Heart Failure

Heart failure (HF) is a clinical syndrome in which the heart is unable to pump blood at a rate commensurate with the metabolic demands of tissues, or can do so only at the cost of elevated filling pressures. It is a final common pathway for almost every form of structural and functional cardiac disease and is one of the most heavily tested topics in NEET PG cardiology — spanning classification, neurohormonal physiology, Framingham criteria, and the rapidly evolving "four pillars" of pharmacotherapy.

Definition & Classification

The 2021 Universal Definition of Heart Failure defines HF as symptoms and/or signs caused by a structural and/or functional cardiac abnormality, corroborated by elevated natriuretic peptides and/or objective evidence of pulmonary or systemic congestion.

The single most important classification for exams is by left ventricular ejection fraction (LVEF):

Type	LVEF	Synonym	Typical patient
HFrEF	≤ 40%	Systolic failure	Post-MI, dilated cardiomyopathy, young male
HFmrEF	41–49%	Mildly reduced EF	Transition group
HFpEF	≥ 50%	Diastolic failure	Elderly, hypertensive, diabetic woman
HFimpEF	Baseline ≤40%, now >40% with ≥10% rise	Improved EF	Treated HFrEF

High-yield: HFpEF (diastolic failure) classically occurs in an elderly hypertensive diabetic obese female; the ventricle is stiff (impaired relaxation/compliance) with a normal EF. HFrEF (systolic failure) is a dilated, poorly contracting ventricle.

Other axes of classification frequently asked:

• Acute vs chronic — new-onset/decompensated vs stable compensated.
• Left vs right vs biventricular — left HF → pulmonary congestion (dyspnoea, orthopnoea); right HF → systemic congestion (raised JVP, hepatomegaly, pedal oedema). The commonest cause of right HF is left HF.
• High-output vs low-output — high-output failure occurs with normal/increased cardiac output: causes include Anaemia, Beriberi (thiamine deficiency, wet beriberi), Arteriovenous fistula, Thyrotoxicosis, Paget disease of bone, and pregnancy (mnemonic: "ABA-TP" / "A BAT in PregnancY").
• Forward vs backward failure — forward = hypoperfusion (fatigue, oliguria); backward = congestion behind the failing chamber.

Etiology

The two dominant causes worldwide are coronary artery disease (ischaemic cardiomyopathy) and hypertension. Others:

• Valvular disease (rheumatic heart disease remains important in India — mitral/aortic).
• Cardiomyopathies — dilated (alcohol, peripartum, viral myocarditis, doxorubicin/trastuzumab, haemochromatosis), hypertrophic, restrictive (amyloid, sarcoid).
• Arrhythmias (tachycardia-induced cardiomyopathy, AF).
• Congenital heart disease, pericardial disease, high-output states.

High-yield: Doxorubicin (Adriamycin) causes dose-dependent dilated cardiomyopathy; trastuzumab cardiotoxicity is usually reversible. Peripartum cardiomyopathy presents in the last month of pregnancy to 5 months postpartum.

Pathophysiology — Neurohormonal Activation

A fall in cardiac output triggers compensatory mechanisms that are initially adaptive but ultimately drive progressive ventricular remodelling and decompensation. This neurohormonal cascade is the conceptual backbone of all modern HF therapy.

Reduced cardiac output → baroreceptor unloading → sympathetic activation + RAAS activation → vasoconstriction & Na⁺/water retention → ↑ preload & afterload → ventricular remodelling → further pump failure (vicious cycle).

1. Sympathetic nervous system (SNS): ↑ heart rate, contractility, vasoconstriction. Chronic catecholamine excess → β-receptor downregulation, myocyte apoptosis, arrhythmias. (Basis for beta-blockers.)
2. Renin–angiotensin–aldosterone system (RAAS): Angiotensin II → vasoconstriction + aldosterone → Na⁺/water retention + myocardial fibrosis. (Basis for ACE inhibitors/ARB/ARNI and MRA.)
3. Natriuretic peptides (ANP, BNP): Released from stretched atria/ventricles; promote natriuresis and vasodilation — a "good" counter-regulatory system that is degraded by neprilysin (basis for sacubitril).
4. Frank–Starling mechanism: ↑ preload ↑ stroke volume — but the failing heart operates on a flattened curve, so this is exhausted.
5. Ventricular remodelling: Eccentric hypertrophy (volume overload), concentric hypertrophy (pressure overload), and chamber dilatation.

