Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterised by complex pathophysiology and extensive genetic and clinical heterogeneity. In most patients, HCM is caused ...by mutations in cardiac sarcomere protein genes and inherited as an autosomal dominant trait. The clinical phenotype ranges from severe presentations at a young age to lack of left ventricular hypertrophy in genotype-positive individuals. No preventative treatment is available as the sequence and causality of the pathomechanisms that initiate and exacerbate HCM are unknown. Sudden cardiac death and end-stage heart failure are devastating expressions of this disease. Contemporary management including surgical myectomy and implantable cardiac defibrillators has shown significant impact on long-term prognosis. However, timely recognition of specific scenarios – including transition to the end-stage phase – may be challenging due to limited awareness of the progression patterns of HCM. This in turn may lead to missed therapeutic opportunities. To illustrate these difficulties, we describe two HCM patients who progressed from the typical hyperdynamic stage of asymmetric septal thickening to end-stage heart failure with severely reduced ejection fraction. We highlight the different stages of this complex inherited cardiomyopathy based on the clinical staging proposed by Olivotto and colleagues. In this way, we aim to provide a practical guide for clinicians and hope to increase awareness for this common form of cardiac disease.
Background
The prevalence of heart failure (HF) is increasing substantially and, despite improvements in medical therapy, HF still carries a poor prognosis. Mechanical circulatory support (MCS) by ...a continuous-flow left ventricular assist device (cf-LVAD) improves survival and quality of life in selected patients. This holds especially for the short-term outcome, but experience regarding long-term outcome is growing as the waiting time for heart transplantation is increasing due to the shortage of donor hearts. Here we present our results from the University Medical Centre Utrecht.
Methods
Data of all patients with a cf-LVAD implant between March 2006 and January 2018 were collected. The primary outcome was survival. Secondary outcomes included adverse events defined according to the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definitions, described per patient year.
Results
A total of 268 patients (69% male, mean age 50 ± 13 years) received a cf-LVAD. After a median follow-up of 542 (interquartile range 205–1044) days, heart transplantation had been performed in 82 (31%) patients, the cf-LVAD had been explanted in 8 (3%) and 71 (26%) had died. Survival at 1, 3 and 5 years was 83%, 72% and 57%, respectively, with heart transplantation, cf-LVAD explantation or death as the end-point. Death was most often caused by neurological complications (31%) or infection (20%). Major bleeding occurred 0.51 times and stroke 0.15 times per patient year.
Conclusion
Not only short-term results but also 5‑year survival after cf-LVAD support demonstrate that MCS is a promising therapy as an extended bridge to heart transplantation. However, the incidence of several major complications still has to be addressed.
Purpose
To analyse patient demographics, indications, survival and donor characteristics for heart transplantation (HTx) during the past 30 years at the University Medical Centre Utrecht (UMCU).
...Methods
Data have been prospectively collected for all patients who underwent HTx at the UMCU from 1985 until 2015. Patients who were included underwent orthotopic HTx at an age >14 years.
Results
In total, 489 hearts have been transplanted since 1985; 120 patients (25%) had left ventricular assist device (LVAD) implantation prior to HTx. A shift from ischaemic heart disease to dilated cardiomyopathy has been seen as the leading indication for HTx since the year 2000. Median age at HTx was 49 years (range 16–68). Median waiting time and donor age have also increased from 40 to 513 days and from 27 to 44 years respectively (range 11–65). Donor cause of death is now primarily stroke, in contrast to head and brain injury in earlier years. Estimated median survival is 15.4 years (95% confidence interval 14.2–16.6) There is better survival throughout these years.
Conclusion
Over the past 30 years, patient and donor demographics and underlying diseases have shifted substantially. Furthermore, the increase in waiting time due to lack of available donor hearts has led to a rise in the use of LVADs as bridge to transplant. Importantly, an improvement in survival rates is found over time which could be explained by better immunosuppressive therapy and improvements in follow-up care.
Background
Machine learning (ML) allows the exploration and progressive improvement of very complex high-dimensional data patterns that can be utilised to optimise specific classification and ...prediction tasks, outperforming traditional statistical approaches. An enormous acceleration of ready-to-use tools and artificial intelligence (AI) applications, shaped by the emergence, refinement, and application of powerful ML algorithms in several areas of knowledge, is ongoing. Although such progress has begun to permeate the medical sciences and clinical medicine, implementation in cardiovascular medicine and research is still in its infancy.
Objectives
To lay out the theoretical framework, purpose, and structure of a novel AI consortium.
Methods
We have established a new Dutch research consortium, the CVON-AI, supported by the Netherlands Heart Foundation, to catalyse and facilitate the development and utilisation of AI solutions for existing and emerging cardiovascular research initiatives and to raise AI awareness in the cardiovascular research community. CVON-AI will connect to previously established CVON consortia and apply a cloud-based AI platform to supplement their planned traditional data-analysis approach.
Results
A pilot experiment on the CVON-AI cloud was conducted using cardiac magnetic resonance data. It demonstrated the feasibility of the platform and documented excellent correlation between AI-generated ventricular function estimates as compared to expert manual annotations. The resulting AI solution was then integrated in a web application.
