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Cardiomyopathy, End Stage

para>Primary
  • Genetic

  • Hypertrophic cardiomyopathy (HCM)

  • Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D)

  • Left ventricular (LV) noncompaction (LVNC)

  • Glycogen storage (Danon type, PRKAG2)

  • Conduction defects

  • Mitochondrial myopathies

  • Ion channel disorders: long QT syndrome, Brugada, short QT syndrome, catecholaminergic ventricular tachycardia (CVPT), Asian SUNDS

  • Mixed

  • Dilated cardiomyopathy (DCM) (genetic or nongenetic)

  • Restrictive

  • Acquired

  • Myocarditis, stress cardiomyopathy, peripartum, tachycardia-induced, infants of type 1 diabetic mothers

  • Secondary (see list below)

  • Specific

    • Ischemic

    • Valvular

    • Hypertensive

    • Congenital heart disease

  • Patients with end-stage cardiomyopathy have stage D heart failure or severe symptoms at rest refractory to standard medical therapy.
  • System(s) affected: cardiovascular; renal

  • Pediatric Considerations
    Etiology: idiopathic, viral, congenital heart disease, and familial �
    Pregnancy Considerations
    May occur in women postpartum �

    Epidemiology


    Predominant age: Ischemic cardiomyopathy is the most common etiology; predominantly in patients aged >50 years. Consider uncommon causes in young. �
    Incidence
    • 60,000 patients <65 years die each year from end-stage heart disease.
    • 35,000-70,000 people might benefit from cardiac transplant or chronic support.

    Prevalence
    Most rapidly growing form of heart disease �

    Etiology and Pathophysiology


    The most frequent causes are in bold: �
    • Ischemic heart disease: most common etiology; up to 66% of patients
    • Hypertension
    • Valvular heart disease
    • Primary genetic causes
    • Congenital heart disease
    • Peripartum/postpartum
    • Endocrine
      • Diabetes mellitus

      • Hyperthyroidism

      • Hypothyroidism

      • Hyperparathyroidism

      • Pheochromocytoma

      • Acromegaly

    • Nutritional deficiencies
      • Beriberi, pellagra, scurvy, selenium, carnitine, kwashiorkor

    • Autoimmune/collagen
      • Systemic lupus erythematosus

      • Dermatomyositis

      • Rheumatoid arthritis

      • Scleroderma

      • Polyarteritis nodosa

    • Infectious causes
      • Viral (e.g., HIV, coxsackievirus, adenovirus)

      • Bacterial and mycobacterial (e.g., diphtheria, rheumatic fever)

      • Parasitic (e.g., toxoplasmosis, Trypanosoma cruzi)

    • Infiltrative (2)
      • Amyloidosis

      • Gaucher disease

      • Hurler disease

      • Hunter disease

      • Fabry disease

    • Storage
      • Hemochromatosis

      • Fabry disease

      • Glycogen storage disease (type II, Pompe)

      • Niemann-Pick disease

    • Neuromuscular/neurologic
      • Duchenne and Emery-Dreifuss muscular dystrophies

      • Friedreich ataxia

      • Myotonic dystrophy

      • Neurofibromatosis

      • Tuberous sclerosis

    • Toxic
      • Alcohol

      • Drugs and chemotherapy: anthracyclines, cyclophosphamide, Herceptin

      • Radiation

      • Heavy metal, chemical agents

    • Inflammatory (granulomatous):
      • Sarcoidosis

    • Idiopathic
    • Endomyocardial
      • Endomyocardial fibrosis

      • Hypereosinophilic syndrome (Loeffler endocarditis)


    Genetics
    Autosomal dominant HCM is the most common form of primary genetic cardiomyopathy (1/500 in the general population). Genetic causes of DCM are less common, accounting for 1/3 cases, with mostly autosomal dominant inheritance. LNC and ARVC are also inherited in an autosomal dominant fashion in addition to LQTS and other ion-channel disorders. �

    Risk Factors


    • Hypertension
    • Hyperlipidemia
    • Obesity
    • Coronary artery diease
    • Diabetes mellitus
    • Smoking
    • Physical inactivity
    • Excessive alcohol intake
    • Dietary sodium
    • Obstructive sleep apnea
    • Chemotherapy

    General Prevention


    Reduce salt and water intake; home BP and daily weight measurement �

    Diagnosis


    History


    • Dyspnea at rest or with exertion
    • Paroxysmal nocturnal dyspnea
    • Orthopnea
    • Postprandial dyspnea
    • Right upper quadrant pain or bloating
    • Midabdominal pain
    • Fatigue
    • Syncope
    • Edema

