Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/145

Click to flip

145 Cards in this Set

  • Front
  • Back
HEART FAILURE: definition & clinical manifestations


congestive symptoms = advanced heart failure
clinical SYNDROME resulting from any structural or functional cardiac disorder

- problem with heart FILLING WITH (diastolic) or EJECTING (systolic) blood.

CARDINAL MANIFESTATIONS:
- Dyspnea & fatigue = exercise intolerance
(^ LVEDP)
- Fluid retention = edema
(^ SNS & RAAS)
- Multiple organ dysfunction
SYSTOLIC vs DIASTOLIC DYSFUNCTION

sys: vent. dilatation
dias: vent. hypertrophy
SYSTOLIC: heart can't PUMP
- less contraction = less ejection fraction & SV
^ LVEDV & LVEDP --> congestion
*common in myocardial ischemia, esp 2' to CAD*

DIASTOLIC: heart can't FILL/relax
- limited VR (same EF & SV)
^ LVEDP (but not LVEDV) --> same congestive symptoms as systolic fail
*1st sign of HYPERTENSIVE heart disease*
DETERMINANTS OF CARDIAC OUTPUT
(myocardial performance)
CO = HR X SV

SV <-- Preload, afterload, & contractility
PRELOAD

- 2 most important factors
- Frank-Starling curve
preload = SUM of all factors contributing 2 end-diastolic wall tension

1. Sarcomere length
2. LVEDV
(3. Amount of VR - total blood volume)

*Frank-Starling Curve: LV SV vs. LVEDV & LVEDP*
- movement along a SINGLE curvilinear line
*As LVEDV Rises, SV will level off, but LVEDP will continue to RISE --> Congestion
Frank-Starling Curve Mechanism
(why does SV change with sarcomere length changes?)
^ Preload = Increase in sarcomere length...

1. Increased passive elastic forces built-up by TITIN (springy myofibrillar protein)
*elastic recoil = main mech

2. Increases sensitivity of contractile proteins to available Ca2+
SYSTEMIC VENOUS RETURN CURVES
CO vs VR (right atrial P)

ex// Increased VR 2' venoconstriction, supine, or ^ reabs = ^ preload = ^ CO
Factors of Preload
(which is a factor of SV)
1. Sarcomere length
2. LVEDV
3. Total blood volume (VR, posture, neurogenic tone, atrial contraction
4. Contractility
Best clinical measures of preload (RV / LV)

- when would it be false or misleading?
RV PRELOAD = JVP

LV PRELOAD = PAWP
- obstructed artery will feel pressure from pulmonary capillaries
<-- pulmonary venous P <---LA Pressure <-- LV EDP

*MITRAL STENOSIS: LA-EDP >> LV-EDP

*PAWP is also falsely elevated in diastolic dysfxn*
(normal LV EDV)
CONTRACTILITY

- how to measure contractility
- changes in Vent performance curves & VR curves
Inherent capacity of mm; Indepent of preload or afterload changes

INCREASED contractility = MORE force generated in SHORTER amount of time.
* ^ CO, ^ VR, Decreased RA-P

*Shifts Vent Performance Curve (F-S) UP and to the LEFT
* Moves up/down SAME VR curve
EJECTION FRACTION (SV/EDV)
- used to measure contractile state
- normal: (50-66%)
*BUT, EF is not always right*
( lower EF doesn't always mean decreased contractility)
FACTORS AFFECTED CONTRACTILITY
1. Rate of cross-bridge activation and AMOUNT OF CALCIUM available to contractile proteins (Trop C)
- major factor = calcium

2. Circulating Catecholamines
3. SNS activation
4. Acid-base status
5. O2 availability
blah blah etc etc #1 only important thing
AFTERLOAD

- main factor
- effect on vent performance curve vs. VR
Sum of loads that contribute to myocardial systolic wall tension
- main factors is TPR

VENT. PERFORMANCE CURVE:
- Moves up/down only (not L/R like contractiliy)


VENOUS RETURN:
- Decrease/Increase; different VRs
- but SAME mean systemic pressure (x-intercept)
* ^ AF (^ TPR) = Dec. CO & SV
BEDSIDE MEASURE OF LV AFTERLOAD

- When do you underestimate AF?
(What do you use then?)
PEAK SYSTOLIC BLOOD PRESSURE

UNDERESTIMATE AF IN AORTIC OUTFLOW OBSTRUCTION
(valvular or subvalvular aoric stenosis)
- Use peak systolic LV pressure
LAW OF LAPLACE IN AFTERLOAD
Amount of systolic wall tension depends on size of ventricular chamber
--> AF decreases throughout ventricular ejection even though systolic BP remains constant

TN = (P inside cavity x chamber radius) / (2 x wall thickness)

^ AF with ^ chamber radius & Decreased wall thickness
(Vent Dilatation = biggest AF ^ )


***When contractility is impaired (sys dysfxn), even a SMALL increase in AF decreases SV a LOT***


T = (P x r) / (2 x h)
HEART RATE & MYOCARDIAL FXN
(CO = HR x SV)

Tachy: Main mechanism 2 increase CO in exercise
>170 is bad: Less diastolic filling = Decreased CO

Force-Freq Relation: Tachy = + Inotropic
- Treppe phenom: ^ cytoplasmic Ca2+

Systolic Dysfxn: REVERSED force-freq
- Tachy decreases contractility
(Impaired ca2+ exchange in SR)
= Reverse Treppe
CAUSES OF HEART FAILURE:
(8)
FAILURE DUE TO...
1. Decreased # of myocardial cells
(MI, amyloidosis, fibrosis)
2. Decreased intrinsic contractility
- sys dysfxn; hypothyroid
3. Excessive External workload
- ^ AF (HTN)
4. Valvular abnormality (stenosis/regurg)
5. Cardiac Dysrhythmia (tachy)
6. Congenital malfomration
7. Decreased Vent. Filling
( tamponade, dias dysfxn)
8. Increased metabolic demand
( hyperthyroid, chronic anemia)
MECHANISM OF DECREASED CONTRACTILITY IN SYSTOLIC DYSFXN
Irregular Ca2+ cycling

*Phosphates are stuck on proteins =
1. Abnormal Ca2+ cycling by SR
(Phospholamban)
2. Abnormal excitation-contraction coupling that links plasma membrane depolarization 2 SR release of Ca2+
3. ^ Cytoplasmic Ca2+ uncouples oxidative phos = less ATP synthesis
4. Less Myosin ATPase activity
(up-reg of beta-myosin heavy chain)
5. Dec activity of phosphocreatine shuttle = less cytoplasmic ATP
6. Less b1-R density/fxn
7. Altered membrane ion channels
SNS Hyperactivity (and PNS hypoactivity) in Heart Failure

*SNS hyperactivity = first finding of Heart failure
- sys or dias
DIRECT EFFECTS OF ^ SNS:
1. Less <3 B1-Rs (protective)
- but B2-R INCREASES
2. ^ Serum Catecholamines
- Depleted NE stores in neurons to <3
- Adrenal gland synth ^^ bc a2-auto-R are desensitized (^ GRK2)
3. Increases contractility& HR (B1-R)
4. Vasoconstriction (a1-R)
5. Redistributes blood flow from skin/kidneys/splanchnics to CNS & <3
PROS AND CONS OF SNS HYPERACTIVITY IN SYS DYSFXN
ACUTE INCREASED CO = GOOD
- Increases contractility& HR (B1-R)
- Vasoconstriction (a1-R)

CHRONIC SNS HYPERACTIVE = BAD:
- Cardiac remodeling --> dec. <3 fxn
- Pulm Edema = ^ LV-AF & ^ LV-Preload
(Increased TPR & VR)
* Increased Preload = HUGE increase in LVEDP bc noncompliant*
- Excess Catecholamines = cytotoxic (b-R) & vent. tachyarrhythmias
SNS HYPERACTIVITY IN DIASTOLIC DYSFXN
Serum catecholamine levels are identical to that of Systolic dysfxn

Diff Consequences:
- ^ Preload (venoconstrict): More normal increase in SV
- ^ AF (^ TPR): Smaller decrease in SV

*overall, less negative effect of hyperactivity in diastolic dysfunction*
COMPENSATORY CARDIAC ADAPTATIONS IN SYSTOLIC DYSFXN

*tries to fight low CO*
1. Sinus tachycardia: 1st bedside symptom
= ^ LV-EDP
- SNS hyperactive (still high b2-R density)
- ^ CO , but at high E cost
- Reverse Treppe phenom
- Eventually dec. CO (dec LV-EDV)

2. Ventricular Dilatation
- Dev when EF decreases
- Increased preload & SV
- Reach elastic limit --> Pulmonary congestion
- ^ AF (increased raidus & dec. wall thickness); may offset ^ preload benefits
- Reduced contractile fxn (slippage of myofibrils)

3. Eccentric Ventricular hypertrophy
- Increased preload --> ecc growth
- Adds sarcomeres in SERIES
--> Cardiomyopathy of overload

