Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement: A Systematic Review and Meta-analysis. Gargiulo Giuseppe,Sannino Anna,Capodanno Davide,Barbanti Marco,Buccheri Sergio,Perrino Cinzia,Capranzano Piera,Indolfi Ciro,Trimarco Bruno,Tamburino Corrado,Esposito Giovanni Annals of internal medicine BACKGROUND:The comparative benefits and harms of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for patients with aortic stenosis are unclear. PURPOSE:To compare clinical outcomes, including early (≤30-day) and midterm (≤1-year) mortality, in adults with severe aortic stenosis undergoing either TAVI or SAVR. DATA SOURCES:MEDLINE, Cochrane, and Scopus databases (without language restrictions) from April 2002 to 5 April 2016; multiple registries and Web sites; scientific meeting presentations. STUDY SELECTION:Five randomized trials and 31 observational matched studies comparing mortality outcomes after TAVI or SAVR. DATA EXTRACTION:Two investigators independently extracted study data and rated risk of bias. DATA SYNTHESIS:16 638 patients were analyzed. Overall, there was no statistically significant difference between TAVI and SAVR in early (odds ratio [OR], 1.01 [95% CI, 0.81 to 1.26]) or midterm (OR, 0.96 [CI, 0.81 to 1.14]) all-cause mortality. Analyses restricted to trials (early: OR, 0.80 [CI, 0.51 to 1.25]; midterm: OR, 0.90 [CI, 0.64 to 1.26]) were inconclusive, with wide CIs, whereas analyses of matched studies were similar to the overall results. Transfemoral TAVI provided mortality benefits over SAVR in trials. Analyses restricted to studies of patients at low to intermediate risk showed statistically nonsignificant reductions in early (OR, 0.67 [CI, 0.42 to 1.07]) and midterm (OR, 0.91 [CI, 0.67 to 1.23]) mortality with TAVI. Incidence of periprocedural myocardial infarction, major bleeding, acute kidney injury, and new-onset atrial fibrillation was lower with TAVI, but risk for pacemaker implantation, vascular complications, and paravalvular leak increased. Overall, there was a statistically nonsignificant increased risk in long-term (2- to 5-year) all-cause mortality with TAVI (OR, 1.28 [CI, 0.97 to 1.69]), whereas long-term mortality outcomes in patients at low to intermediate risk were inconclusive, with wide CIs (OR, 1.06 [CI, 0.59 to 1.91]). LIMITATION:The number of trials was limited, and study designs and patient characteristics were heterogeneous. CONCLUSION:Compared with SAVR, TAVI may have similar or better early and midterm outcomes for adults with aortic stenosis, including those at low to intermediate risk. PRIMARY FUNDING SOURCE:None. 10.7326/M16-0060
    Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of severe aortic stenosis: a meta-analysis of randomized trials. Siontis George C M,Praz Fabien,Pilgrim Thomas,Mavridis Dimitris,Verma Subodh,Salanti Georgia,Søndergaard Lars,Jüni Peter,Windecker Stephan European heart journal AIMS:In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the spectrum of risk and in important subgroups. METHODS AND RESULTS:Trials comparing TAVI vs. SAVR were identified through Medline, Embase, and Cochrane databases. The primary outcome was death from any cause at 2 years. We performed random-effects meta-analyses to combine the available evidence and to evaluate the effect in different subgroups. This systematic review and meta-analysis is registered with PROSPERO (CRD42016037273). We identified four eligible trials including 3806 participants, who were randomly assigned to undergo TAVI (n = 1898) or SAVR (n = 1908). For the primary outcome of death from any cause, TAVI when compared with SAVR was associated with a significant 13% relative risk reduction [hazard ratio (95% CI): 0.87 (0.76-0.99); P = 0.038] with homogeneity across all trials irrespective of TAVI device (P = 0.306) and baseline risk (P = 0.610). In subgroup analyses, TAVI showed a robust survival benefit over SAVR for patients undergoing transfemoral access [0.80 (0.69-0.93); P = 0.004], but not transthoracic access [1.17 (0.88-1.56); P = 0.293] (P = 0.024) and in female [0.68 (0.50-0.91); P = 0.010], but not male patients [0.99 (0.77-1.28); P = 0.952] (P = 0.050). Secondary outcomes of kidney injury, new-onset atrial fibrillation, and major bleeding favoured TAVI, while major vascular complications, incidence of permanent pacemaker implantation, and paravalvular regurgitation favoured SAVR. CONCLUSION:Compared with SAVR, TAVI is associated with a significant survival benefit throughout 2 years of follow-up. Importantly, this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients, and is particularly pronounced among patients undergoing transfemoral TAVI and in females. 10.1093/eurheartj/ehw225
