Cardiovascular

Heart failure with preserved ejection fraction: diagnosis and management

Clinical Overview and When to Suspect HFpEF

— HFmrEF: LVEF 41–49% (managed increasingly like HFrEF)

— HFpEF accounts for ~50% of all HF cases and is rising with population aging

— Often coupled with chronotropic incompetence, atrial myopathy, pulmonary hypertension, and skeletal muscle dysfunction

— Systemic inflammation from comorbidities (obesity, HTN, DM, CKD) drives microvascular endothelial dysfunction

— Older woman (>65), obese, hypertensive, often with atrial fibrillation, CKD, diabetes, or OSA

— Presents with exertional dyspnea, fatigue, and recurrent flash pulmonary edema after a hypertensive surge or dietary indiscretion

— Unexplained exertional dyspnea in an older patient with multiple cardiometabolic comorbidities

— Recurrent HF hospitalizations despite "normal echo" or "normal EF"

— New afib with rapid decompensation suggests underlying HFpEF unmasked by loss of atrial kick

— Bilateral lower extremity edema disproportionate to venous disease in an obese hypertensive woman

Board pearl: A "normal echo" never rules out HFpEF — EF is preserved by definition. Look instead for LA enlargement, LVH, elevated E/e′, and elevated natriuretic peptides. Step 3 stems that say "EF 60%, still dyspneic, BNP 600" are pointing at HFpEF, not deconditioning.

Step 3 management: Initial outpatient workup of unexplained dyspnea in a high-risk phenotype should include BNP/NT-proBNP, ECG, and TTE before chasing pulmonary causes.

Definition: Heart failure syndrome with LVEF ≥50%, evidence of structural heart disease or elevated filling pressures, and symptoms/signs of HF

Pathophysiology: Impaired LV relaxation and increased chamber stiffness → elevated LV end-diastolic pressure → pulmonary congestion and exercise intolerance

Classic patient profile:

When to suspect on Step 3:

Key triggers of decompensation: uncontrolled HTN, atrial fibrillation with RVR, dietary sodium load, NSAID use, nonadherence to diuretics, anemia, infection, ischemia

Presentation Patterns and Key History

— Exertional dyspnea (most common, often the only symptom early)

— Orthopnea and paroxysmal nocturnal dyspnea

— Fatigue and reduced exercise tolerance out of proportion to age

— Lower extremity edema, abdominal bloating, early satiety (right-sided congestion)

— Palpitations from frequent concurrent atrial fibrillation

— Chronic, slowly progressive functional decline punctuated by acute decompensations

— Classic "flash pulmonary edema" precipitated by hypertensive urgency — patient feels well, then severely dyspneic within hours

— Decompensation after large carbohydrate/sodium meal, missed diuretic dose, or new NSAID/steroid course

— HTN control and adherence — most important modifiable driver

— Atrial fibrillation burden and rate control adequacy

— Sleep history: snoring, witnessed apneas, daytime somnolence (OSA prevalence >50%)

— Diabetes duration, A1c, and current SGLT2i use

— Medication review: NSAIDs, pioglitazone, gabapentinoids, dihydropyridine CCBs (peripheral edema mimic), and steroid bursts

— Dietary sodium intake and fluid habits

— Functional capacity in METs (can you climb 2 flights? carry groceries?) — drives NYHA class

— Class I: symptoms only with extraordinary exertion

— Class II: symptoms with ordinary activity

— Class III: symptoms with less-than-ordinary activity

— Class IV: symptoms at rest

Key distinction: HFpEF dyspnea is typically exertional and positional; pure deconditioning dyspnea is exertional only and resolves with rest within minutes. PND and orthopnea push you toward HF over pulmonary disease or deconditioning.

Board pearl: A patient on amlodipine with "worsening edema" may have drug-induced edema, not HF progression — check JVP, BNP, and weight trend before uptitrating diuretics. Misattribution is a classic Step 3 trap.

Cardinal symptoms:

Tempo of presentation:

Targeted history must capture:

NYHA functional classification guides therapy intensity and prognosis

Physical Exam Findings and Hemodynamic Assessment

— JVP: elevated >8 cm H₂O suggests elevated right-sided filling pressures; correlates with left-sided pressures ~80% of the time in HFpEF

— Hepatojugular reflux: sustained JVP rise >3 cm with 10 sec RUQ pressure

— Peripheral edema: pitting, often bilateral, dependent

— Ascites and hepatomegaly in advanced right-sided congestion

— Pulmonary rales (often absent in chronic compensated HFpEF due to lymphatic adaptation)

— S4 gallop — hallmark of stiff, noncompliant LV (atrial kick into stiff chamber)

— Sustained, non-displaced PMI suggesting concentric LVH

— Loud P2 if pulmonary hypertension has developed

— Irregularly irregular rhythm if afib present

— Murmur of functional MR or TR from atrial dilation

— Hypertension at presentation is the rule, not the exception

— Obesity (BMI often >30); central adiposity especially

— Signs of OSA: crowded oropharynx, large neck circumference

— Cool extremities and narrow pulse pressure suggest low cardiac output (uncommon in HFpEF, ominous when present)

— Warm & wet (most common HFpEF decompensation): congested but adequately perfused → diurese

— Warm & dry: euvolemic at baseline → optimize chronic therapy

— Cold & wet: congested and hypoperfused → consider advanced therapies, ICU

— Cold & dry: rare in HFpEF; consider alternative diagnoses

CCS pearl: In a HFpEF admission, order daily weights, strict I/Os, and standing/supine vitals; trend JVP on every exam. Document a Nohria profile in your note — Step 3 CCS rewards systematic volume reassessment over reflexive diuretic uptitration.

