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Background Anemia is an important comorbidity in heart failure (HF), and it is associated with increased adverse disease experience and mortality. Previous reports have focused mainly on HF presenting in healthcare settings. We, therefore, set out to establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US. Aim To establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US. Design The NHANES dataset, conducted by the CDC National Center for Health Statistics was used to collect nationally representative data on the health and nutritional status of the non-institutionalized US population. Methods We utilized the National Health and Nutrition Examination data collected over five survey cycles (2007–16). Included were participants aged 20–80 years with self-reported diagnosis of HF. Anemia was defined using 2 sex specific cut offs of 13 and 12 g/dl (cutoff 1), and 12 and 11 g/dl (cutoff 2), for men and women, respectively. The Chi square test was used to compare prevalence across different categories and survey cycles. Data analysis was done using STATA 16 with P -values < 0.05 considered statistically significant. Results The median hemoglobin in all HF patients was 13.5 g/dl (IQR 12.4–14.5). The prevalence of anemia among community-based patients with HF in the US was 21.34% (cutoff 1) and 9.03% (cutoff 2) and has been stable from 2007 to 2016. The burden of anemia was disproportionately higher in NH Blacks (34.48%, 95% CI 27.12–42.67) and those with BMI < 25 Kg/m2 (17.4%, 95% CI 10.9–26.64). Conclusion The prevalence of anemia in patients with HF in the US is at least 9% and has remained stable over the past decade. This high persistent burden with limited proven interventions should spur further efforts aimed at identifying impactful ways of addressing anemia in patients with HF. [ABSTRACT FROM AUTHOR]

Background: On-line physician education is increasing, but its efficacy in comparison with existing self-study methods is unknown.Objective: To compare knowledge, learning efficiency, and learner satisfaction produced by self-study of World Wide Web-based and print-based guidelines for care after acute myocardial infarction.Design: Randomized, controlled trial.Setting: 12 family medicine and internal medicine residency programs at four universities.Participants: 162 residents.Interventions: In proctored sessions, participants were randomly assigned to study from printed materials or from SAGE (Self-Study Acceleration with Graphic Evidence), a Web-based tutorial system. Both methods used identical self-assessment questions and answers and guideline text, but SAGE featured hyperlinks to specific guideline passages and graphic evidence animations.Measurements: Scores on multiple-choice knowledge tests, score gain per unit of study time, and ratings on a learner satisfaction scale.Results: Immediate post-test scores on a 20-point scale were similar in the SAGE and control groups (median score, 15.0 compared with 14.5; P>0.2), but SAGE users spent less time studying (median, 27.0 compared with 38.5 minutes; P<0.001) and therefore had greater learning efficiency (median score gain, 8.6 compared with 6.7 points per hour; P = 0.04). On a scale of 5 to 20, SAGE users were more satisfied with learning (median rating, 17.0 compared with 15.0; P<0.001). After 4 to 6 months, knowledge had decreased to the same extent in the SAGE and control groups (median score, 12.0 compared with 11.0; P = 0.12).Conclusions: On-line tutorials may produce greater learning efficiency and satisfaction than print materials do, but one self-study exposure may be insufficient for long-term knowledge retention. Further research is needed to identify instructional features that motivate greater final learning and retention. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess whether in patients with syncope and heart failure due to nonischemic cardiomyopathy, treatment with an implantable cardioverter-defibrillator (ICD) compared with conventional medical therapy is associated with a reduction in sudden death and total mortality. Patients with advanced heart failure who have syncope have been shown to be at high risk for sudden death. Further risk stratification has been difficult in patients with nonischemic cardiomyopathy in whom inducibility on electrophysiologic study is not predictive of future risk. Of 639 consecutive patients with nonischemic cardiomyopathy referred for heart transplantation, 147 patients with history of syncope and no prior history of sustained ventricular tachycardia or cardiac arrest were identified. Outcomes were compared for the 25 patients managed with an ICD and 122 patients managed with conventional medical therapy. There were no differences in the baseline variables in the 2 groups of patients, including age, ejection fraction, and medical treatments for heart failure, but patients receiving an ICD were more likely to have had nonsustained ventricular tachycardia (56% vs. 15%, p = 0.001). During a mean follow-up of 22 months, there were 31 deaths, 18 sudden, in patients treated with conventional therapy, whereas there were 2 deaths, none sudden, in patients treated with an ICD. An appropriate shock occurred in 40% of the ICD patients. Actuarial survival at 2 years was 84.9% with ICD therapy and 66.9% with conventional therapy (p = 0.04). Thus, in patients with nonischemic cardiomyopathy and syncope, therapy with an ICD is associated with a reduction in sudden death and an improvement in overall survival. [ABSTRACT FROM AUTHOR]

