Cardiovascular Medicine Book


Systolic Dysfunction

Aka: Systolic Dysfunction, Left Ventricular Dysfunction, Left Ventricular Failure, Systolic Heart Failure, Left Ventricular Systolic Dysfunction, Heart Failure with Reduced Ejection Fraction, HFrEF, Heart Failure with Mildly Reduced Ejection Fraction, HRmrEF, Heart Failure with Improved Ejection Fraction, HRimpEF
  1. See Also
    1. Heart Failure
    2. Heart Failure Causes
    3. Medications that Exacerbate Heart Failure
    4. Diastolic Dysfunction
    5. Cardiomyopathy
    6. Framingham Heart Failure Diagnostic Criteria
    7. Congestive Heart Failure Exacerbation Management
    8. Congestive Heart Failure Exacerbation Decision Rule
    9. Ottawa Heart Failure Risk Score
  2. Definitions
    1. Heart Failure with Preserved Ejection Fraction (HFpEF)
      1. Heart Failure with Diastolic Dysfunction and ejection fraction >50%
    2. Heart Failure with Reduced Ejection Fraction ( HFrEF)
      1. Heart Failure with Systolic Dysfunction and ejection fraction <40%
    3. Heart Failure with Mildly Reduced Ejection Fraction (HRmrEF)
      1. Heart Failure with Systolic Dysfunction and ejection fraction 40 to 49%
    4. Heart Failure with Improved Ejection Fraction (HRimpEF)
      1. Heart Failure with Systolic Dysfunction and prior ejection fraction <40%, but now improved
  3. Causes
    1. See Heart Failure Causes
    2. Coronary Artery Disease is most common cause
  4. Types: High or Low Output
    1. Low output Heart Failure
      1. Classic Systolic Dysfunction with decreased Cardiac Output
      2. Example causes
        1. Coronary Artery Disease
        2. Severe Hypertension
        3. Cardiomyopathy
        4. Heart Valve Disorders
    2. High output Heart Failure
      1. Normal Cardiac Output, but demands of hypermetabolic state outpaces supply
      2. Example causes
        1. Thyrotoxicosis
        2. Severe Anemia
        3. Thiamine deficiency
        4. Valvular regurgitation
  5. Types: Left or Right Sided
    1. Left-Sided Heart Failure
      1. Presents with Pulmonary Edema
      2. Causes (either Systolic Dysfunction or Diastolic Dysfunction)
        1. See Heart Failure Causes
    2. Right-Sided Heart Failure
      1. Presents with systemic edema (JVD, Leg Edema, Hepatomegaly)
      2. Causes
        1. Left sided Heart Failure (most common cause)
        2. Chronic lung disease (e.g. COPD)
        3. Coronary Artery Disease
        4. Right-sided Valvular disease (pulmonic stenosis, Tricuspid stenosis, tricuspid insufficiency)
        5. Pericardial Effusion
        6. Left-to-right shunt
  6. Pathophysiology: Mechanism (with associated symptoms)
    1. Left Ventricular Systolic Dysfunction
      1. Results in decreased contractility and Cardiac Output
      2. Compensatory increase in Catecholamines to drive up cardiac ouput
      3. Catecholamines (e.g. Norepinephrine) increase Afterload (and increased Blood Pressure)
        1. Ultimately results in down-regulation of B-Adrenergic Receptors and decreased contractility
      4. Increased Afterload decreases renal perfusion
      5. Decreased renal perfusion stimulates ADH, Aldosterone and the renin-Angiotensin system
        1. Increases Preload and Afterload
        2. Increases Angiotensin II causing Myocyte and endothelial proliferation
        3. Results in adverse ventricular remodeling
      6. Results in Sodium retention and Fluid Overload
        1. Acute: Increased myocardial wall tension causes Diastolic Dysfunction and increased oxygen demand
        2. Chronic: Ventricular dilation and decreased ejection fraction
    2. Decreased filling pressure (congestion)
      1. Increased left sided pressure: Dyspnea, Orthopnea, paroxysmal nocturnal Dyspnea (PND)
      2. Increased right sided pressure: Edema, Ascites, Jugular Venous Distention (JVD)
    3. Decreased Cardiac Output
      1. Fatigue
      2. Depression
  7. History: Past Medical
    1. See Heart Failure Causes
    2. Primary heart or vascular conditions
      1. Prior Myocardial Infarction
      2. Hypertension
      3. Valvular heart disease
      4. Atrial Fibrillation
    3. Primary pulmonary conditions
      1. Cor Pulmonale
      2. Pulmonary Embolism
      3. Sleep Apnea
    4. Primary renal conditions
      1. Renal Failure
      2. Nephrotic Syndrome
      3. Glomerulonephritis
    5. Cardiotoxins
      1. Alcohol Abuse
      2. Doxorubicin
      3. Catecholamines
      4. Cobalt
      5. Cocaine Abuse
    6. Medications that cause fluid retention
      1. Chemotherapy
      2. COX2 Inhibitors
      3. Sex Hormones (Androgens, Estrogens)
      4. Glitazones (e.g. actos)
    7. Other provocative factors
      1. Anemia
      2. Fluid Overload (Excessive Salt Intake)
      3. Septic Shock
      4. Medications
        1. Beta Blocker
        2. Calcium Channel Blocker
      5. Thyroid disease (Hypothyroidism or Hyperthyroidism)
      6. Hepatic disease
  8. Symptoms
