Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke. METHODS: We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR. RESULTS: A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site. CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

Does study subject diversity influence cardiology research site performance?: Insights from 2 U.S. National Coronary Stent Registries.

BACKGROUND: Minorities and women are underrepresented in cardiovascular research. Whether their higher enrollment can be predicted or influences research site performance is unclear. METHODS: We evaluated 104 sites that enrolled 4,184 patients in the U.S. Platinum Diversity (PD) and Promus Element Plus (PE Plus) studies (2012 to 2016). Research sites were ranked from lowest to highest minority and female enrollment, respectively. United States Census Bureau division and core-based statistical area (CBSA) populations were determined for each site and the following study performance metrics compared across quartiles of minority and female enrollment, respectively: (1) study subject enrollment rate (SER), (2) time to first patient enrolled, (3) rate of follow-up visits not done, (4) rate of follow-up visits out of window, and (5) protocol deviation rate (PDR). Multivariable regression was used to predict SER and PDR. RESULTS: Minority enrollment varied by region (P = .025) and population (P = .024) with highest recruitment noted in the Pacific, West South Central, South Atlantic, Mid-Atlantic and East North Central divisions. Female enrollment bore no relationship to region (P = .67) or population (P = .40). Median SER was similar in sites withi the highest vs lowest quartile of minority enrollment (SER of 4 vs 5 patients per month, respectively, P =0.78) and highest vs. lowest female enrollment (SER of 4 vs 4, respectively, P = .21). Median PDR was lower in sites within the highest vs lowest minority enrollment (0.23 vs 0.50 PDs per patient per month, respectively, P = .01) and highest vs. lowest female enrollment (0.28 vs. 0.37 PDs per patient per month, respectively, P = .04). However, this relationship did not persist after multivariable adjustment. All other site performance metrics were comparable across quartiles of minority and female enrollment. CONCLUSIONS: Minority, but not female enrollment, correlated with research site geographic region and surrounding population. High enrollment of minorities and women did not influence study performance metrics. These findings help inform future strategies aimed at increasing clinical trial diversity. TRIAL REGISTRATION: The PD and PE Plus studies are registered at www.clinicaltrials.gov under identifiers NCT02240810 and NCT01589978, respectively. KEY POINTS: Question: Does the enrollment of more Blacks, Hispanics and women in US cardiovascular research studies influence the overall rate of study subject enrollment and/or other key study site performance metrics and can diverse enrollment be predicted? FINDINGS: In this pooled analysis of 104 sites that enrolled 4,184 patients in the Platinum Diversity and Promus Element Plus Post-Approval Studies, we found that the enrollment of higher proportions of underrepresented minorities and women was univariately associated with lower protocol deviation rates while having no effect on other site performance metrics. A site's geographic location and surrounding population predicted minority, but not female enrollment. Meaning: These findings suggest that cardiovascular research subject diversity may be predicted from site characteristics and enhanced without compromising key study performance metrics. These insights help inform future strategies aimed at improving clinical trial diversity.

Insights on Embolic Protection, Repositioning, and Stroke: A Subanalysis of the RESPOND Study.

RESPOND is a prospective, single-arm study enrolling 1014 transcatheter aortic valve replacement (TAVR) patients. The objective of this analysis is to assess the impact of cerebral embolic protection (CEP) devices and prosthetic valve repositioning on the risk of neurologic complications in patients treated with the fully repositionable Lotus Valve in the RESPOND postmarket study. Valve repositioning and CEP use were at the operators' discretion. Stroke events were adjudicated by an independent medical reviewer. This analysis assessed the baseline differences among patients according to CEP use and valve repositioning and evaluated the neurological complications at 72 hours after TAVR, hospital discharge, and 30-day follow-up. A multivariate analysis was performed to identify the potential predictors of stroke. Of the 996 patients implanted with the Lotus Valve (mean age: 80.8 years, 50.8% female, STS score 6.0 ± 6.9), 92 cases (9.2%) used CEP. The overall rate of acute stroke/transient ischemic attack (TIA) was 3.0% at 72 hours after TAVR. The 72-hour stroke/TIA rate was 1.1% in patients who had CEP and 3.2% in those who did not. Use of CEP was associated with a 2.1% absolute reduction in the risk of acute neurological events (relative risk reduction: 65.6%), although the difference was not statistically significant (p=0.51). Repositioning of the Lotus Valve occurred in 313/996 procedures (31.4%). The 72-hour rate of stroke/TIA was similar in patients who had valve repositioning (2.9%) compared with those who did not (3.1%; p=0.86). The selective use of a CEP device in the RESPOND study was associated with a nonsignificantly lower risk for stroke within 72 hours. The use of the repositioning feature of the Lotus Valve did not increase the stroke risk.

