Heart Failure Mechanisms and Treatments

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Questions and Answers

What is a major cause of heart failure related to the heart's inability to pump sufficient blood?

Chronic obstructive pulmonary disease

Ischemic heart disease (correct)

Acute respiratory distress

Asthma

Which of the following mechanisms is triggered by low blood pressure in heart failure?

Activation of parasympathetic nervous system

Release of insulin

Decreased heart rate

Increased Sympathetic Activity (correct)

How does the renin-angiotensin-aldosterone system (RAAS) contribute to heart failure?

By decreasing blood volume

By promoting vasodilation

By inhibiting fluid retention

By causing vasoconstriction and sodium retention (correct)

What occurs when heart muscle is excessively elongated?

Systolic failure Signup and view all the answers

What is a consequence of chronic sympathetic nervous system activation in heart failure?

Increased workload on the heart Signup and view all the answers

Which condition is characterized by hypertrophy reducing the heart's ability to fill?

HFpEF Signup and view all the answers

Which condition can promote harmful remodeling in cardiac tissues in heart failure?

Excess blood volume Signup and view all the answers

What is the first line pharmacologic treatment for heart failure with reduced ejection fraction (HFrEF)?

ACE inhibitors Signup and view all the answers

What is the role of natriuretic peptides in heart failure?

Counteract fluid overload and promote vasodilation Signup and view all the answers

What cellular changes are associated with cardiac remodeling in heart failure?

Loss of myocytes, hypertrophy, and fibrosis Signup and view all the answers

Which of the following actions do ACE inhibitors perform?

Decrease afterload Signup and view all the answers

What is a common side effect of heart failure that may present as swelling?

Pitting edema Signup and view all the answers

Which of the following is NOT typically a cause of heart failure?

Cardiac arrest Signup and view all the answers

What is the effect of starting ACE inhibitors at low doses?

It reduces the risk of hypotension Signup and view all the answers

What is true about most ACE inhibitors in terms of their activation?

They are prodrugs activated in the liver Signup and view all the answers

Which outcome is NOT improved by ACE inhibitors?

Vascular resistance Signup and view all the answers

Which medication is considered a replacement for ACE inhibitors in symptomatic HFrEF patients?

Beta-Blockers Signup and view all the answers

What is a potential adverse effect common to both ACE inhibitors and the recommended replacement medications?

Hypotension Signup and view all the answers

What is a significant risk when initiating treatment with beta-blockers?

Worsening heart failure symptoms Signup and view all the answers

Which statement is true regarding the use of diuretics in heart failure management?

They are essential for managing fluid overload symptoms. Signup and view all the answers

Which beta-blocker has additional α-blocking and antioxidant properties?

Carvedilol Signup and view all the answers

Ivabradine is specifically contraindicated in which patient condition?

A fib Signup and view all the answers

What dosing practice is crucial when starting beta-blockers?

Gradual dose increase Signup and view all the answers

What condition can become aggravated during initial treatment with diuretics?

Dehydration Signup and view all the answers

What is a significant adverse effect of ACE inhibitors?

Hyperkalemia Signup and view all the answers

Which of the following statements about Angiotensin receptor blockers (ARBs) is true?

They block angiotensin II receptors. Signup and view all the answers

Which of the following is a major risk associated with Mineralocorticoid Receptor Antagonists (MRAs) like spironolactone?

Hyperkalemia Signup and view all the answers

What is the role of neprilysin in the context of Angiotensin Receptor–Neprilysin Inhibitors (ARNIs)?

It breaks down vasoactive peptides. Signup and view all the answers

In what scenario might a doctor choose to prescribe ARBs over ACE inhibitors?

When the patient has a history of angioedema. Signup and view all the answers

Which of the following effects is associated with the combination therapy of ARBs and neprilysin inhibitors?

Decreased myocardial fibrosis Signup and view all the answers

What is the primary therapeutic benefit of using Angiotensin Receptor–Neprilysin Inhibitors (ARNIs)?

To reduce afterload and preload. Signup and view all the answers

What characteristic distinguishes Losartan from other ARBs?

It produces an active metabolite through first-pass metabolism. Signup and view all the answers

What is a common initial indicator of digoxin toxicity?

Blurred vision Signup and view all the answers

What condition primarily predisposes a patient to digoxin toxicity?

Decreased serum potassium levels Signup and view all the answers

Which of the following drugs should be used with caution in conjunction with digoxin?

Diltiazem Signup and view all the answers

What is the primary therapeutic target of milrinone?

Increase intracellular cAMP Signup and view all the answers

What is a well-known effect of B-adrenergic agonists like dobutamine?

