Heart failure (HF) is getting a landmark renovation. A new multisociety consensus statement representing the joint efforts of 38 HF experts from 14 countries on six continents offers a new universal definition for HF, revised stages of development and progression, and new left ventricular ejection fraction (LVEF) classifications.¹

The changes are not academic or just semantic, but something that will have direct impact on patient outcomes, according to writing committee chair Biykem Bozkurt, MD, PhD, FACC, who is also immediate past president of the Heart Failure Society of America (HFSA).

"Our hope is that standardizing the terminology and making it more relevant to the clinical scenarios we see every day in the clinic will help clinicians better recognize, diagnose, refer appropriately and treat patients," she tells Cardiology.

"Also, some of the terminology that we've been using was unclear to patients, so we hope these changes will better resonate with patients and help them be more effectively involved in their own care."

A Universal Definition of HF

The consensus statement provides a new contemporary definition of HF "that is clinically relevant, simple but conceptually comprehensive, with the ability to subclassify and to encompass stages within; with universal applicability globally, and with prognostic and therapeutic validity and acceptable sensitivity and specificity."

Specifically, the statement defines HF as: "A clinical syndrome with current or prior symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion."

The goal is for this definition to be universally accepted, integrated across scientific societies and guidelines, and used both by clinicians and researchers worldwide.

"Heart failure has traditionally been a clinical diagnosis. But by and large, the diagnosis begins much earlier than the clinical signs and symptoms appear. In this consensus statement we've defined HF clinically, but also included the biomarkers as part of the definition," says James L. Januzzi Jr, MD, FACC, one of the authors.

"Since biomarkers may be abnormal well before the clinical diagnosis is made, this may help clinicians be more attuned to the presence of earlier forms of HF."

The definition covers patients with left and right HF. And it provides specificity to exclude conditions that result in marked volume overload, such as end-stage renal disease, which may present with signs and symptoms of fluid overload, but where HF is perhaps a concomitant, not the primary, diagnosis.

"We saw with the universal definition for myocardial infarction that it really helped the field to bring consensus and clarity to what is an MI and what are the different types of MI," says past ACC President Mary Norine Walsh, MD, MACC, who was not part of the consensus statement committee.

"The hope here is the same – that this universal definition will make it easier to communicate to non-cardiologists what HF is and isn't, what type of HF the patient may have, and, really importantly, what the progression is," she adds.

Proposed Revisions to HF Stages

The current ACC/AHA guideline categorizes HF according to Stages A through D. These designations have been widely accepted within the field, although they are not well recognized by non-cardiologists, payers or patients.

The consensus statement affirms the current staging but makes small but potentially clinically-meaningful revisions to terminology that are intended to spur earlier intervention, such as targeted therapies for HF prevention. They also address, like the universal definition, the evolving role of biomarkers.

Among the proposed terminology updates:

• At-risk for HF (Stage A): Patients at risk for HF, but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease.
• Pre-HF (Stage B): Patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels or cardiac troponin.
• HF (Stage C): Patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality.
• Advanced HF (Stage D): Patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support or palliative care.

The risk factors that land a patient in Stage A – hypertension, atherosclerotic cardiovascular disease, diabetes, obesity, known exposure to cardiotoxins, a positive family history of cardiomyopathy, or genetic cardiomyopathies – are seen in about one-third of the population, the authors note.

About 40% to 50% of the adult population can be categorized as Stages A or B. However, while this realization may be uncomfortable to many, the new terminology of "at-risk for heart failure" and "pre-heart failure" avoids the stigma of a HF diagnosis before symptoms of the disease are manifest.

"By refining the definitions with the terminology 'at-risk' and 'pre-HF,' the authors are saying that all these people should not be assigned a disease that is chronic and progressive. But they should be alerted that it could be coming, which I think is really very valuable," says Walsh.

Reframing Stage B as "pre-heart failure" is an attempt to piggyback on other fields that use this terminology to signal an actionable moment.

"Pre-diabetes or pre-cancer are terms widely understood by patients to mean that there's something they can do to potentially prevent progression to the full-on disease," Bozkurt says.

"We want to tap into this successful messaging and embrace the pre-heart failure concept as something that is treatable and preventable, because particularly now with the SGLT2 inhibitors, it potentially is!" she adds.

