Heart failure physiology

Question 1

HF definition

Answer 1

• A syndrome caused by cardiac dysfunction (from myocardial muscle dysfxn or loss) and characterized by either LV dilation, hypertrophy, or both
• HF leads to neurohormonal and circulatory abnormalities including fluid retention, SOB, fatigue and DOE
• Beneficial heart remodeling can be result of therapy or spontaneously
• HF is usually accompanied by pulmonary or systemic venous congestion, or both
• Also often accompanied by inadequate O2 delivery (at rest or stress) due to cardiac dysfxn

Question 2

Components of HF

Answer 2

• Abnormal LV function (systolic, diastolic, or both)
• Abnormal hemodynamic profile
• Activation of neurohormonal systems
• Activation of inflammatory markers, endothelial dysfxn
• Signs and Sx (edema, hepatomegaly, pulm edema, tachycardia)

Question 3

Heart dysfxns

Answer 3

• Ventricular remodeling
• Wall motion abnormalities (desynchrony)
• Endothelial dysfxn
• Electrical abnormalities (arrhythmias)
• Reduced longevity

Question 4

Relevant heart terms

Answer 4

• Contractility (independent of preload and after load)
• SV, CO (based on SV and HR)
• Preload: based on venous pressure (return), approximated as EDV
• Afterload: based on TPR
• Ejection fraction (EF): SV/EDV (the fraction of the EDV that is ejected)
• Normal EF is 55-75%
• Compliance: change in pressure/ change in volume (how easily it changes volume)

Question 5

HF ventricular function curve

Answer 5

• In VF curves, SV (y axis) is compared to preload (EDV, x axis)
• Normal curves are at the top, w/ HF curves down and to the right (+ inotropes up and to left)
• Increasing EDV will increase SV to a point, but after that it has little effect on increasing SV
• But lowering EDV by decreasing blood volume will move a point on a curve down/left on the same curve

Question 6

HF force-tension curves

Answer 6

• In FT curves, SV (y axis) is compared to afterload (TPR, x-axis)
• Normal curves at the tope, w/ HF curves down and to left
• Lower TPR means a larger SV, but during HF there is smaller SV at the same TPR as a normal heart
• However, lowering TPR (after load) in HF can increase SV (positive inotropic effect)
• This moves the curve up one curve

Question 7

Changing the ventricular function curve 1

Answer 7

• Want to move the curve up and to the left (increasing SV while decreasing EDV)
• This is b/c want to decrease EDV to reduce work the heart must do, but also want to increase SV instead of losing SV to increase CO
• In order to accomplish this, certain drugs are required
• Drugs that decrease EDV move the point on a curve down (to the left) the same curve, and drugs that decrease TPR move the point directly up to a new curve (those that do both move the point up and to the left

Question 8

Changing the ventricular function curve 2

Answer 8

• Diuretics: decrease blood volume (thus decreasing EDV), so they move a point on a curve to the left
• Positive-inotropic effects (anything that vasodilates arteries: hydralazine, ACEIs, nitroprusside) moves the point up to a new curve
• Vasodilators can move the curves variably, based on where they vasodilate

Question 9

Changing the ventricular function curve 3

Answer 9

• Isorbide dinitrate (venous only) moves the point down the curve, nitroprusside (both) moves the point up and to the left (also ACEIs, b/c they cause arteriole dilation and decrease EDV), and hydralazine (arteries only) moves the point up
• Combining drugs also can achieve the desired effect, as in giving a diuretic and hydralazine (moves the curve up and to the left)

Question 10

Systolic dysfxn

Answer 10

• Diminished capacity of the ventricle to eject blood due to impaired myocardial contractility or volume overload
• There is reduced SV and increased EDV in return (leads to larger ventricle w/ limited capacity to generate force), therefore EF goes down
• Usually seen w/ dilated ventricle remodeling (LV systolic function impaired)

Question 11

Diastolic dysfxn

Answer 11

• Impaired early diastolic relaxation, increased stiffness of ventricular wall (reduced compliance)
• But LV retains normal systolic function
• There is reduced EDV and reduced SV, thus EF doesn’t change
• Lower compliance leads to increased ED pressure, thus the low EDV/SV
• Hypertrophy usually due to pressure overload (HTN)
• Heart must work more to generate same CO so there is often LV hypertrophy remodeling, exacerbating the low compliance of the ventricle and HF

Question 12

Risk factors for HF

Answer 12

• CAD or Hx of MI
• HTN, diabetes
• EtOH, drugs (coke, meth)
• Age, obesity, smoking, etc

Question 13

Right sided HF

Answer 13

• Cardiac causes: L sided HF, RV infarction, pulm stenosis

- Pulmonary diseases: pulm HTN (often from L sided HF), pulm embolism, COPD, chronic lung infection, etc

Question 14

Compensatory mechanisms

Answer 14

• Frank starling: decrease in SV leads to increase in EDV to increase SV back to normal (leads to dilated LV b/c of constantly large EDV)
• Laplace law: when after load increases the ventricle must compensate by increasing wall thickness (which also decreases radius of ventricle) to maintain normal wall stress (leads to LVH)

