Transcatheter Closure of a Patent Foramen Ovale in an Adult with Hypoxemia after Cardiac Transplantation

Abstract

We describe a case of refractory hypoxemia secondary to a patent foramen ovale immediately after orthotopic heart transplantation in a 60-year-old woman. The patent foramen ovale was successfully closed with a septal occlusion device, with resolution of the hypoxemia. To our knowledge, transcatheter closure of a patent foramen ovale in an adult patient with refractory hypoxemia during the immediate post-transplant period has not previously been reported.

Refractory hypoxemia can be a life-threatening complication during the period immediately after orthotopic heart transplantation. Pulmonary complications, pulmonary hypertension, and acute allograft rejection are the usual causes of hypoxemia during this period. Rarely, structural defects in the donor heart, such as a patent foramen ovale (PFO) or an unrecognized atrial septal defect, have been reported to cause significant hypoxemia.^1–4 Surgical closure of the defect has been the method of treatment in most of these reports. However, the surgical approach after cardiac transplantation can be associated with notable morbidity and mortality. We report a case of refractory hypoxemia after heart transplantation secondary to right-to-left shunting across a patent foramen ovale, which was successfully closed using a transcatheter septal occlusion device. To our knowledge, this is the 1st report in the literature of transcatheter closure of a PFO that manifested with refractory hypoxemia immediately after cardiac transplantation.

Case Report

A 60-year-old woman with a history of non-ischemic cardiomyopathy, atrial fibrillation, and previous aortic and mitral valve replacement presented with refractory heart failure despite optimal medical management. In September of 2002, she underwent successful orthotopic heart transplantation. Review of the transthoracic echocardiogram of the available donor heart before transplantation demonstrated normal left ventricular function without evidence of structural abnormality. The donor heart was also inspected before transplantation and was deemed structurally normal. A few hours after surgery, the patient was successfully extubated and was placed on 4 L of oxygen by nasal cannula. Bedside hemodynamic measurements showed a mean central venous pressure of 15 mmHg, pulmonary artery pressure of 34/21 mmHg, and cardiac output of 4.1 L/min. During the next 24 hours, she developed increasing hypoxemia, which culminated with an oxygen saturation of less than 90%. The patient was then placed on a 100% non-rebreather face mask to maintain a saturation of 90%. Chest radiography was normal. Transthoracic echocardiography demonstrated fair-to-good left ventricular systolic function (estimated ejection fraction, 0.45–0.50), paradoxical septal motion with mild global dysfunction of the right ventricle, and right atrial enlargement. Color-flow Doppler echocardiography showed mild tricuspid valve insufficiency, with an estimated right ventricular systolic pressure of 35 mmHg. Contrast bubble echocardiography with agitated normal saline solution demonstrated the presence of a patent foramen ovale with a large number of microbubbles crossing into the left atrium (paradoxical right-to-left flow). The transthoracic echocardiographic findings were then discussed with the cardiothoracic service, and the decision was made to proceed with transcatheter closure of the PFO.

After obtaining informed consent, we took the patient to the cardiac catheterization laboratory for percutaneous PFO closure on postoperative day 3. Cardiac catheterization was performed under general anesthesia. After placement of the venous sheath, the patient received a 3,000-U bolus of heparin. The activated clotting time (ACT) was maintained at a level of greater than 200 seconds for the duration of the procedure. Because of systemic desaturation, cardiac catheterization was performed with the patient on 100% FiO₂ (fraction of inspired oxygen). The pulmonary-to-systemic flow ratio was 1.0 (the saturation measurement obtained in the superior vena cava of 75% was nearly identical to the pulmonary artery saturation of 74%). The mean pressure recorded in the right atrium was 13 mmHg, and the mean pressure in the left atrium was 11 mmHg. Pressure in the right ventricle was 39/12 mmHg, and pressure in the main pulmonary artery was 34/13 mmHg (mean pressure, 23 mmHg). The transpulmonary gradient was 12 mmHg, and the calculated pulmonary vascular resistance was 3.5 Wood units. Transesophageal echocardiography (TEE) demonstrated bidirectional flow (via color-flow Doppler) through the PFO. A contrast saline injection showed a PFO with paradoxical right-to-left flow (a large number of microbubbles were seen crossing from the right atrium across the PFO into the left atrium) (Fig. 1). Under both fluoroscopic and TEE guidance, balloon sizing of the PFO was performed with a 20-mm NuMED sizing balloon catheter (NuMED; Hopkinton, NY). The stretched diameter of the PFO measured 14 mm by fluoroscopy and TEE. A 28-mm CardioSeal® Septal Occlusion Device (CSO) (NMT Medical, Inc.; Boston, Mass) was used to close the PFO. A contrast bubble study with agitated saline solution showed complete closure of the PFO (Fig. 2). The patient was extubated in the cardiac catheterization laboratory without difficulty. Immediately after the procedure, she had a saturation ranging from 93% to 99% on 4 L of oxygen by facemask. She was started on aspirin (325 mg) later that day. Her hypoxemia improved markedly after PFO closure, and she was weaned off oxygen over the next 2 days. She subsequently underwent endomyocardial biopsy without any problems. She was discharged 1 week later on anti-rejection medication and aspirin. At her 18-month follow-up, she continues to do well without any problems.

