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Friday, March 15, 2019

Safety and durability of infrarenal aorta as distal landing zone in fenestrated or branched endograft repair for thoracoabdominal aneurysm 


Clinical Question:
Does using the infrarenal aorta as a distal landing zone, instead of iliac arteries, for fenestrated or branched endovascular aortic repair (FB-EVAR) decrease the rate of spinal cord and mesenteric ischemia?

Take-away Point:
Termination of an aortic endograft in the infrarenal aorta for fenestrated and branched EVAR is technically feasible with similar rates of paraplegia and mesenteric ischemia however more data is needed to evaluate for future type 1B endoleaks due to aortic degeneration.

Reference:
Law Y, Kölbel T, Rohlffs F, Behrendt C, Heidemann F, Debus ES, Tsilmparis N. (2018). A Safety and durability of infrarenal aorta as distal landing zone in fenestrated or branched endograft repair for thracoabdominal aneurysm. J Vasc Surg, 69(2), 334-341. doi:10.1016/j.jvs.2018.04.052

Click here for abstract

Study Design: Retrospective single-center cohort study

Funding Source: Self-funded

Setting: Department of Vascular Medicine, German Aortic Center Hamburg, University Heart Center of Hamburg, Germany

Summary


Conventional knowledge and manufacturer recommendation supports use of the iliac arteries as the distal landing zone for fenestrated and branched endovascular aneurysm repair (FB-EVAR) however there is no data in the literature to support iliac over distal aorta landing zone. This study retrospectively evaluated 40 patients who received FB-EVAR with the native infrarenal aorta as the distal landing zone. Grafts included the Zenith custom-made, Zenith T-branch and surgeon-modified endografts. Criteria for use of the infrarenal aorta included ≥2 cm of healthy infrarenal aorta, preferably free of thrombus, dissection and calcification. The distal stent graft was oversized by 15-30% diameter; in the event of a severe size mismatch of the distal stent graft modules a Giant Palmaz stent was placed to correct infolding and strengthen the connection.

No immediate or delayed type 1B endoleaks (range 0-72 months) were identified on surveillance CTA. Spinal cord ischemia occurred in 15% of patients (5 temporary and 1 permanent) and zero incidence of mesenteric ischemia, both of which are comparable to literature with iliac distal landing zones. 30-day mortality was 7.5% (sepsis, pneumonia, and multiorgan failure following laparotomy for GDA bleed). Post-operative CTA showed that 92.5% had at least 1 lumbar artery preserved and 74.2% had the IMA preserved. Of note, there was gradual degeneration of the infrarenal aorta at the stent graft landing zone, likely attributable to the aorta expanding to the size of the stent graft from the outward radial force. 


Figure 4. Denervation of infrarenal aorta and iliac arteries over time. The averaged nominal diameter of stent grafts was indicated. The error bars indicate the 95% confidence interval (CI).

Commentary


Termination of the stent graft in the infrarenal aorta for FB-EVAR is technically feasible with similar paraplegia and mesenteric ischemia rates to current reported literature on iliac landing zones. While the rates of paraplegia and mesenteric ischemia reported by the authors are comparable, they question whether their rates may be higher due to a high proportion of emergent cases. Preserving the IMA and lumbar arteries intuitively would minimize this risk. Degeneration of the infrarenal aorta at the site of the stent graft however appears problematic for younger patients as they will likely need distal extension for future type 1B endoleaks. Infrarenal aortic landing zone seems best suited for those patients at highest risk for paraplegia (long total coverage area, prior repair, etc) and mesenteric ischemia. Further work is needed however with comparison studies and longer term follow-up to determine the viability of this treatment option.

Post Author:
Nicole A. Keefe, MD
Resident Physician
Department of Radiology and Medical Imaging
University of Virginia
@NikkiKeefe

Thursday, March 14, 2019

Clinical and Economic Benefits of Stent Grafts in Dysfunctional and Thrombosed Hemodialysis Access Graft Circuits in the REVISE Randomized Trial 


Clinical question
Is it more efficient and cost effective to maintain arteriovenous graft hemodialysis access circuits after rescue with percutaneous transluminal angioplasty with or without concurrent Viabahn stent grafts over 24 months?

