta, skeleton, skin)
• Other
Graves disease
Atrial septal defect?
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FMV/MVP/MVR: Classification
Normal
FMV/MVP – no MVR
FMV/MVP: - mild MVR
FMV/MVP: - moderate MVR
FMV/MVP: - severe MVR
Dynam
ic s
pectr
um
Time (years)
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FMV/MVP/MVR: Symptoms/Complications
• Infective endocarditis
• Cardiac arrhythmias
• Sudden cardiac death
• Thromboembolic complications
• Progressive MVR
• Ruptured chordae tendineae
• Increased LV-LA size
• CHF
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FMV/MVP: Thromboembolic Complications, Endocarditis
• Thrombus formation
• Infective endocarditis
Oral hygiene
Antibiotic?
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FMV/MVP: Sudden Cardiac Death
• Very rare (more common in female)
• Bileaflet prolapse – floppy mitral valve
• History of complex ventricular arrhythmias and/or
syncope
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FMV/MVP: Natural History
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FMV/MVP: Progression of Mitral Valvular
Regurgitation (MVR) Precipitating Factors
Mild MVR
Moderate MVR
Severe MVR
LA-LV dilatation/dysfunction
• Infective endocarditis
• Chordae tendinae rupture
• Stiff aorta
• Papillary muscle displacement
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Left heart Right heart
MVR: Aortic-Ventricular-Pulmonary Interrelationship
Alveolar capillaries
Arterioles
Left Atrium
Vena cava
Pulmonary artery
Pulmonary veins
Mitral Valve
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FMV/MVP/MVR: Therapeutic Considerations
The Heart Team and
Heart Valve Center of Excellence
Medical
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FMV/MVP/MVR: Therapeutic Considerations
Mitral Valve Clip
Echocardiographic and clinical outcomes of central versus
noncentral percutaneous edge-to-edge repair of
degenerative mitral regurgitation.Estevez-Loureiro R, et al. JACC 2013;62:2370-2377
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FMV/MVP/MVR: Therapeutic Considerations
Surgical Approach
• Significant MVR
• Symptoms
• Left ventricular (LV) ejection fraction <60
• LV end systolic diameter >40 mm
• Pulmonary hypertension ≥50 mm Hg, rest
• Left atrial enlargement
• Chordae tendinae rupture
• Atrial fibrillation
• The role of exercise
• Reconstructive vs valve replacement
• Leaflet prolapse
Posterior 67%, 51%
Anterior 10% 11%
Both 23% 37%
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FMV/MVP Syndrome (n = 313)Female (n=227)
Frequency (%)
60
75
48
34
15
Male (n=86)
Frequency (%)
60
46
28
16
15
Symptoms
Chest pain
Palpitations
Fatigue
Dyspnea
Postural phenomena
(syncope/presyncope)
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FMV/MVP Syndrome in Patients Who Had Surgery (n=101)
Symptoms consistent with
FMV/MVP syndrome 41
• Palpitations 25
• Fatigue 5
• Postural phenomena 5
(syncope/presyncope)
• Dyspnea 3
• Chest pain 2
• Headache 1
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FMV/MVP Syndrome: Age of Onset and Duration of Symptoms
• Median age of onset 30 years
(Range 10-65 years)
• Median time of duration 16 years
(Range 3-50 years)
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FMV/MVP Syndrome: Pathogenetic
Mechanisms
• Papillary muscle traction / Stretch receptor
activation
• Mitral valve-brain interaction
• Development of third chamber
• Hypersensitivity to adrenergic stimulation
• Other
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FMV/MVP: Papillary Muscle Traction/Stretch
Receptor Activation
Stretch Receptor
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FMV/MVP: Mitral Valve-Brain Interactions
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FMV/MVP: Third Chamber
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Floppy Mitral Valve/Mitral Valve Prolapse
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Normal
Mitral Valve
Floppy Mitral Valve / Mitral Valve
Prolapse
Courtesy Vlasis Ninios, Agios Loukas Hospital, Thessaloniki
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Floppy Mitral Valve / Mitral Valve Prolapse
Courtesy Subha Raman, MD, The Ohio State University
LV
LA
LV
LA
ALPL
RVRV
Ao
PM
LVLA
AL
PL
RV
RA
PM
AL
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FMV / MVP Syndrome: Orthostatic Phenomena (3rd Chamber)
80 –
–
60 –
–
40 –
–
20 –
–
0 –
LVEDVI
Supine
Upright
Rest 300 Peak
Left Ventricular End-Diastolic Volume Index (LVEDVI) in the Supine and Upright
Posture, at Rest and During Excise
FMV/MVPS (n=16)
Kpm/min
Rest 300 Peak
Control (n=12)
Kpm/min
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–
60 –
–
40 –
–
20 –
–
0 –
D HR
(beats/min)
Control (n = 12)
FMV/MVPS (n = 16)
0.5 mg/min 1 mg/min 2 mg/min
p < 0.01
p < 0.01
p < 0.01
Effect of Isoproterenol Infusion on Heart Rate (HR)
Boudoulas H, et al. JACC 1983;3:638-644
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b1-Adrenergic Receptor Polymorphism in FMV/MVP.
