ADHF HFrEF and HFpEF — corrected Neg format throughout both tiers

Cardiology — Heart Failure

ADHF-HFrEF-Exacerbation

EF <40% · decongest · preserve perfusion · optimize GDMT · Super Compact

HFrEF (EF <40%)

• Sx: DOE→rest · orthopnea · PND · bendopnea · rapid wt gain; S3 · JVD · HJR · bibasilar crackles · pitting edema · displaced PMI; cold profile: cool ext · narrow PP <25 · tachy · AMS · oliguria

• Neg: denies pleuritic CP + tachycardia + hypoxia without JVD (PE) · denies fever + unilateral infiltrate + productive cough (PNA) · denies symmetric edema without SOB or JVD (DVT/venous) · denies anasarca without JVD + no dyspnea (nephrotic/hepatic) · denies no exertional SOB + pericardial knock + Kussmaul sign (constrictive pericarditis)

• SHx: prior HF hosp · known EF · ICD/CRT · PCI/CABG · med+diet non-adherence · ETOH · cocaine · anthracyclines (Adriamycin) · fam hx CM (TTN/LMNA)

• Etiology: ischemic CM ~50%; NICM: idiopathic (TTN) · HTN · ETOH · PPCM · tachy-mediated (AF-RVR) · myocarditis · drug/toxin (Adriamycin/Herceptin) · valvular; triggers: AF/ACS · HTN crisis · non-adherence · NSAIDs/CCB · PE · infection · OSA · new valve lesion

• RF: HTN · CAD · DM · obesity · ETOH · cocaine · anthracyclines · non-adherence · untx AF-RVR · OSA; prior MI · age · male · fam hx CM; CKD · Fe deficiency · amyloid

• Data: BNP/NT-proBNP (>400 likely; <100 r/o; d/c target <300 or ≥30%↓) · trop (ACS/wall stress; elevated=poor prog) · BMP (Na+ prog; K+>5→hold MRA; Cr baseline) · CBC (Hgb trigger; WBC infxn) · LFTs (hepatic congestion; ↑INR=cardiac cirrhosis) · TSH · ferritin+TSAT (ID~50%; Rx if <100 or 100–299+TSAT<20%) · ECG (AF; LBBB+QRS≥150=CRT; low V=amyloid) · CXR (cephalization/Kerley B/cardiomegaly) · echo (EF; E/e'>15; IVC; valve; WMA) · lung US (B-lines>3/zone bilateral=edema) · spot UNa+ 2h post-lasix (<50 mEq/L=inadequate→↑dose) · lactate (>2=shock) · RHC if refractory (PCWP>18; CI<2.2; SvO2<65%)

• DDx: HFpEF (EF≥50% S4 LVH diastolic dysfxn) · PE (RV↑ pleuritic hypoxia CT-PA) · PNA (fever unilat infiltrate — can precipitate) · COPD (wheeze BNP<100 bronchodilator Rx) · Tamponade (Beck triad pulsus>10 RV collapse echo) · Cardiogenic shock (SBP<90 CI<2.2 PCWP>15 lactate>2) · Non-cardiac vol overload (ESRD/nephrotic no S3)

• Home Meds: hold NSAIDs (Advil/Aleve/Celebrex) · TZDs (Actos) · diltiazem (Cardizem)/verapamil (Calan) in HFrEF · metformin (Glucophage); BB→↓50% if HR<50 or SBP<85 — no abrupt stop; hold MRA if K+>5 or Cr↑; hold SGLT2i if eGFR<20; continue ARNI/ACEi (hold if SBP<85 or Cr↑>0.5)

Plan — HFrEF

• Profile first: warm+wet→IV diurese±vasodilators; cold+wet→inotropes/MCS first then cautious diurese | never diurese cold+wet alone — worsens renal perfusion → shock; cold+dry→250 mL IVF→inotropes; warm+dry→oral GDMT

• Support: O2 SpO2≥94%; NIPPV BiPAP IPAP10–14/EPAP5–8 cm H2O if APE (3CPAP: ↓intubation 23%); intubate if fails/AMS; continuous telemetry; Foley; strict I&Os; daily wts same scale

• Diuresis: furosemide (Lasix) 1–2.5× oral dose IV; check UO at 2h; if <100 mL/2h→double dose; goal UO 0.5–1 mL/kg/hr; net −1–2 L/d | spot UNa+<50 at 2h=inadequate→↑dose or add metolazone (Zaroxolyn); Cr↑≤0.3=acceptable azotemia — no stop if still wet

