Multi-Disciplinary Approach to Mitral Disease

MULTI-DISCIPLINARY APPROACH TO MITRAL DISEASE

CARDIOLOGIST

Nikolaos Kakouros, MBBS MRCP PhD MD(Res) FACC FSCAI Director, Structural Heart Disease program Program Director, Interventional Cardiology SHD Fellowship Co-director, TAVR program Assistant Professor of Medicine University of Massachusetts Medical School Conflicts of Interest

▪ I do not have any financial arrangements or affiliations with any of the corporate organizations offering financial support or educational grants for this continuing medical education program Objectives

▪ Understand catheter based approaches to mitral valve disease ▪ Describe the evaluation and indications for catheter based interventions ▪ Describe the common complications associated with catheter based intervention Multi-disciplinary Approach To Mitral Disease

Russell C Brock (1903-1980)  leading British chest and heart surgeon  Pioneer of modern open heart surgery

▪ 1947 - Surgical pulmonary valve dilation and infundibular muscle resection in Fallot’s tetralogy to reduce R-L shunt ▪ Exchange professorships with Dr Alfred Blalock at JHH helped introduce new tech (hypothermia, heart-lung machine) to the nascent field of cardiac surgery Russell C Brock (1903-1980)

1948 – One of first four surgeons to operate on rheumatic mitral stenosis Finger-fracture Valvuloplasty (closed commissurotomy) RC Brock on Intracardiac Surgery

‘Intracardiac surgery is not for the lone worker. Team work is essential … success is due principally to the loyal and unstinted co-operation of my various colleagues who take part with me in this work both at Guy’s and the Brompton Hospital. To give one example, at Guy’s there is a group of some 15 people actively engaged in the work, and as time passes we find that more and more are drawn into the team.’ Peacock Club – 70 years ago

▪ Established 4/21/1948 as meeting of “those concerned in the management of congenital disease of the Heart” convened by RC Brock ▪ Thomas Peacock – author of 19C text on cardiac malformations

▪ Core Members:  Guy’s cardiologists  Clinical scientists from Medical Research Council  Radiologist  Anesthetists  Surgical assistants  Junior doctors and research fellows  Invited speakers and named visitors Peacock Club

▪ Discussions of life threatening risks of the invasive investigations ▪ Shared management planning ▪ Self-critical reviews of operations that often went badly  Hearts of the patients who died were critically examined in the presence of the whole team ▪ Meticulous documentation of treated and untreated cases. THE MITRAL VALVE MDT approach :MITRAL VALVE DISEASE

STENOSIS REGURGITATION MITRAL STENOSIS ETIOLOGY

RHEUMATIC CALCIFIC 60%, nearly all adult MS

•Misc: Congenital (parachute MV), post-inflammatory, mucopolysaccharidosis, LA myxoma The problem

▪ Rheumatic Heart Disease prevalence:  Industrialized nations 1/100 000  Worldwide: 12 000 0000 Rh Fever and Rh Heart Disease cases (Circulation. 2009;119:e211-e219)  0.14/1000 in Japan, 1.86/1000 in China, 0.5/1000 in Korea, 4.54/1000 in India, 1.3/1000 in Bangladesh

▪ Why?  Streptococcal GrpA infection → Type II hypersensitivity  overpopulation, overcrowding, poverty, poor access to medical care, limited availability of PCN Rheumatic Mitral valve stenosis

• Normal Valve area 4-5cm2 • Valve thickening • Commissural fusion • Chordal fusion RHEUMATIC MITRAL STENOSIS RHEUMATIC MITRAL STENOSIS RHEUMATIC MITRAL STENOSIS Mitral Stenosis

Severe mitral stenosis: MVA <1.5cm2 Critical mitral stenosis MVA < 1.0 cm2 • Asymptomatic • Present with incapacitating dyspnea • Pulmonary hypertension • Hemoptysis • Right heart failure, peripheral edema, orthopnea • Atrial fibrillation: 80% • Systemic thromboembolism: 20% MitralCommissurotomy

1902 : Proposed by Brunton 1920s: First successful surgical commissurotomy 1940-1950s: Trans-atrial and transventricular surgical commissurotomy were accepted clinical procedures. Open commissurotomy preferred in the US 1980s: PTMV emerged 1994: Clinically approved 21st Century: PTMV is the preferred procedure • Angelo Thomas Pezzella et al: Ann. Afr. Chir. Thor. Cardiovasc. 2012;7(1) • International Children’s Heart Fund

Treatment for Mitral Stenosis

PMBC vs SURGERY

Balloon vs. Open Surgical

Turi et al, Circulation, 83, 1179-85, 1991 Mitral Valve Area (cm2) 0.5 1.5 2.5 1 2 0 3 PMV 0.9 Baseline P=NS 0.9 vs 0.9 PMV MVA OMC P=NS 2.1 OMC 6 at Months 2.2 vs seven P=0.001 1.6 CMC CMC Farhat P=NS years 1.8 7 et Years al. 1.8 Circulation 1.3 P=0.001 follow 1998 - up CONCLUSIONS

• PTMV and OMC have comparable initial results and low rates of restenosis, and both produce good functional capacity for at least three years.