High-yield: The shift from a "haemodynamic" to a "neurohormonal" model explains why drugs that block SNS and RAAS (and now SGLT2 and neprilysin) improve survival, whereas pure inotropes (which only improve haemodynamics) increase mortality.

Clinical Features

Left heart failure (pulmonary congestion):

• Exertional dyspnoea → orthopnoea → paroxysmal nocturnal dyspnoea (PND).
• Fatigue, weakness (low forward output).
• Basal crepitations, S3 gallop (sensitive sign of raised filling pressure/volume overload), pulsus alternans, displaced apex.
• Acute pulmonary oedema: frothy pink sputum, severe orthopnoea.

Right heart failure (systemic congestion):

• Raised JVP, hepatomegaly (tender, pulsatile in TR), hepatojugular reflux.
• Dependent pitting oedema, ascites, anasarca.
• Cardiac cirrhosis (nutmeg liver) in chronic cases.

High-yield: S3 gallop correlates with volume overload/HFrEF; S4 gallop correlates with a stiff ventricle (HFpEF, hypertensive heart). Kerley B lines on chest X-ray indicate interstitial pulmonary oedema.

Diagnosis — Framingham Criteria

The Framingham criteria require 2 major OR 1 major + 2 minor criteria for the clinical diagnosis of congestive heart failure — a perennial NEET PG favourite.

Major criteria	Minor criteria
Paroxysmal nocturnal dyspnoea	Bilateral ankle oedema
Neck vein distension (raised JVP)	Nocturnal cough
Crepitations (rales)	Dyspnoea on ordinary exertion
Cardiomegaly (on CXR)	Hepatomegaly
Acute pulmonary oedema	Pleural effusion
S3 gallop	Tachycardia (> 120/min)
Raised central venous pressure (> 16 cm H₂O)	Decrease in vital capacity by 1/3 from maximum
Hepatojugular reflux
Weight loss ≥ 4.5 kg in 5 days with treatment*

*Weight loss with diuretic therapy counts as a major criterion (response to treatment). A minor criterion is acceptable only if not attributable to another condition.

NYHA Functional Classification

Used to grade symptom severity and guide prognosis/therapy:

Class	Symptoms
I	No limitation; ordinary activity causes no symptoms
II	Slight limitation; comfortable at rest, ordinary activity → symptoms
III	Marked limitation; less-than-ordinary activity → symptoms
IV	Symptoms at rest; any activity worsens

The ACC/AHA stages (A–D) are complementary and emphasise progression: A = at risk (HTN, DM, no structural disease), B = structural disease but asymptomatic, C = symptomatic, D = refractory/end-stage.

High-yield: NYHA class is dynamic (can improve/worsen) whereas ACC/AHA stages are progressive (cannot regress).

Investigations

• Natriuretic peptides — investigation of choice for diagnosis/rule-out. BNP < 100 pg/mL (or NT-proBNP < 300 pg/mL) has high negative predictive value — useful to rule OUT HF in a breathless patient. Levels rise with age, renal failure, AF; lowered by obesity. ARNI (sacubitril) raises BNP but lowers NT-proBNP (NT-proBNP not a neprilysin substrate — preferred for monitoring on ARNI).
• Echocardiography — single most useful investigation overall; gives LVEF, chamber size, wall motion, valvular function, diastolic parameters (E/e′ ratio for HFpEF).
• ECG: LVH, prior MI Q-waves, LBBB (relevant for CRT), AF. A completely normal ECG makes HF unlikely.
• Chest X-ray: cardiomegaly (CTR > 0.5), upper-lobe diversion (cephalisation), Kerley B lines, perihilar bat-wing oedema, pleural effusions.
• Bloods: FBC, electrolytes, renal/liver function, TFT, iron studies (iron deficiency is common and treatable), HbA1c.
• Coronary angiography if ischaemia suspected; cardiac MRI for cardiomyopathy/infiltrative disease; endomyocardial biopsy for amyloid/myocarditis (selected).

High-yield: Echocardiography is the investigation of choice to determine the type/cause of HF and to measure EF. BNP/NT-proBNP is the best screening/rule-out test in acute dyspnoea (distinguishes cardiac from pulmonary cause).

