Y2 Cardiology Session 2

Meg Mulqueen, Doctorials 2021/2022

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Session Learning Objectives

• Explain the pathophysiology of cor pulmonale versus left-sided heart failure. Explain the signs and symptoms seen in right versus left-sided heart failure. Explain what is meant by congestive heart failure.
• Explain the clinical importance of ejection fraction
• Emphasize the clinical features of angina
• Differentiate between dilated, hypertrophic, and restrictive cardiomyopathies
• Differentiate between hypertensive urgency and hypertensive emergency
• Compare and contrast rheumatic fever and infective endocarditis, including the JONES and DUKES criteria
• Explain the difference between dihydropyridine and non-dihydropyridine CCBs
• Explain the difference between antihypertensives that decrease preload versus those that decrease afterload
• Explain the mechanism of action of digoxin and how digoxin toxicity presents
• Differentiate between antiplatelet agents, anticoagulation, and thrombolytic agents
• Compare and contrast unfractionated heparin, LMWH, and warfarin
• Compare and contrast the key differences between lipid-lowering agents

Meg Mulqueen, Doctorials 2021/2022

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Heart Failure – Cor Pulmonale

FA, 2020

Meg Mulqueen, Doctorials 2021/2022

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• Isolated Right HF due to increased vascular resistance from pulmonary disease
• Right HF most often results from left HF
• Cor Pulmonale is only R HF!
• Causes are pulmonary disease
• Pulmonary HTN
• COPD
• Severe Asthma
• Interstitial lung disease

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Pathophysiology

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Chronic hypoxia

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Pulmonary Vasoconstriction

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Pulmonary HTN

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↑ Right Ventricular Afterload

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Right Ventricular Hypertrophy

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Right Ventricular Failure

Heart Failure – Left sided HF

FA, 2020

Meg Mulqueen, Doctorials 2021/2022

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• Causes
• ↑ Afterload:
• ↑ Mean Aortic pressure, outflow obstruction (aortic stenosis)
• Uncontrolled systemic HTN
• Impaired ventricular contractility
• MI, transient ischemia
• Chronic volume overload (mitral or aortic regurgitation)
• Dilated cardiomyopathy

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Pathophysiology

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Pressure overload

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Decreased CO

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Ventricular remodelling

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Left Ventricular Hypertrophy

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Left Ventricular Failure

Heart Failure – clinical features

FA 2020 p309 & TN 2018 Ch5 p34

Meg Mulqueen, Doctorials 2021/2022

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• Low perfusion (forward failure) & congestion (backward failure) 🡪 accounts for all clinical manifestations
• Congestive Heart Failure – build up of fluid in lungs and tissues

Left-Sided Heart Failure

1. Fatigue, syncope, slow cap refill

2. Orthopnea 🡪 SOB when supine b/c ↑ venous return

3. Paroxysmal nocturnal dyspnea 🡪 Breathless awakening from sleep b/c ↑ venous return

4. Pulmonary edema 🡪 ↑ pulmonary venous pressure leads to transudation of fluid 🡪 Cough & Dyspnea (SOB)

Right-Sided Heart Failure

1. ↓ RV output leads to LV underfilling 🡪 Left sided HF

2. Hepatomegaly (nutmeg liver) – due to ↑ resistance to portal flow

3. Jugular venous distention due to ↑ venous pressure

4. Peripheral edema due to ↑ venous pressure

Ejection Fraction

FA 2019 p306 & TN 2018 Ch5 p34

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Meg Mulqueen, Doctorials 2021/2022

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• Ejection Fraction: % Measurement of how much blood the left ventricle pumps out with each contraction
• Index of contractility
• Contractility is how hard the heart muscle squeezes
• EF = Stroke volume/ End Diastolic volume
• Grade 1: EF > 60% (Asymptomatic)
• Grade 2: EF 40-59% (Mildly Symptomatic)
• Grade 3: EF 20-39% (Moderately Symptomatic)
• Grade 4: EF <20% (Severely Symptomatic)
• Measured in LV by ECHO
• Reduction in EF → reduction in ability of heart to squeeze
• Cardiomyopathies
• MI
• Valvular disease
• Long-standing, uncontrolled HTN

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Angina

Meg Mulqueen, Doctorials 2021/2022

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• Chest pain due to ischemic myocardium 2° to coronary artery narrowing or spasm
• Reversible 🡪 no necrosis

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Angina

FA 2019 p301

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Meg Mulqueen, Doctorials 2021/2022

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Angina vs NSEMI/STEMI

CanadiEM.org, 2021

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Meg Mulqueen, Doctorials 2021/2022

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Cardiomyopathies

FA 2019 p305 & TN 2018 Ch5 p39

Meg Mulqueen, Doctorials 2021/2022

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Hypertrophic Cardiomyopathy

FA 2019 p305 & TN 2018 Ch5 p39

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Meg Mulqueen, Doctorials 2021/2022

