raj r. makkar, md - promedica international€¦ · savr: 27.5% zhao zg. et al. nature reviews in...

Raj R. Makkar, MDRaj R. Makkar, MDDirector, Interventional Cardiology & Cardiac Catheterization LaboratoriesDirector, Interventional Cardiology & Cardiac Catheterization LaboratoriesDirector, Interventional Cardiology & Cardiac Catheterization LaboratoriesDirector, Interventional Cardiology & Cardiac Catheterization Laboratories

Associate Director, CedarsAssociate Director, Cedars--Sinai Heart InstituteSinai Heart InstituteProfessor of Medicine, University of California, Los AngelesProfessor of Medicine, University of California, Los AngelesProfessor of Medicine, University of California, Los AngelesProfessor of Medicine, University of California, Los Angeles

Stephen Corday Chair in Interventional CardiologyStephen Corday Chair in Interventional Cardiology

DisclosuresDisclosuresDisclosuresDisclosures

Consultant and research grant from EdwardsConsultant and research grant from Edwards LifeSciencesLifeSciences,,Medtronic, Abbott, Boston Scientific and Jena ValveMedtronic, Abbott, Boston Scientific and Jena ValveMedtronic, Abbott, Boston Scientific and Jena ValveMedtronic, Abbott, Boston Scientific and Jena Valve

• Aortic Regurgitation• Aortic Regurgitation

• Failed surgical bioprosthetic valves• Failed surgical bioprosthetic valves

• Mixed valvular heart disease-AS+MS/MR• Mixed valvular heart disease-AS+MS/MR

• Failed TAVR valves

Do we need a randomized trial of TAVR vs.Do we need a randomized trial of TAVR vs.Do we need a randomized trial of TAVR vs.Do we need a randomized trial of TAVR vs.SAVR in Bicuspid Aortic Stenosis?SAVR in Bicuspid Aortic Stenosis?

My 5 key arguments for a randomized trial forMy 5 key arguments for a randomized trial forBicuspid ASBicuspid ASBicuspid ASBicuspid AS

• Bicuspid AS will be encountered with greater frequency asTAVR use expands in the younger patients-50% of SAVRin young are bicuspidin young are bicuspid

• The available observational data are limited by treatmentbias..perhaps only favorable anatomies were treatedbias..perhaps only favorable anatomies were treated

• Surgical outcomes in young Bicuspid AS patients areexcellent; reasonable to expect robust evidence for TAVR toexcellent; reasonable to expect robust evidence for TAVR toreplace SAVR

• Anatomically heterogeneous group with frequentaortopathy-unlike what has been treated in previous IDEstudies

• The precedent for label expansion in TAVR in last decade• The precedent for label expansion in TAVR in last decadehas been IDE randomized clinical trials

• Low risk trials: (Mack et al, NEJM; Popma et al, NEJM)

TAVR equal/better than SAVR

• STS/ACC-TVT registry: (Makkar et al, JAMA 2019)

1 year Death/StrokeBicuspid AS =Tricuspid ASBicuspid AS =Tricuspid AS

Prevalence of Bicuspid Aortic ValvePrevalence of Bicuspid Aortic Valve

70

80

6064

69

6050

60

70

33

42

2820

30

40

28

0

10

20

20- 30- 40- 50- 60- 70- 80-

0

Age (years)

Roberts WC et al. Circulation. 2005;111:920-925

Age (years)

Prevalence of Bicuspid Aortic ValvePrevalence of Bicuspid Aortic Valve

Frequencies of Bicuspid Aortic ValveFrequencies of Bicuspid Aortic Valve

Fre

qu

ency

ofB

AV

(%)

646960

70

80

Fre

qu

ency

ofB

AV

(%)

33

6064

69

60

4230

40

50

60

Fedak P W et al. Circulation. 2002;106:900-904

Bicuspid aortic valve

20- 30- 40- 50- 60- 70- 80-F

req

uency

ofB

AV

(%)

3328

0

10

20

30

20- 30- 40- 50- 60- 70- 80-

Roberts WC et al. Circulation. 2005;111:920-925

Age (years)

• The most common congenital cardiac malformation (1-2%)• Serious complications occurred > 30%

Aortic Stenosis (the most common)Aortic RegurgitationAortic RegurgitationAortic dilation and dissection

Prevalence of bicuspid valve in patients undergoingPrevalence of bicuspid valve in patients undergoingisolated AVRisolated AVR--almost 50%!almost 50%!isolated AVRisolated AVR--almost 50%!almost 50%!

Operatively excised, stenotic aortic valves from 932 patientsOperatively excised, stenotic aortic valves from 932 patientsaged 26 to 91 years

Roberts WC. et al. Circulation 2005

Prevalence of bicuspid aortic valve in TAVRPrevalence of bicuspid aortic valve in TAVRstudies is less than SAVR studiesstudies is less than SAVR studiesstudies is less than SAVR studiesstudies is less than SAVR studies

• Less than 7% of patientswith bicuspid aortic valvewith bicuspid aortic valvein TAVR registries

• Septugenerians undergoing• Septugenerians undergoingSAVR: 41.7%

•• Octogenerians undergoingSAVR: 27.5%

Zhao ZG. et al. Nature Reviews in Cardiology 2015

Pivotal Randomized TrialsPivotal Randomized Trials

Inoperable

High Risk

Intermediate Risk

Low Risk

Key Anatomic Exclusion CriteriaKey Anatomic Exclusion CriteriaKey Anatomic Exclusion CriteriaKey Anatomic Exclusion Criteria

