Boards and Beyond: Cardiology A Companion Book to the Boards and Beyond Website Jason Ryan, MD, MPH Version Date: 9-20-2017
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Table of Contents Cardiac Anatomy Cardiac Physiology CV Response to Exercise Blood Flow Mechanics Regulation of Blood Pressure PV Loops Wiggers’ Diagram 23 Venous Pressure Tracings Starling Curve Cardiac Ischemia STEMI Unstable Angina/NSTEMI Stable angina EKG Basics High Yield EKGs Action Potentials AV and Bundle Branch Blocks Atrial Fibrillation AVNRT WPW Antiarrhythmic Drugs
1 3
Heart Sounds Heart Murmurs
7 Heart Failure Basics Heart Failure 9 Systolic and Diastolic 15 Restrictive Cardiomyopathy 19 Acute Heart Failure Chronic Heart Failure 114 25 Cardiac Embryology 27 Shunts 30 Cyanotic Congenital Heart Disease 37 Coarctation of the Aorta 41 Hypertension 43 Secondary Hypertension 49 Hypertension drugs 54 Valve Disease 58 Shock 62 Pericardial Disease 67 Aortic dissection 73 Cardiac Tumors 75 Hypertrophic Cardiomyopathy 77 Endocarditis
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88 92 97 103 106 109 118 121 125 130 133 136 141 149 155 159 165 169 171 175
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The Heart Chambers
PVs
SVC PA LA RA Aorta
Cardiac Anatomy
LV
IVC
Jason Ryan, MD, MPH
RV
The Heart
Anterior-Posterior Structures
Valves
Right Ventricle Anterior PV
AV
Left atrium
Posterior
TV
MV
Coronary Arteries
Coronary Artery Territories
90% Right dominant 10% Left dominant
Heart drains to coronary sinus CS Right atrium
•
•
•
Left Main LCX
RCA
•
LAD
PDA
1
Anterior wall, anterior septum, apex LAD Lateral wall LCX Inferior wall, inferior septum PDA •
RCA 90% of the time
•
10% of people “left dominant” - LCX supplies PDA
Occlusion occurs LAD>RCA>LCX
Mitral Valve
Cardiac ElectricalSystem •
Twopapillary muscles
•
AL has dual blood supply
•
PM single blood supply
•
•
•
AL
•
PM
•
SA/AV node Usuallysupplied by RCA
Anterolateral (AL) Posteromedial (PM) LAD/LCX
SA
RCA (or LCX) AV
Inferior infarction can lead to rupture of PM pap •
•
Severe mitral regurgitation Acute heart failure
SA Node – Right atrial wall AV Node –Interatrial Septum HIS – Interventricular septum
2
LBB His RBB
Purkinje Fibers
Heart Volumes ESV EDV
Cardiac Physiology Jason Ryan, MD, MPH
End diastolic Volume Filling completed Contraction beginning
Important Terms •
•
•
Important Terms
Stroke Volume (SV) = EDV - ESV
•
Venous Return (VR)
•
Total peripheral resistance
Ejection Fraction (EF) = SV / EDV Cardiac Output (CO) = SV * HR
Blood Pressure Terms •
Systolic Blood Pressure (SBP)
•
Diastolic Blood Pressure (DBP)
•
Pulsepressure
•
•
•
•
End systolic Volume Emptying completed Relaxation beginning
•
Blood returned to left ventricle
•
Should be equal to the cardiac output
•
Resistance to blood flow from peripheral structures
•
Vasoconstriction
•
Vasodilation ↓ TRP
↑ TPR
Blood Pressure Terms •
Mean arterial pressure (MAP) • 2/3 DBP + 1/3 SBP
Largely determined by cardiac output •
Largely determined by TRP SBP – DBP Proportional to SV
3
Example: SBP 120/80 • MAP = 80 + 1/3 (40) = 93.3
Cardiac Output
Cardiac Output •
•
•
Determinants
Very important physiology parameter
1. Preload
Must rise to meet demands More cardiac output = more work/O2
2. Afterload 3. Contractility
•
CO = HR x SV
•
More beats per minute = more work
•
More volume per beat = more work
4. Heart rate
Preload
To INCREASE Preload
•
Amount of blood loaded into left ventricle
1. Add volume(blood, IVF)
•
Also how much stretch is on fibers prior to contraction
2. Slow heart rate more filling more volume 3. Constrict veins
•
•
•
Some books say “length” instead of “stretch”
More preload = more cardiac output More preload = more work the heart must do •
↑O2 required
3. Pool blood in veins Relieve angina
•
Lower preload
Response to blood loss
•
Sympathetic stimulation α1 receptors in veins
venous
constriction
•
LVEDV
•
• Volume of blood in the left ventricle when filled LVEDP
2. Raise heart rate(opposite mechanism above)
•
Veins hold LARGE blood volume
•
Important Terms
1. Remove volume(bleeding, dehydration)
Mechanism of action of nitrates
Veins force blood into heart
•
Preload
To DECREASE Preload
•
•
• Pressure in the left ventricle when filled
less work for heart
4
Afterload •
•
•
•
To INCREASE Afterload
Forces resisting flow out of left ventricle
1. Raise mean blood pressure
Heart must squeeze to increase pressure Needs to open aortic valve push blood into aorta This is harder to do if:
2. Obstruct outflow of left ventricle
•
Blood pressure is high
•
Aortic valve is stiff
•
Something in the way: HCM, sub-aortic membrane
•
To DECREASE Afterload
Contractility
1. Lower the mean blood pressure
•
2. Treat aortic valve disease, HCM More afterload = more work
•
•
•
•
More oxygen required
•
Sympathetic innervation to heart
•
Circulating catecholamines (epinephrine, norepinephrine)
•
↑ calcium release from sarcoplasmic reticulum
•
Triggers: stress, exercise
•
Dopamine, dobutamine, epinephrine, norepinephrine
Sympathetic systemblocking drugs
•
Calcium channel blockers
•
Heartfailure
Inhibits Na-K pump ↑ calcium in myocytes
5
Beta blockers
•
Verapamil, diltiazem
•
Less calcium for muscle contraction
•
Digoxin •
Also increases heart rate
•
•
Sympathomimetic drugs •
Ejection fraction = index of contractility Major regulator:sympathetic nervous system
To DECREASE Contractility
Sympathetic nervous system activity •
How hard the heart muscle squeezes
•
To INCREASE Contractility •
Aortic stenosis, HCM
Disease of myocytes
Heart Rate •
Heart Rate
Increases cardiac output under physiologic conditions
•
Mainly regulated bysympathetic nervous system Also increased bysympathomimetic drugs
•
Decreased by beta blockers and calcium blockers
•
•
↑ HR = ↓ stroke volume(less filling time)
Heart Rate
Heart Rate •
Heart Rate
↑HR = ↑ cardiac output
•
•
Sympatheticnervoussystem: ↑HR and ↑contractility Stroke volume rises with increased HR
CO = SV * HR
Heart Rate
Heart Rate
Work of the heart
Heart Rate •
•
Myocardial O2 demand •
At pathologic heart rates↑ HR = ↓ CO High heart rate with arrhythmia can lead to ↓CO
• • •
CO = SV * HR
Preload (LVEDV/P) Afterload(MAP) Contractility (EF) Heart Rate
Hearts starved for O2 Reduce O2 demand Low output Need to increase work
Heart Rate
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Response to Exercise
Cardiovascular Response to Exercise
•
Body’soverall goal: •
Maximize perfusion skeletal muscles and heart
•
Minimize perfusion all other areas
•
Initiator: Muscle hypoxia
•
Mediator:Sympathetic nervous system
Jason Ryan, MD, MPH
Response to Exercise •
•
•
•
•
Response to Exercise
Process begins withmuscle contraction
•
Multiple mediators released into plasma
•
Adenosine generated from ATP consumption
•
Lactate
•
Carbon dioxide, potassium
•
Sympathetic nervous systemactivated ↑contractility(stroke volume) ↑HR Net result: ↑ cardiac output
•
Results in ↑ systolic blood pressure (SBP)
•
Vasoconstriction in some areas (gut, skin)
•
ATP consumed oxygen consumed (need more ATP) Result: Local hypoxia in muscle tissue Vasodilation occurs
•
•
•
Redistributes blood to important areas (i.e. heart/muscles)
Lowers total peripheral resistance (TPR)
Response to Exercise
Response to Exercise
Blood Pressure Summary
Ejection Fraction
•
•
•
•
SBP rises
•
LVEF increases
EF =
EDV - ESV
•
More CO = more blood in arteries = more pressure
•
More vigorous contraction
•
Primary determinant systolic BP = cardiac output
•
Major impact: ESV decreases
•
EDV effects minor/variable
•
More preload but less filling time at fast heart rates
DBP decreases slightly or stays normal •
Local dilation of skeletal muscles
•
Primary determinant diastolic BP = peripheral resistance
Pulse pressure increases TPR goes down
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EDV
Response to Exercise
Response to Exercise
Coronary Perfusion
Preload
•
•
•
Fast HR shortens diastole
•
LESS coronary filling time Coronary vasodilation increased blood flow •
Only way to get more oxygen
•
Cannot extract more O2
•
Cardiac tissue extracts maximum oxygen from RBCs
•
Cannot extract more to meet increaseddemand
•
•
•
Contributes to rise in cardiac output Along with increased heart rate and contractility
Lusitropy
Lusitropy =myocardialrelaxation •
Sympathetic stimulation venous contraction Increases preload/EDV •
Lusitropy •
Preload rises with exercise
•
•
•
Opposite of contractility
Increased with exercise Contributes to increased preload ↑ cardiac output
Key regulatory protein: Phospholamban •
Inhibitor: sarcoplasmic r eticulum Ca2+-ATPase (SERCA)
•
Phosphorylated via beta adrenergic stimulation
•
Stops inhibiting SERCA
•
Result: SERCA takes up calcium
SERCA
relaxation
Exercise Begins
2+-ATPase Sarco/endoplasmic reticulum Ca •
Sympathetic stimulation phosphorylates PLB
•
Inactivates PLB (relieves inhibitory effect)
•
Allows SERCA to uptake more calcium
Muscle Hypoxia
↓TPR (Afterload)
Vasodilation Sympathetic Activation
Beta Adrenergic SERCA
Sarcoplasmic Reticulum
PLB P
↓/- DBP Peripheral
Heart
Stimulation
Vessels
↑ Contractility
↑ HR
ESV
↑ CO
Ca++
↑EF
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↑ Lusitropy
Venous Constriction
↑Preload ↑EDV ↑SBP
Arteriole Constriction
Flow Equations
Blood Flow Mechanics Jason Ryan, MD, MPH
Flow Equations
Resistance and Compliance
Velocity Area
Resistance = resistance to flow Compliance = distensability of vessels
Velocity * Area = Flow Stiff Vessels ↑ resistance ↓ compliance
(m/s) * (m2) = (m3/s)
Stretchy Vessels ↓ resistance ↑ compliance
High resistance = low compliance (vice versa)
Pulse Pressure •
Systolic BP – diastolic BP •
•
•
•
•
Pulse Pressure
Normal = 120 – 80 = 40mmHg
Older patients = ↑ pulse pressure Hypertensive patients =↑ pulse pressure Related tovesselcompliance ↓ compliance =↑ pulse pressure
•
Compliance =Δ volume /Δ pressure
•
Stiff vessel ↓ compliance ↑ pulse pressure
•
Stretchy vessel ↑ compliance ↓ pulse pressure
•
•
Small change in volume for given pressure applied to walls Large change in volume for given pressure applied to walls
C=
P=
9
V/
P
V/C
Flow Equation
Pulse Pressure
Total Peripheral Resistance
•
Pulse pressure varies with vessel compliance
•
Stiff vessels ↓ compliance
P = CO *TPR Distensible Vessel 120/80
Stiff Vessel 170/100
↑ resistance =↑ pressure to maintain flow ↑ pressure = ↑ cardiac work
Total Peripheral Resistance • •
•
Types of Vessels
Easy to push blood out of heart less O2 required Resistance to flow more work for heart What resists forward flow out of heart? 1.
Types of vessels (i.e. pipes/tubes)
2.
Thickness of blood (viscosity)
•
•
Major determinant of total peripheral resistance
•
Large pressure drop
•
Vasoconstriction = ↑ TPR
•
Vasodilation = ↓ TPR
•
Capillaries: 25mmHg
Viscosity
Arterioles= “resistancevessels” •
•
•
Types of Vessels
Aorta: SBP 100mmHg Large arteries: Falls few mmHg Small arteries: 10-20mmHg Arterioles: 35mmHg
•
•
Thickness of blood
•
Low viscosity
•
High viscosity
•
•
Polycythemia
•
Multiple myeloma
•
10
Anemia
Spherocytosis
Series and Parallel Circuits
Poiseuille's Law P = Q XR
•
8
ΔP Q
R =
Changes in radius
Human organs arrangedin parallel Resistances add up differently in series than in parallel
(viscosity) L (length) r (radius)4 large
1 1 = Rtotal R1
change in resistance
1 + R2
Parallel
For two resistances (2 and 2), what is total R?
•
Used to calculate resistance, CO, orΔP
•
Often applied to body and lungs •
1 = Rtotal R
Series
Flow Equation
Series and Parallel Circuits
1
Rtotal = R1 + R2
P= Q*R
For both systems Q = Cardiac Output (CO)
1 + R2
1
Rtotal = R1 + R 2 Rtotal = 2 + 2 = 4
1
=
Rtotal
1
1 2
+
2
Rtotal = 1
Flow Equation •
Body •
•
Mean Arterial Pressure
P= Q*R
P = Arterial pressure –right atrial pressure
•
R = Total peripheral resistance (TPR)
•
R = Systemic vascular resistance (SVR)
Lungs •
•
•
Diastolic plus 1/3 (Systolic – Diastolic)
•
Total body
•
P = Pulmonary artery pressure –left atrial pressure
•
Arterial blood pressure = 120/80 mmHg
•
Mean arterial pressure = 80 + 1/3 (40) = 93 mmHg
Lungs •
R = Pulmonary vascular resistance (PVR)
•
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Pulmonary artery pressure = 40/20 mmHg Mean pulmonary artery pressure = 20 + 1/3 (20) = 27 mmHg
Total Body
Lungs P = CO * TPR
•
P = MAP –RAP
•
•
P = CO * TPR
R = TPR •
MAP = mean arterial pressure
•
RAP = right atrial pressure
CO of 5L/min; BP 155/80 (MAP 105), RA 5
TPR =
P = MAPRAP – = CO
105 –5
5
•
R = PVR
•
ΔP = PA – LAP
•
CO of 5L/min; PA 40/10 (MAP 20), LA 5
•
PA = mean pulmonary artery pressure
•
LAP = left atrial pressure
PVR =
= 20
CO
5
Lung and Body Flow Variables
P = PA LAP – 5
20 –5 5
=
= 3
Velocity and Area •
Flow = Velocity * Area
•
Changes as blood moves through vessels •
Aorta arterioles capillaries veins
•
Cardiac output moves through system (same flow)
•
Different vessels different area, velocity
•
Area ↑↑, velocity ↓↓
Velocity
Area
Flow = Velocity * Area (m3/s) = (m/s) * (m2)
Flow Properties of Blood Vessels
Law of Laplace •
Wall tension or wall stress
•
Applies to vessels and cardiac chambers
•
↑ tension ↑ O2 demand ischemia/angina
P*r Tension
2h Flow = Vel * Area P=QXR
12
Wall Tension •
Wall Tension
Afterload: Increasespressurein left v entricle
•
Preload: Increasesradiusof left ventricle
•
Hypertension, aortic stenosis
•
Chronic valvular disease (aortic/mitral regurgitation)
•
Will increase wall tension
•
Will increase wall tension
•
“Pressure overload”
•
“Volume overload”
P*r
P*r
Tension
Tension
2h
2h
EccentricHypertrophy
Wall Tension •
Hypertrophy: Compensatory mechanism •
Will decrease wall tension
•
Force distributed over more mass
•
Occurs with chronic pressure/volume overload
•
•
•
•
Longer myocytes Sarcomeres added in series Left ventricular mass increased Wall thickness NOT increased
Normal LV Size
Dilated LV
P*r Tension
Increased myocyte size Sarcomeres in series Normal wall thickness
2h
Eccentric Hypertrophy •
•
ConcentricHypertrophy
Volume overload of left ventricle •
Aortic regurgitation
•
Mitral regurgitation
Pressure overload
•
Chronic ↑↑ pressure in ventricle
•
Cardiomyopathy •
•
•
Ischemic and non-ischemic
•
Sarcomeres added in parallel Left ventricular mass increased Wall thickness increased
Normal LV Size
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↓ LV Size
Increased myocyte size Sarcomeres in parallel Increased wall thickness
Concentric Hypertrophy •
Classic causes: Hypertension, Aortic stenosis •
•
•
Both raise pressure in LV cavity
Decreased compliance (stiff ventricle) Often seen in diastolic heart failure
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Blood Pressure
Regulation of Blood Pressure
•
Required for perfusion of tissues
•
Varies with sodium/water intake
•
Regulatedby nervoussystem
Jason Ryan, MD, MPH
Baroreceptors •
•
•
Blood pressure sensors viastretch
Sympathetic and parasympathetic
•
Heart rate/contractility
•
Arterial tone (vasoconstriction)
•
•
Kidneys (renin release)
•
Quick response to changes in blood pressure
•
Rapid response via autonomic nervous system
Venous tone (more tone = more preload to ventricle) Renal renin release
Baroreceptors
•
Aortic arch and carotid sinus
Modify:
•
•
•
Signal central nervous system (brain) Response viaautonomic nervous system •
•
Baroreceptors
Blood PressureControl Sympathetic Parasympathetic
Aortic arch •
Senses elevated blood pressure
•
Poor sensing of low blood pressure
Aortic Arch CN X (Vagus)
Carotid Sinus
Carotid sinus •
Most important baroreceptor
•
Modifies signals over wider range of blood pressure
•
Senses low and high blood pressure
a
Blood Pressure
e
Brain a
Carotid sinus CN IX (GP)
e
Veins/Arteries Constrict/Dilate Heart ↑↓HR
Afferent = Arrive at the brain Efferent = Exit the brain Nucleus Solitarius
Aortic Arch
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Hemorrhage
High Blood Pressure Sympathetic Parasympathetic
Aortic Arch CN X (Vagus) a ↑ Blood Pressure
Veins Dilate Arteries Dilate
e
Brain a
Sympathetic Parasympathetic
Aortic Arch CN X (Vagus)
Heart ↓ HR/Contractility
Carotid Occlusion
Aortic Arch CN X (Vagus) e
Brain a
e
Carotid sinus CN IX (GP)
Sympathetic Parasympathetic
Aortic Arch CN X (Vagus)
Veins Dilate Arteries Dilate
a
Blood Pressure
Heart ↓ HR
e
Brain a
e
Carotid sinus CN IX (GP)
Tricks carotid sinus into thinking ↑ BP Result: ↓ HR, Vasodilation, ↓ BP
Veins Constrict Arteries Constrict Heart ↑HR
Tricks carotid sinus into thinking ↓ BP Result is ↑HR, Vasoconstriction, ↑BP
Severing CN IX
Severing CN X Sympathetic Parasympathetic
Aortic Arch CN X (Vagus) a
Blood Pressure
↑ Salt/Water Retention
Kidney
Retention
Sympathetic Parasympathetic
a
Heart ↑ HR/Contractility
Carotid sinus CN IX (GP)
Carotid Massage
Blood Pressure
e
↓ Salt/Water
Kidney
Veins Constrict Arteries Constrict
Brain a
Carotid sinus CN IX (GP)
Syncope while shaving or buttoning shirt
e
a
↓ Blood Pressure
e
e
Brain a
Carotid sinus CN IX (GP)
e
Sympathetic Parasympathetic
Aortic Arch CN X (Vagus)
Veins Constrict Arteries Constrict
a
Blood Pressure
Heart ↑HR
e
Brain a
Carotid sinus CN IX (GP)
Tricks brain into thinking ↓ BP Result is ↑ HR, Vasoconstriction, ↑BP
e
Veins -Arteries -Heart ↑HR
Vagotomy Unopposed Sympathetic Cardiac Stimulation Result is ↑ HR
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Coronary Blood Flow
Summary of Techniques
120
Aortic Pressure
80
Coronary Flow
Time(s)
•
Regional Blood Flow
In tachycardia, less time in diastole less flow
Organ Circulation Organ
•
Epicardium site of coronary arteries
•
Subendocardium receives smallest amount blood flow
Autoregulation •
Some tissue beds maintainconstant blood flow
•
↑ BP ↑ flow vasoconstriction ↓ flow (normal)
•
Use local metabolites to sense blood pressure
Key Features
Lung
100% of Cardiac Output
Liver
Largest Systemic Blood Flow
Kidneys
Highest blood flow by weight
Heart
Largest 02 (80%) ↑ demand vasodilation
Autoregulation
Kidney, brain, heart: Excellent autoregulation systems Skin: Poor autoregulatory capacity
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Capillary Fluid Exchange •
Two forces drive fluid into or out of capillaries
•
Hydrostatic pressure (P)
•
Capillary Fluid Exchange •
Hydrostaticpressure – fluid PUSHING against walls
•
Oncotic pressure–solutes PULLING fluid in
•
•
Molecules against capillaries walls
•
Pushes fluid out
•
High pressure drives fluid TOWARD low pressure
High pressure draws fluid AWAY from low pressure
Oncotic pressure(∏) •
Solutes (albumin) drawing fluid into capillaries
Pc ∏c Capillary
∏c
Pc
Pi ∏i Net Pressure (NP) = (Pc –Pi) + (∏i - ∏c)
Interstitial Space
Pi
∏i
Flow = (NP) Kf
Edema
Capillary Fluid Exchange •
Hydrostaticpressure – fluid PUSHING against walls •
•
•
High pressure drives fluid TOWARD low pressure
•
Oncotic pressure–solutes PULLING fluid in •
•
High pressure draws fluid AWAY from low pressure
•
Excess fluid movement out of capillaries Tissue swelling Lungs: Pulmonary edema Systemic capillaries: Lower extremity edema
Pc (100) ∏c (50)
Pi (50) ∏i (30) Net Pressure (NP) = 50 - 20 = 30 Flow = (NP) Kf
Edema
3rd Spacing
Net Pressure (NP) = (Pc –Pi) + (∏i - ∏c)
•
Intracellularfluid – 1st space
•
Extracellularfluid – 2nd space
•
Third spacing - fluid where it should NOT be
Capillary
•
∏c
Pc
•
Pi
Interstitial Space
∏i
•
•
↑ capillary pressure, ↑ Pc (heart failure) ↓ plasma proteins, ↓ ∏c (nephrotic syndrome, liver failure) ↑ capillary permeability, ↑Kf (toxins, infections, burns) ↑ interstitial osmotic pressure, ↑ ∏i (lymphatic blockage)
•
18
About 2/3 body fluid
About 1/3 body fluid Pleural effusions
•
Ascites Cerebral edema
•
Low intravascular volume/High total volume
Occurs post-op, sepsis
PV Loops
Pressure Volume Loops Jason Ryan, MD, MPH
LV Vol
Time
PV Loops
PV Loops ESPVR
EDPVR
LV Vol
Time
LV Vol
Time
PV Loops Systole
S2
A
M
A
A
A
Time
M
M
M
S1 LV Vol
EDP
Diastole LV Vol ESV
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EDV
PV Loop Parameters Afterload
•
•
•
•
•
Stroke Volume
Changes in preload Changes in afterload Changes in contractility Changes in compliance In reality, these are inter-related •
Example: ↑ preload ↑ contractility (Frank-Starling)
Preload
Preload Changes Increase
Preload Changes
↑ EDV ↑ SV ↑ EF (slightly)
Decrease
↓ EDV ↓ SV ↓ EF (slightly)
SV = EDV - ESV
SV = EDV - ESV
EF = EDV - ESV
EF = EDV - ESV
EDV
EDV
Afterload Changes
Afterload Changes
Increase
Decrease
↑ ESV ↓ SV ↓EF
↓ ESV ↑SV ↑EF
EF = EDV - ESV
EF = EDV - ESV
EDV
EDV
20
Contractility Changes
Contractility Changes
Decrease
Increase ESPVR
↑ ESV ↓ SV ↓ EF
↓ ESV ↑ SV ↑ EF
EF = EDV - ESV
EF = EDV - ESV
EDV
EDV
Compliance Changes
Work of the Heart
Decreased Compliance
More area = More work
↓EDV ↑ EDP
EDPVR
Commonly Tested PV Loops •
Aortic Stenosis
•
Mitral Regurgitation
•
Aortic Regurgitation
•
Mitral Stenosis
Aortic Stenosis
LV Vol
21
Mitral Regurgitation
Aortic Regurgitation
Isovolumic Contraction Disrupted
Isovolumic Relaxation Disrupted
LV Vol
LV Vol
Mitral Stenosis Ventricle can’t fill properly
LV Vol
22
Wiggers’ Diagram Aorta LV LA
Wiggers’ Diagram
S1 Heart Sounds S2 VenousPressure
Jason Ryan, MD, MPH
EKG
Left Ventricular Volume
Aorta
LV LA
Normal Heart
Normal Heart
Diseased Heart
Diseased Heart
Mitral Stenosis
Aortic Stenosis
23
Normal Heart
Normal Heart
Diseased Heart
Mitral Regurgitation
Diseased Heart
Aortic Regurgitation
24
Venous Pressure a
Venous Pressure Tracings
v c
x
y
Jason Ryan, MD, MPH
Venous Pressure
Venous Pressure
Tricuspid valve
Atrial relaxation Atrial contraction Pressure goes up
TV opens Pressure Falls a
c
a
TV Closes
c
c
v
TV closes
Venous filling Pressure rises
No RV filling RV Contraction
Wiggers’ Diagram
Classic Findings
Aorta
LV Volume S1 S2
c x
Large a wave
•
Cannon a wave
•
LA
a
•
•
LV
v
y
EKG
25
x
y
a wave = Atrial contraction v wave = Venous filling c wave = triCuspid valve x descent = atrial relaXation y descent = emptYing of the atrium
VenousPressure
a
v
x
Heart Sounds
TV Closes
TV Opens
Absent a waves Large v waves
RV filling RV Relaxation
Left AtrialPressure
High Yield Findings •
•
Large a wave (increased atrial contraction pressure) •
Tricuspid stenosis
•
Right heart failure/Pulmonary hypertension
a
•
Complete heart block
•
PAC/PVC
•
Ventricular tachycardia
•
Absent a wave (no organized atrial contraction)
•
Giant V waves
•
•
v c
Cannon a wave (atria against closed tricuspid valve) x
Atrial fibrillation Tricuspid regurgitation
26
y
Frank-Starling Curve
Starling Curves Jason Ryan, MD, MPH
Frank-Starling Curve
Frank-Starling Curve
Left and Right Shifts
Left and Right Shifts ↑ Contractility ↓ Peripheral Resistance (afterload) Normal
↓ Contractility ↑ Peripheral Resistance (afterload)
Stroke Volume
•
Contractility
•
Peripheral resistance:
•
Increase: Exercise, inotropes
•
Decrease: Myocardial infarction, heart failure
•
Total peripheral resistance (TPR)
•
Systemic vascular resistance (SVR)
•
Increase: Vasopressors
•
Decrease: Vasodilators, sepsis
Preload (LVEDP,LVEDV)
Venous ReturnCurve
Right Atrial Pressure
Right Atrial Pressure
Venous Return or Cardiac Output
27
Venous Return Curve
Venous Return Curve
Left and Right Shifts
Volume Venous Tone
↑ Blood Volume Venous constriction (↑ tone)
Venous Return or Cardiac Output
Venous Return or Cardiac Output
Mean Systemic Filling Pressure (MSFP) Pressure if heart stops
Normal
↓ Blood Volume Venous dilation (↓ tone)
Right Atrial Pressure
Right Atrial Pressure
Venous Return Curve
Combined Curves
Changes in Slope
Starling and Venous Return ↓ Total peripheral resistance
Venous Return or Cardiac Output
CO or VR
Normal
↑ Total peripheral resistance
Right Atrial Pressure Right Atrial Pressure or Preload
TPR change shifts curve right/left No change in MSFP Result: change inslope of Venous Return curve
Heart Failure
Hemorrhage ↓contractility ↑ TPR ↑ Fluid volume
CO or VR
Blood loss ↑ TPR ↑ Contractility
CO or VR
Right Atrial Pressure or Preload
Right Atrial Pressure or Preload
* Black = normal
* Black = normal
28
Exercise
•
Decreased afterload (TPR) Venous contraction Increased contractility
•
Net result = increased CO
•
•
AV Fistulas
•
•
•
Net result = increased CO
•
Combined Curves
Vasopressors •
•
Decreased afterload (TPR) Increased contractility Venous contraction
•
Starling and Venous Return
Increased afterload (TPR) Alters VR and Starling Curves Net result = decreased CO
A 15
CO or VR
B 10
5
C
10
12 14
Right Atrial Pressure * Black = normal
29
For a patient on starling curve A with a MSFP of 10 what is the cardiac output?
