Cardiology

Question 1

Between 1990 and 2013 the total deaths related to cardiovascular disease in Australia:

A) Decreased 50%
B) Increased by 5%
C) Increase by 50%

Answer 1

Answer B

Although age-adjusted rates fell by over 50%, because our population has increased and is older, our overall rate has increased. In parts of the world where age adjusted declines did not occur - e.g. South East asia, a massive increase in burden of disease has occurred.

Question 2

Do men or women have higher rates of CVD risk factors and disease?

Answer 2

Men

Question 3

In people with inherited 50% reduction of LDL due to loss of function in PCSK9 their lifetime risk of coronary disease is reduced by:

A) 20%
B) 30%
C) 50%
D) 80%

Answer 3

80%

As these patients have a reduced risk throughout their lifetime, they benefit significantly more.
The longer you live with low cholesterol the better long term outcomes.

Question 4

What are the modifiable environmental risk factors for cardiovascular disease?

Answer 4

Smoking
ApoB/A-I ratio (includes LDLc, nonHDLc, HDLc)
Diabetes
Hypertension
Abdominal obesity
Psychosocial stress

Question 5

What are some modifiable lifestyle points that reduce cardiovascular disease risk?

Answer 5

Higher fruit and vegetable intake
Low alcohol intake
Regular moderate to intense exercise

Question 6

What patient details are used to calculate the Framingham risk score for cardiovascular disease?

What are the different levels of risk for CVD?

Answer 6

Blood pressure
Age
Sex
Smoking status
Total cholesterol to HDL ratio
Diabetes status

High risk = >15% 5 year risk
Intermediate = 10-15%
Low risk = < 10%

Question 7

What are some secondary causes of hypertension?

Answer 7

Coarctation
Renal artery stenosis
Hyperaldosteronism / Cushing’s / Phaeochromocytoma
Renal disease

Idiopathic

Question 8

What is the metabolic syndrome phenotype?

Answer 8

Low HDL
High triglycerides
Insulin resistance
Obesity
Hypertension

Question 9

What is familial hypercholesterolaemia?

Answer 9

Familial hypercholesterolaemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically elevated low-density lipoprotein cholesterol (LDL-C), which leads to an increased risk of cardiovascular disease.

Pathophysiology

FH primarily affects the metabolism of cholesterol in the body, leading to its accumulation in the bloodstream. This is due to defects in the LDL receptor (LDLR) pathway:

1. LDL Receptor Deficiency: In a healthy person, LDL receptors on the liver cells bind LDL particles and remove them from the bloodstream. In FH, mutations in the LDLR gene lead to a reduced number or function of these receptors, preventing efficient clearance of LDL-C.
2. Apolipoprotein B-100 Mutation: Apolipoprotein B-100 (ApoB-100) is the protein component of LDL particles that binds to the LDL receptor. Mutations in the APOB gene can impair this binding, reducing the clearance of LDL-C.
3. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Gain-of-Function Mutation: PCSK9 is a protein that degrades LDL receptors. Gain-of-function mutations in the PCSK9 gene lead to an increased degradation of LDL receptors, reducing their number on liver cells and increasing LDL-C levels.

Genetic Causes

FH is typically inherited in an autosomal dominant manner, meaning a single copy of the mutated gene can cause the disorder.

1. Heterozygous FH: Individuals inherit one mutated gene from one parent and one normal gene from the other. This form is more common and less severe, with LDL-C levels usually between 190-400 mg/dL.
2. Homozygous FH: Individuals inherit mutated genes from both parents. This form is rare but more severe, with LDL-C levels often exceeding 500 mg/dL and early onset of cardiovascular disease.

