Showing papers in "Circulation in 2005"
TL;DR: This statement from the American Heart Association and the National Heart, Lung, and Blood Institute is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults.
Abstract: The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults.
The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors.
The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …
9,982 citations
TL;DR: This document summarizes current capabilities, research and operational priorities, and plans for further studies that were established at the 2015 USGS workshop on quantitative hazard assessments of earthquake-triggered landsliding and liquefaction.
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4,975 citations
TL;DR: It is increasingly recognized that office measurements correlate poorly with blood pressure measured in other settings, and that they can be supplemented by self-measured readings taken with validated devices at home, which gives a better prediction of risk than office measurements and is useful for diagnosing white-coat hypertension.
Abstract: Accurate measurement of blood pressure is essential to classify individuals, to ascertain blood pressure-related risk, and to guide management. The auscultatory technique with a trained observer and mercury sphygmomanometer continues to be the method of choice for measurement in the office, using the first and fifth phases of the Korotkoff sounds, including in pregnant women. The use of mercury is declining, and alternatives are needed. Aneroid devices are suitable, but they require frequent calibration. Hybrid devices that use electronic transducers instead of mercury have promise. The oscillometric method can be used for office measurement, but only devices independently validated according to standard protocols should be used, and individual calibration is recommended. They have the advantage of being able to take multiple measurements. Proper training of observers, positioning of the patient, and selection of cuff size are all essential. It is increasingly recognized that office measurements correlate poorly with blood pressure measured in other settings, and that they can be supplemented by self-measured readings taken with validated devices at home. There is increasing evidence that home readings predict cardiovascular events and are particularly useful for monitoring the effects of treatment. Twenty-four-hour ambulatory monitoring gives a better prediction of risk than office measurements and is useful for diagnosing white-coat hypertension. There is increasing evidence that a failure of blood pressure to fall during the night may be associated with increased risk. In obese patients and children, the use of an appropriate cuff size is of paramount importance.
4,327 citations
TL;DR: The metabolic syndrome accounts for up to one third of CVD in men and approximately half of new T2DM over 8 years of follow-up, and is associated with an increased risk for CVD and T2 DM in both sexes.
Abstract: Background— The incidence of cardiovascular disease (CVD), coronary heart disease (CHD), and type 2 diabetes mellitus (T2DM) has not been well defined in persons with the metabolic syndrome (at least 3 of the following: abdominal adiposity, low HDL cholesterol, high triglycerides, hypertension, and impaired fasting glucose). The objective was to investigate risk for CVD, CHD, and T2DM according to metabolic syndrome traits. Methods and Results— The study followed a cohort of 3323 middle-aged adults for the development of new CVD, CHD, and T2DM over an 8-year period. In persons without CVD or T2DM at baseline, the prevalence of the metabolic syndrome (≥3 of 5 traits) was 26.8% in men and 16.6% in women. There were 174 incident cases of CVD, 107 of CHD, and 178 of T2DM. In men, the metabolic syndrome age-adjusted relative risk (RR) and 95% CIs were RR=2.88 (95% CI 1.99 to 4.16) for CVD, RR=2.54 (95% CI 1.62 to 3.98) for CHD, and RR=6.92 (95% CI 4.47 to 10.81) for T2DM. Event rates and RRs were lower in wome...
1,827 citations
TL;DR: The present report elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.
Abstract: Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, α-adrenergic agonists, β-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred The report of the first consensus conference, published in 2002, focused on diagnostic criteria The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data
1,730 citations
TL;DR: Children and adolescent overweight is one of the most important current public health concerns and several strategies for prevention of abnormal weight gain are presented.
Abstract: The prevalence of overweight among children and adolescents has dramatically increased. There may be vulnerable periods for weight gain during childhood and adolescence that also offer opportunities for prevention of overweight. Overweight in children and adolescents can result in a variety of adverse health outcomes, including type 2 diabetes, obstructive sleep apnea, hypertension, dyslipidemia, and the metabolic syndrome. The best approach to this problem is prevention of abnormal weight gain. Several strategies for prevention are presented. In addition, treatment approaches are presented, including behavioral, pharmacological, and surgical treatment. Childhood and adolescent overweight is one of the most important current public health concerns.
1,640 citations
TL;DR: The third iteration of the Infective Endocarditis "treatment" document developed by the American Heart Association under the auspices of the Committee on Rheumatic fever, endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young was presented in this article.
