Estimation of endothelial shear stress in atherosclerotic lesions detected by intravascular ultrasound using computational fluid dynamics from coronary CT scans with a pulsatile blood flow and an individualized blood viscosity.

INTRODUCTION: Endothelial shear stress (ESS) is a local hemodynamic factor that is dependent on vessel geometry and influences the process of atherogenesis. As in vivo measurements of ESS are not possible, it must be calculated using computational fluid dynamics (CFD). In this feasibility study we explore CFD-models generated from coronary CT-angiography (CCTA) using an individualised blood viscosity and a pulsatile flow profile derived from in vivo measurements. MATERIALS AND METHODS: We retrospectively recruited 25 consecutive patients who received a CCTA followed by a coronary angiography including intravascular ultrasound (IVUS) and generated 3D models of the coronary arteries from the CT-datasets. We then performed CFD-simulations on these models. Hemodynamically non-relevant stenosis were identified in IVUS. They were isolated in the CFD-model and separated longitudinally into a half with atherosclerotic lesion (AL) and one without (NAL). ESS was measured and compared for both halves. RESULTS: After excluding vessels with no IVUS data or relevant stenosis we isolated 31 hemodynamically non-relevant excentric AL from a total of 14 vessels. AL segments showed consistently significantly lower ESS when compared to their corresponding NAL segments when regarding minimum (0.9 Pa, CI [0.6, 1.2] vs. 1.3 Pa, CI [0.9, 1.8]; p = 0.004), mean (5.0 Pa, CI [3.4, 6.0] vs. 6.7 Pa, CI [5.5, 8.4]; p = 0.008) and maximum ESS values (12.4 Pa, CI [8.6, 14.6] vs. 19.6 Pa, CI [12.4, 21.0]; p = 0.005). Qualitatively ESS was lower on the inside of bifurcations and curvatures. CONCLUSION: CFD simulations of coronary arteries from CCTA with an individualised flow profile and blood viscosity are feasible and could provide further prognostic information and a better risk stratification in coronary artery disease. Further prospective studies are needed to investigate this claim.

IMPULSE: the impact of gender on the presentation and management of aortic stenosis across Europe.

AIMS: There is an increasing awareness of gender-related differences in patients with severe aortic stenosis and their outcomes after surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). METHODS: Data from the IMPULSE registry were analysed. Patients with severe aortic stenosis (AS) were enrolled between March 2015 and April 2017 and stratified by gender. A subgroup analysis was performed to assess the impact of age. RESULTS: Overall, 2171 patients were enrolled, and 48.0% were female. Women were characterised by a higher rate of renal impairment (31.7 vs 23.3%; p<0.001), were at higher surgical risk (EuroSCORE II: 4.5 vs 3.6%; p=0.001) and more often in a critical preoperative state (7.0vs 4.2%; p=0.003). Men had an increased rate of previous cardiac surgery (9.4 vs 4.7%; p<0.001) and a reduced left ventricular ejection fraction (4.9 vs 1.3%; p<0.001). Concomitant mitral and tricuspid valve disease was substantially more common among women. Symptoms were highly prevalent in both women and men (83.6 vs 77.3%; p<0.001). AVR was planned in 1379 cases. Women were more frequently scheduled to undergo TAVI (49.3 vs 41.0%; p<0.001) and less frequently for SAVR (20.3 vs 27.5%; p<0.001). CONCLUSIONS: The present data show that female patients with severe AS have a distinct patient profile and are managed in a different way to males. Gender-based differences in the management of patients with severe AS need to be taken into account more systematically to improve outcomes, especially for women.

Management of patients with severe aortic stenosis in the TAVI-era: how recent recommendations are translated into clinical practice.