Question 15

Myocardial hypertrophy

Answer 15

• First stage of HF, can be either concentric (small ventricle) or eccentric (larger ventricle)
• Concentric hypertrophy is due to pressure overload leading to increased systolic wall stress and remodeling to thick walls
• Sarcomeres in parallel
• Eccentric hypertrophy due to volume overload leading to increased diastolic wall stress and remodeling to dilated walls (same thickness)
• Sarcomeres in series

Question 16

Neurohormonal stimulation

Answer 16

• Adrenergic NS stimulation
• Renin angiotensin aldosterone system
• ADH
• Endothelin
• Natriuretic peptide

Question 17

Effects of SNS

Answer 17

• Increased HR and contraction by B1
• Increased BP from A1 vasoconstriction
• These lead to increased myocardial O2 consumption and ischemia, and can limit CO
• Can provide short term benefit but long term can be very damaging

Question 18

Renin-angiotensin-aldosterone system (RAAS)

Answer 18

• Activated due to decreased blood flow to kidneys due to decreased BP and by sympathetic activation of kidneys due to detection of low BP in baroreceptors
• Overall, angiotensin II causes vasoconstriction directly (arteries and veins) and increased Na/H2O retention (via aldosterone/ADH) to increase blood volume
• These two effects thus increase preload and increase after load

Question 19

Effects of Angiotensin II

Answer 19

• Leads to fibrosis of the heart, kidneys, other organs
• Enhances release of NE from SNS
• Stimulates adrenals to produce aldosterone and activates release of ADH, leading to increased blood volume
• Stimulates thirst center to consume more water
• Angiotensin II has multiple receptors, but the AT1 receptors cause the problems (cause vasoconstriction, aldosterone secretion, etc)
• AT1 receptors target for angiotensin receptor blockers (ARBs)

Question 20

RAAS pathway 1

Answer 20

• Liver secretes angiotensinogen, which is converted to angiotensin I by renin (from kidneys)
• Angiotensin I converted to angiotensin II by ACE (secreted from lungs)
• Angiotensin II leads to secretion of aldosterone from adrenal cortex, ADH from post pituitary

Question 21

RAAS pathway 2

Answer 21

• ATII also causes vasoconstriction of arteries/veins, GF stimulation (LVH), and sympathetic activation (catecholamine release)
• Aldosterone also has many effects that contribute to HF, such as increased fibroblast collagen synthesis, increased AT1 receptors, increased ACE activity, increased VSMC hypertrophy, increased endothelin1, etc

Question 22

Overall effects of aldosterone

Answer 22

• Causes edema by increasing Na/H2O absorption and blood volume
• Decreases vascular and ventricular compliance
• Can cause arrhythmias by increasing fibrosis
• Can increase endothelial dysfxn and lead to ischemia/worsening HF

Question 23

Vasopressin and endothelin1

Answer 23

• ADH released in response to increase in plasma osmolality, leads to water retention
• Elevated levels in pts w/ HF
• Endothelin1 has many effects similar to angiotensin II, and increases ATII effects, as well as the effects of catecholamines

Question 24

Counter neurohormonal systems

Answer 24

• Increased production of prostaglandins PGE2 and PGI2, causes vasodilation and Na excretion
• (!) natriuretic peptide (NPs): causes vasodilation, Na/H2O excretion, and decreases thirst
• Most important NPs: ANP (atria) and BNP (brain, ventricles)
• Hallmark of HF is BNP resistance
• BNP most important biomarker in HF

Question 25

Symptoms of HF

Answer 25

- Exercise intolerance and water retention are primary Sx - DOE, fatigue, orthopnea, PND very common - Also: nocturnal cough, nocturia, abdominal discomfort, decreased appetite

Question 26

Signs of HF

Answer 26

- Tachycardia, low BP, tachypnea, elevated JVP, pulses alternance (alternating strong and weak beats) - Displaced and diffuse LV impulse, right ventricular heave, S3, MR and TR murmurs - Pulmonary rales, liver enlargement, nocturia - Leg edema, ascites, cold extremities

Question 27

Classes of HF

Answer 27

- Class I: asymptomatic - Class II: symptomatic w/ normal exercise - Class III: symptomatic w/ little exercise - Class IV: symptomatic at rest

Question 28

ECG results indicating HF

Answer 28

- Tachycardia - LVH - Atrial enlargement - Post MI - Conduction abnormalities (wide QRS, BBB) - Arrhythmias

Question 29

HF on CXR

Answer 29

- Cardiomegaly - Pulmonary edema - Pleural effusion - Upper zone vascular redistribution

Question 30

HF on echo

Answer 30

- Dilated chambers - Wall motion abnormalities - Mitral/tricuspid/Ao regurg - Increase pulmonary pressure - Pericardial effusion - Pleural effusion

Question 31

Hemodynamics of HF

Answer 31

- Increased RAP, pulmonary artery pressure - Decreased SV and CO - Increased TPR and pulmonary vascular resistance