Percutaneous Closure of a Patent Foramen Ovale to Prevent Paradoxical Thromboembolism in a Patient With a Continuous-Flow LVAD

Download a PDF of this article.

Abstract: Patent foramen ovale (PFO) may complicate left ventricular assist device (LVAD) therapy. We report a 70-year-old male with a HeartMate II LVAD at increased risk for thromboembolic stroke secondary to a PFO with right-to-left shunting and a large mobile thrombus on his right atrial pacing lead. Via percutaneous intervention, a 25 mm Cribiform Amplatzer atrial septal occluder was successfully deployed across the PFO without complications. This is the first reported case of percutaneous PFO closure to prevent paradoxical thromboembolism in a normoxic patient with an LVAD. In addition, arterial desaturation and the sequelae of chronic hypoxemia were prevented. Strategies to diagnose PFO at the time of LVAD implantation and physiological implications of a right-to-left atrial shunt during mechanical unloading of the failing left ventricle are reviewed.

J INVASIVE CARDIOL 2013;25(3):154-156

Key words: percutaneous, patent foramen ovale, paradoxical thromboembolism, pacemaker lead, left ventricular assist device

____________________________________________

Over the past decade, left ventricular assist devices (LVADs) have emerged as a standard therapy for patients with advanced heart failure.¹ Multiple devices are commercially available or poised for clinical trials.² 

Common pathologies may complicate prolonged mechanical circulatory support. For example, undiagnosed patent foramen ovale (PFO) predisposes a patient with an LVAD to life-threatening hypoxemia.^3-14 As mechanical circulatory support gains prevalence, it is important to raise awareness of potential complications and to describe interventions that may be performed safely during LVAD support. In this report, we describe the first case of percutaneous PFO closure to prevent paradoxical thromboembolism in a patient with an LVAD. Strategies to diagnose PFO at the time of LVAD implantation and physiological implications of a right-to-left atrial shunt during mechanical unloading of the failing left ventricle are reviewed.

Case Description

A 70-year-old white male with a history of ischemic cardiomyopathy and a dual-chamber pacemaker was implanted with a HeartMate II LVAD (Thoratec Corporation). During the course of therapy, a left middle cerebral artery infarction produced mild dysarthria and right upper extremity weakness. After 7.5 months of LVAD support, the pump was exchanged for a second HeartMate II due to pump thrombosis. After 17 months of support, the patient presented with non-cardiac left upper quadrant pain surrounding the pump. The patient described the pain as intermittent and sharp with no radiation, shortness of breath, dyspnea, or diaphoresis. 

On admission, lipase and amylase were mildly elevated. Abdominal computed tomography was normal. Transesophageal echocardiography (TEE) identified a previously undiagnosed PFO with mild right-to-left shunting during quiet respiration and marked shunting during Valsalva maneuvers (Figure 1A). A 2.1 x 0.6 cm mobile thrombus was noted on the right atrial pacing lead (Figure 1B). Due to the increased risk for thromboembolic stroke and/or spontaneous deoxygenation at rest, the PFO was repaired. In the cardiac catheterization laboratory, the patient received cefazolin 2 g, heparin 50 units/kg (target activated clotting time >250 s), clopidogrel 600 mg, aspirin 325 mg, and midazolam 1 mg. The patient was not intubated. The left groin was prepared and draped in a sterile fashion. Lidocaine 2% solution was administered for local anesthesia. Venous access was obtained via modified Seldinger technique. Due to the potential risk of dislodging the pacing lead thrombus, a right heart catheterization was not performed to measure hemodynamics or shunt fraction. 

A 6 Fr multipurpose catheter back-loaded on a 0.035 mm Wholey wire was placed in the fossa ovalis and easily traversed the interatrial defect. The multipurpose catheter was advanced into the left upper pulmonary vein. A 0.035˝ Amplatzer super-stiff wire was advanced through the multipurpose catheter. The multipurpose catheter was removed. An 18 mm Amplatzer sizing balloon was placed across the interatrial septum and measured the PFO at approximately 12 mm in diameter. Of note, we routinely balloon-size PFOs and ASDs to guide device selection. Balloon sizing demonstrates the relative size, shape, and morphology (aneurysmal, hypertrophic, eccentric, etc.) of the defect as well as the location in the atrial septum. 

A 25 mm Cribiform Amplatzer septal occluder was advanced across the PFO. The left atrial disc was unsheathed. The right atrial disc was unsheathed. Successful deployment of the septal occluder across the interatrial defect was confirmed via cineangiogram (Figure 2A) with radio-opaque contrast material to delineate the right atrial border and exclude a residual shunt.¹⁵ 

The patient tolerated the procedure well. There were no perioperative or postoperative complications. The patient received clopidogrel 75 mg daily for 6 months and continued aspirin 81 mg daily and warfarin 12 mg daily. Postoperative day 1 transthoracic echocardiography (TTE) demonstrated the closure device across the atrial septum with no shunt via bubble study or color Doppler with standard provocative maneuvers (Figure 2B). The patient remained stable and was discharged home on postoperative day 2. 

