Heart Failure — Comprehensive Overview

1. Definition

— Textbook of Family Medicine 9e

2. Types / Classification

A. By Ejection Fraction

B. By Side of Failure

• Left-sided HF: Causes pulmonary congestion → dyspnea, orthopnea, paroxysmal nocturnal dyspnea (PND), pink frothy sputum
• Right-sided HF: Causes systemic venous congestion → JVD, peripheral edema, hepatomegaly, ascites
• Biventricular HF: Both ventricles fail; most chronic HF is ultimately biventricular

C. By Onset

• Acute HF: Rapid onset (e.g., acute MI, flash pulmonary edema)
• Chronic HF: Gradual, compensated or decompensated

D. By Output

• Low-output HF: Most common; reduced cardiac output (IHD, cardiomyopathy, valvular disease)
• High-output HF: Paradoxically high CO (>4 L/min/m²) but still cannot meet demands — causes include hyperthyroidism, beriberi, severe anemia, Paget's disease, arteriovenous malformations, multiple myeloma

E. ACC/AHA Staging (complements NYHA)

F. NYHA Functional Classification

3. Pathophysiology

Primary Mechanism — LV Remodeling

Neurohormonal Activation

• Angiotensin II → cardiac myocyte apoptosis, hypertrophy, ventricular fibrosis
• Angiotensin II → ↑ aldosterone → further adverse remodeling, Na⁺/water retention
• Aldosterone "escapes" ACE inhibitor suppression → need for selective aldosterone blockade

• ↑ Circulating catecholamines → β-adrenoceptor downregulation
• Catecholamines → cAMP-dependent Ca²⁺ overload of myocytes → direct toxicity
• ↑ Myocardial O₂ consumption, LVH, potentially fatal arrhythmias

• ↑ Endothelin-1 (from dysfunctional endothelium) → vasoconstriction
• ↑ Inflammatory cytokines → exacerbate endothelial dysfunction
• ↑ MMPs and tissue inhibitors → cardiac fibrosis and collagen deposition
• Altered Ca²⁺ fluxes, β-adrenergic receptor changes, metabolic shift to glycolysis

Figure: The RAAS and SNS are the primary pharmacological targets in HF. ACE inhibitors/ARBs block Ang II; aldosterone antagonists block aldosterone; β-blockers block catecholamine effects.

Compensatory Mechanisms (and their limits)

Figure (Harrison's): Compensatory responses include ↑ SVR (via SNS/RAAS/ADH), ↑ HR, Frank-Starling mechanism, Na⁺/water reabsorption — all initially preserve CO but worsen HF over time.

4. Clinical Features

Symptoms

Signs

• Displaced, heaving apex beat (LV dilatation)
• S3 gallop (pathological — indicates volume overload/poor systolic function)
• S4 gallop (indicates non-compliant LV — diastolic dysfunction)
• Murmurs (mitral regurgitation from annular dilation)
• Pulsus alternans (severe LV dysfunction)

• Bibasal crepitations (pulmonary edema)
• Dullness to percussion at lung bases (pleural effusion)
• Cheyne-Stokes respiration (in severe HF, low cardiac output to brain)

• Raised JVP
• Hepatojugular reflux
• Pitting pedal/ankle edema → sacral edema (in bedbound)
• Hepatomegaly (tender in acute RHF)
• Ascites (chronic RHF)

Framingham Criteria for HF Diagnosis

5. Diagnosis

Investigations

• May show LVH, LBBB, AF, prior MI (Q waves), or be non-specific
• Wide QRS (>120 ms) — indicates dyssynchrony, relevant for CRT candidacy

• Alveolar edema ("bat-wing" perihilar shadowing)
• B-lines / Kerley B lines (interstitial edema)
• Cardiomegaly (cardiothoracic ratio >0.5)
• Dilated upper lobe veins (cephalization)
• Effusion (pleural — usually bilateral; if unilateral, right > left)

• Confirms LV/RV size and function, wall motion, EF, valve disease, diastolic filling patterns
• Differentiates HFrEF from HFpEF
• Guides therapy (CRT, LVAD, transplant assessment)

• BNP / NT-proBNP: Elevated in HF; highly sensitive; used for diagnosis and monitoring. Elevated BNP (>100 pg/mL) or NT-proBNP (>300 pg/mL) strongly supports HF; levels >400 pg/mL indicate more severe disease
• Troponin: Elevated in acute decompensation or ischemic etiology
• Renal function / electrolytes: Creatinine, eGFR, K⁺ (critical for drug dosing)
• Liver function: ALT, AST, bilirubin (hepatic congestion in RHF)
• CBC: Anemia (precipitant/exacerbant); eosinophilia (eosinophilic myocarditis)
• TFTs: Hypothyroidism/hyperthyroidism as cause

• Cardiac MRI: Gold standard for myocardial viability, infiltrative disease, myocarditis, sarcoidosis
• Coronary angiography: If ischemic etiology suspected or revascularization planned
• Endomyocardial biopsy: For suspected giant cell myocarditis, cardiac sarcoidosis, amyloid (unexplained new HF)
• Cardiopulmonary exercise testing: Objective functional assessment; guides transplant listing (peak VO₂ <14 mL/kg/min = high mortality, transplant consideration)
• Sleep study: OSA/central sleep apnea — highly prevalent and can worsen HF