Cardiac Ischemia •
•
•
Cardiac Ischemia
Caused by coronary atherosclerosis O2 SUPPLY << O2 DEMAND = ISCHEMIA Typical symptoms •
Chest pain (angina)
•
Dyspnea
•
Diaphoresis
Jason Ryan, MD, MPH
Stable Angina •
•
Acute CoronarySyndromes
Stable atherosclerotic plaque •
No plaque ulceration
•
No thrombus
•
Plaque rupture thrombus formation Subtotal occlusion
•
Total occlusion (100%)
•
Must occlude ~75% of lumen to cause symptoms
•
Unstable angina
•
Non-ST elevation myocardial infarction
•
ST-elevation myocardial infarction (STEMI)
NO SYMPTOMS
SYMPTOMS WITH EXERTION (EXERTIONAL ANGINA) Subtotal Occlusion
Sudden Death
Total Occlusion
Risk Factors
•
Common complication of CAD
•
Major risk isprior coronary disease
•
Plaquerupture arrhythmias
•
Coronary risk equivalents
•
CAD is most common cause of sudden death adults •
Younger patients: Hypertrophic cardiomyopathy (HCM)
30
•
Diabetes
•
Peripheral artery disease
•
Chronic kidney disease
Risk Factors •
Extent of Ischemia
Hypertension
•
Hyperlipidemia Family History (1° relative, M<50, F<60) Smoking
•
Obesity, sedentary lifestyle
•
•
•
Transmural ischemia
•
Subendocardial ischemia
•
Occurs with complete 100% flow obstruction (STEMI)
•
Occurs with flow obstruction but some distal blood flow
•
Stable angina, unstable angina, NSTEMI
Subendocardial Ischemia
Subendocardial Ischemia
Transmural Ischemia
Transmural Ischemia
Subendocardial Ischemia
Transmural Ischemia Complete Occlusion
Subtotal Occlusion
Limited distal flow
Ischemic EKG changes
Ischemic EKG changes
ST depressions
T wave inversions •
Many causes other than CAD
•
Raised ICP
•
Resolving pericarditis
•
•
•
Subendocardial Ischemia
31
Cerebral T waves
Bundle branch blocks Ventricular hypertrophy
Ischemic EKG changes
Ischemic EKG changes
T wave inversions
ST Elevations
Subendocardial Ischemia
Seen only with transmural ischemia
Evolution of EKGchanges STEMI
Normal
Acute
Hours
1-2 Days
3-7 Days
Q wave
Hyperacute T waves
Poor R Wave Progression
•
Seen in transmural ischemia
•
•
Early sign of ischemia
•
R wave increases (progresses) in size V1-V6 Normally R>S waves seen by lead V3
•
Seen before ST elevations
•
Poor progression seen inanterior ischemia •
Acute or prior infarction
R
S
32
> 7 Days
Terminology •
•
•
•
Coronary Stents
Revascularization
•
Angioplasty Coronary stenting Coronary bypass surgery
Angioplasty: Reshape vessel
•
Balloon angioplasty: Balloon inflation to open vessel Percutaneous Coronary Intervention (PCI) Stent placement
•
About 600,000 stents/year implanted US
•
•
CABG
Revascularization
Coronary Artery Bypass Surgery
Major Indications
•
“Bypass Surgery”
•
Angina
•
Left Internal Mammary Artery (LIMA) Graft
•
Myocardial infarction
•
Systolic dysfunction
•
•
Saphenous (leg) Vein Grafts Radial (arm) Artery Grafts
•
33
Hibernating myocardium
Ischemic Pathologic Changes
Complications of Ischemia
Myocardium •
Zero to 4 hrs
•
4 – 12 hrs
•
• •
•
•
First 4 days
•
5 – 10 days
•
Gross: Mottled Micro: Necrosis, edema, hemorrhage Gross: Hyperemia Micro: Surrounding tissue inflammation
5 – 10 days • •
•
•
12-24 hrs •
•
No changes!
•
Gross: Central yellowing Micro: Granulation tissue
• •
•
Free wall rupture
•
Tamponade
•
Papillary muscle rupture
•
VSD (septal rupture)
Weeks later •
Dressler’s syndrome Aneurysm
•
LV Thrombus/CVA
•
7 weeks Gross: Gray-white scar Micro: Scar
Arrhythmia
Cause of Death
Cause of Death
0 – 4 days after MI
5-10days after MI •
Free wall rupture
•
Papillarymuscle rupture
•
Ventricular Aneurysm •
Usually fatal – sudden death
•
May lead to tamponade
•
Acute mitral regurgitation (holosystolic murmur)
•
Heart failure, respiratory distress
•
More common inferior MIs
Septal rupture– VSD •
Loud, holosystolic murmur (thrill)
•
Hypotension, right heart failure (↑ JVP, edema)
Ventricular Pseudoaneurysm
Weeks after MI •
•
More commonanterior infarction Risk of thrombus stroke, peripheral embolism
•
Rupture contained by pericardium/scar tissue
•
Not a true aneurysm •
Patrick J. Lynch, medical illustrator/Wikipedia
34
No endocardium or myocardium
•
Mayrupture Presents as chest pain or dyspnea
•
Often seen in theinferior wall
•
Occurs earlier (<2 weeks) than true aneurysm
•
Dressler’s Syndrome
Fibrinous Pericarditis
Weeks to months after MI •
•
•
Form of pericarditis
•
Occurs daysafter MI
•
Chest pain
•
Sometimes called “post-MI” pericarditis
•
Friction rub
•
Not autoimmune
•
Extension of myocardial inflammation
Immune-mediated (details not known) Treatment: NSAIDs or steroids
•
Dressler’s occurs weeksafter MI •
•
Secondary Prevention •
•
•
Secondary Prevention
Any CAD ↑ risk of recurrent events •
Sometimes called “post cardiac injury” pericarditis
Rarely life-threatening
•
STEMI, NSTEMI, stable angina
Preventative therapy used to lower risk Even in asymptomatic patients
Several proven therapies for risk reduction
•
Aspirin Statins
•
Betablockers
•
•
•
Atorvastatin, Rosuvastatin
Used in patients with prior infarction (STEMI/NSTEMI)
Stent Complications
Stent Complications
Restenosis
Thrombosis
•
•
•
•
•
•
Slow, steady growth of scar tissue over stent “Neo-intimal hyperplasia”
•
•
Re-occlusion of vessel Rarely life-threatening
•
•
Slow, steady return of angina Most stents coated“drug eluting stents” •
•
Metal stent covered with polymer Polymer impregnated with drug to prevent tissue growth
•
Sirolimus
35
Acute closure of stent Same as STEMI: life-threatening event Dual anti-platelet therapy for prevention Associatedwithmissed medication doses
Stent Thrombosis Prevention •
•
•
“Dual antiplatelettherapy” Typically one year of: •
Aspirin
•
Clopidogrel, PrasugrelorTicagrelor
After one year, stent metal no longer exposed to blood •
“Endothelialization”
•
Risk of thrombosis is lower (but not zero)
•
Most patients take aspirin only
36
STEMI
ST-Elevation Myocardial Infarction (STEMI)
•
Atherosclerotic plaquerupture
•
Thrombus formation
•
•
Ischemic chest pain ST-elevations on ECG
Jason Ryan, MD, MPH
Leads go together
STEMI •
ST Elevations - Anterior
Transmural ischemia Transmural Ischemia Complete Occlusion
ST-elevation Myocardial Infarction Ulcerated Plaque – Thrombus Complete occlusion No distal blood flow
Leads go together
Leads go together
ST Elevations - Anterior
ST Elevations - Lateral
37
Leads go together
Leads go together
ST Elevations - Lateral
ST Elevations - Inferior
Leads go together
Coronary Artery Territories
ST Elevations - Inferior
•
Left anterior descending artery
•
Left circumflex artery
•
•
•
Anterior
V1-V4
Lateral
I, L, V5, V6
Posterior descending artery •
Inferior II, III, F
•
Branch of right coronary artery 90 %
•
LCX 10%
Special Complications
Special Complications
Inferior MI
Inferior MI
•
Right ventricular infarction •
Loss of right ventricular contractility
•
Elevated jugular venous pressure
•
Decreased preload to left ventricle hypotension
•
Diagnosis: Right sided chest leads
•
Sinus bradycardia and heart block •
38
Vagal stimulationfrom inferior wall ischemia
Left Main Occlusion
Posterior Myocardial Infarction
STEMI
Treatment of STEMI
Special Subtypes •
•
Left main •
ST-elevation aVR
•
Diffuse ST depressions
•
•
•
Posterior •
Anterior ST depressions with standard leads
•
ST-elevation in posterior leads (V7-V9) •
Treatment of STEMI •
Main objective is to open the artery
•
Option 1: Emergency angioplasty
•
•
Mechanical opening of artery
•
Should be done <90min
•
•
•
•
Option 2: Thrombolysis •
•
More likely the patient may die
•
More heart failure symptoms
•
More future hospitalization for heart disease
n=1791
Medical emergency
Treatment of STEMI
“Revascularization”
•
“Time is muscle” Coronary artery occluded by thrombus Longer occlusion more muscle dies
•
Lysis of thrombus with drug Should be done <30min
Time matters •
Medical therapy is supportive
•
Given while working to open artery
Remember: this is athromboticproblem •
Aspirin to inhibit platelet aggregation
•
Heparin to inhibit clot formation
This isblockers also an to ischemic Beta reduce O2problem demand •
“Door to balloon” or “door to needle”
•
39
Nitrates to reduce O2 demand
Cautions •
•
Other STEMI Treatments
Beta blockers
•
Clopidogrel
•
Inferior MI stimulates vagal nerve
•
ADP receptor blocker
•
Bradycardia and AV blockcan develop
•
Inhibits platelets
Nitrates •
Occlusion of RCA can cause RV infarct
•
RV infarction
•
Nitrates ↓ preload hypotension
•
Eptifibatide
•
Bivalirudin
↓ preload
Typical STEMI Course
•
IIB/IIIA receptor blocker
•
Inhibits platelets
•
Direct thrombin inhibitor
•
Inhibits clot formation
Typical STEMI Course
•
Arrival in ER with chest pain 5:42pm
•
Arrival in ER with chest pain 5:42pm
•
EKG done 5:50pm
•
EKG done 5:54pm
•
Meds given in ER
•
•
•
•
Cardiac cath lab activated for emergent angioplasty Meds given in ER
STEMI identified
•
Aspirin
•
Aspirin
•
Metoprolol
•
Metoprolol
•
Nitro drip
•
Heparin bolus
•
Nitro drip Heparin bolus
•
Transport to cath lab 6:15pm
•
•
STEMI identified
•
Artery opened with balloon 6:42pm •
DTB time 60 minutes (i deal <90min)
40
tPA given based on weight 6:07pm •
IV push
•
Door to needle time 25min (ideal <30)
NSTEMI Non-ST-Elevation Myocardial Infarction
NSTEMI and Unstable Angina
•
Atherosclerotic plaquerupture
•
Thrombus formation
•
Subtotal (<100%) vessel occlusion
•
Ischemic chest pain
Jason Ryan, MD, MPH
NSTEMI
Subendocardial Ischemia
ECGChanges •
•
Subendocardial Ischemia
ST depressions T-wave inversions
Subtotal Occlusion
Limited distal flow
Cardiac Biomarkers •
Biomarkers spill into blood with cardiac injury
•
Most common marker used:Troponin I or T
•
•
Increase 2-4 hours after MI
•
Stay elevated for weeks
Cardiac Biomarkers •
CK-MB also used •
•
Increase 4-6 hours after MI
Several types of CK •
MM – Skeletal muscle
•
MB – Cardiac
•
BB – Brain
•
Most tissues have some of all three
•
Ratio of MB to total CK can be used in ischemia •
Normalize within 2-3 days
41
Helpful when total CK also up due to muscle damage
Cardiac Biomarkers •
Treatment of NSTEMI
Some AST found in cardiac cells •
Abdominal pain with isolated ↑ AST could be MI
•
Thrombotic and ischemic syndrome (like STEMI)
•
Unlike STEMI: No “ticking clock”
Presents to ER with chest pain Biomarkers elevated
•
Medical Therapy
•
•
•
•
Aspirin
•
Metoprolol
•
Heparin drip
Heparin
•
Angioplasty (non-emergent)
Diagnosis largely based onpatient history Chest pain increasing in frequency/intensity Chest pain at rest
•
ECG may show ST depressions or T wave inversions
•
Treatment is same as for NSTEMI
•
Condition often called“UA/NSTEMI”
42
Atherosclerotic plaquerupture
•
Thrombus formation Subtotal (<100%) vessel occlusion Ischemic chest pain
•
Normal biomarkers
•
Hospital day 2 angiography 90% blockage of LAD Stent
•
No benefit to thrombolysis
•
•
Admitted to cardiac floor
•
No emergency angioplasty
•
•
•
Unstable Angina •
Some blood flow to distal myocardium
•
Unstable Angina
Typical NSTEMI Course •
Subtotal occlusion
•
Aspirin Beta blocker
•
•
•
Stable Angina •
Ischemic chest pain with exertion
•
Relieved by rest
•
Stable pattern over time Stablecoronary atheroscleroticplaque
•
No plaquerupture/thrombus
•
Stable Angina Jason Ryan, MD, MPH
Stable Angina
Stable Angina
•
Symptoms generally absent until ~75% occlusion
•
Diagnosis: cardiac stress test
•
Distal arteriolar dilation normal flow if <75%
•
Increases demand for O2
Stable Angina
Stable Angina: Typical Case
•
NOT a thrombotic problem
•
65-year old man with chest pain while walking
•
No role for heparin or antithrombotic drugs
•
Relieved with rest
•
In US usually treated with revascularization
•
Presents to ED
•
•
Most common indication PCI, CABG is stable angina Recent clinical trials suggest medical therapy may work just as well as PCI/CABG in some patients
•
•
EKG normal
•
Biomarkers normal
Stresstest •
43
Walks on treadmill chest pain, EKG changes
•
Cardiac catheterization performed
•
90% LAD artery blockage
•
Stent placed angina resolved
Medical Therapy for Ischemia
Nitrates
O2 Demand
•
Converted to nitric oxide vasodilation
•
Predominant mechanism isvenous dilation
O2 Supply
↑O2 Supply Dilate coronary arteries Increase diastole
↓O2 Demand ↓ Heart rate ↓ Contractility ↓ Afterload ↓ Preload
•
•
Bigger veins hold more blood
•
Takes blood away from left ventricle
•
Lowers preload (LVEDV)
Also arterial vasodilation (art<< veins) •
Increase coronary perfusion
•
Some peripheral vasodilation
Nitroglycerine
Nitrates •
•
•
Nitrates
↓ preload ↓ cardiac output Sympathetic nervous system activation Increased heart rate/contractility •
Increases O2 demand
•
Opposite of what we want to do for angina
•
Rare patients with complex CAD angina
•
In most patients, preload reducing effects dominate
•
Co-administer beta-blocker or Ca channel blocker
•
•
Nitrates alone often improve angina
Blunts “reflex” effect
Nitrates
Nitrates
Forms
Adverse Effects
•
•
Nitroglycerin Tablets/Spray •
Rapid action ~5 minutes
•
Takeduring angina attack, before exercise
•
•
Effects last ~6hrs
Once daily drug
TopicalNitroglycerin •
Headache (meningeal vasodilation) Flushing Hypotension Angina •
Isosorbide Mononitrate •
•
•
Isosorbide Dinitrate •
•
•
Topical cream, patches
44
Reflex sympathetic activation
Nitrate Tolerance
Nitrate Withdrawal
•
Drug stops working after frequent use
•
Nitrate withdrawal (rebound) after discontinuation
•
Avoid continuous us for more than 24 hours
•
Occurs when using large doses of long-acting nitrates
•
Does not occur with daily isosorbide mononitrate
•
Angina frequency will increase
Monday Disease •
•
•
•
•
Beta Blockers
Workers in nitroglycerin manufacturing facilities Regular exposure to NTG in the workplace Leads to the development oftolerance Over the weekend workers lose the tolerance "Monday morning headache" phenomenon •
Re-exposed on Monday
•
Prominent vasodilation
•
Tachycardia, dizziness, and a headache
For angina, generally use cardioselective (β1) drugs
•
Some beta blockers are partial agonists
•
Slow heart rate and decrease contractility
•
Increase preload (LVEDV)
•
•
Beta Blockers •
•
Pindolol, Acebutolol
•
Don’t use in angina
Slower heart rate = more filling time
•
Increase O2 demand
•
Blunts some beneficial effect
Reduced blood pressure (↓ afterload) Net effect = less O2 demand
Calcium Channel Blockers •
Metoprolol, atenolol
•
•
•
45
Three major classes of calcium antagonists •
dihydropyridines (nifedipine)
•
phenylalkylamines (verapamil)
•
benzothiazepines (diltiazem)
Vasodilators and negative inotropes
Antianginal Therapy
Calcium Channel Blockers •
•
Nitrates/Beta Blockers
Nifedipine: vasodilator •
Lower blood pressure
•
Reduce afterload
•
Dilate coronary arteries
•
May cause reflex tachycardia
Verapamil/diltiazem: negative inotropes •
Similar to beta blockers
•
Reduced heart rate/contractility
•
Can precipitate acute heart failure if LVEFvery low
Antianginal Therapy
Ranolazine
Calcium Channel Blockers
•
Inhibitslate sodium current Reduces calciumoverload high wall tension
•
Reduces wall tension and O2 demand
•
Late Na influx
Na
•
Ca
Variant (Prinzmetal) Angina
Ranolazine •
Na
Constipation, dizziness, headache QT prolongation (blockade of K channels)
•
46
•
Not caused by atherosclerotic narrowing
•
Often artery is “clean” with nostenosis
•
May also occur near sites of mild atherosclerosis
•
Spontaneousepisodes of angina
•
Transient myocardial ischemia
•
Prolong QT
Ischemia fromvasospasm
ST-segment elevation on ECG
Variant (Prinzmetal) Angina
Variant (Prinzmetal) Angina •
•
Midnight toearly morning Sometimes symptoms improve with exertion
•
Associated with smoking
•
Diagnosis
Episodesusually at rest
•
Usually based on history
•
Intracoronary ergonovine
•
•
Acts on smooth muscle serotonergic (5-HT2) receptors
•
Can be administered duri ng angiography
•
Vasospasm visualized on angiogram
Intracoronary acetylcholine •
Acts on endothelial muscarinic receptors
•
Healthy endothelium
•
•
Variant (Prinzmetal) Angina •
Quit smoking
•
•
Calcium channel blockers, nitrates
•
•
Vasodilators
•
Dilate coronary arteries, oppose spasm Non selective blocker
•
Can cause unopposed alpha stimulation
•
Symptoms may worsen
Coronary Steal •
•
Significant (>75%) narrowing
•
Arterioles maximally dilated to maintain flow
•
•
Arterioles NOT maximally dilated
•
Blood “stolen” from diseased coronary vessels
•
Vasodilatoradministered
•
Stenoticvessels no response •
Normalvessels No or minimal narrowing
•
Coronary Steal
Stenotic vessels •
Mechanism of angina Induced by drugs Blood flow increased to healthy vessels Blood flow decreased in stenotic vessels
•
Avoid propranolol •
vasodilation via nitric oxide
Coronary Steal
Treatment
•
Endothelial dysfunction vasoconstriction Vasospasm visualized on angiogram
47
Arterioles already maximally dilated
•
Normal vessels vasodilation Flow increases to normal vessels
•
Flow decreases to abnormal vessels
•
Results: ischemia due to coronary steal
•
Coronary Steal •
Rarely seen with nitrates, nifedipine
•
Key principle forchemical stress tests •
Adenosine, persantine, regadenoson
•
Potent, short-acting vasodilators
•
Brief ↓ in blood flow to stenotic vessels ischemia
•
Nuclear tracers can detect ↓ blood flow
48
AV Node HIS Bundle Bundle Branches Purkinje Fibers
R A AV
EKG Basics
T
P
HIS Bundle
Jason Ryan, MD, MPH Q
Bundle Branches
S Atrial Depolarization
EKG
Ventricular Depolarization
Purkinje Fibers
EKG ElectricalActivity
SA AV
LBB His Purkinje Fibers
RBB
EKG Electrical Activity
EKG Electrical Activity
I AVR
V1 V2 V3 V4 V5 V6 AVL
II
49
III AVF
EKGs
EKG
Key Principles
Pacemakers SA node is dominant pacemaker of the heart Other pacemakers exist but areslower
•
If SA node fails, others takeover •
SA node (60-100 bpm)
•
AV node (40-60 bpm)
•
HIS (25-40 bpm)
•
Bundle branches (25-40 bpm)
•
Purkinje fibers (25–40 bpm)
#2: EKGs have 12 leads
•
•
Each lead watches the same thing
•
Each lead watches from different vantage point
•
Electrical activity toward lead = upward deflection
•
Electrical activity away from lead = negative deflection
SLOWEST conduction is through AV node •
•
•
Determining Heart Rate •
#1: Waves represent repolarization/depolarizati on
•
Conduction Velocities
•
•
•
Very important so ventricle has time to fill
Purkinje fibers fastest conduction Purkinje > Atria > Vent > AV node
QRS Axis
3 – 5 big boxes between QRS complex
Left Axis Deviation LBBB Ventricular Rhythm
-90o Right Axis Deviation RBBB RVH o
+180
0o Normal QRS Axis -30 and +90 degrees
300 150 100 75 60 50
+90o
50
Axis Quick Method
Determining Axis
•
-90o
•
LAD Lead I (-)
•
(+)
+180o
First, glance at aVr. It should be negative If upright, suspect limb lead reversal
0o Normal Axis
RAD
-30 to +90
+90o
Normal
Axis Quick Method •
If leads I and II are both positive, axis is normal
Axis Quick Method •
For left axis deviation: •
All you need is lead II
Lead I Lead I
Axis -30 to -90°
Axis 0 to 90° Lead II
Lead II
Axis 0 to -30° Physiologic Left Axis
Lead II
Axis Quick Method •
For right axis deviation: •
All you need is lead I
•
Negative = RAD
Axis Quick Method •
Look at aVr: Make sure its negative
•
Look at I, II: If both positive, axis is normal
•
•
If II is negative: LAD If I is negative: RAD Normal
Lead I Axis 90 to 180° Lead I Lead II Lead II
51
Phys Left
Left
Right
PR Interval
QRS Interval Normal QRS <120ms
Normal PR 120-200ms
Right Bundle Branch Block
Prolonged PR 1° AV block
Left Bundle Branch Block
Short PR - WPW
Calcium
Qt Interval
Myocyte Action Potential
Normal Qt
Phase 1 IK+ (out)
ICa+
Phase 2 (in) & IK+ (out)
0mv Short Qt: Hypercalcemia
Phase 3 IK+ (out)
Phase 0 INa+ (in) -85mv
Phase 4
Prolonged Qt Hypocalcemia Drugs LQTS
Torsade de Pointes •
Feared outcome of Qt prolongation
•
Results in cardiac arrest Antiarrhythmic drugs Hypokalemia, hypomagnesemia
•
Rarely from hypocalcemia
•
•
Congenital Long QtSyndrome •
Rare genetic disorder •
Abnormal K/Na channels
K
a
Prolonged QT
52
Congenital Long Qt Syndrome
Acquired Long Qt Syndrome
•
Family history of sudden death (torsades)
•
Antiarrhythmic drugs
•
Classic scenario: Young patient recurrent “seizures”
•
Levofloxacin (antibiotic)
•
•
EKG shows long Qt interval
•
Norway and Sweden
•
Congenital deafness
•
Haldol (antipsychotic) Many other drugs
•
Congenital LQTS: need to avoid these drugs
•
Jervell and Lange-Nielsen Syndrome
T waves
U waves Origin unclear
Peaked T waves ↑K Early ischemia (hyperacute)
U
May represent repolarization of Purkinje fibers Can be normal but also seen in
hypokalemia
53
T
U
EKGs You Should Know 1. Sinus rhythm 2. Atrial Fibrillation/Flutter 3. Ischemia: ST elevations, ST depressions 4. Left bundle branch block 5. Right bundle branch block
High Yield EKGs
6. PAC/PVC 7. 1st, 2nd, 3rd degree AV block 8. Ventricular tachycardia 9. Ventricular fibrillation/Torsades
Jason Ryan, MD, MPH
Step 1: Find the p waves •
Sinus p waves
Are p waves present?
