Cardiology COPY COPY Flashcards
What is the equation for Stroke volume?
EDV-ESV
What is the equation for cardiac output?
CO = HR X SV
What is the equation for Blood pressure?
CO X TPR
What is the equation for pule pressure?
Systolic - Diastolic
What is the equation for mean arterial pressure?
Diastolic pressure + 1/3(PP)
What is the equation for ejection fraction?
SV/EDV
What is Ohms Law?
Flow = pressure gradient / R
What is the equation for Poiseuille Law?
R = 8lu/pi x r^4
Define Preload
Volume of blood in ventricles immediately before contraction. The volume of blood that causes the degree of stretch on the heart muscle for contraction
Define Afterload?
Force against which the ventricles must contract to expel the blood out of the ventricles
Define Contractility?
Inherent strength and vigor of the hearts contraction during systole
Define Elasticity?
The ability of the heart to return to its normal shape after stretching by recoiling once the force has been removed
Define compliance?
How easily the heart chamber will stretch when it is filled with a volume of blood
Define Resistance?
The force that must be overcome to push blood through the circulatory system
What is atherosclerosis?
Inflammatory process characterised by hardened plaques within the intima of a vessel wall. Eventually, plaque will either occlude vessel lumen resulting in a restriction of blood flow (angina) or rupture (thrombus formation - death).
Where do atherosclerotic plaques often occur?
Peripheral and Coronary arteries!
How are atherosclerotic plaques distributed in these arteries?
Focally distributed - governed by haemodynamic factors. For example, changes in flow/ turbulence (e.g. bifurcations)
What is neointima?
As the intima grows (new intima)
Changes in blood flow altering the phenotype of endothelial cells.
Altered gene expression in key; endothelial cells, smooth muscle cells, macrophages and fibroblasts
What makes up the structure of an atherosclerotic plaque?
Lipid
Necrotic core
Connective tissue
Fibrous cap
Lymphocytes
What are the 5 main stages of atherosclerosis progression over the course of the condition?
Fatty Streak
Intermediate Lesions
Fibrous Plaques (advanced lesions)
Plaque Rupture
Plaque Erosion
What is the fatty streak stage of atherosclerosis?
Earliest lesion of atherosclerosis < 10 years:
- Scavenger receptors take up lipids in intima layer of vessel wall
- Aggregations of lipid-laden macrophages (Foam Cells) and T lymphocytes within the intima layer of the vessel wall.
What is the intermediate lesion stage of atherosclerosis?
Lesion progresses to comprise layers of;
Foam cells
Vascular smooth muscle cells
T lymphocytes
Adhesion and aggregation of platelets to vessel walls
Extracellular Lipid Pools
What is the fibrous plaque stage of atherosclerosis?
- Growth of the atheroma.
- Covered by dense fibrous caps made of ECM proteins including; collagen (strength), elastin (flexibility) - these are laid down by SMCs
- Impedes blood flow and prone to rupture
What is the plaque rupture stage of atherosclerosis?
Why might atherosclerotic plaques Rupture?
- Plaque is constantly growing and receding - fibrous cap has to be resorbed and redeposited in order to be maintained
- If balance shifted in favour inflammatory conditions (e.g. increased enzyme activity) the cap becomes weak and plaque ruptures.
- Exposure of basement membrane, collagen, necrotic tissue and haemorrhage of vessels within plaque causes thrombus formation and vessel occlusion
What is the plaque erosion stage of atherosclerosis?
- Small early lesions
- Fibrous cap does not disrupt
- Luminal surface underneath the clot may not have enough endothelium present but is smooth muscle rich
- Prominent lipid core
What are the stages of atherosclerotic plaque formation?
1️⃣ Initiation of inflammation and endothelial cell dysfunction
2️⃣ Stimulus for adhesion of leukocytes - release of chemo-attractants
3️⃣ Dysfunctional endothelial cells allow the transmigration of LDLs into the tunica intima
4️⃣ Accumulation of LDLs tunica intima cause dysfuntional endothelial cells to release ROS and metalloproteases which function to oxidised the LDL → activated oxLDL
5️⃣ The activation of oxLDLs causes endothelial cells to express adhesion receptors for leukcocytes on their surface, leading to uptake of LDLs and monocytes
6️⃣ Surface of macrophages contain a scavenger receptor which facilitates the uptake of oxidised LDLs to form a foam cells
7️⃣ Foam cells have multiple pathophysiological functions:
- Release chemokines to attract more macrophages
- Release IGF-1 into tunica media to promote migration of SMCs (from media to intima) that increase collagen synthesis leading to the hardening of the atherosclerotic plaque
8️⃣ During this process, foam cells will die → releasing lipid content. This drives the growth of the plaque
9️⃣ Death of foam cells also causes release of contents which causes increased inflammation
🔟 T-cells also facilitate inflammation
🔟+ Excessive growth of the plaque causes it to rupture, leading to accumulation of the RBC, platelets and clotting factors → thrombosis
What initiates inflammation and leads to endothelial cell dysfunction in atherosclerosis?
Cholesterol/ high LDLs in the blood damages the endothelial cells
ROS from inflammation.
What chemo attractant is released by the endothelium and what does this lead to?
Selectins cause leukocyte rolling and firm adhesion to the blood vessel walls.
What are the pathological functions of a foam cell?
Release chemokines and attract further macrophages to the tunica intima
Release IGF-1 into the tunica media to promote migration of Smooth muscle cells from the tunica media into the tunica intima which increases the collagen synthesis and leads to the hardening of the atherosclerotic plaque.
What is a foam cell?
A macrophage that has been up take into the tunica intima that expresses scavenger receptors that will uptake oxidised LDLs
This uptake forms a foam cell.
What is a foam cell?
A macrophage that has been up take into the tunica intima that expresses scavenger receptors that will uptake oxidised LDLs
This uptake forms a foam cell.
What does the death of the foam cell release in atherosclerosis?
DNA material that attracts neutrophils
Proinflammatory cytokines
ROS
These all lead to increased inflammation.
What inflammatory cytokines are found in atherosclerotic plaques?
- IL1, 6 and 8.
- IFN-γ - strong proinflammatory cytokine
- TGF-β - involves in wound healing
- Chemokines (e.g. Monocyte Chemoattractant Protein-1)
How can Atherosclerosis (Coronary Heart Disease) be treated?
Percutaneous Coronary Intervention
Drugs
What is Percutaneous Coronary Intervention?
Non-surgical procedure that uses a catheter to place a stent into a narrowed blood vessel
What is Re-stenosis?
The recurrence of abnormal narrowing of an artery or valve after corrective therapy
What drugs are used to reduce restenosis in patients who have undergone corrective surgery?
Taxol and Sirolimus - work by reducing SMC proliferation after placement of stent. The stent is washed (eluted) with these drugs
How does Aspirin help to treat CHD?
Irreversible inhibitor of platelet cyclo-oxygenase to prevent Thromboxane A2 production and further platelet aggregation
How does Clopidogrel/ Ticagrelor help to treat CHD?
Inhibitors of the stimulatory P2Y12 ADP receptor on platelets preventing platelet response amplification
How does Statins help to treat CHD?
Inhibit HMG CoA reductase - reduces cholesterol synthesis
What inflammation-causing cytokine is targeted using drugs alongside statin therapy?
IL-1
What drug therapy is used as an alternative to statins if ineffective or not tolerated?
PCSK9 inhibitors
Give 5 Modifiable risk factors for atherosclerosis.
- Smoking.
- High levels of LDL’s.
- Obesity.
- Low exercise
- Diabetes.
- Hypertension.
- Alcohol consumption
Which histological layer of the artery may be thinned by an atheromatous plaque?
Tunica Media
What is the precursor for atherosclerosis.
Fatty streaks.
What are the functions of chemoattractants?
Chemoattractants signal to leukocytes. Leukocytes accumulate and migrate into vessel walls -> cytokine release e.g. IL-1, IL-6 -> inflammation!
Describe the process of leukocyte recruitment.
- Capture.
- Rolling.
- Slow rolling.
- Adhesion.
- Trans-migration.
Define atherogenesis.
The development of an atherosclerotic plaque.
What is the key principle behind the pathogenesis of atherosclerosis?
It is an inflammatory process!
What are Acute Coronary Syndromes?
Spectrum of acute cardiac conditions ranging from unstable angina to varying degrees of MI
What is the most common causes of Acute Coronary Syndromes?
Atherosclerotic rupture and consequential arterial thrombosis!
What is the mainstay treatment for ACS? why is this?
Anti-platelet medications:
Aspirin
Clopidogrel
Ticagrelor
Since a thrombus formed in a fast flowing artery are mostly made up of platelets.
Name some less common causes of Acute Coronary Syndromes?
Coronary vasospasm without plaque rupture
Drug abuse (amphetamines, cocaine)
Spontaneous Coronary Artery Dissection
What drugs can cause ACS?
Amphetamines
Cocaine
What are the types of Acute Coronary Syndrome (ACS)?
Unstable Angina
ST Elevation Myocardial Infarction (STEMI)
Non-ST Elevation Myocardial Infarction (NSTEMI)
Explain how Spontaneous Coronary Artery Dissection can lead to Acute Coronary Syndrome?
tear in lining, lining comes away from the wall of the artery and blocks vessel.
Briefly describe the pathophysiology of ACS?
Atherosclerosis -> plaque rupture -> platelet aggregation -> thrombosis formation ->
ischaemia -> hypoxia of cells -> angina
infarction -> necrosis of cells -> permanent heart muscle damage and ACS.(MI)
How would you Diagnose someone presenting with ACS symptoms such as Chest pain?
ECG:
If there is ST elevation or new left bundle branch block the diagnosis is STEMI.
If there is no ST elevation then perform troponin blood tests:
If there are raised troponin levels and other ECG changes (ST depression or T wave inversion or pathological Q waves) the diagnosis is NSTEMI
If troponin levels are normal and the ECG does not show pathological changes the diagnosis is either:
unstable angina
Another cause such as musculoskeletal chest pain
What is Cardiac Troponin?
Protein complex functioning to regulate actin and myosin contraction
What would a rise in Troponin suggest?
Consistent with myocardial ischaemia as the proteins are released from the ischaemic muscle.
However they are non specific so a raised troponin does not automatically mean ACS
Why is Cardiac Troponin relevant in diagnosing ACS?
Highly sensitive marker for cardiac muscle injury - increased levels is very indicative of myocardial cause
What is important to remember about Cardiac Troponin when being used for diagnosis?
not specific for ACS → also increases in conditions that causes stress in myocardium (e.g. PE, gram negative sepsis, myocarditis)
Give some other potential causes of raised troponins?
Chronic renal failure
Sepsis
Myocarditis
Aortic dissection
Pulmonary Embolism
Define angina.
Angina is a type of Ischaemic Heart Disease (IHD) characterised by chest pain
It is an imbalance of O2 supply/demand mismatch to the heart due to reduced blood flow from a blockage
What is the most common cause of angina?
Narrowing of the coronary arteries due to atherosclerosis.
What are the different types of Angina Pectoris?
Stable
Unstable
Decubitus
Crescendo Angina
Prinzmetals’s Vasospastic
Microvascular Angina
What type of angina is associated with ACS?
Unstable Angina
What is Unstable angina?
An acute coronary syndrome (ACS) that is defined by the absence of biochemical evidence of myocardial damage but characterised by chest pain at rest/minimal exertion
Give 5 possible causes of angina.
- Narrowed coronary artery = impairment of blood flow e.g. atherosclerosis.
- Increased distal resistance = LV hypertrophy.
- Reduced O2 carrying capacity e.g. anaemia.
- Coronary artery spasm.
- Thrombosis.
Give 5 modifiable risk factors for angina.
- Smoking.
- Diabetes.
- High cholesterol (LDL).
- Obesity/sedentary lifestyle.
- Hypertension.
Give 3 non-modifiable risk factors for angina.
- Increasing age.
- Gender - Males
- Family history/genetics.
What are the symptoms associated with ACS?
Central, Crushing chest pain associated with:
Nausea and vomiting
Sweating and clamminess
Feeling of impending doom
Shortness of breath
Palpitations
Pain radiating to jaw or arms
Briefly describe the pathophysiology of angina that results from atherosclerosis.
On exertion there is increased O2 demand. Coronary blood flow is obstructed by an atherosclerotic plaque -> myocardial ischaemia -> angina.
Briefly describe the pathophysiology of angina that results from anaemia.
On exertion there is increased O2 demand. In someone with anaemia there is reduced O2 transport -> myocardial ischaemia -> angina.
How do blood vessels try and compensate for increased myocardial demand during exercise.
When myocardial demand increases e.g. during exercise, microvascular resistance drops and flow increases!
Why are blood vessels unable to compensate for increased myocardial demand in someone with CV disease?
In CV disease:
Epicardial resistance is high meaning microvascular resistance has to fall at rest to supply myocardial demand at rest.
When this person exercises, the microvascular resistance can’t drop anymore and flow can’t increase to meet metabolic demand = angina!
What percentage of stenosis is associated with stable angina?
70% occlusion of the artery.
This still allows enough blood flow through the artery at rest.
What is Stable angina?
Occlusion of an artery (70%) leading to ischaemia of the myocardial tissue resulting in chest pain.
At rest enough blood can still flow through the artery to meet the demands of the tissue.
Upon exercise or exertion, the tissue requires more oxygen and therefore a greater blood flow at which point the flow through the stenosed artery is not adequate enough and hence results in chest pain upon exertion.
what is the most common type of angina?
Stable angina
What is the most commonly affected region of the heart in stable angina?
Subendocardium.
The coronary arteries struggle to perfuse the deeper layers of the myocardium either due to coronary artery stenosis or LV hypertrophy resulting in ischaemia to this portion of the tissue.
What are the Symptoms of angina?
Central Crushing chest Pain on exertion/rest /emotion/cold/heavy meals.
May radiate to one or both arms, neck, jaws or teeth.
Worsens with time
Other Symptoms: Dyspnoea, nausea, sweatiness, faintness
What is the difference between symptoms of angina in Stable, unstable and decubitus types?
Stable angina occurs in periods of roughly 20 mins upon exertion or exercise.
Unstable angina can be continuously painful at rest or even minimal exertion.
Decubitus angina causes pain when lying down flat.
What is the difference pathophysiologically between stable and unstable angina?
Both are commonly caused by atherosclerotic plaque causing obstruction of a coronary artery.
In unstable angina, the plaque may rupture causing blood to leak out and a secondary thrombus to form which occludes the artery further creating an even narrower lumen for blood to flow through.
What is a key distinction between angina and MI?
Angina results in pain due to myocardial ischaemia where the heart tissue is starved of oxygen but is still alive.
MI is when the ischaemia has resulted in infarction that has led to the death of the heart tissue.
Angina is therefore reversible and MI is not.
What is Prinzmetals Vasospastic angina?
angina where patients may or may not have atherosclerosis of the coronary vessels.
instead ischaemia occurs due to vasospasms of the coronary arteries where they constrict so much they can cause ischaemia.
These can occur at any time not just on rest or on exertion.
What is the mechanism that causes prinzmetals angina?
Not clearly understood but likely due to vasoconstriction factors such as Thromboxane A2 release
What layers of the heart are affected in Prinzmetals angina?
Transmural Ischaemia
All layers of the heart wall supplied by the coronary arteries are affected.
What ECG reading would be shown on stable angina?
AT rest: Normal
On exertion:
ST segment depression due to subendocardium ischaemia.
What ECG reading would be shown in prinzmetals angina?
ST segment elevation due to transmural ischaemia.
How can symptoms of stable angina be relieved?
Relieved upon rest (after approx 5 mins)
OR
Symptoms relieved by GTN spray
What cardiac enzymes are used to aid the diagnosis of ACS?
Cardiac troponin (Troponin T and I):
Released into the blood when cardiac muscle is damaged.
Highly sensitive but not specific.
Creatine Kinase - MB (CK-MB):
Helpful to determine re-infarction as levels should drop back to normal 36-72 hours after.
What is the progression of cardiac troponins following an MI?
Rise within 3-12 hours
Peak at 24-48 hours
Return to baseline by 5-14 days
<14g/l normal = no MI, 14-30 ng/l = possible MI, >30ng/l = definite MI
Are troponin levels elevated in angina?
Often they are normal since the ischaemia has not killed the cells and thus the troponin have not been released
sometimes they may be elevated
Describe the primary prevention of angina.
- Risk factor modification.
- Low dose aspirin.
Describe the secondary prevention of angina.
- Risk factor modification.
- Pharmacological therapies for symptom relief and to reduce the risk of CV events.
- Interventional therapies e.g. PCI.
Name 3 symptom relieving pharmacological therapies that might be used in someone with angina.
- Beta blockers.
- Nitrates e.g. GTN spray.
- Calcium channel blockers.
Describe the action of beta blockers.
Beta blockers are beta 1 specific.
They antagonise sympathetic activation and so are negatively chronotropic and inotropic.
Myocardial work is reduced and so is myocardial demand = symptom relief.
Give 4 side effects of beta blockers.
- Bradycardia.
- Tiredness.
- Erectile dysfunction.
- Cold peripheries.
When might beta blockers be contraindicated?
They might be contraindicated in someone with asthma or in someone who is bradycardic.
Give an example of a cardio-specific beta blocker
Atenolol
Describe the action of nitrates in GTN spray
Nitrates e.g. GTN spray are venodilators. Venodilators -> reduced venous return -> reduced pre-load -> reduced myocardial work and myocardial demand.
Describe the action of Ca2+ channel blockers.
