Heart Failure

• Definition: a clinical syndrome in which structural or functional cardiac impairment causes inadequate ventricular filling or ejection, producing congestion, impaired tissue perfusion, or both. It is a syndrome diagnosed clinically, not a single lesion on imaging — an abnormal ejection fraction without symptoms or signs is asymptomatic LV dysfunction, not heart failure.

Why it matters

• Mortality burden: heart failure carries a prognosis comparable to many malignancies, with high 5-year mortality after first hospitalization; the ACC/AHA/HFSA 2022 Heart Failure Guideline frames the entire management scheme around slowing progression before symptoms appear.
• Readmission burden: acute decompensated heart failure is among the leading causes of hospitalization in adults over 65 in the United States, with frequent 30-day readmission.
• Boards emphasis: nearly every question hinges on separating reduced from preserved ejection fraction, because the two share a presentation but not a treatment.

Epidemiology worth recalling

• Prevalence: over 6 million US adults (AHA Heart Disease and Stroke Statistics), rising with population aging.
• Lifetime risk: roughly one in four to one in five adults will develop heart failure.
• Incidence rises steeply with age; HFrEF skews male and post-ischemic, while HFpEF skews older, female, obese, and hypertensive — exactly the split the existing vignettes describe.
• Disparities: Black patients have higher incidence and earlier onset, largely mediated by hypertension prevalence and control.

Staging vocabulary (ACC/AHA/HFSA 2022)

• Stage A: at risk (hypertension, diabetes, cardiotoxic exposure), no structural disease.
• Stage B: structural disease or elevated natriuretic peptides, never symptomatic (pre-heart failure).
• Stage C: current or prior symptoms.
• Stage D: advanced, refractory to guideline-directed therapy.
• NYHA class I–IV describes functional limitation and can move in both directions; ACC/AHA stages only advance.

Impaired contractility (leads to HFrEF)

• Ischemic heart disease: the single most common cause in the US — infarcted myocardium is replaced by non-contractile scar; hibernating myocardium may recover with revascularization.
• Dilated cardiomyopathy: viral/lymphocytic myocarditis (coxsackie B, parvovirus B19), alcohol, cocaine/methamphetamine, peripartum, familial (titin, lamin A/C), and chemotherapy — anthracyclines (dose-dependent, free-radical mediated) and trastuzumab (usually reversible).
• Tachycardia-mediated: chronic uncontrolled atrial fibrillation or incessant SVT; reversible with rate/rhythm control.
• Infiltrative/metabolic: hemochromatosis, sarcoidosis, amyloidosis, thiamine deficiency (wet beriberi), thyrotoxicosis, and hypothyroidism.

Impaired filling / increased stiffness (leads to HFpEF)

• Long-standing hypertension with concentric LVH — the dominant driver.
• Restrictive cardiomyopathy (amyloidosis, especially transthyretin amyloid in older men), hypertrophic cardiomyopathy, and constrictive pericarditis, which mimics but is pericardial.

Pressure and volume overload

• Aortic stenosis and hypertension impose afterload; mitral or aortic regurgitation, VSD, and ASD impose volume load.

High-output states

• Severe anemia, thyrotoxicosis, arteriovenous fistula, Paget disease, thiamine deficiency — cardiac output is high yet insufficient for demand.

Non-modifiable risk factors

• Older age, male sex (for HFrEF), Black race, family history of cardiomyopathy, prior MI or chemotherapy exposure.

Modifiable risk factors

• Hypertension — the highest population-attributable risk and the target of ACC/AHA/HFSA Stage A prevention; diabetes (an indication for an SGLT2 inhibitor to prevent incident heart failure per the ADA Standards of Care); obesity, tobacco use, excess alcohol, sedentary behavior, dyslipidemia, obstructive sleep apnea, and dietary sodium excess.

• The initiating insult (infarct, pressure load, toxin, mutation) drops stroke volume or raises filling pressure. Cardiac output falls, baroreceptors unload, and the body responds as though it were hemorrhaging.

Neurohormonal cascade — adaptive short-term, lethal long-term

• Sympathetic activation: raises heart rate and contractility, but chronic catecholamine exposure downregulates and uncouples beta-1 receptors, is directly myocyte-toxic, and lowers the arrhythmic threshold. This is precisely why beta blockade improves survival.
• RAAS activation: renal hypoperfusion drives renin → angiotensin II (vasoconstriction, raising afterload against an already failing ventricle) → aldosterone (sodium and water retention plus interstitial fibrosis). ACE inhibition/ARNI and MRAs interrupt this limb.
• Non-osmotic ADH release: free water retention producing dilutional hyponatremia — a marker of severity, not just an electrolyte finding.
• Natriuretic peptides: ventricular wall stretch releases BNP and NT-proBNP, which promote natriuresis and vasodilation. This is the one *counter*-regulatory arm, and it is overwhelmed — the rationale for neprilysin inhibition, which preserves it.