Originate in sinus node
•
Upright in leads II, III, F
Steps 1 & 2
Step 2:Regular or Irregular •
•
Distance between QRS complexes (R-R intervals)
•
Regular •
Irregular
54
P waves present, regular rhythm •
Sinus rhythm
•
Rare: atrial tachycardia, atrial rhythm
No p waves, irregular rhythm •
Atrial fibrillation– irregularly irregular
•
Atrial flutter with variable block
Steps 1 & 2 •
Step 3: Wide or narrow
P waves present, irregular rhythm
•
•
His-Purkinje system works
• Multifocal atrial tachycardia
•
No bundle branch blocks present
• Sinus with AV block •
Narrow QRS (<120ms; 3 small boxes)
• Sinus rhythm with PACs •
No p waves, regular rhythm • Hidden p waves: retrograde
Wide QRS •
Most likely a bundle branch block
•
Ventricular rhythm (i.e. tachycardia)
• Supraventricular tachycardias (SVTs) • Ventricular tachycardia
QRS Interval
Step 4: Check the intervals
Normal QRS
•
•
Right Bundle Branch Block
PR (normal <210ms; ~5 small boxes; ~1 big box) •
Prolonged in AV block
•
Lengthens with vagal tone, drugs
•
Shortens with sympathetic tone
QT (normal <1/2 R-R interval) •
Prolonged with ↓ Ca (tetany; numbness;spasms)
•
Prolonged by antiarrhythmic drugs
•
Shortened with ↑ Ca (confusion, constipation)
Left Bundle Branch Block
Step 5: ST segments •
•
T wave abnormalities •
Inverted: ischemia
•
Peaked: Early ischemia, hyperkalemia(↑K)
•
Flat/U waves: Hypokalemia(↓K)
ST Depression •
•
Normal Sinus Rhythm
Subendocardial ischemia
STTransmural Elevation ischemia •
55
Right Bundle Branch Block
Left Bundle Branch Block
Atrial Fibrillation
Atrial Flutter
VentricularTachycardia
VentricularTachycardia
56
PAC and PVC
Torsades de pointes •
•
•
•
↑ risk withprolonged Qt interval •
Antiarrhythmic drugs
•
Congenital long Qt syndrome
•
Antibiotics (erythromycin, quiniolones)
Hypokalemia Hypomagnesemia Rarely hypocalcemia
57
Cardiac Action Potential
Cardiac Action Potentials
•
Changes in membrane voltage of cell
•
Transmit electrical signals through heart
•
Triggers contraction of myocytes
Jason Ryan, MD, MPH
Myocyte Action Potential
Phase 4
Atrial/ventricular myocytes Phase 1 IK+ (out)
Phase 2 (in) & IK+ (out)
-85mv
•
Na+ and Ca2+ channels are closed
•
0mv Phase 0 INa+ (in)
•
Resting potential: about−85mV Constant outward leak of K+ “Inward rectifierchannels”
•
ICa+
Phase 3 IK+ (out)
Phase 4
Phase 4
Phase 0
Phase 1
Phase 0
•
Nearby myocyte raise membrane potential
•
•
Gap junctions
•
•
•
•
opens“Fast”Na+ channels
Rising potential Threshold potential reached (about -70mV) Large Na+ current rapid depolarization
•
Membrane potential overshoots (>0mV) Fast Na+ channels close
•
Class I antiarrhythmic drugs : block Na channels
•
Phase 4
•
Membrane potential is positive K+ channelsopen Outward flow of K+ returns membrane to ~0 mV Phase 1
58
Phase 2
Phase 3
•
L-type Ca2+ channels
open inward Ca2+ current
•
Contraction trigger:excitation-contraction coupling
•
K+ leaks out (down concentration gradient) Delayed rectifier K + channels
•
Balanced flow in/out= plateau of membrane charge
•
Verapamil/Diltiazem= block L-type Ca channels
•
•
•
•
•
Ca2+ channels inactivated Persistent outflow of K + Resting potential back to−85 mV Class III antiarrhythmic drugs : block K channels
Phase 2 Phase 3
Refractory Period
Skeletal Muscle •
•
•
No plateau (phase 2)
•
No gap junctions Each cell has its own NMJ
•
•
Phase 0 until next possible depolarization Determines how fast myocyte can conduct Many antiarrhythmicdrugs prolongrefractory period Refractory Period
Na+
K+
Myocyte Action Potential
Pacemaker Action Potential
Atrial/ventricular myocytes
SA node, AV node
•
Similar AP in HIS, bundle branches, Purkinje fibers 0mv Phase 0 ICa -40mv
85mv
59
Threshold
Phase 4 If (Na)
Phase 3 IK
Pacemaker Action Potential
Pacemaker Action Potential
SA node, AV node
SA node, AV node
•
Funny current(pacemaker current) •
•
•
Return cell to−60 mV
•
•
Spontaneous flow of Na+
About −40 mV: threshold potential L-type Ca2+ channels open depolarize cell Delayed rectifier K + channels open
•
•
Automaticity •
Do not require stimulation to initiate action potential
•
Capable of self-initiated depolarization
No fast Na+ channel activity •
Fewer inward rectifier K+ channels
•
Membrane potential never lower than −60 mV
•
Fast Na+ channels need −85 mV to function
Pacemaker Action Potential
Pacemaker Action Potential
SA node, AV node
SA node, AV node
•
Any drug that slows this AP may cause two effects:
•
Two key drug classes that affect pacemaker AP
•
Slower heart rate (sinus node)
•
Calcium channel blockers (Verapamil/Diltiazem)
•
Slower AV conduction (AV node)
•
Beta blockers
0mv
0mv Phase 0
-40mv
Threshold
Phase 0
ICa -40mv
-85mv
ICa
-85mv
Pacemaker Action Potential
Beta Blockers
SA node, AV node •
Threshold
Verapamil/Diltiazem= block L-type Ca channels •
Slow rate of sinus depolarization (slow heart rate)
•
Slow AV node conduction
•
•
Modify slope of phase 4 Less slope longer to reach threshold ↓ HR Beta Blocker Normal
0mv Phase ICa 0 -40mv
Threshold
Slower phase 4 (less slope)
-85mv
60
Slope of Phase 4
Beta Blockers
Sinus Node
•
Also prolong repolarization
•
Changes in slope modify heart rate
•
Slow AV node conduction
•
Decrease slope (slower rise)
•
Increased slope (faster rise)
•
Beta Blocker Normal
•
Parasympathetic NS, beta blockers, adenosine
Sympathetic NS, sympathomimetic drugs
Slower repolarization (slows conduction) Phase 4
Pacemakers •
Many cardiac cells capable of automaticity
•
SA node normally dominates
•
Pacemakers: SA Node > AV Node > Bundle of HIS
•
Fastest rise in phase 4
•
Controls other pacemaker cells
•
SA node (60-100 bpm)
•
AV node (40-60 bpm)
•
HIS (25-40 bpm)
61
AV Node HIS Bundle Bundle Branches Purkinje Fibers
R
AV and Bundle Branch Blocks
A AV
T
P
HIS Bundle
Jason Ryan, MD, MPH Q
Bundle Branches
S Atrial Depolarization
Purkinje Fibers
AV Blocks
AV Blocks
Symptoms
•
Slowed or blocked conduction atria ventricles Can cause prolonged PR interval
•
Can cause non-conducted p wave
•
Ventricular Depolarization
•
Often incidentallynoted on EKG
•
Can cause bradycardia
•
Especially milder forms with few/no non-conducted p waves
•
Occurs when many or all p waves not conducted
•
Fatigue, dizziness, syncope
•
Symptomatic AV block often treated with a pacemaker
Non-conducted P wave Prolonged PR Interval
AV Blocks
AV Blocks
Anatomy
Anatomy
•
Caused by disease in AV conduction system
•
Divided into two causes
•
AV node HIS Bundle Branches
•
AV node disease
•
HIS-Purkinje disease
•
Purkinje fibers
•
62
AV node disease •
Usually less dangerous
•
Conduction improves with exertion (sympathetic activity)
HIS-Purkinje disease •
More dangerous
•
Usually does not i mprove with exertion
•
Often progresses to complete heart block
•
Often requires a pacemaker
AV Blocks
1st degree AV Block
Four Types •
•
•
Type 1 •
Prolongation of PR interval only
•
All p waves conducted
Type II •
Some p waves conducted
•
Some p waves NOT conducted
•
Two sub-types: Mobitz I and Mobitz II
Type III •
No impulse conduction from atria to ventricles
Prolonged PR (normal <200ms) Block usually in AV Node Beta blockers Calcium channel blockers Well-trained athletes
2nd degree AVB
2nd degree AVB
Mobitz I/Wenckebach
Mobitz I/Wenckebach
Block usually in AV Node Progressive PR prolongation Grouped Beating RR intervals NOT regular Similar causes as 1st degree AV block
Block usually in AV Node Progressive PR prolongation Grouped Beating RR intervals NOT regular Similar causes as 1st degree AV block
2nd degree AVB
3rd degree AVB
Mobitz II
Block usually in the HIS-Purkinje System Regular RR intervals excludes Wenckebach Block usually in the HIS-Purkinje System Often seen with bundle branch block Usually symptomatic Dizziness, syncope
63
3rd degree AVB
Lyme Disease •
Spirochete infection withBorrelia burgdorferi
•
Stage 2: Lyme carditis Varying degrees of AVblock
•
AV block improves with antibiotics
•
•
1st, 2nd, 3 rd
Block usually in the HIS-Purkinje System Regular RR intervals excludes Wenckebach
Ventricular Tachycardia
Vocabulary •
Complete heart block
•
AV dissociation
•
Impulses cannot be transmitted from atria to ventricle
•
Atria and ventricular depolarization uncoupled (“dissociated”)
•
Can be cased by complete heart block
•
Also occurs if ventricular rate > sinus rate (no heart block)
•
Seen in ventricular tachycardia and other rhythms
Escape Rhythm
Ventricular Tachycardia
•
SA node: Dominant (fastest) pacemaker
•
Heart block: SA cannot send impulses to ventricles
•
Other pacemakers exist but are slower •
SA node (60-100 bpm)
•
AV node (40-60 bpm)
•
HIS (25-40 bpm)
•
•
64
Bundle branches (25-40 bpm) Purkinje fibers (25–40 bpm)
Sites of AV Block
Escape Rhythm •
Heart block: lower pacemaker depolarizes ventricles
•
Rate of lower pacemaker determines symptoms
•
“Escape rhythm”
•
Very slow: dizziness, syncope, hypotension
•
Less slow: fatigue, exercise intolerance
Causes of Heart Block •
•
Drugs •
Beta blockers, calcium channel blockers
•
Digoxin
•
• Often in patients with symptoms (syncope, dizziness)
Athletes
Fibrosis and sclerosis of conduction system
Bundle Branch Blocks •
•
Treatment for “high grade” AV block
• Usually 3rd degree or Mobitz II
High vagal tone •
•
Pacemaker
Right Bundle Branch Block
Both bundle branches blocked •
Results in AV block
•
Form of HIS-Purkinje system disease
ONEbundle branch blocked •
Does not cause AV block
•
Normal PR interval
•
QRS will be prolonged
65
Bundle Branch Blocks
Left Bundle Branch Block
•
Symptoms: None
•
May progress to AV block (need for pacemaker)
•
Interfere with detection of ischemia
•
•
Bundle Branch Blocks Causes •
Often caused by slowly progressive fibrosis/sclerosis
•
More common in older patients Can result from“structural heart disease” LBBB: Prior MI, cardiomyopathy
•
RBBB: Right heart failure
•
•
66
Identified incidentally on ECG
ST elevations, T-wave inversions can be normal
Atrial Fibrillation
Atrial Fibrillation and Flutter Jason Ryan, MD, MPH
J. Heuser/Wikipedia
Atrial Fibrillation
Atrial Fibrillation
Atrial Fibrillation
Atrial Fibrillation
•
Cardiac arrhythmia
•
Results in anirregularly, irregularpulse
•
•
Terminology •
Paroxysmal
•
Persistent
•
Permanent
•
Can cause palpitations, fatigue, dyspnea Diagnosis: EKG
•
67
Comes and goes; spontaneous conversion to sinus rhythm
Lasts days/weeks; often requires cardioversion
Atrial Fibrillation
Cardiomyopathy
Symptoms •
Wide spectrum of symptoms
•
•
•
•
Asymptomatic Heart Rate <100bpm
•
•
Ventricular rate: 70-180bpm
•
Preload
AV node refractory period determines heart rate Young, healthy patients rapid heart rate Older patients slower heart rate Atrial rate in fibrillation: 300-500bpm
•
•
•
Especially in“preload dependent” patients
•
•
•
Aortic stenosis
•
LVH or diastolic heart failure (stiff ventricle)
Valvular Atrial Fibrillation
Cardiac Embolism
•
•
Atrial fibrillation eliminates ventricular pre-filling “Loss of atrial kick” Decreases preload Can lead to low cardiac output and hypotension
•
Atrial Fibrillation •
↓ LVEF Systolicheart failure
Palpitations, Dyspnea, Fatigue Heart Rate >100bpm
Heart Rate •
Caused by untreated,rapidatrial fibrillation “Tachycardia-induced cardiomyopathy”
Brain (stroke) Gut (mesenteric ischemia) Spleen
•
Associated with rheumatic heart disease
•
Usuallymitral stenosis
•
Often refractory to treatment VERY high risk of thrombus
•
Non-valvular: not associated with rheumatic disease
•
68
Atrial Fibrillation
Hyperthyroidism
Risk Factors •
Age
•
•
~10% of patients >80
•
<1% of patients <55
•
More common in women Most common associated disorders:HTN, CAD atrial fibrillation Anything that dilates the atria
•
Key diagnostic test: Echocardiogram
•
•
•
Heart failure
•
Valvular disease
Commonly leads to atrial fibrillation
•
Reversible with therapy for thyroid disease Atrialfibrillationtherapiesless effective
•
Key diagnostic test:TSH
•
Atrial Fibrillation
Atrial Fibrillation
Triggers
Treatment
•
•
•
Often no trigger identified Binge drinking(“holiday heart”) Increased catecholamines
•
Heart Rate
•
Heart Rhythm
•
“Rate control”
•
Ideally <110bpm
•
Infection
•
Surgery
•
“Rhythm control”
•
Pain
•
Restoration of sinus rhythm
•
Anticoagulation
Rate Control
Rate Control
•
Use drugs thatslow AV node conduction
•
Beta blockers
•
•
Usually
•
Metoprolol, Atenolol
Calcium channel blockers •
•
69
Verapamil, Diltiazem
Digoxin •
Beta Blockers Calcium Channel Blockers Digoxin
1 selectiveagents
Increases parasympathetic tone to heart
Rhythm Control •
Cardioversion
Goal: restore sinus rhythm
•
Electrical •
Deliver “synchronized” shock at time ofQRS
•
Administer anesthesia
•
Deliver electrical shock to chest
•
All myocytes depolarize
•
Usually sinus node first to repolarize/depolarize
Cardioversion
Cardioversion •
Cardioversion
Chemical •
Administration of antiarrhythmic medication
•
Often Ibutilide (class III antiarrhythmic)
•
Less commonly used due to drug toxicity
•
•
Cardioversion •
•
•
•
Chemical/electrical cardioversion may cause stroke 48hours required for thrombus formation Symptoms <48hours: cardioversion safe Symptoms>48hours(or unsure) •
Anti-coagulation 3 weeks cardioversion
•
Transesophageal echocardiogram to exclude thrombus
•
Antiarrhythmic medications
•
Administered before/after cardioversion
•
Class I drugs
•
Class III drugs
•
•
Exception: Hypotension/shock •
Often occurs after hours/days
Rhythm Control
Risk of Stroke •
Spontaneous
Emergent cardioversion performed
70
Flecainide, p ropafenone Amiodarone, sotalol, dofetilide
Anticoagulation •
Warfarin
•
•
Requires regular INR monitoring
•
Goal INR usually 2-3
•
Rivaroxaban, Apixaban
•
Dabigatran
•
•
•
Anticoagulation
•
Factor X inhibitors Direct thrombin inhibitor
Aspirin •
Less effective
•
Only used if risk of stroke is very low
•
Less risk of bleeding
Stroke Risk •
•
•
Whether atrial fibrillation persists or sinus rhythm restored anticoagulation MUST beadministered Studies show similar stroke risk for rate control versus rhythm control
Stroke Risk
CHADS Score
•
CHADS VASC Score
•
CHF (1 point)
•
CHF (1point)
•
HTN (1 point)
•
HTN (1pont)
•
Age >75yrs (1 point)
•
Diabetes (1point)
•
Diabetes (1 point)
•
Stroke (2points)
•
Stroke (2 points)
•
Female (1point)
•
Age 65-75 (1point)
•
Age >75yrs (2points)
•
Vascular disease (1point)
Score >2 = Warfarin or other anticoagulant Score 0 -1 = Aspirin •
•
Atrial Fibrillation
Atrial Flutter
Summary New Onset Atrial Fibrillation
Echocardiogram TSH
Rate Control Beta Blockers Calcium Blockers Digoxin
Anticoagulation Aspirin Warfarin Other drugs
Score >2 = Warfarin or other anticoagulant Score 0 -1 = Aspirin
Rhythm Control Cardioversion Antiarrhythmic drugs
71
Atrial Flutter
Atrial Flutter
Symptoms
Treatment
•
•
•
Generally the same as atrial fibrillation
•
May be asymptomatic Palpitations, dyspnea, fatigue
•
•
Anticoagulation based on stroke risk
•
72
Generally the same as atrial fibrillation Rate or rhythm control Rate-slowing drugs Cardioversion
•
PSVT Paroxysmal Supraventricular Tachycardia •
Intermittent tachycardia (HR >100bpm)
•
Sudden onset/offset
•
Electrical activity srcinates above ventricle
•
AVNRT
Contrast with sinus tachycardia
•
“Supraventricular”
•
Contrast with ventricular tachycardia
•
Produces narrow QRS complex (<120ms)
Jason Ryan, MD, MPH
PSVT
AVNRT
Paroxysmal Supraventricular Tachycardia
Atrioventricular nodal reentrant tachycardia
•
Often causessudden-onset palpitations Chest discomfort
•
Rarely syncope
•
•
•
•
•
Most common cause of PSVT More common in young women Mean age onset: 32 years old Requires dual AV nodal pathways
Dual Pathways
Normal Conduction
Sinus Rhythm
Slow Conduction Short RP
Fast Conduction Long RP
SA AV LBB His RBB
Purkinje Fibers
HIS
73
Dual Pathways
Retrograde P Waves
PAC
Slow Conduction Short RP
Fast Conduction Long RP
HIS
AVNRT •
Recurrent episodes of palpitations
•
Many episodes spontaneously resolve ↓ conduction in AV node breaks arrhythmia
•
Carotid massage
•
•
•
•
Carotid Massage •
•
Patient bears down as if moving bowels
•
Increased thoracic pressure
•
Blood forced from lungs to left atrium
•
Rise in stroke volume rise in blood pressure
•
CNS response via vagus nerve
•
•
Gagging
•
Swallowing
•
↓ AV node conduction
AVNRT Chronic Treatment
Valsalva
Breath holding Coughing Deep respirations
•
•
Vagal maneuvers Adenosine
Vagal Maneuvers •
•
•
Will halt conduction is slow pathway
Examiner presses on neck near carotid sinus Stretch of baroreceptors CNS response as if high blood pressure Increased vagaltone
•
•
Many patients need no therapy
•
Beta blockers, Verapamil/Diltiazem
•
Surgical ablation of slow pathway
•
74
Slow conduction in slow pathway
WPW Syndrome Wolff-Parkinson White Syndrome •
Cardiac electrical disorder
•
“Accessoryatrioventricularpathway”
Wolff-Parkinson White •
•
Conducts impulses from atria to ventricles
•
Bypasses AV node
•
“Bundle of Kent”
•
Ventricular depolarization before AV nodal impulse
May lead toarrhythmias
Jason Ryan, MD, MPH
EKG in WPW
WPW EKG Short PR
Delta Wave
AVRT
Cardiac ElectricalSystem
AV Re-entrant Tachycardia
SA AV LBB His Purkinje Fibers
Orthodromic
RBB
75
Antidromic
Bypass Tract Consequences •
•
Atrial Fibrillation in WPW
Most patientsasymptomatic •
EKG with delta wave only
•
Called WPW “pattern”
•
•
•
Some have tachycardias •
Presents aspalpitations
•
Called WPW syndrome
•
AVRT (anti or orthodromic)
•
Rarely causes syncope or sudden death
•
Treatment: Ablation of accessory pathway
•
•
•
•
Slowing AV node conduction is dangerous Allows more impulses over bypass tract Usual atrial fibrillation therapies contraindicated •
Beta blockers
•
Calcium channel blockers
•
Digoxin
•
Adenosine
Acute treatment: Cardioversion or antiarrhythmics •
Ibutilide, procainamide
•
Slow conduction in bypass tract
Atrial depolarization rate 300-500/min AV node conducts <200/min Impulses may conduct rapidly over bypass tract
Wide complex, irregular, tachycardic
Atrial Fibrillation in WPW •
Atrial fibrillation can belife threatening
76
Vaughan Williams Class I Quinidine Procainamide
Antiarrhythmic Drugs
Drugs used to “suppress” arrhythmias
•
Prevent formation of aberrant impulses Most also causearrhythmias Can lead to cardiac arrest and death
•
Used in dangerous arrhythmias
•
Also used in recurrent symptomatic arrhythmias
•
Beta Blockers
b
Flecainide Propafenone
c
Class III
Class IV
Amiodarone Sotalol Dofetilide Ibutilide
Ca-channel Blockers (Verapamil/Diltiazem
Use of Antiarrhythmic Drugs
Use of Antiarrhythmic Drugs •
Ia
Lidocaine Mexiletine
Jason Ryan, MD, MPH
•
Class II
•
Persistent/recurrent ventricular tachycardia
•
Recurrent atrial fibrillation
Ventricular Tachycardia
Rapid Atrial Fibrillation
Myocyte Action Potential
Mechanisms •
•
•
•
Atrial/ventricular myocytes
All drugs slow cardiac electrical activity Class I drugs Block Na channel
Phase 1 IK+ (out)
Class III drugs Block K channels Class II, IV: Slow sinus and AV node conduction
ICa+
Phase 2 (in) & IK+ (out)
0mv Phase 3
Class I, III
Phase 0 INa+ (in)
BB, CCB (Class II, IV)
-85mv
77
IK+ (out)
Phase 4
Na Channel Blockade
K Channel Blockade Prolonged Repolarization
Slow Phase 0
R
Q
S
Prolong QRS
Prolong QT
Myocyte Action Potential
Class I drugs
Atrial/ventricular myocytes
•
•
•
0mv
•
Block sodium channels prolong QRS Some also affect K+ channels prolong Qt Can prolong action potential duration Can prolong effective refractory period
ERP -85mv
AP
Class I drugs
Class Ia Drugs Quinidine, procainamide
Effects onResting Action Potential Ia
Ib
Ic
•
ProlongQRS
•
Can also prolong Qt (↓K+ outflow)
•
Quinidine
•
↑QRS ↑QT
+/-QRS ↓ QT
↑AP ↑ERP
↓AP ↓ ERP
↑ QRS +/-QT
+/-AP
78
•
Oral drug
•
Can decrease recurrence rate of atrial fibrillation
•
Associated with increased mortality
Procainamide •
Intravenous drug
•
Slows conduction in accessory pathways (WPW)
•
Used in arrhythmias associated with bypass tracts
Class Ib Drugs
Procainamide
Lidocaine, Mexiletine
•
Associatedwithdrug-induced lupus
•
Often rash, arthritis, anemia
•
•
•
•
Classic drugs: INH, hydralazine, procainamide
•
Little/no effect on QRS at normal HR
•
Slight decrease in Qt interval (minimal)
•
Least effect on action potential of class 1 drugs
Antinuclear antibody (ANA) can be positive Key features:anti-histone antibodies Resolves on stopping the drug
Class Ib Drugs
Class Ib Drugs
Lidocaine, Mexiletine
Lidocaine, Mexiletine
•
•
•
Most Na channel binding indepolarized state
•
Ischemia more depolarized myocytes Effective drugs in ischemic arrhythmias
•
•
Main use: ischemic ventricular tachycardia
•
Most Na channel block here (depolarized state)