Abstract: Background—Despite advances in medical, surgical, and critical care interventions, infective endocarditis remains a disease that is associated with considerable morbidity and mortality. The continuing evolution of antimicrobial resistance among common pathogens that cause infective endocarditis creates additional therapeutic issues for physicians to manage in this potentially life-threatening illness. Methods and Results—This work represents the third iteration of an infective endocarditis “treatment” document developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It updates recommendations for diagnosis, treatment, and management of complications of infective endocarditis. A multidisciplinary committee of experts drafted this document to assist physicians in the evolving care of patients with infective endocarditis in the new millennium. This extensive document is accompanied by an executive summary that covers the key points of the diagnosis, antimicrobial therapy, and management of infective endocarditis. For the first time, an evidence-based scoring system that is used by the American College of Cardiology and the American Heart Association was applied to treatment recommendations. Tables also have been included that provide input on the use of echocardiography during diagnosis and treatment of infective endocarditis, evaluation and treatment of culture-negative endocarditis, and short-term and long-term management of patients during and after completion of antimicrobial treatment. To assist physicians who care for children, pediatric dosing was added to each treatment regimen. Conclusions—The recommendations outlined in this update should assist physicians in all aspects of patient care in the diagnosis, medical and surgical treatment, and follow-up of infective endocarditis, as well as management of associated complications. Clinical variability and complexity in infective endocarditis, however, dictate that these guidelines be used to support and not supplant physician-directed decisions in individual patient management. (Circulation. 2005; 111:e394-e433.)
1,568 citations
TL;DR: Treatment of coronary atherosclerosis should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid “stabilization” of other plaques that may produce recurrent events.
Abstract: During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
1,547 citations
TL;DR: Although the predominant effect of ACE inhibition may result from the combined effect of reduced Ang II formation and Ang-(1–7) metabolism, the antihypertensive action of AT1 antagonists may in part be due to increased Ang II metabolism by ACE2.
Abstract: Background— Angiotensin-converting enzyme 2 (ACE2) has emerged as a novel regulator of cardiac function and arterial pressure by converting angiotensin II (Ang II) into the vasodilator and antitrop...
1,366 citations
TL;DR: The original conceptualization of this syndrome was on the basis of resistance to the metabolic actions of insulin, and it was maintained that hyperinsulinemia itself contributes to atherogenicity, and thus, insulin is atherogenic, leading to the coronary heart disease and cerebrovascular disease associated with this syndrome.
Abstract: Received June 28, 2004; revision received August 26, 2004; accepted October 15, 2004
The original description of the metabolic syndrome by Reaven1 consisted of obesity, insulin resistance, hypertension, impaired glucose tolerance or diabetes, hyperinsulinemia and dyslipidemia characterized by elevated triglyceride, and low HDL concentrations All of the features described above are risk factors for atherosclerosis, and thus, metabolic syndrome constituted a significant risk for coronary heart disease2–5 (Table) The features of obesity/overweight and insulin resistance also provided a significant risk for developing type 2 diabetes5,6 The risks for coronary heart disease and diabetes with metabolic syndrome are greater than those for simple obesity alone, and therefore, an understanding of the pathogenesis and through it, a rational approach to its therapy are of prime importance
View this table:
Classic Biological Effects of Insulin and Classic Metabolic Syndrome Based on Resistance to the Metabolic Effects of Insulin
As our understanding of the action of insulin evolves to comprehensively include the recent discoveries,7 we can better see that insulin resistance is the basis of most if not all of the features of this syndrome The original conceptualization of this syndrome was on the basis of resistance to the metabolic actions of insulin Thus, hyperinsulinemia, glucose intolerance, type 2 diabetes, hypertriglyceridemia, and low HDL concentrations could be accounted for by resistance to the actions of insulin on carbohydrate and lipid metabolism Although the features described above would to some extent explain the atherogenesis, Reaven has maintained that hyperinsulinemia itself contributes to atherogenicity, and thus, insulin is atherogenic, leading to the coronary heart disease and cerebrovascular disease associated with this syndrome
Obesity probably leads to hypertension through (1) increased vascular tone created by a reduced bioavailability of NO because of increased oxidative stress,8 (2) increased asymmetric dimethylarginine (ADMA) concentrations,9 (3) increased sympathetic …
1,317 citations
TL;DR: Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.
Abstract: Background— Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. Methods and Results— aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated wit...
