Rationale and design of the iCORONARY trial: improving the cost-effectiveness of coronary artery disease diagnosis.

BACKGROUND: In patients with stable coronary artery disease (CAD), revascularisation decisions are based mainly on the visual grading of the severity of coronary stenosis on invasive coronary angiography (ICA). However, invasive fractional flow reserve (FFR) is the current standard to determine the haemodynamic significance of coronary stenosis. Non-invasive and less-invasive imaging techniques such as computed-tomography-derived FFR (FFR-CT) and angiography-derived FFR (QFR) combine both anatomical and functional information in complex algorithms to calculate FFR. TRIAL DESIGN: The iCORONARY trial is a prospective, multicentre, non-inferiority randomised controlled trial (RCT) with a blinded endpoint evaluation. It investigates the costs, effects and outcomes of different diagnostic strategies to evaluate the presence of CAD and the need for revascularisation in patients with stable angina pectoris who undergo coronary computed tomography angiography. Those with a Coronary Artery Disease-Reporting and Data System (CAD-RADS) score between 0-2 and 5 will be included in a prospective registry, whereas patients with CAD-RADS 3 or 4A will be enrolled in the RCT. The RCT consists of three randomised groups: (1) FFR-CT-guided strategy, (2) QFR-guided strategy or (3) standard of care including ICA and invasive pressure measurements for all intermediate stenoses. The primary endpoint will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at 1 year. CLINICALTRIALS: gov-identifier: NCT04939207. CONCLUSION: The iCORONARY trial will assess whether a strategy of FFR-CT or QFR is non-inferior to invasive angiography to guide the need for revascularisation in patients with stable CAD. Non-inferiority to the standard of care implies that these techniques are attractive, less-invasive alternatives to current diagnostic pathways.

The position of renal denervation in treatment of hypertension: an expert consensus statement.

Hypertension is an important risk factor for cardiovascular disease. In the Netherlands, there are approximately 2.8 million people with hypertension. Despite treatment recommendations including lifestyle changes and antihypertensive drugs, most patients do not meet guideline-recommended blood pressure (BP) targets. In order to improve BP control and lower the risk of subsequent cardiovascular events, renal sympathetic denervation (RDN) has been introduced and studied as a non-pharmacological approach. While early data on the efficacy of RDN showed conflicting results, improvements in treatment protocols and study design resulted in robust new evidence supporting the potential of the technology to improve patient care in hypertensive subjects. Recently, 5 randomised sham-controlled trials demonstrated the safety and efficacy of the technology. Modelling studies have further shown that RDN is cost-effective in the Dutch healthcare setting. Given the undisputable disease burden along with the shortcomings of current therapeutic options, we postulate a new, clearly framed indication for RDN as an adjunct in the treatment of hypertension. The present consensus statement summarises current guideline-recommended BP targets, proposed workup and treatment for hypertension, and position of RDN for those patients with primary hypertension who do not meet guideline-recommended BP targets (see central illustration).

The impact and challenges of implementing CTCA according to the 2019 ESC guidelines on chronic coronary syndromes: a survey and projection of CTCA services in the Netherlands.

BACKGROUND: The 2019 ESC-guidelines on chronic coronary syndromes (ESC-CCS) recommend computed tomographic coronary angiography (CTCA) or non-invasive functional imaging instead of exercise ECG as initial test to diagnose obstructive coronary artery disease. Since impact and challenges of these guidelines are unknown, we studied the current utilisation of CTCA-services, status of CTCA-protocols and modeled the expected impact of these guidelines in the Netherlands. METHODS AND RESULTS: A survey on current practice and CTCA utilisation was disseminated to every Dutch hospital organisation providing outpatient cardiology care and modeled the required CTCA capacity for implementation of the ESC guideline, based on these national figures and expert consensus. Survey response rate was 100% (68/68 hospital organisations). In 2019, 63 hospital organisations provided CTCA-services (93%), CTCA was performed on 99 CTCA-capable CT-scanners, and 37,283 CTCA-examinations were performed. Between the hospital organisations, we found substantial variation considering CTCA indications, CTCA equipment and acquisition and reporting standards. To fully implement the new ESC guideline, our model suggests that 70,000 additional CTCA-examinations would have to be performed in the Netherlands. CONCLUSIONS: Despite high national CTCA-services coverage in the Netherlands, a substantial increase in CTCA capacity is expected to be able to implement the 2019 ESC-CCS recommendations on the use of CTCA. Furthermore, the results of this survey highlight the importance to address variations in image acquisition and to standardise the interpretation and reporting of CTCA, as well as to establish interdisciplinary collaboration and organisational alignment.

