Marco Midulla

Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial

BACKGROUND Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. METHODS The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. FINDINGS Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. INTERPRETATION In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. FUNDING French Ministry of Health.

Inferior vena cava agenesis and deep vein thrombosis: 10 patients and review of the literature

Inferior vena cava agenesis (IVCA) is a rare condition, found in almost 5% of patients under 30 years old with unprovoked deep venous thrombosis (DVT). We describe 10 consecutive patients with IVCA-associated DVT and conducted an extensive literature review to investigate the typical spectrum of IVCA-associated DVT. Among our patients (eight men and two women; mean age, 25 ± 4.5 years), DVT followed intense and unusual (major) physical activity for eight of them. DVT was bilateral in six patients and unilateral in four. Ultrasonography was unable to detect IVCA, which was visualized by computed-tomography scans for seven patients, and magnetic resonance imaging and angiography for 10. Hereditary thrombophilia screening, to detect factor V Leiden or prothrombin gene heterozygosity (G20210A mutation), was positive for only two patients. Wearing elastic stockings and taking an indefinite or long-term vitamin K antagonist were prescribed for all 10 patients and nine complied with the latter. To date, 62 patients with IVCA-associated DVT have been reported in the English literature. Analysis of them and our patients yielded a typical spectrum of IVCA-associated DVT characteristics: IVCA occurs in young adults, particularly males, and is revealed by proximal DVT following major physical exertion. All were treated with a prolonged vitamin K antagonist and advised to wear elastic stockings. No precise duration of anticoagulation has been established.

Off-the-Shelf Fenestrated Endografts: A Realistic Option for More Than 70% of Patients With Juxtarenal Aneurysms

Purpose To evaluate the suitability of a standardized fenestrated endograft in patients with juxtarenal abdominal aortic aneurysms. Methods High resolution computed tomographic angiograms from 100 consecutive patients (96 men; mean age 72 years) with juxta- (n=78) and pararenal (n=22) aneurysms treated electively between 2005 and 2010 with custom-made fenestrated endografts were reviewed. A centerline of flow reconstruction was carried out in a 3D imaging workstation to precisely define the aortic morphology, including aortic diameters and distances between visceral and renal arteries. The applicability of 2 different “off-the-shelf” standardized fenestrated endografts designed by the manufacturer was evaluated in this cohort. Both designs included 2 fenestrations for the renal arteries, 1 for the superior mesenteric artery (SMA), and a scallop for the celiac trunk. The designs differed in the lengths of the SMA to renal fenestration and renal to renal fenestration. Results Endovascular treatment with one or both “off-the-shelf” endografts was deemed possible in 72 patients (56 with design 1, 52 with design 2, and 36 with both endografts). Of the 28 patients who were not candidates for a standardized fenestrated stent-graft of either design, the primary cause was a right renal artery that did not match the position of its corresponding fenestration. Conclusion Standardized fenestrated designs suitable for endovascular treatment of >70% of patients with juxta- and pararenal aneurysms currently treated with custom-made fenestrated endografts will soon be available. This new generation of endografts will permit rapid treatment of a large majority of patients requiring fenestrated endograft repair.

Single-centre Prospective Comparison Between Contrast-Enhanced Ultrasound and Computed Tomography Angiography after EVAR

AIM To evaluate contrast-enhanced ultrasound (CEUS) as an effective alternative to CT-angiography (CTA) for endoleak detection and aneurismal sac diameter measurement in the follow-up after endovascular abdominal aortic aneurysm repair (EVAR). METHODS From January 2006 to December 2010, 395 patients underwent EVAR follow-up with both CTA and CEUS. The diameter of the aneurismal sac and the presence of endoleaks were evaluated in all the 395 paired examinations. RESULTS Bland-Altman plots showed a good agreement in aneurismal sac diameter evaluation between the two imaging modalities. The mean diameter was 54.93 mm (standard deviation (SD) ±12.57) with CEUS and 56.01 mm (SD ± 13.23) with CTA. The mean difference in aneurismal sac diameter was -1.08 mm ± 3.3543 (95% confidence interval (CI), -0.75 to -1.41), in favour of CTA. The number of observed agreement in endoleak detection was 359/395 (90.89%). The two modalities detected the same type I and type III endoleaks. McNemars χ(2) test confirmed that CTA and CEUS are equivalent in endoleak detection. CONCLUSIONS CEUS demonstrated to be as accurate as CTA in endoleak detection and abdominal aortic aneurysm diameter measurements during EVAR follow-up, without carrying the risks of radiation exposure or nephrotoxicity. Even if it cannot be proposed as the sole imaging modality during follow-up, our analysis suggests that it should have a major role.