• Diuretic resistance: metolazone (Zaroxolyn) 2.5–10 mg PO 30 min before IV loop; or chlorothiazide (Diuril) 250–500 mg IV q12h; or acetazolamide (Diamox) 500 mg IV/PO daily (ADVOR 2022: ↑decongestion 42% vs 30%); replete K+/Mg2+

• Vasodilators (warm+wet SBP>100): nitroglycerin (NTG/Nitro-Bid) 5–200 mcg/min IV; nitroprusside (Nipride) 0.1–10 mcg/kg/min (w/BB; cyanide risk>72h; art line)

• Inotropes (cold profile only): dobutamine (Dobutrex) 2–20 mcg/kg/min IV; milrinone (Primacor) 0.1–0.75 mcg/kg/min IV (preferred if on BB; ↓50% CrCl<30) | avoid unless truly low CO; norepinephrine (Levophed) 0.01–0.5 mcg/kg/min if cardiogenic shock (SOAP II: preferred over dopamine)

• GDMT (STRONG-HF 2022: ↓rehospitalization 34%): sacubitril/valsartan (Entresto) 24/26→97/103 mg PO BID (PARADIGM-HF: ↓CV death/HF hosp 20%); carvedilol (Coreg) 3.125→25 mg PO BID or metoprolol succinate (Toprol-XL) 12.5→200 mg PO daily (once euvolemic); spironolactone (Aldactone) 25→50 mg PO daily (RALES: ↓mortality 30%) or eplerenone (Inspra) 25→50 mg PO daily (EMPHASIS-HF: ↓CV death 37%); dapagliflozin (Farxiga) 10 mg PO daily (DAPA-HF: ↓26%) or empagliflozin (Jardiance) 10 mg PO daily (EMPEROR-Reduced: ↓25%); ivabradine (Corlanor) 5→7.5 mg PO BID if SR+HR≥70+EF≤35%+NYHA II–IV on max BB (SHIFT: ↓18%)

• IV iron: ferric carboxymaltose (Injectafer) 750 mg IV Day 1+Day 15 if ferritin<100 or 100–299+TSAT<20% (AFFIRM-AHF 2020: ↓rehospitalization 26% NNT~8)

• Anticoag: EF<35%+AF→apixaban (Eliquis) per CHA2DS2-VASc; LV thrombus→apixaban (Eliquis) 5 mg PO BID or warfarin (Coumadin) INR 2–3 ×3–6mo

• Devices: ICD if EF≤35% ≥3mo GDMT; CRT-D if EF≤35%+LBBB+QRS≥150+NYHA II–IV; LifeVest (ZOLL) at d/c if EF<35%; LVAD (HeartMate 3)/transplant if NYHA III–IV+optimal GDMT+peak VO2<14

• PT/OT — early ambulation once decongested; cardiac rehab referral

• Trend daily: BMP (Na+/K+/Cr — hold if Cr↑>0.5 or UO<0.3 mL/kg/hr) · BNP (target <300; failing ≥30%↓=↑readmission) · CBC · wts · I&Os · fever curve

• Escalate: shock (SBP<90 MAP<65 lactate>2 cool ↓UO)→CCU+Impella (Abiomed)/IABP/VA-ECMO · APE refractory NIPPV→intubate · VT/VF→amiodarone (Pacerone) 150 mg IV→1 mg/min×6h+defib · Na+<125→tolvaptan (Samsca) 15 mg PO daily (avoid>30d—hepatotoxicity) · Cr↑>0.5→↓furosemide (Lasix)+stop MRA/ACEi+reassess profile · AV block→atropine 0.5–1 mg IV→pacing · BNP not falling→delay d/c

• Discharge: Entresto+Coreg or Toprol-XL+Aldactone or Inspra+Farxiga or Jardiance at target doses; oral furosemide (Lasix) at effective inpatient dose; Injectafer if ID; diuretic plan (↑Lasix 20–40 mg if wt↑>2 lbs/d×2 days; call if >3 lbs/d); wts daily; <2g Na+; HF clinic 7–14d; ICD/CRT referral 3mo; cardiac rehab

HFpEF (EF ≥50%)

• Sx: dyspnea · orthopnea · PND · rapid wt gain · pitting edema; S4 gallop (stiff LV) · JVD · crackles; classic phenotype: older obese woman + HTN + DM + AF; precipitated by acute HTN surge · AF-RVR · dietary Na+ excess; flash APE if SBP>180