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• 60–70% of cases are familial 🡪 autosomal dominant mutation 🡪 abnormal sarcomere proteins
• Concentric Hypertrophy 🡪 sarcomeres added in parallel (width)
• Septal hypertrophy, myofibrillar disarray and interstitial fibrosis
• Presentation
• Commonly asymptomatic (SCD in young athletes)
• Systolic murmur (similar to AS) 🡪 anterior motion of mitral valve & thick septum 🡪 outflow obstruction 🡪 dyspnea & syncope
• Valsalva's maneuver is used to distinguish between murmur of HOCM & Aortic Stenosis
• Valsalva’s decreases preload 🡪 Enhances HOCM Murmur & Softens AS Murmur
• S4 Heart sound (stiff ventricle)

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Dilated Cardiomyopathy

FA 2020 p308 & TN 2018 Ch5 p39

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Meg Mulqueen, Doctorials 2021/2022

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• Most common cardiomyopathy (90% of cases)
• Eccentric Hypertrophy 🡪 sarcomeres added in series (length)
• Volume overload leads to longer myocytes
• Increased myocyte size, normal wall thickness
• Presentation
• S3 Heart sound (volume overloaded)
• Systolic dysfunction 🡪 HFrEF
• Fatigue, Syncope, Slow Cap Refill, Cough, Orthopnea, PND
• Dilated heart on echocardiogram
• Ballooned heart on CXR
• Causes
• Idiopathic
• Substance Abuse (alcohol, cocaine, doxorubicin)
• Infection – Coxsackie B, Chagas Disease)
• Ischemia
• Systemic conditions – haemochromatosis, sarcoidosis, thyrotoxicosis

Restrictive Cardiomyopathy

FA 2019 p305 & TN 2018 Ch5 p39

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Meg Mulqueen, Doctorials 2021/2022

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• Impaired ventricular filling with preserved systolic function in a non-dilated, non-hypertrophied ventricle 🡪 Diastolic dysfunction
• Hallmark is decreased myocardial compliance 🡪 fibrosis and/or infiltration
• Infiltrative causes
• Amyloidosis 🡪 Abnormal aggregation of proteins into β-pleated linear sheets
• Histology: Congo red stain & polarized light (apple-green birefringence)
• Sarcoidosis 🡪 Systemic disease resulting in the formation of noncaseating granulomas that can infiltrate the myocardium
• Fibrotic causes
• Scleroderma 🡪 Excessive collagen deposition with fibrosis
• Post-radiation fibrosis
• Endocardial fibroelastosis 🡪 Child that has thickening of connective tissues of endocardium
• Other
• Hemochromatosis (DCM also possible) 🡪 Abnormal Iron accumulation in myocardium
• Löffler endocarditis 🡪 abnormal endomyocardial infiltration of eosinophils

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Rheumatic Fever

FA 2019 p308

Meg Mulqueen, Doctorials 2021/2022

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• Complication of pharyngeal infection with group A β-hemolytic streptococci
• Pathophysiology: Molecular mimicry Type II hypersensitivity reaction 🡪 Antibodies produced against M proteins of bacteria cross-react with myocardium and cardiac valves
• Jones RF Criteria: 2 major or 1 major & 2 minors PLUS evidence of preceding strep infection

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• Minor Criteria: Fever, Elevated ESR & CRP, prolonged PR interval, Elevated ASO titers
• Complication of RF 🡪 Mitral Regurgitation 🡪 Mitral Stenosis 🡪 CHF

1. Aschoff body 🡪 granuloma with giant cells (Anitschkow cells enlarged macrophages)

• Scarlet Fever
• Pharyngitis & strawberry tongue
• Diffuse erythematous eruption rash

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• Post-streptococcal Glomerulonephritis (2-3 wks post)
• Nephritic syndrome 🡪 Cola Urine (Hematuria) & HTN
• Puffy face
• Lumpy-Bumpy IF due to IgG, IgM & C3 deposition in GBM

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Endocarditis

FA 2019 p307

Meg Mulqueen, Doctorials 2021/2022

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• Inflammation of inner lining of heart and valves generally caused by infection
• Bacterial infection in the blood that manifests as septic vegetations on the cardiac endothelium
• Vegetations are made of platelet-fibrin thrombi, WBCs, and bacteria

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• Acute 🡪 Rapid onset of large vegetations on previously normal valves 🡪 S. Aureus 🡪 Tricuspid valve 🡪 IV Drug users
• Subacute 🡪 Slower onset of smaller vegetations on congenitally abnormal or diseased valves 🡪 Strep. Viridans 🡪 Mitral valve
• Patient with prosthetic valve 🡪 Strep. Epidermidis
• Patient with endocarditis cultures Strep. Bovis 🡪 What is next step for investigation? 🡪 Colonoscopy for cancer