Recognizing the LVEF Clinical Trajectory

One of the biggest changes the new document proposes is a new LVEF classification scheme. To this end, the authors propose the following four classifications of EF:

• HF with reduced EF (HFrEF): LVEF ≤40%.
• HF with mildly reduced EF (HFmrEF): LVEF of 41-49%.
• HF with preserved EF (HFpEF): LVEF ≥50%.
• HF with improved EF (HFimpEF): baseline LVEF ≤40%, an ≥10-point increase from baseline LVEF, and a second measurement of LVEF >40%.

"It's important to identify both the stage of the patient's natural history, as well as the patient's clinical trajectory," says Januzzi. "Someone whose EF has improved after therapy is very different from someone with mildly reduced EF – it's a different entity and requires different treatment."

"The re-naming of 'midrange EF' to 'mildly reduced EF' may seem like a minor change, but we're understanding more that many therapies that have been restricted to patients with reduced EF clearly have benefit in those with mildly reduced EF," says Januzzi.

"So, by re-naming this category, it will hopefully spur study of new treatments as well as application of proven therapies for these patients. And, again, clarifies that EF should be viewed on a continuum," he adds.

HFmrEF is usually a transition period, notes Bozkurt. "Patients with EFs in this range are likely to see their EFs either increase or decrease over time. So it's important to be cognizant of that trajectory and understand which direction your patient is headed and optimize guideline-directed treatment appropriately," she says.

The last classification – HF with improved ejection fraction (HFimpEF) – represents an important change to the current classification scheme.

"We want to avoid the use of recovered heart failure because this term gives the false impression that medication can be stopped. We know from the TRED-HF trial that this is not the case," says Bozkurt.

"But these patients also should not be confused with HFpEF patients because that is completely wrong," she adds, stressing that HFimpEF only applies if the EF improves to above 40%.

"A move from an EF of 10% or 20% would still see the patient classified as having HFrEF, and their therapy does not change. But a patient whose EF improves from 30% to 45% would be classified as HFimpEF and there might be therapeutic considerations, particularly in terms of device therapies."

"Patients tend to be very focused on their ejection fraction number," notes Walsh. "They come in asking to be tested more than once a year and they track their own progression based on EF. Thus, it is very important to help patients understand that while their EF is improved, they have not actually recovered from their HF and need to continue their therapy."

Not a One and Done

Whether these proposed changes will be worked into the upcoming practice guideline is unclear. Januzzi, who is not on the guideline writing committee, says only that he expects there to be "good synergy."

But the importance of this huge step towards a universal and more contemporary way of approaching HF is well appreciated.

"A milestone event in [HF] has occurred," write Carolyn S. P. Lam, MBBS, PhD, and Clyde Yancy, MD, MSc, MACC, in the Journal of Cardiac Failure, in the first in a series of multidisciplinary perspective pieces commenting on the new HF terminology.² Both were authors of the consensus statement.

The milestone part is referring to the sheer number of societies that all came together and agreed on a new universal definition and classification scheme. But the work isn't done, they say, specifically taking exception to the continued use of EF in classifying HF stages, something they say lacks a biological premise.

"Recent investigations now challenge the upper thresholds for HF with reduced ejection fraction, showing that the 'cut-point' for HF with preserved ejection fraction may begin at a left ventricular ejection fraction of 0.57," they write.

The use of the 50% as the cut-point "revisits old standards that were never standardized." So while the new definition is a milestone, is universal, and "broadly applicable," the march of science continues.

"Heart failure is one of the most important diagnoses in modern cardiology. This update was sorely needed and will represent a starting point," says Januzzi, adding that efforts like this are the starting point for changes not only in clinical decision-making, but also billing and health policy.

"Eventually, we hope diagnosis codes will be developed that accommodate the at-risk and pre-heart failure categories, as well as the mildly-reduced and improved EF classifications, because the treatment approach may differ for these patients," he notes.

The consensus statement, jointly led by the HFSA, Heart Failure Association of the European Society of Cardiology and the Japanese Heart Failure Society, was simultaneously published in the Journal of Cardiac Failure and the European Journal of Heart Failure. It was endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association.

References

1. Bozkurt B, Coats AJ, Tsutsui H, et al. J Card Fail 2021;27:387-413.
2. Lam CSP, Yancy C. J Card Fail 2021;27:509-511.