Objectives To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries. Background Results from clinical trials suggest significant variation in care across the world. However, international comparisons in "real world" registries are limited. Methods We compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n=137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n=45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n=147,438] clinical registries. Results Patients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%). Conclusions The care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement. [ABSTRACT FROM AUTHOR]

Despite clear and consistent clinical-trial evidence that secondary-prevention medical therapies reduce mortality in patients with established coronary artery disease, these therapies are underutilized in patients receiving conventional care. To address this issue, a Cardiac Hospitalization Atherosclerosis Management Program (CHAMP) focused on initiation of aspirin, cholesterol-lowering medication (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitor titrated to achieve low-density lipoprotein [LDL] cholesterol < 100 mg/dL), beta-blocker, and angiotensin-converting enzyme (ACE)-inhibitor therapy in conjunction with diet and exercise counseling before hospital discharge in patients with established coronary artery disease was designed and implemented at the University of California Los Angeles (UCLA) Medical Center starting in 1994. This treatment program was based on the hypothesis that initiation of therapy in the hospital setting would result in higher utilization rates both at the time of discharge and during longer-term follow-up. Implementation of this program involved the use of a focused treatment guideline, standardized admission orders, educational lectures by local thought leaders, and tracking/reporting of treatment rates. To assess the impact of the program, treatment rates and clinical outcome were compared in patients discharged in the 2-year periods before and after CHAMP was implemented. Hospital-based treatment protocols such as CHAMP have the potential to significantly increase treatment utilization of therapies previously demonstrated to improve survival and thus substantially improve the outcome of the 2 million patients diagnosed and hospitalized each year with coronary artery disease. [ABSTRACT FROM AUTHOR]

Despite scientific evidence that secondary prevention medical therapies reduce mortality in patients with established coronary artery disease, these therapies continue to be underutilized in patients receiving conventional care. To address this issue, a Cardiac Hospital Atherosclerosis Management Program (CHAMP) focused on initiation of aspirin, cholesterol-lowering medication (hydroxymethylglutaryl coenzyme A [HMG CoA] reductase inhibitor titrated to achieve low-density lipoprotein [LDL] cholesterol < or =100 mg/dl), beta blocker, and angiotensin-converting enzyme (ACE) inhibitor therapy in conjunction with diet and exercise counseling before hospital discharge in patients with established coronary artery disease. Treatment rates and clinical outcome were compared in patients discharged after myocardial infarction in the 2-year period before (1992 to 1993) and the 2-year period after (1994 to 1995) CHAMP was implemented. In the pre- and post-CHAMP patient groups, aspirin use at discharge improved from 68% to 92% (p <0.01), beta blocker use improved from 12% to 62% (p <0.01), ACE inhibitor use increased from 6% to 58% (p <0.01), and statin use increased from 6% to 86% (p <0.01). This increased use of treatment persisted during subsequent follow-up. There was also a significant increase in patients achieving a LDL cholesterol < or =100 mg/dl (6% vs 58%, p <0.001) and a reduction in recurrent myocardial infarction and 1-year mortality. Compared with conventional guidelines and care, CHAMP was associated with a significant increase in use of medications that have been previously demonstrated to reduce mortality; more patients achieved an LDL cholesterol < or =100 mg/dl, and there were improved clinical outcomes in patients after hospitalization for acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Skin tests to recall antigens are performed as indicators of clinical outcomes in heart failure (HF). A diminution in the response to recall antigens, termed "anergy," is regarded as an indication of poorer clinical prognosis, although little analysis has been done to support that conclusion. Patients with advanced HF (n=222) in New York Heart Association classes III and IV, with complete datasets for all of the variables, were studied. The sample was 77% men, mean age 52+/-12 years, and left ventricular ejection fraction, 21+/-7. Patients with ischemic (n=113) and idiopathic (n=109) disease were analyzed separately. The relation of anergy to 1-year mortality and selected hemodynamic factors, blood chemistries, medications, and nutritional status markers was analyzed. Anergy was present in 45% (47% idiopathic and 42% ischemic) of patients. Anergy was related to 1-year mortality (univariate p=0.038) in patients with ischemic, but not idiopathic, HF. Anergic patients with ischemic HF had shorter survival times (p=0.035). Lower cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were predictors (p <0.001) of mortality in idiopathic HF. In ischemic HF, lower cholesterol, LDL, and triglycerides were univariate predictors (p <0.001, p=0.004, and p=0.005, respectively) of skin test anergy, but not mortality. Thus, there were distinct differences in clinical correlates of skin test anergy in patients with idiopathic and ischemic HF. This study supports evaluation of anergy to skin tests as one of the markers of mortality in patients with ischemic HF. [ABSTRACT FROM AUTHOR]

