Andrew C Cook

• Professor
• Professor (Full) at University College London

In this review, we summarise the ongoing debate surrounding the anatomy of the atrioventricular conduction axis and its relevance to pacing. We highlight previous disagreements and emphasise the importance of understanding the anatomical location of the axis. We give credit and support to the initial descriptions by His and Tawara, in particular th...

Snap‐frozen biopsies serve as a valuable clinical resource of archival material for disease research, as they enable a comprehensive array of downstream analyses to be performed, including extraction and sequencing of nucleic acids. Obtaining three‐dimensional (3D) structural information before multi‐omics is more challenging but can potentially al...

Assessment of the right ventricular outflow tract and pulmonary arteries (RVOT) for percutaneous pulmonary valve implantation (PPVI) uses discrete measurements (diameters and lengths) from medical images. This multi-centre study identified the 3D RVOT shape features prevalent in patients late after surgical repair of congenital heart disease (CHD)....

Introduction Statistical shape analysis (SSA) with clustering is often used to objectively define and categorise anatomical shape variations. However, studies until now have often focused on simplified anatomical reconstructions, despite the complexity of studied anatomies. This work aims to provide insights on the anatomical detail preservation re...

Background . Mitral transcatheter edge-to-edge repair (m-TEER) is a minimally invasive procedure for treating mitral regurgitation (MR). m-TEER is a highly technical procedure, and a steep learning curve needs to be overcome for operators to ensure optimal patient outcomes and minimise procedural complications. Training via online simulation and ob...

Snap frozen biopsies serve as a valuable clinical resource of archival material for disease research, as they enable a comprehensive array of downstream analyses to be performed, including extraction and sequencing of nucleic acids. Obtaining three-dimensional (3D) structural information prior to multi-omics is more challenging but could potentiall...

Despite centuries of investigation, certain aspects of left ventricular anatomy remain either controversial or uncertain. We make no claims to have resolved these issues, but our review, based on our current knowledge of development, hopefully identifies the issues requiring further investigation. When first formed, the left ventricle had only inle...

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: Complications of atrial fibrillation (AF) include ischemic events originating within the left atrial appendage (LAA), a protrusion of the left atrium with variable morphological characteristics. The role of the patient specific morphology and pathological haemodynamics on the risk of ischemia remains unclear. Methods: This work performs...

Inversion of the left atrial appendage is a rare phenomenon, which may occur during the de-airing maneuvers associated to routinely performed surgery procedures, such as cardiopulmonary bypass or left ventricular assist device implantation. In this case, the body of the inverted appendage can obstruct the mitral valve leading to severe complication...

Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that mult...

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...

Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that mult...

Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP...

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...

Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from specialists of congenital cardiac disease. The aim of this review is to provide a classification, from the perspective of these specialists, based on an understanding of normal and abnorma...

Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from specialists of congenital cardiac disease. The aim of this review is to provide a classification, from the perspective of these specialists, based on an understanding of normal and abnorma...

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...

Abnormal aortic arches (AAAs) cover a spectrum of malformations, including abnormal laterality, branching patterns, and flow-limiting narrowing, which themselves vary from tubular hypoplasia, through discrete coarctation, to complete interruption of the arch. Neonatal surgery within the first days of life is necessary for most of these morphologies...

Background A large majority of thrombi causing ischemic complications under atrial fibrillation (AF) originate in the left atrial appendage (LAA), an anatomical structure departing from the left atrium, characterized by a large morphological variability between individuals. This work analyses the hemodynamics simulated for different patient-specifi...

Objectives: This study evaluates predictors of conduction abnormalities (CA) following transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valves (BAV). Background: TAVI is associated with CA that commonly necessitate a permanent pacemaker. Predictors of CA are well established among patients with tricuspid aortic val...

The protein kinase PKN2 is required for embryonic development and PKN2 knockout mice die as a result of failure in expansion of mesoderm, cardiac development and neural tube closure. In the adult, cardiomyocyte PKN2 and PKN1 (in combination) are required for cardiac adaptation to pressure-overload. The specific role of PKN2 in contractile cardiomyo...

