Heart Failure Diagnosis and Treatment: A Practical Guide to Modern GDMT
Clinical Practice Update — Classification, Four-Pillar Therapy for HFrEF, SGLT2 Inhibitors Across the EF Spectrum, and Device Therapy
This is an original clinical education article informed by current guidelines and evidence. See References below for source documents.
- Clinical Focus
- HF classification by EF, four-pillar GDMT for HFrEF, treatment of HFmrEF and HFpEF, device therapy, acute decompensation, and comorbidity management
- Target Audience
- Internists, cardiologists, primary care physicians, residents, nurse practitioners, hospitalists
- Setting
- Primary care, cardiology clinic, emergency department, hospital inpatient
- Source Evidence
- •2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure
- •2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Failure (with 2023 Focused Update)
- •NICE Guideline [NG106] — Chronic Heart Failure in Adults (2018)
- •Key Trials: PARADIGM-HF (ARNi), DAPA-HF & EMPEROR-Reduced (SGLT2i in HFrEF), EMPEROR-Preserved & DELIVER (SGLT2i in HFpEF), VICTORIA (Vericiguat)
Key Clinical Takeaways
The most important actionable points from this Practice Update on heart failure diagnosis and treatment.
- 1HFrEF treatment now rests on four medication pillars: ARNi (or ACEi/ARB), beta-blocker, MRA, and SGLT2 inhibitor — start all four early → Four Pillars of HFrEF
- 2SGLT2 inhibitors (dapagliflozin or empagliflozin) are now recommended across the entire EF spectrum — including HFpEF → HFmrEF and HFpEF
- 3ARNi (sacubitril/valsartan) is preferred over ACEi or ARB in symptomatic HFrEF — switch patients already on ACEi/ARB → Four Pillars of HFrEF
- 4Never stop GDMT when EF improves — patients with HFimpEF (previous LVEF ≤40%, now >40%) have a 44% relapse rate if therapy is withdrawn → HF with Improved EF
- 5Consider vericiguat as a fifth agent in patients with worsening HFrEF despite optimal quadruple therapy → Beyond the Four Pillars
- 6Screen for and treat iron deficiency in all symptomatic HFrEF/HFmrEF patients with IV iron → Comorbidities
- 7Refer for ICD when LVEF remains ≤35% after at least 3 months of optimal GDMT → Device Therapy
- 8After an acute HF hospitalisation, up-titrate GDMT rapidly before discharge and within the first 6 weeks → Acute HF and Transitions
- 9Use natriuretic peptides (BNP or NT-proBNP) to support diagnosis but not as the sole criterion — echocardiography is essential → Making the Diagnosis
- 10Refer patients with stage D (advanced) HF to a specialist HF team early — before they are too sick for transplant or mechanical support → Advanced HF
How Should You Classify and Diagnose Heart Failure?
Heart failure is classified by LVEF because treatment differs substantially across the spectrum. The 2022 AHA/ACC/HFSA guideline introduced updated terminology and staging that every clinician should know.
| Category | LVEF | What It Means Clinically | Treatment Implications |
|---|---|---|---|
| HFrEF | ≤40% | Reduced systolic function — the best-studied HF phenotype | Four-pillar GDMT: ARNi + beta-blocker + MRA + SGLT2i. Strongest evidence base. |
| HFimpEF | Previous ≤40%, now >40% | EF has improved, but myocardial recovery may be incomplete | Continue all GDMT. TRED-HF showed 44% relapse at 6 months if therapy withdrawn. |
| HFmrEF | 41–49% | Mildly reduced EF — may behave more like HFrEF or HFpEF | SGLT2i recommended (AHA Class 2a / ESC Class I). Consider ARNi, ACEi/ARB, MRA, beta-blocker. |
| HFpEF | ≥50% | Preserved systolic function with diastolic dysfunction and/or elevated filling pressures | SGLT2i recommended (AHA Class 2a / ESC Class I). Manage comorbidities. Diuretics for congestion. |
Perform transthoracic echocardiography in all patients with suspected new-onset HF to assess LVEF, chamber dimensions, wall motion, valvular function, and diastolic parameters. This determines the HF category and drives treatment selection.
