Low-density lipoprotein concentration in the normal left coronary artery tree

<p>Abstract</p> <p>Background</p> <p>The blood flow and transportation of molecules in the cardiovascular system plays a crucial role in the genesis and progression of atherosclerosis. This computational study elucidates the Low Density Lipoprotein (LDL) site concentration in the entire normal human 3D tree of the LCA.</p> <p>Methods</p> <p>A 3D geometry model of the normal human LCA tree is constructed. Angiographic data used for geometry construction correspond to end-diastole. The resulted model includes the LMCA, LAD, LCxA and their main branches. The numerical simulation couples the flow equations with the transport equation applying realistic boundary conditions at the wall.</p> <p>Results</p> <p>High concentration of LDL values appears at bifurcation opposite to the flow dividers in the proximal regions of the Left Coronary Artery (LCA) tree, where atherosclerosis frequently occurs. The area-averaged normalized luminal surface LDL concentrations over the entire LCA tree are, 1.0348, 1.054 and 1.23, for the low, median and high water infiltration velocities, respectively. For the high, median and low molecular diffusivities, the peak values of the normalized LDL luminal surface concentration at the LMCA bifurcation reach 1.065, 1.080 and 1.205, respectively. LCA tree walls are exposed to a cholesterolemic environment although the applied mass and flow conditions refer to normal human geometry and normal mass-flow conditions.</p> <p>Conclusion</p> <p>The relationship between WSS and luminal surface concentration of LDL indicates that LDL is elevated at locations where WSS is low. Concave sides of the LCA tree exhibit higher concentration of LDL than the convex sides. Decreased molecular diffusivity increases the LDL concentration. Increased water infiltration velocity increases the LDL concentration. The regional area of high luminal surface concentration is increased with increasing water infiltration velocity. Regions of high LDL luminal surface concentration do not necessarily co-locate to the sites of lowest WSS. The degree of elevation in luminal surface LDL concentration is mostly affected from the water infiltration velocity at the vessel wall. The paths of the velocities in proximity to the endothelium might be the most important factor for the elevated LDL concentration.</p

Adult Congenital Heart Disease Investigated with Cardiac Catheterization Over A 20-Year Period

BACKGROUND: Recent advances in diagnosis and treatment have increased the life expectancy of patients with congenital heart disease. METHODS: To investigate the prevalence of adult congenital heart disease (ACHD) in a large registry of patients over a 20-year period, we retrospectively assessed data of 14,012 males and 4,461 females who underwent clinically indicated cardiac catheterization from 1984 to 2003. RESULTS: ACHD was recorded in 234 subjects aged from 18 to 66 years, [95 males (40.7%) and 139 females (59.3%)]. Females were more likely to present with ACHD than males (p<0.001). Atrial septal defect was the most common defect (43.3%) followed by partial anomalous pulmonary venous return (12.0%), pulmonary valve stenosis (11.3%) ventricular septal defect (8.0%), coarctation of aorta (5.5%) patent ductus arteriosus (4.0%) and Fallot's tetralogy (3.3%). Atrial septal defect was more common in females (p<0.01), while pulmonary valve stenosis was more frequent in males (p<0.05). No difference across sexes was found in the other forms of ACHD. Females with ACHD were significantly older than males at the time of catheterization (median age 41 years, interquartile range 26 to 53 years vs. median age 35 years, interquartile range 22 to 48 years, p<0.05). CONCLUSIONS: In adulthood ACHD is found more commonly in females and is diagnosed later in life than in males. Atrial septal defect is the most prevalent form of ACHD and occurs most commonly in females

Impact of Chaos in the Progression of Heart Failure

Abstract Purpose of review: Cardiologists and researchers are well informed of the advances in chaos theor

Clinical Phenotypes of Cardiovascular and Heart Failure Diseases Can Be Reversed? The Holistic Principle of Systems Biology in Multifaceted Heart Diseases

