Joep A.W. Teijink

The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 × 10−12) and intracranial aneurysm (OR = 1.29, P = 2.5 × 10−6), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

Early Results from the ENGAGE Registry: Real-world Performance of the Endurant Stent Graft for Endovascular AAA Repair in 1262 Patients

OBJECTIVE The ENGAGE registry was undertaken to examine the real-world outcome after endovascular abdominal aortic aneurysm (AAA) repair (EVAR) with the Endurant Stent Graft in a large, contemporary, global series of patients. METHODS From March 2009 to April 2011, 1262 AAA patients (89.6% men; mean age 73.1 years, range 43-93 years) were enrolled from 79 sites in 30 countries and treated with Endurant. Results are described following the reporting standards for EVAR. Follow-up data were tabulated for all 1262 patients at a 30-day follow-up and for the first 500 patients at a 1-year follow-up. RESULTS Intra-operative technical success was achieved in 99.0% of cases. Within 30 days, adverse events were reported in 3.9% of patients, including a 1.3% mortality rate. Type-I or -III endoleaks were identified in 1.5% of cases. Estimated overall survival, aneurysm-related survival and freedom from secondary interventions at 1 year were 91.6%, 98.6% and 95.1%, respectively. At 1 year, aneurysm size increased ≥ 5 mm in 2.8% and decreased ≥ 5 mm in 41.3% of cases. CONCLUSION Early results from this real world, global experience are promising and indicate that endovascular AAA repair with the Endurant Stent Graft is safe and effective across different geographies and standards of practice. Longer-term follow-up is necessary to assess durability of these results.

Endovascular aneurysm repair is superior to open surgery for ruptured abdominal aortic aneurysms in EVAR-suitable patients

OBJECTIVE Efficacy results of endovascular repair (rEVAR) for ruptured abdominal aortic aneurysm (rAAA) compared with open surgery are based on several observational studies containing selection bias. The present study compared rEVAR with open surgery in EVAR-suitable patients with an rAAA who all underwent the same preoperative imaging protocol. METHODS Our policy is to perform a computed tomography angiography on all patients with a suspected rAAA. rEVAR was performed when the rEVAR-vascular surgeon was on call and the patient was suitable for EVAR. Afterwards, two experienced independent blinded experts assessed all computed tomography angiography (CTA) scans on EVAR-suitability. Only EVAR-suitable patients were included in the main analyses. Outcome parameters included mortality (intraoperative, 30-day, and 6-month), complications, reinterventions, and length of hospital stay. RESULTS From April 2002 until March 2008, 132 consecutive patients with suspected rAAAs were presented. Preoperative CTA confirmed rAAA in 104 patients, of whom 25 underwent rEVAR, and 79 underwent open surgery. In retrospect, the 25 rEVAR patients and 33 patients in the open group were judged EVAR-suitable by the experts. At baseline, there was an equal distribution of physiologic and anatomic characteristics as well as comorbidity. In EVAR-suitable patients, the intraoperative, 30-day, and 6-month mortality was 4.0% (1 of 25), 20.0% (5 of 25), and 28.0% (7 of 25) after rEVAR compared with 6.1% (2 of 33; P >.99), 45.5% (15 of 33; P = .04), and 54.5% (18 of 33; P = .04) after open surgery, respectively. Median length of hospital stay was 9.5 days (interquartile range, 5.0-20.5) after rEVAR and 17.0 days (interquartile range, 9.5-28.0) after open surgery (P = .03). CONCLUSIONS In EVAR-suitable patients, an absolute perioperative mortality reduction of 25.5% of rEVAR over open surgery was found, which was still present at 6 months of follow-up. These data suggest that rEVAR is a superior treatment option for EVAR-suitable patients with an rAAA compared with an open surgery.

