JC 06 (Medicine) - Ischaemic heart disease, Angina pectoris Flashcards
6 pathophysiological processes that cause MI
- Critical coronary stenosis
- Vascular Inflammation
- Coagulopathies
- Vasospasm
- Microvascular dysfunction
- Endothelial dysfunction
Explain the pathophysiological changes in epicardial coronary arteries that lead to myocardial ischemia
Insufficient oxygen supply to myocardial tissue by 2 mechanisms:
- Atherosclerotic disease
- Stable plaque > Reduction in CFR > Demand ischaemia +/- angina
- Vulnerable plaque > Plaque rupture > Thrombosis > Acute coronary syndrome/ Infarction - Vasospastic disease
- Focal/ transient vasospasm > Prinzmetal angina
- Persistent vasospasm > Myocardial infarction
Explain the pathophysiological changes in coronary microcirculation that lead to myocardial ischemia
Microvascular dysfunction
> impairs coronary physiology and myocardial blood flow
> myocardial ischaemia in CAD and Cardiomyopathies
> Severe acute ischaemia
Mechanism of ischemic chest pain (referred pain)
Ischemic episodes
> excite chemosensitive and mechanosensitive receptors in heart
> Release adenosin, bradykinin, cytokines
> Excite sensory sympathetic and vagal afferent fibers
> Upper thoracic sympathetic ganglia and thoracic roots of spinal cord
> cardiac sympathetic afferents impulses converge with somatic thoracic structures
> Chest pain
Mechanism of silent myocardial ischaemia
Long term diabetes
> Reduced nerve growth factor
> failed development of cardiac sensory system
> failed afferent signal to thoracic ganglia and impulse convergence with somatic nerve fibers
> no chest pain
Prevalence of angina
Typical presentations
> 60 years old = 25-37% men and 16-23% women
50% present with angina pectoris
50% with acute coronary syndrome
Primary cardiac causes of IHD
- Coronary artery abnormalities:
- Spasm, arteritis, dissection, malformation, myocardail bridging - Valvular
- Aortic stenosis - Structural
- Hypertrophic cardiomyopathy, Dilated cardiomyopathy
Primary non-cardiac causes of IHD
- Decrease oxygen delivery - hypoxemia
- Anemia, Sickle cell disease, carbon monoxide poisoning - Endocrine
- Hyperthyroidism (thyrotoxic AF), Pheochromocytoma
Effect of LDL levels on onset of IHD
Reduce LDL cholesterol = delay onset of IHD
Familial hypercholesterolemia greatly decreases age of IHD onset
Pathogenesis of atherosclerotic plaque formation
- Atherophil (modified smooth muscle cells or macrophages) proliferate
> Atherocyte phagocytizes lipids
> Lipid-laden atherocytes die and release lipids
> Other atherocytes engulf lipid content under sufficient oxygen
> Increasing platelet and fibrin blocks O2 diffusion and astrocytes cannot engulf lipid content
> extra-cellular lipid accumulates, internal elastic membrane fractures and stiffens
> Pathological intimal thickening - Fibrophils (modified fibroblasts or histocytes) produce fibrous tissue and accelerate calcium deposition
> Fibroatheroma formation
> > Formation of atherosclerotic plaque in intima layer
Define risk factors of coronary artery disease
□ Modifiable: abdominal obesity, BP, cholesterol, cigarette smoking, alcohol, diet, DM, lack of exercise, cocaine abuse
□ Non-modifiable: family Hx of CVD, male gender, advanced age
Define stable, unstable angina
Define myocardial infarction
□ Stable angina: ischaemia due to fixed stenosis
□ Unstable angina: ischaemia due to dynamic obstruction (e.g. ruptured atherosclerotic plaque, acute thrombosis)
□ Myocardial infarction: myocardial necrosis due to acute occlusion
Typical presentation of stable angina (ESC Guidelines)
Provoking and relieving factors
Retrosternal chest discomfort with typical quality (dull, constricting) and duration (<30min)
→ ± radiation to arms, shoulder, jaw
Provoked by exertion or emotion
Relieved by rest or sublingual nitrate ≤5min
Clinical grading of angina pectoralis
CCS grading of angina pectoralis 0 – asymptomatic I – angina with strenuous exertion II – angina with moderate exertion (slight limitation of ordinary activities) III – angina with mild exertion (great limitation) → indicated for Tx IV – angina at rest
Patterns of pain radiation in angina pectoris