Ca2+ blockers are arterodilators and negative Chronotropic/ionotropic agents:
Reduced O2 demand -> reduced BP -> reduced afterload -> reduced myocardial demand.
Name 2 drugs that might be used in someone with angina or in someone at risk of angina to improve prognosis.
- Aspirin.
- Statins.
How does aspirin work?
Aspirin irreversibly inhibits COX. You get reduced TXA2 synthesis and so platelet aggregation is reduced.
Caution: Gastric ulcers!
What are statins used for?
They reduce the amount of LDL in the blood.
What ECG reading would be shown on unstable angina?
May be normal
May have some ST depression/T wave inversion/depression
What ECG reading would be shown on unstable angina?
May be normal
May have some ST depression/T wave inversion
What is the treatment for Stable angina?
Immediate Symptomatic Relief - GTN sublingual stray
Long Term Symptomatic Relief - Beta Blocker (Atenolol) or Calcium Channel Blocker (Amlodipine)
Secondary Prevention of CVD:
Aspirin
Atorvastatin
ACE inhibitor
Already on a beta blocker
What are the investigations for stable angina?
Clinical Hx of pain / relief
ECG :
Rest - normal
Exertion - ST depression/Flat T waves
CT Angiography - Stenosed atherosclerotic artery
What treatment should be considered for angina if pharmacology is unsuccessful?
Referral for revascularisation
Through PCI or CABG
What is revascularisation?
Revascularisation might be used in someone with angina. It restores the patent coronary artery and increases blood flow.
Name 2 types of revascularisation.
- PCI.
- CABG.
Give 2 advantages and 1 disadvantage of PCI.
- Less invasive.
- Convenient and acceptable.
- High risk of restenosis.
Give 1 advantage and 2 disadvantages of CABG.
- Good prognosis after surgery.
- Very invasive.
- Long recovery time.
How is unstable angina diagnosed?
History
ECG - may present as ST-segment depression, transient ST-segment elevation, or T-wave inversion
No elevation in troponin - unstable angina not associated with damage to the heart
What is the Clinical Classification of Unstable Angina?
- Cardiac chest pain at rest or during minimal exertion
- Severe and of new onset cardiac chest pain
- Cardiac chest pain with crescendo pattern (distinctly more severe, prolonged, or frequent than before)
Define Myocardial Infarction?
Necrosis of cardiac tissue due to prolonged myocardial ischaemia due to COMPLETE occlusion of an artery by thrombus.
What are the types of MI?
Non-ST Elevated Myocardial Infarction (NSTEMI)
ST Elevated Myocardial Infarction (STEMI)
Silent MI
What would the ECG for a STEMI look like?
ST elevation and tall T waves
Will produce pathological Q waves some tome after an MI
There may be a new LBBB in larger MIs (WiLLiaM)
V1 – W shape
V6 – M shape
What would the ECG for a NSTEMI look like?
ST depression
T wave inversion
Q waves may be present hours/days after infarct
(often a retrospective diagnosis)
What heart sound signs may be heard in an MI?
4th heart sound – due to forceful contraction of the atria to overcome a stiff or dysfunctional ventricle
Pansystolic murmur – due to papillary muscle dysfunction or rupture
What is the difference in an NSTEMI and STEMI when caused by atherosclerosis?
NSTEMI occurs after a partial occlusion of major Coronary artery
STEMI occurs after complete occlusion of a major Coronary artery.
What is the management plan for ACS that is not an STEMI?
Risk Factor modification:
Stop smoking
Lose weight
Healthy diet
Exercise
Anti-platelet therapy:
- Aspirin (300mg initially then 75mg daily)
- Dual therapy with P2Y12 receptor inhibitors - Clopidogrel (300 mg initially then 75mg for 12 months), ticagrelor (180 mg initially then 90 mg twice daily) or prasugrel
Platelet glycoprotein IIb/IIIa receptor inhibitor for high risk patients (Abciximab)
PCI (if risk assessment score (GRACE) is medium/high) and CABG
Anti-coagulants:
Heparin/LMWH e.g. enoxaparin has better efficacy than unfractionated heparin
Fondaparinux
Other Sx Control:
Nitrates – GTN spray or IV infusion
Beta blockers – bisoprolol
Statins
ACE inhibitors - Ramipril
Calcium channel blockers (if beta blocker contraindicated) – amlodipine
What are the complications of ACS?
DARTHVADER:
Death
Arrhythmias
Ruptured septum
Tamponade
HF
Valve disease
Aneurysm of ventricle
Dressler’s syndrome – pericarditis and pericardial effusion after 2-12 weeks
Embolism
Reoccurrence of ACS
What is the acute treatment for ACS (STEMI/NSTEMI)?
MONAC:
Morphine
Oxygen (if Sats < 94%)
Nitrates (GTN)
Aspirin (300mg)
Clopidogrel (dual antiplatelet)
What is the treatment for an NSTEMI following acute treatment of ACS?
GRACE score:
low risk - monitor
Med-High risk - angiogram / PCI
What is the treatment of choice for STEMI?
PCI
May also have thrombolysis (IV alteplase) or CABG
What is the long term treatment/Secondary prevention management following ACS?
6 As
Aspirin (75g once daily)
Another antiplatelet - Ticagrelor/Clopidogrel
Atorvastatin (80mg once dail)
ACE inhibitors (ramipril)
Atenolol (or another bB)
Aldosterone antagonist (spironolactone) in those with clinical heart failure
What is Dressler’s Syndrome?
Post myocardial infarction syndrome
Occurs around 2-6 weeks post MI
Localised immune response causing pericarditis.
What is the pathology of Dresslers Syndrome?
thought to be an autoimmune reaction against antigenic proteins formed as the myocardium recovers. It is characterised by a combination of fever, pleuritic pain, pericardial effusion and a raised ESR. It is treated with NSAIDs.
What are the complications of MI?
DREAD:
Death
Rupture of the heart septum/papillary muscles
Edema (causing heart failure)
Arrythmia and Aneurysm
Dressler’s Syndrome
What are the subsequent complications from rupture of the ventricular septum, LV wall or papillary muscles due to MI?
Ventricular Septum - Right HF
LV wall - Cardiac tamponade
Papillary Muscles - Mitral regurgitation/prolapse
What are the time periods of the consequences of an acute MI?
Immediate:
Ventricular Fibrillation (cardiac arrest) - most common cause of death post MI
<24hrs:
Cardiogenic shock
Bradyarrythmias
3-5 days:
Mitral regurgitation - papillary muscle rupture
Ventricular septal rupture
2-6 weeks:
Dressler syndrome
What are the differential diagnoses for an MI?
MI
Stable/unstable angina
Pericarditis
Aortic aneurysm
Endocarditis
Pulmonary Embolism
Pneumothorax
What heart area and ECG leads correspond to:
Left Coronary Artery
LAD
Circumflex
Right Coronary Artery
Left Coronary Artery:
Heart area - Anterolateral
ECG leads - I, aVL, V3-V6
LAD:
Heart area - Anterior
ECG leads - V1-4
Circumflex:
Heart area - Lateral
ECG leads - I aVL, V5-6
Right Coronary Artery:
Heart area - Inferior
ECG leads - II, III, aVF
What is the Epidemiology for an MI?
600/100,000 for men.
200/100,000 for women
Name some of the function of platelets during arterial thrombosis
- Procoagulant activity; release of thrombin
- Dense granule secretion; contributes to platelet activation
- Alpha granule secretion; contributes to coagulation and inflammation
- Platelet-fibrin clot; fibrin acts as glue that keeps the thrombus growing and allow it block of arteries to cause MI.
Give a brief overview of the process by which platelets cause the platelet plug?
(1) Shear flow
(2) Initial adhesion GPIb/VWF
(3) Rolling GPIb/VWF/α2β1/collagen
(4) Stable adhesion activation/aggregation GPVI, GPIIb/IIIa
(5) Platelets are activated by ADP (vai P2Y12R), causing them to change shape, aggregate and seal off the endothelial breach
What combined therapy is used to manage patients with ACS?
Aspirin, P2Y12 Inhibitors and GPIIb/IIIa antagonists
Give some examples of P2Y12 inhibitors?
Clopidogrel
Ticagrelor
Prasugrel
What is a major side effect of P2Y12 inhibitors?
Increases risk of bleeding!
Serious bleeding must subside prior to administration and risk of thrombosis vs. risk of bleeding must be monitored throughout use.
Why are GPIIb/IIIa Antagonists very useful in STEMI pateints undergoing PCI?
Cover for delayed absorption of oral P2Y12 Inhibitors occuring due to opiates delaying gastric emptying
What is the role of anticoagulants used in the treatment of ACS?
Targets formation and/or activity of thrombin; inhibiting both fibrin formation and platelet activation
What anticoagulant is commony used during Non-STEMI ACS?
Fondaparinux (a pentasaccharide) is used prior to coronary angiography
What anticoagulants are used during PCI?
Full Dose:
Heparin (unfractionated or LMWH)
Bivalirudin
What is a Silent MI?
When a diabetic patient may not experience typical chest pain during an acute coronary syndrome
What umbrella term does Stable Angina come under?
What umbrella Term does Unstable Angina come under?
Ischaemic Heart Disease (IHD)
Acute Coronary Syndrome (ACS)
What determines if Angina is stable?
Angina is stable if symptoms are always relieved by rest or GTN (glyceryl Trinitrate) spray.
What is the gold standard diagnostic investigation for Stable Angina?
CT Coronary Angiography
Name some causes of oxygen supply reduction associated with IHD?
- Common: anaemia and hypoxaemia
- Uncommon: polycythemia, hypothermia, hypovolaemia, hypervolaemia
Name some causes of oxygen demand increase associated with IHD?
- Common: hypertension, tachyarrhythmia, valvular heart disease
- Uncommon: hyperthyroidism, hypertrophic cardiomyopathy
Give some risk factors associated with IHD?
- Age
- Smoking
- Family history
- Diabetes mellitus
- Hyperlipidemia
- Hypertension
- Kidney disease
- Obesity
- Physical inactivity
- Stress
What are the three major physiological factors lending to oxygen mismatch associated with IHD?
- Impairment of blood flow by proximal arterial stenosis (e.g. atherosclerosis)
- Increased distal resistance (e.g. left ventricular hypertrophy)
- Reduced oxygen carrying capacity of blood (e.g. anaemia)
What is Ohms Law?
Flow = Change in pressure / Resistance
What is Poiseuille’s Equation?
Q = R^4
How does Poiseuille’s Law relate to CCS?
Relationship between flow, pressure and resistance; combination of Ohm’s law and vessel resistance equation. Radius has to fall below 75% before symptoms
What are some differential diagnoses of chest pain?
Cardiac – ACS, Aortic dissection, pericarditis, myocarditis
Respiratory – PE, pneumonia, pleurisy, lung cancer
MSK – rib fracture, chest trauma, costochondritis (inflammation of the cartilage between the ribs and sternum)
GORD
Oesophageal spasm
Anxiety/panic attacks
How would you discuss a patients pain when taking a history for IHD?
SOCRATES:
Site
Onset
Character
Radiation
Associated symptoms
Time/Duration
Exacerbating features
Severity
What characteristics of chest pain suggest ischaemic cardiac pain?
- Heavy, tight pain
- Located centrally
- Provoked by cold weather, big meals, exertion
- Relieved by rest, GTN spray
- Associated SOB
What is exercise testing?
Patient undertakes mild exercise on a treadmill and ECG is run simultaneously - any abnormailites, refer patient to catheterisation lab
What is a Perfusion/ Myoview scan?
IV radio-labelled agent travels to the coronary arteries - areas of darkness signify a blockage.
What are Psychosocial factors?
Factors influencing psychological responses (cognitive; behavioural; emotional) to the social environment and pathophysiological changes
What is a Coronary Prone Behaviour Pattern?
Coronary prone behaviour is the collection of behaviours and attitudes associated with heart disorders especially coronary heart disease and cardiovascular disorders.
Give some examples of personality traits associated with Coronary Prone Behaviour Patterns?
- Aggressiveness/Anger (biggest risk factor)
- Ambition
- Competitiveness
- Hostility (biggest risk factor)
- Impatience
- Sense of time urgency
- Need for achievement
Give some psychosocial factors that increase the risk for CHD?
Depression and Anxiety
Low quantity and quality of social support
High demanding jobs/low control of jobs
What are the layers of the pericardium?
Outer Fibrous layer - Continuous with the central tendon of the Diaphragm
Serous layer:
Outer Parietal - lines the inner surface of the fibrous pericardium
Inner Visceral - forms the outer layer of the heart (Epicardium)
What is found between the parietal and Visceral pericardium?
What is the Function of this?
Pericardial cavity:
Contains 50ml of serous fluid to minimise the friction generated when the heart contracts
Which great vessels are Contained within the pericardium?
Roots of the great vessels:
Aortal
Pulmonary Artery
Pulmonary Veins
SVC
IVC
What are the main functions of the pericardium?
- Fixes the heartin the mediastinum and limits its motion.
- Prevents overfillingof the heart. The relatively inextensible fibrous layer of the pericardium limits the filling pressure and volume of the heart
- Lubrication. A thin film of fluid between the two layers of the serous pericardium reduces the friction generated by the heart as it moves within the thoracic cavity
- Protection from infection. The fibrous pericardium serves as a physical barrier between the muscular body of the heart and adjacent organs prone to infection, such as the lungs.
What is the purpose of the small reserve volume associated with the pericardial sac?
Volume of pericardial fluid changes based on the physiological state of the heart.
What is Cardiac Tamponade?
Reduction in cardiac output due to a raised intrapericardial pressure secondary to a pericardial effusion.
As there is a greater pressure, the heart chambers cannot expand during diastole reducing SV and CO
What are some signs associated with cardiac tamponade?
Beck’s Triad
Pulsus Paradoxus
Tachycardia and Hypotension
Soft heart sounds
What is Chronic pericardial effusion?
Slow accumulation of fluid allowing for adaptation of the parietal pericardium
Why does Chronic Pericardial Effusion rarely cause Cardiac Tamponade?
Increased compliance reduces the effect on diastolic filling and therefore slow accumulating effusion does not often cause tamponade.
Define Pericardial Effusion?
Accumulation of excess fluid in the pericardial cavity; the pericardial fluid contains blood components such as fibrin, RBCs and WBCs
Define Acute Pericarditis?
Inflammation of the pericardium commonly due to viral infection.
What are the different types of Pericarditis?
Acute
Chronic effusive
Chronic Constrictive
Who is typically affected by pericarditis?
Males - 20-50yrs
What are some of the main causes of pericarditis?
Infection - Coxsackie Virus
Dressler’s Syndrome
Autoimmune
Neoplastic
Metabolic
Traumatic
Iatrogenic - PCI
What are some infectious causes of pericarditis?
HEAP:
Herpes virus
Enterovirus (Coxsackie)
Adenovirus
Parovirus
What are some Autoimmune causes of Pericarditis?
Sjogren’s Syndrome
SLE
Rheumatoid Arthritis
Scleroderma
Systemic Vasculitides
What is Constrictive Pericarditis?
persistent inflammation of acute pericarditis causes the heart to be encased with a rigid fibrotic calcified pericardial sac which prevents adequate diastolic filling of the ventricles
How is Pericarditis diagnosed?
ECG: (diagnostic) - PeRicardiTiS (PR dep and ST elev)
Concave Saddle Shaped ST elevation (in all leads)
PR depression
ECHO - exclude pericardial effusion/tamponade
CXR - Bottle water silhouette
FBC - increased WCC
Chest Pain
ESR/CRP - High ESR may suggest aetiology
Pericardial Rub
What is the Pathology of Pericarditis?
Pericardium becomes acutely inflamed, with pericardial vascularisation and infiltration with polymorphonuclear leukocytes
A fibrinous reaction frequently results in exudate and adhesions within the pericardial sac, and a serous or haemorrhagic effusion may develop
If this fluid accumulation impacts the hearts function this is cardiac tamponade
What is the nature of the chest pain associated with pericarditis?
Sharp severe pleuritic chest pain - radiate to left shoulder due to phrenic nerve
Pain is relieved when sitting forward
Pain is exacerbated when lying flat or on inspiration
What are the symptoms of pericarditis?
Severe pleuritic chest pain
Dyspnoea
Cough/hiccups - phrenic involvement
Systemic disturbance - weight loss, joint pain, fever
What is Pericardial Rub?
Extra heart sound heard upon auscultation
One systolic - Two diastolic
Sound resembles scratching.
What are the signs of effusion associated with pericarditis?
Pulsus paradoxus
Kussmaul’s Sign - rise in JVP on inspiration
Tachycardia and Hypotension
soft heart sounds - effusion obscures beat and sounds
What is Beck’s Triad?
Three clinical signs associated with pericardial tamponade:
- Falling BP - Hypotension (weak pulse or narrow pulse pressure)
- Muffled heart sounds
- Raised jugular venous pressure.
What are some important differential diagnoses of pericarditis?
MI - has no pericardial rub/not related to lying down (ST elevation not saddle shaped)
pneumonia
Aortic Dissection
PE
What is the management for pericarditis?
Period of sedentary activity until resolution of inflammation
NSAIDS (2 weeks) + Gastric Protection (PPI)
Colchicine (3 weeks)
Consider Abx for bacterial aetiology
What is the Mechanism of action of Colchicine?
Inhibits migrations of neutrophils to site of inflammation to reduce risk of reoccurrence
What are some complications of pericarditis?
Pericardial effusion - cardiac tamponade
myocarditis
constrictive pericarditis
How is Pericardial Effusion Diagnosed?
