Lec 21-22 Acute Coronary Syndromes Flashcards
What types of coronary syndromes with a partially occlusive thrombus?
- unstable angina
- non-ST elevation MI [NSTEMI]
What distinguishes unstable angina from NSTEMI?
NSTEMI = necrosis present
unstable angina = no myocardial necrosis
What type of coronary syndrome with a completely obstructed coronary artery?
ST-elevation MI [STEMI]
What is difference intrinsic vs extrinsic coagulation path?
instrinsic = within bloodstream activating coagulation extrinsic = not in contact with bloodstream
What is action of Factor X?
catalyzes conversion prothrombin to thrombin
What is action of fibrin?
forms mesh-like network that capture debris like red/white cells; forms actual structure of thrombus
What is the sequence of events leading to thrombin generation?
- activated factor VII binds tissue factor
- this complex activates factor X
- activated factor X and factor V together catalyze conversion prothrombin to thrombin
- thrombin stimulates platelets + increases activation of coagulation cascade
What is action of antithrombin? Where does it come from? What increases its activity
- plasma protein in blood
- irreversibly binds thrombin [factor IIa] and inactivates
- increased efficacy by 1000x when its bound to heparan on surface of endothelial cells
What is action of protein C?
- activated protein C [activated by thrombmodulin-thrombin complex]
- activated C degrades factors Va and VIIIa –> inhibiting coagulation
- protein S enhances action of protein C
Which 2 other factors needed in protein C action?
- thrombomodulin activates protein C
- Protein S enhances function of protein C
What enhances action of anti-thrombin?
heparan
What enhances action of protein C?
protein S
What is action of thrombomodulin?
step1
- on surface of endothelial cell
- binds thrombin and prevents it converting fibrinogen –> fibrin
- as bound thrombomodulin-thrombin complex it activates protein C
Which factors does protein C inhibit?
step1
factors Va and VIIIa
What are 2 principal targets of antithrombin?
step1
thrombin and factor Xa
What 6 factors does antithrombin inhibit?
step1
activated forms of
- II [thrombin], VII, IX, X, XI, XII
What is action of TFPI?
TFPI = tissue factor pathway inhibitor
- activated by Xa
- Xa-TFPI complex binds and inactivates TF-VIIa complex that normally triggers extrinsic coagulation path
== negative feedback inhibitor of coagulation
Which endogenous anti-coagulant lyses clots?
- tPA = tissue plasminogen activator secreted by endothelial cells
What is action of tPA?
step1
- secreted by endothelial cells in response to clot formation
- cleaves plasminogen to plasmin which degrades fibrin clot
- when bound to fibrin = activity enhanced
What are actions of plasmin?
step1
- cleaves fibrin mesh
- destroys coagulation factors
What is action of prostacyclin? Where does it come from?
Step1
- secreted by endothelial cells
- increases platelet cAMP –> inhibits platelet activation/aggregation
- also indirectly inhibits coagulation via vasodilation
How does vasodilation guard against thrombosis?
more blood flow = minimize contact between procoagulant factors
less shear stress which is an inducer of procoagulant factors
What is action of NO?
step1
- secreted by endothelial cells
- inhibits local platelet activation
- vasodilates
What is major trigger of coronary thrombosis?
plaque rupture
What is role of ADP in platelet activation?
- activated platelets have ADP
- endothelial cells convert ADP –> adenosine so inhibit activation of platelets
What are endothelial cell mechanisms of platelet inhibition?
- release prostacyclin and NO that inhibit platelet activation
- convert ADP –> adenosine to minimize platelet activation
What are endothelial cell mech of vasodilation?
- release prostacyclin and NO that vasodilate
What are the 3 underlying causes of plaque disruption?
- chemical factors that destabilize fibrous cap: T lymphocytes secrete cytokines that inhibit collagen synthesis + MMP proteins in plaque degrade matrix
- physical stresses: shoulder region of cap due to high stress; high BP; torsion from myocardial contraction [high inotropy]
- triggers that increase chem or phys stress: emotional upset, physical activity; MI in morning when high BP
How does dysfunctional endothelium increase likelihood of thrombus formation?