Fig. 1 Transesophageal echocardiogram shows A) a substantial patent foramen ovale (PFO, indicated by arrow), and B) a paradoxical right-to-left flow across the patent foramen ovale (large number of microbubbles in the left atrium).

LA = left atrium; RA = right atrium

Fig. 2 Transesophageal echocardiogram shows complete closure of the patent foramen ovale with a 28-mm CardioSea® Septal Occlusion Device (arrow). No microbubbles appear in the left atrium.

LA = left atrium; RA = right atrium

Discussion

The overall incidence of PFO varies from 9% to 27% in the general population.^5,6 Screening for atrial septal defect and PFO by visual examination and palpation is done routinely during the pretransplant evaluation of the donor heart; however, a probe-patent foramen ovale can sometimes be missed during this evaluation. An unrecognized PFO can cause substantial hypoxemia early in the post-transplant period due to a combination of several factors. Previous studies both in the canine model of cardiac transplantation⁷ and in human heart transplantation⁸ have demonstrated generalized but reversible myocardial dysfunction, thought to be secondary to anoxic injury during preservation of the donor heart. This, together with the increased workload that can sometimes be imposed on the donor right ventricle in the presence of pulmonary hypertension, can lead to right heart failure.⁸ The right ventricle is also subject to volume overload in the immediate post-transplant period and this, together with right ventricular diastolic dysfunction, can result in elevation of right-sided filling pressure. As right-sided filling pressure increases, right atrial pressure increases until it exceeds left atrial pressure, causing atrial level right-to-left shunting and consequent hypoxemia.

In the case of our patient, the combination of right ventricular diastolic dysfunction (elevated right ventricular end-diastolic pressure) with a right atrial mean pressure that was greater than the left atrial mean pressure resulted in significant right-to-left flow across the PFO, which caused systemic desaturation and hypoxemia. It is important to perform a thorough right heart catheterization with measurement of both the transpulmonary gradient and pulmonary vascular resistance. If both of these are elevated, pulmonary vasodilating agents such as milrinone and nitric oxide can be used to help stabilize the patient before closure of the PFO. Before performing saline contrast microbubble injection, it is important to remove visible air from the syringe to minimize the risk of embolization; as an alternative, color-flow Doppler can confirm the diagnosis by demonstrating paradoxical right-to-left flow.

Our review of the world medical literature reveals that intracardiac shunts are uncommon but reversible causes of hypoxemia during the early post-transplant period. One report describes a PFO detected on postoperative day 3, which was successfully managed with preload reduction and diuretic therapy, thereby avoiding PFO closure.¹ Two reports have described right-to-left shunting through a PFO: one associated with significant hypoxia that required emergent surgical correction³ and another with severe tricuspid regurgitation and paradoxical embolism, which was discovered 19 months after transplantation and also required surgical correction.⁴ Successful transcatheter closure of a residual atrial septal defect has been reported in a 3-year-old boy 3 months after he underwent heart transplantation.⁹ However, to our knowledge, transcatheter closure of a PFO in an adult patient with refractory hypoxemia in the immediate post-transplant period has not previously been reported. Some of the advantages of transcatheter PFO closure include the avoidance of repeat thoracotomy and cardiopulmonary bypass. As demonstrated by this case report, transcatheter closure even in the immediate post-transplant period is a safe and reasonable alternative to surgical PFO closure.

Conclusion

Patent foramen ovale is a relatively common finding in the general population, which, if undetected in the donor heart before transplantation, can lead to substantial hypoxemia during the immediate post-transplant period. Because visual examination and palpation of the septum of the donor heart can sometimes fail to reveal a PFO, transesophageal echocardiography with both color-flow Doppler and contrast saline microbubble injection may be of benefit in determining the presence or absence of a PFO before heart transplantation. As demonstrated by this case report, transcatheter closure of a PFO that causes hypoxemia during the immediate post-transplant period can be performed safely, and should be considered as an alternative to surgical closure of PFO after transplantation.