Heart Failure Treatment Overview

Heart Failure Treatments

• Treatments for heart failure aim to improve cardiac output, reduce preload and afterload, and manage fluid retention.
• Vasodilators: Drugs that relax blood vessels, reducing the workload on the heart and improving cardiac output.
• ACE Inhibitors: These drugs reduce renin release, decrease angiotensin II formation, and lower aldosterone release. This helps regulate sodium and water balance, and reduces fluid retention.
• Diuretics: Medications that increase urine production, removing excess fluid from the body and reducing swelling (edema).
• Positive Inotropes: Drugs that increase the force of cardiac contractions, boosting heart output.

Chronic Heart Failure Treatment

• Fluid retention: If patients experience fluid retention, a loop diuretic is prescribed.
• Thrombosis risk: If a risk of blood clots exists, an anticoagulant (blood thinner) may be considered.
• Verapamil avoidance: Verapamil should be avoided as it blocks cardiac calcium channels.

Loop Diuretics

• Examples include furosemide, bumetanide, and torsemide.
• Used in pulmonary edema due to acute left ventricular failure, chronic heart failure, and resistant hypertension.
• Given intravenously for rapid relief of breathlessness and reducing preload.

Mechanism of Action of Loop Diuretics

• Reduce electrolyte reabsorption in the thick ascending limb of Henle's loop.
• Increase excretion of sodium, chloride, potassium, and water through Na+/K+/2Cl− transporters
• High ceiling effect producing potent diuresis.
• Oral administration with a peak effect at around 30 minutes and a half-life of around 2 hours. The duration of action is about 4 to 6 hours.
• IV administration provides faster effects, lasting around 10 minutes.
• Metabolized mainly by the liver (cytochrome P450).
• Excretes 20-25% of filtered sodium (potent effect).

Side Effects, Cautions, and Contraindications of Loop Diuretics

• Side effects: Dizziness, electrolyte imbalance (fatigue, headache, metabolic alkalosis, muscle spasms, nausea).
• Cautions: Risk of urinary retention in patients with an enlarged prostate.
• Cautions: Risk of hypovolemia (low blood volume), hypotension, and hypokalemia (low potassium). Use lower doses in elderly patients to reduce these risks.
• Contraindications: Anuria, drug-induced renal failure, severe hypokalemia, severe hyponatremia.

Heart Failure with Reduced Ejection Fraction (HFrEF) Treatment

• First line treatment involves ACE inhibitors plus a beta-blocker.
• If symptoms persist, add a mineralocorticoid receptor antagonist (e.g., spironolactone).
• Additional treatments may include ivabradine, digoxin, SGLT2 inhibitors (such as dapagliflozin), sacubitril/valsartan, and hydralazine with nitrate.

Beta-Blockers (e.g., Bisoprolol, Carvedilol, Nebivolol)

• Inhibit beta-1 receptors, reducing adrenaline/noradrenaline effects.
• Slows heart rate, reduces cardiac contraction.
• Common side effects: dizziness, tiredness, blurred vision.
• Start treatment at a low dose and gradually increase for optimal effect.

Spironolactone

• An aldosterone antagonist, used as an add-on therapy for heart failure when first-line treatments aren't sufficient.
• Improves survival in heart failure patients.
• Contraindicated if hyperkalemia or renal impairment exists.
• Steroid pro-drug with effects via canrenone (longer half-life).
• Blocks aldosterone action, reducing sodium and water retention, and increasing potassium retention.
  A K+ sparing diuretic; useful in conjunction with loop or thiazide diuretics.

Ivabradine

• Used to treat angina and mild-to-moderate chronic heart failure.
• Inhibits cardiac pacemaker activity.
• A useful alternative alongside or instead of beta blockers.
• Contraindications include MI, cardiogenic shock, heart blocks, and slow heart rates.

Sacubitril/Valsartan

• Combination of an angiotensin receptor-neprilysin inhibitor (ARNI).
• Used in patients who cannot take ACEIs.
• Reduce blood pressure (avoid if systolic BP <100 mmHg).
• Common side effects: anaemia, cough, diarrhoea, dizziness, electrolyte imbalance, headache, hypotension, syncope, vertigo, renal impairment, nausea.

Hydralazine with Nitrate

• Used for patients intolerant to both ACE inhibitors & ARBs.
• Venodilator, reducing preload (pulmonary congestion).
• Arterial vasodilator, increasing stroke volume.
• Contraindications: porphyrias, severe cor pulmonale, dissecting aortic aneurysms, tachycardia

Digoxin

• Positive inotrope, increasing the force of heart contractions to treat heart failure.
• Blocks Na+/K+ ATPase which increases Ca++ levels in myocardial cells, ultimately increasing the force of contraction.
• Indications include chronic heart failure, supraventricular arrhythmias, and chronic atrial fibrillation.

Digoxin Pharmacokinetics, Contraindications & Cautions

• Orally administered, ~75% bioavailability, peak effect in 1-5 hours (IV), Half-life ~36 hours.

• Narrow therapeutic range: Risk of toxicity.

• Common side effects: Arrhythmias, Cardiac conduction problems, Impairment, dizziness, diarrhoea, nausea, skin reactions, vision disorders, vomiting

• Cautions: Electrolyte imbalances, recent myocardial infarction.

SGLT2 Inhibitors (e.g., Dapagliflozin)

• Used in type 2 diabetes and heart failure.

• Mechanism blocks SGLT2, increasing glucose excretion in urine (glucosuria).

• Reduced fluid and sodium retention, decreasing blood pressure

• Improved pre-load and afterload, reducing cardiac workload.

• Rare serious ketoacidosis is a potential side effect in some patients.

• Contraindicated in diabetic ketoacidosis.