Take-away point
Over 24 months, the use of stent grafts significantly reduced the number of reinterventions for all patients and reduced overall treatment costs for patients presenting with thrombosis.

Study design:
Prospective Randomized Control Study

Funding source:
W. L. Gore & Associates Inc. (Flagstaff, Arizona).

Setting:
Multicenter trial

Citation: 
Mohr, Belinda A. et al. Clinical and Economic Benefits of Stent Grafts in Dysfunctional and Thrombosed Hemodialysis Access Graft Circuits in the REVISE Randomized Trial. Journal of Vascular and Interventional Radiology , Volume 30 , Issue 2 , 203 - 211.e4


Summary


Arteriovenous grafts (AVGs) are an important option for patients on hemodialysis. Unfortunately, AVGs are susceptible to complications that can lead to reinterventions, increased costs and ultimately graft failure/abandonment. The conventional approach for failing grafts related to venous anastomotic stenoses has been percutaneous transluminal angioplasty (PTA). Recently stent grafts (SGs) have emerged as a promising supplemental approach to revising dysfunctional or thrombosed AVGs. In this study, inclusion criteria were patients with an AVG > 30 days old that was dysfunctional or thrombosed with a primary lesion having >50% stenosis and < 30 mm from the venous anastomosis. Patients were split into four groups with either dysfunctional/stenotic or thrombosed grafts and were treated with PTA alone or PTA with SG.

Overall, patients in the SG arm required significantly fewer total reinterventions compared to the patients in the PTA arm and the mean time to reintervention with SG vs PTA was 203 to 108 days. Specifically, patients with thrombosed AVGs treated with SG required 40% less reinterventions of any kind compared to those treated with PTA alone. Patients with graft dysfunction/stenosis initially treated with SG resulted in 16% less reinterventions compared to PTA, which was not statistically significant. Reintervention with PTA was reduced by 44% in patients presenting with thrombosed circuits who were treated with SG (statistically significant). Dysfunctional grafts had reduced PTA reintervention by 17% when the index procedure was augmented with SG (not statistically significant). Thrombosed grafts at presentation resulted in significantly more interventions overall, particularly more thrombectomy/thrombolysis procedures. SG placement in thrombosed grafts reduced future thrombectomy/thrombolysis by 36%.

When randomized by treatment, SG costs were 4% lower than initial PTA alone at 24 months although this was not statistically significant. However, when randomized by presentation, treatment of thrombosed grafts with SG reduced costs by 18% compared to PTA at 24 months. There was no significant cost difference between the two treatment groups with purely stenotic AVGs.



Figure 1
Stent graft placement significantly reduced total reinterventions over 24 months. Subgroup presentation show that reinterventions were significantly reduced at 24 months when thrombosed grafts were treated with stent grafts. Stent graft also decreased reinterventions in dysfunctional grafts, though not significantly. Cost was only statistically significantly reduced when stent grafts were used to treat thrombosed grafts.

Commentary


Maintaining patent vascular access in ESRD patients is an obstacle that has proven to be fraught with difficulties and frustration for both patients and providers. These challenges inevitably translate into multiple vascular interventions and increased healthcare costs. The REVISE trial has demonstrated that AVGs treated with angioplasty and SG placement can reduce subsequent reinterventions and cost over 24 months, most significant in thrombosed circuits. Given that there are an estimated 457,957 ESRD patients on hemodialysis, consistently reducing reintervention would dramatically decrease the overall healthcare cost. The trial calculated that SG placement could reduce cost by $6,877 for each patient with a thrombosed AVG over two years. This would result in millions of dollars saved if even a small portion of the total ESRD population were treated with SG. Cost savings were contingent upon AVG survival to 2 years as initial upfront costs were expectedly higher with SG placement. This trial specifically looked at AVGs, and there is a larger prevalence of patients who receive dialysis via arteriovenous fistulas (AVFs). A similarly structured trial focused on AVFs and central stenoses could further evaluate initial intervention options and the subsequent effect on reinterventions and cost with AVFs. This could potentially lead to findings that would have larger cost savings to the system.

