HFrEF-Exacerbation

EF <40% · complete reference · all trials · full doses + brand names · escalation + discharge checklist · Full Card

Symptoms / Associated Sx

• Progressive DOE → rest; orthopnea (≥2 pillows); PND (awakened gasping, relieved upright); bendopnea (dyspnea leaning forward — specific for elevated filling pressures)

• Rapid wt gain (>2–3 lbs/day); bilateral pitting edema; abdominal distension (ascites); RUQ discomfort (hepatic capsule)

• S3 gallop (most specific for elevated LV filling; apex with bell, left lateral decubitus); JVD (measure at 45°); HJR (10-sec RUQ pressure → JVP rise >3 cm); bibasilar crackles (often absent in chronic HF from lymphatic adaptation — absence does NOT exclude ADHF)

• Low output signs: cool/mottled extremities, narrow PP (<25 mmHg), tachycardia, AMS, oliguria → cardiogenic shock territory

• Cardiogenic pulm edema: severe dyspnea, SpO2↓, pink frothy sputum, accessory muscle use, diaphoresis → immediate NIPPV ± intervention

• NYHA class: I = no limitation; II = slight limitation on exertion; III = marked limitation, comfortable at rest; IV = symptoms at rest — document on every admission

Neg

• Bilateral leg swelling without JVD or dyspnea (DVT/venous insufficiency — Doppler US; CCB/TZD-induced — medication history; hypoalbuminemia)

• Dyspnea + pleuritic CP + tachycardia + hypoxia without JVD or S3 (PE — echo: RV dilation vs LV dilation; BNP elevated from RV strain; CT-PA confirms)

• Fever + productive cough + unilateral infiltrate (PNA — can precipitate ADHF; treat both; procalcitonin helps distinguish)

• Anasarca without JVD (nephrotic — heavy proteinuria, hypoalbuminemia; hepatic failure — ascites-predominant, portal HTN, spider angiomata)

• Cardiomegaly + volume overload without dyspnea (constrictive pericarditis — Kussmaul sign, pericardial knock, RHC equalization, CT pericardial thickening)

Social History (SHx)

• Prior HF hospitalizations (number + recency — strongest readmission predictor); known EF + last echo date; ICD/CRT (type, last interrogation, recent shocks); prior PCI/CABG (date, vessels, stent type)

• Medication adherence (which GDMT, doses, recent changes — missed doses most common trigger); dietary Na+/fluid; ETOH (dose, duration — alcoholic CM reversible with abstinence ≥6 months); cocaine; anthracycline cumulative dose; family hx CM or SCD (TTN most common genetic NICM ~25%; LMNA, SCN5A, MYH7)

Main Etiology

• Ischemic CM (~50%) — prior MI, multivessel CAD, hibernating myocardium; revascularization may recover EF if viable tissue (cardiac MRI, PET, or dobutamine stress echo)

• Non-ischemic CM (~50%): idiopathic/familial (TTN ~25% of NICM), hypertensive, alcoholic, peripartum (PPCM), tachycardia-mediated (AF-RVR — fully reversible with rate control), myocarditis, drug/toxin (anthracyclines, cocaine, trastuzumab [Herceptin]), valvular (MR, AR), Chagas, sarcoid, amyloid (AL vs ATTR)

• Decompensation triggers (CHAMPION): Cardiac ischemia/arrhythmia (most common); HTN crisis; Adherence failure; Medication changes (NSAID/CCB/negative inotrope); Pulmonary embolism; Infection/sepsis; Obesity/OSA worsening; New valvular lesion

RF

• Modifiable: HTN (most important), CAD, DM, obesity, ETOH, cocaine, anthracyclines, non-adherence, excess dietary Na+/fluid, untreated AF-RVR (tachycardia-mediated CM), untreated OSA

• Non-modifiable: prior MI, age, male sex, family hx CM or SCD, genetic CM (TTN, LMNA, SCN5A, MYH7)

• Emerging: CKD, iron deficiency (impairs myocardial function independently of anemia — screen ALL ADHF with ferritin+TSAT), cancer therapy (anthracyclines, trastuzumab [Herceptin], ICI), amyloidosis

Data

• BNP or NT-proBNP (>400 pg/mL = ADHF highly likely; <100 = HF unlikely; predischarge failing to fall ≥30% = ↑30-day readmission; NT-proBNP preferred if BMI >35 — BNP spuriously low in obesity)

• Troponin I/T serial (wall stress injury or ACS trigger; elevated = worse prognosis; dynamic rise/fall = ACS — trend to peak)