Remodeling geometry

• Volume overload / infarction → eccentric hypertrophy, sarcomeres added in series, chamber dilation. By Laplace's law (wall stress ∝ pressure × radius / wall thickness), dilation raises wall stress, worsening oxygen demand and further lowering EF — the vicious cycle noted above. Dilation also tethers the papillary muscles, causing functional mitral regurgitation, which adds more volume load.
• Pressure overload → concentric hypertrophy, sarcomeres in parallel, a small stiff cavity with a steep end-diastolic pressure–volume relationship. Filling now depends critically on atrial kick and on adequate diastolic time, which is why new atrial fibrillation or tachycardia precipitates flash pulmonary edema in HFpEF.

From hemodynamics to findings

• Backward failure: elevated LV end-diastolic pressure → left atrial and pulmonary venous hypertension → transudation once pressures exceed plasma oncotic pressure → crackles, orthopnea, PND. Right-sided pressure transmits to jugular veins, liver, and dependent tissues → JVD, hepatomegaly, edema.
• Forward failure: hypoperfusion → fatigue, cool extremities, prerenal azotemia, narrow pulse pressure.

Left-sided congestion (pulmonary)

• Dyspnea on exertion: the earliest and most sensitive symptom; rising pulmonary capillary wedge pressure stiffens the lungs and stimulates juxtacapillary receptors.
• Orthopnea: recumbency redistributes splanchnic and lower-extremity blood centrally; quantified by pillow count.
• Paroxysmal nocturnal dyspnea: same mechanism plus nocturnal reabsorption of interstitial edema, waking the patient 1–2 hours into sleep with air hunger relieved by sitting.
• Bibasilar crackles and, when severe, pink frothy sputum; Cheyne–Stokes respiration in advanced disease from prolonged circulation time.

Right-sided congestion (systemic)

• Elevated JVP and hepatojugular reflux: the most specific bedside signs of elevated filling pressures.
• Dependent pitting edema (ankles if ambulatory, sacral if bedbound), tender hepatomegaly, ascites, and early satiety from gut edema.

Low-output findings

• Fatigue, exercise intolerance, cool mottled extremities, narrow pulse pressure, and pulsus alternans in severe systolic dysfunction; nocturia from recumbent renal perfusion.

Cardiac exam

• S3 gallop: rapid early filling into a dilated, compliant ventricle — the classic HFrEF sound and, in an adult, highly specific for elevated filling pressure.
• S4 gallop: atrial contraction into a stiff ventricle — think hypertensive HFpEF.
• Laterally displaced, sustained apical impulse in dilation; holosystolic apical murmur of functional mitral regurgitation.

The demographic the stem names

• HFrEF: a middle-aged to older patient, often male, with prior MI, hypertension, alcohol use, or recent anthracycline/trastuzumab chemotherapy.
• HFpEF: an older woman with obesity, long-standing hypertension, diabetes, atrial fibrillation, and chronic kidney disease.
• Peripartum cardiomyopathy: new dyspnea in late pregnancy or the early postpartum months.
• Amyloid: an older man with heart failure plus carpal tunnel syndrome, low-voltage ECG, and thick walls on echo.

Step 1 — clinical suspicion plus initial studies (any dyspneic patient)

• ECG: rarely diagnostic but almost never normal in heart failure; look for prior Q waves, LVH, atrial fibrillation, and conduction disease. A completely normal ECG makes LV systolic dysfunction unlikely. Remember that a new LBBB is not by itself a STEMI criterion — apply Sgarbossa criteria when ischemia is the competing diagnosis.
• Chest radiograph: cephalization of pulmonary vessels, Kerley B lines, perihilar butterfly/bat-wing edema, cardiomegaly, and pleural effusions (right greater than left).
• Natriuretic peptides: BNP or NT-proBNP. Their greatest value is a negative result — a low BNP in an acutely dyspneic patient effectively excludes heart failure as the cause. Values rise with age, renal impairment, and atrial fibrillation, and are falsely low in obesity. Sacubitril/valsartan raises BNP (neprilysin normally degrades it) but not NT-proBNP, so follow NT-proBNP on ARNI.
• Labs: CBC, metabolic panel, TSH, iron studies, and troponin to screen for ischemic precipitants and reversible causes.

