2024 ACC Expert Consensus Decision Pathway for HFrEF

What's New in 2024

STRONG-HF Trial Recognition: Rapid, intensive GDMT initiation in hospitalized acute HF (goal target doses within 6 weeks post-discharge) is safe and reduces 180-day all-cause death/HF readmission by 28%.
SGLT2 Inhibitors as Core Pillar: Dapagliflozin and empagliflozin recommended for all HFrEF (EF ≤40%) with proven mortality and morbidity reduction.
De Novo ARNI Strategy: Safe direct initiation of sacubitril/valsartan without prior ACE/ARB exposure improves early GDMT optimization.
Vericiguat in High-Risk: VICTORIA trial shows class 2b evidence for guanylyl cyclase stimulator reducing HF hospitalization/CV death in high-risk HFrEF with worsening symptoms.
Team-Based Care Priority: Multidisciplinary HF teams improve GDMT adherence, symptom management, and outcomes.

HFrEF Definition and Staging

Definition

LVEF ≤40% with symptoms or signs of clinical instability. This guideline focuses on chronic HFrEF (LVEF ≤40%) in stable ambulatory settings.

Stages

Stage A: At risk (HTN, CAD, diabetes) but no structural disease or symptoms.

Stage B: Structural disease (reduced LVEF, chamber enlargement, valvular disease) without symptoms.

Stage C: Structural disease WITH prior/current HF symptoms. Focus of this ECDP.

Stage D: Refractory HF symptoms with recurrent hospitalizations despite optimal GDMT. Requires advanced HF evaluation.

NYHA Functional Class

I: No limitation; ordinary activity does not cause HF symptoms.
II: Slight limitation; comfortable at rest; less than ordinary activity causes symptoms.
III: Marked limitation; ordinary activity causes symptoms; comfortable only at rest.
IV: Unable to perform any activity without symptoms or symptoms at rest.

Initial Evaluation

Recommended Testing

BNP/NT-proBNP: Support diagnosis, assess prognosis
Echocardiogram: Assess LVEF, chamber size, valvular disease, filling pressures
Labs: CBC, CMP (K+, Cr), liver function, iron, TSH, HbA1c
ECG, Chest X-ray: Assess rhythm, conduction, pulmonary congestion
Angiography/CMR: As indicated for etiology assessment

Initial Medication Titration

Serial clinic visits (1-2 weeks apart) with repeat labs, vitals, and symptoms to assess tolerability and advance GDMT until target/maximally tolerated doses achieved. Repeat assessment cycle until stable on regimen.

GDMT "Big 4" Pillars

Four medication classes with proven mortality/morbidity reduction in HFrEF:

1. ARNI / ACE-I / ARB

Sacubitril/Valsartan (Preferred)

Starting: 24/26 mg or 49/51 mg twice daily
Target: 97/103 mg twice daily
Evidence: Class 1 (PARADIGM-HF: 4.7% reduction CV death/HF hosp vs enalapril)

2. Evidence-Based Beta-Blocker

Bisoprolol: 1.25 → 10 mg daily
Carvedilol: 3.125 → 25 mg twice daily (50 mg if >85 kg)
Metoprolol Succinate (ER): 12.5-25 → 200 mg daily

Titrate every 1-2 weeks. Monitor HR, BP, signs of decompensation.

3. Mineralocorticoid Antagonist

Eplerenone: 25 mg → 50 mg daily
Spironolactone: 12.5-25 → 25-50 mg daily

Monitor K+ and eGFR at baseline, 1-2 weeks, then q3 months.

4. SGLT2 Inhibitor

Dapagliflozin: 10 mg daily (eGFR ≥20)
Empagliflozin: 10 mg daily (eGFR ≥20)

Class 1 evidence for HF hospitalization and CV mortality reduction.

GDMT Initiation Strategy

STRONG-HF Approach (Recommended)

Simultaneous initiation of ARNI + beta-blocker + MRA + SGLT2i at same visit (or within days), with goal of rapid titration to target doses within 6 weeks of hospital discharge. Safe, well-tolerated, improves outcomes.

Patient Phenotypes at Initiation

After Euvolemia Achieved:

Persistent Volume Overload (NYHA III-IV): Titrate diuretics; add hydralazine-isosorbide if BP allows
Persistently Symptomatic (on full GDMT): Consider hydralazine-isosorbide addition (African-American patients: 43% mortality reduction)
High Resting HR (≥70 bpm): Optimize beta-blocker; add ivabradine if HR remains elevated
High-Risk with Worsening: Consider vericiguat (Class 2b)

Individual Drug Initiation Pathways

ARNI Initiation

1. If on ACE-I/ARB, observe 36-hour washout to prevent angioedema.

2. Start 24/26 mg BID (or 49/51 mg BID if on ACE-I ≥10 mg enalapril equivalent for ≥2 weeks).

3. Titrate q1-2 weeks to target 97/103 mg BID. Monitor BP, K+, Cr each visit.

Beta-Blocker Initiation

1. Start low dose (bisoprolol 1.25, carvedilol 3.125, metoprolol ER 12.5-25 mg daily).

2. Increase q1-2 weeks until target or maximum tolerated dose achieved.

3. Monitor HR, BP, signs of decompensation at each titration step.

MRA Initiation

1. Start eplerenone 25 mg or spironolactone 12.5-25 mg daily.

2. Check K+ and Cr at baseline, 1-2 weeks, then q3 months.

3. Monitor for hyperkalemia; adjust if K+ >5.0 mEq/L.

SGLT2i Initiation

1. Confirm eGFR ≥20 mL/min/1.73 m² for dapagliflozin or empagliflozin.

2. Start dapagliflozin 10 mg or empagliflozin 10 mg daily (no titration needed).

3. Monitor K+, Cr after initiation, then q3 months.

Ivabradine (Heart Rate Control)