• BMP (Na+ — <135 poor prognosis; <130 very high risk; K+ — ≥5.0 hold MRA/ACEi; Cr/BUN baseline before diuresis; BUN/Cr >20 = prerenal; CO2 — metabolic alkalosis blunts loop diuretic response)

• CBC (Hgb — anemia trigger; transfuse to Hgb ≥8; WBC — infection; platelets — anticoag safety)

• LFTs + direct bilirubin (hepatic venous congestion → ↑AST/ALT "cardiac hepatitis"; ↑direct bili + ↑INR = "cardiac cirrhosis" in severe right HF)

• TSH (hypothyroidism ↓contractility; hyperthyroidism → tachycardia-mediated HF + AF)

• Iron studies (ferritin + TSAT) (ID in ~50% HF: ferritin <100 or ferritin 100–299 + TSAT <20%; IV iron ↓rehospitalization — AFFIRM-AHF 2020, HEART-FID 2023)

• ECG (AF/flutter — rate control urgency; LBBB + QRS ≥150 ms = CRT candidate; ischemic changes — ACS trigger; low voltage + pseudo-infarct = amyloid)

• CXR (cephalization, Kerley B lines, cardiomegaly, bilateral effusions R>L in HF, "bat wing" alveolar edema in APE)

• Point-of-care lung US (B-lines >3/zone in ≥2 bilateral zones = interstitial edema — more sensitive + faster than CXR; monitor diuresis response at bedside)

• Echo (EF — HFrEF <40%/HFmrEF 40–49%/HFpEF ≥50%; wall motion — ischemic territory; E/e' >15 = elevated filling pressures; IVC collapsibility; pericardial effusion; RV function — prognostic)

• Spot urine Na+ 2h post-IV furosemide (Lasix) (UNa+ <50 mEq/L = inadequate natriuresis → double dose or add thiazide — single most actionable bedside diuresis tool)

• Lactate (>2 mmol/L = tissue hypoperfusion → cardiogenic shock; guides MCS decision)

• RHC (Swan-Ganz) if refractory or hemodynamics unclear (PCWP >18 = cardiogenic pulm edema; CI <2.2 = low CO; SvO2 <65% = ↑O2 extraction; guides vasodilator + inotrope titration)

DDx

HFpEF (EF ≥50%, S4 > S3, concentric LVH, diastolic dysfunction — different GDMT pathway) · PE (pleuritic CP, hypoxia, RV dilation on echo — not LV; BNP elevated from RV strain; CT-PA) · PNA (fever, unilateral infiltrate, leukocytosis; can precipitate ADHF; procalcitonin) · COPD/asthma (wheezing, BNP <100, bronchodilator response) · Tamponade (Beck triad: JVD+hypotension+muffled sounds; pulsus paradoxus >10; RV diastolic collapse on echo) · Cardiogenic shock (SBP <90, CI <2.2, PCWP >15, lactate >2 — Forrester IV; MCS required) · Non-cardiac volume overload (ESRD/nephrotic/cirrhosis — BNP less elevated, no S3, echo distinguishes)

Home Meds

• Continue with adjustment: ACEi (lisinopril [Zestril]/enalapril [Vasotec])/ARB (valsartan [Diovan]/losartan [Cozaar])/ARNI (sacubitril/valsartan [Entresto]) — hold if SBP <85 or Cr rise >0.5; BB (carvedilol [Coreg]/metoprolol succinate [Toprol-XL]/bisoprolol [Zebeta]) — do NOT stop abruptly; reduce 50% if HR <50 or SBP <85; MRA (spironolactone [Aldactone]/eplerenone [Inspra]) — hold if K+ >5.0 or Cr rising; SGLT2i (dapagliflozin [Farxiga]/empagliflozin [Jardiance]) — hold if eGFR <20

• Hold: NSAIDs (ibuprofen [Advil]/naproxen [Aleve]/celecoxib [Celebrex] — avoid indefinitely in HF); TZDs (pioglitazone [Actos]/rosiglitazone [Avandia] — significant fluid retention); verapamil (Calan)/diltiazem (Cardizem) in HFrEF (negative inotropy → decompensation; amlodipine [Norvasc]/felodipine [Plendil] acceptable); metformin (Glucophage) if Cr rising or contrast planned

• Chemotherapy: hold trastuzumab (Herceptin)/pertuzumab (Perjeta) if EF drops >10% below baseline or EF <50%; ICI — rule out ICI myocarditis as cause; cardiology clearance before restarting anthracyclines (doxorubicin [Adriamycin])