•• Aortic annulus diameter < 16mm or 28mmAortic annulus diameter < 16mm or 28mm•• Aortic annulus diameter < 16mm or 28mmAortic annulus diameter < 16mm or 28mm

•• Bicuspid valve (CT imaging)Bicuspid valve (CT imaging)

•• Severe AR or MRSevere AR or MR•• Severe AR or MRSevere AR or MR

•• Severe LV dysfunctionSevere LV dysfunction

•• Severe calcification of aortic valve complexSevere calcification of aortic valve complex

•• Vascular anatomy not suitable for safe femoral accessVascular anatomy not suitable for safe femoral access

•• Complex CAD: LM, Syntax score>32Complex CAD: LM, Syntax score>32

•• Low coronary takeoffLow coronary takeoff•• Low coronary takeoffLow coronary takeoff

First Large Series of TAVR for Bicuspid ASFirst Large Series of TAVR for Bicuspid ASFirst Large Series of TAVR for Bicuspid ASFirst Large Series of TAVR for Bicuspid AS

• A total of 139 patients (mean age 78.0±8.9 and STS score 4.9±3.4%)underwent TAVR with Sapien (n=48) or CoreValve (n=91)underwent TAVR with Sapien (n=48) or CoreValve (n=91)

• Type 1 68%, Type 0 27% (no central core laboratory)• Post-AR ≥ grade 2 in 28.4% • 30-day and 1-year mortality: 5% and 17.5%

Mylotte et al: J Am Colle Cardiol 2014;64:2330-9

Improved Outcomes TAVR with NewImproved Outcomes TAVR with New--generationgenerationDevices for Bicuspid ASDevices for Bicuspid ASDevices for Bicuspid ASDevices for Bicuspid AS

• A total of 301 patients (mean age 77.0±9.2 and STS score 4.7±5.2%)underwent TAVR with Sapien XT (n=87) or CoreValve (n=112), Sapien 3(n=91), Lotus (n=11)(n=91), Lotus (n=11)

• PVL ≥ moderate 0% vs 8.5% (new- vs early-generation devices)

Yoon et al: J Am Colle Cardiol 2016;68:1195-205

Outcomes of TAVR for Bicuspid vs Tricuspid ASOutcomes of TAVR for Bicuspid vs Tricuspid AS

• 546 pairs of patients with bicuspid and tricuspid AS were created with PS-matching

• Bicuspid had more frequent aortic root injury with Sapien XT and PVL withCoreValve, but no differences in complications with Sapien 3/Evolut R/LotusCoreValve, but no differences in complications with Sapien 3/Evolut R/Lotus

• No difference in 1-year mortality between bicuspid and tricuspid AS

Yoon et al: J Am Colle Cardiol 2017;69:2579-89

Contemporary TAVR for Bicuspid vs Tricuspid ASContemporary TAVR for Bicuspid vs Tricuspid ASSTS/ACC TVT RegistrySTS/ACC TVT RegistrySTS/ACC TVT RegistrySTS/ACC TVT Registry

• Of 81822 patients (2726 bicuspid; 79096 tricuspid), 2691 propensity-scorematched pairs of patients with bicuspid and tricuspid AS were analyzedmatched pairs of patients with bicuspid and tricuspid AS were analyzed

• Mean age 74 (66-81) years; STS 4.9% vs 5.1%• No difference in mortality at 30 days (2.6% vs 2.5%) and 1 year (10.5% vs 12.0%)• 30-day stroke rate was higher in bicuspid (2.5% vs 1.6%; HR 1.57 [95% CI, 1.06-

2.33])2.33])

Makkar et al: JAMA 2019;321:2193-202

Contemporary TAVR for Bicuspid vs Tricuspid ASContemporary TAVR for Bicuspid vs Tricuspid ASSTS/ACC TVT RegistrySTS/ACC TVT RegistrySTS/ACC TVT RegistrySTS/ACC TVT Registry

Makkar et al: JAMA 2019;321:2193-202

11--Year Mortality in Unmatched CohortYear Mortality in Unmatched Cohort11--Year Mortality in Unmatched CohortYear Mortality in Unmatched Cohort

11--Year Mortality in Matched CohortYear Mortality in Matched Cohort11--Year Mortality in Matched CohortYear Mortality in Matched Cohort

5 Reasons Why we need RCT for Bicuspid5 Reasons Why we need RCT for Bicuspid5 Reasons Why we need RCT for Bicuspid5 Reasons Why we need RCT for Bicuspid

1.1. Inherent limitation of observational studyInherent limitation of observational study1.1. Inherent limitation of observational studyInherent limitation of observational study

2.2. No central imaging core laboratory for diagnosis ofNo central imaging core laboratory for diagnosis ofbicuspid anatomy (CT is new standard)bicuspid anatomy (CT is new standard)bicuspid anatomy (CT is new standard)bicuspid anatomy (CT is new standard)

3.3. Various bicuspid phenotype and potential selectionVarious bicuspid phenotype and potential selectionbias (bias (ieie, TAVR for favorable anatomy), TAVR for favorable anatomy)

