Secondary Mitral Regurgitation

Definition

Secondary mitral regurgitation (SMR) is MR in which the MV apparatus is structurally normal but regurgitation results from alterations in LV or LA geometry, dyssynchrony, and imbalances between MV closing and tethering forces. Two distinct phenotypes are now formally recognised: ventricular SMR and atrial SMR.

Key Concepts

Ventricular SMR vs Atrial SMR

• Atrial SMR diagnostic criteria: LVEF ≥50%, no/mild LV dilatation (LV end-diastolic dimension <56 mm women / <63 mm men), MA AP diameter >35 mm, LAVI >34 mL/m²
• At advanced stages, overlap between phenotypes may occur — early characterisation is key sources/vhd-esc-2025 very high

Evaluation

• Assessment should be performed in euvolaemic, normotensive state after GDMT optimisation
• Severe ventricular SMR thresholds: EROA ≥30 mm² and/or RVol ≥45 mL (lower than PMR thresholds due to elliptical orifice and low-flow state)
• CMR confirms SMR severity and quantifies myocardial fibrosis (predictor of poor prognosis)
• Exercise echo helps identify severe dynamic SMR when resting values are inconclusive sources/vhd-esc-2025 very high

Management of Ventricular SMR

Step 1: GDMT Optimisation (mandatory before any MV intervention)

• ACE-I/ARB/ARNI + beta-blocker + MRA + SGLT2i at maximum tolerated doses
• Up-titration must be rapid (within 6 weeks) with close follow-up
• ~40% of patients improve MR by ≥1 grade after 1–3 months of GDMT
• CRT (Class I per HF guidelines) should be implemented first if criteria met (LVEF ≤35%, wide QRS); reduces MR in 40–60% of patients

Ventricular SMR Without CAD — Intervention

• Class I A (upgraded 2025): TEER recommended to reduce HF hospitalisations and improve QoL in haemodynamically stable symptomatic patients (NYHA II–V) with LVEF <50% and persistent severe SMR despite GDMT + CRT, fulfilling all specific criteria (COAPT trial, RESHAPE-HF2, meta-analysis)
• Specific criteria for Class I TEER (Table 7):
  • NYHA ≥II; LVEF 20–50%; LVESD ≤70 mm
  • ≥1 HF hospitalisation in prior year or BNP ≥300 pg/mL or NT-proBNP ≥1000 pg/mL
  • SPAP ≤70 mmHg; no severe RV dysfunction; no Stage D/advanced HF
  • No CAD requiring revascularisation; no severe AV or TV disease; no HCM/RCM/amyloidosis
• Class IIb B: TEER for symptom improvement in patients not meeting the specific criteria above (after evaluating LVAD/HTx eligibility)
• Class IIb C: MV surgery in patients with severe ventricular SMR without advanced HF not suitable for TEER (MATTERHORN: TEER non-inferior to surgery with better safety) sources/vhd-esc-2025 very high

Ventricular SMR With Concomitant CAD

• MV surgery Class I B at time of CABG for severe ventricular SMR + CAD
• Isolated undersized annuloplasty: high recurrent MR rates; replacement required in large tenting area (>1.35 cm²/m² BSA)
• MV surgery Class IIb B in moderate SMR undergoing CABG
• PCI + re-evaluation of MR after revascularisation: Class IIb C (MR improves in ~1/3 after PCI)

Management of Atrial SMR (New 2025)

• Treat underlying causes: AF (rhythm control), HFpEF (SGLT2i, diuretics per guidelines)
• Rhythm control may reduce atrial SMR severity and reverse LA dilatation
• Class IIa B (new): MV surgery + surgical AF ablation + LAAO in symptomatic patients on optimal medical therapy
• Class IIb B (new): TEER if ineligible for surgery after optimising medical therapy including rhythm control — risk of gradient increase with planar coaptation must be assessed sources/vhd-esc-2025 very high

Follow-up After Intervention

• Ventricular SMR: clinical, laboratory, and echo every 3–6 months (high ongoing event rate even after TEER — 73.6% cumulative 5-year all-cause death/HF hospitalisation in COAPT device arm)
• Atrial SMR: yearly clinical + echo follow-up
• Asymptomatic moderate or dynamic SMR: at least twice-yearly follow-up

ACC/AHA 2020 — Secondary MR Management

• At time of ACC/AHA 2020 guideline, TEER for secondary MR was rated Class IIa B-NR (subsequently upgraded to Class I A by ESC 2025 based on RESHAPE-HF2)
• COAPT selection criteria (ACC/AHA 2020 standard): LVEF 20–50%; LVESD ≤70 mm; PASP ≤70 mmHg; persistent NYHA II–IV despite optimal GDMT; no CAD requiring revascularisation sources/VHD-AHA-2020 very high
• Class I B-NR (ACC/AHA 2020): Severe secondary MR + CAD undergoing CABG → concomitant MV surgery recommended
• Note: ACC/AHA 2020 does not formally distinguish atrial vs ventricular SMR (that distinction was formalised in ESC 2025) sources/VHD-AHA-2020 very high

Contradictions / Open Questions

• COAPT vs MITRA-FR divergence: TEER reduced mortality in COAPT but not in MITRA-FR; likely due to MITRA-FR including more severely dilated LV (proportionate MR) and less rigid GDMT optimisation — the concept of "disproportionate SMR" (EROA:LV relationship) helps explain divergence but is not fully validated sources/VHD-AHA-2020 very high
• TEER class upgrade: ACC/AHA 2020 rated TEER for secondary MR as Class IIa; ESC 2025 upgraded to Class I A based on RESHAPE-HF2 — this represents one of the most significant recommendation evolutions between the two guidelines sources/VHD-AHA-2020 very high vs sources/vhd-esc-2025 very high
• Atrial SMR: No RCT comparing surgery vs TEER vs medical therapy; all recommendations are based on observational data; not formally recognised in ACC/AHA 2020
• Optimal timing of intervention: When to stop GDMT up-titration and proceed to TEER is not precisely defined
• MV surgery for ventricular SMR: Long-term benefit over TEER not proven; MATTERHORN showed non-inferiority of TEER for 1-year composite endpoint

Connections

• Related to concepts/Valvular-Heart-Disease
• Related to concepts/Primary-Mitral-Regurgitation
• Related to concepts/Tricuspid-Regurgitation
• Related to entities/Heart-Failure
• Related to entities/Atrial-Fibrillation

Sources

• sources/VHD-AHA-2020
• sources/vhd-esc-2025