Lecture 19: Pathophysiology of Heart Failure, Understanding the Basis for Treatment Flashcards
(82 cards)
1
Q
Which of the following is necessary to make the diagnosis of heart failure?
A
Symptoms of exercise intolerance
2
Q
What is heart failure?
A
- The pathophysiologic state in which the heart is unable to pump blood at a rate commensurate with the body’s requirement OR
- can only do so from an elevated filling pressure
The definition of heart failure has nothing to do with the ejection fraction
3
Q
What are the causes of heart failure?
A
Primary cardiac causes i. ischemic heart disease ii. myocardial disease iii. idiopathic dilated cardiomyopathy (DCM) iv. restrictive cardiomyopathy (RCM) v. hypertrophic cardiomyopathy (HCM) vi. inflammatory myocarditis vii. valvular heart disease viii. constrictive pericarditis HTN Diabetes Toxins i. alcohol ii. Adriamycin (which causes DCM) Thyrotoxicosis
4
Q
What is the syndrome of heart failure?
A
Constellation of symptoms including i. dyspnea ii. fatigue iii. exercise intolerance iv. swelling Can be acute OR chronic
5
Q
What are the stages of heart failure?
A
Stage A = high risk patients i. HTN ii. diabetes iii. family history Stage B = structural heart disease i. LVH, MI, low LVEF Stage C = prior or current symptoms Stage D = refractory
6
Q
What HF stage is symptomatic?
A
C
7
Q
What are the classes of heart failure?
A
NYHA Classs
I = asymptomatic
II = Symptoms of heart failure with moderate/strenuous exertion
III = Symptoms of heart failure with mild exertion
IV = Symptoms of heart failure at rest
8
Q
What are the gender and survival differences in heart failure?
A
From 0-74, men have higher prevalence of heart failure
From 75+, women have higher prevalence
Women tend to do better than men
Women have smaller volumes, higher pressure and have less compliance
9
Q
What is the definition of impaired (reduced) LVEF?
A
Referred to as systolic heart failure
<40% of LVEF
HFrEF = heart failure with reduced ejection fraction
10
Q
What is the definition of preserved LVEF?
A
>50% Preserved LVEF Referred to as DIASTOLIC HF HFpEF (heart failure with preserved ejection fraction) i. HFpEF Border is 41-49% ii. HFpEF improved is >40%
11
Q
Does the definition of heart failure have something to do with ejection fraction?
A
NO only the classification does
12
Q
What is the prime directive for compensatory pathophysiologic mechanisms in heart failure?
A
To restore cardiac output regardless of the expense
RESTORE CO NINJAAA
13
Q
When there is myocardial failure, what are the adjustments the heart makes to stabilize or increase myocardial performance?
A
- Increased preload
- Increased contractile elements
- Increased heart rate
- Increased state of contractility
14
Q
What happens to the Frank-Starling relationship of patient with heart failure?
A
It shifts down and to the right
Which means not enough force is generated per
Increase in length
15
Q
What are symptoms due to volume overload?
A
- pulmonary congestion (cough, orthopnea, PND)
- Visceral congestion (ascites)
- Peripheral edema
- anasarca
- diffuse apex
- JVD (jugular venous distension)
16
Q
What is anasarca?
A
Known as generalized extreme edema
Characterized by widespread swelling of the skin due to effusion of fluid into the extracellular space
Caused by anything that can lead to interstitial fluid build up
17
Q
When does LV remodeling happen?
A
Process by which ventricular size, shape and function are regulated by other factors
- HTN
- Acute myocardial infarction
- Cardiomyopathy (DCM, HCM, RCM)
- Valvular heart disease
- Chronic ischemia
18
Q
What is the heart’s response to hemodynamic burden (like volume overload)?
A
- Use Frank-starling mechanism to increase cross-bridge formation
- augment muscle mass to bear extra load
- recruit neurohormones to augment contractility
19
Q
What is relative wall thickness?
A
Determines whether hypertrophy will be concentric or eccentric
If wall thickness is higher than 0.45, you have concentric wall thickness
If wall thickness is lower than 0.34 then you have eccentric wall thickness
20
Q
What are the three responses to LV dysfunction?