The walking impairment questionnaire: An effective tool to assess the effect of treatment in patients with intermittent claudication

OBJECTIVE Assessment of walking distance by treadmill testing is the most commonly used method to evaluate the effect of treatment in patients with peripheral arterial disease. However, treadmill testing is time consuming, relatively expensive, and does not adequately reflect real life functional ability. We hypothesized that the Walking Impairment Questionnaire (WIQ) could be an alternative tool to assess objective improvement in functional walking ability of patients with intermittent claudication. METHODS This was a validation study. It was conducted through the outpatient clinic for vascular surgery. Patients with intermittent claudication were referred for supervised exercise therapy. Treadmill testing (absolute claudication distance [ACD]), WIQ, and quality of life questionnaires (RAND-36 and EuroQol) were administered at study onset and after 3 months of supervised exercise therapy. Responsiveness was determined by mean changes in and correlation coefficients of WIQ, ACD, and quality of life questionnaires. Patients were categorized into quartiles based on the increase in ACD, which were subsequently related to change in WIQ and quality of life. RESULTS The mean pre- and post-treatment total WIQ scores of 91 patients were 0.45 (0.22) and 0.58 (0.22), respectively. The correlation coefficient between the change in total WIQ score and ACD was 0.331 (P = .004). A 0.1 change in total WIQ score corresponded to a change of 345 meters in ACD. Analysis of the four quartiles compared to an increase in ACD showed that a greater increase in ACD corresponded with a greater increase in WIQ score, from 0.06 to 0.25 (P = .011). CONCLUSION These data indicate that the WIQ is a valid tool to detect improvement or deterioration in the daily walking ability of patients with intermittent claudication. Hence, the WIQ can be used as an alternative to treadmill testing for objective assessment of functional walking ability, both in daily practice and in clinical trials.

Endovascular Revascularization and Supervised Exercise for Peripheral Artery Disease and Intermittent Claudication: A Randomized Clinical Trial

IMPORTANCE Supervised exercise is recommended as a first-line treatment for intermittent claudication. Combination therapy of endovascular revascularization plus supervised exercise may be more promising but few data comparing the 2 therapies are available. OBJECTIVE To assess the effectiveness of endovascular revascularization plus supervised exercise for intermittent claudication compared with supervised exercise only. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 212 patients allocated to either endovascular revascularization plus supervised exercise or supervised exercise only. Data were collected between May 17, 2010, and February 16, 2013, in the Netherlands at 10 sites. Patients were followed up for 12 months and the data were analyzed according to the intention-to-treat principle. INTERVENTIONS A combination of endovascular revascularization (selective stenting) plus supervised exercise (n = 106) or supervised exercise only (n = 106). MAIN OUTCOMES AND MEASURES The primary end point was the difference in maximum treadmill walking distance at 12 months between the groups. Secondary end points included treadmill pain-free walking distance, vascular quality of life (VascuQol) score (1 [worst outcome] to 7 [best outcome]), and 36-item Short-Form Health Survey (SF-36) domain scores for physical functioning, physical role functioning, bodily pain, and general health perceptions (0 [severe limitation] to 100 [no limitation]). RESULTS Endovascular revascularization plus supervised exercise (combination therapy) was associated with significantly greater improvement in maximum walking distance (from 264 m to 1501 m for an improvement of 1237 m) compared with the supervised exercise only group (from 285 m to 1240 m for improvement of 955 m) (mean difference between groups, 282 m; 99% CI, 60-505 m) and in pain-free walking distance (from 117 m to 1237 m for an improvement of 1120 m vs from 135 m to 847 m for improvement of 712 m, respectively) (mean difference, 408 m; 99% CI, 195-622 m). Similarly, the combination therapy group demonstrated significantly greater improvement in the disease-specific VascuQol score (1.34 [99% CI, 1.04-1.64] in the combination therapy group vs 0.73 [99% CI, 0.43-1.03] in the exercise group; mean difference, 0.62 [99% CI, 0.20-1.03]) and in the score for the SF-36 physical functioning (22.4 [99% CI, 16.3-28.5] vs 12.6 [99% CI, 6.3-18.9], respectively; mean difference, 9.8 [99% CI, 1.4-18.2]). No significant differences were found for the SF-36 domains of physical role functioning, bodily pain, and general health perceptions. CONCLUSIONS AND RELEVANCE Among patients with intermittent claudication after 1 year of follow-up, a combination therapy of endovascular revascularization followed by supervised exercise resulted in significantly greater improvement in walking distances and health-related quality-of-life scores compared with supervised exercise only. TRIAL REGISTRATION Netherlands Trial Registry Identifier: NTR2249.