- less secretion of NO/prostacyclin that normally inhibits platelets + vasodilate
- less able to fight against platelet products [thromboxane, serotonin] + thrombin promoting vasoconstriction
- –> reduces coronary blood flow and normal clearance of procoagulant factors
What happens to contractility in MI? 3 different types?
impaired contractility
- hypokinesis = reduced contraction
- akinesis = loss of contraction, larger infarct
- dyskinesisa = outward bulging during contraction, aneurysm, very large infarct
Why do you get impaired relaxation and thus diastolic dysfunction in MI? consequences?
relaxation is ATP dependent; less ATP in ischemia –> less compliance and thus increased filling pressures
What is stunned myocardium?
- after MI get prolonged but reversible period of contractile dysfunction
- restored days to wks after episode
- usually in areas adjacent to region of MI
What is ischemic preconditioning?
after episodes of ischemia –> get physiologic adaptations that render you resistant to further episodes = “warm up” phenomenon
- walk a few blocks, get chest pain, stop, now can walk longer w/o pain
If ST segment depression or T wave inversion and positive serum biomarkers with partially occlusive thrombus
what is it?
non-ST-elevation MI
If ST segment depression or T wave inversion and negative serum biomarkers with partially occlusive thrombus
what is it?
unstable angina
When should you suspect that ACS due to reason other than acute thrombus formation?
- young patient
- no coronary risk factors
What are some causes of acute coronary syndrome other than thrombus formation?
- vasculitic syndrome
- coronary embolism [from endocarditis or artificial heart valve]
- congenital anomaly of coronary arteries
- trauma or aneurysm
- severe coronary artery spasm [cocaine]
- increased blood viscosity
- coronary artery dissection
- severe aortic stenosis increasing O2 demand
What happens in early and late remodeling after MI?
early: thinning and elongation of fibrous scar within infarcted zone
late: dilation, transition elliptical to spherical configuration due to myocyte hypertrophy and increase interstitial collagen
What is a transmural infarct?
spans entire thickness of myocardium within zone of perfusion
results from total prolonged occlusion of coronary artery
What is a subendocardial infarct?
exclusively involves innermost layers of myocardium but may expand beyond zone of perfusion
subendocardium = susceptible to highest pressure and has few collateral + farthest from blood supply
What factors determine how much tissue is infarcted?
- mass of myocardium that is perfused by the occluded vessel
- magnitude and duration of impaired coronary blood flow
- oxygen demand of affected region
- presence of collateral vessels
When does irreversible cell injury occur following occlusive thrombosis?
w/in 20 min
What are the earliest histological changes of MI?
wavy myofibers = intercellular edema separates myocardial cells that are being tugged about by surrounding functional myocardium
start to occur in 4-12 hrs
What are contraction bands?
- see near border of infarct
- sarcomeres are contracted and consolidated and appear as bright eosinophilic belts
- can see w/in 12-24 hr
WHen does acute inflammatory response to MI occur?
approx 4-24 hrs after MI
What is hallmark of subendocardial ischemia on EKG?
ST depression
What is most sensitive and specific marker for MI?
troponin I
What types of ventricular remodeling in early post MI period?
infarct expansion
- infarcted ventricular segment enlarges = thinning and dilatation of necrotic zone
What are effects of infarct expansion in early post MI period?
- increases ventricular size which increases wall stress, impairs systolic contractile function, increases likellihood of aneurysm formation
higher mortality + risk of heart failure and ventricular aneurysm
What are clinical findings in infarct expansion?
- impaired systolic function
- new/louder S3 gallop sounds
- new/worsening pulm congestion
What happens in late ventricular remodeling post MI? What initiates it?
myocyte hypertrophy to minimize wall stress
initiated by: neurohormonal activation, myocardial stretch, activation of local tissue RAAS, paracrine/autocrine factors
What are some non-atherosclerotic causes of acute coronary syndrome?
- embolus due to mechanical valve or infective endocarditis
- vasculitis
- spontanoueous coronary dissection in peripartum female]
- cocaine abuse
How does cocain cause ACS?
- potent vasoconstrictor
- increases HR, inotropy, Ox demand
- causes vasospasm which reduces ox supply
- associated with increase risk atherosclerosis
What is MI type 1?
