Clinical impact of MR Determined by the magnitude of the
regurgitant leak Time course of development of the regurgitation
Abrupt onset of severe MR markedly pul venous pr C/c MR exhibit
prominent ventricular enlargement with chamber compliance &
pulmonary venous pressure
Slide 8
Torricelli principle, states that flow through an orifice
varies by the square root of the pressure gradient across the
orifice, the duration of flow, and a discharge coefficient. The
principal determinants of the RV are the regurgitant orifice area
and the systolic pressure gradient between the ventricle and left
atrium
Two factors - maintenance of left ventricular performance
a)increased diastolic volume b)reduction of afterload Primary
response to acute volume overload is the Frank- Starling mechanism
-end-diastolic fiber length- improving vent ejection by ing both
the rate and force of contraction A 2 nd mechanism is the afterload
afforded by the low- impedance pathway to ventricular ejection via
the regurgitant leak
Slide 13
LV stress-volume loop in acute MR in EDV A systolic unloading
that is characteristic of acute MR, A in ESV The Total Stroke
Volume increases
Slide 14
Volume overload of a/cMR preload sarcomere length EDVfrom 150
to 170ml. Ejection of blood into LA afterload ( end-systolic stress
) End-systolic volume (ESV) 50 to 30 ml EF acutely 50% TSV is
regurgitated into the left atrium-RF - 0.50 FSV 100 to 70 ml.
volume in the LAraises pressure -normal to 25 mm Hg
Slide 15
Consequences of Acute severe MR Sudden volume overload of LA
& LV PVH Pulmonary edema Low forward stroke volume, tachycardia
Decreased cardiac output Hypotension/ cardiogenic shock flow work
adds little to the energy requirements of the heart
Slide 16
Acute Severe Mitral Regurgitation Pathophysiology In acute
severe MR, a sudden volume overload is imposed on the left atrium
and left ventricle. Acute volume overload es LV preload, allowing
for a modest in total LV stroke volume. Forward stroke volume and
cardiac output are reduced due to the absence of compensatory
eccentric hypertrophy. Unprepared LA and LV cannot accommodate the
regurgitant volume large v waves in LA pulmonary congestion. The
patient has both ed forward output (even shock) and pulmonary
congestion. In severe MR, the hemodynamic overload often cannot be
tolerated, and MV repair or replacement must often be performed
urgently.
Slide 17
Large volume of regurgitant blood entering a relatively stiff
and nondilated LA will result in a steep rise in the v wave The
entry of a large volume of blood during diastole into a nondilated
LV will raise the diastolic filling pressure in the LV. (The raised
pre-a wave pressure may further add to the v wave height) High v
wave buildup rapidly falling pressure difference between the LV and
LA toward the later part of systole limit the regur flow during the
later part of systole murmur decrescendo Excess flow more low and
medium frequencies harsher
Slide 18
Continuing Medical Implementation ...bridging the care gap MR
Pressure Tracing
Slide 19
V waves correspond to T waves on ECG The PA waveform appears
falsely elevated large V wave reflected back from the LA through
the compliant pulmonary vasculature The Y descent is quite rapid as
the over distended LA quickly empties In C/C MR, an equivalent
volume better tolerated by a markedly dilated LA Compared with a/c
MR LA pr may be less and large V waves may be absent
Slide 20
Slide 21
ACUTE TO CHRONIC
Slide 22
Slide 23
Compensated Stage of MR Major adaptive change that occurs
during the development of a c/c volume overload is LVE Large
compliant ventricle that is well suited to deliver a large stroke
volume Also seen during gradual progression of the severity of the
regurgitation. Remodeling of the extramyocardial matrix
rearrangement and slippage of myocardial fibers and chamber
enlargement New sarcomeres are added in series, and at the
ventricular level, eccentric hypertrophy develops
Slide 24
A/C MR C/C COMPENSATED MR
Slide 25
Dvpt of eccentric hypertrophy - EDV Now larger ventricle has an
in afterload - Laplace eq = (P * R () / T ) ses ESV to normal
Eccentric hypertrophy- in TSV & FSV LA enlargement accommodates
vol overload at lower filling pr EF is supernormal
Slide 26
Cardiomyocytes exhibit an in length, but preload at the
sarcomere level ( sarc length) does not increase progressively
Sarcomere lengths tend to return toward normal despite progressive
LV enlargement preload reserve is reestablished LV systolic
unloading of a/c MR is gradually replaced by nl systolic wall
stress TSV in c/c compensated MR mediated through a normal
performance of each unit of an enlarged circumference. Compensated
stage, preload (at the sarcomere level), afterload (at the
ventricular level), and both contractility and EF are normal TSV is
as a result of the large EDV
Slide 27
Volume overloads-the excess volume ejected into the aorta,
where it widens PP SBP combined Pr and Vol overloads The extra
volume from the LV in MR enters the LA and SBP is nl- PURE VOLUME
OVERLOAD Preload in MR and AR but afterload greatly in AR comp to
