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Importance: Patient selection for transcatheter aortic valve replacement (TAVR) should include assessment of the risks of TAVR compared with surgical aortic valve replacement (SAVR). Existing SAVR risk models accurately predict the risks for the population undergoing SAVR, but comparable models to predict risk for patients undergoing TAVR are currently not available and should be derived from a population that underwent TAVR., Objective: To use a national population of patients undergoing TAVR to develop a statistical model that will predict in-hospital mortality after TAVR., Design, Setting, and Participants: Patient data were obtained from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry. The model was developed from 13 718 consecutive US patients undergoing TAVR in centers participating in the STS/ACC TVT Registry from November 1, 2011, to February 28, 2014. Validation was conducted using 6868 records of consecutive patients undergoing TAVR from March 1 to October 8, 2014. Covariates were selected through a process of expert opinion and statistical analysis. The association between in-hospital mortality and baseline covariates was estimated using logistic regression. The final set of predictors was selected via stepwise variable selection. Data were collected and analyzed from November 1, 2011, to February 28, 2014., Main Outcomes and Measures: In-hospital TAVR mortality., Results: The development sample included 13 718 patient records from 265 participant sites (of 13 672 with data available, 6680 men [48.9%]; 6992 women [51.1%]; mean [SD] age, 82.1 [8.3] years). The final validation cohort included 6868 patients from 314 participating centers (3554 men [51.7%]; 3314 women [48.3%]; mean [SD] age, 81.6 [8.8] years). In-hospital mortality occurred in 730 patients (5.3%). The C statistic for discrimination was 0.67 (95% CI, 0.65-0.69) in the development group and 0.66 (95% CI, 0.62-0.69) in the validation group. The final model covariates (reported as odds ratios; 95% CIs) were age (1.13; 1.06-1.20), glomerular filtration rate per 5-U increments (0.93; 0.91-0.95), hemodialysis (3.25; 2.42-4.37), New York Heart Association functional class IV (1.25; 1.03-1.52), severe chronic lung disease (1.67; 1.35-2.05), nonfemoral access site (1.96; 1.65- 2.33), and procedural acuity categories 2 (1.57; 1.20-2.05), 3 (2.70; 2.05-3.55), and 4 (3.34; 1.59-7.02). Calibration analysis demonstrated no significant difference between the model (predicted vs observed) calibration line (-0.18 and 0.97 for intercept and slope, respectively) compared with the ideal calibration line., Conclusions and Relevance: Data from the STS/ACC TVT Registry have been used to develop a predictive model of in-hospital mortality for patients undergoing TAVR. Validation based on a population of patient records not used in model development demonstrates discrimination and calibration indices that are more favorable than other models used in populations with TAVR. This model should be a valuable adjunct for patient counseling, local quality improvement, and national monitoring for appropriateness of selection of patients for TAVR.

Background: Female sex is associated with poorer outcomes after surgical aortic valve replacement (SAVR). Data on sex-specific differences after transcatheter aortic valve replacement (TAVR) are conflicting., Objective: To examine sex-specific differences in patients undergoing TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) trial., Design: Secondary analysis of the randomized and nonrandomized portions of the PARTNER trial. (ClinicalTrials.gov: NCT00530894)., Setting: 25 hospitals in the United States, Canada, and Germany., Patients: High-risk and inoperable patients (1220 women and 1339 men)., Intervention: TAVR., Measurements: Demographic characteristics, cardiac and noncardiac comorbidities, mortality, stroke, rehospitalization, vascular complications, bleeding complications, and echocardiographic valve parameters., Results: At baseline, women had lower rates of hyperlipidemia, diabetes, smoking, and renal disease but higher Society of Thoracic Surgeons Predicted Risk of Mortality scores (11.9% vs. 11.1%; P < 0.001). After TAVR, women had more vascular complications (17.3% vs. 10.0%; difference, 7.29 percentage points [95% CI, 4.63 to 9.95 percentage points]; P < 0.001) and major bleeding (10.5% vs. 7.7%; difference, 2.8 percentage points [CI, 0.57 to 5.04 percentage points]; P = 0.012) but less frequent moderate and severe paravalvular regurgitation (6.0% vs. 14.3%; difference, -8.3 percentage points [CI, -11.7 to -5.0 percentage points]; P < 0.001). At 30 days, the unadjusted all-cause mortality rate (6.5% vs. 5.9%; difference, 0.6 percentage point [CI, -1.29 to 2.45 percentage points]; P = 0.52) and stroke incidence (3.8% vs. 3.0%; difference, 0.8 percentage point [CI, -0.62 to 2.19 percentage points]; P = 0.28) were similar. At 1 year, all-cause mortality was significantly lower in women than in men (19.0% vs. 25.9%; hazard ratio, 0.72 [CI, 0.61 to 0.85]; P < 0.001)., Limitation: Secondary analysis that included nonrandomized trial data., Conclusion: Despite a higher incidence of vascular and bleeding complications, women having TAVR had lower mortality than men at 1 year. Thus, sex-specific risk in TAVR is the opposite of that in SAVR, for which female sex has been shown to be independently associated with an adverse prognosis., Primary Funding Source: Edwards Lifesciences.

Aims: Controversy exists regarding benefits of raising HDL-C in statin-treated coronary artery disease (CAD) patients. We assessed the anti-atherosclerotic efficacy of raising HDL-C in statin-treated individuals with CAD across a range of achieved LDL-C, including lower (<70 mg/dL) versus higher (≥70 mg/dL) levels., Methods and Results: In seven prospective randomized trials utilizing serial coronary intravascular ultrasound, 3469 statin-treated CAD patients were stratified according to achieved LDL-C (< vs ≥70 mg/dL) and changes in HDL-C (≥ vs < median), as well as across a broader spectrum of changes in HDL-C and achieved LDL-C levels. Changes in coronary percent atheroma volume and MACE (cardiovascular death, non-fatal MI, stroke, coronary revascularization, hospitalization for unstable angina) were evaluated across these groups., Results: Overall, median change in HDL-C was +6.03%, and mean achieved LDL-C in the lower and higher LDL-C groups were 55.1 ± 11 and 97.4 ± 22 mg/dL, respectively. Following multivariable adjustment, in patients with achieved LDL-C < 70 mg/dL, greater HDL-C-raising did not associate with disease progression/regression. In those with achieved LDL-C ≥ 70 mg/dL, greater HDL-C-raising associated with less disease progression (OR 0.80 (95% CI 0.67, 0.97)) and MACE (HR 0.78 (95% CI 0.64, 0.96)). Greater increases in HDL-C (up to 25% from baseline) across the continuous range of on-treatment LDL-C levels associated with less disease progression )OR 0.90 (95% CI 0.83, 0.98)) and lower MACE (HR 0.87 (95% CI 0.77, 0.998))., Conclusions: Increasing HDL-C via a broad spectrum of mechanisms appears beneficial in statin-treated CAD patients, but is likely of greater benefit in patients with achieved LDL-C levels ≥70 mg/dL., (© The European Society of Cardiology 2015.)