Case report: Dobutamine stress intracoronary physiology and imaging to examine the functional and dynamic properties of an apparent malignant intra-arterial right coronary artery.

BACKGROUND: We present a case concerning a 64-year-old female with complaints of palpitations, chest pain, and an anomalous right coronary artery (RCA) from the opposite sinus (R-ACAOS) with a suspected malignant trajectory on computed tomography. She was referred to our clinic for a second opinion to re-assess the suggested treatment of coronary surgery. CASE SUMMARY: A coronary angiogram was performed demonstrating a RCA with a tapered ostium typical for an inter-arterial course. Dobutamine and adenosine stress test during simultaneous intracoronary flow, pressure, and ultrasound assessment, was performed to determine the functional significance. After 120 mcg adenosine, intracoronary baseline flow velocity increased from 14 cm/s to a peak flow velocity of 37 cm/s, demonstrating a sufficient coronary flow velocity reserve (CFVR) of 2.6. No intracoronary pressure drop during maximal hyperaemia was found. After maximum dobutamine stress, CFVR was measured 2.5. Fractional flow reserve measured 0.99. Cross-sectional area measurement through intravascular ultrasound demonstrated a diameter reduction from 14.6 mm2 to 8.5 mm2. Therefore, we concluded this aberrant trajectory was not of any functional relevance and should be considered non-malignant. DISCUSSION: There are several anatomic coronary anomalies which may contribute to coronary compression during exercise and are therefore correlated with sudden cardiac death. Right coronary artery from the opposite sinus is correlated with a low mortality rate of 0.2% in comparison to left-ACAOS at 6.3% over 20 years in participants of competitive sport. Therefore, strong evidence of ischaemia must be present before opting for surgery. Our pragmatic approach provided in our opinion enough evidence for a conservative treatment strategy.

Major threats to early safety after transcatheter aortic valve implantation in a contemporary cohort of real-world patients.

INTRODUCTION: Despite considerable advances in the last decade, major adverse events remain a concern after transcatheter aortic valve implantation (TAVI). The aim of this study was to provide a detailed overview of their underlying causes and contributing factors in order to identify key domains for quality improvement. METHODS: This observational, prospective registry included all patients undergoing TAVI between 31 December 2015 and 1 January 2020 at the St. Antonius Hospital in Nieuwegein and the University Medical Centre in Utrecht. Outcomes of interest were all-cause mortality, stroke, major bleeding, life-threatening or disabling bleeding, major vascular complications, myocardial infarction, severe acute kidney injury and conduction disturbances requiring permanent pacemaker implantation within 30 days after TAVI, according to the Valve Academic Research Consortium­2 criteria. RESULTS: Of the 1250 patients who underwent TAVI in the evaluated period, 146 (11.7%) developed a major complication. In 54 (4.3%) patients a thromboembolic event occurred, leading to stroke in 36 (2.9%), myocardial infarction in 13 (1.0%) and lower limb ischaemia in 11 (0.9%). Major bleeding occurred in 65 (5.2%) patients, most frequently consisting of acute cardiac tamponade (n = 25; 2.0%) and major access-site bleeding (n = 21; 1.7%). Most complications occurred within 1 day of the procedure. Within 30 days a total of 54 (4.3%) patients died, the cause being directly TAVI-related in 30 (2.4%). Of the patients who died from causes that were not directly TAVI-related, 14 (1.1%) had multiple hospital-acquired complications. CONCLUSION: A variety of underlying mechanisms and causes form a wide spectrum of major threats affecting early safety in 11.7% of patients undergoing TAVI in a contemporary cohort of real-world patients.

