Summative 4 Cases

64y/o patient suffers acute MI involving anterior 2/3 of interventricular septum. Hours later, patient develops third degree (complete) AV block.

Which coronary artery was occluded, and why did the conduction abnormality occur?

LAD (Left Anterior Descending Artery)

supplies blood to anterior 2/3 of interventricular septum, which Bundle of His and R/L bundle branches travel through

ischemic necrosis of septum disrupts conduction = severe AV conduction block

Patient diagnosed with cardiac tamponade caused by pericardial effusion.

List layers around/of heart in order from most superficial to deepest, and identify where fluid accumulates.

AKA surrounding excess fluid compresses heart, impairing diastolic filling

out to in:

1. fibrous pericardium

2. parietal serous pericardium

3. parietal cavity

4. visceral serous pericardium / epicardium

5. myocardium

6. endocardium

Distinguish between pectinate muscles and trabeculae carneae, based on location/function.

pectinate muscles:

• parallel, comb-like muscular ridges

• anterior walls of RA/LA

  • most prominent in RA and auricles

trabeculae carneae:

• irregular, “meaty,” beam-like muscular columns

• inner walls of RV/LV

ECG reveals structural depression in interatrial septum of adult patient.

What is this landmark?

Fossa Ovale (in utero, Foramen Ovale)

shunted oxygenated blood directly from RA to LA to bypass non-functional fetal lungs

birth = atmospheric P changed = hole fused closed into smooth depression

3 types of capillaries

1. continuous

   1. tight junctions = no openings

   2. ex. BBB

2. fenestrated

   1. small endothelial pores (AKA fenestrations)

   2. allow some exchange

   3. ex. endocrine glands for hormones, kidneys

3. discontinuous

   1. wide with large intercellular gaps + incomplete basal lamina

   2. allows larger proteins to pass

   3. ex. liver, spleen, bone marrow

purpose of papillary muscles

contract during ventricular contraction

= pulls chordae tendinease (strings) = keeps tricuspid/mitral valves tightly shut to prevent backflow into RA/LA under high P

structural differences between arteries and veins

arteries:

• thicker tunica media

  • middle layer of smooth muscle

• firm, round lumen

• = withstand high systemic arterial P

veins:

• thicker tunica adventitia

  • outer layer of collagen/elastin

• collapsed, irregular lumen

• = allows high stretch as reservoir

pathway of heart supplying ITSELF with blood

oxygenated via lungs, 4 PAs, LA, MV, LV, AV into ascending aorta

2 aortic ostia feed heart muscle directly:

1. LCA splits into:

   1. LAD (Left Anterior Descending) artery

      1. anterior 2/3 of interventricular septum

      2. anterior LV

   2. circumflex artery

      1. LA

      2. posterior LV

2. RCA splits into:

   1. right marginal artery

      1. RV

   2. PDA (Posterior Descending) artery

      1. posterior 1/3 of interventricular septum

      2. inferior LV

coronary arteries branch out into thin myocardial capillaries across myocardium

deoxygenated after myocardium

1. great, middle, and small cardiac veins

2. coronary sinus

   1. large collecting vessel on posterior

3. RA, TV, RV, PV, back into lungs

Patient loses 500mL of blood during donation, stimulating SNS.

What receptors are responsible for this, and what is the purpose of parallel circuits?

alpha-1 vasoconstricts

systemic BVs arranged in parallel circuits between aorta and RA, allows for selective shunting of blood towards priority organs

Patient presents with acute blood loss and HTN. Arterial baroreceptors sense drop in MAP.

What are the compensatory mechanisms, along with RAAS?

