High-Risk Pulmonary Embolism During Labor

Abstract

While in labor, a 37-year-old woman developed acute dyspnea, hypoxemia, and tachycardia. Transthoracic echocardiography demonstrated severe right ventricular dilation and dysfunction, raising the suspicion of acute pulmonary embolism. The patient indeed had bilateral pulmonary embolism, necessitating percutaneous thrombectomy. Her course was complicated by another saddle pulmonary embolus, heparin-induced thrombocytopenia, and COVID-19 infection. This clinical case illustrates the importance of prompt diagnosis of acute pulmonary embolism in a peripartum female patient, the multidisciplinary approach of management, and how to approach clinical complications such as heparin-induced thrombocytopenia. Furthermore, long-term management in acute pulmonary embolism is presented.

Central Illustration

Highlights

• •In patients with suspected PE during pregnancy, echocardiographic features of right ventricular dilatation and systolic dysfunction, McConnell sign, abnormal motion of the interventricular septum, tricuspid regurgitation, lack of collapse of the inferior vena cava during inspiration, and the 60/60 sign can be useful to support the diagnosis and assess the severity of hemodynamic derangement.
• •CTPA can not only establish a diagnosis of PE but also differentiate acute from chronic thromboembolic disease.
• •Management of acute PE intrapartum must be individualized and requires risk stratification. Consideration must be given to the timing of anticipated delivery, stage of labor, and parity. Therapeutic anticoagulation is the mainstay of management, but in cases of high-risk and some cases of intermediate-risk PE, reperfusion therapy may be indicated to prevent hemodynamic decompensation, and in the event of massive PE, mechanical circulatory support can be lifesaving.

Case Presentation

A 37-year-old woman, who was pregnant at 39 weeks 4 days, was undergoing induction of labor with oxytocin. She had a past medical history of 2 spontaneous pneumothoraces 7 years prior, at which point she underwent bullectomy with pleurodesis via video-assisted thorascopic surgery. Sixteen hours into labor, the patient developed acute dyspnea with palpitations. She was normotensive, with a blood pressure of 116/68 mm Hg; tachycardic, with a heart rate of 151 beats/min; and hypoxemic, with oxygen saturation of 88% while breathing room air. On physical examination, she was visibly tachypneic and anxious but speaking full sentences. Her heart examination was tachycardic but regular, and her lung examination was clear bilaterally. An electrocardiogram demonstrated right bundle branch block with pattern incomplete right bundle branch block, S1Q3T3 (Figure 1).

Figure 1.

Electrocardiogram on Admission: Right Ventricle Strain (IRBBB, S1Q3T3)

Electrocardiogram at the time of hemodynamic decompensation: a typical pattern of right ventricular strain with incomplete right bundle branch block (IRBBB), S1Q3T3 setting the initial suspicion of acute pulmonary embolism.

She noted that her dyspnea felt “different” compared to when she had had pneumothoraces. Lung ultrasound demonstrated lung sliding bilaterally, essentially ruling out pneumothorax. Transthoracic echocardiogram (TTE) revealed normal left ventricular size and function, with a left ventricular (LV) ejection fraction of 68%, severe dilation and dysfunction of the right ventricle (RV), paradoxical septal motion, and moderate tricuspid regurgitation (Figure 2, Videos 1A and 1B). Given the concern for acute pulmonary embolism (PE), a computed tomography angiogram (CTA) of the chest was considered but was not possible to obtain because the patient was 9 cm dilated, and delivery of the baby was imminent. The multidisciplinary PE response team was activated, and the patient was transferred to a cardiac operating room. Small-bore sheaths were placed in the right femoral artery, right femoral vein, and left femoral vein that could rapidly be upsized for initiation of venoarterial extracorporeal membrane oxygenation (ECMO) in the case of hemodynamic decompensation during delivery.

Figure 2.

Initial Transthoracic Echocardiogram

(A) Parasternal short axis at the level of left ventricular papillary muscles: the right ventricle is dilated when compared to the left ventricle (red arrow), and the eccentricity index of the left ventricle is >1 in systole (yellow arrows). There is also shifting of the interventricular septum from the right to the left (blue arrow) because of increased right-sided pressures. (B) Apical 4-chamber view: shifting of the interventricular septum from the right to the left (blue arrow) because of increased right-sided pressures.

