Pressure Overload Ventricle & Pathologic Mechanisms affecting Valves

Pressure Overload and Heart Failure

• Pressure overload can lead to heart failure, where the heart cannot pump enough oxygenated blood to meet the body's metabolic demands.
• This results in blood backing up in the venous system, leading to oedema.
• The body's compensatory mechanisms can only handle so much before heart failure occurs.

Pathophysiology of Pressure Overload

• Myocyte damage and death, such as in myocardial infarction (MI).
• Inherited myocyte changes, like cardiomyopathy.
• Hypertension.
• Kidney dysfunction.
• Early response involves baroreceptors and chemoreceptors activating the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS).
• Cardiac Output (CO) is calculated as: CO = HR \, x \, SV where HR is heart rate and SV is stroke volume.
• The SNS increases heart rate and calcium availability to myocytes.
• The RAAS increases blood volume, ventricular filling, and stroke volume.

Ventricular Remodelling

• Compensatory mechanisms become unbalanced, leading to ventricular remodelling.
• Increased SNS activity, but reduced responsiveness of cardiac tissue.
• Decreased activity and sensitivity to parasympathetic nervous system (PNS) innervation.
• Myocyte hypertrophy occurs.

Key Parameters for Heart Function

• Three parameters must be in balance for the heart to function properly:
  1. Preload: Ventricular stretch due to ventricular filling. Reduced in conditions like varicose veins due to venous blood pooling.
  2. Afterload: Pressure the ventricle must overcome to open semilunar valves and eject stroke volume. Increased by atherosclerosis, hypertension, and valve stenosis.
  3. Inotropy (Contractility): Ability of myocytes to contract and relax. Affected by MI.

Left-Sided Heart Failure

• Causes: MI, hypertension, infective endocarditis, congenital heart defects, valve defects, cardiomyopathy.
• Triggered by changes in ANS balance (↑ SNS, ↓ PNS) and myocyte function.
• Leads to:
  • Tachycardia.
  • Increased preload.
  • Shift from α-myosin to β-myosin.
  • Altered contraction and hypertrophy.
  • Decreased calcium mobilisation.
  • Pump failure.
  • Reduced exercise tolerance, oedema, increased jugular venous pressure (JVP), cardiomegaly, pulmonary oedema.
  • Increased hypoxia and oxygen demand of the heart.

Right-Sided Heart Failure

• Causes: Left-sided heart failure, pulmonary hypertension, chronic pulmonary disease, congenital heart defects, valve defects, pulmonary embolism.
• Triggered by changes in ANS balance (↑ SNS, ↓ PNS) and myocyte function.
• Leads to:
  • Tachycardia.
  • Increased afterload.
  • Shift from α-myosin to β-myosin.
  • Altered contraction and hypertrophy.
  • Decreased calcium mobilisation.
  • Pump failure.
  • Reduced exercise tolerance, oedema, increased JVP, cardiomegaly.
  • Pulmonary oedema, increased hypoxia and oxygen demand.

Risk Factors for Heart Failure

1. Ischaemic heart disease.
2. Hypertension.
3. Venous insufficiency (e.g., varicose veins).
4. Valve disorders.
5. Cardiomyopathies.
6. Congenital heart defects.

Hypertrophy vs. Hyperplasia

• Hypertrophy: Enlargement of an organ or tissue due to an increase in the size of its cells, often due to increased demand.
• Hyperplasia: Enlargement of an organ or tissue due to an increase in the number of cells, often an early stage in cancer development.

Infective Endocarditis (IE)

• Common risk with valve or congenital defects.
• Patients with IE often require prophylactic antibiotics before surgical or dental procedures.
• Untreated IE is almost always fatal; treatment reduces mortality to ~30%.
• Common routes of infection: IV drug use (non-sterile needles) and poor oral hygiene.
• Colonization/invasion of heart valves or endocardium by microbes, leading to bulky, friable vegetations composed of fibrin, neutrophils, and organisms.
• Streptococcus viridans typically affects previously damaged valves.
• Staphylococcus aureus can affect healthy or deformed valves.

IE Diagnosis

• Based on modified Duke diagnostic criteria:
  1. Microbiology.
  2. Histology.
  3. Clinical manifestations.
• Positive blood cultures (Streptococcus or Staphylococcus).
• Radiology: Positive echocardiogram and evidence of new valvular regurgitation.
• Other factors: Previous IE diagnosis, predisposition (e.g., prosthetic valve), fever (>38°C), vascular phenomena (arterial emboli, pulmonary infarcts), immunological phenomena (glomerulonephritis, rheumatic factor).

IE Complications

• Can include abscesses in various sites and septic emboli in various organs (kidneys, spleen, brain).

Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD)

• Acute rheumatic fever is a multisystem disease resulting from an autoimmune reaction to group A streptococcus (e.g., Beta-haemolytic strep - S. pyogenes).
• While many body parts can be affected, most manifestations resolve completely.
• Cardiac valvular disease (RHD) may persist.

