Showing papers in "Circulation in 2011"
TL;DR: Dariush Mozaffarian, Michael E. Mussolino, Graham Nichol, Nina P. Paynter, Wayne D. Sorlie, Randall S. Stafford, Tanya N. Turan, Melanie B. Turner, Nathan D. Turner.
Abstract: Rosamond, Paul D. Sorlie, Randall S. Stafford, Tanya N. Turan, Melanie B. Turner, Nathan D. Dariush Mozaffarian, Michael E. Mussolino, Graham Nichol, Nina P. Paynter, Wayne D. Ariane Marelli, David B. Matchar, Mary M. McDermott, James B. Meigs, Claudia S. Moy, Lackland, Judith H. Lichtman, Lynda D. Lisabeth, Diane M. Makuc, Gregory M. Marcus, John A. Heit, P. Michael Ho, Virginia J. Howard, Brett M. Kissela, Steven J. Kittner, Daniel T. Caroline S. Fox, Heather J. Fullerton, Cathleen Gillespie, Kurt J. Greenlund, Susan M. Hailpern, Todd M. Brown, Mercedes R. Carnethon, Shifan Dai, Giovanni de Simone, Earl S. Ford, Véronique L. Roger, Alan S. Go, Donald M. Lloyd-Jones, Robert J. Adams, Jarett D. Berry, Association 2011 Update : A Report From the American Heart −− Heart Disease and Stroke Statistics
5,311 citations
TL;DR: Bleeding complications have been associated with an increased risk of subsequent adverse outcomes, including MI, stroke, stent thrombosis, and death, in patients with ACS and in those undergoing percutaneous coronary intervention (PCI) as well as in the long-term antithrombotic setting.
Abstract: Advances in antithrombotic therapy, along with an early invasive strategy, have reduced the incidence of recurrent ischemic events and death in patients with acute coronary syndromes (ACS; unstable angina, non–ST-segment–elevation myocardial infarction [MI], and ST-segment–elevation MI).1,–,4 However, the combination of multiple pharmacotherapies, including aspirin, platelet P2Y12 inhibitors, heparin plus glycoprotein IIb/IIIa inhibitors, direct thrombin inhibitors, and the increasing use of invasive procedures, has also been associated with an increased risk of bleeding.
Editorial see p 2664
Bleeding complications have been associated with an increased risk of subsequent adverse outcomes, including MI, stroke, stent thrombosis, and death, in patients with ACS and in those undergoing percutaneous coronary intervention (PCI),5,–,10 as well as in the long-term antithrombotic setting.11,12 Thus, balancing the anti-ischemic benefits against the bleeding risk of antithrombotic agents and interventions is of paramount importance in assessing new therapies and in managing patients. Prior randomized trials comparing antithrombotic agents suggest that a reduction in bleeding events is associated with improved survival.13,14
Because prevention of major bleeding may represent an important step in improving outcomes by balancing safety and efficacy in the contemporary treatment of ACS, bleeding events have been systematically identified as a crucial end point for the assessment of the safety of drugs during the course of randomized clinical trials, and are an important aspect of the evaluation of new devices and interventional therapies.15 Unlike ischemic clinical events (eg, cardiac death, MI, stent thrombosis), for which there is now general consensus on end-point definitions,16,17 there is substantial heterogeneity among the many bleeding definitions currently in use. Lack of standardization makes it difficult to optimally organize key clinical trial processes such as adjudication, and even more difficult to interpret relative …
3,215 citations
TL;DR: Alice K. Jacobs, MD, FACC, FAHA, Chair Jeffrey L. Anderson, PhD, CCNS, CCRN, FAH, Chair-Elect - The first female FACC-FAHA board member to be elected in the history of the sport.
Abstract: Alice K. Jacobs, MD, FACC, FAHA, Chair
Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect
Nancy Albert, PhD, CCNS, CCRN, FAHA
Mark A. Creager, MD, FACC, FAHA
Steven M. Ettinger, MD, FACC
Robert A. Guyton, MD, FACC
Jonathan L. Halperin, MD, FACC, FAHA
Judith S. Hochman, MD, FACC, FAHA
3,040 citations
TL;DR: Findings indicate CVD prevalence and costs are projected to increase substantially and effective prevention strategies are needed if the authors are to limit the growing burden of CVD.
