New HF Guidelines Feature ‘Quad’ Therapy, Tweaked Terminology

The new heart failure (HF) guidelines released this week by three North American societies had a lot of catching up to do given the significant, even paradigm-shifting, additions to available treatment options in the last few years.

The landscape now includes both new and repurposed drug therapies that benefit almost without regard to ejection fraction (EF), and evidence-based urgency to engage patients early on with at least four core medication classes, so-called quadruple therapy.

The guideline document offers a roadmap for navigating those key issues and many others and uses some creative tactics. They include the introduction of generalist-friendly labels for the traditional but obscurely named four stages of HF severity that, it is hoped, will have wider reach and expand the use of effective therapies.

It introduces additional disease-staging terminology that characterizes the syndrome as a continuum:  

  • “At risk for HF” for stage A, applied to asymptomatic patients with risk factors such as diabetes or hypertension but no known cardiac changes

  • “Pre-HF” for stage B, which adds cardiac structural changes or elevated natriuretic peptides, still in the absence of symptoms

  • “Symptomatic HF” for stage C, that is, structural disease with current or previous symptoms

  • “Advanced HF” for stage D, characterized by severe debilitating symptoms or repeated hospitalizations even with guideline-directed medical therapy (GDMT)

The new terms should be “easier for primary care physicians as well as nonspecialists” to remember and use effectively “and easier to translate to the patients” compared to the solely alphabetical staging labels appearing in the guidelines for more than 15 years, Biykem Bozkurt, MD, PhD, Baylor College of Medicine, Houston, Texas, told | Medscape Cardiology.

An emphasis on “at risk for HF” and “pre-HF” in the new document may help efforts to expand primary prevention of HF and management of preclinical HF. The guideline, Bozkurt said, includes specific treatment recommendations for those early stages.

The document also updates and sometimes introduces “recommendations for advanced heart failure, acute heart failure, and comorbidities — specifically for atrial fibrillation, iron deficiency, sleep apnea, coronary artery disease, and valvular heart disease,” Bozkurt observed, as well as for cardiomyopathy and HF related to pregnancy and cancer chemotherapy. “So, it’s a very comprehensive guideline.”

Bozkurt is vice chair of the guideline writing committee and helped introduce the guideline at the American College of Cardiology (ACC) 2022 Scientific Session, conducted both virtually and in-person in Washington, DC. The document, developed by the ACC, the American Heart Association (AHA), and the Heart Failure Society of America (HFSA), was published April 1 in the societies’ flagship journals, Journal of the American College of Cardiology, Circulation, and Journal of Cardiac Failure, respectively. It replaces the 2013 guideline from the ACC and AHA and the ACC/AHA/HFSA focused update from 2017.

“We really need to treat early, and then we need to treat appropriately,” emphasized Douglas L. Mann, MD, Washington University School of Medicine, St. Louis, Missouri, in an interview. Mann, who was not involved in development of the new guideline, said he is “enthusiastic” about the new staging terminology.

“I think it makes it easier to convey the message that these people do need medicines, will benefit from medicines, and in some cases heart failure can be preventable,” he said. “I’m in favor of anything that simplifies it and makes it more readily interpretable by busy doctors who aren’t specialists.”

With the new staging terminology and in other ways, the guideline seems to appreciate cardiomyopathy as a journey from preclinical to advanced symptomatic stages — the preclinical “at risk” stage tightening focus on primary prevention — and updated thinking on classification of HF by EF.

For example, there is new consideration of “HF with improved ejection fraction” (HFimpEF), which suggests the patient may be evolving from HF with reduced EF (HFrEF) to HF with EF that is preserved (HFpEF) or mildly reduced (HFmrEF), or vice versa.

With HFimpEF, which identifies patients previously with an EF of 40% or lower that improves to beyond 40% at follow-up testing, patients should continue on the medications they had been previously taking for HFrEF, Bozkurt said.