Plan

• Hemodynamic profile (Stevenson) — determine BEFORE treatment: Warm+Wet (~70%): IV diuresis ± vasodilators; Cold+Wet (~20%): inotropes/MCS before cautious diuresis | treating Cold+Wet as Warm+Wet → aggressive diuresis → worsening AKI + hemodynamic collapse; Cold+Dry (~10%): 250 mL IVF → inotropes if no response; rule out tamponade; Warm+Dry: oral GDMT outpatient

• Monitoring: continuous telemetry; IV ×2; O2 to SpO2 ≥94% (avoid hyperoxia — ↑SVR); NIPPV for APE: BiPAP IPAP 10–14/EPAP 5–8 cm H2O or CPAP 5–10 cm H2O (3CPAP trial: CPAP ↓intubation 23%); HOB 30–45°; Foley; strict I&Os; daily wt same scale same time

• IV diuresis: furosemide (Lasix) 1–2.5× oral daily dose IV (DOSE trial 2011: high-dose [2.5×] ↑decongestion vs low-dose; bolus = infusion equivalent); reassess UO at 2h — if <100–150 mL/2h: double dose; goal UO 0.5–1 mL/kg/hr; net −1 to −2 L/day; bumetanide (Bumex) 1–4 mg IV if poor furosemide bioavailability; torsemide (Demadex) 10–100 mg IV/PO (oral bioavailability 80% vs furosemide 40%; TRANSFORM-HF 2023: no mortality difference vs furosemide)

• Diuretic resistance: spot UNa+ <50 mEq/L at 2h → escalate; metolazone (Zaroxolyn) 2.5–10 mg PO 30–60 min before IV loop (profound K+/Mg2+/Na+ losses — replace daily); chlorothiazide (Diuril) 250–500 mg IV q12h (faster onset than metolazone); acetazolamide (Diamox) 500 mg IV/PO daily (ADVOR 2022: ↑decongestion at Day 3 — 42.2% vs 30.5%; use in metabolic alkalosis + diuretic resistance); ultrafiltration only if truly refractory (CARRESS-HF: no superiority over diuresis)

• IV vasodilators (SBP >100, warm+wet refractory or HTN-driven): nitroglycerin (NTG/Nitro-Bid) 5–10 mcg/min → titrate q5 min (max 200 mcg/min; tolerance at 24–48h); nitroprusside (Nipride) 0.1–0.2 mcg/kg/min → titrate (max 10 mcg/kg/min; require BB for reflex tachycardia; cyanide risk >72h; arterial line required)

• Inotropes (cold+wet or cold+dry — cardiogenic shock, bridge to recovery/transplant/MCS): dobutamine (Dobutrex) 2–20 mcg/kg/min IV (↑CO; tachycardia + arrhythmia risk; tachyphylaxis at 72h); milrinone (Primacor) 0.1–0.75 mcg/kg/min IV (PDE3 inhibitor; preferred in BB-treated — bypasses beta-receptor; OPTIME-CHF: no mortality benefit vs placebo; ↓50% if CrCl <30); norepinephrine (Levophed) 0.01–0.5 mcg/kg/min (preferred pressor in cardiogenic shock — SOAP II: ↓arrhythmia vs dopamine)

• GDMT — initiate BEFORE discharge (STRONG-HF 2022: ↓180-day rehospitalization 34% — stopped early for benefit):

  • ARNI: sacubitril/valsartan (Entresto) 24/26 mg PO BID → 97/103 mg PO BID (PARADIGM-HF 2014: ↓CV death/HF hosp 20%, NNT 21 vs enalapril [Vasotec]; Class I; SBP >100, K+ <5.0, eGFR >30; 36h washout from ACEi; if not tolerated: lisinopril [Zestril/Prinivil] 2.5→40 mg PO daily; A-HeFT: hydralazine [Apresoline] 25–75 mg PO TID + isosorbide dinitrate [Isordil] 20–40 mg PO TID — Class I in self-identified Black patients)

  • BB once euvolemic: carvedilol (Coreg) 3.125→25 mg PO BID (US Carvedilol trial); metoprolol succinate (Toprol-XL) 12.5→200 mg PO daily (MERIT-HF: ↓mortality 34%); bisoprolol (Zebeta) 1.25→10 mg PO daily (CIBIS-II); if decompensated on BB → halve dose, never stop

