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LOW FLOW LOW GRADIENT
AORTIC STENOSIS
25-2-2016
OUTLINE
 Introduction
 Low flow Low gradient AS with Low EF
 Low flow Low gradient AS with Normal EF
 Normal-Flow, Low-Gradient AS.
 Treatment
 Conclusions
LOW FLOW LOW GRADIENT AS
Introduction
Aortic stenosis is one of the common valve
disorders encountered in clinical practice and
one of the most frequent indications for valve
surgery.
Prevalence is 2-7% over the age of 65 years
Evaluation of AS is challenging of all VHD
LOW FLOW LOW GRADIENT AS
 Long asymptomatic phase: risk of sudden death low
 Mortality ↑: exertional chest pain, syncope,
breathlessness
 Mortality up to 12% soon after onset of symptoms
 Significant AS and LV dysfunction: poor prognoses
 Importantly as many as 30% of patients who have a
calculated AVA in the severe range have other
parameters suggesting mild or moderate disease (ie,
mean gradient <30 mm Hg)
LOW FLOW LOW GRADIENT AS
Valvular AS has three principal causes: a
congenital BAV with superimposed
calcification, calcification of a normal trileaflet
valve, and Rheumatic disease
LOW FLOW LOW GRADIENT AS
Major types of aortic valve stenosis. A, Normal aortic valve. B, Congenital bicuspid AS.
A false raphe is present at 6 o’clock. C, Rheumatic AS. The commissures are fused with
a fixed central orifice. D, Calcific degenerative AS.
LOW FLOW LOW GRADIENT AS
STAGES OF VALVULAR AS
LOW FLOW LOW GRADIENT AS
Nishimura RA, Otto CM, Bonow RO, et al: 2014 AHA/ACCF guideline for the management
of patients with valvular heart disease: A report of the American College ofCardiology
Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll
Cardiol 63:e57, 2014.
LOW FLOW LOW GRADIENT AS
 As the severity of AS increses there will be
corresponding increase in the TVPG (ΔP) and
myocardial pressure overload
Though the preload reserve, the LV compensates for
the increased workload until the sarcomeres stretch
to their maximum diastolic length.
Once the preload reserve is exhausted, increases in
afterload are accompanied by a reduction in stroke
volume (SV), resulting in afterload mismatch
LOW FLOW LOW GRADIENT AS
Various Hemodynamic Metrics Used for Assessment
of AS and Their Cutoff Values for Severe AS
LOW FLOW LOW GRADIENT AS
Percentage of patients diagnosed with severe
AS based on various echocardiographic criteria
Minners et al Eur.HEART .journal 2008:29;1043-8
Inconsistencies of echocardiographic criteria for
grading of AS LOW FLOW LOW GRADIENT AS
Moderate stenosis for a normal ventricle
may correspond to a severe stenosis for a
diseased ventricle in terms of hemodynamic
load
LOW FLOW LOW GRADIENT AS
Effect of concurrent conditions ……
Left ventricular systolic dysfunction
Left ventricular hypertrophy
Small ventricular cavity & small LV ejects a
small SV so that, even in severe AS the AS
velocity and mean gradient may be lower than
expected.
 Continuity-equation valve area is accurate in
this situation
LOW FLOW LOW GRADIENT AS
Hypertension
35–45% of patients
primarily affect flow and gradients but less AVA
measurements
Control of blood pressure is recommended
The echocardiographic report should always
include a blood pressure measurement
Effect of concurrent conditions contd…
LOW FLOW LOW GRADIENT AS
Aortic regurgitation
 About 80% of adults with AS also have aortic
regurgitation
High transaortic volume flow rate, maximum
velocity, and mean gradient will be higher than
expected for a given valve area
Effect of concurrent conditions contd…
LOW FLOW LOW GRADIENT AS
High cardiac output
Relatively high gradients in the presence of
mild or moderate AS
The shape of the CWD spectrum with a very
early peak may help to quantify the severity
correctly
Ascending aorta
Aortic root dilation
Coarctation of aorta
LOW FLOW LOW GRADIENT AS
The transaortic gradient depends upon the
severity of the stenosis and upon flow rate, which
is determined by the stroke volume and systolic
ejection period
GRADIENT = Flow Dependent Variable
Gradient calculation- Small reduction in flow can
cause great reductions in gradient
LOW FLOW LOW GRADIENT AS
AVA calculation is a standard and must be incorporated into
a comprehensive evaluation of AS severity
AVA= Flow independent variable
LOW FLOW LOW GRADIENT AS
 The gradients across a stenosd valve are a squared
function of flow, even a modest decrease in flow
may lead to an important reduction in gradient,
even if the stenosis is very severe.
Symptomatic patients with severe AS generally
have a substantial improvement in symptoms and
increased survival after AVR.
 Precise assessment of both the severity of valve
stenosis and the degree of myocardial impairment
is thus crucial for good therapeutic management.
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS
Prevalence of low flow state
Low EF
5- 10 % of all patients of AVA < 1.0
Preserved EF
10-25 % of all patients of AVA < 1.0
Pibarot P, Dumesnil J. Low-Flow, Low-Gradient Aortic Stenosis With Normal and
Depressed Left Ventricular Ejection Fraction. J Am Coll Cardiol 2012;60:1845–53
LOW FLOW LOW GRADIENT AS
Till 2007 low flow due to Low EF
Now Low flow can also be with Preserved
EF “new entity” Paradoxical Low
flow AS
Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low flow, low gradient severe aortic
stenosis despite preserved ejection fraction is associated with higher afterload and reduced
survival. Circulation 2007;115:2856–64
Pibarot P, Dumesnil J. Low-Flow, Low-Gradient Aortic Stenosis With Normal and Depressed
Left Ventricular Ejection Fraction. J Am Coll Cardiol 2012;60:1845–53
LOW FLOW LOW GRADIENT AS
TYPES OF LOW FLOW AS
LOW FLOW LOW GRADIENT AS
Classical Low Flow Low Gradient AS with
Low EF
LOW FLOW LOW GRADIENT AS
Prevalence of LF –LG –AS with Low EF
 A LF-LG severe AS with Low LVEF may be observed in
approximately 5% to 10% of patients with severe AS.
 Such patients are classically characterized by a dilated LV
with markedly decreased LV systolic function, most often
due to IHD and/or to after load mismatch
 Prognosis is usually poor (survival rates 50% at 3-year
follow-up) if treated medically, but operative risk is high
(6% to 33%) if treated surgically
LOW FLOW LOW GRADIENT AS
LF LG AS with Low EF
Low LVEF, LF-LG severe AS is generally
characterized by the combination of an
EOA≤1.0 cm2 or ≤0.6 cm2/m2 when indexed
for BSA, a low mean transvalvular gradient
(i.e.,<40 mm Hg) and a low LVEF (≤40%),
causing an LF state.
LOW FLOW LOW GRADIENT AS
Several criteria have been proposed in the
literature to define the LF state in AS, including a
cardiac index <3.0 l/min/m2 and a stroke volume
index < 35 ml/m2
Given that the gradient essentially depends on
the flow per beat (i.e., the stroke volume) rather
than on the flow per minute (i.e., the cardiac
output), the former is the most frequently used
parameter in this context
LOW FLOW LOW GRADIENT AS
Patients with critical AS, severe LV dysfunction,
and low cardiac output (low TVG) often create
diagnostic dilemmas for the clinician because
their clinical presentation and hemodynamic
data may be indistinguishable from those of
patients with a DCMP and a calcified valve that
is not severely stenotic.
LOW FLOW LOW GRADIENT AS
The main diagnostic challenge in LF-LG AS with
low LVEF is to distinguish true severe from
Pseudo severe AS.
 In the former, the primary culprit is deemed to
be the valve disease, and the LV dysfunction is
a secondary or concomitant phenomenon.
LOW FLOW LOW GRADIENT AS
The predominant factor in pseudosevere AS is
deemed to be myocardial disease, and AS
severity is overestimated due to incomplete
opening of the valve in relation to the LF state.
Distinction between these two entities is essential
because patients with true severe AS generally
benefit from AVR, whereas those with pseudo
severe AS may not benefit.
LOW FLOW LOW GRADIENT AS
PATHOPHYSIOLOGY
 Low Flow secondary to Low EF
 Low EF is due to myocardial dysfunction
“whether this myocardial dysfunction is
-secondary to AS
-secondary to other causes, or
-primary myocardial disease, needs to be
evaluated”
LV dysfunction in patients with AS is referred to as primary if
decreased function is caused primarily by factors other than a
stenotic aortic valve.

secondary if decreased function results directly from the
valvular lesion.