    Antithrombotic therapy in abdominal aortic aneurysm: beneficial or detrimental? Cameron Scott J,Russell Hannah M,Owens A Phillip Blood Abdominal aortic aneurysm (AAA) is a degenerative vascular pathology resulting in significant morbidity and mortality in older adults due to rupture and sudden death. Despite 150 000 new cases and nearly 15 000 deaths annually, the only approved treatment of AAA is surgical or endovascular intervention when the risk for aortic rupture is increased. The goal of the scientific community is to develop novel pharmaceutical treatment strategies to reduce the need for surgical intervention. Because most clinically relevant AAAs contain a complex structure of fibrin, inflammatory cells, platelets, and red blood cells in the aneurysmal sac known as an intraluminal thrombus (ILT), antithrombotic therapies have emerged as potential pharmaceutical agents for the treatment of AAA progression. However, the efficacy of these treatments has not been shown, and the effects of shrinking the ILT may be as detrimental as they are beneficial. This review discusses the prospect of anticoagulant and antiplatelet (termed collectively as antithrombotic) therapies in AAA. Herein, we discuss the role of the coagulation cascade and platelet activation in human and animal models of AAA, the composition of ILT in AAA, a possible role of the ILT in aneurysm stabilization, and the implications of antithrombotic drugs in AAA treatment. 10.1182/blood-2017-08-743237
    Thrombo-embolic prevention after transcatheter aortic valve implantation. Vranckx Pascal,Windecker Stephan,Welsh Robert C,Valgimigli Marco,Mehran Roxana,Dangas George European heart journal Transcatheter aortic valve implantation (TAVI) has emerged as a valuable treatment alternative to surgical aortic valve replacement among patients with symptomatic aortic stenosis at increased surgical risk. The rapid technological evolution from early to current-generation TAVI systems with low-profile delivery catheters, bioprosthetic valves with proven midterm durability, and improved positioning and retrieval features have made important contributions to the widespread clinical use of this minimal invasive therapy. Although peri-procedural and long-term thrombotic and bleeding events after TAVI remain a relevant concern, the optimal antithrombotic strategy and duration to mitigate these risks remain unclear. This review provides an overview of recent insights in this field, and highlights current and future antithrombotic trials focusing on optimizing outcomes in patients undergoing TAVI. 10.1093/eurheartj/ehx390
    Outcomes in Transcatheter Aortic Valve Replacement for Bicuspid Versus Tricuspid Aortic Valve Stenosis. Yoon Sung-Han,Bleiziffer Sabine,De Backer Ole,Delgado Victoria,Arai Takahide,Ziegelmueller Johannes,Barbanti Marco,Sharma Rahul,Perlman Gidon Y,Khalique Omar K,Holy Erik W,Saraf Smriti,Deuschl Florian,Fujita Buntaro,Ruile Philipp,Neumann Franz-Josef,Pache Gregor,Takahashi Masao,Kaneko Hidehiro,Schmidt Tobias,Ohno Yohei,Schofer Niklas,Kong William K F,Tay Edgar,Sugiyama Daisuke,Kawamori Hiroyuki,Maeno Yoshio,Abramowitz Yigal,Chakravarty Tarun,Nakamura Mamoo,Kuwata Shingo,Yong Gerald,Kao Hsien-Li,Lee Michael,Kim Hyo-Soo,Modine Thomas,Wong S Chiu,Bedgoni Francesco,Testa Luca,Teiger Emmanuel,Butter Christian,Ensminger Stephan M,Schaefer Ulrich,Dvir Danny,Blanke Philipp,Leipsic Jonathon,Nietlispach Fabian,Abdel-Wahab Mohamed,Chevalier Bernard,Tamburino Corrado,Hildick-Smith David,Whisenant Brian K,Park Seung-Jung,Colombo Antonio,Latib Azeem,Kodali Susheel K,Bax Jeroen J,Søndergaard Lars,Webb John G,Lefèvre Thierry,Leon Martin B,Makkar Raj Journal of the American College of Cardiology