Cerebral Embolic Protection Devices for Transcatheter Aortic Valve Replacement: Review of the Literature and Future Perspectives.

PURPOSE OF REVIEW: Transcatheter aortic valve replacement (TAVR) has been a revolutionary therapy in the treatment of aortic valve stenosis. The risk of stroke associated with TAVR has decreased significantly since its introduction; however, it remains a devastating complication when it does occur. RECENT FINDINGS: Many of the strokes associated with TAVR occur peri-procedurally and are thought to be due to embolic debris entering the cerebrovascular circulation. A number of different cerebral embolic protection devices (CEPD) have been developed and are in various stages of testing and use. The results from clinical trials evaluating the role for CEPD to reduce the risk of stroke have been mixed. As a result, their uptake has been very heterogeneous. This review provides a summary of the diverse CEPD devices available for use and outlines the clinical evidence available to date.

The Relationship Between Atrial Fibrillation, Mitral Regurgitation, and Heart Failure Subtype: The ARIC Study.

BACKGROUND: Atrial fibrillation (AF) and mitral regurgitation (MR) are closely interrelated in the setting of heart failure (HF). Here we investigate the prevalence and prognostic significance of AF in patients with acute decompensated HF (ADHF) stratified by MR severity. METHODS AND RESULTS: The Atherosclerosis Risk in Communities Study investigated ADHF hospitalizations in residents greater than or equal to 55 years of age in 4 US communities. ADHF cases were stratified by MR severity (none/mild or moderate/severe) and HF subtype (HF with reduced [HFrEF] or preserved [HFpEF] ejection fraction). The odds of AF in patients with increasing MR severity was estimated using multivariable logistic regression, adjusting for age, race, sex, diabetes, hypertension, coronary artery disease, hemodialysis, stroke, and anemia. Cox regression models were used to assess the association of AF with 1-year mortality in patients with HFpEF and HFrEF, stratified by MR severity and adjusted as described, also adjusting for the year of hospitalization. From 2005 to 2014, there were 3,878 ADHF hospitalizations (17,931 weighted). AF was more likely in those with higher MR severity regardless of HF subtype; more so in HFpEF (odds ratio [OR] 1.38, 95% confidence interval [CI], 1.31-1.45) than in HFrEF (OR, 1.19, 95% CI, 1.13-1.25) (interaction P [by HF subtype] < .01). When stratified by HF type, association between AF and 1-year mortality was noted in patients with HFpEF (OR, 1.28, 95% CI 1.04-1.56) but not HFrEF (OR 0.96, 95% CI 0.79-1.16) (interaction by EF subtype, P = .02). CONCLUSIONS: In patients with ADHF, AF prevalence increased with MR severity and this effect was more pronounced in HFpEF compared with HFrEF. AF was associated with an increased 1-year mortality only in patients with HFpEF and concomitant moderate/severe MR. REGISTRATION: NCT00005131, https://clinicaltrials.gov/ct2/show/NCT00005131.

Five-year trends in cause-specific readmissions and cost burden of mitral transcatheter edge-to-edge repair.

OBJECTIVES: The study aimed to evaluate cost trends associated with mitral valve transcatheter edge-to-edge repair (TEER). BACKGROUND: TEER is a treatment option for patients at prohibitive surgical risk with moderate to severe mitral valve regurgitation and NYHA class III or IV symptoms. The 30-day costs and causes of readmission following TEER have not been well studied. METHODS: Patients undergoing mitral TEER in the United States from 2014 to 2018 were identified in the Nationwide Readmission Database. Patient characteristics, cause-specific readmission, and costs of the index hospitalization and readmissions were analyzed. Costs were trended over years using general linear regression. RESULTS: A total of 10,196 patients underwent mitral TEER during the study period. Thirty-day readmissions were stable over time at around 16%. The mean length of stay following TEER decreased from 7 days in 2014 to 5 days in 2018. There was a significant decline in the cost of the index hospitalization of $1311 per year, and a significant decline in the total 30-day cost of $1588 per year (p < 0.001). This was strictly due to a reduction in the cost of the index hospitalization without a change in readmission costs over time (p = 0.23). Infectious causes of readmissions significantly decreased while total cardiovascular readmissions, including heart failure, remained constant. CONCLUSION: The decreasing 30-day cost burden of TEER is primarily driven by the shorter index length of stay, as experience in TEER has grown and, length of stay has declined. However, cardiovascular readmissions, and consequently readmission costs, have remained steady.