Abstract: Background—Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially. Methods and Results—To prepare for future cardiovascular care needs, the American Heart Association developed methodology to project future costs of care for hypertension, coronary heart disease, heart failure, stroke, and all other CVD from 2010 to 2030. This methodology avoided double counting of costs for patients with multiple cardiovascular conditions. By 2030, 40.5% of the US population is projected to have some form of CVD. Between 2010 and 2030, real (2008$) total direct medical costs of CVD are projected to triple, from $273 billion to $818 billion. Real indirect costs (due to lost productivity) for all CVD are estimated to increase from $172 billion in 2010 to $276 billion in 2030, an increase of 61%. Conclusions—These findings indicate CVD prevalence and costs are project...
2,918 citations
TL;DR: This information is current as of May 14, 2012 and located on the World Wide Web at: http://content.onlinejacc.org/cgi/content/full/58/25/2703.
Abstract: Writing committee me tions to which their s ply; see Appendix ACCF/AHATask Fo Surgeons Representa tative Heart Rhythm ography and Int Echocardiography Re ciety of America Rep resentative kkACCF/ Task Force member d This document was app Board of Trustees and ordinating Committee gery, American Soc Cardiology, Heart Fa for Cardiovascular A geons approved the d The American Associat as follows: Gersh BJ Naidu SS, Nishimura Bernard J Gersh, MB, ChB, DPhil, FACC, FAHA, Co-Chair* Barry J Maron, MD, FACC, CoChair* Robert O Bonow, MD, MACC, FAHA, Joseph A Dearani, MD, FACC,§,k Michael A Fifer, MD, FACC, FAHA,* Mark S Link, MD, FACC, FHRS,* Srihari S Naidu, MD, FACC, FSCAI,* Rick A Nishimura, MD, FACC, FAHA, Steve R Ommen, MD, FACC, FAHA, Harry Rakowski, MD, FACC, FASE,** Christine E Seidman, MD, FAHA, Jeffrey A Towbin, MD, FACC, FAHA, James E Udelson, MD, FACC, FASNC, and Clyde W Yancy, MD, FACC, FAHAkk
2,118 citations
American Heart Association1, Centers for Disease Control and Prevention2, American Academy of Family Physicians3, American Congress of Obstetricians and Gynecologists4, Society of Thoracic Surgeons5, American College of Cardiology6, National Institutes of Health7, American College of Physicians8, World Heart Federation9
TL;DR: Major randomized controlled clinical trials such as the Women’s Health Initiative have changed the practice of CVD prevention in women over the past decade and the investment in combating this major public health issue for women has been significant.
Abstract: Substantial progress has been made in the awareness, treatment, and prevention of cardiovascular disease (CVD) in women since the first women-specific clinical recommendations for the prevention of CVD were published by the American Heart Association (AHA) in 1999.1 The myth that heart disease is a “man’s disease” has been debunked; the rate of public awareness of CVD as the leading cause of death among US women has increased from 30% in 1997 to 54% in 2009.2 The age-adjusted death rate resulting from coronary heart disease (CHD) in females, which accounts for about half of all CVD deaths in women, was 95.7 per 100 000 females in 2007, a third of what it was in 1980.3,4 Approximately 50% of this decline in CHD deaths has been attributed to reducing major risk factors and the other half to treatment of CHD including secondary preventive therapies.4 Major randomized controlled clinical trials such as the Women’s Health Initiative have changed the practice of CVD prevention in women over the past decade.5 The investment in combating this major public health issue for women has been significant, as have the scientific and medical achievements.
1,856 citations
TL;DR: The development of the present guideline involved a process of partial adaptation of other guideline statements and reports and supplemental literature searches, which confirmed that in patients with atherosclerotic vascular disease, comprehensive risk factor management reduces risk as assessed by a variety of outcomes.
Abstract: Since the 2006 update of the American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) guidelines on secondary prevention,1 important evidence from clinical trials has emerged that further supports and broadens the merits of intensive risk-reduction therapies for patients with established coronary and other atherosclerotic vascular disease, including peripheral artery disease, atherosclerotic aortic disease, and carotid artery disease. In reviewing this evidence and its clinical impact, the writing group believed it would be more appropriate to expand the title of this guideline to “Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease.” Indeed, the growing body of evidence confirms that in patients with atherosclerotic vascular disease, comprehensive risk factor management reduces risk as assessed by a variety of outcomes, including improved survival, reduced recurrent events, the need for revascularization procedures, and improved quality of life. It is important not only that the healthcare provider implement these recommendations in appropriate patients but also that healthcare systems support this implementation to maximize the benefit to the patient.