Board pearl: Absence of rales does NOT rule out volume overload in chronic HFpEF — trust elevated JVP and weight trends over auscultation.

Volume status assessment (drives every management decision):

Cardiac exam:

Other findings:

Hemodynamic profiles (Stevenson/Nohria framework — applies to all HF):

Diagnostic Workup — Initial Labs, Imaging, ECG, Biomarkers

— BNP >35 pg/mL or NT-proBNP >125 pg/mL (ambulatory) supports HF

— Acute decompensation thresholds higher: BNP >100, NT-proBNP age-adjusted (>450 if <50 yr, >900 if 50–75, >1800 if >75)

— Lower in obesity (false negatives) — adjust interpretation if BMI >35

— Elevated in AKI/CKD, afib, PE, sepsis (false positives)

— Sacubitril/valsartan raises BNP but lowers NT-proBNP — use NT-proBNP for monitoring on ARNI

— LVH with strain pattern

— Left atrial enlargement (P-mitrale)

— Atrial fibrillation (present in 30–40%)

— Old infarct patterns suggesting ischemic contribution

— Cardiomegaly, cephalization, Kerley B lines, perihilar congestion, pleural effusions (often right > left)

— May appear normal in compensated chronic HFpEF

— BMP (Na, K, Cr, eGFR), CBC, LFTs, TSH, fasting glucose/A1c, lipid panel, iron studies (ferritin, TSAT — iron deficiency present in 50% of HF patients), urinalysis with albumin/Cr ratio

— Troponin if acute presentation to rule out ACS trigger

— LVEF ≥50% by definition

— LV hypertrophy (relative wall thickness >0.42 or LVMI elevated)

— Left atrial enlargement (LAVI >34 mL/m²)

— E/e′ ratio >14 (elevated filling pressures)

— Tricuspid regurgitation velocity >2.8 m/s (pulmonary hypertension)

— Preserved or hyperdynamic systolic function

Step 3 management: When BNP is borderline in a high-pretest-probability patient (obese, multiple comorbidities), don't dismiss HFpEF — proceed to echo and consider exercise testing.

Board pearl: Iron deficiency in HF is defined as ferritin <100 OR ferritin 100–299 with TSAT <20% — IV iron repletion improves symptoms and reduces hospitalizations.

Natriuretic peptides (cornerstone):

ECG findings:

Chest X-ray:

Basic labs at every encounter:

Transthoracic echocardiogram (required for diagnosis):

Diagnostic Workup — Advanced and Confirmatory Studies

— Heavy (BMI >30): 2 points

— Hypertension on ≥2 antihypertensives: 1

— Atrial Fibrillation: 3

— Pulmonary hypertension (PASP >35): 1

— Elder (age >60): 1

— Filling pressure (E/e′ >9): 1

— Score ≥6 high probability; 2–5 indeterminate (proceed to invasive testing); 0–1 low

— Exercise echo with measurement of E/e′ during exertion

— Post-exercise E/e′ >15 or TR velocity >3.4 m/s supports HFpEF

— Useful when resting echo is equivocal and symptoms are exertional

— PCWP >15 mmHg at rest OR >25 mmHg with exercise confirms HFpEF

— Allows simultaneous assessment of pulmonary hypertension (precapillary vs postcapillary)

— Cardiac amyloidosis: SPEP/UPEP with immunofixation, serum free light chains; technetium pyrophosphate (PYP) scan for ATTR; suspect if LVH on echo without HTN history, low voltage on ECG, bilateral carpal tunnel, autonomic dysfunction, age >70 with HF

— Hypertrophic cardiomyopathy: asymmetric septal hypertrophy, family history, SAM of mitral valve

— Constrictive pericarditis: prior pericarditis/radiation/TB; septal bounce, pericardial thickening on CMR

— High-output HF: anemia, thyrotoxicosis, AV fistula, beriberi

Key distinction: Always rule out cardiac amyloid before labeling an older patient as garden-variety HFpEF — ATTR amyloid has disease-modifying therapy (tafamidis) and changes prognosis dramatically. Red flags: low-voltage ECG + LVH on echo, intolerance to standard HF meds, bilateral carpal tunnel history.

Board pearl: Invasive hemodynamic exercise testing is the gold standard for diagnosing HFpEF in patients with unexplained exertional dyspnea and a nondiagnostic noninvasive workup.

H2FPEF score (clinical scoring for HFpEF probability):

HFA-PEFF algorithm (European, similar concept): pretest workup → echo/biomarker scoring → functional testing → final etiology

Diastolic stress test:

Right heart catheterization (gold standard when noninvasive is inconclusive):

Rule out HFpEF mimics — mandatory before final diagnosis:

Cardiac MRI: when amyloid, sarcoid, or infiltrative disease suspected — late gadolinium enhancement patterns are diagnostic

Risk Stratification and First-Line Management Logic

— Reduce HF hospitalizations and cardiovascular mortality

— Relieve congestion and improve functional status

— Treat the comorbidities that drive the syndrome (HTN, AF, OSA, DM, obesity, CAD, CKD)

— Identify and treat specific etiologies (amyloid, HCM, ischemia)

— 1. Decongestion with diuretics (symptom control)

— 2. SGLT2 inhibitor (disease-modifying, Class 1A)

— 3. Aggressive comorbidity management (BP <130/80, rhythm/rate control, weight loss, OSA treatment)