Mitral regurgitation is a common valvular disorder. Transcatheter edge-to-edge repair (TEER) is a minimally invasive technique which involves holding together the middle segments of the mitral valve leaflets, thereby reducing regurgitation. To date, MitraClip™ is the only Food and Drug Administration (FDA)-approved device for TEER. The MitraClip pr...

Background The protein kinase PKN2 is required for embryonic development, and PKN2 knockout mice die as a result of failure in expansion of mesoderm tissues, cardiac development and neural tube closure. In the adult, cardiomyocyte PKN2 and PKN1 (in combination) are required for cardiac adaptation to pressure-overload. The role of PKN2 in contractil...

The cardiac conduction system (CCS) comprises critical components responsible for the initiation, propagation, and coordination of the action potential. Aberrant CCS development can cause conduction abnormalities, including sick sinus syndrome, accessory pathways, and atrioventricular and bundle branch blocks. Gene Ontology (GO; http://geneontology...

Aims We aim to determine any additional benefit of virtual reality (VR) experience if compared to conventional cross-sectional imaging and standard 3D modelling when deciding on surgical strategy in patients with complex double outlet right ventricle (DORV). Methods and results We retrospectively selected ten consecutive patients with DORV and com...

Congenital heart disease (CHD) is the most common defect at birth. Effective training for clinical professionals is essential in order to provide a high standard of care for patients. Visual aids for teaching complex CHD have remained mostly unchanged in recent years, with traditional methods such as diagrams and specimens still essential for deliv...

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized world...

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code ( IPCCC ) is now utilized wor...

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,...

It is axiomatic that understanding of abnormal anatomy requires a thorough knowledge of normal findings. Nowadays, this knowledge should be based on the appreciation of the location of the heart within the chest, since the basic rule of anatomy is that all structures should be described relative to the anatomical position. The discrepancy between t...

X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a...

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...

Objectives: To assess the feasibility of retrieval of intact human fetal hearts after first trimester surgical termination of pregnancy (TOP) and subsequent anatomical assessment by postmortem micro-computed tomography (micro-CT). Methods: In a cohort of consenting women undergoing surgical TOP between 8 and 13 weeks' gestation, we attempted the...

Funding Acknowledgements La Fondation Dassault Systèmes, British Heart Foundation Background Virtual reality (VR) provides a unique possibility to interact with three-dimensional objects. Still in its infancy, the integration of VR with advanced cardiovascular imaging technology allows users to handle patient-specific cardiac models. Purpose The...

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...

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...

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...

Background Discussions continue as to whether ventricular septal defects are best categorized according to their right ventricular geography or their borders. This is especially true when considering the perimembranous defect. Our aim, therefore, was to establish the phenotypic feature of the perimembranous defect, and to establish the ease of dist...

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...

During embryogenesis, a mammalian heart develops from a simple tubular shape into a complex 4-chamber organ, going through four distinct phases: early primitive tubular heart, emergence of trabeculations, trabecular remodeling and development of the compact myocardium. In this paper we propose a framework for standardized and subject-independent 3D...

The definition and classification of ventricular septal defects have been fraught with controversy. The International Society for Nomenclature of Paediatric and Congenital Heart Disease is a group of international specialists in pediatric cardiology, cardiac surgery, cardiac morphology, and cardiac pathology that has met annually for the past nine...

Microfocus computed tomography (micro-CT) is an imaging method that provides three dimensional (3D) digital datasets with comparable resolution to light microscopy. Although it has traditionally been used for non-destructive testing in engineering, aerospace industries and in preclinical animal studies, new applications are rapidly becoming availab...

During Atrial Fibrillation (AF) more than 90% of the left atrial thrombi responsible for thromboembolic events originate in the left atrial appendage (LAA), a complex small sac protruding from the left atrium (LA). Current available treatments to prevent thromboembolic events are oral anticoagulation, surgical LAA exclusion, or percutaneous LAA occ...

Differences between hearts of crocodilians and those of mammals and birds are only partly understood because there is no standardised approach and terminology for describing cardiac structure. Whereas most reptiles have an undivided ventricle, crocodilians have a fully septated ventricle. Their hearts, therefore, are more readily comparable with th...