Positive inotropic effects Signup and view all the answers

What class of medication does vericiguat belong to?

Soluble guanylate cyclase stimulators Signup and view all the answers

Which of the following interventions is NOT used for treating digitalis toxicity?

Aspirin for fever Signup and view all the answers

What is the primary use of B-adrenergic agonists like dopamine in heart failure?

Short-term improvement of cardiac output Signup and view all the answers

What is the mechanism through which SGLT2 inhibitors lower preload and afterload?

Induction of glucosuria and natriuresis Signup and view all the answers

Which of the following is an adverse effect associated with hydralazine?

Risk of drug-induced lupus erythematosus Signup and view all the answers

What is a primary clinical use of digoxin?

Management of symptomatic heart failure with reduced ejection fraction Signup and view all the answers

What potential ocular side effect is associated with ivabradine?

Halos and brightness phenomena Signup and view all the answers

Which mechanism do venous dilators primarily utilize to manage heart failure?

Reduce preload Signup and view all the answers

What is necessary when using SGLT2 inhibitors alongside insulin or sulfonylureas?

Regular monitoring for hypoglycemia Signup and view all the answers

What is the main mechanism of action of digoxin in treating certain heart conditions?

Inhibition of sodium-potassium ATPase leading to increased intracellular calcium Signup and view all the answers

In patients unable to tolerate ACE inhibitors or ARBs, what class of drugs is often used for additional vasodilation?

Venous and arterial dilators Signup and view all the answers

Study Notes

Heart Failure Pharmacology

Heart failure (HF) is the inability of the heart to pump sufficient blood due to impaired filling and/or ejection capabilities.
Major causes include ischemic heart disease, hypertension, valvular disorders, arrhythmias, cardiomyopathies, and sometimes certain anticancer drugs like doxorubicin or severe anemia.
Chronic activation of the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) leads to cardiac remodeling, characterized by myocyte loss, hypertrophy, and fibrosis, ultimately decreasing heart function.
Initial myocardial insult decreases cardiac output and/or mean arterial pressure leading to increased wall stress.
Compensatory mechanisms include increased sympathetic activity, RAAS activation, and natriuretic peptides.
- Increased sympathetic activity leads to increased heart rate and contraction strength, raising preload, and workload on the heart.
RAAS activation reduces renal blood flow, leading to renin release, angiotensin II and aldosterone production. Results in vasoconstriction, sodium & water retention, and elevated blood volume and fluid accumulation.
Natriuretic peptides lead to vasodilation and natriuresis (sodium in urine), reducing fluid overload symptoms.

Heart Failure Symptoms

Common symptoms include: shortness of breath, coughing, tiredness, fluid buildup around lungs (pulmonary edema), abdomen swelling (ascites), and swelling in ankles and legs (pitting edema)

Pharmacologic Treatment of HF

Drug classes target different aspects of HF physiology to improve outcomes.
- Reducing preload and afterload improves cardiac output.
- Increasing myocardial contractility.

Angiotensin-Converting Enzyme (ACE) Inhibitors

Decrease vascular resistance and venous tone, lowering afterload and preload.
Improves cardiac output and counteracts angiotensin II-mediated effects
Recommended for all HFrEF patients to reduce mortality and morbidity. Start at low doses.
Most are prodrugs, activated in the liver.
Half-life ranges from 2-12 hours.
Adverse effects include postural hypotension, renal insufficiency, hyperkalemia, cough (due to bradykinin), and angioedema.
Potassium and creatinine monitoring is vital.

Angiotensin Receptor Blockers (ARBs)

Block angiotensin II receptors.
Produce similar effects to ACE inhibitors, but without raising bradykinin, reducing cough and angioedema risk.
Alternative to ACE inhibitors for patients who cannot tolerate them.
Typically given once daily, highly plasma-bound, and some with first-pass metabolism into an active metabolite.
Adverse effects are similar to ACE inhibitors, but with lower risk of cough and angioedema.

Mineralocorticoid Receptor Antagonists (MRAs)

Inhibit aldosterone, reducing sodium retention and cardiac remodeling
Decreases mortality.
Indicated for symptomatic HFrEF patients, especially post-myocardial infarction.
High risk of hyperkalemia.
Can have endocrine side effects such as gynecomastia.

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

Combine angiotensin receptor blockade (ARB) with neprilysin inhibition, increasing natriuretic peptides. Reducing Angiotensin II's harmful effects and decreasing afterload, preload, and myocardial fibrosis.
Recommeded as a replacement for ACE inhibitors in symptomatic HFrEF patients on optimal therapy.
Higher risk of hypotension, not recommended for patients with a history of angioedema.

