Patricia Garcia-Canadilla

Hospital Sant Joan de Déu · Servicio de Cardiología / Enfermedades del corazón

The aim of this study was to investigate the pulmonary vasculature in baseline conditions and after maternal hyperoxygenation in growth restricted fetuses (FGR). A prospective cohort study of singleton pregnancies including 97 FGR and 111 normally grown fetuses was carried out. Ultrasound Doppler of the pulmonary vessels was obtained at 24–37 weeks...

The intricate relationship between atrial fibrillation (AF), blood flow disturbances, and thrombus emergence is well-established in humans. Thrombi primarily form in the left atrial appendage (LAA), but the specific role of LAA morphology in this process remains unclear. Felines, despite rarely experiencing AF, present a valuable model for studying...

Background Cardiac imaging is essential for identifying structural changes in advanced heart failure (HF) and understanding underlying pathophysiology. Synchrotron radiation-based X-ray phase contrast imaging (X-PCI) is a non-destructive imaging modality that can provide high resolution three-dimensional (3D) visualisation of cardiac tissue on the...

Background Analysis of myocardial biopsies using conventional two-dimensional (2D) histological techniques is limited in the detection of important three-dimensional (3D) structural features, such as disarray, due to sectioning and artefacts from dehydration or chemical processing. More advanced techniques such as light-sheet microscopy, micro-comp...

Introduction: Congenital heart diseases (CHDs) are the most common congenital anomalies, and almost one-third of patients require an intervention in the neonatal period or first year of life. Unlike low- and middle-income countries (LMICs), the survival of patients with CHD in high income countries is over 90%. The aim of this study was to compare...

X-ray phase contrast imaging (X-PCI) is a powerful technique for high-resolution, three-dimensional imaging of soft tissue samples in a non-destructive manner. In this technical report, we assess the quality of standard histopathological techniques performed on formalin-fixed, paraffin-embedded (FFPE) human tissue samples that have been irradiated...

Cirrhosis is a prevalent chronic liver disease that causes scarring of the liver, leading to altered mechanics and impaired function. One of its most severe complications is portal hypertension, characterised by an increase in portal vein pressure, associated with abnormal blood flow dynamics. Portal hypertension is usually diagnosed by measuring t...

Immunotherapy has considerably improved clinical outcomes in different types of cancers but has also been associated with the development of myocarditis, especially with that mediated by immune checkpoint inhibitors. To the best of our knowledge, these are the first cases of myocarditis after anti‐GD2 immunotherapy reported to date. We present two...

Artificial placenta (AP) is a promising approach to improve survival in extremely premature fetuses, removing them from the uterus and replacing the placenta by an external oxygenator. In in vivo experiments with lambs, haemodynamic changes were observed in the umbilical artery (UA) post-connection to the AP: decrease in flow pulsatility index (PI)...

Endomyocardial biopsies are the gold standard for surveillance of graft rejection following heart transplantation, and are assessed by classical histopathology using a limited number of previously stained slices from several biopsies. Synchrotron propagation-based X-ray phase contrast imaging is a non-destructive method to image biological samples...

Introduction Cardiac architecture has been extensively investigated ex vivo using a broad spectrum of imaging techniques. Nevertheless, the heart is a dynamic system and the structural mechanisms governing the cardiac cycle can only be unveiled when investigating it as such. Methods This work presents the customization of an isolated, perfused hea...

The mammalian heart, which is one of the first organs to form and function during embryogenesis, develops from a simple tube into a complex organ able to efficiently pump blood towards the rest of the body. The progressive growth of the compact myocardium during embryonic development is accompanied by changes in its structural complexity and organi...

Pediatric congenital heart disease (CHD) patients are at higher risk of postoperative complications and clinical deterioration either due to their underlying pathology or due to the cardiac surgery, contributing significantly to mortality, morbidity, hospital and family costs, and poor quality of life. In current clinical practice, clinical deterio...

Aims We investigated left ventricular (LV) remodelling, mechanics, systolic and diastolic function, combined with clinical characteristics and heart-failure treatment in association to death or heart-transplant (DoT) in paediatric idiopathic, genetic or familial dilated cardiomyopathy (DCM), using interpretable machine-learning. Methods and result...

Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in detail. The o...