Drugrapidly unbinds Slow heart rates: little drug effect by next heart beat More effective in fast heart rates Less time to unbind before Na channels open again
•
0mv
•
Fast heart rates
•
Depolarized Na channels
ERP -85mv Phase 4
Class Ib Drugs
Re-entry •
•
Lidocaine, Mexiletine
Mechanism of arrhythmia in myocyte injury Lidocaine: Unidirectional block bidirectional block
•
Lidocaine also a local anesthetic
•
May causeCNS stimulation
•
Cardiovascular side effects
•
•
Tremor, agitation
•
Tremor in patient on Mexiletine = toxicity
•
A
B
•
79
Na channel nerve block
From excessive block of Na channels Bradycardia, heart block, hypotension
Class Ic Drugs
CAST Trial
Flecainide, Propafenone
The Cardiac Arrhythmia Suppression Trial
•
Block open Na channels
•
Landmark clinical trial of antiarrhythmic drugs
•
Very slow unbinding
•
Tested the suppression hypothesis
•
•
•
Result:QRS can markedly prolong Limited use due to concern of toxicity Especially proarrhythmic effects
•
•
•
•
•
•
•
Class Ic Drugs •
•
•
Patients taking drugs had less arrhythmias Also: 3.6-fold increased risk of arrhythmic death Result:Major ↓ antiarrhythmic drugs Now used only with compelling indication
Use Dependence
Flecainide, Propafenone •
Suppression of arrhythmias with drugs is a good thing
Patients with asymptomatic arrhythmias after MI Encainide and flecainide administered
Only used in patients with structurally normal hearts
•
Effective in reducing recurrence of atrial fibrillation Must monitor forQRS prolongation Prolonged QRS Risk of cardiac arrest
•
Na channels fluctuate between 3 different states Resting, Open and Inactivated
•
Drugs bind more in certain states Class I drugs bind best in open/inactivate states
•
These drug exhibit “use dependence”
•
•
States when Na channel is in “use”
Inactive
Open
Resting
Use Dependence
Use Dependence 3 Seconds
•
Use dependent drugs:more binding fast heart rates
•
All class I drugs have some use dependence
•
•
Bradycardia Na Channels Open/Inactive
3 Seconds
Na Channels Resting
Seen most frequently IC drugs Practical implication: •
Flecainide and propafenone (IC drugs)
•
Marked use dependence
•
•
Tachycardia
80
Toxicity (QRS prolongation) at high heart rates Stress testing often done to screen for toxicity
Class III drugs
Torsade de Pointes
Amiodarone, Sotalol, Dofetilide, Ibutilide
•
•
Delayed Repolarization K+ Channel Blockade
•
IA
Feared outcome of Qt prolongation Results in cardiac arrest Class IA, III drugsprolong Qt
III
+/-QRS ↑QT
↑AP ↑ERP
Amiodarone •
•
•
• •
Amiodarone
Class III drug •
K channel blocker: Prolongs Q t interval
•
Lowest incidence TDP of all class IIIs
•
•
Class I: Prolongs QRS
•
Class II, IV: Slow HR, delay AV conduction
•
Safe in renal disease (biliary excretion)
Very effective drug Suppressesatrial fibrillation Suppresses ventricular tachycardia
Amiodarone
Amiodarone •
Many potential side effects related to accumulation
•
Less likely at lower dosages
•
Risk accumulates over time Young patients on indefinite therapy at greatest risk
•
Often used in older patients
•
•
•
Also has class I, II, and IV effects
Highly lipid soluble Accumulates in liver, lungs, skin, other tissues Half-lifeabout 58 days Once steady state reached, very long washout
•
Side Effects •
Hyper and hypothyroidism
•
Increased LFTs
•
Skin sensitivity to sun
•
•
Usually asymptomatic and mild
•
Drug stopped if elevation is marked
•
81
Contains iodine
Patients easily sunburn
Amiodarone
Amiodarone
Side Effects
Side Effects
•
•
Blue-gray discoloration •
Less common skin reaction
•
“Blue man syndrome”
•
Most prominent on face
•
•
Secretion of amiodarone by lacrimal glands
•
Accumulation on corneal surface
•
Appearance of “cat whiskers” on cornea
• •
•
“Honeycombing” pattern on chest x-ray
Does not usually cause vision problems See in many patients on chronic therapy
Amiodarone
Sotalol and Dofetilide
Side Effects •
•
•
Corneal deposits
Pulmonaryfibrosis Most common cause of death from amiodarone Foamy macrophages seen in air spaces Filled with amiodarone and phospholipids
•
When starting amiodarone •
Chest X-ray
•
Pulmonary function tests (PFTs)
•
Thyroid function tests (TFTs)
•
Liver function tests (LFTs)
•
•
•
•
•
•
Reverse Use Dependence
Both drugs block K channels (class III) Can prolong Qt interval torsade de pointes Practical consideration: •
Patients often admitted to hospital to start therapy
•
Rhythm monitored on telemetry
•
Qt segment checked by EKG each day
Sotalol: Also has beta blocking properties Can be used in patients with cardiomyopathy “Reverse use dependence”
Reverse Use Dependence 3 Seconds
•
K channels also fluctuate between 3 different states
•
Class III drugs bind best in resting state
•
These drug exhibit“reverse use dependence” Bradycardia K Channels Resting
3 Seconds
Tachycardia
82
K Channels Open/Inactive
Sotalol and Dofetilide •
•
Sotalol and Dofetilide
Reverse use dependence:more binding slow rates Practical implication:
•
Commonly used in patients withatrialf ibrillation
•
Typical case
•
Bradycardia in patient on sotalol/dofetilide
•
Recurrent episodes symptomatic atrial fibrillation
•
Qt interval may prolong
•
Sotalol/Dofetilide started
•
Increased risk of torsade de pointes
•
Cardioversion to restore sinus rhythm
•
Sinus rhythm persists on therapy
•
•
•
•
Amiodarone
•
Propafenone
•
Flecainide
Cardioversion
Ibutilide •
Other antiarrhythmic also used in this manner
Intravenous drug
•
Half life of 2 to 12 hours Used for“chemicalcardioversion”
•
Termination of arrhythmias Often atrial fibrillation or flutter
Ibutilide
Chemical Cardioversion Electrical Cardioversion Requires sedation
Beta Blockers
Beta Blockers
Class II Antiarrhythmics
Class II Antiarrhythmics
•
Main effect: Pacemaker cells (SA and AV node)
•
Decrease slope of phase 4
•
Prolong repolarization (phase 3)
↓HR ↓Cond Velocity ↑PR Interval
0mv Phase 0 ICa -40mv
-85mv
Threshold
sedation MayNo cause Torsade
Phase 3 IK
Phase 4 If (Na)
83
Calcium ChannelBlockers
Calcium ChannelBlockers
Verapamil and Diltiazem
Verapamil and Diltiazem
•
•
•
Block calciumchannels Slow heart rate Slow AV node conduction
Normal
Decreased Slope Slower Rise
0mv Phase 0 ICa -40mv
-85mv
Phase 3
Threshold
IK
Phase 4 If (Na)
AV Block •
Atrial Fibrillation
Beta blockers/Ca channel blockers ↓ AV conduction
•
•
Beta blockers and CCBs commonly used Controlventricular rate
Atrial Fibrillation with rapid ventricular response
Type 1 AV block
Wenckebach (Mobitz I)
Rate controlled with beta blocker or CCB
Sudden Cardiac Death •
•
•
↓HR ↓Cond Velocity ↑PR Interval
Ca Blocker
Adenosine
Increased risk among systolic heart failure patients Lower rates among patients onbeta blockers Improved mortality
•
Nucleoside base Used to make ATP
•
Receptors in many locations (purinergic receptors)
•
•
AV nodal tissue
•
Vascular smooth muscle
Ventricular Tachycardia
Adenosine Triphosphate
Ventricular Fibrillation
84
Adenosine •
•
Adenosine
AV nodal cells:
•
•
Activates K+ channels
•
Drives K+ out of cells
•
Hyperpolarizes cells: Takes longer to depolarize
•
Also blocks Ca influx
Result: Slowing of
•
•
Short half life Given IV for acute therapy of SVT Slows AV nodeconduction
conduction through AVnode
Narrow Complex Originates above HIS bundle
Adenosine •
Most common SVT:AVNRT •
•
•
•
Adenosine •
AV node reentrant tachycardia
•
Effects blocked bytheophyllineandcaffeine Block adenosine receptors
Slow and fast circuits in AV node arrhythmia Adenosine slows AV node conduction Arrhythmia with terminate
Adenosine Adenosine
Adenosine
Caffeine
Theophylline
Magnesium
•
Also a vasodilator
•
•
Causes skin flushing, hypotension
•
Acute management oftorsade de pointes Mg blocks influx of Ca into cells
•
Ca influx leads to early afterdepolarizations
•
Some patients also develop dyspnea, chest pain Effects quickly resolve
•
Must warn patients before administration for SVT
•
Phase 1 IK+ (out)
0mv
ICa+
Phase 2 (in) & I K+ (out)
0mv Phase 3
Phase 0 INa+ (out) -85mv
85
IK+ (out)
ERP Phase 4
Atropine
Atropine •
Muscarinic receptor antagonist
•
Used in bradycardia ↑ heart rate
•
Also speeds conduction through AV node
•
Useful for bradycardia especially from AV block
•
Parasympathetic block ↑ HR and AV conduction
Before Atropine
After Atropine
Atropine
Digoxin
•
Mayside effectsrelated to muscarinic block
•
Toxicity: •
Dry mouth
•
Constipation
•
Urinary retention
•
Confusion (elderly)
•
Two cardiac effects
•
#1: Increases contractility
•
#2: Slows AV node conduction
•
•
Used in systolic heart failure with ↓ LVEF Used in atrial fibrillation to slow ventricular rate
Digoxin
Digoxin
Increased Contractility
AV Nodal Slowing
•
Inhibits Na-K-ATPase
•
Suppresses AV node conduction
•
Can be used to↓ heart ratein rapid atrial fibrillation
DIGOXIN X
2 Ca+
K+
1 Na+
•
ATP
Digoxin Na trapped inside of cell Less Na exchange for Ca (pump 2) Result: More Ca inside of cell
86
•
Increased vagal (parasympathetic) tone
•
Separate effect from blockade of Na-K-ATPase
•
Continued atrial fibrillation
•
Fewer impulses to ventricle
slower heart rate
Effects similar to BB and CCB in AV node
Digoxin Toxicity •
Renalclearance
•
Hypokalemiapromotes toxicity
•
•
Digoxin Toxicity •
Gastrointestinal
•
Neurologic
Risk of toxicity in patients with chronic kidney disease
•
Anorexia, nausea, vomiting, abdominal pain
•
Caused by many diuretics, especially loop diuretics
•
Lethargy, fatigue
•
Digoxin patient on furosemide toxicity
•
Delirium, confusion, disorientation
•
Weakness
Levels often need to be monitored •
Visual changes
•
Cardiac arrhythmias
•
Alterations in color vision, scotomas, blindness
Digoxin Toxicity
Digoxin Toxicity
Cardiac Toxicity
Treatment
•
•
•
•
More Na inside of cell ↑ restingpotentialatrial/ventricular cells Increased automaticity Dig toxic rhythms: •
Extra beats: atrial, junctional, ventricular
•
Evidence of AV node block
•
•
87
Digibind •
Digoxin antigen binding fragments (Fab)
•
Produced in animals (sheep)
•
Dig bound to albumin (hapten) antibodies
•
Antibody converted to fragments
Corrects hyperkalemia, symptoms
The Cardiac Cycle Aorta LV LA
Heart Sounds
LV Volume S1 Heart Sounds S2 VenousPressure
Jason Ryan, MD, MPH
EKG
S1 and S2
S1 and S2 •
Normal heart sounds
•
Each hastwo components
•
•
•
S1
•
S2
•
•
One from left sided valves (aortic, mitral)
•
One from right sided valves (tricuspid, pulmonic)
•
Mitral and tricuspid valves close
Aortic and pulmonary valves close
S1 usually “single” •
Two components close together
•
Cannot distinguish separate sounds
S2 can be“split” •
Two components far enough apart to be audible MV TV S1
S1
S1
MV TV
S2
AV
PeRsistent = Right sided delay MV TV
AV PV
S1
S2
S2
Exhalation
MV TV
AV PV
RBBB or Pulmonary Hypertension
S2
Exhalation
Inspiration
MV TV
S2
Persistent S2 splitting
Physiologic S2 splitting S1
AV PV
Inspiration
PV
AV PV
S2
S1
MV TV
AV
PV
Delayed PV closure even during exhalation
Increased venous return delays P2 by 40-60ms Single to split with inspiration
88
Fixed S2 splitting
Paradoxical S2 splitting
Atrial septal defect
Delayed closure of aortic valve
S1
Atrial Septal Defect Fixed split S2 Systolic Ejection Murmur LSB
S2
Exhalation
S1
S2
Exhalation MV TV
AV
PV MV TV
S1
Inspiration
Inspiration
MV TV
PV
AV
S2
AV
S1
S2
PV MV TV
PV AV
Flow across ASD increased right sided flow
Paradoxical Splitting •
•
Summary of S2 Splitting
Electrical causes delayed LV activation •
LBBB
•
RV pacing
•
Mechanical causes delayed LV outflow •
LV systolic failure
•
Aortic stenosis
•
Hypertrophic cardiomyopathy
Physiologic= normalrespiratory variation
•
PeRsistent = RBBB, pulmonary HTN Fixed = Atrial septal defect
•
ParadoxicaL = LBBB,cardiomyopathy
•
ParodoxicaL = Left sided delay
Loud P2
Cardiac Phonography
1, S2
•
Loud pulmonic component of S2
•
Pulmonary hypertension
•
•
Forceful closure of pulmonary valve Normally P2 not heard at apex •
Fixed Split S2
89
If you hear it here, it’s “loud”
S3 and S4 •
•
•
•
•
S3
Pathologic/abnormal heartsounds
•
Occur in diastoleduring filling of left ventricle Low-pitchedsounds heard best with bell S3: Early filling sound S4: Late filling sound
S1
•
S2
Commonly seen inacute heart failure •
High LA pressure rapid early filling of LV S3
•
Associated with ↑ LAP & ↑LVEDP
•
“Pushers” push blood into LV
•
Very specific sign of high left atrial pressure
May be heard in normal hearts •
Young patients (<30), pregnant women
•
These patients are “suckers”
•
S4
S1
S2
S3 •
•
•
Vigorous LV relaxation lowers pressure rapidly
S3
S4
Low frequencybest heard with bell
•
Louder in left lateral decubitus position Loudest atapex •
•
Heard in patients withstiff left ventricle •
Long-standing hypertension
•
Hypertrophic cardiomyopathy
•
Diastolic heart failure
Rapid late filling of LV due to atrial kick Not heard in atrialfibrillation
Atrial Fibrillation
Right Sided S3 & S4 •
Both sounds can occur in right ventricle
•
Same mechanisms as left sounds
•
•
Systolic Clicks
Right heart failure right sided S3 Right ventricular hypertrophy right sided S4
S1
Click S2
Ejection Click Early in systole BEFORE carotid pulse Bicuspid Aortic Valve
90
S1
Click S2
Non-Ejection Click Late in systole AFTER carotid pulse Mitral Valve Prolapse
Mitral ValveProlapse
Mitral Valve Prolapse •
•
•
Systole
Billowingof mitral valve leaflets above annulus Common cause ofmitral regurgitation Causes asystolic click •
Don’t confuse with opening snap of mitralstenosis
Mitral Valve Disorders Proclick Stenosnap
Click S1
Normal
MVP
91
Murmur S2
Diastole
Heart Murmurs •
Cardiac sound heard with stethoscope
•
Caused byturbulent blood flow
•
May be normal or pathologic
Heart Murmurs Jason Ryan, MD, MPH
Murmurs
Laminar vs. Turbulent Flow
Grading •
•
•
V –heard with scope barely touching chest
•
VI - audible with scope not touching the chest
•
Laminar Flow = Quiet(er)
I - barely audible on listening carefully II - faint but easily audible III - loud and easily audible, no thrill IV - loud murmur with a thrill
•
Turbulent Flow = Loud High Flow Rates Narrow Flow Areas
Murmurs
Murmurs
Other Descriptors
S1
Location Systole
Diastole
Systole
S2
S1
LUSB Pulmonic Murmurs PDA
RUSB Aortic Stenosis A
S2
LSB Aortic Regurg HCM Holosystolic Pansystolic
Crescendo
Decrescendo
Crescendodecrescendo
T
LLSB Tricuspid Murmurs VSD
92
P
M
Apex Mitral Murmurs
Murmurs
Innocent/Functional Murmurs
Location •
•
•
Point of maximal impulse (apical impulse) •
Left 5th intercostal space
•
Mid-clavicular line
•
•
•
Lateral shift = Enlarged heart Hyperdynamic
•
•
•
•
Base
•
Caused by normal flow of blood Common in children Also young, thin patients Generally soft murmurs No signs/symptoms of heart disease Stillsmurmur Pulmonic flow murmur Venous hum
Apex
Systolic Murmurs •
•
•
•
•
•
•
•
Diastolic Murmurs
Occur when heartcontracts/squeezes
•
Between S1-S2 Aortic stenosis Mitral regurgitation
•
•
Pulmonic regurgitation
•
Tricuspid stenosis
•
Pulmonic stenosis Tricuspid regurgitation
Occur when heart relaxes/fills Between S2-S1 Aortic regurgitation Mitral stenosis
•
Hypertrophic cardiomyopathy Ventricular septal defect (VSD)
Aortic Stenosis
Aortic Stenosis
Murmur
Severe Disease Findings
•
Systolic crescendo-decrescendo murmur
•
Also called an “ejection murmur”
•
Late-peaking murmur
•
Soft/quiet S2
•
Pulsus parvus et tardus
•
•
•
•
S1
S2
93
Slow flow across stenotic valve Stiff valve can’t slam shut Weak and small carotid pulses Delayed carotid upstroke
HCM
Aortic Regurgitation
Hypertrophic Cardiomyopathy
Murmur
•
Same murmur as aortic stenosis
•
Differentiated bymaneuvers
•
Valsalva •
Decreases venous return/preload
•
Increase HCM murmur
•
Decrease AS murmur
•
Decrescendo,blowingdiastolic murmur
S1
S2
HCM
Mitral Regurgitation •
Mitral Stenosis
Holosystolic murmur heard best at the apex •
•
5th intercostal space, mid-clavicular line
•
Diastolic rumbling murmur Preceded by opening snap Systole
S1
Diastole
Systole
Diastole
S2
Holosystolic (Pansystolic)
S1
Mitral Stenosis
S2 OS
Diastolic Rumble (Murmur)
Tricuspid/Pulmonic Disease
•
No left sided S3, S4 in mitral stenosis
•
Valve lesions sound like left sided-counterparts
•
Time to opening snapassociated with severity
•
Heard in different locations
•
Left upper sternal border
•
Left lower sternal border
•
High left atrial pressure in severe disease
•
Higher left atrial pressure ↓ time to opening snap
•
Short time to opening snap seen in severe disease
•
•
94
Pulmonic stenosis/regurgitation
Tricuspid stenosis/regurgitation
VSD
Carvallo’s Sign •
Ventricular Septal Defect
Most right sided murmurs louder with inspiration
•
Inspiration draws blood volume to lungs Louder right sided murmurs Softer left sided murmurs rIght sidedmurmurs increase with Inspiration
•
lEft sidedmurmurs increase with Exhalation
•
•
•
•
•
Holosystolic murmur similar to MR Small VSD more turbulence loud murmur
3 Causes Holosytolic Murmurs Mitral Regurgitation Tricuspid Regurgitation VSD S1 S2 Holosystolic (Pansystolic)
PDA
Maneuvers
Patent Ductus Arteriosus •
Continuous, “machine -like” murmur
•
•
•
S1
S2
S1
Valsalva Maneuver
Preload/Venous Return
•
•
Increase preload/venous return •
Leg raise – blood falls back toward heart
•
Squatting – blood in legs forced back toward heart
•
Bear down as if moving bowels
•
Phase I (few seconds)
Decrease preload/venous return •
Valsalva- ↑ intra-thoracic pressure vein compression
•
Standing – Blood falls toward feet, away from heart
↓
VR
•
Most HCMmurmurs INCREASE with more preload except:
•
↑ thoracic pressure
•
↓ venous return (compression of veins ↑RA pressure)
•
Transient rise in aortic pressure (compression)
•
↓ heart rate and AV node conduction (baroreceptors)
Phase II ↓ cardiac output ↓ preload •
•
•
May increase or decrease murmur Used to make diagnosis
S2
Maneuvers •
Performed at bedside with patient
MVP
•
95
↑ heart rate and AV node conduction (baroreceptors)
Maneuvers
Maneuvers
Afterload
Afterload
•
Increase Afterload
•
Decrease Afterload
•
•
•
Backward Valve Disorders
Hand grip - clench fist
Amyl Nitrate - vasodilator •
•
•
AR, MR, VSD
•
Louder with more afterload
•
More force pushing blood backward
Forward Valve Disorders •
MS, AS
•
Softer with more afterload
•
Less pressure difference moving blood forward
MVP, HCM •
Softer
•
Increased LVcavity size
Amyl Nitrate
Summary
Clues to Diagnosis •
•
Healthy, young athlete, syncope HCM Immigrant or pregnant Mitral stenosis IV drug abuser Tricuspid regurgitation
•
Turner Syndrome or Aortic Coarctation
•
•
•
Commonly Tested Murmurs S1
Young female, otherwise healthy MVP
•
Bicuspid AV
•
Early stenosis
•
Aortic regurgitation
AS/HCM MR/VSD AR MS
Marfan MVP
PDA
96
S2
S1
S2
Heart Failure •
Impaired ability of the heart to pump blood
•
Hallmark:Low cardiac output
Heart Failure Basics
↓ CO
Jason Ryan, MD, MPH
Heart Failure
Heart Failure
H20 H20 Tank
Tank
Pump
Pump
Heart Failure
Heart Failure
H20
H20
Tank
Tank
Pump
Heart
97
Heart Failure
Heart Failure
Blood
Blood
ank
Tank
Heart
Heart
Heart Failure
Heart Failure
Pathophysiology •
“Failing” chambers Increased pressures
•
Pressuresrise in cardiac chambers
Lungs & Veins
Heart
Heart Failure
Heart Failure
Pathophysiology
Pathophysiology
•
Left ventricular failure ↑ LV pressure •
LV systolic pressure: depends on contractility (can be low)
•
LVEDP = always high in left heart failure
•
Hallmark of left heart failure
•
Less blood pumped out more left behind more pressure
•
Stiff ventricle (diastolic HF) high pressure
•
•
↑ LVEDP ↑ LA pressure ↑ pulmonary capillary pressure •
Dyspnea
•
Pulmonary edema Aorta
LV LA
98
Heart Failure
Heart Failure
Pathophysiology
Pathophysiology •
•
•
↑Pc
↑ pulmonary capillary pressure ↑ PA pressure ↑ PA pressure ↑ RV pressure ↑ RV pressure ↑ RA pressure •
Right atrial pressure = central venous pressure
•
High pressure in venous system
•
↑ jugular venous pressure (neck veins)
•
Capillary leak
pitting edema
Heart Failure
Heart Failure
Signs/Symptoms
Signs/Symptoms
•
Physiologic effects of lying flat (supine)
Left heart failure
Increased venous return
•
Dyspnea especially on exertion
•
Redistribution of blood volume
•
Paroxysmal nocturnal dyspnea (wake up SOB)
•
From lower extremities and splanchnic beds to lungs
•
Orthopnea (can’t breathe lyingflat)
•
Little effect in normal individuals Impaired ventricle cannot tolerate changes
•
Worsens pulmonary congestion and breathing
•
•
•
•
Right heart failure •
Increased jugular venous pressure
•
Lower extremity edema
•
•
Liver congestion (r arely can causecirrhosis)
“Backward failure”
Heart Failure
Heart Failure
Right Heart Failure
Signs/Symptoms
•
Most common cause R heart failure: Left heart failure
•
Occasionally right heart failure occurs in isolation
.