Transcatheter valve-in-valve mitral valve replacement provides treatment options to high-risk patients but is subject to its own complications. We present the migration of a transcatheter balloon-expandable Edwards-SAPIEN XT valve (Edwards Lifesciences, Irvine, CA) within a previously implanted surgical Carpentier-Edwards valve (Edwards Lifesciences) and our novel approach to its treatment., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to compare left ventricular (LV) remodeling using myocardial strain between patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) with and without prosthesis-patient mismatch (PPM)., Methods and Results: In a retrospective study, speckle-tracking echocardiography was used to measure global longitudinal strain (GLS) and strain rate (GLSR), circumferential strain, and rotation before and at mid-term follow-up post-TAVR. Moderate and severe PPM were defined as an effective orifice area ≤0.85 and <0.65 cm(2)/m(2), respectively. A total of 102 patients (median age, 83 years [77-88]) with severe AS were included. At 6±3 months post-TAVR, moderate and severe PPM were found in 32 (31%) and 9 (9%) patients. Patients without PPM had a significant regression in LV mass (from 134±41 to 119±38 g/m(2); P=0.001) at follow-up whereas those with PPM did not. There was a significant improvement in LV GLS (-12.8±4.0 to -14.3±4.3%; P=0.01), GLSR (-0.61±0.20 to -0.73±0.25 second(-1); P<0.001), and early diastolic strain rate (0.52±0.20 to 0.64±0.20 second(-1); P<0.001) in patients without PPM, but not in those with PPM. After adjustment for pre-TAVR ejection fraction and post-TAVR aortic regurgitation, patients without PPM had greater improvement in LV longitudinal strain parameters compared to those with PPM. After a median follow-up of 46.1 months (interquartile range, 35.4-60.8), there was no difference in survival between patients with and without PPM., Conclusions: TAVR was associated with an incidence of PPM of 40%. Greater reverse LV remodeling using myocardial strain was evident in patients without PPM compared to PPM. Presence of PPM was not associated with mortality., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: The Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry has been a joint initiative of the STS and the ACC in concert with multiple stakeholders. The TVT Registry has important information regarding patient selection, delivery of care, science, education, and research in the field of structural valvular heart disease., Objectives: This report provides an overview on current U.S. TVT practice and trends. The emphasis is on demographics, in-hospital procedural characteristics, and outcomes of patients having transcatheter aortic valve replacement (TAVR) performed at 348 U.S. centers., Methods: The TVT Registry captured 26,414 TAVR procedures as of December 31, 2014. Temporal trends between 2012 and 2013 versus 2014 were compared., Results: Comparison of the 2 time periods reveals that TAVR patients remain elderly (mean age 82 years), with multiple comorbidities, reflected by a high mean STS predicted risk of mortality (STS PROM) for surgical valve replacement (8.34%), were highly symptomatic (New York Heart Association functional class III/IV in 82.5%), frail (slow 5-m walk test in 81.6%), and have poor self-reported health status (median baseline Kansas City Cardiomyopathy Questionnaire score of 39.1). Procedure performance is changing, with an increased use of moderate sedation (from 1.6% to 5.1%) and increase in femoral access using percutaneous techniques (66.8% in 2014). Vascular complication rates are decreasing (from 5.6% to 4.2%), whereas site-reported stroke rates remain stable at 2.2%., Conclusions: The TVT Registry provides important information on characteristics and outcomes of TAVR in contemporary U.S. clinical practice. It can be used to identify trends in practice and opportunities for quality improvement.

Aortic atherosclerosis has been linked with worse peri- and post-procedural outcomes following a range of aortic procedures. Yet, there are currently no standardized methods for non-invasive volumetric pan-aortic plaque assessment. We propose a novel means of more accurately assessing plaque volume across whole aortic segments using computed tomography angiography (CTA) imaging. Sixty patients who underwent CTA prior to trans-catheter aortic valve implantation were included in this analysis. Specialized software analysis (3mensio Vascular™, Pie Medical, Maastricht, Netherlands) was used to reconstruct images using a centerline approach, thus creating true cross-sectional aortic images, akin to those images produced with intravascular ultrasonography. Following aortic segmentation (from the aortic valve to the renal artery origin), atheroma areas were measured across multiple contiguous evenly spaced (10 mm) cross-sections. Percent atheroma volume (PAV), total atheroma volume (TAV) and calcium score were calculated. In our populations (age 79.9 ± 8.5 years, male 52 %, diabetes 27 %, CAD 84 %, PVD 20 %), mean ± SD number of cross sections measured for each patient was 35.1 ± 3.5 sections. Mean aortic PAV and TAV were 33.2 ± 2.51 % and 83,509 ± 17,078 mm(3), respectively. Median (IQR) calcium score was 1.5 (0.7-2.5). Mean (SD) inter-observer coefficient of variation and agreement for plaque area among 4 different analysts was 14.1 (5.4), and the mean (95 % CI) Lin's concordance correlation coefficient was 0.79 (0.62-0.89), effectively simulating a Core Laboratory scenario. We provide an initial validation of cross-sectional volumetric aortic atheroma assessment using CTA. This proposed methodology highlights the potential for utilizing non-invasive aortic plaque imaging for risk prediction across a range of clinical scenarios.

Objectives: To assess technical performance learning curves of teams performing transfemoral transcatheter aortic valve replacement (TF-TAVR)., Background: TF-TAVR is a new procedure for treating severe aortic stenosis. The number of cases required for procedural efficiency is unknown., Methods: In the PARTNER-I trial, 1,521 patients underwent TF-TAVR from 4/2007-2/2012. Learning curve analysis of technical performance metrics was performed using institution-specific patient sequence number, interval between procedures, and institutional trial entry date. Learning curve characteristics were assessed using semi-parametric and parametric mixed-effects models., Results: As patient sequence number increased, average procedure time decreased from 154 to 85 minutes (P < 0.0001), and fluoroscopy time from 28 to 20 minutes (P < 0.0001). Procedure time plateaued at an average of 83 minutes (range 52-140). Procedure time plateau was dynamic during the course of the trial, averaging 25 cases (range 21-52) by its end. The later institutions enrolled in the trial, the shorter the initial procedure time. During the trial, percutaneous rather than surgical access increased from 7.9% to 69%., Conclusions: Technical performance learning curves exist for TF-TAVR; procedural efficiency increased with experience, with concomitant decreases in radiation and contrast media exposure. The number of cases needed to achieve efficiency decreased progressively, with optimal procedural performance reached after approximately 25 cases for late-entering institutions. Knowledge and experience accumulated by early TF-TAVR institutions were disseminated, shortening the learning curve of late-entering institutions. Technological advances resulting from learning during the trial moved the field from initial conservative surgical cut-down to percutaneous access for most patients. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Transcatheter aortic valve replacement (TAVR) is a viable option for patients with severe chronic obstructive pulmonary disease (COPD) who are deemed inoperable or high risk for surgery. We sought to determine outcomes of patients with severe aortic stenosis (AS) and severe COPD referred for aortic valve replacement (AVR). One hundred thirty-one patients with severe AS and severe COPD (GOLD criteria) were evaluated at our center between 2008 and 2013 and were divided retrospectively into 4 groups: 1-medical management, 2-balloon aortic valvuloplasty, 3-surgical aortic valve replacement (SAVR), and 4-TAVR. Baseline, clinical, and echo data were recorded. Primary outcome was cardiovascular death. From the study cohort, 54 (41.2%), 29 (22.1%), 21 (16.0%), and 27 (20.6%) were included in groups 1-4, respectively; the age was 74.9 ± 8.8, 76.2 ± 8.8, 78.8 ± 7.4, and 82.8 ± 6.8 years, respectively (P < 0.01). There was no significant difference between the groups for hypertension, diabetes, aortic valve area or gradients, forced expiratory volume in first second, right ventricular systolic pressure, ejection fraction, and Society of Thoracic Surgeons predicted risk of mortality score. At 3 ± 1.5 years, death occurred in 87%, 97%, 47.7%, and 51.8% of patients in groups 1-4, respectively. Heart failure readmissions occurred in 43%, 42%, 9.6%, and 14.8% of patients in groups 1-4, respectively. When SAVR and TAVR groups were compared, there was no significant difference in survival (P = 0.719) or heart failure readmissions (P = 0.19). In patients with severe or very severe COPD and severe AS, replacing the severely stenotic aortic valve by either SAVR or TAVR improves survival and reduces rehospitalization compared with medical therapy or balloon aortic valvuloplasty., (Copyright © 2016. Published by Elsevier Inc.)