The patient subsequently became more tachypneic and developed hypotension with a blood pressure of 83/31 mm Hg. She was started on vasopressors (vasopressin 2.4 U/h, norepinephrine 9 μg/min, and epinephrine 9 μg/min). She was intubated with midazolam and fentanyl as induction agents. A healthy baby was delivered vaginally with forceps. Postdelivery, the patient was still in persistent shock, requiring vasopressors and inotropes. She also demonstrated a high degree of dead-space ventilation, given an elevated Paco₂ of 50 mm Hg despite an extremely high total minute ventilation of 17.8 L/min and a low end-tidal CO₂ of 17 mm Hg. She was started empirically on a heparin drip. A CTA of the chest demonstrated extensive bilateral PE with evidence of RV strain (Figure 3).

Figure 3.

Initial Computed Tomography Angiogram of the Chest

(A) Bilateral large filling defects in the right and left main pulmonary arteries consistent with acute pulmonary embolism (yellow arrow). (B) Dilated right ventricle and right atrium with flattening of the interventricular septum, consistent with right ventricular strain.

Percutaneous thrombectomy was performed using the Inari FlowTriever system (Figure 4). The following day, she remained in shock, requiring norepinephrine 5 μg/min, vasopressin 2.4 U/h, and epinephrine 14 ng/kg/min. A repeat TTE continued to demonstrate severe RV dilation and dysfunction (Figure 5, Videos 2A and 2B). To differentiate whether the RV dysfunction was a result of persistent elevated RV afterload or just a result of RV stunning, a pulmonary artery catheter was placed, demonstrating the following hemodynamic values: central venous pressure 3 mm Hg; pulmonary artery pressure 26/9/14 mm Hg (systolic/diastolic/mean); cardiac output 7.1 L/min; and cardiac index 3.4 L/min/m².

Figure 4.

Surgical Specimen

Fresh pulmonary thrombus removed via percutaneous embolectomy. A repeat pulmonary angiogram was performed immediately after the procedure, demonstrating improved perfusion to both lungs.

Figure 5.

Second Transthoracic Echocardiogram

(A) Apical 4-chamber view: the right ventricle is significantly dilated (red arrow) when compared to the left ventricle (yellow arrow). (B) Parasternal short axis at the level of left ventricular papillary muscles: the right ventricle is significantly dilated (red arrow) when compared to the left ventricle (yellow arrow).

The pulmonary capillary wedge pressure was not directly measured. Assuming the pulmonary capillary wedge pressure was less than or equal to the pulmonary artery diastolic pressure and, therefore, likely between 4 and 9 mm Hg, the calculated pulmonary vascular resistance (PVR) would have been between 0.7 and 1.3 Wood units. Given the normal PVR, treatment was continued conservatively with anticoagulation alone. On postdelivery day 2, the patient was extubated. On postdelivery day 4, she was weaned off all vasopressors. During this time, the patient developed worsening bilateral labial hematomas, requiring 10 units of packed red blood cell transfusions. Two CTAs failed to identify an arterial blush or venous pooling. On postdelivery day 6, an inferior vena cava filter was placed, and anticoagulation was discontinued. It was believed that the patient would be able to tolerate anticoagulation, and thus, an inferior vena cava filter was not placed after thrombectomy. It was only after she had persistent labial bleeding over the ensuing days that an inferior vena cava filter was placed to allow for cessation of therapeutic anticoagulation. By postdelivery day 11, bleeding had ceased, and a heparin drip was restarted at a low dose. The following day, the patient became acutely dyspneic, hypoxemic, and tachycardic (blood pressure 128/81 mm Hg, heart rate 107 beats/min, oxygen saturation 89% breathing room air). Repeat CTA demonstrated a new saddle PE (Figure 6). She was administered a heparin bolus, and the heparin infusion rate was increased to achieve full therapeutic anticoagulation. It was noted that over the preceding 30 hours, the patient’s platelet count had dropped from 185 to 120 platelets/μL. Given the concern for heparin-induced thrombocytopenia (HIT), her anticoagulation was empirically switched to argatroban. Later that day, she was also diagnosed with COVID-19. The following day, the patient’s HIT antibody test result was positive, and HIT was ultimately confirmed with a positive serotonin release assay result. Because she elected not to breastfeed, the patient’s anticoagulation was ultimately transitioned to apixaban. She was discharged home on postdelivery day 24. Three months later, the patient is doing well, and a repeat TTE demonstrated normal RV size and function (Figure 7, Videos 3A and 3B).

Figure 6.