Echocardiogram - Echo free space around heart
CXR – large heart
ECG – low voltage QRS complexes and sinus tachycardia
How is cardiac tamponade diagnosed?
ECHO - diagnostic
Beck’s Triad
ECG - varying QRS peaks
CXR - big globular heart
How is Cardiac Tamponade treated?
Urgent pericardiocentesis
How is Pericardial Effusion treated?
treat underlying cause
NSAIDS
Colchicine
What is the main cause of pericardial effusion?
Typically pericarditis
RF are all factors related to pericarditis
Name some environmental causes of Angina?
Emotional stress
Large meals
Cold weather
What is Poiseuille’s Law?
Resistance = 8lu/pi r^4
l - length of vessel
U - viscosity
R - radius of vessel
What is Crescendo Angina?
patients present with angina over a period of months that gets progressively worse
What is the prevalence of Angina in men and women?
Men - 5% (5000/100,000)
Women - 4% (4000/100,000)
What is a common side effect of nitrates in GTN?
headache due to vasodilation
What are some side effects of Calcium channel blockers?
postural hypotension
Swollen ankles
Flushing
What procedures may be involved in PCI?
Balloon Stent
Angioplasty with Stent
What is the most common cause of Pericarditis?
Viral infection
What are the various causes of pericarditis??
Idiopathic
Infection:
Viral (most common) – HIV, Coxsackie B, echovirus
Bacterial – TB
Fungal – Histoplasma spp.
Malignancy
MI
Autoimmune (immune system attacking the pericardium):
Sjogren’s
RA
SLE
Dressler syndrome (inflammation of pericardium after MI damaging it)
What is Pulsus Paradoxus?
An inspiratory decrease in systolic BP >10mmHg.
(not a paradox but exaggeration of normal physiology)
Caused by increased venous return to the right side of the heart during inspiration
The increased RV volume therefore occupies more space within the rigid pericardium and impairs LV filling
Paradox:
On physical exam, beats are detected on cardiac auscultation during inspiration which cannot be palpated at the radial pulse. This is associated with increased JVP (kussmauls sign)
What is cardiomyopathy?
A disease of the heart muscle tissue where there is impaired ability to contract and/or there is electrical conduction dysfunction.
what is the epidemiology of cardiomyopathy?
Generally they are inherited conditions but can be acquired
What are the general risk factors for cardiomyopathy?
Family history
Hypertension
Obesity
Diabetes
Previous MI
What are the 3 major determinants of myocardial performance?
Preload - the volume of blood entering the ventricles that causes a greater stretch on the ventricles.
Afterload - The pressure that must be overcome in order to eject blood from the ventricles during systole.
Contractility
What are the main types of cardiomyopathy?
Hypertrophic Cardiomyopathy (HCM)
Dilated Cardiomyopathy (DCM)
Arrhythmogenic Right/Left ventricular Cardiomyopathy (ARVC/ALVC)
Restrictive Cardiomyopathy.
What is the most common type of Cardiomyopathy?
Dilated Cardiomyopathy
What is Primary Cardiomyopathy?
Occurs when genes encoding proteins involved in the Myocardial tissue are dysfunctional resulting in poor/altered function myocardial cells and further pathology.
What is Secondary Cardiomyopathy?
Where the Myocardial cells structure and function becomes damaged through:
Toxins
inflammation
infection
systemic disorders
How are cardiomyopathies diagnosed?
ECHO
Some with MRI
Troponins may be elevated.
What is Dilated Cardiomyopathy?
Dilation/thinning of the ventricular walls (chamber enlargement) causing weakness of the ventricular myocardial cell contraction.
Systolic function is impaired leading to poorly ejected blood
Can result in biventricular congestive HF.
What are the Symptoms of Dilated Cardiomyopathy?
Can be Asymptomatic
May present as congestive heart failure.
Dyspnoea
Weakness
Fatigue
Oedema
Raised JVP
Pulmonary congestion
Cardiomegaly
3rd/4th Heart Sounds
What is the Aetiology of Dilated Cardiomyopathy?
Idiopathic - Gene mutations often in cytoskeletal genes.
Infection
Ischaemia
Alcoholism
Thyrotoxicosis
What is the epidemiology of DCM?
More common in males
35/100,000
Median age - 50
How is DCM diagnosed?
ECHO - Marked Dilatation
CXR - Cardiomegaly, pulmonary oedema
ECG - May have tachycardia/arrhythmias
What is the treatment for DCM?
Tx of underlying conditions - AF/ HF
Bed rest
Loop and Thiazide Diuretics for fluid overload
ACEi
Beta Blockers
Heart transplant
What is Hypertrophic Cardiomyopathy (HCM)?
Unexplained primary cardiac hypertrophy (often on LV wall and interventricular septum) leading to impaired diastolic filling and a reduced stroke volume. due to thick heart and reduced compliance
Which is the main issue in HOCM, Systole or diastole?
Diastole is main issue.
Enlarged heart walls. ventricles are stiff
LV does not relax properly and so diastolic filling is impaired.
What is the cause of HCM?
Autosomal Dominant mutation in Sarcomeric genes:
Beta-myosin heavy chain
Troponin T
alpha tropomyosin.
What are the symptoms of HCM?
Most may be asymptomatic
Variable dyspnoea
Chest pain / palpitations
Syncope
Sudden death
What are the main complications of DCM?
Progressive Heart Failure
Sudden Cardiac Death
What may be found upon examination of a patient with HCM?
Forceful Apex beat
Late ejection systolic Murmur (crescendo-decrescendo similar to AS)
S4 Heart sound - stiff ventricle so sound as blood hits non compliant wall.
Jerky Carotid pulse
Alpha wave in JVP.
What is the Epidemiology of HCM?
1/500
Men and black people more likely
What is the most common form of sudden cardiac death in the young population and atheletes?
Hypertrophic Cardiomyopathy
How is HCM diagnosed?
ECG - LVH, ST segment changes, DEEP T wave inversion
CXR - variable, left atrial enlargement
ECHO - large LV walls
What is the treatment of HCM?
Amiodarone - reduce risk of arrythmias and sudden death
Treat chest pain:
Beta blockers and CCB - Verapamil
Implantable cardioverter defibrillator
What medication is contraindicated in HOCM?
Digoxin
Digoxin can increase inotropy which may exacerbate heart symptoms in patients with HCM that have preserved systolic function
What is HOCM the most common cause of?
Most common cause of sudden death in young and adults (especially athletes)
What is a severe complication of HCM?
Sudden Death
What is Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)?
Associated with Desmosome gene mutations
Fibro-fatty replacement of the RV myocytes leading to impaired ability of RV muscle to contract due to muscle cell loss.
What is Naxos disease?
A autosomal recessive genetic condition associated with ARVC and diffuse palmoplantar keratoderma and woolly hair
What are the symptoms of ARVC?
Arrythmias - main feature
Palpitations
Presyncope/syncope
RHF
Death possible on first presentation
What is the most common sustained arrythmia in HCM?
Atrial Fibrillation
What is the cause of ARVC?
Unknown but may be due to apoptosis, inflammation or genetics
What is the Epidemiology of ARVC?
1/2000
Mainly affects males
30-50% of cases have autosomal dominant genetic predisposition
How is ARVC diagnosed?
ECHO - RV wall Dimensions and abnormalities
RV angiography
ECG - In leads V1, 2 and 3, Epsilon wave, T wave inversion
MRI - fatty infiltration and fibrosis on RV wall.
How is ARVC treated?
Standard heart failure medication.
Beta blockers in asymptomatic patients.
Amiodarone - Tx for arrythmias
Heart transplant
What is the most frequent cause of heart transplants?
Dilated cardiomyopathy.
What is Restrictive cardiomyopathy?
Rigid Fibrotic Myocardium
Increased myocardial stiffness despite normal LV cavity size and function.
Increased stiffness restricts diastolic filling as the ventricle is incompliant.
What are the causes of Restrictive cardiomyopathy?
Granulomatous disease - Amyloidosis (Amyloid heart disease) / Sarcoidosis.
infiltrative myocardial disease
Loffler Endo(myo)carditis
Haemochromatosis
What is the epidemiology of Restrictive cardiomyopathy?
between 1/1000 to 1/1500
5% of all cardiomyopathies
Mainly affects the elderly, tropical Africa
What are the symptoms of restrictive cardiomyopathy?
Similar to constructive pericarditis
Features of RV failure
Dyspnoea
Elevated JVP
Hepatomegaly
Ascites
3rd and 4th heart sounds
What are the investigations for Restrictive cardiomyopathy?
ECHO - thickened ventricular walls, valves and atrial septum.
ECG - Low amplitude signals
MRI - to distinguish between cardiomyopathies.
What is the treatment for restrictive cardiomyopathy?
Tx underlying cause
Heart Transplant
What are the complications of restrictive cardiomyopathy?
Heart failure
sudden death
Poor prognosis.
What is the main feature of ARVC?
Arrhythmia
What do all cardiomyopathies carry a risk of?
Developing arrythmia
What is Takotsubo’s Cardiomyopathy?
Also known as ‘stress-induced cardiomyopathy’ or ‘broken-heart syndrome’.
A stressful event can lead to characteristic apical ballooning with transient systolic dysfunction.
Thought to be related to catecholamine-induced spasm of the small vessels in the microvasculature.
The condition preferentially affects postmenopausal women.
What is a channelopathy?
Gene mutations in genes that are involved in ion channel proteins resulting in channelopathies.
What can be a cardiovascular sign of channelopathies?
Arrythmias
Give some examples of cardiac Channelopathies
Long QT
Short QT
Brugada
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
What is the major clinical sign of ARVC?
Ventricular Tachycardia
What is the commonest symptoms of channelopathies?
Recurrent Syncope
What is Brugada Syndrome?
A channelopathy caused by a mutation in the cardiac sodium channel gene
What are the symptoms of Brugada Syndrome?
Asymptomatic
May have syncope
Can cause sudden death
What are the common rhythmic abnormalities associated with Brugada Syndrome?
Ventricular fibrillation
Polymorphic Ventricular Tachycardia
What would the ECG look like with a patient with Brugada?
Characteristic ST elevation with partial RBBB pattern in V1 and V2
What is sudden cardiac death in young people often due to?
Inherited condition likely a cardiomyopathy or channelopathy
What conditions are included in Aortovascular syndromes?
Marfans
Vascular Ehler Danlos (EDS)
Loeys-Dietz
What is Diastolic Distensibility?
The pressure required to fill the ventricle to the same diastolic volume
What are the Consequences of Hypertension?
Stroke (ischaemic and haemorrhagic)
Myocardial Infarction
Heart failure
Chronic renal disease
Cognitive decline
Premature death
What are the different stages of clinical Hypertension?
- Define Stage 1 Hypertension.
Clinical = 140/90
Ambulatory = 135/85 - Define Stage 2 Hypertension
Clinical = 160/100
Ambulatory = 150/95 - Define severe Hypertension.
Clinical = 180/110
How is Hypertension treated?
Lifestyle modification
Antihypertensive drug therapy
Who should be offered antihypertensive drug treatment for hypertension?
Individuals aged 80 or below and individuals who have one or more of the following:
- Target organ damage
- Established CVD
- Renal disease
- Diabetes
- 10-year CVD risk of >20%
Describe mechanisms of BP control - targets for therapy
- Cardiac output and peripheral resistance
- Interplay between the RAAS and sympathetic nervous system (NA)
- Local vascular vasoconstrictor and vasodilator mediators
Describe the renin angiotensin-aldosterone system.
- Kidneys sense low BP and renin is released from juxtaglomerular cells.
- Renin converts angiotensinogen to angiotensin I
- ACE from the lungs converts angiotensin I to angiotensin II
- Angiotensin II (extremely potent vasoconstrictor) stimulates aldosterone release resulting in increased Na+ and thus water reabsorption which leads to increased blood volume and thus blood pressure
Describe the Sympathetic nervous system response to a drop in BP?
Drop in BP results in the release of noradrenaline,
leading to vasoconstriction and increased contractility of the heart
thus increasing peripheral resistance and cardiac output and thus BP.
Also results in renin release which further augments RAAS
What is the MOA of ACE inhibitors?
Prevent ACE converting angiotensin I to Angiotensin II and therefore inhibiting the CVS effects of Angiotensin II
Give examples of ACEis?
- Ramipril
- Enalapril
- Perindopril
- Trandolapril
What are the indications for ACE Inhibitors?
- Hypertension
- Heart Failure
- Diabetic nephropathy
What are the main Adverse effects of ACEi?
Related to reduced Angiotensin II:
Hypotension
Acute renal failure
Hyperkalaemia
Teratogenic effects in pregnancy
Related to increased Kinin Production:
Cough
Rash
Anaphylactoid reactions
Why are there side effects such as cough when using ACEi?
ACE breaks down bradykinin.
If ACE is inhibited then bradykinin levels increase
This can cause a persistent dry cough
What are Angiotensin II Receptor Blockers (ARBs)?
They block the receptors of angiotensin II preventing its binding and it inducing effects.
Give examples of ARBs?
- Candesartan
- Losartan
- Valsartan
- Telmisartan
What are the indications for ARBs?
- Hypertension (and when ACEi is contradicted due to cough)
- Diabetic nephropathy
- Heart failure (when ACEi contraindicated - acts on AT-1 receptor)
What are the ADRs associated with ARBs?
- Symptomatic hypotension (esp. in volume depleted patients)
- Hyperkalaemia
- Potential renal dysfunction
- Rash
- Angiooedema
- Teratogenic in pregnancy
What are Calcium Channel Blockers (CCBs)?
These block the calcium channels from allowing Ca entry into cardiomyocytes.
What are the indications for CCBs?
- Hypertension
- IHD (angina)
- Arrhythmias
Give examples of CCBs.
- Dihydropyridines (e.g.amlodopine, nifedipine, felodipine)
- Phenylalkylamines(e.g. verapamil)
- Benzothiozepines(e.g. diltiazem)
Give an example and explain the actions of Dihydropyridines?
Amlodipine:
Preferentially affect Vascular smooth muscle and act as peripheral arterial vasodilators
Give an example and explain the actions of Phenylalkylamines?
Verapamil:
Directly affects the heart - negatively chronotropic, negatively ionotropic
Give an example and explain the actions of Benzothiozepines?
Diltiazem:
Intermediate heart and peripheral vascular effects
What are the ADRs associated with CCBs?
Due to peripheral vasodilation (Dihydropyridines):
- Flushing
- Headache
- Peripheral oedema
- Palpitations
Due to negative chrontropic effect (Phenylalkylamines and Benzothiozepines):
- Bradycardia
- Atrioventricular block
- Postural hypotension
Due to negative ionotropic effect (Benzothiozepines)
- Worsening of HF
Verapamil causes constipation
What are Beta Blockers?
Beta adrenoceptor blockers that prevent the effects of adrenaline and noradrenaline in the sympathetic nervous system.
They work on B1 and B2 receptors.
Give examples of Beta Blockers?
- Bisoprolol
- Propranolol
- Atenolol
- Carvedilol
What are the indications for beta blockers?
- IHD - angina
- HF
- Arrhythmia
- Hypertension
Which beta blockers are B-1 selective?
Metoprolol
Bisoprolol
(Atenolol is mostly B1 but not entirely cardioselective)
Which beta blockers are non-selective?
Propranolol
Nadolol
Carvedilol
What condition is contraindicative for beta blockers?
Asthma
What are the ADRS associated with Beta blockers?
- Fatigue
- Headache
- Sleep disturbance
- Bradycardia
- Hypotension
- Cold peripheries
- Erectile dysfunction
What conditions can Beta blockers cause exacerbations of
Asthma
PVD - Claudication or Raynauds
Heart Failure - when given in standard doses or acutely
How do Diuretics reduce blood pressure?
Increased excretion of water, salt and metabolites in urine
What are the indictations for Diuretics?
- Hypertension
- Heart failure
What are the different classes of Diuretics?
Thiazide diuretics - act on distal tubule blocking Na/Cl exchanger
Loop diuretics - act on ascending loop of henle, blocks Na/K/2Cl (NKCC2) transporter
Potassium-sparing diuretics(Aldosterone antagonists) - Retain Potassium
Give examples of Diuretics of each class?
- Thiazide diuretics: bendroflumethiazide, hydrochlorothiazide
- Loop diuretics: furosemide, bumetanide
- Potassium-sparing diuretics: spironolactone, eplerenone
What are the ADRs associated with Diuretic?
- Hypovolaemia (mainly loop)
- Hypotension (mainly loop)
- Hypokalaemia
- Hyponatraemia
- Hypomagnesaemia
- Hypocalcaemia
- Hyperuricaemia (gout)
- Erectile dysfunction (thiazides)
- Impaired glucose tolerance (thiazides)
Give an alpha 1 adrenoceptor blocker used as an anti-hypertensive?
Doxazosin
Give examples of centrally acting antihypertensives?
Act on the CNS:
Moxonidine
Methyldopa
When may Methyldopa be used?
During pregnancy for gestational hypertension
Give an example of a direct Renin Inhibitor?
Aliskiren
Outline the treatment programme for hypertension of someone under the age of 55yrs?
First line: ACEi or ARB
Second Line: ACEi/ARB + CCB
Third Line: ACEi/ARB + CCB + Thiazide
Fourth line (Resistance HTN): Consider addition of Spironolactone, alpha blocker, beta blocker
Outline the treatment programme for hypertension of someone over the age of 55yrs or afro-caribbean ?
First line: CCB
Second Line: ACEi/ARB + CCB
Third Line: ACEi/ARB + CCB + Thiazide
Fourth line (Resistance HTN): Consider addition of Spironolactone, alpha blocker, beta blocker
What is malignant hypertension?