MR Unique loading conditions of MR - unique pattern of remodeling
Largest radius-to-thickness ratio and the smallest mass-to-volume
ratio of the 4 left-sided valve lesions Eccentric hypertrophy
greater increase in volume than mass spheric MR- hypertrophy occur
from a decrease in Myosin degradation
Slide 28
MYOSIN TURNOVER IN MR
Slide 29
LV volume allows TSV to - increasing FSV -compensating for the
volume lost to regurgitation Relatively thin LV wall enhances
diastolic filling MR is one of the very few cardiac diseases in
which diastolic function is supernormal Increased radius
to-thickness ratio Adaptive as well as Maladaptive
Slide 30
The loading conditions in MR are favorable to left ventricular
ejection Preload is whereas afterload is nl or occasionally
decreased- lesion itself facilitates left ventricular emptying
Presence of normal muscle function- EF-supernormal in MR (Carabello
BA. Mitral regurgitation: basic pathophysiologic principles;Mod
Concepts Cardiovasc Dis 1988;57:53-8) Once the EF falls below 60
percent, the prognosis worsens (Wisenbaugh T. Does normal pump
function belie muscle dysfunction in patients with chronic severe
mitral regurgitation? Circulation 1988;77:515-25 )
Slide 31
Slide 32
Transitional Stage of MR Transition may occur as a consequence
of:- a progressive increase in the RV a decrease in LV contractile
function an increase in afterload OR combination of these factors.
During this stage - EF declines to 50% to 59%. Structural and
functional remodeling of the ventricle is largely reversible
Slide 33
Decompensated Stage of MR Substantial and progressive LV
dilation LVEDP, systolic wall stress and - an EF of 50% The decline
in EF is a consequence of depressed myocardial contractile state,
LV afterload excess, or both
Slide 34
C/C COMPENSATED TO DECOMPENSATED
Slide 35
Contractility - ESV FSV Cardiac dilatation RF Favorable loading
conditions permit the ejection fraction to remain normal
Slide 36
A decrease in myocardial contractile state or an increase in LV
afterload cause a decrease in the EF
Slide 37
MR is often viewed as a lesion that unloads the LV by creating
a second pathway for ejection A/c MR- ESV and afterload is low As
the ventricle enlarges and adapts to the chronic volume overload
afterload gradually increases Eventually in decompensated MR,
afterload exceeds nl Such afterload excess contributes to a decline
in EF Remodeling pattern-- increasing r/h- increase afterload Only
in acute MR is afterload decreased C/c compensated MR afterload is
normal C/c decompensated MR greater than normal
Slide 38
In MR, the volume-loaded LV faces relatively low impedance to
outflow and nl or subnl afterload, even when myocardial dysfunction
is established In MR- LVEF is higher relative to intrinsic LV
contractility than in the normal LV or in AR A low or borderline EF
(ie, 50% to 55%) indicate depressed LV function if afterload were
low LV function- depressed if the EF were 55% to 60% in the
presence of increased or even normal afterload
Slide 39
LVEF remains the best-validated predictor Prognostically
important myocardial dysfunction exists when LVEF is 10% greater
than the nominal lower normal limit(commonly 50% with
echocardiography) LVEF = 60%, even among asympc/min symp patients
FC I-II, long-term survival after MVR/MV repair worse than if LVEF
is 60 %
Slide 40
Survival of patients with severe MR and EF
Slide 41
LV stress-volume loops in the 3 stages of chronic MR
Progressive in LV EDV and systolicwall stress EF progressively from
65% in compensated MRto 55% during the transitional stage, and
finally to 45% (or lower) in decompensated MR
Slide 42
Slide 43
Passive myocardial stiffness in those with systolic dysfunction
LV dysfunction is associated with myocardial interstitial fibrosis,
reduction in myofiber content, and decrease in myofiber
contractility
Slide 44
Symptamatology and findings Anatomic malcoaptation ofmitral
leaflets during systole ERO pressure gradient between LV and LA
allows abnormal regurgitant flow into the LA Systolic pr gradient
between the LV &LA begins with closure of the mitral valve
(S1)and persists after closure of the aortic valve (S2) up to
mitral opening Regurgitant flow lasts as long as the ERO and is
holosystolic Determinants of R V are the area of ERO, the
regurgitant gradient, and duration of regurgitation In both organic
MR and functional MR ERO increases with afterload or ventricular
volume and with decreased afterload or improved contractility, but
is independent of changes in heart rate
Slide 45
Survival under medical management of patients with organic
mitral regurgitation according to the effective regurgitant orifice
area measurement
Slide 46
In the mitral regurgitant system energy produced by the LV
remains constant Kinetic energy - Rvol and potential energy by LA,
V-wave LA compliance is one of the major determinants of the V-
wave and LA pressure. In a/cc severe MR- LA is smaller and less
compliant compared - a similar RVol will result in higher V-wave
and LA pressure. In c/c MR LA remodels and accommodates the RVol
