Myocarditis and Cardiomyopathies Flashcards
Myocarditis definition
• Inflammatory disorder of the heart muscle
Common causes of myocarditis
Commonly caused by viral infection:
o Coxackievirus B & A, Echovirus, influenze virus A and B, adenovirus, HIV, herpes simplex, cytomegalovirus, mumps, rubella, hepatitis
Less commonly by other infectious agents:
o Parasites: Chagas, toxoplasmosis
o Toxic agents: chemotherapy, radiation
o Bacteria: lyme carditis, bacterial endocarditis
Less commonly by noninfectious agents (ex. Hypersensitivity reactions) o Drugs o Rheumatic fever o Allergic reactions o Autoimmune reactions
Acute vs Chronic myocarditis
Acute Myocarditis
o In children or young adults
o Present with acute heart failure → cardiogenic shock and death
o Severe, likely due to lack of protective antibodies and exuberant immune response
o Majority recover
Chronic myocarditis
o Older adults:
o More insidious process
o Present with dilated cardiomyopathy
Clinical presentation of myocarditis
o Viral symptoms: fatigue, fever, myalgias
o CV symptoms: chest pain, dyspnea, palpitations, syncope, sudden cardiac death
o If acute syndrome is mild or asymptomatic, first symptoms may be heart failure as chronic disease progresses
treatment of myocarditis
Antiviral agents
• Animal models: effective if given within 24 hours of infection
• Impossible in humans to recognize early enough
Immunosuppression
• Ineffective during acute phase (aggravate process)
• Tested during T cell infiltrative phase = no beneficial effect
Bed rest
• Exercise worsens cardiac function
Medications
• ACE-I, Beta blocker, immunosuppressants
Phases/progression of myocarditis
Acute phase (days 0-3)
o Virus enters host via digestive or respiratory tract
• Moves to lymph nodes
• Travels to spleen
• Spreads to heart
o Viral proliferation → direct myocyte injury and destruction
• Within 3 days of infection = pro-inflammatory cytokines
• Interleukins (IL-1, IL-2)
• TNFa
• Interferon
• If death within first 3 days = necrosis without inflammation
Subacute phase (days 4-14)
o Infiltrating cells: NK cells
• Activated by IL-2
• Limit viral replication
• Interact with virus-infected myofibers → lysis
o Continuation of cytokine production
• Assists wit destruction of infected myocytes
• BUT persistent cytokine production (months) depresses myocyte function
o Neutralizing antibodies start at day 8; peak at ~day 14
o Nitric Oxide helps kills infectious agent but depresses myocardial function, may be involved in autoimmune phase
o Virus is eliminated from heart
Chronic Phase (cell mediated pathology) > 14 days
o See fibrosis, cardiac dilation, heart failure
Three theories:
1) Chronic immune activation after viral clearing
• Cytotoxic T cells recruited within 7 days
• Assist with viral clearing
• Response continues after no virus can be cultured
o Often at lower intensity
• Continued myocardial lysis by T cells → presentation of viral elements on normal cells or to immune response to intracellular proteins → myocyte destruction
• Also: antibodies may cross-react with virus and myocardial proteins
2) Persistent viral infection
• Viral RNA may persist in myocytes
• Contribute to ongoing inflammation
• Carrier state may develop = latent viral infection in extra-cardiac tissues = subject to reactivation
3) Virus-induced apoptosis
• Some viruses may initiate apoptosis cascade
o Apoptosis differs from frank necrosis in active viral infection
• Slow continuous myocyte loss over time → dilated cardiomyopathy
Describe the basic genetic abnormalities that result in hypertrophic cardiomyopathy
Mutations in sarcomere proteins: o Beta-myosin heavy chain (most common) o Troponin T and I o Tropomyosin o Actin o Myosin light chains o Myosin binding protein C
• Sarcomere abnormality → compensatory hypertrophy
Time course (varies by mutation):
o Myosin heavy chain mutation:
• At birth = heart appears normal (no evidence of hypertrophy)
• Hypertrophy develops during adolescence
• Amount of hypertrophy remains stable
• Once hypertrophy present → symptoms and disease-related complications
• Find echo hypertrophy in 90% by age 20
o Troponin T: echocardiographic hypertrophy in 90% by age 40
o Myosin binding protein C: echocardiographic hypertrophy in 90% by age 60
Describe the clinical presentation of hypertrophic cardiomyopathy.