— 4. Consider MRA, ARNI, ARB in selected phenotypes

— First-line agents that also treat HFpEF physiology: ACEi/ARB, ARNI, MRA, thiazide if needed

— Avoid nondihydropyridine CCBs (verapamil, diltiazem) if there's any LV systolic dysfunction; acceptable in pure HFpEF for rate control

— Loss of atrial kick is particularly devastating in stiff LV

— Rhythm control (catheter ablation or antiarrhythmics) increasingly favored over rate control in symptomatic HFpEF patients with AF — improves symptoms and reduces hospitalizations

— Anticoagulation per CHA₂DS₂-VASc (HF itself = 1 point)

— Caloric restriction and structured exercise for BMI >30

— GLP-1 agonists (semaglutide, tirzepatide) now show benefit in obesity-phenotype HFpEF — reduce symptoms and improve exercise capacity

— Bariatric surgery consideration for BMI >35 with HFpEF

Step 3 management: A newly diagnosed HFpEF patient gets: loop diuretic for congestion + SGLT2 inhibitor + BP optimization to <130/80 + AF/OSA workup + cardiac rehab referral + dietary sodium counseling (<2–3 g/day). This bundle is the high-yield Step 3 answer.

Board pearl: Unlike HFrEF, beta-blockers are NOT mandatory in HFpEF unless there's another indication (CAD, AF rate control).

Therapeutic goals in HFpEF:

Four pillars conceptually:

Blood pressure target: <130/80 mmHg per AHA/ACC 2017 and HF guidelines

Atrial fibrillation in HFpEF:

Weight management:

Cardiac rehabilitation is now Class 1 indication for HFpEF (improves QOL and exercise tolerance)

Pharmacotherapy — First-Line Drug Regimen

— Empagliflozin 10 mg daily or dapagliflozin 10 mg daily

— EMPEROR-Preserved and DELIVER trials: reduced CV death and HF hospitalization regardless of diabetes status

— Initiate if eGFR ≥20; continue down to dialysis

— Hold for euglycemic DKA risk (perioperatively 3 days before surgery, acute illness, fasting states)

— Monitor for genital mycotic infections, volume depletion, mild Cr bump in first weeks (expected, not a reason to stop)

— Furosemide 20–40 mg PO daily, titrate to euvolemia; bumetanide and torsemide better bioavailability (torsemide preferred in gut edema)

— Monitor K, Mg, Cr, BUN; replace K to >4.0, Mg to >2.0

— Use lowest effective dose; avoid overdiuresis (prerenal AKI, hypotension)

— Spironolactone 25–50 mg daily — Class 2a in HFpEF, strongest benefit when LVEF 50–60% and elevated BNP (TOPCAT post-hoc)

— Requires eGFR >30 and K <5.0; recheck K and Cr at 1 week, 4 weeks, then quarterly

— Gynecomastia in 10% on spironolactone → switch to eplerenone

— Class 2b in HFpEF; greater benefit in LVEF below the median (closer to 50%) and in women

— Dose: start 24/26 or 49/51 mg BID, titrate to 97/103 BID

— 36-hour washout from ACEi to avoid angioedema

— Nitrates and phosphodiesterase-5 inhibitors as routine therapy (no benefit, may harm)

— NSAIDs absolutely (sodium retention, AKI)

— Pioglitazone (fluid retention)

Step 3 management: Sequence: SGLT2i first, then add MRA if BP/K allow, then loop diuretic titration for congestion. ARNI/ARB layered for BP control and selected phenotypes.

Board pearl: Check potassium within 1 week of starting or uptitrating an MRA or ACEi/ARB/ARNI — hyperkalemia is the #1 reason for discontinuation.

SGLT2 inhibitors — Class 1A across the EF spectrum:

Loop diuretics (symptom control, no mortality benefit):

Mineralocorticoid receptor antagonists:

ARNI (sacubitril/valsartan):

ARB (candesartan, valsartan): modest reduction in HF hospitalization, reasonable alternative

Avoid in HFpEF:

Expanded Pharmacology and Comorbidity-Directed Therapy

— Rate control: beta-blocker (metoprolol succinate, bisoprolol, carvedilol) or digoxin add-on; avoid diltiazem/verapamil if any LV dysfunction

— Rhythm control: amiodarone, dofetilide, or catheter ablation (CABANA, CASTLE-AF subgroups support ablation in HF with AF)

— Anticoagulation: DOAC preferred (apixaban, rivaroxaban) over warfarin unless mechanical valve or moderate-severe mitral stenosis

— ACEi/ARB/ARNI, MRA, thiazide diuretic, dihydropyridine CCB (amlodipine) if needed

— Avoid clonidine, hydralazine monotherapy, alpha-blockers as first-line

— SGLT2i and GLP-1 RA are preferred — both improve HF outcomes

— Avoid pioglitazone (fluid retention) and saxagliptin (increased HF hospitalization signal)

— Metformin safe if eGFR ≥30

— Semaglutide 2.4 mg weekly (STEP-HFpEF): reduced symptoms, improved exercise capacity, weight loss ~13%

— Tirzepatide (SUMMIT trial) similarly effective

— Bariatric surgery for BMI ≥35 with HF

Key distinction: Group 1 PAH gets PAH-specific therapy. Group 2 PH from HFpEF does not — pulmonary vasodilators may precipitate flash pulmonary edema. Step 3 loves this trap.

Board pearl: Digoxin has no mortality benefit in HFpEF but can be used for AF rate control when beta-blockers are insufficient — target level <1.0 ng/mL.

