11/4 Ischemic Heart Disease (ACS) - Moreyra Flashcards
myocardial oxygen supply vs. myocardial oxygen demand
factors affecting oxygen supply
- oxygen content
- in clinical practice, anemia/low Hb doesn’t really hold as a cause of oxygenation imbalance bc compensation kicks in
- coronary blood flow
- depends on perfusion pressure and resistance
- resistance is the major determinant of flow; influenced by several addt’l factors:
- external compression: incr resistance/decr flow during systole
- arterial tone
- metabolic factors: hypoxia? ATP→ADP→AMP, releasing ADENOSINE (powerful coronary vacodilator). also lactate, acetate, H, CO2
- endothelial factors: vasodil via cGMP
- neural factors: SNS alpha, beta2 receptors
endothelial factor induced relaxation
endothelial vasoactive factors
myocardial oxygen supply vs. myocardial oxygen demand
factors affecting oxygen demand
- wall stress: S = P*r/2h [h = thickness]
- heart rate
- contractility
atherosclerosis timeline
newer theory about heart ischemia
- not just obstruction of coronary vessels via ischemia
- combo of atherosclerosis AND increased tone of coronary vessels
- both together: DECREASED FLOW OF BLOOD
relationship between stenosis and flow
increasing stenosis decreases the change in flow that will result from vasodilation
- eventually, mismatch in supply and demand
interaction between platelets and endothelial cells
recall: in general, when platelets aggregate, they stimulate sm muscle contraction (vasoconstriction)
endothelial cells produce vasoactive substances: prostacyclin and NO
- cause vasodilation via relaxation of sm muscle
- prevent platelets from aggregating
implication: damage to the endothelium leads to vasoconstriction (directly and indirectly) → contributes to ischemic heart disease along with any existing obstructions
ischemic heart disease
most common cause of ischemia: atherosclerosis
risk factors:
- existing conditions: HTN, diabetes, hypercholesterolemia
- modifiable: lifestyle, smoking, diet
- fixed factors: male sex, age, genetics
cellular composition of atherosclerotic plaques
manifestations of myocardial ischemia
chest pain
decreased contractility
- necrosis (MI)
- stunned myocardium
- hibernating myocardium
congestive heart failure
arrhythmias
sudden death
ischemic syndromes
-
stable angina: chest pain occuring in a predictable fashion
- pt knows what will trigger, can avoid
-
unstable angina: chest pain with an unpredictable pattern
- pt cannot predict/avoid
- myocardial infarction: lack of blood flow → infarct
- variant angina: decrease in blood flow WITHOUT increase in demand! due to transient coronary spasm
- silent ischemia: ischemia minus the pain warning system
-
syndrome X: no obstruction, but yes ischemia/pain
- poss obstruction at capillary level (which can’t be seen in imaging)
effect of nitroglycerine on chest pain (due to decr blood flow)
nitroglycerine is a powerful vasodilator, dilates everything
- dilates coronary artery → incr flow to heart
- dilates peripheral veins → decr venous return → overall decrease in heart size (aka decr in radius) → less tension → less oxygen demand!
aortic dissection pain vs ischemic pain
aortic dissection: TEARING, RIPPING, 10/10 pain, radiating to front/back
ischemic pain: heaviness, tightness, choking, toothache, burning, etc.
lab diagnosis
- creatinine kinase
- CK - isoenzymes
- MM: muscles (cardiac and skeletal)
- MB: cardiac muscle only
- troponins: I & T (specific to myocardium)
- LDH (long lasting, when originating from myocardium)
- myoglobin (impractical and expensive)
treatment of ischemic heart disease
goals
medical treatment for acute angina, recurrent angina, acute events
goals:
- decrease angina attacks
- prevent progression to ACS
- prolong survival
meds for:
- acute angina
* nitroglycerine - prevention of recurrent angina
- organic nitrates
- beta blockers
- Ca channel blockers
- prevention of acute events
- ASA
- clopidogrel
- prasugrel
- ACE inhibitors
- statins
myocardial revascularization techniques
- percutaneous coronary intervention (PCI)
- coronary artery bypass graft (CABG)
acute coronary syndromes
- characterized by thrombus formation
- with increasing severity, see ST elevation
there are lots of factors produced by the endothelium to prevent unnecessary clotting
- atherosclerosis increases the chances of aberrant clotting due to endothelial dysfx
mechanisms of coronary thrombus formation
histo signs of infarction
MI 18-24hr
- loss of nucleus
- contraction bands
- coagulation necrosis
MI 3-4d
- hemorrhage
- inflammation
MI 1-2w
- granulation tissue
MI 2-4w
- resorption
- fibrosis
MI >4-6w
- collagen scar
mechanisms of cell death in MI
hypoxia → no ATP made and switch to anaerobic metabolism
- no ATP made
- function of Na/K ATPase is altered → extracellular K, intracellular Na, intracellular Ca
- altered membrane potential → arrythmia
- intracellular edema
- anaerobic metabolism
* intracellular H → chromatin clumping, protein denaturation
overall, intracellular Ca and damage to chromatin/proteins/lipids/etc →→→ cell death
consequences of coronary thrombosis
algorithm/flowchart
possibilities:
1. small thrombus (non flow-limiting)
- no ECG changes
- outcome: healing, plaque enlargement
2. partially occlusive thrombus
-
ST segment depression and/or T wave inversion
- neg serum biomarkers → unstable angina
- pos serum biomarkers → non-STE MI
3. occlusive thrombus
-
transient ischemia → ST segment depression and/or T wave inversion
- neg serum biomarkers → unstable angina
- pos serum biomarkers → non-STE MI
-
prolonged ischemia → ST elevation (Q waves appear later)
- pos serum biomarkers → STEMI
MI chart
sx
serum biomarkers?
EKG initial findings
likelihood for ACS secondary to CAD
acute coronary syndrome: high, intermed, low likelihood
- history
- exam
- EKG
- cardiac markers
pattern of CK-MB and troponin rise following STEMI (w/ and w/out reperfusion)
- with reperfusion: peak and washout earlier than without reperfusion
- CK-MB returns to normal sooner than cardiac troponin
components of TIMI Risk Score
- age >65yr
- presence 3+ risk factors (DM, HTN, smoking, etc)
- known CAD (stenosis >50%)
- ASA use in last 7 days (aspirin)
- 2+ episodes of angina in last 24h
- ST seg changes >0.05nV
- pos cardiac markers
how does streptokinase work
diff between SK and tPA
leads to formation of plasmin → breaks down fibrin clots
- can cause systemic lytic state (bc it binds to all plasminogen, not just that which is bound to the clot already)
- do not see systemic lytic state with tPA
both tPA and SK have complications: bleeding!
- 1% intracranial bleeding, can be fatal
strategies to treat MI
how do you choose what type of strategy to use? (invasive vs conservative)
- risk score
- pt/physician preference in low risk situations
both of these suggest conservative tx
invasive strategies indicated if..
- hemodynaimcally unstable
- electrically unstable
- high risk score
- elevated TnT or TnI
- reduced LV (LVEF under 40%)
- ‘new’ ST seg depression
- PCI within 6mo/prior to CABG
platelet mediated thrombosis targets
- adhesion: no currently approved antiplatelent agents targeting
- activation: most agents affect this step by blocking ADP and P2Y-12 receptors
- prasugrel
- clopidogrel
- ticlopidine
- aspirin
- aggregation: GP IIb/IIIa inhibitors inhibit “final common pathway”
- abciximab
- eptifibatide
- tirofiban
