Paradoxical embolisation to the brain in right-sided infective endocarditis and patent foramen ovale in a pregnant woman

Abstract

The incidence of infective endocarditis in pregnancy has increased as a result of the opioid epidemic. Right-sided infective endocarditis (RSIE), specifically tricuspid valve endocarditis, is more commonly linked to injection drug use. In pregnant patients, a prompt diagnosis and treatment of infective endocarditis are crucial to prevent fetal and maternal morbidity and mortality. Complications associated with infective endocarditis in pregnancy include death, preterm labour and embolic disease. RSIE is classically linked to septic pulmonary emboli; however, we report a unique case of a pregnant patient with known tricuspid valve infective endocarditis. Our patient unfortunately developed an ischaemic stroke from paradoxical brain embolisation in the setting of a previously undiagnosed patient foramen ovale. Furthermore, we demonstrate the importance of considering how normal cardiac physiological changes associated with pregnancy can impact the clinical course in patients with RSIE.

Background

Infective endocarditis (IE) in pregnancy is an increasing public health concern. In recent years, there has been an increase in the awareness of IE in pregnancy associated with the opioid epidemic.^{1 2} Intravenous drug use is now identified as the major risk factor for IE in pregnancy and the postpartum period.¹ IE in pregnancy is linked to significant rates of morbidity and mortality in both the mother and fetus. Preterm labour, fetal demise, maternal cardiac failure and embolic disease are among the recognised complications of IE.²

Prior to the opioid epidemic, IE in pregnancy was known to involve left-sided valves associated with rheumatic heart disease.¹ Though left-sided IE still represents the majority of endocarditis cases in the general population and pregnant patients, the decrease in rheumatic heart disease and increased use of injection drugs have resulted in a steady increase in right-sided involvement. Right-sided IE (RSIE) is typically associated with septic pulmonary emboli and related pulmonary complications.³ However, in the presence of a right-to-left intracardiac shunt, paradoxical embolisation into the systemic circulation can occur.^{4 5} One potential catastrophic complication of this phenomena is cerebrovascular embolisation leading to stroke. We present a case of a pregnant woman who developed a stroke resulting in permanent hearing loss from paradoxical embolisation of RSIE across a previously undiagnosed patent foramen ovale (PFO).

Case presentation

A pregnant woman in her late 20s was admitted to the maternal-fetal medicine service for treatment of acute opioid withdrawal at 31 weeks gestational age. Her medical history included injection drug use complicated by tricuspid valve IE and septic pulmonary emboli diagnosed approximately 1 year prior to the present hospitalisation (figure 1A). She completed 6 weeks of intravenous antibiotic therapy but was lost to follow-up during which time she had relapsed injection drug use. Shortly on admission, she became acutely dyspnoeic. Vital signs demonstrated a temperature of 36.6°C, heart rate of 118 beats per minute, blood pressure 126/80 mm Hg, respiratory rate of 40 breaths per minute and oxygen saturation of 91% on 2 L/min of oxygen via nasal cannula. Physical examination revealed a II/VI holosystolic murmur over the precordium, respiratory distress, jugular venous distension and lower extremity oedema. Laboratory evaluation demonstrated elevated white cell count of 19.78×10⁹/L (normal reference range: 3.70–10.30), anaemia with haemoglobin of 84 g/L (normal: 112–157), as well as low platelet count at 140×10³/µL (normal: 155–369). ECG revealed sinus tachycardia. Blood cultures on 3 consecutive days returned positive for methicillin-resistant Staphylococcus aureus (MRSA). A transthoracic echocardiogram (TTE) without agitated saline revealed a vegetation on the tricuspid valve with perforated tricuspid valve, severe tricuspid regurgitation (TR) and severe right atrial dilation with bowing of the interatrial septum towards the left atrium (figure 2). CT of the chest revealed several chronic bilateral septic pulmonary emboli, which were improved compared with the study 1 year prior (figure 1B). The patient was diagnosed with tricuspid valve IE as per the modified Duke’s criteria and was treated with intravenous daptomycin and ceftaroline until blood culture was documented as negative at which time she was transitioned to intravenous vancomycin with plans to complete 6 weeks of therapy. The patient remained admitted to the hospital during this time to receive antibiotics and undergo further care for her high-risk pregnancy. Approximately 10 days into her hospitalisation, she reported right-sided hearing loss that had been present since just prior to admission.

Figure 1.

CT of the chest showing (A) septic pulmonary emboli in bilateral lung fields (red arrows) 1 year prior and (B) interval resolution of the emboli on current admission.

