Nonbacterial Thrombotic and Subclinical Myopericarditis in a Patient with Advanced Rectal Cancer Muzzammil Ali (Foundation Doctor) Birmingham Heartlands Hospital, Heart of England Foundation Trust

To investigate this, a transthoracic echocardiogram (TTE) was performed. BACKGROUND This showed a showed a 13x8mm mobile mass on the anterior leaflet with associated mitral regurgitation (Figure 6). The left ventricular (LV) Nonbacterial Thrombotic Endocarditis (NBTE) is rare and is most ejection fraction was 57%. There were no stigmata of 3 commonly diagnosed on post-mortem. It is characterised by the (IE) and the modified Duke-criteria were not satisfied. Because all blood deposition of aseptic thrombi on normal cardiac valves along the lines of cultures taken were persistently negative and there was no prior history of valve closure. The commonly affected valves are the aortic and mitral. In antibiotic use, investigation was turned towards screening for culture- 80% of cases, malignancy is the underlying aetiology (Figure 1)1. There negative endocarditis (CNE). Serological testing for Bartonella sp and C. 4 are no pathognomonic features or diagnostic criteria as patients are burnetti, two of the commonest fastidious causes of CNE , was performed. usually asymptomatic. The most common clinical presentation is sudden Both these screens were negative. neurological deficit as a result of an embolic stroke1. Other sites of embolization include the spleen and the kidneys1.

Figure 2: CT-Thorax-abdomen-pelvis revealing a large rectal mass (*) with areas of local Figure 8: Rectal biopsy showing a well-differentiated squamous cell carcinoma; 1: Normal ENDOTHELIAL DAMAGE perforation evidenced by pre-sacral gas outside of the bowel wall (arrows) epidermis composed of uniform and regularly-spaced squamous cells; 2: Infiltrative island of • Circulang (TNF-α, IL-1) released from malignant squamous cells with enlarged atypical nuclei, mitotic activity and disorder indicative of HYPERCOAGULABLE ssue squamous cell carcinoma STATE OF MALIGNANCY TURBULENT BLOOD • Turbulent blood flow FLOW • Tissue factor producon and • Endothelial damage expression by normal • Platelets brought into and malignant cells close contact with • Procoagulant acvity endothelium expressed by normal • Prolonged acon of host ssues e.g. clong factors platelets, endothelial • Local pockets of stasis cells and monocytes

STERILE Figure 6: Initial TTE; A. 13x8mm mobile mass on the anterior mitral valve leaflet (arrow) THROMBUS which lies between the left ventricle (LV) and left atrium (LA); B. Large regurgitant jet of blood (blue) from the LV to the LA indicative of mitral regurgitation

A cardiac-MRI was subsequently performed which revealed features Figure 1: Pathophysiology of NBTE by applying Virchow's Triad. The three factors of Figure 3: CT-Thorax-abdomen-pelvis revealing a large focus of hypodensity in the left renal consistent with myopericarditis of both the left and right ventricles (Figure hypercoagulability, endothelial damage and abnormal blood flow in advanced parenchyma (*) indicative of left renal infarction 7). This therefore identified the cause for the positive cTnI. However, a Figure 9: TTE 4 weeks after the initiation of LMWH; A. Non-existence of the previous malignancy contribute to the formation of a sterile vegetation on a normal cardiac valve subsequent workup for myopericarditis was unremarkable. thrombus with a normally functioning mitral valve; B. Mild mitral regurgitation (blue)

Myopericarditis describes a primary pericarditic syndrome with minor myocardial involvement. Viral infections are the most common cause. Most cases present subclinically without a defined aetiological agent LEARNING POINTS found. The diagnosis is based on elevated cardiac markers in the absence of another cause, and evidence of myocardial on cardiac 1. Most cases of Myopericarditis present subclinically without a defined MRI, or new left ventricular (LV) systolic dysfunction on aetiological agent. The diagnosis is based on elevated cardiac markers echocardiography2. There are a variety of atypical ECG changes and evidence of myocardial inflammation on imaging. There are a possible. Treatment is largely conservative. variety of ECG changes possible. Treatment is largely conservative.

