Pathophysiology of Cardiac Failure

Question 1

Define inotropy.

Answer 1

The force of muscle contraction.

Question 2

What factors influence inotropy ?

Answer 2

Influenced by Ca2+

– L-type channels
• opening facilitated by cAMP
– Na+/Ca2+ exchange
• inhibited indirectly by cardiac glycosides

Question 3

What is the relation between contractility and CO ?

Answer 3

Increased contractility increases cardiac output independent of preload and afterload.

Question 4

Give examples of classification of heart failures.

Answer 4

• New York Heart Association Classification of Heart Failure (NYHA): Based on patient symptoms
• Systolic vs. Diastolic Dysfunction: Based on ejection fraction (%)
• Right vs. Left Ventricular Dysfunction (long-term heart failure usually involves both sides)

Question 5

Identify the different kinds of heart failures according to the New York Heart Association Classification of Heart Failure.

Answer 5

Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath)

Class II: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).

Class III: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.

Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is
undertaken, discomfort increases.

Question 6

Identify the different kinds of heart failures according to ejection fraction.

Answer 6

Systolic ventricular dysfunction:
– impaired cardiac contractility so ↓ ejection fraction (possibly no chance in EDV)
– (<40%; normal ~50-65%)

Diastolic ventricular dysfunction:
– normal ejection (i.e. normal contraction) fraction but impaired diastolic ventricular relaxation and decreased filling
– ∴↓ in SV and CO

Question 7

What are possible causes of systolic ventricular dysfunction ?

Answer 7

Commonly results from conditions that affect:

1. impaired contractility
   – e.g. IHD, cardiomyopathy, transient MI
2. volume overload
   – mitral and aortic regurgitation
3. pressure overload (increased afterload)
   – valvular stenosis (aortic valve stenosis can lead to increased afterload, reducing CO); hypertension

All of these (systolic dysfunctions) result in ↑EDV (preload), ventricular dilation, ↑ventricular wall tension

Question 8

What are possible causes of diastolic ventricular dysfunction ?

Answer 8

1. impedance of ventricular expansion
   – constrictive pericarditis (prevents heart from relaxing as much as it can do due to inflamed sac) etc.
2. increased wall thickness
   – LV hypertrophy etc.
   (change in vessel thickness changes its ability to fill + issues with getting blood supply deep in heart muscle tissue)
3. delayed diastolic relaxation
   – aging; ischaemia
4. ↑heart rate
   (less time to fill the heart, e.g. in angina)

Question 9

Which of systolic or diastolic ventricular dysfunction is more common ?

Answer 9

Systolic ventricular dysfunction

Question 10

Describe the consequences of R Heart Failure, explaining why they occur)

Answer 10

R Heart Failure → Congestion of peripheral tissues → Edema and ascites + GI tract congestion (→ Anorexia, GI distress, weight loss) + Liver Congestion (impaired liver function)

-Unable to cope with returning blood so blood accumulates in veinous side of circulation (start getting congestion in peripheral tissues)
-This can change hydrostatic P across capillaries in the veinous end (more elevated P), leading to accumulation of fluid in tissues, edema. Ascites is due to congestion of fluid within liver.
-Problems in the liver: toxic metabolites produced in the liver and can’t be excreted, causing liver damage +
liver not detoxifying molecules building up in other parts of the body
-If we change amount of blood flow in the GI system, we do not get as many nutrients from the GI system

Question 11

Describe the consequences of L Heart Failure

Answer 11

L Heart Failure → Decreased CO (because cannot pump as much) + Pulmonary congestion

Decreased CO → Activity Intolerance + Signs of decreased tissue perfusion (cyanosis, signs of hypoxia)
Pulmonary congestion → Cough with frothy sputum + Orthopnea + Paroxysmal Nocturnal Dyspnoea

• Pulmonary congestion occurs because there is flow in but not flow out
• Forthy sputum due to change in hydrostatic P

Question 12

Identify possible causes of R ventricular dysfunction.

Answer 12

Conditions impeding flow into the lungs
– Pulmonary hypertension
– Valve damage/stenosis/incompetence

Pumping ability of right ventricle
– Cardiomyopathy
– Infarction

Left ventricular failure (biggest cause)

Congenital heart defects

Question 13

Identify possible causes of L ventricular dysfunction.

Answer 13

Hypertension (↑TPR)

Acute myocardial infarction

Aortic or mitral valve stenosis or regurgitation

Increase in pulmonary pressure can lead to right ventricular failure

Question 14

How does the body respond to heart failure ?

