Perioperative Duplex Ultrasound Following Endothermal Ablation of the Saphenous Vein: Is it Worthless?

Abstract: Fifteen years ago, radiofrequency ablation of the saphenous vein was introduced as a new and minimally invasive modality for the treatment of superficial venous insufficiency. Three years later, it was followed by endovenous laser ablation. These procedures have revolutionized the treatment of superficial venous insufficiency and have caused a dramatic shift from a highly invasive and morbid inpatient procedure, to a minimally invasive and ambulatory office procedure. Soon after their introduction, a new clinical entity was identified: endothermal heat-induced thrombosis (EHIT). This terminology, a classification system, and treatment strategies were introduced by Kabnick in 2005. Subsequently, advances in technique, along with the discovery of associated risk factors and a better understanding of the pathophysiologic process of endothermal coagulum formation, have reduced the current incidence of EHIT classes 2-4 to between 1%-2%. Still, a paucity of data exists regarding the true incidence of clinically significant pulmonary embolism secondary to EHIT. The authors believe that the rate is less than 0.01%. Furthermore, successful thermal saphenous ablation efficacy in the perioperative period approaches 99%. Despite these excellent numbers, the standard of care is to obtain a duplex ultrasound to evaluate for the presence of EHIT within the first 1-2 weeks post endovenous thermal ablation. Given this information, the authors believe that performing duplex ultrasound in the perioperative period is wasteful and an inefficacious use of limited health-care resources. Thus, the authors advocate against routine duplex to evaluate treatment efficacy and EHIT presence during the perioperative period in asymptomatic patients.

J INVASIVE CARDIOL 2014;26(10):548-550

Key words: endothermal heat-induced thrombosis, deep venous thrombosis (DVT), radiofrequency ablation, endovenous laser ablation

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The past 15 years brought about several significant advances in the treatment of superficial venous incompetency, including the introduction and generalized acceptance of endovenous thermal ablative techniques. These procedures resulted in a dramatic shift from a highly invasive and morbid inpatient procedure to a minimally invasive office-based procedure, revolutionizing the treatment of superficial venous insufficiency.
Each new drug, device, or procedure introduced into the medical field may be associated with potential complications. Many of these adverse effects are poorly understood until sufficient short- and long-term outcome data are analyzed. Such is the case with radiofrequency ablation (RFA) and endovenous laser ablation (EVLA) of the saphenous veins. Soon after the introduction of these ablative techniques, reports began to surface regarding the potential for development of deep venous thrombosis (DVT) beyond the saphenofemoral junction (SFJ) in the immediate postoperative period.
In response to growing concerns, Kabnick introduced the term “endothermal heat-induced thrombosis” (EHIT), along with a classification system and recommended treatment strategies (Table 1) at the 2006 annual meeting of the American Venous Forum.¹

Historical Perspective

Since their introduction in 1999 and 2002, RFA² and EVLA³ have become widely accepted as the new standards of care for patients with symptomatic superficial truncal venous insufficiency. As a result, the number of these operations performed each year in the United States and Europe has increased almost exponentially. Although the exact number of endovenous ablations performed worldwide each year is unknown, our conservative estimate is that >300,000 are performed annually in the United States.⁴
At the inception of RFA and EVLA, our initial understanding of EHIT was poor. We had no understanding of the incidence, pathophysiology, associated risk factors, or the clinical significance of these novel types of thrombus. Some of the first reports of this new clinical entity suggested an incidence as high as 16%, which called into question the safety of endovenous thermal ablative techniques.⁵ Furthermore, we did not understand that these thrombi, from a pathophysiologic perspective, were fundamentally different than classical acute deep venous thromboses (DVTs). Thanks to advances and revisions in technique, a significantly larger data pool from which to sample, and a greater understanding of the pathophysiology of EHIT formation, the incidence of EHIT has decreased precipitously.
Over the last 15 years, large volumes of data have been accumulated regarding the safety and efficacy of these procedures. We can now verify that the efficacy of superficial axial vein ablation at 1 year (measured as the rate of closure) ranges from 95%-98%.⁶ Additionally, the incidence of EHIT of all classes ranges between 3%-4%,⁷ If we exclude EHIT 1, which by definition is not of clinical significance, the EHIT rate is approximately 1%-2%.^8,9 Many authors have reported even lower EHIT rates; for example, Marsh et al reported a rate as low as 0.2% from a series of 2820 cases.¹⁰

