8. Pulmonary Vascular Disease Flashcards
PULMONARY CIRCULATION
• It is the only system through which the entire ____ passes
• It is a low-____, high-____ system
• Similar to airways, branching of vessels increases ____
• In response to increase in flow, increased ____ of vessels and vasodilation
• Kidney’s, stomach, other intestinal organs and muscles do not receive 100% of cardiac output
• When heart pumps, lungs receive 100% of output from right side of the heart
• Capillaries surrounding an alveolus are not fully distended - if there is increased demand (exercise, increased
blood flow, increased cardiac output), then capillaries ____
◦ This allows the change in pressure to be ____
• When you exercise, you are not supposed to develop high pulmonary pressures because you would ____
◦ This is what happens with pulmonary hypertension
cardiac output pressure flow total CSA recruitment engorge minimal syncopize
PULMONARY VASCULAR RESISTANCE
- PVR is calculated as ____ divided by ____
- Resistance in a vessel increases
- ____ of vessel
- Fluid ____
- 1/radius4 -> the ____ make up a substantial portion of PVR
• You need a starting point and an ending point, and you divide by the flow across those two points
• When talking about pulmonary vascular resistance, talking about the mean pulmonary arterial pressure in the ____
• The end point is when it gets to the ____ of the heart - the left atrial pressure
• The blood flow is the ____
• Even though the pulmonary vascular circulation has several branches that increase the total cross sectional area, because at these small vessels you have much higher resistance, most of the micro vessels are what make the highest proportion of the PVR
◦ NOT the____ or the lobar arteries
◦ It’s the tiny ____ that go to the pulmonary capillaries
transvascular driving pressure flow length viscosity microvessels
pulm arteries left side cardiac output large pulm arteries arterioles
PULMONARY VS. SYSTEMIC CIRCULATION
Pulmonary 3.1
mean arterial pressure: ____
resistance: ____
Systemic 3.1
mean arterial pressure: ____
resistance: ____
PC: high ____, low ____, low ____ circuit
• ____ are the same b/w pulmonary and systemic circulation
• The upper limit for the mean arterial pressure in the pulmonary circulation would be 20
• If you calculate the diff b/w the mean arterial pressure and the ____ for pulmonary circulation
divided by CO, you get the resistance
• If you calculate the mean arterial pressure and the ____ (because that is the end point) in the systemic, you get the systemic vascular resistance
◦ Comparing those 2 together, pulmonary circulation is a high capacity, low pressure, low resistance circuit compared to the ____ circulation
9-15
60-100
85-100
900-1200
capacity
pressure
resistance
cardiac indices
left atrial pressure
right atrial pressure
systemic
• The left side of the heart pumps out to the body and returns through the SVC and the IVC into the RA
◦ You use the mean minus the end (____), and you divide it by the CO
◦ Normally CO is 5 L/min
◦ You get a SVR of 17.6 Wood units
◦ If you multiple this by 8 (I think that’s what she said?), you get the other unit of measurement which is 9/ sec/cm^-5
• For the pulmonary circulation, the heart ejects from the right side of the heart into the pulmonary circulation into the lungs and back into the LA
◦ You use the mean arterial pressure in the pulmonary arteries minus the ____ and you divide by CO
◦ You get a PVR of 1.8 Wood units
right atrial pressure
left atrial pressure
Pulmonary artery catheter
• We use the pulmonary artery catheter to measure these pressures
• The catheter has several lumens - a ____ (opens into ____), a ____ (opens at the tip where the ____ is), a
____ that is inflated through the catheter, & a ____
proximal RA distal balloon balloon temp transducer
Right heart catheterization
- When you start in the right atrial pressure, you have an a wave with an ____ descent and a v wave with a ____ descent
- These a and v waves correspond to the ____ contraction - once the atrium contracts you get this bump (a wave)
- As the atrium relaxes, the ____ drops
- Then the ____ closes and you get another bump and an increase in ____ when the valve closes
• Once the catheter enters the ____, a sharp increase in systolic pressure - mid 20s
• in diastole, right ventricle and diastolic pressure is ____ mm Hg
• Catheter floats into ____, see a change in shape of wave
◦ similar systolic pressure unless ____
◦ diastolic pressure ____
◦ Also see ____ - when ____ closes
• once you wedge (let catheter go to smallest vessel it can fit) - see an a and v wave, but it’s ____ pressure
x y atrial pressure tricuspid pressure right ventricle 0-8 pulmonary artery pulmonary valve problem rises dicrotic notch pulmonary valve higher
Wedged PA catheter
- when catheter is wedged, have a closed column of fluid between balloon tip, the ____, the ____, and the ____
- Gives a reflection of the ____ and ____ pressure
- can see if the increase in pressure is ____ (problem with pulmonary arteries and pulmonary vessels) or a problem with ____ of the heart
- when we measure pulmonary wedge pressure, trying to get a reflection of ____
- if left ventricular end diastolic pressure is high & if no ____ valve pathology, it will transmit into the ____ and back all the way up - what the catheter picks up
capillaries
pulmonary veins
LA
left ventricular
diastolic
precapillary left side left ventricular end mitral left atrial pressure
PA Cath Measurements
- ____ pressure
- ____ pressure (systolic and diastolic)
- ____ pressure (systolic, diastolic and mean)
- ____ (PAWP)
RA
RV
PA
PCWP
MEASUREMENT OF CARDIAC OUTPUT
• Fick Principle: The total uptake or release of any substance by an organ is the product of ____ to the organ and the ____ difference of the substance
Qp = (____) / ____
• In absence of a shunt, the systemic blood flow (Qs) is estimated by ____
• There are two ways to measure CO:
◦ Fick principle - Qp = ____ and pulmonary circulation
◦ If know your arterial saturation minus the mixed venus = arteriovenous O2 difference
◦ oxygen consumption measured or estimated
• When have catheter wedged, if pull blood back, we are pulling blood from least oxygenated blood going to lung capillaries to get reoxygenated
• if don’t have abnormal connection b/w right and left side of heart (shunt) can assume that systemic blood flow is same as ____
◦ Qs = ____
blood flow
arteriovenous concentration
oxygen consumption
arteriovenosu O2 difference
pulmonary blood flow (Qp)
cardiac output
pulmonary
Qp
MEASUREMENT OF CARDIAC OUTPUT
- ____ method
- Cardiac output is determined by injecting a cold bolus of a sterile solution in the PA catheter’s ____ port. The temperature probe at the distal tip will sense the change in ____ as the injectate passes the catheter tip located in the PA.
