Abstract
Background
Thrombus in transit through a patent foramen ovale (PFO) is a rare clinical entity that can be associated with concurrent pulmonary embolization and lead to cryptogenic stroke.
Case Summary
A 56-year-old patient presenting with shortness of breath and chest pain was diagnosed with large bilateral pulmonary emboli. Computed tomography demonstrated thrombus in the right atrium. Transthoracic echocardiogram demonstrated a large burden of thrombus in transit trapped in a PFO. After multidisciplinary discussion, emergency surgical thrombectomy and PFO closure were carried out successfully.
Discussion
There are no current guidelines for management of a thrombus of this nature, but potential options include anticoagulation, thrombolysis, and mechanical or surgical thrombectomy. Previous case reviews have found that surgical embolectomy in low-moderate risk surgical patients resulted in fewer embolic events and a lower mortality rate. Compelling imaging of this phenomenon is presented.
Take-Home Messages
Management decisions by a multidisciplinary team need to be on an individual case-to-case basis considering individual bleeding risk, surgical risk, and available expertise. Surgical thrombectomy with PFO closure has shown in a review of previous case studies to have an overall lower associated mortality and embolic risk.
Key Words: cryptogenic stroke, patent foramen ovale, pulmonary embolism, surgical embolectomy, transit thrombus
Visual Summary
History of Presentation and Past Medical History
A 56-year-old man was referred with a unilateral swollen left leg, shortness of breath, and right-sided pleuritic chest pain. He reported intermittent episodes of slurred speech, unsteady gait, and presyncopal episodes while driving. After recent initiation of amlodipine for hypertension, he developed leg swelling that progressed over 2-3 weeks and affected the left leg more than the right. At presentation, he demonstrated sinus tachycardia and oxygen saturation of 97% on room air. He had bilateral pitting edema affecting the left leg more than the right. Systemic examination was otherwise unremarkable.
Past Medical History
His past medical history included obesity (with a current weight of 146 kg) and type 2 diabetes mellitus. He had recently been diagnosed with hypertension and started on amlodipine. He was a former smoker.
Differential Diagnosis
The differential diagnosis was complex in this case. The initial suspicion was for deep vein thrombosis (DVT) associated with a pulmonary embolism (PE), but this did not explain the unusual neurologic symptoms. The differential diagnosis included pneumonia, pneumothorax, arrhythmia-related presyncope, transient ischemic attack, and congestive cardiac failure.
Investigations
A D-dimer level was elevated at 7.01 ug/mL (normal range <0.5 ug/mL). A computed tomography (CT) pulmonary angiogram showed a heavy burden of bilateral emboli involving both the right and left main pulmonary arteries, and there was a suggestion of right heart dysfunction (Figure 1). A further CT thorax/abdomen/pelvis to identify possible underlying malignancy visualized thrombus in the right atrium (Figure 2) along with thrombus in both the right common femoral vein and right external iliac vein. He was admitted under the respiratory team in a district general hospital. He was commenced on therapeutic enoxaparin for a period of 8 days, until transfer to this institution.
Figure 1.
Bilateral Pulmonary Emboli in the Pulmonary Arteries on Computed Tomography Pulmonary Angiogram Imaging
Figure 2.
Thrombus in Right Atrium on Computed Tomography Imaging
It can be appreciated that the large burden of thrombus emanating from the patent foramen ovale (PFO) within the right atrium, corresponding to the surgical findings.
An urgent transthoracic echocardiogram was performed showing thrombus in the right atrium bridging the intra-atrial septum into the left atrium, with a dilated right ventricle (RV) and preserved systolic function. Subsequent transesophageal echocardiography (TEE) (Figures 3A to 3C) demonstrated a large burden of thrombus caught in a patent foramen ovale (PFO) tunnel, measuring 8 × 2 cm in the right atrium, 4 × 2 cm in the left atrium. Brain CT raised suspicion of a subacute infarct in the right temporal area, although a brain magnetic resonance imaging subsequently confirmed this as a chronic lacunar infarct.
Figure 3.