Answer 14

In the early stages of heart failure, compensatory mechanisms (i.e. those involved in hypovolemia) maintain cardiac output (and MABP)

Longer-term, they contribute to the worsening of the condition (because falling CO cannot be distinguished by CV system as being a cause of heart failure, or a cause of loss of V, leading to the same response as against hypovolemia)

Question 15

Why is it a problem that the response for hypovolemia is also used for heart failure ?

Answer 15

In hypovoalemia, vasoconstriction of systemic circulation to increase BP by increasing TPR. In heart failure, this means we are increasing afterload of an already failing heart. Similarly, SNS constricts veins (to increase veinous return) but this causes increasing stretch of ventricles. Finally, sodium and water retention into the system results in increased pressure to the system.

Question 16

Describe the compensatory mechanisms against heart failure.

Answer 16

Decreased CO leads to:

1) Increased SNS activity
2) Decreased renal blood flow

Increased SNS activity leads to vasoconstriction (which increase TPR and afterload), increased HR, and increased contractility

Decreased renal blood flow leads to the renin release (renin → Angiotensin II → vasoconstriction + aldosterone release) and increased sodium and water retention (both directly and through renin release). This is in turn leads to increased vascular V, increase venous return (preload), and the Frank Starling mechanism

Question 17

What are the problems with the compensatory mechanisms ?

Answer 17

1) Sympathetic Activity
Initially, sympathetic activity can be helpful; long-term it is not
– Tachycardia, vasoconstriction, ↓ perfusion of tissues, cardiac arrhythmias, renin release
– ↑ the workload of the heart
• ischaemia, damage to myocytes, ↓ contractility
– Desensitisation of β but not α receptors (beta mediated effect quickly wears off so mainly just leads to increased TPR through effects of alpha receptors)

2) Frank Starling
↑ in vascular volume leads to ↑EDV
↑ in muscle stretch and O2 consumption
At a certain point, this stretch will cause sarcomere length to be higher than optimal, resulting in decreased tension (and decreased SV, because it cannot eject as much)
Decreased SV, therefore CO

3) Renin-Angiotensin
a) ↓ in renal blood flow stimulates release of renin
↑ renin release leads to ↑ angiotensin II formation
– Vasoconstrictor, plus stimulates aldosterone release
Sodium and water reabsorption is ↑ both directly (decreased flow rate through the kidney) and indirectly (via aldosterone)
b) Angiotensin II and aldosterone are also involved inflammatory responses leading to deposition of fibroblasts and collagen in the ventricles. This ↑ the stiffness (changing afterload in the walls of the heart) and ↓ the contractility of the heart, leading to myocardial remodelling and progressing dysfunction

Overall, the result of these mechanisms in the long term is decreased CO, and peripheral edema and pulmonary congestion (last two due to retention of fluid which will be pushed into tissues and lungs).

Question 18

Identify possible strategies for the treatment of heart failure.

Answer 18

↑ cardiac contractility
while simultaneously trying to
↓ 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 (e.g. beta blockers)

Mobilise the oedematous fluids

Question 19

Define Heart Failure.

Answer 19

“Condition in which the heart has lost the ability to pump enough blood to the body’s tissues. With too little blood being delivered, the organs and other tissues do not receive enough oxygen and nutrients to function properly”

Question 20

Explain the pathophysiology of RV failure.

Answer 20

Refer to extra diagram in lecture on “Pathophysiology of Heart Failure” (not present in initial slide, check panopto/galen)

Increased RV afterload → RV dilation (because increasing accumulation of blood until point where it cannot stretch anymore) (⇄ Tricuspid Regurgitation because stretching RV so much that the leaflets do not act in the same way) → RV Failure

Increased RV afterload → Prolonged isovolaemic contraction → Increased myocardial wall stress (to deal with increasing afterload) → Decreased R Coronary perfusion → RV Ischaemia → RV Failure

Increased RV afterload → Prolonged isovolaemic contraction → Increased myocardial wall stress → RV Hypertrophy → RV Ischaemia → RV Failure

Increased RV afterload → Prolonged isovolaemic contraction → Increased myocardial wall stress → RV Hypertrophy
(to deal with said stress) → Shift of IV septum (due to hypertrophy of RV) → LV failure (assuming LV already failing.) → RV Ischaemia → RV Failure

Increased RV afterload → Prolonged isovolaemic contraction → Increased myocardial wall stress → RV Hypertrophy
(to deal with said stress) → Shift of IV septum (due to hypertrophy of RV) → LV failure (assuming LV already failing.) → RV Failure