A combination of fecal calprotectin and human beta-defensin 2 facilitates diagnosis and monitoring of inflammatory bowel disease.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) show a large overlap in clinical presentation, which presents diagnostic challenges. As a consequence, invasive and burdensome endoscopies are often used to distinguish between IBD and IBS. Here, we aimed to develop a noninvasive fecal test that can distinguish between IBD and IBS and reduce the number of endoscopies.We used shotgun metagenomic sequencing to analyze the composition and function of gut microbiota of 169 IBS patients, 447 IBD patients and 1044 population controls and measured fecal Calprotectin (FCal), human beta defensin 2 (HBD2), and chromogranin A (CgA) in these samples. These measurements were used to construct training sets (75% of data) for logistic regression and machine learning models to differentiate IBS from IBD and inactive from active IBD. The results were replicated on test sets (remaining 25% of the data) and microbiome data obtained using 16S sequencing.Fecal HBD2 showed high sensitivity and specificity for differentiating between IBD and IBS (sensitivity = 0.89, specificity = 0.76), while the inclusion of microbiome data with biomarkers (HBD2 and FCal) showed a potential for improvement in predictive power (optimal sensitivity = 0.87, specificity = 0.93). Shotgun sequencing-based models produced comparable results using 16S-sequencing data. HBD2 and FCal were found to have predictive power for IBD disease activity (AUC ≈ 0.7).HBD2 is a novel biomarker for IBD in patients with gastro-intestinal complaints, especially when used in combination with FCal and potentially in combination with gut microbiome data.

2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation : Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups.

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.

The first multicentre study on coronary anomalies in the Netherlands: MuSCAT.

BACKGROUND: Current guidelines on coronary anomalies are primarily based on expert consensus and a limited number of trials. A gold standard for diagnosis and a consensus on the treatment strategy in this patient group are lacking, especially for patients with an anomalous origin of a coronary artery from the opposite sinus of Valsalva (ACAOS) with an interarterial course. AIM: To provide evidence-substantiated recommendations for diagnostic work-up, treatment and follow-up of patients with anomalous coronary arteries. METHODS: A clinical care pathway for patients with ACAOS was established by six Dutch centres. Prospectively included patients undergo work-up according to protocol using computed tomography (CT) angiography, ischaemia detection, echocardiography and coronary angiography with intracoronary measurements to assess anatomical and physiological characteristics of the ACAOS. Surgical and functional follow-up results are evaluated by CT angiography, ischaemia detection and a quality-of-life questionnaire. Patient inclusion for the first multicentre study on coronary anomalies in the Netherlands started in 2020 and will continue for at least 3 years with a minimum of 2 years of follow-up. For patients with a right or left coronary artery originating from the pulmonary artery and coronary arteriovenous fistulas a registry is maintained. RESULTS: Primary outcomes are: (cardiac) death, myocardial ischaemia attributable to the ACAOS, re-intervention after surgery and intervention after initially conservative treatment. The influence of work-up examinations on treatment choice is also evaluated. CONCLUSIONS: Structural evidence for the appropriate management of patients with coronary anomalies, especially (interarterial) ACAOS, is lacking. By means of a structured care pathway in a multicentre setting, we aim to provide an evidence-based strategy for the diagnostic evaluation and treatment of this patient group.