BACKGROUND:Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with bicuspid aortic valve stenosis (AS). OBJECTIVES:This study sought to compare the procedural and clinical outcomes in patients with bicuspid versus tricuspid AS from the Bicuspid AS TAVR multicenter registry. METHODS:Outcomes of 561 patients with bicuspid AS and 4,546 patients with tricuspid AS were compared after propensity score matching, assembling 546 pairs of patients with similar baseline characteristics. Procedural and clinical outcomes were recorded according to Valve Academic Research Consortium-2 criteria. RESULTS:Compared with patients with tricuspid AS, patients with bicuspid AS had more frequent conversion to surgery (2.0% vs. 0.2%; p = 0.006) and a significantly lower device success rate (85.3% vs. 91.4%; p = 0.002). Early-generation devices were implanted in 320 patients with bicuspid and 321 patients with tricuspid AS, whereas new-generation devices were implanted in 226 and 225 patients with bicuspid and tricuspid AS, respectively. Within the group receiving early-generation devices, bicuspid AS had more frequent aortic root injury (4.5% vs. 0.0%; p = 0.015) when receiving the balloon-expanding device, and moderate-to-severe paravalvular leak (19.4% vs. 10.5%; p = 0.02) when receiving the self-expanding device. Among patients with new-generation devices, however, procedural results were comparable across different prostheses. The cumulative all-cause mortality rates at 2 years were comparable between bicuspid and tricuspid AS (17.2% vs. 19.4%; p = 0.28). CONCLUSIONS:Compared with tricuspid AS, TAVR in bicuspid AS was associated with a similar prognosis, but lower device success rate. Procedural differences were observed in patients treated with the early-generation devices, whereas no differences were observed with the new-generation devices. 10.1016/j.jacc.2017.03.017
    Magnitude of Soluble ST2 as a Novel Biomarker for Acute Aortic Dissection. Wang Yuan,Tan Xin,Gao Hai,Yuan Hui,Hu Rong,Jia Lixin,Zhu Junming,Sun Lizhong,Zhang Hongjia,Huang Lianjun,Zhao Dong,Gao Pei,Du Jie Circulation BACKGROUND:Misdiagnosis of acute aortic dissection (AAD) can lead to significant morbidity and death. Soluble ST2 (sST2) is a cardiovascular injury-related biomarker. The extent to which sST2 is elevated in AAD and whether sST2 can discriminate AAD from other causes of sudden-onset severe chest pain are unknown. METHODS:We measured plasma concentrations of sST2 (R&D Systems assay) in 1360 patients, including 1027 participants in the retrospective discovery set and 333 patients with initial suspicion of AAD enrolled in the prospective validation cohort. Measures of discrimination for differentiating AAD from other causes of chest pain were calculated. RESULTS:In the acute phase, sST2 levels were higher in patients with AAD than those with either acute myocardial infarction in the first case-control discovery set within 24 hours of symptom onset or with patients with pulmonary embolism in the second discovery set (medians of 129.2 ng/mL versus 14.7 with <0.001 for AAD versus acute myocardial infarction and 88.6 versus 9.3 with <0.001 for AAD versus pulmonary embolism). In the prospective validation set, sST2 was most elevated in patients with AAD (median [25th, 75th percentile]: 76.4 [49.6, 130.3]) and modestly elevated in acute myocardial infarction (25.0 [15.5, 37.2]), pulmonary embolism (14.9 [10.2, 30.1]), and angina patients (21.5 [13.1, 27.6], all <0.001 versus AAD). The area under receiver operating characteristic curve for patients with AAD versus all control patients within 24 hours of presenting at the emergency department was 0.97 (0.95, 0.98) for sST2, 0.91 (0.88, 0.94) for D-dimer, and 0.50 (0.44, 0.56) for cardiac troponin I, respectively. At a cutoff level of 34.6 ng/mL, sST2 had a sensitivity of 99.1%, specificity of 84.9%, positive predictive value of 68.7%, negative predictive value of 99.7%, positive likelihood ratio of 6.6, and negative likelihood ratio of 0.01. CONCLUSIONS:Among patients with suspected aortic dissection in the emergency department, sST2 showed superior overall diagnostic performance to D-dimer or cardiac troponin I. Additional study is needed to determine whether sST2 might be a useful rule-out marker for AAD in the emergency room. 10.1161/CIRCULATIONAHA.117.030469