LOW FLOW LOW GRADIENT AS
-DCMP(1O Myocardial Dysfunction)
-Ischemic Heart Disease
-HTN Heart Disease (After load mismatch)
In these patients, AVA was misjudged as <1.0
due to incomplete opening of AV due to low EF
and  labelled as “PSEUDO SEVERE AS”
LOW FLOW LOW GRADIENT AS
“ True severe AS”
Removal of the only afterload-AS can lead to
dramatic improvements in patients’
symtoms/survival compared to medical
therapy alone
LOW FLOW LOW GRADIENT AS
DIAGNOSIS
First suspicion Gradient-AVA Mismatch during
routine echo
Gradient < 40 mmhg, AVA <1.0, EF <40 %
• Dobutamine stress echo
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS
 The term “flow reserve” is utilized rather than “contractile
reserve” because several mechanisms not necessarily
related to intrinsic contractility may contribute to the lack of
stroke volume increase during DSE.
1) afterload mismatch due to an imbalance between the
severity of the stenosis and myocardial reserve
2) inadequate increase of myocardial blood flow due to
associated CAD; and/or
3) irreversible myocardial damage due to previous
myocardial infarction or extensive myocardial fibrosis.
LOW FLOW LOW GRADIENT AS
DSE
 De Filippi et al. were the first to demonstrate that low-dose (up
to 20 µg/kg/min) DSE) may be used in these patients to assess
the presence of LV flow reserve and to distinguish true versus
pseudo severe stenosis.
 The use of DSE for this purpose has received a Class IIa (Level of
Evidence: B) recommendation in the (ACC/AHA-ESC/EACTS)
guidelines
DeFilippi CR, Willett DL, Brickner E, et al. Usefulness of dobutamine
echocardiography in distinguishing severe from nonsevere valvular
aortic stenosis in patients with depressed left ventricular function and
low transvalvular gradients. Am J Cardiol 1995;75:191–4.
LOW FLOW LOW GRADIENT AS
Provides information on the changes in aortic
velocity, mean gradient, and valve area as flow rate
increases.
Measure of the contractile response to dobutamine
Helpful to differentiate two clinical situations
Severe AS with LV systolic dysfunction
Moderate AS with another cause of LV dysfunction
LOW FLOW LOW GRADIENT AS
Low dose protocol up to 20 µg/kg/mt
We look for three things:
-Flow reserve
-Change in EOA
-Change in Gradient and velocity
LOW FLOW LOW GRADIENT AS
 The Dobutamine infusion protocol consisted of 8-min
increments of 2.5 to 5 µg/kg/min, starting at 2.5
µg/kg/min up to a maximum dosage of 20 µg/kg/min.
 At high doses there is likelihood of dobutamine-
induced LVOT obstruction and drop in BP and
arrhythmias during the test.
 The infusion should be stopped as soon as
Positive result is obtained
Heart rate begins to rise more than 10–20 bpm over
baseline or exceeds 100bpm
LOW FLOW LOW GRADIENT AS
Monin JL, Monchi M, Gest V, Duval-Moulin AM Dubois-Rande JL, Gueret P. Aortic stenosis with severe left
ventricular dysfunction and low transvalvular pressure gradients: risk stratification by low-dose dobutamine
echocardiography. J Am Coll Cardiol. 2001;37:2101–2107LOW FLOW LOW GRADIENT AS
Role in decision-making in adults with AS is
controversial and the findings recommend as
reliable are
Stress findings of true severe stenosis
AVA<1cm²
Jet velocity>4m/s
Mean gradient>40mm of Hg
Nishimura RA et al. Circulation 2002;106:809-13.
Lack of contractile reserve-
Failure of LVEF to ↑ by 20% is a poor prognostic sign
Monin JL et al. Circulation 2003;108:319-24..
LOW FLOW LOW GRADIENT AS
 Several parameters and criteria have been proposed in
the literature to identify patients with pseudosevere AS
during DSE,
• Including a peak stress mean gradient ≤30 or ≤40
mm Hg depending on studies, a peak stress EOA >1.0
or 1.2 cm2, and/or an absolute increase in EOA >0.3
cm2 thus, the optimal cutoff values remain to be
determined.
• The prevalence of pseudosevere AS is reported to be
between 20% and 30%
LOW FLOW LOW GRADIENT AS
 In patients with fixed AS, dobutamine induced an
increase in peak velocity, mean TVPG, and valve
resistance and no change in valve area.
 Therefore, DSE clearly can help to differentiate patients
with fixed LG AS (who will benefit from AVR) from
those with pseudo-AS (in whom AVR is not indicated).
Monin J, Quéré J, NMonchi M, et al. Low-gradient aortic stenosis operative
risk stratification and predictors for long-term outcome: a multicenter
study using dobutamine stress hemodynamics. Circulation. 2003;108:319–
324.
LOW FLOW LOW GRADIENT AS
Subjects with LG AS who manifest an increase
in peak velocity (>0.6 m/s), SV (>20%), or
mean TVPG (>10 mm Hg) with DSE have LV
flow reserve and would benefit from AVR.
In contrast, the absence of these changes with
DSE identifies patients without LV flow reserve
whose operative risk might be high.
LOW FLOW LOW GRADIENT AS
Patients with no LV flow reserve are defined by a
percent increase in SV <20% during DSE or
catheterization , and have higher operative
mortality (22% to 33%) than those with flow
reserve (5% to 8%).
 They have a higher prevalence of multivessel CAD
The absence of LV contractile reserve should not
preclude consideration of AVR surgery in
symptomatic subjects with severe AS and a TVPG.
 Even for these individuals, valve replacement
surgery is the treatment of choice.
LOW FLOW LOW GRADIENT AS
Some patients shows an ambiguous response
to DSE (e.g., a peak gradient of 29 mm Hg and
an EOA of 0.8 cm2) due to variable increases in
flow , and interpreting the changes in EOA and
gradients without considering the relative
changes in flow may often be problematic.
LOW FLOW LOW GRADIENT AS
The differentiation between true and pseudo-
AS may be improved by using other
noninvasive parameters, such as the projected
valve area at a normal flow rate
An echo method that attempts to control for
the variable augmentation of transaortic flow
induced by dobutamine.
LOW FLOW LOW GRADIENT AS
Projected EOA
 The investigators of the TOPAS(Truly or Pseudo-Severe
AS) study proposed new parameter that is the
Projected EOA that would have occurred at a
standardized flow rate of 250 ml/s (EOA proj).
 This new parameter has been shown to be more
closely related to actual AS severity, impairment of
myocardial blood flow, LV flow reserve, and survival
than the traditional DSE parameters.
 The full potential of the EOAProj remains to be
determined by future studies
LOW FLOW LOW GRADIENT AS
Patients with no increase in SV may nonetheless
have an increase in mean flow rate sufficient to
allow a reliable measurement of EOA Proj; this is
due to shortening of LV ejection time in relation to
an increase in heart rate
 However, there are 10% to 20% of patients in
whom the increase in flow rate is insufficient to
allow calculation of EOA Proj
LOW FLOW LOW GRADIENT AS
Projected EOA
TOPAS (True or Pseudo Severe AS) STUDY
LOW FLOW LOW GRADIENT AS
CT AV Calcium Scoring
Cueff et al. suggested that a score >1,650 Agatston units
provides good accuracy (93 % sensitive, 75 % specific) to
distinguish true severe from pseudosevere AS
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS
Treatment
Symptomatic status
Valvular severity
“Any symptomatic severe AS, Irrespective of
EF and Flow reserve , has to be Intervened
(class I)”
WITHOUT AVR, 1 YR. MORTALITY IS 30-50% (Turina et al EhJ 1987)LOW FLOW LOW GRADIENT AS
Severe ‘Asymptomatic’ AS WITH LOW EF
Recommendation:
AVR for patients who have no symptoms and
whose left ventricular EF is less than 50% (class I C)
LOW FLOW LOW GRADIENT AS
The ACC/AHA guidelines (2014 )& ESC/ EACTS
guidelines support the utilization of AVR
(Class IIa; Level of Evidence: C) in the subset of
patients with LV flow reserve
LOW FLOW LOW GRADIENT AS
• In the ESC/EACTS guidelines AVR received a
Class IIb (Level of Evidence: B) recommendation
for patients with low LVEF, LF-LG AS, and no LV
flow reserve.
