Myocarditis (M/A)

Myocarditis (MA58)

= 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