New heart failure guidelines offer a changing landscape

Heart Failure

Olivia C. Welter, PharmD

Year after year, heart disease is widely recognized as the leading cause of death in the United States. Over 650,000 American lives are lost due to heart disease annually. Because of this, expert bodies have historically published highly detailed guidelines to help practitioners make the best clinical decisions for their heart disease patients.

In early 2022, the American Heart Association (AHA), the American College of Cardiology (ACC), and the Heart Failure Society of America (HFSA) released an updated heart failure guideline. Key aspects of this guideline include the introduction of heart failure with mildly reduced ejection fraction (HFmrEF) as a heart failure classification, recommended use of an additional class of drug for all heart failure classifications, revised categorization of heart failure stages, and actions for advanced heart failure care.

As with most areas of practice, treatment of heart failure has rapidly evolved in the last decade. The 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure is intended to replace both the 2013 iteration of the guideline created by the same groups as well as the 2017 update to the 2013 guideline. This makes the 2022 guideline the first complete refresh of heart failure guidance for clinicians in 9 years. This new guideline will provide health care professionals with contemporary practice standards centered on evidence from recent groundbreaking research studies.

SGLT2 inhibitors: the new frontier

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs most commonly known for their benefits in treating patients with diabetes. They have quickly become a mainstay in diabetes management, even beating out metformin as the first-line recommended therapy. Researchers have now proven that SGLT2 inhibitors are also useful for all classifications of heart failure, however. The new guideline recommends SGLT2 inhibitors as a treatment for heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and HFmrEF.

Although this drug class can now universally be applied in heart failure treatment, there is stronger evidence to support its use in one category in particular: patients who have chronic, symptomatic HFrEF. The previous recommendation called for treating these patients with medications from 3 classes: renin–angiotensin system inhibiting drugs, beta blockers, and mineralocorticoid receptor antagonists (MRAs). The 2022 guideline adds SGLT2 inhibitors as a fourth drug class to use in guideline-directed medical treatment for this type of patient. Not only has the SGLT2 inhibitor class been introduced as a potential solution, but the guideline authors give it a Class 1 Level A recommendation, meaning it has high-quality evidence from multiple studies supporting its status as a strongly recommended therapy choice.

So far, dapagliflozin and empagliflozin are the two SGLT2 inhibitors approved by FDA for use in heart failure regardless of diabetes status. The two other SGLT2 inhibitors, canagliflozin and ertugliflozin, have not been FDA-approved for this purpose, even though clinical trial results recently found that canagliflozin was beneficial in heart failure even if patients do not have diabetes.

A class of its own

Historically, treatment guidance has only been provided to patients with an ejection fraction either lower than 40% or higher than 50%. This meant that clinicians attempting to treat patients with an ejection fraction between 40% and 50% were often referencing ambiguous guidance when making clinical decisions. In the 2013 guideline, these patients were described as having “HFpEF, borderline.” For several years now, clinicians have considered patients with this in-between ejection fraction to be classified as having HFmrEF, formally defined for the first time in this guideline.

There is one type of drug highlighted in the 2022 guideline that carries a strong, high-quality evidence-based recommendation for treating patients with this mildly reduced left ventricular ejection fraction, if needed. Diuretics, which reduce fluid overload are the first line in relieving symptoms of HFmrEF. Treatment could also include any of the other 4 drug classes that are used in HFrEF, but these classes carry weaker recommendations and lower quality evidence supporting their use when ejection fraction is between 40% and 50%.

In addition to new treatment guidance for HFmrEF, efficacious therapies for HFpEF have now been identified in the guideline for the first time. Treatment recommendations for HFpEF are the same as the recommendations for HFmrEF, excluding ACE inhibitors and MRAs.

Setting the stage

The 4 stages of heart failure have been revised as part of the 2022 guideline. The intention of the revision was to place emphasis on patients who are encroaching on a formal heart failure diagnosis, but don’t quite meet all the criteria.

