What is the diagnosis and recommended guideline‑directed medical and device therapy for a patient after mitral valve repair who now has left ventricular ejection fraction (LVEF) 40 %, global longitudinal strain (GLS) –13.1 % to –12.0 % (borderline), septal E/e' 28–33 (elevated filling pressures), tricuspid annular plane systolic excursion (TAPSE) 14 mm (reduced right‑ventricular systolic function), and left atrial volume index (LAVI) 27 ml/m² (significant atrial enlargement) with mild diastolic dysfunction?

Diagnosis: Heart Failure with Reduced Ejection Fraction (HFrEF) Post-Mitral Valve Repair

This patient has developed HFrEF (LVEF 40%) with evidence of biventricular dysfunction, elevated filling pressures, and should be immediately initiated on comprehensive guideline-directed medical therapy (GDMT) including sacubitril/valsartan, beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor, with evaluation for cardiac resynchronization therapy (CRT) given the high likelihood of interventricular dyssynchrony. 1, 2

Primary Diagnosis

The patient meets criteria for HFrEF with LVEF 40%, which by definition is ≤40% 2. The echocardiographic profile reveals:

• Severely impaired myocardial contractility: GLS of -13.1% to -12.0% is markedly abnormal (normal is -18% to -22%, or >20% absolute value) 3, 4
• Elevated LV filling pressures: Septal E/e' of 28-33 is severely elevated (normal ≤8, abnormal >14) 5
• Right ventricular systolic dysfunction: TAPSE 14-16 mm is reduced (normal ≥17 mm) 5
• Borderline left atrial enlargement: LAVI 27 ml/m² approaches the upper limit of normal (normal ≤34 ml/m²) 5

The severely impaired GLS (<7% in absolute terms, or -13.1% to -12.0%) is particularly concerning as it independently predicts adverse outcomes and mortality in patients with reduced ejection fraction, even more reliably than LVEF alone 4.

Critical Context: Post-Mitral Valve Repair

This patient's HFrEF developed after mitral valve repair, which has important implications:

• The preoperative echocardiographic parameters (LVEF 55-61%, borderline GLS) likely concealed underlying LV systolic dysfunction that became unmasked after eliminating the low-impedance leak into the left atrium 6, 7
• Preoperative LVEF of 55% and LVDs approaching 40 mm were warning signs that surgery may have been performed at the threshold where postoperative LV dysfunction was likely 5, 6
• The current LVEF of 40% represents true myocardial contractile impairment, not volume overload from MR 6, 8

Guideline-Directed Medical Therapy (GDMT)

Foundational Therapy (Initiate Immediately)

Angiotensin Receptor-Neprilysin Inhibitor (ARNI):

• Sacubitril/valsartan is the preferred first-line agent over ACE inhibitors or ARBs for HFrEF with LVEF ≤40% 1, 2
• Target dose: 97/103 mg twice daily (referred to as 200 mg in clinical trials) 1
• Start at 24/26 mg or 49/51 mg twice daily and uptitrate every 2-4 weeks as tolerated 1
• In PARADIGM-HF, sacubitril/valsartan reduced cardiovascular death or HF hospitalization by 20% (HR 0.80,95% CI 0.73-0.87, p<0.0001) and all-cause mortality by 16% (HR 0.84,95% CI 0.76-0.93, p=0.0009) compared to enalapril 1

Beta-Blocker:

• Initiate a guideline-recommended beta-blocker (carvedilol, metoprolol succinate, or bisoprolol) unless contraindicated 2
• Uptitrate to maximally tolerated dose 2

Mineralocorticoid Receptor Antagonist (MRA):

• Add spironolactone or eplerenone for persistent symptoms despite ARNI and beta-blocker 2
• Monitor potassium and renal function closely 2

Additional Disease-Modifying Therapy

SGLT2 Inhibitor:

• Dapagliflozin or empagliflozin should be added regardless of diabetes status 2
• SGLT2 inhibitors significantly reduce cardiovascular and all-cause mortality in HFrEF independent of diabetes 2

Diuretics:

• Loop diuretics (furosemide, torsemide, or bumetanide) to achieve and maintain euvolemia given elevated E/e' indicating congestion 2
• Titrate dose based on symptoms, weight, and volume status 2

High-Risk Considerations

Vericiguat:

