Heart Failure - Comprehensive High-Yield Review

1. Definition

• HFrEF (Heart Failure with Reduced EF, formerly "systolic HF"): EF < 40%
• HFpEF (Heart Failure with Preserved EF, formerly "diastolic HF"): EF ≥ 50%
• HFmrEF (Mid-range EF): EF 40-49%

2. Epidemiology & Etiology

• Ischemic Heart Disease (IHD) - most common cause in developed countries
• Hypertension
• Valvular heart disease (aortic stenosis/regurgitation, mitral regurgitation)
• Dilated cardiomyopathy
• Diabetes mellitus

• Alcohol/toxin-induced cardiomyopathy
• Viral myocarditis
• Thyroid disease (both hypo and hyper)
• Haemochromatosis, amyloidosis
• Peripartum cardiomyopathy
• Chagas disease (endemic regions)

3. Pathophysiology

3a. The Central Concept: Cardiac Overload and Hypertrophy

Fig. 12.2 - Causes and consequences of cardiac hypertrophy (Robbins & Cotran)

• Interstitial fibrosis
• Induction of fetal gene program (re-expression of embryonic myosin isoforms - less efficient)
• Mitochondrial dysfunction
• Calcium handling abnormalities (impaired SERCA2a activity)

Fig. 12.1 - Left ventricular hypertrophy. (A) Pressure hypertrophy (LV outflow obstruction). (B) Cross-sections comparing normal (center), concentric pressure-hypertrophied (left), and hypertrophied-dilated (right) hearts. Note: in dilated hearts, wall thickness may appear normal but heart weight is markedly increased (Robbins & Cotran)

3b. The Four Interrelated Systems (Goodman & Gilman)

1. The heart itself - loss of muscle mass, overload, genetic cardiomyopathy
2. The vasculature - increased afterload, impaired peripheral vasodilation
3. The kidney - sodium and water retention, cardiorenal syndrome
4. Neurohumoral regulatory circuits - the most clinically important axis

3c. Neurohumoral Activation (HIGH YIELD)

1. Sympathetic nervous system activation
   • Increases heart rate and contractility (initially compensatory)
   • Causes vasoconstriction (maintains BP)
   • Chronically: downregulates β1-receptors, causes myocyte apoptosis, promotes arrhythmias
2. RAAS activation (Renin-Angiotensin-Aldosterone System)
   • Low renal perfusion → Renin release → Angiotensin I → ACE → Angiotensin II
   • Angiotensin II: vasoconstriction, aldosterone secretion, myocardial fibrosis, sympathetic amplification
   • Aldosterone: Na+ and water retention, K+ wasting, contributes to myocardial fibrosis
3. ADH/Vasopressin (AVP) release
   • Free water retention → hyponatremia in advanced HF
   • Vasoconstriction via V1 receptors
4. Endothelin-1 - potent vasoconstrictor, promotes fibrosis

• Natriuretic Peptides (ANP, BNP, CNP): released in response to wall stretch
  • Cause natriuresis, vasodilation, and oppose RAAS
  • BNP levels are used diagnostically (see biomarkers section)
• Nitric Oxide (NO): vasodilatory, impaired in chronic HF

4. Classification (HIGH YIELD - Must Know)

ACC/AHA Staging (emphasizes disease progression):

NYHA Functional Classification (for therapy eligibility and prognosis):

Key exam point: NYHA class determines eligibility for MRAs (Class II-IV), CRT (Class III-IV), LVAD/transplant (Class IV). The ACC/AHA staging does not go backward - once Stage C, always Stage C.

5. Clinical Features

Left-Sided Heart Failure (Pulmonary Congestion + Low Output)

• Dyspnea - cardinal symptom; initially on exertion, then at rest
• Orthopnea - dyspnea when supine; relieved by sitting up (report by number of pillows)
• Paroxysmal Nocturnal Dyspnea (PND) - sudden dyspnea at night; highly specific for LHF
• Fatigue, reduced exercise tolerance
• Cough (sometimes pink/frothy sputum in severe pulmonary edema)
• Cheyne-Stokes respiration (in advanced HF, often with co-existing sleep apnoea)
• Nocturia (recumbency increases renal perfusion at night)

• Tachycardia
• Displaced apex beat (cardiomegaly)
• S3 gallop (ventricular filling sound; highly specific for volume overload/HFrEF; heard best at apex with bell in left lateral decubitus)
• S4 gallop (atrial kick against a stiff ventricle; more common in HFpEF)
• Fine crepitations/crackles at lung bases (pulmonary edema)
• Reduced air entry + dullness (pleural effusion - typically right-sided or bilateral)
• Pulsus alternans (in severe LHF)
• Raised JVP (when LHF has caused RHF)

• Heart failure cells (hemosiderin-laden macrophages) in alveolar spaces - pathognomonic of previous pulmonary edema
• Heavy, wet lungs
• Perivascular and interstitial edema; alveolar edema
• Left atrial dilation → risk of atrial fibrillation and thrombus (especially in atrial appendage)

Right-Sided Heart Failure (Systemic Venous Congestion)

• Peripheral oedema (pitting; worse at end of day)
• Abdominal distension, ascites
• Right upper quadrant pain/discomfort (liver congestion)
• Loss of appetite, early satiety (gut oedema/bowel wall oedema)
• Anasarca in severe cases

• Raised JVP - most reliable sign of RHF; hepatojugular reflux positive
• Pitting pedal/ankle oedema
• Hepatomegaly (tender, pulsatile in tricuspid regurgitation)
• Ascites
• Nutmeg liver on histology - centrilobular congestion (pericentral red-brown zones, periportal tan areas)
• Congestive splenomegaly
• Right ventricular heave (parasternal lift)
• Cardiac cirrhosis in chronic severe RHF