Genetic Risk Scores Identify Genetic Aetiology of Inflammatory Bowel Disease Phenotypes.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] phenotypes are very heterogeneous between patients, and current clinical and molecular classifications do not accurately predict the course that IBD will take over time. Genetic determinants of disease phenotypes remain largely unknown but could aid drug development and allow for personalised management. We used genetic risk scores [GRS] to disentangle the genetic contributions to IBD phenotypes. METHODS: Clinical characteristics and imputed genome-wide genetic array data of patients with IBD were obtained from two independent cohorts [cohort A, n = 1097; cohort B, n = 2156]. Genetic risk scoring [GRS] was used to assess genetic aetiology shared across traits and IBD phenotypes. Significant GRS-phenotype (false-discovery rate [FDR] corrected p <0.05) associations identified in cohort A were put forward for replication in cohort B. RESULTS: Crohn's disease [CD] GRS were associated with fibrostenotic CD [R2 = 7.4%, FDR = 0.02] and ileocaecal resection [R2 = 4.1%, FDR = 1.6E-03], and this remained significant after correcting for previously identified clinical and genetic risk factors. Ulcerative colitis [UC] GRS [R2 = 7.1%, FDR = 0.02] and primary sclerosing cholangitis [PSC] GRS [R2 = 3.6%, FDR = 0.03] were associated with colonic CD, and these two associations were largely driven by genetic variation in MHC. We also observed pleiotropy between PSC genetic risk and smoking behaviour [R2 = 1.7%, FDR = 0.04]. CONCLUSIONS: Patients with a higher genetic burden of CD are more likely to develop fibrostenotic disease and undergo ileocaecal resection, whereas colonic CD shares genetic aetiology with PSC and UC that is largely driven by variation in MHC. These results further our understanding of specific IBD phenotypes.

Direct comparison of predictive performance of PRECISE-DAPT versus PARIS versus CREDO-Kyoto: a subanalysis of the ReCre8 trial.

BACKGROUND: Multiple scores have been proposed to guide risk stratification after percutaneous coronary intervention. This study assessed the performance of the PRECISE-DAPT, PARIS and CREDO-Kyoto risk scores to predict post-discharge ischaemic or bleeding events. METHODS: A total of 1491 patients treated with latest-generation drug-eluting stent implantation were evaluated. Risk scores for post-discharge ischaemic or bleeding events were calculated and directly compared. Prognostic performance of both risk scores was assessed with calibration, Harrell's c­statistics net reclassification index and decision curve analyses. RESULTS: Post-discharge ischaemic events occurred in 56 patients (3.8%) and post-discharge bleeding events in 34 patients (2.3%) within the first year after the invasive procedure. C­statistics for the PARIS ischaemic risk score was marginal (0.59, 95% confidence interval (CI) 0.51-0.68), whereas the CREDO-Kyoto ischaemic risk score was moderate (0.68, 95% CI 0.60-0.75). With regard to post-discharge bleeding events, CREDO-Kyoto displayed moderate discrimination (c-statistic 0.67, 95% CI 0.56-0.77), whereas PRECISE-DAPT (0.59, 95% CI 0.48-0.69) and PARIS (0.55, 95% CI 0.44-0.65) had a marginal discriminative capacity. Net reclassification index and decision curve analysis favoured CREDO-Kyoto-derived bleeding risk assessment. CONCLUSION: In this contemporary all-comer population, PARIS and PRECISE-DAPT risk scores were not resilient to independent testing for post-discharge bleeding events. CREDO-Kyoto-derived risk stratification was associated with a moderate predictive capability for post-discharge ischaemic or bleeding events. Future studies are warranted to improve risk stratification with more focus on robustness and rigorous testing.

Invasive coronary physiology: a Dutch tradition.

Invasive coronary physiology has been applied since the early days of percutaneous transluminal coronary angioplasty, and has become a rapidly emerging field of research. Many physiology indices have been developed, tested in clinical studies, and are now applied in daily clinical practice. Recent clinical practice guidelines further support the use of advanced invasive physiology methods to optimise the diagnosis and treatment of patients with acute and chronic coronary syndromes. This article provides a succinct review of the history of invasive coronary physiology, the basic concepts of currently available physiological parameters, and will particularly highlight the Dutch contribution to this field of invasive coronary physiology.

