Heart Failure Classification and Management

Understanding Heart Failure Phenotypes and the 2023 ESC Update

Heart failure (HF) is no longer viewed as a single disease entity. The 2023 European Society of Cardiology (ESC) guidelines categorize patients based on left ventricular ejection fraction (LVEF) into three phenotypes: HFrEF (LVEF <40%), HFmrEF (LVEF 40‑49%), and HFpEF (LVEF ≥50%). A 68‑year‑old patient with an LVEF of 42% falls into the mid‑range or HFmrEF group, which often exhibits both systolic and diastolic dysfunction.

For this phenotype, the ESC 2023 update upgraded SGLT2 inhibitors to a Class I recommendation. This reflects robust evidence from trials such as EMPEROR‑Preserved and DELIVER, showing that sodium‑glucose co‑transporter‑2 (SGLT2) inhibitors improve outcomes across the entire LVEF spectrum, not just in reduced‑ejection‑fraction disease.

Acute Decompensated Heart Failure: Clinical Profiles and Initial Therapy

Acute decompensated heart failure (ADHF) is frequently described using a "wet/dry" and "cold/warm" framework. A patient who is warm, wet, and hypertensive (systolic blood pressure ≈120 mmHg) presents with congestion but maintains adequate perfusion. The ESC recommends an intravenous loop diuretic combined with a vasodilator (e.g., nitrates) as the first‑line pharmacologic strategy. This approach rapidly reduces preload and afterload, alleviating pulmonary congestion while preserving systemic perfusion.

Oral ACE‑inhibitor loading doses, high‑dose IV beta‑blockers, or immediate inotropic support are not appropriate initial steps for this hemodynamic profile, as they either risk hypotension or do not address volume overload effectively.

Why IV Loop Diuretics and Nitrates?

• Loop diuretics promote natriuresis and diuresis, directly lowering filling pressures.
• Nitrates cause venous dilation, reducing preload, and arterial dilation, decreasing afterload, which together improve cardiac output without compromising renal perfusion.

Mechanisms of SGLT2 Inhibitors in Heart Failure

Beyond glucose lowering, SGLT2 inhibitors confer cardiovascular benefits through several physiologic pathways. The most relevant for preload reduction is their ability to induce an osmotic diuresis. By inhibiting glucose reabsorption in the proximal tubule, they increase urinary glucose excretion, which pulls water into the urine, leading to a modest but clinically meaningful reduction in intravascular volume.

Other proposed mechanisms—such as direct sodium‑channel blockade, renin activation, or enhanced myocardial calcium handling—are either unsupported or play a secondary role in the context of preload management.

ARNI Initiation and the ACE‑Inhibitor Washout Requirement

Angiotensin receptor‑neprilysin inhibitors (ARNIs) have become a cornerstone of HFrEF therapy. When transitioning from an ARNI to an ACE inhibitor (or vice‑versa), the ESC mandates a 36‑hour washout period to minimise the risk of angio‑edema, a rare but serious adverse event caused by overlapping bradykinin accumulation.

Simultaneous administration or a shorter 12‑hour interval is contraindicated. Even in euvolemic patients, adherence to the washout interval is essential for safety.

NYHA Functional Classification: Recognising Class II Symptoms

The New York Heart Association (NYHA) functional classification remains a simple yet powerful tool for gauging symptom burden. Class II describes patients who experience dyspnoea during ordinary activities—such as climbing a flight of stairs—but are asymptomatic at rest. This contrasts with Class I (no limitation), Class III (symptoms with less‑than‑ordinary activity), and Class IV (symptoms at rest).

Key Trial Evidence: EMPEROR‑Preserved and Hospitalisation Reduction

The EMPEROR‑Preserved trial evaluated empagliflozin in patients with LVEF >40%. While the composite primary endpoint included cardiovascular death and HF hospitalisations, the trial’s benefit was driven primarily by a reduction in heart‑failure hospitalisations. Mortality differences were modest, underscoring the drug’s role in stabilising volume status and preventing acute decompensation.

SGLT2 Inhibitors in Advanced Chronic Kidney Disease

Renal function influences SGLT2‑i prescribing, yet the drugs remain valuable even in advanced chronic kidney disease (CKD). In patients with an eGFR of 22 mL/min/1.73 m², clinicians should anticipate a modest acute decline in eGFR after initiation. This dip reflects haemodynamic changes (reduced intraglomerular pressure) and is typically transient, not requiring dose reduction or discontinuation.

Contrary to older guidance, SGLT2 inhibitors are not outright contraindicated below an eGFR of 25 mL/min; many guidelines now permit use down to 20 mL/min/1.73 m², provided the patient is monitored closely.

Hemodynamic Profiles in Acute Heart Failure: The "Cold & Wet" Patient

The "cold & wet" profile denotes low cardiac output (cold) combined with elevated filling pressures (wet). This scenario reflects systemic hypoperfusion alongside pulmonary congestion—a high‑risk state that often necessitates careful inotropic support and aggressive decongestion.

Understanding this profile guides therapeutic intensity: patients with low output require agents that improve contractility, while the elevated filling pressures demand diuretics and possibly vasodilators, always balancing the risk of further hypotension.

Integrating the Concepts: A Practical Management Algorithm

Below is a concise algorithm that synthesises the key points discussed:

1. Identify HF phenotype (HFrEF, HFmrEF, HFpEF) using LVEF.
2. For HFmrEF (LVEF 40‑49%): initiate SGLT2 inhibitor (Class I).
3. Assess acute presentation:
   • If warm, wet, hypertensive: start IV loop diuretic + nitrates.
   • If cold, wet: consider inotropes plus diuretics.
   • If dry (no congestion): focus on neuro‑hormonal blockade.
4. When prescribing ARNIs, remember the 36‑hour washout before ACE‑inhibitor initiation.
5. Use NYHA class to gauge functional status and guide escalation.
6. Monitor renal function after SGLT2‑i start; expect a small eGFR dip, not a contraindication.
7. Refer to trial data (e.g., EMPEROR‑Preserved) to counsel patients on expected benefits—primarily reduced HF hospitalisations.

Key Take‑aways for Clinicians

• SGLT2 inhibitors are now a cornerstone therapy across all HF phenotypes, including HFmrEF.
• Initial ADHF management should match the patient's haemodynamic profile; IV diuretics + nitrates are first‑line for warm‑wet patients.
• Understanding the osmotic diuretic effect of SGLT2‑i clarifies why they lower preload.
• Always observe a 36‑hour washout when switching between ARNIs and ACE inhibitors.
• NYHA Class II describes dyspnoea with ordinary activity—useful for tracking disease progression.
• Empagliflozin’s main benefit in HFpEF is fewer hospitalisations, not mortality.
• In CKD, a transient eGFR decline after SGLT2‑i initiation is expected and not a reason to stop therapy.
• The "cold & wet" profile signals low output with congestion, guiding combined inotropic and decongestive strategies.

By integrating guideline‑driven recommendations with pathophysiologic insight, clinicians can optimise outcomes for patients across the heart‑failure spectrum.