TL;DR: Disparities in CVD and related risk factors remain pervasive and can be invaluable for policy development and in the planning, implementation, and evaluation of interventions designed to eliminate health disparities.
Abstract: Background Reducing health disparities remains a major public health challenge in the United States. Having timely access to current data on disparities is important for policy and program development. Accordingly, we assessed the current magnitude of disparities in cardiovascular disease (CVD) and its risk factors in the United States. Methods and results Using national surveys, we determined CVD and risk factor prevalence and indexes of morbidity, mortality, and overall quality of life in adults > or =18 years of age by race/ethnicity, sex, education level, socioeconomic status, and geographic location. Disparities were common in all risk factors examined. In men, the highest prevalence of obesity (29.2%) was found in Mexican Americans who had completed a high school education. Black women with or without a high school education had a high prevalence of obesity (47.3%). Hypertension prevalence was high among blacks (39.8%) regardless of sex or educational status. Hypercholesterolemia was high among white and Mexican American men and white women in both groups of educational status. Ischemic heart disease and stroke were inversely related to education, income, and poverty status. Hospitalization was greater in men for total heart disease and acute myocardial infarction but greater in women for congestive heart failure and stroke. Among Medicare enrollees, congestive heart failure hospitalization was higher in blacks, Hispanics, and American Indians/Alaska Natives than among whites, and stroke hospitalization was highest in blacks. Hospitalizations for congestive heart failure and stroke were highest in the southeastern United States. Life expectancy remains higher in women than men and higher in whites than blacks by approximately 5 years. CVD mortality at all ages tended to be highest in blacks. Conclusions Disparities in CVD and related risk factors remain pervasive. The data presented here can be invaluable for policy development and in the planning, implementation, and evaluation of interventions designed to eliminate health disparities.
TL;DR: Reduced levels of circulating EPCs independently predict atherosclerotic disease progression, thus supporting an important role for endogenous vascular repair to modulate the clinical course of coronary artery disease.
Abstract: Background— The maintenance of endothelial integrity plays a critical role in preventing atherosclerotic disease progression. Endothelial progenitor cells (EPCs) were experimentally shown to incorporate into sites of neovascularization and home to sites of endothelial denudation. Circulating EPCs may thus provide an endogenous repair mechanism to counteract ongoing risk factor–induced endothelial injury and to replace dysfunctional endothelium. Methods and Results— In 120 individuals (43 control subjects, 44 patients with stable coronary artery disease, and 33 patients with acute coronary syndromes), circulating EPCs were defined by the surface markers CD34+KDR+ and analyzed by flow cytometry. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, PTCA, CABG, or ischemic stroke) served as outcome variables over a median follow-up period of 10 months. Patients suffering from cardiovascular events had significantly lower numbers of EPCs (P<0.05). Reduced numbers of EPCs were as...
TL;DR: Long-term CCB responders represent <10% of IPAH patients evaluated in a pulmonary vascular referral center, and during acute vasodilator testing, these patients showed significantly lower levels of both mean PAP and PVR, which reached near-normal values.
Abstract: Background— Characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) who benefit from long-term calcium channel blockers (CCB) are unknown. Methods and Results— Acute pulmonary vasodilator testing with epoprostenol or nitric oxide was performed in 557 IPAH patients. Acute responders, defined by a fall in both mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) >20%, received long-term oral CCB. Patients who benefit from long-term CCB were defined as those being in New York Heart Association (NYHA) functional class I or II after at least 1 year on CCB monotherapy. Among the 70 patients who displayed acute pulmonary vasoreactivity (12.6%; 95% CI, 9.8% to 15.3%) and received CCB therapy, only 38 showed long-term improvement (6.8%; 95% CI, 4.7% to 8.9%). Long-term CCB responders had less severe disease at baseline than patients who failed. During acute vasodilator testing, long-term CCB responders displayed a more pronounced fall in mean PAP (−39±11% versus −...
TL;DR: The present review is focused on the potential underlying mechanism by which endothelial dysfunction may contribute to cardiovascular events, and the localization and distribution of the endothelial cell layer.
Abstract: A growing body of evidence suggests that endothelial dysfunction is associated with cardiovascular events. Endothelial dysfunction can be regarded as a syndrome that exhibits systemic manifestations associated with significant morbidity and mortality. The concept of endothelial dysfunction should be extended beyond the conduit vessels into the vascular wall and even to the bone marrow and the progenitor endothelial cells. The present review is focused on the potential underlying mechanism by which endothelial dysfunction may contribute to cardiovascular events. The assessment of endothelial function may emerge as an integral adjuvant test for evaluation of the vulnerable patients at risk for future cardiovascular events.
