Reference [1,4]
EF value Heart failure type
≥ 50% HFpEF
41 - 49% Mid-range heart failure
≤ 40% HFrEF

Reference [1]
NYHA class Symptoms
I No limitation of physical activity. Ordinary physical activity does not result in symptoms.
II Slight limitation of physical activity. Comfortable at rest, but ordinary activity results in fatigue, palpitations, or shortness of breath.
III Marked limitation of activity. Comfortable at rest, but less than ordinary activity results in fatigue, palpitations, or shortness of breath.
IV Symptoms at rest. Unable to carry on any physical activity without discomfort. Any physical activity results in discomfort.

Reference [1]
Stage Findings
A At high risk for HF but without structural heart disease or symptoms of HF
B Structural heart disease but without signs or symptoms of HF
C Structural heart disease with prior or current symptoms of HF
D Refractory HF requiring specialized interventions

  • Reference [7]
Chest X-ray findings in heart failure
Finding Sensitivity Specificity
Cardiomegaly 63.6% 70.5%
Overall radiographic interpretation of HF 53.3% 86.3%
Interstitial edema 29% 92.6%
Kerley B lines 23.4% 95.8%
Bilateral pleural effusion 19.6% 94.7%
Peribronchial cuffing 16.8% 95.8%
Alveolar edema 12.1% 98.9%

  • Reference [4,12]
BNP / NT-proBNP Levels in Heart Failure
Condition BNP level NT-proBNP level
Rule in acute heart failure > 100 pg/ml
  • < 50 years: > 450 pg/ml
  • 50 - 75 years: > 900 pg/ml
  • > 75 years: > 1800 pg/ml
Rule out acute heart failure < 100 pg/ml < 300 pg/ml
Rule out chronic heart failure < 35 pg/ml < 125 pg/ml

  • Reference [1,11]
Factors that may affect BNP and NT-proBNP values
Factor Comment
  • Levels increase naturally with age
Female sex
  • Women have higher levels on average
Kidney disease
  • BNP and NT-proBNP may be elevated in patients with kidney disease
  • Levels begin to rise when CrCl falls to < 60 ml/min
  • NT-proBNP levels may be more sensitive to kidney disease than BNP levels
Heart conditions
  • Heart conditions other than heart failure may cause levels to rise. Examples include acute coronary syndrome, pericardial disease, atrial fibrillation, myocarditis, cardiac surgery, and cardioversion.
Pulmonary disease
  • Pulmonary diseases including ARDS, severe COPD, pulmonary embolism, and primary pulmonary hypertension can cause levels to rise
  • Patients with obesity tend to have lower levels on average. In one study, a BNP of > 54 pg/ml was 90% sensitive for heart failure in patients with a BMI ≥ 35.
High output states
  • BNP and NT-proBNP levels may be elevated in high output states (e.g. sepsis, cirrhosis, hyperthyroidism)

Reference [1,2]
EF value Interpretation
≥ 50%
  • Normal
  • Patients with HFpEF may have an EF in this range
41 - 49%
  • Decreased, but does not typically cause symptoms
  • Patients with HFpEF may have an EF in this range
  • Patients with HFrEF that has improved may have an EF in this range
≤ 40%
  • Decreased function that may cause symptoms
  • Patients with HFrEF have an EF in this range

  • References [14,15,16]
Echocardiographic measures of diastolic function
Finding Measurements
  • Under normal conditions, the E wave is slightly greater than the A wave
  • E/A ratio: 0.75 - 1.50
  • E/a' ratio: < 8
  • Deceleration time: 140 - 240 msec
  • IVRT: ∼ 70 ms (40 year old)
  • Young, physically fit people sometimes have a vigorous ventricular recoil right after systole. This can cause the E value to increase. Supernormal filling should be considered in physically fit patients without signs of heart failure.
  • E/A ratio: > 2
  • E/a' ratio: < 8
  • Deceleration time: 140 - 240 msec
  • IVRT: ∼ 70 ms (40 year old)
Grade 1 diastolic dysfunction
(Impaired relaxation)
  • In grade 1 diastolic dysfunction, ventricular wall stiffness impairs early filling, and the E value decreases. More blood is present in the atrium during late diastole, and this causes the atria to contract harder, increasing the A wave.
  • Grade I diastolic dysfunction is a common finding on echocardiography. It occurs normally with aging and has a prevalence of 25% in people ≥ 40 years old.
  • E/A ratio: < 0.8
  • E/a' ratio: < 8
  • Deceleration time: ≥ 240 ms
  • IVRT: > 100 ms
Grade 2 diastolic dysfunction
(Pseudonormal filling)
  • In grade 2 diastolic dysfunction, progressive ventricular stiffness starts to cause congestion in the atrium, and the resting atrial pressure rises. The increase in atrial pressure creates a gradient that drives early ventricular filling, and the E wave increases. This causes the E/A ratio to return to the normal range (0.75 - 1.5), hence the name "pseudonormal."
  • To distinguish grade II dysfunction from normal diastolic function, the Valsalva maneuver can be performed during echocardiography. The Valsalva maneuver decreases venous return to the left atrium, and atrial pressure drops. Patients with true diastolic dysfunction will have a drop in their E/A ratio to below 1 with Valsalva. An E/e' ratio of > 14 also indicates true diastolic dysfunction, and a ratio of 8 - 12 is suggestive.
  • E/A ratio: 0.75 - 1.5
  • E/a' ratio: ≥ 8
  • Deceleration time: 140 - 240 msec
  • IVRT: < 90 ms
Grade 3 diastolic dysfunction
(Reversible restrictive)
  • In grade 3 diastolic dysfunction, progressive congestion causes the resting atrial pressure to continue to rise. The E wave increases, and the A wave decreases.
  • Grade 3 diastolic dysfunction is distinguished from grade 4 dysfunction by the fact that it is reversible, which means that the E/A ratio returns to the pseudonormal range if the Valsalva maneuver is performed.
  • E/A ratio: ≥ 2
  • E/a' ratio: ≥ 8
  • Deceleration time: < 140 msec
  • IVRT: ≤ 70 ms
Grade 4 diastolic dysfunction
(Irreversible restrictive)
  • Grade 4 diastolic dysfunction is similar to grade 3 dysfunction except that the Valsalva maneuver does not return the E/A ratio to the pseudonormal range
  • E/A ratio: ≥ 2
  • E/a' ratio: ≥ 8
  • Deceleration time: < 140 msec
  • IVRT: ≤ 70 ms

