Myocarditis. Dr. Lewis Au Clinical Research Fellow (melanoma) Royal Marsden Hospital

Transcription

1 Myocarditis Dr. Lewis Au Clinical Research Fellow (melanoma) Royal Marsden Hospital

2 Mrs JR (1) 78yo lady Depression on citalopram Otherwise no other active health problems, ECOG 0 Sept 2015: 25mm neurotropic melanoma (right cheek) Right maxillectomy and flap repair Initially presumed to be a malignant peripheral nerve sheath tumour, but final histology revealed melanoma R1 resection deep margin BRAF/NRAS/KIT wild type Oct 2015: MRI-B and PET-CT restaging no distant disease Nov 2015-Jan 2016: 60Gy in 30 fractions adjuvant RTx

3 Mrs JR (2) Aug 2016: Relapsed disease noted on surveillance PET-CT (anterior ribs, L4 and liver) Aug 2016: Combination ipilimumab / nivolumab (Cycle 1 of 4 ) CMR on PET-CT after 4 cycles; PR on CT (bone sclerosis remaining) Toxicities: G1 fatigue, hypothyroidism (TSH up to 60, T4 6.4 (LLN 9.1) after initial subclinical presumed thyroiditis (suppressed TSH, normal T4) Aug 2016: Developed altered bowel habit & abdo pains Treated for H. pylori prior to this normal UGI & flex sig at RMH; CLO test normal Dec 2016: Maintenance nivolumab commenced June (26 th ) 2017: Cycle 16; maintained PR on CT July (4 th ) 2017 nausea, generally unwell, referred to A&E Pituitary work-up unremarkable Chest heaviness 1 hour after eating, relieved by vomiting, nausea predominant symptom July (21 st ) 2017: ECG abnormal; Admitted to RMH for further investigation

4 Mrs JR (3)

5 Progress (1) New ECG changes?myocarditis O/E BP 130/80, HR 89, afebrile, 99% RA sats Investigations Electrolytes Troponin: 53 (1-40 normal range) BNP 4375 (<250) Referral to cardiology Bedside echo: Good LV function with very mild apical hypokinesia. RV non dilated, normal function. MAPSE 1.6cm. No valvular pathology and no pericardial effusion. Admission plan: Serial ECG Urgent cardiac MRI Aspirin 300mg then 75md od Commence steroids if further ECG changes, troponin rise, or clinical deterioration

6 Day 2 ECG stable V1-V4 T-wave inversions Troponin 35 (decreased) Progress (2) Ongoing nausea (MRI-brain NAD), on syringe driver anti-emetics Day 3 Worsening diarrhoea, 6 times a day For sigmoidoscopy, await cardiac MRI Commenced IVMP 2mg/kg Day 4 (July 26 th, 2016) Cardiac MRI (at Royal Brompton): STIR imaging: Increased signal intensity in all apical segments, mid septum and mid anterior wall. Normal LV volumes and ejection fraction. No LVH Normal RV volumes and ejection fraction. Myocardial oedema/inflammation in the apical segments, mid septum and midanterior wall. No myocaridal infarction, infiltration or convincing fibrosis CMR findings would be in-keeping with acute myocarditis or resolving Tako-tsubo syndrome without residual overt myocardial necrosis

7 Cardiac MRI (July 26 th )

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9 Progress (3) Day 5 Symptomatic improvement including diarrhoea Continue IVMP at 1mg/kg (60mg) Ramipril 1.25mg to be titrated according to BP Daily ECG, weekly troponin and BNP Day 9 (July 31 st, 2016) Weaning dose of steroids, on IVMP 60mg G1 hepatitis (ALT 73, ULN 40) Day 12 Progressive worsening of LFT s (peak ALT 111, AST 98) IVMP escalated (2mg/kg 3mg/kg 500mg) USS liver, hepatitis screen Day LFTs stabilised (ALT 97), troponin 34 (0-40) Addition of mycophenolate mofetil 1g BD Ongoing cardiology input Day 20 With improvements in LFTs, oral prednisolone 100mg od Ongoing blood test, steroid titration, for repeat cardiac MRI

10 Repeat cardiac MRI (Sep 12 th ) STIR-T2 images: There is mild diffuse increase in signal intensity in mid septum, mid anterior wall and all apical segments (not as prominent as the previous study) Suggests partial resolution of the mycardial oedema/inflammation

11 Now: Progress (4) Continues steroid wean, ongoing mycophenolate ALT normalised Restaging scan shows ongoing response Remains off nivolumab Clinically well, continues on ramipril 2.5mg bd & aspirin