Paradoxical cerebral embolism three decades after mustard surgery in a patient with complete transposition of the great arteries: a case report

Abstract

Atrial switch procedures such as the Mustard operation were previously popular for the complete transposition of the great arteries (i.e. dextro-transposition of the great arteries [d-TGA]). Patients with d-TGA who underwent atrial switch procedures approximately three decades ago have now entered adulthood. A female patient in her 30s with d-TGA had a paradoxical embolic stroke following the initiation of a low-dose oestrogen plus progesterone oral pill for dysmenorrhoea. She underwent Mustard surgery when she was 2 years old. Following a series of procedures including implantation of a permanent pacemaker that was required because of sinus node dysfunction, she had reached adulthood, was living by herself and working independently. One month after taking the low-dose oestrogen plus progesterone oral pill, venous thrombosis occurred in the left soleus and left peroneal veins; and she experienced an acute ischaemic stroke in the right middle cerebral artery area. Transoesophageal echocardiography revealed that the shunt was present only during the Valsalva manoeuvre. Based on the examinations, the patient was diagnosed with juvenile ischaemic stroke as a result of a paradoxical embolism. These findings suggest that paradoxical cerebral embolism can occur as a late complication in patients with d-TGA who underwent the Mustard operation as children.

Introduction

Transposition of the great arteries (TGA) is a congenital heart abnormality with a prevalence of 0.31 cases per 1000 live births. ¹ The arterial switch operation (ASO) has recently become the first-line treatment for surgical correction of complete transposition of the great arteries or dextro-TGA (d-TGA). ² In contrast, atrial switch procedures such as the Mustard or Senning operations were previously the most popular surgeries for d-TGA. ³ ASO has become more popular than atrial switch procedures because it has the advantage of utilizing the left ventricle as the systemic ventricle and the mitral valve as the systemic atrioventricular valve.^2,3 Atrial switch procedures might still be associated with rhythm abnormalities and have a lower chance of maintaining the sinus. ² However, patients with d-TGA who underwent atrial switch procedures three or more decades ago are now over 30–40 years old. Due to an increase in the number of mature adult patients with d-TGA who underwent atrial switch procedures, it is essential to accumulate knowledge pertaining to the late complications of these procedures. This current report presents the case of a working female patient in her 30s who previously underwent a Mustard operation for congenital d-TGA and presented with paradoxical cerebral embolism following the intake of a low-dose oestrogen plus progesterone oral pill.

Case report

A female patient in her 30s was initiated on a low-dose oestrogen plus progesterone oral pill for dysmenorrhoea, and not for birth control. One month after initiation, she suddenly developed recurrent hiccups at night. Upon waking the following morning, she experienced left paresis and dysarthria. In February 2018, she was admitted to the Division of Neurology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan 2 days after the onset of these symptoms. The patient had a history of congenital d-TGA. She had undergone balloon atrioseptostomy and Blalock-Hanlon surgery after birth, followed by Mustard surgery when she was 2 years old. She also underwent permanent pacemaker implantation when she was 17 years old due to sinus node dysfunction (Figure 1(a)). Following these procedures, she had reached adulthood, was living by herself and working independently without any obvious health problems.

Figure 1.

Imaging findings for a female patient in her 30s with a history of undergoing Mustard surgery for congenital dextro-transposition of the great arteries when she was 2 years old who subsequently presented with left paresis and dysarthria 1 month after initiating a low-dose oestrogen plus progesterone oral pill for dysmenorrhoea: (a) chest X-ray at 17 years of age showed permanent pacemaker implantation for sinus Continued.node dysfunction; (b and c) cranial computed tomography (CT) at the current admission showed low density in the middle cerebral artery (MCA) area (yellow arrows) and unclear sulcus in the left hemisphere (red arrows), which suggested an acute ischaemic core and an early sign of CT; (d) CT angiography at the current admission with arrows showing recanalization of the right MCA. The imaging shown in b–d was performed at the same time; (e and f) cranial CT scans taken 3 years after the stroke onset. The old cerebral infarction is labelled with yellow allows; (g) enhanced CT of the heart from the axial view and (h) coronal view; (i) ultrasonography showed a venous thrombosis in the left soleus vein and (j) in the left peroneal vein; (k) transoesophageal echocardiography with a bubble test showed that the shunt exists from the left atrium to right atrium when the Valsalva manoeuvre was performed. More than four bubbles appeared in the right atrium from the regressed left atrium (arrows). LV, left ventricle; RV, right ventricle; RA, right atrium; LA, left atrium; IVC, inferior vena cava. The colour version of this figure is available at: http://imr.sagepub.com.

