Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: Rationale and design of the LEGACY study.

BACKGROUND: Early aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI. METHODS: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT. CONCLUSIONS: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.

Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps.

Clinical observations implicate a role of eosinophils in cardiovascular diseases because markers of eosinophil activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cells and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo, which identifies this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi, we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil-inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis.

Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients.

BACKGROUND: Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only. METHODS: A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22-39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves. RESULTS: The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001). Cumulus cell tested patients < 35 years (n = 65) or ≥ 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3-4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3. CONCLUSIONS: This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03659786 / NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered.

Comparison of post-stent optical coherence tomography findings among three subtypes of calcified culprit plaques in patients with acute coronary syndrome.

OBJECTIVES: To compare the postprocedural optical coherence tomography (OCT) findings and in-hospital outcomes among the three subtypes of calcified plaques: eruptive calcified nodules, superficial calcific sheet, and calcified protrusion. BACKGROUND: Recently, three subtypes of calcified culprit plaques were reported in patients with acute coronary syndrome (ACS). How these subtypes respond to stenting is unknown. METHODS: ACS patients with calcified plaque at the culprit lesion were selected from our database. OCT findings at baseline and after stent implantation were compared. RESULTS: In the final analysis, 87 cases were included. Preprocedural OCT showed eruptive calcified nodules in 19 (21.8%) cases, superficial calcific sheet in 63 (72.4%), and calcified protrusion in 5 (5.7%). Stent edge dissection (SED) and incomplete stent apposition (ISA) were frequently observed in the eruptive calcified nodules group compared to superficial calcific sheet or calcified protrusion (SED; 47.4% vs. 17.5% vs. 20.0%; p = .032, ISA; 94.7% vs. 58.7% vs. 0.0%; p < .001). The superficial calcific sheet group had the smallest minimal stent area (MSA) among the three groups (eruptive calcified nodules vs. superficial calcific sheet vs. calcified protrusion: 6.29 ± 2.41 vs. 4.72 ± 1.37 vs. 6.56 ± 1.13; p = .007). The superficial calcific sheet group had a higher rate of periprocedural myocardial infarction compared to the eruptive calcified nodules group (60.3% vs. 31.6%; p = .028). CONCLUSIONS: This study demonstrated eruptive calcified nodules are associated with higher incidence of SED and ISA, whereas superficial calcific sheets are associated with small MSA and higher periprocedural myocardial infarction.

Determinants of ST-segment elevation myocardial infarction as clinical presentation of acute coronary syndrome.

Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the most frequent underlying mechanisms of acute coronary syndromes (ACS). The conditions and medications that are associated with ST-segment elevation myocardial infarction (STEMI) following PR or PE have not been systematically studied. A total of 838 ACS patients (494 with STEMI, 344 with NSTE-ACS) who were diagnosed with PR or PE by optical coherence tomography were included. The patients were categorized into two groups based on underlying pathology, and the baseline characteristics and culprit plaque morphology associated with STEMI were investigated within each group. Among 838 patients, 467 (55.7%) had PR, and 371 (44.3%) were diagnosed with PE. Among patients with PR, older age, hyperlipidemia, no antiplatelet therapy, higher level of low-density lipoprotein cholesterol, and greater lipid burden and macrophage infiltration were associated with increased probability of STEMI. Among patients with PE, no dual antiplatelet therapy and no statin therapy were associated with increased probability of STEMI. The incidence of STEMI caused by PR was significantly lower on antiplatelet therapy (P < 0.001), and the incidence of STEMI caused by PE was significantly lower on antiplatelet therapy (P < 0.001) or on statin therapy (P < 0.001). Antiplatelet therapy is associated with lower probability of STEMI, regardless of underlying pathology, and statin therapy is associated with lower probability of STEMI in PE as clinical presentation of ACS. Statin therapy prior to the onset of acute coronary syndromes (ACS) may reduce the probability of plaque rupture. Antiplatelet therapy prior to the onset of ACS is associated with reduced probability of ST-segment elevation myocardial infarction (STEMI) following both plaque rupture and plaque erosion, and dual antiplatelet therapy offers additional protection compared to a single antiplatelet agent in plaque erosion. The combination of statin and antiplatelet therapy may have an additive effect on reducing the probability of STEMI caused by plaque erosion. Yellow: lipid pool(necrotic core); red: fibrin-rich thrombus; gray; platelet-rich thrombus.