Impact on Patients

1. Increased Cardiovascular Risk: High levels of LDL-C lead to the early development of atherosclerosis, which can cause coronary artery disease, myocardial infarction, and stroke. The risk is significantly higher in individuals with FH compared to the general population.
2. Physical Manifestations:
   
   • Xanthomas: Cholesterol deposits in the skin, particularly on the tendons (e.g., Achilles tendon / commonly extensor tendons).
   • Xanthelasmas: Cholesterol deposits around the eyelids.
   • Corneal Arcus: Cholesterol deposits around the cornea of the eyes.
3. Management Challenges: Patients often require aggressive lipid-lowering therapies, including statins, ezetimibe, PCSK9 inhibitors, and sometimes LDL apheresis (a procedure to remove LDL-C from the blood). Despite treatment, maintaining target LDL-C levels can be challenging.
4. Psychosocial Impact: The chronic nature of the disease and the risk of premature cardiovascular events can cause anxiety and affect the quality of life. Family members might also need genetic testing and counseling due to the hereditary nature of the disorder.

Summary

Familial hypercholesterolaemia is a genetic disorder that severely impacts cholesterol metabolism, leading to elevated LDL-C levels and increased cardiovascular risk. It is primarily caused by mutations affecting the LDL receptor pathway, inherited in an autosomal dominant fashion. Effective management requires early diagnosis and aggressive lipid-lowering therapy to mitigate the risks of cardiovascular complications.

Question 10

Why are risk factor calculators somewhat flawed?

Answer 10

They fail to account for numerous less explicit risk factors such as coronary calcium scores, and they ignore many other risk factors or beneficial behaviours including:
- Exercise behaviour
- Sleep duration and quality
- Nutrition / diet
- Social deprivation and mental health
- Ethnicity
- Environmental pollution

Question 11

In the NVDPA guidelines what are high risk factors for vascular diseases (Kidney, stroke, coronary, etc)?

Answer 11

Some of the high risk factors are:
- Prior vascular disease
- Diabetes and age > 60
- Microalbuminuria
- Chronic kidney disease
- Persistent proteinuria or eGFR < 45mL/min/1.73m2
- Familial hypercholesterolaemia
- Systolic BP > /= 180 mmHg or diastolic >/= 110mmHg
- Serum total cholesterol > 7.5mmol/L

Question 12

What are the classes of Lipoproteins and what are the major protein and Lipid components of each.

Answer 12

Question 13

Lipid lowering drugs.
What are the top 5 drug classes and what are their mechanisms of action?

Answer 13

Question 14

Statins may lower LDL by what percentage?

A) 5-10%
B) 10-20%
C) 30-50%
D) 50-80%

Answer 14

C
Statins can lower LDL by 30-50%, and they also lower triglycerides.

Fibrates may lower LDL 20-50% and PCSK9 inhibitors are also very effective.

Question 15

What are the adverse effects of statins?

Answer 15

Common
- Myalgia, fatigue, GI intolerance, Flu-like symptoms

Increase in liver enzymes
- 0.5 to 2.5% in a dose dependent manner
- Serious liver problems are exceedingly rare

Myopathy
- CK elevation, and in rare cases rhabdomyolysis
Reduce the risk by using statins cautiously in patients with renal impairment. Avoid use with cyclosporins.

Question 16

What drug class can be used to effectively lower Lp(a)?

Answer 16

There are currently none. Those with high Lp(a) are at greater risk of vascular events.
It is an inherited phenotype that may be linked to premature cardiovascular disease.

Question 17

What are the blood pressure targets for:
A) Normal individuals
B) Diabetics
C) Patients with Congestive HF

Answer 17

A = 120/80
B = 140/80
C = < 120/80

Question 18

Based on the NICE guidelines what are the recommended first line drugs?

Answer 18

Question 19

Define Syncope

Answer 19

Syncope is a temporary loss of consciousness and muscle tone, often described as “fainting” or “passing out,” that occurs due to a sudden drop in blood flow to the brain. It typically resolves spontaneously and is usually followed by a rapid and complete recovery. Syncope can result from a variety of underlying causes, including cardiovascular, neurological, metabolic, and situational factors. Common triggers include orthostatic hypotension, vasovagal reactions, cardiac arrhythmias, and certain medications. The evaluation of syncope involves identifying the cause to guide appropriate management and prevent recurrence.

