Pathophysiology of cardiac failure

Question 1

What is after load?

Answer 1

Afterload: 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 another word for myocardial contractility?

Answer 2

inotropy

Question 3

Discuss myocardial contractility

Answer 3

Increased contractility increases cardiac output
independent of preload and afterload
Influenced by Ca2+
– L-type channels
• opening facilitated by cAMP
– Na+/Ca2+ exchange
• inhibited indirectly by cardiac glycosides

Question 4

What are the New York Heart Association Classifications of Heart Failure (NYHA)?

Answer 4

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

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

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

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 5

Discuss Systolic vs 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
Division somewhat artificial

Question 6

Discuss Systolic dysfunction

Answer 6

Commonly results from conditions that affect:
1. contractility
– e.g. IHD, cardiomyopathy
2. volume overload
3. pressure overload
– valvular stenosis; hypertension

Results in ↑EDV (preload), ventricular dilation, ↑ventricular wall tension

Question 7

Discuss diastolic dysfunction

Answer 7

Less common than systolic dysfunction Normal contraction; impaired relaxation

Causes:
1. impedance of ventricular expansion
– constrictive pericarditis etc. 
2. increased wall thickness
– hypertrophy etc.
3. delayed diastolic relaxation
– aging; ischaemia 
4. ↑heart rate

Question 8

Discuss right vs left ventricular dysfunction

Answer 8

Classification according to the side of the heart that is primarily affected
Long-term heart failure usually involves both sides

Question 9

Discuss the causes of right ventricular dysfunction

Answer 9

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

Pumping ability of right ventricle
– Cardiomyopathy
– Infarction

Left ventricular failure

Congenital heart defects

Question 10

Discuss the causes for left ventricular dysfunction

Answer 10

Hypertension (↑TPR)

Acute myocardial infarction

Aortic or mitral valve stenosis or regurgitation

Increase in pulmonary pressure can lead to right ventricular failure

Question 11

Discuss compensatory mechanisms

Answer 11

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

Question 12

Discuss problems with the compensatory mechanisms to do with Frank-Starling mechanisms

Answer 12

↑ in vascular volume leads to ↑EDV

↑ in muscle stretch and O2 consumption

Question 13

Discuss problems with the compensatory mechanisms to do with sympathetic activity

Answer 13

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 b(beta) but not a (alpha) receptors

Question 14

Discuss problems with the compensatory mechanisms to do with renin-angiotensin

Answer 14

↓ in renal blood flow stimulates release of renin

↑ renin release therefore ↑ angiotensin II formation
– Vasoconstrictor, plus stimulates aldosterone release

Therefore sodium and water reabsorp9on is ↑ both directly (decreased flow rate through the kidney) and indirectly (via aldosterone)

Angiotensin II and aldosterone are also involved 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 15

Discuss strategies for treatment of heart failure

Answer 15

↑ 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

Question 16

Learning outcomes

Answer 16

To define heart failure in terms of systolic/diastolic function and severity.
To describe the pathological impact of heart failure on the systemic and pulmonary circulations.
To explain the issues with the compensatory mechanisms that are initiated to deal with low cardiac output and predict how these may worsen the underlying issue in heart failure