LOW FLOW LOW GRADIENT AS
• EURO SCORE, STS SCORE
• PERIOP RISK- FLOW RESERVE (+)=5-8%,FLOW RESERVE (-)=30%*LOW FLOW LOW GRADIENT AS
Concerns after AVR
Patient-Prosthesis Mismatch
Low EF patients are known to be more
vulnerable than patients with normal LVEF to
the excess in LV load
Can cause acute decompensation of LV or
inadequate improvement of LV functions after
AVR
LOW FLOW LOW GRADIENT AS
Role of TAVI
Operative risk for SAVR is generally very high in
absence of flow reserve
TAVI - valuable alternative in these patients
Recent studies reported a greater and more
rapid improvement of LVEF in patients treated
by TAVR than those treated by surgical AVR *
Rationale related to a lesser incidence of
patient–prosthesis mismatch.
LOW FLOW LOW GRADIENT AS
In contrast, TAVR associated with a higher
incidence of paravalvular regurgitation, stroke,
vascular complications which may eventually
have a negative impact on outcomes
*Clavel et al. Circulation 2010;122:1928 –36
Further randomized studies comparing surgery versus
TAVR in LF-LG AS patients are warranted.
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS
• Normal flow reserve:
Medical followup every 6 months vs AVR (ESC class IIa)–based on the clinician’s
judgement
• Low flow reserve:
1.IHD-OMT ± revascularisation
2.HTN- to be treated
3.Optimal heart failure management strategy
4.AVR (ESC class IIb) LOW FLOW LOW GRADIENT AS
Prognosis
 Concomitant CAD
 Low EF severe AS compared to Normal EF severe AS have
higher peri op mortality rates (6-33%), depending on
presence of myocardial contractile reserve (5-8%) or not (22-
33%)
 But irrespective of degree of myocardial dysfunction or
contractile reserve, the patients benefit more from AVR than
medical treatment only
“Severe LV dysfunction is not a CI for AVR, albeit the high
risk of surgery in these patients”
LOW FLOW LOW GRADIENT AS
Group I= Flow reserve +
Group II= Flow reserve -
LOW FLOW LOW GRADIENT AS
Prognstic factors
 Reduced functional capacity as assessed by Duke
Activity Score Index (<20) or by 6-MWT (<320 m),
 Presence of CAD
 More severe stenosis as assessed by EOA Proj< 1.2 cm2,
 Reduced peak stress LVEF (<35%)
 A high plasma BNP level (>550 pg/ml) would also
appear to be a powerful predictor of mortality in
patients with LF-LG AS regardless of treatment (medical
vs. surgical) or the presence and/or absence of flow
reserve
LOW FLOW LOW GRADIENT AS
Predictors of late mortality
Preop. Contractile reserve
EuroSCORE, STS score,
Atrial fibrillation,
Multivessel CAD,
Low pre-operative gradient,
High plasma levels of BNP, and
Patient–prosthesis mismatch
Myocardial viabilty
Myocardial fibrosis
LOW FLOW LOW GRADIENT AS
Low-Flow, Low-Gradient AS With Normal LVEF
LOW FLOW LOW GRADIENT AS
Low-Flow, Low-Gradient AS With
Normal LVEF
 Normally patients with severe AS and preserved LVEF should
necessarily have a high transvalvular gradient.
 However a substantial proportion of patients with severe AS on
the basis of EOA ≤ 1.0 cm2 and/or indexed EOA ≤0.6 cm2/m2
might develop a restrictive physiology, resulting in low cardiac
output (i.e., stroke volume index <35 ml/m2) and lower than
expected TVG (i.e., <40 mm Hg) despite the presence of a
preserved LVEF (i.e., >50%); this clinical entity was labeled
“paradoxical” LF-LG AS
Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low flow,
low gradient severe aortic stenosis despite preserved ejection fraction
isassociated with higher afterload and reduced survival. Circulation
2007;115:2856–64
LOW FLOW LOW GRADIENT AS
First reported in 2007 by Hacicha et al. in 512
pts. (Circulation)
Echo Parameters:
-Mean gradient < 40 mmhg,
-AVA < 1.0 cm2,
-Flow <35 ml/mt2,
-EF≥50 %
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS
MG is directly proportional to the square of transvalvular flow, even small reductions
in SV can result in significant reductions in the pressure gradient.
SV reductions can occur even in the presence of apparently normal LVEF
LOW FLOW LOW GRADIENT AS
Pathophysiology of Paradoxical LF LG AS
It shares many pathophysiological and clinical
similarities with normal LVEF heart failure
The prevalence of these entities increases with
older age, female gender, and concomitant
presence of systemic HTN.
Both entities are also characterized by a restrictive
physiology, whereby LV pump function and thus
SV are markedly reduced despite a preserved LVEF.
LOW FLOW LOW GRADIENT AS
 Reduced systemic arterial compliance (SAC) is a
frequent occurrence in elderly patients with AS in
which SAC independently contributes to increased
after load and decreased LV function.
 In particular, patients with a markedly increased
afterload as a result of the combination of severe AS
and reduced SAC were observed to have decreased
CO, which resulted in lower TVG and pseudo
normalization of peripheral BP.
LOW FLOW LOW GRADIENT AS
 The distinctive features of this entity are: more pronounced
LV concentric remodeling and myocardial fibrosis both
contributing to reduce the size, compliance, and filling of the
LV.
 Marked reduction in intrinsic LV systolic function, not
evidenced by the LVEF, but rather by other more sensitive
parameters directly measuring LV mid-wall or longitudinal
axis shortening.
 Longitudinal shortening is reduced to a larger extent in these
patients due to more advanced fibrosis in the subendocardial
layers.
 Reduced LV longitudinal shortening was measured using
either systolic mitral ring displacement or tissue Doppler
imaging
LOW FLOW LOW GRADIENT AS
Several studies reported that these patients have
a worse prognosis than those with
moderate AS or normal flow severe AS
Mode of presentation of this entity often
complicates the assessment of AS severity and
therapeutic decision making
LOW FLOW LOW GRADIENT AS
 The decrease in SV is primarily due to deficient
ventricular filling in relation with the smaller cavity size
rather than deficient ventricular emptying.
 A normal LVEF should not be construed as being
equivalent to normal LV flow output.
LOW FLOW LOW GRADIENT AS
“Normal LVEF Does Not Mean
Normal Myocardial Function”
LVEF is a late and insensitive marker for study of LV
functions
Not too far that LVEF will be replaced by other better
markers of LV function
LOW FLOW LOW GRADIENT AS
Myocardial fibrosis
Restrictive physiology
Small LV cavity
Resembles heart failure
with preserved EF
Pseudo-normalization
of blood pressure
Impaired LV function
yet normal EF
(around 50-60%)
LOW FLOW LOW GRADIENT AS
 Distinguishing features of PLF when compared with NF
patients are:
(i) a higher level of global LV haemodynamic load
reflected by higher valvulo-arterial impedance (Zva)
(ii) smaller and relatively thicker ventricles;
(iii) lower values for LV mid-wall radius shortening
consistent with more pronounced intrinsic myocardial
dysfunction
(iv) a tendency to have a lower LVEF although remaining
within the normal range.
LOW FLOW LOW GRADIENT AS
Overall, these findings are consistent with a
greater and probably more long standing increase
in LV haemo dynamic load resulting in more
pronounced concentric LV remodeling.
These patients also have a significantly poorer
prognosis than patients with NF; as well, their
prognosis is also much poorer if treated medically
rather than surgically
LOW FLOW LOW GRADIENT AS
Valvulo-Arterial impedance (Zva
 The LV in degenerative AS is often facing a double load,
i.e. valvular plus vascular.
 Zva parameter represents the cost in mmHg for each
ml of blood indexed for BSA pumped by the LV.
 Z va can easily be estimated during Doppler echo by
adding the mean aortic gradient to the pepipheral
systolic pressure measured by sphygmomanometry
and dividing the result by SVi and it has been shown to
be superior to the standard indices of AS severity in
predicting LV dysfunction and patient outcome
LOW FLOW LOW GRADIENT AS
Global LV afterload
As a measure of global LV afterload valvulo
arterial impedence is measured by the formula
Zva= SBP+MAVG
SVI
Zva represents the valvular and arterial factors
that oppose the ventricular ejection.
LOW FLOW LOW GRADIENT AS
The global hemodynamic load imposed on the LV results from the summation of the valvular
load and the arterial load. This global load can be estimated by calculating the valvulo arterial
impedance. In patients with medium or large size ascending aorta, the impedance can be
calculated with the standard Doppler mean gradient in place of the net mean gradient.