--> Diastolic dysfunction eventually (dilatation & ecc. hypertrophy)
ECCENTRIC VENTRICULAR HYPERTROPHY

- Mechanism/stimulus/etc

*adaptation of systolic dysfunction*
^ Diastolic wall tension --> ecc. hypertrophy
Normal heart cells: terminally diff'd (G0)
- growing cells can't contract right
- Constitutive growth: no increase in cell number/size; replace proteins

Dilatation
--> Add sarcomeres in series

FIRST = GOOD
- Decreased AF & ^ LV compliance
- ^ CO & SV

LATER = BAD
- Decreased contractility
( weird Ca2+ cycling & increased E cost)
- ATP depletion --> ischemia & necrosis
- Same stimuli to grow now accelerates apoptosis
- Increased fibrosis
- Surviving cells hypertrophy
--> repeat cycle of death & hypertrophy

= Cardiomyopathy of overload (ventricular remodeling)
DEVELOPMENT OF DIASTOLIC DYSFUNCTION IN SYSTOLIC DYSFXN
PROBLEM RELAXING IN HYPERTROPHIED CELLS
- Less SERCA activity (ATP-dep)
- Weird Phospholamban (reversible inhibitor of SERCA)

*Concentric hypertrophy can develop in pressure overloaded situations
--> also can lead to CM of overload
DRUGS TO TREAT SYSTOLIC FAILURE
Beta blockers & ACE INHIBITORS
- retard cell loss from apoptosis & necrosis
- Inhibits maladpative growth
- Lowers energy expenditure

*both drugs IMPROVE LONG TERM SURVIVAL in SYSTOLIC failure*
(not sure about diastolic)
DEVELOPMENT OF DIASTOLIC DYSFUNCTION IN SYSTOLIC DYSFXN
PROBLEM RELAXING IN HYPERTROPHIED CELLS
- Less SERCA activity (ATP-dep)
- Weird Phospholamban (reversible inhibitor of SERCA)

*Concentric hypertrophy can develop in pressure overloaded situations
--> also can lead to CM of overload
DRUGS TO TREAT SYSTOLIC FAILURE
Beta blockers & ACE INHIBITORS
- retard cell loss from apoptosis & necrosis
- Inhibits maladpative growth
- Lowers energy expenditure

*both drugs IMPROVE LONG TERM SURVIVAL in SYSTOLIC failure*
(not sure about diastolic)
Starling Equation
Qf = K [(HPc - HPis) - o (OPc - OPis)]

+Qf = leaving capillary
Development of pulmonary edema in <3 failure

--> CONGESTIVE HEART FAILURE

- PAWP leading to edema
Normally, lymphatic circulation increases to remove excess fluid, this is not enough at

acute: >25 mmHg
chronic: >28-30 mmHg

Interstitial edema --> alveolar edema

*If liver dysfxn also, serum albumin will be low & edema can develop MUCH more quickly*
Plain Chest X-ray findings of early & late pulmonary edema:


*hypoxic vasoconstriction of lower lobe vessels --> cephalization of vasculature
- Cardiomegaly
- Prominent Upper lobe vessels (Cephalization)
- Alveolar edema in lung bases
- Pleural effusions
- Kerley B lines
PULMONARY MANIFESTATIONS OF LV FAILURE
1. Dysnpea: most common
- Increased work of moving non-compliant (edematous) lungs
- vagal afferents from J receptors, small airway receptors, epithelial irritant receptors
--> tachypnea --> Increased work

2. Dyspnea on Exertion (DOE)
- ACUTE: heart failure
- Gradual onset: chronic lung dz

3. Orthopnea (dyspnea on recumbency)
- ^ VR = ^ LVEDP = ^ HPc

4. PND
- mechanisms similar to orthopnea + dulling of the respiratory center to stimuli
- Edema fluid from legs & lungs take a while to re-enter circulation

5. BL late-inspiratory crackles/rales
- first in lung bases --> apex

6. Hemoptysis
- resp fail, alv. edema, pulm HTN
CV Manifestions of LV FAILURE


- mitral regurg can occur 2' vent. dilatataion (murmur)
- weakness, fatigue, lassitude, etc = decreased CO
1. Catecholamine effects:
- cold/clammy skin
- Heat intolerance
2. Sinus Tachycardia
- Pulsus alternans can occur (EF < 20%)
*RESTING HR IS HIGHEST SPECIFICITY 2 DX <3 FAIL*
3. Abnormal CV response to Valsalva. High spec/sen
- less severe dz: no phase 4 (absent overshoot)
- more severe dz: Square wave
(maintained LVEDP during strain despite super drop in VR)
4. Apical impulse:
- Sustained (concentric LVH)
- Displaced (dilatation)
5. S3
MANIFESTATIONS OF RV FAIL
(cor pulmonale)
1. Left sided parasternal impulse
2. S3
3. Tricuspid regurg (2' dilatation)
4. Elevated systemic venous pressure
---> ^ JVP, Hepatojugular reflux, hepatomegaly & ascities, peripheral dependent edema (pretibial vs presacral)
RAAS ACTIVATION IN SYSTOLIC DYSFUNCTION


- RAAS PATHWAY
- ANGII EFFECTS

*Protects kidney, but damages heart*
1. Increased SNS activity
- kidney, b1-R

2. Reduced renal blood flow
- JG apparaturs (baroreceptors)

--> RENIN RELEASE --> ^ ANG I
(ACE) --> ANG II --> Aldosterone

ANG II:
- potent vasoconstrictor (AT1-R)
- Increased Na+/H2O reabs in proximal tubule
- Enhances <3 contracility & hypertrophy
--> myocardial ischemia, necrosis, apoptosis
RAAS

- ENZYMES
- SOURCES OF ALDOSTERONE


* tissue ACE & tissue chymase are UPREG'd in heart failure
= ^^^ ANGII
Plasma ACE: GOOD
- 10% total ACE
- mostly beneficial: Maintains BP & renal perfusion

TISSUE ACE: BAD
- 90% ACE
- mostly bad: causes inflamm, hypertrophy, and fibrosis

Chymase (interstitial cells): BAD
- mainly in myocardium
- stimulates growth

ANGII stimulates aldosterone synthesis in adrenal glands & vascular endothelial cells & vasc SM cells
ANG II EFFECTS AT THE KIDNEY, HEART, VASCULATURE
Increased GFR
- Vasoconstrict afferent arteriole via ca2+ influx (Ca2+ blockers & ACE-I)
- Vasoconstrict efferent arteriole by using internal stores of Ca2+ (ACE-Is only)
**Can constrict Efferent more to ^ GFR ( >%age of RBF)
Increased Na+/H2O retention = ^ OPc
- stimulates luminal Na+/H+ exchanger in prox tubule

*Potent Vasoconstrictor (AT1-R)
- increased AF (maintains BP, but decreases CO even more)

HEART:
- Increases contractility via cAMP (b1, b2) & IP3 (AT, alpha, ETa)
- Induces proto-oncogenes --> Hypertrophy --> ischemia, necrosis, apoptosis
ALDOSTERONE EFFECTS
HEART:
- Hypertrophy, remodel, & fibrosis
--> CM of overload (^ cell loww)
- Decreased NO = Decreased coronary blood flow = Myocardial ischemia & worse SYSTOLIC DYSFXN

VASCULATURE: ^ BP
- ^ SNS outflow fro CNS = ^ afterload
- Na+ reabs in distal nephron = ^ preload
ADH IN HEART FAILURE
(ARGININE VASOPRESSIN)


- STIMULI FOR RELEASE
- mech of axn

**you get serum hyponatremia, even though total body sodium content is increased**
1. SNS activation: MAIN reason for increased ADH
- decreased CO stimulates SNS activation
- ATN II activation overrides the osmotic control mechanisms of ADH release

2. Serum Hypertonicity

3. Hypovolemia

4. ATN III (cleavage product of ATN II)

A. V2-R to increase H2O reabs in medullary collecting ducts (^ preload)
= hyponatremia (bad prognosis in <3 fail)

B. V1-R: vasoconstrict (^ afterload)
C. V1a --> LV hypertrophy/remodeling
ADH DRUGS
1. V1 & V2-R antags (conivaptan)
- increase free H2O excretion and increase serum Na+ concentration

2. V2 antags (tolvaptan)

*vaptans = aqua-retics
NATRIURETIC PEPTIDES

- what
- where
- levels in heart failure
Stimulus for release: distention
ANP = R Atrium
BNP = Ventricles
CNP = Vasculature

* Neutral endopeptidase clear the NPs.

