Mitral Regurgitation - Braunwald's Heart Disease

Overview

• Primary (organic/degenerative) - disease of the leaflets themselves (e.g., mitral valve prolapse [MVP], fibromuscular dysplasia, rheumatic disease, endocarditis)
• Secondary (ischemic/functional) - leaflets are intrinsically normal; caused by disease of the atrium/ventricle (e.g., ischemic dysfunction, dilated cardiomyopathy, atrial fibrillation)

Mitral Valve Anatomy

1. Annulus - saddle-shaped (not a simple ring); has anterior and posterior peaks; its anterior horn adjoins the aortic annulus (aortomitral curtain/intervalvular fibrosa)
2. Commissures - anterolateral and posteromedial
3. Leaflets - anterior (larger, ~1/3 of annular circumference) and posterior (smaller, 3 scallops: P1, P2, P3)
4. Chordae tendineae - primary, secondary, tertiary chords; primary chords attach to free edge (prevent prolapse)
5. Papillary muscles - anterolateral and posteromedial, arising from posterior half of LV; maintain leaflet closure away from LVOT
6. Left ventricle - LV contraction moves annulus toward apex; LV-annulus-aortic angle becomes more acute during systole to facilitate LVOT flow

Braunwald's Heart Disease, p. 775

Morphologic Classification (Carpentier)

• Myxomatous degeneration (MVP) - most common in developed countries
• Rheumatic heart disease
• Infective endocarditis
• Ischemic heart disease / papillary muscle dysfunction
• Dilated cardiomyopathy
• Mitral annular calcification
• Hypertrophic cardiomyopathy
• Less common: collagen vascular diseases, hypereosinophilic syndrome, carcinoid, drugs, trauma

Braunwald's Heart Disease, p. 775

PRIMARY (ORGANIC) MR

Pathophysiology / Hemodynamics

• The MV leak creates a low-impedance pathway for LV ejection - blood exits both forward (aorta) and backward (LA) during systole
• LA receives regurgitant volume; becomes progressively dilated, absorbing increased volume at low pressure (high compliance)
• LV is volume-overloaded; eccentric hypertrophy ensues; increased EDV, increased total stroke volume, preserved EF early on
• EF is supranormal in compensated MR due to reduced afterload (EF >60% is expected; EF 60% in severe MR actually represents relative impairment)
• End-systolic volume is the most sensitive indicator of LV function; ESV <40 mm (LVESD) indicates preserved function
• As disease progresses: LV contractile dysfunction occurs, ESV rises, EF drops, forward output falls, symptoms appear

Clinical Presentation

• Many patients remain asymptomatic for years, even with severe MR
• Initial symptoms: exertional dyspnea, fatigue, exercise intolerance (from elevated pulmonary venous pressure or LV decompensation)
• Later: orthopnea, paroxysmal nocturnal dyspnea, frank pulmonary edema
• Atrial fibrillation is common; can unmask symptoms in previously asymptomatic patients
• Symptoms may occur even with preserved LV contractile function due to severely elevated pulmonary venous pressures or AF

• S1 is often diminished (defective leaflet closure)
• Wide splitting of S2 - due to shortened LV ejection time and early A2
• S3 (third heart sound) - present in severe MR; represents abnormal increase in flow across mitral orifice during rapid filling; NOT necessarily a sign of HF in this context; may be followed by a brief diastolic rumble
• Systolic murmur: Holosystolic (pansystolic), blowing, high-pitched, loudest at apex, radiates to left axilla and left infrascapular area (for posteriorly directed jets); radiation toward sternum/aortic area with anteriorly directed jets (e.g., posterior leaflet prolapse/flail); starts immediately after soft S1 and continues beyond A2
• Murmur intensity shows little variation with AF (contrast with AS where murmur varies with cycle length); little correlation between murmur intensity and MR severity
• Murmur is intensified by isometric exercise (differentiates from AS and HOCM which decrease)
• With standing: murmur decreases; with squatting: murmur increases
• Valsalva maneuver: murmur softens (strain phase), transient overshoot 6-8 beats after release
• P2 louder than A2 if severe pulmonary hypertension develops

