The sodium-glucose co-transporter 2 (SGLT2) inhibitors empagliflozin and dapagliflozin are now recommended for the treatment of chronic heart failure with reduced ejection fraction (HFrEF), according to the latest 5-year update of the European Society of Cardiology's (ESC) Guidelines in Acute and Chronic Heart Failure, released during the ESC Congress 2021.

Chronic heart failure is a medical disease in which the heart is unable to adequately pump blood throughout the body. It often happens as a result of the heart being overly weak or stiff. The most critical parameter in heart failure is the ejection fraction, which is the proportion of blood inside the ventricles that is expelled throughout the cardiac cycle.

Heart failure with preserved ejection fraction (HPpEF), sometimes referred to as diastolic heart failure, is characterised by poor left ventricular relaxation. Heart failure with a reduced ejection fraction (HFrEF), also known as systolic heart failure, is characterised by decreased left ventricular contraction.

HFpEF is increasing in prevalence across the globe since its probability increases with age and high blood pressure. According to ESC, the prevalence increases from 1% in individuals under the age of 55 to more than 10% in those aged 70 and beyond. Breathlessness, ankle swelling, and fatigue are all symptoms. Once diagnosed, individuals are usually admitted to the hospital once a year and 50% die within five years.

Heart failure is associated with hospitalisation and is a significant contributor to increasing health care expenditures. The update takes into account the fact that patients with heart failure often have co-morbid diseases such as atrial fibrillation and valvular heart disease and makes therapy recommendations accordingly.

Task group head Marco Metra, MD, of Brescia University in Italy, said in a statement:

“It is critical to address the underlying causes of heart failure and its complications. When hypertension, diabetes, and coronary artery disease are properly managed, heart failure may be avoided. Atrial fibrillation, valvular heart disease, diabetes, chronic renal disease, iron insufficiency, and other comorbidities often coexist with heart failure, and the use of particular therapies may have a significant effect on our patients' clinical outcomes.”

Increase in the use of SGLT2 inhibitors in patients with heart failure

Numerous evidence-based therapies, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor neprilysin inhibitors (ARNIs), beta-blockers, and mineralocorticoid receptor antagonists, have been developed to enhance survival in HFrEF (MRAs). However, since their introduction in 2013 for the treatment of type 2 diabetes (T2D), SGLT2 inhibitors have altered cardiometabolic care spanning diabetes, heart failure, and renal illness.

1. The 2015 EMPA-REG OUTCOME trial, which was designed to satisfy FDA requirements for empagliflozin approval in T2D, astounded both diabetes and cardiology communities when the drug demonstrated cardiovascular (CV) benefits, and soon separate trials in heart failure and renal disease were currently ongoing across the drug class.
2. EMPEROR-Reduced and EMPEROR-Preserved were two of these studies that investigated empagliflozin in HFrEF and HFpEF, respectively. Both the EMPEROR-Reduced and DAPA-HF trials of dapagliflozin demonstrated substantial reductions in a composite of cardiovascular mortality or hospitalisation for heart failure, resulting in the revised ESC recommendations.
3. EMPEROR-Preserved findings will be revealed later at the ESC Congress, and preliminary results indicate they will be substantial. As stated during a press conference held prior to the presentation on EMPEROR-Preserved, the most recent modification to the heart failure guidelines may be obsolete within hours.

According to the 2021 ESC Guidelines, “no therapy has been shown to significantly decrease mortality and morbidity in individuals with HFpEF, although improvements have been seen for certain particular phenotypes of patients under the HFpEF category.”

Modifications from 2016

The ESC's heart failure recommendations were last revised in 2016. The authors highlight several concepts that have been incorporated into the guidelines, including:

• A switch from the term "heart failure with mid-range ejection fraction" to "heart failure with mildly reduced ejection fraction" (HFmrEF) to refer to patients with a left ventricle ejection fraction (LVEF) of 41% to 49%.
• A new categorisation system for acute heart failure
• Inclusion of critical quality indicators

Suggested therapies

1. The revised recommendations suggest empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, and sotagliflozin for patients with T2D who are at risk of CV events, with the goal of “reducing hospitalisations for HF, major CV events, end-stage renal dysfunction, and CV death.”
2. Separately, dapagliflozin, empagliflozin, and sotagliflozin were suggested for those with T2D and HFrEF in order to decrease hospitalizations for heart failure and cardiovascular mortality. The FDA has not yet authorised sotagliflozin, an SGLT1/2 inhibitor.
3. Notably, new level 1 recommendations—which indicate that there is evidence or widespread agreement that therapy or practice is helpful, useful, or effective—direct physicians to provide patients with evidence-based oral medicines, including SGLT2 inhibitors, prior to a hospital release.
4. Prior to discharge, guidelines recommend that patients be assessed for congestion to enable doctors to determine the most effective oral treatment regimens. Follow-up visits every 1 to 2 weeks are advised to adjust dosage as required.

Strategies

Apart from particular therapy recommendations, additional updates—if implemented into clinical practice—could have a significant effect on patient care. Additionally, the following Level 1 guidelines apply:

1. HFpEF: In individuals with HFpEF, screening for etiologies and CV and non-CV comorbidities, as well as therapy, is suggested.
2. Prevention and early detection:
   1. Self-management methods are suggested to decrease the risk of hospitalisation and death associated with heart failure.
   2. Home-based and/or clinic-based programmes both enhance outcomes and are recommended for lowering the risk of heart failure hospitalisation and death.
3. Advanced HF management:
   1. Patients selected for long-term mechanical circulatory support must be capable of using the device and have support systems in place
   2. Heart transplantation is suggested for individuals with advanced HF who have failed medical/device treatment and do not have absolute contraindications.
4. Care of patients with congestive heart failure and valvular heart disease:
   1. Aortic valve intervention, either transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR), is indicated in patients with congestive heart failure (HF) with severe high-gradient aortic stenosis to decrease mortality and improve symptoms. 
   2. The decision between TAVI and SAVR should be decided based on the preferences and characteristics of the individual patient, including age, surgical risk, clinical, anatomical, and procedural factors while balancing the risks and benefits of each method.
5. Patients with congestive heart failure and iron shortage: Anaemia and iron deficiency must be tested in patients with HF using a complete blood count, serum ferritin concentration, and transferrin saturation.
6. Patients with congestive heart failure and malignancy: Patients with cancer who are at increased risk of cardiotoxicity, as defined by a history or risk factors for CV disease, prior cardiotoxicity, or exposure to cardiotoxic agents, should have their cardiovascular system evaluated prior to starting scheduled anticancer therapy, preferably by a cardiologist with cardio-oncology experience.
7. Hypertension and amyloidosis:
   1. The guidelines recommend tafamidis (Vyndamax) for patients with transthyretin amyloidosis-cardiac amyloidosis (CA) who have hereditary hTTR-CMP and NYHA class I or II symptoms.
   2. For patients with wtTTR-CA who have NYHA class I or II symptoms in order to reduce symptoms, CV hospitalisation, and mortality.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.