Rapid rise in BP leading to vascular damage
What are the signs and Symptoms of malignant hypertension?
Sx - Headache, Visual Disturbances
Signs:
Systolic BP >200
Diastolic BP > 130
Bilateral renal haemorrhage - exudates - papilloedema
What are the complications of malignant hypertension?
Hypertensive Emergencies:
AKI
HF
Encephalopathy
What is the treatment for malignant hypertension?
Sodium Nitroprusside
Define Heart Failure?
Complex clinical syndrome of signs and symptoms that suggest the efficiency of the heart as a pump is impaired and cannot satisfy the needs of metabolising tissues
What are the different Types of Heart Failure?
Systolic:
Left Ventricular Systolic Dysfunction (Most common) - caused by contractility dysfunction
Diastolic:
Heart failure with preserved ejection fraction (HFPEF) - caused by dysfunction during diastole (filling)
Acute/Chronic Heart Failure
What are the features and main causes of systolic HF?
Failure to contract
Ejection fraction <40% (SV/EDV)
Caused by:
- IHD
- MI
- Hypertension
- Cardiomyopathy
What are the features and main causes of Diastolic HF?
Inability to relax and fill
There is reduced preload because there is abnormal filling of the LV
Ejection fraction >50%
Caused by:
- Constrictive pericarditis
- Cardiac tamponade
- Hypertension
What is the epidemiology of HF?
Annual incidence of 10% in patients over 65
50% of patients die within 5 years
What are the major risk factors of HF?
Age – 65+
Obesity
Gender – male
People who have had a previous MI
What is the underlying principle of treatment of heart failure?
Vasodilator therapy via neurohumoral blockade (RAAS-SNS)
What is used in the symptomatic treatment of heart failure?
Diuretics - often loop
What are the stages involved in disease influencing neurohumoral blockade therapy for heart failure?
A (first Line) - ACEi + BB therapy (low dose titrated up slowly)
B: Aldosterone Antagonist (Spironolactone)
C: ARNI (ARB + Neprilysin inhibitor) - Entresto ( combination of Valsartan + Sacubitril)
D: SGLT2 inhibitor - Dapagliflozin
E: ACEi intolerance - ARB
F: ACEi and ARB intolerance - Hydralazine/nitrate combination
G: consider Digoxin
What are Nitrates when used as a treatment?
Arterial and Venous dilators
These reduce both preload (venous dilation) and afterload (arterial dilation) to lower the BP
What are the main indications for nitrates?
IHD (Angina)
Heart Failure
Give Examples of nitrates?
- Isosorbide mononitrate (tablet)
- GTN spray
- GTN infusion (acute/ severe angina)
What are the ADRs associated with Nitrates?
- Headache
- GTN spray syncope
- Potential tolerance to the drug
What are the cardiac natriuretic peptides (CNPs?)
Atrial Naturetic Peptide (ANP) - Atria
Brain Naturetic Peptide (BNP) - Brain and Ventricles
What causes the physiological release of cardiac natriuretic peptides?
Stretching of atrial and ventricular muscle cells, raised atrial or ventricular pressures and volume overload
What effect do CNPs have on renal excretion?
Increases renal excretion of sodium (natriuresis) and water (diuresis)
What effect do CNPs have on vascular smooth muscle?
Relax vascular smooth muscle (except efferent arteriole) of renal glomeruli to preserve filtration pressure in kidney whilst still removing Na+ and thus water thus no renal damage)
What effect do CNPs have on vascular permeability?
Increased vascular permeability
What effect do CNPs on the release of other chemical mediators?
Reduces aldosterone, angiotensin II, endothelin (most potent vasoconstrictor) and ADH release
What are CNPs a counter-regulatory system to?
Counter-regulatory system to the renin-angiotensin system
What are NPs metabolised by?
NEP or Neprilysin
How can the inhibition of NP metabolism be used for in the treatment of HF?
NEP inhibition increases levels of natriuretic peptides
Name examples of NEP inhibitors.
Sacubitril - is a neprilysin inhibitor
Entresto (ARNI) - is a combination of sacubitril and valsartan (ARB) - VERY EFFECTIVE IN HEART FAILURE
What are the Class I antiarrhythmic Drugs?
Sodium Channel Blockers:
1A: quinidine
1B: lidocaine
1C: flecainide
What are the Class II Anti-arrhythmics?
Beta-blockers:
- non-selective (e.g.propranolol, nadolol, carvedilol)
- beta-1 selective (e.g. bisoprolol, metoprolol)
Why Is Propranolol useful for arrhythmias immediately post MI?
It blocks both Beta adrenoceptors and can block sodium channels too
What are the Class III Anti-arrhythmics?
Prolongs action potential:
Amiodarone blocks potassium channels during repolarisation to increase the AP.
Cause QT prolongation; potential for significant side effects in patient with QT prolongation
What are the Class IV Anti-arrhythmics?
Calcium channel blockers (only phenylalkylamines and benzothiozepines):
Verapamil and Diltiazem
Verapamil is more effective than amlodipine as it does not affect calcium channel at rest
What do Class I and III anti-arrythmics do?
Rhythm control (sympathetic drive, e.g. adrenaline worsens arrhythmias)
What do Class II and IV anti-arrythmics do?
Rate control (sympathetic drive, e.g. adrenaline worsens arrhythmias)
What are the ADRs associated with Amiodarone?
- Bradycardia
- Interstitial Lung Disease
- Thyroid (hyper and hypo)
- Corneal (ocular)/cutaneous (skin)
- Hepatic dysfunction/hypotension when IV (due to solvents)
- Photosensitivity
- Drug interactions
What type of drug is Digoxin?
Cardiac glycoside
By what mechanism does Digoxin affect the heart?
Inhibits Na/K pump;
Therefore Na/Ca exchanger is not active as Na conc increases in the cell
Therefore Ca is not removed from the cell
causes an increase in Ca2+ inside the cells of the heart
Increases contraction of myocytes
What affect does Digoxin have on the heart?
- Bradycardia (increased vagal tone)
- Slows AV conduction (increased vagal tone)
- Increased ectopic activity
- Increased force of contraction (direct +ve inotropic effect) by increasing intracellular calcium
What are the indications for Digoxin?
- Atrial Fibrillation; reduces ventricular rate response
- Severe heart failure; has a positive inotropic effect
What are the ADRs of Digoxin?
- Narrow therapeutic range
- Nausea
- Vomiting
- Diarrhoea
- Gynaecomastia
- Confusion
What are Structural Heart defects?
These are often Congenital defects that occur during pregnancy to the heart that are not necessarily inherited that cause heart problems.
They can range from minor to life incompatible
Give examples of some structural heart defects?
Bicuspid Aortic Valve
Atrial Septal Defect (ASD)
Ventricular Septal Defect (VSD)
Coarctation of the Aorta
Fallot’s Tetralogy
Patent Ductus Arteriosus
Patent Foramen Ovale
What is Tetralogy of Fallot?
Combination of four congenital abnormalities affecting the structure of the heart. This causes oxygen-deficient blood to flow out of the heart and to the rest of the body.
What are the four abnormalities associated with Tetralogy of Fallot?
Ventricular Septal Defect (VSD) - hole between 2 ventricles
Over-riding Aorta - Allows blood from both ventricles to entre the aorta
RV Hypertrophy - thickening of RV muscle
Pulmonary Stenosis - Narrowing of the exit from the RV to pulmonary circulation
What are the consequences of the abnormalities in Tetralogy of Fallot?
There is a greater pressure in the RV than the LV and so blood is shunted into the LV → cyanosis as blood is not oxygenated
What are the symptoms associated with Tetralogy of Fallot?
Severity dependent on degree of pulmonary stenosis
Cyanosis
Clubbing
Poor Feeding / weight gain
Tet spells
Ejection Systolic Murmur (pulm stenosis)
Increase Hb concentration
What is the cause of Tetralogy of Fallot?
Unknown but likely genetic influence
What is the Epidemiology of Tetralogy of Fallot?
Most common complex cardiac abnormality.
10% of congenital heart conditions
What are the investigations for Tetralogy of Fallot?
CXR - boot shaped heart
ECHO CG (doppler)- anatomy and degree of stenosis/assess flow
What is the Treatment for Tetralogy of Fallot?
Early surgical intervention within 2 years
Mortality of 5%
What is Ventricular Septal Defect (VSD)?
An abnormal connection between the LV and RV causing a left to right shunt enabling more blood to enter the pulmonary circulation.
Why is there not cyanosis in VSD?
There is a higher pressure in the LV than the RV and so blood is shunted from the left to right meaning there is an increased amount of blood going to the lungs; not cyanotic.
What are the clinical signs of a small and large VSD?
Size Matters:
Small - Asymptomatic
Large:
Very high pulmonary blood flow in infancy leads to pulmonary hypertension and eventual Eisenmenger’s complex
Small, breathless baby, poor feeding, failure to thrive
Increased respiratory rate
Tachycardia
Big heart on chest X ray
Murmur varies in intensity
What is the epidemiology of VSD?
25% of congenital abnormalities
1-4/1000
What are the treatments for VSD?
May close on its own
Surgical repair
(may provide furosemide/ACEi if moderately sized lesion
What is the pathology of Eisenmenger’s Syndrome?
High pressure pulmonary blood flow leads to damage in pulmonary vasculature
→ increased resistance to blood flow (pulmonary hypertension)
→ RV pressure increases
→ shunt direction reverses (RV to LV)
→ cyanosis
What are the symptoms of Eisenmenger’s Syndrome?
Causes de-oxygenated blood to skip the lungs and go back around the body
Once pulmonary HTN is high enough to cause the reversal, only a transplant is curative
Causes marked cyanosis, clubbing, heart failure, syncope, high RBC
Very poor prognosis
What are the risks associated with Eisenmenger’s syndrome?
- Stroke
- Endocarditis
- Risk of death
What is Atrial Septal Defect (ASD)?
A common structural defect where there is a hole in the septum between the 2 atria
What are the types of ASD?
Ostium Primum - associated with AV valve abnormalities
Ostium Secundum (85% of ASD) - Asymptomatic
What is the epidemiology of ASD?
Typically affects 40-60 years
M>F
What is the pathophysiology of ASD?
There is a higher pressure in the LA than the RA and so blood is shunted from the left to right; not cyanotic.
This may be reverse if Eisenmenger’s Syndrome develops
What are the clinical signs and symptoms of a large ASD?
Pulmonary flow murmur - increased blood to pulm circulation
Fixed split-second heart sound (delayed closure of pulmonary valve because more blood has to get out)
Dyspnoea
Exercise intolerance
Atrial arrhythmias from RA dilation
What are the investigations for ASD?
CXR:
Large heart
Large pulmonary arteries
ECG:
Right bundle branch block (RBBB) due to RV dilatation
ECHO:
Hypertrophy and dilation of right side of heart and pulmonary arteries
How are ASDs treated?
Surgical Repair
Percutaneous repair
What are Atrio-Ventricular Septal Defects (AVSD)?
A hole between the atria and the ventricles
2 per 10,000
Strong association with Downs
What are the symptoms of AVSD?
Complete defect:
Breathlessness
Poor feeding
Poor weight gain
Partial Defect:
Can present in later adulthood.
Similar to ASD/VSD
Tachycardia
Dyspnoea
Exercise intolerance
What are the clinical signs of a large AVSD?
- Enlargement of the heart
- Heart failure - inability to adequately supply body oxygen
- Eisenmenger’s Syndrome
- Exercise intolerance
- Pulmonary hypertension
- Pneumonia
How are AVSDs treated?
Pulmonary artery banding if large defect in infancy – band reduces flow to lungs thereby reducing pulmonary hypertension and Eisenmenger’s syndrome
Surgical repair – very challenging
Partial defect may be left alone if there is no right heart dilatation
What is Patent Ductus Arteriosus (PDA)?
Ductus arteriosus fails to close after birth;
allows abnormal transmission of blood from the aorta to the pulmonary artery.
Pulmonary arterial and left atrial flow increase
Is PDA more common in males or females?
Females
What is the pathophysiology of PDA?
Normally following birth the PDA closes.
If patent then there is a left to right shunt
Increases Pulmonary volume causing Pulm HTN and eisenmenger’s syndrome.
What are the symptoms of PDA?
- Pulmonary hypertension and RHF (due to Eisenmenger’s reaction)
- Breathlessness
- Poor feeding, failure to thrive
- Risk of endocarditis
What are the clinical signs of large PDA?
Large: Develop big heart
Torrential flow from the aorta to the pulmonary arteries in infancy
Breathless, poor feeding, failure to thrive
Continuous “MACHINERY” murmur
Eisenmenger’s syndrome
What are the clinical signs of a small PDA?
Small:
Little flow from the aorta to Pulmonary arteries
Usually asymptomatic
Murmur found incidentally
Endocarditis risk
What are the investigations for PDA?
CXR – large shunt between aorta and pulmonary arterial system may be prominent
ECG – may demonstrate LA abnormality and LV hypertrophy
Echocardiogram – may show dilated LA and LV
What are the treatments of PDA?
Surgical or percutaneous closure
Local anaesthetic
Indomethacin - (prostaglandin inhibitor) can be given to stimulate duct closure.
What is Coarctation of the Aorta?
Narrowing of the Aorta
Excessive sclerosing that normally closes the ductus arteriosus extends into the aortic wall leading to narrowing of the aorta distal to the ductus arteriosus
What is Coarctation of the Aorta associated with?
Associated with
Bicuspid aortic valves
Turner’s syndrome
Berry aneurysms
Patent ductus arteriosus
M>F
What are the Clinical signs of Coarctation of the Aorta?
Right arm Hypertension (may have left arm hypotension)
Lowe pressure in vessels distal to Coarctation
Bruits (buzzes) over the scapulae and back
Murmur
What are the investigations of Coarctation of the Aorta?
CXR – dilated aorta indented at site of coarctation
ECG – LV hypertrophy
CT – can accurately demonstrate coarctation and quantify flow
What is the management of Coarctation of the Aorta?
What is a risk of this?
Surgical repair
Percutaneous repair
Balloon dilation (preferred for re-coarctation) and stenting
RISK OF ANEURYSM FORMATION AT SITE OF REPAIR
What is a Patent Foramen Ovale?
Failure of the foramen ovale to close after birth
What are the effects of a patent foramen Ovale?
No symptoms
If no other abnormalities then normal health
What percentage of people may have a patent foramen ovale?
1/4
What is a bicuspid aortic valve?
Aortic valve has 2 cusps rather than 3.
Get turbulence generation instead of laminar flow in the aorta
What are the issues with a bicuspid aortic valve?
Can work well at birth and go unoticed
Exercise exacerbates complications
Abnormal degradation of the aortic valve over time - requires valve replacement
What is the epidemiology of a bicuspid aortic valve?
1-2% of general Population.
Most common congenital heart defect
What is the investigation and treatment of a Bicuspid Aortic Valve?
Ix - ECHO
Tx - Surgical valve replacement
Which structural heart abnormalities are not cyanotic and why?
VSD
ASD
PDA
Left to right shunt
But this can lead to Eisenmenger’s Syndrome due to the increased pulmonary flow and subsequent Pulmonary HTN.
Which structural heart abnormalities are cyanotic and why?
Tetralogy of Fallot
Right to left shunt.
What is the result of a Coarctation of the aorta on body perfusion?
Blood is diverted massively through the aortic arch branches and therefore you have increased perfusion to the upper body and less to the lower body.
How is Coarctation of the Aorta Diagnosed?
CXR - notched ribs
CT angiogram
What is the most common inherited heart defect?
Bicuspid Aortic Valve
What is the Treatment for restrictive cardiomyopathy?
None
Consider transplant
What condition often leads to Eisenmenger’s Syndrome as a complication?
VSD, ASD, PDA
What is a common complication of bicuspid aortic valves?
Aortic Aneurysm development
What is pulmonary stenosis?
Narrowing of the outflow tracts of the right ventricles
This results in increased resistance of the pulmonary circulation leading to RV hypertrophy
8-12% of Congenital Heart Defects
What are the categories for Hypertension?
Normotensive
Stage 1 Hypertension
Stage 2 Hypertension
Severe Hypertension (Stage 3)
What is the normal range for blood pressure?
90/60 - <120/ <80
Define stage 1 hypertension
- ABP 135/85
- Clinic 140/90
Define Stage 2 Hypertension?
- ABP 150/95
- Clinic 160/100
Define severe hypertension
Clinic 180/120
What is Primary Hypertension?
When it is Idiopathic (no known cause)
95% of cases
What is Secondary Hypertension?
When the underlying cause is known
5% of cases
What are some underlying causes of secondary hypertension?
CHAPS:
Cushings Syndrome/CKD
Hyperaldosteronism (Conn’s Syndrome)
Aorta Coarctation
Phaeochromocytoma
Stenosis of Renal Arteries.
What are the risk factors of hypertension?
Increased Age
Blacker ethnicity
Overweight - biggest RF
Decreased exercise/sedentary lifestyle
smoking
diabetes
stress
increased salt intake
Family Hx
What is the most common cause of secondary hypertension?
CKD as a result of diabetic nephropathy
Define malignant hypertension
Rapid rise in blood pressure which damages vasculature
Pathological hallmark is fibrinoid necrosis
Usually with severe hypertension + bilateral retinal haemorrhages and exudates
When is hypertension an emergency?
When there is sign of immediate damage:
Papilloedema
Acute kidney injury
Acute stroke
ACS
Aortic dissection
What is the pathogenesis of Hypertension?