    1. Early symptoms
      1. Decreased Exercise tolerance
      2. Dyspnea on Exertion
        1. Test Sensitivity: 100%
        2. Test Specificity: 17%
          1. See Dyspnea Causes
    2. Non-specific symptoms
      1. Unexplained confusion or lethargy (often in elderly)
      2. Weight gain
      3. Fatigue
        1. Most common presenting symptom of CHF in the elderly
    3. Left-sided Heart Failure symptoms (left = lung)
      1. Orthopnea
      2. Paroxysmal Nocturnal Dyspnea
        1. Not sensitive or specific for CHF
    4. Right-sided Heart Failure symptoms
      1. RUQ Abdominal Pain or fullness, early satiety
        1. Hepatic engorgement
        2. Ascites
      2. Lower Extremity Edema (often Dependent Edema)
        1. Venous Insufficiency
        2. Lymphedema
  9. Signs: Left sided Heart Failure
    1. Laterally displaced apical impulse (highly specific)
    2. S3 Gallop Rhythm
      1. Most specific CHF indicator over age 40
        1. Test Sensitivity: 24%
        2. Test Specificity: 99%
      2. CHF patients (n=19) with Ejection Fraction <30%
        1. S3 Gallop present in 68% of these patients
      3. Reference
        1. Mattleman (1983) J Am Coll Cardiol 1(2):417-20 [PubMed]
    3. Rales (nonspecific)
      1. Do not clear with cough
      2. Not sensitive or specific for CHF
    4. Pulsus Alternans
      1. Tachycardia accompanied by low volume pulse
  10. Signs: Right-sided Heart Failure
    1. Elevated Jugular Venous Distention (highly specific)
      1. Consider hepatojugular reflex
    2. Pulsatile Liver
    3. Lower Extremity Edema
      1. Not attributable to Dependent Edema
      2. Not sensitive or specific for CHF
    4. Poor perfusion
      1. Poor Capillary Refill
      2. Cool distal extremities
      3. Altered Mental Status
  11. Labs: Initial
    1. Complete Blood Count (CBC)
      1. Evaluate for Anemia
    2. Comprehensive Metabolic Panel or Chemistry panel
      1. Electrolytes
      2. Serum Calcium
      3. Renal Function tests
      4. Liver Function Tests
      5. Serum Magnesium
    3. Urinalysis
    4. B-Type Natriuretic Peptide (BNP) or NT-BNP
      1. Sensitive and specific marker for CHF
      2. Useful for its Negative Predictive Value (CHF is unlikely with a normal BNP)
    5. Serum Albumin
      1. Nephrotic Syndrome
    6. Thyroid Stimulating Hormone (TSH)
      1. Over age 65
      2. Atrial Fibrillation
    7. Troponin I
      1. Acute CHF presentation
  12. Labs: Additional tests to consider (Cardiomyopathy Causes)
    1. Urine Toxicologic screen
      1. If Cocaine Abuse suspected
    2. Lyme Serology
    3. Parvovirus B19Serology
    4. Blood Cultures
      1. If endocarditis or Sepsis suspected
    5. Human Immunodeficiency Virus
  13. Imaging: Chest XRay
    1. See Chest XRay in Congestive Heart Failure
  14. Diagnostics: Electrocardiogram (EKG)
    1. Findings suggestive of CHF
      1. Anterior Q Waves
      2. Left Bundle Branch Block
      3. Efficacy
        1. Test Sensitivity: 94%
        2. Test Specificity: 61%
    2. Other findings
      1. Ventricular hypertrophy
      2. Atrial enlargement
      3. Conduction abnormality
      4. Arrhythmia
      5. Prior Myocardial Infarction
      6. Active ischemia Myocardial Ischemia
  15. Diagnostics: Advanced
    1. See Bedside Lung Ultrasound in Emergency (Blue Protocol)
    2. See Rapid Ultrasound in Shock (RUSH Exam)
    3. See Inferior Vena Cava Ultrasound for Volume Status
    4. Echocardiogram
      1. See Echocardiogram in CHF
      2. Indicated in every Congestive Heart Failure patient
      3. Ejection Fraction 40% or less
      4. Other factors evaluated
        1. Chamber size and shape
        2. Wall thickness
        3. Valvular function
    5. Evaluation for Ischemic Heart Disease
      1. Precautions
        1. Suspected Angina and Left Ventricular Dysfunction warrants angiography
          1. High pretest probability of Ischemic Heart Disease
      2. Modalities
        1. Exercise Stress Testing
        2. Nuclear (Thallium or Cardiolyte-Technetium)
      3. Observe for reversible ischemic changes
        1. Consider cardiac catheterization and possible Angioplasty (PTCA)
        2. Consider Coronary Artery Bypass Graft (CABG)
    6. Ambulatory rhythm monitor (Holter Monitor)
      1. Observe for ventricular Arrhythmia
      2. Consider patient for Implantable Defibrillator
  16. Diagnosis
    1. Sensitive CHF markers (if absent, CHF is unlikely)
      1. Framingham Heart Failure Diagnostic Criteria
      2. Dyspnea on exertion
      3. EKG with anterior Q Waves or Left Bundle Branch Block
      4. B-Type Natriuretic Peptide elevation
        1. Best for its Negative Predictive Value
        2. BNP is more reliable than nt-BNP
        3. BNP <95 pg/ml
        4. nT-BNP <642 pg/ml
    2. Specific CHF markers (if present, suggest CHF)
      1. Displaced Cardiac Apex on palpation
      2. S3 Gallup Rhythm
      3. Jugular Venous Distention