Background: Transfemoral transcatheter aortic valve replacement (TF-TAVR) has enjoyed a rapid diffusion in the US and Europe, but the procedure is resource intensive., Objectives: We sought to identify differences in resource utilization between a US and European center to ascertain opportunities for improvement in the performance of TF-TAVR., Methods: All patients undergoing TF-TAVR using the Edwards SAPIEN valve series at the San Raffaele Hospital (Milan, Italy) and the Cleveland Clinic Foundation (Cleveland, OH) between January 2011 and December 2012 were included. Resource utilization was defined as preprocedural imaging, intraprocedural imaging, and personnel present during the procedure., Results: A total of 158 patients from Cleveland and 113 from Milan were analyzed. Median logistic EuroScore (22.1 vs. 15.5, P = 0.013) and STS-PROM (8.9 vs. 5.0%, P < 0.001) were higher in Cleveland. Thirty-day outcomes were similar. Majority of procedures in Milan were conducted without a cardiac surgeon (79%) or an imaging specialist (99%) present during the case. There was greater reliance on endotracheal intubation (94.3 vs. 3.5%), general anesthesia (GA: 94.3 vs. 4.4%), and intraprocedural TEE (93 vs. 12.4%) in Cleveland, but shorter length of stay (mean: 6.42 vs. 11.16 days)., Conclusions: We characterized resources used for patients undergoing TF-TAVR in Cleveland and Milan. Important differences included less reliance on GA and TEE and streamlining of procedural personnel in Milan, and reduced length-of-stay in Cleveland. Evolution of TF-TAVR to involve fewer operators must be balanced with the need for ready access to a comprehensive group of specialists in case of emergencies. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objectives: To identify number of cases needed to maximize device success and minimize adverse events after transfemoral transcatheter aortic valve replacement (TF-TAVR), and determine if adverse events were linked to the technical performance learning curve., Background: TF-TAVR is a complex procedure with an incompletely characterized learning curve for clinical outcomes., Methods: From 4/2007-2/2012, 1521 patients underwent TF-TAVR in the PARTNER-I trial. Outcomes learning curves were defined as number of cases needed to reach a plateau for device success, adverse events, and post-procedure length of stay. Institutional variation was accounted for by mixed-model non-linear techniques, which were also used to identify contribution of the procedure time learning curve to 30-day major adverse events and length of stay., Results: Eighty percent device success was achieved after 22 cases; major vascular complications fell below 5% after 70 cases and major bleeding below 10% after 25 cases. It took an average of 28 cases to achieve a consistent low risk of 30-day major adverse events, but institutions entering in the middle of the trial achieved it after about 26. The most significant correlate of 30-day major adverse events and post-procedure length of stay was procedure time (P < 0.0001). However, this association was related to patient and unmeasured variables, not the procedure time learning curve (P = 0.6)., Conclusions: By end of trial, a consistent low risk of adverse events was achieved after ∼26 cases. However, these improved results were due to change in patient risk profile; outcomes were not linked to the technical performance learning curve. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: The Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry has been a joint initiative of the STS and the ACC in concert with multiple stakeholders. The TVT Registry has important information regarding patient selection, delivery of care, science, education, and research in the field of structural valvular heart disease., Objectives: This report provides an overview on current U.S. TVT practice and trends. The emphasis is on demographics, in-hospital procedural characteristics, and outcomes of patients having transcatheter aortic valve replacement (TAVR) performed at 348 U.S. centers., Methods: The TVT Registry captured 26,414 TAVR procedures as of December 31, 2014. Temporal trends between 2012 and 2013 versus 2014 were compared., Results: Comparison of the 2 time periods reveals that TAVR patients remain elderly (mean age 82 years), with multiple comorbidities, reflected by a high mean STS predicted risk of mortality (STS PROM) for surgical valve replacement (8.34%), were highly symptomatic (New York Heart Association functional class III/IV in 82.5%), frail (slow 5-m walk test in 81.6%), and have poor self-reported health status (median baseline Kansas City Cardiomyopathy Questionnaire score of 39.1). Procedure performance is changing, with an increased use of moderate sedation (from 1.6% to 5.1%) and increase in femoral access using percutaneous techniques (66.8% in 2014). Vascular complication rates are decreasing (from 5.6% to 4.2%), whereas site-reported stroke rates remain stable at 2.2%., Conclusions: The TVT Registry provides important information on characteristics and outcomes of TAVR in contemporary U.S. clinical practice. It can be used to identify trends in practice and opportunities for quality improvement., (Copyright © 2015 American College of Cardiology Foundation and The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine the safety and effectiveness of the SAPIEN XT versus SAPIEN systems (Edwards Lifesciences, Irvine, California) in patients with symptomatic, severe aortic stenosis (AS) who were not candidates for surgery., Background: Transcatheter aortic valve replacement (TAVR) has become the standard of care for inoperable patients with severe, symptomatic AS. In the PARTNER (Placement of Aortic Transcatheter Valves) IB trial, a reduction in all-cause mortality was observed in patients undergoing TAVR with the balloon-expandable SAPIEN transcatheter heart valve compared with standard therapy, but the SAPIEN valve was associated with adverse periprocedural complications, including vascular complications, major bleeding, and paravalvular regurgitation. The newer, low-profile SAPIEN XT system was developed to reduce these adverse events., Methods: A total of 560 patients were enrolled at 28 sites in the United States from April 2011 to February 2012. Patients were randomized to receive the SAPIEN or SAPIEN XT systems. The primary endpoint was a nonhierarchical composite of all-cause mortality, major stroke, and rehospitalization at 1 year in the intention-to-treat population, assessed by noninferiority testing. Pre-specified secondary endpoints included cardiovascular death, New York Heart Association functional class, myocardial infarction, stroke, acute kidney injury, vascular complications, bleeding, 6-min walk distance, and valve performance (by echocardiography)., Results: Both overall and major vascular complications were higher at 30 days in patients undergoing TAVR with SAPIEN compared with SAPIEN XT (overall: 22.1% vs. 15.5%; p = 0.04; major: 15.2% vs. 9.5%; p = 0.04). Bleeding requiring blood transfusions was also more frequent with SAPIEN compared with SAPIEN XT (10.6% vs. 5.3%; p = 0.02). At 1-year follow-up, the nonhierarchical composite of all-cause mortality, major stroke, or rehospitalization was similar (37.7% SAPIEN vs. 37.2% SAPIEN XT; noninferiority p value <0.002); no differences in the other major pre-specified endpoints were found., Conclusions: In inoperable patients with severe, symptomatic AS, the lower-profile SAPIEN XT is noninferior to SAPIEN with fewer vascular complications and a lesser need for blood transfusion. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves; NCT01314313)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution., Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol., Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa., Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Transcatheter aortic valve replacement is an effective way to treat patients with symptomatic severe aortic valve stenosis who are deemed high risk or inoperable. Current data suggest that the mortality and stroke rates are acceptable compared to surgical aortic valve replacement. There is a possible utility in moderate-risk patients as more data become available., (Copyright © 2015 Cleveland Clinic.)

