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Background Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. Aim To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. Methods This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. Discussion The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website (www.acmregistry.nl) and patient conferences. Electronic supplementary material The online version of this article (10.1007/s12471-019-1270-1) contains supplementary material, which is available to authorized users.

Transcatheter Aortic Valve Implantation (TAVI) is a new minimal-invasive intervention for implanting pros-thetic valves in patients with aortic stenosis. This procedure is associated with adverse effects like paravalvular leakage, stroke, and coronary obstruction. Accurate automated sizing for planning and patient selection is expected to reduce these adverse effects. Segmentation of the aortic root in CTA is pivotal to enable automated sizing and planning. We present a fully automated segmentation algorithm to extract the aortic root from CTA images consisting of a number of steps: first, ascending aorta and aortic root centerline were extracted. Subsequently, high intensities due to calcifications are masked to improve segmentation. Next, the aortic root is represented in cylindrical coordinates. Finally, the aortic root is segmented using 3D normalized cuts. We validated the method against manual delineations by calculating Dice coefficients and aver-age distances. The method successfully segmented the aortic root in all 20 image datasets. The mean Dice coefficient was 0.945±0.03 and mean radial absolute error was 0.74 ± 0.39 mm. The proposed algorithm showed accurate results com-pared to manual segmentations.

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Unlike X-ray, CT, PET and SPECT, which image body tissues based on their interaction with ionizing radiation, MRI exploits the tissues’ interaction with a magnetic field and radio waves. It does so non-invasively, without harming the body, and has become a popular imaging technique in hospitals all over the world. Not only does it allow for the imaging of tissues, it can also measure blood flow velocities, making it a useful technique for the assessment of cardiac disease. Currently, MRI-based assessment of cardiac hemodynamics largely relies on 2D flow MRI, which can characterize blood flow in two-dimensional imaging planes over time. 4D flow MRI offers three-dimensional velocity measurement over time. This thesis concerns the innovation and validation of cardiac 4D flow MRI for blood flow quantification in valvular heart disease and coronary artery disease. We 1) review various 4D flow MRI-derived hemodynamic parameters, together with their diagnostic and prognostic potential for the evaluation of left-sided valvular heart disease, 2) investigate the potential of an analysis technique called flow tracking for 4D flow MRI-based quantification of mitral valve regurgitation (i.e. leakage), 3) compare two accelerated whole-heart 4D flow MRI techniques for quantification of normal and regurgitant blood flow across the heart valves, 4) evaluate a novel, camera-based technique for respiratory motion monitoring and gating in whole-heart 4D flow MRI, and 5) present a framework for coronary blood flow quantification using accelerated 4D flow MRI equipped with respiratory motion correction.

The aim of this thesis is to improve detection of embolic sources of ischemic stroke along the heart-brain axis. The structure of the thesis follows this anatomical pathway. In the first part of this thesis (The Heart), we focused on sources of embolism from the heart which are detected through imaging. We performed three studies on the diagnostic yield of cardiac CT-angiography for detection of high-risk cardio-aortic sources of embolism in acute ischemic stroke patients. In the second part of this thesis (The Arteries), we explored (rare) sources of embolism from the arteries in an effort to increase awareness in the medical community. We conducted studies in ischemic stroke patients with an underlying acute aortic dissection, multiple cervical artery dissections, and a carotid web. In addition, we investigated the hypothesis that patients with ischemic stroke due to cervical carotid atherosclerosis have a more extensive collateral circulation and better outcomes than patients with cardioembolism.