- Disproportionate and inappropriate hypertrophy of LV
- Often septum is involved (asymmetric septal hypertrophy)
• Mitral valve apparatus:
o Larger than normal
o Increased anterior leaflet area
o Anomalous papillary muscle insertion may be seen
• Diastolic dysfunction with impaired ventricular filing
o Ventricle may dilate and develop systolic dysfunction occasionally (late in disease course)
• Clinical signs:
Bisferiens pulse (two components of carotid impulse)
S4
Systolic ejection murmur due to outflow tract obstruction
• Late peaking (Crescendo)
• Accentuated by hypovolemia
Mitral insufficiency murmur:
• Squatting to standing and Valsalva → reduce preload, accentuates murmur
• Handgrip increase afterload → decreases murmur
Explain how the hemodynamic abnormalities associated with hypertrophic cardiomyopathy may limit exercise capacity.
Hyperdynamic systolic function
o Overactive ventricle
o Heart almost ejects to volume of zero at end systole
Diastolic dysfunction
o Impaired relaxation → slowed early diastolic filling → increased dependence on atrial kick
o Can be followed by increased stiffness
Outflow tract gradient
o Dynamic obstruction (varies moment to moment)
o Contributing factors:
• Hyperdynamic LV ejection
• Hypertrophy
• Abnormalities in mitral valve
• Papillary muscle architecture
o Cause mitral valve to move up into outflow tract → reduces size of outflow = obstructs flow
o Severe cases = may limit CO response to exercise
Mitral regurgitation
o Mitral valve in outflow tract obstructs flow, forces it back into LA
o Causes reduced CO, increased congestion and dyspnea
Myocardial ischemia
o From poor perfusion (circulation can’t supply enough O2 and nutrients to hypertrophied and disorganized myocytes)
o Triggers diffuse fibrosis, chest pain
Arrhythmogenicity
o Triggered by micro-infarcts in hypertrophied regions
Causes of Dilated cardiomyopathy
Non-genetic causes (40%): • Myocarditis • Peri partum • Toxic (alcohol) • Idiopathic Genetic causes (20-50%) • Cytoskeleton proteins or mitochondria Idiopathic causes • It’s believed most had asymptomatic viral myocarditis that initiated the pathways leading to chronic LV dysfunction o Result: defective force generation or myocyte signaling
Phenotype of Dilated cardiomyopathy
- Hypertrophy
- Dilation
- Fibrosis
- Intracardiac thrombi
Causes of Hypertrophic cardiomyopathy
o 1/500 people affected Genetic causes (100%) • Automsomal dominant • Phenotypic heterogeneity • Variable penetrance • Sarcomere proteins mutated (missense mutations) Result: defective energy transfer or sarcomere dysfunction • LV volume is normal or reduced • Hemodynamic abnormalities
Phenotype of Hypertrophic cardiomyopathy
- Hypertrophy
- Asymmetrical septal hypertrophy
- Myofiber disarray
- Fibrosis
- LV outflow tract plaque
- Thickened septal vessels
Symptoms of Hypertrophic cardiomyopathy
- Exertional dyspnea
- Chest pain
- Syncope
- Sudden death
Treatment of Hypertrophic cardiomyopathy
Negative inotropic agents to relieve outflow tract obstruction
• Beta-blockers
• Nondihydropyridine Ca2+ channel blockers (Verapamil)
• Disopyramide
Dual chamber pacing
• Preexcitation of RV → alters synchrony of ventricular contraction
• Reduces obstruction
• Effective in only a minority of patients
ICDs
• Prevents risk of sudden cardiac death (SCD)
• Based on SCD risk stratification:
o History of ventricular fib, sustained VT, or SCD events
o Family history of SCD
o Unexplained syncope
o Documented NSVT (3 or more beats >120 bpm on Holter)
o Maximal LV wall thickness >30 mm
o Reasonable to assess BP response during exercise (Q12-24 months)
Surgical myomectomy
Non-surgical septal reduction
• Produce infarction in upper interventricular septum
• Inject ethanol into coronary artery → decrease in septal thickness = reduces obstruction
AVOID: dehydration (diuretics) and vasodilators (nitroglycerin)