Management of Chronic HFrEF — The Four Pillars

Guideline-directed medical therapy (GDMT) for HFrEF now rests on four foundational drug classes, all of which reduce mortality and should be initiated and up-titrated together:

1. ARNI (sacubitril/valsartan) — preferred over ACEi/ARB (PARADIGM-HF). Use ACEi if ARNI unaffordable; ARB if ACEi-intolerant (cough/angioedema).
2. Beta-blocker — only the three proven agents: carvedilol, bisoprolol, metoprolol succinate (and nebivolol). Start low, go slow; never in acute decompensation.
3. MRA (mineralocorticoid receptor antagonist) — spironolactone or eplerenone (RALES, EPHESUS).
4. SGLT2 inhibitor — dapagliflozin or empagliflozin (DAPA-HF, EMPEROR-Reduced) — benefit independent of diabetes.

Initiate all four pillars early → up-titrate to target/maximally tolerated doses → add device therapy and adjuncts as indicated.

High-yield: Drugs proven to reduce mortality in HFrEF: ACEi/ARB/ARNI, beta-blockers, MRA, SGLT2 inhibitors, hydralazine–nitrate (in Black patients / ACEi-intolerant). Diuretics and digoxin relieve symptoms but do NOT improve survival. Digoxin reduces hospitalisations only.

Adjuncts / specific agents:

• Loop diuretics (furosemide) — for congestion/symptom relief (do not improve survival).
• Ivabradine — If channel blocker; add if sinus rhythm with HR ≥ 70 despite max beta-blocker (SHIFT trial).
• Hydralazine + isosorbide dinitrate — especially self-identified Black patients (A-HeFT).
• Vericiguat (soluble guanylate cyclase stimulator), digoxin for rate control in AF or persistent symptoms.
• IV iron (ferric carboxymaltose) for iron deficiency.

High-yield — drugs that WORSEN/are contraindicated in HFrEF: NSAIDs, non-dihydropyridine CCBs (verapamil, diltiazem) — negative inotropes, thiazolidinediones (pioglitazone — fluid retention), class I antiarrhythmics, and sotalol/dronedarone. Amlodipine/felodipine are the "safe" CCBs if one is needed for BP.

Device therapy:

• ICD for primary prevention if LVEF ≤ 35% despite ≥ 3 months GDMT (NYHA II–III).
• CRT (biventricular pacing) if LVEF ≤ 35%, sinus rhythm, LBBB with QRS ≥ 150 ms (greatest benefit).
• LVAD / heart transplantation for end-stage (stage D) disease.

Management of HFpEF

For decades "no therapy improved mortality." The game-changer: SGLT2 inhibitors (empagliflozin/dapagliflozin) are now the cornerstone and reduce HF hospitalisations across the EF spectrum (EMPEROR-Preserved, DELIVER). Otherwise — treat the underlying driver: control hypertension, manage AF and rate, treat ischaemia, and use diuretics for congestion. MRA (spironolactone) and ARNI have a IIb role.

Acute Decompensated Heart Failure (ADHF) — A High-Yield Vignette

The classic exam scenario: acute breathlessness, frothy sputum, basal crepitations, raised JVP.

Initial management mnemonic "LMNOP":

• L — Lasix (IV furosemide) / loop diuretic for fluid overload.
• M — Morphine (used cautiously; relieves anxiety/preload — falling out of favour).
• N — Nitrates (IV nitroglycerin) — venodilator, reduces preload; first-line if BP adequate.
• O — Oxygen / non-invasive ventilation (CPAP) for hypoxia and pulmonary oedema.
• P — Position (sit up) / Pressors if shocked.

Sit up + high-flow O₂/CPAP → IV loop diuretic → IV nitrate (if SBP > 110) → reassess → inotropes/vasopressors only if hypoperfusion/cardiogenic shock.

High-yield: In acute pulmonary oedema with adequate BP, IV nitroglycerin (preload reduction) plus IV furosemide are first-line. Inotropes (dobutamine) and vasopressors (noradrenaline) are reserved for cardiogenic shock — they increase mortality if used routinely.

