Pediatric cardiology in the genomic era

While congenital heart disease, cardiomyopathy, arrhythmias and acquired cardiac diseases are common causes of mortality and morbidity in infants and children, the basic underlying mechanisms of many specific pediatric cardiovascular diseases still remains undetermined. Breakthroughs in molecular genetic technology have just begun to be applied in pediatric cardiology stemming from the use of chromosomal mapping and the identification of genes involved in both the primary etiology and as significant risk factors in the development of cardiac and vascular abnormalities. This review will focus on information obtained thus far by molecular genetic analysis in the diagnosis, treatment and overall understanding of pediatric cardiovascular disease pathogenesis examining both the more prevalent congenital/inherited heart defects, arrhythmias and cardiomyopathies, as well as sporadic and acquired disorders. In addition, a survey of the pediatric cardiologist's armamentarium with regards to molecular and genetic analysis is presented highlighting the current use of molecular diagnostic methods including microarray, gene-mapping, proteomic, transgenic and stem cell technologies as well as future directions in both clinical application and research.     

Modalities to assess myocardial viability in the modern cardiology era

Detection of viable myocardium in patients with left ventricular dysfunction has become an increasingly important guide to prognosis and treatment. This article reviews the current status and future potential for the application of modalities to assess myocardial viability. Imaging and other techniques that are reviewed are myocardial perfusion imaging by single-photon-emission computed tomography, positron-emission tomography, echocardiography, cardiac magnetic resonance technology, computed tomography and catheter-based endocardial mapping.     

Molecular genetic diagnosis in cardiology

Within the next few years the "book of life" will be written, i.e., the sequence of the human genome will be completely assembled. This knowledge will open new avenues for the understanding and treatment of diseases. Causal relationships between mutated genes and disease states have been established for a number of single gene disorders. Although molecular genetic tests are not yet feasible for routine clinical practice in most cases, faster and, eventually, less expensive technologies for the identification of mutations are on the horizon. Clinical guidelines also apply to molecular genetics with diagnostics test being performed only in those individuals who may benefit from it.     

Molecular cardiology and genetics in the 21st century--a primer

The terminology and technology of molecular genetics and recombinant DNA have become an essential part of academic cardiology and will soon be applied at the bedside. The treatise includes a brief summary of the essentials of the DNA molecule, the more common techniques, and their application to genetics and molecular cardiology. It is written to be understood by physicians, scientists, and paramedical personnel who would not necessarily have a background in molecular biology. Inherent in the DNA molecule are three properties fundamental to all of the diagnostic and therapeutic applications, namely, the ability of DNA to separate into single strands, recombine (annealment or hybridization), and the presence of the negative charge enables DNA fragments to be separated easily by electrophoresis. Genetic linkage analysis of a family with an inherited disease enables one to identify the gene without knowing its protein product. Over 50 diseases in cardiology due to single-gene disorders have been identified and multiple mutations have been detected. The new therapeutic frontier will be stem cells and nuclear transfer. Identification of genes responsible for coronary artery disease made possible by genome-wide single nucleotide polymorphism (SNP) mapping techniques paves the way for personalized medicine.     

Molecular biology in cardiology, a paradigmatic shift

Control of the performance of the heart can now be understood in terms of three paradigms: beat-to-beat, length-dependent regulation (Starling's Law of the Heart); short term regulation by biochemical changes within the cardiac cell (excitation-contraction coupling, myocardial contractility); and long term regulation by altered gene expression (molecular biology). The latter may also compensate for inhomogeneities in ventricular function. According to Kuhn's theory, the more recent of these paradigms should provide a better and more complete picture of cardiac function. However, because each of these paradigms explains distinct aspects of cardiac regulation that are not mutually exclusive, this evolution fails to support Kuhn's view that science progresses as a series of revolutionary advances. Instead, it is only by understanding all of these paradigms that we can begin to grasp their complex interactions in governing cardiac function, and so gain insight into these interwoven control mechanisms. It seems likely that this is not an uncommon pattern, and that future work will add new paradigms to the complex body of knowledge of cardiac regulation without invalidating any of the paradigms described in this editorial.     