Repeat Computed Tomography Angiogram of the Chest

Large saddle pulmonary embolism (yellow arrow).

Figure 7.

Last Transthoracic Echocardiogram

(A) Apical 4-chamber view: the right ventricle is now smaller in size (red arrow), almost equal to the size of left ventricle (yellow arrow). (B) Parasternal short axis at the level of papillary muscles: right ventricular size is smaller (red arrow) when compared to previous studies. The left ventricle has a round shape (yellow arrow), indicating that the pressures within the right ventricle have decreased.

Review

Pathophysiology of PE and the vicious cycle of RV failure

Acute pulmonary thromboembolism refers to the acute obstruction of the pulmonary vasculature by thrombus that originated elsewhere in the body. The thrombi acutely increases PVR, which increases RV afterload. Although a normal LV is generally tolerant of increases in afterload, the RV is not. Acute increases in RV afterload lead to decreased RV output,¹ which in turn reduces LV preload and, ultimately, LV cardiac output. Increased RV afterload also increases RV wall stress, which leads to RV ischemia, decreased RV contractility, and further reductions in RV output.² Additionally, increased RV afterload leads to RV dilatation, which widens the tricuspid valve annulus and prevents complete coaptation of the tricuspid valve leaflets, producing significant tricuspid regurgitation. Because of pericardial constraint, increases in RV size lead to bowing of the interventricular septum into the LV, causing both impaired LV filling and decreased LV contractility.³ Decreased LV cardiac output leads to decreased right coronary artery blood flow, further worsening RV ischemia. This vicious cycle of RV failure (Figure 8) is often a self-perpetuating process and manifests as rapidly deteriorating hemodynamics.⁴

Figure 8.

Vicious Cycle of Right Ventricular Failure

In right-sided heart failure, acute increase of right ventricular (RV) afterload leads into acute dilatation and increase of tricuspid regurgitation but also to reduction of left ventricular (LV) preload and eventually cardiogenic shock. This diagram illustrates the physiology of RV afterload increase. RCA = right coronary artery.

PE imaging

One of the first tests that will take place in a patient with suspected acute PE is an electrocardiogram. Together with the brain natriuretic peptide, troponin and D-dimers will help when making the differential diagnosis.⁵ Furthermore, staging of pretest probability with the Wells score is essential in hemodynamically stable patients.⁵ The patient then is categorized into low-, intermediate-, or high-risk probability of acute PE. The simplified PE severity index is another prediction tool used to risk-stratify patients with diagnosed acute PE.⁶ This tool includes the variables history of cancer, chronic cardiopulmonary disease, age >80 years, heart rate ≥110 beats/min, systolic blood pressure (SBP) of <100 mm Hg, and arterial oxyhemoglobin saturation of <90%.

Patients with high and intermediate probability will be the best candidates for a computed tomography (CT) pulmonary angiography (CTPA) as the noninvasive imaging modality of choice. This offers significant sensitivity and specificity as well as positive predictive values of 83%, 96%, and 96% respectively.⁷ CTPA can differentiate between acute and chronic PE. Acute emboli are located at the vessel bifurcation and may completely or partially obstruct the vasculature. A complete obstruction will look like a hypoattenuating contrast defect occupying the entire lumen, maintaining the vessel diameter in most cases (when compared to chronic, in which the vessel is dilated). Complete obstruction will also create distal infarcts, which appear as triangular subpleural consolidations or ground glass opacity with reticular changes. Partial obstructions can be central or eccentric. Our patient had bilateral large filling defects in the right and left main pulmonary arteries consistent with acute PE (Figure 2).

Chronic obstructive PE changes present either as complete obstruction, with lack of contrast distal to the site of obstruction and narrowed vessel, or as partial obstruction, which is identified as partially attenuated vessel or dilation distal to the obstruction and narrow diameter.