Circadian variations in pathogenesis of ST-segment elevation myocardial infarction: an optical coherence tomography study.

Previous studies have reported a circadian variation in the onset of ST-segment elevation myocardial infarction (STEMI). However, underlying mechanisms for the circadian variation have not been fully elucidated. We investigated the relationship between onset of STEMI and the underlying pathology using optical coherence tomography (OCT). Patients with a diagnosis of STEMI were selected from a multicenter OCT registry. Patients were divided into 4 groups based on the estimated time of onset (00:00-05:59, 06:00-11:59, 12:00-17:59, or 18:00-23:59). Underlying pathologies of MI (plaque rupture, plaque erosion, and calcified plaque) were compared among the 4 groups. Among 648 patients, plaque rupture was diagnosed in 386 patients (59.6%), plaque erosion in 197 patients (30.4%), and calcified plaque in 65 patients (10.0%). A marked circadian variation was detected in the incidence of plaque rupture with a peak at 09:00, whereas it was not evident in plaque erosion or calcified plaque. The probability of plaque rupture significantly increased in the periods of 06:00-11:59 [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.30-3.49, p = 0.002] and 12:00-17:59 (OR 2.10, 95% CI 1.23-3.58, p = 0.005), compared to the period of 00:00-05:59. This circadian pattern was observed only during weekdays (p = 0.010) and it was not evident during the weekend (p = 0.742). Plaque rupture occurred most frequently in the morning and this circadian variation was evident only during weekdays. Acute MI caused by plaque rupture may be related to catecholamine surge.

Pulsus Alternans as a Sign of Right Ventricular Failure After Left Ventricular Assist Device Implantation.

Temporary left ventricular assist devices such as the ImpellaTM are increasingly used in patients with cardiogenic shock. The right ventricle remains the Achilles heel of left ventricular assist device-supported circulation. However, right ventricular failure after implantation of a left ventricular assist device remains incompletely defined and understood. We describe the first case of pulsus paradoxus emerging after the initiation of circulatory support using a left ventricular ImpellaTM device, which is an early sign of right ventricular failure, that was completely abolished after the addition of a temporary right ventricular assist device.

Double stent fracture and in-stent restenosis due to nodular calcification treated with Shockwave coronary intravascular lithotripsy.

We describe the fracture of a double layer of stents caused by nodular calcification. This resulted in recurrent in-stent restenosis, which was treated with Shockwave coronary intravascular lithotripsy.

Relative risk of plaque erosion among different age and sex groups in patients with acute coronary syndrome.

Postmortem studies reported plaque erosion is frequent in young women. Recent in vivo studies failed to show age and sex differences in the plaque erosion prevalence. The aim of this study was to investigate the prevalence of plaque erosion by age and sex among acute coronary syndromes (ACS) patients. From 1699 ACS patients, 1083 with plaque erosion or rupture were analyzed. Patients were categorized as 5 age groups (≤ 50, 51-60, 61-70, 71-80, ≥ 81 years). Overall prevalence of plaque erosion was similar between males and females (p = 0.831). Males age ≤ 50 had higher (p = 0.018) and age 71-80 had lower (p = 0.006) prevalence of plaque erosion. Females age 61-70 had higher (p = 0.021) and age 71-80 had lower (p = 0.045) prevalence of plaque erosion. In advanced age groups (≥ 71 years), rupture was the dominant etiology in both sexes. In multivariate analysis of males, age ≤ 50 demonstrated a trend to increase (OR 1.418, 95% CI 0.961-2.093, p = 0.078) the erosion risk. Females age ≤ 70 independently increased (OR 2.138, 95% CI 1.249-3.661, p = 0.006) the risk for erosion. The prevalence of plaque erosion was similar between males and females. Plaque erosion risk was increased in the males age ≤ 50 and in the females age ≤ 70 among ACS patients.