Her symptoms naturally improved, and only dysarthria persisted, with a National Institutes of Health Stroke Scale score of 1 at admission. Magnetic resonance imaging was contraindicated for her due to the implanted pacemaker, so cranial computed tomography (CT) was performed instead. A cranial CT at admission displayed faint low density in the right middle cerebral artery (MCA) branch and cortical regions with an unclear left hemisphere sulcus (Figures 1(b) and 1(c)). Simultaneously, CT angiography was performed, which revealed that the patient’s main cerebral artery, including the right MCA, had already been recanalized (Figure 1(d)).

The patient was diagnosed with acute-phase cerebral ischaemic stroke. Several examinations were performed in order to determine the stroke pathology. Laboratory analyses showed the following: elevated D-dimer of 2.2 µg/ml (normal range, >1.0 µg/ml); brain natriuretic hormone level of 150.0 pg/ml (normal range, >18.4 pg/ml); none of the autoantibodies (antinuclear, anticardiolipin, anticardiolipinß2 glycoprotein 1 complex, anti-SS-A, anti-SS-B, myeloperoxidase-antineutrophil cytoplasmic, or proteinase-3- antineutrophil cytoplasmic antibodies) were positive. Although there were no physical findings, considering her recent intake of a low-dose oestrogen plus progesterone oral pill, ultrasonography was undertaken and it identified venous thrombosis in the left soleus and peroneal veins (Figures 1(i) and 1(j)). The patient’s cardiac structure was validated by enhanced CT and transoesophageal echocardiography (TEE), which showed that the right atrial joints were extended to the left ventricle and the left atrium joints were extended to the right ventricle after the Mustard surgery, while the aorta originated from the right ventricle (Figures 1(g) and 1(h)). A bubble test with the TEE examination revealed a shunt from the left atrium (inflow from the vena cava) to the right atrium (inflow from the pulmonary veins). This was only visible when the Valsalva manoeuvre was performed (Figure 1(k); see supplementary materials, supplemental movie). As a consequence, the patient was diagnosed with paradoxical cerebral embolism following vein thrombosis induced by the intake of a low-dose oestrogen plus progesterone oral pill.

After hospitalization, the oral intake of the low-dose oestrogen plus progesterone pill was discontinued and 10 000 IU/day unfractionated heparin intravenous and 200 mg/day aspirin oral combination therapy was initiated. The patient was switched from the 10 000 IU/day unfractionated heparin intravenous and 200 mg/day aspirin oral combination to 60 mg/day edoxaban oral when dissolution of the venous thrombosis was confirmed 12 days after the onset of stroke. The patient was discharged without any sequelae 15 days after the onset of symptoms and displayed no recurrence. To prevent venous thrombosis, 60 mg/day edoxaban oral was prescribed for 6 months, following which no recurrent thrombosis was observed. Cranial CT scans were taken 3 years after the stroke onset (Figures 1(e) and 1(f)).

All treatments were performed following the patient’s consent and written informed consent was obtained from the patient to publish this case report. The reporting of this study conforms to the CARE guidelines. ⁴ The requirement for ethical approval was waived by the Ethical Committee of Jichi Medical University based on the study design (case report).