-normal or near normal LA pressure is maintained
Slide 47
Slide 48
LV end-diastolic volume and wall stress increase (29) and LV
shape becomes more spherical. LV end-systolic volume is increased,
but end-systolic wall stress is usually within normal limits LV
dysfunction is associated with myocardial interstitial fibrosis,
reduction in myofiber content, and decrease in myofiber
contractility The RVol in ischemic MR is usually less than in
organic MR (39) and the LV and LA dilatation are in excess to the
degree of MR (22). Despite this appearance of low-volume
regurgitation, MR is associated with elevated LA pressure (22) and
poor clinical outcomewith reduced survival
Slide 49
S1 S1 intensity is usually normal, but may be decreased in
chronic severeMR associated with defective leaflets or increased in
rheumatic MR
Slide 50
S3 Presence of S3 is directly related to MR degree in organic
MR In ischemic/functional MR, S3 reflects more restrictive LV
filling than severity of MR Asso with a diastolic rumble which is
low pitched and heard best in the left lateral decubitus position
In AR signifies LV dysfunction
Slide 51
S4
Slide 52
Murmers Systolic pr gradient between the LV &LA begins with
closure of the mitral valve (S1)and persists after closure of the
aortic valve (S2) up to mitral opening Excess flow more low and
medium frequencies harsher A distinguishing feature is the lack of
murmur intensity beat- to-beat variation with MR, such as with post
extrasystolic beats or AF while marked murmur variation would be
expected with aortic stenosis or dynamic left ventricular outflow
tract obstruction Amyl nitrite MR murmur intensity and that of
obstructive lesions. MR murmur with isometric exercise or
phenylephrine, while these maneuvers obstructive murmurs
Slide 53
Slide 54
Slide 55
Hemodynamic characteristics Common Features of AR & MR: LV
volume overload Progressive LV dilatation LV systolic dysfunction
Clinical heart failure Differences in AR & MR: AR- High
afterload, concentric & eccentric LVH MR- Low afterload,
eccentric LVH
Slide 56
Large V waves in a case of mitral regurgitation. Simultaneous
recording of ECG helps identify V waves in mitral valve
regurgitation; V waves correspond to T waves on ECG. The PA
waveform appears falsely elevated because of the large V wave
reflected back from the LA through the compliant pulmonary
vasculature. The Y descent is quite rapid as the overdistended LA
quickly empties. Care must be exercised to distinguish a large V
wave from a systolic PA waveform. Failure to recognize a large V
wave may cause the PAC to be advanced further in an attempt to
record a PCWP pressure, increasing the risk of perforation. In
chronic mitral regurgitation, an equivalent volume of blood may
regurgitate, but this volume is better tolerated by a markedly
dilated LA. Compared with acute mitral regurgitation, LA pressure
may be less and large V waves may be absent.
Slide 57
Two factors identified by this study which may account for the
maintenance of left ventricular performance are increased diastolic
volume andreduction of afterload. A primary compensatory response
to acute volume overload is the Frank- Starling mechanism,
augmented end-diastolic fiberlength- improving ventricular ejection
by increasingboth the rate and force of contraction. A second
potential compensatory mechanism is the reduced afterload afforded
by the low-impedance pathway to ventricular ejection via the
regurgitant leak although mean left atrial pressure was abnormally
high (183 mm Hg), it nevertheless was considerably lower than mean
systolic pressure (91 mm Hg) at any moment during ventricular
contraction; hence, impedance to ventricular emptying was always
lower than normal, and calculated myocardial wall tension,
expressed as average stress per unit of myocardial wall thickness,
did not rise to abnormal levels
Slide 58
Valvular regurgitation increases preload, reflected by greater
left ventricular end- diastolic pressure, volume, circumferential
length, and stress. To accommodatethe larger filling volume in
acute volume overload, existing sarcomeres are stretched, thereby
increasing ventricular volume and circumferential length.14 In
chronic regurgitation, further augmentationof these dimensions is
due to sarcomeres added in series and in parallel, and possibly to
fiber slippage; not to extension of individual sarcomeres beyond
their optimal contractile length.) The effect of the low pressure
left atrium upon ejection and systolic afterload is manifested in
several ways. Early regurgitation allows the ventricle to empty
against a relatively low afterload. The consequently reduced
dimensions and thickened wall act to decrease stress throughout
ejection. Emptying into the low impedance left atrium occurs during
the entire time that the aortic valve is open and it continues
after aortic valve closure. Ventricular pressure is falling in this
latter period. The net effect is to extend ejection time, enhance
overall ventricular emptying, and diminish mean systolic
afterload.