OBJECTIVE: Approximately 3.4% of adults aged >75 years suffer from aortic stenosis (AS). Guideline indications for aortic valve replacement (AVR) distinguish between patients with symptomatic and asymptomatic severe AS. The present analysis aims to assess contemporary practice in the treatment of severe AS across Europe and identify characteristics associated with treatment decisions, namely denial of AVR in symptomatic patients and assignment of asymptomatic patients to AVR. METHODS: Participants of the prospective, multinational IMPULSE database of patients with severe AS were grouped according to AS symptoms, and stratified into subgroups based on assignment to/denial of AVR. RESULTS: Of 1608 symptomatic patients, 23.8% did not undergo AVR and underwent medical treatment. Denial was independently associated with multiple factors, including severe frailty (p=0.024); mitral (p=0.002) or tricuspid (p=0.004) regurgitation grade III/IV, and the presence of renal impairment (p=0.017). Of 392 asymptomatic patients, 86.5% had no prespecified indication for AVR. Regardless, 36.3% were assigned to valve replacement. Those with an indexed aortic valve area (AVA; p=0.045) or left ventricular ejection fraction (LVEF; p<0.001) below the study median; or with a left ventricular end systolic diameter above the study median (p=0.007) were more likely to be assigned to AVR. CONCLUSIONS: There may be considerable discrepancies between guideline-based recommendations and clinical practice decision-making in the treatment of AS. It appears that guidelines may not fully capture the complete clinical spectrum of patients with AS. Thus, there is a need to find ways to increase their acceptance and the rate of adoption.

Impact of selected comorbidities on the presentation and management of aortic stenosis.

BACKGROUND: Contemporary data regarding the impact of comorbidities on the clinical presentation and management of patients with severe aortic stenosis (AS) are scarce. METHODS: Prospective registry of severe patients with AS across 23 centres in nine European countries. RESULTS: Of the 2171 patients, chronic kidney disease (CKD 27.3%), left ventricular ejection fraction (LVEF) <50% (22.0%), atrial fibrillation (15.9%) and chronic obstructive pulmonary disease (11.4%) were the most prevalent comorbidities (49.3% none, 33.9% one and 16.8% ≥2 of these). The decision to perform aortic valve replacement (AVR) was taken in a comparable proportion (67%, 72% and 69%, in patients with 0, 1 and ≥2 comorbidities; p=0.186). However, the decision for TAVI was more common with more comorbidities (35.4%, 54.0% and 57.0% for no, 1 and ≥2; p<0.001), while the decision for surgical AVR (SAVR) was decreased with increasing comorbidity burden (31.9%, 17.4% and 12.3%; p<0.001). The proportion of patients with planned AVRs that were performed within 3 months was significantly higher in patients with 1 or ≥2 comorbidities than in those without (8.7%, 10.0% and 15.7%; p<0.001). Furthermore, the mean time to AVR was significantly shorter in patients with one (30.5 days) or ≥2 comorbidities (30.8 days) than in those without (35.7 days; p=0.012). Patients with reduced LVEF tended to be offered an AVR more frequently and with a shorter delay while patients with CKD were less frequently treated. CONCLUSIONS: Comorbidities in severe patients with AS affect the presentation and management of patients with severe AS. TAVI was offered more often than SAVR and performed within a shorter time period.

Smoking and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients: a substudy from the randomized TROPICAL-ACS trial.

AIMS: Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients. METHODS AND RESULTS: The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64-1.56, P > 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50-0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45-1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20-40)] vs. non-smoker [median 24 U (16-25), P < 0.0001] in the control group and in current smokers [median 42 U, IQR (27-68)] vs. non-smoker [median 37 U, IQR (25-55), P < 0.001] in the monitoring group. CONCLUSION: Guided DAPT de-escalation appears to be equally safe and effective in smokers and non-smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year of potent platelet inhibition this DAPT strategy might be used as an alternative antiplatelet treatment regimen.

Facilitated Data Relay and Effects on Treatment of Severe Aortic Stenosis in Europe.

