Heart; Prevention

Fighting heart failure with ‘Fantastic Four,’ new guidelines

Heart; Prevention

Heart failure guidelines illustration
Updated heart failure guidelines highlight two conditions for which there previously were no effective therapies: ATTR amyloidosis and heart failure with preserved ejection fraction.

Cardiovascular disease continues to be the leading cause of death around the world, and in the last five years, knowledge surrounding the diagnosis and management of heart failure (HF) has increased significantly.

In 2022, the American College of Cardiology (ACC) and American Heart Association (AHA Joint Committee on Clinical Practice Guidelines, and the Heart Failure Society of America (HFSA), collaborated to update the 2017 heart failure guidelines, which give patient-centric recommendations for the prevention, diagnosis, and treatment of HF.

Mark S. Link, M.D., the Section Head of Electrophysiology at UT Southwestern, joined me and other experts as authors of the 2022 guidelines:

While the new heart failure guidelines contain a lot of important recommendations, here are three key highlights for patients and their clinicians:

  1. SGLT2 inhibitors are now recommended for people with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have Type 2 diabetes. This recommendation creates a “Fantastic Four” of effective medications to treat patients with HFrEF. In addition, SGLT2 inhibitors are also the first medication recommended to treat patients with heart failure with preserved ejection fraction (HFpEF).
  2. For some patients, transthyretin cardiac amyloidosis (ATTR-CA) may be diagnosed with less invasive methods – imaging and a blood test rather than a biopsy. We also have effective treatments for ATTR-CA, which can be either acquired or in a genetic form.
  3. “Simple clinical clues” can help physicians identify patients with advanced heart failure. This assessment should be done at each encounter with a patient who has heart failure. Once advanced heart failure is recognized, the patient can be referred to an advanced heart failure center where they can receive specialized therapies.

The challenge we now face is to get the recommendations in the guidelines implemented into clinical practice. Historically, it takes years for the translation of guidelines into routine clinical care, and this is something we hope to improve upon.

Top 3 takeaways from new HF guidelines

Heart failure is classified based on a patient’s left ventricular ejection fraction (LVEF) – how well the left side of the heart is pumping.

Two general categories help guide the treatment of patients with heart failure:

  • HFpEF: Heart failure with preserved ejection fraction, with an LVEF of 50% or more.
  • HFrEF: Heart failure with reduced ejection fraction, with an LVEF of 40% or less.

The new guidelines have significant implications for both sets of patients.

1. SGLT2 inhibitors join three previous medications recommended for HFrEF and become the first to significantly improve outcomes for patients with HFpEF.

The takeaway: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been added as a fourth approved medication to the three already recommended to manage HFrEF. SGLT2i are also the first class of medications with strong evidence to improve long-term outcomes in patients with an LVEF above 40% including those with HFpEF.

Developed to treat adults with Type 2 diabetes, SGLT2i medications were first shown to reduce the risk of developing heart failure by 33% in patients with diabetes.

Following that observation, they were tested as a potential therapy for patients with established heart failure. Remarkably, they reduced the risk of hospitalization or death when given with a background of contemporary medications in patients with HFrEF. More recently, they also were shown to have benefit in patients with HFpEF, a condition for which previously we did not have any effective therapies.

The potential of SGLT2i for heart failure treatment was showcased at the 2021 AHA conference and in 2022 and now are formally incorporated into the heart failure guidelines.

These recommendations represent a paradigm shift in the treatment of patients with HFrEF. Going forward, patients with HFrEF should be prescribed the “Fantastic Four,” even if they do not have diabetes: The other classes of medications, all of which have been shown to improve clinical outcomes in patients with HfrEF, include:

2. A less invasive way to diagnose ATTR and the first effective treatment for it.

The takeaway: Specialists now can diagnose transthyretin cardiac amyloidosis – an abnormal buildup of transthyretin protein in the heart – using imaging and a blood test instead of a biopsy. Additionally, we now have the first effective therapy for transthyretin amyloidosis (ATTR).

The two most common types of cardiac amyloidosis are transthyretin amyloidosis (ATTR) and light chain (AL) amyloidosis:

  • ATTR amyloidosis is caused by the abnormal deposition in the heart of the blood protein transthyretin (TTR). This sometimes can be acquired during a lifetime or may be hereditary.
  • AL amyloidosis is caused by abnormal bone marrow cells, called plasma cells, that make an abnormal monoclonal protein that aggregates into amyloid fibrils and deposits in the heart.