LOW FLOW LOW GRADIENT AS
A measurement of “afterload”
Just quantifies the total load, that helps in
prognostication
Values > 3.5 Zva (mmHg·mL-1·m2) call for
reduction in load- (both valvular and vascular)
Does not differentiate between the type of
load –valvular vs vascular
Does not differentiate moderate vs severe AS
LOW FLOW LOW GRADIENT AS
Several studies reported that the level of
global LV hemodynamic load, (Zva), is
consistently much higher than that observed
in patients with normal flow severe AS
LOW FLOW LOW GRADIENT AS
Paradoxical LF LG AS
Over all survival is impaired compared to NF
Hachicha et al. Circulation. 2007;115:2856 -64
LOW FLOW LOW GRADIENT AS
 Markedly lower survival if medically treated, as compared
with those who underwent AVR
Hachicha et al. Circulation. 2007;115:2856 -64
LOW FLOW LOW GRADIENT AS
J Am Coll Cardiol Img. 2013;6(2):175-183
LOW FLOW LOW GRADIENT AS
AVAproj = AVApeak – AVArest x (250 -Qrest )+ AVArest
Qpeak – Qrest
Q= mean transvalvular flow rate
Q= stroke volume
LV ejection time,
LOW FLOW LOW GRADIENT AS
Diagnosis Paradoxical LFLG AS
• Step 1 ----Is the patient symptomatic
NO --- exercise test --conservative management
YES  Step 2 is the patient HTN
YES ---optimise Anti HTN Rx and reasses
NO or controlled HTN  Step 3 Is stenosis
severe or pseudo severe DSE MDCT AVC
(>1200 AU Female >2000AU Male)AVR
LOW FLOW LOW GRADIENT AS
Differential diagnosis
Patients with paradoxical LF-LG AS should always
be distinguished from patients with True severe AS
based on EOA <1.0 cm2 and LG (i.e.<40 mm Hg)
but normal flow (i.e., stroke volume index >35
ml/m2)
The features of restrictive physiology or of a
marked increase in Zva are conspicuously absent
LOW FLOW LOW GRADIENT AS
 The discordance between EOA and gradient may be
explained by one or more of the following.
1) measurement errors: that is, underestimation of
stroke volume and AVA and/or underestimation of
gradient
2) small body size: AS severity may be overestimated in
a patient with a small body surface area if EOA is not
indexed for body surface area
3) inherent inconsistencies in the guidelines criteria
LOW FLOW LOW GRADIENT AS
Therapeutic management and outcome
 A class IIa recommendation for AVR in the patients with
paradoxical LF-LG and evidence of severe AS is however
included in the recent ACC/AHA& ESC/EACTS guidelines.
 Theoretically these patients were at higher operative risk
given their myocardial impairment and their increased risk
of having patient–prosthesis mismatch due to their small LV
cavity.
LOW FLOW LOW GRADIENT AS
 2014 ACCC guidelines class IIa C
indication for AVR
 “This subgroup of patients
seems to be at a more advanced
stage and has a poorer prognosis
if treated medically rather than
surgically”
 It remains to be determined if
TAVI could not be a better
alternative in these patients
Tarantini G, Covolo E, Razzolini R, et al.
The Annals of Thoracic Surgery, Volume 91(6)
LOW FLOW, NORMAL EF, SEVERE AS
LOW FLOW LOW GRADIENT AS
The advantage of surgery is still present when
other variables such as CAD are taken into
account by performing propensity score–
matched analysis.
 It remains to be determined if TAVR could not
be a better alternative in these patients.
LOW FLOW LOW GRADIENT AS
Prognosis of paradoxical LF LG AS
Worse than moderate AS (albeit contradictory reports)
Worse than severe AS with high gradient group
lower overall 3-year survival (76% versus 86%)
(P<0.006 in 512 patients By Hacicha et al.)
Two-fold increase in mortality and an almost
50% lower referral rate for AVR in the low-
gradient AS compared to the high gradient
group (Barasch et al)
LOW FLOW LOW GRADIENT AS
Normal-Flow, Low-Gradient AS.
Patients with preserved LVEF, normal flow, LG
but small EOA (often between 0.8 and 1.0
cm2) are generally patients with moderate-to-
severe AS who have an EOA– gradient
discordance due to an inherent inconsistency
in the guidelines criteria and/or to a small
body size.
LOW FLOW LOW GRADIENT AS
 However, these patients were an heterogeneous group,
likely comprising without distinction patients with
paradoxical LF AS and patients with normal-flow, LG AS in
conjunction with measurement error, small body size,
and/or inconsistencies due to the guidelines criteria.
 Among patients with EOA <1.0 cm2, the Paradoxical LF LG
AS were found to have the worse prognosis and the Normal
flow LG AS the best prognosis.
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS
Typical Characteristics of the 3 Main
Entities of Severe AS
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS
CONCLUSIONS
LF-LG AS with either normal or reduced LVEF is
among the most challenging of situations
encountered in patients with VHD.
DSE greatly aids risk stratification and clinical
decision making in patients with low
LVEF, LF-LG AS.
LOW FLOW LOW GRADIENT AS
Paradoxical LF-LG AS despite normal LVEF is a
recently described entity that has been shown to
be associated with a more advanced stage of the
disease and worse prognosis.
TAVR may eventually prove to be an attractive
alternative to surgical AVR in both types of LF-LG
severe AS, but this remains to be confirmed by
future randomized studies.
LOW FLOW LOW GRADIENT AS
Low flow/ Low gradient AS with preserved
LVEF is due to intrinsic myocardial dysfunction
as evidenced by Speckle Tracking imaging
 Valve calcification and serum BNP may be
helpful for clinical decision making
LOW FLOW LOW GRADIENT AS
LOW FLOW LOW GRADIENT AS

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Low flow low gradient aortic stenosis

  • 1. LOW FLOW LOW GRADIENT AORTIC STENOSIS 25-2-2016
  • 2. OUTLINE  Introduction  Low flow Low gradient AS with Low EF  Low flow Low gradient AS with Normal EF  Normal-Flow, Low-Gradient AS.  Treatment  Conclusions LOW FLOW LOW GRADIENT AS
  • 3. Introduction Aortic stenosis is one of the common valve disorders encountered in clinical practice and one of the most frequent indications for valve surgery. Prevalence is 2-7% over the age of 65 years Evaluation of AS is challenging of all VHD LOW FLOW LOW GRADIENT AS
  • 4.  Long asymptomatic phase: risk of sudden death low  Mortality ↑: exertional chest pain, syncope, breathlessness  Mortality up to 12% soon after onset of symptoms  Significant AS and LV dysfunction: poor prognoses  Importantly as many as 30% of patients who have a calculated AVA in the severe range have other parameters suggesting mild or moderate disease (ie, mean gradient <30 mm Hg) LOW FLOW LOW GRADIENT AS
  • 5. Valvular AS has three principal causes: a congenital BAV with superimposed calcification, calcification of a normal trileaflet valve, and Rheumatic disease LOW FLOW LOW GRADIENT AS
  • 6. Major types of aortic valve stenosis. A, Normal aortic valve. B, Congenital bicuspid AS. A false raphe is present at 6 o’clock. C, Rheumatic AS. The commissures are fused with a fixed central orifice. D, Calcific degenerative AS. LOW FLOW LOW GRADIENT AS
  • 7. STAGES OF VALVULAR AS LOW FLOW LOW GRADIENT AS
  • 8. Nishimura RA, Otto CM, Bonow RO, et al: 2014 AHA/ACCF guideline for the management of patients with valvular heart disease: A report of the American College ofCardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 63:e57, 2014. LOW FLOW LOW GRADIENT AS
  • 9.  As the severity of AS increses there will be corresponding increase in the TVPG (ΔP) and myocardial pressure overload Though the preload reserve, the LV compensates for the increased workload until the sarcomeres stretch to their maximum diastolic length. Once the preload reserve is exhausted, increases in afterload are accompanied by a reduction in stroke volume (SV), resulting in afterload mismatch LOW FLOW LOW GRADIENT AS
  • 10. Various Hemodynamic Metrics Used for Assessment of AS and Their Cutoff Values for Severe AS LOW FLOW LOW GRADIENT AS
  • 11. Percentage of patients diagnosed with severe AS based on various echocardiographic criteria Minners et al Eur.HEART .journal 2008:29;1043-8 Inconsistencies of echocardiographic criteria for grading of AS LOW FLOW LOW GRADIENT AS
  • 12. Moderate stenosis for a normal ventricle may correspond to a severe stenosis for a diseased ventricle in terms of hemodynamic load LOW FLOW LOW GRADIENT AS
  • 13. Effect of concurrent conditions …… Left ventricular systolic dysfunction Left ventricular hypertrophy Small ventricular cavity & small LV ejects a small SV so that, even in severe AS the AS velocity and mean gradient may be lower than expected.  Continuity-equation valve area is accurate in this situation LOW FLOW LOW GRADIENT AS
  • 14. Hypertension 35–45% of patients primarily affect flow and gradients but less AVA measurements Control of blood pressure is recommended The echocardiographic report should always include a blood pressure measurement Effect of concurrent conditions contd… LOW FLOW LOW GRADIENT AS
  • 15. Aortic regurgitation  About 80% of adults with AS also have aortic regurgitation High transaortic volume flow rate, maximum velocity, and mean gradient will be higher than expected for a given valve area Effect of concurrent conditions contd… LOW FLOW LOW GRADIENT AS
