MITRAL REGURGITATION: SCOPE OF PROBLEM AND

LANDSCAPE OF TMVR

Ailin Barseghian El-Farra, MD, FACCAssistant Professor, Interventional Cardiology

University of California, IrvineDepartment of Cardiology

Prevalence of Mitral Regurgitation Increases with Age

Nkomo VT, et al. Burden of valvular heart disease: a population-based study. The Lancet 2006 368, 1005-1011.

Moderate to Severe MR

Pre

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se (

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MR – Survival and HF hospitalizations

• Patients with MR have:

– 2-fold shorter survival

– 2-fold more heart failure hospitalizations

Prakash R, Horsfall M, Markwick A, et al. Prognostic impact of moderate or severe mitral regurgitation (MR) irrespective of concomitant comorbidities: a retrospective matched cohort study. BMJ Open. 2014;4(7):e004984. Published 2014 Jul 17.

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ANATOMY OF THE MITRAL VALVE

Nyman CB, et al. J Am Soc Echocardiogr 2018;31:434-53.

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PRIMARY vs SECONDARY MITRAL REGURGITATION

Zoghbi WA, et al. J Am Soc Echocardiogr 2017;30(4):303-371.

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NORMAL, PROLAPSE, FLAIL LEAFLET COAPTATION

Nyman CB, et al. J Am Soc Echocardiogr, 2018;31(4):434-53.

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PROLAPSED LEAFLET

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FLAIL LEAFLET

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PRIMARY or “Degenerative”

MITRAL REGURGITATION

Zoghbi WA, et al. J Am Soc Echocardiogr, 2018;30(4):303-371.Fuster V, Walsh RA, Harrington RA: Hurst’s The Heart, 13 th Edition: www.accessmedicine.com. Copyright The McGraw-Hill Companies, Inc.

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SECONDARY or “FUNCTIONAL” MITRAL REGURGITATION

Capoulade R, et al. J Thorac Dis 2017;9(Suppl 7):S640-S660.

Stages of Progression of VHDSTAGE DEFINITION DESCRIPTION

A At Risk Patients with risk factors for development of VHD

B Progressive Patients with progressive VHD (mild-to-moderate severity and asymptomatic).

C Asymptomatic Severe Asymptomatic patients who have the criteria for severe VHD:

• C1 Asymptomatic patients with severe VHD in whom the left or right ventricle remains compensated

• C2 Asymptomatic patients with severe VHD, with decompensation of the left or right ventricle

D Symptomatic Severe Patients who have developed symptoms as a result of VHD

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SCOPE OF MITRAL REGURGITATION

• We are operating after the onset of left ventricular dysfunction

• We need lower risk, effective and durable interventions

• Still need to determine the patients that will benefit

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EVEREST II Randomized Clinical Trial

Feldman T, et al. NEJM 2011;364:1395-406

DEVICE GROUPPercutaneous mitral valve

repair (MitraClip)N=184

CONTROL GROUPSurgical repair or

replacementN=95

279 patients enrolled in 37 sitesSevere MR (3+ or 4+)

73% degenerative MR, 27% functional MRRandomized 2:1

Echo and Clinical Follow up - 5 years

EVEREST II Randomized Clinical Trial

EVEREST II Randomized Clinical Trial

Primary End Point at 1 and 5 years: Freedom from death, MV surgery, or 3-4+ MRDegenerative Mitral Regurgitation, Functional Mitral Regurgitation

Feldman T, et al. NEJM 2011;364:1395-406Feldman T, et al. JACC 2015;66:2844-54

Secondary or Functional MR Due to Left Ventricular Dilation

Asgar AW, et al. J Am Coll Cardiol2015;65:1231-48

ISCHEMIC Cardiomyopathy

IDIOPATHIC DILATED Cardiomyopathy

Top Advances in 20191. Edge-to-Edge Mitral Valve Repair Trials

• MitraClip

– MitraFR

– COAPT

• PASCAL

– CLASP Study

2. Transcatheter Mitral Valve Replacement (TMVR)

• SAPIEN 3 MViV

Khan f, et al. Front. Cardiovasc. Med., 18 September 2019

MITRA-FR Trial

304 patients with SMR due to LV dysfunction, EF 15-40%, NYHA II-IVa, hospitalization for HF within the previous 12 months, not surgical candidates