It is caused by transient global cerebral hypoperfusion.

Features:
- Rapid onset
- Short duration
- Often accompanied by loss of postural tone
- Usually spontaneous complete recovery

Question 20

What are the criteria of orthostatic hypotension?

Answer 20

A drop in systolic BP by 20 mmHg or more after standing within 1-3 mins).

A drop in diastolic BP by 10 mmHg or more after standings (within 1 to 3 minutes)

Systolic BP decreasing to < 90 mmHg after standing.

Orthostatic hypotension often occurs as a result of persistent failure of autoregulatory vasoconstriction.

Question 21

What are red flags of syncope?

Answer 21

Syncope during exertion
Syncope while supine
Palpitations preceding syncope
Family history of premature sudden death < 45 years.
History of structural heart disease

Abnormal baseline ECG

Question 22

Which of the following confers the lowest likelihood that the presenting signs and symptoms represent an ACS (acute coronary syndrome) secondary to CAD (coronary artery disease)?

A) Age > 70
B) Male
C) Diabetes
D) Chest pain reproduced by palpation
E) New, transient ST-segment deviation (>1mm) on ecg

Answer 22

D = chest pain reproduced by palpation

Also of note, pain radiating to the right arm or shoulder, pain on exertion, pain to both arms, pain to left arm, diaphoresis, and pain associated with nausea and vomiting are all things more closely linked with AMI events.

Question 23

What are the NSTE-ACS risk levels and how are they different?

Answer 23

Question 24

What is the management of suspected cardiac chest pain?

Answer 24

Question 25

What is the management for high risk NSTE-ACS?

Answer 25

Firstly ensure they are continuously monitored with frequent vital checks, serial ECGs, and troponins.

Antiplatelet therapy
- Aspirin loading dose (300mg)
- Clopidogrel (300 - 600mg) loading dose or Ticagrelor 180mg

Anti-ischaemic therapy
- Beta blocker e.g. 25mg metoprolol BD
- If contraindicated to BB (e.g. Asthma), consider non-dihydropyridine CCB (e.g. verapamil)
- Nitrates (Sublingual or IV GTN)

Statin
- High dose atorvastatin (80mg) stabilises plaque

Anticoagulant
- IV unfractionated heparin (monitor APTT) or SC LMWH (enoxaparin/clexane).

Symptomatic treatment
- IV GTN
- Morphine

Question 26

What are the major complications of AMI?

Answer 26

Arrhythmia
- VT/VF
- Bradyarrhythmia causing Heart block

Myocardial rupture
- Large infarcts can lead to shock and tamponade

Thrombus, aneurysm
- Mural thrombi may develop due to stasis of the heart wall.
- Thinning and weakening of the heart wall can lead to the formation of an aneurysm.

Cardiac failure/Shock
- Due to depressed LVEF or Valvular incompetence

Myo/pericarditis
- Inflammation arising from adjacent infarcted myocardium

Question 27

How do we monitor post procedural NSTE-ACS patients?

Answer 27

Cardiac monitoring
ECG and enzymes (monitor for post procedure MI)
Watch renal function (contrast nephropathy)
Assess LV function (echo)

Question 28

When patients are stratified into intermediate risk NSTE-ACS they must be reassessed with additional tests to determine if they should be escalated to high risk, or dropped to low risk.

How do we re-stratify these patients?

Answer 28

If the patients have no further chest pain or symptoms and 2 negative troponin tests with no new ECG changes. We perform an exercise stress test.

Positive stress test or recurrence of symptoms or positive troponins or concerning ecg changes means the patient is now stratified to high risk.

Negative stress test with no concerning features identified on additional tests (CT coronary angio or nuclear sestamibi scan) and no further symptoms are stratified to low risk.

High risk patients are managed as such and low risk are discharged and managed as outpatients.

Question 29

What is the long term medical therapy for high risk NSTE-ACS patients?

