15 - Ischemic Heart Disease

CAD most common cause

Atherosclerosis-caused narrowing of the coronary arteries

CAD vs IHD

Coronary artery disease is what happens to the arteries, and the decreased blood supply causes downstream ischemic heart disease

• Since ischemia means mismatch between O2 supply and demand

2 main types of IHD

• Chronic coronary syndrome(Chronic stable angina)

• Acute coronary syndrome

What causes CCS vs ACS?

1. CCS: A stable plaque that grows and occludes the lumen → 70% occlusion leads to symptoms of angina pectoris(chest pain) on exercise

2. ACS: A vulnerable plaque ruptures, triggering thrombosis in the coronary artery, blocking it acutely → angina pectoris(at rest too)

Difference between a vulnerable and stable plaque

• Vulnerable plaques have more fat and less thick of a fibrous cap

• Stable plaques have less fat and a thicker fibrous cap

Types of ACS

• ST elevation ACS: STEMI

• non-ST elevation ACS: Unstable angina, NSTEMI

Unstable angina difference from stable angina

The pain is no longer predictable(with exertion) and it’s a warning sign of worse to come

What is the main point of taking history of a patient with chest pain, and what history do we take?

To clarify if it’s caused by the heart and specifically from ischemia or the heart or not

• Risk factors: DM, smoking, family history, hypertension

• Character of pain: Constricting discomfort of chest/neck/jaw/shoulder, whether or not it’s precipitated by exercise and if it’s relieved by rest within 5 minutes

How do we interpret the results of the character of pain triad?

• If all 3 are present: Typical angina → strongly suggests cardiac ischemia

• If 2/3 are present: Atypical angina → Also suggests cardiac ischemia, but less confidently

• 1 or none: Non-anginal chest pain → More likely something not cardiac related

Let’s say we’ve determined the patient’s chest pain is likely from angina, what do we do next, and why?

We try to see what type of angina it is(Stable or unstable)

1. Rest angina for over 20 minutes: Shows that the artery is so blocked that even the lower O2 demand at rest can’t be met

2. New-onset angina

3. Crescendo angina

How do we interpret the angina type questions?

If any of the 3 are met, we can unstable angina and treat them under ACS guidelines. If they are stable, we can do stress tests to see how severe the CAD is and what kind of treatment is needed

Purpose and examples of functional testing

• Purpose: A moderately narrowed coronary artery can still deliver blood to patients at rest, so we have to put them under stress to see if there’s an underlying issue

• Exercise or pharmacological agents(Dobutamine, adenosine via vasodilation)

What is the red flag sign after doing a exercise/pharmacological stress test?

ST-depression

Coronary CTA vs coronary MRA

• Computed Tomography(CT) Angiography is looking at a cross section of coronary arteries after injecting IV contrast dye and can rule out significant CAD

• Coronary Magnetic Resonance Angiography is a test that avoids radiation exposure but is more difficult to do

Stress echo vs stress MPI

• Stress echocardiography is an ultrasound of the heart, done before and after stress. If a segment of the heart contracts poorly after stress is applied, it shows there’s inadequate supply

• Stress MPI is a method that directly visualizes blood perfusion to heart muscle regions(also done before and after stress)

Invasive coronary angiography

• Invasive but gold-standard test; a catheter that shoots contrast dye into a corornary artery, and we X-ray to see the dye filling the vessel

  • Any narrowing will show up as the dye itself narrowing as it goes through that segment

Occlusion in STEMI, NSTEMI, unstable angina

STEMI: Total

NSTEMI/unstable angina: Partial

Unstable angina vs NSTEMI

No cardiac injury yet vs cardiac injury already has occurrred

What are some atypical presentations of ischemia?

Epigastric pain, diaphoresis, syncope

In a patient who could have ACS, why do we an EKG w/in 10 minutes?

Rule out STEMI

What happens to ions when there is a myocardial ischemic injury, and what does that lead to?