General Anesthesia Versus Monitored Anesthesia Care for Transfemoral Transcatheter Aortic Valve Implantation: A Retrospective Study in a Single Belgian Referral Center.

OBJECTIVE: The objective of this study was to compare the effect of general anesthesia (GA) versus monitored anesthesia care (MAC) on post-interventional outcomes in patients undergoing transfemoral transcatheter aortic valve implantation (TAVI). DESIGN: Retrospective before-after study using a quasi-experimental design. SETTING: University Hospitals Leuven, a single Belgian referral center. PARTICIPANTS: Patients undergoing transfemoral TAVI from March 1, 2014, to December 31, 2017, were included. INTERVENTIONS: GA was switched to MAC at the authors' institution for transfemoral TAVI in April 2016, and outcomes of patients who received GA were compared with those who received MAC. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were length of stay in the intensive care unit and hospital. Secondary outcomes included standardized endpoints for TAVI trials as suggested by the Valve Academic Research Consortium, the incidence of vasopressor use, maximum dose of vasopressors, procedural time, and total anesthesia time. In the period studied, 178 patients underwent transfemoral TAVI (GA: n = 85; MAC: n = 93). Implementation of MAC was associated with a significant reduction in total length of hospital stay (7.6 [6.05-9.15] v 5.48 [4.58-6.38] d; p = 0.02); vasopressor requirements; and procedural and total anesthesia time. Length of intensive care unit stay and Valve Academic Research Consortium endpoints were not significantly different. CONCLUSIONS: In the authors' institution, implementation of MAC for patients undergoing transfemoral TAVI resulted in a significant reduction of hospital length of stay and increased operating room efficiency. Results could be confounded by increasing operator experience and improved implantation techniques.

Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial.

Aims: Inhalation of nitric oxide (iNO) during myocardial ischaemia and after reperfusion confers cardioprotection in preclinical studies via enhanced cyclic guanosine monophosphate (cGMP) signalling. We tested whether iNO reduces reperfusion injury in patients with ST-elevation myocardial infarction (STEMI; NCT01398384). Methods and results: We randomized in a double-blind, placebo-controlled study 250 STEMI patients to inhale oxygen with (iNO) or without (CON) 80 parts-per-million NO for 4 h following percutaneous revascularization. Primary efficacy endpoint was infarct size as a fraction of left ventricular (LV) size (IS/LVmass), assessed by delayed enhancement contrast magnetic resonance imaging (MRI). Pre-specified subgroup analysis included thrombolysis-in-myocardial-infarction flow in the infarct-related artery, troponin T levels on admission, duration of symptoms, location of culprit lesion, and intra-arterial nitroglycerine (NTG) use. Secondary efficacy endpoints included IS relative to risk area (IS/AAR), myocardial salvage index, LV functional recovery, and clinical events at 4 and 12 months. In the overall population, IS/LVmass at 48-72 h was 18.0 ± 13.4% in iNO (n = 109) and 19.4 ± 15.4% in CON [n = 116, effect size -1.524%, 95% confidence interval (95% CI) -5.28, 2.24; P = 0.427]. Subgroup analysis indicated consistency across clinical confounders of IS but significant treatment interaction with NTG (P = 0.0093) resulting in smaller IS/LVmass after iNO in NTG-naïve patients (n = 140, P < 0.05). The secondary endpoint IS/AAR was 53 ± 26% with iNO vs. 60 ± 26% in CON (effect size -6.8%, 95% CI -14.8, 1.3, P = 0.09) corresponding to a myocardial salvage index of 47 ± 26% vs. 40 ± 26%, respectively, P = 0.09. Cine-MRI showed similar LV volumes at 48-72 h, with a tendency towards smaller increases in end-systolic and end-diastolic volumes at 4 months in iNO (P = 0.048 and P = 0.06, respectively, n = 197). Inhalation of nitric oxide was safe and significantly increased cGMP plasma levels during 4 h reperfusion. The Kaplan-Meier analysis for the composite of death, recurrent ischaemia, stroke, or rehospitalizations showed a tendency toward lower event rates with iNO at 4 months and 1 year (log-rank test P = 0.10 and P = 0.06, respectively). Conclusions: Inhalation of NO at 80 ppm for 4 h in STEMI was safe but did not reduce infarct size relative to absolute LVmass at 48-72h. The observed functional recovery and clinical event rates at follow-up and possible interaction with nitroglycerine warrant further studies of iNO in STEMI.

