Heart Failure

Question 1

What is the American College of Cardiology Foundation’s definition of heart failure?

Answer 1

A complex clinical syndrome resulting from any structural or functional impairment of ventricular filling or ejection.

Question 2

What are the signs and symptoms of heart failure?

Answer 2

Signs: Breathlessness, ankle swelling and fatigue.
Symptoms: Increased jugular venous pressure, pulmonary crackles and peripheral odema.

Question 3

What are some heart failure phenotypes and their causes?

Answer 3

HFwith reduced EF: EF <40%. Patients ususally have abnormalities in systolic and diastolic function. Causes include MI, Myocardial ischeamia, congenital heart disease.

HFwith preserved EF: EF is > than 50%. Need to rule out non-cardiac Shortness of breath and fluid retention. Causes include hypertension, obesity and myocarditis.

HF with recovered EF: Usually due to treatment.

HF with mildly reduced EF: EF 40-50%.

Question 4

What is the Frank-Starling law in heart failure?

Answer 4

Based on the link between the initial length of myocardial fibres and the forces of contraction. The more myocardial fibres are stretched, the greater the tension in muscle fibres and the greater the force of contraction, thus greater CO.

Question 5

What is the preload and afterload?

Answer 5

Preload is the maximum stretch experienced in the ventricle just before contraction. Afterload is the pressure required to push blood out of the ventricles.

Question 6

What some precipitating factors for heart failure?

Answer 6

Excess fluid or Na intake, heavy alcohol use, use of meds with negative inotropy, MI, uncontrolled hypertension, systemic infection, anaemia, hyperthyroidism.

Question 7

What is ventricular remodelling and what happens?

Answer 7

Occurs in response to excess cardiac workload. Concentric hypertrophy, the cardiac mass is out of proportion to the volume of the cardiac chamber. Eccentric hypertrophy is an increase in the size or volume of heart chambers to relieve volume overload.

Question 8

What are the vasodilatory hormones and what happens to them?

Answer 8

Counter-regulatory hormones are upregulated. Natriuretic peptides, prostaglandins and bradykinin cause vasodilation.

Question 9

What is endothelin’s role in heart failure?

Answer 9

Endothelin is a potent vasodilator released in the pulmonary circulation and myocardium in response to increased pressure. In the heart it causes myocyte hypertrophy and interstitial fibrosis.

Question 10

What is secondary mitral valve regurgitation?

Answer 10

Seen in patients with HFrEF, occurs due to the distortion of the mitral valve apparatus. Causes include decreased contractile force, mitral valves dont join properly. Spherical shape of ventricle - influences length of valve muscles.

Question 11

What is cardiorenal syndrome?

Answer 11

Increase in blood volume worsen HF and causes disease progression. Decreased CO decreases renal perfusion. This worsens renal function and causes RAAS activation and causes Na & H2O retention.

Question 12

What are symptoms of pulmonary congestions?

Answer 12

Orthopnoea. Dyspnoea in the recumbent position. Paroxysmal noctural dysnoea. (Episodes of SOB that awaken a person suddenly from sleep with a feeling of anxiety and suffocation.

Question 13

What are some symptoms of systemic venous congestion?

Answer 13

Weight gain, oedema of the lower extremities, GI symptoms such as bloating, anorexia, Right upper quadrant pain and nausea/vomiting, poor sleep and mood disturbance.

Question 14

What are the pharmacokinetics of digoxin?

Answer 14

A: Bioavailability: 60-80%. Rate of absorption is reduced by food.
D: Wide distribution. T 1/2 32-48 hours.
M: Not extensively hepatically metabolised
E: Renal, 50-70 as unchanged drug.

Question 15

What is the mechanical effect of digoxin?

Answer 15

Digoxin increases the contraction of cardiac sarcomeres by increasing the amount of free calcium in the region of the contractile proteins (troponins) during systole.

Question 16

How does digoxin increase calcium?

Answer 16

Inhibiting Na/K ATPase results in an increase in intracellular sodium.
Increased intracellular sodium reduces the expulsion of calcium from the cell by the sodium-calcium exchanger

Question 17

What are the electrical effects of digoxin?

Answer 17

An early brief prolongation of the action potential, followed by a shortening. The decrease is due to increased K conductance caused by increased intracellular calcium.

By stimulating the PNS, digoxin slows electrical conduction in the AV node. The increase in calcium prolongs parts of the cardiac action potential thus increasing the refractory period of the AV node.

Question 18

What are digoxin’s effects on other organs?

Answer 18

GIT effects: causes anorexia, nausea and vomiting and diarrhoea. Can also cause headache, drowsiness, facial pain and depression.

Question 19

What are some of digoxin’s interactions with electrolytes?

Answer 19

Hyperkalaemia reduces digoxin’s ability to bind to Na/K - ATPase. May also reduce the toxic effects of digoxin. Hypokalaemia facilitates the ability of digoxin to bind to Na/K-ATPase. Calcium accelerates the accumulation of intracellular calcium stores. Can contribute to digitalis-induced abnormal automaticity.

Question 20

What are some drug interactions of digoxin?

Answer 20

Drugs that may increase serum concentrations of digoxin.

Captopril, verapamil and diltiazem. Quinidine. Tetracycline, trimethoprim, spironolactone.

Drugs with additive depressant effects on AV node conduction verapamil, diltiazem

Question 21

What is dobutamine Mechnism of Action?

Answer 21

Positive ionotropic effects are caused by Beta-1 adrenergic receptor agonism. The ionotropic effect increases contractility, increases cardiac output.

Question 22

What are some drug interactions and side effects of dobutamine?

Answer 22

Beta blockers. Palpatations, ventricular tachycardia, may increase SBP by 10-20 mmHg. Nausea, vomiting headache.

Question 23

What is the MOA of Dopamine?

Answer 23

DA binding to D1 on smooth muscle of visceral vasculature, the proximal renal tubule. This increases diuresis, increases renal perfusion and reduced blood pressure. DA binding to pre-synaptic D2 receptors increases. Na and H2O excretion

Question 24

What are some indications of dopamine?

Answer 24

Cardiogenic shock due to MI, cardiac surgery, renal failure, short term management of refractory HF

Question 25

What are some dopamine’s drug interactions?

Answer 25

Alpha blockers (antagonise beta dilation effect)
Beta blockers, MAOI (effects of DA are prolonged), TCAs and maprotiline.

Question 26

What is neprilysin inhibitors MOA?

Answer 26

Neprilysin is an enzyme that breaks down endogenous vasdilators and proteins such as: bradykinin and natriuretic peptides. Sacubitril is a prodrug that inhibits neprilysin through the active metabolite LBQ657 metabolite resulting in vasodilation and natriuresis. With an ARB it decreases the activation of RAAS and sensitivity to natriuretic peptides.