Step 2 — confirmatory test

• Transthoracic echocardiography is the single best next test and the cornerstone of the ACC/AHA/HFSA 2022 Heart Failure Guideline workup. It assigns the EF-based phenotype (HFrEF ≤40%, HFmrEF 41–49%, HFpEF ≥50%), shows wall-motion abnormalities suggesting ischemia, and quantifies diastolic function through E/A ratio, E/e′, left atrial volume index, and tricuspid regurgitant velocity.

Step 3 — etiologic and advanced testing

• Ischemic evaluation (stress imaging or coronary angiography) whenever coronary disease is plausible, since revascularization changes prognosis.
• Cardiac MRI for infiltrative, inflammatory, or unexplained cardiomyopathy; pyrophosphate scintigraphy for transthyretin amyloid; endomyocardial biopsy only in selected cases such as suspected giant-cell myocarditis.
• Right heart catheterization remains the hemodynamic gold standard when volume status or the cause of shock is genuinely unclear, or when evaluating for advanced therapies.

Acute decompensated heart failure — stabilize first

• Oxygen and non-invasive positive-pressure ventilation (CPAP/BiPAP) for hypoxemic pulmonary edema: raised intrathoracic pressure reduces preload and afterload and recruits alveoli, reducing intubation rates.
• IV loop diuretic (furosemide) is the core therapy for congestion; give at or above the home oral dose equivalent, and follow urine output and daily weights.
• IV vasodilators (nitroglycerin) in the hypertensive, "flash" pulmonary edema patient to cut afterload.
• Inotropes (dobutamine, milrinone) only for hypoperfusion/cardiogenic shock — they increase mortality when used indiscriminately. Escalate to temporary mechanical circulatory support if shock persists.

Chronic HFrEF — the four pillars of guideline-directed medical therapy (ACC/AHA/HFSA 2022), started and titrated in parallel

• ARNI (sacubitril/valsartan), preferred over ACE inhibitor or ARB; requires a 36-hour washout from an ACE inhibitor to avoid angioedema.
• Beta blocker — only the three with mortality data: carvedilol, metoprolol succinate, bisoprolol. Start when euvolemic, never during active decompensation.
• Mineralocorticoid receptor antagonist (spironolactone, eplerenone), with potassium and creatinine monitoring.
• SGLT2 inhibitor (dapagliflozin, empagliflozin), effective irrespective of diabetes status.

Add-on and second-line

• Hydralazine plus isosorbide dinitrate for self-identified Black patients with persistent NYHA III–IV symptoms, and for those intolerant of RAAS blockade.
• Loop diuretics for symptoms only; ivabradine for sinus rate ≥70 on maximal beta blockade; vericiguat or digoxin for refractory symptoms; IV iron for iron deficiency.

Device and definitive therapy

• ICD for primary prevention when EF remains ≤35% after at least 3 months of optimized therapy with reasonable expected survival; CRT when there is LBBB with a widely prolonged QRS.
• LVAD and cardiac transplantation for Stage D disease.

Emergencies

• Acute cardiogenic pulmonary edema: abrupt rise in LV filling pressure floods alveoli; the patient is hypoxemic, diaphoretic, and sitting upright with pink frothy sputum. Immediate diuresis, nitrates, and NIPPV.
• Cardiogenic shock: hypotension with cool extremities, oliguria, and rising lactate despite adequate filling pressures; requires inotropes and consideration of mechanical support.
• Sudden cardiac death from ventricular fibrillation or pulseless ventricular tachycardia: scar and fibrosis create reentry circuits, and sympathetic drive plus electrolyte shifts lower the threshold. These are the shockable rhythms — immediate defibrillation. This risk is the entire rationale for primary-prevention ICDs.

Disease complications

• Cardiorenal syndrome: venous congestion and low forward flow reduce renal perfusion pressure; creatinine rises and diuretic responsiveness falls.
• Atrial fibrillation: atrial stretch and fibrosis; loss of atrial kick can precipitate decompensation, particularly in HFpEF.
• LV mural thrombus and systemic embolism: stasis in an akinetic or aneurysmal segment, especially after anterior MI.
• Functional mitral regurgitation: annular dilation and papillary tethering, heard as a new holosystolic apical murmur, feeding further volume overload.
• Pulmonary hypertension and right ventricular failure: chronic postcapillary pressure transmission, producing ascites, hepatic congestion, and eventually cardiac cirrhosis.
• Cardiac cachexia and hyponatremia: markers of advanced disease with poor prognosis.

Treatment complications

• Loop diuretics: hypokalemia, hypomagnesemia, metabolic alkalosis, contraction alkalosis, prerenal azotemia, and ototoxicity with rapid IV infusion.
• ACE inhibitors/ARNI: hyperkalemia, cough (ACE inhibitor only, from bradykinin), and angioedema — an airway emergency.
• MRAs: hyperkalemia with peaked T waves and widening QRS; gynecomastia with spironolactone (less with eplerenone).
• Beta blockers: transient worsening of symptoms and bradycardia if titrated too quickly or started during congestion.
• Digoxin toxicity: nausea, confusion, yellow-green visual halos, and arrhythmias; potentiated by hypokalemia and renal failure.
• SGLT2 inhibitors: genital mycotic infection, volume depletion, and euglycemic diabetic ketoacidosis.