Major adverse cardiovascular events while awaiting staged non-culprit percutaneous coronary intervention after ST-segment elevation myocardial infarction.

BACKGROUND: The optimal therapeutic strategy for ST-segment elevation myocardial infarction (STEMI) patients found to have multi-vessel disease (MVD) is controversial but recent data support complete revascularisation (CR). Whether CR should be completed during the index admission or during a second staged admission remains unclear. Our main objective was to measure rates of major adverse cardiovascular events (MACEs) during the waiting period in STEMI patients selected for staged revascularisation (SR), in order to determine the safety of delaying CR. For completeness, we also describe 30-day and long-term outcomes in STEMI patients with MVD who underwent in-hospital CR. METHODS: A single-centre retrospective analysis of 931 STEMI patients treated by primary percutaneous coronary intervention (PCI) identified 397 patients with MVD who were haemodynamically stable and presented within 12 hours of chest pain onset. Of these, 191 underwent multi-vessel PCI: 49 during the index admission and 142 patients undergoing a strategy of SR. RESULTS: Our main finding was that waiting period MACE were 2% (three of 142) in patients allocated to SR (at a median of 31 days). In patients allocated to in-hospital CR, 30-day MACE rates were 10% (five of 49). During a median follow up of 39 months, all-cause mortality was 7.0% vs. 28.6%, and cardiac mortality was 2% vs. 8%, in patients allocated to SR or CR, respectively. CONCLUSIONS: Patients with STEMI and MVD who, based on clinical judgement, were allocated to a second admission SR strategy had very few adverse events during the waiting period and excellent long-term outcomes.

Optical Coherence Tomography Findings in Patients With Coronary Stent Thrombosis: A Report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort).

BACKGROUND: Stent thrombosis (ST) is a serious complication following coronary stenting. Intravascular optical coherence tomography (OCT) may provide insights into mechanistic processes leading to ST. We performed a prospective, multicenter study to evaluate OCT findings in patients with ST. METHODS: Consecutive patients presenting with ST were prospectively enrolled in a registry by using a centralized telephone registration system. After angiographic confirmation of ST, OCT imaging of the culprit vessel was performed with frequency domain OCT. Clinical data were collected according to a standardized protocol. OCT acquisitions were analyzed at a core laboratory. Dominant and contributing findings were adjudicated by an imaging adjudication committee. RESULTS: Two hundred thirty-one patients presenting with ST underwent OCT imaging; 14 (6.1%) had image quality precluding further analysis. Of the remaining patients, 62 (28.6%) and 155 (71.4%) presented with early and late/very late ST, respectively. The underlying stent type was a new-generation drug-eluting stent in 50.3%. Mean reference vessel diameter was 2.9±0.6 mm and mean reference vessel area was 6.8±2.6 mm2. Stent underexpansion (stent expansion index <0.8) was observed in 44.4% of patients. The predicted average probability (95% confidence interval) that any frame had uncovered (or thrombus-covered) struts was 99.3% (96.1-99.9), 96.6% (92.4-98.5), 34.3% (15.0-60.7), and 9.6% (6.2-14.5) and malapposed struts was 21.8% (8.4-45.6), 8.5% (4.6-15.3), 6.7% (2.5-16.3), and 2.0% (1.2-3.3) for acute, subacute, late, and very late ST, respectively. The most common dominant finding adjudicated for acute ST was uncovered struts (66.7% of cases); for subacute ST, the most common dominant finding was uncovered struts (61.7%) and underexpansion (25.5%); for late ST, the most common dominant finding was uncovered struts (33.3%) and severe restenosis (19.1%); and for very late ST, the most common dominant finding was neoatherosclerosis (31.3%) and uncovered struts (20.2%). In patients presenting very late ST, uncovered stent struts were a common dominant finding in drug-eluting stents, and neoatherosclerosis was a common dominant finding in bare metal stents. CONCLUSIONS: In patients with ST, uncovered and malapposed struts were frequently observed with the incidence of both decreasing with longer time intervals between stent implantation and presentation. The most frequent dominant observation varied according to time intervals from index stenting: uncovered struts and underexpansion in acute/subacute ST and neoatherosclerosis and uncovered struts in late/very late ST.