Figure 2.

Transthoracic echocardiogram (still images) of the right ventricular inflow view showing (A) perforated tricuspid valve with vegetation (blue arrow), (B) severe tricuspid regurgitation across the perforated valve on colour flow Doppler and (C) apical four-chamber view with right atrium dilation and bowing of the interatrial septum towards the left atrium. RA, right atrium; RV, right ventricle; LA, left atrium.

Investigations

Otolaryngology was consulted for evaluation of hearing loss. A Weber tuning fork exam lateralised to the left ear indicating right-sided sensorineural hearing loss. Brain MRI demonstrated restricted diffusion with hyperintensity in the right occipital lobe and left cerebellar hemisphere suggestive of multiple ischaemic infarcts (figure 3). A magnetic resonance angiogram of the head and neck did not reveal significant stenosis or mycotic aneurysm within the brain or the cervical carotid and vertebral systems.

Figure 3.

(A and B) Axial diffusion-weighted MRI of the brain demonstrate restricted diffusion in the right occipital lobe (blue arrows), (C) T2 FLAIR hyperintensity (blue arrows) and (D) multiple susceptibility artefacts (yellow circles).

Differential diagnosis

Given the multifocal distribution of the cortical infarcts, the suspected source of the stroke was cardioembolic. Most cardioembolic strokes originate from the left heart or aorta; however, our patient’s previous echocardiogram only demonstrated right-heart involvement of her IE.⁶ Due to this discrepancy, several differential diagnoses were considered. Septic emboli still remained high on the differential diagnosis; however, this diagnosis required either the interval development of left-sided IE or the presence of a right-to-left intracardiac shunt to allow for paradoxical embolisation to systemic circulation. Atrial fibrillation was considered as it is the most common cause of cardioembolic stroke; however, we felt this was unlikely given her lack of risk factors or history of the condition.⁶ In light of the ongoing endovascular infection, mycotic aneurysm of the intracerebral, cervical or vertebral arteries was also considered.

Treatment

The patient completed 6 weeks of intravenous antibiotic therapy for MRSA IE vancomycin and was transitioned to daptomycin for the last week of therapy due to acute kidney injury. Her case was discussed by the institution’s multidisciplinary endocarditis team (MDET). After discussion with the patient and the family, a decision was made to delay surgical intervention on her tricuspid valve until after delivery to avoid the maternal and fetal risks associated with cardiac surgery in pregnancy such as uteroplacental insufficiency, sustained fetal hypoxia and maternal or fetal death. While receiving intravenous antibiotic therapy, the patient delivered a healthy infant at 36 weeks gestation.

After delivery, she developed worsening hypoxaemia and peripheral oedema. During this time, her oxygen requirement increased from 2 to 6 L/min of supplemental oxygen via nasal cannula to maintain oxygen saturations >88%. In order to further evaluate her hypoxaemia and the aetiology of the embolic stroke, a transesophageal echocardiogram (TEE) with agitated saline was obtained and revealed elevated right atrial pressures and a large right-to-left shunt consistent with a PFO. The TEE also confirmed her known RSIE and failed to locate any left-sided valve lesions or a visualised thrombus in the left atrial appendage that could have contributed to her stroke (figure 4).

Figure 4.

Transesophageal echocardiogram (still images) showing (A) echogenic tricuspid valve mass consistent with a vegetation, (B) early appearance of agitated saline bubbles in left heart at rest (white arrow) and (C) patent foramen ovale with right-to-left shunt on colour Doppler. RA, right atrium; RV: right ventricle; LA, left atrium.

Her case was again discussed by the MDET. In light of her previous history of being lost to follow-up with relapsed substance use and the high-mortality associated with prosthetic valve endocarditis, it was recommended to further delay valve surgery until she could demonstrate a period of continued follow-up without injection substance use.

Due to ongoing hypoxaemia and systemic emboli in the setting of the confirmed PFO with right-to-left shunt, the MDET recommended transcatheter PFO closure. The patient underwent successful percutaneous PFO closure on hospital day 42, which led to an improvement in her hypoxaemia. Our patient was eventually discharged home with plans to follow-up with infectious diseases, otolaryngology and cardiothoracic surgery. The patient was started on dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel. The patient was also initiated on extended-release buprenorphine injections on discharge to treat her opioid use disorder.