Background: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development., Methods: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time., Findings: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries., Interpretation: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: The study objective was to perform a randomized trial of brain protection during total aortic arch replacement and identify the best way to assess brain injury., Methods: From June 2003 to January 2010, 121 evaluable patients were randomized to retrograde (n = 60) or antegrade (n = 61) brain perfusion during hypothermic circulatory arrest. We assessed the sensitivity of clinical neurologic evaluation, brain imaging, and neurocognitive testing performed preoperatively and 4 to 6 months postoperatively to detect brain injury., Results: A total of 29 patients (24%) experienced neurologic events. Clinical stroke was evident in 1 patient (0.8%), and visual changes were evident in 2 patients; all had brain imaging changes. A total of 14 of 95 patients (15%) undergoing both preoperative and postoperative brain imaging had evidence of new white or gray matter changes; 10 of the 14 patients had neurocognitive testing, but only 2 patients experienced decline. A total of 17 of 96 patients (18%) undergoing both preoperative and postoperative neurocognitive testing manifested declines of 2 or more reliable change indexes; of these 17, 11 had neither imaging changes nor clinical events. Thirty-day mortality was 0.8% (1/121), with no neurologic deaths and a similar prevalence of neurologic events after retrograde and antegrade brain perfusion (22/60, 37% and 15/61, 25%, respectively; P = .2)., Conclusions: Although this randomized clinical trial revealed similar neurologic outcomes after retrograde or antegrade brain perfusion for total aortic arch replacement, clinical examination for postprocedural neurologic events is insensitive, brain imaging detects more events, and neurocognitive testing detects even more. Future neurologic assessments for cardiovascular procedures should include not only clinical examination but also brain imaging studies, neurocognitive testing, and long-term assessment., (Copyright © 2015. Published by Elsevier Inc.)

Objectives: Pathological studies demonstrate the dual significance of plaque burden (PB) and lipid composition for mediating coronary plaque vulnerability. We evaluated relationships between intravascular ultrasound (IVUS)-derived PB and arterial remodeling with near-infrared spectroscopy (NIRS)-derived lipid content in ex vivo and in vivo human coronary arteries., Approach and Results: Ex vivo coronary NIRS and IVUS imaging was performed through blood in 116 coronary arteries of 51 autopsied hearts, followed by 2-mm block sectioning (n=2070) and histological grading according to modified American Heart Association criteria. Lesions were defined as the most heavily diseased 2-mm block per imaged artery on IVUS. IVUS-derived PB and NIRS-derived lipid core burden index (LCBI) of each block and lesion were analyzed. Block-level analysis demonstrated significant trends of increasing PB and LCBI across more complex atheroma (Ptrend <0.001 for both LCBI and PB). Lesion-based analyses demonstrated the highest LCBI and remodeling index within coronary fibroatheroma (Ptrend <0.001 and 0.02 versus all plaque groups, respectively). Prediction models demonstrated similar abilities of PB, LCBI, and remodeling index for discriminating fibroatheroma (c indices: 0.675, 0.712, and 0.672, respectively). A combined PB+LCBI analysis significantly improved fibroatheroma detection accuracy (c index 0.77, P=0.028 versus PB; net-reclassification index 43%, P=0.003), whereas further adding remodeling index did not (c index 0.80, P=0.27 versus PB+LCBI). In vivo comparisons of 43 age- and sex-matched patients (to the autopsy cohort) undergoing combined NIRS-IVUS coronary imaging yielded similar associations to those demonstrated ex vivo., Conclusions: Adding NIRS to conventional IVUS-derived PB imaging significantly improves the ability to detect more active, potentially vulnerable coronary atheroma., (© 2015 American Heart Association, Inc.)

Background: When transcatheter aortic valve replacement (TAVR) cannot be carried out through transfemoral access, alternative access TAVR is indicated. The purpose of this study was to explore inhospital and 1-year outcomes of patients undergoing alternative access TAVR through the transapical (TA) or transaortic (TAo) techniques in the United States., Methods: Clinical records of 4,953 patients undergoing TA (n = 4,085) or TAo (n = 868) TAVR from 2011 to 2014 in The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Centers for Medicare and Medicaid Services hospital claims. Inhospital and 1-year clinical outcomes were stratified by operative risk; and the risk-adjusted association between access route and mortality, stroke, and heart failure repeat hospitalization was explored., Results: Mean age for all patients was 82.8 ± 6.8 years. The median STS predicted risk of mortality was significantly higher among patients undergoing TAo (8.8 versus 7.4, p < 0.001). When compared with TA, TAo was associated with an increased risk of unadjusted 30-day mortality (10.3% versus 8.8%) and 1-year mortality (30.3% versus 25.6%, p = 0.006). There were no significant differences between TAo and TA for inhospital stroke rate (2.2%), major vascular complications (0.3%), and 1-year heart failure rehospitalizations (15.7%). Examination of high-risk and inoperable subgroups showed that 1-year mortality was significantly higher for TAo patients classified as inoperable (p = 0.012)., Conclusions: Patients undergoing TAo TAVR are older, more likely female, and have significantly higher STS predicted risk of mortality scores than patients operated on by TA access. There were no risk-adjusted differences between TA and TAo access in mortality, stroke, or readmission rates as long as 1 year after TAVR., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Opinion Statement: Transcatheter valve therapies represent the newest frontier in interventional cardiology. At present, transcatheter aortic valve replacement and mitral valve edge-to-edge repair are currently approved by the US FDA in appropriately selected patients. These transcatheter therapies are typically employed in patients of advanced age with comorbid conditions. However, many younger adults with congenital heart disease are of comparable surgical risk due to multiple previous open heart surgeries. An array of percutaneous options currently exists for either temporizing or treating such patients (e.g., balloon septostomy, valvuloplasty, coiling of patent ductus arteriosus), but evidence-based treatment options for degenerative valve disease in this population are currently lacking. The most significant advance in this area to date has been the development and validation of transcatheter pulmonic valve implantation. Similarly, catheter-based approaches for the treatment of other valve lesions in patients with congenital valve disease are gaining interest, based in large part on promising evidence from studies of patients with acquired adult valvular heart disease.

