pinak b. shah, md, facc, fscai director, cardiac ......paravalvular leak (pvl) savr = surgical...

Percutaneous Therapies For Valvular Heart Disease

Pinak B. Shah, MD, FACC, FSCAI

Director, Cardiac Catheterization Laboratory

Cardiovascular Division, Department of Internal Medicine

Brigham and Women’s Hospital

Assistant Professor of Medicine

Harvard Medical School

Disclosures

I have received honoraria for physician training programs

and case proctoring from Edwards LifeSciences

• Aortic Valve

• Trans-catheter Aortic Valve Replacement (TAVR)*

• Mitral Valve

• Percutaneous Edge-to-Edge Repair*

• Trans-catheter Mitral Valve Replacement

• Other Trans-catheter Mitral Repair Devices

• Tricuspid Valve

• Tricuspid Repair Devices

* FDA Approved

Percutaneous Trans-Catheter Valve Therapies

Historical Gold Standard for Aortic Valve Replacement

Surgical Aortic Valve Replacement (SAVR)

Catheter based delivery

and implantation of an

aortic valve

Trans-catheter Aortic Valve Replacement (TAVR)

SAVR TAVR

Access Sternotomy Vascular

Cardiopulmonary

Bypass

Yes No

General Anesthesia Yes No

Hospitalization 5-7 Days 1-3 Days

Recovery 4-6 weeks < 1 week

Valve Types mechanical/biological biological

SAVR vs TAVR

FDA Approved in US

FDA Approval Expected

Lotus Edge

2nd Generation

Boston Scientific

Portico

St. Jude Medical

CoreValve Evolut R

2nd Generation

Medtronic

Sapien 3

3rd Generation

Edwards LifeSciences

CoreValve Evolut Pro+4th Generation

Medtronic

TAVR Valves in the United States

Sapien Ultra

4th Generation

Edwards LifeSciences

• Location: CCL vs. Hybrid OR

• Anesthesia: GA vs. IVCS

• Access Points:

• Venous (IJ or femoral): temporary pacer

• 5-6Fr Arterial (radial or femoral): pigtail for aortography

• 14Fr Arterial (femoral): delivery sheath

• Large Sheath Closure

• Suture mediate closure devices: Perclose

• Post-procedure recovery

• CCU vs. floor

• Procedure time: ~60 minutes

• D/C 24 hours, normal activity 72 hours

TAVR 2020

http://riskcalc.sts.org/STSWebRiskCalc273/

Assessing Surgical Risk: STS Score

Assessing Surgical Risk

Trial Year Device Risk Result

PARTNER B 2010 Sapien Inop TAVR > Medical Therapy

PARTNER A 2011 Sapien High TAVR non-inf to SAVR

Corevalve XR 2014 Corevalve Inop TAVR > Performance Goal

Corevalve HR 2014 Corevalve High TAVR non-inf to SAVR, possibly superior

PARTNER 2 2016 Sapien XT Intermed TAVR > SAVR for TF candidates

Sapien 3 HR 2016 Sapien 3 High/Inop Low Event Rates for SAVR

Sapien 3 IR 2016 Sapien 3 Intermed TAVR > SAVR

SURTAVI 2017 Corevalve &

Evolut R

Intermed TAVR non-inf to SAVR

PARTNER 3 2019 Sapien 3 Low TAVR > SAVR

Corevalve Low Risk 2019 Corevalve Evolut R Low TAVR non-inf to SAVR

TAVR Clinical Trials (>10,000 Patients)

TAVR Specific Concerns c/w SAVR

• Stroke/Cerebral Emboli

• Paravalvular Regurgitation

• Need for Permanent Pacemaker

• Leaflet Thrombosis

• Durability

• Coronary Access

• Bicuspid Valves

Sources of Debris Leading to CVA During TAVR

TAVI DEVICES

Foreign material,

thrombus

NATIVE HEART

Myocardium

TRANSVERSE ARCH

Arterial wall, calcific

and atherosclerotic

material

ASCENDING ARCH

Arterial wall, calcific and

atherosclerotic material

STENOTIC VALVE

Leaflet tissue and

calcific deposits

SAVR = surgical aortic valve replacement.