A
- LV remodeling (hypertrophy or dilatation)
- Neurohormonal stimulation
i. Sympathetic nervous system
ii. RAAS - Vasoconstriction of arterioles
21
Q
What are the characteristics of eccentric hypertrophy?
A
Due to VOLUME overload
Same RWT but wall stress is not corrected to normal
Sarcomeres are added in series so you get stretching of muscle
Sarcomeres that are added are ABNORMAL
22
Q
How do LV and RV get remodeled during congestive heart failure?
A
They hypertrophy (and they can do so either concentrically or eccentrically; former is pressure overload, latter is volume overload) If RV is remodeled, eccentric/concentric terminology not used RV remodeling is NOT mentioned in heart failure because it has nothing to do with ejection fraction
23
Q
What are the key characteristics of concentric hypertrophy?
A
In response to pressure overload
-parallel addition of sarcomeres caused increased myocyte width, which in turn increases wall thickness
Increase in RWT because chamber radius does not change
24
Q
What type of remodeling leads to HFrEF?
A
Heart failure with reduced ejection fraction
Eccentric hypertrophy
Ejection fraction is reduced because added sarcomeres are contracting abnormally
25
What type of remodeling leads to HFpEF?
Heart failure with preserved ejection fraction
Concentric hypertrophy
Ejection fraction is preserved (but ESV and EDV are both decreased)
26
What is ejection fraction?
EDV-ESV/EDV
So if you get an equal reduction in both ESV and EDV, you can still get a preserved ejection fraction while still being in heart failure
-concentric hypertrophy
27
What happens to the chordae tendinae in eccentric hypertrophy of the ventricle?
You get mitral/tricuspid regurgitation because the valve leaflets are pulled farther and farther apart since circle is expanding into basketball
28
What is the effect of LBBB on ECG?
Longer QRS complex
QRS duration = 160ms
On V1, you can also see a wide and deep inverted S wave
29
What are the ECG changes in patients with h myocardial disease?
1. patients with cardiac ischemia or cardiomyopathy have increased LBBB ranging from 27-54%
2. LBBB alters the sequence of left ventricular activation thereby affecting mechanical events of the cardiac cycle and resulting hemodynamics
30
What are the symptoms of LBBB on ventricular function?
1. delayed mitral and aortic valve opening and closure
2. prolonging of left ventricular isovolumic contraction time
3. Loss of intraventricular synchrony
4. loss of interventricular synchrony (between LV and RV)
5. abnormal diastolic function
31
What are the hemodynamic effects of LBBB? Consequences?
Delays in contraction time leads to
i. reduced LVEF
ii. paradoxical septal motion
iii. reduced CO and reduced MAP
iv. increased LV filling rate and volume
v. increased duration of MR
Leads to further remodeling and progression of disease
32
What are the principal hemodynamic changes in patients with heart failure?
1. increased ventricular wall stress
2. atrial hypertension due to diastolic dysfunction, fluid overload
3. reduced cardiac output
Prime directive is to restore cardiac output!
33
What is the benefit of neurohormonal on heart failure?
Works very well for self-limited, short-term responses
NOT long-term chronic diseases
Because we didn’t used to live this long
34
What are the neurohormonal pathways activated in heart failure?
1. RAAS (renin-angiotensin-aldosterone system)
2. Sympathetic nervous system activation
-SNS is whats initially activated in heart failure
-increases HR and contractility (but can lead to hypertrophy and injury)
-increases vasoconstriction
Long-term neurohormonal pathways leads to disease progression!
35
What do the plasma NE levels in heart failure indicate?
The higher the NE levels, the greater the mortality risk
36
What is the MoA of sympathetic nervous system on myocardial beta receptors?
Gstimulating protein
| Leads to higher HR and contractility
37
What happens to the SNS response in patients with cardiomyopathy?
Beta receptors are not working normally
If you overstimulate the B receptors, they start to downregulate
That’s why SNS can lead to dysfunction, chronic stimulation leads to downregulation which means not enough CO when you need it!
38
What are the symptoms of sysmpathetic overload?
1. diaphoresis
2. anxious
3. palpitations
4. tachycardia
5. arrhythmias
6. cool, clammy extremities
7. Increased SVR
39
What is the renin-angiotensin-bradykinin system?