4.4. AortopathyAortopathy is poorly understood in TAVR populationis poorly understood in TAVR population

5.5. Excellent surgical outcomesExcellent surgical outcomes5.5. Excellent surgical outcomesExcellent surgical outcomes

Outcomes of Transcatheter Aortic ValveReplacement with Balloon-Expandable Sapien3Replacement with Balloon-Expandable Sapien3Valve in Bicuspid Aortic Stenosis:An analysis of the STS/ACC TVT Registry

Raj R. Makkar, Sung-Han Yoon, Martin B. Leon, Tarun Chakravarty, SreekanthRaj R. Makkar, Sung-Han Yoon, Martin B. Leon, Tarun Chakravarty, Sreekanth

Vemulapalli, Michael Rinaldi, Pinak B. Shah, Eric R. Skipper, Vinod H. Thourani, Vasilis

Babaliaros, Wen Cheng, Alfredo Trento, Samir R. Kapadia, Susheel Kodali, Michael J.

Mack, Gilbert H. L. Tang, Tsuyoshi Kaneko

Study population

25 Covariates used for propensity matching

Age Chronic Lung Disease

92236 SAPIEN 3 Cases in TVT Registry(June 2015 − Nov 2018) Age Chronic Lung Disease

Gender (male) Prior PCI

NYHA III/IV Prior CABG

BMI Porcelain Aorta

3196 Valve-in-Valve136 Prior TAVR

7082 N/A, Uncertain,

552 Sites

Hypertension Mean Gradient

Diabetes LVEF

Creatinine ≥ 2 Mitral Regurgitation

Peripheral Arterial

79096 Tricuspid ASSAPIEN 3 Patients

7082 N/A, Uncertain,Unicuspid, Quadricuspid

2726 Bicuspid ASSAPIEN 3 Patients Peripheral Arterial

DiseaseTricuspid Regurgitation

Carotid Stenosis 5 Meter Walk Test

Atrial Fibrillation Access Site

SAPIEN 3 PatientsSAPIEN 3 Patients

1:1 Propensity Matching

Prior Stroke KCCQ

Immunocompromised Hemoglobin

GFR2691 Tricuspid ASSAPIEN 3 Patients

2691 Bicuspid ASSAPIEN 3 Patients

21

Procedural OutcomesProcedural Outcomes

Characteristic% or mean ± SD

Bicuspid AS(n=2691)

Tricuspid AS(n=2691)

p-value

Device success 96.5 96.6 0.87

Procedure Time, min 100.7 ± 51.80 98.2 ± 52.09 0.08Procedure Time, min 100.7 ± 51.80 98.2 ± 52.09 0.08

Fluoroscopy Time, min 18.5 ± 10.96 17.1 ± 10.17 <0.0001

Conversion to open surgery 0.9 0.4 0.03

Annulus Rupture 0.3 0.0 0.02Annulus Rupture 0.3 0.0 0.02

Cardiopulmonary bypass 1.4 1.0 0.13

Aortic dissection 0.3 0.1 0.34

Coronary Obstruction 0.4 0.3 0.34

Need for a second valve 0.4 0.2 0.16

22

30-Day Outcomes

KM estimate % Bicuspid Tricuspid AS p-valueKM estimate % Bicuspid Tricuspid AS p-value

All-cause mortality 2.6 2.5 0.82

All stroke 2.4 1.6 0.02All stroke 2.4 1.6 0.02

Life-threatening bleeding 0.1 0.1 0.99

Major vascular complication 0.9 1.0 0.68Major vascular complication 0.9 1.0 0.68

New pacemaker 9.1 7.5 0.03

Aortic valve reintervention 0.2 0.3 0.79Aortic valve reintervention 0.2 0.3 0.79

23

1-Year Mortality – Matched1-Year Mortality – Matched

40Bicuspid

P= 0.31HR: 0.90 [95% CI: 0.73, 1.10]

Ca

us

eM

ort

ality

(%)

25

30

35

40Bicuspid

Tricuspid

10.5%

12.0%

Ca

us

eM

ort

ality

(%)

10

15

20

25

10.5%

All-C

au

se

Mo

rta

lity

(%)

0

5

10

0 3 6 9 12

Bicuspid

Tricuspid

2691 1259 1222 1162 934

2691 1367 1326 1256 977

Time in MonthsNumber at risk

24

1-Year Stroke – Matched1-Year Stroke – Matched

Bicuspid40

P= 0.16HR: 1.28 [95% CI: 0.91, 1.79]

Str

ok

e(%

)

Bicuspid

Tricuspid

25

30

35

40

Str

ok

e(%

)

10

15

20

25

3.1%

3.4%

0 3 6 9 12

0

5

10

Bicuspid

Tricuspid

2691 1234 1196 1135 910

2691 1341 1296 1226 952

Time in MonthsNumber at risk

25

Paravalvular Leak – MatchedParavalvular Leak – Matched

p=0.44p=0.17p=0.08

17.0% 15.5%23.6% 20.5% 21.1% 18.7%

[VALUE] [VALUE] [VALUE] [VALUE] [VALUE] [VALUE][VALUE] [VALUE] [VALUE] [VALUE] [VALUE] [VALUE]

80%

100%

81.5% 83.7% 77.2% 75.7% 78.8%40%

60%

80%

Severe

Moderate

Mild81.5% 83.7%74.4% 77.2% 75.7% 78.8%

20%

40% Mild

None/Trace

0%

Bicuspid(n=2179)

Tricuspid(n=2233)

Bicuspid(n=1711)

