Pulmonary Embolism In-Transit Crossing the Mitral and Aortic Valve

Summary

Pulmonary embolisms crossing a patent foramen ovale constitute a life-threatening emergency. This protocol details the steps for the surgical management of a patient with a pulmonary embolism crossing a patent foramen ovale.

Abstract

Hemodynamically significant pulmonary embolisms (PE) in the pulmonary artery or those crossing a patent foramen ovale (PFO) can become life-threatening emergencies requiring immediate removal. While cases of surgical management for a PE crossing a PFO have been reported, there are no documented cases of a PE extending across both the mitral and aortic valves. A 38-year-old female with a medical history of obesity, depression, and thalassemia minor was transferred from an outside hospital with hemodynamic compromise due to a large PE. Transesophageal echocardiography (TEE) revealed a PE crossing the PFO, extending across the mitral valve, and traversing the aortic valve into the ascending aorta. Cardiopulmonary bypass (CPB) was initiated using standard aortic cannulation distal to the known clot, along with bicaval venous cannulation. The heart was arrested, and the right and left atria were opened in a transeptal fashion. The clot, which extended from the PFO through the mitral and aortic valves, was identified and removed en bloc. A small aortotomy was performed, confirming a clear aorta. An additional clot was found in the right atrium crossing the tricuspid valve and was subsequently removed. Finally, the pulmonary artery was opened, and the bulk of the clot burden was extracted, completing the embolectomy. The patient was successfully weaned from CPB without complications and was extubated within 24 h post-surgery. She underwent inferior vena cava filter placement and was discharged on post-operative day seven. Extensive pulmonary emboli are life-threatening emergencies that require immediate intervention. This study presents an extensive clot burden crossing the PFO, mitral valve, and aortic valve. Prompt surgical intervention is crucial to preventing severe complications such as stroke, myocardial infarction, respiratory failure, death, and long-term sequelae, including pulmonary hypertension and future strokes.

Introduction

A pulmonary embolism (PE) is often a life-threatening medical emergency that requires immediate medical intervention. In clinical practice, a PE is defined as a blood clot that has obstructed a patient's pulmonary circulation¹. A PE falls under the umbrella term of venous thromboembolism (VTE) and is a result of a deep vein thrombosis (DVT) released from the systemic circulation, traveling to the right side of the heart, and entering the pulmonary arteries². As of 2020, PE is the third most common cardiovascular cause of death in the United States, behind myocardial infarction and stroke^3,4. Two retrospective studies have recently reported the incidence of pulmonary embolism has risen from 1999 to 2018, particularly in young adults^5,6. While the current burden of PE within the United States is unknown, PE is known to be responsible for 5%-10% of hospital deaths⁷. It is important to note that the true prevalence is expected to be higher as PEs are often undiagnosed or diagnosed at autopsy⁸. This is due to many PEs presenting as asymptomatic in patients⁹. When symptomatic, the most common symptoms include dyspnea (81%), chest pain (56%), and syncope (26%)^3,10. Particularly, acute and/or massive PEs present with these symptoms.

An acute pulmonary embolism is characterized by its quick obstruction that causes sudden heart strain, with over 70% of deaths occurring within the first hour of onset¹¹. Virchow's Triad encompasses the most common risk factors for acute PE: endothelial injury, hypercoagulability, and stasis of the blood. Specifically, the most common risk factor for PE is a prior history of DVT¹². Having a history of DVT causes an increased risk for the formation of future clots. These clots can become dislodged and travel toward the pulmonary circulation. Other factors that increase the risk for an acute PE include immobilization, obesity, older age, smoking, congestive heart failure, and respiratory failure^11,12,13. Particularly, for women, another significant risk factor is the use of hormone therapy or oral contraceptives¹⁴.