Background: Balloon-expandable valves (BEVs) and self-expandable valves (SEVs) are two major types of valves utilized for transcatheter aortic valve replacement (TAVR). We conducted a meta-analysis of available studies to compare the safety and efficacy of these two valve types., Methods: Medline search was conducted using standard search terms to determine eligible studies. Primary outcomes of the meta-analysis included death and stroke at 30days and 1year. Pooled estimates of procedural outcomes were also compared between the valve types. Analysis was performed for entire cohort and separately for patients undergoing transfemoral TAVR (TF-TAVR)., Results: Analysis of entire cohort revealed similar 30-day mortality in the SEV and BEV cohorts. There was no significant difference in the incidence of stroke at 30days between the two study groups. Both pooled comparisons demonstrated a significant heterogeneity with I(2)>50%, necessitating the use of random effect modeling. We observed a significantly higher incidence of new pacemaker implantation, aortic regurgitation≥2+ at 30days, valve embolization, and need for >1 valve following SEV implantation compared with BEV implantation. Analysis of TF-TAVR cohort showed higher 30day [IRR (95% CI): 1.34 (1.19-1.52)] but a similar 1-year mortality [IRR (95% CI): 1.07 (0.96-1.19)] for SEV compared to BEV implantation., Conclusion: Compared to BEV implantation, SEV implantation was associated with a similar risk of mortality and stroke at 30-day and 1-year follow-up duration. Analysis of the TF-TAVR cohort revealed a significantly higher mortality at 30days among patients undergoing SEV implantation, compared with BEV implantation. In addition, there was a significantly higher incidence of other adverse events noted above, following SEV implantation, compared with BEV implantation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Many patients undergoing transcatheter aortic valve implantation (TAVI) have a pre-existing, permanent pacemaker (PPM) or receive one as a consequence of the procedure. We hypothesised that chronic pacing may have adverse effects on TAVI outcomes., Methods and Results: Four groups of patients undergoing TAVI in the Placement of Aortic Transcatheter Valves (PARTNER) trial and registries were compared: prior PPM (n=586), new PPM (n=173), no PPM (n=1612), and left bundle branch block (LBBB)/no PPM (n=160). At 1 year, prior PPM, new PPM and LBBB/no PPM had higher all-cause mortality than no PPM (27.4%, 26.3%, 27.7% and 20.0%, p<0.05), and prior PPM or new PPM had higher rehospitalisation or mortality/rehospitalisation (p<0.04). By Cox regression analysis, new PPM (HR 1.38, 1.00 to 1.89, p=0.05) and prior PPM (HR 1.31, 1.08 to 1.60, p=0.006) were independently associated with 1-year mortality. Surviving prior PPM, new PPM and LBBB/no PPM patients had lower LVEF at 1 year relative to no PPM (50.5%, 55.4%, 48.9% and 57.6%, p<0.01). Prior PPM had worsened recovery of LVEF after TAVI (Δ=10.0 prior vs 19.7% no PPM for baseline LVEF <35%, p<0.0001; Δ=4.1 prior vs 7.4% no PPM for baseline LVEF 35-50%, p=0.006). Paced ECGs displayed a high prevalence of RV pacing (>88%)., Conclusions: In the PARTNER trial, prior PPM, along with new PPM and chronic LBBB patients, had worsened clinical and echocardiographic outcomes relative to no PPM patients, and the presence of a PPM was independently associated with 1-year mortality. Ventricular dyssynchrony due to chronic RV pacing may be mechanistically responsible for these findings., Trial Registration Number: (ClinicalTrials.gov NCT00530894)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Over the last few decades, there has been a significant reduction in hospital length of stay (LOS) among patients undergoing percutaneous intervention (PCI) for ST elevation myocardial infarction (STEMI). Although studies have looked at predictors of long hospital stay after STEMI, the impact of LOS on long-term outcomes after PCI remains unknown. We aimed to evaluate the association between LOS at the time of index hospitalization for PCI and long-term mortality among patients presenting with STEMI., Methods: We examined all patients undergoing PCI for STEMI at the Cleveland Clinic Catheterization Laboratory between 2002 and 2011. Long-term all-cause mortality was assessed using the Social Security Death Index and electronic medical record review. LOS was extracted from the discharge summary of the index hospitalization., Results: A total of 1,963 patients were included in the study. Of these 1,963 patients undergoing PCI for STEMI, 126 (6.4%) died during the index hospitalization. Among survivors of this hospitalization, we observed a significant increase in long-term mortality with an increase in LOS during index hospitalization (P < 0.001). Adjustment for demographic and clinical characteristics yielded statistically significant increased mortality among patients with LOS of 6-10 days [HR (95% CI): 2.2 (1.3-3.5)] and LOS > 10 days [HR (95% CI): 2.6 (1.6-4.3)], in comparison with patients with LOS of 1-2 days., Conclusions: Long hospital stay after PCI among patients with STEMI was associated with an increased long-term mortality. A long hospital stay may be used as a marker to identify patients at higher risk for long-term mortality., (© 2015 Wiley Periodicals, Inc.)

Background: Obesity is associated with adverse atherosclerotic cardiovascular events. While various metabolic abnormalities associated with obesity promote plaque formation, the morphological phenotype of atherosclerotic plaque has not been well characterized in the setting of obesity. Frequency-domain optical coherence tomography (FD-OCT) enables in vivo visualization of plaque microstructures associated with vulnerability. We characterized plaque microstructures in obese patients., Methods: FD-OCT imaging was performed in 308 patients with coronary artery disease undergoing percutaneous coronary intervention. Patients were stratified according to the presence or absence of obesity (body mass index > 30 kg/m(2)). Plaques in obese (n = 129) and non-obese (n = 179) patients were compared with regard to clinical characteristics and FD-OCT-derived features of plaque vulnerability., Results: Obese patients were more likely to be younger (p = 0.01), female (p = 0.01) and have a history of hypertension (p = 0.01). Higher levels of triglyceride (p < 0.0001) and glucose (p = 0.02), whereas a lower level of high-density lipoprotein cholesterol (HDL-C) (p = 0.02) was observed in obese patients. FD-OCT imaging demonstrated thinner fibrous caps (85.3 ± 31.1 vs 110.1 ± 32.4 µm, p = 0.01) and a higher prevalence of thin-cap fibroatheroma (28.8 vs 14.3%, p = 0.01) in obese patients, which remained significant after controlling for differences in clinical characteristics. Achieving a low-density lipoprotein cholesterol (LDL-C) level < 1.8 mmol/l was associated with thicker fibrous caps in obese patients, but only to the level observed in non-obese patients with suboptimal lipid control., Conclusions: Obese patients harbor more vulnerable plaques in association with atherogenic risk factors. The limited benefit of lipid control suggests the need to adopt novel anti-atherosclerotic strategies in higher-risk patients., (© The European Society of Cardiology 2015.)

Background: Paravalvular aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) has been associated with increased mortality. Precise assessment of the degree of AR within the catheterization laboratory is crucial to take counter measures, but it remains challenging. The aim of this study was to determine whether any modification to AR index can improve its performance., Methods: The study included 64 patients treated with the Sapien valve (Edwards Life Sciences, Inc., Irvine, CA). The severity of AR was evaluated using echocardiography, angiography, and invasive hemodynamic parameters. We evaluated the time-integrated aortic regurgitation (TIAR) index as follows: (LV - Ao diastolic pressure time integral)/(LV systolic pressure time integral) × 100. We analyzed the AR index and TIAR index with the receiver operating characteristic (ROC) curve., Results: AR was observed in 58 patients (90.7%) and graded as mild in 33 (51.6%), moderate in 20 (31.3%), or moderate to severe in 5 (7.8%) patients. No severe AR was detected. The AR index and TIAR index decreased proportionately to the increased severity of AR (P = 0.002 and P < 0.001, respectively). TIAR index < 80 was associated with a sensitivity of 86% and a specificity of 83% for ≥mild AR. The area under the curve was greater for the TIAR index compared to the AR index (0.93 vs. 0.74)., Conclusion: The TIAR index provides a better hemodynamic measure for assessing severity of AR compared to the AR index., (© 2015 Wiley Periodicals, Inc.)

