CARDIOMYOPATHY, END-STAGE

CARDIOMYOPATHY, END-STAGE - Tim Fitzgibbons, MD; Theo E. Meyer, MD, DPhil
BASICS
DESCRIPTION
In 1995, the WHO defined cardiomyopathy as a "disease of the myocardium associated with cardiac dysfunction." They proposed a classification system based on pathophysiology. Each class may be caused by many disorders, and some disorders may overlap classes.
• Classification of cardiomyopathy
- Dilated (systolic)
 Characterized by dilation and reduced systolic function of one or both ventricles
- Hypertrophic (diastolic)
 Left and or right ventricular hypertrophy with normal to reduced end diastolic volumes
 May include asymmetric septal hypertrophy
 Cause of SCD in young athletes
- Restrictive (diastolic)
 Restrictive filling and reduced diastolic volume of either or both ventricles
 Systolic function may be near normal
 Etiology: Idiopathic, amyloidosis, etc.
- Arrhythmogenic right ventricular (RV) dysplasia
 Fibrofatty replacement of the RV
 May present with arrhythmia or SCD in the young
- Unclassified
 Cases that do not fit easily into 1 group (i.e., non compacted myocardium)
- Specific: Includes patients with cardiomyopathy in association with a known systemic disorder, for example
 Ischemic
 Valvular
 Hypertensive
 Inflammatory
 Metabolic
 Peripartum
• "End-stage" cardiomyopathy patients have "Stage D" heart failure, or severe symptoms at rest refractory to standard medical therapy.
• System(s) Affected: Cardiovascular; Renal
ALERT
Pediatric Considerations
Etiology: Idiopathic, viral, congenital heart disease, and familial.
Pregnancy Considerations
May occur in women postpartum
GENERAL PREVENTION
Reduce salt and water intake; home blood pressure measurement and a daily weight
EPIDEMIOLOGY
Predominant age: Ischemic cardiomyopathy is the most common etiology; predominantly patients >50 years. Consider uncommon causes in young.
Incidence
• 60,000 patients 65 die each year from end-stage heart disease.
• From 35,000-70,000 of the population might benefit from cardiac transplant or chronic support.
Prevalence
Most rapidly growing form of heart disease
RISK FACTORS
• Hypertension
• Hyperlipidemia
• Obesity
• Diabetes mellitus
• Smoking
• Physical inactivity
• Excessive alcohol intake
• Dietary sodium
Genetics
Hypertrophic, dilated cardiomyopathy, and arrhythmogenic RV dysplasia may present as familial syndromes with autosomal dominant inheritance.
ETIOLOGY
• Ischemic heart disease: Most common etiology; up to 66% of patients
• Hypertension
• Familial cardiomyopathies
• Congenital heart disease
• Peripartum/postpartum
• Toxic/metabolic causes
- Alcoholism
- Radiation
- Beriberi
- Kwashiorkor
- Cobalt
- Selenium deficiency
- Hemosiderosis
- Thyrotoxicosis
• Infectious causes
- Viral (e.g., HIV, coxsackievirus)
- Diphtheria
- Toxoplasmosis
- Trichinosis
- Trypanosomiasis
- Acute rheumatic fever
• Inherited disorders of metabolism
- Glycogen storage disease
- Pompe disease
- Hurler syndrome
- Hunter syndrome
- Fabry disease
• Inherited neuromuscular disorders
- Duchenne muscular dystrophy
- Friedreich ataxia
• Drugs
- Chemotherapy: Anthracyclines, cyclophosphamide, Herceptin
• Inflammatory causes
- Giant cell myocarditis
- Loeffler eosinophilia
- Sarcoidosis
• Idiopathic
• Other causes
- Tachycardia-mediated cardiomyopathy
- Amyloidosis
- Valvular heart disease
- Endomyocardial fibrosis


DIAGNOSIS
SIGNS AND SYMPTOMS
• Dyspnea at rest or with exertion
• Paroxysmal nocturnal dyspnea
• Orthopnea
• Postprandial dyspnea
• Fatigue
• Syncope
• Tachypnea
Physical Exam
• Low pulse pressure
• Cool extremities
• Jugular venous distention
• Bibasilar rales
• Tachycardia
• S3 gallop
• Hepatosplenomegaly
• Ascites
• Edema
TESTS
• ECG: LV hypertrophy, interventricular conduction delay, atrial fibrillation, evidence of prior Q-wave infarction.
• Cardiopulmonary exercise testing: Maximal oxygen consumption 10 mL/kg/mm correlates with 50% 1-year mortality, and >18 mL/kg/mm correlates with >90% 1-year survival. Used in stable outpatients to estimate prognosis and prior to cardiac transplant referral.