Despite ongoing advances in prevention, diagnostic strategies and treatment options, coronary artery disease (CAD) remains a leading cause of death worldwide and has an unfavourable impact on quality of life. The use of upfront computed tomography coronary angiography (CTCA) has shown potential to reduce fatal and nonfatal myocardial infarction in patients with stable CAD. Furthermore, it is a less invasive option compared to standard coronary angiography. In this thesis we examined the impact and challenges of implementing CTCA in the Netherlands and we investigated methods to improve image acquisition. In the third part of this thesis, we evaluated the extended use of CTCA, both for the detection of CAD in the work-up for transcatheter aortic valve implantation (TAVI) and to predict the occurrence of chronic silent brain infarctions following this procedure. Considering implementation, we found that there already is high coverage of CTCA-services in the Netherlands. However, a substantial increase in CTCA capacity is necessary to fully implement CTCA in cardiologic care. Furthermore, we found that implementation of CTCA will result in a substantial reduction in costly and invasive CAG. Considering improved methods of image acquisition, we found that patient tailored contrast delivery protocols for CTCA, adjusting the contrast delivery to body weight and CT-scanner kV settings, improved attenuation values in the coronary arteries and therefore may result in improved diagnostic qualities of CTCA. In the third part of this thesis, we found that CTCA has high diagnostic accuracy to detect CAD in the work-up TAVI and could be used to reduce CAG in these fragile patients by up to 70%. These same pre-TAVI CTCA scans may be used for additional purposes other than the evaluation of CAD. We found that the degree of aortic valve calcifications, measured on these pre-TAVI CTCA scans, was associated with a larger increase in the white matter hyperintensity volume, and therefore shows potential to predict chronic silent brain infarctions.

Over the past decades, the number of individuals with type 2 diabetes has been growing worldwide. Type 2 diabetes is a major health concern, as it is related to several conditions, including heart failure and coronary artery disease. Despite remarkable advances in cardiovascular prevention and treatment, heart disease remains a common cause of death and an important contributor to health loss. The aim of this thesis was to characterize cardiovascular remodeling associated with metabolic disturbances, using a variety of magnetic resonance techniques. This thesis demonstrates that reduced diastolic function is a common characteristic of myocardial remodeling in type 2 diabetes and obesity, but also a potential marker for the detection of patients at increased cardiovascular risk after hematopoietic stem cell transplantation and possibly a contributing factor in the pathogenesis of ventricular arrhythmia after myocardial infarction. Also, in this thesis, it was shown that the evaluation of visceral adiposity and myocardial triglyceride content may help to identify distinct cardiometabolic phenotypes and to better understand the cardiometabolic actions of the glucagon-like peptide 1 receptor agonist liraglutide. With the emergence of non-contrast cardiovascular protocols, magnetic resonance techniques may be increasingly used for cardiometabolic phenotyping in population-based cohorts as well as clinical studies.

This thesis explores the three main risks that are relevant in the management of patients with an abdominal aortic aneurysm (AAA). These risks are the risk of rupture, procedural risks and competing risks and will need to be weighed against each other to tailor the treatment decision to the individual patient. However, making this decision can sometimes be a challenge because it is often difficult to accurately estimate either of these risks. Therefore, any improvement in estimating these risks may help both the vascular surgeon and the patient in making this decision. The first part of this thesis is focused on evaluating biomechanical imaging markers that could potentially be used to estimate rupture risk. The existing literature was critically reviewed in order to determine potentially useful biomechanical imaging markers and a magnetic resonance imaging (MRI) study was undertaken to assess the reproducibility of 4D flow MRI. Part two of this thesis primarily consists out of retrospective cohort studies that evaluated whether certain determinants for procedural and competing risks could be relevant for clinical practice. The final part considers AAA research and the challenges regarding the three risks. It presents the design and protocol of the biobank ‘Pearl AAA’ which was initiated in order to address some of these challenges. Specifically, it is aimed to recruit patients with a small asymptomatic AAA of whom clinical data, imaging data and biomaterials are collected for future study.

This thesis provides insight in the impact of congenital and acquired heart diseases on electrophysiology and hemodynamics in the heart, that could help understand the often complex pathophysiological mechanisms involved in cardiovascular diseases and might aid in the early detection of patients prone to cardiovascular deterioration. The first part of this thesis shows the value of the electrocardiogram and vectorcardiogram in the assessment of patients with right-sided acquired and congenital heart defects. The 3D vectorcardiographic VG and SA could be valuable in the assessment of patients with right ventricular volume or pressure overload. The second part of this thesis shows significant steps towards clinical utility of 4D flow MRI. Valvular flow quantification with 4D flow MRI, especially in combination with automated valve tracking, has great potential as a future clinical standard. The third part of this thesis provides important insights in intraventricular hemodynamics in Fontan patients. In time to come, knowledge on intraventricular hemodynamics could aid in determining follow-up frequency and the ideal timing of initiation of heart failure management, perhaps even on an individual patient’s level. Moreover, these findings can create a platform for further research in the field of intraventricular hemodynamics in healthy subjects and different patient groups.

