Acute Myocardial Infarction Due to Nonbacterial Thrombotic Endocarditis in Advanced Intrahepatic Cholangiocarcinoma: A Case Report

Introduction

While the most common mechanisms of acute myocardial infarction (AMI) are plaque rupture, plaque erosion, and calcified nodules, other less common causes such as coronary embolism must be considered [1]. Coronary embolism accounts for approximately 2.9% of AMI cases and is often associated with atrial fibrillation or cardiomyopathy [2]. However, malignancy-associated thromboembolic events have also been reported. Nonbacterial thrombotic endocarditis (NBTE) is a disease characterized by the formation of sterile thrombotic vegetations composed of fibrin and platelets on heart valves without infection, leading to systemic embolism [3]. The primary underlying conditions are hypercoagulable states such as malignancy, collagen diseases, and antiphospholipid syndrome. Transesophageal echocardiography is considered useful for diagnosis [4]. Treatment centers on anticoagulation therapy, and control of the underlying disease determines prognosis [5]. AMI caused by NBTE mechanisms is rare, and cases progressing to cardiac rupture are exceedingly uncommon. Here, we report the first documented case of AMI complicated by cardiac rupture due to coronary thromboembolism caused by NBTE, secondary to intrahepatic cholangiocarcinoma.

Case Report

PATHOLOGICAL AUTOPSY FINDINGS:

A total of 170 mL of blood was found in the pericardial cavity. The left ventricular apex showed extensive myocardial necrosis, with focal perforation evident within the necrotic region (Figure 3A, 3B). No overt plaque rupture was observed, and stenosis of the epicardial coronary arteries was moderate (approximately 50–60%). However, thrombotic occlusion was identified in both the epicardial coronary arteries and intramyocardial microvasculature within the distal territory of the left anterior descending artery (Figure 4A, 4B), which perfuses the left ventricular apex. Numerous occluded microvessels were noted within the necrotic myocardial tissue. In the capillaries, widespread organized thrombi and marked reactive hyperplasia of endothelial cells were also observed. In one region, an embolus composed of thrombotic material and tumor cells was identified. Immunohistochemical staining revealed that the tumor cells within the embolus were positive for cytokeratin 7 (CK7), consistent with the immunophenotype of the primary intrahepatic cholangiocarcinoma described later (Figure 5A, 5B). In addition, multiple microscopic metastatic lesions were detected within the pulmonary veins. No intracardiac shunts such as patent foramen ovale or pulmonary arteriovenous malformations were detected.

Furthermore, microscopic examination revealed sterile, friable vegetations on the aortic, mitral, and tricuspid valves. These vegetations were composed of fibrin and platelets, without evidence of inflammation or microorganisms, consistent with NBTE as shown in Figure 6A and 6B. The vegetations were small but diffusely distributed across all 3 valves. Histological features of the valvular vegetations were identical to those of the coronary thrombi, consisting of fibrin and platelets. No signs of infective endocarditis were observed. Given the distribution of the vegetations and their histological features, NBTE was definitively diagnosed.

The primary lesion was revealed upon autopsy examination: located in the liver, it consisted of multiple tumors predominantly located in the right lobe but also involving the left lobe. Histopathological examination revealed intrahepatic cholangiocarcinoma, with tumor cells positive for CK7 on immunohistochemistry. The tumor demonstrated infiltration into portal veins, lymphatic vessels within the Glisson’s sheath, and bile ducts. Metastatic dissemination was also evident in the gallbladder, left adrenal gland, bilateral lungs, meningeal vessels, retroperitoneal lymph nodes, peripancreatic lymph nodes, and bilateral hilar lymph nodes.

Based on the autopsy findings, the immediate cause of death was cardiac tamponade due to left ventricular rupture. The underlying cause was AMI precipitated by extensive coronary thromboembolism, secondary to advanced intrahepatic cholangiocarcinoma.

Discussion

Aseptic vegetations were found on the aortic, mitral, and tricuspid valves, consistent with a pathological diagnosis of NBTE. NBTE typically results from a hypercoagulable state, a condition frequently associated with advanced adenocarcinomas [6], including intrahepatic cholangiocarcinoma [7–9]. Although rare, NBTE has been reported to cause thromboembolic events in various organs.

We report a fatal case of AMI caused by NBTE-related coronary embolism in a patient with advanced intrahepatic cholangiocarcinoma. Several cases of NBTE-related coronary embolism have been reported recently [10,11]. In most of these cases, the diagnosis was made clinically, based on echocardiographic findings. On the other hand, in the present case, NBTE-related coronary embolism was pathologically confirmed at autopsy, which provides stronger evidence for the causal relationship between NBTE and coronary occlusion. Furthermore, this case is exceptionally rare, as the first documented instance of NBTE leading to AMI and subsequent cardiac rupture, secondary to intrahepatic cholangiocarcinoma.

NBTE should be suspected when multiple embolisms are observed without signs of infection [4]. Transesophageal echocardiography has the highest sensitivity for diagnosis [5]. In general, once NBTE is diagnosed, long-term anticoagulation such as heparin administration [12] and active treatment of underlying conditions are key.

Although cardiac involvement in malignancy is known to occur through direct invasion, detailed pathological evidence of lymphatic spread, or hematogenous dissemination, remains limited [13]. In this case, pulmonary metastases were identified on CT imaging, and numerous microscopic metastatic lesions were observed in the pulmonary veins at autopsy. Metastases to regional lymph nodes, including the hilar lymph nodes, were also confirmed. These findings suggest that tumor cells had infiltrated into the pulmonary veins via lymphatic or hematogenous spread, and may have entered the left heart circulation. However, a metastatic embolus composed of tumor cells and thrombotic material was observed at only a single site within the coronary microvasculature. The embolus was unlikely to have been large or extensive enough to cause the widespread myocardial infarction seen in this case. Additionally, a few tumor cells were identified in the myocardium, but there was no histological evidence of myocardial infiltration sufficient to induce infarction. Thus, the myocardial infarction in this case was more likely caused by NBTE rather than tumor embolism or direct tumor invasion.

This case underscores the importance of considering NBTE as a potential etiology in cancer patients presenting with unexplained AMI, particularly in the absence of traditional cardiovascular risk factors. Early recognition of this pathophysiological mechanism may be essential for timely diagnosis and intervention, and for preventing fatal outcomes such as cardiac rupture.

Conclusions

We report the first documented case of AMI with cardiac rupture caused by coronary thromboembolism secondary to NBTE in a patient with advanced intrahepatic cholangiocarcinoma. This case emphasizes the need for increased clinical awareness of NBTE in patients with advanced cancer.