  • 16. High cardiac output Relatively high gradients in the presence of mild or moderate AS The shape of the CWD spectrum with a very early peak may help to quantify the severity correctly Ascending aorta Aortic root dilation Coarctation of aorta LOW FLOW LOW GRADIENT AS
  • 17. The transaortic gradient depends upon the severity of the stenosis and upon flow rate, which is determined by the stroke volume and systolic ejection period GRADIENT = Flow Dependent Variable Gradient calculation- Small reduction in flow can cause great reductions in gradient LOW FLOW LOW GRADIENT AS
  • 18. AVA calculation is a standard and must be incorporated into a comprehensive evaluation of AS severity AVA= Flow independent variable LOW FLOW LOW GRADIENT AS
  • 19.  The gradients across a stenosd valve are a squared function of flow, even a modest decrease in flow may lead to an important reduction in gradient, even if the stenosis is very severe. Symptomatic patients with severe AS generally have a substantial improvement in symptoms and increased survival after AVR.  Precise assessment of both the severity of valve stenosis and the degree of myocardial impairment is thus crucial for good therapeutic management. LOW FLOW LOW GRADIENT AS
  • 20. LOW FLOW LOW GRADIENT AS
  • 21. Prevalence of low flow state Low EF 5- 10 % of all patients of AVA < 1.0 Preserved EF 10-25 % of all patients of AVA < 1.0 Pibarot P, Dumesnil J. Low-Flow, Low-Gradient Aortic Stenosis With Normal and Depressed Left Ventricular Ejection Fraction. J Am Coll Cardiol 2012;60:1845–53 LOW FLOW LOW GRADIENT AS
  • 22. Till 2007 low flow due to Low EF Now Low flow can also be with Preserved EF “new entity” Paradoxical Low flow AS Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low flow, low gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation 2007;115:2856–64 Pibarot P, Dumesnil J. Low-Flow, Low-Gradient Aortic Stenosis With Normal and Depressed Left Ventricular Ejection Fraction. J Am Coll Cardiol 2012;60:1845–53 LOW FLOW LOW GRADIENT AS
  • 23. TYPES OF LOW FLOW AS LOW FLOW LOW GRADIENT AS
  • 24. Classical Low Flow Low Gradient AS with Low EF LOW FLOW LOW GRADIENT AS
  • 25. Prevalence of LF –LG –AS with Low EF  A LF-LG severe AS with Low LVEF may be observed in approximately 5% to 10% of patients with severe AS.  Such patients are classically characterized by a dilated LV with markedly decreased LV systolic function, most often due to IHD and/or to after load mismatch  Prognosis is usually poor (survival rates 50% at 3-year follow-up) if treated medically, but operative risk is high (6% to 33%) if treated surgically LOW FLOW LOW GRADIENT AS
  • 26. LF LG AS with Low EF Low LVEF, LF-LG severe AS is generally characterized by the combination of an EOA≤1.0 cm2 or ≤0.6 cm2/m2 when indexed for BSA, a low mean transvalvular gradient (i.e.,<40 mm Hg) and a low LVEF (≤40%), causing an LF state. LOW FLOW LOW GRADIENT AS
  • 27. Several criteria have been proposed in the literature to define the LF state in AS, including a cardiac index <3.0 l/min/m2 and a stroke volume index < 35 ml/m2 Given that the gradient essentially depends on the flow per beat (i.e., the stroke volume) rather than on the flow per minute (i.e., the cardiac output), the former is the most frequently used parameter in this context LOW FLOW LOW GRADIENT AS
  • 28. Patients with critical AS, severe LV dysfunction, and low cardiac output (low TVG) often create diagnostic dilemmas for the clinician because their clinical presentation and hemodynamic data may be indistinguishable from those of patients with a DCMP and a calcified valve that is not severely stenotic. LOW FLOW LOW GRADIENT AS
  • 29. The main diagnostic challenge in LF-LG AS with low LVEF is to distinguish true severe from Pseudo severe AS.  In the former, the primary culprit is deemed to be the valve disease, and the LV dysfunction is a secondary or concomitant phenomenon. LOW FLOW LOW GRADIENT AS
  • 30. The predominant factor in pseudosevere AS is deemed to be myocardial disease, and AS severity is overestimated due to incomplete opening of the valve in relation to the LF state. Distinction between these two entities is essential because patients with true severe AS generally benefit from AVR, whereas those with pseudo severe AS may not benefit. LOW FLOW LOW GRADIENT AS
  • 31. PATHOPHYSIOLOGY  Low Flow secondary to Low EF  Low EF is due to myocardial dysfunction “whether this myocardial dysfunction is -secondary to AS -secondary to other causes, or -primary myocardial disease, needs to be evaluated” LV dysfunction in patients with AS is referred to as primary if decreased function is caused primarily by factors other than a stenotic aortic valve.  secondary if decreased function results directly from the valvular lesion. LOW FLOW LOW GRADIENT AS
  • 32. -DCMP(1O Myocardial Dysfunction) -Ischemic Heart Disease -HTN Heart Disease (After load mismatch) In these patients, AVA was misjudged as <1.0 due to incomplete opening of AV due to low EF and  labelled as “PSEUDO SEVERE AS” LOW FLOW LOW GRADIENT AS
  • 33. “ True severe AS” Removal of the only afterload-AS can lead to dramatic improvements in patients’ symtoms/survival compared to medical therapy alone LOW FLOW LOW GRADIENT AS
  • 34. DIAGNOSIS First suspicion Gradient-AVA Mismatch during routine echo Gradient < 40 mmhg, AVA <1.0, EF <40 % • Dobutamine stress echo LOW FLOW LOW GRADIENT AS
  • 35. LOW FLOW LOW GRADIENT AS
  • 36.  The term “flow reserve” is utilized rather than “contractile reserve” because several mechanisms not necessarily related to intrinsic contractility may contribute to the lack of stroke volume increase during DSE. 1) afterload mismatch due to an imbalance between the severity of the stenosis and myocardial reserve 2) inadequate increase of myocardial blood flow due to associated CAD; and/or 3) irreversible myocardial damage due to previous myocardial infarction or extensive myocardial fibrosis. LOW FLOW LOW GRADIENT AS
  • 37. DSE  De Filippi et al. were the first to demonstrate that low-dose (up to 20 µg/kg/min) DSE) may be used in these patients to assess the presence of LV flow reserve and to distinguish true versus pseudo severe stenosis.  The use of DSE for this purpose has received a Class IIa (Level of Evidence: B) recommendation in the (ACC/AHA-ESC/EACTS) guidelines DeFilippi CR, Willett DL, Brickner E, et al. Usefulness of dobutamine echocardiography in distinguishing severe from nonsevere valvular aortic stenosis in patients with depressed left ventricular function and low transvalvular gradients. Am J Cardiol 1995;75:191–4. LOW FLOW LOW GRADIENT AS
  • 38. Provides information on the changes in aortic velocity, mean gradient, and valve area as flow rate increases. Measure of the contractile response to dobutamine Helpful to differentiate two clinical situations Severe AS with LV systolic dysfunction Moderate AS with another cause of LV dysfunction LOW FLOW LOW GRADIENT AS
  • 39. Low dose protocol up to 20 µg/kg/mt We look for three things: -Flow reserve -Change in EOA -Change in Gradient and velocity LOW FLOW LOW GRADIENT AS
  • 40.  The Dobutamine infusion protocol consisted of 8-min increments of 2.5 to 5 µg/kg/min, starting at 2.5 µg/kg/min up to a maximum dosage of 20 µg/kg/min.  At high doses there is likelihood of dobutamine- induced LVOT obstruction and drop in BP and arrhythmias during the test.  The infusion should be stopped as soon as Positive result is obtained Heart rate begins to rise more than 10–20 bpm over baseline or exceeds 100bpm LOW FLOW LOW GRADIENT AS
  • 41. Monin JL, Monchi M, Gest V, Duval-Moulin AM Dubois-Rande JL, Gueret P. Aortic stenosis with severe left ventricular dysfunction and low transvalvular pressure gradients: risk stratification by low-dose dobutamine echocardiography. J Am Coll Cardiol. 2001;37:2101–2107LOW FLOW LOW GRADIENT AS
  • 42. Role in decision-making in adults with AS is controversial and the findings recommend as reliable are Stress findings of true severe stenosis AVA<1cm² Jet velocity>4m/s Mean gradient>40mm of Hg Nishimura RA et al. Circulation 2002;106:809-13. Lack of contractile reserve- Failure of LVEF to ↑ by 20% is a poor prognostic sign Monin JL et al. Circulation 2003;108:319-24.. LOW FLOW LOW GRADIENT AS
  • 43.  Several parameters and criteria have been proposed in the literature to identify patients with pseudosevere AS during DSE, • Including a peak stress mean gradient ≤30 or ≤40 mm Hg depending on studies, a peak stress EOA >1.0 or 1.2 cm2, and/or an absolute increase in EOA >0.3 cm2 thus, the optimal cutoff values remain to be determined. • The prevalence of pseudosevere AS is reported to be between 20% and 30% LOW FLOW LOW GRADIENT AS
