Heart failure (HF) is a complex clinical syndrome in which there is impairment of ventricular filling or ejection of blood because of a structural or functional cardiac disorder, leading to signs and symptoms such as shortness of breath, coughing or wheezing, fatigue, and fluid retention with swelling of the lower extremities or abdomen.^[1-3] Patients with HF are categorized as having HF with a reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF] ≤ 40%), HF with mildly reduced ejection fraction (HFmrEF; LVEF, 41%-49%), or HF with preserved ejection fraction (HFpEF; LVEF ≥ 50%), each of which has a unique management strategy.^[1,3] It's estimated that 6.2 million people in the United States and > 64 million people worldwide have HF, making this disorder a global pandemic.^[4,5] The prognosis following an HF diagnosis is poor, with 17% to 45% of patients dying within 1 year of diagnosis and up to 60% of deaths occurring within 5 years of hospital admission,^[2,3] making timely diagnosis and appropriate management imperative for improving outcomes.

Numerous HF guidelines have been released over the years to help improve the clinical symptoms and outcomes of patients living with HF; however, despite an abundance of guidance, studies have shown that many patients do not receive optimal guideline-directed medical therapies (GDMT), contributing to worse outcomes.^[6-8] Recently, the 2022 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) Guideline for the Management of Heart Failure was published, updating previous recommendations based on the most recent evidence.^[1] Medscape had the opportunity to discuss this new guideline and strategies for adopting its recommendations into clinical practice with Nasrien E. Ibrahim, MD, FACC, FAHA, FHFSA, Advanced Heart Failure and Transplant Cardiologist and Associate Program Director of the Cardiology Fellowship at Inova Heart and Vascular Institute in Falls Church, Virginia.

Medscape: How has HF treatment evolved between previous guideline iterations and the 2022 AHA/ACC/HFSA guideline?

Nasrien E. Ibrahim, MD, FACC, FAHA, FHFSA: It's an exciting time in HF right now with new drugs and devices, including an angiotensin receptor-neprilysin (ARN) inhibitor and several sodium-glucose cotransporter 2 (SGLT2) inhibitors that further reduce morbidity and mortality and improve patients' symptoms.^[1] We see rapid improvements in LVEF and left ventricular end-diastolic dimension. These drugs also benefit broader patient populations, including those with chronic kidney disease (CKD), a common comorbidity in HF that increases the risk of overall and cardiovascular (CV) mortality.^[9,10] The ARN inhibitor sacubitril/valsartan has been reported to reduce the risk of CV mortality compared with standard therapy with an angiotensin-converting enzyme (ACE) inhibitor in patients with HFrEF in the pivotal PARADIGM-HF trial.^[9] SGLT2 inhibitors slow the progression of CKD, reduce HF, and lower the risk of kidney failure and death in patients with CKD and type 2 diabetes mellitus, and they protect the kidneys of patients with CKD who do not have diabetes.^[10] The approval of ARN and SGLT2 inhibitors provides new strategies for renoprotection. Notably, the benefit of ARN inhibitors and SGLT2 inhibitors is additive to what we previously had available.

With the FDA approval of ARN and SGLT2 inhibitors, we now have 4 treatment pillars for managing HFrEF (Figure 1). The 2022 AHA/ACC/HFSA guidelines emphasize the importance of initiating these treatments early and rapidly titrating patients to reach target doses or maximally tolerated doses as quickly as possible.^[1] All patients with HFrEF should be on these treatment pillars unless there is a compelling contraindication to treatment.

Figure 1. The 4 Pillars of GDMT for HFrEF

MRA, mineralocorticoid receptor antagonist.

*Patients who cannot tolerate ARN inhibitors can be treated with ACE inhibitors or angiotensin receptor blockers (ARBs).

Medscape: What recommendations does the 2022 HF guideline make for HFrEF, including worsening disease?

