Cardiovascular

Heart failure: advanced therapies and transplant referral

Clinical Overview and When to Suspect Advanced Heart Failure

— ≥2 HF hospitalizations or ≥1 ED visit for HF in the past 12 months

— Progressive renal dysfunction or hyponatremia limiting up-titration

— Symptomatic hypotension (SBP persistently <90) precluding GDMT

— Increasing loop diuretic requirement or diuretic resistance

— Cardiac cachexia, refractory volume overload, or recurrent ICD shocks for VT/VF

— Inability to walk one block or climb stairs without dyspnea

Board pearl: The single most powerful Step 3 trigger to refer to an advanced HF center is "I-NEED-HELP" features, especially recurrent hospitalizations on maximal GDMT. Don't wait for cardiogenic shock — early referral is the right answer.

Advanced (Stage D) heart failure = persistent NYHA III–IV symptoms despite guideline-directed medical therapy (GDMT), recurrent hospitalizations, escalating diuretic needs, intolerance of neurohormonal blockade, or end-organ hypoperfusion

Affects roughly 1–10% of the HF population but accounts for disproportionate mortality (~50% 1-year mortality once Stage D criteria are met)

Step 3 framing: the test wants you to recognize the inflection point at which standard outpatient HF management is failing and the patient needs referral to a specialized HF/transplant center — NOT to manage transplant immunosuppression yourself

Suspect advanced HF when a patient on optimized ARNI/ACEi-ARB + beta-blocker + MRA + SGLT2i still has:

Etiologies most likely to progress to advanced HF: ischemic cardiomyopathy, dilated/familial cardiomyopathy, cardiac amyloidosis, peripartum cardiomyopathy that fails to recover, chemotherapy-induced (anthracycline, trastuzumab), and chronic valvular disease

I-NEED-HELP mnemonic flags advanced HF: IV inotropes, NYHA III–IV/elevated NPs, End-organ dysfunction, EF ≤35%, Defibrillator shocks, Hospitalizations >1, Edema/escalating diuretics, Low BP/high HR, Prognostic medication intolerance

Presentation Patterns and Key History

— "Wet and warm" — congestion without hypoperfusion; most common; orthopnea, PND, leg edema, weight gain

— "Wet and cold" — congestion + hypoperfusion; narrow pulse pressure, cool extremities, altered mentation, rising creatinine, this is the cardiogenic shock spectrum

— "Dry and cold" — euvolemic but low output; fatigue, weight loss, cachexia, exercise intolerance; often misdiagnosed as deconditioning

— Hospitalization frequency and trend ("third admission this year")

— Diuretic dose creep (furosemide 40 → 80 → 160 mg PO BID, addition of metolazone)

— Medication intolerance: stopped lisinopril for hypotension, can't tolerate carvedilol due to dizziness, MRA stopped for hyperkalemia

— Functional decline: was walking 4 blocks → now SOB at rest

— ICD shocks, recurrent VT

— Weight loss, anorexia, early satiety (gut edema, cardiac cachexia)

— Sleep position (number of pillows), bendopnea (dyspnea when bending forward → strong sign of elevated filling pressures)

— Uncontrolled AF with RVR, untreated severe valvular disease, ongoing ischemia, thyroid disease, NSAID use, alcohol/methamphetamine, untreated sleep apnea, nonadherence

Step 3 management: Before labeling a patient "advanced HF," document a thorough reversibility check — ischemic workup, rate/rhythm control, valve assessment, substance use, adherence, sleep apnea. Missing a reversible cause is a frequent distractor right answer.

Three clinical phenotypes dominate boards:

Key historical elements the stem will plant:

Don't miss reversible contributors that mimic Stage D:

Family history: dilated cardiomyopathy, sudden cardiac death <50, neuromuscular disease → think genetic cardiomyopathy (lamin A/C, titin, desmin)

Social: alcohol >3 drinks/day, cocaine/methamphetamine use, financial barriers to medications, transportation issues for clinic visits — these affect transplant candidacy

Physical Exam Findings and Hemodynamic Assessment

— Warm & dry (I): compensated

— Warm & wet (II): pure congestion → diurese

— Cold & dry (III): low output, euvolemic → cautious fluid challenge vs inotrope

— Cold & wet (IV): congestion + hypoperfusion → inotrope ± diuresis, consider MCS

— JVP >8 cm, hepatojugular reflux, S3 gallop, rales (late finding — chronic HF often has clear lungs due to lymphatic adaptation), peripheral edema, ascites, hepatomegaly, bendopnea

— Narrow pulse pressure (<25% of SBP), cool/mottled extremities, proportional pulse pressure <25% correlates with cardiac index <2.2

— Altered mentation, oliguria, rising creatinine/BUN, lactic acidosis, hyponatremia

— Carotid bruits, AAA → atherosclerotic/ischemic

— Macroglossia, periorbital purpura, carpal tunnel, bilateral → amyloidosis

— Loud P2, RV heave → pulmonary hypertension component

— Muscle wasting, temporal hollowing → cardiac cachexia (poor prognosis, transplant urgency)

— RA <8, PCWP <18, CI >2.2, SVR 800–1200

— PVR is the gatekeeper for transplant: fixed PVR >3–5 Wood units or transpulmonary gradient >15 → contraindication unless reversible with vasodilator challenge

Key distinction: A patient with clear lungs but JVP of 14 and 3+ edema is still "wet" — chronic HF lungs adapt. Don't be fooled into withholding diuresis because crackles are absent; trust JVP and weight trend.