  • 44.  In patients with fixed AS, dobutamine induced an increase in peak velocity, mean TVPG, and valve resistance and no change in valve area.  Therefore, DSE clearly can help to differentiate patients with fixed LG AS (who will benefit from AVR) from those with pseudo-AS (in whom AVR is not indicated). Monin J, Quéré J, NMonchi M, et al. Low-gradient aortic stenosis operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics. Circulation. 2003;108:319– 324. LOW FLOW LOW GRADIENT AS
  • 45. Subjects with LG AS who manifest an increase in peak velocity (>0.6 m/s), SV (>20%), or mean TVPG (>10 mm Hg) with DSE have LV flow reserve and would benefit from AVR. In contrast, the absence of these changes with DSE identifies patients without LV flow reserve whose operative risk might be high. LOW FLOW LOW GRADIENT AS
  • 46. Patients with no LV flow reserve are defined by a percent increase in SV <20% during DSE or catheterization , and have higher operative mortality (22% to 33%) than those with flow reserve (5% to 8%).  They have a higher prevalence of multivessel CAD The absence of LV contractile reserve should not preclude consideration of AVR surgery in symptomatic subjects with severe AS and a TVPG.  Even for these individuals, valve replacement surgery is the treatment of choice. LOW FLOW LOW GRADIENT AS
  • 47. Some patients shows an ambiguous response to DSE (e.g., a peak gradient of 29 mm Hg and an EOA of 0.8 cm2) due to variable increases in flow , and interpreting the changes in EOA and gradients without considering the relative changes in flow may often be problematic. LOW FLOW LOW GRADIENT AS
  • 48. The differentiation between true and pseudo- AS may be improved by using other noninvasive parameters, such as the projected valve area at a normal flow rate An echo method that attempts to control for the variable augmentation of transaortic flow induced by dobutamine. LOW FLOW LOW GRADIENT AS
  • 49. Projected EOA  The investigators of the TOPAS(Truly or Pseudo-Severe AS) study proposed new parameter that is the Projected EOA that would have occurred at a standardized flow rate of 250 ml/s (EOA proj).  This new parameter has been shown to be more closely related to actual AS severity, impairment of myocardial blood flow, LV flow reserve, and survival than the traditional DSE parameters.  The full potential of the EOAProj remains to be determined by future studies LOW FLOW LOW GRADIENT AS
  • 50. Patients with no increase in SV may nonetheless have an increase in mean flow rate sufficient to allow a reliable measurement of EOA Proj; this is due to shortening of LV ejection time in relation to an increase in heart rate  However, there are 10% to 20% of patients in whom the increase in flow rate is insufficient to allow calculation of EOA Proj LOW FLOW LOW GRADIENT AS
  • 51. Projected EOA TOPAS (True or Pseudo Severe AS) STUDY LOW FLOW LOW GRADIENT AS
  • 52. CT AV Calcium Scoring Cueff et al. suggested that a score >1,650 Agatston units provides good accuracy (93 % sensitive, 75 % specific) to distinguish true severe from pseudosevere AS LOW FLOW LOW GRADIENT AS
  • 53. LOW FLOW LOW GRADIENT AS
  • 54. Treatment Symptomatic status Valvular severity “Any symptomatic severe AS, Irrespective of EF and Flow reserve , has to be Intervened (class I)” WITHOUT AVR, 1 YR. MORTALITY IS 30-50% (Turina et al EhJ 1987)LOW FLOW LOW GRADIENT AS
  • 55. Severe ‘Asymptomatic’ AS WITH LOW EF Recommendation: AVR for patients who have no symptoms and whose left ventricular EF is less than 50% (class I C) LOW FLOW LOW GRADIENT AS
  • 56. The ACC/AHA guidelines (2014 )& ESC/ EACTS guidelines support the utilization of AVR (Class IIa; Level of Evidence: C) in the subset of patients with LV flow reserve LOW FLOW LOW GRADIENT AS
  • 57. • In the ESC/EACTS guidelines AVR received a Class IIb (Level of Evidence: B) recommendation for patients with low LVEF, LF-LG AS, and no LV flow reserve. LOW FLOW LOW GRADIENT AS
  • 58. • EURO SCORE, STS SCORE • PERIOP RISK- FLOW RESERVE (+)=5-8%,FLOW RESERVE (-)=30%*LOW FLOW LOW GRADIENT AS
  • 59. Concerns after AVR Patient-Prosthesis Mismatch Low EF patients are known to be more vulnerable than patients with normal LVEF to the excess in LV load Can cause acute decompensation of LV or inadequate improvement of LV functions after AVR LOW FLOW LOW GRADIENT AS
  • 60. Role of TAVI Operative risk for SAVR is generally very high in absence of flow reserve TAVI - valuable alternative in these patients Recent studies reported a greater and more rapid improvement of LVEF in patients treated by TAVR than those treated by surgical AVR * Rationale related to a lesser incidence of patient–prosthesis mismatch. LOW FLOW LOW GRADIENT AS
  • 61. In contrast, TAVR associated with a higher incidence of paravalvular regurgitation, stroke, vascular complications which may eventually have a negative impact on outcomes *Clavel et al. Circulation 2010;122:1928 –36 Further randomized studies comparing surgery versus TAVR in LF-LG AS patients are warranted. LOW FLOW LOW GRADIENT AS
  • 62. LOW FLOW LOW GRADIENT AS
  • 63. • Normal flow reserve: Medical followup every 6 months vs AVR (ESC class IIa)–based on the clinician’s judgement • Low flow reserve: 1.IHD-OMT ± revascularisation 2.HTN- to be treated 3.Optimal heart failure management strategy 4.AVR (ESC class IIb) LOW FLOW LOW GRADIENT AS
  • 64. Prognosis  Concomitant CAD  Low EF severe AS compared to Normal EF severe AS have higher peri op mortality rates (6-33%), depending on presence of myocardial contractile reserve (5-8%) or not (22- 33%)  But irrespective of degree of myocardial dysfunction or contractile reserve, the patients benefit more from AVR than medical treatment only “Severe LV dysfunction is not a CI for AVR, albeit the high risk of surgery in these patients” LOW FLOW LOW GRADIENT AS
  • 65. Group I= Flow reserve + Group II= Flow reserve - LOW FLOW LOW GRADIENT AS
  • 66. Prognstic factors  Reduced functional capacity as assessed by Duke Activity Score Index (<20) or by 6-MWT (<320 m),  Presence of CAD  More severe stenosis as assessed by EOA Proj< 1.2 cm2,  Reduced peak stress LVEF (<35%)  A high plasma BNP level (>550 pg/ml) would also appear to be a powerful predictor of mortality in patients with LF-LG AS regardless of treatment (medical vs. surgical) or the presence and/or absence of flow reserve LOW FLOW LOW GRADIENT AS
  • 67. Predictors of late mortality Preop. Contractile reserve EuroSCORE, STS score, Atrial fibrillation, Multivessel CAD, Low pre-operative gradient, High plasma levels of BNP, and Patient–prosthesis mismatch Myocardial viabilty Myocardial fibrosis LOW FLOW LOW GRADIENT AS
  • 68. Low-Flow, Low-Gradient AS With Normal LVEF LOW FLOW LOW GRADIENT AS
  • 69. Low-Flow, Low-Gradient AS With Normal LVEF  Normally patients with severe AS and preserved LVEF should necessarily have a high transvalvular gradient.  However a substantial proportion of patients with severe AS on the basis of EOA ≤ 1.0 cm2 and/or indexed EOA ≤0.6 cm2/m2 might develop a restrictive physiology, resulting in low cardiac output (i.e., stroke volume index <35 ml/m2) and lower than expected TVG (i.e., <40 mm Hg) despite the presence of a preserved LVEF (i.e., >50%); this clinical entity was labeled “paradoxical” LF-LG AS Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low flow, low gradient severe aortic stenosis despite preserved ejection fraction isassociated with higher afterload and reduced survival. Circulation 2007;115:2856–64 LOW FLOW LOW GRADIENT AS
  • 70. First reported in 2007 by Hacicha et al. in 512 pts. (Circulation) Echo Parameters: -Mean gradient < 40 mmhg, -AVA < 1.0 cm2, -Flow <35 ml/mt2, -EF≥50 % LOW FLOW LOW GRADIENT AS
  • 71. LOW FLOW LOW GRADIENT AS
  • 72. MG is directly proportional to the square of transvalvular flow, even small reductions in SV can result in significant reductions in the pressure gradient. SV reductions can occur even in the presence of apparently normal LVEF LOW FLOW LOW GRADIENT AS
  • 73. Pathophysiology of Paradoxical LF LG AS It shares many pathophysiological and clinical similarities with normal LVEF heart failure The prevalence of these entities increases with older age, female gender, and concomitant presence of systemic HTN. Both entities are also characterized by a restrictive physiology, whereby LV pump function and thus SV are markedly reduced despite a preserved LVEF. LOW FLOW LOW GRADIENT AS
  • 74.  Reduced systemic arterial compliance (SAC) is a frequent occurrence in elderly patients with AS in which SAC independently contributes to increased after load and decreased LV function.  In particular, patients with a markedly increased afterload as a result of the combination of severe AS and reduced SAC were observed to have decreased CO, which resulted in lower TVG and pseudo normalization of peripheral BP. LOW FLOW LOW GRADIENT AS
