ACC 2015

Jae K. Oh, MDOn Behalf of the US CoreValve Investigators

Remodeling of Self-Expanding Transcatheter Aortic Valve Is Responsible for Regression of Paravalvular Aortic Regurgitation: An Observation from CoreValve US Pivotal Trial

CoreValve US Pivotal Trial

ACC 2015

Consulting for Medtronic, Inc.

Presenter Disclosure Information

Medtronic personnel performed all statistical analyses and assisted in the graphical display of the data presented.

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• Transcatheter aortic valve replacement (TAVR) has become an effective therapy for patients with severe aortic stenosis deemed extreme and high risk for surgical AVR.

• Despite its therapeutic and technical success, paravalvular aortic prosthetic regurgitation (PVAR) is one of the major complications after TAVR.

• However, PVAR was found to regress over time in patients who underwent TAVR with the CoreValve which has a self-expanding Nitinol frame.

Background

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Hypothesis: Outward remodeling of the aortic annulus by continuous self-expansion of the CoreValve bioprosthesis reduces the severity of PVAR

Aims: 1. To assess the prevalence and the natural history of

PVAR2. To perform detailed serial hemodynamic analyses of

forward cardiac output and aortic bioprosthesis

Hypothesis and Aims

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• All implanted patients with severe AS in the CoreValve US Pivotal Extreme Risk Trial were studied (from 41 US sites)

• Annular sizing ratio with CoreValve perimeter using CT of aortic annulus perimeter

• Echocardiography at baseline, discharge, 1, 6, and 12 months analyzed by the Echo Core Lab at Mayo Clinic according to ASE/VARC 1 criteria

Methods

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ACC 2015Determination of PVAR Severityby Integrating Multiple Parameters

<10%(<36°)

10 – 20%(36-72°)

>20%(>72°)VARC-1

Mild Moderate Severe

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RESULTS

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Characteristic, % or mean ± SDTAVR

N=634Age (years) 82.7 ± 8.4Men 47.3STS Predicted Risk of Mortality (%) 10.4 ± 5.6NYHA class III/IV 91.8Body surface area (m2) 1.8 ± 0.3 Creatinine >2 mg/dL 4.1

Baseline Demographics

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ACC 2015Percentage of Echo Exams with Total Aortic Regurgitation and PVAR at Discharge

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ACC 2015PVAR Paired Comparison at Discharge and 1 Year

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1 YearDischarge None

(N=123)Trivial

(N=143)Mild

(N=102)Moderate

(N=14)Severe(N=1)

None 49 18 7 1 0Trivial 50 48 34 2 0Mild 23 66 42 6 0Moderate 1 11 18 5 1Severe 0 0 1 0 0

Of 137 mild PVAR patients at discharge, 89 (65%) had none/trivial at 1 yr Of 36 moderate PVAR at discharge, 30 (83%) had <moderate at 1 yr

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PVAR at Discharge and 1 Year

ACC 2015Impact of PVAR on All-Cause MortalityLandmark Analysis

None/Trace 296 280 254 233

Mild 216 206 173 157

Moderate 49 47 38 37

Severe 7 3 1 1

No. at Risk

0-1 M 1-6 M 6-12 M

All-C

ause

Mor

talit

y (%

)

Months Post Procedure

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ACC 2015Annulus Sizing RatioValve Perimeter – Annulus Perimeter Annulus Perimeter X 100

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Annu

al S

izin

g Ra

tio (%

)

ACC 2015Acute Improvement of AV HemodynamicsTAVR with CoreValve

Mean ± SD (#) Baseline Discharge*

AV peak velocity (m/s) 4.33 ± 0.67 (624)

2.08 ± 0.45 (578)

AV mean gradient (mm Hg) 47.81 ± 15.20 (624)

9.67 ± 4.44 (577)

Effective orifice area (cm2) 0.73 ± 0.24 (518)

1.78 ± 0.51 (509)

* P <0.0001 for all parameters 14

ACC 2015Stroke Volume Changes after TAVR

15Error bars represent standard deviation

ACC 2015Further Improvement in AV HemodynamicsAt 1 Month

Mean ± SD (#) Baseline Discharge 1 Month

Heart rate (bpm) 70.1 ± 13.0 (632)

74.2 ± 12.4 (593)

71.0 ± 12.8 (559)

LVOT velocity time integral (cm) 21.66 ± 5.58 (572)

20.86 ± 4.96 (552)

21.06 ± 5.24 (532)

AV peak velocity (m/s) 4.33 ± 0.67 (624)

2.08 ± 0.45 (578)

1.99 ± 0.46 * (543)

AV velocity time integral (cm) 104.45 ± 22.27 (624)

39.06 ± 9.86 (577)

39.37 ± 11.27 (544)

AV mean gradient (mm Hg) 47.81 ± 15.20 (624)

9.67 ± 4.44 (577)

8.93 ± 4.62 * (544)

Effective orifice area (cm2) 0.73 ± 0.24 (518)

1.78 ± 0.51 (509)

1.85 ± 0.58 ** (500)

16*P <0.0001 **P=0.03

ACC 2015Continuous Reduction in AV Gradient

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ACC 2015AV Velocity and EOA

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*

*****

ACC 2015LVOT DiameterOuter to Outer Edge

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1. PVAR ≥ moderate severity occurred in 9.4% of patients after TAVR; however 83% of these patients experienced a decreased in severity by at least 1 grade at 1-year follow-up.

2. The annular sizing ratio in patients with none to trivial PVAR at 1 year was significantly higher than that of patients with > mild PVAR at 1 year.

3. In addition to acute improvement at discharge, AV velocity, mean gradient, and EOA further improved significantly at 1 month and were sustained up to 1 year, suggesting continuous self-expansion of the CoreValve.

Summary

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Paravalvular aortic regurgitation was common after TAVR with CoreValve, but only severe PVAR was associated with

increased mortality. There was regression of mild to moderate PVAR. This regression is possibly related to

optimal oversizing of the bioprosthesis and continuous outward expansion of the CoreValve with Nitinol frame.

Further confirmation with serial CT or 3D echocardiography is needed.

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Conclusion

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Thank You !

Jae K. Oh, MD; Stephen H. Little, MD; Sahar M.

Abdelmoneim, MD; Michael J. Reardon, MD; Neal S.

Kleiman, MD; Grace Lin, MD; David Bach, MD; Linda

Gillam, MD; Biswajit Kar, MD; Joseph Coselli, MD; Partho

P. Sengupta, MD; Kanny Grewal, MD; James Chang, MD;

Yanping Chang, MS; Mike Boulware, PhD; David H. Adams,

MD; Jeffrey J. Popma, MD

for the CoreValve US Pivotal Trial Clinical Investigators