Bedside profiling drives therapy — Step 3 expects you to assign a Forrester/Stevenson profile:

Signs of congestion (elevated filling pressures):

Signs of hypoperfusion (low cardiac output):

Other exam clues to etiology:

Hemodynamic targets when right heart catheterization is performed (often required for transplant/LVAD workup):

Diagnostic Workup — Initial Labs, Imaging, ECG, Biomarkers

— BMP (Na, K, Cr, BUN) — hyponatremia <130 and BUN/Cr >20 mark advanced disease and worse prognosis

— LFTs — congestive hepatopathy (↑AST/ALT, ↑bilirubin) vs shock liver (AST/ALT in thousands)

— CBC — anemia worsens HF; iron studies (ferritin, TSAT) — iron deficiency in 50% of HFrEF, treat even without anemia

— TSH, HbA1c, lipid panel

— NT-proBNP or BNP — trend matters more than absolute number; values rise with age, AF, renal dysfunction; fall with obesity and ARNI (sacubitril blocks neprilysin → BNP rises but NT-proBNP falls, so use NT-proBNP on ARNI)

— High-sensitivity troponin — chronically elevated in advanced HF, marks myocyte injury

— Lactate if hypoperfusion suspected

— QRS ≥150 ms with LBBB morphology → CRT candidate (Class I if EF ≤35%, NYHA II–IV on GDMT, sinus rhythm)

— Low voltage + pseudoinfarct pattern → amyloidosis

— Ventricular ectopy/NSVT → ICD discussion

— LVEF, chamber sizes, wall motion, valvular function, RV function (TAPSE <14 mm = poor RV → bad for LVAD)

— Estimated PASP, IVC diameter/collapsibility

— Strain imaging — apical sparing on longitudinal strain → amyloid signature

— Diastolic parameters for HFpEF

Board pearl: A patient on sacubitril/valsartan with a "rising" BNP is a common trap — use NT-proBNP for monitoring on ARNI because neprilysin inhibition prevents BNP degradation but does not affect NT-proBNP clearance.

Labs every advanced HF patient needs:

ECG:

CXR: cardiomegaly, pulmonary venous congestion, Kerley B lines, pleural effusions (right > left classically)

TTE is the cornerstone:

Diagnostic Workup — Advanced or Confirmatory Studies

— Confirms hemodynamic profile, measures PVR, transpulmonary gradient, cardiac index

— Vasodilator challenge (nitroprusside, inhaled NO, milrinone) if PVR elevated — reversibility determines transplant eligibility

— Serial RHCs guide inotrope titration and LVAD readiness

— Peak VO₂ ≤14 mL/kg/min (or ≤12 if on beta-blocker) → transplant indication

— VE/VCO₂ slope >35 → poor prognosis

— Achieved when RER >1.05 (confirms maximal effort)

— Late gadolinium enhancement patterns: subendocardial (ischemic), mid-wall (DCM), diffuse (amyloid), epicardial (myocarditis/sarcoid)

— T1 mapping/ECV for amyloid and fibrosis quantification

— Seattle Heart Failure Model, MAGGIC, HFSS (Heart Failure Survival Score)

— INTERMACS profile (1–7) for LVAD/transplant urgency — INTERMACS 1 = crashing on inotropes (highest urgency)

Step 3 management: Order CPET + RHC + coronary angiography as the workup triad when an advanced HF patient is being evaluated for transplant/LVAD — these three studies form the "transplant evaluation core" on exam stems.

Right heart catheterization (RHC) is mandatory before advanced therapies:

Cardiopulmonary exercise testing (CPET) — the single most important objective transplant criterion:

Cardiac MRI — etiology workup:

Coronary angiography — required to exclude ischemic etiology in any new cardiomyopathy (revascularization may obviate transplant)

Endomyocardial biopsy — selective; suspected giant cell myocarditis, cardiac sarcoid, amyloid, rejection post-transplant

Genetic testing — familial DCM, HCM, ARVC, amyloid (TTR variants — tafamidis changes therapy)

Bone scintigraphy (Tc-99m PYP) — diagnoses ATTR cardiac amyloid noninvasively (grade 2–3 uptake + negative serum/urine immunofixation + free light chains)

Risk scores for prognosis/transplant timing:

Risk Stratification and Decision Logic for Advanced Therapies

— Optimize GDMT if not truly maximized (most common right answer — patients are often under-titrated)

— Cardiac transplantation — definitive therapy, best long-term survival (~13-year median)

— Durable LVAD (left ventricular assist device) — bridge to transplant (BTT), bridge to candidacy (BTC), or destination therapy (DT) in non-transplant candidates

— Palliative care/hospice — when therapies are inappropriate or refused

— 1: Cardiogenic shock on inotropes ("crash and burn") — needs MCS within hours

— 2: Declining on inotropes — MCS in days

— 3: Stable on inotropes — LVAD/transplant in weeks

— 4: Resting symptoms off inotropes

— 5: Exertion intolerant

— 6: Exertion limited

— 7: Advanced NYHA III

— Peak VO₂ ≤14 (or ≤12 on BB), refractory NYHA IV, recurrent VT despite ICD, intractable angina without revascularization options, refractory cardiogenic shock

