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Is Primary Prevention a Focus in the Updated Heart Failure Guidelines?

  • Authors: News Author: Steve Stiles; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 5/20/2022
  • Valid for credit through: 5/20/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

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Target Audience and Goal Statement

This activity is intended for cardiologists, internists, family medicine and primary care clinicians, nurses, nurse practitioners, pharmacists, physician assistants, and other members of the healthcare team for patients with heart failure (HF).

The goal of this activity is for learners to be better able to describe patient-centric recommendations to prevent, diagnose, and manage patients with HF, according to updated guidelines developed by the American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Failure Society of America (HFSA), which replace the 2013 ACC/AHA guideline and the ACC/AHA/HFSA focused update from 2017.

Upon completion of this activity, participants will:

  • Describe patient-centric recommendations for pharmacotherapy in patients with HF, according to updated ACC guidelines
  • Determine other patient-centric recommendations in patients with HF, according to updated ACC guidelines
  • Outline implications for the healthcare team


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News Author

  • Steve Stiles

    News Editor, | Medscape Cardiology


    Disclosure: Steve Stiles has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC


    Disclosure: Laurie Barclay, MD, has disclosed the following relevant financial relationships:
    Stocks, stock options, or bonds: AbbVie Inc. (former)

Editor/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Amanda Jett, PharmD, BCACP, has disclosed no relevant financial relationships.

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Is Primary Prevention a Focus in the Updated Heart Failure Guidelines?

Authors: News Author: Steve Stiles; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 5/20/2022

Valid for credit through: 5/20/2023


Clinical Context

Primary prevention is important for persons at risk for HF (stage A) or pre-HF (stage B). Patients at risk for HF have ≥ 1 significant HF risk factors (eg, hypertension, diabetes, coronary disease, genetic cardiomyopathies or cardiotoxic agent exposure). Patients at risk for HF should be managed with primary CV prevention, including weight and BP control, exercise, and healthy diet; persons with diabetes may be eligible for SGLT2is to prevent HF and CV events.

Recent advances in available heart failure (HF) treatment include medications of benefit regardless of ejection fraction (EF) and evidence supporting early initiation of quadruple therapy. More descriptive labels for HF severity stages may facilitate guidelines implementation by nonspecialists. The new HF guidelines released in March by 3 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.

Study Synopsis and Perspective

The treatment 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 4 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 4 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, which 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 with 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 guidelines 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 recently in the societies' flagship journals, the Journal of the American College of Cardiology,[1] Circulation,[2] and the Journal of Cardiac Failure,[3] respectively. It replaces the 2013 guidelines 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 [HF] can be preventable," he said.

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, Tennessee, told | Medscape Cardiology.

Still, he added, "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."

On the other hand, Hauptman 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 [HF], 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."

They may well be eligible for treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors," Mann said. "Now you can give them to diabetics and it's going to prevent [HF] 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 4 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 is the preferred RAS inhibitor, but "if the ARNI cannot be used, then use [angiotensin-converting enzyme (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 (ARB).

"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 Black patients 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.

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

Study Highlights

  • For patients at risk for HF, natriuretic peptide-based screening, followed by team-based care, may prevent left ventricular (LV) dysfunction.
  • GDMT for HFrEF now includes early initiation of drugs from each of 4 medication classes: quadruple therapy with SGLT2is, β blockers, MRAs, and RAS inhibitors.
  • ACEis should be used if ARNIs cannot be used.
  • Patients intolerant of ACEis because of cough or angioedema should receive ARBs.
  • For HFmrEF, SGLT2is have a class of recommendation 2a; ARNis, ACEis, ARBs, MRAs, and β blockers have weaker recommendations (2b).
  • For HFpEF, there are new recommendations for SGLT2is (2a), MRAs (2b), and ARNis (2b).
  • Several prior recommendations have been renewed: treatment of hypertension (class 1) and atrial fibrillation (2a), ARB use (2b), and avoiding routine use of nitrates or phosphodiesterase-5 inhibitors (class 3: no benefit).
  • For HFimpEF (previous EF ≤ 40% that improves to > 40% at follow-up), patients should continue their HFrEF treatment.
  • High-value recommendations include MRAs, hydralazine, and isosorbide dinitrate in otherwise optimally treated Black persons and device therapy in appropriately selected patients.
  • Intermediate-value recommendations include SGLT2is in chronic symptomatic HF and cardiac transplantation in advanced GDMT-resistant HF.
  • New recommendations for amyloid heart disease include screening for serum and urine monoclonal light chains, bone scintigraphy, genetic sequencing, tetramer stabilizer therapy, and anticoagulation.
  • If LVEF is > 40%, HF diagnosis requires evidence supporting increased filling pressures from noninvasive (eg, natriuretic peptide, diastolic function on imaging) or invasive testing (eg, hemodynamic measurement).
  • Patients with advanced HF who wish to prolong survival should be referred to an HF specialty team that reviews HF management, assesses suitability for advanced HF therapies, and uses palliative care, including palliative inotropes when consistent with patient care goals.
  • Recommendations address comorbid iron deficiency, anemia, hypertension, sleep disorders, diabetes, atrial fibrillation, CAD, and malignancy.

Clinical Implications

  • GDMT for HFrEF now includes early quadruple therapy.
  • Primary prevention is important for persons at risk for HF (stage A) or pre-HF (stage B).
  • Implications for the Healthcare Team: Adherence can be enhanced by shared decision making between clinicians and patients, selecting interventions according to the patient’s individual values, preferences, and associated conditions and comorbidities.


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