Propofol Versus Remifentanil Sedation for Transcatheter Aortic Valve Replacement: A Single Academic Center Experience.

OBJECTIVE: Comparison of remifentanil versus propofol for sedation during transcatheter aortic valve replacement (TAVR) procedures to analyze the risk of sedation-related hypoxemia and hypotension. Secondary outcomes included the rate of conversion to general anesthesia, procedure length, rate of intensive care unit (ICU) admission, ICU and hospital lengths of stay, and 30-day mortality. DESIGN: Retrospective cohort study. SETTING: A single tertiary teaching hospital. PARTICIPANTS: Two hundred fifty-nine patients who had propofol or remifentanil sedation for TAVR between March 2017 and March 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: There were 130 patients (50.2%) in the propofol cohort and 129 patients (49.8%) in the remifentanil cohort. The primary outcomes were oxygen saturation nadir values and vasopressor infusion use. Remifentanil was associated with a lower oxygen saturation nadir, as compared to propofol (91.3% v . 95.4%, p < 0.001). Risk factors associated with hypoxemia (defined as <92%) were body mass index (p = 0.0004), obstructive sleep apnea (p = 0.004), and remifentanil maintenance (p < 0.001). Vasopressor infusion use was significantly higher with propofol (64.9% v . 8.5%, p < 0.001). Propofol maintenance and angiotensin-converting enzyme inhibitor/angiotensin II receptor-blocker use were the only variables identified as risk factors for vasopressor use (p < 0.001 and p = 0.009). CONCLUSIONS: For patients undergoing TAVR with conscious sedation, remifentanil was associated with more hypoxemia while propofol was associated with a higher rate of vasopressor use.

Predicting need for pacemaker implantation early and late after transcatheter aortic valve implantation.

OBJECTIVES: To identify associations with either early or late permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR) in order to develop an easily interpretable management algorithm. BACKGROUND: Injury to the conduction system after TAVR occasionally requires PPM. There is limited data on how to identify which patients will require PPM, particularly after discharge from index hospitalization after TAVR. METHODS: All patients having undergone TAVR at the University of North Carolina through August 2019 were identified and records were manually reviewed. Multivariable analyses were performed to identify associations with post-TAVR PPM due to high-degree atrioventricular block (HAVB). Comparisons were made between patients with no PPM (n = 304) and PPM required, stratified into early (during index hospitalization, n = 32) and late (during subsequent hospitalization, n = 11) PPM cohorts. RESULTS: Of the 347 patents included for analysis, 43 (12.4%) underwent post-TAVR PPM. In multivariable regression models, early PPM was associated with baseline bifascicular block (OR: 42.16; p < .001), requiring any pacing on first post-TAVR electrocardiogram (ECG) (OR: 31.55; p < .001), and valve oversizing >15% (OR: 3.61; p < .05). Late PPM was associated with baseline right bundle branch block (RBBB) (OR 12.62; p < .001) and history of atrial fibrillation/flutter (OR 4.83; p < .05). CONCLUSIONS: Bifascicular block, any pacing on first post-TAVR ECG, and >15% valve oversizing are associated with early PPM, while RBBB and history of atrial fibrillation/flutter are associated with late PPM. We suggest a management strategy for post-TAVR surveillance and management of HAVB.

Transcatheter aortic valve replacement for patients with severe bicuspid aortic stenosis.

