Spontaneous Echo Contrast and TAVR: A Smoking Gun?

Since its commercial approval in the United States, transcatheter aortic valve replacement (TAVR) has developed into a viable alternative to traditional surgical aortic valve replacement in high-risk or inoperable patients.^1,2 Clinical outcomes of TAVR procedures have improved over time.³ Possible reasons for the improvement in outcomes of TAVR include improvements in technology and increased operator and center experience, but perhaps more importantly, improved patient selection. TAVR has become an increasingly attractive option for a broader range of patients with aortic stenosis, and there are ongoing efforts to study TAVR in lower-risk patients. As the indications for TAVR continue to expand, patient selection, as well as tailored patient management, will become increasingly important.

In this month’s issue of the Journal of Invasive Cardiology, Ando et al⁴ have reported on the correlation of spontaneous echocardiographic contrast (SEC) in the left atrium at the time of TAVR with negative clinical outcomes. In this single-center, retrospective analysis of 93 consecutive patients undergoing TAVR, a total of 12 patients were noted to have SEC in the left atrium by echocardiography. The primary study endpoint, which was defined as a composite of a cardioembolic event, death from any cause, and admission for decompensated heart failure within 3 months after TAVR, occurred more commonly in patients with SEC (58%) than in patients without SEC (19%). This correlated with a hazard ratio of 5 for SEC after adjusting for sex and STS score. This led the authors to conclude that SEC in the left atrium at the time of TAVR is associated with the primary endpoint. 

The finding of SEC in the left atrium implies a low-flow state and is often associated with the presence of atrial fibrillation. It has previously been described that low-flow, independent of ejection fraction and low transaortic valvular gradient, is predictive of higher early and late mortality in high-risk patients with severe aortic stenosis undergoing TAVR.^5,6 Stroke volume and stroke volume index have been used to characterize flow and to help identify patients with low-flow states who may be at higher risk with TAVR.^5-7 The current study considers that SEC may be a useful tool in identifying patients in low-flow states who may be at higher risk of an adverse event with TAVR. Improving risk stratification of patients undergoing TAVR is critical, as it allows the identification of patients who may ultimately benefit from more aggressive and tailored therapy.

A potential target in these patients is stroke risk reduction. In the current study, there was a trend toward a higher incidence of cardioembolic phenomena post TAVR in the SEC group. Although this did not meet statistical significance, it had the largest effect of the three individual components of the primary endpoint, and likely has clinical significance. Previous analyses have shown that SEC is associated with higher rates of stroke/transient ischemic attack (independent of TAVR).⁸ The presence of SEC may help identify patients at higher risk of an adverse outcome after TAVR, specifically a cardioembolic event. One can surmise that those patients may theoretically benefit from a targeted strategy of cardioembolic protection or aggressive anticoagulation. Cardioembolic protection devices are currently still being evaluated for their role in decreasing stroke in TAVR. Feasibility and randomized studies of embolic filter and deflector devices have been conducted and reported,^9,10 and others, such as the SENTINEL trial (NCT02214277), are currently enrolling patients. Using SEC as a marker of both low-flow and as a risk of cardioembolic events might serve to identify patients at higher risk who may potentially benefit from these devices at the time of TAVR. What remains unclear is the role that the presence of atrial fibrillation may have in our understanding of this risk.

The optimal antithrombotic therapy following TAVR has also not been well defined. The current American College of Cardiology/Society for Thoracic Surgeons guidelines recommend aspirin indefinitely post procedure, and clopidogrel for 3-6 months.¹¹ If warfarin is indicated, then patients are recommended to be treated with aspirin and warfarin without clopidogrel.¹¹ However, these recommendations are largely empiric. Recent data have called into question the value of a thienopyridine in addition to aspirin post TAVR.¹² As stroke remains a dreaded outcome of TAVR, and reducing stroke is a target of therapeutic approaches, the role for antithrombotic and anticoagulant therapy post TAVR needs to be better defined. Trials examining novel oral anticoagulants (NOACs) are currently underway. The Global Study Comparing a rivAroxaban-based antithrombotic strategy to an antiplatelet Strategy After Transcatheter Aortic vaLve rEplacement to Optimize Clinical Outcomes (GALILEO) trial (NCT02556203) will examine whether use of a NOAC vs antiplatelet therapy is associated with lower mortality and cardioembolic events after TAVR. The identification of SEC at the time of TAVR may be beneficial in identifying those patients who are at higher risk of a cardioembolic event post TAVR and thus may benefit from more aggressive antithrombotic therapy.  