1. baroreceptors in carotid sinus and aortic arch detect low BP

   1. alpha1 vasoconstricts

   2. beta1 increases HR + contractility

   3. M2 inhibited

2. RAAS triggered by low BP

   1. renin released to convert angiotensinogen into A1

   2. ACE converts A1 into A2

   3. vasoconstriction + aldosterone released

   4. sodium/water reabsorption to increase BV

determinants of myocardial O2 demand

1. increased HR

   1. via beta1

2. increased preload bc more venous stretch

   1. via alpha1

3. increased afterload bc more SVR to push against

4. increased contractility bc stronger squeeze

   1. via beta1

62y/o patient with long-standing diabetes mellitus and chronic kidney disease (CKD) but normal LDL levels develops an advanced coronary atherosclerotic plaque.

How can this occur despite normal LDL, and what is the progression?

atherosclerosis is caused by endothelial injury

• diabetes’ hyperglycemia causes glycation + damage

• CKD’s hyperphosphatemia causes Ca2+ and phosphate crystal deposition

from there:

1. LDL enters + oxidizes

2. macrophages ingest = foam cells

3. smooth muscle recruits collagen to make fibrous cap

4. plaque rupture caused by:

   1. thin fibrous cap + large necrotic core

   2. inflammation degrades collagen

stable angina vs ACS

stable angina

• stable plaque restricts flow

• chest pain only with exertion

ACS (Acute Coronary Syndrome)

unstable angina

• acute plaque change (erosion)

• = transient/subtotal thrombus formation

• unpredictable chest pain

NSTEMI

• plaque ruptures = thrombus partially blocks

• elevated troponin

• ST-segment depression

STEMI

• plaque ruptures = thrombus completely blocks

• elevated troponin

• ST-segment elevation

sudden cardiac death

critical post-MI complications

arrhythmia

• ischemic tissue disrupts conduction with healthy tissue

  • abnormal automaticity

  • exacerbated by pain/anxiety stimulating SNS

• symptoms:

  • high HR

  • high BP

  • diaphoresis

cardiogenic shock

• ≥40% of LV myocardium is destroyed

  • can no longer eject

  • decreases SV and CO

• symptoms:

  • high HR

  • low BP

  • tissue hypoperfusion

    • confusion, dyspnea

    • cold/clammy skin from intense SNS vasoconstriction

conditions that increase atherosclerosis risk

• hyperlipidemia

• HTN

• smoking

• diabetes mellitus

  • via hyperglycemia

  • causing glycation

• CKD

  • via hyperphosphatemia

  • causing Ca2+ and phosphate crystal deposition

• chronic inflammation

62y/o patient with acute STEMI undergoes emergent PCI via DES.

What should be administered? Compare the P2Y12 antagonist options.

DAPT = aspirin + P2Y12 antagonist

antiplatelets = prevent clot formation on stent via 2 pathways

1. ASA inhibits COX-1 to block TXA2 synthesis

2. P2Y12 antagonist competitively inhibits ADP from binding, for entire platelet lifespan (5-7 days)

P2Y12 antagonist options:

• Clopidogrel

  • once daily

  • lower efficacy

    • especially with CYP2C19 LOF

  • lowest bleeding risk

• Prasugrel

  • once daily

  • higher efficacy

  • higher bleeding risk

    • age > 75yrs

    • weight < 60kg

    • history of stroke/TIA

• Ticagrelor

  • BID

  • higher efficacy

  • higher bleeding risk

    • GI upset

    • dyspnea

GpIIb/IIIa inhibitors

antiplatelet

inhibits fibrinogen activation to prevent cross-linking between adjacent activated platelets

3 types:

1. Abciximab

   1. monoclonal antibody therapy

   2. very long duration (weeks, 1 month)

      1. bc cleared via reticuloendothelial system with whole platelet

      2. = discontinued

2. Eptifibatide

   1. peptide

   2. renally cleared

3. Tirofiban

   1. small molecule

   2. renally cleared

heparins

anticoagulant

binds to AT3 to enhance neutralization of Factor Xa and/or Thrombin

3 types:

1. UFH

   1. equally inhibits both Factor Xa and thrombin

      1. bc long enough chain to also get AT3 to reach thrombin

   2. IV (immediate onset) or SQ

   3. cleared rapidly, ~60min t_1/2

   4. monitor via aPTT

      1. activated Partial Thromboplastin Time

   5. reverse with Protamine Sulfate

      1. bc highest risk of HIT

2. Enoxaparin

   1. LMWH

   2. mostly inhibits Factor Xa

   3. SQ

   4. renally cleared = less monitoring needed

   5. no reversal

3. Fondaparinux

   1. only inhibits Factor Xa

How do DTIs work?

anticoagulants

directly inhibit Factor Xa and/or thrombin = immediate onset

Dabigatran:

• directly inhibits Factor Xa

• reverse with Idarucizumab

direct inhibitors of Factor Xa:

• Apixaban (Eliquis)

• Rivaroxaban (Xarelto)

• reverse with 4F-PCC

Why does Warfarin exhibit a 3-5 day delay in onset, and what’s its initial risk?

anticoagulant

inhibits Vitamin K Epoxide Reductase

= prevents y-carboxylation of Factors 2, 7, 9, 10 (PRO-coagulant) and Proteins C/S (ANTI-coagulant)

3-5 day delay due to synthesis inhibition, not currently circulating clotting factors

monitor via INR

• International Normalized Ratio

• time it takes for blood to clot

initial risk of skin necrosis bc Protein C depletes faster than Factors 2 and 10

• ANTI-coagulant drops faster than PRO-coagulant

  • pro-thrombotic window

• = MUST temporarily pair with heparin

reverse with Vitamin K or 4F-PCC

contraindications:

• pregnancy

• CYP2C9 drugs

• MUST have steady Vitamin K intake

fibrinolytics

convert plasminogen into plasmin, which cleaves fibrin in clots

HIGHEST bleed risk of all CV agents

2 types:

1. Alteplase (t-PA)

   1. short t_1/2 ~3-8min

   2. IV bolus AND infusion

2. Tenecteplase (TNK-tPA)

   1. genetically engineered variant of t-PA

      1. higher fibrin specificity

      2. greater resistance to PAI-1 (Plasminogen Activator Inhibitor)

   2. longer t_1/2 ~20-90min

   3. IV bolus only

MUST be administered within 12 hrs of chest pain symptom in acute STEMI

otherwise risks intracranial hemorrhage

reverse with TXA or Aminocaproic acid

relative bleeding risks, from high to low, among all CV agents

high to low:

1. fibrinolytics

   1. t-PA

   2. TNK-tPA

2. GpIIb/IIIa inhibitors

   1. Abciximab

   2. Eptifibatide

   3. Tirofiban

3. anticoagulants

   1. heparins

   2. Warfarin

   3. DTIs

   4. -xabans (DXaIs)

4. P2Y12 inhibitors

   1. Prasugrel

   2. Ticagrelor

   3. Clopidogrel

5. Aspirin

primary hemostasis steps

1. vWF binds to exposed subendothelial collagen

2. vWF conformationally changes, to also bind GpIb on resting platelets = bridge

3. platelets activate = release granules

   1. small molecules, ex. ADP

   2. proteins, ex. fibrinogen

   3. membrane-derived lipids, ex. TXA2 from COX-1

4. granules activate GpIIb/IIIa on platelets

5. GpIIb/IIIa binds fibrinogen to cross-link adjacent platelets

secondary hemostasis steps

1. Factor 7a binds exposed subendothelial TF = extrinsic tenase complex

2. ETC activates Factor 10a

3. 10a + 5a + calcium = small thrombin burst

4. thrombin activates Factor 5a, 8a, 11a

5. 8a + 9a = intrinsic tenase complex

6. ITC activates Factor 10a further = thrombin explosion

7. thrombin:

   1. cleaves fibrinogen into fibrin

   2. activates Factor 13a to cross-link fibrin

8. = clot