Chronic Ischemic Heart Disease Flashcards
What is ischemic heart diseases and what is its most common manifestation?
A condiition of imbalance between myocardial oxygen supply and demand
Most common manifestation = angina pectoris
What influences myocardial oxygen supply?
Coronary perfusion pressure
Coronary vascular resistance
External compression
Intrinsic regulation
Local metabolites
Endothelial factors
Neural innervation
What influences myocardial oxygen demand?
Wall stress
Heart rate
Contractility
What percentage of oxygen is extracted from blood that travels through the coronary circulation?
75%
Myocardial oxygen supply depends on…
Oxygen content of blood and coronary blood flow
Coronary flow is directly proportional to _____ _______ and inversely related to _____ _______ ______
perfusion pressure; coronary vascular resistance
Perfusion pressure in the heart is dependent on _______ pressure
diastolic
What is the resting coronary flow?
What percentage of cardiac output is this?
225ml/min
4-5% of cardiac output
When is flow fastest?
Diastole > Systole
What processes allow autoregulation of flow?
- Metabolic factors (adenosine, lactate, pH)
- Sympathetic nervous system
- alpha-1 receptors - constriction and increased HR
- beta-2 receptors - dilation (minor)
- Over ridden by metabolic regulation
Smaller arteries derived from epicardial arteries supply which part of the heart?
Supply the inner layers of muscle and feed the subendocardial plexus
Why is flow to the endocardium limited during systole
Compressive forces are greater in the subendocardium
How does increased heart rate and contractility affect oxygen requirement
Increases oxygen requirement
How is wall stress calculated?
Laplace’s law
Wall stress = Pxr/2h
Pressure x radius/(2x thickness)
What is wall stress?
Tangential force acting on the myofibers tending to pull them apart
What is coronary flow reserve?
The maximal increase in blood flow achievable above normal resting flow (increase in demand for oxygen causes arterioles to dilate)
What percentage of obstruction is enough to overcome the saving effects of coronary flow reserve?
>90% obstruction - distal perfusion pressure is not able to maintain normal resting blood flow
(>70% obstruction - distal perfusion pressure is not sufficient to sustain increased flow during periods of increased demand)
What factors decrease myocardial distribution of blood flow with an obstruction during exertion?
- Reduced perfusion pressure
- Elevated LV end-diastolic pressure with exertion impedes subendocardial flow
- Increased heart rate decreases time during diastole (when subendocardium recieves blood flow)
What ECG changes are associated with subendocardial ischemia?
ST-segment depression
T wave inversion
What are collateral blood vessels and what is there function?
- Vascular channels that interconnect epicardial arteries
- Help to supply blood flow to ischemic regions caused by stenosis or occlusion of epicardial arteries
- Normally closed and non-functional because of lack of pressure gradient to drive flow
How does endothelial dysfunction contribute to ischemia?
- Inappropriate vasoconstriction due to imparied release of endothelial vasodilators
- Loss of normal anti-thrombotic properties
What are the main consequences of Ischemia?
- Inadequate oxygenation
- Reduced generation of ATP
- consequent elevation in diastolic pressure → Pulmonary congestion
- Local accumulation of meataboic waste products
- Can activate peripheral pain receptors
- Precipitates arrhythmias
What is stable angina in ischemic syndromes?
A predictable transient chest discomfort with exertion or emotional stress due to a fixed, obstructive plaque in one or more arteries
Causes innapropriate vasoconstriction contributing to reduced oxygen supply
What is unstable angina associated with ischemic syndromes?
- Sudden increase in ischemic episodes, occuring with lesser degrees of exertion
- Results from rupture of an unstable plaque with subsequent platelet aggregation and thrombosis
What is variant angina in ischemic syndromes?
- Episodes of focal coronary artery spasm in the absence of atherosclerotic lesions
- Also known as Prinzmetal’s angina
- Often occurs at rest
What is silent ischemia?
What is syndrome X?
Silent Ischemia: episodes of cardiac ischemia that sometimes occur in the absence of discomfort or pain
Syndrome X: Patients with typical signs of angina who have no evidence of significant athersclerotic stenoses
Describe the quality and location of discomfort associated with chronic stable angina
- Pressure, discomfort, tightness, burning, heaviness in chest
- Usually diffuse, most often located in the retrosternal area or precordium
What are some accompanying symptoms with Chronic stable angina?
Tachycardia, diaphoresis, nausea - due to sympathetic and parasympathetic activation
What are the ECG readings associated with chronic stable angina?
During ischemia, ST segment depression and T wave inversion
Sometimes ST segments elevations are seen indicative of more severe transmural ischemia (intense vasospasm of variant angina)
How do you diagnose chronic stable angina?
Stress testing - provocative exercise or pharmacological stress tests
Standard exercise stress test - monitor ECGs during treadmill exercise
Pharmacological stress test - uses dobutamine (increases myocardial O2 demand) or adenosine (coronary vasodilation)
How are lesions visualized in chronic stable angina?