    Physical Exam


    • Tachypnea
    • Cheyne-Stokes breathing
    • Low pulse pressure
    • Cool extremities
    • Jugular venous distention
    • Bibasilar rales
    • Tachycardia
    • Displaced point of maximal impulse (PMI)
    • S3 gallop
    • Blowing systolic murmur
    • Hepatosplenomegaly
    • Ascites
    • Edema

    Differential Diagnosis


    • Severe pulmonary disease
    • Primary pulmonary hypertension
    • Recurrent pulmonary embolism
    • Constrictive pericarditis
    • Some advanced forms of malignancy
    • Anemia

    Diagnostic Tests & Interpretation


    • ECG: LV hypertrophy, interventricular conduction delay, atrial fibrillation, evidence of prior Q-wave infarction
    • Hyponatremia
    • Prerenal azotemia
    • Anemia
    • Mild elevation in troponin
    • Elevated B-type natriuretic peptide (BNP) or pro-BNP
    • Mild hyperbilirubinemia
    • Elevated liver function tests
    • Elevated uric acid

    Initial Tests (lab, imaging)
    • ECG
    • Chest radiograph
      • Cardiomegaly

      • Increased vascular markings to the upper lobes

      • Pleural effusions may or may not be present.

    • Echocardiography
      • In dilated cardiomyopathy, 4-chamber enlargement and global hypokinesis are present.

      • In hypertrophic cardiomyopathy, severe LV hypertrophy is present.

      • Segmental contraction abnormalities of the LV are indicative of previous localized myocardial infarction.

    • Cardiac MRI
      • May be useful to characterize certain nonischemic cardiomyopathies

    • Myocardial stress perfusion imaging (MPI)
      • Recommended in those with new-onset LV dysfunction or when ischemia is suspected


    Diagnostic Procedures/Other
    Cardiac catheterization �
    • Helpful to rule out ischemic heart disease
    • Characterize hemodynamic severity
    • Pulmonary artery catheters may be reasonable in patients with refractory heart failure to help guide management.

    Treatment


    See "Heart Failure, Chronic"� for detailed treatment protocols. �

    General Measures


    • Reduction of filling pressures
    • Treatment of electrolyte disturbances

    Medication


    First Line
    • Systolic failure syndromes
      • ACE inhibitors: All considered equally effective; initiate at low doses and titrate as tolerated to target doses (3)[A].

      • Loop diuretics

        • May need to be given IV initially and then orally as patient stabilizes

      • Furosemide, 40-120 mg/day or TID (3)[A]

      • β-Blockers

        • Use with caution in acutely decompensated or low-cardiac output states.

        • Initiate with low doses and titrate as tolerated.

      • Metoprolol succinate, 12.5-200 mg/day; carvedilol, 3.125-25 mg BID; or bisoprolol, 1.25-10 mg/day (3)[A]

      • Patients with New York Heart Association (NYHA) II-IV heart failure, ejection fraction (EF) <35%, on standard therapy: aldosterone antagonists: spironolactone or eplerenone (3)[A]

      • Digoxin, 0.125-0.25 mg/day for symptomatic patients on standard therapy (3)[B]

      • Combination hydralazine/isosorbide dinitrate is 1st-line treatment in African American patients with class III-IV symptoms already on standard therapy and for all patients with reduced EF and symptoms incompletely responsive to ACE inhibitor and β-blocker (3)[A].

        • Contraindications

      • β-Blockers: low cardiac output, 2nd- or 3rd-degree heart block

      • Avoid use of diltiazem and verapamil in patients with systolic dysfunction.

      • Aldosterone antagonists: oliguria, anuria, renal dysfunction

      • Loop diuretics: hypokalemia, hypomagnesemia

      • ACE inhibitors: pregnancy, angioedema

    • Precautions
      • In patients with chronic kidney disease, digoxin dosage should be ≤0.125 mg/day and drug levels followed carefully to avoid toxicity.

      • Closely monitor electrolytes.

      • ACE inhibitors: Initiate with care if BP is low. Begin with low-dose captopril, such as 6.25 mg TID.

      • β-Blockers: Avoid in patients with evidence of poor tissue perfusion; they may further depress systolic function.

