The road ahead

The conundrum of mitral regurgitation

in heart failure

Piotr Ponikowski, MD, PhD, FESC Medical University, Centre for Heart Disease

Clinical Military HospitalWroclaw, Poland

The road ahead

Disclosure

Consultancy fees and speaker’s honoraria from: ABBOTT VASCULAR

Primary vs functional MR: key question for the current management

n Primary MRMR→LV volume overload→remodeling with subsequent consequences „correction of primary MR in a timely fashion reverses these consequences”

n Functional MR – damaged LV causes MR„primarily a ventricular problem it is less obvious that correcting the MR by itself will be curative or even beneficial”

Carabello BA, JACC 2008;52:319-26

• Secondary MR„because MR is only 1 component of the disease (severe LV dysfunction, CAD or idiopathic myocardial disease are the others), restoration of mitral valve competence is not by itself curative;

2014 AHA/ACC Valvular Heart Disease Guideline

Primary vs functional MR: key question for the current management

Marwick TH, Zoghbi WA, Narula J. JACC CV Imaging 2014

Potential confounders in the causal pathway linking FMR and adverse events

MR in Heart FailureManagement options: how / when to intervene ?

• Optimal medical therapy• CRT

• Surgery MV surgery Surgical treatment of LV

• Percutaneous techniques

Functional Mitral Regurgitation – management options

Acute effect of CRT on FMR in HF patients (EF<30%) with LBBB

Breithardt OA et al. JACC 2003;41,765-770

…increase in TMP mediated by a rise in maximal rate of LV systolic pressure rise due to more coordinated LV contraction, may facilitate effective MV closure…


Impact of CRT on the severity of FMR

Di Biase L et al. Europace 2011;13, 829–838The distribution of MR in CRT population


CRT in Patients with Moderate-Severe FMR

van Bommel et al. Circulation 2011;124:912-9

100

200

300

BL F-UP BL F-UP

LVEDV (mL)

LVESV (mL)

BL F-UP BL F-UP

LVEDV (mL)

LVESV (mL)

MR improvers MR non-improvers





ESC Guidelines on the Management of VHD 2012

Indications for mitral valve surgery in chronic secondary MR

Euro Heart Survey: why surgery is denied in clinical practice ?

Mirabel et al., Eur Heart J 2007;28:1358-65

Cardiac surgeon

Cardiologist

Anaesthetists

Other specialists:geriatrician, GP, etc Imaging specialist (ECHO, CT, MRI)

Decision-makingin VHD patient

HEART TEAM

‘heart team’ approach is particularly advisable in the management of high-risk patients and is also important for other subsets, such as asymptomatic patients, where the evaluation of valve repairability is a key component in decision-making…

ESC Guidelines on the Management of VHD 2012





Percutaneous Mitral Valve RepairMitraClip® System

WHY to recommend „new procedure” for HF patient ?

Therapy footprint

Economic impact

Patient

Durability

Procedural success

Safety profile

Survival & QoL

MitraClip therapy“The most established PMVR therapy”

n More than 20000 patients treated worldwide n Used in more than 420 centers and 35 countriesn More than 560 clinical papers published to date*n Included in:

– 2012 ESC/HFA/EACTS Guidelines² – 2014 ACC/AHA Guidelines3

– 2012/2013 German Guidelines4,5

– 2014 Italian Guidelines6

• H. Hermann & F. Maisano – Transcatheter therapy of Mitral Regurgitation – Circulation 2014; 130:1712-1722• ESC/EACTS 2012 Guidelines on the management of valvular heart disease. Eur Heart J (2012) 33, 2451–2496.• Nishimura RA, et al. - 2014 ACC/AHA valve guidelines: earlier intervention for chronic mitral regurgitation - Heart June 2014 Vol 100 No 12• Boekstegers P. et.al. Percutaneous interventional mitral regurgitation treatment using the Mitra-Clip system Clin. Res. Cardiol. 2013• Nickenig G. et al. - Consensus of the German Cardiac Society and the German Society for Thoracic and Cardiovascular Surgery on treatment of mitral valve insufficiency -