Braunwald's Heart Disease, pp. 777-778

• Central to diagnosis, etiology determination, severity quantification, and repair planning
• Severity assessment: structural, qualitative (color jet area, vena contracta, flow convergence/PISA), semi-quantitative (pulmonary vein flow reversal), and quantitative (regurgitant volume [Rvol], regurgitant fraction [RF], effective regurgitant orifice area [EROA])
• Severe primary MR criteria: EROA ≥0.40 cm², Rvol ≥60 mL, RF ≥50%
• LV size and function (LVEDD, LVESD, LVEF) are key determinants of surgical timing
• 3D echocardiography and TEE provide superior anatomic detail for repair planning

• Most accurate for measuring LV EDV, ESV, and mass
• Accurate regurgitant flow quantification correlating well with quantitative Doppler
• Important role in identifying myocardial fibrosis in MVP patients with ventricular tachyarrhythmias or mitral annular disjunction (MAD)

• Useful for annular sizing, quantifying annular calcification
• Particularly valuable for planning percutaneous MV replacement

Natural History

• MVP is the most common cause of chronic primary MR in developed countries; prevalence ~2-3% (using strict echocardiographic criteria: >2 mm leaflet displacement beyond annular long-axis plane with >5 mm leaflet thickening)
• Flail leaflet (chordal rupture with eversion into LA) has worse prognosis than MVP without flail
• Community-based study (833 asymptomatic MVP patients): 10-year all-cause mortality 19% ±2%, cardiovascular mortality 9%
• Strong association with HF, need for valve surgery, AF, and increased mortality
• Once symptomatic, 5-year mortality without surgery is ~50%
• Risk factors for adverse outcomes in primary MR: flail leaflet, severe MR (Rvol ≥60 mL), LVESD ≥40 mm, LVEF ≤60%, AF, pulmonary hypertension

Management of Primary MR

• No proven medical therapy to delay surgery in asymptomatic primary MR with preserved LV function
• Vasodilators (ACEi, ARBs, hydralazine) are NOT indicated in asymptomatic patients with normal LV function
• Rate control or rhythm control for AF; anticoagulation if AF is present
• Diuretics for pulmonary congestion symptoms

• Mitral valve repair is strongly preferred over replacement whenever technically feasible - better preservation of LV function, lower operative mortality, no need for long-term anticoagulation with tissue valves, improved durability
• Repair vs. replacement: Repair is preferred if a durable and successful repair can be achieved (especially for Carpentier type II disease with MVP/flail of P2 scallop, which is most repairable)
• MVR (valve replacement) is indicated when leaflets are fused, extensively fibrotic/calcified, or have chordal shortening/fusion (typically rheumatic disease)

Braunwald's Heart Disease, pp. 1463-1464

SECONDARY (FUNCTIONAL) MR

Pathophysiology

• Due to LA and annular dilation from chronic AF or HFpEF
• LV and leaflets are intrinsically normal
• Mechanism: LA dilation → annular dilation and flattening → insufficient leaflet growth relative to annular area → abnormal coaptation
• Restoration of sinus rhythm may reduce MR; rhythm control plays a role

• Mechanisms: (1) Global/regional LV dilation/dysfunction - reduced closing forces; (2) Papillary muscle displacement with leaflet tethering (outweighs closing forces); (3) Annular dilation/dysfunction; (4) Inadequate leaflet adaptation to ventricular or atrial enlargement
• Anatomic predictors of severity and recurrence after repair: leaflet tethering/restricted closure, asymmetric papillary muscle displacement, decreased interpapillary distance, increased LV sphericity

Clinical Presentation

• Patients often present with heart failure symptoms (dyspnea, fatigue, orthopnea); MR may be detected incidentally
• AF is common
• Systolic murmur of secondary MR related to LV dilation is often softer and shorter than in primary MR (due to reduced driving pressure in the failing ventricle)
• An apical S3 is a common finding
• Secondary pulmonary hypertension is common with severe MR, leading to right-sided HF signs (raised JVP, peripheral edema, TR murmur)