Compelling evidence-based results from recent clinical trials and revised practice guidelines provide the impetus for this update of the 2006 recommendations with evidence-based results2–165 (Table 1). Classification of recommendations and level of evidence are expressed in ACCF/AHA format, as detailed in Table 2. Recommendations made herein are largely based on major practice guidelines from the National Institutes of Health and updated ACCF/AHA practice guidelines, as well as on results from recent clinical trials. Thus, the development of the present guideline involved a process of partial adaptation of other guideline statements and reports and supplemental literature searches. The recommendations listed in this document are, whenever possible, evidence based. Writing group members performed these relevant supplemental literature searches with key search phrases including but not limited …
1,825 citations
TL;DR: In this paper, the authors address the management of massive and submassive pulmonary embolisms (PE), iliofemoral deep vein thrombosis (IFDVT), and chronic thromboembolic pulmonary hypertension (CTEPH).
Abstract: Venous thromboembolism (VTE) is responsible for the hospitalization of >250 000 Americans annually and represents a significant risk for morbidity and mortality. Despite the publication of evidence-based clinical practice guidelines to aid in the management of VTE in its acute and chronic forms, the clinician is frequently confronted with manifestations of VTE for which data are sparse and optimal management is unclear. In particular, the optimal use of advanced therapies for acute VTE, including thrombolysis and catheter-based therapies, remains uncertain. This report addresses the management of massive and submassive pulmonary embolism (PE), iliofemoral deep vein thrombosis (IFDVT),and chronic thromboembolic pulmonary hypertension (CTEPH). The goal is to provide practical advice to enable the busy clinician to optimize the management of patients with these severe manifestations of VTE. Although this document makes recommendations for management, optimal medical decisions must incorporate other factors, including patient wishes, quality of life, and life expectancy based on age and comorbidities. The appropriateness of these recommendations for a specific patient may vary depending on these factors and will be best judged by the bedside clinician.
1,776 citations
TL;DR: The role of triglyceride-rich lipoproteins (TRLs) in the evaluation and management of CVD risk was discussed in this article, where the authors highlighted approaches aimed at minimizing the adverse public health-related consequences associated with hypertriglyceridemic states.
Abstract: A long-standing association exists between elevated triglyceride levels and cardiovascular disease* (CVD).1,2 However, the extent to which triglycerides directly promote CVD or represent a biomarker of risk has been debated for 3 decades.3 To this end, 2 National Institutes of Health consensus conferences evaluated the evidentiary role of triglycerides in cardiovascular risk assessment and provided therapeutic recommendations for hypertriglyceridemic states.4,5 Since 1993, additional insights have been made vis-a-vis the atherogenicity of triglyceride-rich lipoproteins (TRLs; ie, chylomicrons and very low-density lipoproteins), genetic and metabolic regulators of triglyceride metabolism, and classification and treatment of hypertriglyceridemia. It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).6,7 In contrast, mean low-density lipoprotein cholesterol (LDL-C) levels have receded.7 Therefore, the purpose of this scientific statement is to update clinicians on the increasingly crucial role of triglycerides in the evaluation and management of CVD risk and highlight approaches aimed at minimizing the adverse public health–related consequences associated with hypertriglyceridemic states. This statement will complement recent American Heart Association scientific statements on childhood and adolescent obesity8 and dietary sugar intake9 by emphasizing effective lifestyle strategies designed to lower triglyceride levels and improve overall cardiometabolic health. It is not intended to serve as a specific guideline but will be of value to the Adult Treatment Panel IV (ATP IV) of the National Cholesterol Education Program, from which evidence-based guidelines will ensue. Topics to be addressed include epidemiology and CVD risk, ethnic and racial differences, metabolic determinants, genetic and family determinants, risk factor correlates, and effects related to nutrition, physical activity, and lipid medications.
In the United States, the National Health and …
1,499 citations
TL;DR: In this article, the authors evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of Rivaroxaban and dabigatran.
Abstract: Background—Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs. Methods and Results—In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus...
1,332 citations
TL;DR: This work presents a meta-analyses of the FACC/FESC/FAHA double-blind, placebo-controlled, and sham drowning experiments that demonstrate the ability of these animals to understand each other and provide real-time information about each other's drowning experiences.