Acute PE presents unique challenges as it can significantly and quickly impact heart function. When the clot becomes lodged within the pulmonary circulation, it can lead to an increase in pulmonary arterial pressure (PAP). Subsequently, the right ventricular (RV) afterload is increased. Increases in both the RV afterload and PAP, neural reflex vasoconstriction, and release of humoral vasoactive mediators all create a sharp increase in pulmonary vascular resistance (PVR)¹⁵. Endothelial cells, thrombocytes, and leukocytes all release vasoconstricting substances: serotonin, thromboxane-A₂, thrombin, histamine, endothelin, and prostaglandin F_2α. These factors further contribute to an increase in PVR^16,17. An increase in resistance within the vasculature adds to the shear stress on the wall of the endothelium, further perpetuating damage¹⁸. The PE drastically diminishes perfusion downstream of the clot. In turn, this creates alveolar dead space as ventilation is occurring with no perfusion¹⁹. This quick decrease in oxygen availability creates hypoxemia, which leads to the production of reactive oxygen species that cause damage to the endothelium⁷. Hypoxemia also leads to diminished oxygen delivery to the cardiac tissue, which leads to cardiac ischemia. In turn, this reduces right ventricular function, thereby decreasing left ventricular output¹⁸. Therefore, acute PE can cause immediate detrimental impacts on cardiac and pulmonary function.

Pulmonary embolisms can be further classified as massive, sub-massive, and non-massive. A commonly accepted definition for a massive PE is an "acute PE with sustained hypotension (<90 mmHg) for at least 15 min or requiring inotropic support, not due to a cause other than PE"²⁰. This definition distinguishes a massive PE as they often present with hemodynamic instability in the form of hypotension or cardiac shock^20,21. Due to their ability to cause hemodynamic instability, massive PEs have a higher mortality rate of 25%-30% compared to sub-massive and non-massive PEs with a combined mortality of 3%-15%²².

There are a multitude of tests that aid in the evaluation and diagnosis of a pulmonary embolism. In patients with a suspected PE, a D-dimer test is particularly useful to exclude the diagnosis of PE due to its high sensitivity (96%-98%)^23,24. However, the D-dimer test's low specificity does not allow the test alone to diagnose a pulmonary embolism. To further evaluate a patient for a PE, the Wells Score followed by CT angiogram (CTA) is often used²³. The Wells Score is the most widely used and validated system used by clinicians to evaluate a patient for a PE^21,23,25. If the original Wells Score is higher than 4 a PE is likely, and a CTA will have to be conducted to rule out a PE²⁶. Otherwise, a D-dimer test will be conducted to further validate that a PE is not present. Each of these detection methods has demonstrated the ability to diagnose PE early and effectively. This was demonstrated by looking at the summary receiver operator characteristics (SROC) area under the curve (a value of 1 corresponds to a model that predicts with 100% accuracy: D-dimer (AUC = 0.74), Wells Score (AUC = 0.79), and lung imaging (AUC = 0.97)²⁷. These results demonstrate the usefulness of all three of these tests in evaluating a patient for PE, as well as the importance of lung imaging when a PE is heavily suspected following a positive D-dimer and high Wells Score.

Patient-specific physiology can increase the risk of mortality from a pulmonary embolism. An example of this is the presence of a patent foramen ovale (PFO). Patients with a PFO and a massive PE can have paradoxical embolization, which increases the risk of death, peripheral arterial embolism, and ischemic stroke^22,28. A PE present in a patient with a PFO can cause right-to-left shunting due to the increase in right atrial pressure²⁹. This accounts for the increased risk patients with a PFO face during a massive PE as it has a higher likelihood of traveling to the left atrium, left ventricle, aorta, and, subsequently, the systemic circulation. Despite the increased mortality in patients with a PFO, the screening for PFO through an echocardiogram or transcranial Doppler study has a Level of Evidence C, meaning that physicians should consider this option^22,30.

Once a definitive diagnosis of an acute, massive PE is made, the management options include either fibrinolysis, percutaneous intervention, surgical embolectomy, extracorporeal membrane oxygenation, or a combination of these²². Regardless of the size of an acute PE, heparin should be given as initial anticoagulation in patients with no contraindications when there is a confirmed PE^22,31,32. Fibrinolysis is considered reasonable, with an acceptable risk of bleeding complications, particularly in patients who have circulatory or respiratory insufficiency or evidence of right ventricular injury^22,33,34,35. A percutaneous intervention has shown to be another effective way to manage an acute massive PE. In the literature, the success rate for percutaneous intervention has been as high as 85% with low complication rates^36,37. For patients who have a paradoxical embolism, a PE refractory to lysis, or hemodynamic instability, a surgical embolectomy serves as an effective treatment option^38,39,40. For patients with contraindications to having surgery, ECMO is a less invasive treatment method. It can be utilized as a bridge or as the main form of treatment when accompanied with heparin⁴¹. Acute massive pulmonary embolisms have a variety of treatment options that require an understanding of patient-specific physiology and circumstances to make the most individualized clinical decision.

