Review sheet learning objects Heart failure

What is the definition of heart failure?

Heart failure is a clinical syndrome caused by the heart's inability to pump a sufficient amount of blood to meet the metabolic demands of the body, or doing so only at elevated filling pressures. It is often characterized by signs and symptoms of fluid overload (edema) and inadequate tissue perfusion.

• Source: HF 1, Slide 3

What is acute decompensated heart failure and what causes it?

This is a sudden worsening of heart failure symptoms (such as severe shortness of breath or edema) that requires urgent medical attention. It is caused by the heart's inability to maintain a "compensated" state, often triggered by factors like excessive salt intake, non-compliance with meds, or a new cardiac event (like an arrhythmia or MI).

• Source: HF 1, Slide 15

How is systolic heart failure different from diastolic heart failure?

Systolic HF (HFrEF): The heart muscle is thin and weak; it cannot pump with enough force, resulting in a reduced Ejection Fraction (EF < 40%).

Diastolic HF (HFpEF): The heart muscle is thick and stiff; the ventricles cannot fill properly with blood during relaxation, though the Ejection Fraction remains "preserved" (EF > 50%).

• Source: HF 1, Slides 4 & 5

Compare and contrast causes of systolic versus diastolic heart failure.

Systolic: Primarily caused by Coronary Artery Disease (CAD), Myocardial Infarction (MI), and dilated cardiomyopathy.

Diastolic: Primarily caused by chronic Hypertension (leading to LV hypertrophy), aging, and aortic stenosis.

• Source: HF 1, Slides 4 & 6

What is cardiac tamponade?

This is a condition where the pericardial sac fills with fluid (blood or effusion), creating external pressure that prevents the heart from expanding and filling with blood. This leads to a drastic drop in cardiac output.

• Source: HF 1, Slide 11

Which four factors control cardiac output?

Preload, Afterload, Contractility (Inotropy), and Heart Rate (Chronotropy).

• Source: HF 1, Slide 8

Preload recruitment in exercise helps increase cardiac output to meet increased metabolic demand. Why doesn't this work in heart failure?

In a healthy heart, the Frank-Starling mechanism increases stroke volume as preload increases. In a failing heart, the curve is flattened; the heart is already operating at near-maximum stretch (high preload). Further increases in preload only increase congestion and wall stress without significantly increasing stroke volume.

• Source: HF 1, Slide 9; HF 2, Slide 26

What does neprilysin do and what is the advantage of blocking it?

Neprilysin is an enzyme that breaks down beneficial natriuretic peptides (like ANP and BNP). Blocking it increases the levels of these peptides, which promote vasodilation, natriuresis (sodium excretion), and inhibit the harmful remodeling effects of RAAS.

• Source: HF 2, Slides 11 & 14

How is sacubitril activated?

Sacubitril is a prodrug that is activated by esterases to its active metabolite, sacubitrilat (LBQ657).

• Source: HF 2, Slide 13

Compare and contrast pro drug and active metabolite?

A prodrug is a pharmacologically inactive compound that must be converted by the body (usually by liver enzymes or esterases) into an active metabolite, which is the form that actually produces the therapeutic effect.

• Source: HF 2, Slide 13

What are adverse effects of beta blockers?

Bradycardia, hypotension, fatigue, exercise intolerance, dizziness, and worsening of asthma/COPD symptoms (due to beta 2 blockade).

• Source: HF 2, Slide 26; HF 4, Slide 22

For a patient in hypertensive emergency, why might you not want to start with metoprolol or propranolol?

In acute emergency/decompensation, these drugs can acutely decrease cardiac output and contractility. Additionally, if the patient has high sympathetic drive, blocking beta-receptors could leave alpha-1 receptors "unopposed," potentially causing a paradoxical increase in peripheral resistance and afterload.

• Source: HF 2, Slide 26

On its own, Sacubitril didn't work in the heart failure clinical trial. But it was approved in combination with another agent anyway. Give pros and cons.

Pros: When combined with Valsartan (forming an ARNI), it significantly reduces mortality and hospitalizations. It targets two pathways: increasing beneficial peptides while blocking harmful Angiotensin II.

Cons: On its own, it increases Angiotensin II (which neprilysin also breaks down), so it must be paired with an ARB. It also carries a risk of angioedema.

• Source: HF 2, Slides 11 & 14

If the patient has edema, why might you use furosemide but not hydrochlorothiazide?

Furosemide is a "high-ceiling" loop diuretic. It is much more potent and can pull off significantly more fluid (20-25% of filtered sodium) compared to HCTZ (5%), making it the drug of choice for symptomatic congestion and edema.

• Source: HF 3, Slide 25

What is diuretic breaking, and how can it be prevented?

Diuretic breaking is a decrease in the diuretic effect over time. Mechanisms: 1) Short-term "braking" due to RAAS activation following volume loss. 2) Long-term hypertrophy of the distal tubule to reabsorb more sodium.

Prevention: Combine a loop diuretic with a thiazide (like metolazone) to block the compensatory sodium reabsorption in the distal tubule.

• Source: HF 3, Slides 2, 4 & 25

Compare and contrast spironolactone and eplerenone.

Both are aldosterone antagonists. Spironolactone is non-selective and can cause endocrine side effects like gynecomastia. Eplerenone is highly selective for the mineralocorticoid receptor and lacks those endocrine side effects.

• Source: HF 3, Slide 25

What is the relevance of SGLT2 inhibition and heart failure? Name drug(s).

SGLT2 inhibitors (e.g., Dapagliflozin, Empagliflozin) were originally for diabetes but are now a "pillar" of HF treatment. They reduce preload through osmotic diuresis and reduce afterload/remodeling.

• Source: HF 3, Slide 25; HF 4, Slide 23

Tolvaptan is a vasopressin 2 receptor antagonist. What is the result?

It results in aquaresis the excretion of free water without affecting electrolytes like sodium. This is useful for treating hyponatremia in HF.

• Source: HF 3, Slide 25

Compare and contrast the MOA of digoxin and milrinone.

Both increase intracellular calcium to improve contractility.

Digoxin: Inhibits the Na+/K+ ATPase pump.

Milrinone: Inhibits Phosphodiesterase-3 (PDE3), preventing the breakdown of cAMP.

• Source: HF 4, Slides 8, 12 & 24

What are the adverse effects of digoxin and how can it be reversed?

AEs: Arrhythmias (PVCs, AV block), yellow-green vision halos, nausea, and vomiting. Reversal: Digoxin Immune Fab (DigiBind).

• Source: HF 4, Slides 10 & 24

Compare and contrast digoxin and dobutamine.

Both are positive inotropes. Dobutamine is a $\beta_1$ agonist used for acute, short-term support (IV). Digoxin is used for chronic management and also has vagomimetic effects to slow heart rate.

• Source: HF 4, Slide 24

What are advantages of ivabradine as compared to metoprolol in the treatment of tachycardia?

Ivabradine specifically inhibits the "$I_f$" (funny) current in the SA node to slow heart rate without decreasing contractility (negative inotropy) or affecting blood pressure.

• Source: HF 2, Slide 2