Pathophysiology of Heart Failure

Question 1

What is afterload?

Answer 1

• The force the contracting heart must generate to eject blood from the heart.
• Main components:
  
  • Vascular resistance; ventricular wall tension.
  • Excessive afterload may impair ventricular ejection and increase wall tension.

Question 2

What is ionotropy and what influences this?

Answer 2

• Ionotropy = myocardial contractility.
• Increased contractility increases CO independent of preload and afterload.
• Influenced by Ca²⁺
  
  • L-type channels - opening facilitated by cAMP.
  • Na⁺/Ca²⁺ exchange - inhibited indirectly by cardiac glycosides.

Question 3

What is heart failure?

Answer 3

In physiological terms, heart failure is a syndrome characterised by either or both pulmonary and systemic venous congestion and / or inadequate peripheral oxygen delivery, at rest or during stress, caused by cardiac dysfunction.

Question 4

Describe the New York Heart Association Classification of Heart Failure (NYHA).

Answer 4

Question 5

Describe the difference between systolic and diastolic dysfunction.

Answer 5

• Classification based on ejection fraction (%).
• Systolic ventricular dysfunction
  
  • Impaired cardiac contractility, therefore ↓ ejection fraction.
  • (<40%; normal ~50-65%).
• Diastolic ventricular dysfunction
  
  • Normal ejection fraction but impaired diastolic ventricular relaxation and decreased filling.
  • Therefore, ↓ in SV and CO.

Question 6

Give examples of conditions that lead to heart failure.

Answer 6

• Those that damage cardiac muscle
  
  • Ischaemic heart disease
  • Cardiomyopathies
  • Myocarditis
• Those that increase the workload of the heart
  
  • Hypertension
  • Valvular disease
  • Severe anaemia
  • Thyrotoxicosis
  • Arteriovenous fistulas

Question 7

What causes systolic dysfunction and what does it result in?

Answer 7

• Commonly results from conditions that affect:
  
  • Contractility
    
    • E.g. IHD, cardiomyopathy
  • Volume overload
  • Pressure overload
    
    • E.g. Valvular stenosis, hypertension
• Results in ↑ EDV (preload), ventricular dilation, ↑ ventricular wall tension.

Question 8

What causes diastolic dysfunction and what does it result in?

Answer 8

• Less common than systolic dysfunction.
• Normal contraction; impaired relaxation.
• Causes:
  
  • Impedance of ventricular expansion
    
    • Constrictive pericarditis etc.
  • Increased wall thickness
    
    • Hypertrophy
  • Delayed diastolic relaxation
    
    • Ageing; ischaemia
  • ↑ heart rate

Question 9

What are the types of cardiomyopathy?

Give examples of each.

Answer 9

• Dilated (85%)
  
  • ​Idiopathic
  • Alcohol toxicity
  • Viral myocarditis
  • Peripartum
  • Drugs (chemotherapeutic)
• Hypertrophic (10%)
  
  • ​Pattern varies
  • Tends to affect the IV septum
• Restrictive (5%)
  
  • ​Amyloidosis
  • Endomyocardial fibrosis

Question 10

Describe how mitral stenosis causes heart failure.

Answer 10

• Ventricle is not filling properly (this is a diastolic dysfunction).
• If blood does not go into L. ventricle, it stays in L. atrium which increases the pressure in the L. atrium. Causes backup into the pulmonary circulation.
• Leads to pulmonary hypertension, pulmonary oedema and inadequate pumping of blood out to the body from the inadequately filled ventricle.
• Most common underlying cause of this is Hx of rheumatic fever.

Question 11

Describe how mitral regurgitation causes heart failure.

Answer 11

• Systolic dysfunction.
• When the heart contracts during systole, rather than the blood going through the aorta into the systemic circulation, some goes back into the left atrium which causes a higher than normal left atrial pressure which leads to pulmonary hypertension, pulmonary oedema and the problem backs up into the right side of the heart.
• Chronic = change in the left side of the heart. Dilated cardiomyopathy driven by mitral regurgitation. If LA pressure is increasing then there is a chronic insidious increase in the EDV inside the ventricle. Less blood is being moved forward into the aorta and there is increased venous return coming into the ventricle leading to a stretch which will decrease the pressure inside the pulmonary circulation because there is greater capacity inside the ventricles.
• The dilated ventricle means change in contractility which exacerbates the systolic dysfunction; there is impaired ability to move blood out of the ventricle and into the aorta and also blood is being lost back into LA because of mitral regurgitation.