*ALL LEVELS ARE HIGHER IN HEART FAILURE*
- ATRIA MAKES WAY MORE BNP & CNP
NATRIURETIC PEPTIDES

AXNS

GOOD! (but not enough to fight RAAS)
1. balanced vasodilatation (^ cGMP & less intracell Ca2+)
= less preload & AF

2 .Redistributes plasma volumes into extravascular space = Reduced Preload

3. NATRIURESIS & DIURESIS
^ GFR : Dilates aff & constricts eff, relaxes mesangial cells
- Inhibits renin release & aldosterone secretion
- Antagonizes vasopressin & ATN ii effcts in kidneys

4. Decreases Cardiac remodeling & decreases myocardial apoptosis

*effects diminish as CHF worsens; receptors are down-reg'd and so much Na+ gets reabs'd early on, not much is excreted in distal nephron*
SERUM BNP & HEART FAILURE
in CHF, atria makes all three types of natriuretic peptides

- Serum BNP correlates with EDP & LV wall TN
- does NOT differentiate b/w Sys vs. Dias dysfxn

- Serium BNP > 100pg/mL has HIGH sens & spec in differentiating dyspnea cuased by <3 failure vs. others causes (lung dz)
WHAT HAPPENS TO THE LIVER IN HEART FAILURE?
1. Liver edema <-- systemic venous congestion (R<3 fail)
- around central liver venules (fibrosis)
- hepatic arteriole areas are spared

2. Hepatocellular Damage
- increased ALT/AST levels
- alkaline phosphatase & bili can also increase 2' intrahepatic cholestasis

3. Cardiac cirrhosis = nutmeg liver

4. Decreased plasma colloid oncotic pressure
- edema is worsened everywhere

5. Ascites <-- increased hepatic sinusoidal pressure
Cytokine storm of heart failure

- what cytokines?
- effects?
1. TNFa = pro-inflamm
- increased in systolic dysfxn
- released by <3 & vasculature
- Cachexia (anorexia, muscle waste, no appetite)
- Slippage of sarcomeres (dilatation)
- ^ myocardial proteins ( hypertrophy)
- Cell loss <--- apoptosis
- decreases contractiliy (NO)

2. NO
- increased cGMP in heart
- negative inotropic effects (inhibits Ca channels)

3. Endothelin-1
- heart also makes this in <3 fail
- ^ preload & AF & stimulate's hypertrophy
- does a LOT of stuff; mostly bad
- initially decreased contractility
- vent remodeling
etc etc etc
APOPTOSIS IN HEART FAILURE
NORMAL: 1-2% cells
HEART FAIL: up to 40%

ATP-DEPENDENT process
- cell membrane remains intact

INDUCERS OF APOPTOSIS:
- NO, Free radicals, TNFa, ATN II,ET-1, Catechoalmines, Ca2+ overload

*Hypertrophy tries to compensate, but ultimately makes things worse
Pharmacotherapy in heart failure


**CAD and Kidney failure are the #1 cardiac & non-cardiac causes of heart failure
Volume of distribution DECREASES in proportion to severity of heart failure

- need to decrease loading dose of meds

- also need to factor in any renal & hepatic dysfxn
CARDIOMYOPATHY

- DEFINE
Diseases of the myocardium associated w/ mechanical/electrical dysfunction
- usually with inappropriate ventricular hypertrophy or dilatation

- can be primary or secondary

*first indication of CM in many pts is SUDDEN DEATH*
CARDIOMYOPATHY

- TYPES OF FUNCTIONAL IMPAIRMENT
1. Dilated (congestive) CM
- systolic dysfxn & vent dilatation

2. Hypertrophic CM
- Diastolic dysfxn& vent. hypertrophy
- conduction disturbances & suddent death
- young adults

3. RESTRICTIVE CM: uncommon
- restricted filling of the ventricle & infiltration/obliteration of myocardium w/ NON-cardiac junk

4. Arrhythmogenic RV CM: uncommon
- RV myocardial electrical instability
- loss of myocytes with fibrofatty tissue replacement
PRIMARY HYPERTROPHIC CARDIOMYOPATHY (HCM)

etiology & morphology


MOST COMMON!!
(auto dom)
Most common primary CM
- most common cause of SUDDEN CARDIAC DEATH in young adults & athletes

Most common: Mutations in b-myosin heavy chain gene & Myosin-binding protein C gene

MORPHOLOGY:
- Concentric hypertrophy
- Asymmetric hypertrophy involves the IV septum more
--> LV outflow obstruction
- Uncontrolled parallel, disorganized hypertrophy = WAVY FIBERS; SWIRLY, perpendicular

*Fibrosis
- if septal hypertrophy & fibrosis --> AV conduction disturbances (bundle block)
*Intramural coronary aa messed up --> myocardial ischemia
PRIMARY HCM

PATHOPHYS

- normal: LA contraction = 10% vent. filling
**A-FIB IS SO BAD**

- FORWARD CO is pretty well preserved unless IHSS is really bad
Normal EJECTION FRACTION
-Concentric LVH = less afterload = ^ SV
- Decreased contractility

LV OUTFLOW OBSTRUCTION
- SAM
- can be labile obstruction caused by ^ contractiliy or decreased Preload/af
*WATCH OUT FOR DIURETICS & VASODILATORS*

Diastolic Dysfxn:
- Hypertrophy & fibrosis = rigid passive relaxation
- Less Ca2+ reuptake = bad active relaxation
- LA contraction = SUPER NECESSARY (60% vent. filling)

SNS increases
- sinus tachy worsens CO
- Increased contractiliy worsens LV outflow obstruction & worsens CO
SAM IN HOCM
LV OUTFLOW OBSTRUCTION
- SAM: Systolic anterior motion of mitral valve contacts IV septum
- Chordal elongation & ant. displacement of papillary mm
= SUBAORTIC STENOSIS (not the norm)
DOC for PRIMARY HCM
BETA-BLOCKERS
- relieve symptoms:

1. decrease HR (improve vent. fillin)
2. Decrease contractility (lessen LV outflow obstruction)
3. Decrease myocardial O2 consumption (less ischemia)
4. Helps prevent a-fib
SIGNS AND SYMPTOMS OF PRIMARY HCM

*valsalva makes the <3 smaller*
^PAWP
- Dyspnea on exertion

Exertional angina
- abnormally small intramural coronary aa can't provide enough blood to hypertrophied heart

Fatigue & Syncope
- low forward CO (in cases of IHSS)

Vent. tachy & fibrillation = most common causes of sudden death
- diastolic heart failure can also be a problem (gradual issue)

Bifid carotid pulse if obstruction present
- S4 in sinus rhythm
- Systolic murmur w/ outflow prob
*murmur increases w/ sustained valsalva & decreases w/ squatting
PRIMARY DILATED/CONGESTIVE CM

1/3 of dilated CM

etiology & morphology
Mainly auto dom
- abnormal cytoskeletal proteins & sarcomere proteins that anchor sarcomeres to cell membrane or nucleus

VIRAL: Coxsackievirus B & adenovirus
- elevated cardiac enzymes (necrosis)

MORPHOLOGY:
- Vent. dilatation (out of proportion to any hypertrophy going on)
- Vacuolated myocardiocytes
- big nuclei (polyploid)
- fibrous infiltration
secondary causes of dilated CM
1. CAD
2. Endocrine: Diabetes, HTN
3. Toxins & Drugs:
- Alcohol
- Chemo: Doxorubicin, Daunorubicin, Herceptin
*generate free radicals*
PATHOPHYSIOLOGY OF DCM (CCM)

*BL VENTRICLE FAILURE IS CHARACTERISTIC OF DCM
= simultaneous pulmonary & systemic venous congestion
Decreased contractiliy is the MAIN PROBLEM
- sarcomere sucks
- decreased myocardiocytes bc cytockeletal proteins suck = apoptosis/necrosis
- Down-reg's B1-R

= DECREASED EJECTION FRACTION
(Major diff from HCM)
- Increased LVEDV

MAIN COMPENSATION: RAAS & SNS
- Acute: ^ CO, ^ BP, ^ Contractiliy
- bad chronically --> CM of overload (already had it)
TX OF DCM
beta-blockers & ACE inhibitors
(carvedilol & enalapril)
- retard cell loss & vent. remodeling
*may acutely decrease contractiliy

also:
- arteriovasodilators (decrease preload & AF)
- contractility enhancers ( ^ CO)
- diuretics (decrease preload)
SIGNS AND SYMPTOMS OF DCM/CCM

*NO EVOLUTION OF SYMPTOMS
- R & L <3 symptoms at the same time
CONSISTENT W/ BIVENTRICULAR FAILURE (simultaneous onset)
- displaced LV & RV impulses
- S3
- Late inspiratory crackles
- Elevated JVP
- hepatomegaly& dep. pitting edema

- Mural thrombi (stagnant blood)
- Arrhythmias: dilatation & excess SNS
*sudden death*

- Exercise intolerance: low forward CO
- Pumonary stuff (high PAWP)
PROGNOSIS OF DCM
50% die of pump failure or sudden death (arrhythmias)
- w/in 5 yrs w/o transplant

Long term tx w/ ACE inhibitors & beta blockers (carvedilol) have improved survival

* need to add warfarin bc of high embolism risk
RESTRICTIVE CM

Etiology & Morphology

RAREST
Rarest, worst prognosis
- mostly secondary causes
= infiltration of cardiac interstitium (amyloidosis) or cells (hemochromatosis)
- obliterative diseases also cause this (carcinoid endomyocardial fibrosis)
PATHOPHYSIOLOGY OF RESTRICTIVE CM