For this specific study, a surgical embolectomy was performed due to the extensive clot burden across the mitral and aortic valve, which caused the patient significant hemodynamic instability. Concurrently, she also had a PFO, which placed her at risk of developing a paradoxical embolism. She also did not have contraindications for surgery, therefore, a surgical embolectomy was a quicker treatment method than placing the patient on ECMO while receiving heparin.

Protocol

This protocol complies with the human care guidelines of the University of Florida. Written informed consent was obtained from the patient who participated in this study. The inclusion criterion was hemodynamic instability due to clot burden or a patent foramen ovale. The exclusion criterion was patients with strict contraindications to surgery. The details of the reagents and equipment used are listed in the Table of Materials.

1. Pre-operative preparation

1. Initial evaluation
   1. Evaluate the patient's hemodynamic status by obtaining vitals, an EKG, and a chest X-ray.
   2. If a pulmonary embolism (PE) is suspected based on patient's clinical presentation, assess the patient's likelihood for a pulmonary embolism by using the Well's Criteria⁴².
2. If the Wells Criteria score is >4.0, then obtain a CTA in order to rule out a PE. An example is shown in Figure 1.
3. When a PE is confirmed, perform a TTE to assess clot burden and right ventricular volume and contractility.
4. If the patient is determined to have a patent foramen ovale (PFO) or life threatening circulatory issues, proceed to emergency thromboembolectomy⁴³.

2. Surgical preparation

1. Patient preparation
   1. Position the patient supine on the operating table.
   2. Induce general anesthesia with orotracheal intubation (following institutionally approved protocols).
   3. Tape the eyes, nose, and pad the head to avoid inadvertent trauma. Next, catheterize the patient.
2. Disinfection
   1. Wipe the thorax, abdomen, and both legs with iodine solution three times following the method of top-down and in-out.
   2. Drape the patient in a sterile fashion.
3. Intraoperative imaging
   1. Perform a transesophageal echocardiogram (TEE) to confirm the extent of the clot burden prior to surgical entry⁴⁴.

3. Initiating cardiopulmonary bypass

1. Median sternotomy
   1. Prior to the procedure, administer heparin to achieve an activated clotting time (ACT) of over 480 s.
   2. Perform a midline skin incision from the sternal notch to just below the xiphoid process.
   3. Dissect through the subcutaneous tissue and pectoral fascia using electrocautery to control bleeding in order to expose the sternum.
   4. Use a sternal saw to longitudinally divide the sternum. Ensure the cut extends from the manubrium to the xiphoid process.
   5. Place sternal retractors on each half of the sternum and open the chest allowing access to the mediastinum.
   6. Incise the pericardium longitudinally, approximately 8-10 cm, to expose the heart and ascending aorta.
   7. Aortic cannulation
   8. Place two concentric 4-0 non-absorbable sutures on the ascending aorta distal to the known clot location.
   9. Make a small incision, 1-2 cm, with a scalpel between the sutures.
2. Aortic cannulation
   1. Insert the aortic cannula through the incision made in step 3.1.9 and advance gently. Tighten the sutures around the cannula to secure it.
   2. Connect the aortic cannula to the arterial line of the CPB circuit to ensure the connection is free of air bubbles.
3. Bicaval venous cannulation
   1. Place two 3-0 non-absorbable sutures on the right atrium at the junction of the superior and inferior vena cava.
   2. Insert venous cannulas directly into the superior vena cava (SVC) and inferior vena cava (IVC) through the right atrium.
   3. Connect both the cannulas to a Y tube.
   4. Connect the Y tube to the venous line of the CPB circuit and ensure there are no air bubbles.