In humans, there is a well-established relationship between atrial fibrillation (AF), blood flow abnormalities and thrombus formation, even if there is no clear consensus on the role of left atrial appendage (LAA) morphologies. Cats can also suffer heart diseases, often leading to an enlargement of the left atrium that promotes stagnant blood flow,...

In humans, there is a well-established relationship between atrial fibrillation (AF), blood flow abnormalities and thrombus formation, even if there is no clear consensus on the role of left atrial appendage (LAA) morphologies. Cats can also suffer heart diseases, often leading to an enlargement of the left atrium that promotes stagnant blood flow,...

Background: Distinguishing the etiology of left ventricular hypertrophy (LVH) is clinically relevant due to patient outcomes and management. Easily obtained, echocardiography-based myocardial deformation patterns may improve standard non-invasive phenotyping, however, the relationship between deformation phenotypes and etiology-related, microstruct...

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Horizon 2020 European Commission Project H2020-MSCA-ITN-2016 (764738) and the Clinical Research in Cardiology grant from the Spanish Cardiac Society. Background The aetiology of left ventricular hypertrophy (LVH) is a relevant clinical challenge...

Background: Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in d...

Abstract Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured,...

The heart is a complex multi-scale system composed of components integrated at the subcellular, cellular, tissue and organ levels. The myocytes, the contractile elements of the heart, form a complex three-dimensional (3D) network which enables propagation of the electrical signal that triggers the contraction to efficiently pump blood towards the w...

Objective: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults; however cardiac structure and function in fetal CoA and the neonatal cardiac adaptation has not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and t...

In fetal cardiology, imaging (especially echocardiography) has demonstrated to help in the diagnosis and monitoring of fetuses with a compromised cardiovascular system potentially associated with several fetal conditions. Different ultrasound approaches are currently used to evaluate fetal cardiac structure and function, including conventional 2-D...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Myoarchitectural disarray-the multiscalar disorganisation of myocytes, is a recognised histopathological hallmark of adult human hypertrophic cardiomyopathy (HCM). It occurs before the establishment of left ventricular hypertrophy (LVH) but its early origins and evolution around the time of birth are unknown. Our aim is to investigate whether myoar...

Intrauterine growth restriction (IUGR) is a fetal condition that affects up to 10% of all pregnancies and is associated with cardiovascular structural and functional remodelling that persists postnatally. Some studies have reported an increase in myocardial coronary blood flow in severe IUGR fetuses which has been directly associated to the dilatat...

Introduction: Understanding the complexity of heart morphogenesis and the associated functional consequences of congenital heart disease is essential for providing appropriate treatment strategies. Since our knowledge on the microstructure of the whole fetal & paediatric heart is limited, novel imaging approaches offered by synchrotron facilities c...

Cardiovascular diseases (CVDs) affect the myocardium and vasculature, inducing remodelling of the heart from cellular to whole organ level. To assess their impact at micro and macroscopic level, multi-resolution imaging techniques that provide high quality images without sample alteration and in 3D are necessary: requirements not fulfilled by most...

Aortic wall remodelling is a key feature of both ageing and genetic connective tissue diseases, which are associated with vasculopathies such as Marfan syndrome (MFS). Although the aorta is a 3D structure, little attention has been paid to volumetric assessment, primarily due to the limitations of conventional imaging techniques. Phase-contrast mic...

Supplementary methods and figures.

Background: In the era of increasingly successful corrective interventions in patients with congenital heart disease (CHD), global and regional myocardial remodeling are emerging as important sources of long-term morbidity/mortality. Changes in organization of the myocardium in CHD, and in its mechanical properties, conduction, and blood supply, r...

Aims Myocardial structural and functional abnormalities are known to occur in fetuses of mothers with diabetes mellitus (FMDM). The main aim of this investigation was to explore the cardiovascular circulatory patterns in FMDM using a validated lumped computational model of the cardiovascular system. Methods This was a multi-institutional study inv...

Experimental studies on isolated cardiomyocytes from different animal species and human hearts have demonstrated that there are regional differences in the Ca²⁺ release, Ca²⁺ decay and sarcomere deformation. Local deformation heterogeneities can occur due to a combination of factors: regional/local differences in Ca²⁺ release and/or re-uptake, intr...

Supplementary methods. (PDF)

Fitting SL-active tension relationship. Fitting of the experimental data obtained by Weiwad et al [33], highlighting the SL-active tension relationship for skinned cardiac cells with the expression Tact given by equation S1.22 in S1 Appendix. Data points series correspond to pCa values of 5.7, 5.46 and 4.9. Solid lines indicate the best solution ob...