The high-throughput 3D visualisation of biological specimens is essential for studying diseases and developmental disorders. It requires imaging methods that deliver high-contrast, high-resolution volumetric information at short sample preparation and acquisition times. Here we show that X-ray phase-contrast tomography using a single grating can pr...

Objectives: To clarify the terms surrounding the posterior aortic root enlarging incisions and correlate them anatomically. Methods: This is a human cadaveric heart study in which measurements were taken along the path of the named incisions in 42 normal and congenitally malformed hearts using calipers. Results: Our results indicate that there...

Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomeric proteins, the commonest being MYBPC3 encoding myosin-binding protein C. It is characterised by left ventricular hypertrophy but there is an important pre-hypertrophic phenotype with features including crypts, abnormal mitral leaflets and trabeculae. We investigated these during...

A comprehensive understanding of left atrial anatomy has become essential as transcatheter therapies have emerged for left atrial appendage (LAA) occlusion, atrial fibrillation (AF) ablation, mitral valvular repair and replacement, and atrial septal defect closures. Furthermore, intentional and inadvertent instrumentation of pulmonary veins and LAA...

Lost treasures: a plea for the systematic preservation of cadaveric heart specimens through three-dimensional digital imaging - Volume 25 Issue 8 - Stephen P. Seslar, Charles W. Shepard, Jorge M. Giroud, Vera D. Aiello, Andrew C. Cook, Diane E. Spicer, James D. St. Louis, Rodney C.G. Franklin, Jeffrey P. Jacobs, Robert H. Anderson, On behalf of the...

We report three cases of an abnormal finding of duplicated left pulmonary artery: two of these occurring in children with Kabuki syndrome and configuring the setting of a pseudo-pulmonary sling without any clinical or cardiac cross-sectional evidence of tracheal compression. The other case instead represents duplicated left pulmonary artery with pu...

The arterial switch operation (ASO) is widely used nowadays as the surgical strategy of choice to repair transposition of the great arteries (TGA). Residual morphological and geometrical abnormalities of the aorta, pulmonary arteries and coronary arteries, however, have not been fully studied in a three-dimensional (3D) domain. These morphometric c...

It is axiomatic that understanding of abnormal anatomy requires a thorough knowledge of normal findings. Nowadays, this knowledge should be based on the appreciation of the location of the heart within the chest, since the basic rule of anatomy is that all structures should be described relative to the anatomical position. The discrepancy between t...

Differentiation of the so-called sinus venosus defect from other defects permitting shunting between the atrial chambers remains problematic. The lesion is not a true septal defect, and current theories to explain the existence of the sinus venosus defect fall short. The presence of persistent systemic to pulmonary venous connections has been propo...

Permanent pacemaker (PPM) requirement is a recognized complication of transcatheter aortic valve implantation. We assessed the UK incidence of permanent pacing within 30 days of CoreValve implantation and formulated an anatomic and electrophysiological model. Data from 270 patients at 10 centers in the United Kingdom were examined. Twenty-five pati...

Although malformations involving the ventricular outflow tracts are often described as conotruncal malformations, there is no consensus as to the lesions included in, or excluded from, this category, reflecting, in part, the current lack of precise definitions of the embryonic truncus and conus. Analysis of development of the outflow tract in terms...

The revised fourth edition of this classic textbook on cardiac anatomy written from the stance of the cardiac surgeon features many new images, including computed tomography angiography. The provision of multiple high quality surgical and pathological photographs makes it essential reading for cardiac surgeons, and of great value to cardiologists,...

Incompetence of the left atrioventricular valve remains the final Achilles' heel of repair of atrioventricular septal defects (AVSDs), despite low operative mortality in the modern era. We have analysed the morphological basis for valvar incompetence in our own series of repairs, and in doing so, reviewed the morphology of the annulus in AVSDs, bef...

In the preceding chapter, we have seen how from the outset of development the right heart has very separate origins from the left. We have learned how the cells from the secondary heart field are responsible for the formation of the right ventricle and outflow tract, and how they are added to the initial linear heart tube slightly later in developm...

When there is obstruction of the left ventricular outflow tract, there are several surgical approaches to the repair of discordant ventriculo-arterial connections in the setting of concordant atrioventricular connections. Choosing the optimal technique demands not only knowledge of the different surgical procedures, but also the understanding of th...