Recent advances in cardiology and biological sciences have improved quality of life in patients with complex cardiovascular diseases (CVDs) or heart failure (HF). Regardless of medical progress, complex cardiac diseases continue to have a prolonged clinical course with high morbidity and mortality. Interventional coronary techniques together with drug therapy improve quality and future prospects of life, but do not reverse the course of the atherosclerotic process that remains relentlessly progressive. The probability of CVDs and HF phenotypes to reverse can be supported by the advances made on the medical holistic principle of systems biology (SB) and on artificial intelligence (AI). Studies on clinical phenotypes reversal should be based on the research performed in large populations of patients following gathering and analyzing large amounts of relative data that embrace the concept of complexity. To decipher the complexity conundrum, a multiomics approach is needed with network analysis of the biological data. Only by understanding the complexity of chronic heart diseases and explaining the interrelationship between different interconnected biological networks can the probability for clinical phenotypes reversal be increased

Clinical Phenotypes of Cardiovascular and Heart Failure Diseases Can Be Reversed? The Holistic Principle of Systems Biology in Multifaceted Heart Diseases

Recent advances in cardiology and biological sciences have improved quality of life in patients with complex cardiovascular diseases (CVDs) or heart failure (HF). Regardless of medical progress, complex cardiac diseases continue to have a prolonged clinical course with high morbidity and mortality. Interventional coronary techniques together with drug therapy improve quality and future prospects of life, but do not reverse the course of the atherosclerotic process that remains relentlessly progressive. The probability of CVDs and HF phenotypes to reverse can be supported by the advances made on the medical holistic principle of systems biology (SB) and on artificial intelligence (AI). Studies on clinical phenotypes reversal should be based on the research performed in large populations of patients following gathering and analyzing large amounts of relative data that embrace the concept of complexity. To decipher the complexity conundrum, a multiomics approach is needed with network analysis of the biological data. Only by understanding the complexity of chronic heart diseases and explaining the interrelationship between different interconnected biological networks can the probability for clinical phenotypes reversal be increased

Progressive nature of heart failure and systems biology

The progressive nature of heart failure (HF) is the predominant cause for the clinical course that the HF syndrome is taking. Systems biology methodology is of the utmost importance to explain and comprehend the built-in mechanisms of adverse clinical progression. Various heart diseases produce myocardial damage with subsequent left ventricular remodeling which is the principal underlying pathophysiological mechanism for the clinical progression of HF. The self-organized positive feedback stabilization mechanisms of left ventricular remodeling, adrenergic stimulation and activation of the renin-angiotensin-aldosterone system and natriuretic peptide systems, are hierarchical adaptive processes. These adaptive processes are responsible for further left ventricular remodeling with subsequent clinical deterioration and for the emergence of clinical phenotypes. These mechanisms are counteracted with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and β-blockers in an attempt to improve the adverse clinical phenomena of HF progression in a new but clinically worse stabilization level. In this review our intention is to underline the progressive nature of the HF syndrome and to demonstrate the significance of ventricular remodeling and the role of self-organized positive feedback adaptive processes

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy

Heart Failure in Patients with Preserved Ejection Fraction: Questions Concerning Clinical Progression

Over the last two decades, important advances have been made in explaining some pathophysiological aspects of heart failure with preserved ejection fraction (HFpEF) with repercussions for the successful clinical management of the syndrome. Despite these gains, our knowledge for the natural history of clinical progression from the pre-clinical diastolic dysfunction (PDD) until the final clinical stages is significantly limited. The subclinical progression of PDD to the clinical phenotype of HFpEF and the further clinical progression to some more complex clinical models with multi-organ involvement, similar to heart failure with reduced ejection fraction (HFrEF), continue to be poorly understood. Prospective studies are needed to elucidate the natural history of clinical progression in patients with HFpEF and to identify the exact left ventricular remodeling mechanism that underlies this progression

Constraints in Clinical Cardiology and Personalized Medicine: Interrelated Concepts in Clinical Cardiology

Systems biology is established as an integrative computational analysis methodology with practical and theoretical applications in clinical cardiology. The integration of genetic and molecular components of a disease produces interacting networks, modules and phenotypes with clinical applications in complex cardiovascular entities. With the holistic principle of systems biology, some of the features of complexity and natural progression of cardiac diseases are approached and explained. Two important interrelated holistic concepts of systems biology are described; the emerging field of personalized medicine and the constraint-based thinking with downward causation. Constraints in cardiovascular diseases embrace three scientific fields related to clinical cardiology: biological and medical constraints; constraints due to limitations of current technology; and constraints of general resources for better medical coverage. Systems healthcare and personalized medicine are connected to the related scientific fields of: ethics and legal status; data integration; taxonomic revisions; policy decisions; and organization of human genomic data