Dr Ibrahim: The recommendations for treatment of HFrEF stages C and D are summarized in Figure 2. A key recommendation is to consider the oral soluble guanylate cyclase stimulator vericiguat to reduce HF hospitalization and CV death in select high-risk patients with stage C HFrEF who are already on GDMT and experiencing worsening HF.^[1] Support for vericiguat in this setting comes from the VICTORIA trial, which showed a lower incidence of hospitalization and death from CV causes with vericiguat vs placebo in patients with worsening HFrEF.^[11] For patients already optimized on the 4 pillars of GDMT who are now having worsening symptoms, whether they are showing up at the emergency department, going to an outpatient clinic to get intravenous diuretics, or they're admitted to the hospital for HF and are having persisting symptoms, vericiguat is one of the next classes of drugs that should be considered.

Figure 2. Treatment Recommendations for Patients With HFrEF

ACEI, angiotensin-converting enzyme inhibitor; ARNi, ARN inhibitor; CRT-D, cardiac resynchronization therapy with defibrillator; HFimpEF, HF with improved ejection fraction; hydral-nitrates, hydralazine and isosorbide dinitrate; ICD, implantable cardioverter-defibrillator; LBBB, left bundle branch block; MCS, mechanical circulatory support; NSR, normal sinus rhythm; NYHA, New York Heart Association; SGLT2i, SGLT2 inhibitor.

*Participation in investigational studies is appropriate for stage C and NYHA classes II and III HF.

Again, it's critical to optimize the 4 classes of GDMT for all patients with HFrEF; however, for Black patients who are optimized on the GDMT, the guidelines recommend adding the combination of hydralazine and isosorbide dinitrate, if they remain symptomatic (Figure 2).^[1] This recommendation stems from benefits observed in 2 randomized controlled trials, V-HeFT I and A-HeFT, the latter of which was terminated early because the combination showed a significantly lower mortality rate compared with placebo (6.2% vs 10.2%).^[12,13]

The guidelines also adequately emphasize the consideration of devices for patients with worsening HF.^[1] For example, they recommend considering the implantation of a hemodynamic monitor to wirelessly monitor pulmonary artery (PA) pressure in selected patients with a history of HF hospitalization in the past year or with elevated natriuretic peptide levels despite being on maximally tolerated stable doses of GDMT and optimal device therapy to reduce HF hospitalizations.^[1] This is a class 2b (weak) recommendation because studies assessing remote monitoring of PA pressure have shown mixed results.

Medscape: What recommendations are made for patients with end-stage HF (stage D)?

Dr Ibrahim: Whether these patients have had HF for a long time or have been newly diagnosed with stage D HF, GDMT may occasionally pose a challenge. Their blood pressure (BP) may be too low to enable the use or continuation of GDMT, or they may not feel well on GDMT, requiring dose reductions. It's critical to identify patients with stage D HF early to ensure timely referral for HF specialty care, as recommended by the guideline.^[1]

We can consider 3 treatment options for patients with stage D HF. The gold standard treatment is cardiac transplantation in patients who are eligible. This treatment has a class 1 (strong) recommendation based on observational cohorts showing improved survival and quality of life (QOL).^[1] If cardiac transplantation is contraindicated or not possible, we can think about a durable left ventricular assist device (LVAD) in eligible patients who have acceptable right ventricular function.^[1] If neither cardiac transplantation nor LVAD is appropriate, we must initiate conversations on palliation and whether or not there may be a role for inotropes.^[1] Although inotropes increase patients' mortality, they improve symptoms, enabling patients to feel better.^[1] It's essential to have conversations about palliative strategies early because stage D HF is highly symptomatic. Patients are very short of breath, and providing palliation helps patients who have exhausted their treatment options to optimize their QOL.

Medscape: There are also several recommendations in the guideline for treating HFpEF (LVEF ≥ 50%). Which ones do you find most exciting?

