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PA26.3 | Heart Failure — SDL Guide (Part 3)

Pathology of the Failing Heart

A multi-panel pathology diagram compares gross and microscopic structural changes in the failing heart, including dilatation, hypertrophy, pale flabby myocardium, mural thrombus, fibrosis, myocyte loss, and ischemic injury stages. — **Panel A:** Normal adult heart, failing enlarged heart, ventricular dilatation, pale flabby myocardium, left ventricular mural thrombus, thickened ventricular wall, widened ventricular cavity. **Panel B:** Concentric LV hypertrophy, eccentric LV hypertrophy, pressure-loaded wall, volume-loaded dilated cavity, LV wall thickness greater than 15 mm. **Panel C:** Hypertrophied cardiomyocytes, enlarged muscle fibers, large box-car nuclei, intercalated discs. **Panel D:** Interstitial fibrosis, replacement fibrosis, collagen deposition, surviving cardiomyocytes, myocyte apoptosis and necrosis. **Panel E:** Acute coagulative necrosis, subacute granulation tissue, healed dense collagenous scar, ischemic heart disease progression.

The heart itself undergoes predictable structural changes that vary by aetiology and duration.

Gross pathology:
- Dilatation: all types of heart failure that have progressed sufficiently show ventricular enlargement. The cavity appears widened; in severe cases the heart may weigh 2-3× normal (normal ~300-350 g in adults).
- Hypertrophy: wall thickness > 15 mm (LV) is hypertrophy. Concentric = pressure-loaded wall, eccentric = volume-loaded thinned wall.
- Pale, flabby myocardium: in dilated cardiomyopathy or end-stage ischaemic disease, the myocardium appears pale and soft (fatty change, atrophy, fibrosis).
- Mural thrombi: in dilated, poorly contractile ventricles, stasis predisposes to mural thrombus formation (see complications below).

Microscopic pathology:
- Cardiomyocyte hypertrophy: enlarged cells with large, "box-car" nuclei.
- Interstitial and replacement fibrosis (activated by angiotensin II, TGF-β, aldosterone).
- Myocyte loss by apoptosis and necrosis.
- In ischaemic heart disease: coagulative necrosis (acute), granulation tissue (subacute), dense collagenous scar (healed).

Complications of Heart Failure

⚑ AI image — pending faculty review (auto-QA score 6/10; best of 3 attempts)

A hub-and-spoke medical diagram shows heart failure causing cardiac arrhythmias, thromboembolism, renal dysfunction, hepatic congestion, cachexia, and respiratory complications. — **Panel A:** Dilated failing heart, hypertrophied myocardium, reduced cardiac output, pulmonary venous congestion, systemic venous congestion. **Panel B:** Atrial fibrillation, ventricular tachycardia, ventricular fibrillation, fibrotic myocardium, sudden cardiac death. **Panel C:** Mural thrombus, fibrillating atrium, systemic arterial emboli, stroke, mesenteric ischaemia, limb ischaemia, deep vein thrombosis, pulmonary embolism. **Panel D:** Reduced renal perfusion, raised renal venous pressure, decreased GFR, acute kidney injury, chronic kidney disease, RAAS activation. **Panel E:** Congestive hepatomegaly, dilated hepatic veins, centrilobular congestion, cardiac cirrhosis, synthetic failure. **Panel F:** Cardiac cachexia, loss of fat and lean mass, TNF-alpha, IL-6, malabsorption, anorexia, pulmonary oedema, respiratory infection.

Heart failure is not a static endpoint — it spawns a cascade of complications across multiple organs.

Cardiac complications:
- Arrhythmias: the hypertrophied, fibrosed, neurohormone-bathed myocardium is an arrhythmogenic substrate. Atrial fibrillation is present in up to 50% of patients with advanced HF. Ventricular arrhythmias (VT/VF) cause sudden cardiac death — the commonest mode of death in HF (competing with progressive pump failure).
- Sudden cardiac death: accounts for ~50% of HF mortality, predominantly via ventricular arrhythmia.

Thromboembolic complications:
- Mural thrombus in dilated ventricles or fibrillating atria → systemic arterial emboli → stroke, mesenteric ischaemia, limb ischaemia.
- Venous stasis (low cardiac output + immobility) → deep vein thrombosis → pulmonary embolism.

Renal dysfunction (cardiorenal syndrome):
- Reduced renal perfusion (low cardiac output) + venous congestion (raised renal venous pressure) → ↓GFR → acute kidney injury or progressive chronic kidney disease. RAAS activation worsens this cycle.

Hepatic dysfunction:
- Congestive hepatomegaly, cardiac cirrhosis (as above). Synthetic failure in advanced cases.

Cardiac cachexia:
- Progressive weight loss (fat + lean mass) in chronic HF. Mechanisms: reduced mesenteric perfusion → malabsorption; elevated pro-inflammatory cytokines (TNF-α, IL-6) → catabolism; anorexia from hepatic distension.

Respiratory failure: in acute decompensated LHF — alveolar oedema → hypoxaemia → respiratory acidosis if severe.