Large Burden of Thrombus Trapped in Tunnel
(A to C) Transesophageal imaging of thrombus in transit through patent foramen ovale. C demonstrates a superior view in 3-dimensional of the atria separated by the interatrial septum with thrombus in the left atrium and a very large, organized thrombus in the right atrium.
Management
After the investigations as discussed earlier, the patient was transferred urgently to our institution for detailed review and consideration of cardiac surgery. On discussion with hematology and further investigations, there was no evidence of inherited forms of hypercoagulability. Enoxaparin was discontinued, and he was commenced on IV heparin. His case was discussed at a multidisciplinary meeting with input from cardiology, cardiothoracic surgeons, hematology and interventional radiology. Multiple treatment strategies were considered, including continuing intravenous heparin infusion, thrombolysis, surgical thrombectomy, and catheter-guided thrombolysis. All options were considered high risk, but the decision was made to proceed to emergency surgery. This was based largely on the fact that there had been no meaningful resolution with low molecular-weight heparin and the size of the thrombus visualized on TEE.
Routine aortic and bicaval cannulation was carried out with particular care under TEE guidance when cannulating the right atrium so as not to dislodge any part of the thrombus. The right and left atria were opened. Initially, the left atrial part of the clot was removed; subsequently, the right atrial part of the clot was removed together with excision of the margins of the PFO, and the interatrial defect was repaired with a pericardial patch. He remained in cardiac intensive care for 3 days and had an uncomplicated postoperative recovery with hospital discharge following a short inpatient stay (Figure 4A). Demonstrating a large burden of thrombus in the right atrium (to the right of the image near the venous cannula) and thrombus in the left atrium (to the left of the septum) (Video 1, Video 2, Video 3).
Figure 4.
Large Burden of Thrombus Trapped in Tunnel
(A) Large burden of thrombus in the right atrium, to the right of the image near venous cannula, and thrombus in the left atrium, to the left of the septum. (B) Thrombus from the right atrium on the left of the image and left atrium, on the right of the picture, correlating very closely with what was visualized on transesophageal echocardiography (TEE), measuring respectively 3 × 7 × 3 mm and 62 × 15 × 9 mm. Histology showed portions of fibrin and fresh hemorrhage with minimal evidence of organization.
Histologic examination of the thrombus revealed 2 samples measuring respectively 3 × 7 × 3 mm and 62 × 15 × 9 mm. Histology showed portions of fibrin and fresh hemorrhage with minimal evidence of organization. Appearances were felt to be consistent with the clinical history, and no additional pathologic process was identified (Figure 4B). Demonstrating thrombus from the right atrium on the left of the image and left atrium, on the right of the picture, correlating very closely with what was visualized on TEE.
Repeat CT imaging of the distal lower limb thrombus showed no change in size. After discussion with Hematology, placement of an inferior vena cava filter was not felt to be of clinical benefit. It was felt here that there had only been a very short period of interruption of anticoagulation, and there is some concern about the longer-term filter-related thrombosis and retrieval failure. Given that surgery was successful, the septum was now intact, and therapeutic anticoagulation was established, it was felt the justification for placing and leaving in place a filter was unclear.
Outcome and Follow-Up
At outpatient clinic follow-up, the patient has been well with only mild shortness of breath. There have been no signs of RV impairment or pulmonary hypertension on follow-up imaging. He remains on lifelong anticoagulation. He has subsequently been diagnosed with severe obstructive sleep apnea; now thought to be the likely cause of his episodes while driving.
Discussion
This case demonstrates the rare phenomenon of a large thrombus in transit through a PFO with associated PE, originating from a DVT. A PFO is present in about 25% of the general population1 and is associated with cryptogenic stroke and systemic embolization.2 Thrombus in transit is defined by a thrombus attached to any structure in the right heart and has a very high associated mortality risk.3 Embolization of these thrombi to the pulmonary arteries may cause PE or paradoxical embolization via right-to-left intracardiac shunts, most commonly a PFO, leading to systemic embolization.4 Detection of these thrombi on cardiac imaging is very uncommon due to the transient nature of their passage through a PFO.