Question 12

Describe how aortic stenosis causes heart failure.

Answer 12

• Major causes in adults:
  
  • Degenerative calcification
  • Calcification of a congenitally bicuspid aortic valve (1-2% of the population)
  • Rheumatic aortic valve disease
• Less blood can get out of the heart and into the systemic circulation to meet demand.

Question 13

Describe how aortic regurgitation causes heart failure.

Answer 13

• Backflow of blood into the ventricle due to lack of competence of aortic valve leads to increased pressure inside the ventricle, then the atrium, then subsequent congestion in the pulmonary circulation.
• Chronically, this leads to dilated state; the increased pressure seen in acute aortic regurgitation can lead to distension and change inside the ventricle which helps to normalise the pressure in the atrium and ventricle.
• Despite normalised pressures, there are still the consequences of dilatation of the ventricle as discussed above.

Question 14

What are the causes of heart failure in patients with congenital heart disease?

Answer 14

• Volume overload resulting from left-to-right shunt lesions and valvular regurgitation.
• Pessure overload resulting from valvular disease and other obstructive lesions.
• Ventricular failure related to intrinsic myocardial dysfunction.
• Pulmonary hypertension caused by CHD lesions, ventricular dysfunction, or comorbidities such as obstructive sleep apnoea.
• Systemic arterial hypertension resulting from coarctation, acquired renal disease, essential hypertension or arteriosclerosis.
• Coronary artery disease related to CHD, atherosclerosis, or comorbidities such as DM.
• Cyanosis.
• Intractable atrial arrhythmias.

Question 15

What are the causes of systolic and diastolic dysfunction?

Answer 15

Question 16

Describe what happens as a result of:

• Right heart failure
• Left heart failure

Answer 16

Question 17

What are the causes of right ventricular dysfunction?

Answer 17

• Conditions impeding flow into the lungs
  
  • Pulmonary hypertension
  • Valve damage / stenosis / incompetence
• Pumping ability of the right ventricle
  
  • Cardiomyopathy
  • Infarction
• Left ventricular failure
• Congenital heart defects

Question 18

Describe the compensatory mechanisms in heart failure.

Answer 18

• In the early stages of heart failure, compensatory mechanisms (i.e. those involved in hypovolemia) maintain cardiac output.
• Longer-term, they contribute to the worsening of the condition.
• Compensatory mechanisms:
  
  • Sympathetic nerve activity
  • RAAS
  • Frank-Starling mechanism
  • Fluid movements

Question 19

What are the problems with the Frank-Starling compensatory mechanism in heart failure?

Answer 19

• ↑ in vascular volume leads to ↑ EDV.
• ↑ in muscle stretch and O₂ consumption.

Question 20

What are the problems with sympathetic activity as a compensatory mechanism in heart failure?

Answer 20

• Initially, sympathetic activity can be helpful; longer-term, it is not:
  
  • Tachycardia, vasoconstriction, ↓ perfusion of tissues, cardiac arrhythmias, renin release.
  • ↑ the workload of the heart
    
    • Ischaemia
    • Damage to myocytes
    • ↓ contractility

Question 21

What are the problems with RAAS as a compensatory mechanism in heart failure?

Answer 21

• ↓ in renal blood flow stimulates the release of renin.
• ↑ renin release, therefore ↑ angiotensin II formation
  
  • Vasoconstrictor, plus stimulates aldosterone release.
  • Therefore, sodium and water reabsorption is ↑ both directly (decreased flow rate through the kidney) and indirectly (via aldosterone).
• Angiotensin II and aldosterone are also involved in inflammatory responses leading to deposition of fibroblasts and collagen in the ventricles.
  
  • Therefore, ↑ the stiffness and ↓ the contractility of the heart, leading to myocardial remodelling and progressing dysfunction.

Question 22

Give an overview of the problems with the compensatory mechanisms involved in heart failure.

Answer 22

Question 23

What are the strategies for treatment of heart failure?

Answer 23

• ↑ cardiac contractility.
• ↓ preload and / or afterload to ↓ cardiac work demand
  
  • By relaxing vascular smooth muscle
  • By reducing blood volume
• Inhibit the RAAS.
• Prevent inappropriate ↑ in heart rate.