Impact of ultra-thin struts on restenosis after chronic total occlusion recanalization: Insights from the randomized PRISON IV trial.

OBJECTIVES: The PRISON-IV trial showed inferior outcome in patients with chronic total occlusions (CTOs) treated with the ultrathin-struts (60 µm for stent diameter ≤3 mm, 81µm >3 mm) hybrid-sirolimus eluting stents (SES) compared with everolimus eluting stents (EES, 81 µm). The aim of this study is to investigate if the use of smaller stents (≤3 mm) was responsible for the inferior outcome reported in the trial. METHODS: In the PRISON-IV trial 330 patients with CTO lesion were randomized 1:1 to receive either hybrid-SES or EES. The hybrid-SES failed to reach the non-inferiority primary endpoint of in-segment late lumen loss (LLL) at 9-month angiographic follow-up. In this sub-analysis, we divided the population according to the different size of stents implanted in those receiving only stents with diameter ≤3 mm (Group-A, 178 patients), only stents >3 mm (Group-B, 59 patients), and those receiving stents of both sizes (Group-C, 93 patients). RESULTS: Baseline and procedural characteristics were comparable in the three groups. At angiographic follow-up, most of the adverse outcomes occurred in Group A, with higher incidence of binary restenosis in the Hybrid-SES versus EES (10.3% vs 1.3%, P = 0.03) and augmented in-stent diameter stenosis (26.04 ± 18.59% vs 21.24 ± 12.84, P = 0.06). Similarly, optical coherence tomography (OCT), which was performed in 60 patients at follow-up, documented a mild trend toward lower values of minimum in stent area in Hybrid-SES arm of Group A (4.4 ± 1.02mm2 vs 5.0 ± 1.28mm2, respectively, P = 0.16). CONCLUSIONS: The present analysis suggests that the inferior performance of the ultra-thin hybrid-SES in CTO-PCI is particularly pronounced when smaller stent (≤3 mm diameter) are adopted, if compared with EES.

Anatomical and functional assessment of Tryton bifurcation stent before and after final kissing balloon dilatation: Evaluations by three-dimensional coronary angiography, optical coherence tomography imaging and fractional flow reserve.