• The other way to measure CO while doing the pulmonary artery catheter is to use
thermodilution
• You see there is a change in temp - temp ____ then goes back to ____
• If you know the volume you injected and the difference in temp, then you can calculate the ____
thermodilution proximal temperature decreases normal body temp blood flow
Resistance calculations
Pulmonary vascular resistance
PVR = (____ / pulmonary blood flow (CO)
Systemic vascular resistance
SVR = (____ / systemic blood flow (CO)
• you start at a point (mean PA pressure) and end point is the mean LA pressure
◦ the mean LA pressure is estimated by the ____ (PCWP)
• CO determined by either ____ method
mean PA pressure - mean LA pressure (PCWP)
mean arterial pressure - mean RA pressure
pulmonary capillary wedge pressure
thermodilution
Pulmonary Hypertension
• Defined as mean PA pressure ≥ ____ mm Hg
• PH is not specific as
Mean PA Pressure = ____
• Important to determine ____ to determine PH treatment
• normal pulmonary artery pressure is between ____ (up to 20) mm Hg
• between 20 and 25 is not technically pulmonary hypertension, but the slight elevations aren’t good for
patient
• If you take PVR equation and shuffle it, you get the mean PA pressure equation
◦ If you look at this equation, many things can raise the pulmonary artery pressure
◦ patients who have ____ - will get pulmonary hypertension because the high wedge pressure will drive the mean PA pressure to be high
◦ someone who’s anemic will have increased ____ - will cause elevation in mean PA pressure
• When we talk about PH, specifically pulmonary arterial hypertension (PAH), we are talking about an
____ problem with the pulmonary vasculature
◦ the little vessels are ____ and the ____ is high
• Treatments differ drastically
25
CO x PVR x PCWP
PH group
9-15 CHF CO intrinsic remodeled PVR
PH classification
• PAH is disease related to the pulmonary vasculature (____)
• PH owing to left heart disease is when you have ____ (____)
◦ all the dysfunctions drive up the PCWP and give you PH
• If have any ____, can give you PH (Group III)
• Special group is group IV
• ____ is a mixed basket of diagnoses
◦ all of the disorders can present as different groups
◦ when they have many different possibilities of presenting, we lump them here and decide on case-by-case
basis
• We will focus on PAH
◦ ____: we don’t know why they develop this pathology
◦ heritable: ____ mutations, ____ mutations, ____ mutations that lead to higher incidence of PAH in
families
group I left heart failure group II lung disease group V idiopathic BMPR2 ALK endoglin
PH classification (cont.)