Abstract: Valentin Fuster, MD, PhD, FACC, FAHA, FESC, Co-Chair; Lars E. Ryden, MD, PhD, FACC, FESC, FAHA, Co-Chair; David S. Cannom, MD, FACC; Harry J. Crijns, MD, FACC, FESC; Anne B. Curtis, MD, FACC, FAHA; Kenneth A. Ellenbogen, MD, FACC, FHRS† Jonathan L. Halperin, MD, FACC, FAHA; G. Neal Kay, MD, FACC
TL;DR: In this article, the authors compared the risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial with dabigatran 150 and 110 mg twice a day and warfarin.
Abstract: Background—Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial. Methods and Results—The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated with a lower risk of major bleeding (2.87% versus 3.57%; P=0.002), whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P=0.32). There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged <75 years (1.89% versus 3.04%; P<0.001) and a similar risk in those aged ≥75 years (4.4...
TL;DR: Benefit of TAVI with the CoreValve Revalving System is maintained over time up to 1 year, with acceptable mortality rates at various time points, although procedural complications are strongly associated with early mortality at 30 days.
Abstract: Background—There is a lack of information on the incidence and predictors of early mortality at 30 days and late mortality between 30 days and 1 year after transcatheter aortic valve implantation (TAVI) with the self-expanding CoreValve Revalving prosthesis. Methods and Results—A total of 663 consecutive patients (mean age 81.0±7.3 years) underwent TAVI with the third generation 18-Fr CoreValve device in 14 centers. Procedural success and intraprocedural mortality were 98% and 0.9%, respectively. The cumulative incidences of mortality were 5.4% at 30 days, 12.2% at 6 months, and 15.0% at 1 year. The incidence density of mortality was 12.3 per 100 person-year of observation. Clinical and hemodynamic benefits observed acutely after TAVI were sustained at 1 year. Paravalvular leakages were trace to mild in the majority of cases. Conversion to open heart surgery (odds ratio [OR] 38.68), cardiac tamponade (OR 10.97), major access site complications (OR 8.47), left ventricular ejection fraction <40% (OR 3.51), ...
Journal Article•
TL;DR: It is shown that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation and delivery of the pro-angiogenic and fibroblast-activating peptides resulted in further improvements in scar area and cardiac function.
TL;DR: This guideline was developed in conjunction with the European Society of Cardiology (ESC) and aims to improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.
Abstract: For new or updated text, view the 2011 Focused Update and the 2011 Focused Update on Dabigatran. Text supporting unchanged recommendations has not been updated.
It is important that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced and tested in the detection, management, or prevention of disease states. Rigorous and expert analysis of the available data documenting absolute and relative benefits and risks of those procedures and therapies can produce helpful guidelines that improve the effectiveness of care, optimize patient outcomes, and favorably affect the overall cost of care by focusing resources on the most effective strategies.
The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have jointly engaged in the production of such guidelines in the area of cardiovascular disease since 1980. The ACC/AHA Task Force on Practice Guidelines, whose charge is to develop, update, or revise practice guidelines for important cardiovascular diseases and procedures, directs this effort. The Task Force is pleased to have this guideline developed in conjunction with the European Society of Cardiology (ESC). Writing committees are charged with the task of performing an assessment of the evidence and acting as an independent group of authors to develop or update written recommendations for clinical practice.
Experts in the subject under consideration have been selected from all 3 organizations to examine subject-specific data and write guidelines. The process includes additional representatives from other medical practitioner and specialty groups when appropriate. Writing committees are specifically charged to perform a formal literature review, weigh the strength of evidence for or against a particular treatment or procedure, and include estimates of expected health outcomes where data exist. Patient-specific modifiers, comorbidities, and issues of patient preference that might influence the choice of particular …
TL;DR: This poster presents a poster presented at the 2016 American Academy of Thoracic Surgeons conference on “Cardiovascular Angiography and Interventions: Foundations of Cardiovascular and Pulmonary Rehabilitation,” presented in Los Angeles, USA.
Abstract: Developed in Collaboration With the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency
TL;DR: Preeclampsia is a systemic vascular disorder that may also affect the liver and the brain in the mothers and is named not only for the liver involvement, but also for the disorder of the coagulation system that develops.