Neck/ throat tightness Lower jaw Left shoulder or arm in ulnar distribution Interscapular Epigastrium Back
Sometimes to right arm
Associated non-chest pain manifestations of myocardial ischemia
Dyspnea:
- rest or exertional
- Paroxysmal nocturnal dyspnea
Abdomen:
- Atypical, sharp pain
- RUQ pain (mimic pancreatitis or gallbladder disease)
- Nausea and vomiting
Psychologial:
- Intense Fear
Diaphoresis
Weakness, syncope, coma
Signs of risk factors of coronary artery disease
- BP: >15mmHg arm BP disparity
- > 30 BMI
- Lipid
- Cutaneous xanthomas, xanthelesma, corneal arcus - DM:
- acathosis nigricans, skin tags - Others:
- Franks sing (ear lobe crease)
- Tar stains, teeth stains
- Wheezing, prolonged expiration (COPD)
Signs of coronary artery disease complications
- CHF:
- Increase JVP
- Abnormal heart sounds
- Displaced apex
- Low-output cardiac failure - Arrhythmia
- PAD:
- Peripheral pulse absence
- Carotid bruit
- Trophic signs
Baseline investigations for suspected coronary artery disease (4 tests)
Blood tests
12-lead ECG:
- Evidence of MI, myocardial damage
Echocardiogram:
- LVEF (prognostic)
- Structural heart diseases
- Regional wall motion abnormalities
CXR:
- Pulmonary cause or complications
Outline full spread of blood test metrics for suspected coronary artery disease
Blood:
- CBC
- Thyroid function test
- Fasting glucose, HbA1c, OGTT > DM
- Fasting lipid profile > Hyperlipidaemia
- RFT/ Creatinine (prognostic)
- LFT, CK (statin)
Markers:
- High-sensitivity C-reactive proteins
- Brain natriuretic peptide (BNP)
- hs- TNT
List diagnostic investigations for suspected coronary artery disease
→ Anatomical test: CT coronary angiography
→ Functional test: exercise tolerance test (ETT), stress echo
→ Myocardial perfusion scintigraphy
→ Cardiac MRI
Modalities of cardiac stress tests (3)
□ Exercise: bicycle ergometer, treadmill test
□ Vasodilators, eg. adenosine, dipyridamole → based on ‘coronary steal phenomenon’
□ Inotropes, eg. dobutamine
Conducted with 12-lead ECG, BP, ECHO
Positive = horizontal or down-sloping ST depression of >0.1mm
Positive ECHO = regional wall motion abnormality, LV dysfunction
Outline the selection process of diagnostic investigations for suspected coronary artery disease
- Contraindicated for stress testing / Clinical findings warrant coronary imaging»_space; CT Coronary angiography
- No contraindication for stress testing + unable to exercise»_space; Pharmacological stress test
- No contraindication for stress test + able to exercise»_space; Exercise stress test
- No contraindication for stress test + able to exercise + no previous revascularization/ resting ECG normal»_space; Exercise tolerance test with ECG
2,3,4 may require follow-up coronary imaging if high risk or inadequate information for diagnosis
Direct indications for coronary angiogram
- Unacceptable angina despite medical therapy
- Non-invasive test results with high-risk features
- Angina or risk of CAF with depressed LVEF
- Unclear non-invasive test results and prognosis
5 principles of management of IHD
Patient education and decision making
Manage comorbid conditions
Aggressive modification of preventable risk factors
Pharmacological management
Revascularization surgery: PCI, CABG
Lifestyle changes for management of IHD
□ Lifestyle: stop smoking, regular exercise
□ Treat precipitating factors: thyrotoxicosis, anaemia
□ Manage risk factors:
→ DM: aim HbA1c <7%, consider SGLT2i or GLP-1a
→ HTN: aim <140/90, use BB if indicated
→ Lipids: ↓LDL to <1.8mmol/L with lifestyle and drug
CVD prevention in patients with diagnosed atherosclerotic cardiovascular disease (4)
LDL-C >50% reduction and <1.8mmol/L
SBP <140 - 130 mmHg
Antithrombotic therapy
Stop smoking and lifestyle recommendations
Outline 6 classes of lipid modifying therapies proven to reduce CVD
Statins (1st line)
Cholesterol absorption inhibitors e.g. Ezetimibe (2nd line)
PCSK9 inhibitors (3rd line)
Bile acid sequestrants
Long-chain omega-3 fatty acids
antisense oligonucleotide inhibitor of apolipoprotein B (for familial hypercholesterolemia ONLY)
Which lipid modifying therapy is most effective in lowering LDL-C and non-HDL-C?