• drugs and toxins: back in 80s, diet pills with fenfluramine that led to the development of PAH, nowadays see same thing with drug users and ____ and amphetamines
• a number of associated conditions lead to PAH
◦ ____ is one of the most common
‣ ____ or systemic sclerosis
‣ ____
‣ any connective tissue diseases can led to PAH
◦ HIV
◦ ____ - liver disease with evidence of portal hypertension
‣ patients with liver disease with increased portal pressure
‣ ____ is elevated but also ____ elevated to diagnose
◦ congenital heart disease ‣ \_\_\_\_ shunt causes PAH • ASD, VSD, PDA ◦ the most common cause of PAH worldwide is \_\_\_\_, which is a parasitic infection ‣ we don't see it here in the US
methamphetamine
connective tissue disease
scleroderma
SLE
portal hypertension
CO
PVR
right to left
schistosomiasis
PAH
- Pulmonary arterial hypertension is defined as:
- Mean PA pressure ≥ ____ mm Hg
- PCWP (Left ventricular end-diastolic pressure) ≤ ____ mm Hg
- PVR > ____ WU or ____ dynes/sec/cm-5
- ____: 10-15 cases per million
- More common in ____ than men
- Average time to appropriate diagnosis ~____ months
• You have to have a normal PCWP, meaning there is no ____
• need to have an elevated ____
◦ 1 Wood unit is 80 dynes/sec/cm^-5
• True PAH is rare
• Patients present with non-specific symptoms (shortness of breath) that are often misdiagnosed
25 15 3 240 rare women 12-18 left heart disease PVR
PAH Survival
• Back in 90s, NIH did a survival of patients with PAH (used to be called Primary Pulmonary Hypertension), and it was dismal
• by 5 years, only 35% were still alive
• nowadays, patients are doing better, but it is still a highly ____ condition
◦ at 5 years, ____% are dead, which is significant considering it is a disease mostly affecting young women
morbid
30
Determinants of survival
• What impacts their survival? • Functional class I = someone who has no limitations of \_\_\_\_ • Functional class II = only have symptoms when \_\_\_\_ with strenuous activity, but okay with doing activities of daily living • Functional class III = problems with \_\_\_\_ ◦ I.e. when walk from my bed to bathroom, short of breath • You should think about what patients might tell you • Functional class IV = uncomfortable at \_\_\_\_, short of breath not doing anything • when a patient presents when functional class they are in impacts their longterm survival • at 3 years, \_\_\_\_% of functional class IV cases are dead ◦ functional class IIs are mostly \_\_\_\_ • important to identify these patients early on so can intervene early on
exercise activity strenuous activity daily activity rest 75 alive
Determinants of survival
____ not hemodynamics determines survival
• other things that are crucial for survival in these patients is their ____ function, not pulmonary hemodynamics
• it doesn’t matter what mean pulmonary artery pressure is, it matters how right heart is dealing with it
◦ if right heart is compensating and can function normally, patient will do okay
• however, if right ventricle (____) is low, that’s when patients do poorly
• If you classify PVR by a cutoff, there is a difference in survival
◦ those who have a ____ PVR will do better
• when you add the right ventricular ejection fraction to PVR, it splits by who has a preserved right ventricular
ejection fraction vs. low right ventricular ejection fraction
• the key is how the ____ is handling the increased pressure
RV function right ventricular right ventricular ejection fraction lower right heart
Hemodynamic progression of PH
• The pulmonary circulation is a high flow, low pressure system
• you start normally with a low ____ and a normal ____
• As PAH starts to progress, start to have medial ____ and intimal ____
◦ as that happens, your New York Heart Association (NYHA) goes from class I to II - start to become symptomatic with more strenuous activity
◦ As you go from this to this, your PVR is ____ and your pulmonary artery pressure is increasing because that vessel has ____
◦ the PVR is inversely proportion to the ____ of the vessel^4
‣ when you have a slight decrease in vessel radius, have a ____ increase in the PVR
◦ your cardiac output is still doing ok - ____ still able to deal with slight increase
PVR CO thickening hypertrophy increasing remodeled radius much higher RV
Hemodynamic progression of PH (cont.)
• then it comes to a tipping point, and that’s when the ____ starts to fail and patients become way more symptomatic
◦ their BNP (brain natriuretic peptide) ____ bc the right side of heart is stressed and dilating
‣ it’s ballooning and failing
‣ start to see that the vessels have completely ____
‣ the vessels develop hypertrophy and in situ ____, and the PVR continues to ____ as the disease progresses
‣ once the ____ starts to fall, the pulmonary artery pressure falls bc the heart can’t generate that much pressure
‣ remember, mean pulmonary artery pressure = CO x PVR
• now CO is failing, the ____ won’t be as high
• that’s why it’s not important what the mean ____ is because it could be on this side of the curve or this side of the curve
‣ so you need to know what the CO is doing
• at this point is death
◦ the right ventricle is extremely ballooned out and hypertrophied
right ventricle elevates thickened thromboses increase CO pulmonary artery
Imbalance of vasoactive factors in PAH
• what drives these pathological changes?
◦ ____, cell proliferation, and ____
• several mediators are driving this
• thromboxane is the most potent ____ the body produces ◦ we have an imbalance in these substances
• everyone of us produces thromboxane, prostaglandin (one of the most potent ____), nitric oxide, etc
◦ it’s a matter of a ____ of these substances against each other
‣ increase thromboxane = more ____
• also decreased prostacyclin (prostaglandin)
• also have decreased NO, another vasodilator
• increased endothelin (another ____)
• increased serotonin
◦ these same drivers lead to cell proliferation
‣ increased VEGF
◦ and increased thromboses
vasoconstriction
thromboses
vasoconstrictor vasodilators balance vasoconstriction vasoconstrictor
PAH PATHOLOGY
____ lesion; ____ hypertrophy; ____ proliferation
• the pathognomonic lesion for PAH is a ____
• this is what should have been a regular vessel
• if you look more closely, the intimal layer is already ____
• the plexiform lesions are conglomerates of ____ cells that are abnormally multiplying
• it’s kind of like a cancer of the pulmonary vasculature
• if you look closely here, you have the muscle layer that is now highly thickened and proliferating
• you have smooth muscle hypertrophy and endothelial proliferation
• at the level of these capillaries, you should have one thin layer of ____, one thin layer of ____ so you can
have gas exchange occur with the alveoli
◦ this is not possible with what we are seeing
plexiform smooth muscle endothelial plexiform lesion thickened endothelial endothelium SMC
PAH PATHOLOG Y
In situ thrombosis
• the other common thing that we see is that these vessels ____ spontaneously
thrombose
RELE VAN T HIS TORY FOR PH
- ____ pain
- Raynaud’s syndrome
- ____conditions/cyanosis
- ____ disease
- Etoh/ drugs/ anorexigens/ tobacco
- ____
- Previous DVT or PE or family history of clots
- ____
• when you suspect pulmonary hypertension, what should you ask about?
