Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention: The SORT OUT IX Trial.

BACKGROUND: In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021. RESULTS: Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; Pnoninferiority=0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66-4.62]; P<0.0001). CONCLUSIONS: The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02623140.

Randomized Comparison of Terumo® Coated Slender™ versus Terumo® Noncoated Traditional Sheath during Radial Angiography or Percutaneous Coronary Intervention.

BACKGROUND: The transradial approach is generally associated with few complications. However, periprocedural pain is still a common issue, potentially related to sheath insertion and/or arterial spasm, and may result in conversion to femoral access. Radial artery occlusion (RAO) following the procedure is also a potential risk. We evaluate whether the design of the sheath has any impact on these variables. METHODS: A total of 1,000 patients scheduled for radial CAG or PCI were randomized (1:1) to the use of a Slender or a Standard sheath during the procedure. Randomization was stratified according to chosen sheath size (5, 6, 7 French) and gender. A radial band was used to obtain hemostasis after the procedure, employing a rapid deflation technique. A reverse Barbeau test was performed to evaluate radial artery patency after removal of the radial band, and level of pain was assessed using a numeric rating scale (NRS). RESULTS: Use of the Slender sheath was associated with less pain during sheath insertion (median NRS 1 versus 2, p=0.02), whereas no difference was observed in pain during the procedure, radial procedural success rates, use of analgesics and sedatives during the procedure, and radial artery patency following the procedure. Rate of RAO was 1.5% with no difference between groups. CONCLUSION: The use of the hydrophilic coated Slender sheath during radial CAG or PCI was associated with less pain during sheath insertion, whereas no difference in other endpoints was observed. A rapid deflation technique was associated with RAO of only 1.5%.

Long Coronary Lesions Treated With Thin Strut Bioresorbable Polymer Drug Eluting Stent: Experience From Multicentre Randomized CENTURY II Study.

OBJECTIVES: To assess performance of new, bioresorbable polymer sirolimus-eluting stent (BP-SES), in patients with long coronary lesions (LL) and to compare it to permanent polymer everolimus-eluting stent (PP-EES). BACKGROUND: LL have been associated with worse clinical outcomes in percutaneous coronary interventions (PCI). The impact of lesion length on the outcomes of drug eluting stent (DES) implantations is not as clear. METHODS: In the frame of a randomized, multicentre CENTURY II study, out of 1119 patients enrolled, 182 patients had LL (defined as ≥25 mm), and were assigned randomly to treatment with BP-SES (101) or PP-EES (81). Primary endpoint was target lesion failure (TLF, composite of cardiac death, target vessel related myocardial infarction [MI], and target lesion revascularization [TLR]) at 9 months. All data were 100% monitored and adverse events were adjudicated by an independent clinical event committee. RESULTS: The baseline patient and lesion characteristics were similar in the 2 study arms. At 9-months, the rates of cardiac death (2.0% vs 1.2%; P = 0.70), MI (3.0% vs 4.9%; P = 0.49) and clinically driven TLR (2.0% vs 3.7%; P = 0.48) and TLF (6.9% vs 8.6%; P = 0.67) were similar for BP-SES and PP-EES, respectively. There was no stent thrombosis (ST) in BP-SES group up to 9 months, while 1 case (1.2%) of ST was recorded in PP-EES group (P = 0.44). CONCLUSIONS: Patients with LL showed similar clinical outcomes when treated with Ultimaster BP-SES and Xience PP-EES.

Cardiopulmonary Exercise Testing in Patients with Asymptomatic or Equivocal Symptomatic Aortic Stenosis: Feasibility, Reproducibility, Safety and Information Obtained on Exercise Physiology.