- looks like?
Myocardial restriction to diastolic filling
- reduced LV & RV volumes
- Nearly normal systolic fxn
- NORMAL EF
- decreased SV & CO & LVEDV

Looks like constrictive pericarditis
- use Plasma BNP to tell the difference
- normal BNP in CP

^ LVEDP at onset of diastole
- Characteristic fillin pattern: square root / dip & plateau / M pattern
- Atrial P is much higher
- Filling is mostly down by mid-diastole (plateau)
- same filling pattern in CP

LV filling pressure > RV filling pressure
- also used to distinguish from CP
TX OF RESTRICTIVE CM
GIVE THE HEART ENOUGH TIME TO FILL - control tachy
- beta blockers
- calcium blockers

*use diuretics w/ caution ( decrease SV too much)

*a-fibs would be DISASTROUS
- atrial contraction is SUPER important to fill the tiny chamber
SIGNS & SYMPTOMS OF RESTRICTIVE CM
1. Normal heart size
2. Biventricular failure
- simultaneous onset of symptoms like in DCM
3. cHARACTERIS FILLING PATTERN
- elevated JVP: large & rapid x & y descents
4.S3 & S4 may be present; apical impulse normal but reduced in amplitude
SECONDARY FORMS OF CARDIAC HYPERTROPHY

- etiology & morphology

*all causes are associated w/ myocardial fibrosis*

***LV HYPERTROPHY = MOST POWERFUL PREDICTOR OF ADVERSE CV OUTCOMES iN HTN PTS ****
1. Concentric hypertrophy
- pressure overload
- add sarcs in parallel
- Causes: HTN & AS, DM, PULM HTN
- 1' vs 2' hypertrophy: In 2' = Orderly, uniform enlargements; no fiber disarry*****

2. Eccentric hypertrophy
- volume overload
- add sarcs in series
- myocardial mass is greater, even tho wall looks thinner
- Causes: ischemia & chronic valvular regurg
*most common cause of RVH eccentric is LV systolic dysfxn
PATHOPHYSIOLOGY OF 2' Cardiac hypertrophy

- initial effects
INITIALLY: ADAPTIVE

1. Decrease AF (normalize systolic wall stres)
- maintain CO

2. Metabolic switching
- Switches from FFA (70% ATP) Powerhouse to a Glucose powerhouse. *except in DM*
- More efficient: more ATP/O2
- Affects tsc of FA oxidation& glucose metab genes
PATHOPHYSIOLOGY OF 2' Cardiac hypertrophy

- later effects/ bad effects


**FIBROSIS distinguishes bw pathologic & physiologic hypertrophy**
1.Decreased relaxation: immediate
- increased collagen synthesis & less degradation
- Affects contractiliy, relaxation rate, passive filling
- ACE inhibis & Aldosterone antags dcrease collagen synth & reverse fibrosis

2. Perivascular fibrosis
- limits coronary blood flow & myocardial E production
- reduced blood flow relative to increased mass it needs to perfuse

3. Diastolic dysfxn --> systolic dysfxn as muscle mass increases

4. Ventricular arrhythmias more likely
- conduction block
- facilitates re-entry
DOC for pathologic hypertrophy
(2' hypertrophy)
ACE-Inhibitors & beta-blockers

- decrease fibrosis & improve <3 fxn

New class of drugs: 3-keto acyl CoA thiolase inhibitor
- swtiches <3 metabolism from FFA to glucose
- not in use yet
PATHOLOGIC HYPERTROPHY

- CHARACTERISTICS
- drugs
MYOCARDIAL FIBROSIS
- distinguishes pathologic vs physiologic
- ^ collagen synthesis and decreased degradation
- Profibrotic substances: prorenin, ATN II, alodsterone, growth factors, catecholamines, etc

*Initially improves CO, but then decreases myocardial relaxation
- plasma concentration of PROCOLLAGEN TYPE 1 correlates w/ amt of fibrosis.
( --> type 1 collagen)

ACE inhibitors & aldosterone antags
- decrease collagen synthesis & partially reverse fibrosis in hypertensive <3 dz
PATHOLOGIC HYPERTROPHY

- CHARACTERISTICS
- drugs
MYOCARDIAL FIBROSIS
- distinguishes pathologic vs physiologic
- ^ collagen synthesis and decreased degradation
- Profibrotic substances: prorenin, ATN II, alodsterone, growth factors, catecholamines, etc

*Initially improves CO, but then decreases myocardial relaxation
- plasma concentration of PROCOLLAGEN TYPE 1 correlates w/ amt of fibrosis.
( --> type 1 collagen)

ACE inhibitors & aldosterone antags
- decrease collagen synthesis & partially reverse fibrosis in hypertensive <3 dz
PATHOLOGIC HYPERTROPHY

- CHARACTERISTICS
- drugs
MYOCARDIAL FIBROSIS
- distinguishes pathologic vs physiologic
- ^ collagen synthesis and decreased degradation
- Profibrotic substances: prorenin, ATN II, alodsterone, growth factors, catecholamines, etc

*Initially improves CO, but then decreases myocardial relaxation
- plasma concentration of PROCOLLAGEN TYPE 1 correlates w/ amt of fibrosis.
( --> type 1 collagen)

ACE inhibitors & aldosterone antags
- decrease collagen synthesis & partially reverse fibrosis in hypertensive <3 dz
PATHOLOGIC HYPERTROPHY

- CHARACTERISTICS
- drugs
MYOCARDIAL FIBROSIS
- distinguishes pathologic vs physiologic
- ^ collagen synthesis and decreased degradation
- Profibrotic substances: prorenin, ATN II, alodsterone, growth factors, catecholamines, etc

*Initially improves CO, but then decreases myocardial relaxation
- plasma concentration of PROCOLLAGEN TYPE 1 correlates w/ amt of fibrosis.
( --> type 1 collagen)

ACE inhibitors & aldosterone antags
- decrease collagen synthesis & partially reverse fibrosis in hypertensive <3 dz
PATHOLOGIC HYPERTROPHY

- progression ---> maladaptive
PERIVASCULAR FIBROSIS
- limits coronary blood blood & myocardial energy production
*normal resting CBF, but reduced RELATIVE to increased <3 mass

- Coronary vasodilatory reserve is much reduced in hypertensive pts w/ concentric LVH

1st. Diastolic dysfxn
2nd. Systolic dysfxn

*ventricular arrhythmias much more likely*
- fibrosis facilitates the development of re-entry (?)
PATHOLOGIC HYPERTROPHY

- progression ---> maladaptive
PERIVASCULAR FIBROSIS
- limits coronary blood blood & myocardial energy production
*normal resting CBF, but reduced RELATIVE to increased <3 mass

- Coronary vasodilatory reserve is much reduced in hypertensive pts w/ concentric LVH

1st. Diastolic dysfxn
2nd. Systolic dysfxn

*ventricular arrhythmias much more likely*
- fibrosis facilitates the development of re-entry (?)
PATHOLOGIC HYPERTROPHY

- progression ---> maladaptive
PERIVASCULAR FIBROSIS
- limits coronary blood blood & myocardial energy production
*normal resting CBF, but reduced RELATIVE to increased <3 mass

- Coronary vasodilatory reserve is much reduced in hypertensive pts w/ concentric LVH

1st. Diastolic dysfxn
2nd. Systolic dysfxn

*ventricular arrhythmias much more likely*
- fibrosis facilitates the development of re-entry (?)
PATHOLOGIC HYPERTROPHY

- progression ---> maladaptive
PERIVASCULAR FIBROSIS
- limits coronary blood blood & myocardial energy production
*normal resting CBF, but reduced RELATIVE to increased <3 mass

- Coronary vasodilatory reserve is much reduced in hypertensive pts w/ concentric LVH

1st. Diastolic dysfxn
2nd. Systolic dysfxn

*ventricular arrhythmias much more likely*
- fibrosis facilitates the development of re-entry (?)
PATHOLOGIC HYPERTROPHY

- CHARACTERISTICS
- drugs
MYOCARDIAL FIBROSIS
- distinguishes pathologic vs physiologic
- ^ collagen synthesis and decreased degradation
- Profibrotic substances: prorenin, ATN II, alodsterone, growth factors, catecholamines, etc

*Initially improves CO, but then decreases myocardial relaxation
- plasma concentration of PROCOLLAGEN TYPE 1 correlates w/ amt of fibrosis.
( --> type 1 collagen)

ACE inhibitors & aldosterone antags
- decrease collagen synthesis & partially reverse fibrosis in hypertensive <3 dz
PATHOLOGIC HYPERTROPHY

- progression ---> maladaptive
PERIVASCULAR FIBROSIS
- limits coronary blood blood & myocardial energy production
*normal resting CBF, but reduced RELATIVE to increased <3 mass

- Coronary vasodilatory reserve is much reduced in hypertensive pts w/ concentric LVH

1st. Diastolic dysfxn
2nd. Systolic dysfxn

*ventricular arrhythmias much more likely*
- fibrosis facilitates the development of re-entry (?)
PATHOLOGIC HYPERTROPHY

