# HFrEF vs HFpEF (USMLE Heart Failure)

> What is the difference between HFrEF and HFpEF?

The ejection fraction cutoffs, the mechanisms behind them, and why only HFrEF has four drug classes that reduce mortality.

HFrEF is heart failure with an ejection fraction ≤40% caused by impaired systolic contraction and eccentric ventricular dilation, and it is treated with four mortality-reducing classes: ARNI or ACE inhibitor, evidence-based beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor. HFpEF has an ejection fraction >=50% with impaired diastolic relaxation, where only SGLT2 inhibitors clearly reduce heart failure hospitalization.

## What is the difference between HFrEF and HFpEF?

**Ejection fraction draws the line, but mechanism is what the exam tests.** In **HFrEF (systolic heart failure)** the ventricle cannot eject: contractility falls, end-systolic and end-diastolic volumes rise, and the chamber remodels **eccentrically** -- sarcomeres in series, dilated with a thin wall.

**HFpEF (diastolic heart failure) is a filling problem, not an emptying problem.** Pressure overload produces **concentric hypertrophy** -- sarcomeres in parallel -- plus interstitial fibrosis, giving a small, stiff cavity. Filling pressures rise sharply, so the patient congests while still ejecting a normal *fraction* of a reduced end-diastolic volume. Long-standing hypertension dominates; hypertrophic cardiomyopathy, amyloidosis, and [aortic stenosis](/blog/valvular-heart-disease-murmur-usmle) are the others.

An EF of 41-49% is **HFmrEF**, treated like HFrEF. Both share congestion -- dyspnea, orthopnea, jugular venous distension, edema -- so **symptoms never distinguish them; echocardiography does.** The [Cardiology](/topics/cardiology) hub covers the rest of the system.

## HFrEF vs HFpEF: side-by-side comparison

**Seven variables separate the two syndromes on a stem.**

| Feature | HFrEF | HFpEF |
| --- | --- | --- |
| **Ejection fraction** | ≤40% | >=50% |
| **Mechanism** | ↓ contractility, ↑ end-diastolic volume, eccentric hypertrophy | ↓ compliance, normal or ↓ end-diastolic volume, concentric hypertrophy |
| **Typical patient** | Older man after MI, dilated cardiomyopathy, alcohol or anthracyclines | Older woman with hypertension, obesity, diabetes, atrial fibrillation |
| **Exam findings** | Displaced, diffuse PMI; **S3 gallop** | Sustained, non-displaced PMI; **S4 gallop**; LVH on ECG |
| **BNP behaviour** | Elevated, tracking wall stress | Elevated but lower for a given filling pressure; blunted by obesity |
| **Treatment** | Quadruple therapy plus loop diuretic for congestion | Loop diuretic, SGLT2 inhibitor, BP and weight control |
| **Mortality benefit** | All four pillars reduce mortality | No class clearly reduces mortality; SGLT2 inhibitors cut hospitalization |

## Why the four mortality-benefit drugs work in HFrEF

**Neurohormonal activation, not low output itself, is what kills patients with HFrEF.** A failing ventricle triggers renin-angiotensin-aldosterone and sympathetic activation, driving hypertrophy, apoptosis, and fibrosis. Each pillar interrupts that loop.

- **ACE inhibitors, ARBs and ARNI** block angiotensin II formation or its receptor, lowering afterload and preload and reducing remodeling. Sacubitril/valsartan adds **neprilysin inhibition** and needs a **36-hour washout** from an ACE inhibitor to avoid angioedema.
- **Evidence-based beta-blockers** -- only **carvedilol, metoprolol succinate, bisoprolol** -- blunt sympathetic drive, reduce arrhythmic death, and raise EF over months.
- **Mineralocorticoid receptor antagonists** block aldosterone-mediated fibrosis and sodium retention.
- **SGLT2 inhibitors** help independent of diabetes, via natriuresis, preload reduction, and improved myocardial energetics.

**HFpEF resists the older three because its problem is stiffness and fibrosis, not a dilated chamber waiting to be reverse-remodeled.** Dropping preload too far pushes output off a steep curve. SGLT2 inhibitors are the exception, cutting hospitalization across the EF spectrum.

## High-yield drug contraindications and cautions in heart failure

**Several common drugs actively worsen heart failure.**

| Drug Class | Mechanism | Use in HFrEF | Use in HFpEF | Key Contraindication |
| --- | --- | --- | --- | --- |
| **ACE inhibitor / ARB** | ↓ angiotensin II formation or receptor binding | First-line, mortality benefit | BP control only | Pregnancy, angioedema, bilateral renal artery stenosis |
| **ARNI (sacubitril/valsartan)** | ARB plus neprilysin inhibition | Preferred over ACEi if tolerated | Not standard | ACE inhibitor within 36 hours; prior angioedema |
| **Beta-blocker (carvedilol, metoprolol succinate, bisoprolol)** | ↓ sympathetic drive | Mortality benefit; start when euvolemic | Rate control only | Acute decompensation, shock, high-grade AV block |
| **MRA (spironolactone, eplerenone)** | Blocks aldosterone-driven fibrosis | Mortality benefit | Selected patients | Hyperkalemia, advanced CKD; gynecomastia with spironolactone |
| **SGLT2 inhibitor (dapagliflozin, empagliflozin)** | Natriuresis, ↓ preload | Mortality benefit, diabetic or not | Recommended; ↓ hospitalization | Type 1 diabetes, prior euglycemic DKA |
| **Loop diuretic (furosemide)** | Blocks Na-K-2Cl transporter | Symptom relief only | Symptom relief only | Sulfa allergy (use ethacrynic acid) |
| **Hydralazine + isosorbide dinitrate** | Arterial and venous dilation | Added benefit in Black patients | Not indicated | Concurrent PDE-5 inhibitor; drug-induced lupus |
| **Non-dihydropyridine CCB (verapamil, diltiazem)** | Negative inotrope | **Avoid** | Acceptable for rate and BP control | Reduced EF -- precipitates decompensation |
| **Thiazolidinedione (pioglitazone)** | PPAR-γ agonist causing fluid retention | **Avoid** | **Avoid** | NYHA class III-IV heart failure |

