Application of Quantitative MRI Techniques in Ischemic and Congenital Heart Disease image-guided therapy

It is estimated that each year, 30,000 people in the Netherlands suffer from myocardial infarction, and is in fact a major public health care burden. Next to ischaemic heart disease (IHD), thanks to modern medicine, more and more patients with congenital heart disease (CHD) reach adulthood, but nonetheless require lifelong professional care. Imaging techniques are essential in these two groups of patients for establishing diagnosis, guiding therapy and predicting outcomes. This thesis investigated the application of cardiac MRI in patients with IHD and CHD and evaluated novel non-invasive MRI techniques in both humans and in a porcine model. In this thesis we showed that cardiac MRI is an excellent tool for the evaluation of atherosclerotic and congenital cardiovascular disease. It is an excellent tool in predicting outcome after STEM! in patients undergoing primary percutaneous coronary intervention. Furthermore, studied in this thesis, the incidence of per procedural complications in patients with CHD seems higher than in the general population suggesting that placement of a pacemaker device might be challenging in this group of patients

Qualitative grading of aortic regurgitation: a pilot study comparing CMR 4D flow and echocardiography.

Over the past 10 years there has been intense research in the development of volumetric visualization of intracardiac flow by cardiac magnetic resonance (CMR).This volumetric time resolved technique called CMR 4D flow imaging has several advantages over standard CMR. It offers anatomical, functional and flow information in a single free-breathing, ten-minute acquisition. However, the data obtained is large and its processing requires dedicated software. We evaluated a cloud-based application package that combines volumetric data correction and visualization of CMR 4D flow data, and assessed its accuracy for the detection and grading of aortic valve regurgitation using transthoracic echocardiography as reference. Between June 2014 and January 2015, patients planned for clinical CMR were consecutively approached to undergo the supplementary CMR 4D flow acquisition. Fifty four patients(median age 39 years, 32 males) were included. Detection and grading of the aortic valve regurgitation using CMR4D flow imaging were evaluated against transthoracic echocardiography. The agreement between 4D flow CMR and transthoracic echocardiography for grading of aortic valve regurgitation was good (j = 0.73). To identify relevant,more than mild aortic valve regurgitation, CMR 4D flow imaging had a sensitivity of 100 % and specificity of 98 %. Aortic regurgitation can be well visualized, in a similar manner as transthoracic echocardiography, when using CMR 4D flow imaging

Parents’ experiences of childhood abuse and neglect are differentially associated with behavioral and autonomic responses to their offspring

Although childhood maltreatment has been shown to compromise adaptive parental behavior, little is known what happens in terms of physiological regulation when parents with a history of childhood maltreatment interact with their offspring. Using a sample of 229 parents (131 women), the present study examined whether childhood maltreatment experiences are associated with parents’ behavioral and autonomic responses while resolving conflict with their offspring. Self‐reported experienced child maltreatment was measured using a questionnaire assessing abuse and neglect. Parents (Mage = 52.7 years, rangeage = 26.6–88.4 years) and their offspring (Mage = 24.6 years, rangeage = 7.5–65.6 years) participated in a videotaped parent–offspring conflict interaction task. Parental warmth, negativity, and emotional support were coded. In addition, their pre‐ejection period and respiratory sinus arrhythmia were measured as indicators of underlying sympathetic and parasympathetic nervous system reactivity, respectively. Findings demonstrated that experiences of abuse and neglect were associated with behavioral and physiological responses in different ways. Separating these two types of maltreatment in research and in clinical practice might be important

Intergenerational transmission of child maltreatment using a multi-informant multi-generation family design

In the current study a three-generational design was used to investigate intergenerational transmission of child maltreatment (ITCM) using multiple sources of information on child maltreatment: mothers, fathers and children. A tota

Not the Root of the Problem—Hair Cortisol and Cortisone Do Not Mediate the Effect of Child Maltreatment on Body Mass Index

Background: Experiencing maltreatment during childhood exerts substantial stress on the child and increases the risk for overweight and obesity later in life. The current study tests whether hair cortisol—a measure of chronic stress—and its metabolite cortisone mediate the relation between abuse and neglect on the one hand, and body mass index (BMI) on the other. Method: The sample consisted of 249 participants aged 8 to 87 years (M = 36.13, SD = 19.33). We collected data on child abuse and neglect using questionnaires, measured cortisol and cortisone concentrations in hair, and BMI. In a structural model, the effects of abuse and neglect on hair cortisol, hair cortisone, and BMI were tested, as well as the covariance between hair cortisol and BMI, and hair cortisone and BMI. Results: Within the sample, 23% were overweight but not obese and 14% were obese. Higher levels of experienced abuse were related to higher cortisone concentrations in hair (β = 0.24, p <.001) and higher B