BACKGROUND: Patients with bicuspid aortic valve stenosis (BAV) were excluded from all the trileaflet aortic valve stenosis (TAV) pivotal trials, and therefore, their outcomes are not clearly defined. The aim of the study was to evaluate the outcomes of transcatheter aortic valve replacement (TAVR) in patients with BAV and compared them with those of TAV. METHODS: We evaluated the outcomes following TAVR of patients with BAV at our institution between April 2011 and November 2016 and compared them with the outcomes of patients with TAV treated with TAVR. The χ2 and the Mann-Whitney U tests were used to compare the groups, and a Kaplan-Meier analysis was performed to estimate long-term survival. RESULTS: TAVR was performed in a total of 567 patients, from which 50 (8.8%) had BAV and 517 (91.2%) had TAV. Patients with BAV were younger and had higher prevalence of chronic obstructive pulmonary disease, lower prevalence of coronary artery disease, higher body mass index, and lower Society of Thoracic Surgeons score (STS PROM). Patients with BAV had a slightly higher mean aortic valve gradient postoperatively (median 12 mm Hg [10-15] vs 10 [7-13], P < .001), but paravalvular aortic regurgitation was not different between the groups (> mild 4.0% vs 3.5%, P = .541). Clinical outcomes were not different between the groups, including stroke (2.0% vs 1.5, P = .567) and the 30-day all-cause mortality (6.0% vs 1.5, P = .064). The 2-year survival (82.0% vs 83.4, P = .476) was similar between the groups. CONCLUSIONS: This initial experience suggests that TAVR can be safely performed in patients with BAV, achieving similar short-term procedural and clinical outcomes when compared with patients with TAV.

Impact of age and comorbidities on the effect of transcatheter versus surgical mitral valve repair on inpatient outcomes.

BACKGROUND: Transcatheter mitral valve repair (TMVR) has shown to be a safe and effective treatment option for symptomatic severe mitral regurgitation (MR) in patients who are at prohibitive surgical risk. Whether age and comorbidities impact the inpatient safety outcomes of TMVR versus surgical mitral valve repair (SMVR) is unknown. METHODS: Using the national inpatient sample, patients undergoing either elective TMVR or SMVR between 2012 and 2015 were analyzed. Logistic, generalized logistic, and linear regression were used to compare inpatient complications, discharge disposition, and length of stay (LOS). Heterogeneity in the effect of TMVR versus SMVR across Charlson comorbidity index (CCI, categorized as <2 and ≥2) and age (categorized as <75 years old and ≥75 years old) were assessed for effect modification. RESULTS: Overall, 8,716 hospitalizations were included, 7,950 (91%) SMVR and 766 (9%) TMVR. Compared with SMVR, patients undergoing TMVR were older (median age 79 vs. 62 years) and more likely to be female (45% vs. 40%) with a higher CCI score (median CCI 2 vs. 1). Despite being older with a higher comorbidity burden, patients undergoing TMVR had a lower incidence of permanent pacemaker implantation (OR 0.23, 95% CI: 0.11, 0.50), cerebrovascular accidents (OR 0.37, 95% CI: 0.15, 0.92), and major bleeding (OR 0.39, 95% CI: 0.32, 0.47). TMVR patients were also discharged 3 days earlier (CIE -3.26; 95% CI: -3.72, -2.80) and were less likely to be discharged to a skilled nursing facility (OR 0.72, 95% CI 0.55, 0.93). Additionally, the relative reduction in complications after TMVR versus SMVR was significantly higher in older (age ≥75 years) and more comorbid (CCI ≥2) patients (p for interaction <.05 for both). CONCLUSION: Patients treated with TMVR, as compared with SMVR, were older and had more comorbidities, but had a lower incidence of inpatient complications, shorter LOS, and better discharge disposition. Therefore, TMVR may be a safer option than SMVR in older patients and those with a higher burden of comorbidities.

Meta-analysis of transfemoral TAVR versus surgical aortic valve replacement.

BACKGROUND: In the recently concluded PARTNER 2 trial, TF-TAVR cohort was shown to have lower risks of death or disabling strokes as compared to SAVR, whereas the outcomes with transthoracic TAVR were comparable with SAVR. METHODS: We searched PubMed, EMBASE, Web of Science, and Google Scholar for all comparison studies between TAVR and SAVR and mortality as an outcome, irrespective of surgical risk. Randomized controlled trials and propensity-score-matched cohort studies that used a transfemoral approach exclusively or stratified results by route of access and reported data for TF-TAVR patients were eligible for inclusion. Outcomes of interest included 30-day and 1-year mortality, and 30-day complications. If significant heterogeneity was found in the random effects meta-analyses, a sensitivity analysis which individually removed each study was conducted. RESULTS: Seven studies reported results on TF-TAVR. Compared with SAVR, TF-TAVR had comparable 30-day mortality (RR 0.79, 95% CI 0.58, 1.06), 1-year mortality (RR 0.91, 95% CI 0.78, 1.08) and 30-day risk of bleeding (RR 0.70, 95% CI 0.31, 1.57). However, TF-TAVR was associated with lower 30-day risks of atrial fibrillation (RR 0.28, 95% CI 0.17, 0.45), acute kidney injury (RR 0.38, 95% CI 0.20, 0.71), and myocardial infarction (RR 0.41, 95% CI 0.23, 0.75) at a cost of higher incidences of vascular complications (RR 6.10, 95% CI 2.92, 12.73) and pacemaker implantations (RR 3.29, 95% CI 1.41, 7.65). CONCLUSIONS: TF-TAVR is associated with lower 30-day risks of myocardial infarction compared to SAVR. Further studies are required to investigate the role of myocardial injury on overall TF-TAVR outcomes.