6. Management

General Principles / Non-Pharmacological

• Salt restriction: <2 g sodium/day
• Fluid restriction: 1.5–2 L/day in moderate-severe HF
• Daily weight monitoring: >2 kg/day rise → contact team
• Cardiac rehabilitation / supervised exercise: Improves functional capacity in stable HFrEF
• Smoking cessation, alcohol limitation (alcohol is a direct myocardial toxin)
• Vaccinations: Annual influenza; pneumococcal
• Avoid NSAIDs (Na⁺ retention, renal impairment), non-DHP CCBs (verapamil/diltiazem in HFrEF), TZDs (fluid retention)

Pharmacological Management — HFrEF (EF <40%)

1. ACE Inhibitors (ACEi) / ARBs

• ACEi (enalapril, ramipril, lisinopril): First-line; block Ang II formation → reduce preload, afterload, and adverse remodeling
• ARBs (valsartan, candesartan): Used if ACEi-intolerant (cough, angioedema)
• Titrate to target dose; monitor renal function and K⁺

2. Beta-Blockers (BB)

• Evidence-based agents: Carvedilol, bisoprolol, metoprolol succinate (not all β-blockers have proven mortality benefit in HF)
• Block SNS activation → ↓ catecholamine toxicity, ↓ HR, ↓ arrhythmias
• Start low, titrate slow; do not initiate in acutely decompensated HF
• CIBIS-II, MERIT-HF, COPERNICUS — landmark mortality-reducing trials

3. Mineralocorticoid Receptor Antagonists (MRA)

• Spironolactone / eplerenone: Block aldosterone's cardiac/renal effects
• Indicated for NYHA class II–IV, LVEF ≤35%
• Monitor K⁺ and creatinine closely (hyperkalemia risk)
• Post-MI with HF → eplerenone (EPHESUS trial)

4. SGLT2 Inhibitors (SGLT2i) — the "new pillar"

• Dapagliflozin / empagliflozin: Reduce HF hospitalization and cardiovascular death
• Benefit seen in both HFrEF and HFpEF
• Recent meta-analysis (PMID: 39731023) confirms safety and effectiveness in acute HF as well

5. ARNI (Angiotensin Receptor-Neprilysin Inhibitor)

• Sacubitril/valsartan (Entresto): Replaces ACEi in symptomatic HFrEF (NYHA II–III)
• Dual mechanism: ARB (blocks AT1R) + neprilysin inhibitor (↑ natriuretic peptides)
• PARADIGM-HF trial: Reduced CV death/HF hospitalization vs. enalapril
• Must washout ACEi for 36 hours before starting to avoid angioedema

6. Diuretics (symptom relief, not mortality benefit)

• Loop diuretics (furosemide, bumetanide): First-line for fluid overload; IV in acute decompensation
• Thiazides: Add-on for diuretic resistance
• Aldosterone antagonists (spironolactone): Both diuretic and prognostic benefit

7. Digoxin

• Reduces hospitalizations; no mortality benefit in HFrEF (DIG trial)
• Consider for symptomatic HFrEF in sinus rhythm refractory to other therapy, or for rate control in AF with HF
• Narrow therapeutic index; target level 0.5–0.8 ng/mL

8. Hydralazine + Isosorbide Dinitrate

• Vasodilator combination; indicated in patients intolerant of ACEi AND ARBs
• Particularly beneficial in African-American patients (A-HeFT trial)

Pharmacological Management — HFpEF (EF ≥50%)

• Symptom control: Diuretics for congestion
• Risk factor treatment: Hypertension (strict BP control), AF rate/rhythm control, diabetes, obesity
• SGLT2 inhibitors: Dapagliflozin (DELIVER trial) and empagliflozin (EMPEROR-Preserved) — reduced HF hospitalizations
• MRAs: Spironolactone may reduce hospitalization (TOPCAT trial, regional subgroup analysis)

Device Therapy

Surgical / Advanced Therapies

• Coronary revascularization (CABG/PCI): When ischemia is the primary etiology and viable myocardium exists
• Valve repair/replacement: For significant mitral or aortic valve disease contributing to HF
• MitraClip: Transcatheter mitral valve repair in HFrEF with secondary MR (COAPT trial)
• Cardiac transplantation: For end-stage HF (NYHA IV), peak VO₂ <14 mL/kg/min, on optimal therapy; ~50% 10-year survival
• CPAP/BiPAP: For coexisting OSA (central sleep apnea may worsen with adaptive servo-ventilation — SERVE-HF trial showed harm)

Management of Acute Decompensated HF

• Positioning: Sit upright (reduces preload)
• O₂/NIV: High-flow O₂; CPAP/BiPAP for pulmonary edema
• IV Loop diuretics: Furosemide IV (reduces preload, relieves congestion)
• Vasodilators: IV nitrates (GTN) for afterload/preload reduction — particularly in hypertensive pulmonary edema
• Inotropes: Dobutamine, milrinone — for cardiogenic shock / severe low output (short-term only; no mortality benefit)
• Vasopressors: Norepinephrine for cardiogenic shock with hypotension
• Continue/restart BB and RAAS therapy as soon as hemodynamically stable
• Identify and treat precipitants: FAILURE mnemonic — Forgot medications, Arrhythmia/Anemia, Ischemia/Infection, Life-style (salt/fluid), Urine output ↓ (renal failure), Raised BP, Embolism (PE)

Summary Table

— Textbook of Family Medicine 9e (Rakel), Braunwald's Heart Disease, Harrison's Principles of Internal Medicine