Continuation versus Interruption of Oral Anticoagulation during TAVI.

BACKGROUND: One third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism. METHODS: We conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI. RESULTS: A total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], -3.1 to 6.6; P = 0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, -3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6). CONCLUSIONS: In patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days. (Funded by the Netherlands Organization for Health Research and Development and the St. Antonius Research Fund; POPular PAUSE TAVI ClinicalTrials.gov number, NCT04437303.).

LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis: a randomised non-inferiority trial.

BACKGROUND: Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1·5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA). METHODS: In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2-4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10·44% and assuming an event rate of 26·10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants. FINDINGS: Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80·0 years (SD 5·7) for those treated with the Myval THV and 80·4 years (5·4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2·6% [IQR 1·7-4·0] vs contemporary 2·6% [1·7-4·0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of -2·3% (one-sided upper 95% CI 3·8, pnon-inferiority<0·0001). No significant difference was seen in individual components of the primary composite endpoint. INTERPRETATION: In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days. FUNDING: Meril Life Sciences.

The impact of unilateral pulmonary artery stenosis on right ventricular to pulmonary arterial coupling in patients with transposition of the great arteries.

BACKGROUND: Unilateral pulmonary artery (PA) stenosis is common in the transposition of the great arteries (TGA) after arterial switch operation (ASO) but the effects on the right ventricle (RV) remain unclear. AIMS: To assess the effects of unilateral PA stenosis on RV afterload and function in pediatric patients with TGA-ASO. METHODS: In this retrospective study, eight TGA patients with unilateral PA stenosis underwent heart catheterization and cardiac magnetic resonance (CMR) imaging. RV pressures, RV afterload (arterial elastance [Ea]), PA compliance, RV contractility (end-systolic elastance [Ees]), RV-to-PA (RV-PA) coupling (Ees/Ea), and RV diastolic stiffness (end-diastolic elastance [Eed]) were analyzed and compared to normal values from the literature. RESULTS: In all TGA patients (mean age 12 ± 3 years), RV afterload (Ea) and RV pressures were increased whereas PA compliance was reduced. RV contractility (Ees) was decreased resulting in RV-PA uncoupling. RV diastolic stiffness (Eed) was increased. CMR-derived RV volumes, mass, and ejection fraction were preserved. CONCLUSION: Unilateral PA stenosis results in an increased RV afterload in TGA patients after ASO. RV remodeling and function remain within normal limits when analyzed by CMR but RV pressure-volume loop analysis shows impaired RV diastolic stiffness and RV contractility leading to RV-PA uncoupling.

Intracardiac echocardiography-guided biopsies for right-sided intracardiac tumors: An optimized diagnostic algorithm and case illustrations.

Intracardiac tumors, though uncommon, necessitate a swift and accurate diagnosis for personalized treatment and prognosis estimation. While multi-modality imaging often determines the etiology of these cardiac masses, histological confirmation remains essential for definitive diagnosis and its specific treatment. Since cardiac tumors are often found in high-risk locations (ventricular free wall or atria), precision biopsy is paramount. The least invasive strategy would be to achieve this by means of endomyocardial biopsy (EMB); however real-time additional imaging is essential to reduce the risk of perforation/tamponade and to minimize sampling error. Intracardiac echocardiography (ICE) emerges as an excellent tool to achieve this goal preventing procedural complications and reducing the likelihood of sampling errors obtaining a definitive histopathological diagnosis in all cases. This paper outlines our diagnostic algorithm for optimal patient selection, details three illustrative cases, and elucidates the steps to acquire histopathology via percutaneous transvenous biopsy with ICE guidance in patients with right-sided cardiac tumors. Given the rarity of intracardiac tumors, we advocate these patients be managed by a dedicated multidisciplinary cardio-oncology team including an interventional cardiologist.

The effects of percutaneous branch pulmonary artery interventions on exercise capacity, lung perfusion, and right ventricular function in biventricular CHD: a systematic review.