Answer 29

Dual antiplatelets (12 months minimum)
Beta blocker
ACE (for BP control or if LV dysfunction)
High dose statin
Take home sublingual nitrates

Cardiac rehabilitation
Modification of risk factors/lifestyle factors

Question 30

What are the contraindications to stress testing?

Answer 30

ABSOLUTE CONTRAINDICATIONS
Recurrent chest pain
Acute MI within last 2 days
High risk unstable angina
Uncontrolled arrhythmias
Symptomatic severe aortic stenosis
Uncontrolled heart failure
Acute PE
Acute myocarditis or pericarditis
Acute aortic dissection

RELATIVE CONTRAINDICATIONS
Critical left main coronary stenosis
Moderate stenotic valvular heart disease
Electrolyte abnormalities
Systolic > 200
Diastolic > 100
Tachyarrhythmia or bradyarrhythmia
New AF
Obstructive outflow disorders (e.g. hypertrophic cardiomyopathy)
Resting ECG that will make interpretation unreliable e.g. (LBBB, LVH with strain, Ventricular pacing, Ventricular preexcitation)

Question 31

What ECG changes are seen on NSTEMI / STEMI?

Answer 31

Question 32

How many Australians have heart failure?
What percentage of people over 65 have heart failure?

Answer 32

300,000 Australians
10% of people aged 65+

Question 33

What are the two types of heart failure?
What is the main difference between them?

Answer 33

Systolic and Diastolic

In Systolic heart failure, your heart fails to contract appropriately due to a weakened and dilated ventricle. (Heart can’t pump)

In Diastolic heart failure, your heart fails to relax appropriately due to an enlarged or stiffened myocardium/narrowed ventricle. (Heart can’t fill)

Fortunately systolic heart failure is becoming less common, however, with an aging population, there are more diastolic heart failure cases.

Question 34

Correctly link the terms:
Heart failure with reduced ejection fraction
Heart failure with preserved ejection fraction

Which one is systolic heart failure which is diastolic heart failure?

Answer 34

HFrEF = Systolic
HFpEF = Diastolic

Question 35

What is the management of Acute heart failure?

Answer 35

Acute Management of Heart Failure: Rationale for Therapies

Medications
High Dose IV Nitrates (GTN)
Reason: Nitrates, such as glyceryl trinitrate (GTN), are potent vasodilators. In heart failure, they primarily reduce preload (the volume of blood returning to the heart) by venodilation, and at higher doses, they can also reduce afterload (resistance the heart must pump against) through arterial dilation. This leads to decreased myocardial oxygen demand, reduced pulmonary congestion, and improved cardiac output.

Low Dose Furosemide (Loop diuretic Na/K/CL2)
Reason: Furosemide is a loop diuretic that helps reduce fluid overload by increasing urine output. Low doses are used initially to cautiously reduce volume status, improve symptoms of pulmonary congestion, and decrease preload without causing significant hypovolemia or electrolyte disturbances.

Morphine
Reason: Morphine provides several benefits in acute heart failure management. It reduces anxiety, which can lower sympathetic drive and myocardial oxygen demand. It also causes mild venodilation, reducing preload. Additionally, morphine can alleviate dyspnea by reducing the sensation of breathlessness.

Oxygen (O2)
Reason: Oxygen therapy is used to ensure adequate oxygenation in patients with acute heart failure who have hypoxemia. Supplemental oxygen can improve oxygen delivery to tissues and reduce the work of breathing.

Inotropes (Dobutamine, Dopamine, Milrinone)
Reason: Inotropes increase the force of myocardial contraction, which can be beneficial in acute heart failure with reduced cardiac output. However, these agents are generally associated with increased mortality, likely due to increased myocardial oxygen demand and arrhythmogenic potential. They are typically reserved for patients with severe systolic dysfunction and low cardiac output, where the benefits outweigh the risks.