Background Many patients with severe aortic stenosis are referred late with advanced symptoms or inappropriately denied intervention. The objective was to investigate whether a structured communication to referring physicians (facilitated data relay) might improve the rate and timeliness of intervention. Methods and Results A prospective registry of consecutive patients with severe aortic stenosis at 23 centers in 9 European countries with transcatheter as well as surgical aortic valve replacement being available was performed. The study included a 3-month documentation of the status quo (phase A), a 6-month intervention phase (implementing facilitated data relay), and a 3-month documentation of a legacy effect (phase-B). Two thousand one hundred seventy-one patients with severe aortic stenoses were enrolled (phase A: 759; intervention: 905; phase-B: 507). Mean age was 77.9±10.0 years, and 80% were symptomatic, including 52% with severe symptoms. During phase A, intervention was planned in 464/696 (67%), 138 (20%) were assigned to watchful waiting, 8 (1%) to balloon aortic valvuloplasty, 60 (9%) were listed as not for active treatment, and in 26 (4%), no decision was made. Three hundred sixty-three of 464 (78%) patients received the planned intervention within 3 months. Timeliness of the intervention improved as shown by the higher number of aortic valve replacements performed within 3 months (59% versus 51%, P=0.002) and a significant decrease in the time to intervention (36±38 versus 30±33 days, P=0.002). Conclusions A simple, low-cost, facilitated data relay improves timeliness of treatment for patients diagnosed with severe aortic stenosis, resulting in a shorter time to transcatheter aortic valve replacement. This effect was mainly driven by a significant improvement in timeliness of intervention in transcatheter aortic valve replacement but not surgical aortic valve replacement. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02241447.

Symptoms, disease severity and treatment of adults with a new diagnosis of severe aortic stenosis.

OBJECTIVE: Contemporary data on patients with previously undiagnosed severe aortic stenosis (AS) are scarce. We aimed to address this gap by gathering data from consecutive patients diagnosed with severe AS on echocardiography. METHODS: This was a prospective, multicentre, multinational, registry in 23 tertiary care hospitals across 9 European countries. Patients with a diagnosis of severe AS were included using echocardiography (aortic valve area (AVA) <1 cm2, indexed AVA <0.6 cm2/m2, maximum jet-velocity (Vmax) >4 m/s and/or mean transvalvular gradient >40 mm Hg). RESULTS: The 2171 participants had a mean age of 77.9 years and 48.0% were female. The mean AVA was 0.73 cm2, Vmax4.3 m/s and mean gradient 47.1 mm Hg; 62.1% had left ventricular hypertrophy and 27.3% an ejection fraction (EF) <50%. 1743 patients (80.3%) were symptomatic (shortness-of-breath 91.0%; dizziness 30.2%, chest pain 28.9%). Patients had a EuroSCORE II of 4.0; 25.3% had a creatinine clearance <50 mL/min, and 3.2% had an EF <30%. Symptomatic patients were older and had more comorbidities than asymptomatic patients. Despite European Society of Cardiology 2017 valvular heart disease guideline class I recommendation, in only 76.2% a decision was made for an intervention (transcatheter 50.4%, surgical aortic valve replacement 25.8%). In asymptomatic patients, 57.7% with a class I/IIa indication were scheduled for a procedure, while 36.3% patients without an indication had their valve replaced. CONCLUSIONS: The majority of patients with severe AS presented at an advanced disease stage. Management of severe AS remained suboptimal in a significant proportion of contemporary patients with severe AS. TRIAL REGISTRATION NUMBER: NCT02241447;Results.

Coronary Angiography With Pressure Wire and Fractional Flow Reserve.