Tricuspid(n=1782)

Biscuspid(n=593)

Tricuspid(n=673)

Discharge 30-day 1-year

26

Discharge 30-day 1-year

Hemodynamics – Matched

Mean Gradient Aortic Valve Area

60

Me

an

Gra

die

nt

(mm

Hg

)

Mean GradientBicuspid Tricuspid

2.5

3

2)

Aortic Valve AreaBicuspid Tricuspid

30

45

Me

an

Gra

die

nt

(mm

Hg

)

p=0.6p=0.15 p=0.86p=0.51

1.5

2

2.5

AV

A(c

m2

p=0.15

15

Me

an

Gra

die

nt

(mm

Hg

)

p=0.69

p=0.15 p=0.86p=0.51

0

0.5

1p=0.15 p=0.34

0Me

an

Gra

die

nt

(mm

Hg

)

0

Baseline Discharge

27

• No central CT core lab to diagnose bicuspid• No central CT core lab to diagnose bicuspidanatomy

• No central adjudication of events• No central adjudication of events• No data on aortopathy• Most importantly.. “Treatment bias-were there• Most importantly.. “Treatment bias-were there

anatomical factors as to why TAVR wasanatomical factors as to why TAVR waschosen rather than surgey? Only 3% of theentire cohort were bicuspid.entire cohort were bicuspid.

NYHA Class – Matched

[VALUE] [VALUE] [VALUE] [VALUE]

NYHA Class – Matched

p=0.93 p=0.80 p=0.70

38.4% 37.7% 32.3% 32.7%

6.3% 6.9% 6.8% 5.3%[VALUE] [VALUE]

[VALUE] [VALUE] [VALUE] [VALUE]

80%

100%

IV

59.7% 60.8%

38.4% 37.7%

59.9% 60.3%

40%

60%

IV

III

II

I

3.4% 3.5%

54.9% 54.7% 59.7% 60.8%

22.2% 22.4%

0%

20%

I

Bicuspid(n=2667)

Tricuspid(n=2664)

Bicuspid(n=1958)

Tricuspid(n=2015)

Biscuspid(n=752)

Tricuspid(n=804)

Baseline 30-day 1-year

29


KCCQ – MatchedKCCQ – Matched

100

120

KC

CQ

Ov

era

llS

um

ma

ry

p=0.87 p=0.52 p=0.15

60

80

KC

CQ

Ov

era

llS

um

ma

ryS

co

re

Bicuspid

Tricuspid

20

40

KC

CQ

Ov

era

llS

um

ma

ryS

co

re

Tricuspid

n=2460 n=2463 n=1992 n=1990 n=732 n=776

0


KC

CQ

Ov

era

llS

um

ma

ry

30

The “easy case”: Little calcium, No RapheThe “easy case”: Little calcium, No Raphe

60 y/o female undergoing TAVR60 y/o female undergoing TAVR60 y/o female undergoing TAVR60 y/o female undergoing TAVR

Congenital bicuspid aortic valveMinimal calcification

Annulus Area 356.2 mm2

Dmin 18.3, Dmax 24.8 mm

Minimal calcification

TAVR with 23mm Sapien3 performedTAVR with 23mm Sapien3 performedTAVR with 23mm Sapien3 performedTAVR with 23mm Sapien3 performed

Trace paravalvular AR

The “ok case”: Little calcium, ModerateThe “ok case”: Little calcium, ModerateThe “ok case”: Little calcium, ModerateThe “ok case”: Little calcium, ModerateCalcified RapheCalcified Raphe

90 y/o male with severe AS referred for TAVR90 y/o male with severe AS referred for TAVRExtreme risk due to age, frailty and comorbiditiesExtreme risk due to age, frailty and comorbiditiesExtreme risk due to age, frailty and comorbiditiesExtreme risk due to age, frailty and comorbidities

BicuspidBicuspidvalvevalvevalvevalve

s/p successfuls/p successful transfemoraltransfemoral TAVR with 29TAVR with 29--mmmmSapienSapien--XT valveXT valveSapienSapien--XT valveXT valve

No significantNo significant paravalvularparavalvular ARAR

87 y/o male referred for TAVR87 y/o male referred for TAVRNYHA 3 heart failure, diastolicNYHA 3 heart failure, diastolicNYHA 3 heart failure, diastolicNYHA 3 heart failure, diastolic

Severely calcified aorticvalvevalve

Severe MR

Bicuspid valve with heavilycalcified raphe

Severe MR

Mean gradient 34mmHgMean gradient 34mmHgAVA 0.5cm2

PrePre--TAVR CTTAVR CTPlan for 29mm Sapien3Plan for 29mm Sapien3Plan for 29mm Sapien3Plan for 29mm Sapien3

Annular dimensions (28.9x32.8, meanAnnular dimensions (28.9x32.8, mean30.9mm), Area 722mm2

HighHigh--risk features on prerisk features on pre--TAVRTAVRHighHigh--risk features on prerisk features on pre--TAVRTAVR

Dilated ascending aortaDilated ascending aorta47.2x48.2mm, mean 47.7mm

Severe LVOT calcification

29mm Sapien 3 deployment29mm Sapien 3 deploymentPredilation with 23mm x 4cm ZPredilation with 23mm x 4cm Z--Med II BalloonMed II BalloonPredilation with 23mm x 4cm ZPredilation with 23mm x 4cm Z--Med II BalloonMed II Balloon