Post Author:
Bradley Unruh, MD PGY-3
Department of Radiology
Wake Forest Baptist Medical Center
@WakeForest_IR


Wednesday, March 13, 2019

Early-Recurrent Overt Hepatic Encephalopathy Is Associated with Reduced Survival in Cirrhotic Patients after Transjugular Intrahepatic Portosystemic Shunt Creation 


Clinical question: How well does the presence of overt hepatic encephalopathy (OHE) occurring within 3 months of a transjugular intrahepatic portosystemic shunt (TIPS) placement predict survival?

Take-away point: Early recurrence of OHE was related to poorer long-term survival for cirrhotic patients who underwent the TIPS procedure.

Reference: Zuo L, Lv Y, Wang Q, et al. Early-Recurrent Overt Hepatic Encephalopathy Is Associated with Reduced Survival in Cirrhotic Patients after Transjugular Intrahepatic Portosystemic Shunt Creation. J Vasc Interv Radiol. 2019 Feb;30(2):148-153.e2. doi: 10.1016/j.jvir.2018.08.023. Epub 2019 Jan 9. PubMed PMID: 30638778.

Click here for abstract

Study design: Retrospective cohort study

Funding sources: Self-funded/NA

Setting: Single institution

Summary

Hepatic encephalopathy (HE) has been shown to have a major impact on survival in patients with decompensated cirrhosis, however the effect of HE following TIPS placement on survival has not been clearly delineated. 304 patients who underwent TIPS placement for variceal hemorrhage or refractory ascites were retrospectively analyzed for the development of OHE within 3 months of TIPS placement, as defined by grade 2-4 HE according to the West Haven Criteria. Multivariate, time-dependent models were applied to assess the impact of early OHE, early-single OHE, and early recurrent OHE. The cumulative rate of OHE occurring within 3 months of TIPS was 27.6% (n=84) with a total of 149 episodes of OHE occurring within this population. Early-recurrent OHE (64.9%) was associated with a statistically significant higher rate of mortality than those without early-recurrent OHE (20.6%) (HR = 4.31; 95% CI: 2.64–7.06; P < .001). In the multivariate analysis, early-recurrent OHE (HR = 2.81; 95% CI: 1.67–4.73; P < .001), MELD score (HR = 1.16; 95% CI: 1.06–1.26; P = .001), age (HR = 1.04; 95% CI: 1.02–1.06; P < .001), and ascites (HR = 1.91; 95% CI: 1.04–3.53, P =.037) were associated independently with survival. Landmark and propensity score analysis confirmed that early-recurrent OHE remained a significant predictor of survival.



Figure 1
(a) Cumulative probability of OHE and survival in 304 cirrhotic patients with TIPS. (b) Cumulative probability of secondary OHE in 304 cirrhotic patients with TIPS. (c) Cumulative probability of survival in 304 patients with cirrhosis undergoing TIPS.





Figure 2
(a) Probability of survival in patients with and without early OHE. (b) Probability of survival in patients with and without early-single OHE. (c) Probability of survival in patients with and without early-recurrent OHE.

Commentary


This study provides valuable insight into a patient’s prognosis following the development of HE after TIPS. Previous research has debated the association between HE and mortality following TIPS, however the results of the present study further supports the conclusion that HE following TIPS is associated with increased mortality. The large sample size coupled with rigorous statistical analyses bolsters the results of this study. Patient’s that develop recurrent OHE within 3 months of TIPS have significantly poorer survival than those with only one occurrence of OHE. Given that 44% of patients who had a first OHE episode after a TIPS would experience recurrent OHE within 3 months, intense surveillance and therapy should be pursued during this time period. It should be noted that a majority of the patients in this study developed cirrhosis secondary to Hepatitis B (84%), so the results may not be completely generalizable to patients with other chronic liver disease.

Post Author:
Jacob Bundy, MD, MPH
PGY-1
Department of Surgery
University of Michigan Health System
@JBundyRad

Friday, March 8, 2019

Polyethylene Glycol Epirubicin-Loaded Transcatheter Arterial Chemoembolization Procedures Utilizing a Combined Approach with 100 and 200 µm Microspheres: A Promising Alternative to Current Standards


Clinical question
How effective and safe is transarterial chemoembolization using 100 µm and 200 µm epirubicin-loaded polyethylene glycol using combined microsphere sizing strategy for hepatocellular carcinoma?