The risk of paradoxical embolization of these thrombi if left untreated is high, with an associated mortality risk up to 66%.5 The resultant embolization can manifest clinically as a potentially severe ischemic stroke. The patient in this case had an established cerebral infarct, the timing of which is uncertain. Previous analysis has suggested that a PFO is involved in between 66% and 80% of cryptogenic stroke in patients under 60 years old.6
PFO closure is increasingly considered an integral part of secondary prevention in patients under the age of 60 years with cryptogenic ischemic stroke and a PFO. A meta-analysis of 6 large randomized controlled trials comparing medical therapy versus closure found a moderate but clinically significant reduction in recurrence of ischemic stroke with PFO closure. Developments in identifying and classifying high-risk features of a PFO continue, with the PASCAL (Patent Foramen Ovale-Associated Stroke Causal Likelihood) and RoPE (Risk of Paradoxical Embolism) risk stratification scores being increasingly adopted to guide management decisions.7 Novel imaging techniques have been investigated, including a recent study using high-resolution optical coherence tomography to identify microthrombi within a PFO, which demonstrated a high frequency of in situ thrombus in patients with ischemic stroke.8
Management of these rare transit thrombi is limited to case studies and small case series, resulting in a scarcity of optimal treatment recommendations for this complex presentation. Impending embolization necessitates rapid multidisciplinary treatment decisions to be made on an individualized case-to-case basis.9 Potential therapeutic options for the thrombus in transit included anticoagulation, thrombolysis, and mechanical or surgical embolectomy.10 As was shown in this case, 8 days of therapeutic anticoagulation with enoxaparin had resulted in no reduction in the size of the large thrombus, and if continued without surgical intervention, could have resulted in catastrophic sequelae of ischemic stroke, peripheral emboli, or sudden death. Anticoagulation, however, may be the only option if a patient has multiple comorbidities, is at high surgical risk, or refuses an invasive strategy.10 In this case, following review of the TEE images, it was felt that the thrombus had a significantly “organized” appearance, suggesting it had formed over weeks and in that context a form of “thrombus removal” was favored.
The authors believe that thrombolysis is associated with a high morbidity and mortality risk and is to be reserved for patients with hemodynamic instability, usually secondary to massive PE.11 In this case, this patient had extensive bilateral PEs on CT imaging but remained hemodynamically stable. It should also be noted that he was hypertensive, thereby increasing the risk of iatrogenic cerebral hemorrhage. The European Society of Cardiology 2019 guidance on PE recommends transthoracic echocardiogram for risk stratification in patients with acute PE, assessing for RV dysfunction and presence of PFO.11 Acute PE can lead to increased right heart pressures, resulting in right-to-left shunting through a PFO, increasing the risk of paradoxical emboli.12 At present, there are no clinical guidelines on the management of patients with concurrent PE and a PFO. Mechanical thrombectomy has shown in one case series to be a potentially safe and effective treatment for these patients, reducing mean pulmonary artery pressures and theoretically reducing the risk of right-to-left shunt, but further investigation is needed.13 It was felt in this case a definitive solution was required and mechanical thrombectomy was somewhat speculative, with concern about embolization, particularly to the systemic circulation, and inadequate removal of all the thrombus.
Surgical embolectomy with closure of the PFO is the most common treatment option for patients with a thrombus in transit at low-to-moderate surgical risk. If there is a large burden of PE, pulmonary thromboendarterectomy is done concurrently intraoperatively.12 A recent systematic review of 194 patients from publications between 1991 and 2015 found that surgical management of thrombi in transit resulted in fewer embolic events and a lower mortality risk, compared with anticoagulation or thrombolysis. However, a caveat to these findings was that thrombolysis should be considered in those presenting with hemodynamic instability, owing to heightened operative risk associated with the hemodynamic collapse associated with PE.12 In this case, a patient was presented and rapidly investigated, and although hemodynamically stable, was in a precarious position. The clinical conundrum therefore was a stable patient with a significant burden of thrombus in the iliofemoral system, the right atrium and the left atrium, trapped via the PFO. An old cerebral infarct and recent PE were demonstrated. After expedient investigation and multi-disciplinary meeting collaboration, it was felt the safest, most predictable outcome could be achieved by early surgery with lifelong anticoagulation thereafter (Table 1). The quality of the images presented permitted clarity as to the burden of thrombus, its position in the heart, and permitted safe bicaval cannulation, institution of cardiopulmonary bypass, and effective cardiac surgical removal.