Atherosclerosis is a chronic, systemic, and diffuse disease with focal complications in different vascular beds. The mechanisms by which a specific site is rendered more prone to the development of symptomatic disease and cardiovascular events are not known. The observation that all stages of atherosclerosis may be at distant and at multiple locations simultaneously but at the same time may spare entire segments may give rise to the hypothesis that the interface and interaction between the vascular wall and the circulation is the primary site of the mechanism underlying cardiovascular events.1
The endothelium is the monolayer of endothelial cells lining the lumen of the vascular beds and is mechanically and metabolically strategically located, separating the vascular wall from the circulation and the blood components.1,2 To fully understand the mechanism by which alteration in endothelial function may lead to cardiovascular events, we need to extend our vision and concepts regarding the nature and function of the endothelium.
### Localization and Distribution of the Endothelium
The first concept that needs to be revised is the localization and distribution of the endothelial cell layer. The focus in the past decade has been on the endothelial layer of the large conduit vessels and the vascular lumen.2 …
TL;DR: A review of recommended components for an effective cardiac rehabilitation/secondary prevention program, alternative ways to deliver these services, recommended future research directions, and the rationale for each component of the rehabilitation and secondary prevention program with emphasis on the exercise training component is provided in this paper.
Abstract: This article updates the 1994 American Heart Association scientific statement on cardiac rehabilitation. It provides a review of recommended components for an effective cardiac rehabilitation/secondary prevention program, alternative ways to deliver these services, recommended future research directions, and the rationale for each component of the rehabilitation/secondary prevention program, with emphasis on the exercise training component.
TL;DR: Noninvasive 64-slice CT coronary angiography accurately detects coronary stenoses in patients in sinus rhythm and presenting with atypical chest pain, stable or unstable angina, or non–ST-segment elevation myocardial infarction.
Abstract: Background—The diagnostic performance of the latest 64-slice CT scanner, with increased temporal (165 ms) and spatial (0.4 mm 3 ) resolution, to detect significant stenoses in the clinically relevant coronary tree is unknown. Methods and Results—We studied 52 patients (34 men; mean age, 59.612.1 years) with atypical chest pain, stable or unstable angina pectoris, or non–ST-segment elevation myocardial infarction scheduled for diagnostic conventional coronary angiography. All patients had stable sinus rhythm. Patients with initial heart rates 70 bpm received -blockers. Mean scan time was 13.30.9 seconds. The CT scans were analyzed by 2 observers unaware of the results of invasive coronary angiography, which was used as the standard of reference. All available coronary segments, regardless of size, were included in the evaluation. Lesions with 50 luminal narrowing were considered significant stenoses. Invasive coronary angiography demonstrated the absence of significant disease in 25% (13 of 52), single-vessel disease in 31% (16 of 52), and multivessel disease in 45% (23 of 52) of patients. One unsuccessful CT scan was classified as inconclusive. Ninety-four significant stenoses were present in the remaining 51 patients. Sensitivity, specificity, and positive and negative predictive values of CT for detecting significant stenoses on a segment-by-segment analysis were 99% (93 of 94; 95% CI, 94 to 99), 95% (601 of 631; 95% CI, 93 to 96), 76% (93 of 123; 95% CI, 67 to 89), and 99% (601 of 602; 95% CI, 99 to 100), respectively. Conclusions—Noninvasive 64-slice CT coronary angiography accurately detects coronary stenoses in patients in sinus rhythm and presenting with atypical chest pain, stable or unstable angina, or non–ST-segment elevation myocardial infarction. (Circulation. 2005;112:2318-2323.)
TL;DR: A reversible cardiomyopathy triggered by psychologically stressful events occurs in older women and may mimic evolving acute myocardial infarction or coronary syndrome.