OBJECTIVE: The aim of this study was to determine the feasibility, reproducibility, safety and information obtained on exercise physiology from cardiopulmonary exercise testing (CPX) in patients with aortic stenosis. METHODS: Patients with an aortic valve area (AVA) <1.3 cm2 who were judged asymptomatic or equivocal symptomatic underwent CPX and an inert gas rebreathing test. Only those where comprehensive evaluation of CPX results indicated haemodynamic compromise from aortic stenosis were referred for valve replacement. RESULTS: The mean patient age was 72 (±9) years; an AVA index <0.6 cm2/m2 and equivocal symptomatic status were found in 90 and 70%, respectively. CPX was feasible in 130 of the 131 patients. The coefficients of repeatability by test-retest were 5.4% (pVO2) and 4.6% (peak O2 pulse). A pVO2 <83% of the expected was predicted by a lower stroke volume at exercise, lower peak heart rate and FEV1, and higher VE/VCO2, but not by AVA index. Equivocal symptomatic status and a low gradient but high valvulo-arterial impedance were associated with a lower pVO2, but not with an inability to increase stroke volume. In total, 18 patients were referred for valve replacement. At 1 year, no cardiovascular deaths had occurred. CONCLUSIONS: CPX was feasible and reproducible and provided comprehensive data on exercise physiology. A CPX-guided treatment strategy was safe up to 1 year.

Real-World Experience with Cangrelor as Adjuvant to Percutaneous Coronary Intervention: A Single-Centre Observational Study.

Background: Reversible P2Y12 inhibition can be obtained with cangrelor administered intravenously. More experience with cangrelor use in acute PCI with unknown bleeding risk is needed. Objectives: To describe real-world use of cangrelor including patient and procedure characteristics and patient outcomes. Methods: We performed a single-centre, retrospective, and observational study including all patients treated with cangrelor in relation to percutaneous coronary intervention at Aarhus University Hospital during the years 2016, 2017, and 2018. We recorded procedure indication and priority, the indications for cangrelor use, and patient outcomes within the first 48 hours after initiation of cangrelor treatment. Results: We treated 991 patients with cangrelor in the study period. Of these, 869 (87.7%) had an acute procedure priority. Among acute procedures, patients were mainly treated for STEMI (n = 723) and the remaining were treated for cardiac arrest and acute heart failure. Use of oral P2Y12 inhibitors prior to percutaneous coronary intervention was rare. Fatal bleeding events (n = 6) were only observed among patients undergoing acute procedures. Stent thrombosis was observed in two patients receiving acute treatment for STEMI. Thus, cangrelor can be used in relation to PCI under acute circumstances with advantages in terms of clinical management. The benefits and risks, in terms of patient outcomes, should ideally be assessed in randomized trials.

Percutaneous coronary intervention without onsite cardiac surgery.

INTRODUCTION: Danish health authorities have major concerns with regard to the risk and the quality of care of percutaneous coronary intervention (PCI) without onsite cardiac surgery. We report the results of the first Danish PCI centre without onsite cardiac surgery. MATERIAL AND METHODS: A total of 245 patients underwent 254 elective PCIs during a six-month study period. The outcome measures were treatment latency, health care costs, mortality rate, major adverse cardiovascular events, symptom relief and quality-of-life at six-month follow-up. RESULTS: The median treatment latency was reduced from 28 to no days (p < 0.05) for patients with stable disease, and from seven to no days (p < 0.05) for patients with unstable disease. Health care costs were reduced by 4,246,652 DKK. The six-month mortality was 0.0% versus a predicted 0.4% New York State PCI-score in patients with stable disease, and a 1.4% observed study score versus a predicted 6.4% GRACE-score in patients with unstable disease. No patients required emergency bypass surgery. At six months, five myocardial infarctions (two periprocedural and two subacute stent thromboses), three restenoses and no in-stent restenosis had occurred, while angina was absent or reduced in 92% and quality-of-life had improved in 73% of the patients. CONCLUSION: Local PCI without onsite cardiac surgery was safe, quality of care was increased, health care costs were reduced and patient-perceived treatment effect was excellent.