All mechanisms where there is increased CO from Increased RAAS and SNS activity.
Mechanisms where there is increased TPR will increase BP
What is the equation for BP?
BP = CO x TPR
What are the vascular causes of Secondary Hypertension?
CKD
OSA
Glomerulonephritis - increased renin
Renal Artery stenosis - increase renin
Coarctation of the Aorta
What are the endocrine causes of Hypertension?
Phaeochromocytoma
Cushings
Conns (hyperaldosteronism)
Acromegaly
Thyroid Dysfunction
What are some autoimmune causes of Hypertension?
Lupus
Scleroderma
What are the symptoms of Hypertension?
Mostly Asymptomatic
May have a pulsatile headache (but no more than general population)
Found on screening
When should you screen to find the cause of a patients hypertension?
Early onset (<30yrs) with no risk factors
Hypertension resistant to 3 drugs
Malignant hypertension
If patient has other specific symptoms indicative of secondary causes
What drugs can increase blood pressure?
Glucocorticoids
Oral contraceptives
SSRIs
NSAIDs
EPO
Stimulants
Anti-TNFs
Which investigations are ordered to quantify overall risk in patients with hypertension?
Fasting glucose
Cholesterol
What investigations should be considered to determine the cause of a Px hypertension?
Underlying secondary causes should be excluded:
Age < 40 years
Reduced eGFR (suggestive of renal disease)
Proteinuria or haematuria (suggestive of renal disease)
Hypokalaemia and hypernatraemia (suggestive of Conn’s syndrome)
Hypertension that is sudden onset, variable or worsening.
How is Hypertension diagnosed?
In clinic:
BP reading in hospital of 140/90 or higher
Then ABPM for 24 hours to confirm diagnosis (BP 135/85 + throughout day twice per hour)
Assess end organ damage
Home BPM:
2 measurements taken daily for 4-7 days
What is White Coat Hypertension?
Elevated BP in a clinical setting
Px should have ABPM monitoing prior to diagnosis of HTN
What investigations are used to assess end organ damage in Hypertension?
ECG/ECHO - LV Hypertrophy
Fundoscopy - papilloderma
U&Es - hypokalaemia in Conns
Urinalysis, Proteinuria and Haematouria
Serum creatine
GLucose
Renal function
What is the lifestyle management of Hypertension?
Stop Smoking
Exercise - lose weight
Control diet
What are the main drugs used to lower blood pressure?
CCBs
ACEi/ARBs
Diuretics
B-blockers
When should you treat hypertension?
Aged < 80 years with stage 1 hypertension and with one of the following; end organ damage, cardiovascular disease, renal disease, diabetes or 10-year cardiovascular risk ≥10%.
of any age with stage 2 hypertension
of any age with stage 3 hypertension (consider immediate treatment)
What is the medical management of hypertension in a patient who is <55yrs old or has T2DM?
1st Line - ACEi/ ARB (if ACEi are Contraindicated)
2nd Line - ACEi/ ARB (if ACEi is CI) + CCB
3rd Line - ACEi/ ARB (if ACEi is CI) + CCB + Thiazide
4th Line (resistant HTN) - ACEi/ (ARB if ACEi is CI) + CCB + Thiazide + 4th drug:
4th drug if K+ > 4.5 = alpha/beta blocker
4th drug if K+ < 4.5 = Spironolactone
What is the Medical Management for a Patient with HTN who is >55+yrs old or from Afro-caribeean origins?
1st Line - CCB
2nd Line - ACEi/ ARB (if ACEi is CI) + CCB
3rd Line - ACEi/ ARB (if ACEi is CI) + CCB + Thiazide
4th Line (resistant HTN) - ACEi/ ARB (if ACEi is CI) + CCB + Thiazide + 4th drug:
4th drug if K+ > 4.5 = alpha/beta blocker
4th drug if K+ < 4.5 = Spironolactone
If a patient is Black, over 55yrs old and has T2DM which medical management line of HTN would you use?
T2DM takes precedence and Therefore first line is ACEi
What are the possible complications of hypertension?
Chronic heart disease
MI
Stroke - Common complication
Heart failure
Peripheral arterial damage
Aortic aneurysm
Chronic kidney disease
Vascular dementia
When should hypertension treatment be withheld?
When patients are undergoing general anaethesia
What is the monitoring for hypertension?
Renal function impairement
Otherwise, no monitoring as concordance with treatment an issue
Evidence shows going off medication causes hypertension to return
What are the thresholds for treatment of hypertension?
Low risk patients - 160/100 (stage 2)
High risk patients (diabetes, sign of end organ damage, risk of coronary events) - 140/90
What are the BP targets when treating for HTN?
Patients < 80 years: clinic BP < 140/90 mmHg / ABPM < 135/85 mmHg
Patients ≥ 80 years: clinic BP < 150/90 mmHg / ABPM < 145/85 mmHg
What is Valvular Heart disease?
Cardiac valves may become incompetent (regurgitant), stenotic (narrow) or both.
Abnormal valves produce turbulent blood flow, which is heard as a murmur on auscultation, a few murmurs are also felt as a thrill on palpation.
What is aortic Stenosis?
Narrowing of the aortic valve
What is the basic overlying pathogenesis of valvular stenosis?
Stiff/thick valve leaflets
Obstructs forward flow
Increasing Afterload
leads to systemic or pulmonary congestion
Stenotic Valve on RHS = Systemic Venous Congestion
Stenotic Valve on LHS = Pulmonary Venous Congestion
What valves are often affected by valvular stenosis?
Mitral
Aortic
Pulmonary
Tricuspid
What would a regurgitant valve cause?
Causes insufficiency and proximal chamber dilation.
This is due to loss of structural chamber integrity and strength
What is a regurgitant valve?
Poorly sealed valve leaflets
Defective and floppy
backflow of the blood through the valve (incompetance)
Valvular Regurgitation on RHS = Systemic Venous congestion
Valvular Regurgitation on LHS = Pulmonary Venous congestion
What occurs as a result of stenosis?
Increased upstream pressure resulting in proximal chamber dilation and hypertrophy
This leads to the heart becoming large and rigid and poorly compliant
What is the difference between a regurgitant valve and a stenotic valve?
Regurgitant - Defective and floppy
Stenotic - Narrowed valve lumen
Which valve defects commonly cause murmurs?
Aortic Regurgitant and stenosis
Mitral Regurgitant and stenosis
When are Right and left sided defects commonly heard as murmurs?
RILE (Right = inspiration and Left = Expiration)
Pulmonary/Tricuspid on RHS on insipration
Where are Left sided defects commonly heard as murmurs?
RILE (Right = inspiration and Left = Expiration)
Aortic/Mitral heard on LHS on Expiration
What is the nmeonic for when you would hear aortic regurgitance/stenosis and mitral valve reguritance and stenosis?
ARMS (Aortic regurgitance / Mitral Stenosis) on Diastolic
ASMR (Aortic Stenosis / Mitral Regurgitance) on Systolic
What is the main cause of Mitral Valve Stenosis?
Rheumatic Heart disease
(Most common - post strep pyogenes infection)
What are some less common causes of Mitral Valve Stenosis?
Valve calcification
Infective endocarditis
What is the pathology of Mitral Valve Stenosis?
Thickening and immobility of valve leads to obstruction of blood flow from LA to LV 🡪 increased LA pressure, pulmonary hypertension and right heart dysfunction
AF is common due to elevation of LA pressure and dilatation
Thrombus may form in the dilated atrium and give rise to systemic emboli e.g. the brain causing a stroke
Chronically elevated LA pressure leads to an increase in pulmonary pressure and pulmonary oedema
What are the symptoms of mitral stenosis?
Progressive exertional dyspnoea
Cough productive of blood-tinged sputum
Haemoptysis – coughing up blood due to rupture of bronchial vessels due to elevated pulmonary pressure
Right HF
Fatigue
Weakness
Abdominal/lower leg swelling
Palpitations – due to AF
Chest pain
What are the Signs of Mitral Valve Stenosis?
Malar Flushed Cheeks - due to low CO2
Pulmonary HTN - Dyspnoea
A wave on JVP
Loud S1 Snap - due to thickend valve cusps
Low pitched MID-DIASTOLIC murmur - loudest at apex and expiration when Px lies on LHS
What murmur is heard in Mitral Valve Stenosis?
Low pitched - due to decreased pulse and decreased CO
MID DIASTOLIC Murmur
Loudest at APEX
Best heard on EXPIRATION when Px is lying on LHS
What is the Diagnosis/investigations for Mitral valve stenosis?
CXR - LA enlarged
ECG - Afib, M shaped P waves due to LA enlarged
GS - ECHO - Assess valve area
What is the Treatment for Mitral Valve Stenosis?
Diuretics - Furosemide for HF
Rate control - BB/digoxin
Anticoagulants if AF (Warfarin)
Surgical:
Percutaneous balloon Valvotomy - Stent opening mitral valve
Mitral valve replacement
What is the main cause of Mitral Valve Regurgitation?
Myxomatous degeneration - Mitral Valve prolapse
Connective tissue disorders - Marfans, Ehlers Danlos
Infective Endocarditis
What are the risk factors for Mitral Valve Regurgiation?
Females
Increased Age
Low BMI
Prior MI or Connective Tissue disorder
What are the symptoms of Mitral Valve Regurgitation?
Exertional dyspnoea
Fatigue and lethargy
Palpitations
Right sided HF and can lead to congestive heart failure
What is the pathogenesis of Mitral Valve regurgitation?
Mitral valve fails to prevent reflux of blood into LA
Increased LA pressure
increased pulmonary pressure
Pulmonary Oedema
What is the Murmur Like in Mitral Valve Regurgitation?
PAN SYSTOLIC BLOWING murmur
RADIATES to AXILLA
Loudest at APEX
Soft S1 and Prominent S3 in heart failure (severe cases)
What is the diagnostic investigations for mitral valve regurgitation?
Gold standard = ECHO - LA size and LV function analysis
ECG
CXR
What is the second most common valvular condition requiring surgery?
Mitral Valve Regurgitation
How is Mitral Valve Regurgitation Treated?
ACEi + beta blockers
IE Prophylaxis
Serial ECHO Monitoring
If severe (Sx at rest) then Valve repair/replacement
What is the normal area of the aortic valve?
3-4cm^2
What is the lumen size of the aortic valve when you get symptoms?
1/4 of the lumen size
What is the most common valve disorder?
Aortic Stenosis
What are the consequences of Aortic Valve Stenosis?
LV dilation and hypertrophy
What are the causes of Aortic Stenosis?
Congenital Bicuspic valve <70yrs
Calcification due to Age >70yrs
Rheumatic Valvular Disease
What are the 3 types of aortic valve stenosis?
Supravalvular
SubValvular
Valvular
What is the pathogenesis of Aortic Valve stenosis?
Ageing leads to aortic valve thickening and clacifications obstructing the normal LV outflow.
Increased afterload
Leads to increased LV pressure and compensatory LV hypertrophy.
May lead to relative ischaemia causing angina arrhythmia and LV failure
What are the symptoms of aortic valve stenosis?
SAD:
Syncope (exertional)
Angina
Dyspnoea - related to HF
What are the signs of Aortic Stenosis?
Slow rising (pulsus tardus) and weak (pulsus parvus) carotid pulse
Heart sounds:
Soft or absent 2nd heart sound – may become soft or inaudible when the valve becomes immobile
Prominent 4th heart sound – due to LV hypertrophy
Ejection systolic murmur – crescendo – decrescendo character
What is the Murmur like in aortic valve stenosis?
Ejection Systolic Crescendo Decrescendo
Radiates to CAROTIDS
At Right sternal Boarder - 2nd IC space
What is the diagnostic investigations for aortic valve stenosis?
ECHO - LV size and function, aortic valve area (doppler derived gradient)
ECG - LVH - ST depression and T-wave inversion in aVL, V5 and V6
CXR
What is the treatment for Aortic Valve stenosis?
Surgical Tx if symptomatic:
Healthy Px - Open repair/replacement
More at risk (>75yrs) TAVI - Transcutaneous Aortic Valve Implant
hat is Aortic Regurgitation?
Leakage of blood into LV during diastole due to ineffective coaptation of aortic cusps
What are the main causes of Aortic valve regurgitation?
Congenital Bicuspid Valve
RHD
Connective tissue disorders - Marfans, Ehlers Danlos
What is the pathophysiology of Aortic Regurgitation?
Leakage of blood back into the LV during diastole due to ineffective closure of the cusps
LV dilation and hypertrophy to maintain CO
Reduced diastolic BP
Relative ischaemia
Leads to LV failure
What are the Symptoms of Aortic Regurgitation?
Exertional dyspnoea
Orthopnoea
Paroxysmal nocturnal dyspnoea
Palpitations
Angina
Syncope
What are the signs of Aortic Regurgitation?
Quincke - nailbed Pulsates when pressed
De Musset - Head nodding with heart beat
Wide pulse pressure
LV failure
Early Diastolic Murmur
Austin Flint Murmur (severe)
What is the murmur like in Aortic Regurgitation?
EARLY DIASTOLIC BLOWING murmur
At RIGHT Sternal boarder - 2nd IC space
Austin Flint murmur (severe)
What is the Diagnostic investigations for Aortic Regurgitation?
ECHO - Evaluate Aortic valve root and dimensions
ECG - Evidence of LVH
CXR - Cardiomegaly
What are the treatments for Aortic Regurgitation?
Consider Infective endocarditis prophylaxis - Also considered as a DDx
Vasodilators (ACEi to improve SV and reduce regurgitance if Px is asymptomatic or HTN)
Surgical Valve replacement if symptomatic
What is Infective Endocarditis?
Infection of the heart valves or other endocardial lined structure within the heart (e.g. septal defects, pacemaker leads, surgical patches)
What is the epidemiology of IE?
Used to be a disease of the young affected by rheumatic heart disease
Now it is a disease of:
- The elderly (in an ageing population)
- Young IV drug abusers
- Young congenital heart disease
- Anyone with prosthetic heart valves or pacemakers
- Poor dental hygiene
More common in males
What are the different types of Infective Endocarditis?
Left-sided Native (mitral or aortic)
Left-sided Prosthetic (early - within a year, late - after a year)
Right-sided IE (rarely prosthetic).
Device related (e.g. pacemakers, defibrillators)
How does the nature of Infective Endocarditis affect the outcome?
Left-sided; are more likely to cause thrombo-emboli systematically.
Right-side more likely to spread to cause a pulmonary embolism
What are the Causes of Infective Endocarditis?
Bacteria:
S.aureus (most common in IVDU, T2DM, surgery)
S. Viridans - Dental problems
P. aeruginosa
S.bovis
HACEK Organisms
What are the risk factors for Infective Endocarditis?
Male, Elderly, Prosthetic Valves
Young IV Drug user
Young w/Congenital heart defect
Rheumatic Heart Disease
Where does Infective endocarditis usually affect?
When may it affect other regions?
Usually Mitral valve (LHS)
In IVDU it will more commonly affect Tricuspid Valve (RHS) due to injecting into veins and travelling to RHS of heart
What is the Pathogenesis of Infective Endocarditis?
Abnormal/damaged endocardium leads to increased platelet deposition.
Bacteria virulence factors can adhere to this
Vegetation Propagation involves activation of clotting cascade
Inhabiting MOs cause cardiac valve distortion and cardiac failure + sepsis
Typically around the valves
What is a common consequence of Infective Endocarditis?
Valvular Regurgitation
Than can lead to Ventricular insufficiency and subsequent increased risk of HF
What are the symptoms of Infective Endocarditis?
Fever + Non-specific Symptoms
New valve regurgitation
Sepsis
Emboli of unknown origin
General Sx:
Headache
Malaise
Confusion
Night sweats
What are the specific signs of infective endocarditis?
FROM JANE:
Fever
Roth’s spots – retinal haemorrhages
Osler’s nodes – painful spots on hand
Murmur - arrhythmia
Janeway lesion – painless spots
Anaemia
Nail-bed splinter haemorrhages (splinter)
Emboli – MI, stroke, PVD
What are the diagnostic Criteria is used for infective endocarditis?
What are the Major and Minor Criteria?
Made using DUKE CRITERIA - 2 major or 1 major + 2 minor:
Major:
- Positive blood culture with typical IE microorganism
- Echocardiograph showing endocardial involvement (e.g. vegetation, abscess) or new valvular regurgitation.
Minor:
- Fever (>38)
- Pre-disposing factor (e.g. predisposing heart condition, IV drug user)
- Vascular phenomena (e.g. major arterial emboli, septic pulmonary infarcts, intracranial haemorrhage, Janeway lesions, conjunctival haemorrhage)
- Immunological problems (e.g. glomerulonephritis, Osler’s nodes, Roth’s spots, rheumatoid factor)
- Microbiological evidence (e.g. positive blood culture (non-IE typical microorganism) or serological evidence of infection with organism consistent with IE)
What investigations are used to diagnose suspected IE?
Transoesophageal Echo (TOE): DIAGNOSTIC
Generally safe but risk of perforation or aspiration
Easiest if ventilated (but never ventilate just for TOE)
Transthoracic echo (TTE):
Safe
Non-invasive
No discomfort
Often poor images so lower sensitivity
ECG - conduction abnormalities, low QRS voltage, ST elevation, heart block, ventricular tachycardia, and supraventricular tachycardia
CXR – cardiomegaly
Blood cultures - IE organisms
What are the two main sites vegetation adheres to in IE?
Atrial surface of AV valves
Ventricular surface of SL valves.
What is the Treatment for Infective Endocarditis?