        1. With or without hepatojugular reflex
      4. Chest XRay with cardiomegaly or vascular congestion
    3. References
      1. Dosh (2004) Am Fam Physician 70:2145-52 [PubMed]
        1. Also cited for efficacy under signs and symptoms
  17. Management: General Measures
    1. See Congestive Heart Failure Exacerbation Management
    2. Limit salt intake: 2-3 gram Sodium Diet (no added salt)
      1. Also limit free water ONLY IF Hyponatremia is also present
    3. Graded Exercise program
      1. Reduces Heart Failure related mortality
      2. Piepoli (2004) BMJ 328:189-92 [PubMed]
    4. Disease Management
      1. Consider initiating after CHF hospital discharge
      2. Case management and disease monitoring programs
      3. Body weight and symptom monitoring
      4. Heart Failure education (self-care, lifestyle measures, Medication Compliance)
    5. Control comorbid conditions
      1. Hypertension
      2. Coronary Artery Disease
      3. Diabetes Mellitus
      4. Obstructive Sleep Apnea
      5. Major Depression
    6. Avoid Provocative Medications
      1. Avoid ARB combined with ACE Inhibitor and Beta Blocker (choose a Beta Blocker with either ACE or ARB)
        1. Valsartan plus ACE Inhibitor showed no benefit
        2. Valsartan + ACE + Beta Blocker increased mortality
        3. Cohn (2001) N Engl J Med 345:1667-75 [PubMed]
      2. Avoid Medications that Exacerbate Heart Failure
        1. See Medications that Exacerbate Heart Failure
        2. Avoid Calcium Channel Blockers (except Amlodipine)
        3. Avoid Beta agonists (if possible, although COPD and Asthma requires these)
        4. Avoid Glitazones (e.g. Pioglitazone)
        5. Avoid Gliptins (e.g. Onglyza)
        6. Avoid Tricyclic Antidepressants (e.g. Amitriptyline)
        7. Avoid Nonsteroidal Anti-inflammatory drugs (NSAIDS)
        8. Avoid high Sodium medications (e.g. effervescent tabs)
        9. Avoid St John's Wort if on Digoxin or Eplerenone (Drug Interactions)
    7. Stop habits associated with hospital readmission
      1. Tobacco Cessation
      2. Alcohol cessation
    8. Establish target ideal volume status weight (not dry weight)
      1. Assess for too dry (Orthostatic Hypotension)
        1. Monitor standing Blood Pressure in clinic
        2. Evaluate Renal Function tests for Azotemia
      2. Assess for too wet
        1. No Orthopnea
        2. No paroxysmal nocturnal Dyspnea
      3. Assess for maintenance of ideal volume status weight
        1. Follow daily weight at home with weight diary
        2. Report weekly weight gain 3-5 lb (1.5 - 2.0 kg)
        3. Patient may adjust their lasix at home (see below)
    9. Sliding scale Diuretics (uses daily weights)
      1. Based on weight variation from maintenance weight
      2. Protocol 1
        1. Criteria: Weight gain of 2 pounds in one day or 5 pounds overall
        2. Increase Diuretics (and Potassium supplement) for 3 days
      3. Protocol 2
        1. Weight gain 1-3 pounds: No change to Diuretic dose
        2. Weight gain 3-5 pounds: Take extra Diuretic dose
        3. Weight gain >5 pounds: Call clinic nurse immediately
    10. Manage Electrolyte abnormalities (medication-induced)
      1. Electrolyte abnormalities are common in CHF Management
        1. Monitor Serum Potassium weekly when titrating Loop Diuretics (every 3-4 months when stable)
        2. Monitor Serum Magnesium as needed (esp. when Hypokalemia is present)
      2. Potassium abnormalities compound the increased Arrhythmia risk of CHF patients
        1. Maintain Serum Potassium ideally between 4.0 and 5.0 mg/dl
      3. Hypokalemia Management
        1. See Prevention of Diuretic-Induced Hypokalemia
        2. See Hypokalemia
        3. See Potassium Replacement
      4. Hyperkalemia Management
        1. See Hyperkalemia Prevention
  18. Management: Medications - Overall protocol (starting dosing listed)
    1. See Acute Pulmonary Edema Management
    2. See Refractory management below
    3. Step 0: Ensure Compliance at each visit
      1. Confirm compliance with lifestyle modifications (see general measures above)
      2. Confirm medication is actually being taken before advancing doses or adding new medications
    4. Step 1: ACE Inhibitor or Angiotensin Receptor Blocker (NYHA Class 1+ or ACC/AHA Class B+)
      1. Lisinopril 2.5 to 5 mg PO daily (and titrate to 20-40 mg daily) OR
      2. Losartan 12.5 to 25 mg orally daily (and titrate to 50-100 mg daily) OR
      3. Entresto (Valsartan and Sacubitril)
    5. Step 2: Beta Blockers (NYHA Class 1+ or ACC/AHA Class B+)
      1. Carvedilol (Coreg) 3.125 mg orally twice dauly (Slowly titrate to 12.5 - 25 mg orally twice daily over 2 weeks) OR
      2. Metoprolol XL 12.5 mg orally daily (and slowly titrate every 2-4 weeks to 100-200 mg daily)
    6. Step 3: Loop Diuretic (if pulmonary congestion, NYHA Class 2+ or ACC/AHA Class C+)
      1. Furosemide (Lasix) 40 mg orally once daily