Abstract: Background— A clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction and triggered by psychological stress is emerging, with reports largely confined to Japan. Methods and Results— Over a 32-month period, 22 consecutive patients with this novel cardiomyopathy were prospectively identified within a community-based practice in the Minneapolis–St. Paul, Minn, area. All patients were women aged 32 to 89 years old (mean 65±13 years); 21 (96%) were ≥50 years of age. The syndrome is characterized by (1) acute substernal chest pain with ST-segment elevation and/or T-wave inversion; (2) absence of significant coronary arterial narrowing by angiography; (3) systolic dysfunction (ejection fraction 29±9%), with abnormal wall motion of the mid and distal LV, ie, “apical ballooning”; and (4) profound psychological stress (eg, death of relatives, domestic abuse, arguments, catastrophic medical diagnoses, devastating financial or gambling losses) immediately preceding and...
TL;DR: In the PAMELA population, risk of death increased more with a given increase in home or ambulatory blood pressure than in office BP, although it was somewhat increased by the combination of office and outside-of-office values.
Abstract: Background— Studies in hypertensive patients suggest that ambulatory blood pressure (BP) is prognostically superior to office BP. Much less information is available in the general population, however. Obtaining this information was the purpose of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Methods and Results— Office, home, and 24-hour ambulatory BP values were obtained in 2051 subjects between 25 and 74 years of age who were representative of the general population of Monza (Milan, Italy). Subjects were followed up for an average of 131 months, during which time cardiovascular and noncardiovascular fatal events were recorded (n=186). Office, home, and ambulatory BP values showed a significant exponential direct relationship with risk of cardiovascular or all-cause death. The goodness of fit of the relationship was greater for systolic than for diastolic BP and for night than for day BP, but its overall value was not better for home or ambulatory than for office BP. The slope of...
TL;DR: This study suggests that postconditioning by coronary angioplasty protects the human heart during acute myocardial infarction.
Abstract: Background— In animal models, brief periods of ischemia performed just at the time of reperfusion can reduce infarct size, a phenomenon called postconditioning. In this prospective, randomized, controlled, multicenter study, we investigated whether postconditioning may protect the human heart during coronary angioplasty for acute myocardial infarction. Methods and Results— Thirty patients, submitted to coronary angioplasty for ongoing acute myocardial infarction, contributed to the study. Patients were randomly assigned to either a control or a postconditioning group. After reperfusion by direct stenting, control subjects underwent no further intervention, whereas postconditioning was performed within 1 minute of reflow by 4 episodes of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Infarct size was assessed by measuring total creatine kinase release over 72 hours. Area at risk and collateral blood flow were estimated on left ventricular and coronary angiograms. No adverse events oc...
TL;DR: BMC biodistribution after therapeutic application in patients with a first ST-segment–elevation myocardial infarction who had undergone stenting of the infarct-related artery is determined and 18F-FDG labeling and 3D PET imaging can be used to monitor the homing and biodist distribution of BMCs after therapeutic applications in patients.
Abstract: Background— Intracoronary transfer of autologous bone marrow cells (BMCs) promotes recovery of left ventricular systolic function in patients with acute myocardial infarction. Although the mechanisms of this effect remain to be established, homing of BMCs into the infarcted myocardium is probably a critical early event. Methods and Results— We determined BMC biodistribution after therapeutic application in patients with a first ST-segment–elevation myocardial infarction who had undergone stenting of the infarct-related artery. Unselected BMCs were radiolabeled with 100 MBq 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) and infused into the infarct-related coronary artery (intracoronary; n=3 patients) or injected via an antecubital vein (intravenous; n=3 patients). In 3 additional patients, CD34-positive (CD34+) cells were immunomagnetically enriched from unselected BMCs, labeled with 18F-FDG, and infused intracoronarily. Cell transfer was performed 5 to 10 days after stenting. More than 99% of the infused tot...
TL;DR: There is compelling histopathologic and clinical data suggesting that calcific valve disease is an active disease process akin to atherosclerosis with lipoprotein deposition, chronic inflammation, and active leaflet calcification.
Abstract: Received October 26, 2004; revision received January 13, 2005; accepted February 4, 2005.
Calcific aortic valve disease is a slowly progressive disorder with a disease continuum that ranges from mild valve thickening without obstruction of blood flow, termed aortic sclerosis, to severe calcification with impaired leaflet motion, or aortic stenosis (Figure 1). In the past, this process was thought to be “degenerative” because of time-dependent wear-and-tear of the leaflets with passive calcium deposition. Now, there is compelling histopathologic and clinical data suggesting that calcific valve disease is an active disease process akin to atherosclerosis with lipoprotein deposition, chronic inflammation, and active leaflet calcification. The overlap in the clinical factors associated with calcific valve disease and atherosclerosis and the correlation between the severity of coronary artery and aortic valve calcification provide further support for a shared disease process.