◦ joint/musculoskeletal pain - trying to figure out if they have any ____ disease
‣ any other signs of scleroderma, ____, lupus
◦ Raynaud’s syndrome - fingers get cold and blue when exposed to cold
◦ childhood heart conditions - ____, cyanosis
◦ liver disease - want to know if have ____
◦ ask about alcohol - can lead to liver disease
◦ dugs - ____ are very common and a common cause of PAH
◦ anorexigens - in recent years ____ diet pills are off the market once they figured out they were
causing PAH
‣ still see patients today who took those pills back in the 90s and are presenting with PAH
◦ smoking - do they have ____
◦ ____ - can lead to PAH
◦ previous history of having deep vein thrombus in their leg or a PE or anyone in their family who has had history of clots
‣ or history of current abortions
◦ other chronic lung diseases - interstitial lung disease, sleep apnea, etc
joint/musculoskeletal childhood heart liver HIV chronic lung disease
CT RA murmurs portopulmonary hypertension methemphatamines fenfluramine COPD HIV
PH S YMP TOMS
- ____
- dyspnea on exertion
- ____
- fatigue, weakness
- ____ swelling &/or abdominal swelling/increased abdominal ____
- light headedness/____
• PH presents very non-specifically
• leg swelling - signs of ____
◦ when heart is not able to push forward, things back up from RV to RA into IVCs and they pool in the ____ system
◦ legs swell and they develop ascites
• lightheadedness is also an ominous sign
◦ tells you that when they try to exert themselves, the RV tries to pump against high pressure in ____ and it can’t
◦ if don’t have a CO from the ____ of the heart into the lungs back to the left side of the heart, you don’t have systemic blood flow
‣ that is when you pass out
non-specific chest pain leg girth syncope right heart failure venous PA right side
Physical Exam Findings in PH
- ____
- Hepatojugular relfux
- ____
- TR murmur
- ____
- Lungs typically clear BS
- ____/pulsatile liver
- Ascites
- LE edema
• Look at their necks and try to see their filling pressures
◦ the RA will back up into the SVC, and if the pressures in the RA are high, the ____ will distend
• hepatojugular reflex is if you have no neck distention, but if you press their ____, you are increasing the ____ pressure
◦ if the ____ in the neck fill, it is ____ hepatojugular reflex
◦ also tells you that the pressures on the right side of the heart are ____
• Loud P2 - second heart sound is loud bc of the ____ artery pressure valve closure
◦ due to the high pulmonary artery pressures
• Tricuspid regurgitation murmur - because the RV tries to unload and it causes regurgitation back into the ____
(low pressure chamber)
• ____ - if put hand across patient’s chest, you will feel something thumping against your palm
◦ bc when right side of heart dilates, the heart rotates ____, so RV will rotate, fill, and grow anteriorly
◦ sign of right heart failure
jugular venous distension loud P2 RV heave hepatomegaly neck veins liver venous veins positive elevated
pulmonary
RA
tricuspid regurgitation murmur
anteriorly
Physical exam findings in PH (cont.)
• typically, you don’t hear crackles in the lungs
◦ this is NOT ____ sided pulmonary edema, NOT increased pressures on the left side flooding the lungs with fluid
◦ you have increased pressures on ____ side, so ____ you get to the lungs
• ____ blood return to the right side of the heart - that’s the pressure that’s elevated
◦ legs are swollen, liver is congested, have ascites, but NOT their ____
◦ lungs are not ____ with water like ____ heart failure
◦ with left heart failure, the left sided pressures are high, they back up into the lungs and you hear the ____
• hepatomegaly/pulsatile liver - when you have right heart failure and liver congestion
left right before venous lungs flooded left crackles
PH diagnostic algorithm
once you have somebody that you suspect has PH, you take a history, examine them
◦ ____, EKG
if index of suspicion is high, first screening is ____
◦ we are looking at how the RV is functioning, how left heart is doing
◦ could tell us if we have ____ or diastolic left heart disease, if any communication or abnormal shunts across the heart
also need to get a ____ scan (ventilation perfusion) to rule out ____
◦ want to look for distal perfusion defects
presenting with an acute pulmonary embolus, ____ is the diagnostic test of choice
chest x-ray EKG systolic VQ CTEPH CT angiogram
PH Diagnostic Algorithm (cont.)
want to obtain ____ and ____ if necessary
◦ in PFTs with someone with PAH - see normal spirometry, normal lung volumes, the only abnormal value is their ____
‣ DLCO reflects the inability of lung to ____ gases
‣ one of the lung’s main functions is to capture oxygen from the air, transmit it across the alveolus to the
capillary bed, oxygenate the blood, and for the diffusion to happen, you need normal alveolus, normal interstitium and normal vessel
◦ with PAH have abnormal vessels so diffusion capacity is low
PFT (pulmonary function tests)
ABG (arterial blood gas test)
PH Diagnostic Algorithm (cont.)