- CHARACTERISTICS
- drugs
MYOCARDIAL FIBROSIS
- distinguishes pathologic vs physiologic
- ^ collagen synthesis and decreased degradation
- Profibrotic substances: prorenin, ATN II, alodsterone, growth factors, catecholamines, etc

*Initially improves CO, but then decreases myocardial relaxation
- plasma concentration of PROCOLLAGEN TYPE 1 correlates w/ amt of fibrosis.
( --> type 1 collagen)

ACE inhibitors & aldosterone antags
- decrease collagen synthesis & partially reverse fibrosis in hypertensive <3 dz
PATHOLOGIC HYPERTROPHY

- progression ---> maladaptive
PERIVASCULAR FIBROSIS
- limits coronary blood blood & myocardial energy production
*normal resting CBF, but reduced RELATIVE to increased <3 mass

- Coronary vasodilatory reserve is much reduced in hypertensive pts w/ concentric LVH

1st. Diastolic dysfxn
2nd. Systolic dysfxn

*ventricular arrhythmias much more likely*
- fibrosis facilitates the development of re-entry (?)
Preload changes and PV loops
Increase preload:
- shifts curve to the RIGHT (and up a little)
- increases diastolic filling & SV

DECREASE:
- Moves it down and to the left

*same F-S curve
AFTERLOAD CHANGES & PV LOOPS
INCREASE AFTERLOAD:
- Moves up, and rectangle gets smaller
- shortened ventricular ejection = longer isovolemic contraction & decreased SV

DECREASED:
- Moves down and to the left

*shifts up/down a F-S curve*
CONTRACTILITY CHANGES & PV LOOPS
INCREASED:
- UP and to the LEFT


DECREASED: down & to the right
(Systolic Dysfxn looks like this - problem contracting)

*different F-S curves, move pts along a slope*
DIASTOLIC DYSFXN
- PV LOOP
moves UP and to the LEFT

if due to LVH
- diastolic filling has an upward slope

if due to SERCA problem (reuptake of Ca2+)
- downward slope of diastolic filling.
MITRAL STENOSIS

- PATHOPHYS
20-40 yr after RHEUMATIC FEVER
- progressive narrowing of orifice (valve fusion)
= diatolic pressure gradient
*Less LV filling = Less forward CO

Exercise causes initial symptoms:
Tachy: decreases time spent in diastole
- reduces SV and Raises LA-P
Increased CO: Increases pressure gradient

--> LEFT ATRIAL CONCENTRIC HYPERTROPHY

--> CHRONIC BUILDUP OF PRESSURE --> PULM HTN --> concentric RVH --> RIGHT HEART FAIL

LEFT VENTRICLE IS FINE IN ALL OF THIS!!
MITRAL STENOSIS

- CAUSES
- PATHOPHYS
-
20-40 yr after RHEUMATIC FEVER
(valve fusion)

diastolic pressure gradient develops from LA to LV
- Chronic Elevation of LA-P = concentric LAH
--> Pulm vasc hypertrophy/HTN
---> concentric RVH
---> Right heart failure
*pulm edema occurs after HPc gets too high*

LV IS TOTALLY NORMAL
- Contractility is fine
- normal afterload?
*Decreased SV & CO & EDV
MITRAL STENOSIS

- Symptoms
- aggravating factors


*IMPORTANT*
- Distance bw A2-OS varies inversely w/ level of LA-P
*short interval = BAD STENOSIS/HIGH LA-P*
#1. DOE: tachy & ^ CO requirement
- Increased work of breathing 2' pulmonary congestion
2. Orthopnea
3. PND
4. Hemoptysis (rupture under high HPc)
5. Palpitations (a-fib)
6. Systemic emboli
7. Right heart failure signs: ascites, high JVP, Hepatomg edema)
8. Normal impulse for a long time ----> sustained parasternal impulse
8.CARDIAC TRIAD:
Loud S1, opening Snap low-pitched, rumbling diast murmur w/ presystolic accentuation

*Anything that produces Tachy & increased CO makes it worse
- less time for LV filling
- Greater pressure gradient developed bw LA & LV (edema)
MITRAL STENOSIS COMPLICATIONS
A-FIB ---> MURAL THROMBI
*a-fib is poorly tolerated*

- No atrial contraction = worse LV filling
- Increased Pulmonary venous congestion
- Systemic & pulmonary thrombi

(Ca2+ channels open more readily 2' dilatation?)

**no presystolic accentuation if a-fib is present*
RADIOGRAPHIC FINDINGS IN MS
4 BUMPS
- Abnormal bump = hypertrophied LA
- Esophageal constriction 2' to LAH
- No clear space bw RV & sternum 2' RVH
CHRONIC MITRAL REGURG
- cause
- PATHOPHYS

^LVEDP --> LV dilatation ---> eccentric hypertrophy

(pretty well tolerated, like other chronic regurg's)

*Afterload is inversely related to SV & max rate of velocity of ejection*
USA- MVProlapse
Others - Rheumatic fever

SHORT isovolemic contraction & LONG ejection phase
- LV afterload = LA-P

Decreased AF
Increased Contractility
Increased Preload
- Increased SV
GREAT ejection fraction (~80%)
Normal-Decreased Forward CO
- ^^^ total CO

Eccentric LVH 2' LV dilatation
---> LV systolic dysfxn
--> backup of pressures (BAD!)
CHRONIC MR

tx?
VASODILATORS
(AF reducers; decrease TPR)

- any increases in AF are dangerous bc they decrease forward CO
- more blood --> LA means pulmonary congestion
RADIOGRAPHIC FINDINGS IN MS
4 BUMPS
- Abnormal bump = hypertrophied LA
- Esophageal constriction 2' to LAH
- No clear space bw RV & sternum 2' RVH
CHRONIC MITRAL REGURG
- cause
- PATHOPHYS

^LVEDP --> LV dilatation ---> eccentric hypertrophy

(pretty well tolerated, like other chronic regurg's)

*Afterload is inversely related to SV & max rate of velocity of ejection*
USA- MVProlapse
Others - Rheumatic fever

SHORT isovolemic contraction & LONG ejection phase
- LV afterload = LA-P

Decreased AF
Increased Contractility
Increased Preload
- Increased SV
GREAT ejection fraction (~80%)
Normal-Decreased Forward CO
- ^^^ total CO

Eccentric LVH 2' LV dilatation
---> LV systolic dysfxn
--> backup of pressures (BAD!)
CHRONIC MR

tx?
VASODILATORS
(AF reducers; decrease TPR)

- any increases in AF are dangerous bc they decrease forward CO
- more blood --> LA means pulmonary congestion
SYMPTOMS OF CHRONIC MR
1. Fatigue with exercise
---> Dyspnea on exertion

2. Dyspnea, orthopnea, & PND
- ^ PAWP (giant V waves)

3. Palpitations (arrhythmias)
4. Hyperdynamic lateral apical impulse
(big SV)
5. Apical holosystolic murmur
- radiates into Left axilla
- intensity correlates w/ severity
- Increased afterload = ^ intensity
6. S3 (does not tell u severity - only in AR)
ACUTE MR

- PATHOPHYS/CAUSE

*same diastolic pressure curves
(decreased in chronic MR)
USUALLY ruptured chordae tendineae after MI
- no time for LA dilatation
- MARKED increase in LA-P
- RAPID pulm edema
- forward CO is severely reduced --> systemic hypoperfusion/hypoTN
MITRAL VALVE PROLAPASE

(probably inherited; auto dom)

CAUSE/PATHOPHYS
Myxomatous degen of mitral valve
- more common in women, worse prognosis in men
- usually benign
*most common cause of MR*

PATHOPHYS:
Chordae get too long for annulus
- decreased LVEDV ---> MVP earlier in LV systole

*many pts have ^ SNS activity and high plasma catecholamines
MVP

- FINDINGS

Timing: Size of heart
Intensity = AF (LV vol)
1. Midsystolic click
- tensing of elongated chordae
- smaller heart move click CLOSER to S1 (standing / sustained Valsalva)
- Bigger heart (squat, handgrip) = move click closer to 2nd heart sound

2. Late systolic murmur
= mild MR
- intensity correlates w/ severity
- Decreased LV Vol (increased contractility/decreased preload) prolong duration & increase murmur
*decreased AF prolongs murmur, but less intense
MVP

- SYMPTOMS
- PROGNOSIS
most are asymptomatic

- palpitations
- brief episodes of sharpk, precordial chest pain
- anxiety (high SNS activity)

PROGNOSIS:
1. 15% (MOSTLY MEN) WILL HAVE PROGRESSIVE MYXOMATOUS DEGEN OF MV
--> severe MR (need replacement)
2. Embolic events (women>men)
- TIAs & storkes
- birth control pills
3. Infective endocarditis
*MVP is the most common predisposing factor
VALVULAR AORTIC STENOSIS

- PATHOPHYS

*VERY similar to atherosclerosis*

(vasodilators won't help, cuz sys BP isn't in picture)
Active inflamm process (like CAD) ----> Valvular calcification (or congenital bicuspid aorta)

