ESC Heart Failure Guidelines: 2021 Standards & 2023 Focused Update

Abstract

Objective: The clinical management of heart failure (HF) is currently governed by the 2021 European Society of Cardiology (ESC) Guidelines, significantly augmented by the 2023 Focused Update. Together, these documents establish a modern framework emphasizing early diagnosis and comprehensive Guideline-Directed Medical Therapy (GDMT). This article provides a concise summary of these combined standards and their implications for healthcare professionals.

Key Updates: The 2023 Focused Update introduced critical revisions, most notably the universalization of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as Class I therapy for all HF phenotypes (HFrEF, HFmrEF, and HFpEF). The guidelines also reinforce the “Quadruple Therapy” approach for Heart Failure with Reduced Ejection Fraction (HFrEF) and refine the diagnostic algorithms for Heart Failure with Preserved Ejection Fraction (HFpEF). Additionally, the update provides revised recommendations for acute HF management (based on the STRONG-HF trial) and comorbidity management.

Clinical Implications: The current consensus mandates a paradigm shift toward rapid initiation and optimization of four drug classes in HFrEF. It underscores the critical role of SGLT2i in improving outcomes across the full spectrum of left ventricular function, requiring clinicians to adhere to meticulous phenotyping to reduce hospitalization and mortality.

Introduction: The Evolving Landscape of Heart Failure Management

Definition and Clinical Burden

Heart failure (HF) remains a global public health crisis, affecting an estimated 64 million people worldwide and contributing substantially to cardiovascular morbidity, mortality, and healthcare costs. While incidence rates in developed countries have stabilized, the prevalence of HF is increasing due to the aging population and improved survival of patients with antecedent conditions like myocardial infarction. This growing burden necessitates continuous refinement of clinical standards.

The 2021 Guidelines and 2023 Focused Update

The management of HF has been revolutionized by landmark clinical trials over the last decade. Current European practice is defined by two foundational documents:

1. The 2021 ESC Guidelines: Established the “Four Pillars” of medical therapy for HFrEF and structured the diagnostic approach.
   
   
2. The 2023 Focused Update: Triggered by pivotal trials such as EMPEROR-Preserved, DELIVER, and STRONG-HF, this update expanded the Class I recommendation for SGLT2 inhibitors to patients with HFmrEF and HFpEF and emphasized high-intensity care in the early post-discharge period.
   
   

Objectives of This Review

The core objective of these combined recommendations is to solidify the prognostic role of Guideline-Directed Medical Therapy (GDMT) across the entire spectrum of Left Ventricular Ejection Fraction (LVEF). This document highlights the key paradigm shifts—specifically the transition to universal SGLT2i use and rapid sequencing of therapy—ensuring clinicians can implement these evidence-based standards into daily practice.

Refined Diagnosis and Phenotyping

The ESC guidelines maintain the classification of heart failure based on the Left Ventricular Ejection Fraction (LVEF), but place greater emphasis on the specific diagnostic pathways and the concept of LVEF trajectories, particularly for non-HFrEF phenotypes. The three established phenotypes remain: HFrEF (≤ 40%), HFmrEF (41% – 49%), and HFpEF (≥ 50%).

Updated Diagnostic Criteria and Algorithm

The diagnosis of heart failure continues to rely on the presence of symptoms and/or signs of heart failure, supported by objective evidence of a cardiac structural and/or functional abnormality. The guideline stresses the mandatory role of Natriuretic Peptides (NPs) and Echocardiography as the primary diagnostic tools.

• Natriuretic Peptides (NPs): Elevated levels of NT-proBNP or BNP serve as the essential initial test to exclude heart failure. Specific diagnostic thresholds are refined based on the clinical setting and the presence of atrial fibrillation.
  
  

Practice Highlight 1: Key Diagnostic Thresholds for NPs Non-acute setting NT-proBNP screening thresholds are critical for initial workup. The guidelines advocate for immediate cardiology referral and further testing when NP levels are elevated to detect subclinical disease.

Phenotyping: HFrEF, HFmrEF, and the New Approach to HFpEF

The updated focus lies in clarifying the diagnostic and management pathway for HFpEF, recognizing the syndrome’s inherent heterogeneity.

• The HFA–PEFF Algorithm: The guidelines reinforce a structured, multi-step diagnostic approach (often citing the HFA–PEFF methodology) that moves beyond simple LVEF measurement. This algorithm integrates Pre-test assessment, Echocardiography/NP scoring, Functional testing (e.g., stress echo), and Final etiology workup.
  
