New HF guideline: Quad therapy, HFmrEF, and more

Hot on the heels of ACC.22 ground-breaking reports, the ACC/AHA/HFSA* released the 2022 heart failure (HF) guideline, with special emphasis on quad therapy for patients with reduced ejection fraction.

The 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure also defines a new category of “mildly reduced HF” and offers new therapeutic options for HF with preserved ejection fraction (HFpEF), among other salient updates. [Circulation 2022, online ahead of print]

The guideline also calls on clinicians to better incorporate and address social determinants of health. It also offers recommendations for managing cardiac amyloidosis, cardio-oncology complications, and consideration for implantable devices and advanced therapies in patients with advanced HF. Referral to an HF specialty team is advised in those who progressed to advanced disease to facilitate guideline-directed medical therapy (GDMT).

Updated recommendations are also provided for HF patients facing a range of comorbidities (iron deficiency, anaemia, hypertension, sleep disorders, diabetes, cancer, coronary artery disease, and atrial fibrillation [AF]). For AF, ablation is considered a “reasonable” option in those with left ventricular ejection fraction (LVEF) of ≤35 percent (class 2a).

There are specific recommendations for HF and pregnancy, targeted counselling, as well as a class 2b recommendation for anticoagulation with peripartum cardiomyopathy.

The new guideline aims to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with HF. It replaces the 2013 HF guidelines, with a focused update released in 2017. “Since that time, there have been multiple studies impacting the care of patients with HF,” said Dr Paul Heidenrich, guideline writing committee chair and professor of Medicine (Cardiovascular) at Stanford University in Stanford, California, US, in an ACC broadcast. “We felt it is important to have the guidelines reflect those changes in care.”

He said one important focus of the guideline is the prevention of HF through “optimization of blood pressure control and adherence to a healthy lifestyle.”

Quad therapy

“GDMT for symptomatic HF now includes four classes of medications, to be initiated in tandem as quickly as possible,” added Dr Biykem Bozkurt, guideline writing committee vice-chair and professor of Medicine-Cardiology at Baylor College of Medicine in Houston, Texas, US.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors made a debut in the HFrEF pharmacotherapy list. Beta-blockers, mineralocorticoid receptor antagonists (MRAs), and renin-angiotensin-aldosterone system (RAAS) inhibition are also recommended, with an angiotensin receptor-neprilysin inhibitor (ARNI) given preference over an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) in patients with class II–III HF.

“All four medications save lives and improve patient outcomes. Standard core therapy with four drug classes can be initiated and optimized as soon as possible. And that should be clear for all clinicians,” emphasized Bozkurt. “Every patient with a reduced EF should receive optimized therapy with these four drug classes.”

Notably absent in the guideline is the recommendation for sequencing of the four drug classes, Bozkurt said. “What we specified is optimization … we did not specify how to sequence, there is a class 2a recommendation for titration and optimization. It could be as frequent as 1–2 weeks, depending on the patient’s profile.”

“Irrespective of diabetes status, the DAPA-HF and EMPEROR-HF trials have shown benefits with SGLT2 inhibitors for HFrEF, showing a 30-percent reduction in HF rehospitalization. This is a major step forward in reducing mortality rates in this vulnerable population,” she emphasized.

SGLT2 inhibitors got a class 2a recommendation for HF with mildly reduced EF (HFmrEF); ARNIs, ACE inhibitors, ARBs, MRAs, and beta-blockers got a class 2b recommendation. As LVEF may change over time, those with HFmrEF should have repeat evaluations of LVEF.

New terminologies and preferences

The syndrome of HF is defined in the guideline “as a complex clinical syndrome with symptoms and signs that result from a structural or functional impairment,” said Bozkurt.

Another salient addition to the guideline is the inclusion of the new HFmrEF to refer to HF with LVEF ranging from 41–49 percent and evidence of increased LV filling pressures.

The use of the term “persistent HF” as opposed to “stable HF” is also emphasized. “Persistent AF,” Bozkurt explains, requires optimization whereas the term “stable” creates inertia. “HF in remission” is also preferred over “HF in recovery” as majority of patients who withdraw from therapy will eventually relapse.

HF stages have been redefined to emphasize prevention:

·       Stage A (At Risk for HF) refers to individuals who are at risk but without symptoms, with structural heart disease or blood tests indicating heart muscle injury. This includes people with high blood pressure, diabetes, metabolic syndrome, and obesity, who are receiving treatments that may damage the heart (eg, chemotherapy drugs), or have a hereditary risk for HF.

·       Stage B (Pre-HF) means individuals have no symptoms or signs of HF but have evidence of one of the following: structural heart disease (reduced ejection fraction, heart muscle enlargement, abnormalities in heart muscle contraction, or valve disease), increased filling pressures as measured via ultrasound, or risk factors from stage A + increased levels of B-type natriuretic peptide or persistently elevated cardiac troponin, which is an indicator of heart muscle injury.

·       Stage C (Symptomatic HF) pertains to structural heart disease with current or previous symptoms of HF, which include shortness of breath, persistent cough, swelling in the legs, feet, abdomen, fatigue, and nausea.

·       Stage D (Advanced HF) refers to HF with symptoms that interfere with daily life, are difficult to control, and result in recurrent hospitalizations despite continued guideline-directed medical therapy.

“In recent years, there has been an increase in rigorous science assessing how best to treat symptomatic HF,” said Heidenreich. “With this new guideline, we hope to inform better treatment options for a broader number of our patients with HF.”

 “This makes for exciting times for both clinicians and patients,” Bozkurt added.

Key takeaways

1.   Primary prevention is important for those “at-risk” for HF (stage A) or pre-HF (stage B).
2.   GDMT for HFrEF now includes a quad therapy, with the addition of SGLT2 inhibitors.
3.   The term HFmrEF debuts in the guideline.
4.   HFmrEF (LVEF 41–49 percent) should be treated first with an SGLT2 inhibitor (class 2a recommendation). Weaker recommendations   (class 2b)  are made for ARNi, ACEi, ARB, MRA, and beta-blockers in this population.