Heart failure with reduced ejection fraction (HFrEF)

Welcome back to AudioBoards. Today we're covering one of the highest-yield topics in cardiovascular medicine: the modern management of heart failure with reduced ejection fraction, or HFrEF.

Heart failure with reduced ejection fraction (HFrEF) has undergone a major transformation in recent years, with powerful therapies that can dramatically reduce mortality, prevent hospitalizations, and improve quality of life. In this AudioBoards episode, we break down the 2024 ACC Expert Consensus Decision Pathway for HFrEF management into a practical, board-relevant discussion.

Transcript

Welcome back to AudioBoards! Today, we're covering one of the highest-yield topics in cardiovascular medicine: the modern management of heart failure with reduced ejection fraction, or HFrEF.

If you trained even a few years ago, the treatment landscape looked VERY different. Today, HFrEF management revolves around rapid initiation of guideline-directed medical therapy—often called GDMT—with the goal of reducing mortality, preventing hospitalizations, improving symptoms, and changing the natural history of the disease. The 2024 ACC Expert Consensus Decision Pathway emphasizes that treatment should be aggressive, streamlined, and focused on getting patients onto all foundational therapies as quickly as possible.

So, the days of slowly adding one medication every few months are gone?

Exactly. The modern philosophy is, "start early, start multiple therapies, and titrate rapidly." Waiting months to optimize therapy means missed opportunities to improve survival.

Let's start with definitions.

HFrEF is clinical heart failure with a left ventricular ejection fraction of 40% or less. Most of our discussion focuses on patients with chronic, stable HFrEF in the outpatient setting.

Remember the ACC/AHA stages:

Stage A: At risk for heart failure.

Stage B: Structural heart disease without symptoms.

Stage C: Structural heart disease with current or prior symptoms.

Stage D: Advanced, refractory heart failure.

Most patients receiving GDMT fall into Stage C heart failure.

What are THE FOUR PILLARS OF MODERN HFrEF THERAPY?

Yes, everything starts with the four foundational therapies.

The ACC emphasizes that every eligible patient should receive:

ARNI!

Evidence-based beta blocker!

Mineralocorticoid receptor antagonist.

SGLT2 inhibitor.

These four classes form the foundation of treatment, and provide the largest mortality and hospitalization benefits.

Can you walk us through each one?

Of course, PILLAR 1 is ARNI!

The preferred renin-angiotensin system inhibitor is an ARNI:

Sacubitril/valsartan.

ARNI therapy is preferred over ACE inhibitors and ARBs whenever possible because of superior reductions in mortality and heart failure hospitalization.

If a patient is already taking an ACE inhibitor, remember the mandatory 36-hour washout period before starting sacubitril/valsartan—to reduce the risk of angioedema.

Common barriers include…

Hypotension…

Renal dysfunction.

Hyperkalemia…

But whenever feasible, ARNI should be the FIRST choice.

PILLAR 2 is EVIDENCE-BASED BETA BLOCKERS!

Not all beta blockers are created equal.

Only three have proven mortality benefit in HFrEF:

Carvedilol!

Metoprolol succinate.

Bisoprolol.

Beta blockers reduce mortality, sudden cardiac death, and hospitalization by counteracting chronic sympathetic activation.

The key is to start low and titrate upward, but don't wait until patients are on target doses before adding other therapies.

So, all four pillars should be started before maximizing any single medication?

Exactly! That's one of the BIGGEST shifts in modern heart failure management.

PILLAR 3 is MINERALOCORTICOID RECEPTOR ANTAGONISTS.

The third pillar is MRA therapy:

Spironolactone.

Eplerenone.

These medications block aldosterone's harmful effects on myocardial remodeling and sodium retention.

Before initiation, monitor:

Potassium.

Renal function.

eGFR

The major concern is hyperkalemia, but the mortality benefits are substantial.

PILLAR 4 is SGLT2 INHIBITORS.

Perhaps the most exciting addition to heart failure treatment over the last several years is the SGLT2 inhibitor class.

The two major agents are:

Dapagliflozin

Empagliflozin

Importantly, these medications improve outcomes, regardless of whether the patient has diabetes.

Benefits include:

Reduced heart failure hospitalization.

Reduced cardiovascular death!

Improved symptoms.

Preservation of kidney function.

One reason they're so attractive is that they require little titration and have minimal effects on blood pressure.

What is tHE NEW TREATMENT STRATEGY?

Historically, clinicians would start an ACE inhibitor, wait months, titrate it, then add a beta blocker, and continue that process sequentially.

The ACC pathway strongly discourages this approach.

Instead, clinicians should rapidly establish all four pillars, often within days to weeks, and ideally achieve optimal four-drug therapy within three months of diagnosis.

The message is simple:

Don't delay life-saving therapy!

WHAT ABOUT DIURETICS?!

Where do loop diuretics fit into all of this?