Endovascular fenestration in aortic dissection with acute malperfusion syndrome: Immediate and late follow-up

OBJECTIVE To evaluate the immediate and long-term results of fenestration in aortic dissection with acute malperfusion syndrome. METHODS Between 1999 and 2007, 35 patients (31 men; age, 57 ± 11 years) with aortic dissection (19 with type A and 16 with type B) were treated by fenestration for malperfusion syndrome (27 renal, 27 bowel, and 14 lower limb) due to dynamic compression. Fenestration was performed with 2 rigid guidewires inserted in one 8F sheath (45 cm long). The mean interval between aortic dissection and fenestration was 5 days (28 patients within 3 days and 7 patients between 9 and 41 days). RESULTS Fenestration (100% technical success rate) with an additional endovascular procedure (29 peripheral stents and 1 thoracic stent graft) resulted in angiographic success in 97% of the patients. Bowel surgery was performed in 7 patients. Mortality within the first month (12/35) was related to bowel ischemia (n = 5), neurologic complications (n = 3), type A surgery (n = 2), and late treatment (n = 2). At a mean follow-up of 48 ± 30 months, 4 of the remaining 23 patients had died and 2 had withdrawn from the study. The diameter of the aorta, as measured using computed tomography/magnetic resonance imaging, remained stable in 12 of the remaining 17 patients and had increased in 5 (1 with Marfan syndrome and 4 with multiple arterial ectasia). CONCLUSIONS In emergencies, fenestration saved 69% of the patients with acute malperfusion syndrome in complicated aortic dissection. During the follow-up period, the aortic diameter remained stable in most of the surviving patients.

Evaluation of Radiation during EVAR Performed on a Mobile C-arm

BACKGROUND The aim of this study was to evaluate radiation exposure during aortic endovascular aneurysm repair (EVAR) on a mobile C-arm using a low dose and pulse mode. METHODS We performed a retrospective analysis of a prospectively maintained database on patients undergoing EVAR. Indirect dose measurements of dose area product (DAP, mGy m²) calculated by the C-arm (OEC 9900MD), fluoroscopic time (FT), type of procedure, contrast media volume and body mass index were analysed. To confirm the correlation between direct and indirect DAP measurements, direct dose was measured with radiochromic films on a sample of 15 patients. Film grey level response was calibrated according to a reference dose measurement performed with a calibrated dosimeter. DAP and peak skin dose (PSD, Gy) were measured on each film. Correlation between DAP from direct and indirect measures, and between DAP and PSD, were analysed. RESULTS From January 2009 to April 2011, 335 patients underwent EVAR. Complete data were available on 301 procedures including 188 bifurcated, 54 fenestrated, 28 thoracic, 20 branched and 11 aorto-uni-iliac endografts implantation. The respective median FT and DAP was 9.36 min (1.8-67) and 3 mGy m(2) (0.4-28); 27.2 min (2-69) and 7.3 mGy m(2) (1.2-29); 7.75 min (1.2-19.1) and 2 mGy m(2) (0.3-11); 42.98 min (2.4-95.4) and 15.95 mGy m(2) (2.98-77.7); 6.2 min (0.5-36.3) and 2 mGy m(2) (0.3-11). Direct DAP measurement on radiochromic films was strongly correlated with DAP values provided by the C-arm (r = 0.98). PSD correlated weakly with DAP. DAP was significantly increased (p < 0.001) in patients with a body mass index >30. Contrast media volume was significantly increased in the branched endograft group. CONCLUSION Indirect DAP values measured by the C-arm are accurate to evaluate radiation exposure. Compared to the literature, our values for standard procedures are significantly decreased by the usage of low dose and pulse mode. DAP for fenestrated and branched procedures was comparable to published DAP values with standard procedures using a regular fluoroscopic mode.

TEVAR in Patients with Late Complications of Aortic Coarctation Repair

Purpose: To review the use of thoracic endovascular aortic repair (TEVAR) for late pseudoaneurysm formation after surgical repair of aortic coarctation. Methods: From May 2001 to May 2005, 8 patients (5 men; mean age 47.6 years, range 18–73) with a history of aortic coarctation repairs 17 to 40 years prior were referred to our institution for an anastomotic thoracic pseudoaneurysm. TEVAR was performed successfully in 7 patients; 1 died of suspected aneurysm rupture before the scheduled procedure. A carotid-subclavian bypass was performed in 3 patients. Results: All the procedures were immediately successful. No type I endoleaks were seen on the final control angiogram, but 2 of the patients with carotid-subclavian bypasses required additional left subclavian artery embolization due to type II endoleak. One of these patients died before embolotherapy on the 5th postoperative day from presumed aneurysm rupture (14% 30-day mortality rate). Over a follow-up period ranging from 15 to 72 months (mean 37), all the false aneurysms have remained thrombosed and the mean diameter has decreased from 44 to 23 mm. No endograft-related complications have occurred, and no further interventions have so far been necessary. Conclusion: TEVAR is a feasible alternative treatment for patients who have already undergone surgical repair of aortic coarctation. Technical issues regarding the endovascular strategy should be discussed with a multidisciplinary team to define the correct interventional plan.