Quantitative and Qualitative Coronary Plaque Assessment Using Computed Tomography Coronary Angiography: A Comparison With Intravascular Ultrasound.

BACKGROUND: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. METHODS: Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. RESULTS: There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm3, bias of -0.06mm3) and per vessel (3.1mm3 ± -2.85mm3, p=0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3±0.09mm3, p<0.001; 95% LoA -6.78 to 2.25mm3, bias of -2.2mm3) and per vessel (33.04±10.3 mm3, p<0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. CONCLUSION: Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.

Hemodynamic and Echocardiographic Comparison of the Lotus and CoreValve Transcatheter Aortic Valves in Patients With High and Extreme Surgical Risk: An Analysis From the REPRISE III Randomized Controlled Trial.

BACKGROUND: Comparative echocardiographic data on transcatheter aortic valve replacement systems from randomized trials are limited. The REPRISE III trial (Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System - Randomized Clinical Evaluation) is a multicenter, randomized comparison of a mechanically expanded (Lotus) versus self-expanding (CoreValve) transcatheter aortic valve replacement device. This analysis rigorously assesses Doppler-derived valve hemodynamics and the impact on outcomes at 1 year in patients with extreme/high surgical risk treated with Lotus and CoreValve from REPRISE III. METHODS: REPRISE III includes patients with extreme- and high-risk aortic stenosis. Patients were enrolled at 55 centers. All transthoracic echocardiograms with Doppler were obtained following a standard protocol up to 12 months postimplant and analyzed by a core laboratory. Valve size, mean gradient, aortic valve area, and Doppler velocity index and their impact on clinical outcomes are reported. Additional parameters including paravalvular leak were evaluated using a multiparametric approach. RESULTS: A total of 912 patients were randomly assigned (2:1 ratio; 607 Lotus:305 CoreValve). Median age was 84 years, 51% of the patients were women, and the Society of Thoracic Surgeons score was 6.8±4.1. CoreValve demonstrated lower gradients and larger aortic valve area and Doppler velocity index than Lotus at discharge; the difference decreased in subsequent follow-up up to a year (all P<0.01). Lotus had lower rates of paravalvular leak that persisted over time (P<0.05). Similar outcomes were seen when comparing each valve type by size group (small, medium, large). The hemodynamic differences between valves did not translate into worse clinical outcomes. All-cause mortality was not different between the 2 groups in any of the 3 valve sizes. When comparing patients with normal valve gradients (<20 mm Hg, n=780) with those with abnormal gradients (>20 mm Hg, n=48) in the entire patient population, all-cause mortality was not different. This was also not significant when evaluating each valve type separately. Similarly, there were no differences for aortic valve area >1.1 cm2 or <1.1 cm2 and for Doppler velocity index >0.35 or <0.35 (all P=not significant). CONCLUSIONS: Lotus had significantly greater freedom from moderate or severe paravalvular leak and smaller valve area and higher gradients than CoreValve. The hemodynamic differences were not associated with any clinical differences in the composite end point of mortality, disabling stroke, and moderate paravalvular leak or with quality of life at 1 year of follow-up. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02202434.

Clinical outcomes in unselected patients treated with the PROMUS Element platinum-chromium, everolimus-eluting stent: Final five-year results from the PE PROVE Study.

