Functional MR: Medical Options and the Timing of Referral ...Objectives of Medical Therapy for the Remodeled (Dilated) LV • Primarily to reverse remodel (shrink) the LV • Improve

Functional MR: Medical Options and the Timing of Referral for

Repair

Andrew Boyle, MDProfessor of Medicine

Thomas Jefferson University Philadelphia, PA

Disclosures• Abbott: Consultant

Left Ventricular Remodeling60%

20%Time (Years)

CompensatoryMechanism

SecondaryDamage

Ejec

tion

Frac

tion

Asymptomatic Symptomatic

Adapted from Mann, Circulation 1999; 100: 999-1008.

Definition of Functional MR

• Valve structure is normal• MR occurs because of failure of MV leaflet

coaptation in the setting of LV remodeling• Apical tethering of one or more MV leaflets

Mortality and Severity of MR Post-MI

Mowakeaa S et al. BMJ Open Heart 2018; 5: e745.

Objectives of Medical Therapy for the Remodeled (Dilated) LV

• Primarily to reverse remodel (shrink) the LV• Improve coordination of papillary muscle

contraction • This will lead to improved coaptation of the

otherwise normal mitral valve leaflets• Note: there is a distinction between

prevention of remodeling and reverse remodeling

ACEI and Mortality: SAVE

Pfeffer M et al. NEJM 1992; 327:669-677.

Enalapril and LV Reverse Remodeling

Konstam M et al. Circulation 1992; 86: 431-438.

Relative Doses of ACEI

• Captopril 50 mg TID• Enalapril 20 mg BID• Lisinopril 40 mg qd• Ramipril 10 mg qd

Target dose

Patients receiving diuretics, ACE inhibitors, ± digoxin; follow-up 6 months; placebo (n=84), carvedilol (n=261).*Multicenter Oral Carvedilol Heart Failure Assessment.†Mortality was not a planned end point in this study.

‡P<.05 vs placebo.§P=.07 vs placebo.ΩP<.001 vs placebo.

Carvedilol

0

2

4

6

8

∆ L

VEF

(EF

units

)

Ejection Fraction

Carvedilol

0

4

8

12

16

Six-

Mon

th M

orta

lity

(%)

Mortality†

****

§

‡ §

Ω

MOCHA*

Placebo 25 mg bid6.25 mg bid 12.5 mg bid Placebo 25 mg bid6.25 mg bid 12.5 mg bid

**P<.005 vs placebo.§P<.0001 vs placebo.

Adapted from Bristow M et al. Circulation. 1996; 94: 2807–2816.

Target Doses of Beta Blockers

• Carvedilol 25 mg BID• Metoprolol Succinate 150 mg qd

Mineralocorticoids and LV Reverse Remodeling

• Mineralocorticoids prevent remodeling post-MI• Mineralocorticoids improve outcomes and

symptoms in symptomatic pre-existing LV systolic dysfunction

• No evidence that mineralocorticoids reverse remodel LV

• Therefore no evidence that mineralocorticoids would influence severity of functional MR

Change in MR Jet Area

-4-3-2

-101

Control(n=118)

CRT(n=116)

cm 2

P<0.001 P=0.009

Change in LVEDD

-6

-4

-2

0

2

Control(n=118)

CRT(n=116)

mm P<0.001

Absolute Change in LVEF

-2

0

2

4

6

8

Control(n=146)

CRT(n=155)

%

Baseline (mm)

69 ± 10

70 ± 10

Baseline (cm2)

7.2 ± 4.9

7.6 ± 6.4

Baseline (%)

22 ± 6

22 ± 6

Paired median change from baseline at 6 months. Error bars are 95% CI.

Abraham W et al. NEJM 2002;346:1845-1853.

CRT Improves Cardiac Function and Structure

CRT and Reverse Remodeling

Yu C et al. Circulation 2002.

Median, 79.5Mean, 78.1

Variation in Outpatient HF Care

Fonarow GC, et al. Circ Heart Fail. 2008;1:98–106.

Median, 87.6Mean, 85.3

Variation in Outpatient HF Care

Fonarow GC, et al. Circ Heart Fail. 2008;1:98–106.

Median, 33.3Mean, 37.3

Variation in Outpatient HF Care

Fonarow GC, et al. Circ Heart Fail. 2008;1:98–106.

2017 ACC/AHA Focused Update on Valvular Heart Disease

Circulation 2017; 135: e1159-e1195.

Conclusions• Before consideration of procedures to correct functional MR, all

medical therapy options for LV reverse remodeling should be exhausted

• Medicines shown to reverse remodel LV include ACEI, ARB, and beta blockers

• CRT, if indicated based on LBBB with width of QRS > 150 msec, should be attempted first

• Analogy would be for the ICD following revascularization • If functional MR persists and is moderate-severe or severe and

associated with symptoms of heart failure, repair should be considered• There is no evidence to support repair of functional MR in the absence

of symptoms, regardless of severity (in contrast to primary MR)