— Fixed pulmonary hypertension (PVR >5 WU unresponsive to vasodilator)

— Active malignancy (most cancers require 5-year disease-free interval)

— Active infection (untreated HIV no longer absolute — well-controlled HIV is OK at experienced centers)

— Severe irreversible end-organ disease (unless multi-organ transplant)

— Active substance use (tobacco, alcohol, illicit drugs — typically 6 months sobriety required)

— Inability to comply with immunosuppression/follow-up

Board pearl: The most common Step 3 distractor is "refer for transplant evaluation" vs "optimize GDMT first." If the patient is not yet on ARNI + BB + MRA + SGLT2i at target doses, optimize first unless they're in INTERMACS 1–2.

Once Stage D is confirmed and reversible causes excluded, the decision tree branches into four pathways:

INTERMACS profile drives urgency:

Transplant indications (REMATCH/ISHLT):

Absolute transplant contraindications:

Relative contraindications: age >70 (center-dependent), BMI >35, DM with end-organ damage, recent PE, severe PVD

Pharmacotherapy — Four Pillars of GDMT Before Advanced Therapies

— 1. ARNI (sacubitril/valsartan) — preferred over ACEi/ARB; PARADIGM-HF showed 20% mortality reduction; must washout ACEi 36 hours before starting (angioedema risk); start 24/26 mg BID, target 97/103 BID; hold if SBP <100

— 2. Beta-blocker — only carvedilol, metoprolol succinate, bisoprolol have HF mortality data; do NOT start in decompensated patient; titrate every 2 weeks

— 3. MRA (spironolactone or eplerenone) — start if K <5.0 and eGFR >30; monitor K and Cr at 1 week, 1 month; eplerenone preferred if gynecomastia

— 4. SGLT2 inhibitor (dapagliflozin or empagliflozin) — benefit regardless of diabetes status; DAPA-HF and EMPEROR-Reduced; reduces HF hospitalization and CV death; hold for euglycemic DKA risk perioperatively

— Loop diuretic — symptom control only, no mortality benefit; furosemide, torsemide (better bioavailability in gut edema), bumetanide

— Hydralazine + isosorbide dinitrate — add for self-identified Black patients with NYHA III–IV on GDMT (A-HeFT); also for ACEi/ARB intolerance

— Ivabradine — if sinus rhythm, HR ≥70 on max BB, EF ≤35%

— Vericiguat — sGC stimulator, for worsening HF after hospitalization (VICTORIA)

— Digoxin — symptomatic, reduces hospitalizations; narrow therapeutic window (0.5–0.9 ng/mL)

Step 3 management: When transplant is being considered, document maximally tolerated doses of all four pillars (or specific intolerances). A patient on "lisinopril 5 mg, metoprolol tartrate 25 mg BID" is not on GDMT — switch to ARNI and metoprolol succinate before referral discussion.

Modern HFrEF (EF ≤40%) GDMT = four pillars, started simultaneously when possible, titrated over 4–6 weeks:

Adjuncts:

IV iron (ferric carboxymaltose) — if ferritin <100 or 100–300 with TSAT <20%, improves symptoms and reduces hospitalization (AFFIRM-AHF)

Procedures — Devices, MCS, and Transplantation

— IABP — modest support (~0.5 L/min), contraindicated in significant AI

— Impella (CP, 5.0, 5.5) — axial flow, 2.5–5.5 L/min; contraindicated in mechanical AV, severe AS, LV thrombus

— VA-ECMO — full cardiopulmonary support; risk of LV distension → often paired with Impella ("ECPELLA")

— TandemHeart — LA-to-femoral artery

— Continuous-flow centrifugal pump; MOMENTUM 3 showed 2-year survival ~80%

— Indications: BTT, BTC, DT

— Complications: GI bleeding (AVMs from acquired vWF deficiency + non-pulsatile flow), pump thrombosis, driveline infection, stroke, RV failure post-implant

— Requires lifelong warfarin (INR 2–3) + aspirin

— ~3,500 performed annually in US; median wait varies by status (1–6 highest)

— Induction: basiliximab or ATG; maintenance: tacrolimus + mycophenolate + prednisone (steroid weaned)

— Surveillance endomyocardial biopsies first year

— Long-term complications: cardiac allograft vasculopathy (CAV) — leading late cause of death; PTLD; CMV; skin cancers; renal failure from CNIs

CCS pearl: For a patient in cardiogenic shock with INTERMACS 1, order in this sequence: IV inotrope (dobutamine or milrinone) → arterial line + central line → echo → consult advanced HF/CT surgery → tMCS (Impella or VA-ECMO) → transfer to transplant center. Don't sit on a crashing patient awaiting "tomorrow's cath."

