Practice Updates – ACC Expert Consensus on Heart Failure with Preserved Ejection Fraction (HFpEF)

The American College of Cardiology had just released an expert consensus on the management of heart failure with preserved ejection fraction (HFpEF) earlier in April. This document is the first to address the management of individuals with HFpEF specifically.  The treatment of HFpEF used to be limited to managing comorbidities. However, with advances in the pathophysiology of HFpEF, increasing evidence in pharmacological agents in HFpEF and improved methods of diagnosis this document seeks to address key clinical questions such as testing and diagnosing patients with suspected HFpEF, management of comorbidities and initiation of GDMTs. 

This article aims to highlight key points from the expert consensus paper – to view the full paper, you may refer to this link. 

Diagnosis of HFpEF 

HFpEF is defined as HF with left ventricular ejection fraction (LVEF) ≥ 50% not attributable to any underlying causes while LVEF between 40-50% is characterised as HF with mildly reduced ejection fraction (HFmrEF). 

It is challenging to definitively diagnose HFpEF given that echocardiogram (ECG) may not demonstrate obvious structural or functional cardiac abnormalities and natriuretic peptide levels may be normal, especially in individuals with obesity. It is also important to note that individuals who present with symptoms of dyspnea and/or oedema may have noncardiovascular conditions that mimic HF, such as kidney failure, liver failure and anaemia.

The use of clinical scoring systems may be useful to aid the diagnostic evaluation of HFpEF. Scoring systems that help to determine the likelihood of HFpEF in a dyspneic person would comprise of both H2FPEF and HFA-PEFF. H2FPEF assesses the presence of hypertension, heavy body mass index (>30 kg/m2), atrial fibrillation, pulmonary hypertension, elderly (>60 years), and elevated filling pressures. 

HFA-PEFF involves pretest assessment of HF, echocardiography and natriuretic peptide score, functional testing including diastolic stress test/right heart catheterisation, and special imaging/biopsy/genetic testing to identify the cause. This guideline recommends that H2PEF scoring may be more useful in clinical practice to establish the diagnosis of HFpEF given the evidence of greater accuracy. (Figure 1 and Figure 2) 

Figure 1: Diagnostic Approach to HFpEF 

Figure 2: H2FPEF Scoring System

Management of HFpEF – Guideline Directed Medical Therapy (GDMT) 

Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors 

SGLT-2 inhibitors should be initiated in all individuals with HFpEF without contraindications. This is taking into account growing evidence of the benefits of SGLT-2 in HFpEF with the DELIVER and EMPEROR-Preserved trials, which showed a significant decrease in hospitalisations for HF. A meta-analysis of clinical trials evaluating SGLT-2 also found a reduction in the composite of hospitalisation for HF and cardiovascular deaths in individuals with HFpEF and HFmrEF. As in-hospital initiation of HF GDMT is associated with greater long-term adherence, initiation of SGLT-2 inhibitors during hospitalisation of acutely decompensated HF is safe and effective once clinically stable. 

Mineralocorticoid Antagonists 

MRAs improve the diastolic function in individuals with HFpEF. In addition, MRAs can also provide benefits such as balanced diuresis with sequential nephron blockade and control of blood pressure. W MRAs should be titrated to the maximum tolerated dosage based on symptoms, blood pressure, potassium and creatinine. 

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs) 

Based on data from the PARAGON-HF trial, FDA had recently expanded sacubitril/valsartan’s indication to include the risk reduction of cardiovascular death and hospitalisation for HF in adults with chronic HF, with benefits most evident in patients with LVEF below normal. ARNIs should be titrated to the maximum tolerated dosage based on symptoms, blood pressure, potassium and creatinine.

Angiotensin Receptor Blockers (ARBs)

ARBs may be used when ARNI is contraindicated or if affordability is a concern. ACE Inhibitors are not considered as an alternative due to the lack of benefit with perindopril shown in the PEP-CHF trial which included patients with LVEF > 40%. 

      Figure 3: Treatment Algorithm for Guideline-Directed Medical Therapy in HFpEF 

There are differences between men and women when it comes to response to therapies for HFpEF. Aside from SGLT-2 inhibitors, sacubitril/valsartan and spironolactone should be considered for women with HFpEF. Women may respond more favourably to these therapies at relatively higher EF due to their smaller LV chamber size, causing them to be more prone to demonstrating higher LVEFs compared to men. 

Management of Comorbidities

1. Hypertension 
   • Uncontrolled blood pressure may precipitate acute HF decompensation and individuals with HF can have an exaggerated hypertensive response to exercise. 
   • Adults with HFpEF should target systolic blood pressure of < 130mmHg
   • Preferred agents would include diuretic agents, ARNIs, ARBs and MRAs 
   • Beta-blockers should be avoided as negative chronotropic effects may reduce tolerability in HFpEF. 
2. Diabetes
   • Diabetes mellitus (DM) and HF often coexist, and each disease independently increases the risk for the other 
   • HbA1c goal of <7% to 7.5% is recommended for individuals with lower comorbidity burden or lesser severity of HF 
   • For patients with higher comorbidity burden, polypharmacy, increased risk of hypoglycemia or advanced HF, a higher target of HbA1c < 8% – 8.5% is acceptable 
   • SGLT-2 inhibitors are recommended first-line therapy for individuals with HFpEF and DM. 
   • GLP-1 receptor agonists can be considered for patients with T2DM and obesity
3. Atrial fibrillation (AF) 
   • AF is a common contributing factor to worse functional status and an increased risk of hospitalisation and mortality in individuals with HF
   • Management of AF should follow existing guidelines, with beta-blockers and non-DHP calcium channel blockers being first-line agents in rate control. Aggressive rate control should be avoided, given low stroke volume at rest and poor stroke volume reserve during exertion. 
4. Sleep Apnea 
   • Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing observed in HFpEF 
   • Patients with HFpEF and high suspicion of sleep apnea should be considered for polysomnography, and any abnormal results should trigger a referral to sleep, specialists. 

Conclusion

Given that HFpEF can be a complex condition with multiple overlapping comorbidities, optimal management will involve a multidisciplinary approach. The management goal would be the timely identification and implementation of therapy to improve outcomes of HFpEF 

Reference: 

1. Kittleson M, Panjrath G, Amancherla K, et al. 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2023 May, 81 (18) 1835–1878.https://doi.org/10.1016/j.jacc.2023.03.393