BACKGROUND: Approximately 800 000 coronary angiography procedures are per- formed in Germany each year, mainly in order to identify coronary artery stenoses. As a rule, revascularization is indicated only when coronary artery stenoses cause relevant ischemia, but this cannot be determined unequivocally by angiography alone. Pressure wire measurement and the measurement of fractional flow reserve (FFR) enable direct evaluation of the hemodynamic relevance of coronary artery stenoses during diagnostic coronary angiography. METHODS: This review is based on publications retrieved by a selective search in PubMed focusing especially on large randomized trials, registry studies, and meta- analyses on either pressure wire measurement or FFR. RESULTS: According to a registry study from France, the hemodynamic evaluation of a stenosis during coronary angiography affected decisions about revascularization in 43% of cases. Randomized multicenter trials have shown that a combined end- point consisting of death, myocardial infarction, or revascularization arose signifi- cantly less commonly in the FFR group than in the group receiving angiography without FFR (13.2% versus 18.3%; p = 0.02), and that patients with one or more hemodynamically significant coronary artery stenoses (FFR ≤ 0.80) benefited more from revascularization than from medical management alone (event rate, 8.1% versus 19.5%; p <0.001). It was also shown that revascularization yields no benefit if relevant ischemia has been ruled out, even if the angiogram shows high-grade coronary artery stenoses. CONCLUSION: All cardiac catheter laboratories should be capable of performing pres- sure wire measurements and measurements of FFR and should do so regularly if ischemia due to coronary artery stenosis cannot be demonstrated non-invasively. A pathological FFR measurement is an indication for revascularization.

Diabetes and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: a pre-specified analysis from the randomised TROPICAL-ACS trial.

AIMS: A guided de-escalation of P2Y12 inhibitor treatment is considered an alternative treatment strategy in ACS patients undergoing PCI. However, the safety and efficacy of this strategy may differ in diabetic vs non-diabetic patients. The aim of this study was to compare the outcomes of platelet function testing (PFT)-guided de-escalation of dual antiplatelet therapy (DAPT) in ACS patients with and without diabetes mellitus. METHODS AND RESULTS: The TROPICAL-ACS trial randomised 2,610 biomarker-positive ACS patients 1:1 to either standard treatment with prasugrel for 12 months (control group) or PFT-guided DAPT de-escalation. The association and interaction of diabetes on clinical endpoints across treatment groups and on platelet reactivity was investigated. In diabetic patients (n=527, 20.2%), the overall event rates were high and the one-year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke or bleeding ≥grade 2) did not differ between guided de-escalation and control group patients (12.5% vs 10.8%; HR 1.17, 95% CI: 0.71-1.93, p=0.55). In non-diabetic patients (n=2,083, 79.8%), the one-year incidence of the primary endpoint was lower in the guided de-escalation vs control group (6.1% vs 8.5%; HR 0.71, 95% CI: 0.52-0.99, p=0.04, pint=0.10). Diabetic patients showed higher platelet reactivity levels in both control (=on prasugrel, p=0.01) and guided de-escalation group (=on clopidogrel, p=0.005) patients. CONCLUSIONS: Although diabetic status did not significantly interfere with the treatment effects of guided DAPT de-escalation, our results suggest that this approach might be safe and effective in non-diabetic patients. Further investigation is definitely warranted in diabetic patients.

Renal Sympathetic Denervation: Does Reduction of Left Ventricular Mass Improve Functional Myocardial Parameters? A Cardiovascular Magnetic Resonance Imaging Pilot Study.