Randomised comparison of a balloon-expandable and self-expandable valve with quantitative assessment of aortic regurgitation using magnetic resonance imaging.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a safe and effective treatment for inoperable, intermediate- or high-risk patients with severe symptomatic aortic stenosis and has been associated with excellent clinical outcomes. A clinically relevant remaining problem is aortic regurgitation (AR) post-TAVI, which is associated with increased mortality. Therefore, we conducted a prospective randomised trial to assess the safety and efficacy of a first-generation self-expandable valve (SEV; CoreValve) and a third-generation balloon-expandable valve (BEV; Sapien 3) with respect to clinical outcomes and AR as determined quantitatively by magnetic resonance imaging (MRI). METHODS: The ELECT study was an investigator-initiated, single-centre trial involving patients with severe symptomatic aortic stenosis and with a clinical indication for transfemoral TAVI. Fifty-six patients were randomly assigned to the BEV or SEV group. RESULTS: AR determined quantitatively by MRI was lower in the BEV than in the SEV group [regurgitant fraction: 1.1% (0-8.0) vs 8.7% (3.0-14.8) for SEV; p = 0.01]. Secondary endpoints according to the criteria of the Second Valve Academic Research Consortium (VARC-2) showed BEV to have better early safety [0 (0%) vs 8 (30%); p = 0.002] at 30 days and a lower risk of stroke [0 (0%) vs 5 (21%); p = 0.01], major adverse cardiac and cerebrovascular events [0 (0%) vs 10 (38%); p < 0.001] or death [0 (0%) vs 5 (19%); p = 0.02] in the 1st year compared with SEV. CONCLUSIONS: The use of the latest generation of BEV was associated with less AR as quantitatively assessed by MRI. Although the use of MRI to quantify AR is not feasible in daily clinical practice, it should be considered as a surrogate endpoint for clinical outcomes in comparative studies of valves for TAVI. ClinicalTrials.gov number NCT01982032.

Prognostic implications of resting distal coronary-to-aortic pressure ratio compared with fractional flow reserve: a 10-year follow-up study after deferral of revascularisation.

INTRODUCTION: The distal coronary-to-aortic pressure ratio (Pd/Pa) is a non-hyperaemic physiological index to assess the functional severity of coronary stenoses. Studies comparing Pd/Pa with fractional flow reserve (FFR) show superior diagnostic efficiency for myocardial ischaemia. Nevertheless, a direct comparison regarding long-term clinical outcomes is still not available. The present observational study compared the prognostic value of Pd/Pa and FFR for major adverse cardiac events (MACE) during a 10-year follow-up period after deferral of revascularisation. METHODS: Between April 1997 and September 2006, we evaluated 154 coronary stenoses (154 patients) in which revascularisation was deferred with intracoronary pressure and flow measurements during the resting and hyperaemic state. Long-term follow-up (median: 11.8 years) was performed to document the occurrence of MACE, defined as a composite of cardiac death, myocardial infarction and target vessel revascularisation. RESULTS: The study population comprised angiographically intermediate coronary stenoses, with a mean diameter stenosis of 53 ± 8%, and intermediate physiological severity with a median FFR of 0.82 (Q1, Q3: 0.76, 0.88). The association of Pd/Pa with long-term MACE was similar to that of FFR [FFR-standardised hazard ratio (sHR): 0.77, 95% confidence interval (CI): 0.61-0.98; Pd/Pa-sHR: 0.80, 95% CI: 0.67-0.96]. In the presence of disagreement between Pd/Pa and FFR, normal Pd/Pa was generally associated with high coronary flow reserve (CFR) and a favourable clinical outcome, whereas abnormal Pd/Pa was generally associated with CFR around the ischaemic cut-point and an impaired clinical outcome, regardless of the accompanying FFR value. CONCLUSION: The present study suggests that Pd/Pa provides at least equivalent prognostic value compared with FFR. When Pd/Pa disagreed with FFR, the baseline index conferred superior prognostic value in this study population.

Safety and efficacy of stenting for aortic arch hypoplasia in patients with coarctation of the aorta.