Risk factors: HTN & hyperlipidemia
- correlates w/ ^ CRP

^ AF (systolic wall TN) causes Systolic P Gradient
(LVESP = AF)
--> LVH Concentric (-->sys dysfxn)
---> LV dilatation (^ preload; then diastolic dysfxn)
bad news bears about AS

- consequences of LVH & DILATATION
LVH CONCENTRIC
- Increases O2 demand in face of ltd CBF
--> Myocardial ischmia
--> Systolic dysfxn
= Dec EF, Inc LVEDV, LVEDP

LV DILATATION
- late development
- ^ preload to sustain SV
- SUCKS bc of diastolic dysfxn (small V increase; HUGE P increase)
SIGNS & SYMPTOMS OF AS

*boot-shaped heart*
- no atrial appendage early in dz
1. TRIAD: angina, exertional dyspnea, & syncopee during exertion
- O2 demand, high PCWP, Decreased CO
2. Systemic Vasodilation (local metabs)
- Decreased VR --> syncope
3. Narrow Pulse Pressure
- decreased sys BP & normal dias
4. Sustained apical impulse
- not late in dz (dilatation)
5. S4 = severe LVH in yount pts
6. Late peaking systolic murmur
- radiates into carotid
- intensity coorrelates w/ severity
- Ejection sound (esp in young)

Murmur
Increases w/ decreased AF (amyl nitrate)
Decreased w/ decreased preload (Valsalva)
- Squatting = louder (^ preload/AF)
chronic AR

- causes


*ALSO BOOT SHAPED*
- can look like chronic MR
Essential HTN & Bicuspid Aortic Valve

1st: ^ AF
2.^ Preload (LVEDV) is initial compensatory mechanism
3. Dilatation
4, eccentric hypertrophy (more efficient)
5. Sys dysfunction & CHF
6. ^ sns
-----> ^ sys vasc r = ^ AF (rpt)

Decreased Diastolic BP + HUGE SV = Wide pulse pressure
CHRONIC AR

- Paradoxical effect of isotonic/aerobic exercise
Exercise --> tachy & vasodilation
- Less time for regurg to happen
- Less AF
= ^ CO

- Symptoms can improve w/ exercise
SYMPTOMS/SIGNS OF AR

DOC = ARTERIOVASODILATORS
(DECREASE AF)
1. Palpitations
- HUGE SV
2. ^ pawp = DOE, orthopnea, PND
3. Angina
- less blood going to coronary aa
- esp in those w/ CAD
4. Peripheral manifestations 2' big SV
- Corrigan's/waterhammers, quincke's, Duroziez's (sys-dias bruit in femoral), Hill's sign(?)
5. Hyperdynamic apical impulse
- displaced down & left
6. S4
7. Left lung can be compressed by massive LV
~ewart's sign: dull, ^VTF, Egophony @ tip of scapula
8. 2 DIASTOLIC MURMURS
- blowing, high pitched
- low, rumbing (austin flint): fxnal mitral stenosis = BAAAD!
ACUTE AR
- causes
- pathophys
#1. Infectious endocarditis (USA)
---> VALVE CUSP PERF

LVEDV only increases a little (compared to Chronic AR), but LVEDP ^^^^^^
---> pulmonary edema & way decreased CO

Pulse pressure may be normal
(Normal Sys BP & Dias BP = LVEDP)

same curves as normal, just increased preload
(normal AF & contractility)
MYOCARDIAL OXYGEN CONSUMPTION (MVO2)

- determinants
- highest/lowest times
65% used for Contraction; 15% = relaxation

TOP 3: HR, Afterload, & Contractility
- Proportional increases

Minor: Diastolic Filling (Preload)

Highest during isovolemic contraction
- MVO2 is greater in pressure overloaded states (increased isovolemic contraction time)
Lowest = late diastolic filling

**CBF is opposite**
DOUBLE PRODUCT

- use
- exceptions/limitations
Used in absence of LV outflow obstruction to predict MVO2
- underestimates MVO2 if obstruction is present (AS)
(Sys BP does NOT = AF)

*O2 consumption = HR x sys BP*

(Ignores the contribution of contractility & preload, but that's ok)
Coronary Circulation
- MVO2 at rest (extraction)

how CBF adjusts to meet increased myocardial O2 demand
Myocardial O2 extraction is almost maximal at rest (>90%)
- more capillaries/mm2 = ^ O2 extraction

*AV O2 difference is the largest for any organ in the body
- extraction is already maximal
- CO needs to increase for higher O2 demand

*O2 consumption is FLOW-LIMITED*
- that's why heart is so susceptible to ischemia
CORONARY BLOOD FLOW

- MAJOR DETERMINANTS
A. Perfusion Pressure
- Aortic Pressure
- Proportion of time <3 spends in diastole
(tachy vs. brady)
- RA-P (drains into RA)


B. Coronary Vascular Resistance
- Extracoronary resistance
- LV diastolic P
- ANS
- Autoregulation:myogenic & chemical
- Vasc Endothelium (NO)
PERFUSION PRESSURE

- determinants
1. Aortic Pressure
- Coronary ostia are partly occluded by aortic valve cusps during systole
= Sys coronary a. P < Sys BP
(diastolic pressures are the same)

2. Proportion of time spent in Diastole
- Perfusion pressure drops during tachycardia

3. Right Atrial Pressure
Q = (Aortic diastolic P - RA P) / Coronary Resistance
- Increases in RA-P = reduced CBF
(coronary aa drain into RA)
*Severe tricuspid stenosis*
CORONARY VASCULAR RESISTANCE

1. Extracoronary resistance
2. LV diastolic pressure
1. Extracoronary Resistance
- systole compresses intramural vessels
--> CBF to LV drops almost completely during systole
*This is only a factor in RVH for Right heart*

2. LV Diastolic Pressure
- High LV-EDP compresses subendocardium --> risk of ischemia
- Endocardium is farthest away from large epicardial coronary aa.
CORONARY VASCULAR RESISTANCE

3. ANS
4. AUTOREG*****
- most important det. of Coronary resistance
5. VASC ENDOTHELIUM
3. ANS
A. Tonic SNS: a1-R = vasoconstrict; B1 = Tachy
- overwhelmed by autoreg in exercise
B. Vagal: little direct effect
- indirect vasoconstriction (decreases metab)
- M2-mediated brady
- M3: vasodilate

4. AUTOREGULATION:
- CBF matched 2 <3s metabolic activity
A. Myogenic: most important in EPICARDIAL prearterioles
B. Chemical: most imp. in Intramural aa.
- Adenosine: best chem. mediator
= Myocardial ischemia/hypoxemia
MECH:
A2-R on endothelium opens Katp channels & closes Ca2+ channels
= hyperpolarize & RELAX coronary smooth mm
= VASODILATE! INCREASE CBF

--> Perfusion pressure rises 2' vasodilation
---> Adenosine is washed out
---> Coronary resistance increases (constant CBF)

*in NON-autoregulating vasc bed, CBF is proprotional to increase in perfusion pressure
VASCULAR ENDOTHELIUM & CORONARY A. RESISTANCE
RELEASES CHEMICAL MEDIATORS

1. NO <--- L-arg
--> Vasc. Smooth mm
---> increases cGMP & opens K+ channels (hyperpolarize = relax!)

*similar to Nitroglycerin (makes NO)

2. NO also has anti-atherogenic properties
(inhib lipid peroxidation platelet aggreg/activation, monocyte adhesion, vasc smooth mm. prolif)

3. Endothelin-1: vasoconstrictor
- opp of NO
- released in response to shear stress & ATN II & catecholamines
--> ET-A receptors
--> PLC, IP3, Ca2+ = CONSTRICT!

