Showing papers in "Current Opinion in Cardiology in 2004"
TL;DR: Recognizing patient nonadherence to medical therapy as a factor leading to poor blood pressure control and adverse outcomes remains a key challenge for clinicians caring for patients with hypertension.
Abstract: Purpose of reviewPatients’ adherence to antihypertensive drug regimens is a complex but important factor in achieving blood pressure control and reducing adverse cardiovascular outcomes. Approximately one half of patients with hypertension adhere to prescribed medications, and fewer than one in thre
410 citations
TL;DR: The results of recent investigations underscore the importance of the autonomic influences as triggers of arrhythmia and provide important mechanistic insights into the ionic and cellular mechanisms involved.
Abstract: Recent progress in our understanding of the role of the autonomic nervous system in the development of cardiac arrhythmias is reviewed. Our focus is on the translation of basic principles of neural control of heart rhythm that have emerged from experimental studies to clinical applications. Recent studies have made significant strides in defining the function of intrinsic cardiac innervation and the importance of nerve sprouting in electrical remodeling. A recurring theme is that heterogeneity of sympathetic innervation in response to injury is highly arrhythmogenic In addition, both sympathetic and parasympathetic influences on ion channel activity have been found accentuate electrical heterogeneities and thus to contribute to arrhythmogenesis in the long QT and Brugada syndromes. In the clinic, heart rate variability continues to be a useful tool in delineating pathophysiologic changes that result from the progression of heart disease and the impact of diabetic neuropathy. Heart rate turbulence, a noninvasive indicator of baroreceptor sensitivity has emerged as a simple, practical tool to assess risk for cardiovascular mortality in patients with ischemic heart disease and heart failure. Evidence of the proarrhythmic influence of behavioral stress has been further bolstered by defibrillator discharge studies and ambulatory ECG-based T-wave alternans measurement. In summary, the results of recent investigations underscore the importance of the autonomic influences as triggers of arrhythmia and provide important mechanistic insights into the ionic and cellular mechanisms involved.
204 citations
TL;DR: The body of current evidence from in vitro studies indicates that oxidative stress plays a major role in cardiovascular disease but the details of molecular events in vivo and in particular in humans remains to be determined.
Abstract: Purpose of reviewThe adoption of immediate reperfusion strategies to treat acutely occluded coronary arteries and the emergence of high-resolution molecular biology techniques have drawn attention to oxidative stress and reactive oxygen species generation in the cardiovascular system. Recent evidenc
175 citations
TL;DR: Genetic analysis of patient populations and the biochemical characterization of the mutated proteins have provided considerable insight into the function of TBX5 in cardiac development and disease pathology.
Abstract: Purpose of reviewMutations in the T-box transcription factor TBX5 cause Holt-Oram syndrome (HOS), an autosomal-dominant condition characterized by a familial history of congenital heart defects and preaxial radial ray upper limb defects. This review summarizes recent developments in the study of TBX
174 citations
TL;DR: Better clinical management of systolic hypertension depends on greater insight into the syndrome as a whole, more critical analysis of existing techniques, and the development of new approaches.
Abstract: Purpose of reviewThis review is intended to provide the background for a new comprehensive hemodynamic view of the syndrome of systolic or wide pulse pressure hypertension and its hallmark abnormality: increased central arterial stiffness.Recent findingsStudies of the pathogenesis of systolic hypert
142 citations
TL;DR: The features of humoral rejection are reviewed, which are believed to be responsible for most episodes of biopsy-negative rejection, which occurs in 10 to 20% of cardiac allograft recipients.
Abstract: Purpose of review As the frequency of cellular rejection after heart transplantation is decreasing, biopsy-negative episodes of rejection are being recognized more often. This article reviews the features of humoral rejection, which we believe is responsible for most episodes of biopsy-negative rejection. Hemodynamic compromise, in the absence of acute cellular rejection, called biopsy-negative rejection occurs in 10 to 20% of cardiac allograft recipients. These episodes of rejection are often more severe, and more difficult to treat, than classical acute cellular rejection. Histologic, immunofluorescence, and immunoperoxidase studies of endomyocardial biopsies from such patients often reveal intravascular macrophages, and immunoglobulin and complement deposition in capillaries, in the absence of lymphoid infiltrates, suggesting an antibody-mediated or humoral form of rejection. Recent findings Humoral rejection is associated with increased graft loss, accelerated transplant coronary artery disease, and increased mortality. Severely ill patients require intense therapy, which includes high-dose corticosteroids, cytolytic agents, intravenous heparin, intravenous gamma globulin, plasmapheresis, and/or antiproliferative agents. Summary Currently, our knowledge of the pathogenesis, diagnostic criteria, and optimal therapy for biopsy-negative rejection is incomplete, and evolving.
