Cardiac
Manifestations: myocarditis, pericarditis, vasculitis, ACS, CHF, conduction abnormalities, atrial and ventricular arrhythmias
sx: chest pain, dyspnea, palpitation, syncope
Mortality 20-50% ( compared to 2-5% with colitis)
Presentation: inflammatory manifestations -->within 3 months or first 4 cycles of rx; non inflammatory after 6 months
Pt on ICI presents with Afib--> check TSH, troponin, rule out myocarditis, rule out ACS.
Troponin I is specific but may take time to result.
Troponin T is non specific but is readily available.
Myocarditis: get Echo, EKG continuous, Cardiac MRI with inflammatory images.
Troponin is elevated in 94% of cases, and NT-BNP is elevated in 2/3 cases. On echo EF can be preserved in 51% of patients with myocarditis and 38% of those with MACE.
Endomyocardial bx is the gold standard for diagnosis.
PET /CT can also show cardiac inflammation.
MRI and bx concordance: 35 % if ICI myocarditis, 94% if viral myocarditis
Use of combination check point ie ipi nivo increases risk of myocarditis
Front line: IV methyl prednisolone 1 mg/kg bwt--> 3 days, improving --> Prednisone 1 mg/kg bwt, slow taper.
Not improving--> tocilizumab, MMF, supportive care as needed ECMO, pacemaker, endomyocardial bx, cardiac cath
uncomplicated IR-pericarditis with oral prednisolone and colchicine :500 μg twice daily
ICI myocarditis is a reason to permanently discontinue the drug.
Other aggressive therapies- IVIG, plasmapheresis, abatacept
Question: What immune related toxicity should you hold the check point inhibitor for grade 1 toxicity?
Ans- suspected cardiac toxicity. However if grade 1 a or 1 b ie inflammatory infiltrate without necrosis, no need for immune suppression. Good long term prognosis.
C4d pericapillary staining may be the reason plasma pheresis is effective.
Additional rx considerations:
1. Abatacept CTLA 4 agonist
2. Alemtuzumab- CD 52Ab, used in cardiac allograft rejection
3. IVIG
4. Infliximab in steroid refractory- use with caution if CHF, 5 mg/kg rather than 10 mg/kg bwt
What is the overlap or 3 M syndrome?
Myocarditis had 44% overlap with myositis and myasthenia gravis
-high dose steroids in myasthenia can lead to need for intubation and worsening resp function
-troponin T remains higher for longer if they also have myositis. Use steroid sparing immunomodulatory therapy earlier on.
Myocarditis does not relapse typically but myositis can relapse.
CV risk factors (cholesterol profile, blood pressure, HbA1c) and optimal CV risk factor management is recommended in all cancer survivors who have received ICI treatment and have a prognosis of >2 years.
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