  
• LVEF Trajectory: A critical, emerging concept is the consideration of LVEF trajectory—whether the LVEF is persistently reduced, worsening, or improved. Patients with an Improved LVEF (previously HFrEF, now LVEF >40%) still require continued GDMT due to the high risk of relapse.
  
  

Universalization of Guideline-Directed Medical Therapy (GDMT)

The most transformative change is the clear directive to achieve optimal GDMT rapidly, establishing SGLT2 inhibitors as universal therapy regardless of LVEF.

SGLT2 Inhibitors as Foundational Therapy

The guidelines award a Class I, Level of Evidence A recommendation to SGLT2 inhibitors (e.g., dapagliflozin or empagliflozin) for patients with symptomatic heart failure across the full range of LVEF.

• Evidence Across the Spectrum: Supported by DAPA-HF and EMPEROR-Reduced (HFrEF), and EMPEROR-Preserved and DELIVER (HFpEF/HFmrEF), the evidence mandates that an SGLT2 inhibitor should be considered as part of the initial core regimen for virtually all eligible patients.
  
  

The Quadruple Therapy: Optimization in HFrEF

For patients with Heart Failure with Reduced Ejection Fraction (HFrEF), the ESC guidelines reinforce the foundational Quadruple Therapy:

1. ARNIs/ACEi/ARBs
   
   
2. Beta-Blockers (beta-blockers)
   
   
3. Mineralocorticoid Receptor Antagonists (MRAs)
   
   
4. SGLT2 Inhibitors
   
   

The emphasis is on simultaneous initiation, rather than sequential addition, to realize the maximal clinical benefit sooner.

Pharmacological Management of HFpEF and HFmrEF

The pharmacologic management of HFpEF and HFmrEF is now centered around the SGLT2 inhibitors.

• HFmrEF: Patients should receive the same core GDMT as HFrEF (ARNI/ACEi/ARB, beta-blockers, MRA, and SGLT2i).
  
  
• HFpEF: Management is primarily focused on SGLT2 inhibitors (Class I) for prognostic benefit, followed by MRAs and ARNIs (Class IIb) in selected patients to manage congestion and associated conditions.
  
  

Device and Procedural Therapy Timing

The ESC guidelines mandate a stronger emphasis on maximal medical therapy optimization before device implantation.

Updated Recommendations for ICD and CRT

• Primary Prevention ICD: A Class I recommendation is upheld for primary prevention ICD in symptomatic HFrEF patients (NYHA Class II–III) with LVEF ≤ 35% despite receiving optimal GDMT for at least 3 to 6 months. This required duration is emphasized to allow for potential reverse remodeling from quadruple therapy.
  
  
• Cardiac Resynchronization Therapy (CRT): CRT remains a Class I recommendation for symptomatic HFrEF patients with LVEF ≤ 35% and a wide QRS duration (≥ 150 ms) with Left Bundle Branch Block (LBBB) morphology.
  
  

Role of Interventional Therapies

• Transcatheter Mitral Valve Repair (TMVr): For patients with severe secondary (functional) mitral regurgitation that persists despite optimal GDMT and LVEF ≥20%, TMVr is considered an option (typically Class IIb) to reduce symptoms and potentially improve quality of life.
  
  

Management of Comorbidities and Special Populations

Optimal outcomes depend on meticulous management of comorbidities, particularly the cardio-renal and cardio-metabolic interactions.

Focus on Cardiorenal Syndrome and Diabetes

• Cardio-Renal Syndrome (CRS): The guidelines emphasize the reno-protective effects of SGLT2 inhibitors (citing trials like EMPA-KIDNEY), supporting their use even in patients with lower eGFRs.
  
  
• Diabetes and Obesity: SGLT2 inhibitors are the preferred antidiabetic agents in HF patients due to their proven CV and renal benefits.
  
  

Management in Advanced Heart Failure

• Multidisciplinary Team (MDT) Approach: Strongly advocated for AHF patients to manage complex needs and guide decisions regarding VADs, transplantation, or palliative care.
  
  
• Iron Deficiency: Screening and treatment for iron deficiency (with or without anemia) using intravenous iron remains a Class IIa recommendation for symptomatic HFrEF patients, based on trials like FAIR-HF and AFFIRM-AHF, to improve functional status.
  
  

Clinical Practice Summary & Key Takeaways

The ESC Heart Failure Guidelines mandate a significant shift in clinical practice toward the rapid implementation of optimized GDMT across all eligible patients.

Summary Table: ESC Core GDMT Recommendations by HF Phenotype