  • 75.  The distinctive features of this entity are: more pronounced LV concentric remodeling and myocardial fibrosis both contributing to reduce the size, compliance, and filling of the LV.  Marked reduction in intrinsic LV systolic function, not evidenced by the LVEF, but rather by other more sensitive parameters directly measuring LV mid-wall or longitudinal axis shortening.  Longitudinal shortening is reduced to a larger extent in these patients due to more advanced fibrosis in the subendocardial layers.  Reduced LV longitudinal shortening was measured using either systolic mitral ring displacement or tissue Doppler imaging LOW FLOW LOW GRADIENT AS
  • 76. Several studies reported that these patients have a worse prognosis than those with moderate AS or normal flow severe AS Mode of presentation of this entity often complicates the assessment of AS severity and therapeutic decision making LOW FLOW LOW GRADIENT AS
  • 77.  The decrease in SV is primarily due to deficient ventricular filling in relation with the smaller cavity size rather than deficient ventricular emptying.  A normal LVEF should not be construed as being equivalent to normal LV flow output. LOW FLOW LOW GRADIENT AS
  • 78. “Normal LVEF Does Not Mean Normal Myocardial Function” LVEF is a late and insensitive marker for study of LV functions Not too far that LVEF will be replaced by other better markers of LV function LOW FLOW LOW GRADIENT AS
  • 79. Myocardial fibrosis Restrictive physiology Small LV cavity Resembles heart failure with preserved EF Pseudo-normalization of blood pressure Impaired LV function yet normal EF (around 50-60%) LOW FLOW LOW GRADIENT AS
  • 80.  Distinguishing features of PLF when compared with NF patients are: (i) a higher level of global LV haemodynamic load reflected by higher valvulo-arterial impedance (Zva) (ii) smaller and relatively thicker ventricles; (iii) lower values for LV mid-wall radius shortening consistent with more pronounced intrinsic myocardial dysfunction (iv) a tendency to have a lower LVEF although remaining within the normal range. LOW FLOW LOW GRADIENT AS
  • 81. Overall, these findings are consistent with a greater and probably more long standing increase in LV haemo dynamic load resulting in more pronounced concentric LV remodeling. These patients also have a significantly poorer prognosis than patients with NF; as well, their prognosis is also much poorer if treated medically rather than surgically LOW FLOW LOW GRADIENT AS
  • 82. Valvulo-Arterial impedance (Zva  The LV in degenerative AS is often facing a double load, i.e. valvular plus vascular.  Zva parameter represents the cost in mmHg for each ml of blood indexed for BSA pumped by the LV.  Z va can easily be estimated during Doppler echo by adding the mean aortic gradient to the pepipheral systolic pressure measured by sphygmomanometry and dividing the result by SVi and it has been shown to be superior to the standard indices of AS severity in predicting LV dysfunction and patient outcome LOW FLOW LOW GRADIENT AS
  • 83. Global LV afterload As a measure of global LV afterload valvulo arterial impedence is measured by the formula Zva= SBP+MAVG SVI Zva represents the valvular and arterial factors that oppose the ventricular ejection. LOW FLOW LOW GRADIENT AS
  • 84. The global hemodynamic load imposed on the LV results from the summation of the valvular load and the arterial load. This global load can be estimated by calculating the valvulo arterial impedance. In patients with medium or large size ascending aorta, the impedance can be calculated with the standard Doppler mean gradient in place of the net mean gradient. LOW FLOW LOW GRADIENT AS
  • 85. A measurement of “afterload” Just quantifies the total load, that helps in prognostication Values > 3.5 Zva (mmHg·mL-1·m2) call for reduction in load- (both valvular and vascular) Does not differentiate between the type of load –valvular vs vascular Does not differentiate moderate vs severe AS LOW FLOW LOW GRADIENT AS
  • 86. Several studies reported that the level of global LV hemodynamic load, (Zva), is consistently much higher than that observed in patients with normal flow severe AS LOW FLOW LOW GRADIENT AS
  • 87. Paradoxical LF LG AS Over all survival is impaired compared to NF Hachicha et al. Circulation. 2007;115:2856 -64 LOW FLOW LOW GRADIENT AS
  • 88.  Markedly lower survival if medically treated, as compared with those who underwent AVR Hachicha et al. Circulation. 2007;115:2856 -64 LOW FLOW LOW GRADIENT AS
  • 89. J Am Coll Cardiol Img. 2013;6(2):175-183 LOW FLOW LOW GRADIENT AS
  • 90. AVAproj = AVApeak – AVArest x (250 -Qrest )+ AVArest Qpeak – Qrest Q= mean transvalvular flow rate Q= stroke volume LV ejection time, LOW FLOW LOW GRADIENT AS
  • 91. Diagnosis Paradoxical LFLG AS • Step 1 ----Is the patient symptomatic NO --- exercise test --conservative management YES  Step 2 is the patient HTN YES ---optimise Anti HTN Rx and reasses NO or controlled HTN  Step 3 Is stenosis severe or pseudo severe DSE MDCT AVC (>1200 AU Female >2000AU Male)AVR LOW FLOW LOW GRADIENT AS
  • 92. Differential diagnosis Patients with paradoxical LF-LG AS should always be distinguished from patients with True severe AS based on EOA <1.0 cm2 and LG (i.e.<40 mm Hg) but normal flow (i.e., stroke volume index >35 ml/m2) The features of restrictive physiology or of a marked increase in Zva are conspicuously absent LOW FLOW LOW GRADIENT AS
  • 93.  The discordance between EOA and gradient may be explained by one or more of the following. 1) measurement errors: that is, underestimation of stroke volume and AVA and/or underestimation of gradient 2) small body size: AS severity may be overestimated in a patient with a small body surface area if EOA is not indexed for body surface area 3) inherent inconsistencies in the guidelines criteria LOW FLOW LOW GRADIENT AS
  • 94. Therapeutic management and outcome  A class IIa recommendation for AVR in the patients with paradoxical LF-LG and evidence of severe AS is however included in the recent ACC/AHA& ESC/EACTS guidelines.  Theoretically these patients were at higher operative risk given their myocardial impairment and their increased risk of having patient–prosthesis mismatch due to their small LV cavity. LOW FLOW LOW GRADIENT AS
  • 95.  2014 ACCC guidelines class IIa C indication for AVR  “This subgroup of patients seems to be at a more advanced stage and has a poorer prognosis if treated medically rather than surgically”  It remains to be determined if TAVI could not be a better alternative in these patients Tarantini G, Covolo E, Razzolini R, et al. The Annals of Thoracic Surgery, Volume 91(6) LOW FLOW, NORMAL EF, SEVERE AS LOW FLOW LOW GRADIENT AS
  • 96. The advantage of surgery is still present when other variables such as CAD are taken into account by performing propensity score– matched analysis.  It remains to be determined if TAVR could not be a better alternative in these patients. LOW FLOW LOW GRADIENT AS
  • 97. Prognosis of paradoxical LF LG AS Worse than moderate AS (albeit contradictory reports) Worse than severe AS with high gradient group lower overall 3-year survival (76% versus 86%) (P<0.006 in 512 patients By Hacicha et al.) Two-fold increase in mortality and an almost 50% lower referral rate for AVR in the low- gradient AS compared to the high gradient group (Barasch et al) LOW FLOW LOW GRADIENT AS
  • 98. Normal-Flow, Low-Gradient AS. Patients with preserved LVEF, normal flow, LG but small EOA (often between 0.8 and 1.0 cm2) are generally patients with moderate-to- severe AS who have an EOA– gradient discordance due to an inherent inconsistency in the guidelines criteria and/or to a small body size. LOW FLOW LOW GRADIENT AS
  • 99.  However, these patients were an heterogeneous group, likely comprising without distinction patients with paradoxical LF AS and patients with normal-flow, LG AS in conjunction with measurement error, small body size, and/or inconsistencies due to the guidelines criteria.  Among patients with EOA <1.0 cm2, the Paradoxical LF LG AS were found to have the worse prognosis and the Normal flow LG AS the best prognosis. LOW FLOW LOW GRADIENT AS
  • 100. LOW FLOW LOW GRADIENT AS
  • 101. Typical Characteristics of the 3 Main Entities of Severe AS LOW FLOW LOW GRADIENT AS
  • 102. LOW FLOW LOW GRADIENT AS
  • 103. LOW FLOW LOW GRADIENT AS
  • 104. CONCLUSIONS LF-LG AS with either normal or reduced LVEF is among the most challenging of situations encountered in patients with VHD. DSE greatly aids risk stratification and clinical decision making in patients with low LVEF, LF-LG AS. LOW FLOW LOW GRADIENT AS
  • 105. Paradoxical LF-LG AS despite normal LVEF is a recently described entity that has been shown to be associated with a more advanced stage of the disease and worse prognosis. TAVR may eventually prove to be an attractive alternative to surgical AVR in both types of LF-LG severe AS, but this remains to be confirmed by future randomized studies. LOW FLOW LOW GRADIENT AS
  • 106. Low flow/ Low gradient AS with preserved LVEF is due to intrinsic myocardial dysfunction as evidenced by Speckle Tracking imaging  Valve calcification and serum BNP may be helpful for clinical decision making LOW FLOW LOW GRADIENT AS
  • 107. LOW FLOW LOW GRADIENT AS

Notas del editor