Careful predilation, heavily calcified valve 29mm Sapien 3

Severely calcifiedaortic valve

Eccentric deployment of Sapien3Eccentric deployment of Sapien3Well expanded valve, but eccentrically locatedWell expanded valve, but eccentrically locatedWell expanded valve, but eccentrically locatedWell expanded valve, but eccentrically located

Eccentric deployment of Sapien3Eccentric deployment of Sapien3

Moderate PVL

PersisentPersisent PVL despite postPVL despite post--dilationdilationPersisentPersisent PVL despite postPVL despite post--dilationdilation

Post-dilation performed with theSapien3 balloon

Persistent PVL despite post-dilationSapien3 balloon dilation

PVL closure performed immediately after postPVL closure performed immediately after post--dilation due to persistent moderate PVLdilation due to persistent moderate PVLdilation due to persistent moderate PVLdilation due to persistent moderate PVL

Step 1: Shuttle sheathacross the leak

Step 2: Amplatz wireremoved from the LV Final result s/p 10mm AVP 2 plug

deploymentdeployment

Leak crossed with Terumoglidewire with a MPA catheter;

wire exchanged for a Amplatz stiffwire

Step 3: 10mm AVP 2plug advanced

Step 4: 10mm AVP 2plug deployed

TEE guidance during the procedureTEE guidance during the procedureTEE guidance during the procedureTEE guidance during the procedure

Position of wire through the PVLconfirmed with TEE

Final result s/p TAVR and PVL closure

10mm AVP2plug

Difficult Anatomy: heavy calcium withDifficult Anatomy: heavy calcium withDifficult Anatomy: heavy calcium withDifficult Anatomy: heavy calcium withcalcified raphecalcified raphecalcified raphecalcified raphe

55 y/o male with severe AS, referred for TAVRPatient turned down for OHT/VAD or SAVR/CABGPatient turned down for OHT/VAD or SAVR/CABG

Mean gradient = 40 mmHg

Severely depressed EF (15-20%)

Baseline Coronary Angiogram

80% calcified stenosis in mid LAD Patent right coronary artery

Cardiac CT for aortic valve evaluationBicuspid aortic valveBicuspid aortic valve

RCAType 1 bicuspid

aortic valve

CalcifiedCalcifiedRaphe

Left Right

Left mainLeft main

Cardiac CT for aortic valve evaluation

STJ

Annulus Maximal aortic dimension

SOV mean = 30.5 mm

Pre TAVR TEE assessment

AnnulusArea; 474 cm2

STJ diameter 2.61 cm

Diameter 2.93 x 2.07 cm

Biventricular systolic dysfunction

TF TAVR – Preparation and valve deployment

Aortogram Valve deployment

Valvuloplasty with Z-MED 16 mm balloon

Aortogram Valve deployment

No contrast in the balloon…

Left main protection and secured venous access with stiff wire

Assessment immediately post valve deployment

Significant PVL after Valve deploymentPatent left main

Diastolic flow reversal Decreased diastolic gradient

Paravalvular closure with 8 mm AVP II

AVP II positioning Persistent PVL after AVP plug positioning

Persistent diastolic flow reversal

Valve-in valve with Sapien XT 26 mm

Valve deployment Mild residual PVL

No diastolic flow reversal Improved diastolic gradient

Hemodynamics improvement post TAVR

Pre valve replacement Post valve replacement

Improved LV systolic function immediately post TAVR

Pre-valve replacement Post-valve replacement

Continuous improvement of LV systolic function post TAVR

Pre-TAVR (EF 15%) Day 1 post-TAVR (EF 40%)

PCI to mid LAD 5 days post TAVR

Baseline left coronary angiogramBaseline left coronary angiogram

2.5 mm balloonunable to cross theunable to cross the

lesion.

Rotationalatherectomy with 1.25

mm burr.mm burr.

Deployment ofDeployment ofXience 3.0 x 18 mm,

followed by postdilatation with 3.0 x 8

mm NC balloon.

PCI to mid LAD 5 days post TAVR

Final angiogramBaseline angiogram

2 years later: Severe paravalvular regurgitation in2 years later: Severe paravalvular regurgitation inthe presence of sinus of Valsalva aneurysmthe presence of sinus of Valsalva aneurysmthe presence of sinus of Valsalva aneurysmthe presence of sinus of Valsalva aneurysm

PatietPatiet underwent surgical AVRunderwent surgical AVR

Repeat CT 2 years later revealedRepeat CT 2 years later revealedpseudoaneurysm of the sinus of Valsalvapseudoaneurysm of the sinus of Valsalvapseudoaneurysm of the sinus of Valsalvapseudoaneurysm of the sinus of Valsalva

Normal leaflet motionNormal leaflet motion

Patient underwent surgical repair of the pseudoaneurysm and bioprosthetic aortic valvePatient underwent surgical repair of the pseudoaneurysm and bioprosthetic aortic valvereplacement

Pseudoaneurysm

Surgical Outcomes for Bicuspid AorticSurgical Outcomes for Bicuspid AorticValveValveValveValve

Total No AgeMortality

30 days 1 year 5 years 10 years30 days 1 year 5 years 10 years

Borger at al 1 201 54±11 2.5% NA NA 19%

Girdauskas et al 2 153(aortopathy)

54±110.7%

(hospital death)NA NA 14%

(aortopathy) (hospital death)