• want to check for ____ in a sleep study to rule out obstructive sleep apnea
• want to check ____
• ____ for CT disease
• liver function test
• want to look for other associated disease with PAH
• want to be able to assess their ____
◦ do a 6 minute walk test - ask patient to walk across 100 meter hallway for 6 minutes and depending on distance they walk adjusted to age, can tell their functional class
• to confirm diagnosis of PH, you do the ____
• if necessary, might want to do ____ as well if they’re older and might have left heart disease
overnight oximetry HIV ANA functional status right heart catheter left heart catheter
PH by ECHO =/= PAH
- Echo is an excellent screening tool but ____ is gold standard for diagnosis
- Data from echo and RHC are ____
• often times echocardiogram says estimated PA pressure is ____ and patient most likely has PH
• echo is good screening tool, but it does not ____
• you need a ____ to really diagnose PH
• only 2.3% of 4500 patients in study above ended up having PAH
• echo takes into account a lot of assumptions, so it is not an accurate diagnosis
◦ but still very useful in telling us how the right heart is doing - is it ____, functioning, is septum
bowed in left side of heart (pressures on right are too high)
◦ data from the echo and right heart cath are complementary, but echo alone is insufficient to
diagnose PH
RHC complimentary high diagnose right heart cath dilated
Right heart catheterization
- Gold standard for diagnosis of ____
- Establishes cause of PH: ____ process
- Required prior to initiating ____ for PAH
- ____ testing
• second bullet point: is it a process involving pre-capillary (____ themselves) or is it post- capillary (involving ____ with elevated wedge)?
PH pre- vs post-capillary therapy acute vasodilator pulmonary vessels left side of heart
ACU TE VASODIL ATOR TES TING
- Using ____, epoprestenol, ____ or iloprost at time of RHC
- Acute vasoresponders:
- Reduction in MPAP by ____ mmHg to below 40 mmHg
- ____ or increased cardiac output
- ~10% of PAH patients
• Use a vasodilator - patients inhale NO, epoprestenol or iloprost, or IV inject adenosine
• at the time of the RHC, have patients inhale or inject one of these substances and we wait
• acute vasodilator response - mean PA pressure must drop from 10 mm Hg to below ____
◦ also need to have an unchanged ____
◦ need to see that pulmonary vasodilator brings down PA pressure, but it is not causing the right side of the
heart not be able to ____
◦ if it depresses the CO and that’s why the PA pressure falls, not a ____ response
• out of all the patients diagnosed with PAH, only 10% are acute vasodilator responders
◦ if put acute vaso responders on ____, have a good long term survival
‣ group of patients behave differently from non-vaso responders
‣ for non-vaso responders, no role for Ca channel blockers - may actually be detrimental b/c Ca blockers can depress ____
nitric oxide
adenosine
10
unchanged
40 CO beat vasodilator calcium channel blockers cardiac function
GOALS OF THERAPY
- Alleviate symptoms, improve ____ and quality of life
- Improve cardiopulmonary hemodynamics and prevent ____
- ____ time to clinical worsening
- Reduce ____ and mortality
• these patients can barely do anything
• most have to go on disability because walking from one room to another will get them
short of breath
• the key is to ____ right heart failure - if the right heart fails, they die
• if the PA pressure is high and their heart is ____, they’re okay
exercise capacity right heart failure delay morbidity prevent compensating
• thinking about what pathways we can potentially attack
• smooth muscles undergo proliferation, hypertrophying, and cause vasoconstriction, so we want to use
____ therapies
◦ oxygen is one of them
◦ ____ in the patients who have vasodilator response
• the endothelium is dysfunctional
• we have more thromboxane, more endothelin, less NO, less prostacyclin
◦ want to mitigate those effects - give ____ analogs, give ____ donors, or we want to decrease ____ of NO (use ____ inhibitors)
• because we see in situ thromboses, we want to ____ the blood
◦ sometimes give medicines as ____ therapies b/c we want them to work directly on that interface b/w
the alveolus and the vessel
◦ the medications we use have ____ properties b/c there’s ongoing inflammation in pulmonary vasculature
vasodilator
calcium channel blockers
prostacyclin
NO
degradation
phosphodiesterase
thin
inhalational
antiinflammatory
Targets for PAH therapy
• 3 major targets for therapy in PAH
◦ 1. ____ pathway
‣ unregulated b/c endothelin is a ____, so we want to block it and we give endothelin
receptor antagonists
◦ 2. NO pathway
‣ NO is a ____
‣ along the pathway of NO, we produce cyclic GMP
• ____ breaks down the cyclic GMP, so we give phosphodiesterase inhibitors
‣ new medicine: ____ stimulator - it stimulates the production of the cyclic GMP
• trials ongoing to supplement them with NO - problem is NO comes in huge tanks and there aren’t ____ devices to give patients
◦ 3. Prostacyclin pathway
‣ it’s a ____ - low in patients with PAH
• prostacyclin induces ____ - want to give prostacyclin replacements, derivatives
◦ newly approved agent - prostacyclin agonist that works to stimulate the same receptor as the prostacyclin
endothelin
vasoconstrictor
vasodilator
phosphodiesterase
soluble guanylate cyclase
portable
vasodilator
cAMP
Current PAH Therapies
Prostanoid: \_\_\_\_ \_\_\_\_ \_\_\_\_ \_\_\_\_
PDE5 inhibitor:
____
____
sGC stimulator:
____
ERA:
____
____
____
epoprostenol
treprotinil
iloprost
selexipag
sildenafil
tadalafil
riociguat
bosentan
ambrisentan
macitentan
Current PAH Therapies
• Prostanoids
◦ Epoprostenol - has a very ____ half life, has to be given as a continuous infusion through ____
‣ patients will have indwelling tunneled catheter that continuously infuses medication
• Flolan is earlier medication
◦ very ____ acting and needs to be kept ____ - patients have fanny pack and accessory ice packs around the pump
• Veletri - ____ form of Epoprostenol
‣ Treprostinil - available in 4 different formulations, also ____ acting
• Remodulin - ____ infusion (needle in skin continuously infusing medicine)
• Tyvaso - ____ form, has to be given ____ times a day, start with ____ breaths and go up to 9 breaths
• Orenitram - ____, ____ formulation, given ____ times a day b/c ____ acting
‣ Iloprost - another derivative of ____
• only available ____
• taken ____ times a day
‣ Selexipag - prostacyclin ____, not a derivative
• available ____ (Uptravi)
• main side effects with prostanoids (vasodilators):
◦ patients get ____, blood flow to extremities, also typical____ with the first bite
◦ leg cramps and muscle cramps are also common
◦ for the IV formulations (Flolan, Veletri, Remodulin IV) - risk of ____
◦ for subcutaneous - injection at the site is very ____
short
IV
short cold thermostable short IV or subcutaneous inhaled 4 3 newest oral 3 short
prostacyclin
inhaled
6-9
agonist orally flushing jaw pain bloodstream infections painful
Current PAH therapies (cont.)