Magnetic Resonance Imaging in Peripheral Arterial Disease Reproducibility of the Assessment of Morphological and Functional Vascular Status

Objectives:The aim of the current study was to test the reproducibility of different quantitative magnetic resonance imaging (MRI) methods to assess the morphologic and functional peripheral vascular status and vascular adaptations over time in patients with peripheral arterial disease (PAD). Materials and methods:Ten patients with proven PAD (intermittent claudication) and arterial collateral formation within the upper leg and 10 healthy volunteers were included. All subjects underwent 2 identical MR examinations of the lower extremities on a clinical 1.5-T MR system, with a time interval of at least 3 days. The MR protocol consisted of 3D contrast-enhanced MR angiography to quantify the number of arteries and artery diameters of the upper leg, 2D cine MR phase contrast angiography flow measurements in the popliteal artery, dynamic contrast-enhanced (DCE) perfusion imaging to determine the influx constant and area under the curve, and dynamic blood oxygen level-dependent (BOLD) imaging in calf muscle to measure maximal relative T2* changes and time-to-peak. Data were analyzed by 2 independent MRI readers. Interscan and inter-reader reproducibility were determined as outcome measures and expressed as the coefficient of variation (CV). Results:Quantification of the number of arteries, artery diameter, and blood flow proved highly reproducible in patients (CV = 2.6%, 4.5%, and 15.8% at interscan level and 9.0%, 8.2%, and 7.0% at interreader level, respectively). Reproducibility of DCE and BOLD MRI was poor in patients with a CV up to 50.9%. Conclusions:Quantification of the morphologic vascular status by contrast-enhanced MR angiography, as well as phase contrast angiography MRI to assess macrovascular blood flow proved highly reproducible in both PAD patients and healthy volunteers and might therefore be helpful in studying the development of collateral arteries in PAD patients and in unraveling the mechanisms underlying this process. Functional assessment of the microvascular status using DCE and BOLD, MRI did not prove reproducible at 1.5 T and is therefore currently not suitable for (clinical) application in PAD.

Contrast-enhanced ultrasound versus computed tomographic angiography for surveillance of endovascular abdominal aortic aneurysm repair.

PURPOSE To compare diagnostic accuracy between contrast-enhanced ultrasound (US) and computed tomographic (CT) angiography to detect changes in abdominal aortic aneurysm (AAA) size and endoleaks during follow-up after endovascular aneurysm repair (EVAR). MATERIALS AND METHODS Between May 2006 and December 2008, 83 patients were consecutively enrolled for contrast-enhanced US and CT angiography imaging during surveillance after EVAR, yielding 127 paired examinations. Comparative analysis was performed for the anteroposterior and transverse maximal diameters of the aneurysm sac and for the presence or absence of endoleak, as determined by US and CT angiography. RESULTS Contrast-enhanced US demonstrated significantly more endoleaks, predominantly of type II, compared with CT angiography (53% vs 22% of cases). The number of observed agreements was 77 of 127 (61%), indicating a low level of agreement (kappa value of 0.237). US was as accurate as CT angiography in the assessment of maximal aneurysm sac diameters, as shown by Bland-Altman analyses and low coefficients of variation (8.0% and 8.6%, respectively). The interobserver variability for AAA size measurement by US was low, given the interclass correlation coefficients of 0.99 and 0.98 for anteroposterior and transverse maximal diameters, respectively. CONCLUSIONS Contrast-enhanced US may be an alternative to CT angiography in the follow-up of patients after EVAR. As US reduces exposure to the biologic hazards associated with lifelong annual CT angiography, including cumulative radiation dose and nephrotoxic contrast agent load, contrast-enhanced US might be considered as a substitute for CT angiography in the surveillance of patients after EVAR.

Reliability of treadmill testing in peripheral arterial disease: a meta-regression analysis.