1. Confirm beta-blocker optimized and patient in sinus rhythm with HR ≥70 bpm.

2. Age ≥75 or prior conduction issues: start 2.5 mg BID with meals.

3. Age <75: start 5 mg BID with meals.

4. Reassess HR at 2-4 weeks; titrate to target HR 50-60 bpm.

Vericiguat (High-Risk Patients)

1. Confirm HFrEF on optimal GDMT with worsening symptoms despite therapy.

2. Start 2.5 mg daily.

3. Double dose q2 weeks to target 10 mg daily. Monitor BP and CBC for anemia.

Special Populations

African-American Patients

ARNIs, SGLT2i, ivabradine efficacious in African-American cohorts. If persistently symptomatic on full GDMT, add hydralazine-isosorbide dinitrate (Class 1 evidence: 43% mortality reduction).

Older Adults (Age >75)

Use lower starting doses, titrate slowly. Monitor closely for adverse effects (headache, dizziness, hyperkalemia). Subgroup analyses support GDMT benefit in elderly.

Chronic Kidney Disease

eGFR Range	Adjustment
30-60	No adjustment; monitor K+ and Cr closely
<30	Reduce ARNI to 24/26 mg BID; consider MRA discontinuation
SGLT2i <25	Dapagliflozin/empagliflozin not recommended

Type 2 Diabetes

SGLT2 inhibitors particularly beneficial (reduce HF events and mortality). Monitor for euglycemic DKA and genital infections.

Atrial Fibrillation + HFrEF

Standard GDMT applies. Rate control target HR <110 bpm; anticoagulation per CHA2DS2-VASc score.

Managing Common Comorbidities

>75% of HFrEF patients have ≥1 additional comorbidity. Key conditions: CAD, AF, HTN, dyslipidemia, CKD, diabetes, anemia, sleep apnea.

CAD: Revascularize per guidelines; no change to GDMT
AF: Rate control (<110 bpm); anticoagulation per stroke risk
CKD: Optimize GDMT per kidney function; SGLT2i offer renal protection
Anemia: Evaluate secondary causes; consider IV iron if ferritin <100 ng/mL (improves exercise capacity)
Sleep Apnea: Refer for evaluation; CPAP may improve outcomes

Medication Adherence

Barriers (20-80% nonadherent)

Patient: Perceived lack of effect, side effects, poor literacy | Medical: Complexity, comorbidities | Therapy: Frequency, side effects | Socioeconomic: Cost, transportation | System: Poor communication, limited refills

Improvement Strategies

Capitalize on post-decompensation opportunities for initiation
Assess patient health beliefs; use teach-back principle
Simplify regimens (fixed-dose combinations when possible)
Address cost barriers (generics, patient assistance programs, copay cards)
Facilitate interprofessional communication (pharmacists, care coordinators)
Provide written, patient-centered education focused on benefits/burden
Recommend adherence tools (pill boxes, mobile apps, reminders)
Monitor adherence via direct assessment, fill patterns, clinic outcomes

Team-Based Adherence: Pharmacists, nurses, care coordinators, and primary care can collaborate to identify and support nonadherent patients via remote monitoring and telehealth.

Advanced Heart Failure and Referral

Specialist Referral Triggers

New-onset HFrEF requiring GDMT optimization
High-risk features (advanced BNP/NT-proBNP, persistent NYHA II-IV symptoms, ≥1 hospitalizations)
LVEF <35% after ≥3-6 months optimal GDMT (device therapy evaluation)
Refractory symptoms, difficult medication tolerability, or need for second opinion
Candidacy for transplantation or mechanical circulatory support (LVAD)

Palliative Care Principles

Palliative care reduces suffering, improves quality of life, integrates psychological/spiritual aspects
Early palliative care consultation beneficial for goals-of-care discussions and symptom management
Hospice transition appropriate when prognosis <6 months or patient/family prioritizes comfort over life-extending therapy

Related Calculators

Evidence-based tools to support HFrEF risk stratification and clinical decision-making:

Clinical Pearls: Do's and Don'ts

Do:

Initiate GDMT promptly in all HFrEF patients after stabilization, even with mild symptoms
Titrate rapidly to target or maximally tolerated doses (goal 3-6 months)
Consider simultaneous initiation of all 4 GDMT classes (STRONG-HF strategy)
Monitor K+ and Cr closely during GDMT initiation/titration
Reassess LVEF after 3-6 months optimal GDMT before device decisions
Use team-based approach to address adherence barriers systematically
Screen regularly for comorbidities (CKD, diabetes, AF, sleep apnea)
Employ shared decision-making for treatment discussions

Don't:

Delay GDMT initiation waiting for symptom resolution with diuretics alone
Use ARNI in ACE-I angioedema history without careful risk discussion
Withhold GDMT for transient Cr elevation if K+ and BP acceptable
Assume tolerated doses without regular monitoring
Omit follow-up labs (K+, Cr) during GDMT titration
Place ICD without ≥3-6 months optimal GDMT trial unless acute indication
Dismiss adherence issues without identifying root causes
Ignore comorbidities that may worsen HF or limit GDMT options