S.aureus - Vancomycin + rifampicin ( +gentamycin if prosthetic valve)
S.viridans - Benzypenicillin + gentamycin for 4-6 weeks
Surgery - remove valve if incompetent and replace with prosthetic
Tx complications
What are the complications of infective endocarditis?
Heart failure
Aortic root abscess
Septic emboli
Sepsis
Define Heart Failure
Inability of the heart to deliver blood thus oxygen that is commensurate with the requirement of the metabolising tissues despite normal or increased cardiac filling
How is HF categorised by the New York Heart Association (NYHA)?
- Class I - no limitation (asymptomatic)
- Class II - slight limitation (mild HF Sx with normal activity)
- Class III - marked limitation (symptomatically moderate HF Sx at less than normal activity)
- Class IV - inability to carry out any physical activity without discomfort (symptomatically severe HF Sx at rest)
What is the median age for Heart Failure?
80-years-old (men; 78, women; 82)
What is Ejection Fraction?
Measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction
What is the normal range for Ejection Fraction?
65-75%
What are the 2 main pathologies of heart failure?
Systolic Heart failure - blood cant be pumped out of the LV well enough
Diastolic Heart Failure - Not enough blood fills the ventricles during diastole
In both cases blood builds up in the lungs causing congestion and fluid build up.2
What are the different types of Heart Failure?
HF-Reduced Ejection Factor (Left Ventricular Ejection Factor <40%)
HF-Preserved Ejection Factor (Left Ventricular Ejection Factor >50% with dilated LA(>34ml/m2 AND and LVH)
HF-Pulmonary Hypertension (Pulmonary Artery Pressure >40mmHg)
HF-Valve (stenosis or regurgitation)
What is the most common aetiology of Heart Failure?
Myocardial dysfunction resulting from IHD
Name some other common causes of Heart Failure.
Hypertension
Ischaemic Heart Disease
Alcohol excess
Cardiomyopathy
Valvular disease - Aortic Stenosis, Mitral Regurgitation
Arrythmias - Atrial Fibrillation
Endocarditis
Pericarditis
What ejection fraction would suggest borderline HF and Systolic HF?
Borderline - 40-50%
Systolic HF - <40%
What can cause Low output HF?
Decreased CO, fails to increase with exertion
Could be due to:
- Pump failure – systolic HF, may be due to decreased heart rate e.g. anti-arrhythmic drugs
- Excessive pre-load - Mitral regurgitation, fluid overload
- Chronic increased afterload – occurs in aortic stenosis, hypertension – difficult for the heart muscle to push against it
What can cause high output HF?
Normal cardiac function but unable to meet increased demands for perfusion.
Anaemia
Pregnancy
Hyperthyroidism
What is the difference between left and right heart failure?
Left heart failure would cause congestion in the pulmonary circulation.
Right heart failure would cause congestion in the systemic circulation
Both can affect each other - eg. RHS HF can cause LHS HF
What are the main causes of Systolic (HFref) heart failure?
Decreased Contractility:
- Coronary Artery Disease
- Volume Overload (Valvular disease, Neurohormonal)
- Dilated Cardiomyopathy
Increased Afterload:
- Hypertension
- Aortic Stenosis
What are the main causes of Diastolic (HFpef) heart Failure?
Stiff non-compliant left ventricle:
Chronic Hypertension, Aortic Stenosis, HOCM can also cause diastolic failure by increasing hypertrophy of LV wall. This then decreases volume of the ventricle leading to a reduced filling room and reduced preload.
Restrictive cardiomyopathy, Pericardial Constriction, Myocardial Fibrosis - less compliant LV walls due to increased stiffness. therefore the walls cannot stretch when filling leading to reduced preload
What are the compensatory changes seen in HF?
Sympathetic Stimulation - increased preload and afterload
RAAS activation - increased preload through increased fluid retention
Cardiac changes - Ventricular dilation, myocyte hypertrophy
Overtime these cause increased stress on heart and contribute to HF
Explain how IHD causes HFref?
Ischaemic heart disease - myocardial damage/infarction can lead to scarring which doesnt contract and so the EF is reduce
Explain the sympathetic stimulation compensatory mechanism for HF?
Activation of SNS improves ventricular function by increasing HR and myocardial contractility
Constriction of venous capacitance vessels redistributes centrally, and increased preload further augments ventricular function (via Frank-Starling mechanism)
Also increases afterload by causing arteriolar constriction which eventually reduces CO and worsens HF
Explain RAAS fluid overload/neurohormonal mechanism for HF?
Fall in CO and increased sympathetic tone lead to diminished renal perfusion 🡪 activation of RAAS 🡪 increased salt and water retention
Further increases venous pressure and maintains stroke volume by Starling mechanism
As salt and water retention increases, This causes fluid overload
peripheral and pulmonary congestion causes oedema and contributes to dyspnoea
Angiotensin II also causes arteriolar constriction which increases afterload increasing myocardial work an exacerbating HF
Explain How Dilated Cardiomyopathy causes HFref?
Dilated cardiomyopathy - chamber grows and there is increases preload leading to increased contraction strength temporarily. over time the muscle walls get thinner and will end up becoming inefficient and reduce contractility
Explain How chronic HTN leads to HFref
Chronic hypertension - increased afterload causes LV hypertrophy. This increases the O2 demand, and squeezes coronary arteries decreasing O2 supply to the myocardium. Overtime the heart muscle fatigues and becomes inefficient at pumping blood.
What are the cardinal symptoms of HF?
SOB
Fatigue
Ankle Swelling - fluid retention
What are the main causes of Left Heart Failure?
IHD
Hypertension
- As arterial pressure increases, harder for LV to pump blood out 🡪 LV hypertrophy 🡪 greater demand for oxygen
- Coronaries squeezed by extra muscle 🡪 less blood delivered to tissue
Cardiomyopathy:
- Dilated – heart chamber dilates (grows in size) in order to fill ventricle with more blood (increased preload)
- Over time, muscle wall gets thinner and weaker 🡪 systolic HF
- Restrictive – heart wall becomes stuff 🡪 less compliant 🡪 can’t stretch
Aortic stenosis – narrowing of aortic valve
What are the symptoms of Left Heart failure?
Breathlessness (dyspnoea)
Cough
Orthopnoea - SOB on lying flat - relieved by standing (causes crackles on auscultation)
Paroxysmal Nocturnal Dyspnoea
Peripheral Oedema
What is Paroxysmal Nocturnal Dyspnoea?
Paroxysmal nocturnal dyspnoea is a term used to describe the experience that patients have of suddenly waking at night with a severe attack of shortness of breath and cough.
What are the signs of Left Heart Failure?
Cardiomegaly (displaced apex beat)
Pulmonary Oedema
Bi-basal Crackles
3rd and 4th heart sounds (S3 in Dilated Ventricle and S4 in a less compliant)
Pleural effusion
Crepitations in lung bases
Tachycardia
Reduced BP
Cool peripheries
Heart murmur
What are the main causes of Right Heart Failure?
Left ventricular failure: (most common cause of RHF)
- Fluid build-up 🡪 increased pressure in pulmonary artery 🡪 harder for right side to pump blood into
Hypertension
Pulmonary stenosis
Lung disease (cor pulmonale) – harder to exchange oxygen
- Pulmonary arterioles constrict 🡪 increase pulmonary BP 🡪 harder for RV to pump against 🡪 hypertrophy and failure
Atrial/ventricular shunt – blood moves from L🡪R
- Leads to increased volume on right side 🡪 RV hypertrophy
- More prone to ischaemia (systolic dysfunction) and has a small filling volume (diastolic dysfunction)
What are the symptoms of Right Heart Failure?
SOB
Peripheral oedema
Ascites
Nausea
Anorexia
What are the signs of Right Heart Failure?
Raised JVP – JVP distension
Hepatomegaly/Splenomegaly
Pitting oedema – sacral/leg oedema in bed-bound patients which causes a “pit” when pressed
Ascites
Weight gain (fluid)
How is Heart Failure diagnosed?
Clinical presentation
BNP blood test (specifically “N-terminal pro-B-type natriuretic peptide” – NT‑proBNP)
ECG - ascertain underlying cause - ischaemia, LVH, HTN, Arrhythmia
GS - Echocardiogram (TTE) - Done if BNP and ECG abnormal (Ascertain underlying cause)
CXR - (ABCDE) Alveolar oedema, Kerley Blue lines, Cardiomegaly, Dilated Upper lobe vessels, Plural Effusions
What are the key signs of Heart Failure?
- Tachycardia and hypotension
- Shortness of Breath
- Fatigue
- Displaced apex beat
- Raised JVP - common in RHF
- Additional heart sounds/ murmurs,
- Hepatomegaly (e.g. pulsatile/ tender) - RHF
- Peripheral/ sacral oedema
- Ascites
What are some Risk Factors of Heart Failure?
Anything that increases myocardial work:
- Age over 65 years
- Men (due to lack of oestrogen protection)
- Obesity
- African descent
- Individuals who have had an MI
- Alcohol excess
- Hyperthyroidism
- Anaemia
- Pregnancy
What Diagnostic scoring criteria are used for HF?
Framingham
Boston
What lifestyle changes are recommended as a treatment for Heart Failure?
- Avoid large meals
- Education
- Weight loss
- Cardiac Rehab
- Smoking cessation
- Exercise
- Vaccination
What is the mainstay treatment algorithm for HFrEF?
ABAL:
ACEi
Beta Blockers
Aldosterone Antagonists (MRA)
Loop Diuretics
What is the recent first line medical management for HFrEF to reduce mortality?
What Medical Treatments can be used to reduce HF symptoms?
Reduce Mortality:
1. ARNI (Entresto) / ACEi / ARB
2. SGLT2 inhibitor
3. Beta Blockers (Bisoprolol)
4. ACEi
5 Aldosterone Antagonists (spironolactone, Eplerenone)
Reduce Sx:
Diuretics - Loop/Thiazide
Digoxin
What is the prognosis of a patient with HFrEF?
50% mortality in 5 years
What is the Medical Treatment for HFpEF?
No therapy to reduce Mortality
Tx underling cause of HFpEF
Symptom Mx - ACEi, BB, Diuretics (loop, thiazide, AA) Digoxin
What is Cor Pulmonale?
Right sided Heart failure caused by respiratory disease.
What is the pathogenesis of Cor Pulmonale?
The increased pressure and resistance in the pulmonary arteries (pulmonary hypertension >25mmHg) results in the right ventricle being unable to effectively pump blood out of the ventricle and into the pulmonary arteries.
Causes RV Hypertrophy and overtime this will become inefficient leading to HF.
This leads to back pressure of blood in the right atrium, the vena cava and the systemic venous system.
What are some common respiratory causes of Cor Pulmonale?
COPD is the most common cause
Pulmonary Embolism
Interstitial Lung Disease
Cystic Fibrosis
Primary Pulmonary Hypertension
How do patients with Cor Pulmonale Present?
Early Cor pulmonale - Asymptomatic
Later:
SOB
Peripheral Oedema
Dyspnoea - on exertion
Syncope
Chest Pain
What are the signs of Cor Pulmonale?
Hypoxia
Cyanosis
Raised JVP (due to a back-log of blood in the jugular veins)
Peripheral oedema
Third heart sound
Murmurs (e.g. pan-systolic in tricuspid regurgitation)
Hepatomegaly due to back pressure in the hepatic vein (pulsatile in tricuspid regurgitation)
How is Cor Pulmonale Diagnosed?
ECHO - Evidence of increased pressure
Spirometry - Chronic lung disease Evidence
GS - Right Heart Catheterisation - Measure Pulm Pressures
What is the Management of Cor Pulmonale?
Treat symptoms and underlying cause.
Long term oxygen therapy may be used.
Give some Non-modifiable risk factors for CVD and atherosclerosis?
Increased Age
Family Hx
Male
What are some end results of Atherosclerosis?
Angina
Myocardial Infarction
Transient Ischaemic Attacks
Stroke
Peripheral Vascular Disease
Mesenteric Ischaemia
What are some end results of Atherosclerosis?
Angina
Myocardial Infarction
Transient Ischaemic Attacks
Stroke
Peripheral Vascular Disease
Mesenteric Ischaemia
What is Primary and Secondary Prevention of CVD?
Primary Prevention – for patients that have never had cardiovascular disease in the past.
Secondary Prevention – for patients that have had angina, myocardial infarction, TIA, stroke or peripheral vascular disease.
What is some advice for Primary and Secondary prevention of CVD?
Advice on diet, exercise and weight loss
Stop smoking
Stop drinking alcohol
Tightly treat co-morbidities (such as diabetes)
What is the management for secondary prevention of CVD?
4 As:
A – Aspirin (plus a second antiplatelet such as clopidogrel for 12 months)
A – Atorvastatin 80mg
A – Atenolol (or other beta-blocker – commonly bisoprolol)
A – ACE inhibitor (commonly ramipril) titrated to maximum tolerated dose
What is Peripheral Vascular Disease?
Major circulatory disorder characterised by arterial obstruction, leading to reduced blood supply and ischaemia in the lower limbs.
Most commonly caused by atherosclerosis
Define Acute Limb Ischaemia?
Acute limb ischaemia (also known as acute limb-threatening ischaemia) describes a sudden decrease in perfusion due to arterial occlusion, and can result in rapid ischaemia.
Define Critical Limb Ischaemia?
Critical limb ischaemia is defined as rest or night pain for greater than 2 weeks, with or without tissue loss such as ulceration.
What is the Pathogenesis of Peripheral Vascular Disease?
Atherosclerosis causing a blockage of blood flow.
Intermittent Claudication:
Blockage causes nerve pain due to release of adenosine in response to ischaemia
Critical Limb Ischaemia:
Severe occlusion of arteries and blood supply is barely adequate to meet metabolic demand leading to pain at rest and increased risk of gangrene and infection.
How can you tell which artery is blocked/affected in PVD?
Hip or buttocks pain – aorta or iliac arteries
Thigh – common femoral artery
Upper 2/3rd of calf – superior femoral artery
Lower 1/3rd of calf – popliteal artery
Foot – tibial or peroneal artery
What is Intermittent Claudication?
Nerve pain caused by the release of adenosine in response to limb muscle ischaemia caused by atherosclerosis (PVD)
What are the symptoms of Peripheral Vascular Disease?
Varying symptoms:
- Asymptomatic
- ABPI (ankle brachial Pressure index) <0.9
- Bruits (pulsatile regions due to turbulent blood flow)
- Aching / burning in the legs
- Intermittent claudication (pain on exercise relieved by rest)
Critical Limb Ischaemia:
- Rest pain (critical limb ischaemia)
- Skin ulceration and gangrene.
What are some Signs of Peripheral Vascular Disease?
Signs: Absent femoral, popliteal or foot pulses. Cold white legs.
What can be a sign of acute limb ischaemia?
Complete occlusion of the vessel - due to embolic/thrombotic event.
Foot pain at rest - relieved by hanging out the side of bed at night
Causes 6 Ps
What are the 6Ps signs of complete limb Ischaemia?
Pulselessness
Pallor
Pain
Perishingly Cold
Paralysis
Paraesthesia
What is the Fontane classification of PVD?
Stage 1. Asymptomatic
Stage 2. Intermittent Claudication (pain on exertion)
Stage 3. Critical Limb Ischaemia (pain at rest)
Stage 4. Ischaemic ulcers - Gangrene
What are the investigations for PVD?
Ankle Brachial Pressure Index (ABPI):
0.5 - 0.9 = Intermitted Claudication
<0.5 = Chronic Limb Ischaemia
Colour Doppler (DUPLEX) ultrasound - confirm site and degree of stenosis.
CT angiography if surgery considered.
What is the Buerger’s Test?
Assessment of Arterial Sufficiency:
- With the patient supine, elevate both legs to an angle of 45 degrees and hold for one to two minutes. Observe the colour of the feet. Pallor indicates ischaemia. It occurs when the peripheral arterial pressure is inadequate to overcome the effects of gravity. The poorer the arterial supply, the less the angle to which the legs have to be raised for them to become pale.
- Then sit the patient up and ask them to hang their legs down over the side of the bed at an angle of 90 degrees. Gravity aids blood flow and colour returns in the ischaemic leg. The skin at first becomes blue, as blood is deoxygenated in its passage through the ischaemic tissue, and then red, due to reactive hyperaemia from post-hypoxic vasodilatation.
What is ABPI and what is the normal range?
Compares Blood in post/ant. tibial artery to brachial artery.
0.9-1.3 = normal
What is the treatment for PVD?
Intermittent Claudication
RF management:
- Quit smoking
- Treat hypertension
- Lower cholesterol
- Improve diabetes
- Improve diet
Medication - Clopidogrel
Chronic Limb Ischaemia:
- Revascularisation surgery (PCI/Bypass graft)
- Local Thrombolysius with t-PA
- In Ischaemic limb emergency - PCI within 4-6 hours otherwise amputation.
What are the Risk Factors for Peripheral Vascular Disease?
Smoking
Hypertension
Ageing
Obesity
CKD
T2DM
What may be some differential diagnoses for Critial leg ischaemia?
Gout / cellulitis
But deep duskiness of skin and sudden deterioration rules this out.
What are the main complications of PVD?
Amputation
Critical Limb/acute limb ischaemia
Permanent limb weakness
Rhabdomyolysis
Increased risk of CVD.
What is an Abdominal Aortic Aneurysm?
Permanent dilation of the aorta exceeding 50% where >3cm diameter.
Often Infra-renal (below renal arteries)
What is the Epidemiology of AAA?
