Makindo Medical Notes

Related Subjects: |Managing Chronic Heart Failure |Heart Failure and Pulmonary Oedema |Loop Diuretics |Entresto Sacubitril with Valsartan |Ivabradine |Furosemide |Angiotensin Converting Enzyme Inhibitors |Cardiac Resynchronisation Therapy (CRT) Pacemaker

Interpreting BNP and NT-proBNP Levels

• BNP:
  • BNP levels below 100 pg/mL are considered normal.
  • Levels between 100-300 pg/mL suggest possible heart failure.
  • Levels above 300 pg/mL strongly suggest heart failure, with higher values indicating more severe dysfunction.
• NT-proBNP:
  • Under 50 years old: NT-proBNP < 300 pg/mL is normal.
  • 50-75 years old: NT-proBNP < 900 pg/mL is typically normal.
  • Over 75 years old: NT-proBNP < 1800 pg/mL is considered normal.

Interpreting Elevated Levels

• Mildly Elevated BNP/NT-proBNP: May suggest early or less severe heart failure or other causes include ACS, pulmonary hypertension, CKD, COPD, and advanced age.
• Moderately to Severely Elevated BNP/NT-proBNP: Usually indicates heart failure, with higher levels correlating with worse prognosis and greater severity.
• NYHA Classification:
  • Class I: BNP < 300 pg/mL (NT-proBNP < 300 pg/mL)
  • Class II: BNP 300-600 pg/mL (NT-proBNP 300-1000 pg/mL)
  • Class III: BNP 600-900 pg/mL (NT-proBNP 1000-1800 pg/mL)
  • Class IV: BNP > 900 pg/mL (NT-proBNP > 1800 pg/mL)

Clinical Considerations

• Heart Failure Diagnosis: Elevated BNP/NT-proBNP in a patient with symptoms like shortness of breath, fatigue, and fluid retention strongly supports heart failure diagnosis. However, consider other causes of elevation.
• Monitoring Heart Failure: Serial measurements can monitor the effectiveness of treatment; decreasing levels often indicate clinical improvement.
• Prognostic Value: Higher levels are associated with a worse prognosis in heart failure, predicting outcomes like hospitalization and mortality.

Factors Affecting BNP/NT-proBNP Levels

• Increased Levels: Can occur due to renal impairment, acute coronary syndrome, advanced age, or pulmonary hypertension.
• Decreased Levels: Obesity can lead to lower levels, potentially masking the severity of heart failure.

Right And Left Heart Failure

Initial Assessment

• Clinical: Assess dyspnoea, fatigue, and fluid retention.
• Identify risk factors: hypertension, coronary artery disease, diabetes, prior MI.
• Echocardiography: to determine ejection fraction (EF) and differentiate between
  • HFpEF (EF ≥50%)
  • HFrEF (EF <40%)
  • HFmrEF (EF 41-49%) mid-range.
• Bloods: BNP or NT-proBNP levels, U&E, TFTs to guide diagnosis and management.
• Assess for Comorbidities: Manage comorbidities such as AF, CKD, frailty, obesity.

Management of HFrEF (EF <40%)

• First-Line Pharmacotherapy:
  • ACE Inhibitors/ARBs: both reduce morbidity and mortality. Titrate to target dose.
  • Beta-Blockers: Choice of bisoprolol, carvedilol, metoprolol succinate after stabilizing with ACE inhibitors/ARBs. Titrate to target dose.
  • Mineralocorticoid Receptor Antagonists (MRAs): Add spironolactone or eplerenone in symptomatic patients with NYHA class II-IV.
• Additional Therapies:
  • ARNI (Sacubitril/Valsartan): replace ACEi/ARB with an ARNI for further mortality reduction.
  • SGLT2 Inhibitors: Add Dapagliflozin/Empagliflozin. Improves outcomes in HFrEF patients, regardless of diabetes status.
  • Ivabradine: symptomatic HF despite optimal beta-blocker therapy and a heart rate ≥70 bpm.
• Device Therapy:
  • Implantable Cardioverter-Defibrillator (ICD): EF ≤35% after optimal medical therapy for primary prevention of sudden cardiac death.
  • Cardiac Resynchronization Therapy (CRT): Consider in patients with symptomatic heart failure, EF ≤35%, and LBBB with QRS duration ≥150 ms.
• Monitoring and Follow-Up: Regularly monitor symptoms, renal function, electrolytes, and adjust medications accordingly. Schedule follow-up echocardiography to reassess EF and heart function.

