UPDATE ON TAVR, MITRACLIP, AND EMERGING

STRUCTURAL INTERVENTIONS

20th Annual SD Heart Failure Symposium

1/11/2020

Ryan Reeves, MD, FACC, FSCAI

Structural Interventions: The Big Two

• Symptomatic severe AS is associated with a high mortality and only valve replacement improves survival.

• With a comprehensive work-up for procedural planning, TAVR:

– improves survival at one year in inoperable patients.

– is feasible and comparable to SAVR in low, intermediate, and high-risk patients and approved for surgical valve failure.

– complications have decreased with device improvements.

– is associated with shorter procedure times, hospital times, and time to recovery compared to SAVR.

Percutaneous Mitral Valve Repair• MitraClip is an edge to edge repair technique that may significantly reduce

mitral regurgitation through venous access, trans-septal puncture, and guidance by trans-esophageal echocardiography that is approved for degenerative and functional MR.

• If the procedure is successful, outcomes are comparable to surgical repair, but the rate of a successful repair is lower than standard surgery.

Transcatheter Aortic Valve Replacement

Operative Risk• Overall AVR operative mortality is 4% (STS Risk Score)

• Comorbidities increase risk from 4-45% and are increasing

Korfer R, et al. J Heart Valve Dis 1995. 4 Suppl 2: 194-7.Connolly HM, et al. Circulation 2000 101(16)1940-6.Powell DE, et al. Arch Int Med 2000 160(9) 1337-41.Iung and Vahanian. Heart 2012;98,iv7-iv13.

• Elderly, COPD, advanced NYHA class, atrial fibrillation, concomitant CABG, severely reduced LV systolic function, prior MI, CAD, height, weight, renal dysfunction, etc.

46%28%28%

41%

Percentage of comorbidities in PARTNER trial, Cohort B,2010

22%

Frailty• Comprehensive Assessment of Frailty

– Weakness (grip strength), self-reported exhaustion, gait speed, IADL (chores, activities, etc), balance and body control (positions, put on and remove a jacket, turn 360 degrees, etc), albumin, creat, BNP, FEV1

Sundermann, et al. Eur J of Cardiac Surgery, 2011;39:33-37.

30-40% of patients with severe aortic stenosiswere NOT being offered surgery due tocomorbidities!

TAVR Trials for FDA and CMS Approval

• Prospective, Randomized-Controlled, multi-center trials

• Determine the safety and effectiveness of thedevice and delivery systems in: inoperable high risk intermediate risk low risk,symptomatic patients with severe aorticstenosis.

• Major cardiovascular outcomes, secondaryoutcomes, long-term follow-up

High Surgical Risk - 2011

Intermediate Surgical Risk - 2016

Inoperable - 2010

Low Surgical Risk - 2019

PARTNER Trial Results

Low Surgical Risk - 2019

Inoperable - 2014 High Surgical Risk - 2014

Intermediate Surgical Risk - 2016

Core/EvolutValve Trial

Results

At 1 year, a paired analysis of the distance covered during a 6-minute walk test showed that there was significant improvement after TAVR (P = 0.002) and no change after standard therapy (P = 0.67).

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Low risk functional data

Baron et al. JACC 2019

Kansas City Cardiomyopathy Questionnaire- Overall SummaryProportion of Patients Achieving Specific Levels of Change

Vascular trauma

Stroke and TIAParavalvular

Aortic Regurgitation

Heart Block

Early trials Increases risk of mortality

Higher total rate than SAVR, but similar stroke rates

Increases risk of mortality

Pacemaker requirement (only with Core Valve)

Why? Large delivery systems & diseased vasculature

Ascending aortic disease and crushing a thick, native aortic valve

Using a round balloon or placing a round valve in an irregularly shaped orifice, undersizing, poor deployment

Exerting pressure on the left ventricular outflow tract with valve deployment, pre-existing conduction disease

Response (operators and industry)

Smaller equipment and operator experience

Smaller equipment, more maneuverabledelivery catheters, better planning, less inflations across the valve

Better pre-procedural planning with CT scans, oversizing, skirt around the valve, inflation after valve placement, easier deployment