Itagaki et al 3 2079 55.3±14.9 1.5% NA NA NA

Desai et al 4 1890 50±14 0.4% 1.0% 4.0% NADesai et al 4 1890 50±14 0.4% 1.0% 4.0% NA

Andrei et al 5

Total: 628Men: 478

Women: 150

Men: 56.3±13.6Women:

60.7±13.80.6%

Men: 3.2%Women: 6.0%

Men: 8.3%Women: 7.8%

NA

1 Borger et al: J Thorac Cardiovasc Surg 2004; 128: 677-832 Girdauskas et al: Eur J Cardiothorac Surg 2012; 42:832-8Girdauskas et al: Eur J Cardiothorac Surg 2012; 42:832-83 Itagaki et al: J Am Coll Cardiol 2015; 65: 2363-94 Desai et al: J Thorac Cardiovasc Surg 2016; 151: 1650-95 Andrei et al: Am J Cardiol 2015;116:250-255

• In the low risk trials the 1and 2 year death,stroke,and rehospitalization rates were verystroke,and rehospitalization rates were verylow and lower than surgerylow and lower than surgery

• Imaging has evolved to help better selectsuitable anatomical subsetssuitable anatomical subsets

Bicuspid Aortic Valve Morphologyand Outcomes After TAVRand Outcomes After TAVR

Sunghan Yoon, MDSunghan Yoon, MD

Raj R. Makkar, MDSmidt Heart Institute at Cedars-Sinai Medical CenterSmidt Heart Institute at Cedars-Sinai Medical Center

On Behalf of BAV TAVR Registry Investigators

Euro PCR 2019 LBCT Presentation

Baseline CharacteristicsBaseline Characteristics

Demographics & Overall Other Comorbidities & OverallDemographics &Risk Factors

Overall(n = 1115)

Other Comorbidities &Echo parameters

Overall(n = 1115)

Age, years 75.1 ± 9.4 Chronic lung disease 24.9%

Male 58.9% Atrial Fibrillation 19.8%

NYHA class III or IV 75.3% Permanent Pacemaker 7.6%

STS score, % 4.2 ± 3.6 Aortic Valve Area (cm2) 0.7 ± 0.2STS score, % 4.2 ± 3.6 Aortic Valve Area (cm2) 0.7 ± 0.2

Diabetes 25.3% Mean Gradient (mmHg) 48.5 ± 17.6

Prior PCI 20.7% LVEF (%) 52.6 ± 15.2Prior PCI 20.7% LVEF (%) 52.6 ± 15.2

Prior CABG 8.6% ≥ Moderate AR 10.8%

Prior CVA 13.5% ≥ Moderate MR 10.0%

% or mean ± SD

CT Findings and Procedural DataCT Findings and Procedural Data

CharacteristicOverall

(n = 1115)Characteristic

(n = 1115)

Type of Bicuspid

No Raphe (type 0) 11.2%

Calcified Raphe (type 1) 46.5%

Non-calcified Raphe (type 1) 42.3%

Calcification Volume in Leaflet (mm3) 381 (190 – 691)Calcification Volume in Leaflet (mm3) 381 (190 – 691)

Aortopathy (diameter ≥ 40 mm) 45.7%

Transfemoral access 90.3%

Device generationDevice generation

Early-generation 23.2%

Newer-generation 76.8%

% or median (IQR)

Various BAV Morphology

Non-calcified Raphe Calcified RapheNo Raphe

Various BAV MorphologyM

ild

Leafl

et

Calc

ific

ati

on

Mild

Leafl

et

Calc

ific

ati

on

Leafl

et

Calc

ific

ati

on

Excess

Leafl

et

Calc

ific

ati

on

Phenotype DistributionNon-calcified Raphe Calcified RapheNo Raphe

Phenotype DistributionM

ild

Leafl

et

Calc

ific

ati

on

Mild

Leafl

et

Calc

ific

ati

on

n = 61 (5.5%) n = 271 (24.3%) n = 225 (20.2%)

Leafl

et

Calc

ific

ati

on

n = 61 (5.5%) n = 271 (24.3%) n = 225 (20.2%)

Excess

Leafl

et

Calc

ific

ati

on

n = 64 (5.7%) n = 201 (18.0%) n = 293 (26.3%)

Yoon S, Makkar R EuroPCR 2019

Overall All-cause and CV Death

4040

Overall All-cause and CV Death

30

Cu

mu

lati

ve

Incid

en

ce

(%)

30

10

20

Cu

mu

lati

ve

Incid

en

ce

(%)

20

10

15.2

9.0

Death fromany cause

0

10

Cu

mu

lati

ve

Incid

en

ce

(%)

0

109.0

Death fromCardiovascular causes

0 180 360 540 7200 180 720360 540

Days

No. at Risk 1115 682 339

All-cause Death According to Raphe

4040 Overall P < .001 by log-rank test

HR for Calcified raphe vs. No raphe,

All-cause Death According to Raphe

30

cau

se

Mo

rtality

(%)

30

HR for Calcified raphe vs. No raphe,

2.70 (95% CI, 1.25 – 5.86); P = .012

HR for Non-calcified raphe vs. No raphe

1.33 (95% CI, 0.59 – 2.99); P =.49

10

20

All-c

au

se

Mo

rtality

(%)