Discussion

The present case experienced a paradoxical cerebral embolism following the intake of a low-dose oestrogen plus progesterone oral pill for dysmenorrhoea three decades after a Mustard operation for congenital d-TGA. Regarding the atrial switch operation for d-TGA correction, several late cardiac complications, such as right ventricular outflow tract obstruction, neoaortic dilation, neoaortic insufficiency and coronary artery stenosis have been reported. ⁵ In contrast, late complications involving the central nervous system are rare and occur in the perioperative period following d-TGA repair. ⁶ The present case is the first report of an ischaemic stroke that occurred as a late complication, as much as three decades later, after the Mustard operation.

The clinical diagnosis of paradoxical embolism requires a venous source of embolism, an intracardiac defect or a pulmonary fistula, as well as evidence of arterial embolism. ⁷ The current case had all three factors (i.e. venous thrombosis, an intracardiac defect and cerebral arterial embolism) confirming a paradoxical cerebral embolism, although the cardiac flow was not the typical right to left atrial shunt. Considering the pathology of the present case, it is important to understand normal flow dynamics in the cardiac system (Figure 2(a)). In a typical paradoxical cerebral embolism case following foramen ovale opening when the Valsalva manoeuvre is performed, a right atrium to left atrium shunt causes for the ischaemic stroke (Figure 2(b)). In contrast, the Mustard operation for d-TGA results in a change in the cardiac flow dynamics from that shown in Figure 2(c) to that shown in Figure 2(d); in which both inter-atrial flows switch. In the normal state, the right atrial pressure is greater than that in the left atrium in patients with d-TGA, because the anatomical right ventricle becomes a functional left ventricle. When the Valsalva manoeuvre was performed, both atrial pressures were reversed and flow was generated from the left atrium to the right atrium if a leak was present (Figure 2(e)). This leak was confirmed by TEE in the current case (Figure 1(k)), although the presence of a cardiac pore was not confirmed because neither reoperation nor autopsy was performed. Small buffer leaks are known to occur, particularly following the Mustard operation. ⁸ Such leaks can be generated by a defect of the patch or another idiopathic shunting route created by the pacemaker leads, as in this current case. The occurrence of hiccups in the initial phase of this current patient’s symptoms was suggestive of spontaneous Valsalva manoeuvres. Recurrent hiccups can cause a variety of diseases, but they can also be induced by a pulmonary embolism. ⁹ Recurrent hiccups in this current case might have also been due to pulmonary embolism. The collective evidence from this current suggests that paradoxical cerebral embolism can occur as a late complication (even three decades later) in patients with d-TGA who underwent a Mustard operation. Considering the risk of stroke, ASO might be superior to atrial switch operations. ¹⁰ In contrast, there are indications that atrial switch operations are still a major important method for d-TGA patients especially in developing countries where there is often late admission of patients to cardiac centres so chances of ASO might be lost. For patients that have d-TGA and have undergone a Mustard operation, low-dose oestrogen plus progesterone oral pill should be avoided.

Figure 2.

Schematic diagrams showing the following: (a) normal cardiac flow dynamics; (b) cardiac flow dynamics of a typical case with paradoxical embolism following foramen ovale opening with the Valsalva manoeuvre; (c) dextro-transposition of the great arteries (d-TGA) flow dynamics at birth; (d) d-TGA flow dynamics after the Mustard operation and (e) cardiac flow dynamics in this current case with paradoxical embolism. Ao, aorta; IVC, inferior vena cava; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium; RV, right ventricle; SVC, superior vena cava. The colour version of this figure is available at: http://imr.sagepub.com.

This current case report describes a patient with d-TGA in whom a paradoxical cerebral embolism occurred even three decades after a Mustard operation. There should be lifelong follow-up of congenital heart disease patients and specific complications need to be carefully considered.

Supplemental Material

sj-mp4-1-imr-10.1177_03000605241291753 - Supplemental material for Paradoxical cerebral embolism three decades after mustard surgery in a patient with complete transposition of the great arteries: a case report

Supplemental material, sj-mp4-1-imr-10.1177_03000605241291753 for Paradoxical cerebral embolism three decades after mustard surgery in a patient with complete transposition of the great arteries: a case report by Kosuke Matsuzono, Masayuki Suzuki, Takafumi Mashiko, Reiji Koide and Shigeru Fujimoto in Journal of International Medical Research