- AAAs have a reported prevalence of 1.3-12.7% in the UK
- M>F
- Most common in the elderly: >60
What are the Risk factors of AAA?
Idiopathic,
Smoking, obesity, HTN, Family Hx
Connective tissue disorders - Marfans, Ehlers Danlos
What is the Pathogenesis of AAA?
Smooth muscle, elastic and structural degradation of the vascular wall in ALL 3 LAYERS of the vascular tunic.
Due to MMPs being released from atherosclerotic inflammation
Increased Leukocyte infiltration leads to increased vessel diameter to > 3cm +
What diameter of an AAA is at increased risk of rupture?
AAA more than 5.5cm diameter
What happens if the AAA ruptures?
Medical Emergency requires immediate surgical repair
80% mortality prior to reaching hospital.
What are the symptoms of an Unruptured AAA?
Usually asymptomatic
What are the symptoms of a ruptured AAA?
Sudden epigastric pain,
Radiating to flank
Pulsatile mass in abdomen
Hypotensive and Tachycardic
What are the signs of a ruptured AAA?
- Pulsatile abdominal mass
- Tachycardia and hypotension: red flags signifying ruptured AAA
- Grey-Turner’s sign: flank bruising secondary to retroperitoneal haemorrhage
- Cullen’s sign: pre-umbilical bruising
What is a differential Diagnosis of a ruptured AAA?
Acute pancreatitis - Does not tend to have a pulsatile feel.
GI bleed
Perforated GI ulcer
Appendicitis
Pyelonephritis
What is the diagnostic investigation of AAA?
Abdominal Duplex Ultrasound High sensitivity and Specificity
If ruptured then none - medical Emergency
What is the Treatment of an AAA?
Unruptured - manage RF and Surveillance
ASx and <5.5cm - monitor
Sx and>5.5 - surgery (endovascular repair or open surgery)
What is the Treatment of a Ruptured AAA?
Stabilise ABCDE + fluids
AAA Graft surgery repair.
What is the incidence of an AAA?
25/100,000 incidence at 50yrs.
Rises with age.
Males
What is an Aortic Dissection?
Tear in the intima resulting in blood dissecting through the tunica media causing separation of the layers of the aortic wall.
Creates a false lumen in the diseased media and splits the wall.
What are the classifications of an Aortic Dissecction?
Type A – involves ascending aorta (most common)
Type B – doesn’t involve ascending aorta
What are causes of Aortic Dissection?
Genetic link, Atherosclerosis, Inflammatory, Trauma:
Mechanical stress causes a tear in the intima of the aortic lining.
This causes blood to enter the aortic wall under pressure causing a haematoma and separates the layers.
What are the risk factors for Aortic Dissection
Connective tissue disorders - Marfans, Ehlers Danlos
Hypertension
Cocaine Use
Aortic Aneurysm
Smoking
Hypercholesterolaemia
What are the most common locations of an Aortic Dissection?
Sinotubular junction - Aortic root near aortic valve
Just distal to Left Subclavian Artery (descending thoracic aorta)
What are the symptoms of Aortic Dissection?
- Sudden onset, severe ‘tearing’ or ‘ripping’ chest pain that may radiate to the back and down the arms
- Syncope: red flag symptom
What are the signs of an Aortic Dissection?
Absent peripheral pulses
Unequal BP in left and right arm
Neurological signs due to involvement of branch arteries
Aortic regurgitation, cardiac tamponade
Compression of other arteries – renal, subclavian
What is the Diagnosis of Aortic Dissection?
Transoesophageal ECHO (if haemodynamically unstable) OR CT angiogram (if Px is haemodynamically stable)
Shows intimal Flap and False lumen
CXR - Shows widened mediastinum
What are the treatments for Aortic Dissection?
Surgical:
Open repair/Endovascular aortic repair
Medication (to reduced HR and BP):
Special Beta Blockers - Esmolol
Vasodilator - Sodium Nitroprusside
What are some complications of Aortic Dissection?
Cardiac Tamponade
Aortic Insufficiency
Pre renal AKI
Stroke - Ischaemic
What is an Arrhythmia?
Arrhythmias are abnormal heart rhythms. They result from an interruption to the normal electrical signals that coordinate the contraction of the heart muscle.
Define tachycardia.
> 100 bpm.
Define bradycardia.
< 60 bpm.
What are the 4 cardiac arrest rhythms?
Which are Shockable/non-shockable?
Shockable rhythms:
- Ventricular tachycardia
- Ventricular fibrillation
Non-shockable rhythms:
- Pulseless electrical activity(all electrical activity except VF/VT, including sinus rhythm without a pulse)
- Asystole(no significant electrical activity)
Give 3 potential consequences of arrhythmia.
- Sudden death.
- Syncope.
- Dizziness.
- Palpitations.
- Can also be asymptomatic.
Give the two broad categories of tachycardia.
- Supra-ventricular tachycardia’s.
- Ventricular tachycardia’s.
Where do supra-ventricular tachycardia’s arise from?
They arise from the atria or atrio-ventricular junction.
Do supra-ventricular tachycardia’s have narrow or broad QRS complexes?
Supraventricular tachycardias are often associated with narrow complexes.
Name 5 supra-ventricular tachycardia’s.
- Atrial fibrillation.
- Atrial flutter.
- AV node re-entry tachycardia (AVNRT) - Most common SVT
- Accessory pathway - Wolfson Parkinson White
- Focal atrial tachycardia. (sinus Tachycardia)
Where do ventricular tachycardia’s arise from?
The ventricles.
Do ventricular tachycardia’s have narrow or broad QRS complexes?
Ventricular tachycardias are often associated with broad complexes.
Name 2 Ventricular Tachycardias?
Ventricular Tachycardia
Ventricular Fibrillation
Name 3 arrhythmias that come under Bradycardia rhythms?
RBBB / LBBB
1, 2, 3 Heart Block
Sinus Bradycardia
What is atrial Fibrillation?
Irregularly irregular atrial firing Rhythm
What are the causes of AF?
Any condition that causes a raised atrial pressure
Heart Failure
CAD
RHD
HTN
secondary to mitral valve stenosis
Idiopathic
What are the risk factors for AF?
60+
T2DM
HTN
Valve defects
Hx of MI
What is the pathogenesis of AF?
Rapid re-entrant ectopic foci (300-600 Bpm)
Causes atrial spasm
Causes atrial blood to pool and therefore reduces CO and increases risk of thromboembolic events.
What are the symptoms of AF?
- Palpitations.
- Shortness of breath.
- Fatigue.
- Chest pain.
- Increased risk of thromboembolism and therefore stroke.
- Syncope
What are the different types of AF?
Paroxysmal (episodic)
Persistent (longer than 7 days)
Permanent (sinus Rhythm unrestorable)
What are the investigations for AF?
ECG is diagnostic
Irregularly Irregular pulse w/ narrow QRSs <120ms
No P waves (fibrillatory squiggles)
What is the Treatment of AF?
- Rate control - beta blockers, CCB and digoxin.
- Rhythm control - electrical cardioversion or pharmacological cardioversion using flecainide.
- Flecainide can be taken on a PRN basis in people with infrequent symptomatic paroxysms of AF.
- Long term - catheter ablation and a pacemaker.
- Anticoagulation (warfarin)
What score can be used to calculate the risk of stroke in someone with atrial fibrillation?
CHADS2 VASc.
What does the CHADS2 VASc score take into account?
CHADS2 VASc:
Congestive HF
Hypertension
Age > 75
Age 65-74
Diabetes Mellitus
Stroke/TIA
Vascular disease
Sex - Female
Used to calculate stroke risk.
0 = No
1 = consider oral anticoagulation / aspirin
2 = Oral Anticoagulation (warfarin/Rivaroxaban)
Atrial fibrillation treatment: what might you give someone to help with rate control?
Beta blockers, CCB and digoxin.
Atrial fibrillation treatment: what might you give someone to help restore sinus rhythm (rhythm control)?
Electrical cardioversion or pharmacological cardioversion using flecainide.
What is the long term treatment of atrial fibrillation?
Catheter ablation - it targets the triggers of AF.
What are some complications of AF?
Heart failure
Ischaemic stroke
Mesenteric Ischaemia
What is Atrial Flutter?
Irregular organised atrial firing
250-350 bpm
What are the risk factors of atrial flutter?
Similar to aetiology of AF
What is the pathogenesis of Atrial flutter?
Atrial flutter is caused by a “re-entrant rhythm” in either atrium.
This is where the electrical signal re-circulates in a self-perpetuating loop due to an extra electrical pathway.
The signal goes round and round the atrium without interruption.
This stimulates atrial contraction at 300 bpm.
The signal makes its way into the ventricles every second lap due to the long refractory period to the AV node, causing 150 bpm ventricular contraction.
It gives a “sawtooth appearance” on ECG with P wave after P wave.
What are the symptoms of atrial flutter?
Dyspnoea
Palpitations
Syncope
What is the diagnosis of Atrial flutter?
F wave - saw tooth pattern
Often has a 2:1 block - 2 p waves for every 1 QRS
What is the treatment of Atrial flutter?
Acutely unstable - DC Synchronised Cardioversion
Stable - Rhythm/Rate (amiodarone + BB) control w/ oral coagulation (prevent thromboemboli)
Radiofrequency ablation - long term
What is Wolf parkinson White?
An AV Reciprocating Tachycardia (AVRT)
There is an accessory pathway that exists for impulse conduction called the bundle of Kent between atria and ventricles
This is a Pre excitation syndrome (excites ventricles early causing a delta wave)
This is not re-entry through the AVN.
Often hereditary
What are the symptoms of Wolf parkinson white?
Palpitations
Dizziness
Dyspnoea
What is the ECG of Wolf parkinson white?
Slurred DELTA WAVES
Short PR interval (<0.12s)
Wide QRS (>0.12s)
What is the treatment of Wolf Parkinson White?
- Valsalva Manoeuvre
If Vagal manoeuvres are ineffective then:
2. IV adenosine (6mg, then 12mg then 12mg) to cease conduction.
3. Consider surgical radiofrequency ablation
What conditions can radiofrequency ablation be curative for?
Atrial Fibrillation
Atrial Flutter
Supraventricular Tachycardias
Wolf parkinson White syndrome
What is Long QT syndrome?
A ventricular Tachyarrhythmia typically caused by a congenital channelopathy where mutations affect ion channels.
This causes the QT interval to be 480ms +
What are some causes of Long QT syndrome?
Romano ward syndrome
Hypokalaemia and Hypocalcaemia
Drugs - Amiodarone/magnesium
What is Torsades De Pointes?
Polymorphic ventricular tachycardia in patients with prolonged QT.
Rapid irregular QRS complexes which twist around baseline.
Can cease spontaneously or develop into ventricular fibrillation.
What is ventricular fibrillation?
This involves very rapid irregular ventricular activation with no mechanical effect i.e. no cardiac output.
Ventricular fibrillation (VF) occurs when the ventricular muscle fibres contract independently.
Shapeless rapid osscillations on ECG
patients becomes pulseless and goes into cardiac arrest - no effective cardiac output
What is the first line treatment for Ventricular fibrillation?
Electrical defibrillation
(DC Cardioversion)
What are the narrow complex tachycardias?
Rapid cardiac rhythm > 100bpm, QRS complex <120ms:
Supraventricular tachycardia
Atrial fibrillation/flutter
What are the broad complex tachycardias?
Rapid cardiac rhythm >100bpm, QRS complex >120ms
Ventricular tachycardia
Supraventicular tachycardia with bundle branch block/pre-excitation
Give 4 causes of sinus bradycardia.
- Ischaemia.
- Fibrosis of the atrium.
- Inflammation.
- Drugs.
Give 3 causes of heart block.
- CAD.
- Cardiomyopathy.
- Fibrosis.
What are the 3 types of AV block?
First degree
prolonged PR interval
Second degree - Mobitz type I and Type II
Some atrial impulses fail to reach the ventricles
Third degree
Complete dissociation between atrial and ventricular activity
What does first degree AV block look like on an ECG?
1:1 conduction - Every P wave has QRS followed
Prolonged PR interval >200ms
What are the symptoms of First Degree AV Block?
No symptoms
No treatment
What can cause first degree AV block
LEV’s disease
IHD – scar tissue from myocyte death blocks conduction pathway
Myocarditis
Hypokalaemia
Drugs - block AVN conduction (BB/CCB/Digoxin)
What does second degree AV block look like on an ECG?
When some P waves are conducted and others aren’t
2:1 conduction - Every other P wave is followed by a QRS complex
What are the types of Second degree AV block?
Mobitz I
Mobitz II
What is Mobitz type I heart block?
PR interval gradually increases until AV node fails and no QRS is seen.
This then Repeats
What is Mobitz type 2 Heart Block.
PR interval is constant but every nth QRS complex is missing.
There is a sudden unpredictable loss of AV conduction and so loss of QRS.
What are the different symptoms a patient may experience with Mobitz Type I and II Heart block?
Type I: Patient often experiences light headedness, dizziness and syncope
Type II: Patients often experience chest pain, SOB, syncope and postural hypotension
What is the treatment for second degree heart block?
Pacemaker
What are some causes of Mobitz Type I and type II?
Type I
- Caused by AV node block
- Beta blockers, CCB, Digoxin, inferior MI
Type II
- Caused by Intra-nodal block
- Inferior MI, Rheumatic Fever
What is 3rd degree AV block?
Complete heart block
Atrial activity fails to conduct to the ventricles.
P waves and QRS complexes therefore occur independently.
What can cause 3rd degree heart block?
Acute MI
HTN
Structural heart disease
What is the treatment for 3rd degree heart block?
IV Atropine
Permanent Pace maker
What is the Pathogenesis of Bundle Branch Block?
Where electrical conduction down the left/right bundle branch in the bundle of HIS/septum is blocked/delayed often by fibrosis.
This causes the impulse conduction to the ventricles to occur at different times creating a second R wave in the leads associated with the right/left ventricles on an ECG.
In LBBB - LV contraction later than RV
In RBBB - RV contraction later than LV
Give the causes of Left/Right Bundle Branch Block?
Acute
Ischaemia and MI
Myocarditis
Chronic
HTN
Cardiomyopathies
Left - IHD, valvular disease
Right - PE, IHD, valvular disease
LBBB: what would you see in lead V1 and V6?
A ‘W’ shape would be seen in the QRS complex of lead V1 and a ‘M’ shape in V6.
WiLLiaM.
RBBB: what would you see in lead V1 and V6?
A ‘M’ shape would be seen in the QRS complex of lead V1 and a ‘W’ shape in V6.
MaRRoW.
What ECG changes are you likely to see in ischaemia and infarction?
T wave flattening and inversion
ST segment depression first → progresses to ST elevation
Q waves (old infarction)
Infarction involving the left anterior descending coronary artery will give rise to changes in which ECG leads?
Anterior leads: V2, V3, V4
Infarction involving the L circumflex coronary artery will give rise to changes in which ECG leads?
Lateral: V5, V6
Infarction involving the R coronary artery will give rise to changes in which ECG leads?
Inferior: II, III, aVF
Give 3 effects of hyperkalaemia on an ECG.
- Tall ‘tented’ T waves.
- Flat P waves.
- Broad QRS.
- Short QT interval
Give 2 effects of hypokalaemia on an ECG.
- Flat T waves.
- Prolonged PR Interval
- QT prolongation.
- ST depression.
- Prominent U waves.
Give an effect of hypocalcaemia on an ECG.
- QT prolongation.
- T wave flattening.
- Narrowed QRS.
- Prominent U waves.
Give an effect of hypercalcaemia on an ECG.
- QT shortening.
- Tall T waves.
- No P waves.
What is Deep Vein Thrombosis?
When a thrombus forms in deep leg vein
Below calf - less concerning and most common
Above calf/thigh - life threatening
What are the Risk factors for DVT?
Virchow’s triad Factors:
Venous Stasis - Immobility,
Hypercoagulability - OCP, HRT, Pregnancy, Polycythaemia
Endothelial Injury - smoking, age, malignancy
What are the Signs of DVT?
- Unilateral swelling
- Oedema
- Tender and erythematous
- Distention of superficial veins
- Phlegmasia cerulea dolens: occurs in a massive DVT, resulting in obstruction of venous and arterial outflow (rare). This leads to ischaemia and a blue and painful leg
What are the symptoms of DVT?
Unilateral calf pain, redness and swelling
What are the investigations for DVT?
Clinical history + WELLs Score >2 = high risk
D-dimer raised and Duplex ultrasound (gold standard)
(D dimer normal excludes DVT, but positive does not confirm)
CT or MR venogram
What is the Diagnostic pathway for DVT?
Clinical Hx
WELLs Score 2 or more = likely DVT –> Duplex Ultrasound (diagnostic)
WELLs Score 1 or Less –> D-Dimer test –> If raised –> Duplex Ultrasound
What is the treatment of DVT?
1st Line
DOAC anticoagulant therapy
Rivaroxaban/Apixaban
2nd Line
LMWH (if above CI in renal impairment)
Warfarin
What are some important differential diagnoses of DVT?
Cellulitis - S.aureus / S.pyogenes
Leukocytosis
What are some preventative measures for DVT?
Compression stockings
Early mobilization
Leg elevation
What are the major complications of DVT?
PE
Post-thrombotic Syndrome
Recurrence of thrombosis
What is the cause of the 3rd Heart sound?
When is it considered normal?
What Pathology is it heard in?
- Caused by diastolic filling of the ventricle
- Considered normal if < 30 years old (may persist in women up to 50 years old)
- Heard in left ventricular failure (e.g. dilated cardiomyopathy), constrictive pericarditis (called a pericardial knock) and mitral regurgitation
What is the cause of the 4th Heart sound?