• Extracellular potassium goes up, which boosts the RMP

  • This matters because the RMP is a readout of the equilibrium point between K+ gradient in and out of the cell(How much K+ leaves, since intracellular has more K+) vs the negative charge inside the cell pulling K+ back in via electrical charge

    • Normally, K+ flows out of the cell via concentration gradient, while K+ also flows back in because when K+ leaves, it makes the inside more negative, which draws the K+ back in, so it settles

    • When there’s more K+ outside, the concentration gradient is smaller(Usually there’s more K+ inside, and K+ wants to leave)

      • As a result, the outward push of K+ is weaker, the inward pull(electrical) doesn’t have to be as strong, so the inside doesn’t need to be as negative, so the RMP equilibrium shifts to a less negative value

What does a increased RMP mean for the heart?

1. Increased RMP keeps Na+ channels inactivated(because they need a certain RMP to reset)

2. Less Na+ channels to allow Na+ in reduces the amplitude of action potential

3. This means that the action potential may not reach the depolarization level needed to activate Ca2+ channels in phase II, so less Ca2+ flows into the cell

4. This makes the plateau phase shorter, so repolarization happens faster → Can cause arrhythmias(reentry)

5. Separately, less Ca2+ enters → Weaker contraction

How are the charges in a resting cardiac cell, what happens in contraction, and what does it mean?

• Inside: Negative

• Outside: Positive

• When depolarization sweeps through, it flips to positive inside, outside negative

  • This creates a dipole(one side is the wave front where the outside is negative and the other, back direction is outside positive) and we draw vectors from the depolarized zone to the not-yet depolarized zone

  • If this wave is traveling to the positive electrode → positive deflection

TP segment

• What is it?

• Normally

• When there’s an infarct → implication on EKG

• Diastole(The end of the T-wave is ventricular repolarization finished, and waiting before the next atrial depolarization)

• Isoelectric

• Becomes more negative

Why does the TP segment become more negative in an infarct? Explain using charges

• Normally, cells are negative on the inside and positive on the outside

• When there’s an infarct, the inside of the cells are more positive than usual, and the outsides are more negative than usual(This is because with more K+ outside, the gradient of K+ leaving the cell is weaker, so the cell needs only a smaller negative charge to pull back the K+ back at equal rates, since not that much is leaving now, so the inside is relatively positive while the other side becomes relatively negative

• EKGs see only the outside surface of these cells, never the inside. So the outside surface of healthy tissues are positive while infarcted tissues are negative

  • This forms a dipole(a negative/positive area next to each other), and vectors point from the negative region to the positive region, so it points away from infarct to the healthy tissue

  • On the EKG most close to the infarct, the vector points away from the close infarct to the healthy tissue on the far sides → negative deflection during the TP segment(that shouldn’t normally have any charge differences in rest)

ST segment

• What is it?

• Equivalent to what phase of action potential

• Normally

• When there’s an infarct → implication on EKG

• Period after ventricular depolarization and haven’t repolarized yet

• Phase 2(Plateau phase) of ventricular action potential

• Isoelectric since charges aren’t moving around

• Elevates

Why does the ST segment become more positive in an infarct? Explain using charges

• Ischemic cells have a shorter action potential(Because less Ca2+ entry and boosted K+ efflux)

  • This means that healthy cells are still depolarized(Inside positive/outside negative), ischemic cells start to repolarize → inside becomes relatively negative and outside becomes relatively positive

  • Remember, EKGs read only the outside of the cells, so it sees that healthy cells are negative on the outside, and ischemic cells are relatively positive on the outside

  • Vectors will point from negative to positive, so the EKG close to the infarcted lead will see the positive charge coming to it → positive deflection

Those last 2 theories are called…

The diastolic and systolic theories for ST elevation

“Subendocardial ischemia is associated w ST segment depression”

• Explain this statement via diastolic and systolic sides

• What kind of disease does this correlate with?