•
Low flow signs/symptoms(“forwardfailure”) •
Loss of appetite
•
Normal left atrial pressure
•
Weight loss (cachexia)
•
High pulmonary artery, right ventricular, right atrial pressure
•
Confusion
•
Usually secondary to a lung process
•
Cool extremities
•
Pulmonary hypertension
•
“Narrow pulse pressure”
•
COPD
•
This is often called “cor pulmonale”
99
•
Seen only with very low cardiac output (systolic HF)
•
Not seen in diastolic heart failure
Heart Failure
Heart Failure
Lung Findings
Lung Findings
•
Classic finding israles •
•
•
•
Fluid filled alveoli “pop” open with inspiration
•
Chest X-ray shows congestion Lungs/CXR can be clear in chronic heart failure •
•
Heart failure cells Hemosiderin (iron) laden macrophages Brown pigment in macrophages
↑lymphatic drainage
Heart Failure
Heart Failure
Signs/Symptoms
Hepatojugular Reflux
•
Elevated jugular venous pressure (normal6-8cmH2O)
•
Look for height of double bounce (cause by a and v waves)
•
Pressure on abdomen raises JVP 1-3cm normally
•
With failing RV, increase is greater
Heart Failure
Heart Failure
Signs/Symptoms
Abnormal Heart Sounds
•
Lower extremity pitting edema
•
S3 (associated with high left atrial pressure)
•
Increased capillary hydrostatic pressure
•
S4 (associated with stiff left ventricle)
•
Fluid leak from capillaries tissues
•
Displaced apical impulse – enlarged heart
•
Gravity pulls fluid to lower extremities
S1
↑Pc S4
100
S1
S2
S2
S3
Heart Failure
Heart Failure
Pathophysiology
Total Peripheral Resistance
•
All forms of heart failure lead to↓ cardiac output
•
Cardiac output falls vasoconstriction
•
Activates two physiologic systems
•
Angiotensin II, sympathetic nervous system
•
•
Activation of sympathetic nervous system
•
Activation of renin-angiotensin-aldosterone system
•
All RAAS hormone levels will rise
•
•
•
Both systems lead to two key effects: •
Increased peripheral vascular resistance (vasoconstriction)
•
Retention of sodium/water (kidneys)
TPR alwayshigh Blood pressure often high but may be low Depends on combined changes CO and TPR
BP = CO X TPR
Heart Failure
Heart Failure
Sodium/Water Retention
Other Hormones
↓ cardiac output
•
↓ Effective Circulating Volume
Atrialstretch (pressure/volume) ANP release Vasodilator (↓TPR)
•
Constricts renal efferents/dilates afferents
•
↑ RAAS
↑ SNS ↑ ADH
ANP (Atrial natriuretic peptide)
•
•
•
↑ diuresis Opposite effects of RAAS system
↑ Na/H2O Afferent
Efferent
↑ Total Body Water
Heart Failure
Nesiritide
Other Hormones •
•
•
•
•
ANP released by atrial myocytes BNP (brain natriuretic peptide):Ventricles Both rise with volume/pressure overload Both counter effects of RAAS system BNP sometimes used for diagnosis in dyspnea •
High levels suggest heart failure
•
Low levels suggest other causes of dyspnea
•
RecombinantBNP
•
Vasodilation
•
•
ANP/BNP RAAS
101
↓ afterload,↑CO Failed to show benefit in clinical trials
Heart Failure Diagnosis •
•
•
Most common: typical signs/symptoms Elevated BNP level Heart catheterization •
Increased LVEDP = left heart congestion/failure
•
Increased RA, RVEDP = right heart congestion/failure
102
Heart Failure Systolic and Diastolic •
Systolic and Diastolic Heart Failure
•
Same congestive signs/symptoms •
Dyspnea, orthopnea, paroxysmal nocturnal dyspnea
•
Rales, ↑ JVP,pitting edema
Exception:Low flow symptomsin systolic only •
Cool extremities
•
Cachexia
•
Confusion
Jason Ryan, MD, MPH
Dilated Cardiomyopathy •
•
Concentric Hypertrophy
Systolic heart failure with LV cavity dilation “Eccentric” hypertrophy •
Volume overload (chronic retention of fluid in cavity)
•
Longer myocytes
•
Sarcomeres added in series
Normal LV Size
Dilated LV
•
Pressure overload
•
Chronic ↑↑ pressure in ventricle: HTN, Aortic stenosis
•
•
Decreased compliance (stiff ventricle) Often seen in diastolic heart failure
Normal LV Size
Increased myocyte size Sarcomeres in series Normal wall thickness
↓ LV Size
Increased myocyte size Sarcomeres in parallel Increased wall thickness
Systolic Heart Failure •
•
•
•
↓ Cardiacoutput Problem in SYSTOLE Can’t get blood out ↓ Stroke volume •
SV = EDV – ESV
•
↑ ↑ ESV (↓ contractility)
•
LV Vol Systolic Heart Failure ↓ Contractility
•
LV Vol
↑ EDV (↑ESV + VR) ↑ LVEDP LV Vol
Diastolic Heart Failure ↓ LV Compliance ↓ Lusitropy
Systolic Heart Failure ↓ Contractility
103
Frank-Starling Curve
Diastolic Heart Failure
•
↓ Cardiacoutput Problem in DIASTOLE Can’t get blood in Small ↓ stroke volume
•
↑↑ LVEDP(stiff ventricle)
•
•
•
Normal
•
↓ Contractility
Stroke Volume
↓ EDV (↓ filling)
LV Vol
Preload (LVEDV)
Diastolic Heart Failure ↓ LV Compliance ↓ Lusitropy
Systolic Heart Failure •
•
Most common cause:Myocardial infarction •
Myocytes replaced by scar tissue
•
“Ischemic” cardiomyopathy
Many causes of“non-ischemic” cardiomyopathy •
•
Diastolic Heart Failure •
Exact cause unknown
•
Many cases have concentric hypertrophy
•
Many associated conditions
•
Terms:
•
About 50% idiopathic Many other causes: viral, familial, peri-partum, chemotherapy toxicity, HIV, alcoholic, sarcoidosis, tachycardia-mediated
•
•
•
Age, diabetes, hypertension
Heart failure preserve d EF HFpEF Diastolic dysfunction
Nonischemic Cardiomyopathy
Nonischemic Cardiomyopathy
Viral
Peri-partum
•
May follow upper respiratory infection
•
•
Many associated viruses
•
•
•
• •
•
Coxsackie
•
Influenza, adenovirus, others
•
Virus enters myocytes Causes myocarditis cardiomyopathy Myocarditis phase may go undiagnosed No specific therapy for virus
104
Late in pregnancy or early post-pregnancy Exact cause unknown(likely multifactorial) Women often advised to avoid future pregnancy
Nonischemic Cardiomyopathy
Nonischemic Cardiomyopathy
Chemotherapy
Familial
•
Usually after treatment with anthracyclines
•
Mutations
•
Antitumor antibiotics
•
Often sarcomere proteins
•
Doxorubicin and daunorubicin
•
Beta myosin heavy chain
•
Alpha myosin heavy chain
•
Troponin
Daunorubicin
•
Many autosomal dominant
•
X-linked, autosomal recessive also described
Doxorubicin (Adriamycin)
Nonischemic Cardiomyopathy
Nonischemic Cardiomyopathy
Tachycardia-mediated
Takotsubo/Apical ballooning
•
Constant, rapid heart rate for weeks/months Leads to depression of LV systolic function
•
Reversiblewith slower heart rate
•
•
•
Chronic consumption can cause cardiomyopathy
•
Believed to be due to toxic metabolites
•
Can recover with cessation of alcohol
•
•
Looks like anterior MI (but no coronary disease)
•
Usually recovers 4-6 weeks
•
Alcohol
Stress-inducedcardiomyopathy
Occurs after severe emotional distress Markedly reduced LVEF Increase CK, MB, Troponin; EKG changes
•
High Output Heart Failure •
Heart in overdrive •
Severe anemia
•
Thyroid disease
•
Thiamine (B1) vitamin deficiency (beriberi)
•
A-V fistulas (post-surgical)
•
Exact mechanism unclear
•
Defining characteristic:HIGH cardiac output
•
105
Decreased LV filling time
•
Heart failure symptoms in absence of low output
•
↑JVP, pulmonary edema
Restrictive Heart Disease •
Restrictive Cardiomyopathy
Something“infiltrates”the myocardium •
Granulomas (Sarcoid)
•
Amyloid protein (Amyloidosis)
•
Heart cannot relax and fill
•
SEVERE diastolic dysfunction
Jason Ryan, MD, MPH
Restrictive Heart Disease
Restrictive Heart Disease •
•
•
•
•
Clinical Features
LVEF = normal Left ventricular volume = normal (not dilated) Restricted filling = ↑ atrial pressure Dilated left and right atria
•
Dyspnea
•
Prominentright heart failure
Classic imaging findings: •
Normal left ventricular function/size
•
Bi-atrial enlargement
•
Markedly elevated jugular venous pressure
•
Lower extremity edema
•
Liver congestion
•
May lead to cirrhosis (“nutmegliver”)
Restrictive Heart Disease
Restrictive Heart Disease
Classic signs
Rhythm Disturbances
•
Kussmaul’s sign •
Inspiration causes rise in JVP
•
Myocardialinfiltrationmaydisruptelectricalactivity
•
Arrhythmias (sudden death)
•
AV block
Ventricular Tachycardia
106
3rd Degree Heart Block
Restrictive Heart Disease
Restrictive Heart Disease
Major Causes
Classic signs
•
Amyloidosis •
Amyloid protein deposits in heart
•
Various forms (primary, secondary, etc.)
•
Can see thickened myocardium
•
Low voltage on EKG
•
Classic finding in amyloidosis andFabry’s disease
Restrictive Heart Disease
Restrictive Heart Disease
Major Causes
Major Causes
•
Sarcoidosis
•
Fabry disease
•
Granuloma formation
•
Lysosomal storage disease
•
Usually involves lungs
•
Deficiency of -galactosidase A
•
Extra-pulmonary or gans include heart
•
Accumulation of ceramide trihexoside
Restrictive Heart Disease
Restrictive Heart Disease
Major Causes
Major Causes
•
Hemochromatosis •
Iron excess
•
Commonly causes dilated cardiomyopathy
•
Rarely may cause restrictive
•
Acutely: May cause inflammation Fibroblast recruitment Extra-cellar matrixdeposition
•
Collagens and fibronectin
•
107
Post-radiation
•
•
Restrictive Heart Disease
Restrictive Heart Disease
Major Causes
Major Causes
•
Pericarditis may occur acutely after therapy
•
Long term effects
•
•
Loeffler’s syndrome •
Hypereosinophilic syndrome
•
Pericardial disease
•
High eosinophil count
•
Coronary artery disease
•
Eosinophilic infiltration of organs
•
Valvular disease
•
Conduction abnormalities
•
Skin (eczema)
•
Lungs (fibrosis)
Restrictive cardiomyopathy •
Fibrous tissue accumulation
•
Diastolic dysfunction
Restrictive Heart Disease
Restrictive Heart Disease
Major Causes
Major Causes
•
•
Primary HES •
Neoplastic disorder
•
Stem cell, myeloid, or eosinophilic neoplasm
•
Reactive process
•
Eosinophilic overproduction due to cytokines
Acute phase
•
Chronic phase
•
Occurs in parasitic infections (ascaris lumbri coides)
•
Some tumors/lymphomas
Idiopathic HES
Major Causes
•
•
•
Restrictive Heart Disease •
Eosinophilic infiltration of myocardium
Secondary HES
•
•
•
Endocardial fibroelastosis •
Endocardial thickening (innermost myocardium)
•
Infants in first year of life
•
Thick myocardium
•
Proliferation of fibrous (collagen) and elastic fibers
Restrictive cardiomyopathy
108
Common mode of death
Myocarditis (often asymptomatic)
•
Endomyocardial f ibrosis and myocyte death
•
Can see restrictive heart disease
•
Thrombus formation common (embolic stroke)
Heart Failure Acute vs. Chronic Acute •
•
•
•
Acute Heart Failure
Chronic
Congested/Swollen Pulmonary Edema Pitting Edema ↑JVP
•
•
•
•
Euvolemic Clear lungs No pitting edema JVP flat
Jason Ryan, MD, MPH
Acute Exacerbations
Dietary Indiscretion
Causes •
•
•
↑Na Intake
#1: Dietary indiscretion
Plasma Na = 140meq/L
High salt intake
↑Plasma Osmolarity
#2: Poor medication compliance
↑ADH ↑Free Water
↑Volume
Normal Plasma [Na]
↓RAAS ↓ADH ↑Urine Output
Acute Exacerbations
Acute Heart Failure Therapy
Causes •
Infection/trauma/surgery • Activation of sympathetic nervous system
•
•
Ischemia (rare) • Decreased cardiac output Inhibit cyclooxygenase (COX) ↓ prostaglandins
• Prostaglandins maintain renal perfusion •
Often treated in the hospital
•
Goal: Symptom relief
•
Often same therapies for diastolic versus systolic
•
NSAIDs •
•
Result: Less renal perfusion salt/water retention
109
Contrast with chronic HF: reducemortality/hospitalizations
Loop Diuretics
Loop Diuretics
Furosemide, Bumetanide, Torsemide, Ethacrynic Acid •
•
•
•
Na •
K 2Cl
•
Inhibit Na-K-Cl pump in ascending loop of Henle Result in salt-water excretion Relieve congestion IV better than PO (gut is swollen) Key side effects •
Hypokalemia
•
Volume depletion (Renal failure; hypotension)
Sulfonamide drugs: allergy (except ethacrynic acid)
Ascending Limb Loop Diuretics
Metolazone •
Thiazide-like diuretic
•
Inhibits Na-Cl reabsorption distal tubule Gives loop diuretics a “kick” Vigorousdiuresis
•
Side effects: additional fluid, K+ loss
•
•
Nitrates •
Predominant mechanism isvenous dilation •
Bigger veins hold more blood
•
Takes blood away from left ventricle
•
Lowers LVEDV (preload), LA pressure
•
Less pulmonary edema improved dyspnea
Vasodilators
Nitrates
“Afterload reduction” •
Side effects •
Headache (meningeal vasodilation)
•
Flushing
•
Hypotension
•
110
ACE inhibitors
•
Hydralazine Cause peripheral vasodilation
•
Reduced afterload increased cardiac output
•
Nitrates plus Hydralazine •
Inotropes • Increase contractility • Only for systolic heart failure
Combination therapy foracute and chronic HF •
Studied in systolic heart failure
•
Reduction in preload (nitrates) and afterload (hydralazine)
•
Acute therapy: Improves symptoms
•
Chronic therapy: Lowers mortality in some studies
•
Largely replaced by ACE inhibitors
•
Some studies suggested benefit inblack patients
•
No role in diastolic heart failure (normal contractility)
•
All activate β1 pathways in myocytes
•
Can also active β2 pathways in smooth muscle
•
•
Increased HR and contractility Vasodilation
hypotension
Inotropes
Inotropes
Milrinone
Dobutamine
•
Phosphodiesterase 3 inhibitor •
PD3 breaks down cAMP in myocyctes
•
Inhibition ↑cAMP contraction
•
Vascular smooth muscle ↑cAMP (β2)
•
↑Inotropy ↑Vasodilation
•
Hypotension
•
•
Mostlybeta-1agonist
•
Weak beta-2 agonist
•
dilation
•
Increases heart rate and contractility
Vasodilation
•
↑Inotropy ↑Vasodilation
•
Hypotension
•
Similar effects to milrinone
•
Inotropes
Inotropes
Dopamine
Epinephrine
•
•
•
Does not cross blood brain barrier (no CNS effects) Peripheral effects highly dependent on dose Low dose: dopamine agonist •
•
•
Low dose: beta-1 and beta-2 agonist
•
High dose: alpha agonist •
Increased heart rate and contractility
High dose: alpha agonist •
Also dose dependent effects
•
•
Vasodilation in kidneys
Medium dose: beta-1 agonist •
•
Vasoconstriction
111
Increased heart rate & contractility, vasodilation
Vasoconstriction
A Typical Acute Heart Failure Course
Inotrope Risks •
•
Numerous registries and clinical trials demonstrate increased mortality with routine use of inotropes Dangerous drugsused in very sick patients under monitored conditions
•
ER presentation:
•
Admitted to hospital
•
•
•
A More Complex Heart Failure Course •
•
•
•
Nitro drip to relieve dyspnea
•
IV Furosemide to remove fluid
Hospital Day 2 •
Weight down 4kg, feels better
•
Nitro drip stopped
•
Changed to oral furosemide
Hospital Day 3: Discharge
A More Complex Heart Failure Course
ER presentation:
•
Hospital Day 3-5
•
Dyspnea, edema, sleeping in chair
•
Good urine output
•
Known LVEF 10%
•
Weight loss 4kg
•
Breathing improves
Admitted to hospital •
Nitro drip to relieve dyspnea
•
IV Furosemide to remove fluid
•
Hospital Day 2 • •
•
Poor urine output, Cool extremities, Cr rises 1.11.4 Dobutamine drip started
Hospital Day 6 •
Dobutamine stopped
•
Furosemide drip stopped
Hospital Day 7 •
•
Heart Failure Readmission •
Dyspnea, edema, sleeping in chair
Oral furosemide given
Hospital Day 8: Discharge
Acute Heart Failure
Recurrence of HF after discharge common
•
Most patients require chronic, daily diuretic
•
Post-discharge follow-up VERY important
•
Helps to maintain euvolemic status
•
“Readmissions” a focus of public health policy
•
Often oral furosemide or other loop diuretic
•
High risk of readmission within 30 days
•
Highest risk category among Medicare population
•
Some patients require daily long acting nitrate •
112
Often oral isosorbide mononitrate
Acute Heart Failure •
Digoxin
Rare patients: continued treatment forlow output •
Systolic heart failure only
•
Chronic, IV infusion inotrope (i.e. “homedobutamine”)
•
Left ventricular assist device (LVAD)
•
Heart transplant
•
•
•
Only availableoralinotrope
“Dig and diuretic” once the mainstay of HF treatment What changed? •
Digoxin shown to have no mortality benefit
•
Digoxin not effective for diastolic heart failure
•
Digoxin carries significant risk of side effects
•
About 50% of all cases
Digoxin Mechanism
Digoxin
Two important cardiac effects
Benefits in Heart Failure
•
•
#1: Inhibits Na-K-ATPase pump •
More Na in cell more Ca++ in cell
•
More Ca++ more contractility
#2 Suppresses AV node conduction (parasympathetic) •
Can be used to slow heart rate in rapid atrial fibrillation
Digoxin Benefits in Heart Failure •
•
•
Increased cardiac output Improved symptoms and quality of life No established mortality benefit
113
•
Useful for systolic HFpatients
•
Can be administered for acute heart failure
•
Can be administered long term to maintain CO
•
Symptoms despite maximal therapy on other drugs
•
i.e. persistent dyspnea despite good volume status
Heart Failure Treatment Pathway Acute Heart Failure
Chronic Heart Failure
Rx Chronic Heart Failure
Jason Ryan, MD, MPH
Chronic Heart Failure •
•
Drugs: ACE-inhibitors, beta blockers, aldosterone antagonists
•
Defibrillators
•
Bi-ventricular pacemakers
Guidelines recommendations: treat HTN, diabetes, A. fib
•
Mainstay of therapy: monitor for symptoms, diuretics
ARBs
•
•
Blockade ↓ mortality and disease progression
•
RAAS Drugs
Renin-Angiotensin System Angiotensinogen
Sympathetic System
•
ACE Inhibitors
•
Angiotensin ReceptorBlockers (ARBs)
•
Both classes: ↓ morality,↓ hospitalizations
+ Renin AI
•
Renal Na/Cl resorption + ACE
•
A2 Arteriolar vasoconstriction
•
•
ACE Inhibitors
Adrenal aldosterone secretion
•
Net Result
Systolic Heart Failure
Chronic over-activation of two physiologic systems Renin-angiotensin-aldosterone system Sympathetic nervous system(β1 stimulation)
•
NO direct therapies for diastolic heart failure •
Diastolic Heart Failure
Systolic Heart Failure
LOTSof therapies for systolic heart failure •
Symptom Relief Loop diuretics Nitroglycerine Inotropes
•
114
Candesartan, Ir besartan, Valsartan Directly block AII receptor
Side effects •
Pituitary ADH secretion
↑Salt/Water Retention ↑Preload ↑TPR ↑Afterload
Captopril, Enalapril, Lisinopril, Ramipril Block conversion AI AII
Hyperkalemia (↓aldosterone) Renal failure (↓GFR)
ACE Inhibitors
Bradykinin
Unique Side Effects •
Due to increasedbradykinin
•
Dry Cough •
•
X
Angioedema •
Swelling of face, tongue
•
Can be life-threatening
•
•
Negative inotropes
Not used in acute heart failure •
AI
May worsen cardiac output andsymptoms •
A2
Three agents beneficial in chronic systolic HF failure •
Metoprolol (β1)
•
Carvedilol (
•
Bisoproplol (β1)
2
1)
Potassium-sparing diuretics •
Sympathetic System
•
Renal Na/Cl resorption
↑Na/H2O excretion (diuretics) “Spare” potassium •
A2 X
1
↓ morality,↓ hospitalizations
Spironolactone, Eplerenone
Aldosterone Antagonists
Arteriolar vasoconstriction
X
Beta Blockers
Once contraindicated in systolic heart failure •
ACE Inhibitors
Inactive Metabolites
Beta Blockers •
Cough Vasodilation
Bradykinin
Occurs in ~10% of patients
•
Spironolactone Eplerenone
•
•
Adrenal aldosterone secretion Pituitary ADH secretion
115
Unlike other diuretics, do not increase K+ excretion
HYPERkalemia is side effect Reduced mortality Reduced hospitalization rate
Spironolactone, Eplerenone
Neprilysin Inhibitors
Potassium-sparing diuretics
Sacubitril
•
•
Similar structureto testosterone •
Blocks testosterone effects
•
Gynecomastia in men
•
Eplerenone: No gynecomastia
•
Neprilysin: Degrades atrial/brain natriuretic peptide
•
Inhibition ↑ANP/BNP
Derivative ofprogesterone •
Activates progesterone receptors
•
Amenorrhea in women
Eplerenone
•
Antagonists to RAAS system
•
Vasodilatation
•
Natriuresis (sodium excretion)
•
Diuresis (water excretion)
•
Reduced sympathetic tone
ANP/BNP RAAS
Spironolactone
estosterone
Progesterone
Neprilysin Inhibitors
Neprilysin Inhibitors
Sacubitril
Side Effects
•
Entresto: oral combination sacubitril/valsartan •
• •
•
Valsartan: angiotensin receptor blocker (ARB)
↓ morality ↓ hospitalizations
Studied in combination with valsartan
•
Many side effects similar to ARBs Hypotension Hyperkalemia
•
Angioedema
•
•
ANP/BNP
•
Rare, feared adverse effect
•
Neprilysin also degrades bradykinin (like ACE)
•
Angioedema may occur
•
Cannot be given together with ACE inhibitors
RAAS
Chronic Systolic Heart Failure
Ivabradine
Drug Therapy
•
Selective sinus node inhibitor