20

10

11.9

19.9Calcified raphe

Non-calcified raphe

0

10All

0

10

8.5No raphe

0 180 360 540 7200 180 720360 540

Days

Calcified raphe

No. at Risk

Non-calcified raphe

518 292 154

472 310 154

No raphe

Non-calcified raphe

125 80 31

472 310 154

40HR, 1.72 (95% CI, 1.19–2.49)

P = .003 by log-rank test

40

All-cause Death According to Leaflet Calcium

30

cau

se

Mo

rtality

(%)


30

Excess leaflet

10

20

All-c

au

se

Mo

rtality

(%)

20

10

19.1Excess leaflet

calcification

0

10All

0

10 11.5

Mild leafletcalcification

0 180 360 540 7200 180 720360 540

Days

Excess leaflet ca

No. at Risk

558 321 157

Mild leaflet ca 557 361 182

Independent Correlates of All-cause MortalityIndependent Correlates of All-cause MortalityUnivariate Analysis Multivariate Analysis

HR (95% CI) P Value HR (95% CI) P Value

Age 1.03 (1.01 – 1.05) 0.006 – –

STS score 1.06 (1.03 – 1.09) < 0.001 1.04 (1.01 – 1.08) 0.02

MR ≥ moderate at baseline 1.77 (1.10 – 2.87) 0.02 1.65 (1.02 – 2.68) 0.04

Prior MI 1.64 (1.05 – 2.54) 0.028 –Prior MI 1.64 (1.05 – 2.54) 0.028 –

Atrial Fibrillation 1.61 (1.08 – 2.40) 0.021 – –

Type of Bicuspid AV < 0.001 0.001

No raphe (Sievers’ type 0) Reference – Reference –No raphe (Sievers’ type 0) Reference – Reference –

Non-calcified raphe (Sievers’ type 1) 1.33 (0.59 – 2.99) 0.49 1.55 (0.69 – 3.50) 0.29

Calcified raphe (Sievers’ type 1) 2.70 (1.25 – 5.86) 0.01 2.80 (1.29 – 6.08) 0.009

Excess leaflet calcification 1.72 (1.19 – 2.49) 0.004 1.53 (1.05 – 2.22) 0.03

Aortopathy 1.61 (1.13 – 2.32) 0.009 – –

Non-transfemoral access 2.05 (1.29 – 3.25) 0.002 1.70 (1.05 – 2.75) 0.03Non-transfemoral access 2.05 (1.29 – 3.25) 0.002 1.70 (1.05 – 2.75) 0.03

Early-generation devices 1.89 (1.31 – 2.73) 0.001 1.71 (1.17 – 2.50) 0.005

Independent Correlates ofIndependent Correlates ofAll-cause Mortality

HR (95% CI) P ValueHR (95% CI) P Value

STS score 1.04 (1.01 – 1.08) 0.02

MR ≥ moderate at baseline 1.65 (1.02 – 2.68) 0.04MR ≥ moderate at baseline 1.65 (1.02 – 2.68) 0.04

Type of Bicuspid AV 0.001

No raphe (Sievers’ type 0) Reference –

Non-calcified raphe (Sievers’ type 1) 1.55 (0.69 – 3.50) 0.29

Calcified raphe (Sievers’ type 1) 2.80 (1.29 – 6.08) 0.009

Excess leaflet calcification 1.53 (1.05 – 2.22) 0.03Excess leaflet calcification 1.53 (1.05 – 2.22) 0.03

Non-transfemoral access 1.70 (1.05 – 2.75) 0.03

Early-generation devices 1.71 (1.17 – 2.50) 0.005

All-cause Mortality and BAV Phenotype1115 Bicuspid AS patients, Central CT Core Lab, 25 Centers

4040Overall P < .001 by log-rank test

HR for Calcified raphe plus Excess leaflet calc vs. Calcified raphe or Excess leaflet calc

2.17 (95%CI, 1.46 – 3.25); P < .001

30

cau

se

Mo

rtality

(%)

3025.5

2.17 (95%CI, 1.46 – 3.25); P < .001

HR for Calcified raphe plus Excess leaflet calcification vs. None

2.97 (95% CI, 1.82 – 4.84); P < .001 Calcified rapheplus

Excess leaflet calc

10

20

All-c

au

se

Mo

rtality

(%)

20

10

12.3

Calcified rapheor

Excess leaflet calc

0

10All

0

1010.8

None

0 180 360 540 7200 180 720360 540

Days

Ca-raphe plus excess calc

No. at Risk

293 156 80

Ca-raphe or excess calc 490 301 151

None 332 225 108

Ca-raphe or excess calc 490 301 151

Yoon S, Makkar R EuroPCR 2019

Procedural and 30-day OutcomesAccording to BAV Phenotype

Both Calcified raphe plusExcess leaflet calcification

Either Calcified raphe orExcess leaflet Calcification

None

According to BAV Phenotype

18.0

20.0

Excess leaflet calcification Excess leaflet Calcification

p < 0.001

(n = 293) (n = 490) (n = 332)

14.012.0

14.0

16.0

18.0

Inc

ide

nc

e(%

)

p < 0.001 p = 0.006 p = 0.004

9.2

5.56.1

4.0

6.0

8.0

10.0

Inc

ide

nc

e(%

)

4.85.5

6.1

1.2

4.1

1.62.8

0.6

4.5

2.10.0

2.0

4.0

PVL ≥ moderate Aortic Root Injury Major VascularCompication

30-day MortalityCompication

All-cause Mortality and BAV PhenotypeAmong Low-Risk Patients with New Devices

4040

Overall P < .001 by log-rank test

30

cau

se

Mo

rtality

(%)