123 citations
TL;DR: Recently, significant improvement was achieved in cardiac output measurement by bioimpedance with both newer thoracic and whole body techniques, implying that this measure may be of value in managing some cardiovascular disorders.
Abstract: Purpose of reviewTo describe recent developments in bioimpedance technique and its application in cardiovascular diseases. Cardiac output determination has been used selectively during recent years because of the need for invasive right heart catheterization. Hence, experience with its application i
101 citations
TL;DR: It is demonstrated that heterotaxy can be caused by single gene mutations, and that there is probably extensive locus heterogeneity.
Abstract: Purpose of review Heterotaxy is a complex set of birth defects in which the normal concordance of asymmetric thoracic and abdominal organs is disturbed. In this review the authors summarize recent research on the etiology of heterotaxy syndromes. Improved understanding of the genetic control of left-right patterning in the early embryo is leading to the identification of candidate genes that may be mutated in heterotaxy patients, and epidemiologic studies are helping to define nongenetic mechanisms of embryopathy. Recent findings Several genes have now been implicated in heterotaxy and related isolated congenital heart malformations. These studies indicate that heterotaxy can be caused by single gene mutations. They also demonstrate that there is probably extensive locus heterogeneity. Heterotaxy may be caused by teratogenic exposures, especially maternal diabetes. Isolated congenital heart defects resulting from isomerisms and disturbed looping may be caused by mutations in genes that control early left-right patterning and the earliest steps in cardiogenesis. Genes currently implicated in human heterotaxy include ZIC3, LEFTYA, CRYPTIC, and ACVR2B. Roles for NKX2.5 and CRELDA are suggested by recent case reports. Summary Active research on the etiology of heterotaxy is leading to a reformulation of the likely etiologies. Its complex inheritance likely results from a mix of teratogenic and single gene disorders with variable expression and incomplete penetrance.
101 citations
TL;DR: Advances have provided hope that allograft vasculopathy may finally be manageable, and new preventive and treatment strategies are outlined.
Abstract: PURPOSE OF REVIEW To discuss the current understanding of the pathogenesis, natural history, and diagnosis of cardiac allograft vasculopathy, and to outline new preventive and treatment strategies. RECENT FINDINGS The central event in the development of allograft vasculopathy is the inflammatory response to immune or nonimmune-mediated endothelial damage. This response is characterized by the release of inflammatory cytokines, upregulation of cell-surface adhesion molecules, and the subsequent binding of leukocytes. Once induced, vascular smooth muscle cells proliferate and migrate from the media to form a neointima. Circulating progenitor cells are recruited to sites of arterial injury where they may then differentiate into smooth muscle cells. Because of its diffuse nature, allograft vasculopathy is best detected by intravascular ultrasound. Noninvasive tests, such as dobutamine echocardiography, are gaining in favor. Although the only definitive treatment is retransplantation, the immunosuppressant rapamycin can limit disease progression. Its synthetic derivative, everolimus, effectively prevented intimal hyperplasia in de novo transplant recipients. SUMMARY These advances have provided hope that allograft vasculopathy may finally be manageable.
86 citations
TL;DR: LVAD technology is continuing to evolve quickly, while transplantation is here to stay, and the interaction between these two powerful modalities requires continued thoughtful evaluation for maximal benefit to patients.