• The better hemodynamic results at three years, lower cost, and elimination of the need for thoracotomy suggest that PTMV should be considered for all patients with favorable mitral-valve anatomy. Mechanism of PTMV

PTMV relieves mitral stenosis by splitting fused commissures, similar to surgical commissurotomy PTMV Technique

Transseptal antegrade approach

Double balloon technique Inoue balloon technique Multitrack Cribie dilator

Retrograde approach Double Balloon Technique Inoue Balloon

Kanji Inoue performed first PTMV with the eponymous balloon in 1984 FDA approved in 1994

Inoue Balloon Stages Transeptal TEE/ICE

RHEUMATIC MITRAL STENOSIS post RHEUMATIC MITRAL STENOSIS post RHEUMATIC MITRAL STENOSIS ASD Define success

▪ MVA >2 cm2 or ▪ MV gradient <5 mmHg ▪ Others markers:  50% improvement in valve area  MVA increased to >1 cm2/m2 BSA  STOP when increase in MR by ONE grade (1-4) Inoue Balloon Stepwise Technique

Feldman et al. Cath CV Diag 28: 199, 1993 Minute Inoue 15 30 45 60 75 90 0 vs Procedural 56 Double 84 time Balloon Procedural Double Inoue Fluoroscopic p<0.05 15 Park Balloon Balloon SJ et 25 al. Technique Am time technique J time Coll 1993 Event-free survival (%) 100 20 40 60 80 0 Event 0 Death, 1 - 2 free MVR, Double Inoue 3 Survival Balloon Balloon 4 redoPMV, 5 Kang DH, 6 et p=NS 76 83 NYHA≥3 Years al ± ± J 7 7% 5% Am Coll Cardiol 2000 Complications of PTMV

• Mortality 0-0.6% • Systemic embolization 0-4.5% • Severe MR(+4) 0.9-3% • Left to right shunt (>1.5:1) <5% • Transient heart block and tamponade <5% • Hemopericardium 0.5-5% Contraindication of PMV

• Left atrial thrombus • Apical LV thrombus • MR>2+ • Bleeding diathesis • Severe cardiothoracic deformity Patient selection is fundamental in predicting outcome of PMV

Mitral valve morphology

Echocardiographic Score !!! Echo Score Mitral valve morphology

1 2 3 4

Rigidity mobile valve immobile valve

Thickening thin severe thickening

Calcium no bright echos multiple bright echo

Subvalvular sparse echos multiple thick chordae apparatus Mitral Valve Area (cm2) MVA 0.5 1.5 0 2 1 according 1.0 Pre P<0.001 ES ES - PMV > ≤ 0.8 8 8 (n=601) (n=278) to 2.0 ES Post P<0.001 - PMV Palacios 1.6 Circulation 2002 Success according to ES

Post-PMV MVA ≥ 1.5, 50% increase in MVA, MR ≤ 2+ % 100 P=0.0002

80 86.5% 76.6% 60

0 ES ≤ 8 (n=601) ES > 8 (n=278) Palacios Circulation 2002 Changes Mitral Valve Area (cm2) 0.5 1.5 2.5 1 2 3 0 1 87% 4 2.2 1 90% 5 2.2 in 1 80% 6 MVA 2.1 Echocardiographic 0.9 80% 1.9 7 0.9 & 67% 1.8 8 Success 0.9 68% 1.8 9 0.8 score 59% 1. Post Pre 6 10 0.8 - PMV - 50% 11 PMV 1.5 0.7 29% 12 1.4 10% 20% 30% 40% 50% 60% 0% 70% 90% 80%

Success (%) In-Hospital Events

ES ≤ 8 (n=601) ES > 8 (n=278) P=0.007 6

% 5 P<0.006 5.7

4 4.3 P=NS 3 P=NS

2 2.2 2.1 1 1.3 0.8 1 1 0 Death Tamponade MVR Stroke Palacios Circulation 2002 Survival