Atrial fibrillation management:

Hypertension agents preferred in HFpEF:

Diabetes:

Obesity:

OSA: polysomnography, CPAP titration; treating OSA reduces afib recurrence and HF hospitalizations

Iron deficiency: IV iron (ferric carboxymaltose or ferric derisomaltose) if ferritin <100 or ferritin 100–300 with TSAT <20%; oral iron is ineffective in HF

CAD: statin + antiplatelet per ASCVD guidelines; revascularize symptomatic ischemia

Cardiac amyloidosis (ATTR): tafamidis 61 mg daily — reduces mortality and HF hospitalizations; patisiran/inotersen for hereditary forms

Pulmonary hypertension from HFpEF (Group 2 PH): treat the HF — do NOT use sildenafil, bosentan, or epoprostenol routinely (worsened outcomes)

Special Populations — Elderly and Renal/Hepatic Impairment

— Polypharmacy and falls risk dominate decision-making

— Start low, go slow with diuretics — overdiuresis → orthostasis → falls → hip fracture

— Beers Criteria cautions: avoid NSAIDs, alpha-blockers, first-gen antihistamines, nondihydropyridine CCBs in HFpEF

— Cognitive screening (MoCA) before complex regimens; involve caregivers in teach-back

— Functional status assessment (ADLs, IADLs, gait speed) — frailty changes goals of care

— De-prescribe when benefit/burden ratio shifts (life expectancy <1 year)

— eGFR thresholds:

— SGLT2i: initiate if eGFR ≥20; continue to dialysis

— Spironolactone/eplerenone: avoid if eGFR <30 or K >5.0

— ACEi/ARB/ARNI: monitor closely; expect 20–30% Cr rise (acceptable); stop if >50% rise or hyperkalemia

— Metformin: stop if eGFR <30

— Cardiorenal syndrome in acute decompensation: diurese carefully, consider ultrafiltration only if diuretic resistance with refractory congestion

— Loop diuretic dose typically needs to double with each halving of GFR

— Use bumetanide or torsemide when furosemide absorption is unreliable (gut edema, CKD)

— Hepatic congestion from right HF can elevate transaminases and bilirubin — distinguish from primary liver disease

— Spironolactone preferred for ascites in cirrhosis; combined with furosemide in 100:40 ratio

— Avoid hepatotoxic statins at high doses; rosuvastatin and pravastatin safer

— Volume management via dialysis prescription rather than diuretics

— SGLT2i can be continued; MRA contraindicated

Step 3 management: When Cr rises 25% after starting ACEi/ARB/SGLT2i, continue the medication and recheck in 2 weeks — this hemodynamic effect is expected and not nephrotoxic. Stopping prematurely is a common Step 3 wrong answer.

Board pearl: In the frail elderly with HFpEF, fewer drugs at lower doses often outperform aggressive guideline-directed regimens — goals shift toward symptom control and avoiding hospitalization.

Elderly (the typical HFpEF patient):

Renal impairment:

Hepatic impairment:

Dialysis patients:

Special Populations — Pregnancy, Pediatrics, and Demographic Subgroups

— Primary HFpEF in pregnancy is rare; consider peripartum cardiomyopathy (usually HFrEF), HCM, congenital heart disease, or preexisting HFpEF in older gravidas

— Contraindicated in pregnancy: ACEi, ARB, ARNI, MRA, SGLT2i (all teratogenic or insufficient safety data)

— Safe options: loop diuretics (cautiously, can reduce placental perfusion), hydralazine, methyldopa, labetalol for BP; metoprolol for rate control

— Preconception counseling for women with HFpEF and HCM is mandatory

— Anticoagulation: LMWH preferred over warfarin (teratogen 6–12 wks) and DOACs (contraindicated)

— HFpEF is more common in women (~65% of cases)

— Women appear to derive greater benefit from ARNI (PARAGON-HF subgroup) and possibly MRA

— Microvascular dysfunction and INOCA contribute disproportionately

— Higher prevalence of HFpEF and worse outcomes

— Hypertension-driven phenotype dominant; aggressive BP control critical

— Hydralazine/isosorbide dinitrate combo has Class 1 evidence in HFrEF in Black patients — not established benefit in HFpEF

— HFpEF in children typically reflects HCM, restrictive cardiomyopathy, congenital heart disease, or chemotherapy-induced cardiomyopathy

— Refer to pediatric cardiology; adult HFpEF algorithms do not apply

— Anthracycline and chest radiation can cause late-onset diastolic dysfunction → HFpEF phenotype

— Surveillance echo per ASCO survivorship guidelines

Key distinction: Peripartum cardiomyopathy is HFrEF with EF <45%, presenting late pregnancy through 5 months postpartum — distinct from HFpEF and requires bromocriptine consideration, anticoagulation if EF <35%, and counseling against future pregnancy if EF doesn't fully recover.

Board pearl: Stop SGLT2i, ACEi, ARB, ARNI, and MRA immediately upon confirmed pregnancy; transition to pregnancy-compatible regimen and involve MFM and cardio-obstetrics team.