Abstract: PURPOSE OF REVIEW The decrease in useable donor organs means an increasing number of patients are requiring support with a left ventricular assist device (LVAD) for survival when their clinical status deteriorates before transplantation. We address whether these patients should be transplanted, if so, with what priority, and when and if they are not transplanted, what are the alternatives? RECENT FINDINGS The perioperative mortality and morbidity of LVAD insertion remains high. Infection and device failure still limit the safety of long periods of bridging and might necessitate earlier transplantation. Early results suggest that the smaller impeller pumps may be associated with a lower incidence of device failure and infection, but with more thromboembolic and hemorrhagic complications. Transplantation of LVAD patients results in survival rates as good as those with conventional transplantation, and the survival benefit is better than for non-LVAD-supported patients. A small number of LVAD patients have shown a significant improvement in myocardial function, sufficient enough to allow explantation of the device. The proportion of these patients has previously been reported to be as low as 5%, but a strategy to maximize recovery has allowed pump removal in approximately two thirds of dilated cardiomyopathy patients. In a recent destination therapy trial, survival in LVAD patients was superior to those on medical therapy, but the frequency of infection, bleeding, and malfunction of the device was higher. SUMMARY LVAD technology is continuing to evolve quickly, while transplantation is here to stay. The interaction between these two powerful modalities requires continued thoughtful evaluation for maximal benefit to patients.
77 citations
TL;DR: The Tbx1 genetic pathway and the cell biology of tissues contributing to pharyngeal arch arteries and cardiac outflow tract are the foundation for understanding congenital heart disease in DiGeorge syndrome.
Abstract: Purpose of review This article is an update on DiGeorge syndrome research focusing on the synergy of human and model systems genetics toward the understanding of conotruncal and aortic arch defects. Recent findings The identification of mutations of the human T-Box1 (TBX1) gene and progress on research of Tbx1 function in mouse development demonstrate the pathogenetic role of this gene in DiGeorge syndrome and generate new hypotheses about its function in cardiovascular development. Summary The Tbx1 genetic pathway and the cell biology of tissues contributing to pharyngeal arch arteries and cardiac outflow tract are the foundation for understanding congenital heart disease in DiGeorge syndrome.
TL;DR: It is suggested that DNA testing may become standard for many forms of congenitals heart defects, improving clinicians' ability to anticipate complications for their patients and predict recurrence risk for families of children with congenital heart defects.
Abstract: Purpose of review Although the care of infants and children with congenital heart defects has been revolutionized over the past 50 years, their underlying causes have been obscure. Recent progress, accelerated through the Human Genome Project, has resulted in the rapid identification of disease genes causing congenital heart defects. Recent findings In this review, progress in identifying new congenital heart defect genes for specific lesions and in understanding their disease pathogenesis in the past year are detailed. Specifically, genes relevant for atrial and atrioventricular septal defects, patent ductus arteriosus, bicuspid aortic valve, and coarctation of the aorta as well as pulmonary valvar and branch stenosis are reviewed. Summary The information in this review provides insights into the state-of-the-art knowledge about the molecular genetic causes of congenital heart defects. It suggests that DNA testing may become standard for many forms of congenital heart defects, improving clinicians' ability to anticipate complications for their patients and predict recurrence risk for families of children with congenital heart defects.
TL;DR: This review summarizes the latest evidence that breaking collagen crosslinks may be an efficient new therapeutic approach to the adverse cardiovascular and renal consequences of aging and diabetes and indicates that ALT-711, a breaker of advanced glycation end-products—related protein crosslinks, is a new approach to cardiovascular therapy.
Abstract: PURPOSE OF REVIEW Advanced glycation end-products accumulate on body proteins with aging, and their formation is greatly enhanced with rising plasma glucose level. Advanced glycation end-products bond together and, consequently, increase protein crosslinking. In the circulatory system, increased collagen crosslinking caused by advanced glycation end-products increases cardiovascular stiffness as well as the risk for cardiovascular morbidity and mortality. A breaker of advanced glycation end-products-related crosslinks, ALT-711, has been recently discovered. This review summarizes the latest evidence that breaking collagen crosslinks may be an efficient new therapeutic approach to the adverse cardiovascular and renal consequences of aging and diabetes. RECENT FINDINGS The results of recent studies clearly demonstrated that ALT-711, a breaker of advanced glycation end-products-related protein crosslinks, ameliorated the adverse cardiovascular and renal changes associated with aging, diabetes, and hypertension. In diabetic animals, ALT-711 improved left ventricular function, decreased ventricular collagen content and improved its solubility, reduced aortic stiffness, ameliorated diabetic nephrosclerosis, and improved renal function. In older spontaneously hypertensive rats, it reduced left ventricular mass and collagen content, reduced proteinuria, and extended survival. The results of recent studies also indicated that the effects of crosslinks breakers may be mediated in part via reduction in oxidative stress and profibrotic cytokines. SUMMARY The results of experimental studies and one clinical trial have clearly established the usefulness of ALT-711 in the therapy of the cardiovascular and renal disorders associated with aging, diabetes, and hypertension. Thus, breaking advanced glycation end-products-related collagen crosslinks has emerged as a new approach to cardiovascular therapy.