Take-away point
Staged embolization with 100 µm embolic followed by 200 µm embolic with epirubicin was technically feasible and demonstrated excellent imaging response compared to commonly sited data within the literature suggesting an advantage to sequential administration during embolization.

Reference
Lucatelli, Pierleone, et al. Polyethylene Glycol Epirubicin-Loaded Transcatheter Arterial Chemoembolization Procedures Utilizing a Combined Approach with 100 and 200 µm Microspheres: A Promising Alternative to Current Standards. Journal of Vascular and Interventional Radiology. 2019

Click here for abstract

Study design: Prospective

Funding source: Self-funded or unfunded

Setting: Single-center 

Summary


Drug eluting embolic (DEE) transarterial chemoembolization (TACE) is a well-established procedure for the treatment of hepatocellular carcinoma. However, there is no consensus protocol for embolic sizing with a wide range employed throughout the literature. The authors hypothesized that a combination of particle calibers, 100 µm and 200 µm, could combine tumoral blood stasis and proximal embolization. In this single center, prospective trial, a combined embolization protocol using LifePearl (Terumo, Tokyo, Japan) 100 µm and 200 µm particles loaded with epirubicin was evaluated for clinical outcomes in patients with hepatocellular carcinoma. 

36 patients with 54 hepatocellular carcinoma tumors were enrolled. DEE TACE was performed with epirubicin, first with 100 µm particles followed by 200 µm particles with embolization endpoint of 10 heart beats stasis. Study primary endpoints were tumoral response at follow up intervals, tumoral diameter and administered dose correlated with mRECIST response, and toxicity. By mRECIST criteria, complete response at 1 month, 3-6 months, 9-12 months and 15-18 months was 61.1% 65.9%, 63.6%, and 62.5%. Disease control rate was 100%, 92.7%, 90.0%, and 93.7% (1, 3-6, 9-12, and 15-18 month follow up). Notably, 47.6% of tumors < 2 cm reached 10 beats stasis with 100 µm particles alone, while only 18.5% of all tumors required only 100 µm particles. Among all treatments, only 3 adverse events occurred, all mild (grade 2) which resolved within 24 hours.



Commentary


There is a significant amount of heterogeneity among the protocols used within the literature for TACE procedure. The complete response rate and disease control rates demonstrated in this study were superior to much of the current TACE literature. With multiple factors being involved, such as drug of choice (epirubicin versus doxorubicin), embolic of choice (LifePearl a polyethylene glycol particle versus numerous other beads and conventional TACE), and embolization protocol (sequential usage of two sizes), it is difficult to determine which or which combination are responsible for the results. The authors did include pathologic data demonstrating the smaller particles were predominantly found intratumorally which the larger particles were seen in the peritumoral arterioles, suggesting the two sizes could serve different purposes during treatment combing enhanced intra-tumoral dose delivery with effective proximal ischemic embolization. While mainly limited do to the small sample size of 36 patients, this does provide evidence that we can optimize our embolization protocols. While further research is necessary, large randomized control trials would be difficult and unlikely to parse out the optimal medication, particle size(s), and bead for TACE.

Post Author:
David M Mauro, MD
Assistant Professor
Department of Radiology, Vascular and Interventional Radiology
University of North Carolina
@DavidMauroMD



Wednesday, March 6, 2019

Endovascular treatment of TransAtlantic Inter-Society Consensus II D femoropopliteal lesions in patients with critical limb ischemia


Clinical question
Is endovascular treatment technically feasible and effective in treating TASC II D femoropopliteal lesions in patients with critical limb ischemia?

Take-away point
Endovascular treatment of TASC II D femoropopliteal lesions is feasible and with good results. The primary patency in patients with popliteal artery occlusions involving the trifurcation vessels was better but the need for stent in this subgroup was associated with a low rate of limb salvage.

Reference
Biagioni RB, Brandão GD, Biagioni LC, Nasser F, Burihan MC, Ingrund JC. Endovascular treatment of TransAtlantic Inter-Society Consensus II D femoropopliteal lesions in patients with critical limb ischemia. J Vasc Surg. 2019 Jan 2. pii: S0741-5214(18)32245-6. doi: 10.1016/j.jvs.2018.08.176. [Epub ahead of print] PubMed PMID: 30611581.