• Consider adding vericiguat (soluble guanylate cyclase stimulator) if the patient remains high-risk with recent HF hospitalization or elevated natriuretic peptides despite optimal GDMT 2
• Vericiguat reduces HF hospitalization in high-risk HFrEF patients 2

Device Therapy Evaluation

Cardiac Resynchronization Therapy (CRT)

The patient should undergo 12-lead ECG to assess for interventricular dyssynchrony:

• CRT is indicated if QRS duration ≥150 ms with left bundle branch block morphology and LVEF ≤35% (NYHA Class II-IV) 2
• CRT may be considered if QRS 120-149 ms with LBBB and LVEF ≤35% 2
• The reduced TAPSE (14 mm) and biventricular dysfunction make CRT particularly important to evaluate 2

Implantable Cardioverter-Defibrillator (ICD)

ICD for primary prevention should be considered:

• Indicated if LVEF remains ≤35% after ≥3 months of optimal GDMT and life expectancy >1 year 2
• Particularly important if ischemic etiology or high-risk features 2
• Can be combined with CRT (CRT-D) if dyssynchrony criteria are met 2

Transcatheter Mitral Valve Intervention

Re-evaluate for recurrent or residual MR:

• The current echocardiogram shows trivial MR post-repair, which is acceptable 2
• If moderate-to-severe secondary MR recurs despite GDMT, transcatheter edge-to-edge repair may be considered 2, 4
• However, patients with severely impaired GLS (<7% absolute value) have higher mortality after transcatheter mitral intervention 4

Prognostic Implications

Global Longitudinal Strain

The GLS of -12.0% to -13.1% (absolute value <7% when considering the severely reduced LVEF context) is a powerful independent predictor of adverse outcomes 4:

• Patients with GLS <7% (absolute) have significantly higher 2-year mortality (38.2% vs 25.9%, p=0.003) and combined mortality/HF hospitalization (52.5% vs 36.3%, p<0.001) 4
• GLS provides incremental prognostic information beyond LVEF alone 4

Elevated Filling Pressures

The E/e' of 28-33 indicates severely elevated LV filling pressures 5:

• E/e' has a pooled correlation coefficient of 0.56 with invasively measured filling pressures in HFpEF, though the correlation is likely stronger in HFrEF 5
• Each unit increase in E/e' confers a hazard ratio of 1.05 (95% CI 1.03-1.06) for mortality or cardiovascular hospitalization 5

Right Ventricular Dysfunction

TAPSE of 14 mm indicates reduced RV systolic function and portends worse prognosis 5:

• RV dysfunction in the setting of LV failure suggests advanced disease and pulmonary hypertension 5
• Requires aggressive decongestion and optimization of GDMT 2

Monitoring and Follow-Up

Serial echocardiography every 3-6 months:

• Assess for LV reverse remodeling with GDMT (improvement in LVEF, LV volumes, GLS) 8
• Monitor RV function (TAPSE), filling pressures (E/e'), and LA size 5
• Evaluate for recurrent MR 2

Natriuretic peptides:

• Obtain baseline BNP or NT-proBNP and monitor serially 2
• Persistently elevated or rising levels indicate inadequate response to therapy 2

Functional assessment:

• NYHA functional class at each visit 2
• Consider cardiopulmonary exercise testing if symptoms are disproportionate to objective findings 2

Common Pitfalls to Avoid

Do not delay GDMT initiation:

• All four pillars (ARNI, beta-blocker, MRA, SGLT2 inhibitor) should be initiated and uptitrated as rapidly as tolerated, not sequentially over months 2

Do not dismiss the severely impaired GLS:

• GLS of -12.0% to -13.1% indicates profound myocardial dysfunction that may not fully recover even with optimal therapy 4, 6
• This patient likely had subclinical LV dysfunction preoperatively that was masked by the MR 6, 7

Do not overlook RV dysfunction:

• TAPSE of 14 mm indicates biventricular failure requiring aggressive medical optimization 5
• RV dysfunction limits candidacy for certain interventions and worsens prognosis 2

Do not assume the mitral repair failed:

• Trivial residual MR is an excellent surgical result 2
• The HFrEF represents unmasking of underlying cardiomyopathy, not surgical failure 6, 8

Do not forget device therapy evaluation:

• After 3 months of optimal GDMT, if LVEF remains ≤35%, the patient requires ICD and potentially CRT evaluation 2