TL;DR: It is appropriate to conduct safety and efficacy studies which, if carefully done, should allow assessment of the extent to which this concept of regenerative therapy can be made a clinical reality.
Abstract: PURPOSE OF REVIEW The last few years have witnessed a growing interest in regenerative therapy of the failing heart by cell transplantation. Special emphasis has been put on skeletal myoblasts and bone marrow-derived stem cells, with a flurry of experimental studies generating overall positive but occasionally conflicting results. It is thus appropriate to review the most important of these studies in light of the major issues that still impede widespread clinical use of cell therapy. RECENT FINDINGS Recent laboratory data demonstrate the ability of autologous skeletal myoblasts to engraft into scarred myocardium and improve its function. Equally successful results have been reported with bone marrow-derived cells which, in contrast to myoblasts, are credited with a plasticity that might allow their transdifferentiation into cardiac or endothelial cells in response to organ-specific cues. However, some major questions remain unanswered; they include the choice of the optimal cell type in relation with the target patient population, the strategies for enhancing cell survival and functional integration, the clarification of the mechanisms of improvement, and the means of reducing invasiveness of cell delivery. SUMMARY Although laboratory research attempts to overcome these persisting hurdles, the accumulated body of evidence warrants implementation of clinical trials. The earliest ones have now documented the feasibility of cell therapy. It is now appropriate to conduct safety and efficacy studies which, if carefully done, should allow assessment of the extent to which this concept of regenerative therapy can be made a clinical reality.
TL;DR: Complication rates remain low but constant with extraction of larger numbers of leads using new technologies, and design of leads that are easier to remove remains of paramount importance.
Abstract: PURPOSE OF REVIEW Continued growth in the elderly population and expanding indications have resulted in a progressive increase in the number of implants of pacemakers and defibrillators. Concomitant with these expanding numbers, more leads require removal, due especially to mechanical dysfunction, the need to upgrade to more complex devices, or local or systemic infection. Further, leads have become more complex, particularly for defibrillator systems, resulting in the development of powered extraction sheaths to expedite their removal. For these reasons, it is important to understand the expanding indications, procedural aspects, and limitations of arrhythmia device extraction. RECENT FINDINGS Expanded indications for lead extraction include upgrade to more complex systems, particularly pacemaker to defibrillator or biventricular device, extraction through occluded vasculature to produce a conduit for reimplantation, more frequent removal due to vascular overload with multiple leads, and a finite frequency of infection, occurring particularly with device replacement or revision. Powered sheaths now include laser and electrocautery systems, both improving the ease of lead explantation. SUMMARY Complication rates remain low but constant with extraction of larger numbers of leads using new technologies. Expansion of the use of biventricular systems, with implantation of coronary sinus electrodes, will continue to challenge lead extraction in terms of technology and safety. Design of leads that are easier to remove remains of paramount importance.
TL;DR: The modification of specific high-density lipoprotein subpopulations to reach the maximum atheroprotective effects under various pathologic conditions bears great potential in lipid research.
Abstract: PURPOSE OF REVIEW The purpose of this review is to summarize the current understanding of the potentially antiatherogenic properties of high-density lipoprotein related to its different components. RECENT FINDINGS Recent findings on the role of the different high-density lipoprotein subspecies in reverse cholesterol transport, inflammation, endothelial dysfunction, and low-density lipoprotein oxidation are covered. Special emphasis is put on the heterogeneity of high-density lipoprotein and functional changes related to specific high-density lipoprotein particles with the potential therapeutic alterations of high-density lipoprotein metabolism. SUMMARY The diverse action of high-density lipoprotein observed could be explained by the heterogeneity of high-density lipoprotein particles with completely different composition and properties. The modification of specific high-density lipoprotein subpopulations to reach the maximum atheroprotective effects under various pathologic conditions bears great potential in lipid research.