Click here for abstract

Study design: Retrospective

Funding source: Self-funded or unfunded

Setting: Single center

Summary


Researches from Brazil published their results on endovascular approach to treat TASC II D lesions involving the femoropopliteal segment. The primary objective was to evaluate limb salvage and primary patency. A total of 91 patients were included (91 procedures). All patients had critical limb ischemia and were considered poor surgical candidates. The mean length of occlusions was 27.2 cm +/- 7.6 cm. Plain balloon angioplasty was performed in all patients and stenting in 61 patients. Limb salvage at 30 days, 1 year, 2 years, 3 years, and 4 years was 95.2%, 82.2%, 76.9%, 71.8%, and 63.7%, respectively. Primary patency at 30 days, 1 year, 2 years, and 3 years was 91%, 60.1%, 55.7%, and 50.6%, respectively. Unsuccessful recanalization occurred in 4 patients (4.3%). Reintervention rate was 11.1%. Complications occurred in seven patients (7.7%), including acute thrombosis, perforation and slow-flow phenomenon. All successfully resolved after appropriate management. Sub-analysis demonstrated significant higher 60-day primary patency in patients with popliteal/infra-popliteal lesions compared to SFA lesions (standard error, <10%; log-rank, P = .039). Nevertheless, when stents were used in the popliteal/infra-popliteal segment the rate of major limb loss was significantly higher(log-rank, P = .033). The authors concluded that endovascular treatment of TASC II D femoropopliteal lesions is feasible and with good results. The primary patency in patients with popliteal artery occlusions involving the trifurcation vessels was better compared to the isolated SFA lesions, but the need for stent in the popliteal group was associated with a low rate of limb salvage.



Fig 1. A, Initial angiogram. A 20-cm occlusion from the middle superficial femoral artery (SFA) to the P2 popliteal segment. B, Arteriography after 5- 100-mm balloon inflation. Limiting flow dissection of the SFA. C, Nitinol 6- 200-mm stent. D, Completion angiogram. E, Diagnostic angiogram. F, After dilation. Note the limiting flow dissection at P3 popliteal segment. G, Spotting stent with a nitinol 4- 8-mm stent. H, Completion angiogram.

Commentary


This paper presents the results of a retrospective analysis of 91 patients with critical limb ischemia submitted to endovascular treatment of TASC II D lesions involving the femoropopliteal segment. These types of lesions are better suited to surgical repair according to the most recent TransAtlantic Inter-Society Consensus. However, ideal surgical candidates would present with acceptable overall state of health and an appropriate autologous bypass. Therefore, endovascular treatment is the only option for many patients with this condition. The study shows that this approach has high successful recanalization rate (95.7%) and acceptable low complication rate (7.7%). Overall limb salvage, which is the critical clinical outcome in this patient population was comparable to surgical repair. In addition, sub-analysis demonstrated that primary patency in patients with popliteal artery occlusions involving the trifurcation vessels was better compared to isolated SFA lesions, but the need for stent in the popliteal group was associated with low rate of limb salvage. Limitations of the study included the selection bias (only non-surgical candidates) and the utilization of conventional angioplasty balloons and stents instead of drug-coating balloons and drug-eluting stents. However, clinical results were still comparable to surgical repair reinforcing that even complex lesions are suitable for endovascular recanalization which will eventually become the first therapeutic option for all patients.

Post Author:
Ricardo Yamada, MD
Assistant Professor
Department of Radiology
Division of Vascular and Interventional Radiology
Medical University of South Carolina

Monday, March 4, 2019

Proton Beam Therapy Outcomes for Localized Unresectable Hepatocellular Carcinoma


Clinical question 
What is the safety and efficacy of PBT for the treatment localized and unresectable HCC?

Take away point
PBT appears to show acceptable local control (81%) and overall survival (62%) at 2 years, with improved outcomes when the effective dose is over 90 GyE.

Study design
Retrospective review of 46 patients

Funding Source
MD Anderson Cancer Center Support grant, John E. and Dorothy J. Harris Endowed Professorship.