Non-Drug Therapies
CPAP/BIPAP (Continuous Positive Airway Pressure / Bilevel Positive Airway Pressure)
Reason: Non-invasive ventilation (NIV) with CPAP or BIPAP can improve oxygenation and reduce the work of breathing in patients with acute pulmonary oedema. CPAP provides continuous positive pressure, which helps keep alveoli open and reduces preload and afterload. BIPAP provides additional inspiratory support, further assisting in ventilation and unloading the heart.

Intra-Aortic Balloon Pump (IABP)
Reason: The IABP is a mechanical device that helps reduce afterload and increase coronary perfusion. It inflates during diastole, augmenting coronary blood flow, and deflates during systole, reducing the resistance against which the left ventricle must eject blood. It’s used in cases of cardiogenic shock to stabilize patients while definitive therapies are planned.

Impella
Reason: The Impella device is a percutaneous mechanical circulatory support device that assists the left ventricle in pumping blood. It reduces myocardial workload and improves cardiac output. It is used in severe cases of heart failure, particularly in cardiogenic shock, to provide temporary support.
These therapies are tailored to stabilize the patient, relieve symptoms, and improve haemodynamics, with the ultimate goal of reducing morbidity and mortality in acute heart failure scenarios.

Question 36

Diuretics used in heart failure. What is the mechanism of action of each:

Thiazides
K-sparing
Loop diuretics

Answer 36

Thiazide Diuretics
Mechanism of Action: Thiazides inhibit the sodium-chloride (Na-Cl) cotransporter in the early distal convoluted tubule of the nephron. This inhibition prevents the reabsorption of sodium and chloride ions, leading to an increase in the excretion of sodium, chloride, and water. This also reduces blood volume and decreases blood pressure.
Example Drugs: Hydrochlorothiazide, Chlorthalidone, Indapamide, Metolazone.

Potassium-Sparing Diuretics
Mechanism of Action: Potassium-sparing diuretics act on the distal convoluted tubule and the cortical collecting ducts. They either inhibit the epithelial sodium channels (ENaC) or antagonize the effects of aldosterone. This results in decreased sodium reabsorption and potassium excretion.
ENaC Inhibitors: Block the sodium channels in the principal cells of the late distal tubule and cortical collecting ducts.
Aldosterone Antagonists: Compete with aldosterone for receptor sites, thereby inhibiting sodium reabsorption and promoting potassium retention.
Example Drugs:
ENaC Inhibitors: Amiloride, Triamterene.
Aldosterone Antagonists: Spironolactone, Eplerenone.

Loop Diuretics
Mechanism of Action: Loop diuretics inhibit the sodium-potassium-chloride (Na-K-2Cl) cotransporter in the thick ascending limb of the loop of Henle. This inhibition prevents the reabsorption of sodium, potassium, and chloride ions, leading to significant diuresis. Loop diuretics are potent because they affect a large portion of sodium reabsorption in the nephron, resulting in increased excretion of water, sodium, potassium, calcium, and magnesium.
Example Drugs: Furosemide, Bumetanide, Torsemide, Ethacrynic Acid.

Question 37

There are a number of drugs that can cause vasodilation. Order the drugs below into 3 categories.
1. Venous (primarily)
2. Mixed
3. Arterial (Primarily)

ACEi
ARBs
CCB
Nitrates
K+ channel activators
Alpha adrenergic blockers
Nitroprusside
Minoxidil
Hydralazine

Answer 37

Venous
- Nitrates

Mixed (More venous effects top (e.g. CCB) , more arterial effects bottom)
- CCB
- Alpha adrenergic receptor blockers
- ACEi
- ARBs
- K+ channel activators
- Nitroprusside

Arterial
- Minoxidil
- Hydralazine

Question 38

What are the three primary aspects of treatment for acutely decompensated heart failure?

Answer 38

1. Reduce fluid volume (Diuretics)
2. Decrease preload and afterload (Vasodilators)
3. Augment contractility (Inotropes)

Question 39

What inotropes are used in heart failure and how do they work in heart failure?