• Neg: denies EF<40% on echo (HFrEF — diltiazem [Cardizem] OK in HFpEF but lethal in HFrEF) · denies exertional SOB with asymmetric septal hypertrophy+SAM on echo (HCM) · denies pericardial knock+Kussmaul sign without dyspnea on exertion (constrictive pericarditis) · denies bilateral carpal tunnel+low ECG voltage+thick walls without family hx HCM (ATTR amyloid — 99mTc-PYP scan needed)

• SHx: HTN duration+home BPs (primary driver) · DM · BMI · AF hx+anticoag · prior HF hosp · med adherence · OSA (CPAP) · bilateral carpal tunnel (ATTR red flag)

• Etiology: hypertensive concentric LVH ~70%; aging myocardial fibrosis; obesity CM; DM stiffness; AF (atrial kick = 25–40% of LV filling); ATTR amyloid (elderly male+carpal tunnel+low ECG voltage — tafamidis [Vyndaqel]); AL amyloid; HCM; severe AS

• RF: HTN (primary) · DM · obesity · AF · OSA · high Na+ intake · NSAIDs · age>65 · female post-menopausal · prior MI w/ preserved EF; ATTR screen: elderly male+carpal tunnel+low ECG voltage+thick echo walls→99mTc-PYP

• Data: BNP/NT-proBNP (often lower than HFrEF; NT-proBNP preferred if BMI>35) · echo (EF≥50%; E/e'>15; LA vol index>34 mL/m2; concentric LVH) · H2FPEF score (Heavy BMI≥30+2; HTN≥2 agents+1; AF+3; Pulm HTN+1; Elder>60+1; Filling E/e'>9+1; ≥6=HFpEF ~90%) · 99mTc-PYP (ATTR: Grade 2–3+negative FLC/SPEP=confirmed) · FLC+SPEP/UPEP (exclude AL before ATTR diagnosis) · sleep study (OSA >50% HFpEF; STOP-Bang≥3→refer)

• DDx: HFrEF (EF<40% dilated LV S3 — ARNI/BB/MRA benefit) · Constrictive pericarditis (Kussmaul pericardial knock RHC equalization CT thickening) · ATTR/AL amyloid (thick walls low ECG voltage biatrial enlargement 99mTc-PYP) · HCM (ASH SAM LVOT obstruction fam hx SCD) · Pulm HTN (RV failure mPAP>25 PCWP<15) · Severe AS (AVA<1.0 preload-sensitive — careful diuresis)

• Home Meds: hold NSAIDs (Advil/Aleve) indefinitely (↑afterload — more dangerous in HFpEF); continue ALL antihypertensives (hold only SBP<90); initiate SGLT2i before discharge; diltiazem (Cardizem)/verapamil (Calan) acceptable for rate control in true HFpEF (EF≥50%)

Plan — HFpEF

• Decongestion: furosemide (Lasix) 1–2.5× oral dose IV; net −0.5–1.5 L/day | Cr↑>0.3→slow diuresis immediately; HFpEF has less preload reserve than HFrEF

• HTN control (~50% admissions): flash APE→NTG (Nitro-Bid) IV 5–200 mcg/min + furosemide (Lasix) IV + NIPPV simultaneously; chronic target SBP<130/80; ACEi/ARB + amlodipine (Norvasc) 5–10 mg PO daily + loop diuretic + SGLT2i

• AF rate control (critical — atrial kick 25–40% LV filling): target HR<80 bpm; metoprolol succinate (Toprol-XL) 50–100 mg PO daily or diltiazem (Cardizem) ER 120–360 mg PO daily; cardioversion if hemodynamically unstable

• SGLT2i: empagliflozin (Jardiance) 10 mg PO daily (EMPEROR-Preserved 2021: ↓CV death/HF hosp 21%) or dapagliflozin (Farxiga) 10 mg PO daily (DELIVER 2022: ↓worsening HF 18%); Class IIa ACC/AHA 2022

• Spironolactone (Aldactone) 25 mg PO daily — Class IIb (TOPCAT Americas: ↓HF hosp); if K+<4.5+eGFR>30

• Semaglutide (Wegovy) 2.4 mg SQ weekly (titrate from 0.25 mg) if BMI≥30 (STEP-HFpEF 2023: ↑KCCQ +7.8 pts ↓wt 13.3%); Class IIa AHA 2024

• Tafamidis (Vyndaqel/Vyndamax) 80 mg PO daily if confirmed ATTR-CM (ATTR-ACT 2018: ↓mortality 30% NNT 7); screen Black HFpEF patients with thick walls+low ECG voltage→99mTc-PYP

• PT/OT — cardiac rehab; supervised aerobic training ↑peak VO2; fall risk

• Trend daily: BMP (K+/Cr — over-diuresis risk) · BNP · BP (target<130/80) · wts · I&Os · glucose