Management of HFpEF (EF ≥50%)

• Control Hypertension: Lower blood pressure with ACEi, ARBs, or beta-blockers.
• Diuretics: loop diuretics e.g. furosemide to manage fluid retention symptoms.
• Manage Comorbidities:
  • Atrial Fibrillation: Rate control and rhythm management are critical.
  • Coronary Artery Disease: antiplatelet therapy and revascularization as indicated.
  • Obesity: weight loss and exercise to improve symptoms and overall prognosis.
• Exercise Training: cardiac rehabilitation program to improve exercise capacity and quality of life.
• Emerging Therapies: Consider SGLT2 inhibitors (e.g. Empagliflozin) for reducing hospitalization in HFpEF patients.
• Regular Monitoring: worsening symptoms, manage exacerbations promptly, and reassess comorbidities periodically.

Lifestyle and Supportive Measures

• Dietary Recommendations: Low-sodium diet to reduce fluid retention.
• Fluid Management: monitor weight and fluid restriction if severe fluid retention.
• Smoking Cessation: Key for long term survival.
• Patient Education: Educate patients and caregivers. Compliance with medication adherence.
• Psychosocial Support: Manage depression and anxiety related to chronic heart failure.

Pharmacological Management of Heart Failure: Drugs, Assessment, Side Effects, and Evidence-Based Dosing

Heart failure (HF) is a chronic, progressive condition in which the heart is unable to pump sufficient blood to meet the body's needs. It can result from various causes, including coronary artery disease, hypertension, and valvular heart disease. The pharmacological management of HF aims to alleviate symptoms, reduce hospitalizations, and improve survival rates. Medications are selected based on their ability to reduce preload, afterload, or neurohormonal activity. This essay explores the main classes of drugs used to treat HF, their mechanisms, dosages, side effects, and evidence supporting their use.

1. Angiotensin-Converting Enzyme (ACE) Inhibitors

ACE inhibitors are considered foundational in the management of HF, especially in patients with reduced ejection fraction (HFrEF). They work by blocking the conversion of angiotensin I to angiotensin II, thereby reducing vasoconstriction, aldosterone secretion, and sodium retention.

• Mechanism of Action: By inhibiting ACE, these drugs lower angiotensin II levels and reduce afterload, preload, and blood pressure. They also help prevent cardiac remodeling.
• Common Drugs and Dosing:
  • Enalapril: Initial dose of 2.5 mg twice daily, titrated up to 10-20 mg twice daily.
  • Lisinopril: Initial dose of 2.5-5 mg daily, titrated up to 20-40 mg daily.
• Side Effects: ACE inhibitors may cause a persistent dry cough, hyperkalemia, renal dysfunction, and, in rare cases, angioedema.
• Evidence: Trials such as the SOLVD and CONSENSUS trials have demonstrated that ACE inhibitors improve survival, reduce HF symptoms, and decrease hospitalizations.

2. Angiotensin II Receptor Blockers (ARBs)

ARBs are typically used as an alternative to ACE inhibitors for patients who experience cough or angioedema. They work by blocking the angiotensin II receptors, thus reducing vasoconstriction and aldosterone effects.

• Mechanism of Action: ARBs block angiotensin II from binding to its receptors on blood vessels, leading to vasodilation, reduced sodium retention, and decreased afterload.
• Common Drugs and Dosing:
  • Losartan: Initial dose of 25-50 mg daily, titrated up to 50-150 mg daily.
  • Valsartan: Initial dose of 40 mg twice daily, titrated up to 160 mg twice daily.
• Side Effects: Hyperkalemia, hypotension, and renal dysfunction are common side effects. ARBs are less likely to cause cough compared to ACE inhibitors.
• Evidence: The CHARM trial series demonstrated that ARBs improve outcomes for HF patients, especially when combined with beta-blockers.

3. Beta-Blockers

Beta-blockers reduce the heart rate and myocardial contractility, which decreases oxygen demand and mitigates the adverse effects of sympathetic nervous system activation in HF.

• Mechanism of Action: Beta-blockers block the beta-adrenergic receptors, reducing sympathetic nervous system activity. This helps lower heart rate, blood pressure, and myocardial oxygen consumption.
• Common Drugs and Dosing:
  • Carvedilol: Initial dose of 3.125 mg twice daily, titrated up to 25 mg twice daily.
  • Metoprolol Succinate: Initial dose of 12.5-25 mg daily, titrated up to 200 mg daily.
  • Bisoprolol: Initial dose of 1.25 mg daily, titrated up to 10 mg daily.
• Side Effects: Common side effects of beta-blockers include bradycardia, fatigue, dizziness, and, in some cases, worsening HF symptoms initially. Careful titration and monitoring are necessary to avoid these issues.
• Evidence: Landmark trials such as MERIT-HF (Metoprolol), COPERNICUS (Carvedilol), and CIBIS-II (Bisoprolol) have shown that beta-blockers significantly improve survival, reduce hospitalizations, and enhance quality of life for HF patients with reduced ejection fraction.