PCSK9 inhibitors
List classes of drugs for prognostic improvement of IHD
- Antiplatelets/ anticoagulants
- Statins/ lipid modifying drugs: in all patients regardless of LDL, first line
- ± ACEI only in those with HTN, LVEF ≤40%, DM/CKD
- ± ARB only in those with SIHD, HTN, DM, Poor LVEF and refractory to ACEI
List specific antiplatelet/ anticoagulant combinations for prognostic improvement of IHD
- Aspirin (1st line)
- Clopidogrel (2nd line, refractory/ CO to aspirin, post MI)
- Aspirin + P2Y12 blocker (Ticagrelor/ Prasugrel): after PCI/ Mutli-vessel CAD/ Post-MI
- Aspirin + Rivaroxaban: High risk CAD/ PAD, Post-MI
List specific drugs for angina relief (standard first line treatment)
Symptomatic → relieve ischaemia during
angina episodes
□ 1st-line:
Urgent: PRN sublingual nitrates
Long-term: Long-acting nitrates + Beta-blocker or CCB/ Beta-blocker + DHP- CCB if severe
□ 2nd-line: long-acting nitrates, ivabradine,
trimetazidine, ranolazine, nicorandil
Contraindications for ACEI/ ARB use in IHD patients
Bilateral renal artery stenosis
Indications for CABG over PCI
Two vessel disease and proximal LAD lesion
Triple vessel disease
Unprotected left main coronary artery disease
Indication for B-blocker use in IHD
- First-line monotherapy or combination with CCB or nitrate to decrease angina
- Systolic LV failure (LVEF < 40%) and past-MI
- Ventricular rate control in A-fib
Side effects and contraindications of B-blocker use in IHD
Side effects:
- Bradycardia, syncope, hypotension, bronchial spasm
Contraindications: (electrical and veqssel problems)
- AV block, sinus node dysfunction
- Bronchial asthma (vasocontriction)
- Vasospasm angina, PAD, Raynaud’s phenomenon
- Depression
Indication for CCB use in IHD
Monotherapy if refractory/ intolerant to B-blocker
Combination with B-blocker or nitrates to decrease angina
Vasospasm angina ** (B-blocker C/O)
Ventricular rate control in A-fib
Side effects and contraindications of CCBs
Side effects:
Bradycardia (non-DHP CCBs)
syncope, hypotension, peripheral edema, headache, dizziness, constipation
C/O:
AV block, Heart failure, sinus node dysfunction
Differences and similarities between Amlodipine, Nifedipine, Diltiazem and Verapamil action on heart (different CCBs)
Amlodipine and Nifedipine: (for low basal HR)
- Increase HR
- No effects on SA and AV node conduction
Diltiazem and Verapamil: (for tachycardia)
- Decrease HR
- Decrease SA and AV node conduction
ALL:
- Decrease myocardial contractility
- Increase neurohormonal activation
- Increase vascular dilation
- Increase coronary flow
Indications of nitrate use for IHD
Releive acute anginal pain
Prophylaxis to increase exercise tolerance and prevent exercise-induced ischaemia
Long-acting nitrate to decrease angina
Side effects and C/O of nitrate use in IHD
Side effects:
- Hypotension, syncope, tachycardia, headache
C/O:
- HOCM
- Same-day use with Selective Phosphodiesterase Inhibitors (PDE-5) e.g. Sildenafil
- SBP <90mmHg/ Severe hypotension
List 4 novel agents for use in IHD
Ivabradine (funny current blocker, decrease HR and myocardial oxygen consumption)
Ranolazine (reduce Ca overload, anti-arrhythmic)
Trimetazidine (Increase energy for myocardial contraction)
Nicorandil (dilation of coronary resistance arterioles and vasodilation)
Side effects of Ivabradine
Phosphenes (seeing ring of light)
Bradycardia and AFib
Headache, dizziness
Ventricular extrasystoles, 1st degree heart block
Side effects of Ranolazine
Long QT
headache, dizziness, syncope, postural hypotension
nausea, constipation
C/O liver or renal failure
Side effects of Trimetazidine
Nausea vomiting fatigue dizziness myalgia
Induce Parkinsonism symptoms
Side effects of Nicorandil
- c/o corticosteroids - GI perforation
2. c/o sulphonylureas - antagonizing effect
Explain INOCA and first line treatment
Microvascular dysfunction > angina and ischemia without occlusion
INOCA = Ischemia with no-obstructive CAD
First line:
Antiplatelet, anti-ischemic, nitrates
Characterize Prizmetal angina
Vasospastic disease
- Focal/ transient vasospasm > Prinzmetal angina
Cyclical Occurs at rest
Common after cold exposure
Risk of Ventricular arrhythmia