TL;DR: Tissue Doppler imaging is a powerful new echocardiographic tool that is now becoming the standard for assessing ventricular function in a variety of situations and diseases.
Abstract: Purpose of review Tissue Doppler imaging is being increasingly used for assessing global ventricular function in systole and diastole, and for quantifying regional wall motion abnormalities both in systolic heart failure with mechanical dyssynchrony and ischemic heart disease. Its use as a predictive tool is recent and the authors review publications relating to this aspect. Recent findings Peak early diastolic mitral annular velocity is a powerful predictor of outcome in a variety of cardiovascular conditions and adds incremental value to clinical parameters and standard mitral Doppler inflow velocities. Tissue Doppler imaging can also predict the development of hypertrophic cardiomyopathy in asymptomatic individuals carrying the genetic mutation even before the onset of overt left ventricular hypertrophy. In addition, the standard deviation of the time to peak systolic velocity is a good marker of mechanical asynchrony and can predict reverse remodeling. It may also be useful in identifying individuals with ischemic heart disease and regional wall motion abnormalities who have an adverse outcome. Summary Tissue Doppler imaging is a powerful new echocardiographic tool that is now becoming the standard for assessing ventricular function in a variety of situations and diseases.
TL;DR: Tissue Doppler imaging is being used in an ever-widening group of patients for the assessment of LV diastolic function, and its correlation to, and comparison with, B-type natriuretic peptide is an active area of current investigation.
Abstract: Purpose of reviewDescribe the rationale behind, and clinical use of, tissue Doppler (TD) imaging in the assessment of left ventricular (LV) diastolic function, with a focus on recent developments.Recent findingsTissue Doppler imaging is a novel echocardiographic technique that directly measures myoc
TL;DR: The antiatherogenic effects of HDL, recent insights into the mechanisms of action of currently available, and emerging HDL-based therapies are reviewed, showing that increasing total HDL cholesterol may not be as important as increasing the functional properties of HDL.
Abstract: PURPOSE OF REVIEW Despite the best efforts in reduction of low-density lipoprotein cholesterol, most cardiovascular events are not being prevented. Because high-density lipoprotein (HDL) promotes reverse cholesterol transport and other antiatherogenic effects, interventions aimed at raising HDL cholesterol or mimicking its beneficial effects may greatly improve treatment and prevention of cardiovascular disease. This article reviews the antiatherogenic effects of HDL, recent insights into the mechanisms of action of currently available, and emerging HDL-based therapies. RECENT FINDINGS New insights into the basic science of HDL function and metabolism (such as the discovery of beta-chain ATP synthase as a hepatic catabolic HDL receptor) are further characterizing the importance of HDL in atheroprotection and identifying novel targets of drug development. Nicotinic acid, fibrates, statins, and thiazolidinediones not only increase HDL cholesterol but also alter HDL subpopulation size and composition. Furthermore, these drugs promote direct antiatherogenic effects of HDL (antioxidation, anti-inflammation, antithrombotic effects, endothelial stabilization). Emerging HDL-raising therapies (such as cholesteryl ester transfer protein inhibitors and 1,2-dimyristoyl-sn-glycero-phosphocholine) and novel interventions that mimic HDL's beneficial effects (such as apolipoprotein AImilano and apolipoprotein AI mimetic peptides) are proving beneficial in animal and human studies. SUMMARY An understanding of the atheroprotective mechanisms of HDL is essential for the rational use of currently available drugs and directed development of new drugs. Increasing total HDL cholesterol may not be as important as increasing the functional properties of HDL. Cardiovascular disease treatment and prevention can be improved by combining current low-density lipoprotein-based strategies with effective HDL-based interventions.
TL;DR: It is believed that the primary treatment for coarctation beyond the neonatal period as well as for muscular ventricular septal defects should be the transcatheter approach.