• The subendocardium is the last territory reached by coronary blood flow, meaning it is most vulnerable to drops in blood supply

  • These ischemic subendocardial cells will have a less negative RMP, so in diastole, they stay relatively positive compared to their neighbors and their outsides(read by the EKG) are relatively negative

  • All of it’s neighbors are negative on the inside, positive on the outside

  • Vectors will point from negative to positive(outside the cells), so here it’ll point from ischemic subendocardium to healthy tissue. However, the healthy tissue is closer to the chest wall/electrode(Since it’s the epicardium), so the vector points to the electrode, creating a positive deflection

  • This positive TP will make the ST seem depressed, even if it isn’t.

• In systolic, remember that the ischemic cells repolarize early, which means that their outside becomes positive relative to the negative outsides of the normal cells(inside positive, still depolarized). So the vectors are pointing to the ischemic subendocardium, and since the subendocardium is deeper/further away from the electrode than the healthy tissues, it points away from electrode and shows up as ST depression

• Correlates with NSTEMI and unstable angina

These walls of the heart are supplied by which arteries?

1. Inferior

2. Anteroseptal

3. Anteroapical

4. Anterolateral

5. Posterior

1. Inferior: RCA

2. Anteroseptal: LAD

3. Anteroapical: Distal LAD

4. Anterolateral: CFX

5. Posterior: RCA

An infarction of these vessels will be shown as ST elevations and depressions in which leads?

RCA: II, III, aVF, inverted in I, aVL

LAD: V1, V2

Distal LAD: V3, V4

CFX: V5-V6, I, aVL, inverted in II, III, aVF

RCA: none, inverted in V1-V3

Pathological Q-wave is ___, and why?

• Pathological Q-waves in V1-V6 mean?

A sign of dead heart muscle because the actual dead muscle the lead is measuring makes nothing, yet the lead sees across the other side of the heart and sees it’s R wave(but going away, since it’s on the other side) so it appears as a Q wave, just wide and deep

• Pathological Q waves in V1-V6 mean a proximal LCA occlusion → MI of the anterior wall(entirely since both LAD and LCX lose supply)

What troponin types are used in measurement?

Type I and T

What does troponin measure

Cardiac myocyte death

High sensitivity troponin

New assay technology that can detect troponin at much smaller amounts, even to the point of normal, healthy range

What two conditions does high troponin differentiate?

• N-STEMI: Has high troponin

• Unstable angina: Normal troponin

Troponin measurement flow chart

• Why do we need it

• What is it?

• We need it because troponin doesn’t rise right as a plaque ruptures → we need to wait for the damaged cardiomyocytes to leak troponin in detectable amounts

• We use hs-cTn(high sensitivity cardiac troponin) measured at arrival and 3 hours later

  • Branch 1:If troponin is normal on arrival, and the patient has had chest pain for 6 hours, it means it’s normal for real. If the pain has been present for less than 6 hours, wait 3 hours then test again, only if there’s no change, we rule out injury(N-STEMI)

  • Branch 2: If troponin is elevated on arrival, it tells us cardiac injury has already occurred. If the elevation is mild/moderate, we retest at 3 hours and if there’s a significant change(50% or more increase with one value above ULN if it wasn’t already above, or a 20% or more increase if it was already above ULN), it confirms a evolving NSTEMI. If the elevation is high, we suspect ACS and go to invasive management right away

Triphenyltetrazolium chloride test

• Done in what, and what are the results?