Pregnancy:

Women:

Black patients:

Pediatrics:

Cancer survivors:

Complications and Adverse Outcomes

— Most common complication; ~25% 30-day readmission rate

— Triggers: HTN surge, AF, dietary indiscretion, NSAID use, medication nonadherence, ischemia, infection, anemia, thyroid disease

— Flash pulmonary edema is the HFpEF signature acute presentation

— Develops in 30–40%; once present, often refractory and recurrent

— Loss of atrial kick → 20–30% drop in CO in stiff LV → rapid decompensation

— Increased stroke risk; anticoagulation per CHA₂DS₂-VASc

— Develops in up to 80% of advanced HFpEF

— Progresses to right heart failure with hepatic congestion, ascites, TR

— Combined post- and pre-capillary PH (Cpc-PH) carries worst prognosis

— Type 1: acute HF → AKI

— Type 2: chronic HF → progressive CKD

— Drives diuretic resistance and limits ACEi/ARB/MRA dosing

— Sarcopenia, deconditioning, falls

— Depression and cognitive impairment (cardiogenic dementia component)

— Overdiuresis → AKI, hypotension, hypokalemia → arrhythmia

— Hyperkalemia from MRA/ACEi combinations

— Hyponatremia from thiazide + loop combination

CCS pearl: On every readmission, identify the specific precipitant and document it — "patient ran out of furosemide 3 days ago" is actionable; "HFpEF exacerbation" is not. Step 3 CCS rewards precipitant identification and targeted intervention (e.g., medication reconciliation, pharmacy delivery program, patient education).

Board pearl: A patient with HFpEF and new AF who decompensates within hours is the classic stem — restoring sinus rhythm or controlling rate aggressively is the answer, not just diuresis.

Acute decompensated HF:

Atrial fibrillation:

Pulmonary hypertension (Group 2):

Renal dysfunction (cardiorenal syndrome):

Sudden cardiac death: less common than in HFrEF but still elevated; usually arrhythmic

Functional decline and frailty:

Iatrogenic complications:

Mortality: 5-year mortality 50–75%, comparable to HFrEF in many cohorts

When to Escalate — ICU, Consult, and Inpatient Triage

— Stable congestion, oral diuretics effective

— BP and HR controlled

— No signs of hypoperfusion

— Adherent patient with reliable follow-up

— Acute dyspnea with SpO₂ <90% on room air

— Hypertensive emergency with pulmonary edema

— New or rapid AF with hemodynamic compromise

— Suspected ACS as trigger (troponin elevation)

— Failed outpatient diuretic intensification (no weight loss in 48–72 hours)

— Severe electrolyte derangement, AKI, hyponatremia <130

— Telemetry for AF, frequent ectopy, QT-prolonging drugs, ischemic trigger, electrolyte abnormalities

— Floor acceptable for straightforward volume overload without arrhythmia

— Respiratory failure requiring NIV or intubation

— Hypotension/cardiogenic shock (rare in HFpEF but ominous)

— Refractory hypertensive emergency requiring IV nicardipine/clevidipine/nitroprusside

— Need for invasive hemodynamic monitoring (PA catheter)

— Malignant arrhythmia

— Cardiology for new diagnosis, refractory disease, suspected amyloid/HCM, advanced therapies

— Nephrology for cardiorenal syndrome requiring UF or dialysis

— Electrophysiology for AF ablation or pacing decisions

— Palliative care for advanced HFpEF, recurrent hospitalizations, NYHA IV

— Pulmonary/sleep for OSA evaluation

— Euvolemic (or at dry weight goal)

— On stable oral regimen for ≥24 hours

— BP and HR controlled

— Renal function and electrolytes stable

— Follow-up scheduled within 7 days (reduces readmission)

CCS pearl: For hypertensive flash pulmonary edema, the immediate orders are: NIV (BiPAP), IV loop diuretic, IV nitroglycerin or nicardipine drip for afterload reduction, telemetry, ABG, troponin, BNP, CXR. Diuresis alone without afterload reduction misses the physiology.

Step 3 management: The 7-day post-discharge clinic visit is the single highest-yield intervention to reduce 30-day readmission — make this a reflex order.

Outpatient management appropriate when:

ED evaluation and likely admission when:

Floor vs telemetry:

ICU admission criteria:

Consults to consider:

Discharge criteria:

Key Differentials — Same-Category (Cardiac) Causes

— Same symptoms but reduced systolic function on echo

— Requires the four pillars: ARNI/ACEi/ARB + beta-blocker + MRA + SGLT2i

— Beta-blockers mandatory; not so in HFpEF

— Behaves more like HFrEF — apply HFrEF pillars

— Often a transitional category (recovering or worsening)

— Asymmetric septal hypertrophy, dynamic LVOT obstruction, SAM of mitral valve

— Family history, sudden cardiac death history

— Genetic testing; ICD if high risk

— Mavacamten (cardiac myosin inhibitor) for obstructive HCM

— ATTR (wild-type or hereditary) or AL amyloid

— Concentric LVH with low ECG voltage (mismatch), bilateral carpal tunnel, autonomic neuropathy

— Diagnose with PYP scan (ATTR) or biopsy; rule out AL with serum/urine immunofixation and free light chains

— Tafamidis for ATTR; chemotherapy for AL

— Prior radiation, cardiac surgery, TB, viral pericarditis

— Kussmaul sign, pericardial knock, septal bounce, respiratory variation in mitral inflow

— CMR shows thickened, tethered pericardium; surgical pericardiectomy curative

— Sarcoidosis, hemochromatosis, endomyocardial fibrosis

— Biventricular enlargement of atria with normal-sized ventricles

— Severe AS, MR, MS can mimic HFpEF symptoms with preserved EF

— Echo identifies; consider TAVR/SAVR or MitraClip

Key distinction: Amyloidosis vs HFpEF: look for ECG-echo voltage mismatch (low voltage despite LVH), bilateral carpal tunnel, autonomic symptoms, age >70, intolerance to standard HF meds, "sparkly" myocardium on echo, and apical sparing on strain imaging. PYP scan is the noninvasive confirmatory test for ATTR.