    7. Step 4: Add adjunct (NYHA Class 2+ or ACC/AHA Class C+)
      1. Aldosterone Antagonist: Spironolactone 12.5 mg daily OR
      2. Hydralazine 37.5 mg with Isordil 20 mg three times daily (especially effective in black patients)
    8. Step: 5: Consider additional agents (NYHA Class 3+ or ACC/AHA Class C+)
      1. SGLT2 Inhibitor (e.g. Farxiga)
      2. Ivabradine (Corlanor) 5 mg orally twice daily
      3. Guanylate cyclase stimulator (e.g. Verquvo or Vericiguat)
    9. Step 6: Consider additional agents (NYHA Class 2+ or ACC/AHA Class C+)
      1. Thiazide Diuretic (Hydrochlorothiazide 25 mg daily or Metolazone 2.5 mg daily)
      2. Digoxin 0.125 mg orally daily
  19. Management: Medications - Primary Medical Management (Class I, II, III)
    1. ACE Inhibitor (most important agent in CHF)
      1. See ACE Inhibitor in CHF for management protocol
      2. See ACE Inhibitor in CHF for alternative agents
        1. Angiotensin Receptor Blocker is alternative if ACE Inhibitor cannot be used
        2. Do not combine ACE Inhibitors with Angiotensin Receptor Blocker
      3. Consider adding Spironolactone early (see below)
        1. Blocks Aldosterone escape from ACE Inhibitor
    2. Beta Blocker
      1. Protocol
        1. Avoid in decompensated CHF (start when stable)
        2. Start with low doses
        3. Titrate doses slowly (double dose every 2-4 weeks)
        4. Evaluate worse Dyspnea, failure or Hypotension
          1. Decrease or discontinue Beta-Blocker dose
          2. Consider increasing Diuretic dose
        5. Expect initial drop in ejection fraction
          1. Patients will feel more Fatigued in first month
          2. Beta Blocker benefits realized by 3 months
      2. Agents
        1. Metoprolol (Toprol XL)
          1. Start at 12.5 to 25 mg daily (max: 200 mg/day)
        2. Bisoprolol (Zebeta)
          1. Start: 1.25 mg (25% of 5 mg tablet) daily (maximum: 10 mg/day)
        3. Carvedilol (Coreg)
          1. Start at 3.125 mg orally twice daily
          2. Slowly titrate to 12.5 - 25 mg orally twice daily over 2 weeks
          3. Superior to Metoprolol in increasing Ejection Fraction
            1. Raiput (2003) Am J Cardiol 92:218-21 [PubMed]
      3. Outcomes
        1. Safe and well tolerated even in Class IV CHF
        2. Reduces mortality and hospitalization rates
        3. Improved CHF related symptoms
        4. Goldstein (2001) J Am Coll Cardiol 38:932-8 [PubMed]
  20. Management: Medications - Relief of Congestive Heart Failure symptoms
    1. Diuretics (reduce volume overload)
      1. First Line: Loop Diuretics
        1. Use as adjunct to other drugs above for pulmonary congestion
        2. Diuretics are for symptom control and not the primary CHF treatment
        3. Start Furosemide (Lasix) 20-40 mg orally daily in AM (increase to 40 to 160 mg per dose, twice daily)
          1. Double the dose until Urine Output increases (exceeds threshold)
          2. Higher doses are needed in those with impaired Renal Function (up to 600 mg/day in renal disease)
        4. Consider changing to more potent Loop Diuretics in CHF pulmonary congestion refractory cases
          1. No evidence that other Loop Diuretics are more effective, and cost much more
          2. However, consider switching to these agents if Furosemide at max dosing
          3. Bumetanide (Bumex) 1 mg once daily (up to 10 mg daily)
          4. Ethacrynic Acid (Edecrin) 25 mg once daily (up to 200-400 mg daily)
          5. Torsemide (Demadex) 20 mg once daily (up to 100-200 mg daily)
      2. Second: Spironolactone or Eplerenone (Aldosterone Antagonists)
        1. Indicated for NYHA Class III or IV Heart Failure
          1. Consider 3-14 days after MI, if decreased EF and symptomatic Heart Failure or diabetes
        2. Serum Creatinine must be <2.5 mg/dl (GFR > 30 ml/minute/1.73m2)
        3. Serum Potassium must be normal (below 5.0 to 5.5 meq/L)
        4. Agents
          1. Spironolactone (Aldactone) 12.5 mg orally daily (may increase to 25 mg) OR
          2. Eplerenone (Inspra) 25 mg orally daily (may increase to 50 mg orally daily)
        5. Monitor Serum Potassium at 3 days, 7 days and then monthly for the first 3 months
        6. Bozkurt (2003) Am J Cardiol 41:211-4 [PubMed]
      3. Third: Thiazide Diuretic
        1. Dosing does not need to be timed before the Loop Diuretic
        2. Agents
          1. Hydrochlorothiazide 25 mg orally daily OR
          2. Metolazone 2.5 mg orally daily (preferred for eGFR <30 ml/min)
      4. References
        1. (2020) Presc Lett 27(2): 7
    2. Digoxin (Increased contractility)
      1. Consider as adjunct for symptomatic Heart Failure refractory to current management
      2. Typical dose: 0.125 mg daily (up to 0.25 mg daily)
        1. Decrease to 0.0625 if Drug Interactions or Chronic Renal Insufficiency
      3. Does not decrease mortality, but significantly improves quality of life
