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Heart Failure with Reduced Ejection Fraction (HFrEF), also known as systolic heart failure, is a specific type of heart failure characterized by a reduced ejection fraction. Ejection fraction (EF) is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction. In HFrEF, the EF is typically less than 40%, indicating a reduced ability of the heart to pump blood effectively.


  1. Reduced Ejection Fraction: In HFrEF, the heart's left ventricle becomes weakened and cannot contract effectively, leading to a reduced ejection fraction.

  2. Cardiac Remodeling: Chronic pressure or volume overload leads to changes in the size, shape, and function of the heart, particularly the left ventricle.

  3. Neurohormonal Activation: There is an activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system, which initially helps maintain cardiac output but eventually worsens heart failure.

  4. Reduced Cardiac Output: As the heart's pumping ability decreases, cardiac output falls, leading to inadequate perfusion of tissues.

Clinical Presentation

  • Dyspnea: Shortness of breath, especially during exertion or while lying down (orthopnea).

  • Fatigue: Feeling tired easily due to decreased cardiac output.

  • Edema: Fluid retention, leading to swelling in legs, ankles, and abdomen.

  • Reduced Exercise Tolerance: Inability to engage in physical activities without symptoms.

  • Cough: Often worse at night.



  • Primary Purpose: Measures ejection fraction (EF) to assess the pumping efficiency of the heart. An EF less than 40% typically indicates HFrEF.

  • Additional Findings: Can show left ventricular dilation, wall motion abnormalities, valvular heart diseases, and signs of increased filling pressures.

  • Types:

  • Transthoracic Echocardiography (TTE): Most common, non-invasive, provides a detailed view of heart structure and function.

  • Transesophageal Echocardiography (TEE): Used when TTE is inconclusive; offers a closer and clearer view of the heart, especially the posterior structures.

Clinical Assessment

  • History Taking: Focuses on symptoms like dyspnea, fatigue, orthopnea, and edema. Past medical history for risk factors like hypertension, coronary artery disease, diabetes, and previous cardiac events.

  • Physical Examination: Includes assessing jugular venous pressure, auscultation for heart sounds (S3 gallop, murmurs), lung examination for crackles (indicative of pulmonary edema), and checking for peripheral edema.

Laboratory Tests

  • BNP or NT-proBNP: Elevated levels are indicative of heart failure. These biomarkers are proportional to the severity of heart failure.

  • Complete Blood Count (CBC): Checks for anemia or signs of infection.

  • Metabolic Panel: Assesses kidney function (creatinine, BUN), electrolyte imbalances, and blood glucose levels.

  • Liver Function Tests (LFTs): Elevated levels can indicate congestion of the liver due to heart failure.

  • Thyroid Function Tests: Hypothyroidism or hyperthyroidism can contribute to or exacerbate heart failure.

Other Imaging

  • Chest X-ray: Helps identify cardiac silhouette size (cardiomegaly), signs of fluid overload (pulmonary edema), and other lung pathologies.

  • Cardiac MRI: Provides detailed images of the heart’s structure and function. Useful in assessing myocardial scarring, mass, or viability.

  • CT Scan: Less commonly used but can help in the diagnosis of concomitant thoracic diseases and in the assessment of coronary artery calcification.

Additional Diagnostic Considerations

  • Electrocardiogram (ECG): Identifies arrhythmias, ischemic changes, or signs of previous myocardial infarction.

  • Stress Testing: May be used to assess cardiac function during exercise and to identify underlying ischemic heart disease.

  • Cardiac Catheterization: Invasive procedure, primarily used if ischemic heart disease is suspected as the underlying cause of HFrEF.

Differential Diagnosis

  • It's crucial to differentiate HFrEF from other forms of heart failure like Heart Failure with Preserved Ejection Fraction (HFpEF) and from conditions with similar presentations such as chronic obstructive pulmonary disease (COPD) or pulmonary hypertension.

In the context of diagnosing HFrEF, it’s essential to use a multifaceted approach incorporating both diagnostic imaging and clinical assessment, supported by laboratory data. This comprehensive evaluation helps not only in confirming the diagnosis of HFrEF but also in assessing its severity, identifying potential underlying causes, and guiding appropriate management.