  • MRA: spironolactone (Aldactone) 25→50 mg PO daily (RALES 1999: ↓all-cause mortality 30% in EF <35% + NYHA III–IV); eplerenone (Inspra) 25→50 mg PO daily (EMPHASIS-HF 2011: ↓CV death/HF hosp 37%); hold if K+ >5.0 or Cr >2.5M/>2.0F; check K+ at 1 week

  • SGLT2i: dapagliflozin (Farxiga) 10 mg PO daily (DAPA-HF 2019: ↓CV death/worsening HF 26%, NNT 21; benefit regardless of DM) or empagliflozin (Jardiance) 10 mg PO daily (EMPEROR-Reduced 2020: ↓CV death/HF hosp 25%); hold if eGFR <20

  • Ivabradine (Corlanor) 5→7.5 mg PO BID: add if SR + HR ≥70 + EF ≤35% + NYHA II–IV on max BB (SHIFT 2010: ↓CV death/HF hosp 18%)

  • Vericiguat (Verquvo) 2.5→10 mg PO daily: persistent sx on optimal GDMT (VICTORIA 2020: ↓CV death/HF hosp in worsening HF; NNT ~24)

• IV iron: ferric carboxymaltose (Injectafer) 750 mg IV Day 1 + Day 15 if ferritin <100 or ferritin 100–299 + TSAT <20% (AFFIRM-AHF 2020: ↓rehospitalization 26%, NNT ~8; HEART-FID 2023: ↓HF events + CV death); oral iron (ferrous sulfate [Feosol]) ineffective in HF (↓gut absorption from hepcidin elevation)

• Anticoagulation: EF <35% + AF → DOAC per CHA2DS2-VASc — apixaban (Eliquis) preferred; LV thrombus → apixaban (Eliquis) 5 mg PO BID or warfarin (Coumadin) INR 2–3 ×3–6 months; EF <35% + sinus rhythm without thrombus → anticoag NOT routinely indicated (WARCEF: warfarin ↑bleeding, no mortality benefit)

• Device therapy: ICD if EF ≤35% after ≥3 months optimal GDMT (MADIT-II: ↓mortality 31%; SCD-HeFT: ↓23%); CRT-D if EF ≤35% + LBBB + QRS ≥150 ms + NYHA II–IV (COMPANION, CARE-HF); LifeVest (ZOLL) at discharge if EF <35%; LVAD/transplant referral if NYHA III–IV + optimal GDMT + recurrent hosp + peak VO2 <14 mL/kg/min

• PT/OT eval and treat — early ambulation once decongested; cardiac rehab referral (HF-ACTION: ↑QoL + trend ↓mortality/hosp); fall risk assessment

• Trend daily: BMP (Na+, K+, Cr — acceptable Cr rise ≤0.3; hold diuretic if >0.5 or UO <0.3 mL/kg/hr); BNP (predischarge <300; failing to fall ≥30% = ↑readmission); CBC; LFTs if congestion; troponin if ACS suspected; daily wts; strict I&Os; fever curve — early = infection; Days 5+ = drug fever/line infection

• Escalation triggers: cardiogenic shock (SBP <90, MAP <65, lactate >2, cool, ↓UO) → CCU + MCS (Impella CP preferred; VA-ECMO biventricular); APE refractory NIPPV → intubation; VT/VF → amiodarone (Pacerone/Nexterone) 150 mg IV → 1 mg/min ×6h + defibrillation; Cr rise >0.5 → reduce diuretic, stop MRA/ACEi temporarily, reassess profile; Na+ <125 → tolvaptan (Samsca) 15 mg PO daily (avoid >30 days — hepatotoxicity); Na+ <120 + neuro sx → hypertonic saline + nephrology; new high-degree AV block → atropine 0.5–1 mg IV → transcutaneous → transvenous pacing; predischarge BNP not falling → delay discharge + HF specialist

• Discharge: 4-pillar GDMT (Entresto/ACEi + carvedilol [Coreg] or metoprolol succinate [Toprol-XL] + spironolactone [Aldactone] or eplerenone [Inspra] + dapagliflozin [Farxiga] or empagliflozin [Jardiance]) at target/tolerated doses; oral furosemide (Lasix) at effective inpatient IV-equivalent dose; ferric carboxymaltose (Injectafer) if ID; written diuretic titration plan (↑furosemide [Lasix] 20–40 mg if wt ↑>2 lbs/day ×2 days; call if ↑>3 lbs/day); daily home weights; fluid restriction if Na+ <130; <2 g Na+/day; HF clinic f/u 7–14 days; ICD/CRT referral if EF ≤35% at 3 months; cardiac rehab; LVAD/transplant evaluation if advanced HF; smoking cessation + ETOH counseling