Paravalvular Leak (PVL)


Paravalvular Leak (PVL)

Risk Factors

• Undersized prosthesis

• Hi/Low THV positioning

• Severe LVOT/annular calcium

• Irregularly shaped annulus

Pacemaker after TAVR

P < 0.001

• Trauma to conduction

system

• Higher risk with baseline

conduction disease

• Higher risk with lower

implants

• PPM rates and PVL rates

are inversely proportional

TAVR Clinical Trials

Trial Year Device Risk Death

(1yr)

Stroke

(30d)

Mod/Sev

PVL (30d)

PPM (30d)

PARTNER B 2010 Sapien Inop 30.7 6.7 10.5 3.4

PARTNER A 2011 Sapien High 24.2 5.5 12.2 3.8

Corevalve XR 2014 Corevalve Inop 26.0 4.0 11.4 21.6

Corevalve

HR

2014 Corevalve High 14.2 4.9 9.0 19.8

PARTNER 2 2016 Sapien XT Intermed 14.5 6.4 3.7 8.5

Sapien 3 HR 2016 Sapien 3 High/Inop 14.4 2.4 2.5 16.9

Sapien 3 IR 2016 Sapien 3 Intermed 7.4 2.4 1.5 10.2

SURTAVI 2017 Corevalve

& Evolut R

Intermed 8.1 5.4 5.3 25.9

PARTNER 3 2019 Sapien 3 Low 1.0 0.6 0.8 6.5

CoreValve LR 2019 Evolut R Low 2.3 3.4 3.5 17.4

TAVR Specific Concerns c/w SAVR

• Stroke/Cerebral Emboli

• Paravalvular Regurgitation

• Need for Permanent Pacemaker

• Leaflet Thrombosis

• Durability

• Coronary Access

• Bicuspid Valves

• TAVR improves mortality in inoperable patients.

• TAVR is at least as effective at reducing mortality in high,

intermediate, and low surgical candidates.

• TAVR highly effective at improving symptoms/functional

class

• Durability of TAVR valves appears to be excellent out to 5

years

TAVR Clinical Trials: What Have We Learned?

“Inoperable” or “Extreme Risk”

• Patients in whom two cardiac surgeons feels the risk of mortality from sAVR is

likely > 50%

“High Risk”-

• Patients with a Society of Thoracic Surgeons Risk Score (STS) of ≥ 8%

• Patients with STS Risk Score < 8% but in whom the estimated risk of mortality

from sAVR is ≥ 15% by two surgical assessments

“Intermediate Risk”

• Patients with STS score between ≥ 4% but < 8%

• Patients with STS score < 4% but in whom estimate risk of mortality is between

4-8% by surgical assessment

“Low Risk”

• Patients with STS < 4%

FDA APPROVED FOR TAVR

FDA APPROVED FOR TAVR

August 2019

TAVR Candidacy and Surgical Risk

Severe Native Aortic Stenosis in a Tri-leaflet Aortic Valve

Life expectancy >12 months

Heart Team Evaluation

• Interventional Cardiologist

• Cardiac Surgery

Intermediate or High Risk or Inoperable

• Two cardiac surgeon evaluation

• STS > 3.0% OR

• Surgical assessment deems patient intermediate risk

Severe Aortic Stenosis in a Failed Surgically Implanted Bioprosthetic Valve in

High Risk Patients

Cardiac Surgeon and Interventional Cardiologist must be present for

procedure

FDA/CMS Indication for TAVR

• Device improvments

• Reduce PVL

• Reduce PPM

• Smaller device profiles

• Optimal anticoagulant/antithrombin regimens

• Several on-going Trials

• Reducing stroke risk

• Shields

• Filters

• Formal assessment of durability

• 10 year f/u in PARTNER 3

• Bicuspid valves

• Defining optimal timing of treatment of AS

• EARLY TAVR

TAVR: The Future

• Aortic Valve


• Mitral Valve




• Tricuspid Valve


* FDA Approved

Percutaneous Approaches to Valvular Heart Disease

Edge-to-Edge Trans-catheter Mitral Valve Repair

MitraClip (Abbott)FDA Approved

Pascal (Edwards)In Clinical Trials

Alfieri Stitch

Degenerative vs. Functional MR

Trial Year Comparator Risk No. Patients Result

EVEREST 1 2006 Single Arm Operable 107 MC feasible and safe

EVEREST 2 2011 MV Repair Operable 178 MC

80 MV Repair

MV repair > MC

EVEREST 2

HR

2012 Single Arm High 78 MC > Performance Goal

EVEREST 2

HR

REALISM

2014 Single Arm High

Non-High

628

271

Improved MR, NYHA, and

reduced readmissions

MitraClip: Early Clinical Trials

Based on these data,

MitraClip presently

approved for patients with

degenerative MR who are

too high risk for surgery.

