Low flow Aortic Stenosis-latest explanations

LOW FLOW AS

DR. DEEP CHANDH RAJA S

• Aortic stenosis is the 3 rd most common CV disease after HTN and CAD (in western world)

• Prevalence is 2-7% over the age of 65 years• Evaluation of aortic stenosis is the most

challenging of all valvular heart diseases

Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol 1997; 29:630–634.

2 MAJOR GUIDELINES

• ACC 2006• ESC 2012A FEW IMPORTANT NEW CONCLUSIONS IN ESC

2012 BASED ON EVOLVING NEW CONCEPTS AFTER 2007 (MISSING IN ACC 2006)

ACC/AHA GUIDELINES PUBLISHED IN JACC, 2006

GRADIENT = FLOW DEPENDENT VARIABLEGradient calculation-Small reduction in flow can cause great reductions in gradient

AVA calculation is a standard and must be incorporated into a comprehensive evaluation of AS severity

AVA=FLOW INDEPENDENT VARIABLE

MISMATCH BETWEEN GRADIENTS AND VALVE AREA

1. INDEXING TO BSA

2. INACCURACY IN CALCULATION OF LVOT DIAMETER

3. WHO SAID AVA < 1.0 CORRESPONDS TO GRADIENTS > 40 ???

4. LOW FLOW STATE (DEFINED SVi <35 ml/mt2)

• INDEXING TO BSA

Eg: AVA of 0.9 cm2, BSA=1.3, iAVA= 0.7 cm²/m²

AVA of 1.2 cm2, BSA=2.1, iAVA= 0.57 cm²/m²

•INACCURACY IN CALCULATION OF LVOT DIAMETER

CSA= .785 X LVOT D 2

Eg: D=2.8, CSA= 6.15 D=2.2, CSA= 3.75

• WHO SAID AVA < 1.0 CORRESPONDS TO GRADIENTS > 40 ???

Carabello demonstrated in 2427 patients, that“a mean gradient of 26 mmHg actually yields to an AVA of 1.0 cm², whereas a

mean gradient >40 is corresponding with a AVA of 0.8 cm2”

INCONSISTENCIES IN GUIDELINES- “FOR NOW, WE NEED TO ACCEPT AVA <1.0, AS THE REFERENCE CUT OFF TO DEFINE SEVERE AS”

• INDEXING TO BSA

• INACCURACY IN CALCULATION OF LVOT DIAMETER

• WHO SAID AVA < 1.0 CORRESPONDS TO GRADIENTS > 40 ???

• LOW FLOW STATE (DEFINED AS SVi<35 ml/mt2)

• H/O72 yr old ManHTN,

Dyslipidemia,CAD• C/ODOE & AOE

CLASS II

• AV GRADIENTS=43/28

• LVEF= 32 %• iAVA= 0.5 cm2

Case Scenario

• H/O72 yr old ManHTN,

Dyslipidemia,CAD• C/ODOE & AOE

CLASS II

• AV GRADIENTS=43/28

• LVEF= 52 %• iAVA= 0.5 cm2

Case Scenario

Causes of low flow state

• Till 2007 low flow due to LOW EF

• NOW low flow can also be secondary to Preserved EF “new entity” Paradoxical Low flow 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 IMPLICATION-“IF WE DON’T CALCULATE AVA, WE WILL MISS 15-35 %

OF CASES OF CRITICAL AS, MORE IMPORTANTLY WE WILL DEPRIVE THESE PATIENTS OF THE POTENTIAL BENEFIT OF AVR ON THEIR SYMPTOMS/SURVIVAL”

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 STATE

• LOW EF

• PRESERVED EF

• PATHOPHYSIOLOGY

• DIAGNOSIS

• TREATMENT OPTIONS

• PROGNOSIS

LOW FLOW, LOW EF, SEVERE AS

Case Scenario• H/O72 yr old ManHTN,

Dyslipidemia,CAD• C/ODOE & AOE

CLASS II

• AV GRADIENTS=44/26• iAVA= 0.5 cm2

• LVEF= 30 %

LOW FLOW, LOW GRADIENT, SEVERE AS WITH LOW EF

Prevalence of low flow state

LOW EF 5- 10 % of all patients of AVA < 1.0PRESERVED 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

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”

MYOCARDIAL DYSFUNCTION SECONDARY TO CAUSES OTHER THAN AS

-DILATED CARDIOMYOPATHIES (1O MYOCARDIAL DYFUNCTION)

-ISCHEMIC HEART DISEASE

-HTN HEART DISEASE (AFTER LOAD MISMATCH)

In all these patients, AVA was misjudged as <1.0 due to incomplete opening of AV due to low EF and labelled as “PSEUDO SEVERE AS”

MYOCARDIAL DYSFUNCTION SECONDARY TO AS

• “ True severe AS”• Removal of the only afterload-AS can lead to

dramatic improvements in patients’ symtoms/survival compared to medical therapy alone

DIAGNOSIS

DIAGNOSIS

• FIRST SUSPICION GRADIENT-AVA MISMATCH during routine echo

• GRADIENT < 40 mmhg, AVA <1.0, EF <40 %

• Dobutamine stress echo (exercise stress echo)Class IIA recommendation

Dobutamine stress echo

• Low dose protocol upto 20 µg/kg/mt• We look for three things:-Flow reserve -Change in EOA-Change in Gradient

30-40%

20-30%

Projected EOA

TOPAS (True or Pseudo Severe AS) STUDY

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

Treatment Decisions

• SYMPTOM 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)

Severe ‘Asymptomatic’ AS WITH LOW EF

• WITH NORMAL EF-management is challenging, an abnormal response to exercise stress testing and elevated BNP may identify a higher-risk group that might benefit from closer followup and earlier surgery

Recommendation:AVR for patients who have no symptoms and whose left ventricular ejection fraction is less than 50% (class I indication, level of evidence C)

• EURO SCORE, STS SCORE• PERIOP RISK- FLOW RESERVE (+)=5-8%,FLOW RESERVE (-)=30%*

Role of TAVI• Operative risk for open heart surgery 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.