Post-truth era and cardiology: After ORBITA,before CABANA

The evidence-based medicine is rooted in the scientific truth. Oxford Dictionaries has released its 2016 word of the year: “Post-truth,” which they define as “relating to or denoting circumstances in which objective facts are less influential in shaping public opinion than appeals to emotion and personal belief”. In everything from climate change denial to the anti-vaccine movement, we’re seeing the consequences of a failure to engage with scientific evidence. Fake news and post-truth pronouncements are increasingly common in social media and political era and are unfortunately also progressively being applied to the medical science. We also see some evidence of post-truth signals in daily cardiology procedures and guidelines including both interventional cardiology and cardiac electrophysiology. Guideline recommendations made before the randomized-controlled trials (RCT) are published might result in a scenario that the interventions or procedures have been performed on millions of people, costing billions of dollars, leading to unnecessary use of health care resources and often, ending up being even accepted as routine procedures in certain clinical situations. “Justice delayed is justice denied” is a legal cliché meaning that if timely justice is not provided to the sufferer, it loses it importance and violates human rights. In medicine, “The RCT delayed is justice denied”, as highlighted by ORBITA (Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina) trial and as may happen with CABANA (Catheter Ablation versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) in the post-truth era.     

Deciphering the mystery of the leaky pulmonary valve in a new era of interventional cardiology.

Deciphering the effect of pulmonary regurgitation on right ventricular(RV) function in patients after tetralogy of Fallot correctionand deciding on timing for valve replacement seems like crackingthe Da Vinci code. This question has become the Holy Grail ofcongenital cardiology in the 21st century. Every piece of informationbringing us closer to an answer based on sound scientific datatherefore is of great importance. The study by Coats et al.,¹looking at the haemodynamic effect of percutaneous pulmonaryvalve implantation (PPVI) in patients with predominantly pulmonaryregurgitation and RV volume overload, provides new insight intothe physiological consequences of relieving chronic pulmonaryregurgitation. The great advantage of this unique model is thatit avoids the confounding effects of cardiopulmonary bypassand cardiac surgery. When prospectively studying their patients     

The changing landscape of interventional cardiology: A survival guide in the era of health system consolidation

Practice environments for interventional cardiologists have evolved dramatically and now include small independent practices, large cardiology groups, multispecialty groups, and large integrated health systems. Increasingly, cardiologists are employed by hospitals or health systems. Data from MedAxiom and the American College of Cardiology (ACC) demonstrate an exponential increase in the percentage of cardiologists in employed positions from 10% in 2009 to 87% in 2020. This white paper explores these profound changes, considers their impact on interventional cardiologists, and offers guidance on how interventional cardiologists can best navigate this challenging environment. Finally, the paper offers a potential model to improve the employed physician experience through greater physician involvement in decision making, which may increase jobs satisfaction.     

Molecular dimension explored in evolution to promote proteomic complexity

The architecture of present-day protein interaction networks depends on how protein associations evolved. Here, we explore how and why evolution-related mutations influence protein structure to promote protein associations, and thereby network development. We specifically address two questions: (i) How can protein folds remain conserved while proteins accommodate new binding partnerships as genes duplicate? (ii) What is the structural/molecular basis for hub proteins being the most likely to acquire new connections? The answers stem from the examination of the structure wrapping, or protection from water attack. Wrapping is shown to be a crucial consideration in the exploration and evolution of proteomic interactivity.     

Molecular biology in cardiology: what is and where is the mutated gene?]

In this paper the role of molecular biology research and development in establishing etiology and pathogenesis of cardiovascular disease is discussed. Several examples of our own practice in the field (namely, Di George sequence, hereditary protein S deficiency, and hyperhomocysteinaemia) are provided as an illustration of the currently applied strategies.     

Molecular biology in cardiology: recent developments and opportunities for clinical applications

The revolution in molecular biology that has taken place in the last decade has provided powerful research methods that are changing our understanding of cardiovascular physiology and disease. This editorial commentary will highlight several areas of current research activity within the broad and expanding field of molecular cardiology, with a special emphasis on prospects for clinical applications in cardiovascular medicine.