Board pearl: Always rule out severe aortic stenosis in elderly HFpEF — symptoms overlap, and TAVR is life-changing.

HFrEF (EF <40%):

HFmrEF (EF 41–49%):

Hypertrophic cardiomyopathy:

Cardiac amyloidosis:

Constrictive pericarditis:

Restrictive cardiomyopathy (other than amyloid):

Valvular disease:

High-output HF: anemia, thyrotoxicosis, AV fistula, Paget disease, beriberi

Key Differentials — Non-Cardiac (Same Presentation) Causes

— Exertional dyspnea, edema (cor pulmonale), but with smoking history, prolonged expiration, wheeze

— PFTs show obstruction (FEV1/FVC <0.7)

— BNP usually normal or modestly elevated

— Can coexist with HFpEF — both treated

— Acute dyspnea with pleuritic chest pain, tachycardia, hypoxia

— Wells score, D-dimer, CTPA

— Right heart strain on echo, elevated troponin

— Idiopathic or associated with connective tissue disease, HIV, drugs (methamphetamine, fenfluramine), portal HTN

— Right heart catheterization: mPAP >20, PCWP ≤15, PVR >2

— Treated with PAH-specific therapy (PDE5i, ERA, prostacyclins, riociguat)

— Progressive dyspnea, dry cough, Velcro crackles

— HRCT shows reticulation, honeycombing, ground glass

— PFTs: restriction with reduced DLCO

— Often comorbid with HFpEF; can mimic with fatigue and dyspnea

— Polysomnography diagnostic; CPAP improves outcomes

— BMI >30, daytime hypercapnia, sleep-disordered breathing

— Overlap with HFpEF physiology

— Often the precipitant rather than mimic; CBC essential

— Hyperthyroidism → high-output HF, AF; hypothyroidism → diastolic dysfunction, pericardial effusion

— Diagnosis of exclusion; normal BNP, normal echo, normal exercise hemodynamics

— Episodic, not exertion-driven; normal cardiopulmonary workup

Key distinction: HFpEF vs COPD — both elderly with dyspnea and edema. BNP, echo (E/e′, LA size), and PFTs separate them; the two often coexist and both must be treated for symptom relief.

Board pearl: A negative BNP (<35 ambulatory, <100 acute) has high negative predictive value for HF in non-obese patients — in obesity (BMI >35), use a lower threshold (~50% reduction) before excluding HF.

COPD:

Pulmonary embolism:

Pulmonary arterial hypertension (Group 1):

Interstitial lung disease:

Obstructive sleep apnea:

Obesity hypoventilation syndrome:

Anemia:

Thyroid disease:

Deconditioning/obesity alone:

Anxiety/hyperventilation:

Secondary Prevention, Discharge Medications, and Long-Term Plan

— SGLT2 inhibitor (empagliflozin or dapagliflozin 10 mg daily)

— Loop diuretic at lowest effective dose, with PRN sliding scale if patient educated

— MRA (spironolactone 25 mg) if eGFR >30 and K <5.0

— ACEi/ARB/ARNI for BP control and HF benefit

— Beta-blocker if AF, CAD, or post-MI (not mandatory otherwise)

— Statin per ASCVD risk

— Anticoagulation if AF

— BP <130/80

— A1c individualized (typically 7–8% in elderly with HF)

— LDL <70 if ASCVD; <100 otherwise

— OSA treatment with CPAP

— Weight loss to BMI <30 (semaglutide if obesity phenotype)

— Sodium restriction <2–3 g/day

— Fluid restriction 1.5–2 L/day if hyponatremic or severe congestion

— Daily weights — call provider if >2 lb in 1 day or >5 lb in 1 week

— Smoking cessation, alcohol <1 drink/day

— Cardiac rehabilitation referral (Class 1)

— Annual influenza (high-dose for ≥65)

— Pneumococcal (PCV20 or PCV15 + PPSV23)

— COVID-19 boosters per CDC

— RSV for ≥60

— Tdap, zoster (Shingrix) per age

— Discuss goals of care, code status, healthcare proxy at every annual visit

— Document POLST/MOLST when appropriate

— Palliative care co-management for NYHA III–IV or recurrent hospitalizations

Step 3 management: The post-discharge "transition of care" bundle: 7-day clinic visit, medication reconciliation, daily weight log, sodium/fluid education with teach-back, pharmacy delivery if access issues, and remote BP/weight monitoring — this combination has the strongest evidence for reducing 30-day readmissions.

Board pearl: Influenza vaccination reduces HF hospitalization by ~20% — never skip it on Step 3.