At 6-week follow-up, the patient reported no complaints. TTE again demonstrated an appropriate position of the interatrial occluder in the interatrial septum without evidence of a shunt (Figure 2C). 

Discussion

It is estimated that 20%-35% of humans are born with a PFO.¹⁶ Similarly, TEE identifies a PFO in 27% of adult cardiac surgery patients.¹⁷ However, even with color Doppler and bubble contrast studies during Valsalva and Mueller maneuvers, the diagnostic sensitivity of TEE in the general population is only 86%.¹⁸ In patients with congestive heart failure, the diagnosis of a PFO becomes more difficult.¹⁹ If left ventricular dysfunction predominates, left atrial pressure exceeds right atrial pressure. The left-to-right pressure gradient may appose the septum primum across the limbus of the fossa ovalis and create an anatomical one-way flap valve that obstructs a left-to-right shunt and prevents a right-to-left shunt. As a result, standard maneuvers cannot easily provoke flow across the interatrial septum. 

Nonetheless, at the time of LVAD implantation, TEE is routinely attempted to identify a PFO for prophylactic closure. Multiple investigators have devised intraoperative techniques to increase diagnosis. For example, manual compression of the pulmonary artery acutely increases right atrial pressure, decreases left atrial pressure, and provokes right-to-left shunting through a subclinical PFO.²⁰ Positive end-expiratory pressure (PEEP) may aid in the diagnosis of a PFO by a similar mechanism. PEEP increases intrathoracic pressure, which temporarily increases pulmonary vascular resistance and right atrial pressure. In patients with a PFO, this technique increases the transatrial shunt fraction.²¹ Alternatively, intraoperative TEE performed with the LVAD running may facilitate diagnosis.²² During mechanical unloading with a continuous-flow LVAD, the left ventricular pressure-volume relationship collapses, and left ventricular pressure remains low throughout the cardiac cycle.²³ Left atrial pressure decreases, and the pressure gradient across the interatrial septum reverses. If a PFO is present, a right-to-left shunt may emerge on intraoperative TEE. Indeed, in a patient with a PFO, when the LVAD was turned off, right-to-left shunting ceased.⁸

Despite these techniques, a PFO may not be identified during LVAD implantation. Multiple reports have documented PFOs that complicated LVAD therapy.^3-14 In these cases, right-to-left shunting predisposed to arterial desaturation, hemodynamic instability, paradoxical embolism, ventricular volume overload, myocardial hypertrophy, and (worsening of) heart failure. Patients typically reported periodic episodes of symptoms related to intermittent hypoxemia despite adequate pulmonary function and arterial blood flow.^5-7 In these patients, mechanical unloading of the failing left ventricle reduced left atrial pressure below right atrial pressure. Since a PFO was present, deoxygenated venous blood followed the pressure gradient, entered the left atrium, and decreased systemic arterial oxygen saturation. The severity and onset of symptoms were unpredictable, but likely related to the pressure gradient across the interatrial septum, PFO size, shunt fraction, preload and afterload conditions (volume status), specific anatomy of the defect, and the influence of gravity with positional changes. 

The hypercoagulable blood dyscrasia associated with prolonged blood contact with the interior of the LVAD may cause devastating thromboembolic events. Yet in most patients, the LVAD is not the only potential source for thrombus. Many patients with advanced heart failure are referred for LVAD therapy only after electrical resynchronization therapy has failed. As a result, most candidates for long-term mechanical circulatory support have intracardiac pacemaker leads in situ prior to LVAD implantation.²⁴ Consequently, intracardiac leads may be an under-recognized nidus for thrombus formation. Indeed, thrombus is identified on 9%-32% of permanent transvenous pacemaker leads.^25,26 Furthermore, paradoxical thromboembolic stroke attributed to a pacemaker lead thrombus has been described.^27,28 These findings suggest that indwelling pacing leads should be considered as a source for unexplained thromboembolic complications, especially in patients in whom an LVAD may be blamed as the default source of thrombus. 

Management of a patient with a history of cryptogenic stroke and evidence of a PFO includes thrombolysis, chronic anticoagulation, and closure of the PFO. Percutaneous PFO closure is a standard treatment for patients with hypoxemia secondary to right-to-left shunting.²⁹ Importantly, percutaneous PFO closure to correct hypoxemia has also been described in hypoxemic adult^6,9,10,12,13 and pediatric³ patients with an LVAD. In these reports, PFO closure resulted in rapid reoxygenation and permanent symptom resolution. 