      4. Increased mortality if serum Digoxin >1.0 ng/ml
        1. Keep serum Digoxin level 0.5 to 0.8 ng/ml (measure 6-8 hours after dose)
        2. Rathore (2003) JAMA 289:871-8 [PubMed]
      5. May be associated with increased mortality in women
        1. Rathore (2002) N Engl J Med 347:1403-11 [PubMed]
  21. Management: Medications - Adjunctive measures
    1. Coronary revascularization (e.g. PTCA) if ischemia
    2. Atrial Fibrillation treatment if present
    3. Cardiac resynchronization
      1. Indications
        1. Ejection fraction <=35% and
        2. QRS Duration >120 ms and
        3. Symptomatic despite maximal medical therapy
      2. Efficacy
        1. Reduces mortality and hospitalization rate
        2. Pacemaker with Defibrillator was most effective
      3. References
        1. Bristow (2004) N Engl J Med 350:2140-50 [PubMed]
        2. McAlister (2004) Ann Intern Med 141:381-90 [PubMed]
    4. Implantable Defibrillator
      1. Indications
        1. LVEF <35% due to Ischemic Heart Disease
        2. LVEF <35% with NYHA Class II and III
      2. Reduces mortality (Amiodarone does not)
        1. Bardy (2005) N Engl J Med 352:225-37 [PubMed]
    5. Warfarin (Coumadin)
      1. Aspirin is a reasonable alternative
      2. Indicated for Arrhythmia
      3. Indicated for Thromboembolism risk (especially while hospitalized)
      4. Not indicated in standard Cardiomyopathy
      5. No data to support use in low ejection fraction
    6. Eplerenone (Inspra)
      1. Mechanism: Aldosterone blockade
      2. Effective in CHF from acute Myocardial Infarction
      3. See Spironolactone above for containdications (GFR<30, Serum Potassium >5)
      4. Start at 25 mg orally daily and may titrate to 50 mg orally daily
      5. Alternative to Spirinolactone, but more expensive
        1. Did not previously warrant additional cost, but is now generic ($65/month)
        2. Consider if severe Gynecomastia on Spironolactone
      6. References
        1. Pitt (2003) N Engl J Med 348:1309-21 [PubMed]
    7. Hydralazine and Isosorbide Dinitrate
      1. Especially effective in younger black patients
      2. Indicated for NYHA Class III or Class IV Heart Failure
      3. Start
        1. Hydralazine 12.5 mg orally and
        2. Isosorbide Dinitrate or Isosorbide Mononitrate
          1. Dinitrate 5-10 mg tid with 12 hour-free or
          2. Mononitrate 30 mg orally daily
      4. Maintenance
        1. BiDil 37.5/20 one orally three times daily (max two tabs per dose) or
        2. Hydralazine 37.5-75 mg/day and Dinitrate 20-40 mg/day
    8. Ivabradine (Corlanor)
      1. Sinus nodemodulator
      2. Indications
        1. Persistent symptoms in stable patients in sinus rhythm with Heart Rate >70, EF <35
        2. Adjunct following ACE Inhibitor, Beta Blocker, Aldosterone Antagonist
      3. Dose
        1. Start at 5 mg orally twice daily
        2. Increase to 7.5 mg twice daily after 2 weeks if Heart Rate >60/min
        3. Decrease to 2.5 mg twice daily after 2 weeks if Heart Rate <50/min
      4. Adverse effects
        1. Bradycardia (especially if combined with Beta Blockers, Amiodarone, Digoxin)
          1. Monitor carefully while titrating dose and avoid for Heart Rate <70
        2. Atrial Fibrillation (1%)
        3. Visual Field increased brightness (2%)
      5. References
        1. (2015) Presc Lett 22(6): 31
        2. Swedberg (2010) Lancet 376(9744):875-85 +PMID:20801500 [PubMed]
    9. Sacubitril and Valsartan (Entresto)
      1. Sacubitril (neprilysin inhibitor) increases vasodilation and Sodium excretion
      2. Appears effective, but based on only one large trial
      3. Risk of Hypotension (NNH 21) and Angioedema (NNH 200)
      4. Consider as replacement for ACE Inhibitor or Angiotensin Receptor Blocker
      5. Dosing
        1. Valsartan 103 mg salt in Entresto is equivalent to 160 mg salt in Diovan
        2. Start at Sacubitril/Valsartan 49/51 mg twice daily
        3. Titrate to Sacubitril/Valsartan 97/103 mg twice daily
      6. References
        1. (2015) Presc Lett 22(9): 49
        2. McMurray (2014) N Engl J Med 371(11):993-1004 +PMID:25176015 [PubMed]
    10. Soluble Guanylate cyclase stimulator
      1. Verquvo (Vericiguat) is first agent in class (released in 2020)
      2. Vasodilation via nitric oxide path
      3. Vericiguat is marketed as adjunct to triple therapy (ACE/ARB, Beta Blocker, Aldosterone Antagonist)
        1. Reduces hospitalization and cardiovascular death rates (but at NNT 33 for $580/month)
      4. References
        1. (2021) Presc Lett 28(4): 24
    11. SGLT2 Inhibitors
      1. Heart Failure with Reduced Ejection Fraction
        1. Jardiance is associated with a decreased hospitalization and CV death rate when taken over 16 months (NNT 14)
        2. Packer (2020) N Engl J Med 383:1413-24 <p /> [PubMed]
  22. Management: Disproven therapies or serious adverse effects (avoid these)
