= inflmy infiltrate of myocardium, w necrosis and/or degeneration of adjacent myocytes, not typical of the ischemic damage assoc w cor art dz.
Etiology
-in US/West Eu - most are fr viral infection
-1970-80s- coxsackievirus #1
-1990-00s- adenovirus, and enterovirus (cox A, B, echo, poliovirus), especially coxsackie B
-lately, parvo B19 is more common too
-other causes too: influenza, CMV, HIV, RSV HSV, hep C, rubella, VZV, mumps, EBV
-nonviral causes: rickettsiae, bacteria, protozoa, parasites, fungi, yeasts
-drugs: antibiotics, hypersensitivity rxns, a/i xx, collagen vasc dz- SLE, rh fever, rh arthritis, scleroderma, toxic rxns to infectious agents, Kawasaki dz, sarcoidosis
-Most cases are idiopathic
Epi
-incidence reports range fr 4% to 21% in kids/young adults
-underdiagnosed
-usually sporadic, but can be epidemic- seen in newborns, assoc w cox B virus; can also have intrauterine epidemics
Sx/Si
-Sx d/o age
-may have nonSp flulike illness or GE Sx before Sx of CHF
Newborns/Infants
-decr PO, f, irritability, listless, pallor episodes, diaphoresis
-sudden death in some
-PE: pale, mild cyanosis, and classic CHF sx
-younger pt are more likely to have had intrauterine myocarditis and now has sx of ch dz (!)
Children & Adolescents
-often recent URI within 10-14 days of Sx
-Sx start as tired, low fever, pale, decr appetite, abd pain
-sweating, palp'ns, rash, exercise intolerance, malaise common
-then, resp sx mainly, syncope, sudden death fr cv shock
-JVD and rales (unlike newborns)
-arrhythmias- a-fib, SVT, VT, and AV block
Dx
-hard to establish Dx, but c/s in pt w unexplained CHF or VT
CXR- cardiomegaly, prominent pulm vn markings fr pulm edema
ECG- sinus tachy
-low voltage QRS +/- T wave inversion
- +/-MI pattern w Q waves and ST changes
-VT, SVT, a-fib, AV block in some kids
Echo- dilated, dysfx'l LV consistent w DCM
-check for segmetnal motion abNly- common, but usually has global hypokinesis
-pericardial effusion common
-check for MR on doppler
Endomyocardial Bx
-cath shows low CO and incr ventric EDP
-Bx fr RV shows inflmn that is patchy and scattered across the ventricle
-mononuclear cell infiltrate is Dx'ic
-Bx has Sn of 3-63% (would need 17 specimens to ID 80% of cases!), so not done routinely
Dallas Criteria for Dx
-defines it as above
-at Bx, specimen may be classified as active, borderline, or no myocarditis, d/o if there's inflmy infiltrate in assoc w myocyte degen or necrosis, too sparse an infiltrate, or none at all.
Viral Studies
-in past +viral Cx has been c/s as diagnostic
-viral cx fr periph specimens- blood, stool, urine is not reliable to ID the causative infection
-4x incr Ab titers correlates w infectoin, but they are not Sp bc prior infection w the virus is common...
-PCR fr cardiac tissues is very Sn and also usually Sp.