Survival (%) 100 20 40 60 80 0 0 20 according Time 40 60 of Follow 80 100 - Echo Total Echo up to 120 (months) Group Score Score ES 140 Palacios > ≤ P<0.001 160 8 8 Circulation 180 2002 Survival (%) 100 20 40 60 80 0 0 Event 20 according Time 40 - 60 of Free Follow Death, Echo 80 Total Score 100 Echo Survival Survival P<0.0001 - up to Group MVR, 120 > Score (months) 8 ES 140 ≤ Palacios 8 redoPMV 160 Circulation 180 2002 Events Survival (%) 100 20 40 60 80 0 0 20 according Time 40 Echo 60 of Score Follow Death, Echo 80 ≥ 100 Score 12 - to up Echo P<0.0001 MVR, 120 9 (months) ES - 11 Score 140 Palacios redoPMV ≤ 160 8 Circulation 180 2002 Long-Term Events

Independent predictors; Redo MVP, MVR, Death

Variables OR CI P

Age 1.02 1.01-1.03 <0.00001 NYHA IV 1.35 1.00-1.81 0.05 Prior commissurotomy 1.50 1.16-1.92 0.002 Echo score 1.31 1.02-1.67 0.03 Pre-PMV MR ≥ 2+ 1.56 1.09-2.22 0.02 Post-PMV MR ≥ 3+ 3.54 2.61-4.72 <0.00001 Post PMV Pul A pressure 1.02 1.01-1.03 <0.00001

Palacios Circulation 2002 CONCLUSIONS

• PTMV is the procedure of choice the treatment of patients with MS for optimal candidates from morphologic and clinical points

• Immediate post-PTMV variables in conjunction with pre-PTMV clinical and mitral morphologic variables identify most likely to benefit long-term Russell C Brock (1903-1980)

1948 – One of first four surgeons to operate on rheumatic mitral stenosis Finger-fracture Valvuloplasty (closed commissurotomy)

“the mitral valve was too calcified to permit dilation; immoderate enlargement of the mitral orifice might convert mitral stenosis into severe mitral regurgitation; and patients in whom mitral regurgitation was the chief problem were not candidates for the procedure” CALCIFIC MITRAL STENOSIS

✓ Not amenable to valvuloplasty

✓ Surgery is high risk

✓ Would benefit from specialized mitral valve surgical expertise RHEUMATIC MITRAL STENOSIS

2014 AHA/ACC Valve Disease Guidelines Mitral Regurgitation Normal leaflet Excess leaflet Leaflet restriction Leaflet restriction motion motion systole & diastole systole only Prolapse or flail Endocarditis leaflet Rheumatic Ischemic Heart Dilated annulus Carcinoid disease Atrial fibrillation MVP SLE Dilated CM Restrictive CM Papillary rupture Radiation Trauma Drugs Endocarditis Mitral Regurgitation

Degenerative MR

Redundant Leaflets

Elongated or ruptured chords

Functional MR

Annular dilation

Annular Calcification

Pap muscle dysfxn: fixed or transient

Rheumatic changes

Endocarditis Secondary MR

▪ Secondary MR (cf. primary)

▪ Functional MR (cf. degenerative) ▪ Ischemic MR (cf. Non-ischemic)

▪ MR that occurs in the setting of LV dysfunction with normal (or near normal) mitral leaflet and chordal structure Degenerative Mitral Regurgitation MR Pathophysiology

Increase in LA Rupture of Pulm HTN LVEDV dilatation chordae

Increase in LV Atrial Accelerated RV dysfxn total SV dilatation fibrillation course

Maintain LV dysfxn CHF CO MR: classification of severity

MILD MOD SEVERE Angiographic 1 + 2 + 3-4 + grade < 4 cm2 or >40% LA area, Color Doppler jet < 20% LA Wall-impinging jet of any area area size, swirling in the LA Doppler vena < 0.3 0.3 – 0.69 > 0.7 contracta width Regurgitant < 30 30 - 59 > 60 volume (ml/beat) Regurgitant < 30 30 - 49 > 50 fraction (%) Regurgitant < 0.2 0.2 – 0.39 > 0.4 orifice area (cm2) Mitral Valve Repair cf Replacement

▪ Preserves the native valve  and, almost always, the subvalvular apparatus ▪ Improved long-term survival ▪ Improved cardiac function ▪ Lower risk of complications (incl. stroke, SBE) ▪ Usually eliminates need for anticoagulants

Multiple surgical options

Full sternotomy Partial sternotomy

Right thoracotomy Robotic All degenerative MR is repairable

▪ Create durable zone of coaptation  Leaflet procedures  Mitral Ring Annuloplasty All degenerative MR is repairable