    1. Avoid Nesiritide (Natrecor)
      1. Recombinant Human Brain Natriuretic Peptide
      2. Results in venous and arterial vasodilation
      3. Dosing
        1. Bolus: 2 mcg/kg IV bolus
        2. Maintenance: 0.01 mcg/kg/min for 24-48 hours
      4. Improved CHF symptoms at the expense of increased mortality
      5. Sackner-Bernstein (2005) JAMA 293:1900-5 [PubMed]
    2. Tolvaptan
      1. Mechanism: Vasopressin Receptor Antagonist
      2. Reduces volume overload and congestion immediately
      3. Appears to have longterm benefit in CHF
        1. Gheorghiade (2004) JAMA 291:1963-71 [PubMed]
      4. However, risk of Liver Failure and FDA limits to 30 days of use
  23. Management: Based on Heart Failure Classification
    1. Asymptomatic (NYHA Class I)
      1. ACE Inhibitor in CHF (or Angiotensin Receptor Blocker)
      2. Beta Blocker
    2. Symptomatic (NYHA Class II and IIIa)
      1. ACE Inhibitor in CHF
      2. Beta Blocker
      3. Loop Diuretic
      4. Consider Digoxin if symptoms persist despite above
    3. Symptomatic with recent rest Dyspnea (NYHA Class IIIb)
      1. ACE Inhibitor in CHF
      2. Beta Blocker
      3. Loop Diuretic
      4. Spironolactone OR Eplerenone OR Isosorbide/Hydralazine
      5. Digoxin
      6. Ivabradine (Corlanor)
    4. Symptomatic with Dyspnea at rest (NYHA Class IV)
      1. ACE Inhibitor in CHF (with caution)
      2. Loop Diuretic
      3. Spironolactone OR Eplerenone OR Isosorbide/Hydralazine
      4. Digoxin
      5. Ivabradine (Corlanor)
  24. Management: Refractory CHF
    1. Indicated for lack of response to above measures
    2. Step 0: Ensure Compliance
      1. Confirm compliance with lifestyle modifications (see general measures above)
      2. Confirm other superimposed comorbidities are being managed consistently
      3. Confirm medication is actually being taken before advancing doses or adding new medications
        1. Up to 50% of patients are non-compliant, with inconsistent use of the medications they are prescribed
    3. Step 1: Maximize key agent doses
      1. Increase doses every 2-4 weeks and consider split daily dosing to prevent Hypotension
      2. Maximize ACE Inhibitor or Angiotensin Receptor Blocker dose
      3. Maximize Beta Blocker dose
    4. Step 2: Loop Diuretic
      1. Double dose (not twice daily) if no response
      2. Double dose if Serum Creatinine remains >2.0
    5. Step 3: Add second Diuretic with caution
      1. Spironolactone (offers Aldosterone blockade)
        1. Dose: 25 mg orally daily
        2. Indicated in Class III or Class IV CHF
        3. Contraindicated if Serum Creatinine >2.5 mg/dl
        4. Alternative: Eplerenone
      2. Thiazide Diuretic
        1. Hydrochlorothiazide 25 mg orally daily
        2. Metolazone (Zaroxolyn)
          1. Dose 5-10 mg twice weekly 1 hour before Furosemide
    6. Step 4: Add Hydralazine with Isosorbide (see dosing above)
    7. Step 5: Loop Diuretic IV
    8. Step 6
      1. See Other agents above
      2. Dobutamine with low dose Dopamine
        1. Intermittent Dobutamine reduces mortality
        2. Nanas (2004) Chest 125:1198-204 [PubMed]
      3. Consider Milrinone
    9. Step 7
      1. Consider for Revascularization if indicated
      2. Bi-Ventricular Pacing (especially in Left Bundle Branch Block)
      3. Left Ventricular Assist Device (LVAD)
      4. Consider for Cardiac Transplantation
      5. Consider Palliative Care
  25. Prognosis
    1. Congestive Heart Failure Exacerbation Decision Rule
    2. Six-Minute Walk Test
      1. Predicts mortality and hospitalization
    3. Survival for Hypertensive Heart Failure
      1. Men: 24% five-year survival
      2. Women: 31% five-year survival
  26. References
    1. (2021) Presc Lett 28(1): 3-4
    2. Ryan (2001) CMEA Internal Medicine Lecture, San Diego
    3. Chavey (2017) Am Fam Physician 95(1):13-20 [PubMed]
    4. Chavey (2001) Am Fam Physician 64(5):769-74 [PubMed]
    5. Chavey (2001) Am Fam Physician 64(6):1045-54 [PubMed]
    6. Evangalista (2000) Am J Cardiol 86:1339-42 [PubMed]
    7. Heidenreich (2022) Circulation 145(18):e895-e1032 +PMID: 35363499 [PubMed]
    8. Hoyt (2001) Am Fam Physician 63(8):1593-8 [PubMed]
    9. Hunt (2009) Circulation 119(14):e391-479 [PubMed]
    10. Jessup (2003) N Engl J Med 348:2007-18 [PubMed]
    11. King (2012) Am Fam Physician 85(12): 1161-8 [PubMed]
    12. Senni (1997) Mayo Clin Proc 72:453-60 [PubMed]
    13. Whorlow (2000) Am J Cardiol 86:886-9 [PubMed]
    14. (1999) J Card Fail 5:357-82 [PubMed]
    15. (1997) N Engl J Med 336:525 [PubMed]
    16. (1996) JAMA 275(20):1549-56 [PubMed]
    17. (1995) Circulation 92:2764-84 [PubMed]

Left-Sided Heart Failure (C0023212)

Definition (NCI_FDA) Failure of adequate output by the left ventricle despite an increase in distending pressure and in end-diastolic volume, with dyspnea, orthopnea, and other signs and symptoms of pulmonary congestion and edema.