    Forced diuresis with matched hydration during transcatheter aortic valve implantation for Reducing Acute Kidney Injury: a randomized, sham-controlled study (REDUCE-AKI). Arbel Yaron,Ben-Assa Eyal,Puzhevsky Daniela,Litmanowicz Batia,Galli Naama,Chorin Ehud,Halkin Amir,Sadeh Ben,Konigstein Maayan,Bassat Orit Kliuk-Ben,Steinvil Arie,Bazan Samuel,Banai Shmuel,Finkelstein Ariel European heart journal AIMS:Acute kidney injury (AKI) is a common complication following transcatheter aortic valve implantation (TAVI) and is associated with increased risk for short- and long-term mortality. In patients undergoing percutaneous coronary intervention (PCI), forced diuresis with matched hydration has been shown to reduce the incidence of AKI by ∼50%. The aim of the present study was to evaluate whether forced diuresis with matched intravenous hydration reduces AKI in patients undergoing TAVI. METHODS AND RESULTS:Reducing Acute Kidney Injury (REDUCE-AKI) was a single-centre, prospective, randomized, double-blind sham-controlled clinical trial, designed to examine the effect of an automated matched saline infusion with urine output for the prevention of AKI in patients undergoing TAVI. A total of 136 TAVI patients were randomized, 68 in each group. Mean age was 83.9 ± 5 years and 41.2% were males. There were no differences in baseline characteristics between the two groups. The rate of AKI was not statistically different between the groups (25% in the active group vs. 19.1% in the sham group, P = 0.408). There was a significant increase in long-term mortality in the active group (27.9% vs. 13. 2% HR 3.744, 95% CI 1.51-9.28; P = 0.004). The study was terminated prematurely by the Data Safety Monitoring Board for futility and a possible signal of harm. CONCLUSIONS:Unlike in PCI, forced diuresis with matched hydration does not prevent AKI in patients undergoing TAVI, and might be associated with increased long-term mortality. Future studies should focus on understanding the mechanisms behind these findings. CLINICALTRIALS.GOV REGISTRATION:NCT01866800, 30 April 2013. 10.1093/eurheartj/ehz343
    Descending Aorta Rupture During Transcatheter Aortic Valve Replacement. de Agustin Jose Alberto,Jiménez-Quevedo Pilar,Nombela-Franco Luis,Almeria Carlos,Gomez de Diego José Juan,Rodrigo Jose Luis,Marcos-Alberca Pedro,Mahia Patricia,Nuñez-Gil Ivan Javier,de Isla Leopoldo Perez,Fernandez-Ortiz Antonio,Macaya Carlos Circulation 10.1161/CIRCULATIONAHA.115.019824
    The long-term outcomes of open and endovascular repair for abdominal aortic aneurysm: A meta-analysis. Chen Zuo-Guan,Tan Shu-Ping,Diao Yong-Peng,Wu Zhi-Yuan,Miao Yu-Qing,Li Yong-Jun Asian journal of surgery To provide a meta-analysis of studies evaluating long-term all-cause mortality, aneurysm-related mortality and re-intervention after open or endovascular repair for abdominal aortic aneurysm. Electronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies comparing the long-term outcomes of open and endovascular repair for abdominal aortic aneurysm. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used. We retrieved 4 randomized controlled trials (RCTs; 2,783 patients), 7 nonrandomized trials (86,035 patients). The primary outcome was all-cause mortality. Heterogeneity was high and publication bias could not be excluded. Despite these limitations, the analysis showed that open and endovascular abdominal aortic aneurysm repair had similar all-cause mortality (OR 1.16, 95% CI, 0.89-1.51) over 5 years follow up, which was maintained after at least 10 years of follow-up (OR 0.87, 95% CI, 0.73-1.03). There was no significant difference in aneurysm-related mortality by 5 years or longer follow-up. A significantly lower proportion of patients undergoing open repair required reintervention (OR 0.38, 95% CI 0.24-0.64), which was maintained over 5 years of follow-up. There is no long-term survival difference between the patients who underwent open or endovascular aneurysm repair. There is significantly higher risk of reinterventions after endovascular aneurysm repair. 10.1016/j.asjsur.2019.01.014