When renin is activated, leads to Angiotensin II which
i. increases aldosterone release and fluid retention
ii. increases calcium current to promote vasoconstriction
iii. augments sympathetic activation
iv. ULTIMATELY you get increased BP
ACE also degrades bradykinin
40
What is the role of bradykinin?
Stimulates production of prostaglandins which in turn lead to vasoDILATION
Is degraded by ACE
41
What is the relationship between bradykinin and ACE?
ACE degrades bradykinin (thereby having two roles in promoting vasoconstriction)
42
What does angiotensin II act on?
1. heart
2. adrenal
3. brain
4. Kidneys
5. vasculature
43
What does angiotensin II do for the heart?
1. positive inotrope and chronotrope
2. LV growth/hypert rophy/remodeling if activated chronically
3. leads to decrease in compliance due to INCREASE in interstitial fibrosis
44
How does angio II affect the brain?
1. Potentiates SNS
2. stimulates thirst and sodium appetite
3. Increases ADH release
4. Suppresses renin release (feedback inhibition)
5. Increases NE release
45
How does angio II affect the kidney?
1. Constricts afferent and efferent vasculature
2. Contricts mesangial cells (SMCs in kidney)
3. Stimulates proximal tubular reabsorption of Na and HCO3-
46
How does angio II affect the vasculature?
Hypertrophy of the smooth muscle
47
What are mesangial cells?
Specialized cells around blood vessels in the kidney
Specialized smooth muscle cells that regulate blood flow through the capillaries
Divided into
I. extraglomerular mesangial cells
II. intraglomerular mesangial cells
48
What is the pathophysiology of interstitial fibrosis as caused by angio II?
Two methods
1. Angio II + Angio II receptor = increase in Calcium signals = upregulation in genes for collagen
2. Aldosterone (stimulated by angio II) leads to upregulation of genes for collagen
Collagen = interstitial fibrosis
This is what happens in the HEART
49
What is the role of aldosterone?
1. sodium retention
2. potassium and magnesium loss
3. myocardial and vascular fibrosis
4. baroreceptor dysfunction
5. impairs arterial compliance (fibrotic deposition)
6. prevention of myocardial NE uptake
50
What are two pathophysiologic mechanisms of secondary aldosteronism in CHF?
1. increased production by zona glomerulosa?
- due to increased angiotensin stimulation
2. decreased rate of hepatic clearance of aldosterone
51
What are the symptoms of heart failure in relation to the RAA system?
Patients complain of thirst and salt craving
Volume overload
Increased SVR and LV hypertrophy
52
What are the key characteristics of arginine vasopressin?
Angiotensin 2 stimulates ADH release
Increases SVR
Reduces water clearance from kidney
53
What are the roles of cytokines in heart failure?
Not felt to be causative but does contribute to progression
1. Stimulates apoptosis or necrosis
2. stimulates myocardial fibrosis
54
What are the symptoms of heart failure that correlate with cytokines?
1. muscle wasting
2. cardiac cachexia
3. remodeling
4. fatigue
5. anorexia
55
What is the role of endothelial dysfunction in heart failure?
1. increased cytokine levels imparing EDRF synthesis (NO)
-EDRF = endothelium derived relaxing factor
2. Increased ACE activity = increased bradykinin breakdown
3. Oxygen radicals inactivating NO
4. Chroncally reduced blood flow with decreased NO synthase
5. increased endothelial dependent vasoconstrictors like endothelin
Basically you are losing the endothelial cytokines that can vasodilate your vessels for you
56
What do you need to do hemodynamically to improve symptoms?
Vasodilate and growth inhibiting cytokines are upregulatd
Vasoconstricting and growth promoting = worsening symptoms because of progressive remodeling
In CHF, vasoconstrictors > vasodilators
57
What is the relationship between skeletal muscle and heart failure?
1. Intrinsic abnormalities noted in skeletal muscle
2. Metabolic alterations due to inadequate oxygen utilization by mitochondria
- not related to tissue hypoxia
3. Impaired endurance due to reduced oxidative capacity
4. Decreased strength due to smaller muscle bundle cross-sectional area
58
How does neurohormonal activation lead to downfall of the patient?