The Benefits of EVAR Planning Using a 3D Workstation

OBJECTIVES To evaluate the influence of planning endovascular aneurysm repair (EVAR) with a three-dimensional (3D) workstation on early and midterm outcomes. METHODS All patients undergoing infrarenal EVAR performed between 2006 and 2009 at our institution were included in the current study. Prior to 2008 (group 1), endograft sizing was performed by interrogation of computed tomography angiography axial images. After 2008 (group 2), endograft sizing was routinely performed using a 3D workstation (Aquarius, Terarecon), allowing for multiplanar reconstruction and centerline analysis. Pre-, peri-, postoperative, and follow-up data were prospectively entered in an electronic database. All postoperative complications and subsequent secondary interventions depicted during the 2-year period following EVAR were compared. Secondary intervention and mortality rates were defined at 2 years and compared. Freedom from secondary intervention and overall survival rates were calculated using the Kaplan-Meier method during follow-up and compared by log-rank test. RESULTS A total of 295 patients (149 patients in group 1 and 146 patients in group 2) were included. All patients had completed a minimum of 2 years of follow-up. During this 2-year period following EVAR, the type 1 endoleak rate was 8.7% in group 1 and 1.4% in group 2 (p = .004) respectively. Secondary intervention rates related to type 1 endoleak was 5.4% in group 1 and 0 in group 2 (p < .001). No difference was observed regarding all-cause mortality, aneurysm-related death, and freedom from secondary intervention rates during follow-up. CONCLUSION The routine use of 3D workstations for EVAR planning significantly reduces the rate of type 1 endoleaks and, therefore, the rate of related secondary interventions.

Contrast-Enhanced Ultrasound vs. CT Angiography in Fenestrated EVAR Surveillance: A Single-Center Comparison

Purpose To evaluate contrast-enhanced ultrasound (CEUS) as an effective alternative to computed tomographic angiography (CTA) during follow-up after fenestrated endovascular aneurysm repair (EVAR) of juxtarenal aortic aneurysms. Methods Between January 2008 and April 2011, 62 patients (all men; mean age 72 years) underwent fenestrated EVAR follow-up with both CTA and CEUS. In a retrospective analysis, the first CTA and CEUS postoperative examinations after EVAR were compared for endoleak detection, aneurysm sac diameter, and target vessel patency. The examinations were performed within 30 days of the procedure and the interval between the 2 scans was <7days. Only fenestrated endografts with up to 3 fenestrations (with or without a scallop) were eligible so that the entire implant could be visualized with standard abdominal ultrasound. Results The mean diameters of the aneurysm sac were 56.58 ± 8.56 mm with CEUS and 57.70 ± 8.59 mm with CTA. The mean difference in aneurysm sac diameter was –1.13 ± 3.19 mm (95% CI –0.34 to –1.92), with CTA measurements tending to be slightly larger. Bland-Altman plots showed good agreement between the imaging modalities with respect to aneurysm sac diameter (Spearman correlation coefficient rs=0.921, p<0.01). Endoleaks were detected by CTA in 7 (11.3%) of 62 patients and by CEUS in 6 (9.7%). In 59 (95.16%) cases, the tests agreed, and their equivalence was confirmed by binomial distribution testing. There was complete agreement between CEUS and CTA in the assessment of target vessels (144/146 patent target arteries; 1 had a significant stenosis and another was thrombosed). Conclusion CEUS is as accurate as CTA in endoleak detection, abdominal aortic aneurysm diameter measurement, and the evaluation of target vessels during surveillance of fenestrated stent-grafts. Although it cannot yet be proposed as the only imaging modality during follow-up, CEUS could be usefully employed with the self-evident advantage of reducing lifetime exposure to ionizing radiation.

''Right-Sided'' May-Thurner Syndrome

The May-Thurner syndrome is a well-known anatomical anomaly where the left common iliac vein (LCIV) is compressed between the right common iliac artery and the fifth vertebral body. This report describes the case of a “right-sided” May-Thurner syndrome where the right common iliac vein (RCIV) is compressed by the left common iliac artery in a patient with a left-sided inferior vena cava (IVC). A 26-year-old woman was admitted to our institution with acute edema of the right lower limb. The diagnosis of May-Thurner syndrome was done by CT scan and confirmed by phlebography. An endovascular treatment with stenting was carried out, with good patency and clinical result at 12-month follow-up.