Frequency of CC (Arginine 389) Genotype
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0 –
%
Control
FMV/MVP
Total Male Female
45.5%
51%
48% 48% 48%
61%
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b1-Adrenergic Receptor Polymorphism in Females.
Frequency of CC (Arginine 389) Genotype
100 –
90 –
80 –
70 –
60 –
50 –
40 –
30 –
20 –
10 –
0 –
%
Control FMV/MVP FMV/MVP
Syndrome
48%
61%
81%
p = 0.025
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Floppy Mitral Valve: Factors Contributing to Symptoms in
FMV/MVP Syndrome
Prolapsing Mitral Valve
Development
3rd Chamber
↓ Stroke Volume
(especially in
upright position)
Orthostatic
Phenomena
FMV Nerve
Ending
Stimulation
↑ Papillary
Muscle Traction
Brain-Heart
Interaction
Stretch
Receptor
Activation
↑ β1-Receptor
Sensitivity
Neurohumoral
Activation
Tachycardia
Arrhythmia
Chest Pain
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Floppy Mitral Valve/Mitral Valve Prolapse Syndrome:
Pathogenesis of Symptoms
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FMV/MVP Syndrome: Therapeutic Considerations
• Explain and reassure
• Avoid caffeine, catecholamines or other cyclic - AMP
stimulants
• Avoid volume depletion and diuretics
• Avoid long-term drug therapy
• Treat the specific symptoms if persistent (chest pain,
postural phenomena, etc.)
• Management requires understanding the underlying
pathophysiologic mechanisms, natural history of the
disease and caring for the patient.
The Superior Physician
He is skeptical toward the data of his own profession, welcomes discoveries
which upset his previous hypothesis, and still animated by human sympathy
and understanding. Alfred North Whitehead, Dialoges (Lucien Press) 1954
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Initial Diagnostic Evaluation
Heritable Connective
Tissue Disorder
Isolated FMV/MVP
Diagnostic Classification
FMV/MVP: Individual Patient Analysis
FC
IV –
III –
II –
I –
Time (years)
Sym
pto
ms / E
ve
nts
Periodic
Evaluation
Frequent
Evaluation
Intervention
FMV/MVP/MVR
FMV/MVP Syndrome
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Initial Diagnostic Evaluation
Heritable Connective
Tissue Disorder
Isolated FMV/MVP
Diagnostic Classification
FMV/MVP: Individual Patient Analysis
FC
IV –
III –
II –
I –
Time (years)S
ym
pto
ms / E
ve
nts
Periodic
Evaluation
Frequent
Evaluation
Intervention
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FMV/MVP/MVR: The Role of the Aorta
Normal AortaStiff Aorta
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A randomized controlled phase IIb trial of beta1-receptor
blockade for chronic degenerative mitral regurgitation.Ahmet MI, et al. JACC 2012;60:833-838 (FMV/MVP/MVR, n=38; Toprol-XL, MRI, 2 year
study)
Modulation of transforming growth factor-b signaling and
extracellular matrix production in myxomatous mitral valves
by angiotensin II receptor blockers.Geirsson A, et al. Circulation 2012;126(Suppl 1):S189-S197 (Cultured valve tissue
obtained from patients undergoing mitral valve repair or organ donors without mitral valve
disease)
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Incidence of FMV/MVP in Females
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Mitral Valve Repair vs ReplacementMedicare database 47,279, >65 years, 2000-2009
Surgical Mortality
Survival
1 year
5 years
10 years
MV Repair
3.9%
90.9%
77.1%
53.6%
MV Replacement
8.9%
82.6%
64.7%
37.2%
Vassileva CM, et al. Circulation 2013;127:1870-1876
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Survival
David TE, et al. Circulation. 2013;127:1485-1492
Freedom from moderate and
severe MVR
FMV/MVP/MVR: Late Outcome of Mitral
Valve Repair
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Hemodynamics in Acute Mitral Regurgitation
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• Diffuse thickening (3rd chamber) – 40 patients
– Symptoms consistent with FMV/MVP syndrome - 21 (52.5%)
• Regional thickening – 61 patients
– Symptoms consistent with FMV/MVP syndrome – 19 (31%)
FMV/MVP Syndrome
60 –
-
40 –
-
20 –
-
0 –
Diffuse Regional
%
p = 0.025
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Mitral Valve Prolapse (MVP): Definition
MVP results from the systolic movement of portion(s) or
segments of the mitral valve leaflet(s) into the left atrium
during left ventricular systole.