NSAIDs are a classic precipitant of decompensation in established heart failure, because they inhibit renal prostaglandins and cause sodium retention plus **diuretic resistance**. **Class I antiarrhythmics** such as flecainide are negatively inotropic and proarrhythmic in structural heart disease -- **amiodarone and dofetilide** are safe. And **never start a beta-blocker during acute decompensation**; wait for euvolemia, though an established dose is continued unless the patient is hypotensive or on inotropes.

## How to identify the type from the vignette

> **10-second exam strategy:** Find the EF. None given? Use the gallop -- **S3 = dilated, volume-overloaded ventricle (HFrEF)**; **S4 = stiff, hypertrophied ventricle (HFpEF)**. Then check the patient: post-MI with a displaced PMI is HFrEF; obese and hypertensive with LVH on [ECG](/blog/how-to-read-ecg-usmle) is HFpEF.

## How this is tested on the exam

- **Post-MI man, dyspnea, displaced PMI, S3, EF 30%** -> HFrEF; start all four pillars, not just a diuretic.
- **Obese 74-year-old woman, hypertension, atrial fibrillation, S4, EF 60%** -> HFpEF; loop diuretic, SGLT2 inhibitor, BP control.
- **Cool extremities, hypotension, on dobutamine** -> do *not* start or uptitrate a beta-blocker.
- **Diabetic with HFrEF on new pioglitazone, now edematous** -> stop the thiazolidinedione.

## Common wrong-answer traps

- **Trap: dismissing preserved EF as "not really heart failure."** HFpEF causes real congestion, repeated hospitalization, and substantial mortality.
- **Trap: verapamil or diltiazem for rate control in AF with HFrEF.** Use a beta-blocker, or digoxin when hypotensive.
- **Trap: assuming digoxin improves survival.** Digoxin reduces symptoms and hospitalizations only; hypokalemia worsens toxicity.
- **Trap: following BNP on sacubitril/valsartan.** Neprilysin inhibition raises BNP, so **NT-proBNP** is the valid marker.

## Sources

- [ACC/AHA heart failure guidelines](https://www.acc.org/Guidelines)
- [USMLE Step 2 CK content outline](https://www.usmle.org/step-exams/step-2-ck)

Heart failure pharmacology becomes pattern recognition after enough vignettes -- [Master heart failure pharmacology with StepGenie](https://dashboard.stepgenie.app/sign-up) and drill adaptive cardiology questions on the EF cutoffs, four pillars, and contraindications.

## Frequently asked questions

### What ejection fraction defines HFrEF versus HFpEF?

HFrEF is defined by an ejection fraction of 40% or less, and HFpEF by an ejection fraction of 50% or more. The band in between, an ejection fraction of 41 to 49 percent, is called HFmrEF, or heart failure with mildly reduced ejection fraction, and boards expect you to manage it the same way you manage HFrEF.

### Why do beta-blockers reduce mortality in HFrEF but not in HFpEF?

In HFrEF, chronic sympathetic activation drives myocyte hypertrophy, apoptosis and fibrosis in a dilated ventricle, so blocking that signal reverses adverse remodeling and raises ejection fraction over months. HFpEF has no dilated ventricle to reverse-remodel; its problem is a stiff, fibrotic, hypertrophied chamber. Beta-blockers there only control rate and blood pressure, without a demonstrated mortality benefit.

### Can BNP tell you whether a patient has HFrEF or HFpEF?

No. BNP and NT-proBNP rise with ventricular wall stress in both syndromes, so an elevated level supports the diagnosis but never identifies the type, and it also rises with renal failure, atrial fibrillation and pulmonary embolism. Levels tend to be lower in HFpEF for a given filling pressure and are blunted by obesity. Only echocardiography gives the ejection fraction. Note that sacubitril raises BNP through neprilysin inhibition, so follow NT-proBNP instead.

### Which drugs should be avoided in a patient with heart failure?

Avoid non-dihydropyridine calcium channel blockers such as verapamil and diltiazem in HFrEF because they are negative inotropes, and avoid thiazolidinediones such as pioglitazone because they cause fluid retention. NSAIDs promote sodium retention and diuretic resistance, and class I antiarrhythmics such as flecainide are proarrhythmic in structural heart disease. Never start a beta-blocker during acute decompensation.

### What are the four pillars of HFrEF therapy?

The four mortality-reducing classes are an ARNI (sacubitril/valsartan) or an ACE inhibitor or ARB, an evidence-based beta-blocker limited to carvedilol, metoprolol succinate or bisoprolol, a mineralocorticoid receptor antagonist such as spironolactone or eplerenone, and an SGLT2 inhibitor such as dapagliflozin or empagliflozin. Loop diuretics relieve congestion but do not improve survival.

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Canonical page: [HFrEF vs HFpEF (USMLE Heart Failure)](https://www.stepgenie.app/blog/hfref-vs-hfpef-usmle)
Topic hub: [Cardiology](https://www.stepgenie.app/topics/cardiology)