BACKGROUND: Branch pulmonary artery stenosis is common after surgical repair in patients with biventricular CHD and often requires reinterventions. However, (long-term) effects of percutaneous branch pulmonary artery interventions on exercise capacity, right ventricular function, and lung perfusion remain unclear. This review describes the (long-term) effects of percutaneous branch pulmonary artery interventions on exercise capacity, right ventricular function, and lung perfusion following PRISMA guidelines. METHODS: We performed a systematic search in PubMed, Embase, and Cochrane including studies about right ventricular function, exercise capacity, and lung perfusion after percutaneous branch pulmonary artery interventions. Study selection, data extraction, and quality assessment were performed by two researchers independently. RESULTS: In total, 7 eligible studies with low (n = 2) and moderate (n = 5) risk of bias with in total 330 patients reported on right ventricular function (n = 1), exercise capacity (n = 2), and lung perfusion (n = 7). Exercise capacity and lung perfusion seem to improve after a percutaneous intervention for branch pulmonary artery stenosis. No conclusions about right ventricular function or remodelling, differences between balloon and stent angioplasty or specific CHD populations could be made. CONCLUSION: Although pulmonary artery interventions are frequently performed in biventricular CHD, data on relevant outcome parameters such as exercise capacity, lung perfusion, and right ventricular function are largely lacking. An increase in exercise capacity and improvement of lung perfusion to the affected lung has been described in case of mild to more severe pulmonary artery stenosis during relatively short follow-up. However, there is need for future studies to evaluate the effect of pulmonary artery interventions in various CHD populations.

The value of computed tomography for head trauma in patients presenting with out-of-hospital cardiac arrest before emergency percutaneous coronary intervention.

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) caused by an ST-elevation myocardial infarction (STEMI) is often accompanied by a sudden loss of consciousness that may cause the patient to collapse with resulting head trauma, leading to a suspicion of possible intracranial haemorrhage. To rule out intracranial haemorrhage before emergency percutaneous coronary intervention (PCI), emergency computed tomography (CT) of the head might be useful but also causes a delay in percutaneous STEMI treatment. METHODS: The medical records of all adult patients that presented with OHCA to the emergency department (ED) of the University Medical Centre Utrecht (UMCU), the Netherlands between 16 February 2020 and 16 February 2022 were reviewed. RESULTS: A total of 263 patients presented to the ED with an OHCA; 50 presented with a STEMI requiring emergency PCI. Thirty-nine (78%) patients with a STEMI were immediately referred to the catheterisation laboratory and 11 (22%) STEMI patients underwent a CT scan prior to emergency angiography; in no case was PCI deferred on the basis of the CT findings. The dominant indication for CT of the head was collapse, reported by 10 patients and resulting in a visible traumatic head injury in 7 patients. In none of the patients was intracranial haemorrhage detected. However, there was a delay between presentation to the ED and arrival at the catheterisation laboratory in patients who underwent CT of the head (mean 63 ± 25 min) before emergency PCI compared to patients without a CT scan (mean 37 ± 21 min). CONCLUSION: CT of the head did not result in a diagnosis of intracranial haemorrhage or deferral of PCI but did delay PCI treatment for STEMI in patients presenting with OHCA.

ECPELLA as a bridge-to-decision in refractory cardiogenic shock: a single-centre experience.

BACKGROUND: In refractory cardiogenic shock, temporary mechanical support (tMCS) may be crucial for maintaining tissue perfusion and oxygen delivery. tMCS can serve as a bridge-to-decision to assess eligibility for left ventricular assist device (LVAD) implantation or heart transplantation, or as a bridge-to-recovery. ECPELLA is a novel tMCS configuration combining venoarterial extracorporeal membrane oxygenation with Impella. The present study presents the clinical parameters, outcomes, and complications of patients supported with ECPELLA. METHODS: All patients supported with ECPELLA at University Medical Centre Utrecht between December 2020 and August 2023 were included. The primary outcome was 30-day mortality, and secondary outcomes were LVAD implantation/heart transplantation and safety outcomes. RESULTS: Twenty patients with an average age of 51 years, and of whom 70% were males, were included. Causes of cardiogenic shock were acute heart failure (due to acute coronary syndrome, myocarditis, or after cardiac surgery) or chronic heart failure, respectively 70 and 30% of cases. The median duration of ECPELLA support was 164 h (interquartile range 98-210). In 50% of cases, a permanent LVAD was implanted. Cardiac recovery within 30 days was seen in 30% of cases and 30-day mortality rate was 20%. ECPELLA support was associated with major bleeding (40%), haemolysis (25%), vascular complications (30%), kidney failure requiring replacement therapy (50%), and Impella failure requiring extraction (15%). CONCLUSION: ECPELLA can be successfully used as a bridge to LVAD implantation or as a bridge-to-recovery in patients with refractory cardiogenic shock. Despite a significant number of complications, 30-day mortality was lower than observed in previous cohorts.