• In contrast, TAVR associated with a higher incidence of paravalvular regurgitation, stroke, vascular complications which may eventually have a negative impact on outcomes

• PARTNER A & B and STACCATO TRIALS*Clavel et al. Circulation 2010;122:1928 –36

• 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 treated3.Optimal heart failure management strategy4.AVR (ESC class IIb)

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

• Paravalvular leak, Stroke in TAVI (Kodali et al.NEJM 2012)

PROGNOSIS

Prognosis • Concomitant CAD (46-79 %)• LOW EF SEVERE AS compared to Normal EF severe AS

have higher periop 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”

Group I= Flow reserve +Group II= Flow reserve -

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

• Low Flow due to low EF

• DSE to differentiate True from Pseudo Severe AS

• EOA (proj) & CT AV Ca Score

• AVR irrespective of EF and Flow reserve

LOW FLOW NORMAL EF SEVERE AS“PARADOXICAL”

Case Scenario• H/O72 yr old ManDyslipidemia,CAD• C/ODOE & AOE

CLASS II

• AV GRADIENTS=53/32

• LVEF= 62 %• iAVA= 0.5 cm2

• Gr 2 DD e/e’=12

LOW FLOW, LOW GRADIENT, SEVERE AS WITH NORMAL EF

Prevalence of low flow state

LOW EF 5- 10 % of all patients of AVA < 1.0PRESERVED EF 10-25 % of all patients of AVA < 1.0

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

New Entity

• First reported in 2007 by Hacicha et al. in 512 pts. (CIRCULATION)

• ECHO PROFILE:-Mean gradient < 40 mmhg,-AVA < 1.0 cm2,-Flow <35 ml/mt2,-EF≥40 %

PATHOPHYSIOLOGY AND CHARACTERISTICS OF LOW FLOW

NORMAL EF SEVERE AS

• Myocardial fibrosis• Restrictive physiology• Small LV cavity• Resembles heart failure

with preserved EF (Diastolic Heart failure)

• Pseudo-normalization of blood pressure

• Impaired LV function yet normal EF

(around 50-60%)

DIAGNOSIS

“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

ALTERNATIVES TO ‘EF’

• Valvulo-Arterial Impedance (Zva) • MPI (Tei Index)• Mitral annular displacement (By TDI)• Global LV Strain• CT AV Calcium Scoring• BNP levels

>5.5

>0.42

< 12 mm

< 10%

>1650 AU

>550 pg/ml

Valvulo-Arterial impedance (Zva)• 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

(SBP + Mean AV Gradient) / i SV

TREATMENT DECISIONS

• 2012 ESC guidelines class IIa 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

PROGNOSIS

LOW FLOW, N.EF, SEVERE AS

• Worse than moderate AS (albeit contradictory reports)

• Worse than severe AS with high gradient grouplower 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)

FUTURE TERMINOLOGY

• SEVERE AS WITHOUT MYOCARDIAL DYSFUNCTION

• SEVERE AS WITH MYOCARDIAL DYSFUNCTION

-SEVERE AV STENOSIS BASED ON AVA -IRRESPECTIVE OF FLOW, GRADIENTS, EF

SUMMARY

• ACCURATE AVA CALCULATION BY CONTINUITY EQUATION MUST BE A STANDARD IN EVALUATION OF A.S BY ECHO

• ELSE WE ARE GOING TO MISS 30 % CASES OF SEVERE AS

• LOW FLOW AS COULD BE DUE TO BOTH NORMAL AND REDUCED EF

• INSTITUTION PROTOCOLS TO BE DESIGNED FOR EVALUATION AND TREATMENT OF LOW FLOW STATES

• Low Flow due to low EF

• DSE to differentiate True from Pseudo Severe AS

• EOA (proj) & CT AV Ca Score

• AVR irrespective of EF and Flow reserve

• Low Flow due to intrinsic myocardial dysfunction

• Better picked up by novel methods of LV function like MAD, Tei index, Strain apart from Zva, BNP levels

• AVR better than medical management

SEVERE AS (indexed AVA < 0.6 cm2)

ASYMPTOMATIC NORMAL EF NORMAL FLOW EXERCISE TESTING(IIa) &FOLLOW UP

ASYMPTOMATIC LOW EF LOW FLOW AVR (I)

SYMPTOMATIC NORMAL EF NORMAL FLOW AVR (I)

SYMPTOMATIC LOW EF(EVEN IF FLOW RESERVE IS LOW)

LOW FLOW AVR (I)

SYMPTOMATIC NORMAL EF LOW FLOW AVR (IIa)

PSEUDO-SEVERE AS (AVA <1.0 cm2 in ECHO, AVA >1.2 cm2 in DSE)

SYMPTOMATIC LOW EF NORMAL FLOW RESERVE AVR (IIa)

SYMPTOMATIC LOW EF LOW FLOW RESERVE AVR (IIb)

MODERATE AS (AVA 1-1.5 cm2)

ASYMPTOMATIC NORMAL EF FOLLOW UP

SYMPTOMATIC NORMAL EF FOLLOW UP, AVR (IIb)

Simplified Statement

“Irrespective of AV Gradients and LVEF, symptomatic patients with iAVA < 0.6 cm2, and CT AV calcium score > 1650 AU, should be referred for AVR”

GREY AREAS

• AS WITH AR• AS WITH MITRAL VALVE DISEASE• RHEUMATIC AS

“Inadequate, less reliable literature”

“TAVI 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”