Most patients with advanced congestive heart failure have altered thyroid hormone metabolism. A low triiodothyronine level is associated with impaired hemodynamics and is an independent predictor of poor survival. This study sought to evaluate safety and hemodynamic effects of short-term intravenous administration of triiodothyronine in patients with advanced heart failure. An intravenous bolus dose of triiodothyronine, with or without a 6- to 12-hour infusion (cumulative dose 0. 1 5 to 2.7 microg/kg), was administered to 23 patients with advanced heart failure (mean left ventricular ejection fraction 0.22 +/- 0.01). Cardiac rhythm and hemodynamic status were monitored for 12 hours, and basal metabolic rate by indirect calorimetry, echocardiographic parameters of systolic function and valvular regurgitation, thyroid hormone, and catecholamine levels were measured at baseline and at 4 to 6 hours. Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect. Acute intravenous administration of triiodothyronine is well tolerated in patients with advanced heart failure, establishing the basis for further investigation into the safety and potential hemodynamic benefits of longer infusions, combined infusion with inotropic agents, oral triiodothyronine replacement therapy, and new triiodothyronine analogs. [ABSTRACT FROM AUTHOR]

Background: Anemia is an important comorbidity in heart failure (HF), and it is associated with increased adverse disease experience and mortality. Previous reports have focused mainly on HF presenting in healthcare settings. We, therefore, set out to establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US., Aim: To establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US., Design: The NHANES dataset, conducted by the CDC National Center for Health Statistics was used to collect nationally representative data on the health and nutritional status of the non-institutionalized US population., Methods: We utilized the National Health and Nutrition Examination data collected over five survey cycles (2007-16). Included were participants aged 20-80 years with self-reported diagnosis of HF. Anemia was defined using 2 sex specific cut offs of 13 and 12 g/dl (cutoff 1), and 12 and 11 g/dl (cutoff 2), for men and women, respectively. The Chi square test was used to compare prevalence across different categories and survey cycles. Data analysis was done using STATA 16 with P-values < 0.05 considered statistically significant., Results: The median hemoglobin in all HF patients was 13.5 g/dl (IQR 12.4-14.5). The prevalence of anemia among community-based patients with HF in the US was 21.34% (cutoff 1) and 9.03% (cutoff 2) and has been stable from 2007 to 2016. The burden of anemia was disproportionately higher in NH Blacks (34.48%, 95% CI 27.12-42.67) and those with BMI < 25 Kg/m2 (17.4%, 95% CI 10.9-26.64)., Conclusion: The prevalence of anemia in patients with HF in the US is at least 9% and has remained stable over the past decade. This high persistent burden with limited proven interventions should spur further efforts aimed at identifying impactful ways of addressing anemia in patients with HF., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent., Methods: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days., Results: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11)., Conclusions: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Objectives: The study aimed to evaluate the role of obesity in the prognosis of patients with heart failure (HF)., Background: Previous reports link obesity to the development of HF. However, the impact of obesity in patients with established HF has not been studied., Methods: We analyzed 1,203 patients with advanced HF followed in a comprehensive HF management program. The patients were subclassified into categories of body mass index (BMI) defined as: underweight BMI <20.7 (n = 164), recommended BMI 20.7 to 27.7 (n = 692), overweight