Abstract: Purpose of review This review summarizes important publications and advances in the field of interventional pediatric cardiology. The article focuses on new interventional techniques, devices, and catheter equipment and reviews modifications and advances made in already well-established techniques such as atrial septal defect device closure. Some interventions that reflect mainly the adult population, such as patent foramen ovale device closure and closure of postinfarct ventricular septal defects, are also discussed. Recent findings The recent results of device closure of perimembranous ventricular septal defects using the Amplatzer membranous ventricular septal defect device have been encouraging. We discuss a modification of the delivery system for the membranous ventricular septal defect device that is aimed to overcome the difficulty in correctly positioning the device and delivery sheath. Important device modifications discussed in this article include the angled Amplatzer Ductal Occluder, the cribriform atrial septal defect device for use in multifenestrated atrial septal defects and the fenestrated atrial septal defect device. The hybrid approach to congenital heart disease is discussed in this article. Summary Interventional pediatric cardiology is a constantly evolving specialty. Surgical procedures are being partially replaced by percutaneous interventions or hybrid approaches. We believe that the primary treatment for coarctation beyond the neonatal period as well as for muscular ventricular septal defects should be the transcatheter approach.
TL;DR: It has been demonstrated that the imbalance in beta-blocker use cannot explain the better survival in the ICD patients, and inducibility of ventricular tachyarrhythmias on electrophysiology did not predict death.
Abstract: Purpose of reviewControlled trials for secondary prevention of sudden death—Antiarrhythmics Versus Implantable Defibrillators (AVID), Canadian Implantable Defibrillator Study (CIDS), and Cardiac Arrest Study Hamburg (CASH)—have been published and subanalyses of them provide useful clinical informati
TL;DR: Although prospective clinical trials are lacking, the use of echocardiography to segregate risk should be incorporated into current strategies to treat congestive heart failure and influence clinical listing for cardiac transplantation.
Abstract: Purpose of reviewThe growing epidemic of systolic congestive heart failure mandates strategies to identify accurately people with high morbidity and mortality. Echocardiography remains the most widely available noninvasive tool for the assessment of cardiac structure, function, and hemodynamics. Cli
TL;DR: It is imperative to identify strategies that favorably impact this deadly syndrome, and it seems plausible that a Mediterranean-style diet exhibits most of the desired attributes.
Abstract: Purpose of reviewMetabolic syndrome affects almost a quarter of the adult American population and its incidence is rising in the rest of the world. Its treatment involves both pharmacologic and nonpharmacologic interventions. In this review the authors focus on foods with potential benefits for this
TL;DR: Invasive and noninvasive markers of disease severity, either biomarkers or physiologic parameters and tests that can be widely applied, have been proposed to reliably diagnose PAH and monitor the clinical course.
Abstract: Purpose of review Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterized by a progressive increase of pulmonary vascular resistance leading to right ventricular failure and premature death. The purpose of this review is to analyze the current knowledge of the evaluation of PAH patients. Recent findings Recently, the diagnostic approach has been more clearly defined according to the new clinical classification and with consensus reached on algorithms of various investigative tests and procedures that exclude other causes and ensure an accurate diagnosis of PAH. The diagnostic procedures include clinical history and physical examination, ECG, chest radiography, transthoracic Doppler echocardiography, pulmonary function tests, arterial blood gases, ventilation and perfusion lung scan, high-resolution CT of the lung, contrast-enhanced spiral CT of the lung and pulmonary angiography, blood tests and immunology, abdominal ultrasound scan, exercise capacity assessment, and hemodynamic evaluation. Summary Invasive and noninvasive markers of disease severity, either biomarkers or physiologic parameters and tests that can be widely applied, have been proposed to reliably diagnose PAH and monitor the clinical course.
TL;DR: Increasing evidence suggests that endothelial lipase plays a significant role in high-density lipoprotein metabolism, and could be an important new target for novel therapies to raise high- density lipop protein levels.