OBJECTIVES: Left ventricular (LV) hypertrophy in resistant hypertensive patients is associated with a reduced intramyocardial perfusion. Renal sympathetic denervation (RDN) has been shown to reduce blood pressure (BP) and sympathetic tone. We aimed to prospectively investigate the effect of RDN on functional myocardial parameters and myocardial perfusion reserve (MPR) using cardiac magnetic resonance imaging (cMRI) in patients with resistant hypertension. METHODS: A total of 15 resistant hypertensive patients (11 male individuals, mean age 62±13 y) were included. Adenosine stress-induced cMRI was performed at baseline, 3, 6, and 12 months after RDN. RDN was performed using a single soft-tip radiofrequency catheter (Symplicity). cMRI semiquantitative perfusion analysis was performed using the upslope of myocardial signal enhancement to derive the myocardial perfusion reserve index. RESULTS: Both systolic-BP and diastolic-BP significantly decreased from 148±14 to 133±14 mm Hg and 87±14 to 80±10 mm Hg, respectively (P<0.05). LV septal wall thickness was significantly reduced (P<0.001). LV ejection fraction and MPR lacked significant trends 12 months after RDN. CONCLUSIONS: In this pilot study, RDN significantly reduced LV mass and LV septal wall thickness, as diagnosed by cMRI, with no significant changes in MPR. cMRI may help in diagnosing clinically relevant changes of functional myocardial parameters after interventional therapy in resistant hypertensive patients.

Platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor in comparison to clopidogrel: a retrospective pharmacodynamic analysis.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a mainstay of the prevention of stent thrombosis following percutaneous coronary intervention (PCI). In the 2015 European guidelines for the management of acute coronary syndrome (ACS), prasugrel (PRA) and ticagrelor (TICA) combined with aspirin are recommended as first-line therapy. Clopidogrel (CLO) is recommended as an alternative medication for patients with contradictions to these new drugs. This single-center study analyzed the platelet function of 809 ACS patients undergoing PCI and treatment with DAPT. The platelet response to ADP was determined using Multiplate® analyzer at a median of 3 days after PCI in 254 patients treated with PRA (loading dose [LD] 60 mg, 10 mg qd), 162 patients receiving TICA (LD 180 mg, D 90 mg bid), and 393 CLO-treated patients (LD 600 mg, 75 mg qd). An aggregation >468 arbitrary units (AU)*min was defined as "high on-treatment platelet reactivity" (HPR), <188 AU*min as "low on-treatment platelet reactivity" (LPR). Platelet response in PRA-treated patients was lower compared to CLO or TICA (median; interquartile range: PRA 220 [163-275] AU*min vs. CLO 268 [186-387] AU*min, p < 0.001 vs. TICA 245 [190-320] AU*min, p = 0.001). Only 1.6% of PRA patients were stratified as HPR and 34.6% as LPR, while in the TICA group 1.9% fulfilled the criteria of HPR and 24.1% criteria of LPR. Sixteen percent of CLO patients were stratified as HPR and 26.2% as LPR. In a real-world cohort of ACS patients following PCI, PRA results in more potent inhibition of platelet function compared to CLO and TICA. TICA achieves a consistent antiplatelet effect with reduced rates of HPR and LPR in relation to CLO.

Do acute coronary events affect lipid management and cholesterol goal attainment in Germany? : Results from the Dyslipidemia International study II.

OBJECTIVE: To document utilization of lipid-lowering therapy, attainment of low-density lipoprotein cholesterol target values, and cardiovascular outcomes in patients hospitalized for acute coronary syndrome in Germany. METHODS: The Dyslipidemia International Study II was a multicenter, observational study of the prevalence of dyslipidemia and lipid target value attainment in patients surviving any acute coronary syndrome event. Among patients on lipid-lowering therapy for ≥3 months, use of lipid-lowering therapy and lipid profiles were assessed at admission and again at 120 ± 15 days after admission (the follow-up time point). Multivariate logistic regression was used to identify variables predictive of low-density lipoprotein cholesterol target value attainment in patients using lipid-lowering therapy. RESULTS: A total of 461 patients hospitalized for acute coronary syndrome were identified, 270 (58.6%) of whom were on lipid-lowering therapy at admission. Among patients on lipid-lowering therapy, 90.7% and 85.9% were receiving statin monotherapy at admission and follow-up, respectively. Mean (SD) low-density lipoprotein cholesterol levels in patients on lipid-lowering therapy were 101 (40) mg/dl and 95 (30) mg/dl at admission and follow-up, respectively. In patients with data at both admission and follow-up (n = 61), low-density lipoprotein cholesterol target value attainment rates were the same (19.7%) at both time points. Smoking was associated with a 77% lower likelihood of attaining the low-density lipoprotein cholesterol target value. CONCLUSION: Hospitalization for an acute event does not greatly alter lipid management in acute coronary syndrome patients in Germany. Both lipid-lowering therapy doses and rates of low-density lipoprotein cholesterol target value attainment remained essentially the same several months after the event.