Excellent question!

Loop diuretics are critical for symptom control and decongestion.

Common agents include:

Furosemide

Torsemide.

Bumetanide

But unlike the four pillars, diuretics do not improve survival.

They make patients feel better by relieving congestion, edema, and dyspnea, but they don't alter long-term mortality.

Think of them as symptom-management drugs, rather than disease-modifying therapy.

What do we MONITOR DURING GDMT INITIATION?

Whenever medications are started or titrated, monitor:

Blood pressure

Heart rate.

Renal function…

Potassium.

Symptoms of congestion.

Weight trends.

The ACC emphasizes frequent reassessment during titration because many patients can tolerate more aggressive therapy than clinicians initially assume.

What are the ADDITIONAL THERAPIES?

After foundational therapy, certain patients benefit from additional medications.

One important example is hydralazine plus isosorbide dinitrate.

This combination is recommended particularly for self-identified Black patients who remain symptomatic despite optimized foundational therapy.

It can also be used when patients cannot tolerate ACE inhibitors, ARBs, or ARNIs.

What about Ivabradine?

Ivabradine is another specialized therapy.

Consider it when:

Sinus rhythm is present.

LVEF remains reduced.

Heart rate remains elevated despite maximally tolerated beta blocker therapy.

It works by slowing the sinus node and reducing heart failure hospitalizations.

And Vericiguat?

Vericiguat is a soluble guanylate cyclase stimulator.

It's generally considered in patients with persistent, high-risk heart failure despite optimal therapy, particularly after recent worsening heart failure events.

When do DEVICEs come into the picture?

Medications are only part of the story.

Patients with persistent LVEF of 35% or less, despite at least three months of optimized GDMT, should be evaluated for device therapy.

Options include:

Implantable Cardioverter-Defibrillator (ICD).

Used primarily to prevent sudden cardiac death.

Cardiac Resynchronization Therapy (CRT).

Particularly beneficial for patients with ventricular dyssynchrony, often identified by a wide QRS complex—especially left bundle branch block.

So, medications first, then reassess EF before considering devices?

Exactly. Many patients improve significantly after GDMT optimization.

Do COMORBIDITIES MATTER?

Of course! Successful heart failure management requires attention to comorbid conditions.

Important targets include:

Hypertension.

Diabetes.

Chronic kidney disease.

Atrial fibrillation.

Iron deficiency.

Obesity.

Sleep apnea.

Coronary artery disease.

Treating these conditions can significantly improve outcomes and quality of life.

WHEN TO THINK ABOUT ADVANCED HEART FAILURE?

Not every patient responds adequately to GDMT.

Red flags for advanced heart failure include:

Recurrent hospitalizations.

Persistent NYHA Class III or IV symptoms.

Chronic hypotension.

Worsening renal function…

Need for inotropes.

Progressive ventricular dysfunction…

Recurrent ventricular arrhythmias.

These patients should be referred early to an advanced heart failure center for consideration of…

LVAD therapy.

Heart transplantation.

Advanced palliative care strategies…

The ACC stresses early referral, rather than waiting until patients are critically ill.

When do we start discussions of PALLIATIVE CARE?

Another important reminder from the consensus pathway is that palliative care is not reserved for end-of-life situations.

Palliative care can improve:

Symptom burden.

Quality of life.

Goal-concordant decision making.

Caregiver support.

For patients with advanced disease, hospice discussions should occur proactively, rather than during a crisis.

Let's finish with the board-style takeaways.

Yes, if you remember nothing else, remember these:

HFrEF equals LVEF 40% or less.

The four pillars are:

ARNI!

Evidence-based beta blocker.

MRA!

SGLT2 inhibitor.

Start all four foundational therapies rapidly!

Aim for maximally tolerated doses within approximately three months.

Diuretics improve symptoms, but not survival.

Evaluate for ICD or CRT after at least three months of optimized GDMT.

Consider hydralazine-isosorbide dinitrate, ivabradine, and vericiguat in selected patients.

Monitor blood pressure, renal function, and potassium closely.

Recognize advanced heart failure early.

Early GDMT optimization saves lives!

So if there's one theme from the 2024 ACC pathway, it's that HFrEF treatment should be rapid, comprehensive, and focused on getting patients onto all four foundational therapies as soon as possible.

Exactly! The era of slow, sequential treatment escalation is over. Modern HFrEF management is built around rapid implementation of evidence-based therapies that dramatically reduce mortality and hospitalization. The earlier we initiate and optimize GDMT, the better the outcomes for our patients.

Thanks for listening to AudioBoards. Stay tuned for more educational content in our next episode! The views and opinions expressed on the AudioBoards Podcast do not necessarily reflect those of our employers. This podcast is for educational purposes only and should not be used to diagnose or treat any medical conditions. It is not a substitute for professional medical advice. Always consult a qualified, board-certified healthcare provider for any medical concern.