Abstract: Preeclampsia is a clinical syndrome defined as the new onset of hypertension and proteinuria during the second half of pregnancy1 It afflicts 3% to 5% of pregnancies and is a leading cause of maternal mortality, especially in developing countries2,3 Because the only known remedy is delivery of the placenta, in developed countries preeclampsia is an important cause of premature delivery, usually medically indicated for the benefit of the mother This results in infant morbidity and substantial healthcare expenditure4 Despite the considerable morbidity and mortality, the cause of preeclampsia has remained enigmatic
Both hypertension and proteinuria implicate the endothelium as the target of the disease The hypertension of preeclampsia is characterized by peripheral vasoconstriction and decreased arterial compliance5,6 The proteinuria of preeclampsia is associated with a pathognomonic renal lesion known as glomerular endotheliosis, in which the endothelial cells of the glomerulus swell and endothelial fenestrations are lost7,8 Podocyturia has been recently associated with preeclampsia during clinical disease9; however, whether this is the cause or effect of proteinuria is unknown The glomerular filtration rate is decreased compared with normotensive pregnant women; in rare cases, acute renal failure may develop
Preeclampsia is a systemic vascular disorder that may also affect the liver and the brain in the mothers When the liver is involved, women may present with abdominal pain, nausea, vomiting, and elevated liver enzymes Pathological examination of the liver reveals periportal and sinusoidal fibrin deposition and, in more extreme cases, hemorrhage and necrosis10 The severe preeclampsia variant HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurs in ≈20% of women with severe preeclampsia,11 and is named not only for the liver involvement, but also for the disorder of the coagulation system that develops12 Approximately 20% of …
TL;DR: In this paper, the authors performed an aggregate data meta-analysis of epidemiological studies investigating physical activity and primary prevention of coronary heart disease and found that individuals who engaged in the equivalent of 150 min/wk of moderate-intensity leisure-time physical activity (minimum amount, 2008 US federal guidelines) had a 14% lower heart disease risk.
Abstract: BackgroundNo reviews have quantified the specific amounts of physical activity required for lower risks of coronary heart disease when assessing the dose-response relation. Instead, previous reviews have used qualitative estimates such as low, moderate, and high physical activity. Methods and ResultsWe performed an aggregate data meta-analysis of epidemiological studies investigating physical activity and primary prevention of CHD. We included prospective cohort studies published in English since 1995. After reviewing 3194 abstracts, we included 33 studies. We used random-effects generalized least squares spline models for trend estimation to derive pooled dose-response estimates. Among the 33 studies, 9 allowed quantitative estimates of leisure-time physical activity. Individuals who engaged in the equivalent of 150 min/wk of moderate-intensity leisure-time physical activity (minimum amount, 2008 US federal guidelines) had a 14% lower coronary heart disease risk (relative risk, 0.86; 95% confidence inter...
TL;DR: The current and former chairs and vice-chairs of the FACC are: David Hillis, MD, FACC, Chair, Peter K. Smith,MD, F ACC, Vice Chair*, and Ola Selnes, PhD, PhD.
Abstract: L. David Hillis, MD, FACC, Chair†; Peter K. Smith, MD, FACC, Vice Chair*†; Jeffrey L. Anderson, MD, FACC, FAHA*‡; John A. Bittl, MD, FACC§; Charles R. Bridges, MD, SCD, FACC, FAHA*†; John G. Byrne, MD, FACC†; Joaquin E. Cigarroa, MD, FACC†; Verdi J. DiSesa, MD, FACC†; Loren F. Hiratzka, MD, FACC, FAHA†; Adolph M. Hutter, Jr, MD, MACC, FAHA†; Michael E. Jessen, MD, FACC*†; Ellen C. Keeley, MD, MS†; Stephen J. Lahey, MD†; Richard A. Lange, MD, FACC, FAHA†§; Martin J. London, MD ; Michael J. Mack, MD, FACC*¶; Manesh R. Patel, MD, FACC†; John D. Puskas, MD, FACC*†; Joseph F. Sabik, MD, FACC*#; Ola Selnes, PhD†; David M. Shahian, MD, FACC, FAHA**; Jeffrey C. Trost, MD, FACC*†; Michael D. Winniford, MD, FACC†
TL;DR: The role of nutritional and environmental challenges in generational inheritance and epigenetic modifications, concentrating on examples that relate to complex cardiovascular diseases, is discussed, and the mechanisms by which homocysteine modifies epigenetic tags are dissected.