BACKGROUND: Despite a successful repair procedure for coarctation of the aorta (CoA), up to two-thirds of patients remain hypertensive. CoA is often seen in combination with abnormal aortic arch anatomy and morphology. This might be a substrate for persistent hypertension. Therefore, we performed endovascular aortic arch stent placement in patients with CoA and concomitant aortic arch hypoplasia or gothic arch morphology. The goal of this retrospective analysis was to investigate the safety and efficacy of aortic arch stenting. METHODS: A retrospective analysis was performed in patients who underwent stenting of the aortic arch at the University Medical Center Utrecht. Measurements collected included office blood pressure, use of antihypertensive medication, invasive peak-to-peak systolic pressure over the arch, and aortic diameters on three-dimensional angiography. Data on follow-up were obtained at the date of most recent outpatient visit. RESULTS: Twelve patients underwent stenting of the aortic arch. Mean follow-up duration was 14 ± 11 months. Mean peak-to-peak gradient across the arch decreased from 39 ± 13 mm Hg to 7 ± 8 mm Hg directly after stenting (p < 0.001). There were no major procedural complications. Mean systolic blood pressure decreased from 145 ± 16 mm Hg at baseline to 128 ± 9 mm Hg at latest follow-up (p = 0.014). CONCLUSION: This retrospective study shows that stenting of the aortic arch is successful when carried out in a state-of-the-art manner. A direct optimal angiographic and haemodynamic result was shown. No major complications occurred during or after the procedure. At short- to medium-term follow-up a decrease in mean systolic blood pressure was observed.

Correction to: The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1.

Following publication of the original article [1], the authors.

Incidence, angiographic and clinical predictors, and impact of stent thrombosis: a 6-year survey of 6,545 consecutive patients.

OBJECTIVE: We sought to determine the incidence, angiographic predictors, and impact of stent thrombosis (ST). BACKGROUND: Given the high mortality after ST, this study emphasises the importance of ongoing efforts to identify angiographic predictors of ST. METHODS: All consecutive patients with angiographically confirmed ST between 2010 and 2016 were 1:4 matched for (1) percutaneous coronary intervention (PCI) indication and (2) index date ±6 weeks to randomly selected controls. Index PCI angiograms were reassessed by two independent cardiologists. A multivariable conditional logistic regression model was built to identify independent predictors of ST. RESULTS: Of 6,545 consecutive patients undergoing PCI, 55 patients [0.84%, 95% confidence interval (CI) 0.63-1.10%] presented with definite ST. Multivariable logistic regression identified dual antiplatelet therapy (DAPT) non-use as the strongest predictor of ST (odds ratio (OR) 10.9, 95% CI 2.47-48.5, p < 0.001), followed by: stent underexpansion (OR 5.70, 95% CI 2.39-13.6, p < 0.001), lesion complexity B2/C (OR 4.32, 95% CI 1.43-13.1, p = 0.010), uncovered edge dissection (OR 4.16, 95% CI 1.47-11.8, p = 0.007), diabetes mellitus (OR 3.23, 95% CI 1.25-8.36, p = 0.016), and residual coronary artery disease at the stent edge (OR 3.02, 95% CI 1.02-8.92, p = 0.045). ST was associated with increased rates of mortality as analysed by Kaplan-Meier estimates (27.3 vs 11.3%, plog-rank < 0.001) and adjusted Cox proportional-hazard regression (hazard ratio 2.29, 95% CI 1.03-5.10, p = 0.042). CONCLUSIONS: ST remains a serious complication following PCI with a high rate of mortality. DAPT non-use was associated with the highest risk of ST, followed by various angiographic parameters and high lesion complexity.

The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data generated from the same IBD patients. CONSTRUCTION AND CONTENT: We initiated the 1000IBD project ( https://1000ibd.org ) to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1215 participants have been enrolled in the project and enrolment is on-going. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing. UTILITY AND DISCUSSION: All molecular data generated within the 1000IBD project will be shared on the European Genome-Phenome Archive ( https://ega-archive.org , accession no: EGAS00001002702). The first data release, detailed in this announcement and released simultaneously with this publication, will contain basic phenotypes for 1215 participants, genotypes of 314 participants and gut microbiome data from stool samples (315 participants) and biopsies (107 participants) generated by tag sequencing the 16S gene. Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models. CONCLUSIONS: We report on the establishment and future development of the 1000IBD project: the first comprehensive multi-omics dataset aimed at discovering IBD biomarker profiles and treatment targets.