In the absence of hypoxemia, a PFO is not an absolute indication for prophylactic closure unless recurrent paradoxical thromboembolism is suspected.³⁰ In our normoxic patient with a history of embolic stroke, a large mobile thrombus on his right atrial pacing lead, and a PFO with intermittent shunting, recurrent cryptogenic stroke was a major concern. Consequently, percutaneous PFO closure was an appropriate prophylactic intervention.

Of note, when pacemaker leads reside in close proximity to a PFO, lead entrapment in the atrial septal occluder may interfere with adequate anchoring of the device within the interatrial septum. Incorrect device deployment may prevent closure of the foramen and impair endothelialization of the device.^31,32 In patients who undergo percutaneous closure of a PFO, entrapment of pacing leads in the right atrial disc of the atrial septal occluder should be avoided.

In summary, we have presented the first case of percutaneous PFO closure to prevent paradoxical thromboembolism in a normoxic patient with an LVAD. Prior history of cryptogenic stroke should raise suspicion for a PFO. Intracardiac pacing/defibrillator leads may be a source of thrombus. If a PFO is identified in a patient undergoing long-term mechanical circulatory support, prophylactic closure should be considered. 

Conclusion

A PFO discovered during the implantation of an LVAD is routinely closed to prevent sequelae of right-to-left shunting during prolonged mechanical circulatory support. Simple screening maneuvers may assist in the intraoperative diagnosis of a PFO via TEE. In a normoxic patient in whom a PFO is identified during ongoing LVAD therapy, percutaneous PFO closure may be appropriate if there is concern for paradoxical thromboembolism. 

Acknowledgments. The authors acknowledge and thank the University of Louisville Division of Cardiology VAD Coordinators.

References

1. Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361(23):2241-2251.
2. Bartoli CR, Dowling RD. The future of adult cardiac assist devices: novel systems and mechanical circulatory support strategies. Cardiol Clin. 2011;29(4):559-582.
3. Gagliardi MG, Papavasileiou L, Pongiglione G. Rescue treatment by percutaneous closure of interatrial septal defect or PFO in infants with Berlin heart. Catheter Cardiovasc Interv. 2011;77(4):577-579.
4. Baker JE, Stratmann G, Hoopes C, Donateillo R, Tseng E, Russell IA. Profound hypoxemia resulting from shunting across an inadvertent atrial septal tear after left ventricular assist device placement. Anesth Analg. 2004;98(4):937-940, table of contents. 
5. Baldwin RT, Duncan JM, Frazier OH, Wilansky S. Patent foramen ovale: a cause of hypoxemia in patients on left ventricular support. Ann Thorac Surg. 1991;52(4):865-867.
6. Nguyen DQ, Das GS, Grubbs BC, Bolman RM 3rd, Park SJ. Transcatheter closure of patent foramen ovale for hypoxemia during left ventricular assist device support. J Heart Lung Transplant. 1999;18(10):1021-1023.
7. Kilger E, Strom C, Frey L, et al. Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device. Acta Anaesthesiol Scand. 2000;44(1):125-127.
8. Shapiro GC, Leibowitz DW, Oz MC, Weslow RG, Di Tullio MR, Homma S. Diagnosis of patent foramen ovale with transesophageal echocardiography in a patient supported with a left ventricular assist device. J Heart Lung Transplant. 1995;14(3):594-597.
9. Bonvini RF, Verin V, Lerch R, Gerard I, Sierra J, Spratt JC. Percutaneous closure of patent foramen ovale in a patient presenting arterial hypoxaemia and supported with bi-ventricular assist device. Intensive Care Med. 2005;31(4):602-603.
10. Srinivas CV, Collins N, Borger MA, Horlick E, Murphy PM. Hypoxemia complicating LVAD insertion: novel application of the Amplatzer PFO occlusion device. J Card Surg. 2007;22(2):156-158.
11. Kyo S, Matsumura M, Takamoto S, Omoto R. Transesophageal color doppler echocardiography during mechanical assist circulation. ASAIO Trans. 1989;35(3):722-725.
12. Weig T, Dolch ME, Frey L, Bruegger D, Boekstegers P, Sodian R, Irlbeck M. Delayed intracardial shunting and hypoxemia after massive pulmonary embolism in a patient with a biventricular assist device. J Cardiothorac Surg. 2011;6:133.
13. Kavarana MN, Rahman FA, Recto MR, Dowling RD. Transcatheter closure of patent foramen ovale after left ventricular assist device implantation: intraoperative decision making. J Heart Lung Transplant. 2005;24(9):1445.
14. Magovern JA, Pae WE Jr, Richenbacher WE, Pierce WS. The importance of a patent foramen ovale in left ventricular assist pumping. ASAIO Trans. 1986;32(1):449-453.
15. Wahl A, Praz F, Stinimann J, et al. Safety and feasibility of percutaneous closure of patent foramen ovale without intra-procedural echocardiography in 825 patients. Swiss Med Wkly. 2008;138(39-40):567-572.

16. Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc. 1984;59(1):17-20.
17. Augoustides JG, Weiss SJ, Weiner J, Mancini J, Savino JS, Cheung AT. Diagnosis of patent foramen ovale with multiplane transesophageal echocardiography in adult cardiac surgical patients. J Cardiothorac Vasc Anesth. 2004;18(6):725-730.
18. Sukernik MR, Mets B, Bennett-Guerrero E. Patent foramen ovale and its significance in the perioperative period. Anesth Analg. 2001;93(5):1137-1146.
19. Siostrzonek P, Lang W, Zangeneh M, et al. Significance of left-sided heart disease for the detection of patent foramen ovale by transesophageal contrast echocardiography. J Am Coll Cardiol. 1992;19(6):1192-1196.
20. Majd RE, Kavarana MN, Bouvette M, Dowling RD. Improved technique to diagnose a patent foramen ovale during left ventricular assist device insertion. Ann Thorac Surg. 2006;82(5):1917-1918.
21. Cujec B, Polasek P, Mayers I, Johnson D. Positive end-expiratory pressure increases the right-to-left shunt in mechanically ventilated patients with patent foramen ovale. Ann Intern Med. 1993;119(9):887-894.
22. Liao KK, Miller L, Toher C, Ormaza S, Herrington CS, Bittner HB, Park SJ. Timing of transesophageal echocardiography in diagnosing patent foramen ovale in patients supported with left ventricular assist device. Ann Thorac Surg. 2003;75(5):1624-1626.
23. Bartoli CR, Giridharan GA, Litwak KN, et al. Hemodynamic responses to continuous versus pulsatile mechanical unloading of the failing left ventricle. Asaio J. 2010;56(5):410-416.
24. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140-2150.
25. Alizadeh A, Maleki M, Bassiri H, et al. Evaluation of atrial thrombus formation and atrial appendage function in patients with pacemaker by transesophageal echocardiography. Pacing Clin Electrophysiol. 2006;29(11):1251-1254.
26. Korkeila PJ, Saraste MK, Nyman KM, Koistinen J, Lund J, Juhani Airaksinen KE. Transesophageal echocardiography in the diagnosis of thrombosis associated with permanent transvenous pacemaker electrodes. Pacing Clin Electrophysiol. 2006;29(11):1245-1250.
27. Michaels AD, Burlew BS. Pacemaker lead thrombus causing cryptogenic stroke in a patient referred for percutaneous patent foramen ovale closure. J Invasive Cardiol. 2009;21(11):E224-E225.
28. Allie DE, Lirtzman MD, Wyatt CH, Vitrella DA, Walker CM. Septic paradoxical embolus through a patent foramen ovale after pacemaker implantation. Ann Thorac Surg. 2000;69(3):946-948.
29. Ilkhanoff L, Naidu SS, Rohatgi S, Ross MJ, Silvestry FE, Herrmann HC. Transcatheter device closure of interatrial septal defects in patients with hypoxia. J Interv Cardiol. 2005;18(4):227-232.
30. Windecker S, Wahl A, Chatterjee T, et al. Percutaneous closure of patent foramen ovale in patients with paradoxical embolism: long-term risk of recurrent thromboembolic events. Circulation. 2000;101(8):893-898.
31. Demkow M, Malek LA, Ruzyllo W. Avoiding pacemaker lead entrapment during PFO closure. Catheter Cardiovasc Interv. 2008;72(1):97-99.
32. Meltser H, Hoyer MH, Kalaria VG. Entrapment of right atrial pacemaker lead by patent foramen ovale closure device: successful percutaneous salvage. Catheter Cardiovasc Interv. 2005;65(4):593-596.

___________________________________

From the ¹MD/PhD Program, University of Louisville School of Medicine, Louisville, Kentucky, ²Division of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky, and ³Division of Thoracic and Cardiovascular Surgery, University of Louisville, Louisville, Kentucky.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Birks reports honoraria and a research grant from Thoratec. The other authors report no conflicts of interest regarding the content herein.

Manuscript submitted August 30, 2012, provisional acceptance given October 9, 2012, final version accepted December 5, 2012.

Address for correspondence: Mark S. Slaughter, MD, Division of Thoracic and Cardiovascular Surgery, University of Louisville, 201 Abraham Flexner Way, Suite 1200, Louisville, KY 40202. Email: mark.slaughter@louisville.edu