Conclusion
CVON-AI is a new consortium meant to facilitate the implementation and raise awareness of AI in cardiovascular research in the Netherlands. CVON-AI will create an accessible cloud-based platform for cardiovascular researchers, demonstrate the clinical applicability of AI, optimise the analytical methodology of other ongoing CVON consortia, and promote AI awareness through education and training.
In relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy, early detection of disease onset is essential to prevent sudden cardiac death and facilitate early ...treatment of heart failure. However, the optimal screening interval and combination of diagnostic techniques are unknown. The clinical course of disease in index patients and their relatives is variable due to incomplete and age-dependent penetrance. Several biomarkers, electrocardiographic and imaging (echocardiographic deformation imaging and cardiac magnetic resonance imaging) techniques are promising non-invasive methods for detection of subclinical cardiomyopathy. However, these techniques need optimisation and integration into clinical practice. Furthermore, determining the optimal interval and intensity of cascade screening may require a personalised approach. To address this, the CVON-eDETECT (early detection of disease in cardiomyopathy mutation carriers) consortium aims to integrate electronic health record data from long-term follow-up, diagnostic data sets, tissue and plasma samples in a multidisciplinary biobank environment to provide personalised risk stratification for heart failure and sudden cardiac death. Adequate risk stratification may lead to personalised screening, treatment and optimal timing of implantable cardioverter defibrillator implantation. In this article, we describe non-invasive diagnostic techniques used for detection of subclinical disease in relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy.
Essentials Prospective studies of pharmacogenetic-guided (PG) coumarin dosing produced varying results. EU-PACT acenocoumarol and phenprocoumon trials compared PG and non-PG dosing algorithms. ...Sub-analysis of EU-PACT identified differences between trial arms across VKORC1-CYP2C9 groups. Adjustment of the PG algorithm might lead to a higher benefit of genotyping.
Background The multicenter, single-blind, randomized EU-PACT trial compared the safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep vein thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. Objectives To explore possible reasons for the lack of differences between trial arms by performing a secondary analysis of EU-PACT data in order to evaluate the performance of both dosing algorithms across VKORC1-CYP2C9 genetic subgroups. Patients/Methods Anticoagulation control measured according to an International Normalized Ratio (INR) below (INR of < 2), within (INR of 2-3) and above (INR of > 3) the therapeutic range was compared across VKORC1-CYP2C9 subgroups. Owing to a low number of patients in each subgroup, trials for acenocoumarol and phenprocoumon were combined for analysis. Results Four weeks after therapy initiation, genotype-guided dosing increased the mean percentage of time in the therapeutic INR range (PTIR) in the VKORC1 GG-CYP2C9*1*1 subgroup as compared with the non-genetic dosing (difference of 14.68%, 95% confidence interval CI 5.38-23.98). For the VKORC1 AA-CYP2C9*1*1 subgroup, there was a higher risk of under-anticoagulation with the genotype-guided algorithm (difference of 19.9%; 95% CI 11.6-28.2). Twelve weeks after therapy initiation, no statistically significant differences in anticoagulation control between trial arms were noted across the VKORC1-CYP2C9 genetic subgroups. Conclusions EU-PACT genetic-guided dose initiation algorithms for acenocoumarol and phenprocoumon could have predicted the dose overcautiously in the VKORC1 AA-CYP2C9*1*1 subgroup. Adjustment of the genotype-guided algorithm could lead to a higher benefit of genotyping.
Childhood obesity coincides with increased numbers of circulating classical CD14
CD16
and intermediate CD14
CD16
monocytes. Monocytes are key players in the development and exacerbation of ...atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults.
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.
Architectural design education: in varietate unitas van Dooren, E. J. G. C.; van Merriënboer, J.; Boshuizen, H. P. A. ...
International journal of technology and design education,
06/2018, Letnik:
28, Številka:
2
Journal Article
Recenzirano
Odprti dostop
A fascinating and rich landscape of personal views and approaches can be seen in architectural design and in architectural design education. This variation may be confusing for students. This paper ...focuses on the question: is the framework of generic elements that we developed for explicating the design process helpful to compare the differences in architectural design approaches? The results of interviewing a variety of 15 architectural, urban and landscape designers show all kinds of personal approaches that have a set of five underlying generic elements in common. Therefore, the framework may be helpful for teachers and students to describe these personal approaches and may help students in understanding differences and similarities and in finding out what their own personal approach may be.
In 2011 the Netherlands Heart Foundation allocated funding (CVON, Cardiovasculair Onderzoek Nederland) to stimulate collaboration between clinical and preclinical researchers on specific areas of ...research. One of those areas involves genetic heart diseases, which are frequently caused by pathogenic variants in genes that encode sarcomere proteins. In 2014, the DOSIS (
D
eterminants
o
f
s
usceptibility
i
n inherited cardiomyopathy: towards novel therapeutic approache
s
) consortium was initiated, focusing their research on secondary disease hits involved in the onset and progression of cardiomyopathies. Here we highlight several recent observations from our consortium and collaborators which may ultimately be relevant for clinical practice.
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