ICD (primary prevention): EF ≤35%, NYHA II–III on GDMT ≥3 months, expected survival >1 year; wait ≥40 days post-MI and ≥90 days post-revascularization to reassess EF

CRT-D: EF ≤35%, LBBB with QRS ≥150 ms, sinus rhythm, NYHA II–IV on GDMT (Class I); QRS 120–149 or non-LBBB has weaker indication

Mitral TEER (MitraClip) — COAPT trial: severe secondary MR despite GDMT, EF 20–50%, LVESD ≤70 mm → mortality and hospitalization benefit

Temporary mechanical circulatory support (tMCS) — for INTERMACS 1–2 or peri-procedural support:

Durable LVAD (HeartMate 3):

Heart transplant:

Special Populations — Elderly and Renal/Hepatic Impairment

— Age alone is not an absolute transplant contraindication, but most centers cap at 70–72; biologic age, frailty, and comorbidity matter more

— Destination therapy LVAD is the typical advanced option for transplant-ineligible elderly

— Frailty assessment (Fried criteria, gait speed) is now standard pre-LVAD/transplant

— Polypharmacy: deprescribe NSAIDs, anticholinergics; watch orthostasis with GDMT up-titration

— Cardiorenal syndrome type 1 (acute HF → AKI) and type 2 (chronic HF → CKD) are the rule, not the exception

— eGFR 30–60: most GDMT continues with monitoring

— eGFR <30: ARNI cautious, SGLT2i — dapagliflozin and empagliflozin can be initiated down to eGFR 20–25, continued until dialysis

— MRA: contraindicated if eGFR <30 or K >5.0

— Diuretic resistance: switch furosemide PO → IV, double dose, add thiazide (metolazone, chlorothiazide IV) 30 min before loop; consider acetazolamide (ADVOR trial — improves decongestion)

— Severe CKD/ESRD limits transplant candidacy → consider combined heart-kidney transplant if CrCl <30–40

— Congestive hepatopathy is reversible with decongestion

— Cardiac cirrhosis (from chronic RV failure) — MELD-XI score guides whether combined heart-liver transplant is needed

— Avoid hepatotoxic meds; dose-adjust amiodarone, statins

Key distinction: Worsening creatinine during aggressive diuresis of a congested patient is expected and acceptable if the patient is decongesting — don't reflexively hold the diuretic. Stop only if Cr rises >0.3 with worsening symptoms or signs of hypoperfusion.

Elderly (>70):

Renal impairment:

Hepatic impairment:

Right heart failure (often from pulmonary HTN, RV infarct, or post-LVAD) — diuresis + pulmonary vasodilators (sildenafil, riociguat for group 1; avoid in left-heart PH group 2)

Special Populations — Pregnancy, Peripartum, and Younger Patients

— New HF with EF <45% in last month of pregnancy or within 5 months postpartum, no other cause

— Higher incidence in Black women, multiparity, preeclampsia, age >30, twin gestation

— 50% recover EF within 6 months; 25% persistent dysfunction; 25% progressive — some require transplant or LVAD

— Treatment during pregnancy: avoid ACEi/ARB/ARNI/MRA/SGLT2i (teratogenic) — use hydralazine + nitrates, beta-blocker (metoprolol/bisoprolol preferred; avoid atenolol), loop diuretic cautiously

— Postpartum: full GDMT; bromocriptine controversial, sometimes used at specialized centers

— Subsequent pregnancy risk: if EF has not normalized, pregnancy is contraindicated (high mortality)

— mWHO class IV (EF <30%, NYHA III–IV) → pregnancy contraindicated, counsel before conception

— Pre-pregnancy counseling, contraception management, and genetic counseling for familial DCM are Step 3 favorites

— Higher likelihood of genetic cardiomyopathy → family screening, genetic testing

— Congenital heart disease (ACHD) — Fontan failure, systemic RV failure (transposition) — refer to ACHD-experienced transplant center

— Myocarditis (viral, giant cell, lymphocytic, eosinophilic, checkpoint-inhibitor-induced) — endomyocardial biopsy guides therapy; giant cell needs urgent immunosuppression + transplant evaluation

Board pearl: PPCM patient who recovers EF must be counseled that any subsequent pregnancy carries significant risk of recurrence and mortality, especially if EF did not fully normalize — this is a recurrent Step 3 ethics/counseling stem.

Peripartum cardiomyopathy (PPCM):

Pregnancy in established cardiomyopathy:

Younger patients with advanced HF:

Pediatric advanced HF (rare on Step 3): Berlin Heart EXCOR is the pediatric VAD; pediatric transplant lists prioritize by status

Transplant in pregnancy-capable patients: post-transplant pregnancy possible after ≥1 year stable graft function, on pregnancy-compatible immunosuppression (mycophenolate is teratogenic → switch to azathioprine pre-conception)

Complications and Adverse Outcomes

— Forgot meds (nonadherence), Arrhythmia/Anemia, Ischemia/Infection/Infarct, Lifestyle (Na/fluid), Upregulation (pregnancy, thyroid), Renal failure/Rx (NSAIDs, glitazones), Embolism (PE)

— Atrial fibrillation — rate vs rhythm control; CASTLE-AF supports catheter ablation in HFrEF with AF (mortality benefit)

— VT/VF — ICD, antiarrhythmics (amiodarone for symptom control; dofetilide if QT-stable); ablation for refractory VT

— Electrical storm (≥3 VT episodes/24 hr) — sedation, beta-blockade, amiodarone, urgent EP consult, consider stellate ganglion block

— GI bleeding (acquired vWD + AVMs) — most common; manage with PPI, octreotide, reduce anticoagulation