Dr Ibrahim: One of the most exciting things in the guidelines is that we now have several treatment options for HFpEF (Figure 3).^[1] The only option with a class 1 recommendation is diuretics, which we only give to symptomatic patients with HFpEF; however, the exciting news is that SGLT2 inhibitors have a class 2a (moderate) recommendation in decreasing HF hospitalizations and CV mortality in patients with HFpEF. In addition, ARN inhibitors and MRAs have a class 2b recommendation in decreasing hospitalizations. Although the level of recommendation is the same for these agents in patients with HFpEF, we have some data that may help guide treatment decision-making. For example, women compared with men with HFpEF seem to do better with ARN inhibitors,^[14] whereas MRA benefit appears consistent regardless of sex.^[15]

*Greater benefit in patients with LVEF closer to 50%.

Notably, several recommendations from prior guidelines have also been renewed, including:

• Using ARBs as a treatment for HFpEF to decrease hospitalizations, particularly among patients with an LVEF on the lower end of the spectrum (class 2b)
• Titrating BP medications in patients with HFpEF and hypertension to attain BP targets in accordance with published clinical guidelines to prevent morbidity (class 1)
• Managing atrial fibrillation (AF) to improve symptoms (class 2a)
• Avoiding routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or improve QOL, as these may be harmful (class 3; no benefit)^[1]

Medscape: What strategies can clinicians use to adopt these new guidelines into clinical practice? Please share some strategies that have worked for you.

Dr Ibrahim: Because patients will be on many medications, the first strategy concerns communication. When I first meet a patient with HFrEF, I make sure to set the expectation that there are 4 treatment pillars and the quicker we titrate each agent to reach the target or maximum tolerated dose, the less often they will have to see me. We know early treatment initiation and rapid titration are essential because we see clinical benefits early on. I like to tell patients that their risk of hospitalization and mortality will reduce, their symptom burden will reduce, and their cardiac structure and function will improve within a few weeks of starting of the treatment. During these discussions, I make sure to tell patients their ejection fraction, explain what is normal (usually an LVEF ≥ 55%), and give them a target to work toward. I explain that their medication regimen will help their heart function improve and that our goal is to get it to a normal ejection fraction and help them feel better.

The second strategy is to use all available resources to ensure that the novel therapies are affordable to patients because access has been challenging, especially with the newer treatments. Some pharmaceutical companies have patient assistance programs that clinicians can help patients apply to if they find these medications unaffordable. When I meet with patients, I let them know that the newer therapies, such as ARN inhibitors, may cost more than older treatments, such as beta blockers, but that if they receive a hefty bill to let us know and we'll figure out how we can make the medication more affordable. It's essential to be transparent about costs, so there is no surprise for patients when they fill their prescriptions at the pharmacy.

The third strategy may make life easier for healthcare providers and patients: the use of telehealth. Patients do not need to be seen in the clinic for their GDMT to be titrated. Patients can routinely monitor their BP at home if they have a BP monitor, be asked about their symptoms during virtual visits, and go to a local lab for blood work. Some of the pillars are easy to titrate, such as SGLT2 inhibitors, because the starting dose is the target dose, and these agents have minimal to no effects on BP. Beta blockers are also easy to titrate because you don't have to monitor labs. The tricky agents are the MRAs and ARN inhibitors, but using a multidisciplinary team approach can be helpful. Patient navigators, if available, can help reach patients in their community to guide their care, pharmacists can create titration schedules, nurses and nurse practitioners can monitor patients, and social workers can help patients who have trouble obtaining medications because of the costs. In summary, a multipronged strategy that always keeps the patient at the center of all decisions and ensures they understand the importance of the 4 classes of GDMT is essential.

Medscape: Was there anything else in the guidelines you found striking?

Dr Ibrahim: This is the first time I've seen a guideline recommending assessing social determinants of health and addressing any that make it difficult for patients to get GDMT. These recommendations are given a class 1 indication.^[1] We know historically marginalized and socioeconomically disadvantaged patient populations are disproportionately affected by and have the highest mortality risk from HF. Therefore, it is reassuring to see that these guidelines emphasize HF risk assessments and management strategies that target known risks for CV disease and social determinants of health as a means of not only identifying the disparities but also developing strategies to eliminate them.

This transcript has been edited for style and clarity.