New HF Definition, Stage Updates Outlined in 2022 ACC/AHA/HFSA Guidelines

During a panel at the American College of Cardiology’s (ACC) 70th Scientific Session, experts highlighted updates to the 2022 American Heart Association (AHA)/ACC/Heart Failure Society of America (HFSA) guidelines for the management of heart failure (HF) and offered a new definition of the condition.

“The syndrome of HF is defined as a complex clinical syndrome with symptoms and signs that result from structural or functional impairment,” said Biykem Bozkurt, MD, PhD, guideline writing committee vice-chair and professor of Medicine-Cardiology at Baylor College of Medicine.

With regard to terminologies for HF trajectory, the guidelines emphasized the use of “persistent HF” as opposed to “stable HF,” as the term “stable” creates inertia, while “persistent HF requires optimization,” Bozkurt added. The phrase “HF in remission” is also preferred over “HF in recovery” as the majority of patients who withdraw from therapy will relapse.

Among the updates included are a redefinition of HF stages to emphasize prevention and the addition of sodium–glucose co-transporter 2 (SGLT2) inhibitors for the treatment of symptomatic HF.

This latter inclusion comes off the heels of an FDA approval for empagliflozin, (Jardiance , an SGLT2 inhibitor from Eli Lilly and Boehringer Ingelheim) for a broader range of patients with HF, including those with preserved ejection fraction (HFpEF)—a condition with a poor prognosis and very limited treatment options.

Changes reflect the Class 1A (strong) recommendation of SGLT2 inhibitor use in patients with HF with reduced ejection fraction (HFrEF), while the drugs also have a “Class of Recommendation 2a [moderate] in heart failure with mildly reduced ejection fraction (HFmrEF). Weaker recommendations (Class of Recommendation 2b) are made for angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin-converting-enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA), and beta blockers in this population,” authors wrote.

These medication classes are also recommended for certain patients with HFrEF.

“After careful evaluation of new evidence, guideline-directed medical therapy now includes 4 medication classes that include SGLT2 inhibitors. Irrespective of diabetes status, the DAPA-HF and EMPEROR-HF trials have shown the benefit of treating patients with HFrEF with SGLT-2 inhibitors, showing a 30% reduction in heart failure rehospitalization,” said Bozkurt. “This is a major step forward in reducing mortality rates in this vulnerable population.”

New HF classifications based on left ventricular ejection fraction (LVEF) are as follows:

• HFrEF=LVEF ≤ 40%
• HF with improved EF (HFimpEF) = previous LVEF ≤40% and a follow-up measurement of LVEF >40%
• HFmrEF = LVEF 41%–49% and evidence of spontaneous or provokable increased LV filling pressures (eg, elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)
• HFpEF = LVEF ≥ 50% and evidence of spontaneous or provokable increased LV filling pressures (eg, elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)

Patients with previous HFrEF who have a LVEF over 40% are now classified as having “improved LVEF” and should continue HFrEF treatment. “If the LVEF is 41% to 49% (mildly reduced) or ≥ 50% (preserved), evidence of spontaneous or provokable increased LV filling pressures is needed to confirm a diagnosis of HF,” authors wrote.

Inclusion of SGLT2 inhibitors in the guidelines was welcomed by the Boehringer Ingelheim and Lilly Alliance, which stated the recommendations “are encouraging news, as they reflect the availability of more proven treatment options for adults with heart failure across the spectrum of ejection fraction.”

Updated guidelines replace those from 2013 and 2017 and are intended to provide patient-centric, evidence-based recommendations for clinicians. Relevant clinical trials published through September 2021 were included in the guidelines’ formulation, along with findings of a literature search conducted between May and September 2020.

An additional goal of the new guidance was “prevention of heart failure through optimizing blood pressure control and adherence to a healthy lifestyle,” said Paul A. Heidenreich, MD, MS, guideline writing committee chair and professor and vice chair for quality in the Department of Medicine at Stanford University.

Prior recommendations on the treatment of hypertension and atrial fibrillation have been updated, along with updates recommending avoidance of routine use of nitrates or phosphodiesterase-5 inhibitors.

Apart from medication recommendations, the guidelines also include newly created value statements for treatments, with high value defined as <$60,000/quality-adjusted life year gained and low value as >$180,000/ quality-adjusted life year gained.

Tafamidis for cardiac amyloidosis was the only low-value therapy identified. ARNi, ACEi, ARB, beta blocker, MRA, implantable cardioverter-defibrillator, and cardiac resynchronization therapy were classified as high value, with SGLT2 inhibitors and cardiac transplantation classified as intermediate value therapies.

Treatment by an HF specialty team is recommended for patients with advanced HF who wish to prolong survival, while additional updated recommendations are outlined for select patients with HF and comorbidities including iron deficiency, anemia, hypertension, sleep disorders, type 2 diabetes, atrial fibrillation, coronary artery disease and malignancy.

Under the new guidance, stages were adjusted to identify risk factors for HF early (stage A), and identify those at risk of HF. In addition, the guidelines will help provide treatment before structural changes or signs of decreased heart function occur (stage B).

In other words, stage A is defined as “at risk for HF,” stage B as “pre-HF,” stage C as “symptomatic HF,” and stage D as “advanced HF.”

Blood pressure control is recommended for all individuals in stage A, including those with high blood pressure, obesity, and diabetes.

“We also have recommendations for vulnerable patient populations at risk for health disparities,” Bozkurt said. “In these patients, heart failure risk assessment and multidisciplinary management strategies should target both known risks for cardiovascular disease and social determinants of health as a means towards elimination of disparate HF outcomes.”

Addressing and monitoring health disparities should be carried out at both the clinical practice and health system levels, she stressed.

Overall, the new definitions, classifications and stages of HF “are the first steps for us to achieve clarity and uniformity of care to timely diagnose and target appropriate guideline therapies,” Bozkurt concluded.