Kardiologe 2013 · 7:76–90• Maisano et al. - Transcatheter treatment of chronic mitral regurgitation with the MitraClip system: an Italian consensus statement - J Cardiovasc Med 2014, 15:173–188

Therapy footprint

EVEREST II: 279 patients with moderately severe or severe (grade 3+ or 4+) MR randomized in a 2:1 ratio to percutaneous repair or conventional surgeryLVEF – 60%, functional MR – 27%

12 months

Surgery better Percutaneous repair better

Feldman T et al., N Engl J Med 2011

MitraClip therapy“The most established PMVR therapy”

Therapy footprint

MitraClip therapySafety profile

• T. Feldman, et al., The New England journal of medicine 364, 1395 (2011)/ 2. P. L. Whitlow, et al., Journal of the American College of Cardiology 59, 130 (2012)/ 3. F. Maisano, et al., Journal of the American College of Cardiology 62, 1052 (2013)/ 4. S. Kar, Presented at TCT, 2013, San Francisco, CA (2013)/ 5. W. Schillinger, et al., EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 9, 84 (2013)/4. C. Grasso, et al., The American journal of cardiology 111, 1482 (2013)

Safety profile

• Low Major Adverse Events (MAEs) • Low post-procedural mortalityLow Major Adverse Events (MAEs) Low post-procedural mortality

SMC

MitraClip as therapeutic option for MRfirst (and strong) evidence

EVEREST II: 4-year results

Sustained clinical benefits comparable to those after surgeryImprovement in MR durable through 4 years

Mauri et al., JACC 2013

Survival & QoL

MitraClip as therapeutic option for MRfirst (and strong) evidence

EVEREST II: 4-year results

Mauri et al., JACC 2013

Differences in rates of the efficacy endpoints: freedom from death, MV surgery and from +3/+4 MR

Survival & QoL

MitraClip as therapeutic option for MRReal World Experience

ACCESS-EU: 567 pts with significant MR who underwent MitraClip therapy at 14 European sites; 69% functional MR, 85% NYHA III-IV, 53% LVEF <40%Implant rate – 99.6%; mortality: 30-day – 3.4%,1-year – 81.8%

Maisano F et al., JACC 2013;62:1052–61

Severity of MR at baseline and during follow-up Changes in 6MWT in patients with MitraClip

Survival & QoL


TCVT – ESC : 628 consecutive pts with significant MR who underwent MitraClip therapy at 25 European sites; 72% functional MR: 88% NYHA III-IV, 42% LVEF <30%, EuroScore - 22

Nickenig G al., JACC 2014;64:875–84

Survival & QoL

Composite of death and HF rehospitalisation


139 consecutive pts with MitraClip therapy vs 53 treated surgically vs 59 treated conservativelyMitraClip: EuroScore: 24±16%NYHA II-III: 77%; LVEF: 37±15%FMR: 77%

Swaans et al., JACC Interv 2014;7:875-81

Conclusion: high-surgical-risk

patients treated with TMVR displayed

survival benefit vs those treated

conservatively.

Survival & QoL

Grades A & BAt risk of MR → Progressive MR•Primary myocardial disease with LV dilation and systolic dysfunction•Symptoms due to CAD/HF •OMT/devices/revascularization

Grade CAsymptomatic severe MR•Abnormal valve hemodynamics – ERO, RF•Symptoms due to CAD/HF•OMT/devices/revascularization

Grade DSymptomatic severe MR•Abnormal valve hemodynamics – ERO, RF•Symptoms due to MR, persist even after OMT/devices/revascularization

Modified from 2014 AHA/ACC Valvular Heart Disease Guideline

strategy:1.Treat HF optimally2.MR - watch and see

strategy:1.Treat HF optimally2.MR – consider intervention

Ready to challenge this paradigm ?

Is there enough evidence ?

FMR in Heart Failurehow / when / WHY to intervene ?

Healthcare

The road ahead