Discharge medication bundle (every HFpEF patient):

Treat comorbidities aggressively:

Lifestyle prescription:

Vaccinations:

Advance care planning:

Follow-Up, Monitoring, and Rehab/Counseling

— 7 days post-discharge (in-person or telehealth) — most important visit

— 2-week visit for medication titration and labs

— Monthly until stable on optimized regimen

— Every 3–6 months when stable; annual TTE not required if clinically stable

— Cardiology co-management for moderate-severe disease or specific etiology (amyloid, HCM)

— Weight trend, BP (target <130/80), HR, NYHA class

— Volume exam: JVP, edema, lung auscultation

— Symptom assessment (KCCQ score in research/value-based settings)

— Medication adherence and side effects

— BMP and Mg 1 week after diuretic, ACEi/ARB/ARNI, or MRA initiation/uptitration

— Then every 3–6 months when stable

— BNP/NT-proBNP trend: optional, may guide titration; rising values suggest decompensation

— A1c quarterly if diabetic; ferritin/TSAT annually

— Lipid panel annually

— Class 1 recommendation for HFpEF

— 36 sessions over 12 weeks, supervised aerobic + resistance training

— Improves VO₂ max, quality of life, and reduces hospitalizations

— Daily morning weights, recorded

— Sodium label reading

— Symptom recognition: increased dyspnea, orthopnea, edema, weight gain → call provider, take extra diuretic per sliding scale, do not wait

— Medication purpose and adherence

— Avoid OTC NSAIDs, decongestants, high-sodium antacids

— Bluetooth scales, BP cuffs, smartphone apps

— Implantable hemodynamic monitors (CardioMEMS) for NYHA III with recent hospitalization

Step 3 management: When a patient reports 3-lb weight gain over 2 days, the answer is "increase furosemide per sliding scale and call clinic" — not "go to ED" and not "continue current regimen."

Board pearl: Skipping the 7-day post-discharge visit is the single biggest driver of 30-day readmission.

Follow-up cadence:

Monitoring parameters at each visit:

Lab monitoring:

Cardiac rehabilitation:

Patient education (teach-back required):

Remote monitoring:

Behavioral health: screen for depression (PHQ-2/9) annually — present in 30% and worsens outcomes

Ethical, Legal, and Patient Safety Considerations

— HFpEF carries 5-year mortality of 50–75% — comparable to many cancers

— Initiate goals-of-care discussions early, not at end of life

— Document healthcare proxy, code status, and POLST/MOLST

— Revisit at every hospitalization and annually

— Concurrent (not replacement) palliative care reduces symptoms and improves QOL

— Refer for NYHA III–IV, recurrent hospitalizations (≥2/year), declining functional status, or patient/family request

— Hospice eligibility: NYHA IV with optimized therapy, life expectancy <6 months

— Average HFpEF patient takes 10+ medications

— Deprescribe when burden exceeds benefit (cognitive decline, falls, end-stage frailty)

— Ethical balance: respecting autonomy while avoiding nihilism

— 30-day readmission rate ~25% — most occur due to medication errors, missed follow-up, social barriers

— Medication reconciliation at every transition (admission, transfer, discharge)

— Teach-back confirmation of discharge instructions

— Direct hand-off to outpatient provider; warm transfer if possible

— Address social determinants: transportation, pharmacy access, food security, caregiver availability

— Tafamidis for ATTR amyloid costs >$200,000/year — discuss financial toxicity and prior authorization

— SGLT2i euglycemic DKA risk — counsel on sick-day rules and perioperative hold

— Anticoagulation for AF — shared decision-making on bleeding vs stroke risk

— Recent syncope or ICD shock may trigger driving restrictions (state-dependent)

— Document discussion

— Implantable device malfunctions reportable to FDA MAUDE

— Suspected elder abuse/neglect (caregiver withholding meds) mandates APS report in most states

Step 3 management: A patient discharged on a new regimen who cannot afford the SGLT2i is a patient destined to readmit — at discharge, verify formulary coverage, use patient assistance programs (manufacturer or 340B), or substitute a covered alternative. The right answer on Step 3 includes "address cost barrier before discharge," not "see how it goes."

Board pearl: A 7-day post-discharge appointment scheduled before the patient leaves the hospital (not "will be called to schedule") is the single most-tested transition-of-care intervention.

Goals of care and advance directives:

Palliative care integration:

Polypharmacy and deprescribing:

Transitions of care (high-risk handoff):

Informed consent edge cases:

Driving and disability:

Reportable conditions:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: When the stem mentions "EF 60%, BNP elevated, elderly hypertensive woman, exertional dyspnea, S4, LVH" — the answer is HFpEF management, not "reassure and recheck."

Key distinction: EF alone never separates HFpEF from amyloid, HCM, or constriction — always look for the secondary clues.

HFpEF accounts for ~50% of all HF; prevalence rising with aging population

Female predominance (~65%); elderly, obese, hypertensive phenotype dominant

H2FPEF score ≥6 = high probability of HFpEF

E/e′ >14, LAVI >34 mL/m², TR velocity >2.8 m/s on echo suggest elevated filling pressures

NT-proBNP cutoffs (acute): <50yr >450; 50–75yr >900; >75yr >1800

BNP is lower in obesity (false negative) and higher in afib, CKD, sepsis (false positive)

Sacubitril/valsartan raises BNP, lowers NT-proBNP → use NT-proBNP for monitoring on ARNI

SGLT2 inhibitors are the only drug class with Class 1A evidence in HFpEF

MRAs (spironolactone) Class 2a — strongest benefit when EF 50–60%

ARNI Class 2b — benefit greater in women and lower-range EF

Beta-blockers NOT mandatory in HFpEF unless other indication

Avoid in HFpEF: NSAIDs, pioglitazone, nondihydropyridine CCBs (if any LV dysfunction), Group 1 PAH drugs (sildenafil), saxagliptin

Cardiac rehab is Class 1 in HFpEF

Semaglutide improves symptoms in obesity-phenotype HFpEF (STEP-HFpEF trial)

IV iron for ferritin <100 or 100–300 with TSAT <20%

AF rhythm control increasingly favored over rate control in symptomatic HFpEF

Tafamidis for ATTR cardiac amyloidosis (mortality benefit)

PYP scan diagnostic for ATTR; rule out AL with free light chains + SPEP/UPEP first