    Optimizing Surveillance and Re-intervention Strategy Following Elective Endovascular Repair of Abdominal Aortic Aneurysms. Kim Lois G,Sweeting Michael J,Epstein David,Venermo Maarit,Rohlffs Fiona E V,Greenhalgh Roger M Annals of surgery BACKGROUND:EVAR for abdominal aortic aneurysm has an initial survival advantage over OR, but more frequent complications increase costs and long-term aneurysm-related mortality. Randomized controlled trials of EVAR versus OR have shown EVAR is not cost-effective over a patient's lifetime. However, in the EVAR-1 trial, postoperative surveillance may have been sub-optimal, as the importance of sac growth as a predictor of graft failure was overlooked. METHODS:Real-world data informed a discrete event simulation model of postoperative outcomes following EVAR. Outcomes observed EVAR-1 were compared with those from 5 alternative postoperative surveillance and re-intervention strategies. Key events, quality-adjusted life years and costs were predicted. The impact of using complication and rupture rates from more recent devices, imaging and re-intervention methods was also explored. RESULTS:Compared with observed EVAR-1 outcomes, modeling full adherence to the EVAR-1 scan protocol reduced abdominal aortic aneurysm (AAA) deaths by 3% and increased elective re-interventions by 44%. European Society re-intervention guidelines provided the most clinically effective strategy, with an 8% reduction in AAA deaths, but a 52% increase in elective re-interventions. The cheapest and most cost-effective strategy used lifetime annual ultrasound in primary care with confirmatory computed tomography if necessary, and reduced AAA-related deaths by 5%. Using contemporary rates for complications and rupture did not alter these conclusions. CONCLUSIONS:All alternative strategies improved clinical benefits compared with the EVAR-1 trial. Further work is needed regarding the cost and accuracy of primary care ultrasound, and the potential impact of these strategies in the comparison with OR. 10.1097/SLA.0000000000003625
    Oral Fluoroquinolones and Risk of Mitral and Aortic Regurgitation. Etminan Mahyar,Sodhi Mohit,Ganjizadeh-Zavareh Saeed,Carleton Bruce,Kezouh Abbas,Brophy James M Journal of the American College of Cardiology BACKGROUND:Recent studies have linked fluoroquinolones (FQs) to cardiac adverse events, including aortic dissection and aneurysm. To date, whether FQs can increase the risk of aortic or mitral regurgitation has not been studied. OBJECTIVES:This disproportionality analysis and case-control study examined whether FQs increase the risk of aortic and mitral regurgitation. METHODS:Data from the U.S. Food and Drug Administration's adverse reporting system database was used to undertake a disproportionality analysis, and a random sample of 9,053,240 patients from the U.S. PharMetrics Plus database (IQVIA) was used for the matched nested case-control study. Current FQ exposure implied an active prescription at the index date or 30 days prior to the event date. Recent FQ exposure was defined as FQ use within days 31 to 60 and past within days 61 to 365 prior to the event date. Rate ratios (RRs) were compared to users of amoxicillin and azithromycin. Conditional logistic regression was used to compute RRs adjusting for confounders. RESULTS:The reported odds ratio for the disproportionality analysis was 1.45 (95% confidence interval [CI]: 1.20 to 1.77). A total of 12,505 cases and 125,020 control subjects were identified in the case-control study. The adjusted RRs for current users of FQ compared with amoxicillin and azithromycin users were 2.40 (95% CI: 1.82 to 3.16) and 1.75 (95% CI: 1.34 to 2.29), respectively. The adjusted RRs for recent and past FQ users when compared with amoxicillin were 1.47 (95% CI: 1.03 to 2.09) and 1.06 (95% CI: 0.91 to 1.21), respectively. CONCLUSIONS:These results show that the risk of aortic and mitral regurgitation is highest with current use followed by recent use. No risk was observed with past use of FQs. Future studies are necessary to confirm or refute these associations. 10.1016/j.jacc.2019.07.035