Outcome and follow-up

The patient followed up with infectious diseases, cardiothoracic surgery and otolaryngology posthospital discharge. At 2 months, she had persistent lower extremity oedema and dyspnoea on exertion; however, these symptoms had slowly improved since discharge from the hospital. The patient endorsed compliance with her DAPT regimen and long-acting buprenorphine injections. Given her improved-to-stable symptom burden, the decision was made to repeat a TTE in 2 months and re-assess timing of definitive valve surgery. Her right-sided hearing loss remained unchanged, and otolaryngology provided her with a contralateral routine of signals device.

Discussion

As a result of the opioid epidemic, we have witnessed an increase in the incidence of IE in pregnancy related to injection drug use.¹ IE during pregnancy is life-threatening for both the mother and fetus. Given the scarcity of reported literature, an accurate incidence of endocarditis in pregnancy is not available. However, recent studies estimate fetal and maternal mortality rates ranging from 15% to 30%.^{1 7} Complications associated with IE in pregnancy may include, but are not limited to preterm delivery, maternal valve destruction and failure, and embolic disease.²

Left-sided IE is more commonly associated with embolisation to the central nervous system and systemic circulation, while RSIE is often accompanied by septic pulmonary emboli.^{3 4} Rarely, paradoxical embolisation can occur in RSIE, usually in the setting of an atrial septal defect and shunting. Here, we present a case of tricuspid valve IE complicated by paradoxical embolisation to the brain through a previously undiagnosed PFO in a pregnant woman. Although rare, this complication is important to recognise due to the potentially devastating implications to the mother and fetus.

PFOs are thought to be present in roughly one-fourth of the population.⁸ Most PFOs are clinically silent and are either discovered incidentally or through poststroke evaluation. Typically, PFOs are associated with left-to-right intracardiac shunting; however, in certain conditions where right-heart pressures overcome the left, such as severe TR, right-to left shunting may develop.^{5 9} In the setting of a PFO with right-to-left shunt, paradoxical embolisation from the right heart to the central nervous system may potentially occur.⁵ In addition to having severe TR from IE, the physiological changes of pregnancy also contributed to our patient’s right-to-left shunt. During pregnancy, upregulation of the renin-angiotensin-aldosterone system leads to sodium and water retention, which increases the total plasma volume by 30%–50%.¹⁰ This, in combination with increased red blood cell mass from hormone-mediated haematopoiesis, results in a precipitous increase in cardiac preload.¹⁰ Like severe TR, increased preload also elevates right-heart pressure which may cause the shunt reversal that potentially allowed for paradoxical embolisation.

Endocarditis in pregnancy is by itself rare and paradoxical embolisation in the setting of PFO is an uncommon yet documented complication of RSIE. Consequently, there are no guidelines for management of pregnant patients with RSIE and PFO with paradoxical embolisation. Current guidelines from the Society for Cardiovascular Angiography and Interventions recommend PFO closure in all patients between ages 18 and 60 with prior PFO-associated stroke.¹¹ Though these guidelines do not comment on pregnancy status, the recommendations could be generalised to the population based on age range alone. Due to the inherent maternal and fetal risks, valve surgery poses an extremely high risk in the later stages of pregnancy and postpartum state.¹² Additionally, patients with right-sided endocarditis may be too critically ill to undergo valve surgery and concomitant surgical PFO closure. In our previously reported case series, we have demonstrated the safety and short-term feasibility of transcatheter PFO closure devices in high-risk RSIE patients receiving antibiotic therapy as a bridge to definitive valve surgery.⁴ The present society guidelines in conjunction with this limited reported evidence suggests that providers may consider the use of a transcatheter PFO closure device to correct hypoxaemia or prevent future systemic embolic events in high-risk pregnant patients until the patient is stable enough to undergo valve surgery. However, this decision should be made by an MDET with input from specialists in cardiac surgery, obstetrics, cardiology, infectious disease and internal/hospital medicine.

Learning points.

• Fetal and maternal mortality rates ranging from 15% to 30% for infective endocarditis in pregnancy are studied.

• The incidence of infective endocarditis in pregnancy is increasing due to the opioid epidemic.

• Right-sided infective endocarditis is typically associated with septic pulmonary emboli but can lead to paradoxical system embolisation in patients with intracardiac shunts such as a patent foramen ovale (PFO).

• Right-heart pressures can become elevated in pregnancy due to increased cardiac preload from physiological increases in total plasma volume and red blood cell mass.

• PFO closure can be considered as a bridge to definitive valve repair in patients with high emboli burden that are at high risk to undergo surgery.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).