Heart failure

Question 1

Definition of heart failure

Answer 1

Question 2

Physiological control of cardiac output

Answer 2

Question 3

Response to increased demand on the heart in physiological state vs heart failure

Answer 3

Question 4

Significance of the circulatory system . being a closed loop

Answer 4

Because the circulatory system is a closed loop, heart failure on either side would eventually lead to biventricular failure

Question 5

Overview of causes of heart failure

Answer 5

Question 6

Common causes of heart failure

Answer 6

• Ischaemic heart disease
• hypertension
• valvular disease- mitral and aortic
• shock

Question 7

Molecular changes that occur in heart failure

Answer 7

1. induction of foetal genes: alpha myosin to beta myosin, which is less efficienct at contracting
2. abnormal protein synthesis: ion channels, contractile proteins. abnormal excitation/contraction coupling.
3. production of cytokines, growth factors and neurohormones: eg noradrenaline, angiotensin by myocytes or stromal cells. results in autocrine/paracrine loops causing local myocyte damage–once initiated they may result in ongoing myocardial damage

Question 8

Myocardial Remodelling in heart failure

Answer 8

(debate as to whether it’s a cause or effect of heart failure)

Myocardial cells

• hypertrophy: thickening by increasing the number of sarcomeres eg left ventricular wall
• lengthening: sarcomeres overlap. associated with ventriuclar dilatation and more advanced disease

Changes in ECM

-fibrosis triggered by Ang2 and aldosterone. Alter the way forces are transmitted through the myocardium

Myocardial death

Apoptosis triggered by SNS, Ang2 and other local factors

Changes in heart shape

• heart becomes more globular and spherical
• this is a macroscopic change
• poor mechanics- increases end-diastolic wall stress
• pulls apart papillary muscles of mitral/tricuspid valves

Question 9

Macroscopic appearance of heart in heart failure

Answer 9

• ventricular dilatation
• compensatory hypertrophy: weight and thickness

General rule of thumb:

a) Pressure overload–>hypertorphy
b) Volume overload–>hypertrophy AND dialtation
- might detect underlying cause: amyloid, HOCM, infarction etc

Question 10

Microscopic appearance of heart in heart failure

Answer 10

Question 11

What are the broad categories of intrinsic diseases of the heart?

Answer 11

Ones affecting the:

myocardium

endocardium

pericardium

valves

(but main cause of HF is obviously IHD)

Question 12

3 patterns of myocardial disease (Cardiomyopathies)

Answer 12

1. dilated cardiomyopathy
2. hypertorphic cardiomyopathy
3. restrictive cardiomyopathy

Question 13

Most common cardiomyopathy

Answer 13

Dilated cardiomyopathy

Question 14

What happens in Dilated cardiomyopathy?

Answer 14

• increased mass- slight, due to hypertrophy
• but most importantly- THINNED walls as CHAMBER DILATES
• macro: globular heart
• micro: (non-specific) hypertrophy and fibrosis

Question 15

Patohgenesis of DCM

Answer 15

Question 16

Inflammatory causes of dilated cardiomyopathy (i.e. myocarditis)

Answer 16

Infection: viral, bacterial (less common), protozoal (trypanosome)

Drug: hypersensitivity reaction to a drug

Systemic: SLE, amyloid

Idiopathic: giant cell myocarditis

Question 17

Familial hypertrophic cardiomyopathy

Answer 17

A cause of hypertrophic cardiomyopathy

Question 18

Microscopic changes in Familial HOCM

Answer 18

Myocyte disarray (not aligned) and fibrosis.

This leads to arrythmias.

Question 19

Pathogenesis of HOCM

Answer 19

Question 20

What is restrictive cardiomyopathy?

Answer 20

Heart muscle is unable to relax so ventricles can’t fill properly.

This could be because of abnormalities in the heart MUSCLE itself (myocardium) or because of abnormalities in the PERICARDIUM/ENDOCARDIUM.

Myocardial: amyloid

Pericardial fibrosis

Endocardial fibrosis

Question 21

2 broad categories of cardiac amyloid (a cause of restrictive cardiomyopathy)

Answer 21

1. senile atrial amyloid
   - amyloid is derived from ANP
   - normal ageing change
2. systemic
   - AL amyloid: produced in myeloma
   - AA amyloid: produced in autoimmune diseases like RA
   - can be hereditary

Essentially amyloid protein deposits in the myocardium and impairs normal function of muscle

Question 22

Causes of endomyocardial fibrosis

Answer 22

Question 23

How can disease of pericardium cause heart failure?

Answer 23

Constrictive pericarditis

Can happen following bacterial or viral pericarditis, for eg

Question 24

Which valve diseases can cause heart failure and how?

Answer 24

Mitral

Mitral regurgitation- leads to volume overload

Aortic

Aortic stenosis- leads to pressure overload

Aortic regurgitation- leads to volume overload

Question 25

Macro changes in valvular heart failure

Answer 25

Question 26

How does congenital heart disease cause heart failure?

Answer 26

**Ventricular septal defect** Causes right ventricular hypertrophy as blood flows from left ventricle into the right ventricle upon systole. Pressure in thin walled right ventricle rises, causing right heart failure

Question 27

Extrinsic causes of heart failure

Answer 27

1. Pulmonary hypertension--\>right heart failure 2. Systemic hypertension--\>right heart failure

Question 28

Causes of pulmonary hypertension

Answer 28

**obstruction or destruction of pulmonary vessels** - pulmonary fibrosis - pulmonary thromboembolic disease eg DVT **chronic hypoxia**- this will cause pulmonary vessels to vasoconstrict (to shunt blood away from poorly ventilated areas) - COPD - lung fibrosis - cystic fibrosis

Question 29

Complications of heart failure

Answer 29

**Local** 1. arrythmias, sudden cardiac death 2. further ischaemic myocardial damage **Systemic** 1. Left sided HF a) Forward failure: **hypoperfusion** of Kidneys, GI tract and brain b) Backward failure: pulmonary congestion and oedema 2. Right sided HF a) Forward failure: not that important b) Backward failure: systemic oedema and organ congestion (**nutmeg liver-** impaired liver function)

Question 30

Schematic of systemic hypoperfusion of kidneys

Answer 30