Setting: 
MD Anderson Cancer Center

Click here for abstract

Reference:
Chadha AS, Gunther JR, Hsieh CE, et al. Proton beam therapy outcomes for localized unresectable hepatocellular carcinoma. Radiotherapy and Oncology, 2019, 133, 54-61.

Summary


The authors evaluated the safety and efficacy of Proton Beam therapy (PBT) in localized HCC patients that were not surgical candidates. Patients included in this study had either 1 or up to 3 tumors without extrahepatic disease, were CP class A or B, ECOG 0-2 and had no prior radiation. PBT offers advantages over conventional X-ray by sparing surrounding tissues that is often diseased in cirrhotic patients. The tumor also has to be located greater than 1cm away from the gastrointestinal tract.

46 patients were included, the majority were CP A and ECOG 0-1. Eleven patients had undergone TACE, 6 patients TACE and sorafenib and 4 patients sorafenib only. Median tumor size was 6 cm (1.5-21 cm range), 22% had multiple tumors, and 28% had vascular invasion. Median dose was 67 GyE that was delivered over 21 days.

Median follow up was 14.5 months, median OS was 30.7 months (95% CI, 12.6-48.9 months), 1 year and 2 year PFS rates were 74% and 57% respectively. Local control rate at 1 and 2 years were 95% and 81%, respectively. Patients with tumors larger than 5 cm had a lower 2 year LC rate (62% vs 100%). 70% of patients had no progression at the time of last follow up. 14 patients developed recurrence, 6 of which outside of the treated field but within the liver. Thirteen patients had vascular invasion with 1 and 2 year OS rate of 58% and 44%, respectively. The authors found that patients that received biologically effective doses greater than 90GyE had better OS (49.9% vs 15.8 months. Multivariate analysis found higher BED as a predictor of improved OS. Grade 1 toxicities observed included fatigue (33%), erythema (24%), anorexia (11%) and vomiting (13%) . Thirteen percent of patients suffered acute grade 3 toxicities, including 9% ascites, 4% hyperbilirubinemia, and 2% with diarrhea and upper GI hemorrhage. CP score worsening was seen in 13% of patients. No grade >3 CTCAE toxicities were recorded.

The authors highlight that PBR offers dose deposition in a short distance which allows to cover large targets and minimize damage to surrounding structures. Their results also found that in 13 patients with tumor vascular thrombosis the 1 and 2 year OS rates were 58% and 44%, respectively, which the authors mention that is higher than historical outcomes using transcatheter infusion chemotherapy. PBT has it limitations compared to SBRT and include tumor distance greater than 1 cm from bowel, high cost, susceptibility to motion. The authors mention that the theoretical advantages, have not been proven and therefore need to be confirmed with further studies. Compared to SBRT, PBT has a lower risk of worsening CP score.

The study is limited by the retrospective nature of the study, the small sample size and the lack of control group. The authors conclude that PBT should be considered in the treatment algorithm for unresectable HCC, and that further studies are needed to evaluate the efficacy and cost compared to photon radiotherapy, TACE and sorafenib.



Figure 1- 85 year old patient with a 9.5 cm HCC treated with PBT. Pre-procedure Arterial and delayed images (a), Planning images (b), and subsequent follow up images show no residual tumor out to 2.5 years. Post radiation calcification and tumor shrinkage was seen on the last images.

Commentary


This study provides important data supporting the use of PBT in the treatment of unresectable HCC in patients with good CP score and good functional status. PBT offers the theoretical advantage for delivering high dose in a concentrated area without damaging surrounding liver, which is detrimental in cirrhotic patients. The authors use the term tumor vascular thrombosis, which appears to be different from portal vein tumor thrombosis, since they are separated on table 3. It is unclear what it is meant by that term, which the authors use to support the use of PBT when compared to transcatheter infusion therapy. The authors reference 2 articles to support this statement, however the articles were published on 2005 and 2002, which is likely outdated. In addition, the lack of a similar control group makes it difficult to interpret the results. It is likely that PBT has a role in the treatment of unresectable HCC however it is unclear at this point where PBT falls in the algorithm of treatment, and as the authors mentioned the theoretical benefits need to be validated by head to head comparison with proton radiation therapy .