Current Evidence and Future Trends

Regarding class 3 and 4 EHIT and clinically significant PE after endovenous ablation, the true incidence is difficult to ascertain. Some evidence suggests that the incidence of symptomatic pulmonary embolism (PE) after RFA or EVLA is at most 0.03%.9 However, this statistic is substantiated by only two studies that include over 8000 combined cases. In addition, these studies are underpowered with regard to the complication of symptomatic PE.^8,10 The authors believe this to be a gross overestimation, and that the true incidence of symptomatic PE secondary to endovenous ablations is <0.01%. Furthermore, Sufian reports that 4.5% of cases diagnosed with EHIT (all classes) are related to thrombus progression; however, all of these patients have resolution of their EHIT within 4 weeks.⁸
Even now, 15 years after the introduction of RFA, we have little knowledge about the true clinical significance of EHIT 2. The majority of these thrombi will disappear within 7-10 days with no additional sequelae. What happens to them? Do they dissolve, retract, or embolize? The natural history is likely the latter; however, the thrombus burden is insignificant and has no detrimental physiologic effect on cardiopulmonary circulation.¹¹
An unreported series of 7 of our own patients with ultrasonographic evidence of EHIT 2 were monitored with serial ultrasound. Six of the 7 patients were placed on therapeutic enoxaparin. All 7 patients had resolution of their EHIT 2 within 14 days.12 Immediately after EHIT resolution on duplex ultrasound, these patients underwent chest computed tomography (CT) angiography. Two of the 7 asymptomatic patients’ CT scans were reported positive for PE. No patient suffered significant sequelae from either their EHIT or PE. Although these data are not statistically significant, they do suggest that our initial reaction to EHIT may have been extreme; perhaps, we are in fact dealing with a benign clinical entity.
An additional indication for obtaining a duplex ultrasound in the immediate postoperative period is the evaluation of treatment efficacy. The rate of saphenous vein closure in the immediate postoperative period approaches 99%.⁶ Given this high rate of initial success, assessing the efficacy of treatment during this period is futile. The process of vein occlusion and the subsequent tissue remodeling that follows takes several months. Using duplex to assess the efficacy of vein obliteration before 3 months is analogous to announcing the winner of a race before the horses leave the starting gate. Furthermore, current trends for the evaluation of treatment efficacy are moving away from surrogate markers like clinical outcomes, and toward patient-reported outcomes. What does it matter if a patient with previous symptomatic C2 disease has asymptomatic great saphenous vein recanalization post ablation? The answer is: it does not.

