Heart Failure

Question 1

General factors

Answer 1

• 5.8 million Americas have it
• 670,000 new cases per year
• 3.5 million hospitalization per year
• mortality 50%
• $34.6 billion/year
• prognosis improving- mortality increasing
• the more we increase longevity, the more cases there are

Question 2

Definition of heart failure

Answer 2

• inability of the heart to meet the metabolic needs of the body
• to be distinguished from cardiac dysfunction with successful adaptation
• when adaptation fails and becomes part of the problem
• clinical: no single one finding,a complex of findings

Question 3

Causes of heart failure

Answer 3

1. Decreased circulatory supply to the body: coronary heart disease (MI, ischemic cardiomyopathy), valvular heart disease, cardiomyopathy
2. Increased circulatory demand from the body: hypertension, thyrotoxicosis, anemia, A-V fistula
3. Heart failure- final common pathway

Question 4

Adaptive mechanisms of heart failure

Answer 4

1) Frank-Starling (short term)
2) Neuro-hormonal (intermediate) - Renal
3) Hypertrophy

Question 5

Frank Starling Mechanism

Answer 5

Normal curve- shows improved ventricular performance when the EDV is increased (increased preload or venous return)

• normal curve moves upward and to the left with exercise or increased sympathetic stimulation
• heart failure: down and to the right with impaired ventricular performance: you can still increase EDV but the ventricular performance isn’t getting much better
• short term adaptation
• with increasing severe LV dysfunction the LV filling pressure reaches 25 mm Hg where the oncotic pressure of the plasma is exceeded and fluid crosses the alveolar membrane and enters the pulmonary alveoli

Question 6

Neurohumeral Sympathetic Stimulation

Answer 6

Increased plasma NE:

• increase release from neurohumoral nerve endings
• decrease uptake by those endings
• decrease rate of degradation
• increase B1 receptor exhaustion due to chronic stimulation
• decrease B1 receptor synthesis (low levels of B1 in CHF patients)
• increase coronary sinus NE output

-increasing levels of PNE are associated with decreasing length of survival in heart failure

• redistribution of cardiac output
• maintain flow to brain, heart at expense to the skin, skeletal muscle and kidneys

Question 7

Adaptive Mechanisms: Renal

Answer 7

• Stimuli:
• Decrease GFR, RBF
• Increase aldosterone

Response:

• increase Na and H2O retention
• increase plasma volume
• increase venous return and pressure

Question 8

Effects of Angiotensin II

Answer 8

• activated by adrenergic stimulation of J-G Apparatus and decrease renal blood flow
• increase vasoconstriction and blood pressure
• increase aldosterone release
• vessel hypertrophy, mycocardial hypertrophy, increased NE release, Na+ retention, CNS dypsogenia, efferent constriction

Question 9

Atrial natiretic factor

Answer 9

• counter- regulatory

- promotes vasodilation, natriuresis, suppresses RAS

Question 10

Brain Natiretic factor

Answer 10

• from ventricle
• counter-regulatory
• similar to ANP- promotes vasodilation, natriuresis, suppresses RAS

Question 11

Endothelin

Answer 11

• from endothelial cells

- potent vasoconstrictor

Question 12

Inflammatory cytokines

Answer 12

• TNF alpha

- promotes cell hypertrophy- apoptossi

Question 13

Neurohormal stimulation in heart failure

Answer 13

-norepinephrine, plasma renin, arginine vasopressin, atrial natriuretic factor and endothelin are all much higher in patients with heart failure

Question 14

Adaptive Mechanism: Hypertrophy

Answer 14

• increase in myocardial mass- remodeling
• if abnormality is not corrected, myocardial dysfunction will worse and become permanent
• when? pressure vs. volume overload
• maintain or increase contractility
• Ejection fraction= (EDV-ESV)/EDV x 100

Question 15

Effects of hypertrophy

Answer 15

• poor contracile function despite hypertrophy

- force velocity relationship- much lower for CHF

Question 16

Clinical Hypertrophy

Answer 16

• Two types: pressure( aortic stenosis) or volume overload(mitral insufficiency)
• effort to return wall stress toward normal
• though individial muscles show reduced contractility
• hypertrophy maintains pump function (cardiac output) by keeping wall stress near normal

Question 17

Concentric/ Eccentric hypertrophy

Answer 17

• pressure overload -> increase systolic wall stress -> mechanical transducers -> extracellular and intracellular signals -> ventricular remodeling -> parallel sarcomeres -> concentric hypertrophy (LV thickness greater)
• volume overload -> increase diastolic wall stress -> mechanical transducers ->extracellular and intracellular signals -> ventricular remodeling -> series sarcometers -> eccentric hypertrophy (LV volume greater)

Question 18

Adaptation Disadvantages

Answer 18

1) Frank Starling- high LVEDP- pulmonary edema
2) Neuro-humoral
- increases myocardial O2 consumption
- arrhymias
- diminished response to sympathetic stimulation
- blunted baroreceptor function
- increased systemic vascular resistance
3) Renal
- perpherial/organ edema
- decreased renal function
4) Myocardial hypertrophy- remodeling
- decreased contractility
- necrosis and apoptosis
- decreased coronary reserve
- changes in matrix (diastole)

Question 19

Failure Mal adaptation

Answer 19

• worsening LV function
• fluid retention- Pulmonary edema
• excessive increase in vascular resistance
• renal failure

Question 20

Right vs Left heart failure

Answer 20

• Right: Pulmonary embolism, cor pulmonale, mitral stenosis

- Left: mitral insufficiency, aortic stenosis and insufficiency, hypertension, cardiomyopathy

Question 21

Acute vs chronic CHF

Answer 21

• acute: MI, endocarditis

- chronic: cardiomyopathy, hypertension

Question 22

Low vs High Cardiac Output

Answer 22

• Low: cardiomyopathy, coronary heart disease

- High: Thyrotoxicosis, Anemioa, AV fistula

Question 23

Forward vs. Backward

Answer 23

• Forward: effect of low cardiac output

- Backward: effects of high venous pressure

Question 24

Systole vs. Diastole

Answer 24

• Systolic: MI etc
• Diastolic:preserved ejection fraction 40-50% of patients
  a) Delayed relaxation, elderly, hypertension, early ischemia
  b) increased stiffness- rare, infiltrative disease, amlyoidosis

Can be both

Question 25

Therapy for CHF

Answer 25

1) Treat underlying cause
2) Inotropic agents- digitalis, dobutamine
3) Diuretics- Loop (Furosemide {lassix}), distal tubule (Thiazide)
4) Venodilator- reduce pre load- Nitrates, BNP
5) Arterial vasodilation- reduce afterload, angiotensin converting enzyme inhibitors, angiotensin receptor blockers
6) Beta blockers- blunt sympathetic stimulation
7) Aldosterone antagonist (good for diastolic CHF)
8) Pace maker
9) Internal Cardiac Defribrillator
10) Left ventricular assist device (LVAD)
11) Transplantation