• PDE5 inhibitors and sGC inhibitors side effects - not only dilate ____, but also dilate the ____
◦ sometimes get ____
◦ can’t give them ____ for heart disease if on PDE5 inhibitor
◦ Sildenafil and Riociguat or Tadalafil and Riociguat should NOT be combined
‣ we can combine anything else, but can’t combine these 2 b/c will drop blood pressure severely
• ERA (endothelin receptor antagonists)
◦ Bosentan - can affect the liver, patients need to have ____ liver function blood tests
‣ taken ____ a day
◦ Ambrisentan - once a day with less ____ on the liver, don’t need ____ liver testing monitoring
◦ Macitentan - ____ and does not need liver monitoring
◦ main side effects of ERAs - can cause ____
‣ uncomfortable to patient b/c they swell, but can also affect ____ side of heart
‣ have to watch patients closely for volume overload b/c may need to adjust fluid pills
◦ can also cause ____ and nasal congestion b/c of vasodilation
pulmonary circulation
systemic circulation
hypotension
nitrates
monthly twice side effects constant once volume overload right headaches
RIsk Assessment in PAH
- have to risk access patients to decide what medication to start patients on
- patients who have low risk can be started on a ____
- patients with high risk need an upfront ____ therapy and will need to have one of the ____
- intermediate risk depends on individual patients
• the drivers of the risk assessment:
◦ signs of ____
◦ progression of symptoms ____
◦ recurrent ____
◦ NYHA/WHO class ____
◦ can’t do >165 m during 6 minute walk
◦ ____ is low
◦ ____ levels high - right heart is stretched
◦ echo - signs of RA being ____ - pressure is high
◦ haemodynamics - high RA pressure means ____
◦ low ____ - right heart is failing
◦ low mixed ____ - not enough blood flow, so body extracts most of oxygen out
monotherapy
combo
prostacycline
right heart failure quickly syncope IV maximum peak VO2 NP-proBNP dilated volume overload cardiac index venous oxygen saturation
Survival based on number of low risk criteria achieved on 1st follow-up
- if at first follow-up patient doesn’t achieve low risk criteria, survival at 3 years is ____%
- if achieve 2 low risk criteria, goes to ____%
- 4 low risk criteria, ____% at 3 years
- bring patients back at ____ basis - not longer than ____ weeks
- if not doing okay, need to adjust what you’re doing
40 81 97 regular 12
PH treatment algorithm
• This is an algorithm with how we do it
• treatment for naive patient - do ____ and confirm PAH
• do ____ testing - if positive, give ____
◦ if not reactive, try to risk clarify them
◦ if high risk - need initial ____ and ____
◦ if low risk - start with ____ drug
◦ if intermediate risk - use a combo
• if you see them on follow-up, here is where you’re starting off
◦ if not doing okay, double or triple therapy
◦ start adding one medication from each class
◦ if not achieving adequate clinical response, maybe refer for lung transplantation
right heart cath vasoreactivity Ca channel blocker combo therapy prostacyclin one
Monotherapy vs. initial combination therapy
• a list of what is approved for mono therapy and for combo therapies
• there is no combo that includes PDE5 inhibitor and a ____
◦ b/c of risk of hypotension
sGC inhibitor
Continue risk assessment
- assess them at baseline, assess at initial treatment, keep reassessing them every ____ months
- monitoring for disease stability and any signs of progression
- if progressing, need to be aggressive about treating them
- patients already coming in ____ b/c diagnosis that’s often ____
3-6
late
missed
Role of anticoagulation
- Vascular thrombotic lesions
- Abnormalities in coagulation and fibrinolytic pathways
- Non-specific increased risk factors for ____
- Heart failure
- Immobility
• on pathology, there are in situ thromboses that occur
◦ the endothelium is abnormal, so platelets are abnormal
◦ have non-specific increase in risk factors for venous thromboembolism b/c have ____ and don’t
have a high normal ____
‣ they’re immobile and can’t walk
• recommendation for oral anticoagulation comes from small ____ studies
◦ weak evidence and only considered in patients that are ____, heritable, or PAH from ____
• don’t anticoagulant patients with ____ disease and PAH or ____ disease (b/c already at high risk of bleeding)
venous thromboembolism right heart failure cardiac flow retrospective and observational idiopathic anorexigens connective tissue liver
Anticoagulation & dental procedures
Anticoagulant
- ____
Antiplatelet agents •\_\_\_\_ (Plavix®) •ticlopidine (Ticlid®) •\_\_\_\_ (Effient®) •ticagrelor (Brilinta®) •\_\_\_\_