General Anesthesia for Transcatheter Aortic Valve Replacement: Total Intravenous Anesthesia is Associated with Less Delirium as Compared to Volatile Agent Technique.

OBJECTIVE: Investigate the effect of volatile anesthesia versus total intravenous anesthesia on the incidence of postoperative delirium and length of stay in patients undergoing transcatheter aortic valve replacement under general anesthesia. DESIGN: Retrospective study. SETTING: Single institution, academic medical center. PARTICIPANTS: Adult patients who underwent transcatheter aortic valve replacement under general anesthesia between November 2014 and February 2017. INTERVENTIONS: This study was not an interventional study. MEASUREMENTS AND MAIN RESULTS: Electronic medical records were reviewed for intraoperative maintenance anesthetic technique, hospital and intensive care unit length of stay, 30-day mortality, and documentation of delirium. Delirium was defined as either 1) positive Confusion Assessment Method for the Intensive Care Unit score or 2) documentation of delirium or confusion by the care team within 2 days of surgery. Overall, 116 patients were included and 84 (72%) received a total intravenous anesthesia technique. Twenty-three patients (20%) had postoperative delirium. The odds of delirium were lower in patients undergoing transcatheter aortic valve replacement with total intravenous anesthesia, compared with volatile anesthesia, even after adjusting for procedure approach (odds ratio 0.22, 95% confidence interval 0.06, 0.79, p = 0.02). No significant difference in hospital or intensive care unit length of stay was seen after adjusting for procedural characteristics. CONCLUSIONS: While postoperative delirium is a complex and multifactorial problem, the type of general anesthetic maintenance may contribute to the incidence of postoperative delirium in patients undergoing transcatheter aortic valve replacement, and total intravenous anesthesia may be an attractive alternative to volatile-based general anesthesia maintenance.

Aortic valve surgery and survival in patients with moderate or severe aortic stenosis and left ventricular dysfunction.

AIMS: We aimed to determine the frequency of aortic valve surgery (AVR) with or without coronary artery bypass grafting (CABG), among patients with moderate/severe aortic stenosis (AS) and left ventricular systolic dysfunction (LVSD), and its relationship with survival. METHODS AND RESULTS: The Duke Echocardiographic Database (N = 132 804) was queried for patients with mean gradient ≥25 mmHg and/or peak velocity ≥3 m/s and LVSD (left ventricular ejection fraction ≤50%) from 1 January 1995-28 February 2014. For analyses purposes, AS was defined both by mean gradient and calculated aortic valve area (AVA) criteria. Time-dependent indicators of AVR in multivariable Cox models were used to assess the relationship of AVR and all-cause mortality. A total of 1634 patients had moderate (N = 1090, 67%) or severe (N = 544, 33%) AS by mean gradient criteria. Overall, 287 (26%) patients with moderate AS and 263 (48%) patients with severe AS underwent AVR within 5 years of the qualifying echo. There were 863 (53%) deaths observed up to 5 years following index echo. After multivariable adjustment in an inverse probability weighted regression model, AVR was associated with higher 5-year survival amongst patients with moderate AS and severe AS whether classified by AVA or mean gradient criteria. Over all, AVR ± CABG compared with medical therapy was associated with significantly lower mortality [hazard ratio, HR = 0.49 (0.38, 0.62), P < 0.0001]. Compared with CABG alone, CABG + AVR was associated with better survival [HR = 0.18 (0.12, 0.27), P < 0.0001]. CONCLUSIONS: In patients with moderate/severe AS and LVSD, mortality is substantial and amongst those selected for surgery, AVR with or without CABG is associated with higher survival. Research is required to understand factors contributing to current practice patterns and the possible utility of transcatheter approaches in this high-risk cohort.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Lower Surgical Risk Scores: A Systematic Review and Meta-Analysis of Early Outcomes.