• Escalate: flash APE (SBP>200+SpO2<90%)→NTG IV+Lasix IV+NIPPV simultaneously · new AF+RVR+instability→cardioversion · ATTR identified→tafamidis (Vyndaqel)+cardiology+genetics · severe AS→TAVR/SAVR · Cr↑>0.3→slow diuresis

• Discharge: Jardiance or Farxiga + furosemide (Lasix) + ACEi/ARB + amlodipine (Norvasc) ± spironolactone (Aldactone); Wegovy if BMI≥30; Vyndaqel if ATTR confirmed; AF anticoag; diuretic plan; wts daily; <2g Na+; sleep study if OSA undiagnosed; HF clinic 7–14d; cardiac rehab

ADHF — HFrEF & HFpEF Exacerbation

EF <40% (HFrEF) and EF ≥50% (HFpEF) · complete reference · all trials · full doses + brand names · Full Card

HFrEF (EF <40%) — Full Card

Symptoms / Associated Sx

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

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

• 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); displaced PMI (dilated LV)

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

• Cardiogenic pulmonary 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

• Pt denies pleuritic/positional chest pain + sharp quality + worse with inspiration, and denies tachycardia out of proportion to dyspnea without JVD or S3 — argues against PE (PE: pleuritic CP + RV strain on echo + CT-PA confirms; BNP elevated from RV strain, not LV)

• Pt denies fever + productive cough + unilateral lung findings on exam — argues against PNA as primary diagnosis (note: PNA can coexist with and precipitate ADHF; treat both if infiltrate present; procalcitonin helps distinguish)

• Pt denies edema limited to lower extremities without any dyspnea, orthopnea, or JVD — argues against DVT/venous insufficiency or medication-induced edema (CCB [amlodipine/Norvasc], TZDs); check medication list

• Pt denies severe generalized edema (anasarca) without any dyspnea or elevated JVP — argues against nephrotic syndrome (heavy proteinuria, hypoalbuminemia) or hepatic failure (ascites-predominant, portal HTN signs, spider angiomata)

• Pt denies exertional dyspnea with audible pericardial knock + Kussmaul sign (JVP rises with inspiration) without classic HF exam — argues against constrictive pericarditis (RHC: equalization of diastolic pressures; CT: pericardial thickening/calcification)

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 (doxorubicin [Adriamycin]) cumulative dose; family hx CM or SCD (TTN truncating variants most common ~25% of NICM; 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 (doxorubicin [Adriamycin], trastuzumab [Herceptin], cocaine), valvular (MR, AR), Chagas, sarcoid, amyloid

• Decompensation triggers (CHAMPION): Cardiac ischemia/arrhythmia (most common); HTN crisis; Adherence failure; Medication changes (NSAIDs/CCB/negative inotrope); Pulmonary embolism; Infection/sepsis; Obesity/OSA; 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 (doxorubicin [Adriamycin], 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 in ADHF; 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 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 at bedside)

• Echo (EF — HFrEF <40%/HFmrEF 40–49%/HFpEF ≥50%; wall motion — ischemic territory; E/e' >15 = elevated filling; 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 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 mmHg; 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] — 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% or EF <50%; ICI — rule out ICI myocarditis; cardiology clearance before restarting doxorubicin (Adriamycin)

Plan — HFrEF

• 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 — most dangerous profiling error; Cold+Dry (~10%): 250 mL IVF bolus → inotropes if no response; rule out tamponade; Warm+Dry: oral GDMT outpatient

• Monitoring: continuous telemetry; IV access ×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 rate 23%); HOB 30–45°; Foley for accurate UO; 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×] ↑symptom relief + ↑decongestion vs low-dose; Cr rise acceptable; 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%)

• Diuretic resistance: spot UNa+ <50 mEq/L at 2h → escalate; metolazone (Zaroxolyn) 2.5–10 mg PO 30–60 min before IV loop; chlorothiazide (Diuril) 250–500 mg IV q12h; acetazolamide (Diamox) 500 mg IV/PO daily (ADVOR 2022: ↑decongestion at Day 3 — 42.2% vs 30.5%; mechanism: blocks proximal tubule HCO3 reabsorption → prevents metabolic alkalosis blunting Lasix); ultrafiltration only if truly refractory (CARRESS-HF: no superiority over diuresis)

• IV vasodilators (SBP >100, warm+wet refractory): 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; cyanide risk >72h; arterial line required)