Figure 1. Gross specimen of minimally diseased aortic valve (left) and severely stenotic aortic valve (right). In the severely stenotic valve, there are prominent lipocalcific changes on aortic side of valve cusps (arrow), with sparing of commissures.
### Anatomy of Normal Aortic Valve
The normal aortic valve comprises 3 layers. The ventricularis, on the ventricular side of the leaflet, is composed of elastin-rich fibers that are aligned in a radial direction, perpendicular to the leaflet margin. The fibrosa, on the aortic side of the leaflet, comprises primarily fibroblasts and collagen fibers arranged circumferentially, parallel to the leaflet margin. The spongiosa is a layer of loose connective tissue at the base of the leaflet, between the fibrosa and ventricularis, composed of fibroblasts, mesenchymal cells, and a mucopolysaccharide-rich matrix. These layers work in concert to provide tensile strength and pliability for decades of repetitive motion.
### Early Lesion of Aortic Sclerosis
Histopathologic studies of aortic sclerosis show focal subendothelial plaquelike lesions on the aortic side of the leaflet that extend to the adjacent fibrosa layer. Similarities to …
TL;DR: The effects of secondhand smoke are substantial and rapid, explaining the relatively large risks that have been reported in epidemiological studies.
Abstract: Background— Secondhand smoke increases the risk of coronary heart disease by ≈30%. This effect is larger than one would expect on the basis of the risks associated with active smoking and the relative doses of tobacco smoke delivered to smokers and nonsmokers. Methods and Results— We conducted a literature review of the research describing the mechanistic effects of secondhand smoke on the cardiovascular system, emphasizing research published since 1995, and compared the effects of secondhand smoke with the effects of active smoking. Evidence is rapidly accumulating that the cardiovascular system—platelet and endothelial function, arterial stiffness, atherosclerosis, oxidative stress, inflammation, heart rate variability, energy metabolism, and increased infarct size—is exquisitely sensitive to the toxins in secondhand smoke. The effects of even brief (minutes to hours) passive smoking are often nearly as large (averaging 80% to 90%) as chronic active smoking. Conclusions— The effects of secondhand smoke ...
TL;DR: Plasma resistin levels are correlated with markers of inflammation and are predictive of coronary atherosclerosis in humans, independent of CRP.
Abstract: Background— Resistin, a plasma protein, induces insulin resistance in rodents. Recent reports suggest that circulating levels of resistin are elevated in obese and insulin-resistant rodents and humans. Whereas rodent resistin is made in adipocytes, macrophages are a major source of human resistin. Given the convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and atherosclerosis in humans. Methods and Results— We examined whether plasma resistin levels were associated with metabolic and inflammatory markers, as well as with coronary artery calcification (CAC), a quantitative index of atherosclerosis, in 879 asymptomatic subjects in the Study of Inherited Risk of Coronary Atherosclerosis. Resistin levels were positively associated with levels of inflammatory markers, including soluble tumor necrosis factor-α receptor-2 (P<0.001), interleukin-6 (P=0.04), and lipoprotein-associated phospholipase A2 (P=0.002), but not measures of insul...
TL;DR: Spectral analysis and frequency mapping identify localized sites of high-frequency activity during atrial fibrillation in humans with different distributions in paroxysmal and permanent AF, indicating their role in the maintenance of AF.
Abstract: Background— The identification of sites of dominant activation frequency during atrial fibrillation (AF) in humans and the effect of ablation at these sites have not been reported. Methods and Results— Thirty-two patients undergoing AF ablation (19 paroxysmal, 13 permanent) during ongoing arrhythmia were studied. Electroanatomic mapping was performed, acquiring 126±13 points per patient throughout both atria and coronary sinus. At each point, 5-second electrograms were obtained to determine the highest-amplitude frequency on spectral analysis and to construct 3D dominant frequency (DF) maps. The temporal stability of the recording interval was confirmed in a subset. Ablation was performed with the operator blinded to the DF maps. The effect of ablation at sites with or without high-frequency DF sites (maximal frequencies surrounded by a decreasing frequency gradient ≥20%) was evaluated by determining the change in AF cycle length (AFCL) and the termination and inducibility of AF. The spatial distribution ...
TL;DR: OCT is a safe and effective modality for characterizing coronary atherosclerotic plaques in vivo and thin-cap fibroatheroma was more frequently observed in patients with AMI or ACS than SAP.