Definition (NCI) Failure of adequate output by the left ventricle despite an increase in distending pressure and in end-diastolic volume, with dyspnea, orthopnea, and other signs and symptoms of pulmonary congestion and edema.
Definition (MSH) Heart failure involving the LEFT VENTRICLE.
Concepts Disease or Syndrome (T047)
MSH D006333
ICD9 428.1
ICD10 I50.1
SnomedCT 195113008, 155376009, 85232009
English CARDIAC FAILURE LEFT, PULMONARY EDEMA CARDIAC CAUSE, PULMONARY OEDEMA CARDIAC CAUSE, Left Ventricular Failure, Heart Failure, Left-Sided, Left Sided Heart Failure, Heart Failure, Left Sided, Left-Sided Heart Failure, Pulmonary edema cardiac cause, Pulmonary oedema cardiac cause, Cardiac failure left, Left cardiac failure, Failure heart left, Failure left heart, left ventricular failure, failure left ventricular, heart failure left, left-sided heart failure, Failure;ventricular;left, left side heart failure, failure heart left sided, lvf, failure heart left side, LVF, Left ventricular failures, Left ventricular failure (disorder), left heart failure, left heart failure (diagnosis), cardiac failure left, VENTRICULAR FAILURE, LEFT, FAILURE, LEFT VENTRICULAR, LEFT VENTRICULAR FAILURE, Left ventricular insufficiency, Left heart failure, Left ventricular failure, LVF - Left ventricular failure, Left heart failure (disorder), Left-sided heart failure, edema; lung, acute, meaning failure, left ventricle, lung; edema, acute, meaning failure, left ventricle
French Défaillance ventriculaire gauche, Défaillances ventriculaires gauches, Défaillance du coeur gauche, Oedème pulmonaire d'origine cardiaque, Insuffisance ventriculaire gauche, Insuffisance cardiaque gauche, Défaillance cardiaque gauche, DEFAILLANCE CARDIAQUE GAUCHE, OEDEME PULM ORIGINE CARDIAQUE, FVG
Italian Insufficienza ventricolare sinistra, Insufficienze ventricolari sinistre, Edema polmonare cardiogeno, Insufficienza cardiaca sinistra, Insufficienza parte sinistra del cuore, Scompenso cardiaco sinistro, Scompenso cardiaco del lato sinistro
Dutch longoedeem cardiale oorzaak, hartfalen links, links decompensatie, linker ventriculaire insufficiëntie, linkerhartfalen, pulmonaal oedeem cardiale oorzaak, falen linker harthelft, LVF, long; oedeem, acuut, in de betekenis van decompensatie, linker ventrikel, oedeem; long, acuut, in de betekenis van decompensatie, linker ventrikel, Linker-ventrikeldecompensatie, falen linkerventrikel, linkerventrikelfalen
German pulmonales Oedem verusacht durch Herzproblem, linksventrikulaere Insuffizienz, Versagen Herz rechts, linkes Herzversagen, Herzversagen links, Versagen links Herz, Linksherzinsuffizienz, Linksinsuffizienz, LINKSHERZVERSAGEN, LUNGENOEDEM KARDIAL, LVF, Formen der Linksherzinsuffizienz
Portuguese Insuficiência cardíaca esquerda, Edema pulmonar de causa cardíaca, Insificiência ventricular esquerda, EDEMA PULMONAR DE CAUSA CARDIACA, INSUFICIENCIA CARDIACA ESQUERDA, Insuficiência do ventrículo esquerdo, Insuficiências do ventrículo esquerdo
Spanish Insuficiencia del corazón izquierdo, Fallo cardiaco izquierdo, Edema pulmonar de origen cardiaco, Insuficiencia cardiaca izquierda, Fallo del corazón izquierdo, Fallo ventricular izquierdo, EDEMA PULMONAR, CAUSA CARDIACA, INSUFICIENCIA CARDIACA IZQUIERDA, IVI, insuficiencia ventricular izquierda (trastorno), insuficiencia ventricular izquierda, Insuficiencia ventricular izquierda, Insuficiencias del ventrículo izquierdo
Japanese 左心室不全, 左室不全, 左心不全, 心性肺水腫, サシンフゼン, シンセイハイスイシュ, サシツフゼン, サシンシツフゼン
Czech Levostranné srdeční selhání, Kardiogenní plicní edém, Selhání levé komory srdeční, Selhání levé komory, Plicní edém kardiogenní, Insuficience levé komory, levostranné selhání srdce, srdce - selhání levostranné, levostranné srdeční selhání, Přetížení levé komory
Korean 좌심실 기능상실
Hungarian Bal ventricularis elégtelenségek, Bal kamrai elégtelenség, Cardialis eredetű pulmonalis oedema, Bal ventricularis elégtelenség, Bal szívfél elégtelensége, Szív bal felének elégtelensége, LVF, Cardialis okú pulmonalis oedema, Balszívfél-insufficientia, Balszívfél-elégtelenség
Norwegian Venstresidig hjertesvikt, Hjertesvikt, venstresidig