— Pump thrombosis — rising LDH, hemolysis, power spikes; consider pump exchange

— Driveline infection — most common infection; long-term suppressive antibiotics

— Stroke — hemorrhagic > ischemic on newer devices

— RV failure — major early post-op cause of death

— Acute cellular rejection — most common first 6 months; surveillance biopsies

— Antibody-mediated rejection — DSA-driven, harder to treat

— Cardiac allograft vasculopathy (CAV) — diffuse intimal hyperplasia, "silent" because graft is denervated (no angina) — surveillance with annual coronary angiography or IVUS

— Infections: CMV (prophylaxis with valganciclovir), PJP (TMP-SMX), fungal

— Malignancy: skin cancer, PTLD (EBV-driven lymphoma)

— Renal failure from CNIs — 10–20% need renal replacement at 10 years

Step 3 management: A transplant patient with dyspnea but no chest pain at 5 years out — think CAV (denervated heart doesn't feel ischemia); order coronary angiography, not just stress testing.

Decompensation triggers (FAILURE mnemonic):

Cardiogenic shock: SBP <90 >30 min, CI <2.2, PCWP >15, end-organ hypoperfusion; mortality 30–50%

Arrhythmias:

LVAD-specific complications:

Post-transplant complications:

Cardiac cachexia — independent predictor of mortality; nutritional support, treat depression, screen for malabsorption

When to Escalate Care — ICU, Consult, and Inpatient Triage

— Cardiogenic shock (SBP <90, lactate elevated, end-organ hypoperfusion)

— Respiratory failure requiring NIV/intubation

— Hemodynamically unstable arrhythmias (VT, VF, AF with RVR causing shock)

— Acute MI with HF

— Need for IV inotropes or vasopressors

— Post-cardiac arrest

— Acute decompensated HF with stable hemodynamics needing IV diuresis

— New-onset HF with ongoing diagnostic workup

— Initiation of high-risk medications (ARNI in borderline-pressure patient)

— INTERMACS 1–3 features

— Recurrent HF hospitalizations despite GDMT

— Inability to tolerate GDMT

— Suspected infiltrative cardiomyopathy (amyloid, sarcoid)

— Pre-transplant evaluation

— LVAD complication

— Refractory ventricular arrhythmias

— Patient on escalating inotropes (milrinone, dobutamine) — needs MCS evaluation

— Refractory cardiogenic shock — VA-ECMO/Impella may bridge to definitive therapy

— Step 3 favors early transfer rather than waiting for multi-organ failure

— Should be offered early, not only at end of life

— Symptom management (dyspnea, pain, depression)

— Goals of care, advance directives, ICD deactivation discussions

— IV furosemide at 2.5× home oral dose (DOSE trial — bolus or continuous infusion both acceptable)

— Strict I/O, daily weights, telemetry

— BMP q12h initially, then daily

— Continue beta-blocker unless hypoperfusion

— Hold/avoid NSAIDs, thiazolidinediones

— Na restriction <2 g/day, fluid restriction <2 L/day if hyponatremic

— DVT prophylaxis (enoxaparin if not on anticoagulation)

CCS pearl: In ADHF, continue beta-blocker unless the patient is in shock or on inotropes — abrupt withdrawal worsens outcomes. Dose reduction by 50% is often the right answer, not full discontinuation.

Immediate ICU/CCU admission if:

Step-down/telemetry for:

Consult advanced HF/cardiology when:

Transfer to transplant center:

Palliative care consult:

Initial CCS orders for ADHF "wet and warm":

Key Differentials — Same-Category Cardiac Causes

— Hibernating myocardium → revascularization (CABG, STICH trial showed benefit) may improve EF and avoid transplant

— Viability imaging: PET, dobutamine echo, cardiac MRI (LGE <50% wall thickness = viable)

— Severe AS, MR, AR causing LV dysfunction — TAVR/surgical replacement or repair often reverses HF

— Functional MR in HFrEF — GDMT first, then COAPT-eligible patients get MitraClip

— Chronic AF with RVR, frequent PVCs (>10% burden), incessant SVT

— EF recovers with rate control or ablation — always rule out before transplant listing

— Apical ballooning, postmenopausal women, emotional trigger; supportive care; typically recovers in weeks

— Cardiac amyloidosis — ATTR (wild-type or hereditary) treated with tafamidis; AL amyloid treated with plasma cell-directed chemotherapy + autoSCT; both can be transplant candidates at experienced centers

— Cardiac sarcoidosis — immunosuppression (prednisone ± methotrexate), ICD often indicated even at higher EF due to arrhythmia risk

— Hemochromatosis — phlebotomy/chelation can reverse

— End-stage burnt-out HCM with LV dilation/dysfunction — transplant candidate

— Mavacamten (cardiac myosin inhibitor) for obstructive HCM

Key distinction: Restrictive cardiomyopathy vs constrictive pericarditis — both have elevated filling pressures and clear lungs. Constriction shows respirophasic discordance (RV/LV systolic pressure variation in opposite directions) on cath; restriction shows concordance. Get this right because pericardiectomy is curative.