Answer 39

Inotropes are medications that increase the strength of myocardial contraction, which can be crucial in the management of heart failure, particularly in cases of acute decompensated heart failure or cardiogenic shock. They work by different mechanisms to enhance cardiac output and improve haemodynamics. Here are the primary ways inotropes work in heart failure:

Mechanisms of Action of Inotropes:

Beta-Adrenergic Agonists
Mechanism: Beta-adrenergic agonists, such as dobutamine and dopamine, bind to beta-1 adrenergic receptors on cardiac myocytes. This activation leads to an increase in cyclic adenosine monophosphate (cAMP) via the activation of adenylate cyclase. Increased cAMP levels activate protein kinase A (PKA), which phosphorylates various proteins involved in calcium handling. This results in increased calcium influx into the cardiac cells, enhancing the contractility of the heart muscle.
Example Drugs:
Dobutamine: Predominantly stimulates beta-1 receptors, with mild beta-2 and alpha-1 activity, leading to increased inotropy (contractility) with less effect on heart rate and peripheral resistance.
Dopamine: Has dose-dependent effects—low doses stimulate dopaminergic receptors causing renal vasodilation, moderate doses stimulate beta-1 receptors increasing cardiac contractility, and high doses stimulate alpha-1 receptors leading to vasoconstriction.

Phosphodiesterase Inhibitors
Mechanism: Phosphodiesterase inhibitors, such as milrinone, inhibit the enzyme phosphodiesterase type 3 (PDE3) in cardiac and vascular smooth muscle. This inhibition prevents the breakdown of cAMP, leading to increased levels of cAMP. As a result, calcium influx is increased, enhancing myocardial contractility. Additionally, elevated cAMP levels in vascular smooth muscle cause vasodilation, reducing afterload (systemic vascular resistance).
Example Drugs:
Milrinone: Increases inotropy and causes vasodilation, thereby reducing afterload and improving cardiac output.

Cardiac Glycosides
Mechanism: Cardiac glycosides, such as digoxin, inhibit the sodium-potassium ATPase pump in cardiac myocytes. This inhibition increases intracellular sodium levels, which in turn reduces the activity of the sodium-calcium exchanger, leading to increased intracellular calcium levels. The elevated calcium enhances myocardial contractility. Digoxin also has vagomimetic effects, which can decrease heart rate and improve ventricular filling.
Example Drugs:
Digoxin: Increases contractility and has a mild chronotropic effect, slowing the heart rate, which can be beneficial in heart failure, especially when accompanied by atrial fibrillation.

Clinical Considerations
Indications: Inotropes are primarily used in acute settings for patients with severe heart failure, particularly those with low cardiac output states or cardiogenic shock, where they can provide temporary support. They may also be used in certain cases of acute decompensated heart failure with evidence of organ hypoperfusion.

Risks and Limitations: While inotropes can improve haemodynamics and symptoms, they are associated with increased mortality in chronic heart failure due to their potential to increase myocardial oxygen consumption, provoke arrhythmias, and cause ischemia. Therefore, they are generally reserved for short-term use in acute settings and not recommended for long-term management.

Inotropes can provide vital support in acute heart failure but must be used judiciously, with close monitoring for potential adverse effects.

Question 40

What is the mechanism of action of Levosimendan?

Answer 40

Mechanism of Action of Levosimendan:

Levosimendan is an inotropic agent with a unique mechanism of action, primarily used in the management of acute decompensated heart failure. It exerts its effects through three main pathways: calcium sensitization, ATP-sensitive potassium channel activation, and PDE III inhibition. NOTE: this drug is has not been shown to be any more effective than the inotropes, sadly.