Strong RecHigh EvidenceAHA/ACC/HFSA 2022ESC 2021Measure BNP or NT-proBNP to support the diagnosis and for prognostication. In the acute setting, BNP <100 pg/mL or NT-proBNP <300 pg/mL makes HF unlikely. In the ambulatory setting, BNP <35 pg/mL or NT-proBNP <125 pg/mL makes HF unlikely.
Strong RecHigh EvidenceAHA/ACC/HFSA 2022ESC 2021What Are the Four Pillars of GDMT for HFrEF?
The 2022 AHA/ACC/HFSA guideline establishes four foundational drug classes for HFrEF (LVEF ≤40%). Each class independently reduces mortality and/or hospitalisation. The goal is to initiate all four as quickly as tolerated, then up-titrate to target doses. The order of initiation is less important than getting all four on board.
Prescribe an ARNi (sacubitril/valsartan) for patients with symptomatic HFrEF who can tolerate it, in preference to an ACEi or ARB. PARADIGM-HF demonstrated a 20% reduction in the composite of CV death or HF hospitalisation compared with enalapril. If ARNi is not feasible, use an ACEi or ARB.
Strong RecHigh EvidenceAHA/ACC/HFSA 2022PARADIGM-HFPrescribe an evidence-based beta-blocker (bisoprolol, carvedilol, or sustained-release metoprolol succinate) for all patients with HFrEF. Start at a low dose when the patient is euvolaemic and up-titrate to target dose every 2 weeks as tolerated.
Strong RecHigh EvidenceAHA/ACC/HFSA 2022ESC 2021Prescribe an MRA (spironolactone or eplerenone) for patients with symptomatic HFrEF (NYHA II–IV) already on an ARNi/ACEi/ARB and beta-blocker, provided eGFR >30 mL/min and K+ <5.0 mmol/L. Monitor potassium and renal function within 1 week and at 4 weeks.
Strong RecHigh EvidenceAHA/ACC/HFSA 2022Prescribe an SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg) for all patients with symptomatic HFrEF, regardless of diabetes status. DAPA-HF showed a 26% reduction in CV death or worsening HF; EMPEROR-Reduced showed a 25% reduction. The benefit is additive to the other three pillars.
Strong RecHigh EvidenceAHA/ACC/HFSA 2022ESC 2021Prescribe the combination of hydralazine and isosorbide dinitrate for patients who self-identify as African American with NYHA class III–IV HFrEF who are already on optimal therapy with ARNi/ACEi/ARB, beta-blocker, and MRA. This is based on the A-HeFT trial.
Strong RecModerate EvidenceAHA/ACC/HFSA 2022What Should You Do for HFmrEF and HFpEF?
For years, HFpEF was a therapeutic desert. The EMPEROR-Preserved and DELIVER trials changed this by demonstrating that SGLT2 inhibitors reduce HF hospitalisation across the entire EF spectrum. The 2023 ESC focused update now recommends SGLT2 inhibitors as Class I for both HFmrEF and HFpEF.
Prescribe an SGLT2 inhibitor (dapagliflozin or empagliflozin) for symptomatic patients with HFmrEF or HFpEF to reduce the risk of HF hospitalisation and CV death. EMPEROR-Preserved showed a 21% reduction and DELIVER showed an 18% reduction in the primary composite, both driven primarily by reduced hospitalisation.
Strong RecHigh EvidenceESC 2023 UpdateManage volume overload in HFpEF with diuretics. Treat hypertension, atrial fibrillation, coronary artery disease, and obesity aggressively — comorbidity management is the cornerstone of HFpEF care beyond SGLT2 inhibitors.
Strong RecModerate EvidenceAHA/ACC/HFSA 2022ESC 2021Consider a GLP-1 RA or dual GIP/GLP-1 RA (tirzepatide) for patients with HFpEF who have obesity (BMI ≥30). The STEP-HFpEF and SUMMIT trials demonstrated improvements in symptoms, exercise capacity, and weight in this population.