CTPA has multiple advantages such as the high positive predictive value, accuracy, speed of acquiring images, widespread availability, superior spatial resolution, and multiplanar reconstruction. Wide-array CT provides substantial length per rotation and reduced motion artifacts. Dual-energy CT has also a combination of advantages such as ruling out acute segmental and subsegmental PE with iodine or Z-effective mapping. Iodine maps accentuate iodine-containing tissue and improve the sensitivity of perfusion defects. Furthermore, dual-energy CT can salvage suboptimal studies and reduce the contrast exposure to patients.^5,8

Ventilation/perfusion scanning was the diagnostic method of choice before the development of CT. It can be used on pregnant patients, those who cannot fit in a CT scanner, and those who have renal failure or contrast allergy. It has proven to have 75% to 93% positive predictive value for acute PE on various studies.^9,10 It is an important tool, together with CT, for the diagnosis of chronic thromboembolic disease as per the new guidelines for pulmonary hypertension.¹¹

Echocardiography in PE

Echocardiography can be helpful in diagnosing acute PE and is central in the risk stratification of acute PE. Because of the acute RV dilation and pressure overload, quite often, the tricuspid annulus acutely increases in size, and there is significant tricuspid regurgitation.⁵ Because of the acute pressure overload, there is hemodynamically significant systolic and diastolic dysfunction. In our patient, there was severe RV systolic dysfunction, and the RV was dilated almost 3 times the size of the LV.

In acute PE, qualitative echocardiographic assessment includes RV dilatation and hypokinesis, abnormal motion of the interventricular septum, tricuspid regurgitation, and lack of collapse of the inferior vena cava during inspiration. Among patients in shock, there is a small difference in LV area during diastole and during systole indicating low cardiac output. Sometimes, the PE can be identified within the RV or pulmonary artery.¹² The 60/60 sign in echocardiography refers to the coexistence of a truncated RV outflow tract acceleration time (of <60 ms) with a pulmonary arterial systolic pressure of <60 mm Hg (but >30 mm Hg). In the presence of RV failure, it is consistent with an acute elevation in afterload, commonly caused by an acute PE.^5,13 McConnell’s sign is a distinct echocardiographic finding described in patients with acute PE. There is a distinct regional pattern of RV dysfunction, with akinesia of the mid-free wall and hypercontractility of the RV apex, which makes it a distinctive feature of massive PE.^5,13 With the exception of these distinct echocardiographic indices, there are also indirect echocardiographic markers to demonstrate acute RV pressure overload, such as reduction of tricuspid annular plane systolic excursion, reduced RV outflow tract acceleration time, prolonged isovolumic relaxation time, and reduced fractional area change.¹⁴

Risk stratification of PE

Anticoagulation is the cornerstone of treatment for acute PE. The primary purpose of anticoagulation is to prevent new formation of thrombus while allowing the patient’s own fibrinolytic system to dissolve the clot in the pulmonary vasculature. However, for sicker patients with impaired hemodynamics, immediate reperfusion therapy with thrombolysis or embolectomy (surgical or percutaneous) may be necessary. The decision to use these advanced therapies depends on the risk of decompensation of the patient from acute PE, where patients at higher risk of PE decompensation warrant more aggressive interventions, whereas those with lower risk can be treated conservatively with anticoagulation alone. The European Society of Cardiology guidelines have stratified PE risk into high risk (previously called “massive”), intermediate risk (previously called “submassive”), and low risk.⁵ High-risk PE is defined as having either: cardiac arrest; obstructive shock (SBP of <90 mm Hg or vasopressors required to achieve SBP of >90 mm Hg, in combination with end-organ hypoperfusion); or persistent hypotension (systolic SBP of <90 mm Hg or SBP drop of >40 mm Hg for more than 15 minutes, not caused by new-onset arrhythmia, hypovolemia, or sepsis).

Intermediate risk is further stratified into intermediate-high and intermediate-low risk.

Intermediate-high risk is defined as SBP of >90 mm Hg but having both imaging signs of RV dysfunction and also elevated cardiac troponin levels. Intermediate-low risk is defined as SBP of >90 mm Hg with either imaging signs of RV dysfunction or elevated cardiac troponin levels. Low risk is defined as SBP of >90 mm Hg and the absence of both RV dysfunction and cardiac troponin elevations.