Slide 59
The short-term response to volume overload is an increase in
left ventricular volume with a lengthening of sarcomeres along
their normal length-tension curve.29 Progressive dilation of the
ventricle leading to augmented volume in the chronic state is a
result of the increased number of sarcomeres added in series and in
parallel as the myocardium hypertrophies. Sarcomere length remains
relatively constant during this period and the fiber is not
extended beyond its optimal contractile length.14 301, 31 In both
control and chronic volume overloaded ventricles, extension and
recruitment of sarcomeres constitute the functional reserve of
Starling's curve30; this reserve is used to an increasing extent as
diastolic pressure and stress are elevated.
Slide 60
Slide 61
Slide 62
Slide 63
Slide 64
Pulmonary venous pulsed-wave Doppler in severe mitral
regurgitation. Systolic flow reversal (ie, systolic flow into the
pulmonary vein) is present (arrows).
Slide 65
Slide 66
Why do we need careful timing? Patients with pure regurgitant
lesions may remain asymptomatic for long time. Some of them may
develop LV dysfunction without warning symptoms. Onset of
significant LV dysfunction increases the risk of surgery, and LV
dysfunction may become irreversible. Valve replacement has
important implications like risk of surgery, long term
anticoagulation in mechanical valves, risk of valve failure in
future for bioprosthetic valve and risk of endocarditis.
Left ventricular performance can also be gauged in MR by
assessing the diameter to which the LV can contract at the end of
systole. End-systolic dimension is less dependent on preload than
is ejection fraction When the end-systolic dimension exceeds 45 mm,
the prognosis worsens
Slide 69
Slide 70
Slide 71
LV and LA pressures showing large V wave and persistent LALV
gradient of mixed mitral regurgitation and stenosis
Slide 72
RV/EDV RATIO A high ratio indicates severe MR that is a
potential target for corrective surgery. Alow ratio suggests
severedecompensated MR or a cardiomyopathic process {If a patient
end-diastolic diameter of 65 mm or end-diastolic volume of 130
mL/m, an EF of 30%, a regurgitant fraction of 50%, and a
regurgitant volume of 20 mL/m2, the ratio of regurgitant volume to
end-diastolic volume would be only 20/130, or 0.15. This should
suggest severe, irreversible LV dysfunction. By contrast, a patient
EDV 130 mL/m2, an EF of 50%, and a regurgitant fraction of 50%
would have a ratio of regurgitant volume to end-diastolic volume of
33/130, or 0.25. The higher ratio of 0.25 indicates a potentially
reversible phase of chronic MR}
Slide 73
Slide 74
Cardiac cycle-Systolic events EM delay-Q to LV pressure rise.
ICT- LV pressure rise to LV-Ao pressure crossover. PEP-
EM+ICT(QS2-LVET) LVET-Ao pre.rise & incisura.Duration of
ejection. QS2- Q in ECG to first high frequency vibrations of A2 in
ACG.
Slide 75
PEP/LVET- independent of heart rate PEP, LVET & PEP/LVET
correlated significantly with angiographic EF &EDV. Closest
correlation b/w EF& ratio. (Weissler et al Circulation 42
;1970.) Echo FS of LV correlation with this ratio. ( McDonald
&Hobson,1974) PEP-0.10-0.14 sec. PEP/LVET 0.34-0.42,children
have shorter ratios than adults Adult value by 13 years
Slide 76
Slide 77
Slide 78
Pure MR- N PEP Pure MR- ET short PEP Prolongation>0.12
sec-LV dysfunction MR with N LV function- Ratio prolonged d/t short
LVET, but ratio >0.5indicates LVD. PEP/LVET >0.5 indicates an
EF