These categories include stage A (at risk for heart failure) and stage B (pre-heart failure). Stage A focuses on those patients who have chronic diseases such as diabetes, hypertension, and obesity as well as patients who may have a genetic predisposition for cardiomyopathy. In stage B, the focus shifts to patients who may not have ever exhibited symptoms of heart failure, but who have structural heart disease, increased filling pressures, and/or risk factors concurrently with abnormal biomarkers.

For patients in stages A or B, primary prevention is key. Any strategy that can prevent symptomatic heart failure from developing is considered primary prevention, including general healthy lifestyle habits such as maintaining a healthy diet and regular physical activity. The guideline notes that pharmacotherapy may be considered in patients with certain disease states.

Advanced disease calls for advanced care

Patients with advanced heart failure are considered to be in stage D according to the 2022 guideline. Despite following guideline-directed medical therapy recommendations, their heart failure symptoms cause disruptions in their daily lives and even lead to recurrent hospitalizations.

When the evidence-based regimen doesn’t work, as is the case with stage D patients, then the guideline states that specialists should be added to the equation. Generally, a specialty team based at an advanced heart failure center will be able to make well-informed decisions in initiating advanced therapies such as a heart transplant.

Palliative care is also an option for patients who fall into this category. When receiving palliative care, the patient’s care goals should always be prioritized when making clinical decisions. Palliative inotropes like milrinone and dobutamine may be prescribed in instances where their use aligns with the patient’s goals.  ■

Take-home messages

The AHA, ACC, HFSA guideline offers 10 take-home messages for clinicians to consider when treating their heart failure patients.

1. Guideline-directed medical therapy for heart failure (HF) with reduced ejection fraction (HFrEF) now includes 4 medication classes that include sodium-glucose cotransporter-2 (SGLT2) inhibitors.
2. SGLT2 inhibitors have a 2a class of recommendation in HF with mildly reduced ejection fraction (HFmrEF). Weaker recommendations (class of recommendation 2b) are made for angiotensin receptor-neprilysin inhibitors, angiotensin converting enzyme ihibitors, ARBs, MRAs, and beta blockers in this population.
3. New recommendations for HFpEF are made for SGLT2 inhibitors (class of recommendation 2a), MRAs (class of recommendation 2b), and ARNis (class of recommendation 2b). Several prior recommendations have been renewed including treatment of hypertension (class of recommendation 1), treatment of atrial fibrillation (class of recommendation 2a), use of ARBs (class of recommendation 2b), and avoidance of routine use of nitrates or phosphodiesterase-5 inhibitors (class of recommendation 3).
4. Improved left ventricular ejection fraction (LVEF) is used to refer to those patients with previous HFrEF who now have an LVEF > 40%. These patients should continue their HFrEF treatment.
5. Value statements were created for select recommendations for which high-quality cost-effectiveness studies of the intervention have been published.
6. Amyloid heart disease has new recommended treatments, including screening for serum and urine monoclonal light chains, bone scintigraphy, genetic sequencing, tetramer stabilizer therapy, and anticoagulation.
7. Evidence supporting increased filling pressures is important for the diagnosis of HF if LVEF is > 40%. Evidence for increased filling pressures can be obtained from noninvasive (e.g., natriuretic peptide, diastolic function on imaging) or invasive testing (e.g., hemodynamic measurement).
8. Patients with advanced HF who wish to prolong survival should be referred to a team specializing in HF. An HF specialty team reviews HF management, assesses suitability for advanced HF therapies, and uses palliative care including palliative inotropes where consistent with the patient’s goals of care.
9. Primary prevention is important for those at risk for HF (stage A) or pre-HF (stage B). Stages of HF were revised to emphasize the new terminologies of “at-risk” for HF for stage A and pre-HF for stage B.
10. Recommendations are provided for select patients with HF and iron deficiency, anemia, hypertension, sleep disorders, type 2 diabetes, atrial fibrillation, coronary artery disease, and malignancy. ■