•
•
Elevated HR worse prognosis
•
•
•
• •
Slows heart rate without↓ contractility Inhibits SA pacemaker“funnycurrent”(If) Used in patients on max-dose beta blocker with ↑HR Limited evidence of↓ morality and↓hospitalizations
•
ACE inhibitors/ARB Beta Blockers Aldosterone antagonists Neprilysin inhibitors
•
Ivabradine
•
116
ICD
ICD
Implantable Cardiac Defibrillator
Implantable Cardiac Defibrillator
•
Annual risk SCD >20% some studies
•
Improve mortality in appropriate patients
•
Most due to ventricular tachycardia
•
Implantation carries some risk: •
Bleeding, infection
•
Inappropriate shocks
Heart Failure Treatment Pathway
Biventricular Pacemakers Cardiac Resynchronizat ion Therapy (CRT), BiV pacer
Acute Heart Failure Out of Synch
After Pacemaker
Rx
Lasix Nitroglycerine Inotropes
Chronic Heart Failure Diastolic Heart Failure No specific therapy
117
Systolic Heart Failure Drugs ICD Bi-V Pacer
Primitive Heart 22 days
Cardiac Embryology Jason Ryan, MD, MPH
Sinus Venosus
OpenStax Colleg/Wikipedia
Primitive Heart
Sinus Venosus
22 days
Left Horn
Right Horn
Aorta Pulmonary Artery Smooth LV/RV
Smooth Right Atrium
Trabeculated LV/RV
Coronary Sinus
(sinus venarum)
Trabeculated Atria Sinus Venosus Right Atrium Coronary Sinus OpenStax Colleg/Wikipedia
OpenStax Colleg/Wikipedia
Cardinal Veins
Primitive Heart
•
Form SVC/IVC (not from heart tube)
•
Connect to right atrium
•
Superior vena cava
•
Inferior vena cava
•
•
R common cardinal vein and R anterior cardinal vein
Posterior veins
OpenStax Colleg/Wikipedia
118
Ventricular Septum Formation
Cardiac Looping •
•
•
•
Heart tube“loops” at about 4 weeks gestation
Aorticopulmonary Septum
Establishes left-right orientation in chest Requirescilia anddynein Dextrocardia (heart on the right side of body) •
Seen in in Kartagener syndrome
•
Part of primary ciliary dyskinesia
Muscular Ventricular Septum
Ventricular Septum Pathology •
Membranous VSD (most common type)
•
Muscular VSD
AP Twist
Membranous Septum Forms
AP Fuses Muscular Septum
Endocardial Cushions Separate R/L atria R/L ventricle
Endocardial Cushions •
•
Contribute to several cardiac structures •
Atrial septum
•
Ventricular septum
•
AV valves (mitral/tricuspid)
•
Semilunar valves (aortic/pulmonic)
Endocardial cushion defects •
•
Atrioventricular canal defects
•
Atrioventricular septal defects ASD, VSD, Valvular malformations
•
Common in Down syndrome
Endocardial Cushions Separate R/L atria R/L ventricle
Aorticopulmonary septum
Aorticopulmonary septum
Spiral Septum
Spiral Septum
•
Formed from neural crest cells
•
Abnormal formation congenital pathology
•
Migrate to truncal and bulbar ridges
•
Transposition of great vessels
•
Separates aorta and pulmonary arteries
•
Fuses with interventricular septum
•
TetralogyofFallot
•
Persistent truncus arteriosus
•
OpenStax Colleg/Wikipedia
•
•
Wikipedia/Public Domain
119
Failure to spiral
Skewed septum development
Partial/incomplete septum development
Atrial Septum Septum Primum
Atrial Septum Septum Primum
Septum primum fuses Endocardial cushion
Foramen Secundum
Septum secundum grows
RA RA
LA Foramen Secundum
LA
Foramen Primum Future Ventricles
Endocardial Cushion
Future Ventricles
Future Ventricles
PFO
Fetal Circulation
Patent Foramen Ovale
•
Found in ~25% adults Failure of foramen ovale to close after birth
•
Septum primum/secundum fail to fuse
•
Future Ventricles
•
High resistance to flow in lungs
•
Oxygenated blood umbilical veins
•
Travels directly to right atrium
•
•
•
•
RA
About 80% saturated (30mmHg O2)
Bypasses liver via ductus venosus
Bypasses lungs via foramen ovale Some blood gets to RV (SVC) •
Bypasses lungs viaductus arteriosus
•
Left pulmonary artery to aorta
LA
Changes at Birth
Changes at Birth
•
Pulmonaryresistancefalls
•
Placenta haslow resistance to flow
•
More blood to left atrium
•
In utero: helps keep LA pressure low
•
LA pressure > RA pressure Foramen ovale closes (fossa ovalis)
•
Ductus arteriosus closes
•
•
•
•
At birth:increase in peripheral resistance Rise in systemic blood pressure
•
Rise in left ventricular pressure
•
Contributes to rise in LA pressure
•
In utero: ↓ O2, ↑ prostaglandins maintainpatency Birth: ↑ O2, ↓ prostaglandins (loss of placenta)
120
Remaining Opening Foramen Ovale
Shunts RA
LA
RV
LV
PA
Ao
Shunts Jason Ryan, MD, MPH
Shunts •
•
Shunts
Left side pressures >> Right side pressures •
LA ~10mmHg >> RA ~6mmHg
•
LV ~120/10 >> RV ~24/6
•
Ao ~ 120/80 >> PA ~24/12
•
At birth:
•
YEARS later (untreated)
Left to right connection Left to right flow
•
Left to right flow volume overload of right heart
•
Blood flow to lungs unimpaired
VSD (LVRV)
•
Right ventricle hypertrophies
•
ASD (LARA)
•
Right sided pressures rise
PDA (Aorta
•
Left pulm artery)
•
•
Shunt reverses (now R L) Cyanosis occurs (Eisenmenger syndrome)
“Blue kids” not “blue babies”
VSD
VSD
Ventricular Septal Defect
Ventricular Septal Defect
•
•
•
Most common congenital anomaly
•
CommunicationLV/RV Harsh, holosystolic murmur •
Tricuspid area (LLSB)
121
no cyanosis
Pulmonary vessels become stiff/thick
•
•
•
Characterized in many ways •
Size
•
Location
•
Associated defects
VSD
ASD
Ventricular Septal Defect
Atrial Septal Defect
•
•
Small VSD
•
•
Tiny hole resists flow across defect (“restrictive”)
•
Lots of turbulence loud murmur
•
Small shunt (small volume of flow across defect)
•
Large hole (“non-restrictive”)
•
Significant shunting
•
Often closed surgically
•
•
Rarely a mid-diastolic murmur
•
•
Large VSD
Communication between left/right atrium Adds volume to RA/RV Delays closure of pulmonic valve Wide, fixed splitting of S2 Increased flow across PV/TV Systolic ejection murmur
•
•
ASD
ASD
Atrial Septal Defect
Atrial Septal Defect
•
•
•
Oxygenated blood LA RA ↑ O2 saturation in RA, RV, PA “Shuntrun” •
Series of blood samples
•
SVC = 65%
•
IVC = 65%
•
RA = 75%
•
•
•
Secundum typeis most common •
Defects at site of foramen ov ale/ostium secundum
•
Poor growth of secundum septum
•
Or excessive absorption of primum septum
•
Located mid-septum
•
Often isolated defect Foramen Ovale
“Stepup”
RV = 75% PA = 75%
R
Septum secundum Septum primum L
ASD
ASD
Atrial Septal Defect
Atrial Septal Defect •
Septum Secundum Too Short
Foramen Ovale
L
•
Defect at site of ostium pri mum
•
Failure of primum septum to fuse with endocardial cushions
•
Located near AV valves; often occurs with other defects
•
Seen in endocardial cushion defects (Down syndrome) Primitive Atria
Atria
L
L
Primum type
Primitive
R
R
R
Septum Primum Excessive Reabsorption
fusion
Septum secundum Septum primum
entricle
122
Septum primum Endocardial cushion
Ventricle
PDA
PDA
Patent Ductus Arteriosus
Patent Ductus Arteriosus
•
Ductus arteriosus shunts blood in utero
•
Closes close after birth
•
•
Left pulmonary artery aorta
•
Rarely remains patent (3 to 8 per 10,000 births)
•
Associatedwithcongenitalrubella syndrome •
ToRCHeS infection
•
“Functional” closure 18 to 24 hours (smoothmuscle)
•
Mother: Rash, fever, lymphadenopathy
•
“Anatomic” occlusion over next few days/weeks
•
Baby: Deafness, cataracts, cardiac disease
•
Becomes ligamentum arteriosum
•
PDA common
•
Rare in developed countries (vaccination)
•
Consider in infants whose mothers are immigrants
Patency maintained by prostaglandin E2 •
Major source in utero is placenta
PDA
Alprostadil
Patent Ductus Arteriosus •
Continuous, machine-like murmur
•
•
Widened pulse pressure
•
•
•
Loss of volume in arterial tree through PDA
•
Low diastolic pressure
•
Increased pulse pressure
•
Differential cyanosis •
Occurs when shunt reverses R L
•
Blue toes, normal fingers
Indomethacin
Prostaglandin E1
Maintains patency of ductus arteriosus Key effect: delivers blood to lungs Useful when poor RV PA blood flow •
Tetralogy of Fallot
•
Pulmonary atresia
Qp:Qs
•
NSAID
•
Qp = Pulmonary blood flow
•
Inhibits cyclooxygenase
•
Qs = Systemic blood flow
•
•
Decreases prostaglandin formation Can be used to close PDA
•
•
Qp:Qs should be 1:1 In shunts, Qp:Qs may be > 1:1 •
123
1.5:1, 2:1, 3:1, etc.
Eisenmenger’s Syndrome
Fetal Alcohol Syndrome
•
Uncorrected ASD/VSD/PDA
•
•
Right heart chronically overloaded
•
•
•
RV Hypertrophy
•
Pulmonary hypertension
•
•
Shunt reverses right left •
Cyanosis
•
Clubbing
•
Polycythemia (very high Hct)
PFO Patent Foramen Ovale •
•
•
Found in ~25% adults Failure of foramen ovale to close after birth Can lead tostroke in patients with DVT/PE
124
Caused by prenatal exposure to alcohol (teratogen) Characteristic facial features Impaired neurologic function Congenitalheartdefects •
Atrial septal defect
•
Ventricular septal defect
•
Tetralogy of Fallot
Cyanosis
Cyanotic Congenital Heart Disease
•
Centralcyanosis
•
Peripheral cyanosis
•
Cardiac output normal
•
Low blood flow
•
Blood is flowing
•
Severe heart failure
•
Not enough O2
•
Cold extremities
•
Lips
•
Nail beds
•
Conjunctivae
•
Warm extremities
Jason Ryan, MD, MPH
Blue Babies •
Centralcyanosis early in life
•
Blood not going through lungs after birth
Tetralogy of Fallot •
Constellation of four abnormalities •
Ventricular septal defect (VSD)
Tetralogy of Fallot
•
Rightward deviation of aortic valve (“overriding aorta”)
•
Transposition of great vessels
•
Subpulmonary stenosis
•
Truncus arteriosus
•
Right ventricular hypertrophy
•
Tricuspid atresia
•
Total anomalous pulmonary venous return
•
Infundibulum
Infundibulum
Conus Arteriosus
Conus Arteriosus
•
•
•
“Funnel” leading to pulmonic valve Developsfrom bulbuscordis Smooth, muscular structure at RV outflow to PA
•
Septum displaced (moves toward RV) in TOF
•
Causes “overridingaorta”
•
Causes VSD
•
•
125
5-95% of aorta may lie over RV
Usually large (“non-restrictive”)
Infundibulum
Tetralogy of Fallot
Conus Arteriosus
Physiology
•
•
“Infundibular stenosis” •
Subpulmonary stenosis
•
RV outflow tract obstruction
High resistance to flow RV pulmonary artery •
•
•
Mild obstruction: less shunting(“pink”tets)
•
Rarely main cause of obstruction
Flow obstruction RVH
RV outflow pulmonic stenosis
Diverts blood across VSD to left ventricle Severity of flow obstruction determines symptoms Severe obstruction: severe cyanosis
•
Abnormal pulmonary valve •
•
•
Tetralogy of Fallot
Tetralogy of Fallot
Physiology
Murmur
•
Poor blood flow RV lungs
•
Left to right shunts beneficial
•
Systolic ejection murmur •
Crescendo-decrescendo
Bring back to pulmonary artery
•
RV outflow and pulmonic stenosis
•
Diverts blood to lungs
•
Heard best at left sternal border
•
Improves oxygenation
•
Patent ductus arteriosus
•
Aortopulmonary collateral arteries
•
•
•
•
Surgical shunt
Single S2 •
S2 = closure of aortic and pulmonic valves
•
TOF: Diseased pulmonic valve no sound
VSD murmur (holosystolic) not typically heard •
Large VSD no murmur
Tetralogy of Fallot
Tetralogy of Fallot
Other Features
Other Features
•
Squattingimproves symptoms
S1
•
“Tetspells”
•
Increased afterload/TPR (resists flow out of LV)
•
Sudden cyanosis often when agitated
•
Pressure rises in the aorta/left ventricle
•
Severe/complete RVOT obstruction
•
Less blood shunted RV LV via VSD
•
O2, knees to chest, beta blockers (propranolol)
•
More blood to lungs
126
S2
Truncus Arteriosus •
•
•
Transposition of Great Vessels
Common arterial trunk Mixing of blood
•
Failure of neural crest cells to drive formation ofaorticopulmonary septum
•
Aorta is posterior and to right of pulmonary artery
Almost always has VSD
Transpositionof Great Vessels
Transposition of Great Vessels •
Normal heart:
D-transposition (most commontype): •
Aorta forms anteriorand rightward of pulmonary artery
•
Aorta arises from right ventricle
•
Pulmonary artery from left ventricle
•
•
•
•
RV Aorta body RA RV LV Pulmonary artery LA LV Two completely separate circuits NOT compatible with life unless shunt present •
Usually PDA or VSD
No Lungs
L-TGA
Maternal Diabetes
L-Transposition of the Great Arteries •
“Double switch”: Aorta/PA and LA/RA
•
“Congenitally correctedTGA” Venous blood RA LV PA Lungs Lungs PV LA RV Aorta Two circuitsnot separated Wrong connections(RV-Aorta, LV-PA)
•
Eventuallyrightventriclefails
•
•
•
•
No Body
127
•
Infants at increased risk congenital anomalies
•
Common congenital heart defects •
Transposition of great vessels
•
Truncus arteriosus
•
Tricuspid atresia
•
VSD
•
PDA
Tricuspid Atresia •
•
•
Tricuspid Atresia
Abnormal AV valves from endocardial cushions
•
All cases have RL shunt • Always seen with ASD
No tricuspid valve No blood RA RV
• Allows blood flow to LA •
LA
All cases have LR shunt • Allows blood flow to lungs
ASD RA
LV RV
VSD
•
LV RV via VSD
•
Ao PA via PDA
LA ASD RA
LV RV
VSD
TAPVR
TAPVR
Total Anomalous Pulmonary Venous Return
Total Anomalous Pulmonary Venous Return
•
Normal: pulmonary veins drain to left atrium
•
•
TAPVR: pulmonary veins drain to venous system
•
•
Innominate (brachiocephalic) veins SVC
•
Coronary sinus
•
Portal vein
Ebstein’s Anomaly •
•
•
•
RV Lungs Pulm Veins RA RV
•
RA and RV dilate Must have a right to left shunt
•
Mixed (low O2) blood to body
•
ASD (most common)
•
PDA
Ebstein’s Anomaly
Apical displacement of TV small RV
•
Right to left shunting and cyanosis if ASD
“Atrialization”of RV tissue Severe tricuspid regurgitation Can lead to right heart failure
•
Associated withWPW
•
128
High RA pressure
•
Electrical bypass tract often present
•
Delta wave on EKG
Maternal Lithium •
Teratogen
•
Completely equilibrates across the placenta Teratogenic effects primarily involve heart
•
Ebstein’sanomalymost common
•
Pulmonary Atresia •
Failure of pulmonic valve orifice to develop
•
No flow from RV to lungs In utero blood bypasses lungs (normal development) At birth: No blood flow to lungs through PV
•
Often co-exists with VSD for outflow of RV
•
•
•
•
•
•
Alprostadil •
•
•
•
•
Maintains patency of ductus arteriosus Key effect:delivers blood to lungs Useful when poor RV PA blood flow Tetralogy of Fallot
•
Pulmonary atresia
Similar to a severe form of Tetralogy of Fallot
Survival depends on ductus arteriosus Alprostadilgiven to keep DA open
Conotruncal Heart Defects
Prostaglandin E1
•
PVR should fall but does not
•
Trunk = Truncus arteriosus
•
Conus = Conus arteriosus
•
TetralogyofFallot Truncus arteriosus Transposition of the great arteries
•
22q deletion syndromes
•
•
129
Outflow tract anomalies
•
DiGeorge syndrome (Thymic Aplasia)
•
Immunodeficiency, hypocalcemia
•
Conotruncal anomalies
Coarctation of the Aorta BC Artery
Left Carotid
Subclavian
Coarctation of the Aorta Jason Ryan, MD, MPH
Coarctation of the Aorta •
•
•
•
•
•
Coarctation of the Aorta
Congenital disorder Usually involves thoracic aorta distal to subclavian Near insertion of ductus arteriosus “Juxtaductal”aorta Subtypes based on location of ductus arteriosus High resistance to flow in aorta
Ductus Arteriosus Ductus Arteriosus
Pre-ductal Coarctation
Ductus Arteriosus
Post-ductal Coarctation
Coarctation of the Aorta Preductal or Infantile
•
Shunts blood in utero
•
Ductusarteriosussupplies lower extremities
•
Left pulmonary artery aorta
•
Poor development ofcollateralvessels
•
•
•
Patency maintained by↓O2 and ↑ prostaglandins At birth: ↑O2 and ↓ prostaglandins “Functional”closure 18 to 24 hours after birth •
•
•
Smooth muscle constriction
“Anatomic”occlusion over next few days/weeks Becomes ligamentum arteriosum
130
Coarctation of the Aorta
Coarctation of the Aorta
Preductal or Infantile
Preductal or Infantile
•
At birth ductus arteriosus open (not closed yet)
•
Ductus closure symptoms may develop
•
Deoxygenated blood to lower extremity
•
All flow through aorta with severe narrowing
•
Lowerextremitycyanosis may occur
•
•
Abrupt increaseafterload Rise in LVEDP
•
Acute heart failure LV can dilate fail shock
•
All caused byclosure of DA
•
Coarctation of the Aorta
Coarctation of the Aorta
Preductal or Infantile
Postductal or Adult type
•
•
•
Key associations: Turner syndrome (45, XO)
Coarctation of the Aorta •
•
•
↑ Renin release
•
Salt/water retention
•
Vasoconstriction (AII)
•
Weak pulses (“brachio-femoral delay”)
Ductus arteriosus does not supply lower extremities Collaterals develop
•
May go undetected until adulthood
Coarctation of the Aorta
Lower extremities low blood pressure •
•
•
Short stature, webbed neck 5-10% have coarctation of the aorta
Upper extremities and head high blood pressure Secondary hypertension
131
•
Key association:bicuspid aorticvalve
•
Found in up to 60% of coarctation cases
Coarctation of the Aorta
Coarctation of the Aorta
Signs/Symptoms
•
Key association:intracranial aneurysms
•
•
Occur in about 10% of patients with coarctation
•
Only sign may behypertensionin arms
•
Murmur over back betweenscapula Weak femoral pulses
•
Pain with walking (claudication)
Coarctation of the Aorta
Coarctation of the Aorta
Signs/Symptoms
Signs/Symptoms
•
Rib notching
•
•
High pressure above coarctation
•
Intercostals enlarge to carry blood around obstruction
•
Bulge into ribs
•
“Rib notching” seen on chestx-ray
3-sign •
Bulge before and after coarctation
•
“3 sign” on chest x-ray
Coarctation of the Aorta
Coarctation of the Aorta
Physiology
Complications
•
Autoregulationmaintains regional blood flow
•
Upper extremities
•
•
•
•
Heartfailure
•
Aortic rupture/dissection
•
Endocarditis/endarteritis
Normal upper/lower perfusion despite high/low pressures
•
High blood pressure
•
Arterioles constrict to limit flow to normal level
•
Local effect – not mediated by sympathetic/parasympathetic
•
Resistance to flow is high (Q =
•
high flow
P/R)
•
Low blood pressure
•
Arterioles dilate to increase flow to normal level(Q =
•
High-low pressure across narrowing
•
Endothelial injury
•
Lower extremities
•
P / R)
Result is normal (“compensated”)flow
132
Pressure overload of left ventricle
Low pressure distal to narrowing Bacteria may attach more easily
Hypertension •
Bloodpressure>140/90
•
Need more than one measurement
Hypertension Jason Ryan, MD, MPH
Hypertension
Etiology •
•
•
Risk Factors
Most (90%) is primary(“essential”) HTN Cause not clear
Remainder (10%) secondary
•
Family history
•
African-American race
•
High salt intake Alcohol
•
Obesity
•
Physicalinactivity
•
Hypertension
Sodium Intake
Associations
↑ Na
•
Stroke
•
Heart disease
↑ Posm •
↑ ADH
•
•
↑ H2O
↑ ECV
↑ BP
[Na] = 140meq/L
133
•
MI
•
Heart failure
Renal failure Aortic aneurysm Aortic dissection
Hypertension Effects
Hypertension Effects
•
Atherosclerosis– lipid/fibrous plaques in vessels
•
Arteriosclerosis– thickening of artery wall •
•
Response to chronic hypertension
Hyperplastic arteriosclerosis •
Arteries look like “onion skin”
•
Occurs when hypertension is severe (usually DBP>120)
•
“Malignant” hypertension
•
Thickening of small arteries
•
Seen with aging
•
Also common with diabetes
•
Loss of arterioles
•
Arterioles close off and get resorbed
Retinal hemorrhages, exudates, or papilledema
Hypertension Effects •
•
Arteriolar Rarefaction
Hypertension Effects •
Hyaline arteriosclerosis
Pulse pressure may increase •
Example: Normal 120/80; HTN 170/100
•
Stiff arteries ↓compliance
Distensible Vessel 120/80
C=
P=
V/
Hypertension Effects
P
V/C
Stiff Vessel 170/100
134
•
Afterload on heart is increased
•
Left ventricle: concentric hypertrophy •
Large voltage on EKG
•
Displaced apical impulse
•
S4
Hypertensive Urgency
Hypertensive Emergency
•
Severe hypertension without end-organ damage
•
•
No agreed upon BP value
•
•
Usually>180/120
•
Also no definite value
•
BPusually >180/120 Patient longstanding HTN, stops meds Neurologic impairment
•
Renal impairment
•
•
Hypertensive Emergency •
•
•
Retinal hemorrhages, encephalopathy
•
Acute renal failure
•
Hematuria, proteinuria
Cardiac ischemia
Malignant Hypertension • Historicalterm Mostcases hypertension: “benign”
Associated with MAHA Endothelial injury thrombus formation Improved with BP control
•
•
•
Modestly elevated blood pressure
•
Stable over years
“Malignant hypertension” •
Rare form, often fatal
•