OBJECTIVES: The goal of this analysis was to evaluate the final 5-year safety and effectiveness of the PROMUS Element platinum-chromium everolimus-eluting stent in unselected patients treated in routine clinical practice. BACKGROUND: The prospective, open-label PROMUS Element™ European Post-Approval Surveillance Study (PE-PROVE) enrolled 1,010 "real-world" patients who received the PROMUS Element stent. Adverse event rates were low at 1-year, and the incidence of stent thrombosis was 0.6%. METHODS: The primary endpoint was target vessel failure (TVF; overall and PE stent-related), a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel revascularization (TVR) at 1-year post-implantation. Five-year clinical outcomes were evaluated in overall as well as high-risk patient subgroups. RESULTS: The overall 5-year TVF rate was 14.9%, with 7.0% being related to the study stent. Cardiac death, MI and TVR related to the study stent occurred in 0.5%, 3.2%, and 5.7%, respectively. Stent thrombosis through 5-year follow-up was 1.0%. The rates of overall and study stent related TVF were numerically higher in patients with medically treated diabetes, long lesions (≥28 mm), and small diameter vessels (≤2.5 mm) compared to the overall study population. Additionally, favorable stent thrombosis rates through 5 years were reported for the PROMUS Element stent in these high-risk subgroups. CONCLUSIONS: The final 5-year data from the PE-PROVE study demonstrate favorable outcomes and low rates of adverse events with the PE stent when used in "real-world" patients with coronary artery disease.

Clinical outcomes of the Lotus Valve in patients with bicuspid aortic valve stenosis: An analysis from the RESPOND study.

AIMS: Patients with bicuspid valves represent a challenging anatomical subgroup for transcatheter aortic valve implantation (TAVI). This analysis evaluated the clinical outcomes of the fully repositionable and retrievable Lotus Valve System in patients with bicuspid aortic valves enrolled in the RESPOND post-market registry. METHODS AND RESULTS: The prospective, open-label RESPOND study enrolled 1,014 patients at 41 centers in Europe, New Zealand, and Latin America, 31 (3.1%) of whom had bicuspid aortic valves. The mean age in the bicuspid patient cohort was 76.4 years, 64.5% were male, and the baseline STS score was 6.0 ± 10.2. Procedural success was 100%, with no cases of malpositioning, valve migration, embolization, or valve-in-valve. Repositioning was attempted in 10 cases (32.3%). There was one death (3.2%) and one stroke (3.2%) at 30-day follow-up. Mean AV gradient was reduced from 48.7 ± 17.0 mmHg at baseline to 11.8 ± 5.1 mmHg at hospital discharge (P < 0.001); mean effective orifice area (EOA) was increased from 0.6 ± 0.2 cm2 to 1.7 ± 0.4 cm2 (P < 0.001). There were no cases of moderate or severe paravalvular leak (PVL) adjudicated by the core laboratory; four subjects (13.8%) had mild PVL, 5 (17.2%) had trace PVL. The rate of pacemaker (PM) implantation for PM-naïve patients was 22.2% (6/27). CONCLUSIONS: Data from the RESPOND registry demonstrate good clinical and echocardiographic outcomes up to 1 year postimplantation in patients with bicuspid aortic valves using the repositionable Lotus Valve.

Small-vessel PCI outcomes in men, women, and minorities following platinum chromium everolimus-eluting stents: Insights from the pooled PLATINUM Diversity and PROMUS Element Plus Post-Approval studies.