Visualized radiographically following the injection of a radiopaque contrast media into the artery
Goals of IHD therapy
Decrease frequency of anginal attacks
Prevent acute coronary syndromes such as MI
Slow disease progression and prolong survival
Anti- Angina therapy
Decrease O2 demand
Increase O2 supply
Nitrates MOA
- Enzymatically denitrated in smooth muscle - converted to NO
- NO activates guanylyl cyclase increasing cGMP
- cGMP activates protein kinase
- Kinase phosphorylates targets leading to decreased calcium and phosphorylation of myosin
What effects do Nitrates have on the ischemic heart?
- Increase venous capacitance (decrease preload)
- Small reduction in systemic arterial blood pressure
- Coronary dilator
How do nitrates cause reflex tachycardia
Increased contractility due to reduction in blood pressure
How is nitroglycerin inactivated?
High capacity organic nitrate reductase in the liver - low bioavailability due to extensive 1st pass metabolism
Which nitrate is metabolized to its active form?
Isosorbide dinitrate is metabolized by liver to mononitrate form: Mononitrate is biologically active
How are nitrates administered?
Administered sublingually as rapid dissolvable tablets or aerosol spray - fast onset and short duration of action
How are nitrates used in cronic therapy?
Nitrates provide prophylaxis against angina episodes in patients with more than occaisonal angina
What are differences between Isosorbide Dinitrate, Isosorbide Mononitrate and Nitroglycerin?
- Isosorbide Dinitrate
- 25% orally bioavailable
- Metabolized to mononitrate form that is active
- Isosorbide Mononitrate
- No 1st pass metabolism
- Half life is about 5 hours
- Nitroglycerin
- Orally as controlled release tablets
- Available as a patch and ointment/paste applied to skin
How are Nitrates associated with tolerance?
Complete tolerance can develop if used continually for more than a few hours - reverses rapidly (24 hours after stopping drug)
How do you overcome tolerance in treatment with Nitrates?
Use smallest effective dose
Schedule nitrate-free period of at least 8 hours to reduce or prevent tolerance particularly with patches
Adverse effects of nitrates
- Due to cardiovascular actions
- Headache
- Hypotension
- Reflex tachycardia
- Flushing
How do ß-adrenergic receptor blockers work?
- Exert anti-anginal effect primary by reducing oxygen demand
- Decrease the force of ventricular contraction and heart rate due to blockade of effects of endogenous catecholamines on ß1 receptors
What are non-selective ß-blockers?
What are the selective ß blockers?
- Non-selective
- Propanolol; timolol
- ß1-selective antagonists
- Metoprolol, atenolol
What are ß-blockers effects on the ischemic heart?
- Decrease oxygen demand
- Small increase in oxygen supply to ischemic areas
- Decrease cardiac output → increase in preload that can result in increased wall tension
ß-blockers - adverse effects and contraindications
- Patients with significant obstructive airway disease
- Not used in patients with acutely decompensated heart failure
- Patients with marked bradycardia or heart block
- Patients with insulin treated diabetes
- Adverse effects: fatigue, sexual dysfunction
Two types of calcium channel blockers?
Dihydropyridines and Non-Dihydropyridines
What drugs are Dihydropyridines? What do they do?
Nifedipine and amlodipine
- Potent vasodilators
- Decrease oxygen demand
- Increases oxygen supply by coronary vasodilation
- Potent agents for relief of vasospasm
What drugs are non-dihydropyridines? What do they do?
Verapamil and diltiazem
- Vasodilators (less potent than dihydropyridines)
- Decrease oxygen demand by reducing the force of contraction and heart rate
- Verapamil, diltiazem
Adverse effects of calcium channel blockers (and the specific drugs for each)
- Headache, flushing
- Decrease contractility (V, D)
- Bradycardia (V, D)
- Edema (especially N, D)
- Constipation (especially V)
There are potential benefits of combining a ______ with a __ ________
Nitrate with a ß blocker
ß blockers prevent reflex increase in heart rate and contractility produced by nitrates
Nitrates prevent potential increase in wall tension produced by ß blockers
Care should be taken in combining a ß blocker with a ________________
nondihydropyridine calcium blocker
Additive negative inotropic effect can cause excessive cardiodepression
What is the function and MOA of Ranolazine?
Decreases the frequency of anginal episodes and increases exercise capacity
Inhibits the late sodium current (INa+) in cardiac myocytes (blocks ion channel allowing calcium to come into cell)
What types of medical therapy are used to prevent acute cardiac events?
Antiplatelet therapy - platelet aggregation and thrombosis are key elements in the pathophysiology of acute MI and unstable angina
Lipid-regulating therapy - HMG-CoA reductase inhibitors (statins)
In antiplatelet therapy if asprinin is contraindicated, what else can be used?
ADP P2Y12 receptor blockers
How is revascularization achieved?
Percutaneous coronary intervention (PCI)
Coronary artery bypass graft surgery (CABG)
What is PCI?
Percutaneous Coronary intervention (including percutaneous transluminal coronary angioplasty (PTCA))
Coronary stents including drug-eluting stents reduce the rate of restenosis (also balloon tipped catheters)
What is CABG?
Involves grafting portions of a patient’s native blood vessel to bypass an obstructed artery
- Use of native veins
- Arterial grafts