Long-term follow-up of contemporary drug-eluting stent implantation in diabetic patients: Subanalysis of a randomized controlled trial.

OBJECTIVE: The elevated risk of adverse events following percutaneous coronary intervention in diabetic patients persists with newer-generation DES. The polymer-free amphilimus-eluting stent (PF-AES) possesses characteristics with a potentially enhanced performance in patients with diabetes. Data from the 1-year follow-up period has been previously published. The aim of this subanalysis was to assess long-term performance of two contemporary drug-eluting stents (DES) in a diabetic population. METHODS: In the ReCre8 trial, patients were stratified for diabetes and troponin status, and randomized to implantation of a permanent polymer zotarolimus-eluting stent (PP-ZES) or PF-AES. The primary endpoint was target-lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. Clinical outcomes between discharge and 3 years follow-up were assessed. RESULTS: A total of 302 patients with diabetes were included in this analysis. After 3 years, TLF occurred in 12.5% of PP-ZES patients versus 10.0% in PF-AES patients (p = 0.46). Similarly, the separate components of TLF were comparable between the two study arms. The secondary composite endpoint of NACE was higher in the PP-ZES arm with 45 cases (29.6%) versus 30 cases (20.0%) in the PF-AES arm (p = 0.036). In the insulin-dependent diabetic population, TLF occurred in 19.1% of PP-ZES patients versus 10.4% of PF-AES patients (p = 0.21). NACE occurred in 40.4% of PP-ZES patients versus 27.1% of PF-AES patients (p = 0.10). CONCLUSIONS: This subanalysis shows that the use of PF-AES results in similar clinical outcomes as compared to PP-ZES, yet some benefits of use of PF-AES in diabetic patients may prevail. Future dedicated trials should confirm these findings.

Anatomical predictors for suture-based closure of the patent foramen ovale: A multicenter experience.

BACKGROUND: NobleStitch EL is a novel suture-based technique used for patent foramen ovale (PFO) closure and an alternative to traditional double-disc devices without the need for antithrombotic therapy. However, successful closure rates are still unknown, and certain anatomies may be unfavorable for successful closure. AIMS: We assessed the efficacy of the NobleStitch EL and sought to identify patient-related anatomical features associated with successful suture-based closure. METHODS: We included 55 patients who underwent PFO closure with the NobleStitch EL in The Netherlands and Switzerland. Successful closure was defined as residual right-to-left shunt grade ≤1 with Valsalva maneuver at a cardiac ultrasound. Predefined possible anatomical determinants for effective closure included PFO length, atrial septal aneurysm, PFO entry- and exit diameter. RESULTS: Successful closure was achieved in 33 patients (60%). The PFO length was shorter in patients with successful closure compared to unsuccessful closure with a median length of 9.6 mm (IQR 8.0-15.0) versus 13.3 mm (IQR 11.4-18.6) on preprocedural ultrasound (p = 0.041) and 9.9 mm (IQR 8.0-13.1) versus 12.5 mm (IQR 9.7-15.4) on angiography (p = 0.049). Additionally, the PFO exit diameter and PFO volume were smaller in patients with successful closure than unsuccessful closure, with a mean diameter of 7.0 ± 3.1 mm versus 9.5 ± 3.8 mm (p = 0.015) and a median volume of 381 mm3 (IQR 286-894) versus 985 mm3 (IQR 572-1550) (p = 0.016). CONCLUSION: In our study cohort, the successful PFO closure rate using NobleStitch EL was relatively low (60%). With this alternative procedure, patients with a small PFO driven by a short PFO tunnel length and small exit diameter seem to be eligible for successful suture-based closure.