Repositionable,easier deployment, shorter frame extension into LVOT

Contemporarytrials

Reduced vascularcomplications by > 50%

At least equivalent to and trending lower than SAVR

Reduced 60-80% Reduced pacemaker implantations by 40-50%

TAVR Complications update

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

P1B(TF) P1A P2B (TF) P2BXT(TF) S3HR S3IR P3

6.3%

5.2%

4.5%

3.5%

2.2%

1.1%

0.4%

All Cause Mortality at 30 Days

TAVR Over Time

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

P1B(TF) P1A P2B (TF) P2BXT(TF) S3HR S3IR P3

6.7%

5.6%

4.1%4.3%

1.5%

2.6%

0.6%

All Strokes at 30 Days in TAVR Patients

TAVR Over Time

0%

5%

10%

15%

20%

25%

P1B(TF) P1A P2B (TF) P2BXT(TF) S3HR S3IR P3

12%11.5%

16.9%

24.2%

2.9%

4.2%

0.8%

Moderate/Severe Paravalvular Leak at 30 days

TAVR Over Time

Edwards S3 Valve

Core Valve: self-expanding, nitinol frame, porcine pericardium leaflets; 23, 26, 29, and 31mm valves (and as of three weeks ago, 34mm)

Core Valve

CT scan based measurements include:

• Aortic annular area and perimeter

• LVOT and aortic diameters

• Height of coronary artery ostia

• Artery size and tortuosity

CT scan based measurements include:

• Aortic annular area and perimeter

• LVOT and aortic diameters

• Height of coronary artery ostia

• Artery size and tortuosity

CT scan based measurements include:

• Aortic annular area and perimeter

• LVOT and aortic diameters

• Height of coronary artery ostia

• Artery size and tortuosity

CT scan based measurements:Artery size and tortuosity

CT scan based measurements:Artery size and tortuosity

CT scan based measurements:Artery size and tortuosity

Sapien 3 Deployment

Temporary pacemaker in RV

CoreValveNitinol – ‘memory metal’

Percutaneous Mitral Valve Repair

• Degenerative MR affects up to 600,000 persons in the US, some of which areconsidered at prohibitive risk for standard surgical intervention.

• The MitraClip percutaneous mitral valve repair system was approved inOctober 2013 for use in symptomatic patients with 3+ or worse degenerativeMR at prohibitive risk for surgery after the EVEREST trial.

• The COAPT trial published in 2018 showed that after optimization of medicaltherapy, patients with functional MR had improved outcomes with MitraCliptherapy.

Alegria-Barrero et al. Eurointervention 2012.

Percutaneous Mitral Valve Repair

Percutaneous Mitral Valve Repair

Percutaneous Mitral Valve Repair

Percutaneous Mitral Valve Repair

Reduction of mitral regurgitation from moderate-severe to mild with one MitraClip device.

Percutaneous Mitral Valve Repair

EVEREST IIRepeat Surgical Intervention

Feldman et al. J Am Coll Cardiol, 2015.

Functional MR Trials

Major Inclusion Criteria

Severe secondary MR

Regurgitant Volume >30mLOr ERO >20mm2

EF 15-40%

NYHA ≥II

Heart failure hospitalization within 1 year

Investigator determined optimal MT

Not surgical candidate

Major Inclusion Criteria

Secondary 3+/4+ MR

Optimal therapy for CAD, CHF, LV dysfunction, MR

EF 20-50%, LVED ≤ 70mm

NYHA ≥II

Heart failure hospitalization within 1 year or BNP≥300

MitraClip feasible

Not surgical candidate

MITRA-FR• 2013-2017, France,

307 patients randomized

COAPT• 2012-2017, US/Canada,

614 patients randomized

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MITRA-FR: more Implantation Failure and more device group

events and less MT events

COAPT NNT to prevent one hospitalization = 3.1 and to

save one life = 5.9.

LV End-Diastolic Volume and EROA Ratio Further Defines MR

Packer and Grayburn. JACC Heart Failure 2019

Percutaneous Tricuspid Repair (US off label)

Propensity matched registry patients

LA-RA shunting Systolic or Diastolic Heart Failure

• Theory: decrease pulmonary congestion by relieving excess left atrial volume and pressure

• Small trials have shown a decrease in pressure with exercise but an improvement in functional status has yet to be seen.

Guimares et al. Eurointervention 2019

Other Structural Interventions• Left Atrial Appendage Occlusion

– Stroke Prevention in Atrial Fibrillation patients at high-risk for bleeding

• Pulmonary Valve Reugurgitation or Stenosis:– Melody or Edwards valve placement (More in development)

• Mitral Stenosis: – Percutaneous Balloon Mitral Valvotomy (acceptable durability)

• Atrial Septal Defect:– Secundum: Closure up to 36mm in diameter despite deficient

rims; fenestrated if RV failure– Sinus Venosus Defect: creative percutaneous procedures are

possible

• Persistent Ductus Arteriosus– Percutaneous Closure Thank ou