Abstract: Purpose of reviewElevating high-density lipoprotein levels is increasingly being identified as an essential strategy for the prevention of atherosclerosis. Plasma levels of high-density lipoprotein cholesterol and its major protein, apoAI, are largely influenced by the rate of turnover. Lipases play
TL;DR: Current treatment strategies have significant limitations and have not been shown to improve morbidity or mortality, and a number of new agents are under investigation with the goal of improving patient outcomes.
Abstract: Purpose of reviewAcute decompensated heart failure represents a major, growing health problem in the developed world. However, until recently, relatively little research has been performed in this field to provide a basis for rational treatment strategies. The purpose of this review is to discuss th
TL;DR: This review summarizes the data derived from major clinical trials about the complications related to implantation, hardware, and programming of biventricular devices.
Abstract: Purpose of reviewCardiac resynchronization therapy, a biventricular pacemaker-based therapy for heart failure, is increasingly being used based on a variety of clinical studies. However, the complications and risks related to different aspects of this novel therapy are not well documented. This revi
TL;DR: The development of two recipient lists as a way to provide cardiac transplantation as an option to recipients who would be otherwise ineligible, and its impact on expanding the donor pool are reviewed.
Abstract: Purpose of review Advances in immunosuppression and surgical techniques have allowed cardiac transplantation to become a viable option and the treatment of choice for select patients with end-stage heart failure. The success of the procedure has, however, led to a discrepancy between the number of donors available and the number of patients awaiting cardiac transplantation. As wait times for heart transplant recipients increase, nonstandard donor hearts are increasingly being used for higher risk recipients and critically ill (Status I) patients. We review the development of two recipient lists as a way to provide cardiac transplantation as an option to recipients who would be otherwise ineligible, and determine its impact on expanding the donor pool. Other methods of expanding the donor pool are also reviewed. Recent findings The alternate list appears to be successful in offering transplantation to patients (mostly older patients) who would not normally be eligible for this life-saving procedure. The alternate list (by changing donor organ acceptance criteria) and ongoing programs to increase organ donation have helped to expand the donor pool. Summary The donor organ shortage will continue as an increasingly older population develops end-stage organ disease. Expanding the donor pool by a variety of methods will be essential to extend the lives of these patients.
TL;DR: It is suggested that, taken as a whole, evidence for a psychological and social impact on CAD morbidity and mortality is convincing.
Abstract: Purpose of reviewCoronary artery disease (CAD) is the leading cause of death in the United States and other developed countries. Along with a number of other factors thought to contribute to the high prevalence of CAD in developed societies (longer life expectancy, obesity, sedentary lifestyles), va
TL;DR: The discovery of cysteine rich with EGF domains (CRELD) 1 as the first recognized genetic risk factor for AVSD provides new insight into the genetic basis of sporadically occurring AVSD and the potential for genetic overlap with syndromic AVSD.
Abstract: PURPOSE OF REVIEW Atrioventricular septal defects (AVSDs) occur as a clinical feature of several different syndromes, as autosomal dominant defects, and as sporadically occurring malformations. Consequently, it is clear that there is genetic heterogeneity, but until recently, little else was known about the genes involved in the pathogenesis of AVSD. Recent advances in understanding the molecular genetic basis of AVSD are reviewed. RECENT FINDINGS Atrioventricular septal defect is most often found associated with trisomy 21 (Down syndrome), but the responsible gene or genes on chromosome 21 have not been identified. However, promising candidates exist, and the current status of those efforts is presented. AVSD not associated with trisomy 21 usually occurs as a sporadic trait with no indication of the genetic basis. The discovery of cysteine rich with EGF domains (CRELD) 1 as the first recognized genetic risk factor for AVSD provides new insight into the genetic basis of sporadically occurring AVSD and the potential for genetic overlap with syndromic AVSD. Mutation of CRELD1 increases susceptibility to AVSD but is not alone sufficient to cause the defect, indicating that AVSD is multigenic. Consequently, additional genes must be identified to understand the genetic basis of AVSD. SUMMARY Because most nonsyndromic cases of AVSD are sporadic, opportunities for genetic analyses in humans are limited. An abundance of candidate genes have been identified through animal models and biochemical studies, but determining which actually contribute to the pathogenesis of AVSD will be difficult. Painstaking investigation of these candidate genes in humans may ultimately be necessary to identify the remaining genetic risk factors for AVSD.