Management of Secondary MR

• ACEi/ARBs, beta-blockers, diuretics for HF symptoms and LV remodeling
• Cardiac resynchronization therapy (CRT) for patients with LBBB and LVEF ≤35% - may reduce secondary MR by improving LV synchrony and geometry
• Rhythm/rate control of AF

• More controversial than primary MR - surgery improves MR but does not reliably improve LV function or long-term outcomes in secondary MR
• Surgical repair (ring annuloplasty) has high recurrence rate (~60% at 5 years) in ischemic MR
• MVR may be preferred over repair in some secondary MR scenarios given high repair recurrence

• COAPT trial (most important trial for secondary MR): In patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite maximally tolerated GDMT (mean age 72 years), TEER resulted in significantly lower rate of HF hospitalization and all-cause mortality over mean 24-month follow-up vs. medical therapy alone
• FDA-approved for heart failure patients with LV dysfunction and secondary MR despite optimal medical therapy
• MitraClip replicates the Alfieri edge-to-edge stitch technique, creating a double-orifice MV
• 2020 ACC/AHA guidelines: TEER is recommended (Class IIa) for symptomatic severe secondary MR despite GDMT in patients with LVEF 20-50%, LVESD ≤70 mm, and anatomy favorable for repair

Braunwald's Heart Disease, p. 784

ACUTE MITRAL REGURGITATION

Causes

• Spontaneous rupture of chordae tendineae (most common)
• Infective endocarditis with leaflet/chordal disruption
• Ischemic papillary muscle rupture - complicating acute MI (especially posteromedial papillary muscle, supplied by single coronary artery)
• Malfunction of prosthetic valve
• Trauma

Pathophysiology and Clinical Features

• LA is normal-sized (low compliance) → LA pressure rises abruptly → acute pulmonary edema
• Marked elevation of v wave in LA/pulmonary artery tracing
• Forward stroke volume drops sharply; right heart failure develops

• Murmur may be decrescendo rather than holosystolic - as elevated LA v wave reduces LV-LA gradient in late systole, murmur ends before A2
• Murmur is usually lower-pitched and softer than chronic MR
• Left-sided S4 is frequently present
• Pulmonary hypertension → loud P2, pulmonary regurgitation murmur, TR murmur, right-sided S4
• Paradoxical splitting of S2 may rarely occur (elevated LA v wave causes premature pulmonary valve closure and early P2)
• Chest X-ray: only mild cardiac enlargement or normal heart size despite severe hemodynamic compromise (no time for compensatory dilation); marked pulmonary edema
• Echo: Minimal LV/LA dilation despite severe MR; elevated PASP; characteristic triangular CW Doppler profile (vs. parabolic in chronic MR) due to early cessation of regurgitation

Management of Acute MR

• IV nitroprusside - afterload reduction is critical; reduces regurgitant fraction and improves forward output; may be lifesaving in papillary muscle rupture complicating acute MI
• If hypotensive: add dobutamine (inotrope) with nitroprusside
• Intra-aortic balloon counterpulsation (IABP) - to stabilize the patient hemodynamically while preparing for surgery (reduces afterload, augments diastolic coronary perfusion)

• Emergency MVR (with resection of ruptured papillary muscle and infarct zone if post-MI) is the treatment of choice
• Emergency surgery carries higher mortality than elective surgery for chronic MR, but mortality without surgery in acute severe MR with HF is extremely high
• Surgery should not be delayed unless the patient can be rapidly stabilized

Braunwald's Heart Disease, pp. 1470-1471

TRANSCATHETER THERAPY (Summary)

Key Numbers to Remember

Clinical Stages of Primary MR (ACC/AHA)

All content sourced from: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 12th Edition (ISBN: 9780323722193), Chapter 76 (Mitral Regurgitation) and Chapter 78 (Transcatheter Therapies for Valvular Heart Disease).