Eugene Braunwald

Bio: Eugene Braunwald is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Myocardial infarction & TIMI. The author has an hindex of 230, co-authored 1711 publications receiving 264576 citations. Previous affiliations of Eugene Braunwald include Boston University & University of California, San Francisco.

Stunning of the myocardium: an update.

Abstract: When severely ischemic myocardium is reperfused, prolonged myocardial dysfunction—a phenomenon named myocardial stunning—frequently occurs. Stunning also occurs in a variety of other situations. These include myocardium located adjacent to infarcted tissue, transient increase in myocardial O2 demands in the presence of incomplete coronary obstruction, during both systole and diastole, in isolated perfused hearts rendered ischemir or anoxic, and in a variety of clinical situations, such as following ischemic arrest in cardiac surgery, thrombolytic reperfusion, and after episodes of severe ischemia in Prinzmetal's angina or unstable angina. Although the fundamental mechanism (s) responsible for myocardial stunning has not been elucidated, in experimental preparations calcium antagonists, free-radical scavengers, and neutrophil depletion have each been found to be helpful in minimizing it.

Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients Design and Rationale of the EXACT-HF Study

Abstract: According to the most recent National Health and Nutrition Examination Survey, an estimated 5.1 million adult Americans have heart failure (HF), and projections show that by the year 2030 the prevalence of HF in the United States will increase by 25%.1 Despite guideline-recommended therapy for patients with HF and reduced ejection fraction,2 the overall 5-year mortality remains ≈50%, and the 1-year mortality in patients with New York Heart Association functional class III to IV HF on maximal medical therapy is 35% to 40%. Given the public health burden of HF, there is a clear need for improved medical therapies. Reduced myocardial antioxidant activity and increased oxidant damage have been demonstrated in animal models of HF, and markers of oxidative stress are increased in HF patients.3 These data support the thesis that reactive oxygen species may contribute to the progression of myocardial failure. Xanthine oxidase (XO) is among the potential stimuli of formation of reactive oxygen species in HF and may be an important target for therapy.4 Current evidence supports the hypothesis that HF is associated with an increase in the activity of XO, which, in turn, increases production of superoxide and uric acid (UA) during purine metabolism. The resulting nitroso-redox imbalance5 may be exacerbated by decreased activity of nitric oxide synthase (Figure 1). Significant hyperuricemia (ie, serum UA ≥9.5 mg/dL) is present in ≈25% of patients with HF and reduced ejection fraction.6,7 In addition to nitroso-redox imbalance, other contributors to hyperuricemia in HF include activation of proinflammatory cytokines, impaired vascular function, and renal insufficiency, as well as loop diuretic therapy.8 In patients with HF, there is a strong relationship between elevated UA levels and worsening symptoms,9 impaired exercise tolerance,10 and increased mortality.6 On the basis of these findings, …

The Effects of Mitral Regurgitation on the Pattern of Instantaneous Aortic Blood Flow Clinical and Experimental Observations

Abstract: Instantaneous ascending aortic blood flow was recorded at operation in five patients with severe, pure mitral regurgitation, and in nine dogs in which mitral regurgitation was produced experimentally under controlled conditions. In both the patients and the experimental animals, the pattern of aortic flow was abnormal during mitral regurgitation: peak flow occurred early, the percentage of total forward flow was abnormally high during the first half of the ejection period and abnormally low during the last quarter. When stroke volume, heart rate, and aortic pressure were maintained constant, mitral regurgitation also resulted in increases in peak flow, mean ejection rate, and maximum acceleration of flow. These abnormalities of the aortic flow patterns are attributable to inability of the ventricle to sustain forward ejection during late systole in the presence of severe regurgitant flow through the mitral valve.

Effects of hypertension on cardiac performance in rats with myocardial infarction.

Abstract: To determine the effects of hypertension and myocardial infarction on cardiac performance, hemodynamic studies were performed on etheranesthetized, female spontaneously hypertensive rats and on two strains of normotensive rats, Wistar-Kyoto and American Wistar, 26 days after coronary arterial ligation. Baseline measurements of ventricular and arterial pressures and cardiac output (electromagnetic flowmeter) were obtained. Peak cardiac pumping and pressure-generating capacities were determined during a volume load and aortic occlusion, respectively. Infarct size was determined by planimetry. There was a progressive reduction in mean arterial pressure in relation to infarct size in both hypertensive and normotensive rats, but this reduction was twice as great in spontaneously hypertensive rats as in the normotensive rats, such that the arterial pressure of hypertensive rats with a moderate or large infarction decreased to within the “normotensive range.” However, spontaneously hypertensive rats still maintained significantly higher arterial pressures than did normotensive rats at comparable infarct sizes. There was also a progressive reduction in the peak pressure developed during an afterload stress, and this reduction was greater in hypertensive rats than in normotensive rats with a large infarct. Maximal flow-generating capacity was similarly altered in rats with infarction: Peak stroke volume index varied inversely with infarct size and the reduction in this index was significantly greater in spontaneously hypertensive rats than in normotensive rats with a large infarct. Moreover, peak stroke work index was reduced to a greater extent in spontaneously hypertensive rats than in both normotensive strains of rats at any infarct size. Thus, after myocardial infarction, greater reductions in both pressure and flow-generating capacities occurred in hypertensive rats than in normotensive rats.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

Cochrane Handbook for Systematic Reviews of Interventions

Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

Atherosclerosis — An Inflammatory Disease

Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .

Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication

Abstract: Context Little is known about lifetime prevalence or age of onset of DSM-IV disorders. Objective To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Main Outcome Measures Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Results Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. Conclusions About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.