The Fontan procedure is currently the palliative solution for children born with a univentricular heart. Despite an improved survival rate, many patients still suffer from complications, such as... Show moreThe Fontan procedure is currently the palliative solution for children born with a univentricular heart. Despite an improved survival rate, many patients still suffer from complications, such as heart failure. For this reason, both patients with and without heart failure are often treated with angiotensin-converting enzyme (ACE) inhibitors, although the effectiveness is unclear. In this thesis, we investigated various aspects of the Fontan circulation to assess not only the efficacy and side effects of ACE inhibition, but also the limitations of exercise capacity and the response of the circulation of these patients to acute volume loading tests. We showed that short-term ACE inhibition had no positive effects on exercise capacity, haemodynamics and cardiac function. It also appeared to have no negative effect on the Fontan circulation, apart from side effects during the titration period. Furthermore, we found that even relatively healthy young Fontan patients have reduced exercise capacity associated with diastolic dysfunction and aortic stiffness. Nevertheless, we found that paediatric Fontan patients are able to respond adequately to acute volume changes and they seem to adapt well to the Fontan circulation. Show less
To improve the predictive capability of pre-clinical models and reduce the use of animal models in drug discovery and disease modelling, advanced in vitro models are being developed. These... Show moreTo improve the predictive capability of pre-clinical models and reduce the use of animal models in drug discovery and disease modelling, advanced in vitro models are being developed. These microphysiological systems (MPS) or “Organs-on-Chip” (OoC) are being developed to include all aspects of the human physiology to improve the in vitro cellular response. OoCs combined with differentiated human induced pluripotent stem cells (hiPSC) allow the use of cells with patient specific genotypes and aid the development of personalized and precision medicine.In this thesis, the development of tractable models of the vasculature is described. These models allow for the combination of hiPSC-derived vascular and tissue specific cells with haemodynamics to recapitulate essential stimuli of blood vessels. Show less
Assadi, H.; Grafton-Clarke, C.; Demirkiran, A.; Geest, R.J. van der; Nijveldt, R.; Flather, M.; ... ; Garg, P. 2022
Objectives: Mitral regurgitation (MR) and microvascular obstruction (MVO) are common complications of myocardial infarction (MI). This study aimed to investigate the association between MR in ST... Show moreObjectives: Mitral regurgitation (MR) and microvascular obstruction (MVO) are common complications of myocardial infarction (MI). This study aimed to investigate the association between MR in ST-elevation MI (STEMI) subjects with MVO post-reperfusion. STEMI subjects undergoing primary percutaneous intervention were enrolled. Cardiovascular magnetic resonance (CMR) imaging was performed within 48-hours of initial presentation. 4D flow images of CMR were analysed using a retrospective valve tracking technique to quantify MR volume, and late gadolinium enhancement images of CMR to assess MVO. Results: Among 69 patients in the study cohort, 41 had MVO (59%). Patients with MVO had lower left ventricular (LV) ejection fraction (EF) (42 +/- 10% vs. 52 +/- 8%, P < 0.01), higher end-systolic volume (98 +/- 49 ml vs. 73 +/- 28 ml, P < 0.001) and larger scar volume (26 +/- 19% vs. 11 +/- 9%, P < 0.001). Extent of MVO was associated with the degree of MR quantified by 4D flow (R = 0.54, P = 0.0003). In uni-variate regression analysis, investigating the association of CMR variables to the degree of acute MR, only the extent of MVO was associated (coefficient = 0.27, P = 0.001). The area under the curve for the presence of MVO was 0.66 (P = 0.01) for MR > 2.5 ml. We conclude that in patients with reperfused STEMI, the degree of acute MR is associated with the degree of MVO. Show less
Grafton-Clarke, C.; Crandon, S.; Westenberg, J.J.M.; Swoboda, P.P.; Greenwood, J.P.; Geest, R.J. van der; ... ; Garg, P. 2021
Objectives Four-dimensional flow CMR allows for a comprehensive assessment of the blood flow kinetic energy of the ventricles of the heart. In comparison to standard two-dimensional image... Show moreObjectives Four-dimensional flow CMR allows for a comprehensive assessment of the blood flow kinetic energy of the ventricles of the heart. In comparison to standard two-dimensional image acquisition, 4D flow CMR is felt to offer superior reproducibility, which is important when repeated examinations may be required. The objective was to evaluate the inter-observer and intra-observer reproducibility of blood flow kinetic energy assessment using 4D flow of the left ventricle in 20 healthy volunteers across two centres in the United Kingdom and the Netherlands. Data description This dataset contains 4D flow CMR blood flow kinetic energy data for 20 healthy volunteers with no known cardiovascular disease. Presented is kinetic energy data for the entire cardiac cycle (global), the systolic and diastolic components, in addition to blood flow kinetic energy for both early and late diastolic filling. This data is available for reuse and would be valuable in supporting other research, such as allowing for larger sample sizes with more statistical power for further analysis of these variables. Show less
Roehr, C.C.; Pas, A.B. te; Dold, S.K.; Breindahl, M.; Blennow, M.; Rudiger, M.; Gupta, S. 2013