BACKGROUND: The results from the PARTNER 2 trial showed the feasibility of transcatheter aortic valve replacement (TAVR) in intermediate surgical risk patients. Although low risk clinical trials will take time to conclude, some data has emerged comparing TAVR with surgical aortic valve replacement (SAVR) in lower risk patients. METHODS: A Medline search was conducted using standard methodology to search for studies reporting results comparing TAVR and SAVR. Studies were included if the overall mean Society of Thoracic Surgeons Score was less than 4% (or equivalent Euroscore). A meta-analysis comparing the 30-day risk of clinical outcomes between TAVR and SAVR in the lower surgical risk population was conducted. RESULTS: A total of four studies, including one clinical trial and three propensity-matched cohort studies met the inclusion criteria. Compared to SAVR, TAVR had a lower risk of 30-day mortality (RR 0.67, 95% CI 0.41, 1.10), stroke (RR 0.60, 95% CI 0.30, 1.22), bleeding complications (RR 0.51, 95% CI 0.40, 0.67) and acute kidney injury (RR 0.66, 95% CI 0.47, 0.94). However, a higher risk of vascular complications (RR 11.72, 95% CI 3.75, 36.64), moderate or severe paravalvular leak (RR 5.04, 95% CI 3.01, 8.43), and permanent pacemaker implantations (RR 4.62, 95% CI 2.63, 8.12) was noted for TAVR. CONCLUSION: Among lower risk patients, TAVR and SAVR appear to be comparable in short term outcomes. Additional high quality studies among patients classified as low risk are needed to further explore the feasibility of TAVR in all surgical risk patients.

Renal failure in patients with ST-segment elevation acute myocardial infarction treated with primary percutaneous coronary intervention: Predictors, clinical and angiographic features, and outcomes.

BACKGROUND: Among patients presenting with ST-segment elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI), the associations between clinical outcomes and both baseline renal function and the development of acute kidney injury (AKI) have not been reported in a trial population with unselected baseline renal function. METHODS: Patients enrolled in the APEX-AMI trial who underwent primary PCI for the treatment of STEMI were categorized according to (a) baseline renal function and (b) the development of AKI. Patient characteristics, clinical outcomes, and treatment patterns were analyzed according to baseline renal function and the development of AKI. A prediction model for AKI after primary PCI for STEMI was also developed. RESULTS: A total of 5,244 patients were included in this analysis and stratified according to baseline estimated glomerular filtration rate (eGFR) (milliliters per minute per 1.73 m(2)) of >90, 60 to 90, 30 to 59, or <30 or as dialysis dependent. Patients with lower eGFR were older, more often female, and less often treated with evidence-based medicines and had worse angiographic outcomes and higher mortality. The rates of AKI for patients with a baseline eGFR of >90, 60 to 90, 30 to 59, and <30 were 2.5%, 4.1%, 8.1%, and 1.6%, respectively (P < .0001). The strongest predictors of AKI were age and presenting in Killip class III or IV. CONCLUSIONS: Among patients undergoing primary PCI for STEMI, impaired renal function at presentation and development of post-PCI AKI were highly associated with worse clinical and angiographic outcomes, including death. The risk of developing AKI was low and only modestly associated with baseline renal function.

TAVR in Intermediate-Risk Patients: A Review of the PARTNER 2 Trial and its Future Implications.

BACKGROUND: Following publication of the results of the PARTNER trial, the American College of Cardiology/American Heart Association recognized the success of transcatheter aortic valve replacement (TAVR) by incorporating it as a feasible option in high-surgical risk patients, and recommending it as the standard of care for patients at prohibitive risk of surgery. Although this was recognized as a major success in the field of percutaneous valve replacement, surgical aortic valve replacement (SAVR) continued to be realized as the procedure of choice for low and intermediate surgical risk patients. Meanwhile, observational studies - predominantly from Europe - showed encouraging results for TAVR in lower-risk populations. With a lack of any large randomized controlled clinical trial, however, the advantages of TAVR continued to be limited to only a minority of patients with severe, symptomatic aortic stenosis. METHODS: Between December 2011 and November 2013, the PARTNER 2 investigators enrolled a total of 2,032 intermediate-risk patients with severe symptomatic aortic stenosis at 57 centers in the United States and Canada. Patients were randomized 1:1 to undergo either TAVR or SAVR. The primary end point was death and neurological events after two years. RESULTS: The study results showed similar rates for death and neurological events in the TAVR and SAVR groups. The TAVR group was found to have a larger valve area and a lower incidence of acute kidney injury, bleeding events, and atrial fibrillation. Conversely, the SAVR group experienced fewer vascular complications and lower rates of paravalvular regurgitation. CONCLUSIONS: The results of the PARTNER 2 trial are reviewed, and its implications for the future discussed.