Post Author: 
Carlos J. Guevara, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Sciences, Houston
@CarlosGuevaraIR

Thursday, February 28, 2019

Adventitial Drug Delivery of Dexamethasone to Improve Primary Patency in the Treatment of Superficial Femoral and Popliteal Artery Disease: 12-Month Results From the DANCE Clinical Trial 


Clinical Question:
Does adventitial delivery of dexamethasone as an adjuvant to standard endovascular revascularization improve outcomes in femoropopliteal peripheral artery disease?

Take-away Point:
Adventitial delivery of dexamethasone may be an effective and safe therapy to prevent restenosis of femoropopliteal popliteal artery disease.

Reference:
Razavi, M. K., Donohoe, D., D’Agostino, R. B., Jaff, M. R., & Adams, G. (2018). Adventitial Drug Delivery of Dexamethasone to Improve Primary Patency in the Treatment of Superficial Femoral and Popliteal Artery Disease. JACC: Cardiovascular Interventions, 11(10), 921-931. doi:10.1016/j.jcin.2017.12.015

Click here for abstract

Study Design: Prospective, multicenter, single-arm, open-label study

Funding Source: Mercator MedSystems, Inc.

Setting: Multicenter, 27 US sites

Summary 


The DANCE study enrolled 262 patients for a total of 283 limbs across 27 sites for the evaluation of adventitial delivery of dexamethasone as an adjunct to standard endovascular treatment of femoropopliteal PAD. The patient population consisted of more high-risk patients - increased calcification, popliteal artery involvement, complex TASCII B-D lesions and Rutherford category 4 disease – compared to those in the trials used to generate performance goals. Patients were categorized into two cohorts: atherectomy (ATX) and angioplasty (PTA). Adventitial access was achieved using the Bullfrog device in which a compliant balloon adapts to the vessel wall and a microneedle punctures into the perivascular tissue. An 80% dexamethasone to 20% contrast 3.2 mg/mL solution was used with an intended ratio of 1.6 mg drug per 1-cm of lesion length.

The overall 12-month primary patency in DANCE was 74.6% (95% CI 68.7-79.7%); 74.8% (66.6-81.5%) in the ATX cohort and 74.3% (65.6-81.5%) in the PTA cohort. This was noninferior to the 72.3% contemporary performance goal (met-analysis of pooled DCB studies) and superior to the 52.5% historical performance goal for both primary patency and intention to treat. ABI/TBI improved from baseline of 0.77 ± 0.24 to 12-month follow-up 0.94 ± 0.25 (p < 0.001). There were more stents placed in the DANCE trial than compared to pooled DCB studies however primary patency rates did not vary significantly in limbs with or without stents. There were no 30-day device or drug related severe adverse events. Of note, there was no concurrent control group that did not receive dexamethasone therapy.



Figure 5. The Kaplan-Meier estimates from (A) DANCE-ATX and (B) DANCE_PTA) are shown, with 12- and 130month data highlighted. ATX = atherectomy; CD-TLD = clinically driven targe lesion revascularization; DANCE = Dexamethasone to the Adventitia to Enhance Clinical Efficacy After Femoropopliteal Revascularization; PTA = percutaneous transluminal angioplasty.

Commentary


Dexamethasone is known to down-regulate cells linked to inflammatory re-stenosis. The delivery of dexamethasone is not a new concept, previously studied with systemic dosing and coronary drug-eluting stents, however those studies showed mixed results. Moreover, the concentration delivered in this study is more than 30 times the dosage concentration delivered from prior coronary stents.

Adventitial delivery offers many attractive qualities for drug delivery. The adventitia functions to regulate all cell trafficking into and out of the intimal cells; it is primed for the treatment of intimal disease such as restenosis. Tesfamarian states that “the adventitia appears to be an attractive therapeutic target to effectively inhibit inflammatory mediators,” in Vascular Pharmacology. This delivery system has the potential to modify the way drug delivery is performed for endovascular procedures, perhaps not just dexamethasone but alternative agents in the future.

Post Author:
Nicole A. Keefe, MD
Resident Physician
Department of Radiology and Medical Imaging
University of Virginia
@NikkiKeefe