      • Milrinone, dobutamine: long-term use associated with increased mortality

    • Medications TO AVOID
      • NSAIDs

      • Glitazones

      • Cilostazol


    Second Line
    • Angiotensin receptor blockers as an alternative to ACE inhibitors
    • Inotropic therapy (e.g., dobutamine or milrinone) for cardiogenic shock and support prior to surgery or cardiac transplantation (3)[B]
    • Continuous inotrope infusion may be considered in stage D outpatients for symptom control in those who are not eligible for transplantation or mechanical circulatory support (3)[B].

    Issues for Referral


    Management by a heart failure team improves outcomes and facilitates early transplant referral. �

    Additional Therapies


    • Prophylactic implantable cardioverter defibrillator (ICD) should be considered for patients with a left ventricular ejection fraction (LVEF) <35% and mild to moderate symptoms (3)[A].
    • Cardiac resynchronization therapy (CRT) is recommended and should be considered for patients in sinus rhythm with a QRS >150 msec, LVEF <35%, in FC I-III and ambulatory FC IV patients (3)[A].
    • Patients with severe, refractory heart failure with no reasonable expectation of improvement should not be considered for an ICD.
    • Consideration of an LV assist device as "permanent"� or destination therapy or cardiac transplantation is reasonable in selected stage D patients.

    Ongoing Care


    Diet


    Low-fat, low-salt, fluid restriction �

    Prognosis


    ~20-40% of patients in NYHA functional class IV die within 1 year. With a transplant, 1-year survival is as high as 94%. �

    Complications


    Worsening congestive heart failure syncope, renal failure, arrhythmias, or sudden death �

    References


    1.Maron �BJ, Towbin �JA, Thiene �G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation.  2006;113(14):1807-1816. �[View Abstract]2.Seward �JB, Casaclang-Verzosa �G. Infiltrative cardiovascular diseases: cardiomyopathies that look alike. J Am Coll Cardiol.  2010;55(27):1769-1779. �[View Abstract]3.Yancy �CW, Jessup �M, Bozkurt �B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation.  2013;128:1-375.

    Additional Reading


    See Also


    Alcohol Abuse and Dependence; Alcohol Withdrawal; Amyloidosis; Congestive Heart Failure; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Hypertension, Essential; Hypothyroidism, Adult; Idiopathic Hypertrophic Subaortic Stenosis; Protein Energy Malnutrition; Rheumatic Fever; Sarcoidosis �

    Codes


    ICD10


    • I42.9 Cardiomyopathy, unspecified
    • I42.2 Other hypertrophic cardiomyopathy
    • I42.1 Obstructive hypertrophic cardiomyopathy
    • I43 Cardiomyopathy in diseases classified elsewhere
    • I42.4 Endocardial fibroelastosis
    • I42.5 Other restrictive cardiomyopathy
    • I42.8 Other cardiomyopathies
    • I42.6 Alcoholic cardiomyopathy
    • I42.3 Endomyocardial (eosinophilic) disease
    • I42.7 Cardiomyopathy due to drug and external agent
    • I42.0 Dilated cardiomyopathy

    ICD09


    • 425.4 Other primary cardiomyopathies
    • 425.18 Other hypertrophic cardiomyopathy
    • 425.11 Hypertrophic obstructive cardiomyopathy
    • 425.8 Cardiomyopathy in other diseases classified elsewhere
    • 425.5 Alcoholic cardiomyopathy
    • 425.7 Nutritional and metabolic cardiomyopathy
    • 425.9 Secondary cardiomyopathy, unspecified

    SNOMED


    • 85898001 Cardiomyopathy (disorder)
    • 233873004 Hypertrophic cardiomyopathy (disorder)
    • 45227007 Hypertrophic obstructive cardiomyopathy (disorder)
    • 195029002 Cardiomyopathy associated with another disorder (disorder)
    • 83521008 Dilated cardiomyopathy secondary to alcohol (disorder)
    • 399020009 Congestive cardiomyopathy (disorder)
    • 415295002 Restrictive cardiomyopathy (disorder)
    • 195023001 Nutritional and metabolic cardiomyopathies (disorder)
    • 89461002 Primary cardiomyopathy

    Clinical Pearls


    • Cardiomyopathy represents the end-stage of a large number of disease processes involving the heart muscle.
    • Ischemic, hypertensive, postviral, familial, alcoholic, and incessant tachycardia-induced are the most common cardiomyopathy varieties seen in the United States.
    • Core therapy for heart failure applies: salt restriction, diuretics, ACE inhibitors, β-blockers, digoxin, and electrical treatments, such as cardiac resynchronization and implantable defibrillators, as appropriate.
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