Transcatheter aortic valve implantation (TAVI) has been fully integrated as a therapeutic option for patients with aortic valve stenosis. This thesis focuses on screening, complications and outcome of aortic valve implantation, mainly by TAVI. The first section concentrates on computed tomography angiography (CTA) in screening prior to TAVI. Intravenous hydration is used to mitigate the effects of contrast media administered during CTA. We found no significant difference on renal outcome between conventional, long, hydration compared to shorter hydration. We also demonstrated that the presence of potentially malignant incidental findings, described on pre-TAVI CTA, is an independent predictor of (non-cardiovascular) mortality. In the second section, periprocedural complications are evaluated. Histopathologic analyses of thrombectomy material in 3 cases of thromboembolic complications after TAVI are described. Additionally we demonstrated that also with the newest prosthesis, vascular complications after TAVI remain an issue. The third section focuses on clinical outcome. We used 4D flow magnetic resonance imaging (MRI) to analyze the hemodynamic performance of two bioprostheses types 1-year after surgical aortic valve replacement. Moreover, we evaluated procedural outcome after TAVI with two different prostheses in a low to intermediate surgical risk population and described the trends in patient-, procedural characteristics and outcome after TAVI over the last 8-years. Finally, we provide an overview of autopsy findings in patients with TAVI in their medical history and the added value of autopsy over a solely clinical determined cause of death was demonstrated. In the final part of the thesis the findings and future considerations are discussed.

Aortic stenosis is the most common and frequent cause of sudden death among all valvular heart diseases. Symptomatic aortic stenosis is considered to be a fatal disease if left untreated. Aortic valve replacement is the mainstay of treatment of symptomatic aortic stenosis. Traditional treatment of severe aortic valve stenosis is aortic valve replacement (AVR) by open-heart surgery. Various novel techniques have been introduced for less invasive AVR, including trans-catheter aortic valve implantation (TAVI) and minimally invasive aortic valve replacement (mini-AVR). For both techniques, careful patient selection and preoperative planning play an important role in the successful deployment of the new prosthetic and reducing the AVR complications. Despite the progress made in the preoperative planning, there is still need for further improvement. In this thesis, we proposed a fully automated aortic root segmentation technique to extract the aortic root surface and landmarks from TAVI patients CTA images which facilitates the automated pre-procedural sizing. Then, we studied the dynamics of the aortic annulus by evaluating the annular dimensions using 4D CTA specifically for TAVI population. Furthermore, an automatic planning tool of the mini-AVR surgery was proposed and a clinical feasibility study is presented that validates our tool retrospectively by analyzing patients who underwent the mini-AVR surgery and compared the tool measurements with the patients on-site difficulty scores. In another study, we reported the comparison results between Non-Contrast MRA and Contrast-Enhanced MRA of the aortic image quality by evaluating the vessel sharpness.

In 1993, professor Reekers of the Academic Medical Center (AMC) Radiology department was the first to describe a traumatic aneurysm of the posterior circumflex humeral artery (PCHA) in a volleyball player, suggesting a causal relationship. Fifteen years later, between 2008 and 2010, several elite male volleyball players presented themselves in the AMC in Amsterdam with ischemic digits in the spiking hand due to arterial emboli originating from an aneurysmal and thrombosed PCHA in the dominant shoulder. At that time, just five case reports had been published worldwide on volleyball players with this injury. Knowledge about this sports-related overuse injury needs to be extended on an international scale considering the potential amputation of a finger as the devastating end result in a population of young, healthy and fit elite volleyball players. In this thesis, the first steps of elucidating the unexplored entity of Shoulder PCHA pathology and digital Ischemia in Known Elite volleyball players (SPIKE) are made in order to provide an effective contribution to knowledge about this vascular overuse injury. In volleyball, spiking is the act of scoring a point by slamming the ball over the net into the opposing court effectively. Hence the title SPIKE the PCHA. The first part of the thesis (PART I) covered our research on clinical characteristics like symptomatology and associated risk factors. PART II focused on research on optimal imaging strategies for detection and prevention. Combining new findings with conclusions from Part I and II generates suggestions for clinical management, discussed in PART III.