RHD Pathophysiology

• Group A Streptococcus leads to inflammation and scarification of cardiac valves.
• All three heart layers (endocardium, myocardium, pericardium) can be affected.
• Attack on cardiac valves is an extension of myocardial damage.
• Cell death in valves leads to scar tissue build-up, causing valve stiffening and potential permanent opening.

Pathological Changes in Acute RF

• Focal inflammatory lesions in various tissues.
• Aschoff bodies in the myocardium (interstitial, perivascular) – collections of lymphocytes and plump macrophages around fibrinous necrosis.
• Characteristic Anitschkow cells are present.

Chronic RF - RHD

• Aschoff bodies are replaced by fibrosis.
• Affects valves: sterile vegetations, dystrophic calcification, valvular insufficiency (most commonly mitral valve > aortic valve).

Classification of Valve Defects

• Valve Stenosis: Increased volume overload due to failure to eject adequate volume.
• Valve Regurgitation: Increased volume overload due to ejected volume returning to the chamber.

Valve Stenosis

• More common on the left side of the heart.
• Senile stenosis: Wear and tear with age → calcifications → vegetations → stiffening → scarification → fusion of leaflets → chamber struggles to open valve → myocyte hypertrophy.
• Stenosis increases afterload pressure on the chamber facing the valve; AV valve stenosis reduces preload.

Valve Regurgitation

• All cardiac valves can be affected.
• Primary problem: volume overload → increased preload → valve damage → failure to eject adequate stroke volume → decreased cardiac output → ventricular hypertrophy → increased regurgitation.

Consequences of Mitral Stenosis

• Left atrial dilatation, thrombus formation, and subsequent embolism.
• Pulmonary congestion.
• Right ventricular hypertrophy.
• Right heart failure.

Aortic Regurgitation Causes

• Rigidity (rheumatic, degenerative).
• Destruction (microbial endocarditis).
• Collapse (prolapse through VSD, myxomatous degeneration).
• Diseases of aortic valve ring (dilatation).
• Cystic medial degeneration.
• Marfan's Syndrome.
• Dissecting aneurysm (medial degeneration/hypertension).
• Syphilitic aortitis.
• Ankylosing spondylitis.

Myxomatous Mitral Valve/Mitral Valve Prolapse

• Clinical presentation: Middle-aged woman, shortness of breath, chest pain, mid-systolic click, late systolic murmur; echocardiogram shows mitral valve billowing backwards, regurgitation.
• Morphology: Stretched, redundant valves (usually mitral).
• Histology: Increased glycosaminoglycans (prominent on Alcian Blue stain).
• Complications: Mitral prolapse, insufficiency, secondary infective endocarditis, sudden cardiac death (uncommon); some patients may have Marfan's.

Oedema

• Excessive accumulation of serous fluid in intercellular spaces due to:
  1. Increased capillary permeability.
  2. Increased blood hydrostatic pressure.
  3. Decreased blood osmotic (oncotic) pressure.
  4. Obstruction of lymphatic flow.
  5. Combination of the above.
• Pitting oedema: Indentation remains after finger pressure is removed.

Risk Factors for Oedema

1. Pregnancy.
2. Congestive heart failure.
3. Kidney disease.
4. Obstructive kidney disease (e.g. cirrhosis).
5. Lymphatic obstruction.
6. DVT.
7. Chronic venous insufficiency.
8. Medications: Vasodilators and NSAIDs.

Mechanisms of Oedema Formation

• Venous obstruction, increased intake/retention of H2O/Na+, endocrine imbalance, lymphatic obstruction, plasma protein deficit, increased inflammatory mediators, increased ADH and RAAS, increased capillary hydrostatic pressure, decreased capillary osmotic pressure, increased capillary permeability.
• Can lead to lymphoedema, cerebral oedema, pulmonary oedema, ascites, peripheral oedema.

Clinical Manifestations of Oedema

• Location: One region (finger, foot, organ) or systemic (ascites).
• Manifestations: Depends on the tissue affected; organ dysfunction (heart, lungs, brain) can be life-threatening.
• Hypoxaemia and hypoxia.
• Hypercapnia.
• Altered blood pressure and tissue perfusion.
• Headaches, convulsions, loss of consciousness.

Oedema vs. Ascites

• Oedema: Fluid accumulated in interstitial space.
• Ascites: Fluid accumulates in interstitial space and leaks into the peritoneal cavity.

Summary

• Myocardial damage, cardiomyopathies, hypertension, and renal dysfunctions lead to pressure overload on the heart.
• Pressure overload leads to cardiac failure.
• Valve defects (stenosis and regurgitation) contribute.
• Risk factors include IHD, HT, valve disorders, cardiomyopathies, congenital heart diseases.
• Infective endocarditis is a high risk in valve and congenital defects; untreated is 100% fatal.
• IE diagnosis is based on blood culture, imaging (Echo), and clinical features.
• IE leads to complications: abscess, septic emboli, septic infarctions.
• Oedema is the accumulation of excess fluid in interstitial spaces.