Neurohormonal activation = Angiotensin II + Norepinephrine
i. Hypertrophy
ii. Apoptosis
iii. Ischemia
iv. Arrhythmias
v. Remodeling
vi. Fibrosis
59
What does the heart do to counteract cardiomyopathy?
1. Decrease in number and function of beta receptors (to neutralize their efficacy and downregulate SNS effect)
2. Decrease in ATP consumption to save energy
-this prevents calcium from coming to
Decrease contractility
3. ANP and BNP (counterregulatory hormones)
60
What are the key characteristics of ANP and BNP?
Both are part of the hearts counterregulatory system in response to ischemia
Opposes vasoconstrictive and salt/water retention of activated RAA and sympathetic function
61
What are the characteristics of B-type Natriuretic Peptide (BNP)?
1. Causes
i. vasodilation
ii. promotes sodium excretion
iii. decreases aldosterone levels
iv. inhibits RAAS
2. Found in cardiac ventricles
3. Activated by:
i. myocardial stretch in ventricles
ii. volume expansion
iii. pressure overload
4. BNP levels are related to LVend-diastolic pressure
62
Which of the following is characteristic of eccentric hypertrophy?
Increased myocyte length
63
What is the prime directive of compensatory mechanisms of heart?
Restore cardiac output!
64
What is the prime directive of treatment?
Prevent or reverse disease progression
For stage A = prevent remodeling
For stage B-D = delay or reverse remodeling
65
What are ways to inhibit angiotensin action (RAA system)?
1. ACE inhibtors
2. ARBs (ACE receptor blocker)
3. Aldosterone receptor antagonist
66
What is the first line therapy for systolic heart failure (reduced ejection failure)?
1. beta blockers
i. Beta 1 selective blockers
2. ACE inhibitors
67
What are the downfalls of ACE inhibition alone?
Angiotensin 2 is only half of the equation for disease progression (the other side is increased norepinephrine)
68
How does inhibiting aldosterone aid congestive heart failure patients?
Less Na retention
Less myocardial/vascular effects
Limits potassium loss
Spironolactone group had great survivability for Class III and IV heart failure patients (those with symptoms already)
69
What is an example of an ACE inhibitor?
Enalapril
| -decreases heart size increase and also decreases EDV
70
What are examples of Aldosterone receptor inhibitor?
1. spironolactone
2. Eplerenone
Used for class III and IV heart
Failure patients
71
What are the beta1 selective blockers?
Metoprolol
72
Why don’t you want to use a non-selective beta blockers?
Because beta 2 is a bronchodilator
73
What is metoprolol?
A selective beta 1 blocker
74
What is the relationship between LVEF and beta-blockers?
Taking beta blockers increase the level of LVEF, thereby counteracting the effects of myocyte remodeling
Beta blockers are used to increase LVEF to prevent the downregulation of the beta receptors on the heart
-remember, beta receptors are downregulated when there is chronic SNS stimulation, so patients have reduced cardiac output when needed
-therefore, giving beta blockers will prevent this downregulation and allow patients to better respond to acute SNS stimulation when the body needs it
75
Why does vasoconstriction occur in patients with LV dysfunction?
Because of angiotensin II release in order to preserve BP since there is a decreased EF and decreased CO
Therefore, increasing vasodilation = decreasing afterload = increasing EF and CO
76
What is the relationship between vasodilators and heart failure patients?
Greater survivability because vasodilation = decrease afterload
77
What are the primary targets of treatment in heart failure?
1. beta blockers
2. ACE inhibitors, ARBs, aldosterone antagonists (all first line)
3. digoxin/inotropes
4. diuretics
5. Cardiac resynchronization therapy
78
What does CRT mean? Significance?
Cardiac resynchronization therapy
Shrinks the heart size
And increases LVEF
79
What are the indications of CRT?
1. symptomatic heart failure
| 2. LVEF 150ms
80
What is the treatment of HF with preserved LVEF?
1. Treat underlying condition
2. Treat hypertension
3. Diuretics as needed
4. ACE inhibitor or ARB
5. Beta-blockers in some cases
Only one study on which to base treatment
Hard to treat
81
What is the classic presentation of HFpEF?
Old woman with HTN and shortness of breath
82
What is Nesiritide?
A recombinant BNP medication
Given to increase sodium and fluid excretion
Counteracts the RAAS system