OBJECTIVE A meta-regression analysis was conducted to identify the most reliable treadmill protocol for the assessment of patients with peripheral arterial disease (PAD). BACKGROUND Treadmill testing is the main assessment method to evaluate walking ability in patients with PAD in clinical studies. Reported treadmill protocols are continuous (C) and graded (G) protocols and outcome measurements are initial claudication distance (ICD) and absolute claudication distance (ACD). Variety in protocols might hamper the ability to compare results of different studies. Ideally, future studies should use a protocol with highest reliability. METHODS We searched PubMed and EMBASE (until February 2008) and we hand searched the reference lists. Trials assessing reliability of treadmill testing were identified. Inclusion criteria were the use of a C- or G-protocol, repetition of this protocol, and a retrievable intraclass correlation coefficient (ICC). We identified eight studies in which 658 patients were included. RESULTS For ICD, the estimated reliabilities of the C- and G-protocol (as assessed by the ICC) were 0.85 (95% confidence interval [CI]: 0.82-0.88) and 0.83 (95% CI: 0.80-0.85), respectively, without dependency of the reliability on velocity or grade. For ACD, the reliability was significantly better for the G-protocol (0.95, 95% CI: 0.94-0.96) than for the C-protocol. Moreover, the reliability of the C-protocol was dependent on grade of the treadmill (0%, 10%, and 12%) with a mean ICC of 0.76 (95% CI: 0.54-0.88), 0.89 (95% CI: 0.86-0.91), and 0.91 (95% CI 0.88-0.92), respectively. CONCLUSION Treadmill assessment has the highest reliability when using a G-protocol together with the ACD as the primary outcome measure.

Validation of the Dutch version of the Walking Impairment Questionnaire.

OBJECTIVES The Walking Impairment Questionnaire (WIQ) is a frequently used questionnaire to evaluate patients with intermittent claudication (IC). The aim of this study is to validate the Dutch WIQ for the European situation using the metric system. DESIGN Validation study. MATERIALS After translation and cultural adaptation of the WIQ, 130 patients with IC completed the Dutch WIQ, the RAND-36, and the EuroQol questionnaire. Walking distances were determined by treadmill testing. METHODS Correlations between the WIQ, the two quality of life questionnaires, and walking distances were calculated to determine validity. Reliability and internal consistency were determined using the intraclass correlation coefficient (ICC) and Cronbachs alpha, respectively. RESULTS Significant correlations were found between the WIQ and the absolute claudication distance (ACD) (0.52), EuroQol (0.33) and seven domains of the RAND-36. Test-retest reliability expressed by the ICC was 0.89. The internal consistency determined by Cronbachs alpha was 0.92 for the total WIQ score. Furthermore, a lower WIQ score corresponds to a shorter ACD. CONCLUSIONS This study shows that the Dutch version of the WIQ using the European metric system is a valid, reliable and clinically relevant instrument for assessing walking impairment in patients with intermittent claudication.

Sexual Dysfunction after Conventional and Endovascular AAA Repair: Results of the DREAM Trial

Purpose: To assess sexual function in the first postoperative year after elective endovascular aneurysm repair (EVAR) and open repair (OR) of abdominal aortic aneurysm (AAA). Methods: In the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial, 153 patients (141 men; mean age 71 years, range 53–85) were randomly allocated to EVAR (n=77) or OR (n=76). Sexual functioning was evaluated preoperatively and at 5 times in the first postoperative year (3, 6, 13, 26, and 52 weeks) using a questionnaire derived from the Medical Outcomes Study. The proportions of patients reporting sexual dysfunction for any of 5 aspects (interest, pleasure, engagement, orgasm, and erection) and any increase in the magnitude of dysfunction were compared between EVAR and OR. Results: Preoperatively, the proportion of patients reporting sexual dysfunction in at least 1 aspect was 66% for the OR group and 74% in the EVAR group (p=NS). Surgery had a clear impact on sexual dysfunction. The proportion of patients reporting sexual dysfunction on at least 1 aspect increased to 79% in the OR group and 82% in the EVAR group. The magnitude of sexual dysfunction increased in both groups on all 5 aspects at 3 weeks postoperatively, but this was more pronounced in the OR group (interest: OR p=0.038 vs. EVAR p=0.071; pleasure: OR p=0.009 vs. EVAR p = 0.065; engagement: OR p=0.006 vs. EVAR p=0.054; orgasm OR p=0.023 vs. EVAR p=0.112, and erection: OR p=0.046 vs. EVAR p=0.030). At 6 weeks, the OR group still reported a significant increase in 3 aspects (pleasure p=0.031, engagement p=0.010, and orgasm p=0.003), whereas the EVAR group no longer showed a significant difference. From 3 months on, both groups had returned to baseline. Conclusions: EVAR and open elective AAA repair both have an impact on sexual function in the early postoperative period. After EVAR, recovery to preoperative levels is faster than after open repair, but at 3 months, sexual dysfunction levels are similar in both groups.