The Forrester/clinical "wet–cold" classification guides ADHF therapy:

Profile	Congestion (wet/dry)	Perfusion (warm/cold)	Action
A	Dry	Warm	Adjust oral therapy
B	Wet	Warm	Diuretics ± vasodilators
C	Wet	Cold	Inotropes + diuretics (cardiogenic shock spectrum)
L	Dry	Cold	Cautious fluids/inotropes

Complications

• Arrhythmias — AF (worsens HF), ventricular tachyarrhythmias → sudden cardiac death (a leading mode of death in HF).
• Cardiorenal syndrome — bidirectional heart–kidney dysfunction.
• Cardiac cachexia — poor prognostic marker.
• Thromboembolism — mural thrombus, stroke (especially with AF / low EF).
• Cardiac cirrhosis, functional mitral/tricuspid regurgitation, hepatic/renal congestion.
• Cardiogenic shock — end-stage acute decompensation.

Key Differentials

The breathless, oedematous patient — distinguish HF from:

• COPD/asthma exacerbation — BNP normal, history of smoking/wheeze; "cardiac asthma" can mimic.
• Pneumonia/ARDS — fever, consolidation, normal BNP.
• Nephrotic syndrome / cirrhosis / hypoalbuminaemia — oedema with normal JVP and clear lungs.
• Pulmonary embolism — sudden dyspnoea, pleuritic pain, raised JVP but clear lungs.
• Constrictive pericarditis / tamponade — raised JVP with Kussmaul sign/pulsus paradoxus.
• Venous insufficiency — bilateral leg oedema without congestion.

Recently asked / exam angle

• Framingham criteria — number of major/minor required (2 major OR 1 major + 2 minor); weight loss with treatment is a major criterion; identifying whether S3, PND, hepatojugular reflux are major or minor.
• Four pillars of HFrEF and which classes reduce mortality vs only symptoms (diuretics/digoxin = symptomatic only).
• SGLT2 inhibitors now benefiting HFpEF (EMPEROR-Preserved/DELIVER) — a hot, frequently tested update.
• ARNI vs ACEi (PARADIGM-HF), and the BNP vs NT-proBNP caveat on sacubitril.
• Contraindicated drugs in HFrEF — NSAIDs, verapamil/diltiazem, pioglitazone.
• CRT criteria — LBBB with QRS ≥ 150 ms, EF ≤ 35%, sinus rhythm.
• ADHF / acute pulmonary oedema vignette — first-line nitrate + furosemide; inotropes only for shock.
• High-output failure causes (anaemia, beriberi, thyrotoxicosis, AV fistula, Paget, pregnancy).
• Investigation of choice — echo (structural), BNP (rule-out).
• S3 vs S4 gallop correlation with systolic vs diastolic dysfunction.

Rapid revision

1. HFrEF = EF ≤ 40% (systolic); HFpEF = EF ≥ 50% (diastolic, elderly hypertensive diabetic female).
2. Commonest cause of right HF = left HF; commonest causes of HF overall = CAD and hypertension.
3. Framingham: 2 major OR 1 major + 2 minor; weight loss with diuretic = major criterion.
4. Echo = investigation of choice for type/EF; BNP/NT-proBNP = best rule-out test in acute dyspnoea.
5. Four pillars of HFrEF: ARNI + beta-blocker + MRA + SGLT2 inhibitor — start early, up-titrate.
6. Mortality-reducing classes: ACEi/ARB/ARNI, beta-blockers, MRA, SGLT2i, hydralazine-nitrate; diuretics & digoxin = symptomatic only.
7. Only carvedilol, bisoprolol, metoprolol succinate (± nebivolol) are proven beta-blockers in HF.
8. Avoid in HFrEF: NSAIDs, verapamil/diltiazem, pioglitazone.
9. SGLT2 inhibitors help HFpEF too (EMPEROR-Preserved, DELIVER) — newest high-yield update.
10. CRT: LVEF ≤ 35% + LBBB + QRS ≥ 150 ms + sinus rhythm; ICD: LVEF ≤ 35% on GDMT.
11. Acute pulmonary oedema: sit up, O₂/CPAP, IV nitrate + IV furosemide; inotropes only in cardiogenic shock.
12. S3 gallop = volume overload/HFrEF; S4 = stiff ventricle/HFpEF; Kerley B lines = interstitial oedema.