  • Reference [1,2,3]
AHA/ACC Medical Therapy Recommendations for HFrEF
All patients with AHA stage C HFrEF

  • RAAS inhibitor therapy (one of the following):

  • Beta blocker

  • Diuretics as needed
    • Start with a loop diuretic and titrate dose over days to weeks to relieve fluid overload. Monitor blood pressure, electrolytes, and renal function.
    • If reaching a high dose of loop diuretic (e.g. 80 mg furosemide twice daily), consider one of the following:

For patients who are still symptomatic (NYHA II - IV), consider adding one or more of the following in a stepwise manner:
Aldosterone antagonist therapy (spironolactone, eplerenone)
  • Consider adding an aldosterone antagonist in patients who meet all of the following criteria:
    • NYHA class II - IV heart failure with an EF ≤ 35%
    • Patients with NYHA class II should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels
    • Serum creatinine levels should be ≤ 2.5 mg/dl in men, and ≤ 2.0 mg/dl in women (alternatively, GFR should be > 30 ml/min)
    • Potassium levels should be < 5.0 mEq/L

  • Monitoring
    • Monitor electrolytes (especially potassium), and kidney function 2 - 3 days following initiation, and at 7 days after initiation or drug titration. After that, check monthly for 3 months and then every 3 months from then on.
    • See aldosterone antagonist review and aldosterone antagonist dosing for more

  • AHA recommended dosing
    • Spironolactone
      • Starting: 12.5 - 25 mg once daily
      • Maintenance: 25 mg once daily OR 25 mg twice a day
      • Average dose achieved in trials: 26 mg once daily
      • Increase dose at intervals of 2 weeks as tolerated
    • Eplerenone
      • Starting: 25 mg once daily
      • Maintenance: 50 mg once daily
      • Average dose achieved in trials: 42.6 mg once daily
      • Increase dose at intervals of 2 weeks as tolerated
SGLT2 inhibitor therapy (dapagliflozin, empagliflozin)
  • Consider dapagliflozin or empagliflozin in patients who meet all of the following criteria:
    • NYHA class II, III, or IV heart failure with EF < 40%
    • CrCl ≥ 25 ml/min for dapagliflozin and ≥ 30 ml/min for empagliflozin

  • See SGLT2 inhibitor review and SGLT2 inhibitor dosing for more
Hydralazine + Isosorbide dinitrate
  • Consider hydralazine + isosorbide dinitrate in patients who meet one of the following criteria:
    • Symptomatic (NYHA III - IV) Black patients despite therapy with sacubitril-valsartan, beta blocker, aldosterone antagonist, and/or SGLT2 inhibitor (strong recommendation)
    • Symptomatic (NYHA III - IV) patients of any race who cannot tolerate an ACE inhibitor or ARB (moderate recommendation)

  • See vasodilators review and vasodilator dosing for more
Ivabradine (Cordalor®)
  • Consider ivabradine in patients who meet all of the following criteria:
    • Normal sinus rhythm with a resting heart rate ≥ 70 bpm on maximally tolerated beta blocker
    • NYHA class II - III heart failure with EF ≤ 35%

  • See ivabradine review and ivabradine dosing for more
Vericiguat (Verquvo®)
  • Vericiguat was FDA-approved in 2021 and is not included in any guidelines yet
  • Vericiguat was approved based on the results of the VICTORIA study. Main inclusion criteria were NYHA class II - IV heart failure and an EF < 45%.
  • See vericiguat review and vericiguat dosing for more