To investigate the congenital heart disease (CHD) found in association with an increased nuchal translucency (NT) at 11-14 weeks of gestation in chromosomally normal and abnormal fetuses. Patients referred from January 1998 until May 2007 with an increased NT (> or = 95th percentile) where CHD was diagnosed were included. Chromosome analysis, fetal...

Congenital heart diseases are the most common congenital malformations, affecting six to eight per 1,000 live births [1–3], and their prevalence in abortuses has been shown to be even higher [4, 5]. Moreover, heart diseases are the leading cause of death among infants with congenital anomalies, causing nearly 20% of neonatal deaths and up to 50% of...

Once the laterality, visceroatrial arrangement, and cardiac position of the fetus have been established, the next step is to analyze the heart in a sequential segmental approach. Sequential analysis allows description of all congenital heart malformations, even the more complex ones, simply and unambiguously [1–3]. All hearts, whether normal or abn...

In the normal human, the midline sagittal plane divides the body into two sides that are mirror images of each other in term of their skeletal and muscular structure. However, many organs within the body, even those that are paired (such as lungs, bronchi, kidneys), show a distinctly lateralized arrangement. This lateralization is most striking in...

This series of transverse sections of the fetal body will be not discussed in detail here. The reader should refer to books and papers dealing with this subject. Among these sections, the portal sinus view holds a crucial role, not only because it is close to the section used for biometry of the upper abdomen, but also because it is crucial in the...

In the sequential segmental approach to diagnosing congenital heart disease, the morphological arrangement of the atria is the starting point [1, 2]. The appendages are the most constant component of the atria. Their shape and the morphology of their junction with the atria always show a morphologically right or left pattern. The morphologically le...

Cranially to the transverse view of the ductal arch, the transverse view of the aortic arch is obtained. The level of this section is shown in Figures 11.1, 11.2. These images illustrate that when the plane of this section is truly horizontal, the arterial duct and the pulmonary artery are no longer visible because they are lying in an inferior pla...

Although in most individuals two thirds of the heart is in the left side of the chest, the heart can be unusually positioned. All cardiac positions can be described in terms of overall location of the heart and orientation of its axis. The cardiac position and ax-is can be assessed by fetal echocardiography in the four-chamber view. In this view, b...

Visualization of the long-axis views of the aorta and arterial duct is facilitated in the fetus if one refers to a transverse section of the upper mediastinum as the starting point. For instance, the long-axis view of the aortic arch is obtained from the transverse view of the fetal thorax by rotating the scan plane 90° when the ascending and the d...

Because the diaphragm in the fetus is at a higher level within the chest, making the heart more horizontal than it is after birth, the four-chamber view of the heart lies closer to a transverse section of the fetal thorax just above the diaphragm (Fig. 7.1) [1]. This view is easily obtained from a transverse plane of the upper abdomen by tracing th...

With cranial angulation from a four-chamber view, the left ventricular outflow tract appears wedged between the two atrioventricular valves. With further cranial angulation, the aortic valve and the aortic root are imaged (Fig.8.1). Fig. 8.1 The plane of the five-chamber view on the fetal body (a) and on a heart diagram (b). AoV aortic valve, MV mi...

This view is obtained by orienting the scan plane along the true sagittal plane of the fetal body immediately to the right of the midline (Fig. 13.1). Alternatively, it is easily obtained with slight translation from a long-axis view of the aortic arch obtained from a parasagittal view of the right chest (Fig. 13.2b). Because this view shows the co...

Because of the horizontal position of the fetal heart, sections along its short axis lie on planes close to a sagittal plane of the fetal body. From a sagittal plane parallel to the fetal spine, these sections are obtained with a slight rotation toward the left side of the fetus, so that the examining plane is from the right hypochondrium to the le...

This view is obtained with the scan plane perpendicular to the long axis of the left ventricle. Because of the horizontal position of the fetal heart, these views lie on planes close to the sagittal plane of the fetal body. In normal hearts, this is obtained by cutting the fetal body on a parasagittal plane slightly rotated to the left shoulder. Tw...