• Inotropes (cold+wet or cold+dry): 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; ↓50% if CrCl <30; OPTIME-CHF: no mortality benefit vs placebo); norepinephrine (Levophed) 0.01–0.5 mcg/kg/min (preferred pressor in cardiogenic shock — SOAP II: ↓arrhythmia vs dopamine [Intropin])

• GDMT — initiate BEFORE discharge (STRONG-HF 2022, Lancet: ↓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] 2.5→40 mg PO daily)

  • 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 1999: ↓all-cause mortality 34%); bisoprolol (Zebeta) 1.25→10 mg PO daily (CIBIS-II 1999); 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 NNT ~24)

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

• Anticoagulation: EF <35% + AF → apixaban (Eliquis) per CHA2DS2-VASc; LV thrombus → apixaban (Eliquis) 5 mg PO BID or warfarin (Coumadin) INR 2–3 ×3–6 months; EF <35% + SR 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 (HeartMate 3 [Abbott])/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 mg/dL; hold if Cr rise >0.5 or UO <0.3 mL/kg/hr); BNP/NT-proBNP (predischarge target <300 pg/mL; failing to fall ≥30% = ↑readmission); CBC; LFTs if hepatic congestion; 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 <0.3 mL/kg/hr) → CCU + MCS: Impella CP (Abiomed) preferred; VA-ECMO biventricular · APE refractory NIPPV → intubation · VT/VF → amiodarone (Pacerone) 150 mg IV → 1 mg/min ×6h + defibrillation · Cr rise >0.5 → reduce furosemide (Lasix) + stop MRA/ACEi temporarily + reassess profile · Na+ <125 → tolvaptan (Samsca) 15 mg PO daily (avoid >30 days — hepatotoxicity) · new high-degree AV block → atropine 0.5–1 mg IV → transcutaneous → transvenous pacing · predischarge BNP not falling → delay discharge + HF specialist

• Discharge: sacubitril/valsartan (Entresto) or lisinopril (Zestril) + 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 (↑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

HFpEF (EF ≥50%) — Full Card

Symptoms / Associated Sx

• Dyspnea, orthopnea, PND, rapid weight gain, bilateral pitting edema — clinically indistinguishable from HFrEF without echocardiography

• S4 gallop (active atrial contraction against stiff non-compliant LV; more common in HFpEF than S3); JVD, bibasilar crackles

• Hypertensive HFpEF/"flash APE": severe dyspnea + SBP often >180 mmHg — acute afterload mismatch → ↑LVEDP; extremely responsive to IV vasodilators + diuretics

• AF with RVR as precipitant: loss of atrial kick (25–40% of LV filling in stiff LV) → acute decompensation; target HR <80 bpm critical

• Classic phenotype: older obese woman + HTN + DM + AF

Neg

• Pt denies EF <40% on echocardiography — argues against HFrEF (different GDMT pathway entirely; diltiazem [Cardizem] acceptable in HFpEF but causes hemodynamic collapse in HFrEF; ARNI/BB/MRA with strong mortality benefit in HFrEF, not established in HFpEF)

• Pt denies exertional chest pain or syncope with asymmetric septal hypertrophy and dynamic LVOT murmur that increases with Valsalva and standing — argues against HCM (SAM on echo; mavacamten [Camzyos] or disopyramide [Norpace]; septal reduction therapy if refractory)

• Pt denies audible pericardial knock + Kussmaul sign (JVP rises with inspiration, does not fall) + diastolic equalization of pressures on RHC — argues against constrictive pericarditis (CT pericardial thickening/calcification; pericardiectomy is curative)

• Pt denies bilateral carpal tunnel syndrome + low ECG voltage despite thick echo walls + no family hx of HCM — argues against ATTR amyloid (99mTc-PYP scan: Grade 2–3 + negative serum FLC/SPEP = ATTR confirmed; tafamidis [Vyndaqel] indicated; Val122Ile variant in ~3–4% of Black Americans)

• Pt denies severe exertional dyspnea with calcified aortic valve + systolic murmur radiating to carotids + diminished and delayed carotid upstroke — argues against severe AS as primary etiology (AVA <1.0 cm2; preload-dependent — aggressive diuresis → hemodynamic collapse; TAVR/SAVR evaluation)

SHx

• HTN duration + home BP readings (most important — primary driver); DM management; BMI; AF history + anticoag status; prior HF admissions; medication + dietary adherence; OSA (CPAP use — STOP-Bang ≥3)

• Prior cardiac surgeries (pericardial disease risk); prior chest radiation; family hx HCM or amyloidosis; prior bilateral carpal tunnel surgery (ATTR amyloid red flag); bilateral carpal tunnel + spinal stenosis in elderly male = ATTR until proven otherwise

