Stewart R, Morrow M, Hammond SA, et al.Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody Cancer Immunol Res 31052C10622015 [PubMed] [Google Scholar] 11. unique antigen-bound serum autoantibodies, highlighting a potential role for Th1-cell-dependent induction Praziquantel (Biltricide) of autoantibody production in irAEs. CASE Initial Presentation A 67-year-old woman presented to the emergency department with severe sudden-onset chest pain 2 days after receiving the 12th cycle of PD-L1 inhibitor (48 weeks after starting ICI) for the treatment of metastatic urothelial carcinoma (Fig ?(Fig1A).1A). She had no previous history of cardiovascular disease but was an ex-smoker with a 20 pack-year history. She had no other known cardiovascular risk factors and no previous history of autoimmune disease. She was previously treated for remote triple-negative right-sided breast invasive ductal carcinoma with surgery; cyclophosphamide, epirubicin, and 5-fluorouracil chemotherapy; and radiation. Subsequently, she was diagnosed with multifocal transitional cell carcinoma of the kidney 2 years before this emergency department admission and was treated with nephroureterectomy and pelvic node dissection. PD-L1 inhibitor was commenced after subsequent investigations revealed intra-abdominal metastasis. Her treatment was largely uneventful, with only a noted diagnosis of hypothyroidism after receiving the 7th cycle of PD-L1 inhibitor, which was treated with hormone replacement therapy without interruption of ICI. Open in a separate window FIG 1. Cardiac laboratory data during initial immune checkpoint inhibitorCassociated myocarditis and at recurrence reveal elevated brain natriuretic peptide (BNP) but not troponin I. The course of clinical presentation, diagnostic workflow, and key timepoints of immunosuppressive initiation (A). Each box represents a day since the initial clinical presentation with the break in the timeline representing the recurrent presentation. The initial presentation(Continued). was marked by strikingly elevated troponins Praziquantel (Biltricide) (B), elevated BNP (C), and by low ejection fraction (D). By contrast, Praziquantel (Biltricide) the recurrent presentation, although displaying low ejection fraction and elevated BNP (C and D), did not display markedly elevated troponin levels (B). ACE, angiotensin-converting enzyme; ANGIO, angiogram; CC, cardiology clinic; CMR, cardiovascular magnetic resonance; ECG, electrocardiogram; ECHO, echocardiogram; ED, emergency department; IV, intravenous; LMWH, low-molecular-weight heparin. Although the patient was hemodynamically stable, cardiac laboratory investigations revealed high-sensitivity troponin I levels were elevated at 4,114 ng per L (reference range, 26 ng per L), and brain natriuretic peptide levels (BNP) were elevated at 2,275 pg per mL (reference range, 100 pg per mL) (Figs ?(Figs1B1B and ?and1C,1C, Data Supplement). Electrocardiogram (ECG) displayed diffuse ST elevation. She was transferred to the catheterization lab, and coronary angiogram revealed patent coronary arteries. 2D echocardiogram demonstrated severely decreased biventricular systolic function, with a left ventricular ejection fraction (LVEF) of 20%, right ventricular (RV) fraction area change of 22%, and a left ventricular (LV) thrombus (Fig ?(Fig1D1D and Video 1). With a history of ICI treatment, together with clinical, ECG (Fig ?(Fig2A),2A), and imaging findings, a diagnosis of ICI-associated myocarditis was made. Treatment with intravenous methylprednisolone (2 mg/kg/d), furosemide, beta-blocker, angiotensin-converting enzyme inhibitor, and Praziquantel (Biltricide) low-molecular-weight heparin was initiated. Cardiovascular magnetic resonance (CMR) imaging confirmed severe biventricular dysfunction, mild pericardial effusion, and demonstrated late gadolinium Praziquantel (Biltricide) enhancement (LGE) involving the basal and apical segments predominantly in a subepicardial distribution (Video 2, Data Supplement). Follow-up ECG remained abnormal with low-voltage QRS complex as well as persistent ST elevation (Fig ?(Fig22B). Open in a separate window FIG 2. Results of ECG (initial and recurrence) as well as immune effects in cardiac muscle at recurrence. ECG at the time of initial presentation shows sinus tachycardia and diffuse ST elevation (A). Follow-up ECG after initial presentation shows persistence of ST elevation and development of low-voltage ECG (B). ECG one month after initial presentation shows low-voltage ECG and development of right bundle branch block (RBBB, C). ECG at recurrence displayed persistence of low-voltage QRS and RBBB without new Rabbit polyclonal to CD24 (Biotin) acute changes (D). Myocardial biopsy (E) demonstrated mixed inflammation (yellow arrow) with some associated myocyte damage (orange arrow) and some healing injury (green star) near relatively uninvolved myocardium (cyan star); higher-power image is also shown (F); hematoxylin and eosin staining; digital acquisition; scale bars as shown = 100 m. Immunohistochemistry demonstrated that most of this infiltrate was composed of CD3-positive T cells (G, stained cells in brown).