4. Mineralocorticoid Receptor Antagonists (MRAs)

MRAs, such as spironolactone and eplerenone, are potassium-sparing diuretics that block aldosterone’s effects. They are especially beneficial in reducing mortality in HF with reduced ejection fraction (HFrEF).

• Mechanism of Action: MRAs block the binding of aldosterone to its receptors, reducing sodium and water retention, which helps lower blood pressure and prevent cardiac remodeling.
• Common Drugs and Dosing:
  • Spironolactone: Initial dose of 12.5-25 mg daily, titrated up to 50 mg daily.
  • Eplerenone: Initial dose of 25 mg daily, titrated up to 50 mg daily.
• Side Effects: Common side effects include hyperkalemia, gynecomastia (with spironolactone), and renal impairment. Regular monitoring of potassium and renal function is essential.
• Evidence: The RALES and EMPHASIS-HF trials demonstrated that MRAs significantly reduce mortality and hospitalizations in patients with HFrEF.

5. Loop Diuretics

Loop diuretics are used in HF to reduce fluid overload, relieving symptoms of pulmonary congestion and edema. These are often used for symptom control but do not directly improve survival.

• Mechanism of Action: Loop diuretics, such as furosemide, act on the loop of Henle in the kidneys, inhibiting sodium, potassium, and chloride reabsorption, leading to increased diuresis.
• Common Drugs and Dosing:
  • Furosemide: Typical starting dose of 20-40 mg daily, adjusted based on response.
  • Bumetanide: Starting dose of 0.5-1 mg daily, with titration based on fluid status.
• Side Effects: Common side effects include electrolyte imbalances (hypokalemia, hyponatremia), dehydration, hypotension, and, in rare cases, ototoxicity.
• Evidence: While loop diuretics do not improve survival, they are crucial for symptom management and can improve quality of life for HF patients with fluid overload.

6. Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

ARNIs, specifically sacubitril/valsartan, are a newer class of drugs that combine an angiotensin receptor blocker with a neprilysin inhibitor. They are effective in reducing mortality and hospitalization rates in HFrEF.

• Mechanism of Action: The neprilysin inhibitor (sacubitril) prevents the breakdown of natriuretic peptides, promoting vasodilation, natriuresis, and diuresis. Valsartan blocks the angiotensin II receptor, complementing sacubitril’s effects.
• Common Drug and Dosing:
  • Sacubitril/Valsartan (Entresto): Initial dose of 49/51 mg twice daily, titrated up to 97/103 mg twice daily based on tolerance.
• Side Effects: Hypotension, hyperkalemia, renal dysfunction, and angioedema. Patients should avoid ACE inhibitors when on an ARNI to prevent angioedema risk.
• Evidence: The PARADIGM-HF trial showed that ARNIs significantly reduce mortality and HF hospitalizations compared to ACE inhibitors.

7. SGLT2 Inhibitors

SGLT2 inhibitors, originally developed for diabetes, have shown substantial benefits in HF, especially HFrEF, by promoting diuresis and improving cardiovascular outcomes.

• Mechanism of Action: SGLT2 inhibitors promote glucose and sodium excretion in the kidneys, leading to osmotic diuresis. They reduce preload and afterload and have beneficial effects on cardiac metabolism.
• Common Drugs and Dosing:
  • Empagliflozin: 10 mg once daily.
  • Dapagliflozin: 10 mg once daily.
• Side Effects: Genitourinary infections, dehydration, and, rarely, diabetic ketoacidosis (in patients with diabetes).
• Evidence: Trials like DAPA-HF and EMPEROR-Reduced have shown that SGLT2 inhibitors reduce HF hospitalizations and improve survival, even in non-diabetic patients with HFrEF.

8. Ivabradine

Ivabradine is used as an add-on therapy in patients with HFrEF who have a heart rate above 70 bpm despite beta-blocker therapy.

• Mechanism of Action: Ivabradine selectively inhibits the funny current (If) in the sinoatrial node, reducing heart rate without affecting blood pressure.
• Common Drug and Dosing: Initial dose of 5 mg twice daily, titrated up to 7.5 mg twice daily based on heart rate and tolerance.
• Side Effects: Bradycardia, visual disturbances, and headache.
• Evidence: The SHIFT trial demonstrated that ivabradine reduces HF hospitalizations in patients with chronic HFrEF and elevated heart rates.

Conclusion

The pharmacological management of heart failure includes a combination of drugs that target different aspects of the disease. These medications not only provide symptomatic relief but also improve survival, reduce hospitalizations, and slow disease progression. Treatment regimens should be individualized, taking into account the patient's tolerance, renal function, and comorbidities. Evidence from large clinical trials supports the efficacy of these medications in improving outcomes for HF patients, making them integral components of HF management. Regular monitoring and dose adjustments are essential to minimize side effects and optimize therapeutic benefits.