Apical sparing on strain echo and ECG-echo voltage mismatch suggest amyloid

7-day post-discharge visit reduces 30-day readmission

Influenza vaccination reduces HF hospitalization by ~20%

Daily weights with 2 lb/day or 5 lb/week trigger threshold

5-year mortality 50–75%, similar to many cancers

Sodium restriction <2–3 g/day; fluid restriction reserved for hyponatremia/severe congestion

OSA prevalence >50% in HFpEF; treating reduces AF recurrence

Cardiorenal syndrome Type 1 (acute) vs Type 2 (chronic) — both common

Group 2 PH (from HFpEF): treat the HF, NOT with PAH-specific therapy

Board Question Stem Patterns

72-year-old obese woman with HTN, T2DM, AF presents with exertional dyspnea and bilateral edema. EF 60%, E/e′ 16, LAVI 40, BNP 600.

→ Answer: Diagnose HFpEF; start SGLT2 inhibitor, optimize BP <130/80, loop diuretic for symptoms, MRA if eGFR/K allow, refer cardiac rehab.

68-year-old with HTN presents with acute dyspnea, BP 210/110, SpO₂ 85%, bilateral crackles, EF 65%.

→ Answer: NIV + IV nitroglycerin or nicardipine + IV furosemide; admit telemetry; outpatient HFpEF regimen on discharge.

78-year-old man with bilateral carpal tunnel history, "HFpEF" not responding to diuretics, low ECG voltage, LVH on echo, intolerant to ACEi (hypotension).

→ Answer: Order PYP scan; rule out AL with free light chains/SPEP; start tafamidis if ATTR confirmed.

HFpEF patient discharged on empagliflozin returns 2 weeks later with worsening symptoms; admits he never filled the script due to cost.

→ Answer: Address cost barrier (manufacturer assistance, formulary alternative), schedule 7-day follow-up, medication reconciliation, social work referral.

Stable HFpEF patient presents with worsening edema after starting ibuprofen for knee pain.

→ Answer: Stop NSAID; advise acetaminophen/topical NSAID; resume baseline regimen.

Hypertensive 70-year-old develops new AF with RVR and acute pulmonary edema; converts back, symptoms resolve.

→ Answer: HFpEF with AF; consider rhythm control (cardioversion ± ablation), anticoagulate per CHA₂DS₂-VASc, start HFpEF regimen.

HFpEF with elevated PASP; resident proposes sildenafil.

→ Answer: Do NOT use PAH-specific therapy; optimize HFpEF management instead.

Severely obese woman (BMI 38) with HFpEF, normal-low BNP, persistent symptoms.

→ Answer: Add semaglutide; counsel weight loss; reassess BNP interpretation in obesity.

HFpEF admission, Cr rises from 1.4 to 1.8 on diuresis and new spironolactone.

→ Answer: Continue careful diuresis if congested; recheck K and Cr; do not stop MRA unless K >5.5 or Cr rise >50%.

Board pearl: When you see "EF preserved, BNP elevated, multiple comorbidities," the answer is almost always SGLT2 inhibitor + comorbidity optimization.

Stem 1 — The classic phenotype:

Stem 2 — Flash pulmonary edema:

Stem 3 — Amyloid in disguise:

Stem 4 — Cost/access transition of care:

Stem 5 — Iatrogenic decompensation:

Stem 6 — AF unmasking HFpEF:

Stem 7 — Group 2 PH trap:

Stem 8 — Obesity phenotype:

Stem 9 — Cardiorenal:

One-Line Recap

HFpEF is the syndrome of heart failure symptoms with LVEF ≥50% driven by stiff, noncompliant ventricles in the setting of HTN, obesity, AF, diabetes, and CKD — and is managed with SGLT2 inhibitors, aggressive comorbidity control, diuretics for congestion, and selective use of MRA/ARNI, while always ruling out amyloidosis, HCM, and constriction.

Board pearl: EF ≥50% never rules out heart failure — it defines a category that is half of all HF, more deadly than commonly appreciated, and increasingly treatable with SGLT2 inhibitors and comorbidity-directed therapy.

Diagnosis triad: symptoms + EF ≥50% + evidence of elevated filling pressures (E/e′ >14, elevated BNP/NT-proBNP, LAVI >34) — use H2FPEF score when uncertain, invasive hemodynamic exercise testing when noninvasive is inconclusive.

Therapeutic core: SGLT2 inhibitor is the only Class 1A drug; loop diuretic for symptoms; MRA, ARNI, ARB layered based on phenotype; treat HTN to <130/80, manage AF aggressively (rhythm control increasingly favored), screen and treat OSA, address obesity with GLP-1 agonists, repair iron deficiency with IV iron, and refer to cardiac rehab.

Always rule out the masqueraders: cardiac amyloidosis (ECG-echo voltage mismatch, bilateral carpal tunnel, intolerance to standard HF meds → PYP scan, free light chains, tafamidis if ATTR), HCM (asymmetric septal hypertrophy → mavacamten), constrictive pericarditis (CMR), severe valvular disease, and Group 1 PAH — each has disease-modifying therapy that changes everything.

Transitions of care win Step 3: 7-day post-discharge clinic visit, medication reconciliation with cost verification, teach-back of sodium/fluid/weight rules, daily weights with 2-lb/day or 5-lb/week threshold, vaccination bundle (flu, pneumococcal, COVID, RSV), and early goals-of-care conversation — these structural interventions reduce 30-day readmissions and mortality more reliably than any single drug.