Severe elevation of blood pressure (diastolic >120mmHg)
•
•
135
Rapidly progressive over 1 to 2 years Renal failure, retinal hemorrhages, ischemia
Etiology •
Most (90%) is primary (“essential”) HTN
•
Remainder (10%) secondary
•
Secondary Hypertension
Cause not clear
Jason Ryan, MD, MPH
Blood Pressure
Chronic Kidney Disease
Determinants •
Cardiac output •
•
•
Increased with renal salt/water retention
•
Total peripheral resistance
Over 80% of patients have hypertension Multiple causes: •
Sodium retention
•
Key vessels: arterioles
•
Increased renin-angiotensin-aldosterone activity
•
Increased by vasoconstrictors (i .e. catecholamines)
•
Increased sympathetic nervous system activity
•
Increased by sympathetic nervous system
BP = CO X TPR
NSAIDs
Obstructive Sleep Apnea
Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac
•
Sleep-related breathing disorder
•
•
Apnea during sleep
•
•
•
Often associated with hypertension Treatment may reduce BP
136
Nonsteroidalanti-inflammatory drugs
•
Inhibit cyclooxygenase inkidneys Decrease synthesis of prostaglandins
•
PGE-2: Renalvasodilator
NSAIDs
Oral Contraceptive Pills
Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac
OCPs
•
•
•
↓ Na/Water excretion May causehypertension May exacerbateheart failure
Pseudoephedrine
Estrogen and progesterone analogs
•
Cause mild increase in blood pressure
Cyclosporine & Tacrolimus
•
Nasal decongestant Alpha-1 agonist
•
Vasoconstriction ↓ nasal blood flow
•
•
•
•
•
•
Epinephrine
Immunosuppressants Calcineurin inhibitors Renal vasoconstriction salt/water retention Diltiazem: drug of choice •
Impairs metabolism (↑ druglevels)
•
Treats HTN and allows lower dose cyclosporine to be used
Pseudoephedrine
Primary Aldosteronism
Primary Aldosteronism
•
Excessive levels of aldosterone secretion
•
•
Not due to increased activity of RAAS system
•
↑Na reabsorption distal nephron ↑ECV ↑CO Hypertension
•
↑K excretion hypokalemia
•
•
Adrenal adenoma(Conn’s syndrome) Bilateral idiopathic adrenal hyperplasia
137
Aldosterone Escape •
•
•
•
Primary Aldosteronism
Excess aldosterone does not lead to volume overload
•
Usually no pitting edema, rales, increased JVP Na/Fluid retention hypertension Compensatory mechanisms activated •
•
Increased ANP
•
Increased sodium and free water excretion
•
Result:diuresis normal volume status •
Clinical features •
Resistant hypertension
•
Hypokalemia
•
Normal volume status on physical exam
Diagnosis •
Renin-independent aldosterone section
•
Low plasma renin activity
•
High aldosterone levels
Drugs of choice: Spironolactone/Eplerenone •
Liddle’s Syndrome
Aldosterone antagonists
Collecting Duct
•
•
•
•
Genetic disorder
Hypertension
•
Hypokalemia
Na+
Na+
Increased activity of ENaC Similar clinical syndrome to hyperaldosteronism •
Interstitium/Blood
Principal Cell
Lumen (Urine)
Aldosterone
ATP K+
K+ H2O
Aldosterone levelslow Intercalated Cell
Aldosterone H+
Cushing’s Syndrome
Pheochromocytoma •
Catecholamine-secreting tumor •
•
•
•
•
Epinephrine, norepinephrine, dopamine
Usually arises from adrenal gland Triad: Palpitations, headache, episodic sweating •
•
Excesscortisol
•
Often from steroid administration
•
Other causes
PHEochromocytoma
Most patient have hypertension •
Diagnosis: Catecholamines breakdown products •
Metanephrines
•
Vanillylmandelic acid (VMA)
Cl-
•
Cushing’s Disease (pituitary oversecretesACTH)
•
Tumors (i.e. small cell lung cancer secretes ACTH)
•
Adrenal tumor secretes cortisol
Cortisol hypertension •
138
Increased vascular sensitivity to adrenergic agonists
Aldosterone
Renal Artery Stenosis •
•
•
Renal Artery Stenosis
Vascular disease of renal arteries
•
Decreased blood flow to kidneys Key exam finding:renal bruit
Increased renin, salt-water retention HTN
•
Often unilateral stenosis Normal kidney compensates
•
Results: No signs of volume overload
•
Kidney
Renal Artery Stenosis
Renal Artery Stenosis
Angiotensin II
↑RAAS ↑ BP Euvolemia ↑Renin ↑ Na
•
Vascular disease obstruction to flow
•
Common amongwomen
•
•
•
•
•
ACE inhibitors can precipitate renal failure
•
AII efferent arteriole vasoconstriction
•
Maintains GFR
Normal
Fibromuscular Dysplasia
•
Normal GFR depends onangiotensin II
↓Renin ↓Na
Stenotic
•
•
Coarctation of the Aorta BC Artery
Often occurs in 40s-50s Non-atherosclerotic, non-inflammatory Often involvesmedial layerfibroplasia Stenosis and aneurysms of vessels(“stringof beads”) Most common in renal and carotid arteries Can lead to renal artery stenosis
139
Left Carotid
Subclavian
ADPKD Autosomal dominant polycystic kidney disease •
Genetic disorder
•
Mutations of PKD1 or PKD2 Presents in adulthood with HTN and renal cysts
•
Increased RAAS activity
•
140
BP = CO X TPR
Antihypertensives
Heart Rate Contractility
Circulating Volume
Vascular Tone
Jason Ryan, MD, MPH
Beta Blockers
Beta Receptors •
•
β1-selective antagonists
β1 receptors in heart, kidneys •
Increase heart rate and contractility
•
Stimulate renin release
•
Blockade ↓ CO, ↓ ECV ↓ BP
Dilate blood vessels (muscle, li ver)
•
Bronchodilate
•
•
•
•
•
•
Metoprolol: Systolic heart failure
Blockade ↓ CO, ↓ ECV ↓ B P
•
Blocks sympathetic stimulation of heart
•
Reduces mortality
Beta Blockers
2 (nonselective) antagonists
β1β2α1
Propranolol,Timolol,Nadolol Can be used for hypertension Nadolol, Propranolol: Used in portal hypertension •
Beta 1 blockade: ↓ CO, ↓ ECV ↓ BP
•
Beta 2 blockade: ↓ portal blood flow
•
Carvedilol,Labetalol
•
Labetalol: Hypertensive Emergency
•
Carvedilol:Systolicheart failure
•
Timolol: Used inglaucoma •
Used for hypertension
Blockade does not lead to lower blood pressure
Beta Blockers 1
Atenolol, Metoprolol, Esmolol
•
•
β2 receptors •
•
Beta 1 and Beta 2 aqueous humor production
141
Rapid reduction in blood pressure
•
Blocks sympathetic stimulation of heart
•
Reduces mortality
Beta Blockers
Beta Blockers
Partial Agonists
Side effects
•
Pindolol: β1β2 (nonselective) Acebutolol: β1-selective
•
“Intrinsic sympathomimeticactivity”
•
•
Fatigue, erectile dysfunction, depression
•
Hyperlipidemia
•
More common with older beta blockers (propranolol)
•
Beta agonist when sympathetic activity is low
•
Mild increase i n triglycerides
•
Beta blocker when sympathetic activity is high
•
Mild decrease in HDL
•
Effect varies with different beta blockers
•
Can causeanginathrough beta 1 activation
•
Special pharmacologic properties
Beta Blockers
Beta Blockers
Side effects
Side effects
•
Caution indiabetes
•
Blockade of epinephrine effects •
•
•
•
•
•
Epinephrine raises glucose levels Blockade
Caution inasthma/COPD
•
hypoglycemia •
Blockade of hypoglycemia symptoms
2 receptors:bronchodilators 2 blockade may cause aflare β1 blockers (“cardioselective”) often used
Decompensatedheart failure
•
↓ glucose sweating/tachycardia
•
β1 blockers lower cardiac ou tput worsening of symptoms
•
Symptoms “masked” by beta blockers
•
Commonly used in compensated heart failure
•
Mortality benefit
Beta Blockers
Beta Blockers
Overdose
Overdose
•
Depression of myocardial contractility shock
•
Bradycardia/AV block
•
Treatment: Glucagon •
Activates adenyl cyclase at different site from beta receptors
•
↑ cAMP ↑ intracellular Ca
•
Increased contraction and heart rate
Glucagon
β1 AMP
142
AC cAMP
1 Blockers
Alpha 2 Receptors
Tamsulosin, Alfuzosin, Doxazosin, Terazosin •
•
•
•
•
α1receptors in periphery: vasoconstrict Blockade vasodilation ↓ TPR ↓ BP Used inbenign prostatic hyperplasia •
Relax smooth muscle of bladder/prostate
•
Increase urine flow
2 receptors in CNS Presynaptic receptor Feedback to nerve when NE released Activation leads to ↓NE release
Common side effect:Postural hypotension Tamsulosin: “Uroselective” •
Neuron
α2
Less hypotension effect
Norepinephrine
NE
Vascular Smooth Muscle
Clonidine
Methyldopa
2 agonist
2 agonist
•
Old, rarely used hypertension drug
•
•
Key side effect:Rebound hypertension
•
Drug of choice in pregnancy Also causes sedation
•
Key side effect (rare):Hemolytic anemia
•
•
Abrupt cessation of drug (usually at high dose)
•
Severe hypertension (SBP>200; DBP>120)
•
Symptoms of high BP and sympathetic over-activity
•
Nervousness, sweating, headache, chest pain
Also causessedation
RBC
Calcium Channel Blockers •
•
Calcium Channel Blockers
Three major classes of calcium antagonists •
dihydropyridines (nifedipine)
•
phenylalkylamines (verapamil)
•
benzothiazepines (diltiazem)
•
Vascular smooth muscle effects
•
Heart rate/contractility effects
•
•
Vasodilatorsandnegative chronotropes/inotropes
143
Nifedipine>Diltiazem>Verapamil
Verapamil>Diltiazem>Nifedipine
Calcium Channel Blockers
Calcium Channel Blockers •
Dihydropyridines (nifedipine) vasodilators
•
Non-dihydropyridines (Verapamil, diltiazem)
•
Dihydropyridines (nifedipine)
Main effect: ↓TPR
•
Similar to
•
Main effects: ↓HR; ↓ contractility
•
Used for hypertension
•
Flushing, headache, hypotension
•
Key side effect: edema
•
1blockers
Peripheral vasodilation
•
Increased capillaryhydrostatic pressure
•
Pre-capillary arteriolar vasodilation
Calcium ChannelBlockers
Calcium Channel Blockers
Dihydropyridines (nifedipine)
Verapamil, diltiazem
Pre- Capillary Arteriole
100
Capillary
50
Systemic
•
Used for hypertension
•
Also used in heart disease
•
Potential side effect: Negative inotropes
50
•
Arrhythmias (atrial fibrillation)
•
Stable angina (lower oxygen demand)
•
Can precipitate heart failure
Pre-Capillary Arteriole
80
Capillary
60
60
Systemic
Calcium Channel Blockers
Calcium Channel Blockers
Other Side Effects
Other Side Effects
•
Constipation •
•
Most commonly withverapamil
144
Hyperprolactinemia •
Seen with verapamil
•
Blocks calcium channels CNS ↓ dopamine release
•
Causes hypogonadism
•
Men: ↓ libido, impotence
•
Pre-menopausal women: irregular menses,galactorrhea
Calcium Channel Blockers
Angiotensin II
Other Side Effects •
Angiotensinogen
Gingival hyperplasia
Sympathetic System
+ Renin
•
Seen in all types CCB
•
Also with phenytoin, cyclosporine
AI
Renal Na/Cl reabsorption + ACE
A2 Arteriolar vasoconstriction
Adrenal aldosterone secretion
Net Result
Pituitary ADH secretion
↑Salt/Water Retention ↑Preload ↑Afterload ↑BP
AII Drugs
Angiotensin II Inhibition Angiotensinogen
ARBs
Sympathetic System
•
ACE Inhibitors
•
Angiotensin Receptor Blockers (ARBs)
+ Renin
•
Renal Na/Cl reabsorption
Aliskiren
AI
+ ACE
A2
•
Arteriolar vasoconstriction
•
X
•
Adrenal aldosterone secretion
Candesartan, Ir besartan, Valsartan
Side effects •
ACE Inhibitors
Captopril, Enalapril, Lisinopril, Ramipril
Hyperkalemia (↓aldosterone) Renal failure (↓GFR)
Pituitary ADH secretion
Net Result ↑Salt/Water Retention ↑Preload ↑Afterload ↑BP
ACE Inhibitors
Bradykinin Bradykinin
Unique Side Effects Cough asodilation
AI
•
Due to increasedbradykinin
•
Dry Cough
•
Angioedema
•
X
Inactive Metabolites
ACE Inhibitors
X
A2
145
Occurs in ~10% of patients
•
Swelling of face, tongue
•
Can be life-threatening
Aliskiren
Diuretics
•
Direct renin inhibitor
•
Reduces angiotensin I levels (unique effect)
•
Loopdiuretics
•
Thiazide diuretics
•
Potassium sparing diuretics
•
•
Angiotensinogen
•
Furosemide, bumetanide, torsemide, ethacrynic acid
Hydrochlorothiazide; chlorthalidone; metolazone
Spironolactone, Eplerenone, Triamterene, Amiloride
+ Renin AI
+ ACE
A2
Hydralazine •
•
•
•
•
Drug-induced Lupus
Direct arteriolar vasodilator
•
Rarely used for hypertension Combined with nitrates for heart failure Safe in pregnancy •
Causes drug-induced lupus
•
Syndrome similar to lupus •
Often rash, arthritis, low blood cell counts
•
Milder than SLE
•
Usually no associated renal failure/CNS disease
Key finding:anti-histone antibodies Three drugs •
• •
Hypertensive Emergency •
Unique drugs used for therapy
•
Lowering BP too fast can cause ischemia
•
•
Hydralazine Procainamide Isoniazid
Hypertensive Emergency •
Intravenous, rapid acting Autoregulation of vascular beds vasoconstriction
•
146
Nitroprusside •
Short acting drug
•
↑ intracellular cGMP
•
↑ nitric oxide release
•
Venous and arteriolar vasodilation
•
↓ preload (VR); ↓ afterload
Cyanide toxicitywith prolonged use •
Multiple cyanide groups per molecule
•
Inhibits electron transport
•
Toxic levels with prolonged infusions
Sodium Nitroprusside
Hypertensive Emergency •
Hypertensive Emergency
Fenoldopam •
D1 agonist
•
Arteriolar vasodilation
•
Increased urinary sodium/water excretion
•
Maintains renal perfusion while vasodilating
•
Labetalol
•
Esmolol
•
Nicardipine, Clevidipine
•
•
•
1 and
1Blocker
Rapid acting intravenous
1blocker
Intravenous dihydropyridine calcium channel blocker
Orthostatic Hypotension
Orthostatic Hypotension
Postural Hypotension; Orthostasis
Postural Hypotension; Orthostasis
•
•
•
↓blood pressure due to gravity with standing Compensation fromsympathetic nervous system
Alpha-1blockers
•
ACE-inhibitors
•
Increased VR, CO, HR, TPR
•
Especially in patients on diuretics
•
Impaired with low volume, low TPR, blunted ANS
•
Volume depletion ↑RAAS
•
“First dose hypotension”
Severe ↓BP (>20mmHg) = orthostatic hypotension •
•
•
Dizziness, syncope
Common etiologies: •
•
Hypovolemia Hypertensive medications
Reflex Tachycardia •
Vasodilation ↓BP ↑SNS
•
Reflex response:↑ HR
•
Can be caused by vasodilators •
•
Hydralazine
•
Alpha-1 blockers
•
Dihydropyridine calcium channel blockers
•
Choosing Drugs
•
Nitroglycerine
•
May exacerbate chronic stable angina
•
Drugs may be co-administered withβ blocker
147
Diabetes •
ACE inhibitors: Protective of kidneys
•
Beta blockers can lower glucose and mask hypoglycemia
•
HCTZ can increase glucose
Systolic Heart Failure •
ACEi, beta blockers, aldosterone blockers: mortality benefit
•
Calcium channel blockers ↓ contractility
Choosing Drugs •
•
Hypertension in Pregnancy •
Methyldopa
•
Beta blockers, nifedipine, hydralazine
•
Avoid: ACE inhibitors, ARBs, direct renin inhibitors
•
Associated with congenital malformations
Significant renal failure or↑K •
Avoid: ACE-inhibitors, ARBs (↓AII, ↓aldsoterone)
•
Avoid: Potassium sparing diuretics (↑ K)
• •
Avoid: Other diuretics (↓ECV ↓GFR) Calcium blockers, beta blockers usually ok
148
Heart Valves
Pulmonic
Valve Disease
Aortic
Tricuspid Mitral
Jason Ryan, MD, MPH
Valve Disease •
•
Valve Lesions - Systole
Stenosis •
Stiffening/thickening of valve leaflets
•
Obstruction to forward blood flow
•
•
Malcoaptation of valve leaflets
•
Leakage of blood flow backwards across valve
•
•
Tricuspid regurgitation
•
Regurgitation
Valve Disorders
Valve Lesions - Diastole
Treatments
•
Occur when heart relaxes/fills
•
•
Aortic regurgitation
•
•
Mitral stenosis Pulmonic regurgitation
•
Tricuspid stenosis
•
Occur when heartcontracts/squeezes Aortic stenosis Mitral regurgitation Pulmonic stenosis
•
Only severevalvularlesions treated
•
Mostlysurgicaldiseases Surgical repair
•
Valve replacement
•
Valvuloplasty (stenotic lesions)
•
•
•
149
Often done for mitral valve prolapse mitral regurgitation
Bioprosthetic (pig or cow) Mechanical (requires life-long anticoagulation)
Stenotic Valve Disorders •
•
•
•
Rheumatic Fever
Stiffvalve
•
“Gradient” acrossvalve Highpressureupstream Lower pressure downstream
Rheumatic Fever •
Joints: Polyarthritis (>5 joints)
•
♥:
•
Nodules (subcutaneous)
•
Erythema marginatum (rash on trunk)
•
Sydenham chorea (jerking movement disorder)
Common inchildren Autoimmune: type II hypersensitivity reaction
•
Antibodies to bacterialM proteinscross-react
Rheumatic Heart Disease
Jones criteria •
•
Carditis (valvulitis, myocarditis, pericarditis)
•
•
Common indeveloping countries
•
•
•
Secrete serotonin
•
•
Serotonin inactivated by lungs
•
Left sided lesions rare
Limited access to medical care for pharyngitis
•
Often seen in immigrants to US
Pathophysiology
Caused by carcinoid tumors of intestines Fibrousdepositstricuspid/pulmonic valves Leads to stenosis and regurgitation
•
Aortic Stenosis
•
•
Damage to heart valves by rheumatic fever Mitral valvemost commonly involved Often presents years after acute rheumatic fever Many patients do not recall acute symptoms
•
Carcinoid Heart Disease
•
Occursweeksafter streptococcal pharyngitis
•
•
•
150
Stiff aortic valve Systolicproblem Increased afterload
Aortic Stenosis
Aortic Stenosis
Hemodynamics
Clinical features
•
•
LV pressure systolic >> aortic pressure •
LVSP = 160mmHg (normal = 120)
•
SBP = 120mmHg (normal = 120)
•
Gradient = 40mmHg
•
•
•
•
↑ LVEDPdue to ↑ afterload
Normal
Supravalvular Aortic Stenosis
Causes
•
•
Senile aortic stenosis •
“Wear and tear”
•
Collagen breakdown
•
Calcium deposition
Syncope: failure to↑CO due to ↑ afterload Angina: ↑ LVEDP ↓ coronary blood flow Left heart failure: ↑ LVEDP
Aortic Stenosis
Aortic Stenosis •
Systolic crescendo-decrescendo murmur
•
•
•
Narrowing of ascending aorta above aortic valve Seen inWilliams syndrome Genetic deletion syndrome
Bicuspid aortic valve Rarely rheumatic heart disease
Mitral Stenosis
Mitral Stenosis
Pathophysiology
Clinical features
•
•
•
•
Stiff mitral valve Diastolic problem LA pressure >> LV diastolic pressure •
Left atrial pressure 20mmHg (normal = 10)
•
LVEDP 5mmHg (normal =10)
•
Gradient = 15mmHg
•
Caused by rheumatic fever
•
Most common symptom: dyspnea
•
Murmur: diastolic rumble with opening snap
•
Decreased preload
151
↑ LA pressure
pulmonary congestion
Tricuspid Stenosis •
Very rare valve disorder
•
Diastolic murmur at left lower sternal border Caused by rheumatic fever (with mitral disease)
•
Carcinoid heart disease
•
Pulmonic Stenosis
•
•
Congenitaldefect in children
•
Carcinoid heart disease
•
Tricuspid regurgitation more common
Aortic Regurgitation
Regurgitant Lesions
Pathophysiology
•
Acute and chronic forms
•
•
Acute regurgitation (often from endocarditis)
•
•
•
May cause shock
•
Activation of sympathetic nervous system
•
Increased contractility
•
Increased afterload
•
No shock Leads to chronic heart failure
•
Sympathetic activation only if severe heart failure
Blood leaks across aortic valve
•
Diastolic problem Increased preload, stroke volume Increased afterload
•
Blowing diastolic murmur
•
•
Chronic regurgitation •
Fused commissures with thickened leaflets
More stroke volume
aorta ↓ compliance (stiffening)
Aortic Regurgitation
Aortic Regurgitation
Causes
Clinical features
•
•
•
•
Dilated aortic root leaflets pull apart
•
Leaking blood back into LV causeslow diastolic BP
•
Often from HTN or other aortic aneurysm
•
120/80 (normal) 120/40
•
Rarely from tertiary syphilis (aortitis)
•
Low diastolic pressure
Bicuspid aortic valve •
Turner syndrome
•
Coarctation of the aorta
Wide pulse pressure
•
Wide pulse pressure symptoms
•
•
Endocarditis Rheumatic heart disease •
•
Almost always with mitral disease
152
High cardiac output with low diastolic pressure
•
“Water hammer” pulses Head bobbing
•
Many, many others (mostly historical)
Mitral Regurgitation
Mitral Regurgitation
Pathophysiology
Causes
•
•
Blood leaks across mitral valve Increased LA volume Starling mechanism
•
•
•
Reduced afterload
•
•
Primary MR caused bymitral valve prolapse •
Increased left ventricular filling from LA Increased preload,stroke volume
•
•
Also called degenerative or myxomatous
Billowing of mitral valve leaflets above annulus Common cause ofmitral regurgitation Causes asystolic click •
Don’t confuse with opening snap of mitralstenosis
Mitral Regurgitation
Mitral Regurgitation
Secondary causes
Causes
•
Ischemia damage to papillary muscle
•
•
Left ventricular dilation
•
•
•
Dilated cardiomyopathy
•
Leaflets pulled apart
•
“Functional”MR
•
Hypertrophic cardiomyopathy
Endocarditis Rheumatic heart disease Congenital •
Cleft mitral valve
•
Endocardial cushion defect
•
Down syndrome
Mitral Regurgitation
Afterload Reduction
Clinical Features
Aortic and Mitral Regurgitation
•
Holosystolic murmur at apex
•
For severe, acute regurgitation this helps For chronic disease, clinical trials with mixed results In general, these are surgical diseases
•
Common test scenario“Best medicaloption?”