Randomized 1:137 French centers

MitraClip + Medical TherapyN=152

Medical Therapy aloneN=152

Primary Endpoint: Freedom from death or HF hospitalization through 12 months

Obadia JF, et al. N Engl J Med. 2018;379:2297-306

MITRA-FR Trial

COAPT Trial

610 patients with heart failure and moderate-to-severe (3+) or severe (4+) secondary MR who remained symptomatic despite

maximally-tolerated goal-directed medical therapyRandomized 1:1

MitraClip + Medical TherapyN=305

Medical TherapyN=305

Primary Endpoint: All HF hospitalizations through 24 months

COAPT Trial

Primary Effectiveness Endpoint: All hospitalizations for HF within 24 months

NNT to prevent 1 death

1. Packer M, et a l NEJM 19962. SOLVD Investigators. NEJM 1991;325:294-3023. Swedberg K, et a l. Lancet 2010;376:19884. Zannad F, et al. NEJM 2011;364:11-215. McMurray JJV, et a l . NEJM 2014;371:993-10046. Stone GW, et al. NEJM 2018;379-2307-18

Landscape following COAPT trial

• Optimism with MV therapies

• Heart failure specialists are now more actively involved

COMMERCIALLY AVAILABLE TMVR DEVICES

MitraClip• Primary (Degenerative) MR

• Prohibitive surgical risk

• 10/24/2013

• Secondary (Functional) MR

• All surgical risk

• 3/14/2019

TREATMENT OPTIONS: MITRAL REPAIR VS REPLACEMENT

Courtesy of E Grube

Courtesy of E Grube

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ALFIERI STICH

Alfieri O. (2015) The Genesis of the Edge-to-Edge Technique. In: Alfieri O., De Bonis M., La Canna G. (eds) Edge-to-Edge Mitral Repair. Springer, Cham

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MitraClip

Delgado V, et al. Eur Heart J Suppl 2010;12:E10-E23.

• Standard therapy for select patients

• Excellent safety

• Comparable efficacy

• Durability up to 4 years

PERCUTANEOUS THERAPY FOR MR

The 4th Generation MitraClipMitraClip G4

• WIDER CLIP ARMS

• 4 CLIP SIZES– BETTER COAPTATION

• CONTROLLED GRASPING

• CONTINUOUS LEFT ATRIAL PRESSURE MONITORING

• MORE PRECISE AND PREDICTABLE STEERING

REPAIR-MR

• RANDOMIZED CLINICAL TRIAL

• INTERMEDIATE SURGICAL RISK

• MITRAL VALVE SURGICAL REPAIR VS MITRACLIP

• INCLUSION: AGE >75, OR >65 WITH RISK

TREATMENT OPTIONS: MITRAL REPAIR VS REPLACEMENT

Courtesy of E Grube

Andersen Stent-Valve 1989The valve was constructed of a handmade wire frame to which was sewn a porcine valve.

Transcatheter aortic valve implantation: The evolution of prostheses, delivery systems and approaches - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/The-Andersen-valve-The-valve-was-constructed-of-a-handmade-wire-frame-to-which-was-sewn_fig9_224809453 [accessed 21 Jan, 2020]

https://healthcare-in-europe.com/en/news/tavi-s-unsung-hero.html

First In Man - Alain Cribier

Cribier, Alain. (2017). The development of transcatheter aortic valve replacement (TAVR). Global Cardiology Science and Practice. 2016.

APRIL 16, 2002

COMMERCIALLY AVAILABLE TMVR DEVICES

MitraClip• Primary (Degenerative) MR

• Prohibitive surgical risk

• 10/24/2013

• Secondary (Functional) MR

• All surgical risk

• 3/14/2019

SAPIEN 3:• Mitral Valve-In-Valve

• High or greater surgical risk

• 6/5/2017

Guerrero M, et al. Transseptal transcatheter mitral valve‐in‐valve: A step by step guide from preprocedural planning to postprocedural care. CCI May 2017;92:E185-E196.

MITRAL VALVE-IN-VALVE OPTION

All-Cause Mortality According to TMVR

Yoon SH, EHJ 2018;40:441

TRANSCATHETER MITRAL VALVE REPLACEMENT

Courtesy of E Grube

TMVR

• Devices in Randomized Controlled Trials in US

1. Tendyne (Abbott)

– SUMMIT

2. Intrepid (Medtronic)

– APOLLO

MITRAL REGURGITATION IN THE US

• Most PRIMARY MR patients are better served with surgical repair

• Most SECONDARY MR patients are best treated with optimal or guideline-directed medical therapy.

• Interventional population is unknown

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