Hypertension

FA 2019 p298 & TN 2018 Ch10 p34

Meg Mulqueen, Doctorials 2021/2022

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• First Aid: Persistent systolic BP >130 mmHg and/or diastolic BP >80 mmHg
• Toronto Notes: Persistent systolic BP >140 mmHg and/or diastolic BP >90 mmHg
• Hypertensive Urgency: >180/120 mmHg HTN without acute end-organ damage
• Hypertensive Emergency: >180/120 mmHg HTN with evidence of acute end-organ damage
• Encephalopathy, retinal hemorrhages/exudates, papilledema, kidney injury (proteinuria), eclampsia

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• Primary HTN (90% of Cases)
• Age
• Obesity
• Family History
• Sedentary
• Excessive salt & Alcohol Consumption
• Stress
• Smoking
• African American Ancestry

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• Secondary HTN (10% of Cases)
• Renovascular Disease (Stenosis, Fibromuscular dysplasia)
• Primary Hyperaldosteronism
• Pheochromocytoma
• Cushing’s Syndrome/Disease
• Hyperthyroidism
• Drugs (COCP, NSAIDs, Cocaine, Amphetamines)

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CCBs

FA 2019 p298 & TN 2018 Ch10 p34

Meg Mulqueen, Doctorials 2021/2022

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• Both classes used as HTN treatment
• MOA : bind and block L-type Ca2+ channels in cardiac & vascular smooth muscle cells
• Decreases the frequency of Ca2+ channel opening in response to cell membrane depolarization
• Effect is SM relaxation, vasodilation, decreased peripheral vascular resistance, decreased afterload, decreased BP
• Also decreases contractility therefore decreases CO (less work and O2 requirement for the heart)

• Dihydropyridine CCBs
• Primarily act on vascular smooth muscle
• More potent vasodilators
• Minimal myocardial depressant activity

• Non-dihydropyridine CCBs
• Primarily act on the heart
• Marked negative inotropic effect
• Moderate vasodilator

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Digoxin

FA 2019 p298 & TN 2018 Ch10 p34

Meg Mulqueen, Doctorials 2021/2022

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• MOA : inhibits Na+/K+ ATPase resulting in increased intracellular Na+ concentration
• Reduces efficacy of Na+/Ca2+ exchangers →higher intracellular Ca2+
• Leads to ↑ contractility and ↓ AV conduction rate and HR

• Digoxin Toxicity Presentation
• Irregular heartbeat
• ECG abnormalities
• Severe bradycardia
• Visual disturbances – yellow and green patches
• Nausea, vomiting, abdominal pain, anorexia

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Toxicity: Factors predisposing (renal failure, hypokalemia) 🡪 Blurry yellow vision, hyperkalemia, arrhythmias

Antidote: Normalize K+, anti-digoxin Fab fragments, cardiac pacemaker

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Anti-Hypertensives ↓ Preload

FA 2019 p595-596

Meg Mulqueen, Doctorials 2021/2022

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• Preload – initial stretching of cardiac myocytes prior to contraction
• Think volume when you think of preload
• Goal is to dilate veins or promote excretion to decrease volume
• ACEi/ARB
• MOA: ↓ ATII 🡪 Know how this affects RAAS
• ADR: CATCHH 🡪 Cough, Angioedema, Teratogenic, ↑Cr (efferent a. vasodilation), Hyperkalemia, Hypotension
• ↑ Bradykinin causing cough 🡪 Switch to ARB
• ARB
• MOA: receptor antagonists that block type 1 ATII receptors in BVs and other tissues
• ADR: Cough, Angioedema, Teratogenic, ↑Cr (efferent a. vasodilation), Hyperkalemia, Hypotension
• Thiazides
• MOA: ↓ NaCl reabsorption in early DCT
• ADR: HyperGLUC (glucose, lipids, uric acid, calcium) & HypoKNa

Anti-Hypertensives ↓ Afterload

FA 2019 p595-596

Meg Mulqueen, Doctorials 2021/2022

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• Afterload – amount of pressure needed to eject during ventricular contraction
• Think of resistance when you think of afterload
• Goal is to decrease vascular resistance
• Beta blockers
• MOA: bind to beta receptors on cardiac and smooth muscle cells to induce smooth muscle relaxation
• ADR: angina, headache, tremor, fatigue, cold fingers/toes, nausea
• Nitro dilators
• MOA: mimic endogenous NO which acts on smooth muscle cells to cause relaxation
• ADR: headache, flushing, postural hypotension, reflex tachycardia
• Alpha blockers
• MOA: cause vasodilation by blocking binding of NE to smooth muscle receptors
• ADR: fluid retention, dizziness, orthostatic hypotension, nasal congestion, headache, reflex tachycardia