Here’s a detailed breakdown:

Calcium Sensitization
Binding to Troponin C: Levosimendan binds to cardiac troponin C in a calcium-dependent manner. Troponin C is part of the troponin complex involved in regulating the contraction of cardiac muscle.
Increased Sensitivity to Calcium: By binding to troponin C, levosimendan increases the sensitivity of cardiac myofilaments to calcium. This means that for any given intracellular calcium concentration, the contractile proteins in the heart muscle generate a stronger contraction.
Positive Inotropic Effect: This calcium sensitization results in a positive inotropic effect (increased force of contraction) without a significant increase in intracellular calcium levels, thereby avoiding the increased risk of arrhythmias and excessive oxygen consumption associated with other inotropic agents.

Activation of ATP-Sensitive Potassium Channels (K_ATP)
Vasodilation:
Levosimendan opens ATP-sensitive potassium channels in the vascular smooth muscle cells of blood vessels. This leads to hyperpolarization of the cell membrane, causing relaxation of the smooth muscle cells and resulting in vasodilation.
Reduction in Afterload and Preload: Vasodilation decreases both the preload (venous return to the heart) and afterload (resistance the heart must pump against), which reduces the workload on the heart and improves cardiac output. This can also improve symptoms of congestion and dyspnea in heart failure patients.

Phosphodiesterase III (PDE III) Inhibition:
Increased cAMP Levels: By inhibiting PDE III, levosimendan prevents the breakdown of cyclic adenosine monophosphate (cAMP) in cardiac myocytes. Elevated cAMP levels lead to increased activation of protein kinase A (PKA), which enhances calcium entry into the cells during the action potential.
Enhanced Contractility: Although the primary mechanism of levosimendan is through calcium sensitization, the inhibition of PDE III contributes to its positive inotropic effects by slightly increasing intracellular calcium levels.

Summary of Effects:
Positive Inotropy: Enhanced myocardial contractility through calcium sensitization, leading to increased cardiac output without significantly raising intracellular calcium levels.
Vasodilation: Opening of K_ATP channels leads to arterial and venous dilation, reducing both preload and afterload, which decreases the heart’s workload and improves hemodynamics.

Cardioprotection: The activation of K_ATP channels may also provide cardioprotective effects by helping to stabilize the myocardial cell membrane and reduce ischemia-reperfusion injury.

Clinical Implications:
Acute Decompensated Heart Failure: Levosimendan is often used in patients with acute decompensated heart failure where improved contractility and reduced cardiac workload are needed.

Bridge to Transplant or Mechanical Support: It can be used as a bridge therapy for patients awaiting heart transplantation or the implementation of mechanical circulatory support.

Perioperative Use: In some cases, levosimendan is used perioperatively in high-risk cardiac surgery patients to enhance cardiac function and reduce the risk of postoperative heart failure.

Levosimendan’s unique combination of increasing contractility through calcium sensitization and providing vasodilation through K_ATP channel activation makes it a valuable tool in the management of acute heart failure, offering benefits in both hemodynamic improvement and symptom relief.

Question 41

What is the long term management of chronic heart failure patients?

Answer 41

Fluid restriction - extremely important across food and water
NSA diet, alcohol reduced/stopped
Daily wt - if it increases by 2 kg, they need to tighten fluid restriction or use diuretic
Diuresis - give patients a small supply for their use.

Management by cardiologist / heart failure clinic.
Exercise training program.
Immunisations.

Question 42

What is the first line medication choice for heart failure management?

Answer 42

ACEi are first line as they offer a mortality benefit, are more easily managed and they can be used by patients with mild to severe CHF and even post-myocardial infarction.

Very good drug choice.

Ramipril (possibly better in MI) otherwise enalapril is a good choice.

ARBs can be used as an alternative in patients who get coughs from using ACEi. ARBs are less effective and offer less mortality benefit.

Question 43

What is a major risk of spironolactone?

Answer 43

Hyperkalaemia as it is a potassium sparing diuretic.
Can make patients sick, impact renal function, or cause cardiac issues.

Spironolactone is useful however, and can be given post MI or from mild to severe CHF.

Eplerenone (an alternative to spiro) can be given 3-14 days post MI.

Question 44

What beta blockers are appropriate for heart failure?

