Acute Decompensated Heart Failure (ADHF): 2025/2026 Guideline-Directed Medical Therapy

Phenotype-Based Framework (Harrison's 2025)

Step 1: Identify and Treat Precipitants (All Cases)

• Medication nonadherence / dietary salt excess (most common)
• Ischemia - investigate and consider revascularization in all patients with atherosclerotic CVD
• Arrhythmia (AF, VT) - antiarrhythmic therapy, cardioversion, or ablation as appropriate
• Valvular disease - echocardiography to identify candidates for intervention
• Infection / pulmonary embolism
• Nephrotoxins: NSAIDs, thiazolidinediones, TNF inhibitors, some antidepressants, cold/flu preparations, selected chemotherapy agents

Step 2: Immediate Pharmacologic Management

A. Decongestion - IV Loop Diuretics (FIRST PRIORITY)

• Initiate IV loop diuretic within 1 hour of presentation (AHA 2025, Class I)
• Starting dose should equal or exceed the patient's chronic oral daily dose
• Bolus vs. continuous infusion: no definitive superiority of one over the other from RCT data - use clinical judgment
• Target: euvolemia (JVP normalization, clearance of rales, resolution of edema) - residual congestion drives readmission
• Monitor: urine output, daily weight, serum electrolytes, creatinine

• Sequential nephron blockade: add thiazide (metolazone, chlorothiazide) or hydrochlorothiazide on top of loop diuretic. The CLOROTIC trial confirmed hydrochlorothiazide significantly improved weight loss vs. placebo in patients on oral furosemide admitted for decompensation (monitor for hypokalemia and creatinine rise)
• Acetazolamide (ADVOR trial): facilitates greater decongestion but no reduction in HF readmission or mortality - use selectively
• Ultrafiltration (aquapheresis): reserved for patients refractory to maximal diuretic therapy; controlled fluid removal with electrolyte-neutral effect
• A 2025 systematic review and meta-analysis (Fioretti et al., Eur J Heart Fail 2025, PMID 41367306) confirmed combination diuretic therapy improves decongestion in ADHF

B. Vasodilators (Hypertensive / Pulmonary Edema Phenotype)

• IV nitroglycerin or nitroprusside for patients with elevated systolic BP (>140 mmHg) and volume redistribution ("flash pulmonary edema" pattern)
• Reduce preload and afterload rapidly
• Do not use in hypotensive or low-output patients

C. Oxygen / Non-Invasive Ventilation

• Titrate O2 to SpO2 ≥92-94% - do not target hyperoxemia
• The 2026 ESC Heart Failure meeting presented the Redox A-CHF trial confirming that restrictive oxygenation (SpO2 ~90%) leads to significantly greater reduction in estimated lung fluid content vs. liberal O2 (>96%) in ADHF - now guideline-endorsed
• NIV (CPAP/BiPAP): first-line for acute cardiogenic pulmonary edema with hypoxia. Reduces need for intubation
• Opiates (morphine): use cautiously - may reduce dyspnea and venodilate, but associated with adverse outcomes in some registries

D. Inotropic Therapy (Low-Output / Cardiogenic Shock)

• Reserved for hypoperfusion states: low pulse pressure, cold extremities, rising lactate, oliguria, hepatic congestion
• Options: dobutamine (preferred), milrinone (alternative, especially with beta-blocker use or pulmonary hypertension), norepinephrine (cardiogenic shock with hypotension)
• Use lowest effective dose; bridge to recovery, definitive therapy (LVAD, transplant), or palliation
• Avoid long-term intermittent inotropic therapy - no mortality benefit and potentially harmful (AHA 2025)
• Pulmonary artery catheter: not routine - reserve for refractory cases, suspected cardiogenic shock, complex cardiorenal syndrome, or suspected pulmonary arterial hypertension

E. Mechanical Circulatory Support (Cardiogenic Shock)

• IABP (intra-aortic balloon pump): widely available, modest hemodynamic benefit
• Percutaneous VAD (Impella, TandemHeart): stronger hemodynamic support for refractory cardiogenic shock
• Consider as bridge to decision (recovery, LVAD, or cardiac transplantation)

Step 3: The Paradigm Shift - In-Hospital GDMT Initiation (2025/2026 KEY UPDATE)

"Management of AHF has shifted from focusing solely on symptomatic decongestion to the rapid initiation of disease-modifying therapies during hospitalization."

• Heart failure evidence update 2026, PMC

Quadruple GDMT (HFrEF, LVEF <40%) - Initiate/Continue During Hospitalization

SGLT2i in ADHF - Special Note

• Start empagliflozin or dapagliflozin as soon as clinically feasible during the hospitalization (even within 24-48 hours of admission)
• The 2025 Canadian (CCS/CHFS) and Japanese (JCS/JHFS) guidelines now explicitly recommend SGLT2i across the EF spectrum (HFrEF, HFmrEF, HFpEF)
• Evidence supports osmotic diuretic + natriuretic effects that aid decongestion

HFpEF and HFmrEF (LVEF ≥40%)

• SGLT2 inhibitor: recommended (empagliflozin/dapagliflozin) - Class IIa, AHA/ACC/HFSA; now Class I in 2025 Canadian guidelines
• Finerenone (non-steroidal MRA): REDEFINE-HF trial (NCT06008197) ongoing for post-acute HFmrEF/HFpEF - results anticipated; guideline position may change
• ARNI: reasonable to use in HFpEF; 2025 CCS guidelines support this
• Diuretics: still cornerstone for symptom relief in volume-overloaded HFpEF

Step 4: Monitoring Parameters

• Fluid intake/output, body weight
• Heart rate, rhythm, blood pressure, SpO2
• Serum electrolytes (Na, K, Mg), creatinine, BUN
• BNP or NT-proBNP (pre-discharge level strongly predicts post-discharge mortality and readmission)
• Signs of congestion (JVP, rales, edema)

• BUN >43 mg/dL
• sBP <115 mmHg
• Creatinine >2.75 mg/dL
• Elevated troponin or markedly elevated natriuretic peptides

Step 5: Pre-Discharge and Transition Planning

• Do not discharge with residual congestion - this is the strongest modifiable predictor of 30-day readmission
• Pre-discharge BNP/NT-proBNP measurement to stratify risk
• Resume/optimize oral loop diuretic at discharge
• Ensure quadruple GDMT is prescribed before discharge (or documented rationale for omission)
• "High-intensity care" strategy: rapid up-titration of quadruple therapy with frequent clinical and laboratory reassessment (AHA 2025)
• Early follow-up: telephone contact within 3 days post-discharge; in-person visit within 7-14 days

Medications to Avoid in ADHF / Heart Failure

Key 2025/2026 Citations