Everolimus-Eluting Versus Biolimus-Eluting Stents With Biodegradable Polymers in Unselected Patients Undergoing Percutaneous Coronary Intervention: A Randomized Noninferiority Trial With 1-Year Follow-Up (SORT OUT VIII Trial).

OBJECTIVES: The aim of this study was to compare the thin-strut biodegradable-polymer everolimus-eluting platinum-chromium stent (EES) with the biodegradable-polymer biolimus-eluting stainless-steel stent (BES). BACKGROUND: Currently available drug-eluting coronary stents have been refined to reduce the risk for coronary events following implantation. METHODS: This randomized, multicenter, all-comers, noninferiority trial was undertaken at 3 sites in western Denmark. Patients with clinical indications for percutaneous coronary intervention were eligible for inclusion. Patients were randomly assigned (1:1) to either EES or BES. The primary endpoint, target lesion failure, was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a nontarget lesion) and efficacy (target lesion revascularization) at 12 months, analyzed using intention-to-treat principles. The trial was powered to assess target lesion failure noninferiority of the EES compared with the BES with a predetermined noninferiority margin of 3%. RESULTS: A total of 1,385 patients were assigned to treatment with EES and 1,369 patients to treatment with BES. The analysis showed that 55 patients (4.0%) assigned to the EES and 60 (4.4%) assigned to the BES met the primary endpoint (absolute risk difference 0.4%; upper limit of 1-sided 95% confidence interval: 1.7%; p < 0.001). CONCLUSIONS: At 1-year follow-up, the EES was found to be noninferior to the BES with respect to target lesion failure. (Everolimus-eluting SYNERGY Stent Versus Biolimus-Eluting Biomatrix NeoFlex Stent-SORT-OUT VIII; NCT02093845).

Iatrogenic aortocoronary dissection: the case for immediate aortoostial stenting.

Aortoostial dissection is a serious but rare complication of coronary intervention that may require surgical aortic repair. Here we present four cases which were immediately sealed with stenting of the coronary ostium abruptly terminating spread of the aortic dissection and obviating the need for surgical repair. Long-term outcome in this small series was universally event free. Review of the literature suggests that such a strategy is frequently successful without major added risk. We propose that immediate ostial stenting (irrespective of whether the dissection starts from the ostium or further downstream in the coronary) should be strongly considered in all cases as it may prevent the need for high-risk emergent surgical aortic repair.

Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease.

OBJECTIVES: A phase I safety and efficacy study with granulocyte colony stimulating factor (G-CSF) mobilization of bone marrow stem cells to induce vasculogenesis in patients with severe ischemic heart disease (IHD) was conducted. DESIGN, PATIENTS AND RESULTS: 29 patients with IHD participated in the study. Thirteen patients were treated with G-CSF for 6 days and 16 patients served as controls. G-CSF treatment was without any serious adverse events. Four patients were "poor mobilizers" with a maximal increase in CD34+ cells to 5,000+/-700/mL blood (mean+/-S.D.) compared to 28,900+/-5,100/mL blood in "mobilizers". At the follow-up, G-CSF treated had improved in CCS classification, NTG consumption and angina attacks, but the controls only in CCS classification. No difference was seen between the two groups. The decline in NTG consumption tended to be significant in "mobilizers" compared to controls. Myocardial perfusion was unchanged at adenosine stress single photon emission computerized tomography (SPECT) or magnetic resonance images (MRI). Left ventricular ejection fraction decreased from 57% to 52% (p<0.01, MRI) and from 48% to 44% (p=0.07, SPECT) in G-CSF treated, but was unchanged measured with echocardiography. CONCLUSIONS: Treatment by G-CSF improved symptoms but not signs of myocardial ischemia in patients with severe IHD. The effects seemed related to mobilization of stem cells. An adverse effect on ejection fraction could not be excluded.

Prolonged ischemic heart disease and coronary artery bypass - relation to contractile reserve.

