What is the initial treatment approach for a patient with Aortic Stenosis (AS) and Heart Failure with reduced Ejection Fraction (HFrEF)?

Initial Treatment Approach for Aortic Stenosis with HFrEF

Optimize guideline-directed medical therapy (GDMT) for heart failure immediately while determining the true severity of aortic stenosis through multi-imaging evaluation, then proceed to aortic valve replacement once severe AS is confirmed, as medical HF treatment is imperative and must be optimized concurrently with AS severity determination. 1

Immediate Diagnostic Priorities

Confirm AS severity through comprehensive echocardiographic assessment, as up to 30% of AS patients present with HF symptoms and many have low-flow states (aortic valve area ≤1.0 cm² with mean gradient <40 mmHg and peak velocity <4.0 m/s), making determination of true severity essential for correct management. 1 Transthoracic echocardiography is mandatory to confirm reduced ejection fraction, assess myocardial structure and function, and identify patients suitable for device therapy. 2

Assess blood pressure (supine and standing), heart rate, renal function (eGFR and creatinine), volume status, and evaluate for underlying causes including coronary artery disease. 2 This baseline assessment guides medication selection and dosing.

Initiate All Four Core GDMT Classes Simultaneously

The modern approach abandons the traditional step-by-step strategy. Start all four core medication classes simultaneously at low doses within the first 4-6 weeks of HFrEF diagnosis, beginning with SGLT2 inhibitors and mineralocorticoid receptor antagonists first, followed by beta-blockers and ARNI/ACE inhibitors. 2, 3

First-Line: SGLT2 Inhibitors and MRAs

Start SGLT2 inhibitors immediately as they have minimal blood pressure effects, provide rapid benefits within weeks, require no dose titration, and work independently of background therapy. 2, 3 Use empagliflozin if eGFR ≥30 ml/min/1.73 m² or dapagliflozin if eGFR ≥20 ml/min/1.73 m². 4, 2

Initiate mineralocorticoid receptor antagonists (spironolactone or eplerenone) concurrently for patients with LVEF ≤35% and NYHA class II-IV symptoms, as they also have minimal BP-lowering effects and reduce mortality. 4, 2, 3 Monitor potassium closely—creatinine should be ≤2.5 mg/dL in men or ≤2.0 mg/dL in women (eGFR >30 mL/min/1.73 m²), and potassium <5.0 mEq/L. 4

Second-Line: Beta-Blockers and ARNI/ACE Inhibitors

Start beta-blockers at low dose if heart rate >70 bpm, using one of the three evidence-based agents: carvedilol, metoprolol succinate, or bisoprolol. 4 Selective β₁ receptor blockers (metoprolol or bisoprolol) are preferred in patients with borderline blood pressure due to lesser BP-lowering effects. 2

Sacubitril/valsartan (ARNI) is preferred over ACE inhibitors for patients with NYHA class II-III symptoms. 4, 2 Start at 24/26 mg twice daily if on <10 mg enalapril equivalent, or 49/51 mg twice daily if on ≥10 mg enalapril equivalent, with target dose of 97/103 mg twice daily. 4 Ensure 36 hours off ACE inhibitor before initiation. 4 If ARNI is not tolerated due to hypotension or is not feasible, use ACE inhibitors or ARBs. 2, 3

Diuretics for Congestion

Diuretics are recommended for patients with evidence of fluid retention to improve symptoms. 4 Start with loop diuretics (furosemide 20-40 mg once or twice daily, bumetanide 0.5-1.0 mg, or torsemide 10-20 mg) and titrate to relief of congestion. 4

Managing Low Blood Pressure in AS with HFrEF

If systolic BP <100 mmHg but patient is asymptomatic or mildly symptomatic with adequate organ perfusion, do not withhold GDMT. 4, 2 Instead:

• Discontinue non-HF hypotensive medications 2
• Start with SGLT2 inhibitors and MRAs first (minimal BP effects) 4, 2
• Use very low starting doses of sacubitril/valsartan or ACE inhibitors 2
• Consider ivabradine if beta-blockers are not tolerated hemodynamically 4
• Space out medications to reduce synergistic hypotensive effects 4
• Implement compression leg stockings and exercise training to improve orthostatic hypotension 4

Asymptomatic or mildly symptomatic low BP should not be a reason for GDMT reduction or cessation. 4 Only reduce or stop GDMT if systolic BP <80 mmHg or low BP with relevant symptoms. 4

Titration Strategy

Gradually up-titrate one medication at a time using small increments every 2-4 weeks until target or maximally tolerated doses are achieved. 4, 2, 3 Monitor blood pressure, heart rate, renal function (especially creatinine and eGFR), and potassium after initiation and during titration. 4, 3

Aortic Valve Intervention Timing

Current guidelines recommend clinical surveillance with multimodality imaging, with aortic valve replacement deferred until stenosis becomes severe. 5 However, all patients with severe aortic stenosis in clinical heart failure should be offered aortic valve replacement, as long-term survival improves dramatically, functional class improves, and left ventricular ejection fraction increases markedly (from 0.34 to 0.63 in historical series). 6

For patients with only moderate AS and HFrEF, continue GDMT optimization and close surveillance. 5 The TAVR UNLOAD trial is investigating whether earlier transcatheter aortic valve replacement in moderate AS with HFrEF provides benefit beyond GDMT alone. 5

Device Therapy Evaluation

ICD implantation should be considered for primary prevention in patients with LVEF ≤35%, NYHA class II-III symptoms, and ≥3 months of optimal medical therapy, provided life expectancy >1 year with good functional status. 2 Wait at least 40 days post-myocardial infarction before ICD implantation. 2

Cardiac resynchronization therapy (CRT) is indicated for symptomatic patients with LVEF ≤35% and broad QRS complex with left bundle branch block morphology. 2

Critical Pitfalls to Avoid

Do not use the traditional step-by-step approach that delays one drug class until another is optimized. 2 Do not discontinue GDMT for asymptomatic hypotension or mild renal function changes. 2 Never use diltiazem or verapamil in HFrEF patients, as calcium channel blockers with negative inotropic effects are not recommended. 4 Avoid combining ACE inhibitors with ARBs and MRAs. 2 Do not over-diurese, as this can worsen hypotension and renal function. 2

If persistent low BP with major symptoms occurs despite optimization attempts, refer to an advanced HF team for evaluation of advanced therapies. 4