Objectives: The study objectives were to (1) compare the safety of high-risk surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves (PARTNER) I trial with Society of Thoracic Surgeons national benchmarks; (2) reference intermediate-term survival to that of the US population; and (3) identify subsets of patients for whom aortic valve replacement may be futile, with no survival benefit compared with therapy without aortic valve replacement., Methods: From May 2007 to October 2009, 699 patients with high surgical risk, aged 84 ± 6.3 years, were randomized in PARTNER-IA; 313 patients underwent surgical aortic valve replacement. Median follow-up was 2.8 years. Survival for therapy without aortic valve replacement used 181 PARTNER-IB patients., Results: Operative mortality was 10.5% (expected 9.3%), stroke 2.6% (expected 3.5%), renal failure 5.8% (expected 12%), sternal wound infection 0.64% (expected 0.33%), and prolonged length of stay 26% (expected 18%). However, calibration of observed events in this relatively small sample was poor. Survival at 1, 2, 3, and 4 years was 75%, 68%, 57%, and 44%, respectively, lower than 90%, 81%, 73%, and 65%, respectively, in the US population, but higher than 53%, 32%, 21%, and 14%, respectively, in patients without aortic valve replacement. Risk factors for death included smaller body mass index, lower albumin, history of cancer, and prosthesis-patient mismatch. Within this high-risk aortic valve replacement group, only the 8% of patients with the poorest risk profiles had estimated 1-year survival less than that of similar patients treated without aortic valve replacement., Conclusions: PARTNER selection criteria for surgical aortic valve replacement, with a few caveats, may be more appropriate, realistic indications for surgery than those of the past, reflecting contemporary surgical management of severe aortic stenosis in high-risk patients at experienced sites., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Stroke is a widely recognized complication after aortic valve replacement (AVR), especially among elderly patients. The literature contains substantial variability in reports of the actual incidence of stroke after AVR among high-risk patients. Our objective was to define risk of stroke in patients undergoing surgical AVR, using a large national database., Methods: We used the 2002 to 2011 Nationwide Inpatient Sample database for this analysis. All patients undergoing isolated AVR, or AVR with coronary artery bypass grafting (AVR + CABG), were identified using standard International Classification of Diseases codes. In-hospital mortality and any adverse neurologic event were the primary outcomes of the study., Results: The incidence of in-hospital mortality was 3.0% and 5.1%, respectively, among patients undergoing isolated AVR and AVR + CABG; it was significantly lower in high-volume centers. The incidence of any adverse neurologic event was 2.0% and 2.9%, respectively, among patients undergoing isolated AVR, and AVR + CABG. We demonstrated a progressive increase in the risk of in-hospital mortality and adverse neurologic events with increasing age. Neurologic events increased with age, from 1.3% for patients aged <70 years, to 3.2% for those aged >85 years, for isolated AVR; and from 2.3% to 3.6% for AVR + CABG. The incidence of in-hospital mortality was as high as 5.7% and 7.4%, respectively, among patients aged >85 years undergoing isolated AVR, and AVR + CABG. Similarly, the incidence of any adverse neurologic event was 3.2% and 3.6%, respectively, among patients aged >85 years undergoing isolated AVR, and AVR + CABG. In addition, the risk of adverse neurologic events was significantly higher in the high-risk surgical cohort, compared with the low-risk surgical cohort (odds ratio [95% confidence interval]; isolated AVR: 2.38 [1.99-2.86]; AVR + CABG: 1.88 [1.57-2.24])., Conclusions: The incidence of in-hospital mortality and adverse neurologic events was significantly higher among patients with advanced age and elevated surgical risk., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

There is a paucity of evidence on the impact of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on long-term outcomes in patients with ejection fraction (EF) >40% after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). We compared long-term all-cause mortality between patients with left ventricular ejection fraction (LVEF) >40% discharged on ACEi/ARB with patients who were discharged on neither of these agents. Patients discharged after percutaneous intervention for STEMI from our catheterization laboratories from January 2002 to December 2011 were considered for inclusion. Patients were excluded if they had LVEF <40% or chronic kidney disease or hypotension (systolic blood pressure <90 mm Hg any time after the procedure). Long-term mortality and discharge medications were determined using the Social Security Death Index and electronic medical record review, respectively. A total of 988 patients were included. The median follow-up duration was 4.6 years. Kaplan-Meier analysis showed no significant difference in long-term all-cause mortality in patients discharged on ACEi/ARB compared with those who were not discharged on these medications. The number needed to treat to prevent 1 death at 1 year was 714. In addition, multivariable Cox proportional hazard modeling failed to demonstrate any beneficial effect of ACEi/ARB similar to Kaplan-Meir analysis (hazard ratio 0.88, 95% confidence interval 0.57 to 1.36). In conclusion, we found no significant benefit in long-term mortality using ACEi/ARB in patients with LVEF >40% after primary percutaneous coronary intervention for STEMI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Patients with severe aortic stenosis due to BAV are excluded from transcatheter aortic valve replacement (TAVR) due to concern for asymmetric expansion and valve dysfunction. We sought to characterize the aortic root and annulus in bicuspid aortic valve (BAV) and tricuspid aortic valves (TAV)., Methods and Results: We identified patients with severe AS who underwent multi-detector computed tomographic (MDCT) imaging prior to surgical aortic valve replacement (SAVR, n = 200) for BAV and TAVR (n = 200) for TAV from 2010 to 2013. The presence of a BAV was confirmed on surgical and pathological review. Annulus measurements of the basal ring (short- and long-axis, area-derived diameter), coronary ostia height, sinus area (SA), sino-tubular junction area (STJ), calcification and eccentricity index (EI, 1-short axis/long axis) were made. Patients with TAV were older (78.8 years vs. 57.8 years, P = 0.04) than those with BAV. The aortic annulus area (5.21 ± 2.1 cm(2) vs. 4.63 ± 2.0 cm(2) , P = 0.0001), sinus of Valsalva diameter (3.7 ± 0.9 cm vs. 3.1 ± 0.1 cm, P = 0.001) and ascending aorta diameter (3.5 ± 0.7 cm vs. 2.97 ± 0.6 cm, P = 0.001) were significantly larger with BAV. Bicuspid aortic annuli were significantly less elliptical (EI, 1.24 ± 0.1 vs. 1.29 ± 0.1, P = 0.006) and more circular (39% vs. 4%, P < 0.001) compared to the TAV annulus. There was more eccentric annular calcification in BAV vs. TAV (68% vs. 32%, P < 0.001). The mean distance from the aortic annulus to the left main coronary ostium was less than the right coronary ostium. Less than 10% of the BAV annuli would not fit a currently available valved stents., Conclusion: Bicuspid aortic valves have a larger annulus size, sinus of Valsalva and ascending aorta dimensions. In addition, the BAV aortic annuli appear circular and most will fit currently available commercial valved stents., (© 2015 Wiley Periodicals, Inc.)