OBJECTIVE: A major effect of coronary artery bypass grafting (CABG) in patients with ischemic heart disease and impaired left ventricular (LV) contractile function is believed to be an improvement in LV function due to recovery of dysfunctional, but viable myocardium. However, recent studies have indicated a time limit for such a recovery. We therefore investigated the extent of viable myocardium in patients with impaired LV function due to ischemic heart disease after a prolonged strategy of medical treatment and its relation to changes in clinical variables after CABG. METHODS: Forty-five consecutive patients with a mean duration of ischemic heart symptoms of 9 years and LV ejection fraction (EF) <45% referred for CABG were included and LV extent of viable myocardium was measured preoperatively by glucose metabolism--blood flow positron emission tomography imaging and dobutamine stress echocardiography. Symptoms, exercise-capacity and LV function were evaluated before and 7 months after surgery in event-free survivors. RESULTS: LV extent of myocardial viability was <30% in most patients. In event-free survivors, LVEF decreased from 31+/-7 to 26+/-8% 7 months after CABG. The decrease in LVEF was correlated to the LV extent of myocardial metabolism--blood flow reverse mismatch. Most of the patients experienced an improvement in their angina pectoris, heart failure symptoms and exercise capacity after CABG; the overall 3-year survival was 77%. CONCLUSIONS: Patients with chronic ischemic heart disease and impairment of LV function, in whom an initial long-standing conservative treatment has been practiced, benefit from CABG, despite a lack of LV functional reserve.

Echocardiographic Assessment of Regional and Global Left Ventricular Function Wall-Motion Scoring in Parasternal and Apical Views Versus Apical Views Alone.

The aim of the study was to examine the value of echocardiographic wall-motion scoring in apical views as compared to a conventional combination of apical and parasternal views. In 50 consecutive patients referred to coronary arteriography for potential revascularization, echocardiographic digital image loops of the left ventricle (LV) were recorded in parasternal long- and short-axis views and in apical long-axis, two-, and four-chamber views. Eight of 16 standardized LV segments appear both in the apical and in the parasternal views (group 1 segments). The remaining eight segments are visualized in the apical views only (group 2). Using a cross-over design, two cardiologists independently performed regional wall-motion scoring based on apical views, respectively, based on the combination of parasternal and apical views. Using the conventional approach (parasternal and apical views) 98% of the total 800 segments were scored as compared to 95% when using the mere apical approach (P < 0.05); 94% of the 800 segments were scored from both approaches. The regional wall-motion score was identical in 76% of group 1 segments and in 77% of group 2 segments. It diverged, at most, one score in 94% of group 1 segments and in 91% of group 2 segments (P > 0.05). LV ejection fraction (EF) calculated on the basis of average wall-motion score exclusively assessed from the apex differed little from angiographic EF (mean difference 2.0%, 95% confidence limits +/- 6.6%). Intraobserver variability of wall-motion scores (n = 25 patients) was small and almost identical for the two cardiologists. Similarly, interobserver variability was small and identical for apical views and conventional views. We conclude that there is no substantial loss of information when echocardiographic evaluation of regional and global left ventricular function is performed solely from the apical approach.

Field triage to primary angioplasty combined with emergency department bypass reduces treatment delays and is associated with improved outcome.