MI due to plaque rupture with thrombus
What is MI type 2?
MI due to supply/demand imbalance w/o rupture
What is MI type 3?
cardiac death
What is MI type 4/5?
MI in setting of revascularization procedure
Which type of MI has historical Q wave?
transmural [vs subendocardial = non-Q wave MI]
What are 3 different types of patterns of symptoms that could represent unstable angina?
- rest angina: at rest w/o provocation
- new onset: angina < 2 mo very severe
- crescendo/increasing: pt with chronic stable angina sudden increase in frequency/ duration/ intensity of episodes
What are clinical symptoms of MI vs unstable angina?
MI: more severe chest pain, radiates, longer duration, will no improve with rest or nitroglycerine, sympathetic response [tachy, nausea, diaphoresis, clammy cool skin], SOB, fever
unstable angina: may get better w/ rest, improves with nitroglycerine
What specific pt population do you worry about asymptomatic MI?
diabetics
What are physical findings [sounds] in MI?
- S4 due to atrial contraction against non-compliant LV
- S3 due to volume overload/HF
- systolic murmur –> MR if papillary muscle dysfunction or VSD
What are 2 examples of times you hear an S4?
- myocardial infarction
- hypertrophic obstructive cardiomyopathy
= sign of ventricular hypertophy
How do you distinguish pleuropericardial syndrome [pericarditis or pleuritis] from MI clinically?
pleuropericardial syndrome = pain worse w/ inspiration or position; diffuse elevated ST
How do you distinguish aortic dissection from MI clinically?
aortic dissection = tearing/ripping discomfort; BP asymmetry; widened mediastinum
What is order of EKG changes in STEMI?
before = normal
minutes/hrs = ST elevation
hrs/days = ST elevation, T inversion + Q wave
1 wk = coronary inverted T + Q wave deeper
mos = normal ST/T + Q wave
What is management for STEMI vs NSTEMI?
STEMI = immediate reperfusion with preferred door to balloon time < 90 min
NSTEMI = depends on risk stratification score
What are markers of myocardial necrosis?
- troponin [troponin-I]
- creatine kinase -MB
What is action of troponin?
controls Ca-mediated interactions between actin and myosin in cardiac and skeletal muscle
Where does troponin come from in cardiac injury?
- released from cytosolic pool and muscular pools as necrotic cell membranes degrade
What are normal values troponin I?
not normally detected in blood!
When can you detect troponin I in blood after MI?
- starts to rise after 4 hours and peaks in 24ish hrs
- declines slowly over 7-10 days
What will be values of troponin I and CK-MB at time 0 of infarct?
both may be 0; need a little time to rise up
What is creatine kinase?
enzyme involved in generation of ATP
When can you detect CK-MB in blood after infarct?
- peaks slightly faster than troponin [~24 hr] and returns to normal before troponin [~48 hr]
What do positive biomarkers tell you?
that MI occurred –> either STEMI or NSTEMI
Why is it important to measure CK-MB?
useful in diagnosis reinfarction following acute MI b/c should be totally normal w/in 48 hrs
What is general medical treatment for all ACS patients [NSTEMI and STEMI]?
- anti-ischemic [Bblocker, nitrates]
- general [pain control = morphine, give O2]
- antiplatelet [aspirin or clopidogrel]
- anticoagulant [heparin]
- adjunct [statin, ACE-I]
Why do you give B-blockers for ACS pts?
- relieve ischemia + ischemic pain
- reduce risk of arrhythmia
- mortality benefit; usually give w/in 24 hr
avoid in: bardycardia, bronchospasm, decompensated HF, hypotension
Why do you give nitrates for ACS pt?
- venodilation –> lower O2 demand/wall stress
- improve coronary flow/vasodilation, decrease risk vasospasm
- no mortality benefit = just symptomatic
- don’t give long acting due to changes in hemodynamic status
Who should not get nitrates in ACS?
- if hypotensive
- if STEMI pt w/ inferior MI and suspected RV infarction –> change in volume status could influence CO a lot and worry about hypotension
What is use of Ca channel blockers in ACS?
- nondihydropyridines [verapamil, diltiazem] reduce HR and contractility = anti-ischemic
- no mortality benefit
- use if contraindicated to BBlockers
What is use of aspirin in ACS?