Background: The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that mortality at 1 year, 2 years, and 3 years is much the same with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) for high-risk patients with aortic stenosis. We report here the 5-year outcomes., Methods: We did this randomised controlled trial at 25 hospitals, in Canada (two), Germany (one), and the USA (23). We used a computer-generated randomisation sequence to randomly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-expandable bovine pericardial tissue valve by either a transfemoral or transapical approach. Patients and their treating physicians were not masked to treatment allocation. The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year, we present here predefined outcomes at 5 years. The study is registered with ClinicalTrials.gov, number NCT00530894., Findings: We screened 3105 patients, of whom 699 were enrolled (348 assigned to TAVR, 351 assigned to SAVR). Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 11·7%. At 5 years, risk of death was 67·8% in the TAVR group compared with 62·4% in the SAVR group (hazard ratio 1·04, 95% CI 0·86-1·24; p=0·76). We recorded no structural valve deterioration requiring surgical valve replacement in either group. Moderate or severe aortic regurgitation occurred in 40 (14%) of 280 patients in the TAVR group and two (1%) of 228 in the SAVR group (p<0·0001), and was associated with increased 5-year risk of mortality in the TAVR group (72·4% for moderate or severe aortic regurgitation vs 56·6% for those with mild aortic regurgitation or less; p=0·003)., Interpretation: Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes., Funding: Edwards Lifesciences., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Based on the early results of the Placement of Aortic Transcatheter Valves (PARTNER) trial, transcatheter aortic valve replacement (TAVR) is an accepted treatment for patients with severe aortic stenosis who are not suitable for surgery. However, little information is available about the late clinical outcomes in such patients., Methods: We did this randomised controlled trial at 21 experienced valve centres in Canada, Germany, and the USA. We enrolled patients with severe symptomatic inoperable aortic stenosis and randomly assigned (1:1) them to transfemoral TAVR or to standard treatment, which often included balloon aortic valvuloplasty. Patients and their treating physicians were not masked to treatment allocation. The randomisation was done centrally, and sites learned of the assignment only after a patient had been screened, consented, and entered into the database. The primary outcome of the trial was all-cause mortality at 1 year in the intention-to-treat population, here we present the prespecified findings after 5 years. This study is registered with ClinicalTrials.gov, number NCT00530894., Findings: We screened 3015 patients, of whom 358 were enrolled (mean age 83 years, Society of Thoracic Surgeons Predicted Risk of Mortality 11·7%, 54% female). 179 were assigned to TAVR treatment and 179 were assigned to standard treatment. 20 patients crossed over from the standard treatment group and ten withdrew from study, leaving only six patients at 5 years, of whom five had aortic valve replacement treatment outside of the study. The risk of all-cause mortality at 5 years was 71·8% in the TAVR group versus 93·6% in the standard treatment group (hazard ratio 0·50, 95% CI 0·39-0·65; p<0·0001). At 5 years, 42 (86%) of 49 survivors in the TAVR group had New York Heart Association class 1 or 2 symptoms compared with three (60%) of five in the standard treatment group. Echocardiography after TAVR showed durable haemodynamic benefit (aortic valve area 1·52 cm(2) at 5 years, mean gradient 10·6 mm Hg at 5 years), with no evidence of structural valve deterioration., Interpretation: TAVR is more beneficial than standard treatment for treatment of inoperable aortic stenosis. TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement to improve their survival and functional status. Appropriate selection of patients will help to maximise the benefit of TAVR and reduce mortality from severe comorbidities., Funding: Edwards Lifesciences., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The higher risk of adverse outcomes after transapical (TA) versus transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be attributable to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity score matching., Methods and Results: From April 2007 to February 2012, 1100 Placement of Aortic Transcatheter Valves (PARTNER)-I patients underwent TA-TAVR and 1521 underwent TF-TAVR with Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 preprocedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 versus 8 days; P<0.0001), and slower recovery (New York Heart Association class I, 31% versus 38% at 30 days, equalizing by 6 months at 51% versus 47%); stroke risk was similar (3.4% versus 3.3% at 30 days and 6.0% versus 6.7% at 3 years); mortality was elevated for the first 6 postprocedural months (19% versus 12%; P=0.01); but aortic regurgitation was less (34% versus 52% mild and 8.9% versus 12% moderate to severe at discharge, P=0.001; 36% versus 50% mild and 10% versus 15% moderate to severe at 6 months, P<0.0001)., Conclusions: The likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation is less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894., (© 2015 American Heart Association, Inc.)

Background: We aimed to determine the incidence, predictors, clinical characteristics, management, and outcomes of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI)., Methods and Results: This multicenter registry included 53 patients (mean age, 79±8 years; men, 57%) who suffered IE after TAVI of 7944 patients after a mean follow-up of 1.1±1.2 years (incidence, 0.67%, 0.50% within the first year after TAVI). Mean time from TAVI was 6 months (interquartile range, 1-14 months). Orotracheal intubation (hazard ratio, 3.87; 95% confidence interval, 1.55-9.64; P=0.004) and the self-expandable CoreValve system (hazard ratio, 3.12; 95% confidence interval, 1.37-7.14; P=0.007) were associated with IE (multivariate analysis including 3067 patients with individual data). The most frequent causal microorganisms were coagulase-negative staphylococci (24%), followed by Staphylococcus aureus (21%) and enterococci (21%). Vegetations were present in 77% of patients (transcatheter valve leaflets, 39%; stent frame, 17%; mitral valve, 21%). At least 1 complication of IE occurred in 87% of patients (heart failure in 68%). However, only 11% of patients underwent valve intervention (valve explantation and valve-in-valve procedure in 4 and 2 patients, respectively). The mortality rate in hospital was 47.2% and increased to 66% at the 1-year follow-up. IE complications such as heart failure (P=0.037) and septic shock (P=0.002) were associated with increased in-hospital mortality., Conclusions: The incidence of IE at 1 year after TAVI was 0.50%, and the risk increased with the use of orotracheal intubation and a self-expandable valve system. Staphylococci and enterococci were the most common agents. Although most patients presented at least 1 complication of IE, valve intervention was performed in a minority of patients, and nearly half of the patients died during the hospitalization period., (© 2015 American Heart Association, Inc.)

Percutaneous left atrial appendage (LAA) occlusion has emerged as an exciting and effective modality for stroke prophylaxis in patients with non-valvular atrial fibrillation who are deemed too high risk for anticoagulation with warfarin or newer anticoagulants. The Amplatzer devices have been used in LAA occlusion for more than a decade, starting with off label use of an atrial septal occluder device for LAA occlusion. This was followed by introduction of a dedicated Amplatzer cardiac plug (ACP) 1 for LAA occlusion, and more recently, the second generation Amulet device, with reported better stability enhancing features, has been introduced. Both these devices are widely used outside the United States, however in the US only the WATCHMAN device has been FDA approved. Unlike the WATCHMAN device, where the evidence is continuously building as the data from two pivotal randomized controlled trials are emerging, most of the evidence for ACP devices is from pooled multicenter registry data. In this article, we review the device design, implantation techniques and the most recently published evidence for both the Amplatzer cardiac plug 1 and the newer Amulet device. Our goal is to summarize the most recent literature and discuss the current role of the Amplatzer devices in the exciting and rapidly growing field of percutaneous LAA occlusion.