OBJECTIVE: We evaluated 1-year outcomes after platinum chromium everolimus-eluting stents (PtCr-EES) in small versus non-small coronary arteries within a large, diverse sample of men, women, and minorities. BACKGROUND: There exists limited outcomes data on the use of second-generation drug-eluting stent to treat small diameter coronary arteries. METHODS: We pooled patients from the PLATINUM Diversity and PROMUS Element Plus stent registries. Small-vessel percutaneous coronary intervention (SV-PCI) was defined as ≥1 target lesion with reference vessel diameter (RVD) ≤2.5 mm. Endpoints included major adverse cardiac event (MACE; death, myocardial infarction [MI] or target vessel revascularization [TVR]), target vessel failure (TVF; death related to the target vessel, target vessel MI or TVR) and definite/probable stent thrombosis (ST). Multivariable Cox regression was used to risk-adjust outcomes. RESULTS: We included 4,155/4,182 (99%) patients with available RVD, of which 1,607 (39%) underwent small-vessel PCI. SV-PCI was not associated with increased MACE (adjHR 1.02; 95%CI 0.81-1.30) or TVF (adjHR 1.07; 95%CI 0.82-1.39). MI risk was lower in white men compared to women and minorities, both in the setting of SV-PCI (adjHR 0.41; 95%CI 0.23-0.74 and adjHR 0.39; 95%CI 0.20-0.75, respectively) and for non-SV-PCI (adjHR 0.61; 95%CI 0.38-0.99 and adjHR 0.45; 95%CI 0.27-0.74, respectively). There was no significant interaction between RVD and sex or minority status for any endpoint. CONCLUSION: In a large diverse contemporary PCI outcomes database, SV-PCI with PtCr-EES was not associated with increased MACE or TVR and did not account for the increased MI risk noted in women and minorities compared to white men.

Comparison of Magnetic Resonance Analysis of Myocardial Scarring With Biomarker Release Following S-T Elevation Myocardial Infarction.

BACKGROUND: Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) is commonly assumed to represent myocardial fibrosis; however, comparative human histological data are limited, and there is no consensus on the most accurate method for LGE quantitation. We evaluated the relationship between CMR assessment of regional fibrosis and infarct size assessment using serial biomarkers after ST elevation acute myocardial infarction (STEMI). METHODS: Ninety-three patients treated for STEMI (59±10 years, 86% male) underwent CMR 6 months after infarction. Infarct size was quantified by CMR-LGE using manual and range of semi-automated thresholds (range: 2-10 standard deviations [SD]) above reference myocardium and the full width-half maximum (FWHM) technique, and compared with the rise in serum biomarkers. The agreement between CMR and biomarker in the identification of large infarcts based on peak troponin (TnI) levels was also analysed. RESULTS: Quantification methods had a strong influence on the infarct size assessment with CMR-LGE. Significant correlations were observed between LGE and biomarkers across all of the signal intensity thresholds. Whilst there was a wide variation with respect to the estimation of total LGE size (from 6.8±7.7 to 32.1±11.3 grams), the variation in the correlation with peak troponin level was much smaller (r-values ranging from 0.670 to 0.876). There was good agreement between CMR-LGE and biomarker assessment of infarct size; the best agreement between CMR-LGE and large infarction using a threshold of 8SD for peak TnI>50ng/mL (Cohen's kappa (κ)=0.722), and a threshold of 4SD for peak TnI >95ng/mL (κ=0.761). CONCLUSIONS: The correlation between CMR-LGE quantification of infarct size and biomarker release following STEMI at a range of semi-automated thresholds was consistently strong, with good agreement between measures across a range of thresholds.

Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk.

BACKGROUND: Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month. METHODS: In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual antiplatelet therapy. The primary safety end point, tested for both noninferiority and superiority, was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target-lesion revascularization. RESULTS: We enrolled 2466 patients. At 390 days, the primary safety end point had occurred in 112 patients (9.4%) in the drug-coated-stent group and in 154 patients (12.9%) in the bare-metal-stent group (risk difference, -3.6 percentage points; 95% confidence interval [CI], -6.1 to -1.0; hazard ratio, 0.71; 95% CI, 0.56 to 0.91; P<0.001 for noninferiority and P=0.005 for superiority). During the same time period, clinically driven target-lesion revascularization was needed in 59 patients (5.1%) in the drug-coated-stent group and in 113 patients (9.8%) in the bare-metal-stent group (risk difference, -4.8 percentage points; 95% CI, -6.9 to -2.6; hazard ratio, 0.50; 95% CI, 0.37 to 0.69; P<0.001). CONCLUSIONS: Among patients at high risk for bleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet therapy. (Funded by Biosensors Europe; LEADERS FREE ClinicalTrials.gov number, NCT01623180.).