Before labeling "advanced HFrEF needing transplant," rule out treatable cardiac mimics that can dramatically alter management:

Ischemic cardiomyopathy with viable myocardium:

Valvular cardiomyopathy:

Tachycardia-induced cardiomyopathy:

Stress (Takotsubo) cardiomyopathy:

Infiltrative cardiomyopathies:

Hypertrophic cardiomyopathy:

ARVC, LV noncompaction, peripartum — discussed elsewhere

Constrictive pericarditis — mimics restrictive cardiomyopathy; pericardiectomy is curative; cardiac MRI and invasive hemodynamics (ventricular interdependence, square-root sign) distinguish

Key Differentials — Other-Category Causes

— Severe COPD, ILD, chronic thromboembolic PH (CTEPH — potentially curable with pulmonary endarterectomy), idiopathic PAH

— JVD, edema, but no orthopnea typically; lungs abnormal; PFTs and high-resolution CT chest needed

— Right heart failure phenotype; treat with PAH-specific therapy (endothelin receptor antagonists, PDE5 inhibitors, prostacyclins)

— Lung or heart-lung transplant in severe cases

— Severe anemia, thyrotoxicosis, AV fistula (hemodialysis access, traumatic), Paget disease, beriberi (thiamine deficiency), pregnancy

— Warm extremities, bounding pulses, wide pulse pressure — opposite of low-output

— Treat the underlying cause

— Spider angiomata, caput medusae, low albumin, abnormal LFTs/INR; SAAG >1.1 ascites

— Distinguish from cardiac ascites (also SAAG >1.1, but elevated JVP and BNP)

— Anthracyclines (dose-dependent), trastuzumab (often reversible), immune checkpoint inhibitor myocarditis (urgent steroids), CAR-T cardiotoxicity

— Cardio-oncology referral; consider GDMT initiation early

Board pearl: A dialysis patient with an AV fistula and new HFrEF — consider high-output HF from the fistula; cardiology may recommend banding or ligation of the fistula. Don't reflexively transplant-list before addressing reversible high-output physiology.

Non-cardiac mimics of advanced HF that Step 3 loves to plant:

Pulmonary disease causing right HF (cor pulmonale):

Pulmonary hypertension (Group 1 PAH):

High-output heart failure:

Cirrhosis with ascites and edema:

Nephrotic syndrome: edema with proteinuria >3.5 g/day, hypoalbuminemia, normal JVP

Chronic kidney disease with volume overload: managed with dialysis ultrafiltration, not loop diuretics if anuric

Severe hypothyroidism (myxedema): can cause low-output state, pericardial effusion, bradycardia

Obesity hypoventilation/OSA: mimics HF with edema and dyspnea; PSG, weight loss, CPAP

Deconditioning, anxiety, anemia: common in elderly; CPET helps distinguish cardiac from non-cardiac exercise limitation

Chemotherapy-induced cardiotoxicity:

Secondary Prevention, Discharge Medications, and Long-Term Plan

— All four GDMT pillars initiated before discharge when tolerated (in-hospital initiation improves uptake — STRONG-HF trial supports rapid up-titration)

— Loop diuretic at appropriate oral dose, with PRN escalation plan ("if weight up 3 lb in 2 days, take extra 40 mg furosemide and call clinic")

— Anticoagulation review (AF, LV thrombus, LVAD)

— Statin if indicated (ischemic etiology, ASCVD)

— Iron repletion if deficient

— Influenza, pneumococcal, COVID, RSV vaccines updated

— Tobacco/alcohol/substance cessation counseling

— Cardiac rehab referral (Class I, NYHA II–III)

— NSAIDs (worsen renal function, blunt diuretics, retain Na)

— Thiazolidinediones (pioglitazone — fluid retention)

— Most CCBs in HFrEF (verapamil, diltiazem are negative inotropes); amlodipine and felodipine are safer for BP control

— Class IC antiarrhythmics (flecainide, propafenone) in structural heart disease

— CardioMEMS implantable PA pressure sensor — reduces hospitalizations in NYHA III with prior admission (CHAMPION trial)

— Home BP cuffs, scales, pulse oximetry

— Tacrolimus + MMF + low-dose steroid (often steroid-free after year 1)

— TMP-SMX for PJP prophylaxis (6–12 months)

— Valganciclovir for CMV prophylaxis (D+/R−, 6 months)

— Statin (reduces CAV) — Class I regardless of LDL

— Annual coronary angiography or IVUS for CAV surveillance

— Skin cancer screening annually

Step 3 management: The post-HF-hospitalization follow-up visit should occur within 7–14 days, ideally with a "transitional care" RN call within 48–72 hours. This is a high-yield quality-metric/value-based-care fact.

