ORCID Profile
0000-0002-4978-8965
Current Organisations
University of Oxford
,
St Peter's College, University of Oxford
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2022
DOI: 10.1161/HYPERTENSIONAHA.122.19115
Abstract: Approximately 10% of infants are born preterm. Preterm birth leads to short and long-term changes in cardiac shape and function. By using a rat model of neonatal high-oxygen (80%O 2 ) exposure, mimicking the premature hyperoxic transition to the extrauterine environment, we revealed a major role of the renin-angiotensin system peptide Angio II (angiotensin II) and its receptor AT1 (angiotensin receptor type 1) on neonatal O 2 -induced cardiomyopathy. Here, we tested whether treatment with either orally active compounds of the peptides Angio-(1–7) or alamandine included in cyclodextrin could prevent postnatal cardiac remodeling and the programming of cardiomyopathy induced by neonatal high-O 2 exposure. Sprague-Dawley pups were exposed to room air or 80% O 2 from postnatal day 3 (P3) to P10. Neonatal rats were treated orally from P3 to P10 and assessed at P10 and P28. Left ventricular (LV) shapes were characterized by tridimensional computational atlases of ultrasound images in addition to histomorphometry. At P10, high O 2 -exposed rats presented a smaller, globular and hypertrophied LV shape versus controls. Treatment with cyclodextrin–Angio-(1–7) significantly improved LV function in the O 2 -exposed neonatal rats and slightly changed LV shape. Cyclodextrin-alamandine and cyclodextrin–Angio-(1–7) treatments similarly reduced hypertrophy at P10 as well as LV remodeling and dysfunction at P28. Both treatments upregulated cardiac angiotensin-converting enzyme 2 in O 2 -exposed rats at P10 and P28. Our findings demonstrate LV remodeling changes induced by O 2 -stress and the potential benefits of treatments targeting the cardioprotective renin-angiotensin system axis, supporting the neonatal period as an important window for interventions aiming at preventing cardiomyopathy in people born preterm.
Publisher: Oxford University Press (OUP)
Date: 25-07-2023
Abstract: There is an immediate need to optimize cardiovascular (CV) risk management and primary prevention of childhood obesity to timely and more effectively combat the health hazard and socioeconomic burden of CV disease from childhood development to adulthood manifestation. Optimizing screening programs and risk management strategies for obesity-related CV risk in childhood has high potential to change disease trajectories into adulthood. Building on a holistic view on the aetiology of childhood obesity, this document reviews current concepts in primary prevention and risk management strategies by lifestyle interventions. As an additional objective, this scientific statement addresses the high potential for reversibility of CV risk in childhood and comments on the use of modern surrogate markers beyond monitoring weight and body composition. This scientific statement also highlights the clinical importance of quantifying CV risk trajectories and discusses the remaining research gaps and challenges to better promote childhood health in a population-based approach. Finally, this document provides an overview on the lessons to be learned from the presented evidence and identifies key barriers to be targeted by researchers, clinicians, and policymakers to put into practice more effective primary prevention strategies for childhood obesity early in life to combat the burden of CV disease later in life.
Publisher: Oxford University Press (OUP)
Date: 28-04-2023
Abstract: Hypertrophic cardiomyopathy (HCM) is characterized by hypercontractility and diastolic dysfunction, which alter blood flow haemodynamics and are linked with increased risk of adverse clinical events. Four-dimensional flow cardiac magnetic resonance (4D-flow CMR) enables comprehensive characterization of ventricular blood flow patterns. We characterized flow component changes in non-obstructive HCM and assessed their relationship with phenotypic severity and sudden cardiac death (SCD) risk. Fifty-one participants (37 non-obstructive HCM and 14 matched controls) underwent 4D-flow CMR. Left-ventricular (LV) end-diastolic volume was separated into four components: direct flow (blood transiting the ventricle within one cycle), retained inflow (blood entering the ventricle and retained for one cycle), delayed ejection flow (retained ventricular blood ejected during systole), and residual volume (ventricular blood retained for & two cycles). Flow component distribution and component end-diastolic kinetic energy/mL were estimated. HCM patients demonstrated greater direct flow proportions compared with controls (47.9 ± 9% vs. 39.4 ± 6%, P = 0.002), with reduction in other components. Direct flow proportions correlated with LV mass index (r = 0.40, P = 0.004), end-diastolic volume index (r = −0.40, P = 0.017), and SCD risk (r = 0.34, P = 0.039). In contrast to controls, in HCM, stroke volume decreased with increasing direct flow proportions, indicating diminished volumetric reserve. There was no difference in component end-diastolic kinetic energy/mL. Non-obstructive HCM possesses a distinctive flow component distribution pattern characterised by greater direct flow proportions, and direct flow-stroke volume uncoupling indicative of diminished cardiac reserve. The correlation of direct flow proportion with phenotypic severity and SCD risk highlight its potential as a novel and sensitive haemodynamic measure of cardiovascular risk in HCM.
Publisher: BMJ
Date: 06-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-12-2022
Abstract: Preterm birth affects 10% of live births and is associated with an altered left ventricular and right ventricular phenotype and increased cardiovascular disease risk in young adulthood. Because left atrial (LA) and right atrial (RA) volume and function are known independent predictors of cardiovascular outcomes, we investigated whether these were altered in preterm‐born young adults. Preterm‐born (n=200) and term‐born (n=266) adults aged 18 to 39 years underwent cardiovascular magnetic resonance imaging. LA and RA maximal and minimal volumes (absolute, indexed to body surface area, and as a ratio to ventricular volumes) were obtained to study atrial morphology, while LA and RA stroke volume, strain, and strain rate were used to assess atrial function. Secondary analyses consisted of between‐group comparisons based on degree of prematurity. Absolute RA volumes and RA volumes indexed to right ventricular volumes were significantly smaller in preterm‐born compared with term‐born adults. In addition, RA reservoir and booster strain were higher in preterm‐born adults, possibly indicating functional compensation for the smaller RA volumes. LA volumes indexed to left ventricular volumes were significantly greater in preterm‐born adults as compared with term‐born adults, although absolute LA volumes were similar between groups. LA and RA changes were observed across gestational ages in the preterm group but were greatest in those born very‐to‐extremely preterm. Preterm‐born adults show changes in LA and RA structure and function, which may indicate subclinical cardiovascular disease. Further research into underlying mechanisms, opportunities for interventions, and their prognostic value is warranted.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Adam Lewandowski.