Arterial & Venous Thromboembolism

Thrombus

• Blood clot in either an artery or vein
• Caused by activation of clotting cascade

Embolus

• Any intravascular material that migrates from its original location to occlude a distal vessel
• Causes: “FAT BAT” → Fat, Air, Thrombus, Bacteria, Amniotic Fluid, Tumor Tissue

McMaster Pathophysiology Review

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Meg Mulqueen, Doctorials 2021/2022

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Anti-Platelets

• General Indications: ACS, Unstable Angina, Ischemic Stroke
• ADR’s: Bleeding
• Aspirin
• MOA: Irreversible inhibitor of COX via acetylation 🡪 reduces production of TXA2
• Adenosine diphosphate (P2Y12) Inhibitors (Clopidogrel, prasugrel, ticagrelor, ticlopidine)
• MOA: Blocks ADP receptor 🡪 preventing expression of GpIIb/IIIa receptor
• GpIIb/IIIa Inhibitors (Abciximab, eptifibatide, tirofiban)
• MOA: Blocks GpIIb/IIIa receptor 🡪 preventing final step in aggregation of platelets
• Antiplatelet Phosphodiesterase Inhibitors (Cilostazol, dipyridamole)
• Indication: Patient with PVD risk factors who has clinical features of intermittent claudication
• MOA: Inhibits PDE 🡪 preventing breakdown of cAMP 🡪 impairs aggregation & promotes vasodilation

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Meg Mulqueen, Doctorials 2021/2022

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FA 2019 p429

Anti-Coagulants

Meg Mulqueen, Doctorials 2021/2022

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• Unfractionated Heparin
• Indication: Immediate anticoagulation for PE, ACS, MI, DVT
• MOA: Activates antithrombin 🡪 reduces action of factors Xa and IIa (thrombin)
• Benefits: Rapid onset, Safe in pregnancy, Reversable (Protamine Sulfate)
• Monitoring: PTT (Intrinsic pathway)
• ADR: Bleeding & Heparin Induced Thrombocytopenia (development of IgG antibodies against heparin bound platelet factor 4 (PF4) 🡪 thrombosis & platelet destruction)

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• Low Molecular Weight Heparin (Enoxaparin, Dalteparin)
• Same MOA, benefits and ADR, but LMWH has greater effect on factor Xa
• 2–4X longer half life than unfractionated heparin

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FA 2019 p427

Anti-Coagulants

Meg Mulqueen, Doctorials 2021/2022

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• Warfarin
• Indication: Chronic anticoagulation for VTE prophylaxis, Atrial Fibrillation, Valve Replacements
• MOA: Inhibits epoxide reductase (VKOR) 🡪 prevents γ-carboxylation of vitamin K dependent clotting factors II, VII, IX, X (1972) and proteins C&S
• Benefits: Long half-life, Cheap, Reversable (Vitamin K, FFP, PCC)
• Monitoring: PT (Extrinsic pathway), INR
• ADR
• Bleeding & Teratogenic
• Initially Hypercoagulable (protein C depletes before existing factors II and X) 🡪 Heparin Bridge used to reduce transient hypercoagulable state
• Skin/tissue necrosis within first few days of large doses
• Warfarin metabolized by cytochrome P-450
• CYP Inducers (ex. Phenytoin) reduces INR 🡪 Hypercoagulation
• CYP Inhibitors (ex. Azole antifungals) increases INR 🡪 Bleeding

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FA 2019 p428

Modern Anti-Coagulants & Fibrinolytics

Meg Mulqueen, Doctorials 2021/2022

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• Direct Factor Xa inhibitors (Apixaban, Rivaroxaban)
• Indication: Used for acute treatment & prophylaxis of DVT, PE, Atrial Fibrillation
• ADR: Bleeding
• Does not require monitoring, but not easily reversible
• Expensive
• Direct Factor IIa (Thrombin) Inhibitors (Dabigatran, Argatroban, Bivalirudin)
• Used similarly as above
• Thrombolytics (Alteplase, Reteplase, Streptokinase, Tenecteplase)
• Indication: MI (if no PCI available), ischemic stroke, thrombolysis of severe PE
• MOA: Conversion of plasminogen to plasmin, which cleaves thrombin mesh
• ADR: Bleeding

FA 2019 p429

Lipid Transport

FA 2019 p315

Meg Mulqueen, Doctorials 2021/2022

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If you are confused about lipid transport watch 3 part dirtyUSMLE video: https://www.youtube.com/watch?v=wxjwAD6WXP8

Lipid Lowering Medications

Meg Mulqueen, Doctorials 2021/2022

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Thanks & Questions?