Systolic Dysfunction

Aka: Systolic Dysfunction, Left Ventricular Dysfunction, Left Ventricular Failure, Left Heart 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

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II. 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

III. Causes

  1. See Heart Failure Causes
  2. Coronary Artery Disease is most common cause

IV. 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

V. 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

VI. 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

VII. 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

VIII. 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

IX. 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

X. 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

XI. 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

XII. Labs: Additional tests to consider (Cardiomyopathy Causes)

  1. Urine Toxicologic screen
    1. If Cocaine Abuse suspected
  2. Lyme Serology
  3. Parvovirus B19 Serology
  4. Blood Cultures
    1. If endocarditis or Sepsis suspected
  5. Human Immunodeficiency Virus

XIII. Imaging: Chest XRay

  1. See Chest XRay in Congestive Heart Failure

XIV. 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

XV. 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

XVI. 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

XVII. 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
  11. Symptomatic Hypotension
    1. Stop or decrease Antihypertensives that do not specifically improve CHF (e.g. Amlodipine, Thiazide Diuretics)
    2. Consider decreasing Diuretic dosing if hypovolemic or euvolemic
    3. May further decrease other Antihypertensive doses as needed

XVIII. Management: Medications - Overall protocol (starting dosing listed)

  1. See Acute Pulmonary Edema Management
  2. See Refractory management below
  3. Step 0: Strategy
    1. 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
    2. Rapid titration of CHF medications (over weeks) reduces hospitalization rates over 6 months
      1. Continue to optimize medications with reassessment, titrating drugs and doses every 1-2 weeks
        1. Triple therapy: ACE (or ARB, Entresto) AND Carvedilol AND Spirololactone (or Eplerenone)
        2. Quadruple therapy: SGLT2 Inhibitor added to Triple therapy
      2. Address adverse effects early and tailor management
      3. Requires close monitoring (Hyperkalemia or Hypokalemia, Hypotension, Acute Kidney Injury)
        1. Keep Serum Potassium >3.4 meq/L and <5.5 meq/L
        2. Keep systolic Blood Pressure >95 mmHg
        3. Keep Heart Rate >60/min
        4. Limit eGFR decrease to <30% from baseline
      4. References
        1. Mebazaa (2022) Lancet 400(10367): 1938-52 +PMID: 36356631 [PubMed]
  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 Eplerenone (Inspra) 25 mg orally 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

XIX. 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. Avoid in COPD or Asthma (use Metoprolol or Bisoprolol instead)
        4. 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]

XX. 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. Although combined with other Diuretics here, Aldosterone Antagonists are considered first-line agents beyond symptom control
        1. Important component of triple therapy (with ACE/ARB, Beta Blocker)
      2. 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
      3. Serum Creatinine must be <2.5 mg/dl (GFR > 30 ml/minute/1.73m2)
      4. Serum Potassium must be normal (below 5.0 to 5.5 meq/L)
      5. 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)
      6. Monitor Serum Potassium at 3 days, 7 days and then monthly for the first 3 months
      7. 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]

XXI. 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 and smoth Muscle relaxation via nitric oxide path and stimulation of soluble guanylate cyclase
    3. Indicated in symptomatic chronic Heart Failure with Reduced Ejection Fraction (<45%)
    4. Adverse effects include symptomatic Hypotension (avoid with PDE5 Inhibitors)
    5. 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)
    6. References
      1. (2021) Presc Lett 28(4): 24
      2. Elmes (2022) Am Fam Physician 106(5): 582-3 [PubMed]
  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]

XXII. 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
      1. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm

XXIII. Management: Based on Heart Failure Classification

  1. Asymptomatic (NYHA Class I)
    1. ACE Inhibitor in CHF (or Angiotensin Receptor Blocker)
    2. Beta Blocker (Metoprolol, Carvedilol)
  2. Symptomatic (NYHA Class II and IIIa)
    1. ACE Inhibitor in CHF (or Angiotensin Receptor Blocker with Neprilysin Inhibitor, e.g. Entresto)
    2. Beta Blocker (Metoprolol, Carvedilol)
    3. Loop Diuretic
    4. SGLT2 Inhibitor
  3. Symptomatic with recent rest Dyspnea (NYHA Class IIIb)
    1. ACE Inhibitor in CHF (or Angiotensin Receptor Blocker with Neprilysin Inhibitor, e.g. Entresto)
    2. Beta Blocker
    3. Loop Diuretic
    4. SGLT2 Inhibitor
    5. Spironolactone OR Eplerenone OR Isosorbide/Hydralazine
    6. Ivabradine (Corlanor)
  4. Symptomatic with Dyspnea at rest (NYHA Class IV)
    1. ACE Inhibitor in CHF (with caution)
    2. Loop Diuretic
    3. SGLT2 Inhibitor
    4. Spironolactone OR Eplerenone OR Isosorbide/Hydralazine
    5. Ivabradine (Corlanor)

XXIV. Management: Comorbid Chronic Kidney Disease

  1. General
    1. Consult nephrology regarding CHF medications if eGFR <30 ml/min/1.73m2 or Serum Potassium >5 meq/L
    2. Monitor labs (e.g. Serum Creatinine, Serum Potassium) at baseline, 1-2 weeks after a medication change, and every 3 months
  2. ACE Inhibitors or Angiotensin Receptor Blockers (ARB) or Sacubitril/Valsartan (Entresto)
    1. Risk of Hyperkalemia (hold medication if Serum Potassium >5.4 meq/L)
    2. Typically may be started at low dose (e.g. Lisinopril 2.5 mg daily)
    3. Monitor Serum Creatinine and Potassium while titrating dose
  3. Beta Blockers (e.g. Carvedilol)
    1. No restriction regardless of eGFR
  4. Diuretics
    1. Caution regarding Hypovolemia risk with Acute Kidney Injury on Chronic Kidney Disease
  5. SGLT2 Inhibitors (e.g. Farxiga)
    1. Improves outcomes in both HFrEF and Chronic Kidney Disease
    2. Consider lowering Diuretic dose when starting SGLT2 Inhibitors to reduce risk of Hypovolemia and Acute Kidney Injury
    3. May be used if eGFR >20 ml/min/1.73m2
    4. Hold SGLT2 Inhibitor if Serum Creatinine increases >50%
  6. Aldosterone Antagonist (e.g. Spironolactone)
    1. Limit to eGFR >30 ml/min/1.73m2 and Serum Potassium <5.0 meq/L
    2. Monitor Serum Creatinine and Serum Potassium closely
  7. References
    1. (2022) Presc Lett 29(9): 50-1

XXV. 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

XXVI. 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

XXVII. References

  1. (2021) Presc Lett 28(1): 3-4
  2. (2023) Presc Lett 30(1)
  3. Ryan (2001) CMEA Internal Medicine Lecture, San Diego
  4. Chavey (2017) Am Fam Physician 95(1):13-20 [PubMed]
  5. Chavey (2001) Am Fam Physician 64(5):769-74 [PubMed]
  6. Chavey (2001) Am Fam Physician 64(6):1045-54 [PubMed]
  7. Evangalista (2000) Am J Cardiol 86:1339-42 [PubMed]
  8. Heidenreich (2022) Circulation 145(18):e895-e1032 +PMID: 35363499 [PubMed]
  9. Hoyt (2001) Am Fam Physician 63(8):1593-8 [PubMed]
  10. Hunt (2009) Circulation 119(14):e391-479 [PubMed]
  11. Jessup (2003) N Engl J Med 348:2007-18 [PubMed]
  12. King (2012) Am Fam Physician 85(12): 1161-8 [PubMed]
  13. Senni (1997) Mayo Clin Proc 72:453-60 [PubMed]
  14. Whorlow (2000) Am J Cardiol 86:886-9 [PubMed]
  15. (1999) J Card Fail 5:357-82 [PubMed]
  16. (1997) N Engl J Med 336:525 [PubMed]
  17. (1996) JAMA 275(20):1549-56 [PubMed]
  18. (1995) Circulation 92:2764-84 [PubMed]

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