Beta-Blockers

Mitigate harmful SNS activation and prevent norepinephrine-induced cardiac remodeling.
Some Beta-Blockers are non-selective, also containing a-blocking and antioxidant properties.
Recommended for chronic HFrEF and some HFpEF patients needing heart rate control.
Gradual dose increase vital to avoid adverse effects.
Potential for worsening HF symptoms initially, but gradual dosing helps.

Diuretics

Primarily loop diuretics like furosemide reduce plasma volume and preload, improving symptoms of fluid overload.
Primarily used in fluid-overloaded HF patients.
Adverse effects include dehydration, hyponatremia, and hypokalemia, requiring regular electrolyte monitoring.

Hyperpolarization-activated cyclic nucleotide-gated channel blockers (HCN channel blockers)

Ivabradine selectively slows the If current in the SA node, reducing heart rate without affecting contractility, AV conduction, ventricular repolarization, or blood pressure.
Used in HFrEF for patients with a heart rate above 70 bpm who are on optimized therapy, especially if beta-blockers are not tolerated.
Adverse effects include bradycardia, and in some cases, atrial fibrillation risk. May cause luminous phenomena (e.g., brightness or halos) due to eye channel inhibition.

Vaso- and Venodilators

Venous dilators (eg., nitrates, nitroprusside) reduce preload.
Arterial dilators (eg., hydralazine) reduce afterload.
Useful for patients who can't tolerate ACE inhibitors or ARBs, or need additional vasodilation support.
Potential adverse effects include headache, dizziness, and drug-induced lupus erythematosus (hydralazine).

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

Reduce plasma volume through glucosuria and natriuresis, consequently lowering preload & afterload.
May prevent cardiac fibrosis.
SGLT2 inhibitors like dapagliflozin reduce HF hospitalizations and mortality in HFrEF patients.
Adverse effects include volume depletion, renal issues, and urogenital infections. Additional monitoring needed for hypoglycemia if used with insulin or sulfonylureas.

Inotropic Drugs

Increase cardiac contractility via enhanced intracellular calcium.
Typically reserved for acute, severe HF due to association with increased mortality in long-term use.
Examples include digitalis glycosides, phosphodiesterase inhibitors, and beta-adrenergic agonists.

Digitalis Glycosides

Inhibit Na+/K+ ATPase, increasing calcium and contractility; improve symptomatic HFrEF and atrial fibrillation.
Low serum digoxin concentration (0.5-0.9 ng/mL) typically beneficial in HFrEF.
Primarily excreted by the kidneys, requiring dosage adjustments in renal dysfunction.
Has a narrow therapeutic range, requiring careful dosing and monitoring.
Initial signs of toxicity include anorexia, nausea, vomiting, blurred vision, or yellow vision.
Decreased serum potassium levels (hypokalemia) increase risk of digoxin toxicity.
Use with caution with other drugs that slow AV conduction (e.g., beta-blockers, verapamil, diltiazem).

Phosphodiesterase Inhibitors

Milrinone increases intracellular calcium and therefore contractility via phosphodiesterase inhibition and increase intracellular cAMP level.
Usually used for short-term treatment of acute decompensated HF with low cardiac output.
Can also reduce pulmonary vasculature resistance, beneficial for treating acute pulmonary hypertension and right heart failure.

β-Adrenergic Agonists

Improve cardiac performance by causing positive inotropic effects and vasodilation (Dobutamine).
Increased calcium ion entry into myocardial cells enhances contraction.
Typically administered intravenously.
Used primarily in short-term treatment of acute decompensated HF.

Soluble Guanylate Cyclase Stimulators (Vericiguat)

Directly stimulates sGC and sensitizes it to endogenous NO.
Increases cGMP, improves left ventricular compliance and reduces inflammation and prevents hypertrophy and fibrosis.
Contraindicated in pregnancy and breastfeeding, avoided with nitrates or phosphodiesterase inhibitors due to increased hypotension.

Acute vs. Chronic HF Management

Chronic HF: Managed through lifestyle modifications and optimized drug combinations. Emphasizes RAAS and SNS inhibitors depending on subtype (HFpEF or HFrEF).
Acute Decompensated HF: Treatment involves inotropes and IV vasodilators for rapid stabilization. Drugs known to worsen HF, such as NSAIDs, should be avoided.

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Description

This quiz explores various mechanisms and treatments associated with heart failure. It covers the causes, effects on heart function, pharmacological interventions, and the role of different systems like RAAS and natriuretic peptides. Test your knowledge on this vital topic in cardiovascular health.