"เราใช้ยาอะไรบ้างน้องเอายา neurohormonal blockade"

ARNI (Angiotensin Receptor-Neprilysin Inhibitors)

  • Drug Name: Sacubitril/Valsartan (Entresto)

  • Usage: It combines neprilysin inhibitor (sacubitril) with an ARB (valsartan). It's used to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction.

  • Mechanism: Sacubitril inhibits neprilysin, an enzyme that degrades natriuretic peptides, thereby enhancing their beneficial effects on vasodilation, natriuresis, and diuresis. Valsartan blocks the angiotensin II type-1 receptor, counteracting the vasoconstrictive and sodium-retentive effects of angiotensin II. Together, they reduce blood pressure, decrease fluid overload, and improve cardiac function, which can be particularly beneficial in HFrEF.

ACE Inhibitors

  • Drug Names: Lisinopril, Enalapril, Ramipril

  • Usage: These drugs help to relax blood vessels and reduce blood volume, which makes it easier for the heart to pump and improves heart function over time.

  • Mechanism: ACE inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to vasodilation, reduced blood pressure, decreased afterload, and preload, which helps to alleviate the heart's workload and improve cardiac output in HFrEF patients.

  • Nakorn - Core Physiology and medical science

Angiotensin II Receptor Blockers (ARBs)

  • Drug Names: Losartan, Valsartan, Candesartan

  • Usage: ARBs block the action of angiotensin II, which is a substance in the body that narrows blood vessels and releases hormones that can raise blood pressure.

  • Mechanism: ARBs selectively block the binding of angiotensin II to the AT1 receptor, preventing its harmful cardiovascular effects, which include vasoconstriction, sodium retention, and sympathetic activation. This results in decreased blood pressure and reduced strain on the heart, providing clinical benefits to patients with HFrEF.

  • Nakorn - Core Physiology and medical science


  • Drug Names:

  • Carvedilol

  • Bisoprolol

  • Metoprolol Succinate (specifically the extended-release form, marketed as Toprol-XL)

  • Usage: These medications decrease the heart rate and the force of contraction, thus reducing the heart's demand for oxygen. They are particularly useful in patients with HFrEF, as they have been shown to reduce mortality and hospitalization rates.

  • Mechanism: Beta-blockers block the effects of epinephrine (adrenaline) and norepinephrine (noradrenaline) on the beta-adrenergic receptors of the heart, leading to a decrease in heart rate and contractility. This reduction in myocardial oxygen demand and improvement in diastolic filling can be lifesaving in HFrEF, as it slows the progression of heart failure and reduces mortality.

Aldosterone Antagonists aka. Mineralocorticoid Receptor Antagonists (MRAs)

  • Drug Names: Spironolactone, Eplerenone

  • Usage: These drugs help the body eliminate excess sodium while retaining potassium, reducing fluid buildup and the workload on the heart.

  • Mechanism: MRAs block the effects of aldosterone, a hormone that causes sodium and water retention, leading to edema and hypertension. By antagonizing aldosterone, MRAs promote the excretion of sodium and water, which decreases blood volume, reduces myocardial fibrosis, and prevents cardiac remodeling, thereby benefiting patients with HFrEF.

SGLT2 Inhibitors (Sodium-Glucose Cotransporter 2 Inhibitors)

  • Drug Names: Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Canagliflozin (Invokana)

  • Usage: These medications work by blocking the reabsorption of glucose in the kidneys, leading to glucose excretion through urine. Though originally developed for the treatment of type 2 diabetes, SGLT2 inhibitors have been found to benefit patients with HFrEF significantly. They help reduce heart failure hospitalizations and can improve cardiovascular outcomes.

  • Mechanism: Besides promoting glucose excretion, they also induce diuresis and natriuresis, which contribute to reducing preload and afterload on the heart. Moreover, they are believed to improve cardiac metabolism and function, although the exact cardiovascular protective mechanisms are still being studied.

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