Statistical Analysis

The incidence of EHIT 2 is approximately 2%.⁹ If approximately 300,000 endovenous thermal ablations are performed per annum in the United States, then 6000 patients each year are at risk for the development of an EHIT class 2 or higher. The incidence of clinically symptomatic PE is in the order of 0.01%. Therefore, only 30 (of these 300,000 patients) will have a clinically symptomatic PE. Thus, the number of patients needed to treat in order to find just 1 of these 30 patients is 10,000. If the average charge for a duplex ultrasound in the United States is between $350 and $500,¹³ then physicians are collectively charging 3.5-5.5 million dollars in order to detect and treat 1 EHIT class 2 or greater, thereby potentially preventing 1 PE. By foregoing duplex ultrasound in the immediate postoperative period, healthcare providers can save at least 100-150 million dollars per annum in unnecessary costs.
Furthermore, duplex ultrasound is not 100% accurate in diagnosing DVT. The reported accuracy of duplex ultrasound from more recent studies in the diagnosis of DVT ranges from 90%-100%.^14,15 For the purposes of this discussion, the authors can conservatively estimate that the false positive rate of duplex ultrasound in the detection of DVT is 1%. This would translate to 3000 false positive studies and potentially 3000 patients being placed on therapeutic low-molecular-weight heparin (LMWH). The rate of spontaneous major bleeding with LWMH is 1.2%;¹⁶ therefore, 36 patients would suffer from major spontaneous bleeding. Considering that only 30 patients per annum will have a clinically symptomatic PE (not necessarily fatal) secondary to EHIT, physicians are collectively doing more harm than good by obtaining duplex ultrasounds to discover an EHIT.
There have been several recently published articles on clinical factors that may be able to predict the relative risk of EHIT. These clinical predictors include a history of prior DVT, male gender, CEAP class 3 or higher, and a higher Caprini risk assessment score.^8,17 The preoperative evaluation of risk factors may yield useful clinical information, and could help separate a subset of patients who may benefit from postoperative duplex to evaluate for EHIT. However, given the questionable clinical significance of EHIT (which we believe to be insignificant), the relative benefit of such screening is difficult to assess. In the presence of abnormal postprocedural symptomatology, individual practitioners should use their best clinical judgment in determining whether or not to obtain a duplex ultrasound.
This paper has several limitations. As EHIT is fundamentally different from DVT, the accuracy of duplex ultrasound in the detection of these thrombi may differ significantly from that of traditional acute DVTs. Also, given that clinically significant PE after ablation of the saphenous vein is such a rare event, the true incidence is difficult to estimate. We believe that the data and statistics presented in this paper represent useful extrapolations of the data that is currently available. Furthermore, although the vast majority of EHITs represent only small extensions of thrombus into the common femoral vein, there is a distinct paucity of literature regarding the exact size of thrombus (sonographically) that is needed in order to cause a clinically significant PE. Lastly, although we know from animal studies and imaging data that endothermal heat-induced thrombus is fundamentally different in composition from a classical acute DVT, there have been no reported histological analyses of these thrombi obtained from human subjects. Therefore, statements made as to the nature of these coagula refer more to their observed clinical and pathophysiologic behavior, not their histologic composition.

Conclusion

Perioperative duplex ultrasound following endovenous thermal ablation of the saphenous vein is wasteful and not efficacious for the prevention of complications or treatment failure. Hundreds of millions of health-care dollars can be saved per annum by not performing routine duplex ultrasound on asymptomatic patients in the 1-2 week postoperative period following endothermal ablation. Moreover, there may be a significant “over-treatment” effect to performing these studies on asymptomatic patients, in the form of therapeutic doses of LMWH prescribed to patients at minimal risk for PE. The concomitant episodes of spontaneous major hemorrhage that would occur secondary to this overtreatment meet or exceed the risk of clinically symptomatic PE from EHIT. Given the above conclusions, it seems obvious that duplex ultrasound following endothermal ablation of the saphenous vein is in fact worthless and should be removed from future venous ablation guidelines.