▪ Quality of repair  Degree of residual MR

▪ Durability of repair  Rate of recurrent MR  Rate of reoperation Added surgical bonus

▪ Concurrent revascularization  CABG

▪ AF-therapies  e.g. surgical Maze, left atrial appendage closure Transcatheter Mitral Valve repair

▪ Mitral valve repair surgery remains optimal

▪ The only FDA-approved TMVr device is MitraClip

▪ Other approaches – leaflet tethering, transcatheter annuloplasty in development Transcatheter Mitral Valve Replacement

▪ In development – FDA-approved clinical trials ▪ Deployment of artificial valve across native mitral to fix MR ▪ Trans-apical via left thoracotomy and transeptal The MitraClip ▪ The only FDA approved percutaneous therapy for Mitral Regurgitation in the US ▪ Edge-to-edge repair (cf. Alfieri stitch)

Alfieri Ottavio. , De Bonis M. The role of the edge-to-edge repair in the surgical treatment of mitral regurgitation, J Card Surg 2010, 25(5): 536-541. Everest II Trial

Enrolled from 09-2005 to 11-2008, 37 centers US & Canada

Everest II Trial ▪ Grade 3+ to 4+ Chronic MR • Primary Safety Endpoint: ▪ Symptomatic: LVEF >25%, LVESD ≤55 mm • •PrimaryRate of Efficacy MAE Endpoint:at 30 d: composite of death, MI, reop ▪ Asymptomatic: LVEF • forFreedom failed MVfrom Surgery,death, surgery non- 25-60%, LVESD 40-55 electivefor MV DysfxnCV surgery & grade for 3+ to 4+ adverseMR at 12 events, mo CVA, Ren mm, New afib or Pulm Failure, deep wound Hypertension infection, Vent for >48 hrs, GI complications req Surg, new ▪ Were candidates for afib, sepsis and transfusion ≥ MVRepr or MVRepl 2 U blood 2:1 randomization

Conclusions

▪ MitraClip clearly reduces symptoms, although less than MVR in candidates who can have surgery ▪ MitraClip improves quality of life post procedure ▪ MitraClip is non-inferior to surgery in safety ▪ MitraClip 5 year results are durable ▪ MitraClip is reasonable for patients who are at prohibitive risk for surgery

Future of MitraClip

▪ COAPT: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation

Case Presentation

▪ 96-year old woman ▪ Active until July 2016 ▪ Developed worsening dyspnea  admitted to the hospital with congestive cardiac failure  Improved after introduction of the diuretics ▪ Severe AS and severe degenerative MR

Case Presentation

Results

▪ LVEF normalized ▪ No severe pulmonary hypertension ▪ No severe MR (reduced to mild) ▪ No severe AS

▪ Asymptomatic and independent (98 yrs. old) Take home points

• Patients with mitral valve disease are complex –

• symptoms may be multifactorial,

• require careful diagnostic workup,

• multidisciplinary approach,

• detailed stepwise treatment plan, and

• post procedure surveillance by dedicated teams. Take home points

• Transcatheter balloon mitral valvuloplasty is the preferred treatment option for patients with mitral stenosis and favorable anatomy.

• Mitral Valve Repair surgery is the gold standard.

• MitraClip is approved for very high surgical risk patients with MR >3+ and degenerative mitral valve disease if reasonable survival expected.

• 5 year follow-up data show durable result. Landmark analysis shows after 6 months, event free survival improved.

• Ongoing trial for functional mitral regurgitation ECHO

CARDIO-PCP MS TEE Interventional Cardiac Surgeon

Unfavorable MS

PTBMV MV surgery ECHO

CARDIO-PCP

TEE DMR Interventional Cardiac Surgeon

High-risk DMR

MitraClip MV surgery ECHO

CARDIO-PCP MS TEE DMR Interventional Cardiac Surgeon

Unfavorable MS High-risk DMR

MDT

PTBMV MitraClip Medical ℞ MV surgery ECHO

CARDIO-PCP MS TEE DMR Interventional Cardiac Surgeon

Unfavorable MS High-risk DMR

MDT

PTBMV MitraClip Medical ℞ MV surgery Peacock Club – MDT approach 70 yrs ago

▪ Discussions of life threatening risks of the invasive investigations /interventions ▪ Shared management planning ▪ Self-critical reviews of operations that often went badly  Hearts of the patients who died were critically examined in the presence of the whole team ▪ Meticulous documentation of treated and untreated cases. (national registries – STS/ACC TVT) MULTI-DISCIPLINARY APPROACH TO MITRAL DISEASE

CARDIOLOGIST