Transcatheter Mitral Valve-in-Ring for Progressive Mitral Stenosis after Prior Repair with Annuloplasty: A Novel Balloon Sizing Technique.

An 83-year-old man with a previous mitral valve repair using a semi-rigid annuloplasty ring was found to have severe mitral stenosis. A transcatheter approach for mitral valve-in-ring replacement was selected due to the patient's high surgical risk. Pre-procedural computed tomography scans for transcatheter valve size selection were inconsistent with previously published recommendations. To determine the appropriate valve size, a 25 mm compliant balloon was inflated intraoperatively within the stenotic mitral ring, but yielded no resistance to movement and no 'waist'. Thus, a 29 mm balloon-expandable prosthetic valve was selected and deployed with no paravalvular leak. This novel balloon sizing technique helped lead to a successful outcome in this case. Video 1: Angiographic video displaying mitral valve-in-ring balloon sizing technique. The 25 mm compliant balloon was inflated within a stenotic mitral ring to determine which prosthetic transcatheter valve size was appropriate. As shown, this technique yielded no 'waist' and no resistance to movement, suggesting that a 29 mm valve was necessary.

Assessment of single-bolus contrast administration technique using hybrid dual-source ECG-gated thoracic and dual-source non-ECG-gated high-pitch abdominopelvic CT acquisitions for procedural planning before transcatheter aortic valve replacement.

PURPOSE: This study aimed to assess vascular contrast opacification and homogeneity using single-bolus contrast administration with hybrid thoracic and abdominopelvic computed tomographic angiography in patients with severe aortic valve stenosis. MATERIALS AND METHODS: Combination electrocardiogram-gated thoracic and dual-source, high-pitch abdominopelvic computed tomographic angiography examinations of 50 patients with severe aortic stenosis between December 2013 and March 2014 were reviewed. Contrast administration was individualized to patient-specific physiology. Image analysis of vascular opacification was obtained and interdependencies of vascular contrast and homogeneity of contrast distribution were assessed. RESULTS: The mean volume of contrast administered was 106 ± 11.7 mL. Mean attenuation was 371 ± 90.7 Hounsfield units (HU) in the thoracic aorta and 388 ± 95.9 HU in the abdominal aorta. Homogeneous opacification was obtained throughout with coefficient of variation of 11%. CONCLUSIONS: Procedural planning for transcatheter aortic valve replacement can be achieved using a single-injection bolus contrast protocol in combination with a 2-part multidetector computed tomographic image acquisition technique with optimal opacification of major arterial structures.

Role of cardiac evaluation before thoracic endovascular aortic repair.