Moderate RecModerate EvidenceADA 2025Clinical Decision Pathway
Monitoring and Follow-Up
| Parameter | When | Action Threshold | Common Pitfalls |
|---|---|---|---|
| Renal function + K+ | 1–2 weeks after starting/changing ARNi, ACEi, ARB, MRA, or SGLT2i; then every 3–6 months | K+ >5.5 or creatinine rise >30% → reduce MRA or RAAS blocker dose | Stopping GDMT for a small creatinine rise that may be haemodynamic and reversible |
| Weight & volume status | Daily home weight; clinical assessment at each visit | Weight gain >2 kg in 3 days → increase diuretic and seek review | Not educating patients on daily weights and when to seek help |
| Iron studies | At diagnosis and annually; more often if symptomatic | Ferritin <100 or ferritin 100–299 with TSAT <20% → IV iron | Using oral iron instead of IV iron — oral absorption is poor in HF |
| Repeat echo | 3–6 months after GDMT optimisation; at any clinical change | LVEF still ≤35% → device evaluation. LVEF >40% → reclassify as HFimpEF, continue all GDMT. | Not repeating echo after optimisation — EF may improve enough to change device eligibility |
Evidence in Context
Where AHA/ACC/HFSA 2022 and ESC 2021/2023 Agree
Both frameworks agree on the four-pillar GDMT for HFrEF, the preference for ARNi over ACEi/ARB, the central role of SGLT2 inhibitors across the EF spectrum, the importance of up-titrating to target doses, the need to continue GDMT in HFimpEF, IV iron for iron deficiency, ICD for LVEF ≤35%, and CRT for LBBB with QRS ≥150 ms. Both also emphasise comorbidity management in HFpEF and early referral for advanced HF.
Where They Differ
SGLT2i class of recommendation: The 2023 ESC update gives SGLT2 inhibitors Class I-A for HFmrEF and HFpEF. The 2022 AHA/ACC/HFSA gives Class 2a (published before the DELIVER trial). In practice, the stronger ESC recommendation reflects the more complete evidence base.
Vericiguat: Both guidelines recommend it for worsening HFrEF, but positioning differs slightly. The ESC is more explicit about it as a fifth drug after worsening despite quadruple therapy.
Finerenone for HF prevention: The 2023 ESC update recommends finerenone (Class I-A) for patients with T2D and CKD to reduce HF hospitalisation. This is not addressed in the 2022 AHA/ACC/HFSA HF guideline.
The Trials That Changed Everything
PARADIGM-HF (2014) established ARNi superiority over ACEi in HFrEF with a 20% reduction in CV death/HF hospitalisation. DAPA-HF (2019) and EMPEROR-Reduced (2020) added SGLT2 inhibitors as the fourth pillar, showing 26% and 25% reductions respectively in worsening HF/CV death, regardless of diabetes status. EMPEROR-Preserved (2021) and DELIVER (2022) extended SGLT2i benefit across the EF spectrum. VICTORIA (2020) showed a 10% reduction in CV death/HF hospitalisation with vericiguat in worsening HFrEF. STRONG-HF (2022) demonstrated the safety and efficacy of rapid GDMT up-titration post-discharge.
What We Still Don’t Know
References
- 1.Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2022;79(17):e263–e421. doi:10.1016/j.jacc.2021.12.011
- 2.McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–3726. doi:10.1093/eurheartj/ehab368
- 3.McDonagh TA, Metra M, Adamo M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627–3639. doi:10.1093/eurheartj/ehad195
- 4.McMurray JJV, Packer M, Desai AS, et al. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure (PARADIGM-HF). N Engl J Med. 2014;371(11):993–1004. doi:10.1056/NEJMoa1409077
- 5.McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF). N Engl J Med. 2019;381(21):1995–2008. doi:10.1056/NEJMoa1911303
- 6.Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER). N Engl J Med. 2022;387(12):1089–1098. doi:10.1056/NEJMoa2206286
How to Read the Evidence Tags
Every recommendation carries two tags. These are Medaptly’s own simplified interpretations for educational clarity.
Recommendation Strength
| Tag | Meaning | In Practice |
|---|---|---|
| Strong Rec | Benefits clearly outweigh risks. | Standard practice. |
| Moderate Rec | Evidence favours benefit. | Most patients should receive this. |
| Conditional Rec | Right choice depends on individual. | Shared decision-making. |
| Against | Risks outweigh benefits. | Avoid. |
Evidence Quality
| Tag | Meaning | Confidence |
|---|---|---|
| High Evidence | Multiple RCTs or meta-analyses. | Very confident. |
| Moderate Evidence | Single RCT or large observational studies. | Reasonably confident. |
| Low Evidence | Expert consensus or small studies. | May change. |
These are Medaptly’s simplified interpretations. Consult original documents in References for full classification systems.