**HTN, Hypercholesterolemia, smoking, & DM = Decrease NO & Increase Endothelin-1
MYOCARDIAL ISCHEMIA VS. HYPOXIA
ISCHEMIA
Decreased coronary perfusion
---> Myocardial O2 deprivation & inadequate removal of cellular metabolites
- Develops whenever O2 demand > supply
= chronic stable angina
(does NOT explain acute coronary syndromes, esp stunning & reperfusion)

HYPOXIA:
Adequate perfusion, but reduced O2 supply
MYOCARDIAL STUNNING

- what
- mech
- tx
Acute, brief, sever ischemia --->
Reversible contractile dysfunction
*Duration of stunning proportional to duration of ischemia

MECH:
Transient accum of Ca2+
= proteolysis of troponin I & uncouples cardiac excitation from contraction

tx:
- Beta agonists
- milrinone
- digitalis glycosides

*If its the cause of sys dysfxn after acute ischemia --> be aggressive!*
- CABG or angioplasty
REPERFUSION INJURY
- what
- mech
- results


*can increase final infarct size by as much as 50%!*
1. Acute ischemia
2. Coronary reperfusion w/ t-PA, angioplasty, stenting, or CABG
3. ischemic myocardiocytes = irreversible necrosis

MECH:
1. bring in O2 radicals & neutrophils
2. destroys cell membranes (lipid peroxidation)
3. Massive Ca2+ overload
- opens mitochondrial permeability transition pore (PTP)
- uncoupled oxidative phos
= ATP depletion; cell dies
*Also proteolysis*
4. Irreversible systolic dysfxn

*UNLIKE stunning, beta agnoists or digitalis is NOT going to help
oxygen derived free radicals in ischemic myocardium

- how do they get there?
- why are they increased in ischemic injury?
By-product of purine metabolism

*Normal: xanthine is end product of purine
- Xanthine dehydrogenase reduces NAD+ to make uric acid
- no free radicals made

ISCHEMIC INJURY:
xanthine dehydrogenase --> xanthine oxidase (2' Ca2+ accum)
- also converts it to uric acid, but makes tons of superoxide radicals

*Reperfusion brings in lots of O2 so the large amts of converted xanthine oxdiase can make free radicals*
ISCHEMIC MYOCARDIAL METABOLISM

- mech of switching
- WHY?
- when CBF stops altogether
1. PPAR-a
- activation upreg's genes involved in mitochondrial fatty acid oxidation
- DOWN-reg'd in severe ischemia

2. PPAR-y
- UPreg'd during severe ischemia
- Upreg's genes for glucose metabolism
- also upregulated in fetal heart, concentric hypertrophy (pressure overload), etc.
- Glucose metab is more efficient than FFAs
(6.3 vs 4.6 ATP / O2)

*NO CBF:
1. glucose runs out w/in minutes
2. Anaerobic glycosis
3. Glycogen stores depleted in 20-30 min.
= NO MORE ATP!
ISCHEMIC MYOCARDIAL METABOLISM

effects of:
- lactic acid
- ATP depletion

tx:
- lysosomes
- free radicals

**DIASTOLIC DYSFXN IS 1ST FUNCTIONAL MANIFESTATION OF ISCHEMIA***!!!!
ischemia --> anaerobic glycosis

1. LACTIC ACID: end product
- intracellular acidosis inhibits regulatory proteins
- stops glycogen/glucose breakdown
- Inhibits acyl-CoA transfer from cyto to mito (no beta-ox)

2. ATP DEPLETION: Na/K ATPase stops
- ATP-dep K+ channels open
- Na+ builds up inside (increased NHE & no NK pump)
- Ca2+ builds up inside
(reverse-mode Na+/Ca2+ xchange)
--> necrosis / apoptosis --> diastolic dysfxn

tx: (Ca2+ overload = reduced ATP production)
- Beta blockers
- Ca2+ channel blockers: protect mitos from calcium overload

*BOTH Reduce amt of necrosis following ischemic injury*
ISCHEMIC MYOCARDIAL METABOLISM


- lysosomes
- free radicals
LYSOSOMES:
- spit out acid hydrolases activated by intracellular acidosis
- intracellular digestion

O2-DERIVED FREE RADICALS:
- Accum & damage cell organelles & membranes
- ischemia > 20 min = membrane peroxidation = necrosis
= elevated CPK-MB & troponins in circulation
FUNCTIONAL CONSEQUENCES OF ISCHEMIA
ACUTE CORONARY A. OCCLUSION -->
1. Regional systolic dysfxn
- high intracell H+ vs. Ca2+ for troponin binding sites
- Subendocardial surface = highest risk (farthest away from epicardial aa)
2. Systolic dysfxn
- Decreased SV, EF, CO
- higher LV- EDP & EDV
3. LV FAIL
- CO decreases even more
= decreased coronary perfusion & worse ischemia

*Electrical conduction system is vulnerable
--> ventricular dyssynchrony
--> worse systolic fxn

ISCHEMIA = IMPAIRED RELAXATION
- diastolic dysfxn (much worse when + LVH)
MECH: Impaired serca
- Ca2+ channel blockers kinda work
--> pulmonary congestion worsens
WHICH ARTERIES SUPPLY WHICH AREAS OF THE HEART
LAD: Anterior LV & RV
- also anterolateral RV
- septum (along w/ RCA)

LCX: Lateral LV

RCA: Posterior LV & RV
ECG LEADS

- area of myocardium
- coronary a.
A. 2,3, aVF: Inferior; RCA

B. V1-V2 (R waves): Posterior, RCA

C. V1-V2 (Qwaves): Septal, RCA or LAD

D. V1-V3: Anteroseptal; LAD
E. V3-V4: Apical; LAD
F. I, aVL: Basolateral, marginal br of LCX or diagonal br of LCA

G. V5-V6: Apicolateral, LAD or Post. desc br of RCA, or marginal br of LCX
ETIOLOGIES OF MYOCARDIAL ISCHEMIA

- ATHEROSCLEROSIS (lipid oxidation theory of atherosclerosis)

(TNFa & IL-1 = inflam cytokines)
- NF-kB = p50 & p65

*Predilection for proximal segments of coronary aa & branch points (turbulence)


*Also HTN/DM/SMOKING
- infxn
- Homocysteine
Most important cuase of ischemic HD
- Chronic infalmm process
*Endothelial cell Dysfxn = cardinal features
- known risk factors injure endothelium

Lipid Ox. Theory
1. Fatty Streak
a. Endothelium binds oxidized-LDL (PUFAs got peroxidized by free radicals)
- apoB in LDL has neg charge = sticky
b. Internalized LDL activates NF-kB cascade (inflamm & ICAMs)
c. CAMs attract monocytes & T cells
d. Oxidized-LDL accum & explodes endothelial cell: contents in subintimal space
e. Monocyte-derived macros eat oxidized LDL = foam cells
2. Fibrous-capped plaques
- prone to thrombosis, hemorrhage & ulceration
a. Oxizided LDL inhibits NO & increases Endothelin-1
= proliferation of vasc smooth mm & collagen in subintimal space
b. Fibrous cap = vasc smooth mm & collagen
- Th1 CD4 degrades the cap
(unstable angina & MI
- Th2 CD4 stabilizes/thickens cap
(chronic stable angina)

*W/ Athero, Coronary vasodilation does NOT occur during exercise bc they are maximally dilated at rest & NO can't be released*
ETIOLOGIES OF MYOCARDIAL ISCHEMIA

(Atherosclerosis)
- HTN/DM/SMOKING
(- INFXN)
(- HOMOCYSTEINE)
(-CRP)
1.HTN: decreases NO, ^ PGs & Endothelin 1
- Increases Physical stress on plaques
= increased rate of complicated plaque formation

2. DM:
- increases LDL cholesterol
- lipoproteins are glycosylated = injured endothelium
--> less NO & ^ platelet reactivity

3. Smoking/Nicotine:
- Lowers HDL cholesterol
- increases platelet reactivity & fibrinogen levels
- injures endothelial cells
ETIOLOGIES OF MYOCARDIAL ISCHEMIA

- INFXN
- HOMOCYSTEINE
(atherosclerosis & htn/dm/smoking & CRP)
INFXN
- possible chronic infxn can exacerbate coronary atherosclerosis
- Chlamydia pneumoniae
(intracell parasite)
- contribues to plaque rupture

HOMOCYSTEINE
- AA made from methionine metabolism
- SAM = activated methionine
- FATES: re-methylated = folate & vit. B12 or condensed to make cysteine
(if either pathway is limited, plasma homocysteine increases)

*homocysteinE IS bad
- TOXIC to endothelium
- Mitogenic for vasc smooth mm
- ^ Platelet aggreg
- Impairs fibrinolysis (inhibits t-PA & protein C)

*Hereditary elevations of plasma homocysteine = linked w/ CAD*
ETIOLOGIES OF MYOCARDIAL ISCHEMIA


CRP
- what
- from where?
- FXN
-tx
(+ atherosclrosis, HTN/DM/SMOKING, Homocysteine, Infxn)
C reactive Protein = Acute phase reactant
- inflamm; increased in atherosclerosis
- strong predictor for presence of CAD
- worsens athero

HOW IT'S MADE:
1. Activated t cells & macros in plaque = IL-6 by plaque & adipose
2. IL-6 tells liver to make CRP

WHAT IT DO
1. DOWNreg's NO synthase & increases NO degradation
2. UPREGs endothelin-1
3. UPregs NF-kB
4. UPregs MMPs
- destabilizes fibrous cap
5. UPregs ATN-II receptors on vasc smooth m.

