What is the initial management for a new diagnosis of heart failure with reduced ejection fraction (HFrEF)?

Initial Work-Up for New Heart Failure with Reduced Ejection Fraction (HFrEF)

Start all four core medication classes simultaneously at low doses within the first 4-6 weeks of diagnosis, beginning with SGLT2 inhibitors and mineralocorticoid receptor antagonists first, followed by beta-blockers and ARNI/ACE inhibitors, while performing essential diagnostic testing to confirm the diagnosis and identify reversible causes. 1

Essential Diagnostic Testing

Transthoracic echocardiography (TTE) is mandatory to confirm reduced ejection fraction, assess myocardial structure and function, and establish the diagnosis of HFrEF. 2 This imaging also identifies patients suitable for device therapy (ICD, CRT) based on LVEF measurements. 2

Additional baseline assessments should include:

• Blood pressure measurement (both supine and standing to assess for orthostatic hypotension) 2
• Heart rate assessment to guide beta-blocker and ivabradine use 1
• Renal function (eGFR and serum creatinine) to guide medication dosing 2
• Serum potassium before initiating ACE inhibitors/ARNIs and MRAs 3
• Volume status assessment to guide diuretic therapy 1
• Evaluation for underlying causes including coronary artery disease, hypertension, and valvular disease 2

Immediate Pharmacological Management: The Four Pillars

Step 1: Initiate SGLT2 Inhibitors and MRAs First (Week 1-2)

SGLT2 inhibitors should be started immediately as they have minimal effect on blood pressure, provide rapid benefits within weeks, require no dose titration, and work independently of background therapy. 2, 1 Use empagliflozin (eGFR ≥30 ml/min/1.73 m²) or dapagliflozin (eGFR ≥20 ml/min/1.73 m²). 2

Mineralocorticoid receptor antagonists (spironolactone or eplerenone) should be initiated concurrently as they also have minimal BP-lowering effects and reduce mortality in symptomatic patients. 2, 1 Ensure serum creatinine is ≤2.5 mg/dL in men or ≤2.0 mg/dL in women, and potassium is <5.0 mEq/L before starting. 3

Step 2: Add Beta-Blockers (Week 2-3)

Start a beta-blocker at low dose if heart rate >70 bpm, using carvedilol, metoprolol succinate, or bisoprolol. 1, 4 Selective β₁ receptor blockers may be preferred in patients with borderline blood pressure due to lesser BP-lowering effects. 2

Step 3: Initiate ARNI or ACE Inhibitor (Week 3-4)

Sacubitril/valsartan (ARNI) is preferred over ACE inhibitors for patients with NYHA class II-III symptoms, starting at 25-50 mg twice daily. 2, 1 If ARNI is not tolerated due to hypotension, use a low-dose ACE inhibitor instead. 1 ARBs are reserved for patients intolerant to ACE inhibitors due to cough or angioedema. 2

Critical caveat: Do not combine ARNI with ACE inhibitors, and allow a 36-hour washout period when switching from ACE inhibitors to ARNI. 2

Step 4: Add Diuretics as Needed

Diuretics should be used only for symptomatic congestion and adjusted according to volume status. 2, 1 Avoid overdiuresis, which can cause hypotension and impair tolerance of other HF medications. 1

Management of Low Blood Pressure During Initiation

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

• Discontinue non-HF hypotensive medications (calcium channel blockers, alpha-blockers, centrally acting antihypertensives) 2
• Start with SGLT2 inhibitors and MRAs as they minimally affect BP 2, 1
• Use very low starting doses of sacubitril/valsartan (25 mg twice daily) or ACE inhibitors 2
• Consider ivabradine if beta-blockers are not tolerated hemodynamically and patient is in sinus rhythm 2, 1

If systolic BP <80 mmHg with symptoms of hypoperfusion, hospitalization or referral to advanced HF program is warranted. 2

Dose Titration Strategy (Weeks 5-12)

Gradually up-titrate one medication at a time using small increments until target or maximally tolerated doses are achieved. 2 Close monitoring of BP, heart rate, renal function, and potassium is essential during titration. 2

Do not delay initiation of all four drug classes while attempting to reach target doses of individual medications—even lower-than-target doses provide significant mortality benefits. 1

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, 5

Common Pitfalls to Avoid

• Do not use the traditional step-by-step approach that delays one drug class until another is optimized—this delays life-saving benefits 1
• Do not discontinue GDMT for asymptomatic hypotension or mild renal function changes during hospitalization 1
• Avoid combining ACE inhibitors with ARBs and MRAs due to increased risk of renal dysfunction and hyperkalemia 2
• Never use diltiazem or verapamil in HFrEF patients as they worsen outcomes 2
• Do not over-diurese as this impairs tolerance of neurohormonal antagonists 1

Follow-Up and Specialist Referral

Patients seen in a heart failure clinic have significantly higher rates of appropriate GDMT initiation across all medication classes. 4 Consider early referral to HF specialists, particularly for patients with persistent hypotension preventing GDMT optimization or those requiring advanced therapies. 2