Abstract: Background— The current understanding of the pathophysiology of coronary artery disease is based largely on postmortem studies. Optical coherence tomography (OCT) is a high-resolution (≈10 μm), catheter-based imaging modality capable of investigating detailed coronary plaque morphology in vivo. Methods and Results— Patients undergoing cardiac catheterization were enrolled and categorized according to their clinical presentation: recent acute myocardial infarction (AMI), acute coronary syndromes (ACS) constituting non-ST-segment elevation AMI and unstable angina, or stable angina pectoris (SAP). OCT imaging was performed with a 3.2F catheter. Two observers independently analyzed the images using the previously validated criteria for plaque characterization. Of 69 patients enrolled, 57 patients (20 with AMI, 20 with ACS, and 17 with SAP) had analyzable images. In the AMI, ACS, and SAP groups, lipid-rich plaque (defined by lipid occupying ≥2 quadrants of the cross-sectional area) was observed in 90%, 75%, an...
TL;DR: In cardiac amyloidosis, CMR shows a characteristic pattern of global subendocardial late enhancement coupled with abnormal myocardial and blood-pool gadolinium kinetics and may prove to have value in diagnosis and treatment follow-up.
Abstract: Background— Cardiac amyloidosis can be diagnostically challenging. Cardiovascular magnetic resonance (CMR) can assess abnormal myocardial interstitium. Methods and Results— Late gadolinium enhancement CMR was performed in 30 patients with cardiac amyloidosis. In 22 of these, myocardial gadolinium kinetics with T1 mapping was compared with that in 16 hypertensive controls. One patient had CMR and autopsy only. Subendocardial T1 in amyloid patients was shorter than in controls (at 4 minutes: 427±73 versus 579±75 ms; P<0.01), was shorter than subepicardium T1 for the first 8 minutes (P≤0.01), and was correlated with markers of increased myocardial amyloid load, as follows: left ventricular (LV) mass (r=−0.51, P=0.013); wall thickness (r=−0.54 to −0.63, P<0.04); interatrial septal thickness (r=−0.52, P=0.001); and diastolic function (r=−0.42, P=0.025). Global subendocardial late gadolinium enhancement was found in 20 amyloid patients (69%); these patients had greater LV mass (126±30 versus 93±25 g/m2; P=0.009...
TL;DR: The data from this large study of adults having isolated aortic valve replacement for aortsic stenosis and without associated mitral stenosis or mitral valve replacement strongly suggest that an underlying congenitally malformed valve, at least in men, is more common than a tricuspid aortIC valve.
Abstract: Background— Aortic valve stenosis (with or without aortic regurgitation and without associated mitral stenosis) in adults in the Western world has been considered in recent years to most commonly b...
TL;DR: Recent advances in the field of heart failure are summarized, with a focus on the new therapeutic strategies that have been developed for treating systolic heart failure.
Abstract: Received August 25, 2004; revision received December 23, 2004; accepted January 19, 2005.
Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure, no single conceptual paradigm for heart failure has withstood the test of time. Whereas clinicians initially viewed heart failure as a problem of excessive salt and water retention that was caused by abnormalities of renal blood flow (the “cardiorenal model”1), as physicians began to perform careful hemodynamic measurements, it also became apparent that heart failure was associated with a reduced cardiac output and excessive peripheral vasoconstriction. This latter realization led to the development of the “cardiocirculatory” or “hemodynamic” model for heart failure,1 wherein heart failure was thought to arise largely as a result of abnormalities of the pumping capacity of the heart and excessive peripheral vasoconstriction. However, although both the cardiorenal and cardiocirculatory models for heart failure explained the excessive salt and water retention that heart failure patients experience, neither of these models explained the relentless “disease progression” that occurs in this syndrome. Thus, although the cardiorenal models provided the rational basis for the use of diuretics to control the volume status of patients with heart failure, and the cardiocirculatory model provided the rational basis for the use of inotropes and intravenous vasodilators to augment cardiac output, these therapeutic strategies have not prevented heart failure from progressing, nor have they led to prolonged life for patients with moderate to severe heart failure.1,2⇓
In the present review we will summarize recent advances in the field of heart failure, with a focus on the new therapeutic strategies that have been developed for treating systolic heart failure. For a complete discussion on recent advances in the diagnosis and treatment of diastolic heart failure, the interested reader is referred to several …