Patients at risk for HF, in stage A by the older terminology, are characterized by one or more significant HF risk factors, such as hypertension, diabetes, or coronary disease, as they have been in prior guidelines. But the new document, she observed, adds genetic cardiomyopathies and exposure to cardiotoxic agents to the list.

With progress, the guidelines “have gotten more complicated for the HFrEF patient population, but one could argue things have become a bit simpler for HFpEF and in mildly reduced EF” because “there’s been greater clarity about what works and what doesn’t work,” Paul Hauptman, MD, University of Tennessee Graduate School of Medicine, Knoxville, told | Medscape Cardiology.

Still, “what’s needed is a plan for dissemination in a format that is palatable to internal medicine and family medicine, and nurse practitioners in the field as well. That’s where you get the greatest bang for your buck.” On the other hand, he said, referral to cardiologists, including heart failure specialists, “if feasible, should be pursued” for many such patients.  

“I think the days of ignoring the risk factors for heart failure, especially ignoring stage A, stage B, because they don’t have symptoms, is over. You can make a meaningful impact and you have to be proactive.” Hauptman called the new guideline “a mature and thoughtful document.”

Perhaps surprisingly, the guideline also includes elevated natriuretic peptides as an indicator of “at risk for HF,” with implications for screening. The evidence suggests, Bozkurt said, that “for patients who are at risk for heart failure, natriuretic peptide-based screening, followed by team-based care, can prevent development of left ventricular dysfunction in heart failure.”

Persons at risk for HF realistically encompass a huge swath of the population given the world prevalence of high blood pressure (BP), obesity, and diabetes. Management of stage A, therefore, focuses on established tenets of primary cardiovascular prevention, such as weight and BP control, exercise, and healthy dietary choices.

They may well be eligible for treatment with sodium/glucose cotransporter 2  (SGLT2) inhibitors, which have been “game changers,” Mann said. “Now you can give them to diabetics and it’s going to prevent heart failure and CV events. We didn’t have a drug like that before, so I think that places a lot of emphasis on aggressive treatment of diabetes.”

For patients with symptomatic HF, the document touts multidisciplinary care and early initiation of drugs from each of four drug classes. Such quadruple therapy includes an SGLT2 inhibitor along with a β-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin system (RAS) inhibitor: the “core foundational therapies” for patients with HFrEF, Bozkurt observed.

Of note, she said, the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Entresto, Novartis) is the preferred RAS inhibitor. But “if the ARNI cannot be used, then use ACE inhibitors.” If the patient is intolerant of ACE inhibitors because of cough or angioedema, she added, then the choice should be an angiotensin-receptor blocker.

“We have very effective therapies offering survival and morbidity benefits as well as improvements in quality of life and reverse remodeling,” Bozkurt observed. “The most important message is that optimization of therapies, including all of these medication classes, saves lives.”

The guideline also includes, for the first time, a series of “value statements” on cost-effectiveness of different therapies that assign a “high-value” rating to MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated self-identified African Americans, and device therapy in appropriately selected patients. The statements hold SGLT2 inhibitors in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF to be of “intermediate” value.

The value statements, Bozkurt noted, “are included throughout the document when there is evidence; when there is a high-quality cost-effectiveness study published.”

Bozkurt discloses receiving honoraria or consulting fees from Amgen, AstraZeneca, Baxter International, Bristol Myers Squibb, Sanofi ‐Aventis, scPharmaceuticals, and Vifor Pharma; serving on a data safety monitoring board for LivaNova USA; and holding other relationships with Abbott Laboratories and Relypsa. Mann discloses receiving honoraria or consulting fees from MyoKardia, Novartis, and Novo Nordisk.  Hauptman has reported consulting for Corvia, LivaNova, Pfizer, and BTG Pharma.

American College of Cardiology (ACC) 2022 Scientific Session. P0resented April 2, 2022. 

J Am Coll Cardiol. Published online April 1, 2022. Full text

Follow Steve Stiles on Twitter: @SteveStiles2. For more from | Medscape Cardiology, follow us on Twitter and Facebook.


Leave a Reply

Your email address will not be published. Required fields are marked *