References

1. Kabnick L, Ombrellino M, Agis H, et al. Endovenous heat induced thrombosis (EHIT) following endovenous vein obliteration: to treat or not to treat? A new thrombotic classification. Third International Vein Congress: In-Office Techniques. April 14-16, 2005.
2. Harris EJ. Radiofrequency ablation of the long saphenous vein without high ligation and stripping for primary varicose veins: pros and cons. Semin Vasc Surg. 2002;15(1):34-38.
3. Navarro L, Min R, Bone C. Endovenous laser: a new minimally invasive method of treatment for varicose veins – preliminary observations using a 810 nm diode laser. Dermatol Surg. 2001;27(2):117-122.
4. Data estimated from sales projections provided by Covidien and AngioDynamics.
5. Hingorani A, Ascher E, Markevich N, Schutzer R, et al. Deep venous thrombosis after radiofrequency ablation of greater saphenous vein: a word of caution. J Vasc Surg. 2004;40(3):500-504.
6. Proebstle MP, Vago B, Alm J, et al. ClosureFast Clinical Study Group. Treatment of the incompetent great saphenous vein by endovenous radiofrequency postered segmental thermal ablation: first clinical experience. J Vasc Surg. 2008;47(1):151-156.
7. Rhee SJ, Cantelmo NL, Conrad MF, Stoughton J. Factors influencing the incidence of endovenous heat-induced thrombosis (EHIT). Vasc Endovasc Surg. 2013:47(3):207-212.
8. Sufian S, Arnez A, Labropoulos N, et al. Incidence, progression, and risk factors for endovenous heat induced thrombosis after radiofrequency ablation. J Vasc Surg: Venous Lymphat Disord. 2013;1(2):159-164.
9. Dexter D, Kabnick L, Berland T, et al. Complications of endovenous lasers. Phlebology. 2012;27(Suppl 1):40-45.
10. Marsh P, Price B, Holdstock J, Harrison C, Whitely M. Deep vein thrombosis (DVT) after venous thermoablation techniques: rates of endovenous heat-induced thrombosis (EHIT) and classical DVT after radiofrequency and endovenous laser ablation in a single center. Eur J Vasc Endovasc Surg. 2010;40(4):521-527.
11. Sufian S, Arnez A, Lakhanpal DG. Case of the disappearing heat-induced thrombus causing pulmonary embolism during ultrasound evaluation. J Vasc Surg. 2012;55(2):529-531.
12. Nwaejike N, Srodon PD, Kyriakides C. Pulmonary embolism following endovenous laser ablation (EVLA) of the great saphenous vein. J Radiol Case Rep. 2008;2(2):9-12.
13. Data obtained from independent surveillance by the authors of online quotes for duplex ultrasound from multiple websites including: https://www.jcl.com/hospitals/average-pricing-information/ultrasound-procedures; https://healthcarebluebook.com.
14. Tomkowski WZ, Davidson BL, Wisniewska J, et al. Accuracy of compression ultrasound in screening for deep venous thrombosis in acutely ill medical patients. Thromb Haemost. 2007;97(2):191-194.
15. Ozbudak O, Erogullari I, Ogus C, et al. Doppler ultrasonography versus venography in the detection of deep vein thrombosis in patients with pulmonary embolism. J Thromb Thrombolysis. 2006;21(2):159-162.
16. Crowther MA, Warkentin TE. Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents. Blood. 2008;111(10):4871-4879.
17. Rhee SJ, Cantelmo NL, Conrad MF, Stoughton J. Factors influencing the incidence of endovenous heat-induced thrombosis (EHIT). Vasc Endovascular Surg. 2013;47(3):207-212.
18. Kabnick L, Ombrellino M, Agis H, et al. Endovenous heat-induced thrombosis (EHIT) at the superficial-deep venous junction: a new post-treatment clinical entity, classification and potential treatment strategies. 18th Annual Meeting of the American Venous Forum, Miami, Florida, 2006.

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From the Division of Vascular and Endovascular Surgery, New York University Langone Medical Center, New York, New York.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Jones reports no conflicts of interest regarding the content herein. Dr Kabnick reports consultancies with AngioDynamics, Amsel, BTG, Vascular Insights, and Veniti; royalties from AngioDynamics.

Manuscript submitted March 6, 2014, provisional acceptance given May 8, 2014, final version accepted May 30, 2014.

Address for correspondence: Lowell S. Kabnick, MD, RPhS, FACS, New York University, NYU Vein Center, 530 1st Avenue, New York, NY 10016. Email: Lowell.Kabnick@nyumc.org