Introduction: Aortic coarctation is one of the most difficult cardiac defects to diagnose before birth, and it accounts for 8% of congenital heart diseases. Antenatal diagnosis is crucial for early treatment of the neonate and to decrease the risk of morbidity and mortality; however the fetal hemodynamic changes are not fully understood and current...

Nowadays, unexplained cardiovascular diseases (CVD) and heart transplant response are assessed by qualitative histological analysis of extracted endomyocardial biopsies (EMB), which is a time consuming procedure involving structural damage of the tissue and the analysis in only a few slices of a 3D structure. In this paper we propose synchrotron ra...

Background: While individual cardiac myocytes only have a limited ability to shorten, the heart efficiently pumps a large volume-fraction thanks to a cell organization in a complex 3D fibre structure. Subclinical subtle cardiac structural remodelling is often present before symptoms arise. Understanding and early detection of these subtle changes...

Objective: The aortic isthmus (AoI) blood flow has a characteristic shape with a small end-systolic notch observed during the third trimester of pregnancy. However, what causes the appearance of this notch is not fully understood. We used a lumped model of the fetal circulation to study the possible factors causing the end-systolic notch and the c...

Background Intrauterine growth restriction (IUGR) induces fetal cardiac remodelling and dysfunction, which persists postnatally and may explain the link between low birth weight and increased cardiovascular mortality in adulthood. However, the cellular and molecular bases for these changes are still not well understood. We tested the hypothesis tha...

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been propose...

Automatic quantification of cardiac muscle properties in tissue sections might provide important information related to different types of diseases. Second harmonic generation (SHG) imaging provides a stain-free microscopy approach to image cardiac fibers that, combined with our methodology of the automated measurement of the ultrastructure of musc...

To assess whether abnormal cardiac function in human fetuses with intrauterine growth restriction (IUGR) is associated with ultrastructural differences in the cardiomyocyte sarcomere. Nine severe early-onset IUGR and nine normally grown fetuses (AGA, appropriate growth for gestational age) that died in the perinatal period were prospectively includ...

Intrauterine growth restriction (IUGR) affects 7-10% of pregnancies and is associated with cardiovascular remodeling and dysfunction which persists into adulthood. The underlying subcellular remodeling and cardiovascular programming events are still poorly documented. Cardiac muscle is central in the fetal adaptive mechanism to IUGR given its high...

Intrauterine Growth Restriction due to placental insufficiency leads to cardiac dysfunction in utero which can persist postnatally. Brain sparing by flow redistribution is an adaptive mechanism used by the restricted fetus to ensure delivery of oxygenated blood to the brain. The quantification of reversed flow in the aortic isthmus is used in clini...

Polarization Second Harmonic Generation enables to quantify some of the underlying molecular details of key biological structures within muscle, axons and collagen at suboptical scales. However, it is only available in dedicated labs. In this work we detail a procedure to adapt and calibrate a commercial multiphoton microscope (Leica TCS-SP5) to ac...

Purpose: Intrauterine growth restriction (IUGR) is associated with cardiovascular remodelling and dysfunction persisting into adulthood, resulting in dilated and less efficient hearts. However, evidence of direct fetal programming of cardiac cytoarchitecture is scarce, and the underlying molecular mechanisms remain to be elucidated. Here we show th...

Purpose: As it has been reported that ultrasound (US) backscattering changes according to tissue microstructure, we evaluated whether exists an association between invariant image features of B-mode ultrasound (US) and histological changes in arteries of rabbits with induced Atherosclerotic Vascular Disease (AVD) at early stages. Methods: AVD was...

cAMP generated in response to β-adrenoceptor stimulation modulates excitation-contraction coupling via activation of PKA. It is now widely accepted that cAMP signalling is compartmentalised in the heart and that PDEs, the only cAMP degrading enzyme, play a central role in spatial control of signal propagation. We have previously demonstrated that P...

Cardiovascular diseases are one of the main causes of mortality in the world. For this reason it is important to develop techniques that allow for better understanding of cardiac remodelling prior to heart failure. In this line, Second Harmonic Imaging (SHI) provides a label-free microscopy approach to image cardiac fibers. In this work, we automat...