Table 1.
Timeline Summary
| 1 Month Preadmission | Diagnosis of Hypertension and Commenced on Amlodipine. Developed Unilateral Leg Swelling, Worsening Over the Next 2-3 wks. Developed Worsening Shortness of Breath |
|---|---|
| D 1 | Contacted a GP out of hours with unilateral left leg swelling, shortness of breath, and right pleuritic chest pain. Referred to accident and emergency department. D-dimer elevated. CT pulmonary angiogram showed large bilateral pulmonary emboli. Commenced on therapeutic subcutaneous low-molecular-weight heparin and admitted under respiratory team. |
| D 4 | Transthoracic echocardiogram showed large thrombus in transit from right to left atrium via a PFO. Urgent cardiology opinion sought. |
| D 5 | CT brain showed a potential subacute infarct. MRI head subsequently showed a chronic lacunar infarct. |
| D 6 | Transesophageal echocardiogram confirmed a large 8 × 2 cm thrombus in the right atrium with a 4 × 2 cm portion in the left atrium through a PFO. |
| D 7 | Transferred to tertiary center for consideration of emergency cardiac surgery. Commenced on IV heparin infusion. Multidisciplinary decision for surgery. |
| D 8 | Surgical embolectomy of interatrial clot and patch repair of PFO. |
| 7 mo postsurgery | Repeat transthoracic echocardiogram showed persistent mild dilatation of the right ventricle with preserved systolic function. Low probability of pulmonary hypertension. |
CT = computed tomography; GP = general practitioner; MRI = magnetic resonance imaging; PFO = patent foramen ovale.
Conclusions
A PFO acting as a conduit for thrombus formed within the venous system to pass into the systemic circulation is well recognized. It is rarely captured with imaging of such clarity. This case presents compelling imaging evidence of a thrombus in transit, likely embolized from a DVT, through a PFO with associated bilateral PEs. We emphasize the multispecialty but individualized management decisions in recognizing that it was unlikely that anticoagulation was going to be effective and, therefore, to reduce longer-term risk of significant embolization events, it was appropriate to proceed to emergency cardiac surgery
Take-Home Messages
-
•
Management decisions by a multidisciplinary team need to be on an individual case-to-case basis considering individual bleeding risk, surgical risk, and available expertise.
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•
Surgical thrombectomy with patent foramen ovale closure has been shown in a review of previous case studies to have an overall lower associated mortality and embolic risk.
.
Visual Summary.
Timeline of Events in the Diagnosis and Management of a Large Thrombus-in-Transit Through a Patent Foramen Ovale
CTPA = computed tomography pulmonary angiogram; MDT = multi-disciplinary meeting; PE = pulmonary embolism; PFO = patent foramen ovale; RV = right ventricle; TEE = transesophageal echocardiography; TTE = transthoracic echocardiography.
Funding Support and Author Disclosures
This study was supported in part by the Brave Hearts Northern Ireland paid the open access fee. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Acknowledgments
The authors thank Brave Hearts NI for their support in publishing this case.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For supplemental videos, please see the online version of this paper.
Appendix
Video in Theater Demonstrating Thrombus in Both Right and Left Atria, Attached at the Interatrial Septum via the PFO
Intraoperative 3-Dimensional Transthoracic Echocardiogram Showing Thrombus in Both Right and Left Atria, Attached at the Interatrial Septum via the PFO
2-Dimensional Transthoracic Echocardiogram Demonstrating Thrombus in Both Right and Left Atria, Attached at the Interatrial Septum via the PFO
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Associated Data
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Supplementary Materials
Video in Theater Demonstrating Thrombus in Both Right and Left Atria, Attached at the Interatrial Septum via the PFO
Intraoperative 3-Dimensional Transthoracic Echocardiogram Showing Thrombus in Both Right and Left Atria, Attached at the Interatrial Septum via the PFO
2-Dimensional Transthoracic Echocardiogram Demonstrating Thrombus in Both Right and Left Atria, Attached at the Interatrial Septum via the PFO