4. En bloc removal

1. Identifying the clot
   1. Arrest the heart following the institution-preferred cardioplegia.
   2. Open the right and left atrium transeptally. Identify the clot burden and the PFO.
2. Removal of the clot
   1. Remove the identified clot in an en bloc fashion.
   2. Perform a small aortotomy by making a 2-3 cm incision transversely to ensure no remaining clot crosses into systemic circulation⁴⁵.
   3. If a clot is present, extract it with forceps.
   4. Close the aortotomy with a running 4-0 polypropylene suture.
   5. Make a small incision, 2-3 cm, in the pulmonary artery.
   6. Use forceps and Fogarty catheters to remove clot burden from the pulmonary circulation.
   7. If the patient is at high risk, consider concurrent placement of an inferior vena cava filter.

5. Post-operative monitoring and care

1. Hemodynamic monitoring
   1. Immediately monitor the vital signs including heart rate, blood pressure, and oxygen saturation.
   2. Monitor for respiratory complications or if the patient requires supplemental oxygen or mechanical ventilation.
2. Anticoagulation therapy
   1. Begin anticoagulation therapy through IV heparin. Administer oral anticoagulants such as warfarin.

Results

Following the intervention, the patient was successfully weaned off cardiopulmonary bypass without incident. Figure 2A,B demonstrate clot removal using the en bloc technique. Post-operatively, the patient remained intubated and was placed on intravenous (IV) heparin but remained hemodynamically stable. The patient was extubated within 24 h of surgery. Post-operative CT angiography confirmed restored pulmonary artery blood flow, with the pulmo...

Discussion

Extensive pulmonary emboli in transit are life-threatening emergencies that require immediate intervention. We present a case of extensive clot burden crossing the PFO, mitral valve, and aortic valve. Removal of the clot burden and closure of the PFO is a vital part of therapy when a clot is this vast. Immediate surgery not only prevents urgent life-threatening problems of stroke, heart attack, respiratory failure, and death but also prevents long-term consequences of pulmonary hypertension from clotting or future strok...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Aortic clamps	Wexler Surgical	AL2238.1
Aortic punch	Scanlan international	1001-600
arterial line filter (40 micron)	Lifeline Systems Pvt. Ltd.	ALF-01
Arterial tubing circuits	Medtronic	4949
Ascending aorta arterial cannula	Terumo Cardiovascular Systems	203879S
Bone wax	Ethicon	W810
Bubble detector	Quest Medical	Integrated into MPS 3 ND System
Bulldog clamps	Wexler Surgical	AL2102.1
Cardioplegia delivery system	Terumo Cardiovascular Systems	165720
Cardioplegia filter	Terumo Cardiovascular Systems	CPS-02
Cooley forceps	JJ International Instruments	356002
DeBakey forceps	Wexler Surgical	AL2412.1
Fine suction tips	Wexler Surgical	AL1171.1F.
Fogarty embolectomy catheters	Edward Lifesciences	120404F
Gerald forceps	Amber Surgical	190660053741
Heart lung machine	LivaNova	S5 Heart Lung Machine
Heat exchanger	LivaNova	D921
Heavy needle drivers	Ambler surgical	50-100
IVC filter	Boston Scientific	M001503010	Filter placed to prevent future PE/strokes
Left ventricular vent catheter	Medtronic	E060
Mayo scissors	KLS Martin Group	11-171-17-07
Membrane oxygenator	Terumo Cardiovascular Systems	Capiox FX Series
Metzenbaum scissors	Securos surgical	45070
Plegeted sutures for PA closure	Ethicon	D7143
Potts scissors	Novo Surgical	G1567-88
Pulmonary artery venting catheter	Edwards Lifesciences	774F75
Single stage venous cannula	Medtronic	69328
Sternal retractors	Integra LifeSciences	300-165
Sternal saw	Stryker Corportation	REF 8207-000-. 000
Sternal wire	Zimmer Biomet	ASTM F138
TEE probe	Philips Healthcare	X11-4t FUS9364 xMatrix
Tissue retractors	Integra LifeSciences	200-155
Vascular forceps	Ambler surgical	34-135.
Vascular needle holders	Ambler surgical	50-850
Vascular scissors	Ambler Surgical	78-742
Vascular sutures: Prolene 4-0, 5-0, 6-0	Ethicon	D7143
Venous clamps	JJ International Instruments	CV6011 -10T
Venous tubing circuits	Terumo Cardiovascular Systems	66112