Answer 44

Cardiac specific beta blockers.

Bisoprolol
Carvedilol
Metoprolol succinate
Nebivolol

Also useful across the spectrum of patients post MI to severe CHF.

Question 45

What is the first, second, and third line drug treatment strategy for heart failure?

Answer 45

1) ACEi or ARB
2) Beta blocker
3) Aldosterone antagonist (K+ sparing diuretic)

Question 46

What is the MOA of ARNIs?

Answer 46

Angiotensin and neprilysin inhibitors (ARNIs) are a class of drugs used primarily in the management of heart failure with reduced ejection fraction (HFrEF). The most commonly known ARNI is the combination of sacubitril and valsartan. The mechanism of action involves two key components: inhibition of neprilysin and blockade of the angiotensin II receptor. Here’s a detailed explanation:

1. Neprilysin Inhibition (Sacubitril Component)
   Neprilysin: Neprilysin is an enzyme that degrades several vasoactive peptides, including natriuretic peptides (ANP, BNP, and CNP), bradykinin, and adrenomedullin. These peptides have beneficial effects, such as promoting natriuresis (excretion of sodium), diuresis, vasodilation, and inhibition of the renin-angiotensin-aldosterone system (RAAS).

Mechanism: Sacubitril is a prodrug that is converted into its active metabolite, sacubitrilat, which inhibits neprilysin. By inhibiting neprilysin, sacubitrilat increases the levels of natriuretic peptides, bradykinin, and other vasoactive substances. This leads to enhanced natriuresis, diuresis, vasodilation, and inhibition of pathologic growth and remodeling of the heart and vasculature.

2. Angiotensin II Receptor Blockade (Valsartan Component)
   Angiotensin II: Angiotensin II is a potent vasoconstrictor that also stimulates the secretion of aldosterone, leading to sodium and water retention. It plays a crucial role in the RAAS, which regulates blood pressure and fluid balance.

Mechanism: Valsartan is an angiotensin II receptor blocker (ARB) that selectively inhibits the binding of angiotensin II to the angiotensin II type 1 (AT1) receptor. By blocking the AT1 receptor, valsartan prevents the vasoconstrictive and aldosterone-secreting effects of angiotensin II. This leads to vasodilation, reduced blood pressure, decreased sodium and water retention, and reduced sympathetic nervous system activity.

Combined Effect of ARNIs
The combination of neprilysin inhibition and angiotensin II receptor blockade provides a comprehensive approach to heart failure management by:

Promoting Natriuresis and Diuresis: Increased levels of natriuretic peptides lead to enhanced excretion of sodium and water, reducing blood volume and preload.
Vasodilation: Both increased bradykinin levels (due to neprilysin inhibition) and blockade of angiotensin II effects contribute to vasodilation, reducing afterload and lowering blood pressure.
Inhibition of Pathologic Remodeling: The beneficial effects on cardiac remodeling are mediated by the reduction in the harmful effects of angiotensin II and the protective effects of increased natriuretic peptides.
Reduction in Sympathetic Activity: By blocking the effects of angiotensin II, ARNIs reduce the sympathetic nervous system’s contribution to heart failure progression.
Clinical Benefits
ARNIs, like sacubitril/valsartan (Entresto), have been shown to reduce the risk of cardiovascular death and heart failure hospitalization in patients with HFrEF. The dual mechanism targets different pathways involved in heart failure pathophysiology, providing a synergistic effect that improves outcomes more effectively than traditional RAAS inhibitors alone.

In summary, ARNIs work by inhibiting neprilysin, leading to increased levels of beneficial vasoactive peptides, and by blocking the AT1 receptor, counteracting the deleterious effects of angiotensin II. This dual action results in a net effect of reduced blood pressure, decreased volume overload, and improved cardiac function in patients with heart failure.

NOTE: To test heart failure in these patients use NT-proBNP blood test as it is not affected by ARNIs.

Contraindicated in patients with angioedema, or patients who have used ACEi in last 36 hours.