Discharge bundle after HF hospitalization (reduces 30-day readmission):

Avoid:

Sodium restriction: <2–3 g/day; fluid restriction <2 L/day mainly for hyponatremia

Daily weights, BP, HR log — patient-empowered self-management

Telehealth/remote monitoring:

Transplant patients on lifelong:

Follow-Up, Monitoring, and Rehab/Counseling

— Post-discharge: clinic within 7–14 days, RN phone check within 48–72 hours

— Stable Stage C: every 3–6 months

— Stage D on inotropes at home: weekly to monthly, depending on stability

— LVAD patients: weekly initially, then monthly at VAD center; INR weekly

— Transplant patients: weekly first 1–3 months, then tapered; lifelong follow-up

— BMP within 1–2 weeks of any GDMT change (K, Cr)

— NT-proBNP trend at major clinical changes (not routinely q-visit)

— Iron studies annually

— HbA1c, lipid panel annually

— Tacrolimus trough at each transplant visit

— TTE every 6–12 months in Stage C/D, or with clinical change

— Repeat EF after 3–6 months of GDMT before ICD/CRT decisions (recovery may obviate device)

— Class I for stable HFrEF, NYHA II–III

— Improves VO₂ max, QOL, reduces hospitalizations

— 36 sessions covered by Medicare

— Medication adherence (pillbox, pharmacist MTM, 90-day refills)

— Daily weights — "call if up 2 lb overnight or 5 lb in a week"

— Sodium and fluid education

— Activity: regular aerobic exercise, avoid isometric heavy lifting in LVAD

— Sexual activity: safe if can climb 2 flights without symptoms; avoid PDE5i with nitrates

— Driving: ICD shock → 6 months no driving (commercial license usually permanent loss); LVAD patients have variable state laws

— Travel: pack extra meds, carry device card, identify nearest VAD/transplant center

— Mental health: screen for depression (PHQ-9), strongly associated with worse outcomes

Board pearl: Depression in HF is grossly underdiagnosed and is an independent mortality predictor. Step 3 stems will include a fatigued, withdrawn HF patient — the right answer is often screen with PHQ-9 and initiate SSRI (sertraline preferred; avoid TCAs and citalopram >20 mg due to QT).

Outpatient cadence:

Labs:

Imaging:

Cardiac rehab:

Counseling pillars:

Ethical, Legal, and Patient Safety Considerations

— Listing decisions involve multidisciplinary committees (cardiology, surgery, social work, psychiatry, ethics)

— Psychosocial criteria (adherence history, support system, financial resources, substance use) are valid considerations but must not be used in discriminatory ways

— Race, insurance status, geographic location have documented disparities in transplant access — Step 3 may test recognition of these inequities and referral to social work and patient advocacy

— Undocumented immigrants face structural barriers; some states (CA, NY, IL) cover transplant for them, others do not

— LVAD/transplant consent must cover risks (death, stroke, infection, bleeding), alternatives (continued medical management, hospice), and realistic expectations

— Shared decision-making is mandatory — patients should understand that LVAD is a commitment, not a cure

— Deactivating an ICD is ethically and legally permissible at patient request — it is not physician-assisted suicide

— Failure to discuss deactivation in dying patients leads to distressing shocks at end of life — a major patient safety failure

— Magnet placement temporarily inhibits shocks; programmer required for permanent deactivation

— Should be revisited at each major clinical inflection (new hospitalization, EF decline, candidacy change)

— Document who is the surrogate decision-maker

— Palliative care should be offered alongside disease-directed therapy, not only when "nothing more can be done"

— Medication reconciliation at every transition (admission, discharge, clinic) — common source of errors (e.g., duplicate beta-blockers, inadvertent NSAID re-start)

— Discharge summary must reach PCP within 48 hours

— Pending labs and follow-up appointments explicitly communicated

Step 3 management: A terminal HF patient with an ICD and a DNR who is actively dying — deactivate the ICD (per patient/surrogate wishes) to prevent inappropriate shocks. This is consistent with DNR goals and is not euthanasia.

Transplant candidacy and equity:

Informed consent for advanced therapies:

ICD deactivation at end of life:

Advance directives and goals of care:

Transition-of-care safety:

Driving and occupational restrictions — explicit counseling and documentation after ICD shocks or syncope

Living-donor and deceased-donor allocation ethics — UNOS uses a 6-tier status system; manipulation of listing status is professional misconduct

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: When a stem features a HF patient who has been hospitalized within 6 months and is NYHA III despite GDMT, the answer is often add vericiguat (VICTORIA population) — a frequent newer-drug Step 3 distractor.

Peak VO₂ ≤14 mL/kg/min (≤12 on beta-blocker) → transplant criterion

PVR >5 Wood units unresponsive to vasodilator → transplant contraindication

INTERMACS 1 = crashing on inotropes → urgent MCS

Sacubitril/valsartan washout from ACEi = 36 hours

NT-proBNP preferred over BNP on ARNI

SGLT2i continues down to eGFR ~20; stop at dialysis

MRA contraindicated if K >5.0 or eGFR <30

CRT-D Class I: EF ≤35%, LBBB, QRS ≥150 ms, NYHA II–IV, sinus rhythm

ICD wait period: 40 days post-MI, 90 days post-revascularization, 3 months of GDMT for non-ischemic

Tafamidis for ATTR cardiac amyloidosis

Mavacamten for obstructive HCM

Vericiguat after recent HF hospitalization (VICTORIA)

Ivabradine if sinus rhythm, HR ≥70 on max BB

CardioMEMS for NYHA III with prior HF hospitalization

COAPT mitral TEER criteria: EF 20–50%, LVESD ≤70 mm, severe secondary MR on GDMT

HeartMate 3 = current durable LVAD; warfarin + ASA

LVAD GI bleed = AVMs + acquired vWD from non-pulsatile flow

Cardiac allograft vasculopathy = leading late cause of death post-transplant; denervated heart → no angina, presents as HF or arrhythmia