Comparison of Four-Dimensional Flow MRI, Two-Dimensional Phase-Contrast MRI and Echocardiography in Transposition of the Great Arteries.

Pulmonary artery (PA) stenosis is a common complication after the arterial switch operation (ASO) for transposition of the great arteries (TGA). Four-dimensional flow (4D flow) CMR provides the ability to quantify flow within an entire volume instead of a single plane. The aim of this study was to compare PA maximum velocities and stroke volumes between 4D flow CMR, two-dimensional phase-contrast (2D PCMR) and echocardiography. A prospective study including TGA patients after ASO was performed between December 2018 and October 2020. All patients underwent echocardiography and CMR, including 2D PCMR and 4D flow CMR. Maximum velocities and stroke volumes were measured in the main, right, and left PA (MPA, LPA, and RPA, respectively). A total of 39 patients aged 20 ± 8 years were included. Maximum velocities in the MPA, LPA, and RPA measured by 4D flow CMR were significantly higher compared to 2D PCMR (p < 0.001 for all). PA assessment by echocardiography was not possible in the majority of patients. 4D flow CMR maximum velocity measurements were consistently higher than those by 2D PCMR with a mean difference of 65 cm/s for the MPA, and 77 cm/s for both the RPA and LPA. Stroke volumes showed good agreement between 4D flow CMR and 2D PCMR. Maximum velocities in the PAs after ASO for TGA are consistently lower by 2D PCMR, while echocardiography only allows for PA assessment in a minority of cases. Stroke volumes showed good agreement between 4D flow CMR and 2D PCMR.

Percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis.

OBJECTIVE: The importance of revascularisation of significant coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) is unclear. Despite the lack of randomised controlled trials comparing different revascularisation strategies, guidelines currently recommend percutaneous coronary intervention (PCI) in patients with significant proximal CAD undergoing TAVI. METHODS: In this systematic review and meta-analysis, a systematic search was conducted to identify studies comparing TAVI with and without PCI in patients with significant CAD on pre-TAVI coronary angiography. Endpoints were all-cause mortality, cardiac death, stroke, myocardial infarction and major bleeding. RESULTS: In total, 14 studies were included, involving 3838 patients, of whom 1806 (47%) underwent PCI before TAVI. All-cause mortality did not differ significantly between TAVI with and without preceding PCI at 30 days, 1 year and > 1 year. There were no significant differences in risk of cardiac death, stroke or myocardial infarction between the groups. However, TAVI performed with PCI resulted in a higher risk of major bleeding within 30 days after TAVI (odds ratio: 0.66; 95% confidence interval: 0.46-0.94). CONCLUSION: This systematic review and meta-analysis showed no significant differences in clinical outcomes between patients with concomitant significant CAD who were treated with TAVI with and without preceding PCI at both short- and long-term follow-up. However, there was a higher risk of major bleeding at 30 days in patients undergoing TAVI with preceding PCI. In the context of serious risk of bias in the included studies, results of randomised controlled trials are warranted.

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.

BACKGROUND: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain. METHODS: In this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit. RESULTS: At 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P = 0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points. CONCLUSIONS: Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, NTR4973.).

Rationale and Design of the Groningen Intervention Study for the Preservation of Cardiac Function with Sodium Thiosulfate after St-segment Elevation Myocardial Infarction (GIPS-IV) trial.