LOWER CRP:
- STOP SMOKING
- WORK OUT
- BP CONTROL
- LOWER CHOLESTEROL (HMG-CoA inhibis)
CORONARY THROMBOSIS


- how does it develop?
- ECG manifestations

*Abciximab: anti-GP2B/3A-R Ab*
*Agonists: Adenosine, thrombin, TXA2, collagen, Epi, etc*
(anything making platelets sticky)
Dynamic interaction bw damaged vasc endothlium - platelet aggregs - coronary vasoconstriction

1. Trigger: Ruptured plaque (thin cap -Th1, necrotic core)
2. Exposed subendothelial collagen --> Platelet aggreg
(Upreg's GP2b/3a receptors)
3. Activated platelet receptors bind FIBRINOGEN
4. Platelet link to form a thrombus

*Vasoconstriction triggered by TX-A2 (platelets) & bleeding into vessel wall

ECG:
- ST-elevation MI (STEMI): complete occlusion = transmural infarction
vs.
- Partial occlusion = NSTEMI (necrosis) or unstable angina (UA - subendocardial ischemia)
CAUSES OF MYOCARDIAL ISCHEMIA

COMMON VS RARE
#1. Atherosclerosis
#2. Coronary Thrombosis

rare:
3. coronary emboli
4. Global HypoTN
5. Increased O2 demand (AS)
CORONARY ARTERY SPASM/vasoconstriction

mechanism

vasospasm = ischemia & rarely MI
1. Endothelial dysfxn
- more ET-1 & less NO

2. Parasympathetic hypoactivity / vagal withdrawal
- w/ or w/o increase in alpha-adrenergic tone

3. Overactive GTP rho-kinase in VSM
- phosphorylates myosin lt chain
- inhibits myosin phosphatase
- increases sensitivity of vsm TO CA2+

**Coronary vasoconstriction = mechanism of injury in cocaine & amphetamine users
GLOBAL HYPOTN & MI
- States of hemodynamic shock
- may precipitate myocardial ischemia even in absence of critical coronary a. atenosis

Hemodynamic shock:
- increases myocardial O2 demand
- decreases coronary a. perfusion pressure
(esp. in subendocardium)

*can progress to global subednocardial MI*
INCREASED O2 DEMAND & MI
^ O2 demand in presence of moderate coronary a stenosis can ---> severe ischemia

*already maximally dilated at rest*

CAD + STATESOF HIGH DEMAND (old pts):
1. Anemia
2. infxn
3. hyperthyroidism
4. LVH (as)

when coronary arteris are normal: (young pts)
1. severe AS & LVH
2. Tachyarrhythmia+ systemic hypoTN
3. HCM
- intramural coronary aa are abrnomally small
CLINICAL MANIFESTATIONS OF CAD (Cardiac Ischemia)
1. Chronic stable angina
2. Unstable angine
3. Variant/Prinzmetal's angina
4. MI
5. Sudden Death
6. Asymptomatic
CHRONIC STABLE ANGINA

- TYPE OF PLAQUE
- WHEN?
- DESCRIBE
- ECG
Uncomplicated plaque
- thick, fibrous cap
- fixed obstruction
- not prone to rupture

Any situation that increases O2 demand > supply
(tachy, pregnancy, fever, HTN, HCM, Anemia, etc, increased AF/ cold shower)

CONSISTENT pattern, frequency & intensity of pain
(does NOT progress/worsen with time); relieved w/ same dose of nitroglycerin each time
1. Retrosternal chest pain/pressure of SHORT duration
2. Precipitated by certain things
3. Radiates to ulnar aspect of L arm, lower jaw, neck/shoulders
4. Relieved w/ rest & nitroglycerin

also: nauea, dyspnea, diaphoresis, feelings of anxiety

ECG during an attack
- ST segment depression
- T wave inversion
*normal ECG during attack*
CHRONIC STABLE ANGINA

- PAIN MEDIATOR
- SILENT ISCHEMIA
Pain mediator = ADENOSINE
- low CBF prevents removal, stimulates A1-R of perivascular aff SNS

Silent ischemia: ischemia w/ chest discomfort
- people w/ messed up pain receptors/mechanism
= Elderly, previous MI, DM, CABG
VARIANT ANGINA

(PRINZMETAL'S ANGINA)

- mech
- population type
- ecg
- describe
Coronary a. spasm
- often suprimposed on single vessel stenosis
**in younger pts - normal coronary a. spasms (no stenosis)**

1. Chest pain
- usually at rest or nighttime
- wakes u up!
- similar symptoms as stable angina
- LESS THAN 20 min.

ECG:
- ST segment elevation (less often depression)
= transmural ischemia
(leakage of K+ lowers baseline; "looks like elevation")
unstable angina

- mech
- describe
- course
- tx
Multiple, complicatd plaques
- thin fibrous cap
- prone to rupture

Partially occluding thrombus + vasoconstriction (after rupture) = Unstable Angina
- CBF restored in <20 min (>20 min = MI)

INCREASE in freq, duration or severity of pain
- not attributale to obvious increase in O2 demand
- NEW ONSET chest pain (during past 4-6 wks) in prev. asymptomatic

TX: LIKE AN MI
- At SUPER high risk for MI and should be hospitalized
UNSTABLE ANGINA VS. MI

- DURATION
- EXTENT OF OCCLUSIONS
DURATION:
MI: >20 MIN
U. Angina: <20 min

EXTENT OF OCCLUSION
- Transmural: ST elevation
- Subendocardial: ST depression
MYOCARDIAL INFARCTION

= DESCRIBE
= TYPES
= ECG
- DX
1. STEMI: ST seg elevation
- COMPLETE coronary a. occlusion + complicated plaque
= majority of MIs; higher mortality

2. Non-STEMIs: plaque rupture + incomplete coronary a. occlusion

SEVERE chest pain > 20 min.
- precordial/retrosternal pain
- radiation
- NOT releived w/ NG or cessation of activity
- Pain usually FOLLOWS exertion/excitement
(angina = pain DURING exertion)

1/4 of MIs = no chest discomfort
- any NEW ONSET heart failure, arrhythmias, hypoTN, normalization of BP in HTN pts, or confusion in elderly
= ECG!!!
(silent infarcts)
MI

- PHYSICAL EXAM
= ECG
- DX
NORMAL PE: small infarcts
- ANS hyperactivity = common
- LV FAIL: pulmonary congestive signs & S3

ECG:
- STEMI: ST elevation + Q waves in affected arteriolar distribution
(don't always have Q waves)

dx:
- serial ECGs
- Serum markers: CPK-MB, Troponin-T, Troponin-I
(elevated post-MI; normal in chronic/stable angina)
*serum levels take several hours to rise
COMPLICATIONS OF MI
#1. ARRHYTHMIAS
- most common cause of death post-MI
#2. CARDIOGENIC SHOCK
- 2nd most common cause of death post-MI
3. Ventricular septal rupture
4. Papillary Muscle Rupture
5. Ventricular Free wall rupture
6. LV thrombus
ARRHYTHMIAS & MI
MOST COMMON CAUSE OF DEATH POST-MI

1. V-fib: most deaths during first 24 hrs
- reduced CO
2. A-fib/flutter: further myocardial damage
- increased O2 demand
3. 2nd-3rd degree AV block
- decrease HR
- 3rd Degree block = most likely after anterior MI

*Sinus brady is HELPFUL as long as HR is adequate to maintain CO
- decreases O2 demand & protects heart from further ischemia
CARDIOGENIC SHOCK & MI

lv vs rv

- tx
2ND most common cause of death post-MI
- develops when >40% of ventricular mm. is damaged

LV shock <-- systolic pump failure
- Low CO
- Systemic hypoTN
- Elevated systemic vasc R
- Elevated LV-EDV & LV-EDP
- Elevated PAWP (>15 mmHg) & congestion

RV SHOCK: limited LV filling
- low CO
- same as above
- LOW PAWP (<6 mmHg)
- HIGH JVP

TX:
For LV SHOCK: Diuretics & venous vasodilators
- lower LVEDP, improve pulmonary congestion / PCWP
**BUT NOT FOR RV SHOCK**
- makes it worse (reduced RVEDV)
---> SUPER LOW CO
VENTRICULAR SEPTAL RUPTURE & MI
5% of MI-related deaths
- 3-4 dyas or 10-12 days post-MI
- Septal rupture is more common in anterior MI (vs inferior MI)

= Cardiogenic shock + new holosytolic murmur
- pulmonary edema --> dyspnea
- Increased oxygenation in Right heart
PAPILLARY MUSCLE RUPTURE & MI
2-7 days post-INFERIOR MI

= Acute pulmonary edema & low CO
- early systolic murmur
- Decrescendos towards S2
- milder forms of papillary dysfxn = new holosystolic murmur

*Post papillary mm is most often afftected*
- only fed by 1 artery (post. desc br of RCA)
VENTRICULAR FREE-WALL RUPTURE & MI
15-20% of in-hospital MI-related deaths
(3rd most common cause of death post-MI)

3-5 days post-MI
female, old, HTN, recent NSAID use
- occluded LCA predisposes pts
(Anterior or lateral STEMI)

SYMPTOMS:
- repetitive vomiting
- pleuritic chest pain
- restless; agitated
- SYSTEMIC HYPOTN
- ELEVATED JVP
(cardiac tamponade)
--> Equalization of diastolic pressures across all FOUR <3 chambers)

= ELECTROMECHANICAL DISSOCIATION
- electrical activity persists in absence of BP, PULSE, OR audible heart sounds
LV THROMBUS FORMATION & MI
Anterior MI & apical MI of LV
--> predisposis to LV thrombus
--> systemic emboli

first few days post-MI
- pedunculated & movile thrombi are more likely to embolize

*UNCOMMON after inferior MI*