    Short-Term Risk of Aortoiliac Aneurysm or Dissection Associated With Fluoroquinolone Use. Maumus-Robert Sandy,Bérard Xavier,Mansiaux Yohann,Tubert-Bitter Pascale,Debette Stéphanie,Pariente Antoine Journal of the American College of Cardiology 10.1016/j.jacc.2018.12.012
    Aortic Dissection With Severe Aortic Regurgitation. Ho Ming-Yun,Yeh Jih-Kai,Wang Chao-Yung,Hsieh I-Chang Circulation 10.1161/CIRCULATIONAHA.115.019952
    Fluoroquinolone and Aortic Dissection: Is It a Class Effect? Dolladille Charles,Chrétien Basile,Sassier Marion,Fedrizzi Sophie,Alexandre Joachim Journal of the American College of Cardiology 10.1016/j.jacc.2018.09.091
    Impact of Carotid Artery Involvement in Type A Aortic Dissection. Kreibich Maximilian,Rylski Bartosz,Czerny Martin,Beyersdorf Friedhelm,Itagaki Ryo,Okamura Homare,Kimura Naoyuki,Yamaguchi Atsushi,Vallabhajosyula Prashanth,Szeto Wilson Y,Bavaria Joseph E,Desai Nimesh D Circulation 10.1161/CIRCULATIONAHA.118.038099
    Response by Morello et al to Letters Regarding Article, "Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study". Morello Fulvio,Mueller Christian,Soeiro Alexandre de Matos,Leidel Bernd A,Salvadeo Sibilla Anna Teresa,Nazerian Peiman, Circulation 10.1161/CIRCULATIONAHA.118.034861
    Do Fluoroquinolones Increase the Risk of Aortic Aneurysms and Aortic Dissection? Singh Sonal,Nautiyal Amit Journal of the American College of Cardiology 10.1016/j.jacc.2018.07.018
    Pregnancy and the Risk of Aortic Dissection or Rupture: A Cohort-Crossover Analysis. Kamel Hooman,Roman Mary J,Pitcher Alex,Devereux Richard B Circulation BACKGROUND:Case series have described aortic dissection and rupture in pregnancy. Few population-based data exist to support an association. METHODS:We performed a cohort-crossover study using data on all emergency department visits and acute care hospitalizations at nonfederal healthcare facilities in California, Florida, and New York. We included women ≥12 years of age with labor and delivery or abortive pregnancy outcome between 2005 and 2013. Our outcome was a composite of aortic dissection or rupture. Based on the timing of reported aortic complications during pregnancy, we defined the period of risk as 6 months before delivery until 3 months after delivery. We compared each patient's likelihood of aortic complications during this period with an equivalent 270-day period exactly 1 year later. Incidence rates and incidence rate ratios were computed using conditional Poisson regression with robust standard errors. RESULTS:Among 6 566 826 pregnancies in 4 933 697 women, we identified 36 cases of aortic dissection or rupture during the pregnancy or postpartum period and 9 cases during the control period 1 year later. The rate of aortic complications was 5.5 (95% confidence interval, 4.0-7.8) per million patients during pregnancy and the postpartum period, in comparison with 1.4 (95% confidence interval, 0.7-2.9) per million during the equivalent period 1 year later. Pregnancy was associated with a significantly increased risk of aortic dissection or rupture (incidence rate ratio, 4.0; 95% confidence interval, 2.0-8.2) in comparison with the control period 1 year later. CONCLUSIONS:The risk of aortic dissection or rupture is elevated during pregnancy and the postpartum period. 10.1161/CIRCULATIONAHA.116.021594
    Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. Pasternak Björn,Inghammar Malin,Svanström Henrik BMJ (Clinical research ed.) OBJECTIVE:To investigate whether oral fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection. DESIGN:Nationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and cases of aortic aneurysm or dissection. SETTING:Sweden, July 2006 to December 2013. PARTICIPANTS:360 088 treatment episodes of fluoroquinolone use (78%ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360 088). MAIN OUTCOME MEASURES:Cox regression was used to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection, defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment. RESULTS:Within the 60 day risk period, the rate of aortic aneurysm or dissection was 1.2 cases per 1000 person years among fluoroquinolone users and 0.7 cases per 1000 person years among amoxicillin users. Fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection (hazard ratio 1.66 (95% confidence interval 1.12 to 2.46)), with an estimated absolute difference of 82 (95% confidence interval 15 to 181) cases of aortic aneurysm or dissection by 60 days per 1 million treatment episodes. In a secondary analysis, the hazard ratio for the association with fluoroquinolone use was 1.90 (1.22 to 2.96) for aortic aneurysm and 0.93 (0.38 to 2.29) for aortic dissection. CONCLUSIONS:In a propensity score matched cohort, fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection. This association appeared to be largely driven by aortic aneurysm. 10.1136/bmj.k678
    Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study. Nazerian Peiman,Mueller Christian,Soeiro Alexandre de Matos,Leidel Bernd A,Salvadeo Sibilla Anna Teresa,Giachino Francesca,Vanni Simone,Grimm Karin,Oliveira Múcio Tavares,Pivetta Emanuele,Lupia Enrico,Grifoni Stefano,Morello Fulvio, Circulation BACKGROUND:Acute aortic syndromes (AASs) are rare and severe cardiovascular emergencies with unspecific symptoms. For AASs, both misdiagnosis and overtesting are key concerns, and standardized diagnostic strategies may help physicians to balance these risks. D-dimer (DD) is highly sensitive for AAS but is inadequate as a stand-alone test. Integration of pretest probability assessment with DD testing is feasible, but the safety and efficiency of such a diagnostic strategy are currently unknown. METHODS:In a multicenter prospective observational study involving 6 hospitals in 4 countries from 2014 to 2016, consecutive outpatients were eligible if they had ≥1 of the following: chest/abdominal/back pain, syncope, perfusion deficit, and if AAS was in the differential diagnosis. The tool for pretest probability assessment was the aortic dissection detection risk score (ADD-RS, 0-3) per current guidelines. DD was considered negative (DD-) if <500 ng/mL. Final case adjudication was based on conclusive diagnostic imaging, autopsy, surgery, or 14-day follow-up. Outcomes were the failure rate and efficiency of a diagnostic strategy for ruling out AAS in patients with ADD-RS=0/DD- or ADD-RS ≤1/DD-. RESULTS:A total of 1850 patients were analyzed. Of these, 438 patients (24%) had ADD-RS=0, 1071 patients (58%) had ADD-RS=1, and 341 patients (18%) had ADD-RS >1. Two hundred forty-one patients (13%) had AAS: 125 had type A aortic dissection, 53 had type B aortic dissection, 35 had intramural aortic hematoma, 18 had aortic rupture, and 10 had penetrating aortic ulcer. A positive DD test result had an overall sensitivity of 96.7% (95% confidence interval [CI], 93.6-98.6) and a specificity of 64% (95% CI, 61.6-66.4) for the diagnosis of AAS; 8 patients with AAS had DD-. In 294 patients with ADD-RS=0/DD-, 1 case of AAS was observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1.9) and an efficiency of 15.9% (95% CI, 14.3-17.6) for the ADD-RS=0/DD- strategy. In 924 patients with ADD-RS ≤1/DD-, 3 cases of AAS were observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1) and an efficiency of 49.9% (95% CI, 47.7-52.2) for the ADD-RS ≤1/DD- strategy. CONCLUSIONS:Integration of ADD-RS (either ADD-RS=0 or ADD-RS ≤1) with DD may be considered to standardize diagnostic rule out of AAS. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifier: NCT02086136. 10.1161/CIRCULATIONAHA.117.029457
    Endothelial progenitor cells enhance blood-brain barrier permeability in subacute stroke. Sargento-Freitas João,Aday Sezin,Nunes César,Cordeiro Miguel,Gouveia Ana,Silva Fernando,Machado Cristina,Rodrigues Bruno,Santo Gustavo Cordeiro,Ferreira Carlos,Amorim André,Sousa Susana,Gomes Ana Catarina,Castelo-Branco Miguel,Ferreira Lino,Cunha Luís Neurology OBJECTIVE:To study the association among endothelial progenitor cells (EPCs), subacute blood-brain barrier (BBB) permeability, and clinical outcome after ischemic stroke, determining the micro RNAs of EPCs responsible for good clinical outcome. METHODS:We included consecutive patients with nonlacunar acute ischemic strokes in the territory of a middle cerebral artery and ages between 18 and 80 years. Clinical outcome was defined as modified Rankin Scale score at 3 months. Neuroimaging was performed at day 0 and 