• Autopsy to confirm if there was an infarct. Healthy cells have lactate dehydrogenase which will turn the TTC molecule red, but infarcted tissue won’t have this enzyme, so the tissue stays white

Reperfusion pros and cons

• Pros: Saves ischemic muscle that isn’t dead yet

• Cons: Can damage cells and push them over the edge to death

Organic Nitrates

• Names

• Mechanism

• Isosorbide dinitrate, isosorbide mononitrate, nitroglycerin, peritrate

• Organic NO donor, helps with vasodilation(venodilation at low/moderate dose, coronary artery vasodilation at high dose)

  • NO → boosts cGMP → lowers Ca2+ in smooth m. → less contraction → relaxation

Sublingual organic nitrate tablet use case

• Acute anginal pain in CCS patients

IV, lingual spray organic nitrates use case

• Acute anginal pain in ACS

Oral form organic nitrates use case

Long term prevention of angina in CCS/ACS, but keep 12 hours a day nitrate free to prevent tolerance

Don’t take organic nitrates with…

Sildenafil(viagra) or else there will be too much vasodilation → potentially fatal

What do beta blockers treat in coronary artery disease/ischemic heart disease, and what is their use case?

1. Angina: Reduces the HR and contractility so we demand less O2

2. Lengthens diastole: Allows for the coronary arteries to perfuse more

3. First line prophylactic therapy in CCS, and treatment of ACS

What do CCBs treat in coronary artery disease/ischemic heart disease, and what is their use case?

CCBs, specifically non-DHP CCBs act on the heart and has the same effects as beta blockers to help relieve O2 demand and boost diastole

• Relieves angina and boost diastole

• CCS and ACS in pt. who can’t use beta blockers

Brief function and use case of

• Ivabradine

• Ranolazine

• Trimetazidine

• Ivabradine: Blocks funny current → reduces chronotropy → slows HR → use in CCS

• Ranolazine: Blocks late Na+ current → reduces intracellular Na+ and then Ca2+ → reduces O2 demand(by also shifting the heart’s preference to burn more glucose which is more O2 efficient) → use in CSS as add-on to BBs/CCBs, not as a replacement

• Trimetazidine: Inhibits fatty acid oxidation → O2 efficiency increases → use in CSS as add-on to BBs/CCBs, not as a replacement

Use case of ___

• Aspirin

• Long term low dose in CCS to make sure platelet plugs don’t form

• Single high dose(chewed) in ACS to stop current episode, then long term low dose

Use case of ___

• ADP receptor antagonist

  • What types are there?

• Aspirin alternative in CCS or as dual treatment in ACS if needed

• 2 types of ADP receptor antagonists: Clopidogrel(prodrug) and ticagrelor(active drug)

Use case of ___

• UFH

• Continuous IV infusion in ACS management

Use case of ___

• LMWH

  • Name example

• SC injection in ACS

  • Enoxaparin

Use case of ___

• Fondaparinux

• SC injection in ACS

Use case of ___ and why?

• Fibrinolytics

  • Types of fibrinolytics

• Reperfusion in STEMI if PCI isn’t available quickly enough

  • Streptokinase: Binds plasminogen, forms a SK-plasminogen complex to activate other plasminogens to make them become plasmin(One time use!)

  • -teplase: Acts as an enzyme to help activate plasminogen

Absolute contradictions of anticlotting drugs

• Prior hemorrhagic stroke, ischemic stroke w/in past 3 months, aortic dissection, internal bleeding

How do statins and RAAS inhibitors help in CAD?

1. Statins: Lowers LDL, stops new plaque formation/progression and also stabilizes existing plaques

2. RAAS inhibitors: Decrease BP(less endothelial damage), reduces cardiac workload

PCI stands for

Percutaneous coronary intervention

In STEMI, when do we pick PCI, when do we pick fibrinolytics?

• PCI because it is more effective, but if we can’t do it within 120 minutes of medical contact, we should give fibrinolytics

Why do we have to give parenteral anticoagulants with tPA, but not with SK?

Because SK causes widespread plasminogen activation which can use up fibrinogen, so adding parenteral anticoagulants would just make it worse and risk bleeding. Meanwhile, tPA is fibrin specific and work at the clot, but this also means that the underlying ruptured plaque can just re-thrombose, so we have to give parenteral anti-coagulants to stop this