Lab
• Hyponatremia
• Prerenal azotemia
• Anemia
• Elevated BNP or pro-BNP
• Mild hyperbilirubinemia
• Elevated liver function tests
• Elevated uric acid
Imaging
• Chest radiograph
- Cardiomegaly
- Increased vascular markings to the upper lobes
- Pleural effusions may or may not be present
• ECG
- In dilated cardiomyopathy 4-chamber enlargement and global hypokinesis are present.
- In hypertrophic cardiomyopathy, severe left ventricular (LV) hypertrophy is present.
- Segmental abnormalities in contraction of the LV are indicative of previous localized myocardial infarction.
• Cardiac MRI
- May be useful to characterize particular nonischemic cardiomyopathies
Diagnostic Procedures/Surgery
Cardiac catheterization:
• Helpful to rule out ischemic heart disease
• PA catheters may be reasonable in patients with refractory HF to help guide management (3)[C].
DIFFERENTIAL DIAGNOSIS
• Severe pulmonary disease
• Primary pulmonary hypertension
• Recurrent pulmonary embolism
• Hypothyroidism
• Some advanced forms of malignancy
TREATMENT
GENERAL MEASURES
• Reduction of filling pressures
• Treatment of electrolyte disturbances
Diet
Low fat, low salt, fluid restriction
MEDICATION (DRUGS)
First Line
• Systolic failure syndromes
- ACE inhibitors
 Lisinopril 5-40 mg/d or captopril 6.25-50 mg t.i.d. (3)[A]
- Loop diuretics
 May need to be given IV initially, and then orally as patient stabilizes
 Furosemide 40-120 mg/d or t.i.d.(3)[A]
- -Blockers:
 Use with caution in acutely decompensated or low cardiac output states
 Metoprolol succinate 12.5-200 mg/d, carvedilol 3.125-25 mg b.i.d., or bisoprolol 1.25-10 mg/d (3)[A]
- Aldosterone antagonists
 Patients with NYHA III-IV CHF, EF35%, on standard therapy
 Spironolactone 12.5-25 mg/d (3)[A]
- Digoxin 0.125-0.250 mg/d for symptomatic patients on standard therapy (3)[A]
- BiDil (hydralazine/nitrates)
 BiDil 1 tablet t.i.d is recommended in addition to standard treatment in African American patients with Class III-IV symptoms (3)[A]
• Diastolic failure
- Few evidence-based therapies for diastolic heart failure. Empiric management goals include
 Management of hypertension
 Reduction of congestive states (i.e., diuretics)
 Prevention of progression of LVH (i.e., RAAS blockade)
 Maintenance of sinus rhythm
• Contraindications
- -Blockers: Low cardiac output, 1st- or 2nd-degree heart block
- Aldosterone antagonists: Oliguria, anuria, renal dysfunction
- Loop diuretics: Hypokalemia, hypomagnesemia
- ACE inhibitors: Pregnancy, angioedema
• Precautions
- In patients with CKD, digoxin dosage should be 0.125 mg/d, and drug levels followed carefully.
- Closely monitor electrolytes
- ACE inhibitors: Initiate with care if blood pressure is low. Begin with low-dose captopril, such as 6.25 mg t.i.d.
- -Blockers: Avoid in patients with evidence of poor tissue perfusion; they may further depress systolic function.
- Milrinone, amrinone: Contraindicated for long-term use due to increased mortality
Second Line
• Nesiritide .01 mcg/kg/min IV for 48 hours in HF patients with dyspnea at rest (3)[C]
• Angiotensin receptor blockers as an alternative to, or in addition to ACE inhibitors
SPECIAL THERAPY
• Prophylactic ICD should be considered for patients with an LVEF 30% (3)[A].
• Biventricular pacing should be considered for patients with QRS interval >120 ms, LVEF 35%, and Class III CHF despite medical therapy(3)[A].
• Patients with severe, refractory HF with no reasonable expectation of improvement should not be considered for an ICD (3)[C].
FOLLOW-UP
DISPOSITION
Issues for Referral
• Consider referral to a heart failure center.
• Management by a heart failure team improves outcomes and facilitates early transplant referral.
PROGNOSIS
20-40% of patients in New York functional class IV die within 1 year. With a transplant, a 1-year survival is as high as 94%.
COMPLICATIONS
Worsening congestive heart failure, syncope, arrhythmias, or sudden death
REFERENCES
1. Richardson P. Report of the 1995 WHO on the definition and classification of cardiomyopathies. Circulation. 1996;93:841-842.
2. Noria A, Stevenson LW. Medical management of advanced heart failure. JAMA. 2002;287:628-640.
3. Hunt SA, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in adults. J Am Coll Cardiol. 2005;46:1116-1143.
MISCELLANEOUS
See also: Alcohol use disorders; Amyloidosis; Diabetes mellitus, type 1; Diabetes mellitus, type 2; Hypertension; Hypothyroidism, adult; Idiopathic hypertrophic subaortic stenosis; Malnutrition, protein-calorie; Rheumatic fever; Sarcoidosis