Overall, as the use of TAVR continues to expand, the role for identifying which patients are at a higher risk of an adverse outcome post procedure has become increasingly important. It may allow for the development of an individualized therapeutic approach (which may include use of a cardioembolic protection device at the time of the procedure, or more intensive postprocedural antithrombotic therapy). Ultimately, this may lead to the appropriate use of targeted aggressive interventions in higher-risk patients, and allow the avoidance of higher-risk treatments in lower-risk subsets. The use of SEC, as demonstrated in this retrospective analysis by Ando et al,⁴ may have significant prognostic value in helping to identify patients who may be at higher risk of an adverse event with TAVR, and, therefore, may guide targeted treatment strategies. As clinical trials are designed to test therapeutic adjuncts to help reduce the risk of cardioembolic events and their sequelae, it may be important to identify and enroll those patients at higher risk of events using markers such as SEC.   

References

1.     Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597-1607.

2.     Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364:2187-2198.

3.     Webb J, Cribier A. Percutaneous transarterial aortic valve implantation: What do we know? Eur Heart J. 2011;32:140-147.

4.     Ando T, Slovut D, Holmes AA, Taub CC. Spontaneous echocardiographic contrast in the left atrium is associated with worse outcomes following transcatheter aortic valve replacement. J Invasive Cardiol. 2016;28:152-157.

5.     Le Ven F, Freeman M, Webb J, et al. Impact of low flow on the outcome of high-risk patients undergoing transcatheter aortic valve replacement. J Am Coll Cardiol. 2013;62:782-788.

6.     Herrmann HC, Pibarot P, Hueter I, et al. Predictors of mortality and outcomes of therapy in low-flow severe aortic stenosis: a placement of aortic transcatheter valves (PARTNER) trial analysis. Circulation. 2013;127:2316-2326.

7.     Pibarot P, Dumesnil JG. Low-flow, low-gradient aortic stenosis with normal and depressed left ventricular ejection fraction. J Am Coll Cardiol. 2012;60:1845-1853.

8.     Kupczynska K, Kasprzak JD, Michalski B, Lipiec P. Prognostic significance of spontaneous echocardiographic contrast detected by transthoracic and transesophageal echocardiography in the era of harmonic imaging. Arch Med Sci. 2013;9:808-814.

9.     Rodes-Cabau J, Kahlert P, Neumann FJ, et al. Feasibility and exploratory efficacy evaluation of the Embrella Embolic Deflector System for the prevention of cerebral emboli in patients undergoing transcatheter aortic valve replacement: the PROTAVI-C pilot study. JACC Cardiovasc Interv. 2014;7:1146-1155.

10.     Lansky AJ, Schofer J, Tchetche D, et al. A prospective randomized evaluation of the TriGuard HDH embolic DEFLECTion device during transcatheter aortic valve implantation: results from the DEFLECT III trial. Eur Heart J. 2015;36:2070-2078. Epub 2015 May 19. 

11.     Holmes DR Jr, Mack MJ, Kaul S, et al. 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement: developed in collabration with the American Heart Association, American Society of Echocardiography, European Association for Cardio-thoracic Surgery, Heart Failure Society of America, Mended Hearts, Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Thorac Cardiovasc Surg. 2012;144:e29-e84.

12.    Hassell ME, Hildick-Smith D, Durand E, et al. Antiplatelet therapy following transcatheter aortic valve implantation. Heart. 2015;101:1118-1125.

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From the Cardiovascular Medicine Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Fiorilli reports no conflicts of interest regarding the content herein. Dr Anwaruddin is a speaker/consultant for Edwards Lifesciences; consultant for Medtronic; and reports institutional research support for a clinical trial from Claret Medical. 

Address for correspondence: Saif Anwaruddin, MD, FACC, FSCAI, Assistant Professor of Medicine, Co-Director, Transcatheter Valve Program, Perelman School of Medicine at the University of Pennsylvania, Hospital of the University of Pennsylvania, 9036 Gates Pavilion, 3400 Spruce Street, Philadelphia, PA 19104. Email: saif.anwaruddin@uphs.upenn.edu