•
S1
S2
153
In theory,↓ afterload can improve forward flow
•
•
Tricuspid Regurgitation •
•
•
Pulmonic Regurgitation
Small amount of TR normal(“physiologicTR”) Holosystolic murmur at left sternal border Pathologic causes •
Functional TR from RV enlargement
•
Endocarditis - classically IV drug users
•
Carcinoid
•
Ebstein’s anomaly
•
Most common cause: repairedTetralogy of Fallot
•
Endocarditis (rare)
•
Rheumatic heart disease (rare)
•
Repair of RVOT obstruction damages valve
Tetralogy of Fallot
154
Shock •
•
•
Shock
•
Life-threatening fall in blood pressure Poor tissue perfusion Lowcardiac output •
Loss of contractility
•
Low intravascular volume
Peripheral validation
Jason Ryan, MD, MPH
BP = CO X TPR
Types of Shock •
Cardiogenic •
•
Types of Shock
Cardiac disorder
fall in cardiac output
•
Different treatmentsfor different types of shock
•
Often can determine type fromhistory
•
Shock of unclear etiology: Swan-Ganz catheter
Hypovolemic •
Fall in intravascular volume
•
Hemorrhage
•
Distributive
•
Obstructive
•
Peripheral vasodilation
•
Septic, anaphylactic
fall in cardiac output
Swan-Ganz Catheter
•
Myocardial infarction
•
Massive bleeding hypovolemic shock
cardiogenic shock
Swan-Ganz Data
Pulmonary artery catheter
•
RA Pressure (Normal ~ 5mmHg)
•
RV Pressure (20/5)
•
PA Pressure (20/10) PCWP Pressure (10)
•
Mixed venous O2 sat
•
Pulmonary Capillary Wedge Pressure PCWP “Wedge Pressure” Equal to LA pressure
•
155
Oxygen concentration after all veins mix
Fick Equation
Flow Equation
Oxygen Consumed = O2 Out Lungs– O2 In Lungs
•
Used to determinesystemic vascular resistance
= CO (Art O2– Ven O2)
P = CO * SVR MAP – RAP = CO * SVR
Cardiac Output= O2 Consumption (Art O2 – Ven O2)
O2 Consumption
SVR = MAP– RAP CO
body size
Arterial O2 Content = O2 sat on finger probe Venous O2 Content = O2 from Swan-Ganz
Swan-Ganz Catheter gives SVR
Swan-Ganz catheter gives cardiac output
Swan-Ganz Data •
•
Hemodynamic of Shock
Direct •
RA Pressure (Normal ~ 5mmHg)
•
RV Pr essure (20/5)
•
PA Pressure (20/10)
•
PCWP Pressure (10)
•
Mixed venous O2 sat
•
•
•
Calculated •
•
Four major classes of shock All have different hemodynamics from Swan Swan can be used to determine etiology of shock •
Cardiogenic
•
Hypovolemic
•
Distributive
•
Obstructive
Cardiac output Systemic Vascular Resistance
Cardiogenic Shock
Hypovolemic Shock
•
Hallmark is low cardiac output
•
Poor fluid intake
•
High cardiac pressures
•
High fever, insensible losses
•
High SVR (sympathetic response) Classic cause: large myocardial infarction
•
Also seen in advanced heart failure (depressed LVEF)
•
•
Hemorrhage Lowcardiac output
•
Low cardiac pressures
•
High SVR (sympathetic response)
•
156
Type of Shock
Distributive Shock •
Hallmark is low SVR
•
Diffuse vasodilation and/or endothelial dysfunction Sepsis (most common) Anaphylaxis Neurogenic
•
Cardiac output classically high (variable)
•
Cardiac pressures variable
•
•
•
Physical Exam
Major Shock Types SVR
•
Cold skin high SVR and low CO
•
Warm skin low SVR and high CO
Low
High
Distributive
Cardiogenic
•
•
Low
•
Obstruction to blood flow from heart
•
Low cardiac output despite normal contractility
•
Distributive
Jugular venous pressure high RA pressure Pulmonary rales high LA pressure
Treatment of Shock
•
•
High SVR
•
Cardiogenic: inotropes
•
Hypovolemic: volume
•
Distributive: vasopressors
•
Tamponade Tension pneumothorax Massive pulmonary embolism Low cardiac output
•
Hypovolemic
Hypovolemic
Obstructive Shock
•
Cardiogenic
•
•
Pressures High
•
•
•
•
Blood transfusions, IV fluids Phenylephrine, epinephrine, norepinephrine
Obstructive: resolve obstruction •
157
Milrinone, Dobutamine
Treat tamponade, embolism, tension pneumothorax
Swan in Valve Disease
Swan in Valve Disease
Mitral Stenosis
Aortic Stenosis
Swan in Valve Disease
Left AtrialPressure
a
v c
x
Aortic Regurgitation
Giant V waves •
•
Seen inmitral regurgitationin PCPW tracing Similar to giant V waves in tricuspid regurgitation •
Seen in venous pressure tracing
a
v c
158
y
Pericardium •
•
•
Pericardial Disease
•
•
•
Jason Ryan MD, MPH
Pericardial Diseases •
•
•
Three layers Fibrous pericardium Serous pericardium •
Parietal layer
•
Visceral layer
Pericardial cavity between serous layers Innervatedbyphrenic nerve Pericarditis
referred pain to the shoulder
Pericarditis
Pericarditis
•
Tamponade Constrictive pericarditis
•
•
•
Most common pericardial disorder Inflammation of the pericardium Immune-mediated (details not known) May recur after treatment
Pericarditis
Pericarditis
Clinical Features
EKG Findings
•
•
•
•
Chest pain •
Sharp
•
Worse with deep breath (pleuritic)
•
Worse lying flat (supine)
•
Better sitting up/leaning forward
Fever Leukocytosis Elevated ESR
159
Pericarditis
Pericarditis
EKG Findings
EKG •
Technically, 4 stages of EKG changes
•
Stage 1: diffuse ST elevations, PR depressions Stage 2 (~1 week later): Normal Stage 3: T wave inversions
•
Stage 4: Normal
•
ST Elevation
•
PR Depression
Pericarditis Diffuse ST elevation PR depression
Pericarditis
Pericarditis
Physical Exam
Etiology
•
Pericardial friction rub Scratchysound
•
Systole and diastole
•
•
Usually idiopathic
•
Viral • Classic cause is Coxsackievirus • Often follows viral upper respiratory infection (URI)
•
Bacterial • Spread of pneumonia • Complication of surgery • Tuberculosis
•
Fungal
Pericarditis
Pericarditis
Etiology
Treatment
•
Uremic (renal failure)
•
•
Post-myocardial infarction
•
•
•
Fibrinous (days after MI)
•
Dressler’s syndrome (weeks after MI)
•
Autoimmune disease (RA, Lupus)
160
NSAIDs Steroids Colchicine •
Inhibits WBCs via complex mechanism
•
Useful in gout and familial Mediterranean fever
•
Added to NSAIDs to lower risk of recurrence
Myopericarditis
Tamponade
•
Myocarditis = inflammation of myocardium
•
•
Similar presentation to ischemia
•
•
Chest pain
•
EKG changes
•
Increased CK-MB, Troponin
•
•
Accumulation of pericardial fluid High pericardial pressure Filling restriction of cardiac chambers Amount of fluid variable •
Acute accumulation (bleeding): small amount of fluid
•
Chronic accumulation (cancer): large amount of fluid
Tamponade
Tamponade
Causes
Clinical features
•
•
•
•
•
Cancer metastases to pericardium Uremia Pericarditis Trauma Treatment: Drainage of effusion
Tamponade
•
•
•
Beck’s Triad •
Distant heart sounds
•
Elevated JVP
•
Hypotension
Distant heart sounds
•
Dyspnea
•
Elevatedjugularvenous pressure
•
High left atrial pressure
•
Pulmonary edema
Pulsus Paradoxus
Clinical features •
•
•
Classic finding in tamponade
•
Systolic BP always falls slightly on inspiration
•
•
Seen in rapidly-developing traumatic effusions Severe impairment LV function low cardiac output Slower effusions: Pericardium stretches/dilates
161
Exaggerated fall (>10mmHg) = pulsus paradoxus Severe fall = pulse disappears
Pulsus Paradoxus
Pulsus Paradoxus
Inspiration
•
•
↑ VR
•
•
↑ RV Size Septum bulges
•
Also seen in asthma and COPD Inspiration: ↓ left sided flow Caused by pulmonary pressure fluctuation Exaggerated in lung disease •
Normal lungs: 0 to -5mmHg
•
Lung disease: Change up to 40mmHg
Large drop in left sided flow pulsus paradoxus
↓ LV Size ↓ CO
Pulsus Paradoxus
Tamponade
Measurement Technique
EKG
•
•
Raise cuff pressure until no sounds heard NORMAL respirations
•
Slowly lower cuff pressure First point (P1): intermittent sounds
•
Second point (P2): constant sounds
•
Pulsus = P1 – P2
•
v
c
v Blunted y descent Poor RV filling in diastole
Prominent x descent ↓ RA pressure during RV contraction a in systole
Low voltage – EKG sees less electricity due to effusion
Equalization of Pressures
Prominent x descent, Blunteddescent y
a
Sinus tachycardia
•
lectrical Alternans
Tamponade a
•
v
162
•
Occurs when cardiac chambers cannot relax
•
Pressure in RA, RV, LA, LV falls but then abruptly stops
•
Seen in tamponade and pericardial constriction
Constrictive Pericarditis
Constrictive Pericarditis •
•
•
Clinical Features
Fibrous, calcified scar in pericardium Loss of elasticity: stiff, thickened, sticky Can result from many pericardial disease processes
•
Markedly elevated jugular venous pressure
•
Lower extremity edema
•
Radiation to chest
•
Liver congestion
Heart surgery
•
May lead to cirrhosis (“nutmegliver”)
Kussmaul’sSign
Other Features
•
•
Prominentright heart failure
Pericarditis
Constrictive Pericarditis •
Dyspnea
•
•
•
•
•
Pulsus paradoxus uncommon (~20%)
ac
High RA, RVEDP, PCPW pressures Equalization of pressures Pericardial knock
•
•
S1
•
Ventricle cannot accept ↑VR
•
Constrictive pericarditis
•
Pericardial Knock
•
•
Pulsus paradoxus: classic sign of tamponade
•
Kussmaul’s sign: classic sign of constriction
Restrictive cardiomyopathy RV myocardial infarction
Not seen in tamponade
ConstrictivePericarditis
Pulsus and Kussmaul’s •
Inspiration ↑ VR slight fall in mean JVP Kussmaul’ssign = ↑ JVP with inspiration
•
S2
v
Rapid/prominent y descent v
Pulsus in tamPonade
•
Also seen in restrictive heart disease
•
Kussmaul’s inKonstriction/Restriction
a
c
v
Rapid y descent Rapid filling of RV Abrupt stop in filling
Myocardium adherent to pericardium In diastole: rapid relaxation and suction of RA volume
163
Dip and Plateau
Venous Pressure Findings
Square Root Sign Right Ventricular Pressure Rapid filling, abrupt stop
Normal
Constriction and Restriction •
Constrictive pericarditis/Restrictive heart disease
•
Many common features Prominent right heart failure Kussmaul’s sign
•
Rapid y descent
•
Dip and plateau
•
•
164
Dip & Plateau Constrictive Pericarditis
Aortic Dissection •
Aortic Dissection
Adventicia
Three layers to aorta •
Intima
•
Media
•
Adventicia
•
Dissection tear in intima
•
Blood “dissects” intima and media
Jason Ryan, MD, MPH
ComCarotid
Propagation •
Blood enters dissection plane Spreadsproximal,distal
•
Can disrupt flow to v essels
•
Brachiocephalic
Types
Subclavian
Diaphragm
•
Type A
•
Type B
•
Involves ascending aorta and/or arch
•
Treated surgically
•
Descending aorta
•
Can be treated medically
•
Control hypertension/symptoms
•
Surgical mortality high
Illiacs
Symptoms •
Other symptoms
“Tearing” chest pain radiating to back
•
•
165
Propagation to aortic root •
Aortic regurgitation
•
Pericardial effusion/tamponade
•
Myocardial ischemia (obstruction RCA srcin)
Propagation to aortic arch •
Stroke (carotids)
•
Horner’s syndrome
•
Vocal cord paralysis
Media Intima
Recurrent Laryngeal Nerve •
•
•
Other findings
Branch of vagus nerve Supplies larynx and voice box Compression: •
Aortic dissection
•
Massive left atrial enlargement
Suggested by history, exam, chest x-ray
•
Definitive diagnosis
Widened mediastinumon chest x-ray
General Principles •
Medial layerof aorta •
Tensile strength and elasticity
CT scan
•
Key proteins: collagen and elastin
•
MRI
•
Weakness of medial layer dissection/aneurysms
•
Transesophageal echocardiogram (TEE)
•
Common aneurysm feature: medial damage/destruction
•
•
Blood pressure differentialbetween arms
•
Risk Factors
Diagnosis •
•
•
D-dimer •
Sensitive but not specific
•
Normal value makes aortic dissection unlikely
Vasa vasorum •
•
•
Network of small vessels primarily in adventitial layer Supplies blood to medial layer in thick vessels (i.e. aorta) Thickening (HTN) weakening of medial layer
Risk Factors
Risk Factors
General Principles
General Principles
•
•
Requirestensionon wall •
Common in proximal aorta (near aortic valve)
•
High tension from blood moving out of heart
•
Worsened by hypertension
•
•
Requiresweakness of media layer •
Also caused by hypertension
•
Seen in collagen disorders (genetic)
Cystic medial necrosis •
•
•
166
Development of cysts and necrosis in medial layer
Occurs to mild degree with aging More rapid with: •
Bicuspid aortic valve
•
Marfan syndrome
Common inascendingthoracic aneurysms
Risk Factors
Aortic Aneurysms
Aortic Dissection
• Aortic damage •
HTN - #1 risk factor
•
Atherosclerosis
•
Thoracic aneurysm
•
•
Marfan Syndrome
•
Ehlers-Danlos
•
•
Abdominal (AAAs)
•
• Abnormal collagen
Dilation/bulge of aorta More than 1.5x normal Involves all three 3 layers Thoracic (TAAs)
•
• Others •
Bicuspid aortic valve
•
Turner Syndrome (bicuspid, coarctation)
•
Tertiary syphilis: Aortitis
Thoracic Aortic Aneurysms
Thoracic Aortic Aneurysms •
•
Usually occur in proximal/ascending aorta Usually seen inassociation with another disorder
•
Family history of aneurysm important
•
May be associated withatherosclerosis
•
Symptoms
Important risk factor for dissection
•
•
•
•
•
More common in descending aorta
•
Occur in association with atherosclerosis risk factors
•
HTN, smoking, high cholesterol
Abdominal Aortic Aneurysms Risk Factors
•
More common than thoracic aneurysms
•
•
Classically taught as a disease ofatherosclerosis
•
•
Infrarenal aortamost affected by atherosclerosis Also most common site of AAA
•
Current research suggests many factors •
Can causeaortic regurgitation Surgery if size >5.0cm
Marfan, Turner, Bicuspid aortic valve,Syphilis
Abdominal Aortic Aneurysms
•
Most are asymptomatic
•
•
Genetic, environmental, hemodynamic, immunologic
167
Smoking:strongest association with AAA Males: 10x more common men vs. women Age •
Rare before 55
•
As high as 5% in men >65
HTN, hyperlipidemia
Abdominal Aortic Aneurysms •
Most are asymptomatic
•
Some detected on physical exam Pulsatile massfrom xiphoid to umbilicus Natural history is enlargement rupture Followed withultrasoundor CT scan
•
Surgery if >5.0cm
•
•
•
Aortic Rupture •
•
Usually from trauma Most common site is isthmus
Isthmus
168
Cardiac Tumors •
Myxoma
•
Rhabdomyomas
•
Metastatic tumors
•
•
Cardiac Tumors
•
Most common 1° cardiac tumor
Most common 1° cardiac tumor children
Most common cardiac tumor overall
Jason Ryan, MD, MPH
Myxoma •
•
Myxoma
Common in theleft atrium (80%) •
Usually attached to atrial septum
•
Often at the border of fossa ovalis
•
•
•
Benign (do not metastasize)
•
Myxoma •
•
Mesenchymal cells (undifferentiated cells) Endothelial cells Thrombus/clot Mucopolysaccharides
Myxoma
Often cause systemic symptoms
•
May disrupt mitral valve function
•
“B symptoms”
•
Regurgitation
•
Fevers, chills, sweats
•
Heart failure
Can embolize stroke
•
•
169
Can sit in mitral valve •
“Ball in valve”
•
Mitral stenosis symptoms
•
Syncope or sudden death
Auscultation: Diastolic“tumorplop”
Cardiac Rhabdomyomas •
Tumors of muscle cells
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Benign (do not metastasize) Usually children (most <1year) Sometimes detected prenatal Tumor embedded in ventricular wall
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Most regress spontaneously
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Rare symptoms from obstruction of blood flow
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Cardiac Rhabdomyomas •
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Mutations widespread tumor formation
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Tuberous Sclerosis Involves MULTIPLE organ systems Numerous hamartomas and other neoplasms Seizures – most common presenting feature “Ashleaf spots”: Pale, hypopigmented skin lesions Facial skin spots (angiofibromas) Mental retardation
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Associated withtuberous sclerosis (90%) Autosomal dominant genetic syndrome Mutation in TSC1 or TSC2 gene TSC1: Hamartin TSC2: Tuberin
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Hypertrophic Cardiomyopathy
Hypertrophic Cardiomyopathy Jason Ryan, MD, MPH
Hypertrophic Cardiomyopathy
HCM
Names •
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Hypertrophic cardiomyopathy (HCM)
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Hypertrophic obstructive cardiomyopathy (HOCM) Idiopathic hypertrophic subaortic stenosis (IHSS)
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Point mutation altered amino acid in protein
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15+ genes with 1500+ mutations identified Beta-myosin heavy chain (40% cases)
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Myosin binding protein (40% cases)
Significant variation in severity of symptoms
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Many variations in location/severity of hypertrophy
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Myocyte disarray (excessive branching) Hypertrophy
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Interstitial fibrosis
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Often involve genes forcardiac sarcomere proteins •
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Histology
Oftensingle-point missense mutations •
About 50% cases familial (50% sporadic) Autosomal dominant Variable expression
HCM
HCM •
Genetic disorder caused by gene mutations
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HCM
HCM
Clinical Features
Clinical Features
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Many patients asymptomatic
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Heartfailure
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Diastolic dysfunction
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Impaired emptying due to LVOT obstruction
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Sudden cardiac death
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Syncope
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Chest pain (angina) •
Abnormal myocytes ventricular arrhythmias
• Most common cause SCD in young patients • Arrhythmias may lead to syncope
Increased O2 demand
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Thickened myocardium
HCM
HCM
Clinical Features
Clinical Features
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Problem #1: Arrhythmia problem
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LVOT obstruction
Problem #2: Outflow obstruction problem
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Thick myocardium vulnerable to arrhythmias
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Thickened myocardium obstructs blood leaving LV
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Most serious is ventricular tachycardia sudden death
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Same physics and symptoms as aortic stenosis
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Exercise (catecholamines) increase risk SCD
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Heart failure, chest pain, exercise-induced syncope
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Sudden death in athletes
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Treated with surgery
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Defibrillators for high risk patients
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Beta blockers (↓ contractility)
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Avoidance of exercise
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Ca blockers (verapamil)
HCM
HCM
Clinical Features
Clinical Features
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Mitral regurgitation
#3: Mitral valve problem •
High velocity in LVOT tugs mitral valve chords and leaflets
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Causes systolic anterior motion (SAM) of mitral valve
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Over time this leads tomitral regurgitation
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Systolic ejection murmur
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Caused by outflow tract obstruction
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Sounds just like AS unless you do maneuvers Lots of associated abnormal heart sounds •
S4
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Holosystolic murmur of MR
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Paradoxical split S2
S1
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S2
HCM
HCM
Maneuvers
Maneuvers
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For any HCM maneuver, think about size of LV
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↑ LV size ↓ murmur
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↓ LV size ↑ murmur
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Valsalva •
Patient bears down as if having a bowel movement
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Or blows out against closed glottis
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Increase thoracic pressure compression of veins ↓ VR
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Less VR Less preload Smaller LV cavity
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Obstructing septum moves further into the outflow tract
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Murmur INCREASESin intensity
HCM
HCM
Maneuvers
Other maneuvers
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Squatting
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Raising the legs
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Forces blood volume stored in legs to return to heart
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Increases venous return
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Preload rises size of LV increases
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More VR More preload
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Murmur DECREASESin intensity
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This moves the obstructing septum out of the way
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Murmur DECREASESin intensity
less obstruction
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Murmur INCREASESin intensity
Maneuver Summary
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Both HCM and AS cause a systolic ejection murmur
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Less effect of maneuvers on aortic stenosis
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Opposite effects of maneuvers in aortic stenosis •
Opposite mechanism of leg raise
HCM
Aortic Stenosis
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Fixed obstruction
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Less preload less flow quieter AS murmur
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Bigger LV cavity
Standing •
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Valsalva INCREASE Standing INCREASE Squatting DECREASE Leg Raise DECREASE
HCM
HCM
Associations
Associations
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Maternal diabetes
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Friedreich Ataxia
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Infants: transient hypertrophic cardiomyopathy
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Autosomal recessive CNS disease
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Usually thickening of interventricular septum
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Trinucleotide repeat disorder
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obstruction in newborn May have small LV chamber
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Spinocerebellar symptoms
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Resolves by a few months of age
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Often have concentric left ventricular hypertrophy
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Also septal hypertrophy
Cardiac Hypertrophy
Cardiac Hypertrophy
Other Causes
Rare Pathologic Causes
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Hypertension
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Valve disease Athlete’sheart
Cardiac Hypertrophy Rare Pathologic Causes •
Pompe Disease •
Glycogen storage disease (develops in infancy)
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Acid alpha-glucosidase deficiency
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Enlarged muscles, hypotonia
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Cardiac enlargement
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Fabry Disease •
Lysosomal storage disease
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Deficiency of -galactosidase A
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Neuropathy, skin lesions, lack of sweat
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Left ventricular hypertrophy
Endocarditis •
Inflammation of endocardium of heart
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Usually involves cardiac valves Often causesnew regurgitation murmur
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Consequence of bacteremia
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Endocarditis Jason Ryan, MD, MPH
Regurgitant Valve Disease
General Symptoms •
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Fever
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Chills Sweats Petechiae •
Small vessel inflammation
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Leakage of blood
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Embolic Symptoms
Aortic regurgitation Mitral regurgitation Tricuspid regurgitation
Endocarditis Stigmata
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Brain (stroke)
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Physicalexamfindings in endocarditis
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Spinalcord (paralysis)
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Caused by septic emboli and immune complexes
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Very rare in modern era
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Eye (blindness) Legs (ischemia)
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Splenic or renal infarction Pulmonary embolism (tricuspid)
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Coronary artery (acute myocardial infarction)
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Endocarditis Stigmata •
Roth spots
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Retinal lesions
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Positive blood cultures
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Red with pale center
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Vegetation on echocardiogram
Osler nodes
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Janeway lesions
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Nontender red macules on palms and soles •
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Staphylococcus aureus Viridans streptococcus Streptococcus Bovis Enterococcus
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Staphylococcus epidermidis
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Culture negative endocarditis
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Risk factors
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Roth spots, Osler nodes, Janeway lesions, splinters
2 major, 1 major 3 minor, or 5 minor
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Gram positive cocci
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Catalase positive Coagulase positive
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May infecttricuspid valve in IV drug users
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Libman-Sacks
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Causesacuteendocarditis
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Rapid, severe infection
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Fever
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Staph Aureus
Staph Aureus
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Reddish-brown l ines under fingernails
Microbiology •
Minor Criteria
Painful bumps on pads of fingers and toes
Splinter hemorrhages
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Major Duke Criteria
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Diagnosis
Viridans Streptococcus Group of gram positive cocci
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Catalase negative
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Mouth flora
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Endocarditis may occur afterd ental procedure
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Symptoms occur over days Can occur in patients withnormal heart valves •
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No pre-disposing valvular heart condition
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S. mitis, S. mutans, S. sanguinis
Viridans Streptococcus
Viridans Streptococcus
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Low virulence bacteria
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Causes subacuteendocarditis
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Often affectdamaged valves
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Less severe symptoms
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Symptoms occur over days to weeks
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Bacteria synthesize dextran
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Dextran adheres to fibrin
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Fibrin found with endothelial damage
Classic predisposing condition:mitral valve prolapse
Streptococcus Bovis •
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Enterococcus Endocarditis
Gram positive cocci
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Lancefield group D Normal gut bacteria Associatedwithcolon cancer •
All subtypes associated with cancer
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Strongest association: S. gallolyticus (S. bovis type 1)
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Commonly occurs in older men
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Associated with manipulation of GI/GU tract
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Prosthetic Valve Endocarditis
Gram positive cocci Lancefield group D Normal gut bacteria Usually a subacute endocarditis course
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Abdominal surgery
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Urinary catheter
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TURP for treatment of BPH
Staphylococcus Epidermidis
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Occurs with mechanical or biologic valves
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Catalase positive
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Rarely cured with antibiotics
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Coagulase negative (unlike S. Aureus)
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Usually requires repeat valve surgery Similar bacteria to native valve endocarditis Staphylococcus epidermidis •
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Rarely cause endocarditis except in prosthetic valves
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Most common coagulase negative staphylococcus Normal skin flora Low virulence Commonly cause infection ofprosthetic material •
Cardiac valves
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Intravascular catheters
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Prosthetic joints
Coxiella Burnetii
Culture Negative Endocarditis •
Evidence of endocarditis with sterile blood cultures
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Caused by rare bacteria difficult to culture Coxiella burnetii
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Bartonella
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• Zoonotic bacteria (transferred from animals) • Obligate intracellular bacteria • Found in farm animals • Cattle, sheep and goats •
Abortions in farm animals: Coxiella placentainfection
• Humansinhale aerosolized bacteriafrom animals • Causes Q fever
Coxiella Burnetii
Bartonella
• Acute Q fever
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Bartonella quintana
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Flu-like illness
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Small, gram-negative rod
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May present as pneumonia
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Transmitted by lice
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More than half of cases: no symptoms
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Patients with poor hygiene
• Chronic Q fever •
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Most common manifestation is endocarditis
Bartonella henselae •
Found in cats
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Causes cat scratch fever
NBTE
NBTE
Non-bacterial, thrombotic endocarditis
Non-bacterial, thrombotic endocarditis
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Libman-Sacks Endocarditis or Marantic endocarditis
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Lesions on valves that look like endocarditis Found onboth sides of valve Mitral valve most common Formed by thrombus, immune complexes Seen in hypercoagulable states •
Advanced malignancy
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Systemic lupus erythematosus
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Can cause myocardial infarction
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Often asymptomaticidentified at autopsy Rarely cause regurgitation or murmurs Thrombus easily dislodges embolization Most patients asymptomatic until embolism occurs May embolize to spleen, kidney, skin, extremities May cause stroke
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Bacterial Endocarditis
Bacterial Endocarditis
Treatment
Complications
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Several weeks appropriate antibiotics Broad spectrum antibiotics initially Drug therapy changes when bacteria identified Valve surgery sometimes required •
Large vegetation
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Severe valve disease heart failure
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May form abscess beneath valve annulus
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Persistent fever, bacteremia often indicates abscess
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Aortic valve abscess can lead to heart block •
AV node dysfunction
Prophylaxis
Prophylaxis •
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Primary prevention for bacterial endocarditis Done before high-risk medical procedures Antibiotics given to some high-risk patients New guidelines restrict to highest risk circumstances
Amoxicillin Clindamycin
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