2. When a valvular mass is found on TTE, IE must first be ruled out by applying the modified Duke-Criteria. If blood cultures remain negative, CNE must then be ruled out by considering prior antibiotic exposure, Figure 4: MRI-abdomen-pelvis illustrating the large invasive rectal mass staged as T4N2M0 and intracellular fastidious bacteria such as Bartonella, sp, C burnetti CASE PRESENTATION Figure 7: Cardiac-MRI showing global late gadolinium enhancement within the anterior, mid and Tropheryma whipplei4. If CNE is ruled out, this effectively indicates As part of the pre-operative assessment for a palliative de-functioning and apical left ventricular (LV) segments indicative of myopericarditis that said vegetation is sterile. A 57-year-old gentleman presented to the surgical assessment unit with end-colostomy, the ECG showed T-wave inversion in the anterolateral rectal . He had a 6-week history of painless rectal bleeding, frequent leads (Figure 5). Troponin-I (TnI) was positive at 1437ng/L without any Differentials of sterile cardiac masses were then considered. The background 3. Malignancy is associated with a significant hypercoaguable state that bowel motions, and 45 kilograms of weight loss. He was an active clinical features of myocardial . His second TnI was 871ng/L. of advanced malignancy in the absence of systemic infection made it possible increases the risk of thromboembolism. In cancer patients, cardiac smoker. On examination he had a tender circumferential exophytic for a diagnosis of NBTE to be made; this mass was therefore a sterile vegetations in the absence of systemic infection provide strong rectal mass with associated bilateral inguinal . thrombus. Therapeutic low molecular weight heparin (LMWH) was evidence to diagnose NBTE. Definitive therapy includes antitumour commenced. There was little change in his bleeding. therapy and indefinite systemic anticoagulation with unfractionated or 1 Blood tests revealed a microcytic anaemia with an associated low molecular weight heparin . Vitamin K antagonists such as warfarin 1 inflammatory picture; haemoglobin 102g/L, mean corpuscular volume Post-operative histopathological analysis of the rectal biopsy showed well- are less effective in preventing thromboembolic recurrence . 77.2fL, white cell count 13.02x109/L, neutrophils 10.96x109/L, and C- differentiated rectal squamous cell carcinoma (Figure 8). reactive protein 217mg/L. Biochemistry and liver function tests were unremarkable. Discharge planning and treatment effect warranted a repeat TTE four weeks after starting LMWH. This showed that the mitral valve thrombus was no REFERENCES A CT-thorax-abdomen-pelvis showed a large invasive rectal mass with longer present, and that there was only trivial mitral regurgitation (Figure 9). associated local bowel perforation (Figure 2), and foci of left renal 1. El-Shami K, Griffiths E, Streiff M. Nonbacterial thrombotic endocarditis in cancer patients: pathogenesis, diagnosis, and There was no clinical evidence to suggest embolization. The patient was treatment. Oncologist 2007; 12:518 infarction (Figure 3). MRI staging was T4N2M0 (Figure 4). discharged on lifelong LMWH. 2. Imazio M, Trinchero R. Myopericarditis: Etiology, management, and prognosis. Int J Cardiol 2008; 127:17. 3. Horstkotte D, Follath F, Gutschik E et al. Guidelines on prevention, diagnosis and treatment of infective endocarditis executive summary; the task force on infective endocarditis of the European society of cardiology. Eur Heart J. 2004 Feb; Figure 5: Pre-operative ECG with diffuse T-wave inversion in the anterolateral leads 25(3):267-76 4. Tattevin P. Update on blood culture-negative endocarditis. Med Mal Infect. 2015 Jan-Feb;45(1-2):1-8. doi: 10.1016/ j.medmal.2014.11.003