Abstract: The term epigenetics was first used to refer to the complex interactions between the genome and the environment that are involved in development and differentiation in higher organisms. Today, this term is used to refer to heritable alterations that are not due to changes in DNA sequence. Rather, epigenetic modifications, or tags, such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. These processes are crucial to normal development and differentiation of distinct cell lineages in the adult organism. They can be modified by exogenous influences, and as such, they can contribute to or be the result of environmental alterations of phenotype or pathophenotype. Importantly, epigenetic programming has a crucial role in the regulation of pluripotency genes, which become inactivated during differentiation. Here, we review the major mechanisms in epigenetic regulation; highlight the role of stable, long-term epigenetic modifications that involve DNA methylation; and discuss those modifications that are more flexible (short-term) and involve histone modifications, such as methylation and acetylation. We will also discuss the role of nutritional and environmental challenges in generational inheritance and epigenetic modifications, concentrating on examples that relate to complex cardiovascular diseases, and specifically dissect the mechanisms by which homocysteine modifies epigenetic tags. Lastly, we will discuss the possibilities of modifying therapeutically acquired epigenetic tags, summarizing currently available agents and speculating on future directions.
Chromatin is the complex of chromosomal DNA associated with proteins in the nucleus (for review, see Campos and Reinberg1). DNA in chromatin is packaged around histone proteins, in units referred to as nucleosomes. A nucleosome has 147 base pairs of DNA associated with an octomeric core of histone proteins, which consists of 2 H3-H4 histone dimers surrounded by 2 H2A-H2B dimers. N-terminal histone tails protrude from nucleosomes into the nuclear lumen. …
TL;DR: There is a need for improved assessment of adiposity in daily clinical practice, given the clear association between excess adiposity and adverse health consequences such as cardiovascular disease and type 2 diabetes mellitus.
Abstract: The prevalence of obesity in the United States and the world has risen to epidemic/pandemic proportions. This increase has occurred despite great efforts by healthcare providers and consumers alike to improve the health-related behaviors of the population and a tremendous push from the scientific community to better understand the pathophysiology of obesity. This epidemic is all the more concerning given the clear association between excess adiposity and adverse health consequences such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The risks associated with overweight/obesity are primarily related to the deposition of adipose tissue, which leads to excess adiposity or body fatness. Furthermore, weight loss, specifically loss of body fat, is associated with improvement in obesity-related comorbidities. Before weight loss interventions can be recommended, however, patients must be assessed for their adiposity-related risk. Unfortunately, healthcare providers and systems have not done a good job of assessing for excess adiposity even in its simplest form, such as measuring body mass index (BMI). It is for these reasons that we must emphasize the importance of assessing adiposity in clinical practices. Although it can be argued that the entire population should be targeted as an important public health issue with a goal of prevention of weight gain and obesity, there are currently so many “at risk” individuals that simple strategies to identify and treat those individuals are necessary. We must identify those individuals at highest risk of comorbidities in order to identify those who might benefit the most from aggressive weight management.
This scientific statement will first briefly review the epidemiology of obesity and its related comorbidities, supporting the need for improved assessment of adiposity in daily clinical practice. This will be followed by a discussion of some of the challenges and issues associated with assessing adiposity and then by a review …
TL;DR: The purposes of this article are to evaluate contemporary sex/gender differences in the burden of CVD, to assess the impact of recent clinical trials on recommendations for the prevention ofCVD in women, and to examine factors that may facilitate or impede quality CVD preventive care in women.
Abstract: Over the past decade, scientists, healthcare providers, the public, and policy makers have made substantial efforts to improve understanding of the sex/gender*differences in cardiovascular disease (CVD)†and to recognize the importance of heart disease in women. Federal and American Heart Association (AHA) initiatives to raise awareness and to reduce gender disparities in research and clinical care are listed in Table 1. There was a near doubling of the rate of awareness of heart disease as the leading cause of death in women between 1997, when the AHA launched its first campaign for women, and 2009; during that same period, the death rate resulting from CVD decreased by nearly half.2–4 The extent to which efforts to close research gaps and to heighten awareness of heart disease in women are causally linked to lower CVD mortality or have resulted in improved clinical outcomes for women is not established. The purposes of this article are to evaluate contemporary sex/gender differences in the burden of CVD, to assess the impact of recent clinical trials on recommendations for the prevention of CVD in women, and to examine factors that may facilitate or impede quality CVD preventive care in women. Recommendations for the design and analyses of future CVD clinical trials in women are also provided.
View this table:
Table 1.