OBJECTIVES: To assess the anatomical and functional impact of final kissing balloon inflation (FKBI) after implantation of a dedicated bifurcation stent system. BACKGROUND: Current evidence suggests clinical benefit of FKBI in patients undergoing bifurcation dilatation using the Tryton side branch stent (Tryton-SBS). We hypothesized that FKBI improves anatomical reconstruction and functional results of bifurcation treated by Tryton-SBS. METHODS: An unselected group of patients with complex bifurcation coronary lesions undergoing percutaneous coronary intervention (PCI) with Tryton-SBS underwent paired anatomical assessment with two- and three-dimensional quantitative coronary analysis (2D- and 3D-QCA), and optical coherence tomography (OCT), including 3D reconstruction before and after FKBI. Functional assessment by fractional flow reserve (FFR) was performed in the main branch (MB) and side branch (SB) before and after FKBI. RESULTS: Paired pre- and post-FKBI data were obtained in 10 patients. By OCT imaging, FKBI increased both the SB ostial area (4.93 ± 2.81 vs. 7.43 ± 2.87 mm2 , P < 0.001) and the SB maximum diameter (3.12 ± 0.98 vs. 3.82 ± 1.10 mm, P = 0.003). These findings were associated with a significant increase in FFR in the SB (0.90 ± 0.05 vs. 0.94 ± 0.03; P = 0.011), with no significant change in the MB (0.91 ± 0.05 vs. 0.92 ± 0.04; P = 0.470). CONCLUSIONS: In patients with complex bifurcation stenosis undergoing PCI with a dedicated bifurcation system, FKBI is associated with improved anatomical and functional results at the SB level, without compromising the result at the MB. © 2016 Wiley Periodicals, Inc.

Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium.

BACKGROUND: Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multicentre study to evaluate thrombus specimens in patients with ST across Europe. METHODS: Patients presenting with ST and undergoing thrombus aspiration were eligible for inclusion. Thrombus collection was performed according to a standardized protocol and specimens were analysed histologically at a core laboratory. Serial tissue cross sections were stained with haematoxylin-eosin (H&E), Carstairs and Luna. Immunohistochemistry was performed to identify leukocyte subsets, prothrombotic neutrophil extracellular traps (NETs), erythrocytes, platelets, and fibrinogen. RESULTS: Overall 253 thrombus specimens were analysed; 79 (31.2%) from patients presenting with early ST, 174 (68.8%) from late ST; 79 (31.2%) were from bare metal stents, 166 (65.6%) from drug-eluting stents, 8 (3.2%) were from stents of unknown type. Thrombus specimens displayed heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments most abundant; mean platelet coverage was 57% of thrombus area. Leukocyte infiltrations were hallmarks of both early and late ST (early: 2260 ± 1550 per mm(2) vs. late: 2485 ± 1778 per mm(2); P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm(2) vs. late: 1428 ± 1023 per mm(2); P = 0.81). Leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction. Neutrophil extracellular traps were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-and everolimus-eluting stents. CONCLUSION: In a large-scale study of histological thrombus analysis from patients presenting with ST, thrombus specimens displayed heterogeneous morphology. Recruitment of leukocytes, particularly neutrophils, appears to be a hallmark of ST. The presence of NETs supports their pathophysiological relevance. Eosinophil recruitment suggests an allergic component to the process of ST.

Aortic Regurgitation after TAVR: From Bad to Worse.

Transcatheter aortic valve replacement (TAVR) is a valuable alternative in surgical high-risk patients with symptomatic aortic valve stenosis. Here, the case is presented of very early transcatheter heart valve degeneration, probably caused by a 'Venturi effect' of a severe paravalvular regurgitant jet. This ultimately led to a leaflet being in the open position, creating severe valvular regurgitation that necessitated classical surgical revision. The occurrence of paravalvular regurgitation, and its known relationship with an adverse prognosis after TAVR, demonstrates the clear need for innovative alterations in valve design to prevent this complication. Video 1: Angiography immediately after implantation of an Edwards SAPIEN 23 mm transcatheter heart valve, showing severe paravalvular aortic valve regurgitation. The implantation position is rather low. Video 2: Transesophageal echocardiography with 2-D color imaging showing aortic valve long-axis view at 131°, three days after implantation of an Edwards SAPIEN 23 mm transcatheter heart valve. Severe eccentric paravalvular aortic valve regurgitation is shown without a significant valvular component. The implantation position is rather low. Video 3: Transesophageal echocardiography with 2-D color imaging showing aortic valve long-axis view at 120°, one month after implantation of an Edwards SAPIEN 23 mm transcatheter heart valve. Severe combined valvular and paravalvular aortic valve regurgitation (grade 4/4) is shown.