Rationale and design of the EVOLVE Short DAPT Study to assess 3-month dual antiplatelet therapy in subjects at high risk for bleeding undergoing percutaneous coronary intervention.

BACKGROUND: While extended dual antiplatelet therapy (DAPT) with aspirin and a platelet (P2Y12) inhibitor after percutaneous coronary intervention (PCI) reduces the risk of stent thrombosis (ST) and myocardial infarction (MI), it also increases bleeding. Newer generation drug-eluting stents with bioabsorbable polymer coatings may reduce thrombotic events and allow abbreviated DAPT in selected patients. The EVOLVE Short DAPT study is designed to evaluate the safety of 3-month DAPT in high bleeding risk subjects treated with the SYNERGY bioabsorbable polymer everolimus-eluting stent. TRIAL DESIGN: EVOLVE Short DAPT is a prospective, single-arm, international study that enrolled 2009 high risk bleeding subjects (defined as age ≥75 years, chronic anticoagulation, major bleeding within 12 months, history of stroke, renal insufficiency/failure, or thrombocytopenia) who underwent PCI with the SYNERGY stent. Subjects presenting with acute MI or complex lesions were excluded. After 3 months treatment with DAPT (except those on anticoagulant in whom aspirin is optional), subjects free from stroke, MI, revascularization or ST will be eligible to discontinue P2Y12 inhibitor, but continue aspirin. Co-primary endpoints assessed between 3-15 months are: i) death/MI compared for non-inferiority with propensity-adjusted historical group receiving 12-month DAPT, and ii) definite/probable ST compared to a performance goal. The secondary endpoint is the rate of bleeding in subjects not receiving chronic anticoagulation compared for superiority against a propensity-adjusted historical control. CONCLUSION: The EVOLVE Short DAPT study will prospectively define the safety of DAPT discontinuation at 3 months in high bleeding risk patients treated with the SYNERGY stent.

Effect of aorto-ventricular angulation on procedural success in transcatheter aortic valve replacements with the Lotus Valve system.

OBJECTIVE: To determine the effect of aorto-ventricular angulation (AA) on procedural success with the Lotus Valve system. BACKGROUND: AA, the angulation of the aortic valve basal plane, may affect the deployment of transcatheter aortic valve replacements (TAVRs). The Lotus Valve system is fully repositionable and delivered on a pre-shaped catheter which may alter the impact of AA on its deployment. The effect of AA on procedural and clinical outcomes with the Lotus valve is unreported. METHODS: Consecutive patients who underwent transfemoral TAVR with the Lotus Valve system were analyzed. AA was determined on pre-procedural multi-detector computed tomography imaging. Device success, procedural characteristics, and clinical events were assessed according to Valve Academic Research Consortium-2 (VARC2) definitions. RESULTS: One hundred sixty-five patients were analyzed (48% male, mean age 84 years). The mean AA was 47.8 degrees. Patients were, therefore, divided into low AA (AA < 48°) or high AA (AA ≥ 48°). Baseline characteristics were similar in both cohorts. Device success and procedural outcomes were also similar including procedure time, contrast dose, and need to reposition. There was no difference in degree of moderate or greater para-valvular regurgitation (PVR) (0% vs. 3%, P = 0.09). Clinical outcomes of death, stroke, myocardial infarction, and other major VARC2 endpoints were similar. CONCLUSION: AA did not affect device success or clinical outcome with the Lotus Valve system. The Lotus' unique design features may have mitigated the impact of AA by improving the accuracy, ease of valve positioning, and reducing PVR.

Impact of a public awareness campaign on out-of-hospital cardiac arrest incidence and mortality rates.