- inhibits platelet synthesis of thromboxane A2 = mediator of platelet activation
- huge mortality benefit in all forms ACS
- give immediately on presentation
What is use of clopidogrel in ACS?
irreversible inhibitor platelet P2Y12 ADP receptor = anti-platelet
use in pt allergic to aspirin
can use in all pts with USA/NSTEMI unless surgery planned
What is treatment-risk balance of antithrombotics?
- helpful preventing clot formation or dissolving existing thrombus
- can cause thinning blood and bleeding risk –> higher risk for complications and death over time
What is use of prasugrel in ACT?
newer generation of clopidogrel
irreversible inhibitor P2Y12 platelet ADP receptor = more selective
use only if pt undergoing PCI
What is use of glycoprotein IIb/IIIa receptor inhibitors?
bind glycoprotein receptor IIb/IIIa on activated platelets and prevent aggregation
use primarily in pt undergoing PCI
What is use of heparin in ACS?
anticoagulant –> inhibit coagulation factor Xa
What are 2 alternative to heparin in ACS treatment?
direct thrombin inhibitors = only use w/ PCI
factor Xa inhibitir
What is difference unfractionated vs low molecular weight heparin?
UF-heparin = can bind factor Xa or thrombin
LMW heparin = binds preferentially factor Xa
What is conservative vs early invasive approach to USA/STEMI?
conservative: give meds alone; if clinical worsening or evidence of ischemia do angiography/revascularization
invasive: do urgent cardiac catheterization
do more invasive in higher risk pts
What is TIMI risk score calculator?
- age > 65
- > 3 risk factors for CAD
- known CAD w/ stenosis > 50%
- ASA used in past 7 days
- severe angina [> 2 episodes in 24 hrs]
- cardiac markers
more factors you have –> worse you do
early invasive recommended in score >=3
What is goal of STEMI treatment?
reperfusion via fibrinolysis or mechanical revascularization
What is optimal door to balloon time?
< 90 min
How effective is fibrinolysis vs primary PCI?
fibrinolysis –> 70-80% flow
PPCI –> 90% flow
greater benefit in PPCI esp if pt are sicker = good for elderly and tohse at risk for bleeding complications
Any mortality benefit to PCI?
depends on the scenario
- no benefit in stable ischemic heart disease
- clear benefit with STEMI
When do you prefer fibrinolysis over invasive strategy in STEMI pt?
- early presentation [< 3 hrs from symtpoms onset]
- invasive strategy not an option
- delay to invasive strategy [> 1 hr to invasive vs fibrinolysis now]
When do you prefer invasive strategy over fibrinolysis for STEMI pt?
- skilled PCI lab available
- door to balloon < 90 min
high STEMI risk [risk of cardiogenic shock] - contraindications to fibrinolysis
- later presentation
- diagnosis of STEMI is in doubt
What medical treatments for STEMI?
- antiplatelet [ASA, clopidogrel]
- anticoagulant [heparin]
- ACEI
- Statins
What type of MI has greatest benefit w/ ACE inhibitor?
anterior MI and systolic dysfunction
WHat is most cause of sudden cardiac death in early MI?
ventricular fibrilation
What do you do if you see signs of right heart failure in MI?
treat with volume expansion to correct hypotension
RV infarct wil cause high JVP and LV underfilling b/c of lack of RV compliance
What types of arrhythmias in MI?
supraventricular
- bradycardia
- tachycardia
- atrial fibrillation
ventricular fibrillation
What happens in free wall rupture?
happens in first 2 wks after MI = surgical emergency
get tamponade and die
What happens in pseudoaneurysm after MI?
get a contained myocardial rupture that is plugged by mural thrombus = at risk for rupture and thus tamponade
What happens in LV aneurysm in MI?
happens wks to mos after MI
no communication between LV cavity and pericardium
tissue bulges with cardiac contractions
can manifest on EKG as ST elevation
What happens in papillary muscle rupture in MI?
happens days to wks after MI
complete rupture –> severe MR –> HF or death
partial –> moderate MR and symptoms of HF
happens with RCA infarct usually
What is dressler syndrome?
autoimmune pericarditis happens wks to mos after MI