Derived from the NIH UMLS (Unified Medical Language System)

Systolic dysfunction (C0749225)

Concepts Pathologic Function (T046)
SnomedCT 371037005
English systolic dysfunction, Systolic dysfunction (finding), Systolic dysfunction
Spanish Disfunción sistólica, disfunción sistólica (hallazgo), disfunción sistólica
Portuguese Disfunção sistólica
Dutch systolische disfunctie
French Dysfonctionnement systolique
German Stoerung in der Systole
Hungarian Systoles dysfunctio
Czech Systolická dysfunkce
Italian Disfunzione sistolica
Japanese 収縮機能障害, シュウシュクキノウショウガイ
Derived from the NIH UMLS (Unified Medical Language System)

Heart Failure, Systolic (C1135191)

Definition (MSH) Heart failure caused by abnormal myocardial contraction during SYSTOLE leading to defective cardiac emptying.
Concepts Disease or Syndrome (T047)
MSH D054143
ICD9 428.20, 428.2
ICD10 I50.20
SnomedCT 417996009
Spanish insuficiencia cardíaca sistólica (trastorno), insuficiencia cardíaca sistólica, Insuficiencia Cardíaca Sistólica, Insuficiencia cardiaca sistólica
English Systolic Heart Failure, Heart Failure, Systolic, Heart Failures, Systolic, Systolic Heart Failures, Systolic hrt failure NOS, Unspecified systolic (congestive) heart failure, Heart Failure, Systolic [Disease/Finding], failure heart systolic, systolic heart failure, heart failure systolic, Systolic heart failure, unspecified, Systolic heart failure, Systolic heart failure (disorder)
Portuguese Insuficiência Cardíaca Sistólica, Insuficiência cardíaca sistólica
Finnish Systolinen sydämen vajaatoiminta
French Défaillance cardiaque systolique, Insuffisance cardiaque systolique
German Herzinsuffizienz, Systolische, Systolische Herzinsuffizienz, Systolisches Herzversagen
Italian Scompenso cardiaco sistolico, Insufficienza cardiaca sistolica
Swedish Hjärtsvikt, systolisk
Czech systolické srdeční selhání, srdce - selhání systolické, Systolické srdeční selhání
Polish Niewydolność serca skurczowa, Skurczowa niewydolność serca
Japanese 心不全-収縮期, 収縮期心不全, 収縮性心不全, シュウシュクキシンフゼン
Norwegian Systolisk hjertesvikt, Hjertesvikt, systolisk
Dutch systolisch hartfalen
Hungarian Systolés szívelégtelenség
Derived from the NIH UMLS (Unified Medical Language System)

Left ventricular systolic dysfunction (C1277187)

Definition (NCI_CDISC) The degree of impairment of the left cardiac ventricle to contract efficiently.
Definition (NCI) The degree of impairment of the left cardiac ventricle to contract efficiently. (ACC)
Definition (NCI_CTCAE) A disorder characterized by failure of the left ventricle to produce adequate output despite an increase in distending pressure and in end-diastolic volume. Clinical manifestations may include dyspnea, orthopnea, and other signs and symptoms of pulmonary congestion and edema.
Concepts Disease or Syndrome (T047)
SnomedCT 366829001, 366910008, 134401001
English Left Ventricular Systolic Dysfunction, Left ventricular systolic dysfunction, Left Cardiac Ventricular Systolic Dysfunction, Left ventricular systolic dysfunction (diagnosis), myocardial dysfunction left cardiac ventricular systolic, Left ventricular systolic dysfunction (disorder)
Spanish Disfunción sistólica del ventrículo izquierdo, disfunción sistólica del ventrículo izquierdo (trastorno), disfunción sistólica del ventrículo izquierdo
Portuguese Disfunção sistólica do ventrículo esquerdo
French Dysfonctionnerment systolique ventriculaire gauche
Italian Disfunzione sistolica del ventricolo sinistro
German linksventrikulaere systolische Dysfunktion
Dutch systolische disfunctie van linkerventrikel
Czech Systolická dysfunkce levé komory
Japanese 左室収縮機能障害, サシツシュウシュクキノウショウガイ
Hungarian Bal oldali ventricularis systolés dysfunkció
Derived from the NIH UMLS (Unified Medical Language System)

Heart failure with reduced ejection fraction (C3839346)

Concepts Disease or Syndrome (T047)
SnomedCT 703272007
English Heart failure with reduced ejection fraction (disorder), Heart failure with reduced ejection fraction
Derived from the NIH UMLS (Unified Medical Language System)

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