Systolic Dysfunction

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

1. See Also
   1. Heart Failure
   2. Diastolic Dysfunction
   3. Cardiomyopathy
   4. Framingham Heart Failure Diagnostic Criteria
   5. Congestive Heart Failure Exacerbation Management
   6. Congestive Heart Failure Exacerbation Decision Rule
2. Causes
   1. See Heart Failure Causes
   2. Coronary Artery Disease is most common cause
3. Types
   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
4. 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 increase afterload (and increased Blood Pressure)
      4. Increased afterload decreases renal perfusion
      5. Decreased renal perfusion stimulates ADH, Aldosterone and the the renin-Angiotensin system
      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, PND
      2. Increased right sided pressure: Edema, Ascites, JVD
   3. Decreased cardiac output
      1. Fatigue
      2. Depression
5. 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
6. 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
   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
7. 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
   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
8. 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
9. 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
   3. Serum Magnesium
   4. Urinalysis
   5. B-Type Natriuretic Peptide (BNP) or NT-BNP
      1. Sensitive and specific marker for CHF
   6. Serum Albumin
      1. Nephrotic Syndrome
   7. Thyroid Stimulating Hormone (TSH)
      1. Over age 65
      2. Atrial Fibrillation
10. Labs: Additional to consider
    1. Urine Toxicologic screen
       1. If Cocaine abuse suspected
    2. Lyme serology
    3. Troponin I
       1. If acute chest Pain Evaluation
    4. Blood Cultures
       1. If endocarditis or Sepsis suspected
    5. Human Immunodeficiency Virus
11. Imaging: Chest XRay
    1. Most useful initial test to assess for Congestive Heart Failure (as well as other causes of Dyspnea)
    2. Findings suggestive of CHF
       1. Cardiomegaly
       2. Pulmonary venous congestion
          1. Cephalization (upper lung field fluid accumulation)
          2. Bat-winging
          3. Alveolar fluid
          4. Pleural Effusion
          5. Kerley B Lines
       3. Efficacy
          1. Test Sensitivity: 71%
          2. Test Specificity: 92%
    3. Other findings
       1. Underlying lung disease
       2. Chamber enlargement
       3. Valve calcifications
12. 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
13. Diagnostics: Advanced
    1. Echocardiogram in CHF
       1. Indicated in every Congestive Heart Failure patient
       2. Ejection Fraction 40% or less
       3. Other factors evaluated
          1. Chamber size and shape
          2. Wall thickness
          3. Valvular function
    2. Evaluation for Ischemic Heart Disease
       1. Modalities
          1. Exercise Stress Testing
          2. Nuclear (Thallium or Cardiolyte-Technetium)
          3. Cardiac catheterization
       2. Observe for reversible ischemic changes
          1. Consider Angioplasty (PTCA)
          2. Consider Coronary Artery Bypass Graft (CABG)
    3. Ambulatory rhythm monitor (Holter Monitor)
       1. Observe for ventricular arrhythmia
       2. Consider patient for Implantable Defibrillator
14. 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 not elevated
          1. BNP is more reliable than nt-BNP
          2. BNP <95 pg/ml
          3. 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
          1. Also cited for efficacy under signs and symptoms
15. Management: General Measures
    1. See Congestive Heart Failure Exacerbation Management
    2. Limit salt intake: 2-3 gram Sodium Diet (no added salt)
    3. Graded Exercise program
       1. Reduces Heart Failure related mortality
       2. Piepoli (2004) BMJ 328:189-92
    4. Control comorbid conditions
       1. Hypertension
       2. Coronary Artery Disease
       3. Diabetes Mellitus
       4. Obstructive Sleep Apnea
       5. Major Depression
    5. Avoid Provocative Medications
       1. Avoid Nonsteroidal Anti-inflammatory drugs (NSAIDS)
          1. Block ACE Inhibitors
          2. Block Diuretics
       2. Avoid Calcium Channel Blockers (except Amlodipine)
       3. Avoid beta agonists unless absolutely indicated
          1. Higher hospitalization and mortality rates in CHF
             1. Au (2003) Chest 123:1964-9
          2. May be started slowly once CHF is stable and compensated
       4. Avoid ARB with ACE Inhibitor and Beta Blocker
          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
    6. Stop habits associated with hospital readmission
       1. Tobacco Cessation
       2. Alcohol cessation
    7. Establish target Ideal 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 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)
    8. 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
16. Management: Medications
    1. See Acute Pulmonary Edema Management
    2. Overall protocol (starting dosing listed)
       1. Step 1: Loop Diuretic: Lasix 20-40 mg PO 1-2x/day
       2. Step 2: ACE Inhibitor: Lisinopril 2.5 mg PO daily
       3. Step 3: Beta Blockers: Metoprolol XL 12.5 mg PO daily
       4. Step 4: Add adjunct (choose one line)
          1. Angiotensin Receptor Blocker: Losartan 25 mg qd or
          2. Aldosterone Antagonist: Spironolactone 12.5 mg qd or
          3. Hydralazine with Isosorbide
       5. Step 5: Add Digoxin
    3. 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