AIMS: Increased public awareness of the warning signs of a heart attack and the importance of early medical intervention may help to prevent premature deaths from out-of-hospital cardiac arrest (OHCA). We sought to investigate the impact of the Heart Foundation's public awareness campaigns on the monthly incidence of, and deaths from, OHCA in Melbourne, Australia. METHODS AND RESULTS: Between July 2005 and June 2015, we included registry data for 25 060 OHCA of presumed cardiac aetiology. Time series models with distributed lags were used to explore the effect of campaign activity on OHCA outcomes. A sensitivity analysis involving segmented regression of the pre-intervention, intervention, and post-intervention time segments was also performed. The mean monthly incidence of, and deaths from, OHCA was 207 and 189 events respectively. After adjustment for temporal trends, campaign activity was associated with a 6.0% [95% confidence interval (CI): 2.8-9.0%; P < 0.001] reduction in the monthly incidence of OHCA, or 11.7% (95% CI: 7.7-15.5%, P < 0.001) with the addition of residual effects in two additional lag months. Similarly, the rate of deaths from OHCA reduced by 6.4% (95% CI: 2.8-10.0%; P = 0.001) during months with campaign activity. Campaign activity had a greater effect in males and patients aged ≥65 years, and reduced the incidence of OHCA in unwitnessed and initial non-shockable arrests. In the segmented regression analysis, the intervention period was associated with a 15.2% (95% CI: 9.2-20.9%; P < 0.001) reduction in the mean monthly incidence and a 16.6% (95% CI: 9.9-22.7%; P < 0.001) reduction in deaths from OHCA. CONCLUSION: A comprehensive mass media campaign targeting the community's awareness of heart attack symptoms was associated with a substantial reduction in the incidence of OHCA and associated deaths.

Effect of Mechanically Expanded vs Self-Expanding Transcatheter Aortic Valve Replacement on Mortality and Major Adverse Clinical Events in High-Risk Patients With Aortic Stenosis: The REPRISE III Randomized Clinical Trial.

Importance: Transcatheter aortic valve replacement (TAVR) is established for selected patients with severe aortic stenosis. However, limitations such as suboptimal deployment, conduction disturbances, and paravalvular leak occur. Objective: To evaluate if a mechanically expanded valve (MEV) is noninferior to an approved self-expanding valve (SEV) in high-risk patients with aortic stenosis undergoing TAVR. Design, Setting, and Participants: The REPRISE III trial was conducted in 912 patients with high or extreme risk and severe, symptomatic aortic stenosis at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015, with final follow-up on March 8, 2017. Interventions: Participants were randomized in a 2:1 ratio to receive either an MEV (n = 607) or an SEV (n = 305). Main Outcomes and Measures: The primary safety end point was the 30-day composite of all-cause mortality, stroke, life-threatening or major bleeding, stage 2/3 acute kidney injury, and major vascular complications tested for noninferiority (margin, 10.5%). The primary effectiveness end point was the 1-year composite of all-cause mortality, disabling stroke, and moderate or greater paravalvular leak tested for noninferiority (margin, 9.5%). If noninferiority criteria were met, the secondary end point of 1-year moderate or greater paravalvular leak was tested for superiority in the full analysis data set. Results: Among 912 randomized patients (mean age, 82.8 [SD, 7.3] years; 463 [51%] women; predicted risk of mortality, 6.8%), 874 (96%) were evaluable at 1 year. The primary safety composite end point at 30 days occurred in 20.3% of MEV patients and 17.2% of SEV patients (difference, 3.1%; Farrington-Manning 97.5% CI, -∞ to 8.3%; P = .003 for noninferiority). At 1 year, the primary effectiveness composite end point occurred in 15.4% with the MEV and 25.5% with the SEV (difference, -10.1%; Farrington-Manning 97.5% CI, -∞ to -4.4%; P<.001 for noninferiority). The 1-year rates of moderate or severe paravalvular leak were 0.9% for the MEV and 6.8% for the SEV (difference, -6.1%; 95% CI, -9.6% to -2.6%; P < .001). The superiority analysis for primary effectiveness was statistically significant (difference, -10.2%; 95% CI, -16.3% to -4.0%; P < .001). The MEV had higher rates of new pacemaker implants (35.5% vs 19.6%; P < .001) and valve thrombosis (1.5% vs 0%) but lower rates of repeat procedures (0.2% vs 2.0%), valve-in-valve deployments (0% vs 3.7%), and valve malpositioning (0% vs 2.7%). Conclusions and Relevance: Among high-risk patients with aortic stenosis, use of the MEV compared with the SEV did not result in inferior outcomes for the primary safety end point or the primary effectiveness end point. These findings suggest that the MEV may be a useful addition for TAVR in high-risk patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02202434.

Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: A 16-Year Australian Single Centre Experience.

BACKGROUND: Alcohol septal ablation (ASA), is a well-established treatment for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). We report the acute, short and long-term clinical and echocardiographic outcomes of our experience in a single Australian centre over 16 years. METHODS: We retrospectively analysed consecutive patients presenting to our centre for ASA between March 2000 and July 2016. Local databases were interrogated along with direct patient or physician contact occurred where required. RESULTS: Alcohol septal ablation was performed in 80 patients with symptomatic, medication refractory HOCM (mean age 61±15 years; range 22-84 years; 50% male). All patients had transthoracic echocardiography prior to the procedure, within 48hours of the procedure, 6 weeks, 6 months, 1 year and yearly thereafter to a median follow-up of 80±40months. At baseline, mean resting and provoked LVOT gradients were 80±49mmHg and 97±40mmHg respectively. Compared with baseline, ASA led to a reduction in resting LVOT gradients at all time points, particularly at 2 days-52±41mmHg, p<0.001; 12 months-29±34mmHg, p<0.001; and last follow-up 12±21mmHg, p<0.001. Provoked LVOT gradients were also reduced at 2 days-64±44mmHg and last follow-up of 19±29mmHg, p<0.001. Compared to baseline (19.8±4.2mm), ASA was associated with a reduction in interventricular septal (IVS) thickness at all time intervals with last echocardiographic follow-up at 80 months being 16.0±4.9mm, (

Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study.

BACKGROUND: Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis. METHODS AND RESULTS: After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%, P<0.001), increased death (2.5% versus 1.4%, P<0.001), and MI (4.2% versus 2.6%, P<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%, P=0.06, and rates of MI were 3.5% versus 4.8%, P=0.058; and among patients without DM the rates were 0.4% versus 1.4%, P<0.001 (stent thrombosis, P interaction=0.21) and 1.6% versus 3.6%, P<0.001 (MI, P interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction P=0.61). CONCLUSIONS: In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.

Incidence and predictors of permanent pacemaker implantation following treatment with the repositionable Lotus™ transcatheter aortic valve.

OBJECTIVES: To determine the incidence and predictors of permanent pacemaker (PPM) requirement following transcatheter aortic valve replacement (TAVR) with the mechanically expanded LotusTM Valve System (Boston Scientific). BACKGROUND: Pacemaker implantation is the most common complication following TAVR. Predictors of pacing following TAVR with the Lotus valve have not been systematically assessed. METHODS: Consecutive patients with severe aortic stenosis who underwent Lotus valve implantation were prospectively recruited at a single-centre. Patients with a pre-existing PPM were excluded. Baseline ECG, echocardiographic and multiple detector computed tomography as well as procedural telemetry and depth of implantation were independently analyzed in a blinded manner. The primary endpoint was 30-day incidence of pacemaker requirement (PPM implantation or death while pacing-dependent). Multivariate analysis was performed to identify independent predictors of the primary endpoint. RESULTS: A total of 104 consecutive patients underwent TAVR with the Lotus valve with 9/104 (9%) with a pre-existing PPM excluded. New or worsened procedural LBBB occurred in 78%. Thirty-day incidence of the primary pacing endpoint was 28%. The most common indication for PPM implantation was complete heart block (CHB) (69%). Independent predictors of the primary endpoint included pre-existing RBBB (hazard ratio [HR] 2.8, 95% CI 1.1-7.0; P = 0.032) and depth of implantation below the noncoronary cusp (NCC) (HR 2.4, 95% CI 1.0-5.7; P = 0.045). CONCLUSIONS: Almost a third of Lotus valve recipients require pacemaker implantation within 30 days. The presence of pre-existing RBBB and the depth of prosthesis implantation below the NCC were significant pacing predictors. © 2016 Wiley Periodicals, Inc.