Qualitative grading of aortic regurgitation: a pilot study comparing CMR 4D flow and echocardiography

Over the past 10 years there has been intense research in the development of volumetric visualization of intracardiac flow by cardiac magnetic resonance (CMR). This volumetric time resolved technique called CMR 4D flow imaging has several advantages over standard CMR. It offers anatomical, functional and flow information in a single free-breathing, ten-minute acquisition. However, the data obtained is large and its processing requires dedicated software. We evaluated a cloud-based application package that combines volumetric data correction and visualization of CMR 4D flow data, and assessed its accuracy for the detection and grading of aortic valve regurgitation using transthoracic echocardiography as reference. Between June 2014 and January 2015, patients planned for clinical CMR were consecutively approached to undergo the supplementary CMR 4D flow acquisition. Fifty four patients (median age 39 years, 32 males) were included. Detection and grading of the aortic valve regurgitation using CMR 4D flow imaging were evaluated against transthoracic echocardiography. The agreement between 4D flow CMR and transthoracic echocardiography for grading of aortic valve regurgitation was good (κ = 0.73). To identify relevant, more than mild aortic valve regurgitation, CMR 4D flow imaging had a sensitivity of 100 % and specificity of 98 %. Aortic regurgitation can be well visualized, in a similar manner as transthoracic echocardiography, when using CMR 4D flow imaging

Echocardiographic parameters of severe pulmonary regurgitation after surgical repair of tetralogy of Fallot

Aims: Reliable evaluation of the severity and consequences of pulmonary regurgitation (PR) in patients with repaired tetralogy of Fallot (TOF) is crucial to timely identify the need for pulmonary valve intervention. We aimed to identify the accuracy of echocardiographic parameters to differentiate between moderate and severe PR, using phase contrast cardiac magnetic resonance imaging (CMR) as gold standard. Methods and results: In this cross-sectional study, 45 TOF patients with both echocardiographic and CMR measurements of PR were enrolled. All quantitative and semiquantitative echocardiographic measurements such as pressure half time (PHT), Color flow jet width (CFJW), ratio CFJW/right ventricle outflow tract (RVOT) diameter, PR index and the presence of early termination of the PR jet, end-diastolic antegrade flow and diastolic backflow in main pulmonary artery (MPA), and PA branches correlated significantly with PR fraction on CMR. Qualitative assessment with color flow on echocardiography overestimated PR Multivariate linear regression analysis identified the ratio of CFJW/RVOT diameter and PHT as independent predictors of PR fraction. Accuracy of echo parameters was tested to differentiate between mild-to-moderate and severe PR Combining different echocardiographic parameters increased sensitivity and specificity. The addition of diastolic flow reversal in the PA branches to PHT below 167 milliseconds increased the NPV from 87% to 89% and PPV from 62% to 76%. Conclusions: Comparison with CMR confirms that echocardiographic parameters are reliable in predicting PR severity. Combined measurement of diastolic flow reversal in the pulmonary artery branches and PHT is reliable in the detection of severe PR in the follow-up of TOF patients

Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: A proof-of-concept study in the preoperative window period (ImPACCT)

Background: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cance

Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening

Aims More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities. Methods and results DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6 months. Eight female healthy swine on normal pig-chow served as controls. The DM + HC + HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure-volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained. Conclusions The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction

Estimating the Heritability of Experiencing Child Maltreatment in an Extended Family Design

Child-driven genetic factors can contribute to negative parenting and may increase the risk of being maltreated. Experiencing childhood maltreatment may be partly heritable, but results of twin studies are mixed. In the current study, we used a cross-sectional extended family design to estimate genetic and environmental effects on experiencing child maltreatment. The sample consisted of 395 individuals (225 women; Mage = 38.85 years, rangeage = 7–88 years) from 63 families with two or three participating generations. Participants were oversampled for experienced maltreatment. Self-reported experienced child maltreatment was measured using a questionnaire assessing physical and emotional abuse, and physical and emotional neglect. All maltreatment phenotypes were partly heritable with percentages for h2 ranging from 30% (SE = 13%) for neglect to 62% (SE = 19%) for severe physical abuse. Common environmental effects (c2) explained a statistically significant proportion of variance for all phenotypes except for the experience of severe physical abuse (c2 = 9%, SE = 13%, p =.26). The genetic correlation between abuse and neglect was ρg =.73 (p =.02). Common environmental variance increased as socioeconomic status (SES) decreased (p =.05), but additive genetic and unique environmental variances were constant across different levels of SES