What Pathology is it heard in?
- Caused by atrial contraction against a stiff ventricle
- therefore coincides with the P wave on ECG
- in HOCM a double apical impulse may be felt as a result of a palpable S4
- May be heard in aortic stenosis, HOCM, hypertension
What causes the first Heart Sound?
When is it Soft?
When is it Loud?
- Closure of mitral and tricuspid valves
- Soft if long PR or mitral regurgitation
- Loud in mitral stenosis
What is the cause of the Second Heart Sound?
When is it soft?
- Closure of aortic and pulmonary valves
- Soft in aortic stenosis
splitting during inspiration is normal
What pathophysiological features will cause a murmur
Increased Turbulent blood flow:
Increased Velocity of blood:
- Through a stenosed valve/ narrow VSD/ASD
- Increased contractile strength of myocardium
- Decreased Diameters - through HOCM narrowing the exit of the ventricle to the Aorta
Decreased Viscosity of blood - through anaemia
Blood flow back across incompetent valves
Where do you listen to different Murmurs/ Heart sounds?
What is the Mnemonic to remember them?
All Physicians Earn Too Much:
Aortic Valve - R. 2nd ICS - CoA, AS, AR
Pulmonic Valve - L. 2nd ICS - PS, PR, ASD
ERBS Point - L 3rd ICS - S1 +S2, HOCM
Tricuspid Valve - L 4th ICS - TS, TR, VSD
Mitral Valve - L 5th ICS, (MCL) - MR, MS
Where would a murmur caused by Aortic Stenosis best be heard and where would it radiate to?
Best Heard - Right parasternal boarder, 2nd intercostal space
Radiates to - Carotids as it flows up through the aortic arch vessels
Where would a murmur caused by Aortic Regurgitation best be heard and where would it radiate to?
Best Heard - Right Parasternal Boarder, 2nd intercostal space
Radiates to - Left upper sternal boarder (2nd/3rd ICS) due to blood flowing back across the left side of the heart
Where would a murmur caused by mitral regurgitation best be heard and where would it radiate to?
Best Heard - Left 5th ICS, mid clavicular line
Radiates to - Axilla as blood is flowing up into the left atria which is towards the axilla
What would a blowing (musical Murmur) suggest?
Blowing Murmurs are usually regurgitation murmurs:
Aortic Regurgitation
Mitral Regurgitation
What would a Rumbling (Harsh) murmur suggest?
Valvular Stenosis:
Aortic Stenosis
Mitral Stenosis
What would a Machine Like Murmur suggest?
Patent ductus Arteriosus
what kind of pitch would a VSD murmur have?
High pitch
due to high pressure gradients as the blood flows from the LV to the RV through the VSD
What kind of pitch would a Mitral stenosis murmur have?
Low pitch
Due to low pressure gradient from the atria to the ventricles
But high blood flow across the valve creates a low pitch
What kind of pitch would a Aortic Stenosis/ Aortic Regurgitation /Mitral regurgitation murmur have?
Harsh High pitch
High pressure gradients
High blood flow across the valve
What conditions would cause an Early Systolic Murmur?
What is the motion of the murmur?
Aortic/Pulmonic Stenosis:
Valves are rigid and so upon LV contraction the valves bow (not open properly) causing an EJECTION CLICK sound as blood hits the underside of the valve.
CRESCENDO DECRESCENDO murmur as the blood velocity increases during systole and then falls of as the blood is ejected
HOCM:
CRESCENDO DECRESCENDO murmur with NO ejection click
Coarctation of the Aorta
What conditions would cause an Holo-Systolic Murmur?
What is the motion of the murmur?
Mitral/Tricuspid Regurgitation:
Murmur occurs through entire systolic time period as blood is flowing back across the valve into the atria the entire time the ventricles contract
VSD:
As the LV contracts blood is flowing across the VSD into the RV causing turbulent flow in the RV.
What conditions would cause an Diastolic Murmur?
What is the motion of the murmur?
Aortic/Pulmonic Regurgitation:
During Early diastole (right at the start) the LV pressure decreases so blood can back flow across the Aortic valve hitting the LV wall causing turbulent flow Lots of blood flows in early diastole which falls off in late diastole. This causes a DECRESCENDO Murmur
Mitral/Tricuspid Stenosis:
OPENING SNAP (immediately at the start of diastole) followed by lots of blood entering the ventricles in early diastole which then reduces as diastole progresses causing a DECRESCENDO murmur
What kind of murmur would be heard in a Patent Ductus Arteriosus?
A Continuous “Machine” Murmur
due to a constant shunt from the aorta to the pulmonary artery
Where does thrombosis occur?
Arterial circulation - High pressure (platelet rich)
Venous Circulation - Low pressure (fibrin rich)
What are the main sites for Arterial thrombosis?
Coronary
Cerebral
Peripheral
Other sites
What can lead to arterial thrombosis development?
Atherosclerosis
Inflammatory
Infection
Trauma
Tumours
Unknown
What conditions can arterial thrombosis lead to?
Myocardial Infarction
Cerebral Vascular Disease
Peripheral Vascular Disease
What is the Treatment for Arterial thrombosis?
Anti-platelets:
Aspirin
LMWH or Fondraparinux
Thrombolytic therapy:
Streptokinase OR TpA
Reperfusion - PCI
Why is heparin avoided to treat cerebral vascular disease/ cerebral thrombosis
Heparin has a high risk of bleeding
What are the main sites of venous thrombosis?
Peripheral - Ileofemoral, Femoro-popliteal
Other sites - Cerebral, Visceral
What diagnostic tests are required for Venous thrombosis diagnosis?
Signs and Sx are very non-specific
Blood tests - D-dimer - sensitive but not specific
Imaging usually required
What is the main group of factors that leads to venous thrombosis?
Virchows Triad
What are the treatments for Venous thrombosis?
Anti-Coagulants:
Heparin/LMWH
Warfarin
DOAC
What is Heparin and how does it work?
Glycosaminoglycan
Given by Infusion
Binds to anti-thrombin and increases its activity.
Indirect thrombin inhibitor
What is LMWH?
Smaller molecule of heparin that is excreted renally.
Weight adjusted dose given via SC injection
Used for Tx and Prophylaxis
What is Warfarin?
Anticoagulant that prolongs the Prothrombin time
Prevents synthesis of Active factors II, VII, IX, X
Antagonist of Vitamin K
What is the half life of Warfarin?
36 hours
What are NOACs/DOACs?
New oral anticoagulant drugs/ Direct oral anticoagulant drugs
Directly act on Factor II or X
What is important for Venous thrombosis prevention?
Mechanical/chemical thromboprophylaxis
Early mobilisation and good hydration
What is the half life of Heparin and how is it monitored?
4 hours
Monitor with APTT (anti-prothrombin time)
What is the Half lifeof LMWH?
12 hours and therefore can be given once daily and not necessarily needed to be monitored
What is NOAC/DOAC used for?
When would NOAC/DOAC not be used
Extended thromboprophylaxis and treatment of AF, DVT and PE
Not used in pregnancy
What is the mechanism of action of Aspirin?
Inhibits Cyclo-oxygenase irreversibly.
Prevents thromboxane formation and therefore inhibits platelet aggregation
How can warfarin be reversed?
Give Vitamin K
How can DVT be prevented?
Mechanical:
Hydration
Early mobilisation
Compression stockings
Chemical:
LMWH
What is the prevalence of DVT/PE?
25,000 people die per year due to DVT/PE in the UK
Why does DVT lead to ischaemia and loss of leg?
DVT leads to increased compartment pressure resulting in venous hypertension.
This can compress the arterioles reducing their blood suplly and resulting in ischaemia to the local tissues.
What is a pulmonary embolism?
When an embolus (often from a thrombus/DVT) travels through the venous circulation and into the pulmonary circulation to get lodged in the pulmonary vasculature.
What are the symptoms of PE?
Signs:
Tachycardia
Tachypnoea
Pleural rub
SX:
Breathlessness
Pleuritic chest pain
High RFs
What are some differential diagnoses to think of for PE?
DDx of chest pain and SOB
What are the initial investigations for PE?
CXR - usually normal
ECG - Sinus Tachy - S1Q3T3
D-Dimer and CTPA (GS - CT scan and Pulmonary angiogram)
Blood gases - Type I resp failure (Decreased O2/CO2)
What is the treatment of PE?
Supportive Tx and Tx underlying cause
Apixaban
DOAC
LWMH (if CI for renal impairment)
What can be done to prevent PE?
Early mobilisation and hydration.
Anticoagulation
How would a Massive PE be Tx?
Thrombolytics - Alteplase (clot buster)
What are the types of aneurysms?
True - weakening of arterial wall leading to dilation
False
Mycotic
When would you hear S3 in pathology?
Left ventricular failure (DCM)
Constrictive pericarditis
Mitral Regurgitation
When would you hear S4 in pathology?
Aortic stenosis
HOCM
Hypertension
What is Rheumatic Fever?
An autoimmune condition triggered by streptococcus bacteria that causes an inflammatory reaction in cardiac and joint tissue.
What is the cause of Rheumatic fever?
Pharyngeal infection with Group A strep (S. pyogenes)
What is the pathophysiology of Rheumatic Fever?
2-4 weeks post Strep infection:
Body produces antibodies against S. pyogenes M protein toxin.
Abs cross react with Px own tissues through molecular mimicry
Abs attack Px Joint, heart, skin and NS tissues causing an inflammatory reaction.
What type of hypersensitivity reaction is Rheumatic fever?
Type 2 hypersensitivity reaction.
What is the typical presentation of Rheumatic Fever?
Recent sore throat (infection)
Chest pain (pleuritic)
SOB
Joint pain - oligo/poly arthritis
Non-pruritic rash
Sydenham’s Chorea
What are the signs of Rheumatic Fever?
Heart:
Heart Murmur - MR or AR
Tachycardia/Bradycardia
HF
Joints - Tender joints
Skin:
Erythema marginatum rash
Subcutaneous nodules
What is Sydenham’s Chorea?
Irregular, uncontrolled rapid movements of the limbs
How is Rheumatic fever Diagnosed?
Jones Criteria: 2 Major OR 1 Major + 2 Minor
Major (JONES):
J – Joint arthritis
O – Organ inflammation, such as carditis
N – Nodules
E – Erythema marginatum rash
S – Sydenham chorea
Minor: (FEAR)
F - Fever
E - ECG Changes (prolonged PR interval) without carditis
A - Arthralgia without arthritis
R - Raised inflammatory markers (CRP and ESR)
What investigations will support a Diagnosis of Rheumatic Fever?
Throat swab for bacterial culture
ASO (anti-strep Antibodies) titres
ECHO/ECG/CXR for heart involvement
How is Rheumatic Fever treated?
Conservative Mx: Bed rest, analgesia
Antibiotics:
IV Benzylpenicillin STAT followed by
Penicillin V for 10 days
Tx system involvement:
NSAIDs - joint pain
Aspirin/Steroids - Carditis
Diazepam - Sydenham’s Chorea
What are the complications of Rheumatic fever?
Rheumatic Heart Disease: (occurs in 30-50% of rheumatic fever cases)
Valvular Heart Disease - Mitral stenosis (and aortic)
Heart Failure
Infective endocarditis
Atrial fibrillation
What is the most common cause of mitral stenosis?
Rheumatic Fever
What cardiac enzymes are used to aid the diagnosis of ACS?
Cardiac troponin (Troponin T and I)
Released into the blood when cardiac muscle is damaged.
Highly sensitive but not specific.
What are some differential diagnoses of chest pain?
Cardiac – ACS, Aortic dissection, pericarditis, myocarditis
Respiratory – PE, pneumonia, pleurisy, lung cancer
MSK – rib fracture, chest trauma, costochondritis (inflammation of the cartilage between the ribs and sternum)
GORD
Oesophageal spasm
Anxiety/panic attacks
What is Shock?
Acute circulatory failure with inadequate or inappropriately distributed tissue perfusion (meaning there is inadequate glucose and oxygen for aerobic cellular respiration), resulting in generalised hypoxia and/or inability of cells to utilise oxygen.
What is the pathophysiology of Shock?
- Hypotension stimulates baroreceptors in aortic arch and carotid sinuses causing increased sympathetic nervous activity with “spill-over” of noradrenaline into the circulation
- Later this is augmented by the release of adrenaline from the adrenal medulla which causes vasoconstriction
- Vasoconstriction, together with increased myocardial contractility and HR help to restore BP and CO
- Reduced perfusion of the renal cortex stimulates the juxtaglomerular apparatus to release renin
- Renin converts angiotensinogen to angiotensin I which is then converted into angiotensin II (in the lungs by ACE) which stimulates the release of aldosterone from the zona glomerulosa causing water and sodium retention
- This helps to restore the circulating volume
What are the different Types of Shock?
- Septic – infection with any organism 🡪 acute vasodilation from inflammatory cytokines
- Anaphylactic – Type-I IgE-mediated hypersensitivity, release of histamine
- Neurogenic – spinal cord injury, epidural or spinal anaesthesia
- Hypovolaemic – loss of >20% of body’s blood or fluid supply, severe fluid loss makes it impossible for the heart to pump a sufficient amount of blood around the body
What are the causes of Hypovolaemic Shock?
Hypovolaemic (reduced preload) – low blood volume
Haemorrhagic:
-Trauma
-GI bleeding
-Fractures
-Ruptured aortic aneurysms
Non-haemorrhagic (fluid loss):
-Burns – heat increases permeability of capillaries so more plasma leaks
-Severe diarrhoea and vomiting 🡪 dehydration
-Intestinal obstruction (fluid accumulates in intestines)
-Pancreatitis
What are the causes of Cardiogenic Shock?
Pump failure- Heart isn’t Pumping
- Acute MI
- Myocarditis
- Atrial and ventricular arrhythmias
- Bradycardias
- Rupture of valve cusp
Obstructive:
- Obstruction to outflow
- Massive PE
- Tension pneumothorax
Restricted cardiac filling:
- Cardiac tamponade
- Constrictive pericarditis
How can you recognise Shock?
Skin is pale, cold, sweaty and vasoconstricted
Rapid, weak pulse
Reduced pulse pressure – MAP may be maintained (note – arterial BP NOT a good indicator of shock since it will be maintained until a very large amount of blood loss
Reduced urine output
Confusion, weakness, collapse and coma
Capillary refill time (CRT) – if it takes more than 3 seconds to turn pink after 5 seconds of compression, this is the earliest and most accurate sign of shock
What is the general management of Shock?
- Airways – ensure patency
- Breathing – give 100% O2 and correct immediately life-threatening problems e.g. congestive cardiac failure, bronchospasm, tension pneumothorax
- Circulation
IV access
Give fluid and blood if acute blood loss
Ensure haemostasis i.e. stop bleeding
- Stabilise BP
Fluid replacement
Medications that increase heart contractility, vasoconstriction and retain fluid
Vasoconstriction - adrenaline
- Supplemental oxygen or airway intubation
What is SIRS?
Systemic Inflammatory Response syndrome (SIRS) defined as:
Temperature of >38˚C or <36˚C
Tachycardia >90 BPM
Respiratory rate >/= 20 breaths per minute OR PaCO2 <4.3kPa
WBC > 12 x 109/L or < 4 x 109/L
What are the signs and symptoms of Septic Shock?
Current ore recent Infection +
Pyrexia and rigors
Nausea and vomiting
Vasodilation with warm peripheries
Bounding pulse
What is the management for Septic Shock?
Airways
Breathing
Circulation
Antibiotics
- Community-acquired pneumonia – ceftriaxone
- MRSA – vancomycin
- Pseudomonas – cefepime + metronidazole
Treat underlying cause:
- Haemorrhage
- Sepsis
- Anaphylaxis
What is the Pathology of Anaphylactic Shock?
Type I Hypersensitivity - Massive release of mediators from mast cells and basophils induced by cross-linking of surface IgE with trigger antigen leads to an increase in vascular permeability, vasodilation and respiratory smooth muscle contraction
What are the signs and symptoms of Anaphylactic Shock?
Onset of symptoms usually within 5-60 minutes of antigen exposure
Swollen tongue, lips
Laryngeal oedema
Swollen epiglottis
`Warm peripheries and hypotension due to profound vasodilation
Urticaria
Angio-oedema
Wheezing and SOB due to bronchospasm
Upper airway obstruction due to laryngeal oedema
Low BP – due to vasodilation, increased vascular permeability and fluid loss from vascular space
What is the management of Anaphylactic Shock?
Remove the precipitating cause e.g. stop administration of offending drug
Oxygen – high flow
Adrenaline – 0.5mL injected IM, IV if patient is in cardiac arrest, half doses for patients taking amitriptyline, imipramine or beta blockers
Fluids – 500-1000mL 0.9% saline
Chlorphenamine (antihistamine)
Hydrocortisone
Admit for observation due to risk of second late reaction
Prevent further attacks
What are the signs and Symptoms of Hypovolaemic Shock?
Inadequate tissue perfusion
Skin – cold, pale, clammy, slate-grey
Brain – drowsiness and confusion
Increased sympathetic tone
Tachycardia – narrow pulse pressure and weak pulse
Sweating
BP may be maintained initially but hypotension develops later
Bradycardia
What are the signs and Symptoms of Cardiogenic Shock?
Signs of myocardial failure
Characterised by
- Chest pain
- Respiratory distress
- JV distension
- Hypotension
- Crackles in lung
ECG – ST elevation V1-6
Gallop rhythm
Pulmonary oedema