• The single best next step in a new dyspneic patient with congestion is transthoracic echocardiography — it separates HFrEF from HFpEF and therefore determines every subsequent management choice. BNP supports the diagnosis; echo defines it.
• S3 = dilated, volume-overloaded ventricle (HFrEF); S4 = stiff, hypertrophied ventricle (HFpEF). Elevated JVP and hepatojugular reflux are the most specific bedside signs of elevated filling pressures; crackles are common but far less specific.
• A low natriuretic peptide level is the most useful result — it argues strongly against heart failure as the cause of acute dyspnea. Beware the obese patient, in whom BNP runs falsely low, and the patient with renal failure or atrial fibrillation, in whom it runs high without decompensation.
• On sacubitril/valsartan, follow NT-proBNP, not BNP. Neprilysin inhibition blocks BNP degradation so BNP rises; NT-proBNP is not a neprilysin substrate. A rising BNP on ARNI is a pharmacologic artifact, not worsening failure.
• HFrEF therapy is four classes, not three: ARNI (or ACE inhibitor/ARB), beta blocker, MRA, and SGLT2 inhibitor, per the ACC/AHA/HFSA 2022 guideline. Only carvedilol, metoprolol succinate, and bisoprolol have mortality data — atenolol and metoprolol tartrate are the distractors.
• Never start or up-titrate a beta blocker in an acutely decompensated, volume-overloaded patient; diurese to euvolemia first. Conversely, do not stop a chronic beta blocker at admission unless the patient is in shock.
• Verapamil, diltiazem, NSAIDs, and thiazolidinediones worsen HFrEF and are the classic "new medication before admission" in a decompensation stem.
• The one association examiners love: an older man with heart failure, thick ventricular walls on echo but low QRS voltage on ECG, plus bilateral carpal tunnel syndrome — cardiac amyloidosis, not hypertensive hypertrophy.

• HFrEF (EF ≤40%): systolic dysfunction; treat with ACE-I/ARB, beta-blockers, aldosterone antagonists, SGLT2 inhibitors
• HFpEF (EF ≥50%): diastolic dysfunction; no mortality benefit from standard HF drugs; manage hypertension and rate control
• HFmrEF (EF 41-49%): intermediate phenotype
• Acute decompensation presents with dyspnea, orthopnea, PND, peripheral edema, crackles, elevated JVP
• BNP/NT-proBNP elevated in HF; used for diagnosis and prognosis

• CHADS₂ risk: Common comorbidities—Coronary disease, Hypertension, Atrial fibrillation, Diabetes, prior Stroke
• "ABCDE" therapy: ACE-I/ARB, Beta-blockers, aldosterone antagonists (Carvedilol/spironolactone), SGLT2 inhibitors—all reduce mortality in HFrEF
• Acute decompensation triggers: Infection, MI, arrhythmia, medication non-adherence, dietary sodium/fluid excess
• Ejection fraction decline: Leads to increased wall stress → ventricular dilation → further EF reduction (vicious cycle)
• B-type natriuretic peptide: Released by stretched ventricular myocytes; BNP >400 or NT-proBNP >2000 highly specific for HF diagnosis

• Assuming HFpEF responds to standard HF meds: ACE-I/ARB and beta-blockers have NOT shown mortality benefit in HFpEF; focus on symptom relief and comorbidity management (BP, rate control)
• Over-diuresing in acute HF: While diuretics relieve congestion, excessive use worsens renal function and activates RAAS; use "dry weight" target cautiously
• Missing HFmrEF: Intermediate EF (41-49%) often overlooked; SGLT2 inhibitors and ACE-I/ARB may provide benefit but evidence is emerging

HFrEF (Systolic)

• ACE-I/ARB or ARNI (sacubitril/valsartan) + beta-blocker (bisoprolol, carvedilol) + aldosterone antagonist (spironolactone)
• SGLT2 inhibitor (dapagliflozin, empagliflozin)—proven mortality/HF hospitalization benefit
• Diuretics (furosemide) for volume overload; ivabradine if HR >70 with EF <35%

HFpEF

• Diuretics for congestion and dyspnea
• Aggressive BP/rate control; finerenone (non-steroidal aldosterone antagonist) or SGLT2i emerging options
• Treat comorbidities: hypertension, diabetes, atrial fibrillation