Main Etiology

• Hypertensive concentric LVH (~70%): chronic pressure overload → impaired LV relaxation + ↑stiffness → diastolic dysfunction → elevated filling pressures

• Aging-related myocardial fibrosis; obesity CM (epicardial fat, pericardial restraint); DM (AGE-related stiffness, microvascular disease)

• Infiltrative: ATTR amyloid (wild-type: elderly male + carpal tunnel + spinal stenosis; hereditary Val122Ile in Black Americans ~3–4%; tafamidis [Vyndaqel/Vyndamax] — ATTR-ACT 2018: ↓mortality 30%, NNT 7); AL amyloid (plasma cell dyscrasia — serum FLC + SPEP + UPEP); HCM; Fabry disease

• Valvular: severe AS (pressure overload → LVH → diastolic dysfunction; preload-sensitive — aggressive diuresis → hemodynamic collapse)

RF

• Modifiable: HTN (primary — most important intervention target), DM, obesity, AF, physical inactivity, high Na+ intake, NSAIDs (ibuprofen [Advil]/naproxen [Aleve]), OSA (untreated), excessive ETOH

• Non-modifiable: older age >65, female sex (post-menopausal → ↑fibrosis), prior MI with preserved EF, genetic CM (HCM, TTR amyloid)

• ATTR screen: elderly male + carpal tunnel or spinal stenosis + low ECG voltage despite thick echo walls + EF ≥50% → 99mTc-PYP scan; if positive → tafamidis (Vyndaqel) 80 mg PO daily

Data

• BNP or NT-proBNP (often lower than HFrEF for same sx severity; NT-proBNP preferred if BMI >35; resting BNP may be normal in exertional HFpEF → exercise echo or RHC needed)

• Echo with Doppler (EF ≥50%; concentric LVH — ↑LV mass index + relative wall thickness; E/e' >15 = elevated filling pressures; LA volume index >34 mL/m2; TR velocity >2.8 m/s = ↑PA pressure; valvular disease severity)

• H2FPEF Score (Heavy BMI ≥30 [+2]; Hypertensive on ≥2 agents [+1]; AF [+3]; Pulmonary HTN on echo [+1]; Elder >60 [+1]; Filling pressure E/e' >9 [+1]; 0–9 total; ≥6 = HFpEF ~90% probability; ≤1 = ~18%; 2–5 = exercise echo or RHC to confirm)

• 99mTc-PYP scan (ATTR amyloid: Grade 2–3 cardiac uptake + absent serum/urine monoclonal protein = ATTR with very high specificity; if positive → genetic testing [TTR gene]; tafamidis [Vyndaqel] 80 mg PO daily — ATTR-ACT 2018: ↓all-cause mortality 30%, NNT 7 over 30 months)

• Serum FLC + SPEP/UPEP (AL amyloid screening — must be negative before attributing cardiac uptake on 99mTc-PYP scan to ATTR)

• Sleep study (OSA in >50% of HFpEF; STOP-Bang ≥3 → formal sleep study; CPAP ↓sympathetic activation + ↓BP + ↓LV remodeling)

• RHC with exercise (exercise PCWP >25 mmHg = exertional HFpEF confirmed — gold standard when resting studies normal; for H2FPEF score 2–5)

DDx — HFpEF

HFrEF (EF <40%, dilated LV, S3 — responds to Entresto/BB/MRA; distinct GDMT pathway) · Constrictive pericarditis (Kussmaul sign, pericardial knock, diastolic equalization on RHC, CT thickening/calcification — pericardiectomy definitive) · ATTR/AL amyloid (thick walls + low voltage ECG + biatrial enlargement; 99mTc-PYP for ATTR; cardiac MRI for AL + sarcoid) · HCM (asymmetric septal hypertrophy, SAM, LVOT obstruction, Valsalva ↑murmur; mavacamten [Camzyos]) · Pulmonary HTN (RV failure signs, mPAP >25 on RHC, PCWP <15; sildenafil [Revatio]/ambrisentan [Letairis]) · Severe AS (AVA <1.0 cm2, mean gradient >40 mmHg; preload-dependent — aggressive diuresis → hemodynamic collapse; TAVR/SAVR)

Home Meds — HFpEF

• Hold NSAIDs indefinitely (ibuprofen [Advil]/naproxen [Aleve]/celecoxib [Celebrex] — ↑Na+/H2O retention, ↑afterload — more dangerous in afterload-sensitive HFpEF than HFrEF)