30

22.4

Overall P < .001 by log-rank test

HR for Calcified raphe plus Excess leaflet calc vs. Calcified raphe or Excess leaflet calc

3.73 (95%CI, 1.72–8.13); P = .001

HR for Calcified raphe plus Excess calcific vs. None

4.37 (95% CI, 1.73–10.99); P = .002 Calcified rapheplus

10

20

All-c

au

se

Mo

rtality

(%)

20

10 8.0

22.4plus

Excess leaflet calc

Calcified rapheor

0

10All

0

10 8.0

5.0None

orExcess leaflet calc

0 180 360 540 7200 180 720360 540

DaysNo. at Risk

132 61 28

246 143 54

Ca-raphe plus excess calc

Ca-raphe or excess calc

169 102 40

246 143 54

None

Ca-raphe or excess calc

Outcomes According to BAV PhenotypeAmong Low-Risk Patients with New Devices

Both Calcified raphe plusExcess leaflet calcification

Either Calcified raphe orExcess leaflet Calcification

None

Outcomes According to BAV PhenotypeAmong Low-Risk Patients with New Devices

18.0

20.0

Excess leaflet calcification Excess leaflet Calcification(n = 132) (n = 246) (n = 169)

12.0

14.0

16.0

18.0

Inc

ide

nc

e(%

)

p < 0.001 p < 0.001 p = 0.006 p = 0.004

5.6 6.1

7.6

4.0

6.0

8.0

10.0

Inc

ide

nc

e(%

)

5.6 6.1

3.8

2.1 1.2

3.7

0.01.8 1.23.6

0.60.0

2.0

4.0

PVL ≥ moderate Aortic Root Injury Major VascularCompication

30-day MortalityCompication

All-cause Mortality and AortopathyAortopathy was not associated with All-causeMortality with Multivariate Analysis

4040 HR, 1.61 (95% CI, 1.13–2.32)


Mortality with Multivariate Analysis

30

cau

se

Mo

rtality

(%)

30


10

20

All-c

au

se

Mo

rtality

(%)

20

10

18.5

12.5

Aortopathy

0

10All

0

10

No Aortopathy

0 180 360 540 7200 180 720360 540

Days

Aortopathy

No. at Risk

509 302 147

No Aortopathy 606 380 192

ConclusionConclusion• BAV morphology such as calcified raphe and excess leaflet

calcification were independently associated with increasedcalcification were independently associated with increasedprocedural complications and 2-year all-cause mortality

• Highest risk BAV phenotype (both calcified raphe plus excess• Highest risk BAV phenotype (both calcified raphe plus excessleaflet calcification) was found in 26% of patients andassociated with 3-fold higher mortality

• The impact of BAV morphology on outcomes was consistent in• The impact of BAV morphology on outcomes was consistent inlow surgical risk patients as well as in patients who had TAVRwith newer generation devices

• Aortopathy was not independently associated with all-causemortality

Clinical Implications

• CT assessment of morphology in bicuspid aortic stenosis

Clinical Implications

• CT assessment of morphology in bicuspid aortic stenosishelps assess anatomical risk of TAVR

• In absence of randomized clinical trial data in treating• In absence of randomized clinical trial data in treatingBicuspid Aortic Stenosis, CT based anatomicalassessment may identify patients favorable for TAVR andin conjunction with surgical risk help triage patients toin conjunction with surgical risk help triage patients toTAVR vs. SAVR

Pivotal Randomized Trials have been the standardPivotal Randomized Trials have been the standardfor indication expansion for TAVRfor indication expansion for TAVR

Inoperable

High Risk

Intermediate Risk

Low Risk

Hierarchy of Evidence and Research Designs

Meta-Analysis

SystemicSystemicReviews

RandomizedControlled TrialControlled Trial

Cohort Studies

Case Control Studies

Case Report/ Case SeriesCase Report/ Case Series

Background Information & Expert Opinion

• Low risk trials: (Mack et al, NEJM; Popma et al, NEJM)

TAVR equal/better than SAVRWhy infer? Let us do the randomized clinical trial!

• STS/ACC-TVT registry: (Makkar et al, JAMA 2019)

1 year Death/StrokeBicuspid AS =Tricuspid ASBicuspid AS =Tricuspid AS

My 5 key arguments for a randomized trial forMy 5 key arguments for a randomized trial forBicuspid ASBicuspid ASBicuspid ASBicuspid AS

• Bicuspid AS will be encountered with greater frequency asTAVR expand in the younger patients-50% of SAVR inyoung are bicuspidyoung are bicuspid

• The available observational data are limited by treatmentbias..perhaps only favorable anatomies were treatedbias..perhaps only favorable anatomies were treated

• Surgical outcomes in young Bicuspid AS patients areexcellent; reasonable to expect robust evidence for TAVR toexcellent; reasonable to expect robust evidence for TAVR toreplace SAVR

• Anatomically heterogeneous group with frequentaortopathy-unlike what has been treated in previous IDEstudies

• The precedence for label expansion in last decade has been• The precedence for label expansion in last decade has beenIDE randomized clinical trials

raj r. makkar, md - promedica international€¦ · savr: 27.5% zhao zg. et al. nature reviews in...

Documents