Molecular Dx
-PCR amplification for virus detection- usually doesn't ID the virus fr blood sample, but does fr trach aspirates in intubated kids w myocarditis, thus less need for Bx
Pathophysiology
-viral infection trigger--> inflmn or myocardial injury--> cardiac enlarge and incr ventric EDV
-Nly this incr EDV--> incr force of contraction, w improved EF and CO (Starling mech), but w myocarditis, the myocardium can't respond to the stimuli, so CO is reduced
-Domino effect:
-infctn--> inflmn/cell injury--> decr myocardial contractility--> big hrt w incr LVEDP
-->decr CO--> incr symp tone (--> vasoconstrict) &incr AL--> sinus tachy/diaphoresis --> CHF
&-->incr LVEDP--> incr LAP--> incr pulm vn P--> pulm edema/systemic vn engorge--> CHF
&-->cardiac healing--> cardiac scarring--> VT or complete AV block
Pathology
Gross & Microscopic Findings
-nonspecific path findings
-big heart, all 4 chamber affected
-flabby, pale muscle w petechial hemorrhages on epicaridium
-bloody pericardial effusion may be seen if pericarditis
-thin ventric wall but also can see hypertrophy
-doesn't affect valves or endocardium, except for ch myocarditis the valve can be glistening white, suggestive of endocardial fibroelastosis
-mural thrombi in LV, small emboli in cor art and cerabral arts
-interstitial mononuclear cells- lymphs, plasma cells, eosinophils seen in early myocarditis
-myocardial necrosis w loss of cross-striation of muscle fibers, and edema- if severe infection
-perivasc accum of lymphos and plasma cells seen w cox B virus, rickettsiae, VZV, parasites, sulfa rxn
-microabscess if bacterial cause
Immunology
-NK cells important in the process, activated by IFN
-fibroblasts are targeted by cytotoxic T cells sensitized by the virus
--> accum macros, Ab production, etc
...
-in humans, Ab mediated cytolysis found in 30% pts w suspected myocarditis
...
Autoimmunity
-persistent viral infection in myocardium--> induce autoAb against adenine nucleotide translocator & myosin
Role of Cytokines in Myocarditis and DCM
-IL1 and TNFa...
-IL2...
Role of Cell Adhesion Molecules in Myocarditis and DCM
-...
Apoptosis
-a big part of the xx
-apoptosed cells are eaten up by adjacent macros/epithelail cells w/o resulting in an inflmy response
...
Long-Term Sequelae
-if the cardiac dysfx doesn't resolve, pt will get DCM
-? exact cause of the long term xx - ?persistence of the virus, or a/i xx, ?xx w dystrophen gene/prtn
Support for Viral Cause-and-Effect Relationship with Myocarditis
-limited definitive data to prove that the virus causes the ventricular xx directly
-it could be a 1y inflammatory d/o
Tx
-many pts have only mild Sx, w/o resp xx and only mild CHF sx
--> monitor closely
-animal studies: bed rest may prevent an incr in intramyocardial viral replication in acute stage
-no specific Tx to reverse myocardial injury is widely rec'd, but you should maint CO for tissue Q
-if CHF, digox may be used, can dramatically improve sx
-w acute inlfmn, the myocardium may be hyperSx to digox, so avoid rapid adm to achieve Tx levels
-often give diuretics w digox to pts w CHF
-anticoagulation Rx- ASA, warfarin, heparinppx
Positive Inotropic Agents Support CO
-Nitroprusside- decr SVR
-Milrinone for inotropy and AL reduction
-AL reduction Rx- captopril, enalapril w digox/diuretics
-Tx arrhythmia well
-SVT w digox or alt Rx
-ventric arrhythmias w amiodarone or lidocaine
-temporary pacer if AV block
-Immunosuppressive Rx- controversial for viral myocarditis, might worsen virus producing capabilities
-steroids/immsupp Rx... -Myocarditis Tx Trial in adults--> no diff among Tx for azathiprine, prednisone, cyclosporine or conventional Tx
-IVIG in kids- based on results of a test that showed better LV fx at f/u and higher survival at 1yr, but it wasn't statistically signif results bc small number of pts studied.
-IFNb use- fx by clearing out the virus, data yet to be seen
-LVADs and Ao balloon pumps vs ECMO
Px
-Px in newborn is poor- 75% mortality in 25 pts w suspected coxB virus, most in first week of illness
-Px in older infants/kids- better Px- mortality 10-25% in clinically apparent cases, w complete recovery in 1/2 of pts, and 25% having continued CXR/ecg xx but ASx
-adults might recover and be ASx, but still reduced working capacity on exercise stress test