  1. But even after ava calculation, we will find a lot of discrepancies between…..
  2. UNDERSTANDING THESE PREVALENCE RATES HAS A VERY STRONG IMPLICATION COS…IF WE CLASSIFY PATIENTS BASED ON ONLY GRADIENTS THEN WE ARE GOING TO MISS ALL THESE PATIENTS OF SEVERE AS…..TRUE THAT THOSE WITH LOW EF MAY HAVE PSEUDO SEVERE AS Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low flow, low gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation 2007;115:2856–64 Pibarot P, Dumesnil J. Low-Flow, Low-Gradient Aortic Stenosis With Normal and Depressed Left Ventricular Ejection Fraction. J Am Coll Cardiol 2012;60:1845–53
  3. LV dysfunction in patients with AS is referred to as primary if decreased function is caused primarily by factors other than a stenotic aortic valve and as secondary if decreased function results directly from the valvular lesion.
  4. Lond standing ASmyo dysfunctionlow eflow flow
  5. Suspect a low flow state…
  6. Monin JL, Monchi M, Gest V, Duval-Moulin AM, Dubois-Rande JL, Gueret P. Aortic stenosis with severe left ventricular dysfunction and low transvalvular pressure gradients: risk stratification by low-dose dobutamine echocardiography. J Am Coll Cardiol. 2001;37:2101–2107
  7. Flow= CSA X VTI
  8. Cueff C, Serfaty JM, Cimadevilla C, et al. Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction. Heart 2011;97:721– 6.
  9. UNIKE ASYMTOMATIC AS, severe as WITH NORMAL EF, WHERE MANAGEMENT IS CHALLENGING WITH NEED FOR ADDITIONAL EXERCISE , BNP TESTING, THOSE WITH LOW EF HAVE A CLASS 1 REC FOR AVR…. abnormal blood pressure response, ST segment changes, symptoms such as limiting dyspnea, chest discomfort, or dizziness on a modified Bruce protocol, or complex ventricular arrhythmias
  10. PERI OP RISK FOR N EF= 1.3% Brown et al J Thorac Cardiovasc Surg 2009; 137:82–90. 5-year survival rate in patients with no contractile reserve who underwent aortic valve replacement than in similar patients who received medical management (65% ± 11% vs 11 ± 7%, P = .019) * Burwash IG. Low-flow, low-gradient aortic stenosis: from evaluation to treatment. Curr Opin Cardiol 2007; 22:84–91
  11. PPM= EOA <0.85 /mt2
  12. *Clavel MA, Webb JG, Rodés-Cabau J, et al. Comparison between transcatheter and surgical prosthetic valve implantation in patients with severe aortic stenosis and reduced left ventricular ejection fraction. Circulation 2010;122:1928 –36 *Gotzmann M, Lindstaedt M, Bojara W, Ewers A, Mugge A. Clinical outcome of transcatheter aortic valve implantation in patients with low-flow, low gradient aortic stenosis. Catheter Cardiovasc Interv 2012;79:693–701 Procedural success rates 95%.. PARTNER A AND B---TAVI VS MEDICAL MANAGEMENT VS BALLOON ANGIOPLASTY VS SURGICAL AVR
  13. These pts of PseuSevere AS have an underlying myocardial dysfunction…. Balance between the myocardial disease and AS severity.. …but, periop mortality rates appraoch 50 % in these patients cos of underlying heart dysfunction and hence benefit more from medical management….but it also true that what is moderate stenosis for a normal ventricle may correspond to a severe stenosis for a diseased ventricle…NO SPECIFIC ACC GUIDELINES…ESC 2012 GUIDELINES… Connolly HM, Oh JK, Schaff HV, et al. Severe aortic stenosis with low transvalvular gradient and severe left ventricular dysfunction: result of aortic valve replacement in 52 patients. Circulation 2000; 101:1940–1946
  14. Connolly HM, Oh JK, Schaff HV, et al. Severe aortic stenosis with low transvalvular gradient and severe left ventricular dysfunction. Result of aortic valve replacement. Circulation 2000; 101:1940–6 PERI OP RISK FOR N EF= 1.3% Brown et al J Thorac Cardiovasc Surg 2009; 137:82–90. 5-year survival rate in patients with no contractile reserve who underwent aortic valve replacement than in similar patients who received medical management (65% ± 11% vs 11 ± 7%, P = .019) * Burwash IG. Low-flow, low-gradient aortic stenosis: from evaluation to treatment. Curr Opin Cardiol 2007; 22:84–91
  15. APART FROM CONTRACTILE RESERVE…. BNP level 550 pg/mL predicts both overall 1-year survival (47% if BNP 550 versus 97% if BNP 550) and 1-year survival after AVR (53% if BNP 550 versus 92% if BNP 500)* TOPAS Study. Circulation. 2007;115:2848 –2855.
  16. Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low flow, low gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation 2007;115:2856–64 It is generally assumed that patients with severe AS and preserved LVEF should necessarily have a high transvalvular gradient. However, recent studies revealed that this perception is erroneous and that a substantial proportion of patients with severe AS may indeed have a low transvalvular flow and thus a low gradient despite a preserved LVEF
  17. Specially affected by comorbidities like htn, ihd
  18. -Higher prevalence of women, older age, smaller LV end-diastolic volume, -Signs of AS severity can be masked by the presence of concomitant hypertension, blood pressure should routinely be measured at the time of the echocardiogram in every patient with AS -Patients with severe AS and LV concentric remodelling often tend to have relatively higher EF’s than normal (e.g. .70%)…and that is why in these patients we go other better markers of lv function…..
  19. Hachicha et al
  20. The Annals of Thoracic Surgery, Volume 91(6), Tarantini G, Covolo E, Razzolini R, et al. No ACC guidleines as it was formulated in 2006, the time when this new entity was not even introduced….
  21. Barasch E, Fan D, Chukwu EO, et al. Severe isolated aortic stenosis with normal left ventricular systolic function and low transvalvular gradients: pathophysiologic and prognostic insights. J Heart Valve Dis 2008;17:81-8. Hachicha Z, Dumesnil JG, Bogaty P, et al. Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation 2007;115:2856-64. Jander N, Minners J, Holme I, et al. Outcome of patients with low-gradient "severe" aortic stenosis and preserved ejection fraction. Circulation 2011;123:887-95.
  22. In pseudo severe AS, peri AVR mortality rates approach 50 % due to underlying myoc. Dysfunction unrelated to AS…and hence benefit better from HF management…. If the clinician needs better markers for LV function than EF, he can always go for other params like Mitral annular displacement, Tei index, global strain measurements…..