Cardiovascular · Topic 7 of 48

Heart Failure with Reduced EF (HFrEF)

Cardiovascular · heart failure

Heart Failure with Reduced EF (HFrEF)

LVEF 40% or less. Start all four mortality-lowering drug classes — ARNI, beta-blocker, MRA, SGLT2 inhibitor — and titrate to target doses.

Key numbers

HFrEF: LVEF 40% or lessLVEF ≤ 40%

No ARNI within 36 h of ACEi36-h ACEi washout

MRA: eGFR above 30, potassium below 5.0K⁺ < 5.0 mEq/L

Primary-prevention ICD when LVEF stays ≤ 35%LVEF ≤ 35%

CRT for LBBB, QRS ≥ 150 msQRS ≥ 150 ms

01 · Defined byHFrEF: LVEF 40% or less

HF is classified by LVEF: HFrEF ≤ 40%, HF with mildly reduced EF 41–49%, HFpEF ≥ 50%; HF with improved EF is a prior LVEF ≤ 40% that has risen above 40%.

02 · GiveFour pillars: ARNI, beta-blocker, MRA, SGLT2i

Every symptomatic HFrEF patient gets the four foundational classes — ARNI (or ACE inhibitor/ARB), an evidence-based beta-blocker, an MRA and an SGLT2 inhibitor — each lowering mortality; titrate to target or maximum tolerated doses.

03 · DoPrimary-prevention ICD when LVEF stays ≤ 35%

Implant a primary-prevention ICD for LVEF ≤ 35% with NYHA II–III symptoms on chronic GDMT, at least 40 days after an MI, when meaningful survival over 1 year is expected.

What it is

Core idea

ACC/AHA stages A to DStages: A at risk, no structural disease; B structural disease, no symptoms; C structural disease with current or prior symptoms; D refractory HF needing advanced therapy or palliation. Asymptomatic stage C stays stage C.

Diagnosis & monitoring

Work-up

Accept a creatinine rise up to 30%Check potassium and creatinine before and after starting RAAS inhibitors and MRAs; an early creatinine rise of 20–30% is expected and is not a reason to stop. Stop the MRA if K⁺ exceeds 5.5 mEq/L.

Management

Orders

Use carvedilol, metoprolol succinate or bisoprololOnly carvedilol (target 25 mg twice daily; 50 mg if ≥ 85 kg), metoprolol succinate (200 mg daily) and bisoprolol (10 mg daily) have HFrEF outcome evidence; start low and titrate over weeks.

Sacubitril/valsartan: start 49/51 mg twice dailySacubitril/valsartan is preferred over an ACE inhibitor or ARB: start 49/51 mg twice daily (24/26 mg if ACEi/ARB-naive, low-dose or hypotension-prone), titrating every 2–4 weeks to 97/103 mg twice daily.

Dapagliflozin or empagliflozin 10 mg dailySGLT2 inhibitors (dapagliflozin or empagliflozin 10 mg daily) cut HF hospitalization and cardiovascular death with or without diabetes; expect a small nonprogressive eGFR dip and watch for genital infection and euglycemic ketoacidosis.

Hydralazine–isosorbide dinitrate for African American patientsAdd hydralazine plus isosorbide dinitrate for self-identified African American patients with NYHA III–IV HFrEF on optimal therapy; the combination also substitutes when ARNI, ACE inhibitor and ARB cannot be used.

CRT for LBBB, QRS ≥ 150 msCardiac resynchronization therapy is indicated for LVEF ≤ 35%, sinus rhythm, LBBB with QRS ≥ 150 ms and NYHA II, III or ambulatory IV symptoms on GDMT; it lowers mortality and hospitalization.

Ivabradine if sinus rate ≥ 70 on beta-blockerIvabradine can be added for NYHA II–III HFrEF with LVEF ≤ 35% in sinus rhythm with resting heart rate ≥ 70 bpm despite a maximally tolerated beta-blocker; it does nothing in atrial fibrillation.

IV iron for iron deficiencyCheck iron studies: iron deficiency (ferritin < 100 ng/mL, or 100–300 with transferrin saturation < 20%) is treated with IV iron, which improves functional status and quality of life; oral iron absorbs poorly.

Red flags & don'ts

Avoid harm

No ARNI within 36 h of ACEi avoidSacubitril/valsartan must not be given with an ACE inhibitor or within 36 hours of the last ACE inhibitor dose, or with any history of angioedema; switching from an ARB needs no washout.

MRA: eGFR above 30, potassium below 5.0 avoidSpironolactone or eplerenone is indicated for NYHA II–IV HFrEF if eGFR is above 30 mL/min/1.73 m² and potassium is below 5.0 mEq/L; stop potassium supplements and recheck K⁺ and creatinine closely.

Avoid NSAIDs, diltiazem, verapamil and thiazolidinediones avoidDrugs that worsen HFrEF: NSAIDs (sodium retention), nondihydropyridine calcium channel blockers (negative inotropes), thiazolidinediones (fluid retention) and class IC antiarrhythmics; avoid them when LVEF is reduced.

The rules

Know these

Keep GDMT when EF improvesWhen LVEF improves above 40% on treatment (HFimpEF), continue the full GDMT regimen, even if asymptomatic — stopping it in recovered dilated cardiomyopathy led to relapse in 44% within 6 months (TRED-HF).

ICD or CRT?

Commonly confused

LVEF	35% or less
ECG requirement	None
Symptoms	NYHA II–III on chronic GDMT
Other conditions	40+ days after MI; expected survival over 1 year
What it does	Prevents sudden cardiac death

More detail

Reference

Show 6 reference facts

Digoxin reduces HF hospitalizations but not mortality; start 0.125 mg daily without a load, use lower doses in renal dysfunction, and watch for toxicity, which hypokalemia and hypomagnesemia make more likely.

Vericiguat, an oral soluble guanylate cyclase stimulator, can be added for worsening HFrEF (a decompensation within 6 months) despite GDMT.

Teach daily morning weights: a gain over 2 kg in a few days means sodium and water retention — adjust the diuretic or call; limit sodium and get annual influenza vaccination.

Stage D HFrEF is referred to an advanced HF center: heart transplant (typically under 70 years) or a durable LVAD as bridge to transplant or destination therapy.

Transcatheter edge-to-edge mitral repair reduces death and HF hospitalization in selected patients with moderate-to-severe secondary MR despite optimal GDMT; CABG improves survival in selected ischemic cardiomyopathy with LVEF ≤ 35% and suitable coronary anatomy.

On sacubitril/valsartan, follow NT-proBNP rather than BNP: neprilysin inhibition raises BNP levels but not NT-proBNP.

Pearl

Four pillars, all four, as early as tolerated: ARNI, beta-blocker, MRA and SGLT2 inhibitor each lower mortality on their own.

Sources · Heidenreich PA et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol 2022;79:e263–e421 · Merck Manual Professional — Chronic Heart Failure · Merck Manual Professional — Overview of Heart Failure · Merck Manual Professional — Medications for Heart Failure · Entresto (sacubitril/valsartan) prescribing information — DailyMed · ACC — 2022 AHA/ACC/HFSA Heart Failure Guideline: Key Perspectives · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).