BACKGROUND: Ischemia and subsequent reperfusion cause myocardial injury in patients presenting with ST-segment elevation myocardial infarction (STEMI). Hydrogen sulfide (H2S) reduces "ischemia-reperfusion injury" in various experimental animal models, but has not been evaluated in humans. This trial will examine the efficacy and safety of the H2S-donor sodium thiosulfate (STS) in patients presenting with a STEMI. STUDY DESIGN: The Groningen Intervention study for the Preservation of cardiac function with STS after STEMI (GIPS-IV) trial (NCT02899364) is a double-blind, randomized, placebo-controlled, multicenter trial, which will enroll 380 patients with a first STEMI. Patients receive STS 12.5 grams intravenously or matching placebo in addition to standard care immediately at arrival at the catheterization laboratory after providing consent. A second dose is administered 6 hours later at the coronary care unit. The primary endpoint is myocardial infarct size as quantified by cardiac magnetic resonance imaging 4 months after randomization. Secondary endpoints include the effect of STS on peak CK-MB during admission and left ventricular ejection fraction and NT-proBNP levels at 4 months follow-up. Patients will be followed-up for 2 years to assess clinical endpoints. CONCLUSIONS: The GIPS-IV trial is the first study to determine the effect of a H2S-donor on myocardial infarct size in patients presenting with STEMI.

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm. DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial. SETTING: Nineteen hospitals in The Netherlands. PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups. CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

Clinical outcomes after permanent polymer or polymer-free stent implantation in patients with diabetes mellitus: The ReCre8 diabetes substudy.

OBJECTIVES: The purpose of this analysis was to compare target-lesion failure (TLF) of a permanent polymer zotarolimus-eluting stent (PP-ZES) versus a polymer-free amphilimus-eluting stent (PF-AES) in diabetics. BACKGROUND: The improvement of outcomes with new-generation drug-eluting stent as seen in the general population is less pronounced among diabetics. The PF-AES introduces an elution-technology with potential enhanced performance in diabetics. METHODS: In this subanalysis of the ReCre8 trial, patients were randomized to either a PP-ZES or PF-AES after stratification for diabetes and troponin status. The primary device-oriented endpoint was TLF, a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. RESULTS: In the ReCre8 trial, 304 (20%) patients were diabetic and 96 (6%) had insulin-dependent diabetes mellitus. There was no statistically significant difference between the two study arms regarding the primary endpoint (PP-ZES 7.2% vs. PF-AES 4.0%; p = .21), although the composite of net adverse clinical events was higher in the PP-ZES arm (15.7 vs. 8.0%; p = .035). Stent thrombosis was low in both groups with no cases in the PP-ZES arm and 1 case in the PF-AES arm (p = .32). Regarding insulin-treated diabetics, TLF was higher in the PP-ZES arm (14.9 vs. 2.1%; p = .022). CONCLUSIONS: Diabetics could potentially benefit from a dedicated stent, releasing sirolimus with a lipophilic carrier (amphilimus-formulation). Future trials should confirm the potential benefit of a PF-AES in this population.

Patient-tailored antithrombotic therapy following percutaneous coronary intervention.

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice.

Donor genetic variants as risk factors for thrombosis after liver transplantation: A genome-wide association study.

Thrombosis after liver transplantation substantially impairs graft- and patient survival. Inevitably, heritable disorders of coagulation originating in the donor liver are transmitted by transplantation. We hypothesized that genetic variants in donor thrombophilia genes are associated with increased risk of posttransplant thrombosis. We genotyped 775 donors for adult recipients and 310 donors for pediatric recipients transplanted between 1993 and 2018. We determined the association between known donor thrombophilia gene variants and recipient posttransplant thrombosis. In addition, we performed a genome-wide association study (GWAS) and meta-analyzed 1085 liver transplantations. In our donor cohort, known thrombosis risk loci were not associated with posttransplant thrombosis, suggesting that it is unnecessary to exclude liver donors based on thrombosis-susceptible polymorphisms. By performing a meta-GWAS from children and adults, we identified 280 variants in 55 loci at suggestive genetic significance threshold. Downstream prioritization strategies identified biologically plausible candidate genes, among which were AK4 (rs11208611-T, p = 4.22 × 10-05 ) which encodes a protein that regulates cellular ATP levels and concurrent activation of AMPK and mTOR, and RGS5 (rs10917696-C, p = 2.62 × 10-05 ) which is involved in vascular development. We provide evidence that common genetic variants in the donor, but not previously known thrombophilia-related variants, are associated with increased risk of thrombosis after liver transplantation.

Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial.

BACKGROUND: Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding [superiority hypothesis]). Co-primary net clinical benefit outcome consisted of all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013-001403-37). FINDINGS: Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 [18%] of 500 patients) than in the ticagrelor group (118 [24%] of 502; hazard ratio 0·71, 95% CI 0·54 to 0·94; p=0·02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 [28%]) versus ticagrelor (161 [32%]; absolute risk difference -4%, 95% CI -10·0 to 1·4; p=0·03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35). INTERPRETATION: In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk. FUNDING: ZonMw.

Comparison of the Sapien 3 versus the ACURATE neo valve system: A propensity score analysis.

OBJECTIVES: To compare the outcomes of transfemoral ACURATE neo (NEO) and Sapien 3 (S3) patients in terms of device success and clinical safety outcomes using a propensity score analysis. BACKGROUND: Differences in clinical outcomes between the latest-generation balloon-expandable S3 and self-expanding NEO in a "real-world transfemoral TAVI population" are still unclear. METHODS: We compared up to 6 months clinical outcomes using a propensity score analysis (inverse probability of treatment weighting [IPTW]) to account for differences in baseline characteristics. RESULTS: A total of 345 patients underwent transfemoral transcatheter aortic valve implantation (TAVI) with either NEO or S3 at two centers in the Netherlands. Composite device success and early safety endpoints were comparable between NEO and S3 (Device success: IPTW-adjusted OR: 0.35 [95% CI: 0.12-1.18], and early safety: IPTW-adjusted OR: 0.51 [95% CI: 0.19-1.38]). Six-months mortality was 5.3 versus 3.6%, stroke was 2.8 versus 3.3%, and pacemaker rate was 6.1 versus 8.6%, respectively with p = NS. Mean aortic gradient was lower in the NEO group (5.72 ± 2.47 vs. 9.05 ± 3.48; p = <.001), with a comparable rate of moderate or severe paravalvular leak (0 versus 2.1%; p = NS). CONCLUSIONS: Device success and clinical safety outcomes were comparable for both valves. Up to 6-months follow-up clinical outcomes and mortality rate remained excellent. Mean aortic gradient was lower after ACURATE neo implantation.

Environmental factors associated with biological use and surgery in inflammatory bowel disease.

BACKGROUND AND AIM: While major efforts were made studying the complex etiology of inflammatory bowel disease (IBD) including environmental factors, less is known about underlying causes leading to the heterogeneous and highly variable course of disease. As cigarette smoking cessation is the best-known environmental factor with beneficial effect in Crohn's disease (CD), more exposome factors are likely involved. Further insights into the role of the exposome in heterogeneity of disease might not only further knowledge of underlying pathways, but also allow for better risk stratification. METHODS: Seven hundred twenty-eight IBD patients completed the validated Groningen IBD Environmental Questionnaire, collecting exposome data for 93 exposome factors. Associations with disease course, that is, for need for surgery or biological therapy, were evaluated using univariate and multivariate-adjusted logistic regression modeling. RESULTS: No significant associations were seen after Bonferroni correction. However, 11 novel exposome factors were identified with P < 0.05. Two factors were associated with course of CD and ulcerative colitis (UC): beer (CD OR0.3/UC OR0.3) and cannabis (0.5/2.2). While in CD, carpet flooring (0.5) was associated with biological use, and four factors were associated with surgery: working shifts (1.8), appendectomy (2.4), frequent tooth brushing (2.8), and large household size (0.1). For UC, migrants more often required biologicals (10.2). Childhood underweight (3.4), amphetamine use (6.2), and cocaine use (4.8) were associated with surgery. Five factors were replicated. CONCLUSIONS: We identified 16 environmental factors nominally associated with biological use and surgery in established IBD. These new insights form an important stepping stone to guide research on biological pathways involved, risk stratification, tailor-made interventions, and preventive strategies in IBD.