Target-specific oral anticoagulants •\_\_\_\_ (Pradaxa®) •rivaroxaban (Xarelto®) •\_\_\_\_ (Eliquis®) •edoxaban (Savaysa® [Lixiana® in Europe, Japan, elsewhere])
- Typical Patient
- No need to discontinue ____; use local measures to control bleeding
- Patients with Higher Risk of Bleed
- Take into account underlying need for anticoagulation
- Modification in consultation with patie physician
• list of all the anticoagulants that are available
◦ do with consultation with their physician to see if they need to be bridged with something ____-acting or stop ____ altogether, then resume when done with dental procedure
warfarin clopidogrel prasugrel aspirin dabigatran apixaban
medication
short
medication
Pulmonary embolism
- PE: obstruction of the pulmonary artery or one of its branches by material (____) that originates elsewhere in body
- Incidence ~50 cases per 100,000; M>F
- PE accounts for ~100,000 annual deaths in US
- Contributes to about 15% of all hospital deaths
• when have someone who breaks a ____, parts of the fat from inside bone marrow can travel and cause an obstruction - fat embolus
• air happens when someone has a ____ and pushing medication but don’t empty syringe of extra bubble
◦ bubble can obstruct and occlude vesse
thrombus vs air vs fat
long bone
central line
Classification
CLASSIFICATION • Temporal pattern for PE • \_\_\_\_: present immediately with signs and symptoms after occlusion of vessel • \_\_\_\_: days to weeks from obstruction • \_\_\_\_: develop symptoms over many years
- Hemodynamic stability
- Hemodynamically unstable/massive: hypotension present SBP < ____ mmHg or a drop in SBP ≥ ____ mmHg for > 15 minutes or requiring ____
- Sub-massive: ____ present
- Hemodynamically stable
RV dysfunction • RV/LV ratio > \_\_\_\_ or RV systolic dysfunction on • RV/LV ratio > \_\_\_\_ on CT • Elevation of BNP (>\_\_\_\_ pg/mL) • Elevation of NTpro-BNP (>\_\_\_\_ pg/mL) • ECG changes • new complete or incomplete \_\_\_\_ • \_\_\_\_ elevation or depression • \_\_\_\_ inversion
• they can tell you exact moment they started feeling short of breath
◦ e.g someone gets off plane after 5 hours, start walking and clot in leg goes to IVC to right side of heart then into pulmonary artery - keeps traveling till it clogs vessel
• sub-massive: don’t have low ____, but have signs of ____ seen on EKG or echo or
elevated BNP/NP-proBNP
• hemodynamically stable: have a PE but not ____, no arrhythmia, ____ maintaine
acute
subacute
chronic
90
40
vasopressors
RV dysfunction
0.9
0.9
90
500
RBBB
anteroseptal ST
anteroseptal T-wave
BP
RV dysfunction
tachycardic
BP
CLASSIFICATION
- Anatomic location
- Saddle
- Lobar
- Segmental
- Subsegmental
• This is a CT scan of the chest
• this is a saddle PE and this is the ____
◦ vessels are completely opacified except for where the saddle ____ is
‣ sitting at bifurcation of pulmonary artery into the right side and the left side
• this would be a ____ PE b/c it’s blocking the branch of the right ____
• ____ are PE that are at higher generations of the pulmonary artery
• the main pulmonary artery trunk leaves the RA and divides into the right and left side
◦ right divides into the main right upper lobe, right middle lobe, right lower lobe
◦ left into the lingula, left upper lobe, left lower lobe and keeps branching
• see here there is a filling defect in one of the ____ arteries
• here you can see that filling defect - the ____
• all the vessels should fill completely if there are no clots
main pulmonary artery clot lobar pulmonary artery segmental and subsegmental right lower lobe dark spot
PE Prognosis
Recurrent thromboembolism
Cumulative risk of VTE similar after ____ months of initial treatment
Decision about prolonged anticoagulation at 3 months
• ACCP 2016: unprovoked VTE with low/intermediate risk of bleeding > indefinite
Chronic thromboembolic pulmonary pertension
Death – mortality of up to 30% if left ntreated
• first time you have a PE, more likely to have ____
• when you see patient at time 0 and they have PE, have to treat them for at least 3 months with an anticoagulant
◦ after 3 months, risk of them having another PE or DVT is ____
• but if you treat for 4-6 weeks, risk of having another PE is ____
• have to make a decision about long term treatment
◦ we think about whether it was provoked or unprovoked
◦ provoked VTE - have a definitive condition that predisposed person to clot, had major surgery, had
broken bone and were immobilized, had very long flight, etc.