Initiatives Affecting Women and Cardiovascular Disease
Although CVD remains the leading killer of both women and men in the United States, there are substantial sex/gender differences in the prevalence and burden of different CVDs, as outlined in Table 2. For both women and men, coronary heart disease (CHD) is the largest contributor to CVD morbidity and mortality. The absolute numbers of women living with and dying of CVD and stroke exceed those of men, as does the number of hospital discharges for …
Papworth Hospital1, Katholieke Universiteit Leuven2, Charles University in Prague3, University of Amsterdam4, Aarhus University5, Wrocław Medical University6, Slovak Medical University7, University of Barcelona8, University of Toronto9, Hannover Medical School10, University College Dublin11, Complutense University of Madrid12, Medical University of Graz13, University of Paris-Sud14
TL;DR: Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions.
Abstract: Background—Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. Methods and Results—The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%– 60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and...
TL;DR: These updated guideline recommendations reflect a consensus of expert opinion after a thorough review primarily of late-breaking clinical trials identified through a broad-based vetting process as being important to the relevant patient population.
Abstract: Keeping pace with the stream of new data and evolving evidence on which guideline recommendations are based is an ongoing challenge to timely development of clinical practice guidelines. In an effort to respond promptly to new evidence, the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Task Force on Practice Guidelines (Task Force) has created a “focused update” process to revise the existing guideline recommendations that are affected by the evolving data or opinion. New evidence is reviewed in an ongoing fashion to more efficiently respond to important science and treatment trends that could have a major impact on patient outcomes and quality of care. Evidence is reviewed at least twice a year, and updates are initiated on an as-needed basis and completed as quickly as possible while maintaining the rigorous methodology that the ACCF and AHA have developed during their partnership of >20 years.
These updated guideline recommendations reflect a consensus of expert opinion after a thorough review primarily of late-breaking clinical trials identified through a broad-based vetting process as being important to the relevant patient population, as well …
TL;DR: There is a significant improvement in the safety of Watchman left atrial appendage closure with increased operator experience, and the functional impact of these safety events, as defined by significant disability or death, was statistically superior in the Watchman group compared with the warfarin group in PROTECT AF.
Abstract: Background—The Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) randomized trial compared left atrial appendage closure against warfarin in atrial fibrillation (AF) patients with CHADS2 ≥1. Although the study met the primary efficacy end point of being noninferior to warfarin therapy for the prevention of stroke/systemic embolism/cardiovascular death, there was a significantly higher risk of complications, predominantly pericardial effusion and procedural stroke related to air embolism. Here, we report the influence of experience on the safety of percutaneous left atrial appendage closure. Methods and Results—The study cohort for this analysis included patients in the PROTECT AF trial who underwent attempted device left atrial appendage closure (n=542 patients) and those from a subsequent nonrandomized registry of patients undergoing Watchman implantation (Continued Access Protocol [CAP] Registry; n=460 patients). The safety end point included bleeding- and pro...
TL;DR: Alice K. Jacobs,MD, FACC, FAHA, Chair Jeffrey L. Anderson, MD, F ACC, FAH, Chair-Elect Nancy Albert, PhD, CCNS, CCRN,FAHA, chair-Elect.
Abstract: Alice K. Jacobs, MD, FACC, FAHA, Chair
Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect
Nancy Albert, PhD, CCNS, CCRN, FAHA
Mark A. Creager, MD, FACC, FAHA
Steven M. Ettinger, MD, FACC
Robert A. Guyton, MD, FACC
Jonathan L. Halperin, MD, FACC, FAHA
Judith S. Hochman, MD, FACC, FAHA
TL;DR: No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances), and heart failure patients with New York Heart Association class I or II and LBBB derive substantial clinical benefit from CRT-D: a Reduction in heart failure progression and a reduction in the risk of ventricular tachyarrhythmias.
Abstract: Background—This study aimed to determine whether QRS morphology identifies patients who benefit from cardiac resynchronization therapy with a defibrillator (CRT-D) and whether it influences the risk of primary and secondary end points in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) trial. Methods and Results—Baseline 12-lead ECGs were evaluated with regard to QRS morphology. Heart failure event or death was the primary end point of the trial. Death, heart failure event, ventricular tachycardia, and ventricular fibrillation were secondary end points. Among 1817 patients with available sinus rhythm ECGs at baseline, there were 1281 (70%) with left bundle-branch block (LBBB), 228 (13%) with right bundle-branch block, and 308 (17%) with nonspecific intraventricular conduction disturbances. The latter 2 groups were defined as non-LBBB groups. Hazard ratios for the primary end point for comparisons of CRT-D patients versus patients...