Until recently, diagnosing cardiac ATTR amyloidosis was challenging. Doctors rarely looked for it because there was no effective treatment and diagnosis often would require a catheter-based endomyocardial biopsy, an invasive and expensive test that is not widely available. Because of this, the condition was considered to be somewhat rare.

The 2022 heart failure guidelines highlighted that ATTR cardiac amyloidosis is easier to diagnose – and more treatable – than once believed.


We can now diagnose ATTR amyloidosis using a two-pronged strategy. One part is a nuclear medicine scan, which uses a repurposed “bone-radiotracer.” In the United States, this special tracer is called “Technetium Pyrophosphate.” These scans can detect deposition of transthyretin amyloidosis in the heart. The other crucial component of this work-up is a blood and urine sample to test for abnormal monoclonal proteins, which may indicate the presence of AL amyloidosis.

As knowledge about amyloidosis spreads in the medical community, cardiologists are beginning to look more closely for the condition. Clinicians are finding that amyloidosis is far more common – with more obvious symptoms – than once believed. For example, about 10-20% of patients diagnosed with HFpEF also have amyloidosis.

If you are seeing a cardiologist for heart failure, ask about getting tested for cardiac amyloidosis. Potential symptoms outside of those typically seen with heart failure include:

  • Carpal tunnel syndrome
  • Enlarged tongue
  • Purple color around the eyes
  • Narrowing of the spine (spinal stenosis)
  • Spontaneous tendon rupture
  • The feeling of pins and needles in the legs, arms, or feet
  • Chronic diarrhea or constipation
  • Loss of bladder control
  • Low blood pressure


UT Southwestern has a dedicated cardiac amyloidosis team, led by Justin Grodin, M.D., M.P.H., and Gurbakhash Kaur, M.D., to diagnose, treat, and manage even the rarest and most complex subtypes of amyloidosis. Our researchers and clinicians have been on the forefront of developing the latest amyloidosis medications, and our patients can receive the most cutting-edge treatments via clinical trials offered at UT Southwestern for those interested.

The first FDA-approved medication for ATTR cardiomyopathy is Tafamidis. It has fundamentally changed the outcome of patients with ATTR by helping to:

  • Slow disease progression
  • Reduce heart-related hospitalization
  • Reduce risk of cardiac death by 30%

This combination of less invasive diagnostic methods and effective therapies has given new hope to patients with amyloidosis and their cardiologists.

Related reading: New drugs for cardiac amyloidosis provide hope for patients

3. 'Simple clinical clues’ can help identify patients with advanced heart failure, allowing them to get the care they need.

The takeaway: All patients with heart failure should be evaluated at each encounter for the presence of advanced heart failure. The diagnosis of advanced heart failure allows referral to specialized centers where patients can be treated appropriately. Unfortunately, these “simple clinical clues” are too often overlooked.

If patients had any of these experiences in the past 12 months, then referral to an advanced heart failure center should be considered.

  • More than one hospitalization or emergency department visit for heart failure
  • Systolic blood pressure (the top number) routinely less than 100 mm Hg
  • Deterioration in kidney function, such as higher levels of creatinine and urea nitrogen as measured in the blood
  • An inability to tolerate components of guideline directed medical therapy, such as beta blockers or ACEi or ARNI, often due to low blood pressure, kidney failure, or buildup of excess fluid
  • Shortness of breath while dressing, showering, or walking less than one block
  • Unintentional weight loss

Earlier detection of advanced heart failure may prevent a patient from becoming too ill to be eligible for lifesaving treatments, such as a heart transplant or a left ventricular assist device (LVAD).

Indeed, the guidelines recommend that patients with heart failure be routinely assessed at each visit to see if they have progressed to an advanced state so that fewer patients slip through the cracks, Processes should be developed to streamline the referral process to advanced heart failure centers. Patients can also be empowered to seek consultation at advanced heart failure centers.

Related reading: LVADs no longer just a bridge, but a long-term alternative to heart transplant

Moving forward faster in heart care

Successful implementation of the recommendation in the new heart failure guidelines will be a collaborative effort between leading organizations involved in the release of the guidelines (AHA, ACC, HFSA), medical centers, health organizations, heart failure specialists, other clinicians on the frontline, and patients.

These new heart failure guidelines will only make a positive impact if they are implemented as real-world solutions. My sincere hope is that we will do better with the implementation of these guidelines than we have in the past. Together, we can make that possible – and save a lot of lives in the process.

To meet with one of our heart failure specialists, call 214-645-8300 or request an appointment online.