◦ unprovoked VTE - just develops for no clear reason
‣ if ____ risk of bleeding, keep patient on anticoagulant indefinitely (all their life)
3 future PE similar higher low to intermediate
CTEPH
- Likely more common than appreciated
- Range of incidence estimates ____ %
- Risk factors:
- Prior ____ (25 – 65% without hx of VTE)
- Age > ____ years
- ____
- ____
- ____/ lupus anticoagulant
- ____
0.6-9.1 VTE 60 malignancy submassive PE antiphospholipid splenectomy
C TEPH
- ____t lining vessel
- ____ deposition
- ____
- ____
- ____ and calcification
• Potentially ____ form of PH
- these clots become more like fibrin glue inside these vessels
- good news is that CTEPH is potentially curable
- DON’T have a cure for ____ - just medicine to delay progression of disease
chronic clot collagen hemosiderin inflammation atherosclerosis
curable
PAH
CTEPH diagnosis algorithm
someone coming in with dyspnea on exertion
◦ history suggests ____ in the past get an echo
◦ suggestive of PH - get a ____ ◦ also get ____ (ventilation perfusion scan)
example of abnormal perfusion scan
give them ____ that they inhale, then you scan the lungs and should see clear contours of lungs
◦ left lung usually has part that’s missing - where heart sits
in this case, see moth-eaten defects
◦ not a ____ contour
◦ ____-shaped defects
◦ these are all tiny clots that have blocked perfusion to distal part of the lung
if have a normal VQ scan and not a CT angiogram that you get when you suspect an acute PE, ____ scan is more sensitive to detect these chronic clots and distal perfusion defects
if normal VQ scan, ____ is excluded
if abnormal, refer to ____ expert center
◦ need to get a ____ and ____
‣ ____ and inject dye into pulmonary artery so you can visualize and plan for surgery
‣ also do right heart cath to confirm presence of ____
clots
right heart catheter
VQ
radio tracer
straight wedge VQ CTEPH CTEPH
CT angiogram
PA angiogram
right heart cath
PH
CTEPH Diagnosis
- Confirm with ____
- Evaluate for surgical candidacy for pulmonary endarterectomy (PEA)
• an example of PA angiogram
• right PA trunk filling with contrast
• it should look like a tree branching all the way out, but see that the tree is cut off
◦ no vessels visible here
• see the contrast where the vessels are and where it’s occluded
• complete occlusion of right upper load branch
• on the left side of the heart, the main left pulmonary artery trunk is ____
◦ don’t see any vessels in the distal portion of the lung
• when send patients for surgery (major open heart surgery - go on cardiopulmonary bypass), go into each side ____ and strip clot ____ of the vessel
◦ not taking out pulmonary artery, just taking out the junk
◦ have to go under bypass 2 times - once for the ____, once for the ____
◦ high morbidity surgery
• not everyone is a candidate
• ____ is curable if can get all stuff out of vessels
PA angiogram opacified separately outside right left CTEPH
Treatment of CTEPH
Medical therapy: Anticoagulation + Riociguat – FDA approved
Other PAH approv therapies – observational/ retrospective studies
Balloon pulmonar angioplasty
if surgical candidate, send to OR
most people are cured
some people have more distal disease
◦ surgeon can only dissect major arteries - once starts to branch smaller, cannot get into there so have to leave some clot
◦ some patients may have ____ even after surgery - usually milder form
Some people have CTEPH but are not surgical candidates
◦ once stack decks against them with risk factors
inoperable patients or those with residual PH you treat medically
◦ need to be on life-long ____ and you need to treat PH
◦ only FDA approved indication for CTEPH is ____
◦ doesn’t mean we don’t use other medications, but evidence that comes for other medicines (I.e. prostacyclins, ERAs) are from ____ studies
◦ Riociguat studied in ____ trials in CTEPH, inoperable, and those with residual PH
‣ shown to have good benefits
balloon pulmonary angioplasty - the same way treat ____ by balloon-dilating vessel
◦ currently studied in CTEPH and has promising results
residual PH anticoagulants observational and retrospective prospective randomized controlled CAD
PREOP PULMONARY EVALUATION
- Any form of PH uniformly increases the perioperative risks of ____ surgery
- Assess patient risk factors
- Functional class ____
- Severity of PH disease:
- Elevated ____
- ____ dysfunction
- Echocardiogram +/- RHC
• if you just listen to what patient tells you, you will learn a lot
• elevated right atrial pressure - do they have more volume? is RV happy or not?
• sometimes might even repeat a right heart cath to decide on their preoperative surgical
risk
cardiac and non-cardiac
III/IV
right atrial pressure
right ventricular
Preop-periop optimization
- Euvolemic – if volume overloaded > ____
- Ideally MPAP < ____ mm Hg and PVR < ____ Wood units (may not be attainable)
- Decision is ____ specific
- Choice of anesthesia: avoid agents with ____
- Continue ____ and consult PH physician
- Avoid ____ with anesthesia
- Avoid ____ and/or hypoxemia
• if euvolemic - diurese them to keep them dry
• if on oral meds, give them oral meds ____ of surgery and resume as soon as can ____ afterwards
• if on infusion, must continue with ____
• a lot of patients can only undergo surgery in highly specialized tertiary care centers
• when induce somebody, BP drops
◦ patients with PH will not do well
• must ventilate patients appropriately
diurese 35 3 patient & procedure negative inotropy hypotension hypercapnia day eat infusion
