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Professor of Medicine
Division of Cardiovascular Medicine
Department of Medicine
Section Chief, Advanced Heart Failure and Cardia Transplant
University of Pennsylvania
Lee R. Goldberg, MD, MPH, FACC, has disclosed that he has received funds for research support from Zoll/Respicardia and consulting fees from Abbott, VisCardia, and Zoll/Respicardia.
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The 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure included various interesting and important updates. In this commentary, I will provide a brief overview of key updates and how they impact best practice for managing patients with heart failure.
New Definition of Heart Failure
The guidelines refine some new terminology around the stages of heart failure. In addition to the New York Heart Association classification, we have stages A, B, C, and D, but the new guidelines provide additional detail. Stage A is now defined as “at risk for heart failure,” which is something we have talked about for a long time. Stage B is “pre–heart failure,” which could include structural changes to the heart in the absence of symptoms, evidence of increased filling pressures, and/or risk factors such as high levels of natriuretic peptides. Stage C is “symptomatic heart failure” either currently or in the past, and stage D is “advanced heart failure.” I think this staging will be helpful to healthcare professionals, as the therapies are linked to both the stage of heart failure and current symptoms.
In addition to new staging, the guidelines expanded the definitions of heart failure. HFrEF is classified by an ejection fraction ≤40%. There is a new classification of heart failure with improved ejection fraction (HFimpEF), defined as previous ejection fraction ≤40% that improved with medical therapy. This is a nuanced definition informed in part by data from the TRED-HF trial, which demonstrated the importance of continuing GDMT in patients with an ejection fraction that recovered to >40% after starting treatment. Translational research has suggested that myocardium that has been injured may remain abnormal on a cellular level even if the global function improves. For this reason, patients need ongoing neurohormonal blockade to prevent relapse.
The next definition is heart failure with mildly reduced ejection fraction (HFmrEF), defined by an ejection fraction of 41% to 49%. We want this group to be the focus of future clinical trials because of differences in management compared with classic heart failure classifications. Finally, patients with an ejection fraction ≥50% are categorized as having heart failure with preserved ejection fraction (HFpEF). Taken together, these updated definitions provide clearer delineation for each patient, which enables healthcare professionals to choose the best medicines for each group.
Regarding GDMT, the newest guidelines establish 4 pillars of drugs for managing heart failure, especially HFrEF. These include RAAS inhibitors, β-blockers, MRAs, and SGLT2 inhibitors. Among RAAS inhibitors, there is a preference for an angiotensin receptor–neprilysin inhibitor (ARNI) as a first-line medication, with angiotensin-converting–enzyme (ACE) inhibitors or angiotensin (II) receptor blockers (ARBs) recommended when an ARNI is not feasible.
The guidelines also highlight the importance of initiating all 4 classes of drugs and subsequently titrating. This guidance is slightly different than previous philosophies. Rather than optimizing the dose for 1 or 2 drugs before adding additional drug classes, we should ensure that patients initiate a low dose of all 4 GDMT drug classes before discharging them from the hospital, with titration-to-target doses occurring in the outpatient setting. This recommendation, which agrees with the European Society of Cardiology heart failure guidelines, circumvents the clinical inertia that can occur wherein many patients never get offered MRAs and SGLT2 inhibitors as outpatients. It is an important development in our approach to GDMT.
Another update specific to SGLT2 inhibitors is the recommendation that patients with HFrEF receive them regardless of diabetes status. Moreover, they should be considered for patients with HFmrEF and HFpEF, albeit with a lower strength of recommendation (class 2A). I think this new guidance underscores the need for cardiovascular healthcare professionals to change our mindset around SGLT2 inhibitors. Rather than thinking of them as glucose-lowering drugs, we must think of them as cardiovascular drugs that also lower blood glucose. I agree that a new perspective is necessary so that we feel more comfortable prescribing them.
Vericiguat is a novel oral soluble guanylate cyclase stimulator approved for reducing the risk of heart failure hospitalization and cardiovascular death in high-risk patients with HFrEF and recent worsening despite receiving GDMT. In the 2022 AHA/ACC/HFSA heart failure guidelines, vericiguat is included for the first time as a therapy that may be considered to reduce heart failure hospitalizations and cardiovascular death in this scenario. Specifically, vericiguat would be indicated for patients with symptomatic HFrEF with ejection fraction <45% who are receiving GDMT and have elevated natriuretic peptides and recent heart failure worsening. In practice, these are patients with pretty advanced disease who, despite receiving GDMT, have been hospitalized or continue to require IV diuretic therapy outside the hospital. Adding vericiguat is an attempt to prevent rehospitalization, thereby improving quality of life.
As we get more experience with the compound, I think we may be able to further refine the ideal candidates for vericiguat. For example, an open question is whether we would use vericiguat to stave off the need for mechanical support in a patient who is awaiting transplant and beginning to decline. There also may be benefit of vericiguat for patients who are not candidates for advanced therapy. However, historically, these patients had not received MRAs or SGLT2 inhibitors, so based on new guidance, we would want to prioritize those agents first.
The updated guidelines highlight the identification and consideration of amyloid, including when to screen for it and how to differentiate between transthyretin amyloid (aTTR) and light-chain (AL) amyloid cardiomyopathy. Of importance, since the last guidelines, there are now effective therapies for both major forms of amyloid and new imaging and genetic diagnostics. Therefore, it is important to consider amyloid in patients for whom there is clinical suspicion, as early initiation of therapy leads to the best outcomes.
The guidelines further extend recommendations for managing common comorbidities in patients with heart failure, such as diabetes, anemia, hypertension, and sleep disorders. I think this guidance is useful because heart failure rarely occurs in isolation. Most patients have some comorbidity that will impact the care of heart failure. Indeed, in many cases, the treatment for the comorbidity may work against the heart failure therapies. Identifying those potential drug–drug interactions is critical. In addition, effectively managing of some of those comorbidities ultimately can improve the heart failure.
My one concern is that we are asking a lot of healthcare professionals in the guidelines. We are asking them to initiate 4 different classes of medications and subsequently titrate them to the appropriate doses, perform appropriate surveillance and laboratory checks, and screen for adverse events. Understanding all of these considerations for the 4 classes of GDMT is complex. Plus, we are asking them to make decisions regarding device therapies such as implantable cardioverter defibrillators and biventricular pacemakers and to educate patients on lifestyle changes such as exercise and dietary restrictions. On top of that, they must consider other groups of pharmacotherapy in the second and third line, depending on symptoms and disease progression, all while managing important comorbidities.
These complexities highlight the utility of referring patients to a heart failure specialty clinic, particularly those with advanced disease and/or several comorbidities. Many moving parts require multidisciplinary support from nutritionists, pharmacists, nurses, physicians, etc, to help balance each patient’s goals. Indeed, the new AHA/ACC/HFSA guidelines emphasize referring patients to heart failure specialty care if their disease begins to progress. Specialized heart failure centers are well equipped to make sure patients are receiving GDMT, and they are staffed by multidisciplinary teams capable of supporting lifestyle changes and other aspects of care. For patients with advanced heart failure, timely referral to specialty care is helpful so that GDMT is maximized and cardiac transplant, ventricular assist device, or palliative therapies can be offered.
Which updates to the AHA/ACC/HFSA heart failure guidelines do you anticipate will most impact your practice? Answer the polling question and join the discussion by posting a comment.
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