Effect of a mass media campaign on ambulance use for chest pain.

OBJECTIVES: To evaluate the impact of comprehensive public awareness campaigns by the National Heart Foundation of Australia on emergency medical service (EMS) use by people with chest pain. DESIGN, SETTING AND PARTICIPANTS: A retrospective analysis of 253428 emergency ambulance attendances for non-traumatic chest pain in Melbourne, January 2008 - December 2013. Time series analyses, adjusted for underlying trend and seasonal effects, assessed the impact of mass media campaigns on EMS use. MAIN OUTCOME MEASURE: Monthly ambulance attendances. RESULTS: The median number of monthly ambulance attendances for chest pain was 3609 (IQR, 3011-3891), but was higher in campaign months than in non-campaign months (3880 v 3234, P<0.001). After adjustments, campaign activity was associated with a 10.7% increase (95% CI, 6.5-14.9%; P<0.001) in monthly ambulance use for chest pain, and a 15.4% increase (95% CI, 10.1-20.9%; P<0.001) when the two-month lag periods were included. Clinical presentations for suspected acute coronary syndromes, as determined by paramedics, increased by 11.3% (95% CI, 6.9-15.9%; P<0.001) during campaigns. Although the number of patients transported to hospital by ambulance increased by 10.0% (95% CI, 6.1-14.2%; P<0.001) during campaign months, the number of patients not transported to hospital also increased, by 13.9% (95% CI, 8.3-19.8%; P<0.001). CONCLUSION: A public awareness campaign about responding to prodromal acute myocardial infarction symptoms was associated with an increase in EMS use by people with chest pain and suspected acute coronary syndromes. Campaign activity may also lead to increased EMS use in low risk populations.

PCSK9 Monoclonal Antibodies in 2016: Current Status and Future Challenges.

Cardiovascular disease remains the leading cause of morbidity and mortality in developed nations, with elevated low-density lipoprotein-cholesterol (LDL-C) levels being a major modifiable risk factor for coronary atherosclerosis. While lipid-lowering therapies such as statins are effective in lowering LDL-C, a proportion of patients do not achieve target LDL-C goals with statins or are intolerant to statins necessitating other treatment options. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of agents that reduce LDL-C beyond the maximum achievable LDL-C reductions with statins, and have been well studied in different patient groups. However, there are concerns regarding their potential adverse effects and cost, given that morbidity and mortality benefits have not yet been demonstrated. This state-of-the art review provides an overview of the development of PCSK9 inhibitors, the evidence regarding their clinical efficacy in specific target populations, and highlights future trials and challenges that need to be addressed before PCSK9 inhibitors are widely adopted into contemporary clinical practice.

Imaging Guidance for Transcatheter Aortic Valve Replacement: Is Transoesophageal Echocardiography the Gold Standard?

Transcatheter aortic valve replacement (TAVR) is traditionally performed under cardiac imaging guidance. In the early TAVR experience, intra-procedural transoesophageal echocardiography (TOE) is recommended to guide device deployment, in the context of general anaesthesia (GA). Intra-procedural TOE imaging is particularly useful during TAVR deployment as a contrast-saving strategy for patients with renal impairment. Evidence has emerged recently demonstrating that in selected patients, transthoracic echocardiography (TTE) can be used to provide intra-procedural guidance for TAVR. Additionally, there is a growing body of evidence supporting the performance of TAVR using fluoroscopy alone, without additional cardiac imaging. This article aims to provide a contemporary review of the various procedural imaging approaches for TAVR guidance, comparing the relative strengths and weaknesses of each approach (Table 1).