Peripartum and intrapartum considerations in PE

Generally speaking, acute PE that occurs intrapartum or peripartum should not be treated any differently than that in a nonpregnant individual. Management of acute PE intrapartum must be individualized and requires risk stratification. High-risk PE requires immediate reperfusion therapies, although the optimal advanced therapy should be individualized based on the patient and circumstance. Intravenous unfractionated heparin is the preferred, initial anticoagulant in high-risk PE. Intravenous unfractionated heparin preference is based on its short half-life and near-complete reversal with protamine if the anticoagulant effect needs to be stopped because of excessive bleeding. Consideration must be given to the expected interval to delivery, depending on the stage of labor and parity. There is no consensus regarding the optimal mode of delivery. Delivery despite full anticoagulation may occur. Many patients who deliver while anticoagulated will not have excessive intrapartum bleeding.¹⁵ However, anticoagulated patients are at increased risk for a spinal hematoma if a neuraxial anesthesia catheter is inserted.^16,17 Neuraxial anesthesia should not be administered to an anticoagulated patient. If high-risk PE is confirmed, immediate thrombolysis should be considered. Teratogenicity caused by thrombolytic agents has not been reported, but the risk of maternal hemorrhage is high. As a result, thrombolytic therapy should be reserved for pregnant patients with life-threatening acute PE.¹⁸ Observational studies provide the only data about the efficacy and safety of thrombolytic therapy and/or thrombectomy during pregnancy.19, 20, 21, 22, 23 In a systematic review of case series and case reports (172 pregnant women treated with thrombolysis), the maternal mortality rate was 1%, the incidence of fetal loss was 6%, and incidence of maternal hemorrhagic complications was 8%.²⁴

Role of percutaneous interventions in PE

The mainstay of treatment for PE is therapeutic anticoagulation. After a PE, therapeutic anticoagulation greatly reduces the risk of new thromboembolic events while allowing the patient’s own fibrinolytic system to break up the thrombus that has formed. For high-risk PE and some cases of intermediate-high–risk PE, immediate reperfusion therapy may be necessary to prevent hemodynamic decompensation. Although systemic thrombolysis has been shown to reduce the risk of short-term hemodynamic decompensation in patients with intermediate-high–risk PE,²⁵ bleeding complications, particularly intracerebral hemorrhage, have reduced the enthusiasm for this modality. Low doses of thrombolytic agents can be administered directly to the pulmonary thrombi via catheter-directed thrombolysis. With catheter-directed thrombolysis, the low dose of thrombolysis improves the safety profile, and the direct delivery of the thrombolytic agent to the pulmonary thrombi theoretically maintains efficacy.²⁶ Recent technological advances have increased the excitement for percutaneous catheter mechanical embolectomy. With these improved devices, in select patients, large thrombi can be percutaneously removed, circumventing the need for thrombolysis or surgical embolectomy. In this case, the Inari FlowTriever system was used to remove large pulmonary thrombi.

Role of mechanical circulatory support in PE

In the event of massive PEs, including those complicated by cardiac arrest, institution of mechanical circulatory support can be lifesaving. The most robustly studied and frequently used type of mechanical support in this context is ECMO in a venoarterial configuration.²⁷ This is preferred because it can provide hemodynamic support by directly offloading the RV and bypassing the pulmonary circulation and also provide oxygenation and ventilation, which may be impaired by the ventilation perfusion mismatch and functional intrapulmonary shunting.²⁸ It can serve as a bridge to medical therapy, percutaneous embolectomy,²⁹ or surgical embolectomy.³⁰ The use of ECMO in the peripartum period in recent years has increased, with relatively high rates of survival for both the mother and fetus when compared with all comers who require ECMO.³¹ In this case, ECMO was available to serve as a rescue tool in the event of significant hemodynamic compromise or cardiac arrest during the vulnerable time periods of induction of anesthesia and delivery. Fortunately, the patient remained stable on medical therapy and did not require mechanical circulatory support.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Appendix

Supplemental Video 1

Initial Transthoracic Echocardiogram. (A) Parasternal short axis at the level of left ventricular papillary muscles: the right ventricle is dilated when compared to the left ventricle.

Supplemental Video 1

Initial Transthoracic Echocardiogram. (B) Apical 4-chamber view: shifting of the interventricular septum from the right to the left because of increased right-sided pressures.

Supplemental Video 2

Second Transthoracic Echocardiogram. (A) Apical 4-chamber view: the right ventricle is significantly dilated (red arrow) when compared to the left ventricle.

Supplemental Video 2

Second Transthoracic Echocardiogram. (B) Parasternal short axis at the level of left ventricular papillary muscles: the right ventricle is significantly dilated (red arrow) when compared to the left ventricle.

Supplemental Video 3

Last Transthoracic Echocardiogram. (A) Apical 4-chamber view: the right ventricle is now smaller in size, almost equal to the size of left ventricle.

Supplemental Video 3

Last Transthoracic Echocardiogram. (B) Parasternal short axis at the level of papillary muscles: right ventricular size is smaller when compared to previous studies. The left ventricle a has round shape, indicating that the pressures within the right ventricle have decreased.