6. HFpEF vs HFrEF - High-Yield Comparison

7. Investigations

Biomarkers (HIGH YIELD)

• BNP and NT-proBNP: Released from ventricular myocytes in response to wall stretch; supported by ACC/AHA Class I recommendation for diagnosis of acute HF and prognosis in chronic HF
  • BNP >100 pg/mL supports diagnosis; NT-proBNP >300 pg/mL (acute) or >125 pg/mL (chronic)
  • Both can be elevated by: CKD, AF, PE, sepsis, obesity (falsely low in obesity)
  • Useful to guide therapy titration in outpatient setting

ECG

• Usually not normal in HF but non-specific
• LVH pattern, LBBB (associated with dyssynchrony - indicates CRT benefit)
• AF (very common comorbidity)
• Old MI changes (Q waves indicating ischemic etiology)
• Prolonged QRS > 120 ms with LBBB → CRT candidate

Chest X-Ray (CXR)

• A - Alveolar oedema ("bat-wing" hilar haziness)
• B - Kerley B lines (horizontal lines in costophrenic angles - interstitial oedema in interlobular septa)
• C - Cardiomegaly (CTR > 0.5 on PA film)
• Upper lobe venous diversion (earliest sign)
• Pleural effusion (blunting of costophrenic angles)

Echocardiography (Most Important Investigation)

• Confirms diagnosis, measures EF, identifies etiology
• Assesses wall motion abnormalities, valvular disease, pericardial disease
• E/A ratio, E/e' ratio for diastolic dysfunction
• Pulmonary artery pressure estimation (TR jet)

Other Investigations

• FBC - anaemia (common, worsens HF)
• Renal function/electrolytes - essential before starting RAAS blockers; CRS
• TFTs - hypo/hyperthyroidism as cause
• LFTs - hepatic congestion (raised bilirubin, ALP, GGT)
• Blood glucose/HbA1c - DM major risk factor/comorbidity
• Iron studies - iron deficiency common, treatable
• Cardiac MRI - gold standard for myocardial characterisation, viability

8. Management (HIGH YIELD)

The "Fantastic Four" - Disease-Modifying Therapy for HFrEF

All four should be initiated and up-titrated to maximum tolerated doses. Diuretics provide symptom relief but do NOT improve survival.

Diuretics (Symptomatic Relief)

• Loop diuretics (Furosemide): First-line for decongestion; rapid onset
• Thiazides (Hydrochlorothiazide): Used in combination with loop diuretics in resistant oedema ("sequential nephron blockade")
• Metolazone: Potent; used with furosemide in refractory oedema - monitor electrolytes closely
• Monitor: Hypokalemia, hyponatremia, prerenal azotemia

Contraindicated/Caution in HF

• NSAIDs - cause sodium retention, worsen renal function, block diuretic effect
• Non-DHP Calcium channel blockers (Diltiazem, Verapamil) - negative inotrope; contraindicated in HFrEF
• Class I antiarrhythmics - proarrhythmic
• Thiazolidinediones (Pioglitazone) - cause fluid retention

Device Therapy (HIGH YIELD)

Acute Decompensated Heart Failure (ADHF)

• LMNOP mnemonic: Lasix (furosemide IV), Morphine (with caution), Nitrates, O2, Positioning (sit upright)
• IV loop diuretics - cornerstone of acute management
• Non-invasive ventilation (CPAP/BiPAP) for respiratory failure
• Inotropes (Dobutamine, Milrinone) for cardiogenic shock
• Nitroprusside for hypertensive emergency with acute HF

9. Prognosis and Prognostic Markers

• 5-year mortality ~50% - worse than most cancers
• Poor prognostic markers:
  • Very low EF (< 20%)
  • NYHA Class IV
  • Very high BNP/NT-proBNP
  • Hyponatremia (reflects severe neurohumoral activation)
  • Renal dysfunction (cardiorenal syndrome)
  • Wide QRS / LBBB
  • Cardiac cachexia (weight loss > 6% in 6 months)

10. High-Yield Exam Points Summary

1. "Heart failure cells" = hemosiderin-laden macrophages in alveoli (from Robbins) - hallmark of old pulmonary oedema
2. "Nutmeg liver" = centrilobular congestion in right-sided HF (pericentral red-brown, periportal tan)
3. S3 gallop = most specific sign of systolic HF/volume overload (Ken-TUC-KY rhythm)
4. Orthopnea and PND are most specific symptoms for left HF
5. JVP raised + pedal oedema = systemic venous congestion (right HF)
6. First-line FOUR drugs (ARNI/ACEi + BB + MRA + SGLT2i) ALL have mortality benefit in HFrEF
7. ICD for EF ≤ 35% (primary SCD prevention); CRT for EF ≤ 35% + QRS ≥ 150 ms LBBB
8. BNP rules out HF if very low; elevated in HF, PE, AF, CKD
9. NYHA Class III-IV = spiro benefit (RALES); Class II = eplerenone benefit (EMPHASIS-HF)
10. Pressure overload = concentric hypertrophy; Volume overload = eccentric/dilated (Robbins)
11. HFpEF = normal or near-normal EF, stiff ventricle, mostly elderly women with hypertension and DM
12. ACC/AHA Stage A = risk factors only, no structural disease - intervene to prevent progression
13. SGLT2 inhibitors now have Class I indication in HFrEF even in non-diabetics
14. Cor pulmonale = right HF from LUNG disease (not from left HF)
15. Kerley B lines on CXR = interstitial pulmonary oedema (fluid in interlobular septa)