⚠ Red Flags

• Cardiogenic shock (SBP <90, MAP <65, CI <2.2, lactate >2, cool extremities, AMS, UO <0.5 mL/kg/hr) → CCU; Impella CP preferred (LV unloading + ↑CI); VA-ECMO if biventricular failure; early MCS before end-organ failure (SCAI Stage C–E)

• APE (SpO2 <90%, frothy sputum, severe respiratory distress) → NIPPV + IV nitroglycerin (NTG) + IV furosemide (Lasix) simultaneously; intubate if NIPPV fails, AMS, or respiratory fatigue

• VT/VF → amiodarone (Pacerone) 150 mg IV → 1 mg/min ×6h + defibrillation; identify trigger (electrolytes, ischemia, drug toxicity); EP consult

• Worsening renal function (Cr >0.5 above baseline, UO <0.3 mL/kg/hr despite adequate diuretic) → reassess hemodynamic profile; reduce furosemide (Lasix); stop spironolactone (Aldactone)/ACEi temporarily; RHC if hemodynamics uncertain

• Severe hyponatremia (Na+ <125) → fluid restrict 1–1.5 L/day; tolvaptan (Samsca) 15 mg PO daily (avoid >30 days — hepatotoxicity); Na+ <120 + neurologic sx → hypertonic saline + nephrology

• Predischarge BNP >300 or not falling ≥30% from admission → delay discharge; reassess fluid status (echo + lung US); intensify diuresis; HF specialist consult

• New high-degree AV block → atropine 0.5–1 mg IV; transcutaneous → transvenous pacing if hemodynamically unstable; check K+ + digoxin (Lanoxin) level

Senior IM Resident Pearls

• 4 hemodynamic profiles (Stevenson): Cold+Wet is the most dangerous misclassification — treating Cold+Wet as Warm+Wet → aggressive diuresis alone → worsening AKI + hemodynamic collapse; Cold+Wet requires inotropes/MCS first, then cautious diuresis; profile BEFORE touching diuretic dose

• DOSE trial (2011, NEJM): high-dose furosemide (Lasix; 2.5× oral dose) ↑decongestion vs low-dose; Cr rise ≤0.3 = acceptable azotemia — do NOT stop if still wet; bolus = infusion equivalent; use high-dose strategy for most ADHF

• Spot UNa+ <50 mEq/L at 2h: inadequate natriuresis → double furosemide (Lasix) or add metolazone (Zaroxolyn); UNa+ >50 + ↑Cr = over-diuresed → reduce dose; single most actionable bedside diuresis monitoring tool

• STRONG-HF (2022, Lancet): in-hospital GDMT (Entresto + BB + spironolactone/eplerenone + SGLT2i) + intensive post-discharge f/u → 34% ↓180-day rehospitalization; stopped early for benefit; do NOT defer GDMT to outpatient — start 4-pillar therapy before discharge

• PARADIGM-HF (2014, NEJM): sacubitril/valsartan (Entresto) vs enalapril (Vasotec) → ↓CV death/HF hosp 20%, NNT 21; ↓all-cause mortality 16%; Entresto is Class I first-line; 36h washout from ACEi required (angioedema risk)

• ADVOR (2022, NEJM): acetazolamide (Diamox) + furosemide (Lasix) → ↑decongestion at Day 3 (42.2% vs 30.5%); mechanism: Diamox blocks proximal tubule HCO3 reabsorption → prevents metabolic alkalosis blunting Lasix response; use in diuretic resistance + ↑serum HCO3

• AFFIRM-AHF (2020) + HEART-FID (2023): ferric carboxymaltose (Injectafer) ↓HF rehospitalization 26% (NNT ~8) + ↓HF events + CV death; ID in ~50% of HF; screen ALL ADHF; oral iron (ferrous sulfate [Feosol]) ineffective in HF

• ICD timing — wait ≥3 months GDMT: EF often recovers substantially in NICM (20–30% common with Entresto + BB + spironolactone + SGLT2i); premature ICD = unnecessary device; LifeVest (ZOLL) bridges until 3-month reassessment

• Common mistake: stopping furosemide (Lasix) for Cr rise ≤0.3 mg/dL = acceptable azotemia; persistent congestion more harmful long-term; use spot UNa+ to distinguish: <50 = inadequate dose (escalate); >50 + ↑Cr = over-diuresed (reduce dose)