TL;DR: The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase in advanced heart failure, supporting larger confirmatory trials.
Abstract: Background—Adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results—Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase or placebo. Seven efficacy parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving efficacy at 6 months in the group-level (concordant improvement in 7 efficacy parameters and no clinically significant worsening in any parameter), individual-level (total score fo...
TL;DR: It is found that inflammasomes are formed by I/R and that its subsequent activation of inflamMASomes leads to interleukin-1&bgr; production, resulting in inflammatory responses such as inflammatory cell infiltration and cytokine expression in the heart.
Abstract: Background— Inflammation plays a key role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury; however, the mechanism by which myocardial I/R induces inflammation remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by tissue damage is mediated through a multiple-protein complex called the inflammasome. Therefore, we hypothesized that the inflammasome is an initial sensor for danger signal(s) in myocardial I/R injury.
Methods and Results— We demonstrate that inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, is crucially involved in the initial inflammatory response after myocardial I/R injury. We found that inflammasomes are formed by I/R and that its subsequent activation of inflammasomes leads to interleukin-1β production, resulting in inflammatory responses such as inflammatory cell infiltration and cytokine expression in the heart. In mice deficient for apoptosis-associated speck-like adaptor protein and caspase-1, these inflammatory responses and subsequent injuries, including infarct development and myocardial fibrosis and dysfunction, were markedly diminished. Bone marrow transplantation experiments with apoptosis-associated speck-like adaptor protein–deficient mice revealed that inflammasome activation in bone marrow cells and myocardial resident cells such as cardiomyocytes or cardiac fibroblasts plays an important role in myocardial I/R injury. In vitro experiments revealed that hypoxia/reoxygenation stimulated inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, and that hypoxia/reoxygenation–induced activation was mediated through reactive oxygen species production and potassium efflux.
Conclusions— Our results demonstrate the molecular basis for the initial inflammatory response after I/R and suggest that the inflammasome is a potential novel therapeutic target for preventing myocardial I/R injury.
# Clinical Perspective {#article-title-31}
Northwestern University1, National Institutes of Health2, Harvard University3, Rice University4, University of California, Los Angeles5, University of Iowa6, University of Toronto7, University of Wisconsin-Madison8, Laval University9, University of Washington10, Washington University in St. Louis11, Georgia Institute of Technology12
TL;DR: Calcific aortic valve disease (CAVD) encompasses the range of disease from initial alterations in the cell biology of the leaflets to end-stage calcification resulting in left ventricular outflow obstruction as mentioned in this paper.
Abstract: Calcific aortic valve disease (CAVD) encompasses the range of disease from initial alterations in the cell biology of the leaflets to end-stage calcification resulting in left ventricular outflow obstruction. The first detectable macroscopic changes in the leaflets, seen as calcification, or focal leaflet thickening with normal valve function, is termed aortic valve sclerosis, but it is likely that the initiating events in the disease process occur much earlier. Disease progression is characterized by a process of thickening of the valve leaflets and the formation of calcium nodules—often including the formation of actual bone—and new blood vessels, which are concentrated near the aortic surface. End-stage disease, eg, calcific aortic stenosis, is characterized pathologically by large nodular calcific masses within the aortic cusps that protrude along the aortic surface into the sinuses of Valsalva, interfering with opening of the cusps. There is no disease along the ventricular surface. For decades, this disease was thought to be a passive process in which the valve degenerates with age in association with calcium accumulation. Moreover, although CAVD is more common with age, it is not an inevitable consequence of aging. Instead, CAVD appears to be an actively regulated disease process that cannot be characterized exclusively as senile or degenerative.
The National Heart, Lung, and Blood Institute convened a group of scientists from different fields of study, including cardiac imaging, molecular biology, cardiovascular pathology, epidemiology, cell biology, endocrinology, bioengineering, and clinical outcomes, to review the scientific studies from the past decade in the field of CAVD. The purpose was to develop a consensus statement on the current state of translational research related to CAVD. Herein, we summarize recent scientific studies and define future directions for research to diagnose, treat, and potentially prevent this complex disease process.
### Key Structure-Function Correlations
Heart valves permit unobstructed, unidirectional forward flow through the circulation. …