Background: Statins can regress coronary atheroma and lower clinical events. Although pre-clinical studies suggest procalcific effects of statins in vitro, it remains unclear if statins can modulate coronary atheroma calcification in vivo., Objectives: This study compared changes in coronary atheroma volume and calcium indices (CaI) in patients receiving high-intensity statin therapy (HIST), low-intensity statin therapy (LIST), and no-statin therapy., Methods: In a post-hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound, serial changes in coronary percent atheroma volume (PAV) and CaI were measured across matched coronary segments in patients with coronary artery disease., Results: Following propensity-weighted adjustment for differences in baseline and changes in clinical, laboratory, and ultrasonic characteristics, HIST (n = 1,545) associated with PAV regression from baseline (-0.6 ± 0.1%; p < 0.001), whereas both LIST (n = 1,726) and no-statin therapy (n = 224) associated with PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%; p < 0.001, respectively; p < 0.001 for both HIST vs. LIST and HIST vs. no-statin; p = 0.35 for LIST vs. no-statin). Significant increases in CaI from baseline were noted across all groups (median [interquartile range] HIST, +0.044 [0.0-0.12]; LIST, +0.038 [0.0-0.11]; no-statin, +0.020 [0.0-0.10]; p < 0.001 for all), which could relate to statin intensity (p = 0.03 for LIST vs. no-statin; p = 0.007 for HIST vs. no-statin; p = 0.18 for HIST vs. LIST). No correlations were found between changes in CaI and on-treatment levels of atherogenic and antiatherogenic lipoproteins, and C-reactive protein, in either of the HIST groups or the no-statin group., Conclusions: Independent of their plaque-regressive effects, statins promote coronary atheroma calcification. These findings provide insight as to how statins may stabilize plaque beyond their effects on plaque regression., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized., Methods and Results: Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively (P<0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality (P<0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50-6.82; P=0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02-2.52; P=0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity (P=0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation., Conclusions: In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01314313., (© 2015 American Heart Association, Inc.)

The MitraClip is an US Food and Drug Administration-approved device for inoperable patients with severe degenerative mitral regurgitation (MR) and is under investigation for use in patients with severe functional MR. Simultaneously grasping both leaflets of the mitral valve can be technically challenging, however, in patients with a restricted posterior leaflet. We present one such case in which a pigtail catheter, placed retrograde into the left ventricle, was able to push the ventricular surface of the posterior leaflet into closer approximation with the anterior leaflet, and facilitate successful clip placement. We provide this report in hopes that it will provide a useful strategy for interventionalists faced with this challenging situation., (© 2014 Wiley Periodicals, Inc.)

Objective: Lowering low-density lipoprotein cholesterol (LDL-C) with statins has been demonstrated to slow plaque progression. This antiatherosclerotic effect in patients with minimal LDL-C lowering has not been investigated., Approach and Results: Six hundred forty-seven patients with angiographic coronary artery disease who were commenced on statin therapy underwent serial imaging with intravascular ultrasound. Responders were defined as a percentage reduction in LDL-C of <15%. Disease progression was compared in responders (n=517) and hyporesponders (n=130) to statin therapy. Twenty percentage of patients demonstrated minimal changes in LDL-C, despite commencement of statin therapy. Statin hyporesponders were younger (55 versus 57 years; P=0.01), more likely to be male (79% versus 66%; P=0.005), and obese (body mass index, 31.5 ± 6.1 versus 30.3 ± 5.9 kg/m(2); P=0.04) and less likely to have a history of dyslipidemia (50% versus 66%; P<0.001). Baseline levels of systolic blood pressure (127 ± 15 versus 132 ± 17 mm Hg; P=0.01) and LDL-C (2.5 ± 0.6 versus 3.4 ± 0.8 mmol/L; P<0.001) were lower in statin hyporesponders. Baseline percent atheroma volume was similar between statin hyporesponders and responders (36.9 ± 9.8% versus 38.3 ± 9.2%; P=0.13). On serial evaluation, greater progression of percent atheroma volume (1.19 ± 0.48% versus 0.09 ± 0.43%; P=0.003) was observed in statin hyporesponders. After adjusting for baseline clinical characteristics and measures of plaque burden, statin hyporesponders still exhibited greater atheroma progression (+0.83 ± 0.58% versus -0.21 ± 0.52%; P=0.006)., Conclusions: A substantial proportion of patients with coronary artery disease fail to achieve effective reductions in LDL-C, despite prescription of statin therapy. Greater progression of atherosclerosis is observed in these patients. Our current study underscores monitoring LDL-C level after the commencement of statin to ensure adequate response to statin therapy., (© 2015 American Heart Association, Inc.)

Importance: Introducing new medical devices into routine practice raises concerns because patients and outcomes may differ from those in randomized trials., Objective: To update the previous report of 30-day outcomes and present 1-year outcomes following transcatheter aortic valve replacement (TAVR) in the United States., Design, Setting, and Participants: Data from the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapies Registry were linked with patient-specific Centers for Medicare & Medicaid Services (CMS) administrative claims data. At 299 US hospitals, 12 182 patients linked with CMS data underwent TAVR procedures performed from November 2011 through June 30, 2013, and the end of the follow-up period was June 30, 2014., Exposure: Transcatheter aortic valve replacement., Main Outcomes and Measures: One-year outcomes including mortality, stroke, and rehospitalization were evaluated using multivariate modeling., Results: The median age of patients was 84 years and 52% were women, with a median STS Predicted Risk of Operative Mortality (STS PROM) score of 7.1%. Following the TAVR procedure, 59.8% were discharged to home and the 30-day mortality was 7.0% (95% CI, 6.5%-7.4%) (n = 847 deaths). In the first year after TAVR, patients were alive and out of the hospital for a median of 353 days (interquartile range, 312-359 days); 24.4% (n = 2074) of survivors were rehospitalized once and 12.5% (n = 1525) were rehospitalized twice. By 1 year, the overall mortality rate was 23.7% (95% CI, 22.8%-24.5%) (n = 2450 deaths), the stroke rate was 4.1% (95% CI, 3.7%-4.5%) (n = 455 stroke events), and the rate of the composite outcome of mortality and stroke was 26.0% (25.1%-26.8%) (n = 2719 events). Characteristics significantly associated with 1-year mortality included advanced age (hazard ratio [HR] for ≥95 vs <75 years, 1.61 [95% CI, 1.24-2.09]; HR for 85-94 years vs <75 years, 1.35 [95% CI, 1.18-1.55]; and HR for 75-84 years vs <75 years, 1.23 [95% CI, 1.08-1.41]), male sex (HR, 1.21; 95% CI, 1.12-1.31), end-stage renal disease (HR, 1.66; 95% CI, 1.41-1.95), severe chronic obstructive pulmonary disease (HR, 1.39; 95% CI, 1.25-1.55), nontransfemoral access (HR, 1.37; 95% CI, 1.27-1.48), STS PROM score greater than 15% vs less than 8% (HR, 1.82; 95% CI, 1.60-2.06), and preoperative atrial fibrillation/flutter (HR, 1.37; 95% CI, 1.27-1.48). Compared with men, women had a higher risk of stroke (HR, 1.40; 95% CI, 1.15-1.71)., Conclusions and Relevance: Among patients undergoing TAVR in US clinical practice, at 1-year follow-up, overall mortality was 23.7%, the stroke rate was 4.1%, and the rate of the composite outcome of death and stroke was 26.0%. These findings should be helpful in discussions with patients undergoing TAVR.

Transcatheter aortic valve replacement (TAVR) using a balloon-expandable valve is an accepted alternative to surgical replacement for severe, symptomatic aortic stenosis in high risk or inoperable patients. Intraprocedural transesophageal echocardiography (TEE) offers real-time imaging guidance throughout the procedure and allows for rapid and accurate assessment of complications and procedural results. The value of intraprocedural TEE for TAVR will likely increase in the future as this procedure is performed in lower surgical risk patients, who also have lower risk for general anesthesia, but a greater expectation of optimal results with lower morbidity and mortality. This imaging compendium from the PARTNER (Placement of Aortic Transcatheter Valves) trials is intended to be a comprehensive compilation of intraprocedural complications imaged by intraprocedural TEE and diagnostic tools to anticipate and/or prevent their occurrence., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)