          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 q2-4 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 (Lopressor)
                1. Toprol XL
                   1. Start at 12.5 to 25 mg qd (max: 200 mg/day)
             2. Bisoprolol (Zebeta)
                1. Start: 1.25 mg daily (maximum: 10 mg/day)
             3. Carvedilol (Coreg)
                1. Start at 3.125 mg bid
                2. Slowly titrate to 12.5 - 25 mg bid over 2 weeks
                3. Superior to Metoprolol in increasing Ejection Fraction
                   1. Raiput (2003) Am J Cardiol 92:218-21
          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
    4. Relief of Congestive Heart Failure symptoms
       1. Diuretics (reduce volume overload)
          1. First Line: Loop Diuretics
             1. Use as adjunct to other drugs above
             2. Diuretics are not the primary CHF treatment
             3. Start Furosemide 20-40 mg PO daily to bid
             4. Consider changing Furosemide to Torsemide in CHF refractory cases
          2. Second: Spironolactone or Eplerenone (Aldosterone Antagonists)
             1. NYHA Class III or IV
             2. Serum Creatinine must be <2.5 mg/dl (GFR > 50 ml/minute/1.73m2)
             3. Serum Potassium must be normal (<5.5 meq/L)
             4. Bozkurt (2003) Am J Cardiol 41:211-4
       2. Digoxin (Increased contractility)
          1. Typical dose: 0.125 mg daily (up to 0.25 mg daily)
             1. Decrease to 0.0625 if drug interactions or Chronic Renal Insufficiency
          2. Does not decrease mortality, but significantly improves quality of life
          3. 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
          4. May be associated with increased mortality in women
             1. Rathore (2002) N Engl J Med 347:1403-11
    5. Consider Additional Management
       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
             2. McAlister (2004) Ann Intern Med 141:381-90
       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
       5. 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. Alternative to Spirinolactone, but much more expensive
             1. Does not warrant additional cost in most cases
             2. Consider if severe Gynecomastia on Spironolactone
          4. References
             1. Pitt (2003) N Engl J Med 348:1309-21
       7. Tolvaptan
          1. Mechanism: Vasopressin Receptor Antagonist
          2. Reduces volume overload and congestion immediately
          3. Appears to have longterm benefit in CHF
          4. Gheorghiade (2004) JAMA 291:1963-71
       8. Hydralazine and Isosorbide Dinitrate
          1. Especially effective in younger black patients
          2. Start
             1. Hydralazine 12.5 mg PO and
             2. Isosorbide Dinitrate or Isosorbide Mononitrate
                1. Dinitrate 5-10 mg tid with 12 hour-free or
                2. Mononitrate 30 mg qd
          3. Maintenance
             1. BiDil 37.5/20 1 po tid (max 2 tid) or
             2. Hydralazine 37.5-75 mg/day and Dinitrate 20-40 mg
    6. Disproven therapies (avoid these)
       1. 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. Improves CHF symptoms but may increase mortality
          5. Sackner-Bernstein (2005) JAMA 293:1900-5
17. Management: Based on Heart Failure Classification
    1. Asymptomatic (NYHA Class I)
       1. ACE Inhibitor in CHF
       2. Beta Blocker
    2. Symptomatic (NYHA Class II and IIIa)
       1. ACE Inhibitor in CHF
       2. Beta Blocker
       3. 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. Diuretic
       4. Spironolactone (Aldactone) or Eplerenone
       5. Digoxin
    4. Symptomatic with Dyspnea at rest (NYHA Class IV)
       1. ACE Inhibitor in CHF
       2. Diuretic
       3. Spironolactone (Aldactone) or Eplerenone
       4. Digoxin
18. Management: Refractory CHF
    1. Indicated for lack of response to above measures
    2. Assumes ACE Inhibitors and Beta Blockers above
    3. Step 1: Loop Diuretic
       1. Double dose (not twice daily) if no response
       2. Double dose if Serum Creatinine remains >2.0
    4. Step 2: Add second Diuretic with caution
       1. Thiazide Diuretic
       2. Spironolactone (offers aldosterone blockade)
          1. Dose: 25 mg qd
          2. Indicated in Class III or Class IV CHF
          3. Contraindicated if Serum Creatinine >2.5 mg/dl
          4. Alternative: Eplerenone
       3. Metolazone (Zaroxolyn)
          1. Dose 5-10 mg twice weekly 1 hour before lasix
    5. Step 3: Add Hydralazine and Nitrates
    6. Step 4: Loop Diuretic IV
    7. Step 5
       1. Dobutamine with low dose Dopamine
          1. Intermittent Dobutamine reduces mortality
          2. Nanas (2004) Chest 125:1198-204
       2. Consider Milrinone
    8. Step 6
       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
19. 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
20. References
    1. Ryan (2001) CMEA Internal Medicine Lecture, San Diego
    2. Chavey (2001) Am Fam Physician 64(5):769-74
    3. Chavey (2001) Am Fam Physician 64(6):1045-54
    4. Evangalista (2000) Am J Cardiol 86:1339-42
    5. Hoyt (2001) Am Fam Physician 63(8):1593-8
    6. Hunt (2009) Circulation 119(14):e391-479
    7. Jessup (2003) N Engl J Med 348:2007-18
    8. King (2012) Am Fam Physician 85(12): 1161-8
    9. Senni (1997) Mayo Clin Proc 72:453-60
    10. Whorlow (2000) Am J Cardiol 86:886-9
    11. (1999) J Card Fail 5:357-82
    12. (1997) N Engl J Med 336:525
    13. (1996) JAMA 275(20):1549-56
    14. (1995) Circulation 92:2764-84