7 by MRI, including assessment of BBB permeability by dynamic contrast enhancement. EPCs were isolated from peripheral venous blood, quantified, and submitted to in vitro functional tests, including migratory and angiogenic assays. Stroke hemodynamics were evaluated serially by ultrasound. Statistical significance was set at < 0.05. RESULTS:We included 45 patients; mean age was 70.0 ± 10.0 years. The in vitro functional properties of EPCs were associated with BBB permeability, particularly at day 7. The number of each EPC subset at both timepoints was not associated with BBB permeability. Permeability of BBB at day 7 was independently associated with improved clinical outcome (odds ratio 0.897; 95% confidence interval 0.816-0.986; = 0.025). The EPCs (CD34+ cell subset) of patients with good clinical outcome showed 24 differentially expressed miRNAs, with a common effect on adherens junction pathway. CONCLUSIONS:The functional properties of EPCs are associated with enhanced subacute permeability of BBB and improved clinical outcome after acute ischemic stroke. 10.1212/WNL.0000000000004801
    Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis. Ulug Pinar,Sweeting Michael J,von Allmen Regula S,Thompson Simon G,Powell Janet T, Lancet (London, England) BACKGROUND:Prognosis for women with abdominal aortic aneurysm might be worse than the prognosis for men. We aimed to systematically quantify the differences in outcomes between men and women being assessed for repair of intact abdominal aortic aneurysm using data from study periods after the year 2000. METHODS:In these systematic reviews and meta-analysis, we identified studies (randomised, cohort, or cross-sectional) by searching MEDLINE, Embase, CENTRAL, and grey literature published between Jan 1, 2005, and Sept 2, 2016, for two systematic reviews and Jan 1, 2009, and Sept 2, 2016, for one systematic review. Studies were included if they were of both men and women, with data presented for each sex separately, with abdominal aortic aneurysms being assessed for aneurysm repair by either endovascular repair (EVAR) or open repair. We conducted three reviews based on whether studies reported the proportion morphologically suitable (within manufacturers' instructions for use) for EVAR (EVAR suitability review), non-intervention rates (non-intervention review), and 30-day mortality (operative mortality review) after intact aneurysm repair. Studies had to include at least 20 women (for the EVAR suitability review), 20 women (for the non-intervention review), and 50 women (for the operative mortality review). Studies were excluded if they were review articles, editorials, letters, or case reports. For the operative review, studies were also excluded if they only provided hazard ratios or only reported in-hospital mortality. We assessed the quality of the studies using the Newcastle-Ottawa scoring system, and contacted authors for the provision of additional data if needed. We combined results across studies by random-effects meta-analysis. This study is registered with PROSPERO, number CRD42016043227. FINDINGS:Five studies assessed the morphological eligibility for EVAR (1507 men, 400 women). The overall pooled proportion of women eligible (34%) for EVAR was lower than it was in men (54%; odds ratio [OR] 0·44, 95% CI 0·32-0·62). Four single-centre studies reported non-intervention rates (1365 men, 247 women). The overall pooled non-intervention rates were higher in women (34%) than men (19%; OR 2·27, 95% CI 1·21-4·23). The review of 30-day mortality included nine studies (52 018 men, 11 076 women). The overall pooled estimate for EVAR was higher in women (2·3%) than in men (1·4%; OR 1·67, 95% CI 1·38-2·04). The overall estimate for open repair also was higher in women (5·4%) than in men (2·8%; OR 1·76, 95% CI 1·35-2·30). INTERPRETATION:Compared with men, a smaller proportion of women are eligible for EVAR, a higher proportion of women are not offered intervention, and operative mortality is much higher in women for both EVAR and open repair. The management of abdominal aortic aneurysm in women needs improvement. FUNDING:National Institute for Health Research (UK). 10.1016/S0140-6736(17)30639-6