Angiographic and clinical performance of a paclitaxel-coated balloon compared to a second-generation sirolimus-eluting stent in patients with in-stent restenosis: the BIOLUX randomised controlled trial.

AIMS: Although several studies have shown positive outcomes after the use of drug-coated balloons (DCB) for in-stent restenosis (ISR), data on randomised controlled trials versus latest-generation drug-eluting stents (DES) are limited. Therefore, in this randomised trial, we sought to evaluate whether a butyryl-tri-hexyl citrate (BTHC)-based paclitaxel DCB is non-inferior to a biodegradable polymer sirolimus-eluting stent (BP-SES) therapy in patients with ISR in either a bare metal stent (BMS) or DES. METHODS AND RESULTS: A total of 229 patients with ISR in BMS or DES from 13 German centres and one Latvian centre were 2:1 randomly allocated to DCB (n=157) or DES (n=72). The primary efficacy endpoint was defined as in-stent late lumen loss (LLL) at six months, and the primary safety endpoint was target lesion failure (TLF) at 12 months. LLL in the DCB arm was 0.03±0.40 mm compared to 0.20±0.70 mm in the DES arm (p=0.40). DCB proved to be non-inferior to DES (Δ = -0.17±0.52 mm, 97.5% CI -∞; -0.01]; p<0.0001). At 12 months, Kaplan-Meier TLF estimates were 16.7% in the DCB arm and 14.2% in the DES arm (p=0.65) and remained similar at 18 months (DCB versus DES: 17.4% versus 19.5%, p=0.88). CONCLUSIONS: In patients with DES or BMS ISR, treatment with a paclitaxel DCB showed similar LLL at six months and TLF rates up to 18 months compared to a second-generation sirolimus DES.

Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial.

BACKGROUND: Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). METHODS: In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. FINDINGS: Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (pnon-inferiority=0·0004; hazard ratio [HR] 0·81 [95% CI 0·62-1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59-1·13]; p=0·23). INTERPRETATION: Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. FUNDING: Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

Performing and Interpreting Fractional Flow Reserve Measurements in Clinical Practice: An Expert Consensus Document.

Fractional flow reserve (FFR) measurements can determine the haemodynamic relevance of coronary artery stenoses. Current guidelines recommend their use in lesions in the absence of non-invasive proof of ischaemia. The prognostic impact of FFR has been evaluated in randomised trials, and it has been shown that revascularisation can be safely deferred if FFR is >0.80, while revascularisation of stenoses with FFR values ≤0.80 results in significantly lower event rates compared to medical treatment. Left main stenoses, aorto-ostial lesions, as well as patients with left ventricular hypertrophy and severely-impaired ejection fraction, have been excluded from large, randomised trials. While FFR measurements are relatively straightforward to perform, uncertainty about procedural logistics, as well as data acquisition and interpretation in specific situations, could explain why they are not widely used in clinical practice. We summarise the clinical data in support of FFR measurements, and provide recommendations for performing and interpreting the procedure.

A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI. Rationale and design of the Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Trial.

Outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) have been significantly improved with the use of potent P2Y12 receptor inhibitors like prasugrel. While most of the ischaemic risk reduction for prasugrel versus clopidogrel was demonstrated in the early treatment period, the risk of bleeding became particularly prominent during the chronic course of therapy. It may therefore be a valid approach to substitute prasugrel for clopidogrel in the early phase of chronic antiplatelet treatment after PCI. In the Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial, we aim to compare standard prasugrel therapy with a de-escalating antiplatelet treatment approach guided by platelet function testing (PFT). The study is an investigator-initiated European multicentre, randomised clinical trial in biomarker-positive ACS patients after successful PCI. Two thousand six hundred patients will be randomised prior to hospital discharge in a 1:1 fashion to either receive standard prasugrel therapy (control group) or de-escalating therapy (one-week prasugrel followed by one-week clopidogrel and PFT-guided maintenance therapy from day 14 after hospital discharge, monitoring group). Patients of the monitoring group with high on-clopidogrel platelet reactivity (HPR) based on Multiplate analyzer testing (HPR: ≥ 46U per consensus definition) will be switched back to prasugrel, whereas those without HPR (<46 U) will continue clopidogrel treatment. The overall study treatment duration will be one year in both groups. The primary endpoint of the study is net clinical benefit (combined incidence of cardiovascular death, myocardial infarction, stroke and bleeding ≥ grade 2 according to BARC criteria) one-year after randomisation. TROPICAL-ACS is the first large-scale, randomised controlled trial assessing the clinical value of a PFT-guided de-escalation of antiplatelet treatment in biomarker positive ACS patients undergoing PCI.

Final results of a self-apposing paclitaxel-eluting stent fOr the PErcutaNeous treatment of de novo lesions in native bifurcated coronary arteries study.

AIMS: We aimed to evaluate the long-term safety and efficacy of the STENTYS self-apposing paclitaxeleluting stent (STENTYS-PES) in bifurcation lesions in routine clinical practice. METHODS AND RESULTS: The primary endpoint of the study was the composite major adverse cardiac events (MACE: cardiac death, myocardial infarction, clinically driven target lesion revascularisation, or emergent bypass surgery) assessed at six months after enrolment. This was reported in 21 patients (10.1%), mainly due to clinically driven target lesion revascularisation (TLR). At 12 months, 27 patients experienced MACE (13.0%). CONCLUSIONS: The long-term results of OPEN II show that the STENTYS-PES is safe and effective in the treatment of all-comers with coronary bifurcation lesions.

Coronary computed tomography angiography based assessment of endothelial shear stress and its association with atherosclerotic plaque distribution in-vivo.

PURPOSE: The relationship between low endothelial shear stress (ESS) and coronary atherosclerosis is well established. ESS assessment so far depended on invasive procedures. The aim of this study was to demonstrate the relationship between ESS and coronary atherosclerosis by using non-invasive coronary computed tomography angiography (CTA) for computational fluid dynamics (CFD) simulations. METHODS: A total number of 7 consecutive patients with suspected coronary artery disease who received CTA and invasive angiography with IVUS analysis were included in this study. CTA examinations were performed using a dual-source scanner. These datasets were used to build a 3D mesh model. CFD calculations were performed using a validated CFD solver. The presence of plaque was assumed if the thickness of the intima-media complex exceeded 0.3 mm in IVUS. Plaque composition was derived by IVUS radiofrequency data analysis. RESULTS: Plaque was present in 32.1% of all analyzed cross-sections. Plaque prevalence was highest in areas of low ESS (49.6%) and high ESS (34.8%). In parts exposed to intermediate-low and intermediate-high ESS few plaques were found (20.0% and 24.0%) (p<0.001). Wall thickness was closely associated with local ESS. Intima-media thickness was 0.43±0.34 mm in low and 0.38±0.32 mm in high ESS segments. It was significantly lower when the arterial wall was exposed to intermediate ESS (0.25±0.18 mm and 0.28 ± 0.20 mm) (p<0.001). Fibrofatty tissue was predominately found in areas exposed to low ESS (p≤0.023). CONCLUSIONS: In this study a close association of atherosclerotic plaque distribution and ESS pattern could be demonstrated in-vivo. Adding CFD analysis to coronary CTA offers the possibility to gather morphologic and physiologic data within one non-invasive examination.