MitraClip for Functional MR

Mitra-FR

Primary End Point:

Death or Unplanned

Hospitalization at 12

Months

NEJM 2018; 379: 2297-2306

COAPT

NEJM 2018; 379: 2307-2318

Asgar et al. JACC, 2015.

Clinical Trials of MitraClip for Functional MR

• Access to MV more difficult• Trans-apical access

• Trans-septal access

• MV annulus very large• Larger device sizes

• MV annulus not rigid• Requirement for active fixation

• Proximity to LVOT• LVOT obstruction

• MV complex structure• Chords, papillary muscles

TMVR: Challenges to TMVR Development

Intrepid (Medtronic) Tendyne (Abbott)

TMVR Devices in Clinical Trials

• Both devices in pivotal trials

• Both require trans-apical access

Evoque (Edwards) M3 (Edwards)

• In early feasibility studies

• Can be delivered trans-septally

Other Mitral Valve Repair Devices

Cardioband (Edwards) Carillon (Cardiac Dimensions) Monarc (Edwards)

Harpoon (Harpoon Medical) Mitralign (Mitralign)

• Aortic Valve


• Mitral Valve




• Tricuspid Valve


* FDA Approved

Percutaneous Trans-Catheter Valve Therapies


Tricuspid Repair Devices- Investigational

Tricuspid Clipping- TRILUMINATE Trial


Tricuspid Repair Devices- Investigational

• SAVR = surgical aortic valve replacement.

Valve-in-Valve Procedures

Aortic Valve-in-Valve Mitral Valve-in-Valve Tricuspid Valve-in-Valve

• Approved for high-

risk

• Ongoing studies of

intermediate and

low risk

• Approved for high-

risk

• Ongoing studies of

intermediate and

low risk

• Not FDA approved

• TAVR is standard of care (compared to surgical AVR) in patients who are

deemed inoperable or high risk for surgical AVR and is the preferred treatment

for all patients independent of surgical risk for AVR.

• Mitra-clip can be considered in patients high risk for surgical MVR with severe

symptomatic MR due to degenerative mitral valve disease.

• Outcomes with Mitra-clip in selective patients with functional MR are

encouraging

• Transcatheter mitral valve replacement and tricuspid repair technologies are on

the horizon

Conclusions

Question 1

Per current FDA guidelines, which of the following patients with

severe symptomatic aortic stenosis can be considered for

TAVR?

A. 65 year old man with severe aortic regurgitation, STS 1.5%,

surgical assessment low risk

B. 65 year old man with failed surgically placed bioprosthetic

valve, STS 1.5%, surgical assessment low risk

C. 82 year old woman with heavily calcified aorta, STS 1.5%,

surgical assessment high risk

D. 82 year old woman, Stage IV ovarian cancer, STS 4.7%,

surgical assessment intermediate risk

Question 1- Explanation

At the present time, TAVR is only approved for patients aortic stenosis, not aortic

regurgitation. Therefore, answer A. is incorrect. Risk is determined by a combination of STS

score and a surgeons assessment. Answer B. is incorrect since valve-in-valve procedures

are approved only for patients who are high risk for re-do AVR. Answer D. is incorrect in that

this patient likely has a survival of less than 6 months and CMS requires expected survival of

at least 12 months for a patient to be considered for TAVR. Answer C. is correct because

despite the STS score being in the low-risk range, the patient has a calcified aorta which

increases surgical risk significantly. This patient would likely be deemed a high risk surgical

candidate by surgical assessment and therefore can be considered for TAVR.

Question 2

Which of the following statements is incorrect regarding

the risks of trans-catheter aortic valve replacement?

A. This risk of requiring a permanent pacemaker after

TAVR is ~10%.

B. Moderate to severe paravalvular aortic regurgitation

occurs in 10% of patients.

C. The risk of stroke is ~2%.

D. The risk of myocardial infarction due to coronary

obstruction is <<1%.

Question 2- Answer

Which of the following statements is incorrect regarding

the risks of trans-catheter aortic valve replacement?

A. This risk of requiring a permanent pacemaker after

TAVR is ~10%.