AIMS: We investigated the net benefit in the outcome of reducing treatment delay through field triage and emergency department (ED) bypass in patients with ST-elevation myocardial infarction (STEMI) treated with primary angioplasty. METHODS AND RESULTS: In a prospective registry study, consecutive patients with suspected STEMI were assigned to: (i) pre-hospital ECG and triage or (ii) ECG and triage at the closest ED, solely based on ambulance availability. Four district hospitals and one regional heart centre serviced the 890,000 population metropolitan area and primary angioplasty was the only reperfusion strategy employed. Baseline characteristics were similar in STEMI patients triaged in the field (108) and the EDs (193). Symptom onset to balloon times: 154 [inter-quartile range (IQR) 120-233) vs. 249 (IQR 184-405) min (P<0.001) and peak creatine kinase in early presenters (<2 h): 1435 (95 %CI: 904-1966) U/L vs. 2320 (95% CI: 1881-2762) U/L (P=0.009) were lower in field- than in ED-triaged patients. Mortality in the PCI treated were 1.1 and 8.2% [P=0.025, RR 0.14 (95% CI: 0.01-1.08)] and overall mortality were 1.9 and 7.3% [P=0.046, RR 0.26 (95% CI: 0.05-1.11)]. CONCLUSION: Field-triage and ED bypass were feasible means of reducing treatment delay in patients with suspected STEMI and resulted in smaller infarct size in early presenters and a trend towards a reduction in mortality.

Between observer variation is not eliminated by standardised analysis of dobutamine-atropine stress echocardiography.

AIMS: The conventional analysis of dobutamine-atropine stress echocardiography (DASE) is poorly defined and subject to considerable variation. The aim of this study was to investigate the reproducibility of strictly standardised qualitative analysis in DASE. METHODS AND RESULTS: Strict criteria for standardised DASE interpretation were defined through logistic regression analysis on categorical parameters obtained from 20 patients with coronary artery disease (CAD) and 20 healthy controls subjected to DASE. Three expert echocardiographers analysed DASE recordings from 100 consecutive patients referred for coronary angiography. Specificity for CAD and for predicting significant stenosis of a major coronary artery was 94% (95% CI: 83-100%) and 79% (95% CI: 63-96%), whereas sensitivity was 49% in both cases (95% CI: 38-60% and 37-61%). Within and between observer reproducibility was moderate to fair (kappa = 0.56 and 0.38; 95% CI: 0.40-0.72 and 0.24-0.52). In patients without prior myocardial infarction and in echogenic patients within observer reproducibility was good (kappa = 0.72 and 0.74; 95% CI: 0.52-0.92 and 0.56-0.92). CONCLUSIONS: Observer variation was not eliminated in standardised qualitative DASE interpretation based on criteria that predicted the presence of CAD with a high specificity and reproducibility was good only in certain subgroups of patients.

Low whole-body insulin sensitivity in patients with ischaemic heart disease is associated with impaired myocardial glucose uptake predictive of poor outcome after revascularisation.

We tested the hypothesis that low whole-body insulin sensitivity in patients with ischaemic heart disease and impaired left ventricular (LV) function is associated with abnormalities of insulin-mediated myocardial glucose uptake affecting outcome after coronary bypass surgery (CABG). We studied 29 patients with ischaemic heart disease and impaired LV ejection fraction (EF) and age-matched healthy volunteers ( n = 30). As assessed by euglycaemic glucose-insulin clamp, 15 patients had a low and 14 a normal whole-body insulin sensitivity. Using positron emission tomography, patterns of fluorine-18 fluorodeoxyglucose and nitrogen-13 ammonia uptake in addition to quantified glucose uptake, blood flow and hyperaemic blood flow were assessed before CABG in 16 myocardial segments of the left ventricle. Major adverse cardiac events and LVEF were evaluated 7 months after CABG. Glucose uptake in normokinetic PET-normal myocardium was found to be higher in patients with normal whole-body insulin sensitivity ( P < 0.001), whereas in patients with low whole-body insulin sensitivity more segments displayed a pattern of reduced glucose uptake in normoperfused myocardium (PET-reverse mismatch) ( P < 0.05). Hyperaemic blood flow was impaired in both patient groups. A major cardiac event after CABG could partly be predicted by the LV extent of normoperfused segments with PET-reverse mismatch. We conclude that low whole-body insulin sensitivity in patients with ischaemic heart disease and impaired LV function is associated with impaired insulin-mediated myocardial glucose uptake, which is partially predictive of a worse outcome after CABG.