• Continue ALL antihypertensives (hold only if SBP <90; intensify regimen before discharge — most important medication decision in HFpEF)

• Initiate before discharge: SGLT2i (empagliflozin [Jardiance] 10 mg or dapagliflozin [Farxiga] 10 mg — Class IIa ACC/AHA 2022); GLP-1 agonist if BMI ≥30 (semaglutide [Wegovy] 2.4 mg SQ weekly)

• Diltiazem (Cardizem)/verapamil (Calan): acceptable for AF rate control in HFpEF (EF ≥50%) — unlike HFrEF where these agents cause hemodynamic collapse; metoprolol (Toprol-XL) also acceptable

Plan — HFpEF

• Confirm HFpEF diagnosis: EF ≥50% + symptoms of HF + objective filling pressure elevation (E/e' >15, NT-proBNP >125 pg/mL, or exercise-provoked ↑PCWP); H2FPEF score ≥6 = ~90% probability; exclude constrictive pericarditis (RHC), ATTR amyloid (99mTc-PYP), severe AS (echo), HCM (echo)

• Decongestion: furosemide (Lasix) 1–2.5× oral daily dose IV; net −0.5 to −1.5 L/day (less aggressive — smaller safe preload range in HFpEF) | Cr rise >0.3 mg/dL → slow diuresis immediately; HFpEF patients have less preload reserve than HFrEF — over-diuresis causes AKI + hemodynamic collapse faster

• HTN control (precipitant in ~50%): flash APE (SBP >180 + APE) → nitroglycerin (NTG/Nitro-Bid) 5–200 mcg/min IV + furosemide (Lasix) IV + NIPPV simultaneously; target 20–25% MAP↓ in first hour; chronic target SBP <130/80; preferred agents: ACEi/ARB + amlodipine (Norvasc) 5–10 mg PO daily + loop diuretic + SGLT2i; add spironolactone (Aldactone) 25 mg PO daily if K+ <4.5 + eGFR >30

• AF rate control (critical — loss of atrial kick = 25–40% of LV filling in stiff ventricle): target HR <80 bpm; metoprolol succinate (Toprol-XL) 50–100 mg PO daily or diltiazem (Cardizem) ER 120–360 mg PO daily; cardioversion if hemodynamically unstable; anticoag per CHA2DS2-VASc

• SGLT2i: empagliflozin (Jardiance) 10 mg PO daily (EMPEROR-Preserved 2021: ↓CV death/HF hosp 21%) or dapagliflozin (Farxiga) 10 mg PO daily (DELIVER 2022: ↓worsening HF/CV death 18%); Class IIa ACC/AHA 2022; hold if eGFR <20

• Spironolactone (Aldactone) 25 mg PO daily — Class IIb (TOPCAT 2014 Americas subgroup: ↓HF hosp); use if K+ <4.5 + eGFR >30 + persistent congestion or HTN

• GLP-1 agonist: semaglutide (Wegovy) 2.4 mg SQ weekly (titrate from 0.25 mg over 20 weeks; STEP-HFpEF 2023: ↑KCCQ +7.8 pts, ↓wt 13.3%, ↑6MWD — if BMI ≥30); Class IIa AHA 2024

• Tafamidis (Vyndaqel/Vyndamax) 80 mg PO daily if confirmed ATTR-CM (ATTR-ACT 2018: ↓all-cause mortality 30%, ↓CV hosp 32%, NNT 7; Val122Ile in ~3–4% of Black Americans — screen all Black HFpEF with thick walls + low ECG voltage)

• PT/OT eval and treat — cardiac rehab referral; supervised aerobic training ↑peak VO2 + ↑KCCQ; fall risk assessment (elderly population)

• Trend daily: BMP (K+ — MRA + ACEi monitoring; Cr — over-diuresis risk in HFpEF; Na+); BNP/NT-proBNP; BP (target <130/80); blood glucose; daily weights; strict I&Os; fever curve

• Escalation triggers: flash APE (SBP >200 + SpO2 <90%) → NTG (Nitro-Bid) IV + furosemide (Lasix) IV + NIPPV simultaneously · hemodynamic instability → CCU · new AF + RVR + hemodynamic compromise → cardioversion · Cr rising >0.3 → reduce furosemide (Lasix) · ATTR amyloid confirmed → tafamidis (Vyndaqel) urgently + cardiology + genetic counseling · severe AS as trigger → TAVR/SAVR evaluation