B. Moderate to severe paravalvular aortic regurgitation

occurs in 10% of patients.

C. The risk of stroke is ~2%.

D. The risk of myocardial infarction due to coronary

obstruction is <<1%.


Paravalvular regurgitation is a limitation of TAVR that is not seen with SAVR. Because a

TAVR valve is being forced to conform with an annulus that may be irregular, there are likely

going to be areas where the device does not fully conform resulting in leakage around the

device. As long as the paravalvular regurgitation is graded as mild or less, it is unlikely to

have long-term consequences to the patient. However, there is a large body of data showing

that patients left with moderate to severe paravalvular regurgitation are at higher risk for

adverse events post TAVR. The estimated rate of moderate to severe paravalvular

regurgitation after TAVR is ~2% in the modern era of TAVR. The risk of permanent

pacemaker after TAVR is decreasing with device and technique modifications but in general,

the risk for a patient needing a permanent placement is ~10%. Patients with pre-existing

conduction disease (first degree AV block, left anterior fascicular block, right bundle branch

block) are at increased risk of requiring a permanent pacemaker after TAVR. The remainder

of the TAVR related complication rates in this question are correct. Review of the NCDR TVT

database, a mandatory database that all centers performing TAVR report to, shows that the

stroke risk is ~2% and the myocardial infarction risk is well below 1%.

Question 3

Which of the following patients is the best candidate for Mitra-Clip

therapy?

A. 79-year old man with severe functional MR, class III CHF symptoms,

EF 25%, STS score 8.2%, on beta-blocker monotherapy

B. 79-year old man with severe functional MR, class III CHF symptoms,

EF 25%, STS score 8.2% on maximal medical therapy with beta-

blocker, ACE-I, diuretic, and CRT device.

C. 79-year old man with severe functional MR, class III CHF symptoms,

EF <10%, STS score 8.2% on maximal medical therapy with beta-


D. 65-year old man with severe mitral regurgitation due to flail P2

segment and class II CHF symptoms, STS score 1.7%.

Question 3- Answer

Which of the following patients is the best candidate for Mitra-Clip

therapy?

A. 79-year old man with severe functional MR, class III CHF symptoms,

EF 25%, STS score 8.2%, on beta-blocker monotherapy

B. 79-year old man with severe functional MR, class III CHF symptoms,

EF 25%, STS score 8.2% on maximal medical therapy with beta-


C. 79-year old man with severe functional MR, class III CHF symptoms,

EF <10%, STS score 8.2% on maximal medical therapy with beta-


D. 65-year old man with severe mitral regurgitation due to flail P2

segment and class II CHF symptoms, STS score 1.7%.


Mitra-Clip is now FDA approved for patients with severe degenerative mitral regurgitation who

are considered to be too high risk for surgical mitral valve repair/replacement and for patients

with severe functional mitral regurgitation who are high risk for mitral valve repair/replacement

and who have been maximized on medical therapy yet remain symptomatic. Answer B. is the

best answer as this patient is a high surgical risk patient who has been maximally medically

managed. Answer A. is incorrect as the patient is not on guideline directed medical therapy

for reduced LV function. Answer C. is not the best answer as this patient has severe left

ventricular dysfunction which was an exclusion for participation in clinical trials that showed

benefit of the Mitra-clip in patients with functional mitral regurgitation. Answer D. describes a

low surgical risk patient with degenerative MR who will do better with traditional surgery.

Given that this patient is a low risk patient, this patient would not be indicated for Mitra-clip

under current guidelines.

References:

The PARTNER Trial. NEJM 2011: 2187-2198.

The CoreValve Extreme Risk Study. JACC 2014: 1972-1981.

The PARTNER 2 Trial. NEJM 2016: 1609-1620.

The CoreValve Hi-Risk Study. NEJM 2014: 1790-1798.

The SURTAVI Study. NEJM 2017: 1321-1331.

The EVEREST II Trial. NEJM 2011: 1395-1406.

The MITRA FR Trial. NEJM 2018: 2297-2306.

The COAPT Trial. NEJM 2018: 2307-2318.

The PARTNER 3 Trial. NEJM 2019: ePublication March 2019

The CoreValve Evolut Low Risk Trial. NEJM 2019: ePublication March 2019

pinak b. shah, md, facc, fscai director, cardiac ......paravalvular leak (pvl) savr = surgical...

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