BACKGROUND: Patients with thoracic aortic disease undergoing thoracic endovascular aortic repair (TEVAR) often have concomitant coronary artery disease and are at risk for perioperative adverse cardiac events. Despite this risk, the need for and extent of preoperative cardiac workup before TEVAR remain undefined. This study seeks to assess the adequacy of a limited cardiac evaluation before TEVAR, including assessment of cardiac symptoms, resting electrocardiography (ECG), and transthoracic echocardiography (TTE), as well as to estimate the incidence of perioperative cardiac events in patients undergoing TEVAR. METHODS: Retrospective analysis of a prospectively maintained Institutional Review Board-approved database was performed for all patients undergoing TEVAR at a single referral institution between May 2002 and June 2013. The analysis identified 463 TEVAR procedures. All procedures involving median sternotomy were excluded, and 380 procedures (343 patients) were included in the final analysis. Degree of cardiac workup was classified on the basis of the highest level of preoperative testing: no workup, resting ECG only, resting TTE, exercise/pharmacologic stress testing, or coronary angiography. Standard workup consisted of cardiac symptom assessment along with resting ECG or TTE, with further workup indicated for unstable symptoms, significantly abnormal findings on ECG or TTE, or multiple cardiac risk factors. Categorical and continuous variables were compared by Fisher's exact test and analysis of variance, respectively. RESULTS: No preoperative cardiac workup was performed for 28 patients (7.4%); 127 patients (33.4%) had resting ECG only, 208 patients (54.7%) had resting echocardiography, 12 patients (3.2%) underwent stress testing, and five patients (1.3%) had coronary angiography. Patients undergoing stress testing or coronary angiography were older and had a higher incidence of known coronary artery disease (P < .01) and prior myocardial infarction (P = .01). Complex hybrid aortic repairs and TEVAR for aneurysmal disease were more likely to have an extensive workup, whereas nonelective procedures more commonly had no workup. A total of nine patients (2.4%) experienced a perioperative cardiac event (myocardial infarction or cardiac arrest), with no significant difference noted among all groups (P = .45), suggesting that the extent of cardiac workup was appropriate. The incidence of 30-day/in-hospital mortality (5.5%) and cardiac-specific mortality (0.8%) was similar among all groups. CONCLUSIONS: The risk of a postoperative cardiac event after TEVAR is low (2.4%), and initial screening with either resting TTE or ECG, in addition to assessment of cardiac symptom status, appears adequate for most TEVAR patients. As such, we recommend resting TTE or ECG as the initial cardiovascular screening mechanism in patients undergoing TEVAR, with subsequent more invasive studies if initial screening reveals cardiovascular abnormalities.

Warfarin use and long-term outcomes in patients with acute myocardial infarction and atrial fibrillation.

Warfarin use in patients with acute myocardial infarction (AMI) and atrial fibrillation (AF) remains challenging. We describe use of warfarin up to 1 year after hospitalization among patients with AMI and AF according to stroke and bleeding risk, and identify factors associated with long-term mortality in this population. Patients with AMI and AF who underwent cardiac catheterization during their AMI hospitalization in 1995-2007 were identified from the Duke Databank for Cardiovascular Disease. Warfarin use at discharge, 6 months, and 1 year as well as long-term vital status were assessed by surveys. Rates of warfarin use were presented according to CHADS2 and CHA2DS2VASc stroke and ATRIA bleeding risk scores. Cox proportional hazards modeling was used to determine whether warfarin use at discharge was independently associated with 1-year mortality. A total of 879 patients hospitalized with AMI with AF were identified. Median age was 72 (25th, 75th percentiles: 64, 79), and median follow-up was 4.1 years (1.3, 7.4). The rate of warfarin use at discharge was 24 % and did not differ by CHADS2, CHA2DS2VASc, or ATRIA risk scores. Warfarin use remained similar at 6 months (26 %) and 1 year (27 %). Long-term mortality was high and did not differ by whether warfarin was or was not prescribed at discharge (72 and 71 %, respectively). Factors associated with 1-year mortality were history of heart failure (HR 1.58, 95 % CI 1.32-1.90), higher Charlson comorbidity index (HR 1.19, 95 % CI 1.11-1.28), and older age (HR 1.03 per 1-year increase, 95 % CI 1.02-1.05). Warfarin use at discharge among patients hospitalized for AMI who had comorbid AF was low and remained low at 1 year. Warfarin use at hospital discharge was not associated with either 1-year mortality or long-term mortality.

A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial.

AIMS: We sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined. METHODS AND RESULTS: Non-ST-elevation ACS patients (n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25, 50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7, and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively. CONCLUSION: At least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation.

Rescuing clinical trials in the United States and beyond: a call for action.

Numerous challenges-financial, regulatory, and cultural-are hindering US participation and performance in multinational clinical trials. Consequently, it is increasingly unclear how the results of these trials should be applied to American patients, practice patterns, and systems of care. Both incremental and transformative changes are needed to revitalize US participation as well as the broader clinical trial enterprise. To promote consensus around the solutions needed to address the adverse trends in clinical research, the Duke Clinical Research Institute convenedstakeholders from academia, industry, and government. article summarizes the proceedings of this meeting and addresses: (1) adverse trends in the United States and multinational clinical trials, (2) the key issues that underlie these adverse trends, and (3) potential solutions to these problems.