• Discharge: empagliflozin (Jardiance) or dapagliflozin (Farxiga) + furosemide (Lasix) at effective dose + aggressive antihypertensive (ACEi/ARB + amlodipine [Norvasc] ± spironolactone [Aldactone]); semaglutide (Wegovy) if BMI ≥30; tafamidis (Vyndaqel) if ATTR confirmed; AF anticoag; written diuretic titration plan; daily weights; <2 g Na+/day; sleep study if OSA undiagnosed; HF clinic f/u 7–14 days; cardiac rehab

⚠ Red Flags — ADHF (HFrEF + HFpEF)

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

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

• Hypertensive flash APE (HFpEF) — SBP >200 + APE → NTG IV + Lasix IV + NIPPV; most responsive HF phenotype — dramatic improvement expected within 1–2h

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

• Worsening renal function (Cr >0.5 above baseline, UO <0.3 mL/kg/hr) → reassess hemodynamic profile; reduce furosemide (Lasix); stop MRA/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 + neuro sx → hypertonic saline + nephrology

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

• ATTR amyloid identified (HFpEF) → urgent tafamidis (Vyndaqel); genetic counseling; screen first-degree relatives; HF specialist referral before discharge

Senior IM Resident Pearls

• 4 hemodynamic profiles (Stevenson — HFrEF): Cold+Wet is the most dangerous misclassification — treating Cold+Wet as Warm+Wet → aggressive furosemide (Lasix) diuresis → worsening AKI + hemodynamic collapse; Cold+Wet = dobutamine (Dobutrex) or milrinone (Primacor) first, then cautious diuresis; profile BEFORE touching diuretic dose — this decision changes the entire management course

• DOSE trial (2011, NEJM): high-dose furosemide (Lasix; 2.5× oral dose) ↑symptom relief + ↑decongestion vs low-dose (1× dose); Cr rise ≤0.3 = acceptable azotemia — do NOT stop if still wet; bolus = infusion equivalent; use high-dose strategy for most ADHF admissions

• Spot UNa+ <50 mEq/L at 2h post-Lasix: inadequate natriuresis → double furosemide (Lasix) or add metolazone (Zaroxolyn); UNa+ >50 + ↑Cr = over-diuresed → reduce Lasix; these two findings require opposite actions — the UNa+ is the only way to tell them apart at the bedside

• STRONG-HF (2022, Lancet): high-intensity in-hospital GDMT (Entresto + Coreg/Toprol-XL + Aldactone/Inspra + Farxiga/Jardiance) + intensive post-discharge f/u → 34% ↓180-day rehospitalization/death; stopped early for overwhelming benefit; do NOT defer all GDMT to outpatient — initiate all 4 pillars 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 for HFrEF; 36h washout from ACEi required (angioedema when ACEi + neprilysin inhibitor [Entresto] overlap)

• ADVOR (2022, NEJM): acetazolamide (Diamox) + furosemide (Lasix) → ↑decongestion at Day 3 (42.2% vs 30.5%); Diamox blocks proximal tubule HCO3 reabsorption → prevents metabolic alkalosis that blunts Lasix response; use in diuretic resistance + ↑serum HCO3 (CO2 >28–30)

• ATTR-ACT (2018, NEJM): tafamidis (Vyndaqel) vs placebo in ATTR-CM → ↓all-cause mortality 30%, ↓CV hosp 32%, NNT 7; Val122Ile TTR variant in ~3–4% of Black Americans — screen all Black HFpEF patients with thick echo walls + low ECG voltage + bilateral carpal tunnel; 99mTc-PYP scan: Grade 2–3 + negative serum FLC/SPEP = ATTR confirmed; do not miss this diagnosis — tafamidis is transformative

• AFFIRM-AHF (2020) + HEART-FID (2023): ferric carboxymaltose (Injectafer) ↓HF rehospitalization 26% (NNT ~8) + ↓HF events + CV death; ID in ~50% of HF (ferritin <100 or ferritin 100–299 + TSAT <20%); oral iron (ferrous sulfate [Feosol]) ineffective in HF — hepcidin elevation blocks gut absorption; screen ALL ADHF admissions

• Common mistake — HFrEF: stopping furosemide (Lasix) for Cr rise ≤0.3 = acceptable azotemia — persistent congestion is more harmful long-term; use spot UNa+: <50 → escalate Lasix/add Zaroxolyn; >50 + ↑Cr → reduce Lasix. Common mistake — HFpEF: diagnosing HFpEF by exclusion without objective filling pressure evidence; always require E/e' >15 or ↑NT-proBNP or exercise-provoked ↑PCWP; always exclude ATTR (99mTc-PYP) and constrictive pericarditis (RHC) in the right clinical context