Post-transplant immunosuppression: tacrolimus + MMF + prednisone

PTLD = EBV-driven lymphoma post-transplant; treat by reducing immunosuppression + rituximab

Apical sparing on strain = amyloid signature

Low voltage + thick walls on echo = amyloid (mismatch is the clue)

Tc-99m PYP scan grade 2–3 + negative immunofixation = ATTR amyloid (no biopsy needed)

STRONG-HF: rapid in-hospital GDMT initiation reduces 180-day death/HF readmission

DAPA-HF/EMPEROR: SGLT2i benefit regardless of diabetes

PARADIGM-HF: ARNI > enalapril

DAPA / EMPA-Kidney: SGLT2i also benefits CKD

CASTLE-AF: ablate AF in HFrEF for mortality benefit

Board Question Stem Patterns

Step 3 management: The single highest-yield discriminator across these stems: "Is GDMT truly maximized?" If not, the answer is to optimize GDMT before any advanced therapy referral or device.

Pattern 1 — "When to refer": 58-year-old man with EF 20%, NYHA III, two hospitalizations this year on ARNI/carvedilol/spironolactone/dapagliflozin at target doses. Best next step? → Refer to advanced HF/transplant center

Pattern 2 — "Optimize first": 62-year-old woman with EF 25%, NYHA III, on lisinopril 5 mg, metoprolol tartrate 25 mg BID. Asks about transplant. → Switch to sacubitril/valsartan + metoprolol succinate, add MRA and SGLT2i, then reassess

Pattern 3 — "Cardiogenic shock triage": Patient on outpatient milrinone now hypotensive, lactate rising. → Transfer to advanced HF center for MCS evaluation (Impella/VA-ECMO)

Pattern 4 — "Transplant contraindication": Patient with EF 15%, peak VO₂ 11, PVR 7 WU unresponsive to nitroprusside challenge. → Not a transplant candidate (fixed PH); consider DT-LVAD

Pattern 5 — "Reversible cause": Tachycardia-mediated cardiomyopathy from chronic AF with RVR — control rate/rhythm first; do not list for transplant

Pattern 6 — "Amyloid clue": Elderly man with HF, bilateral carpal tunnel history, low ECG voltage, thick septum on echo, apical sparing on strain → Tc-99m PYP scan + light chains; if ATTR, start tafamidis

Pattern 7 — "Post-discharge bounce-back": ADHF patient sent home without follow-up scheduled. → Schedule clinic visit within 7–14 days, RN call in 48–72 hours

Pattern 8 — "ICD at end of life": Terminal HF patient with DNR who keeps getting ICD shocks. → Deactivate ICD per patient wishes

Pattern 9 — "PPCM counseling": Woman 6 months postpartum with EF still 35%, asks about future pregnancy. → Counsel against another pregnancy due to high recurrence/mortality risk

Pattern 10 — "LVAD complication": LVAD patient with melena, normal pump parameters. → Acquired vWD + GI AVMs; EGD/colonoscopy, hold anticoagulation, octreotide

Pattern 11 — "Post-transplant dyspnea": 5 years post-transplant, new exertional dyspnea, no chest pain. → Coronary angiography for CAV (denervated heart doesn't produce angina)

Pattern 12 — "Worsening Cr during diuresis": Decongesting nicely, Cr up from 1.2 to 1.5, symptomatically improving. → Continue diuresis (acceptable rise)

One-Line Recap

Advanced heart failure is defined by persistent NYHA III–IV symptoms, recurrent hospitalizations, or GDMT intolerance despite optimization of all four pillars (ARNI, beta-blocker, MRA, SGLT2i) — and the Step 3 task is to recognize "I-NEED-HELP" features, exclude reversible causes, and refer early to an advanced HF/transplant center where CPET (peak VO₂ ≤14), RHC (PVR reversibility), and coronary angiography determine whether the patient becomes a transplant candidate, an LVAD recipient (BTT, BTC, or DT), or a palliative-care priority.

Board pearl: When in doubt on a Step 3 advanced HF stem, the correct next step is almost always either (1) optimize GDMT to target doses if not yet done, or (2) refer to an advanced HF center if it already has been — with palliative care woven in throughout the trajectory.

Recognize early: Recurrent admissions, escalating diuretics, GDMT intolerance, hyponatremia, cardiorenal syndrome, low BP, ICD shocks — all are referral triggers, not endpoints

Optimize before escalating: Maximize ARNI + evidence-based beta-blocker + MRA + SGLT2i; add vericiguat post-hospitalization, ivabradine for residual tachycardia, IV iron for deficiency, CRT/ICD per criteria; rule out tachycardia-induced, ischemic, valvular, infiltrative, and substance-related cardiomyopathy

Match therapy to candidacy: Transplant for younger patients with peak VO₂ ≤14 and reversible PVR; durable LVAD as BTT/BTC/DT (HeartMate 3, lifelong warfarin + ASA, watch for GI bleed, pump thrombosis, driveline infection, RV failure); palliative care offered in parallel, not at end-stage only

Manage transitions safely: 7–14 day post-discharge clinic visit, 48–72 hour RN call, medication reconciliation, depression screening, advance care planning including ICD deactivation discussion, cardiac rehab referral, vaccination updates, and equitable access to transplant evaluation regardless of race, insurance, or geography