Staging, Classification, and BNP as Biomarker

Three-panel medical infographic comparing NYHA symptom classes, ACC/AHA heart failure stages, and BNP release from a stretched ventricle as a biomarker. — **Panel A:** NYHA Functional Classification with Class I, Class II, Class III, and Class IV symptom severity tiers and activity/rest icons.. **Panel B:** ACC/AHA heart failure staging from Stage A to Stage D with unidirectional progression and heart silhouettes showing increasing structural and clinical severity.. **Panel C:** BNP biomarker mechanism showing ventricular wall stretch, cardiomyocyte BNP release, bloodstream transport, BNP/NT-proBNP blood test, and diagnostic/prognostic clinical relevance..

NYHA Functional Classification (symptoms-based):

Class	Description
I	No limitation; ordinary activity does not cause symptoms
II	Slight limitation; comfortable at rest; symptoms on moderate exertion
III	Marked limitation; comfortable at rest; symptoms on minimal exertion
IV	Unable to carry out any activity without symptoms; symptoms at rest

ACC/AHA Staging (structural disease progression — unidirectional, not reversible):

Stage	Description
A	Risk factors present; no structural heart disease
B	Structural heart disease; no symptoms
C	Structural disease + current or prior HF symptoms
D	Refractory HF requiring advanced intervention (LVAD, transplant)

Note: A patient can remain at Stage C while fluctuating between NYHA Class II and IV. Stages A/B represent the preventable window.

Brain Natriuretic Peptide (BNP):
BNP (and its cleavage product, NT-proBNP) is synthesised and secreted by ventricular cardiomyocytes in response to wall stretch and increased filling pressure. It acts as an endogenous counter-regulator: promotes natriuresis, vasodilation, and inhibits RAAS — but is insufficient at advanced stages.

Clinical utility:
- BNP < 100 pg/mL: HF very unlikely in a patient presenting with dyspnoea (high negative predictive value).
- BNP > 400 pg/mL: HF highly likely.
- Serial BNP guides treatment intensity — falling BNP with treatment correlates with improved prognosis.
- Elevated in: any cause of ventricular wall stress (PE, severe hypertension, CKD — the latter reduces clearance).

SELF-CHECK

A 65-year-old man with ischaemic cardiomyopathy has NYHA Class III symptoms. He is admitted with decompensation and a new stroke due to systemic embolism. Which mechanism BEST explains the embolic stroke?

A. Paradoxical embolism through a patent foramen ovale

B. Mural thrombus in a poorly contractile, dilated left ventricle

C. Right ventricular thrombus dislodging into the pulmonary circulation

D. Atherosclerotic plaque rupture in the carotid artery

Reveal Answer

Answer: B. Mural thrombus in a poorly contractile, dilated left ventricle

In dilated, hypokinetic left ventricles — characteristic of ischaemic cardiomyopathy — stasis of blood promotes mural thrombus formation on the endocardial surface, particularly at the apex. Fragments can embolise systemically causing stroke, mesenteric ischaemia, or limb ischaemia. This is a direct complication of impaired LV systolic function. RV thrombus would embolise to the pulmonary circulation (not systemic), and carotid atherosclerosis is a separate pathology.

Integrated Summary: Left vs Right Heart Failure at a Glance

Side-by-side diagram comparing left heart failure causing pulmonary venous hypertension and pulmonary oedema with right heart failure causing systemic venous hypertension, raised JVP, liver congestion, ascites, and dependent oedema. — **Panel A:** Left heart failure with left atrium, left ventricle, pulmonary veins, pulmonary venous hypertension, pulmonary oedema, crepitations, dyspnoea, orthopnoea, PND, normal or mildly raised JVP, and late systemic oedema.. **Panel B:** Right heart failure with right atrium, right ventricle, superior vena cava, inferior vena cava, raised JVP, systemic venous hypertension, congestive hepatomegaly, nutmeg liver, cardiac cirrhosis, ascites, splenomegaly, and bilateral dependent pitting oedema.. **Panel C:** Integrated comparison table summarizing primary causes, haemodynamic effects, main affected organs, lung involvement, liver findings, JVP changes, oedema pattern, ascites, and splenomegaly..

Feature	Left Heart Failure	Right Heart Failure
Primary cause	IHD, HTN, mitral/aortic valve disease, dilated CM	LHF (most common), cor pulmonale, right-sided MI
Haemodynamic effect	Pulmonary venous hypertension	Systemic venous hypertension
Lungs	Pulmonary oedema (orthopnoea, PND, crepitations)	Relatively spared (unless also left-sided)
Liver	Normal or mildly congested	Congestive hepatomegaly, nutmeg liver, cardiac cirrhosis
JVP	Normal or mildly raised	Markedly raised
Oedema	Pulmonary (+ later systemic if biventricular)	Bilateral dependent pitting oedema
Ascites/splenomegaly	Absent unless biventricular	Present in significant RHF
Characteristic cell	Heart failure cells (alveolar siderophages)	Centrilobular hepatocyte necrosis
BNP	Elevated	Elevated (both ventricles can release BNP)

When both ventricles fail — congestive heart failure (CHF) — all of the above features coexist. In clinical practice, biventricular failure is far more common than pure left- or right-sided failure in late disease.