BMI 27.8 to 31 (n = 168) and obese BMI >31 (n = 179). This sample size allows the detection of small effects (0.02), with a power of 0.80 and an alpha level of 0.05 for comparing one-year survival between BMI groups., Results: The four BMI groups had similar profiles in terms of ejection fraction (mean 0.22), sodium, creatinine and smoking. The obese and overweight groups had significantly higher rates of hypertension and diabetes, as well as higher levels of cholesterol, triglycerides and low density lipoprotein cholesterol. The four BMI groups had similar survival rates. Ejection fraction, HF etiology and angiotensin-converting enzyme inhibitor use predicted survival on univariate analysis (p < 0.01), although BMI did not. On multivariate analysis, cardiopulmonary exercise tests, pulmonary capillary wedge pressure and serum sodium were strong predictors of survival (p < 0.05). Higher BMI was not a risk factor for increased mortality, but was associated with a trend toward improved survival., Conclusions: In a large cohort of patients with advanced HF of multiple etiologies, obesity is not associated with increased mortality and may confer a more favorable prognosis. Further studies need to delineate whether weight loss promotion in medically optimized patients with HF is a worthwhile therapeutic goal.

At the time of initial transplant evaluation, we evaluated the information and counseling needs of 82 outpatients with advanced heart failure and compared them with the needs of 74 of their caregivers. Both groups answered a 23-item questionnaire, which used a 5-point Likert scale to assess needs across 6 sub-scales specific to heart failure and the process of determining transplant eligibility. The 5 most important learning needs of patients and caregivers were similar, and we found significant differences only in the groups' responses to 3 individual questions. We conclude that nurses can meet the needs of patients and their caregivers by providing honest explanations, focusing on enhanced quality of life issues, and giving information for dealing with an emergency.

In heart failure (HF) patients, reflex renal vasoconstriction during exercise is exaggerated. We hypothesized that muscle mechanoreceptor control of renal vasoconstriction is exaggerated in HF. Nineteen HF patients and nineteen controls were enrolled in two exercise protocols: 1) low-level rhythmic handgrip (mechanoreceptors and central command) and 2) involuntary biceps contractions (mechanoreceptors). Renal cortical blood flow was measured by positron emission tomography, and renal cortical vascular resistance (RCVR) was calculated. During rhythmic handgrip, peak RCVR was greater in HF patients compared with controls (37 +/- 1 vs. 27 +/- 1 units; P < 0.01). Change in (Delta) RCVR tended to be greater as well but did not reach statistical significance (10 +/- 1 vs. 7 +/- 0.9 units; P = 0.13). RCVR was returned to baseline at 2-3 min postexercise in controls but remained significantly elevated in HF patients. During involuntary muscle contractions, peak RCVR was greater in HF patients compared with controls (36 +/- 0.7 vs. 24 +/- 0.5 units; P < 0.0001). The Delta RCVR was also significantly greater in HF patients compared with controls (6 +/- 1 vs. 4 +/- 0.6 units; P = 0.05). The data suggest that reflex renal vasoconstriction is exaggerated in both magnitude and duration during dynamic exercise in HF patients. Given that the exaggerated response was elicited in both the presence and absence of central command, it is clear that intact muscle mechanoreceptor sensitivity contributes to this augmented reflex renal vasoconstriction.

Background: The present study aimed to assess use of lipid-lowering medication at discharge in a current national sample of patients hospitalized with acute myocardial infarction and to evaluate factors associated with prescribing patterns., Methods and Results: Demographic, procedural, and discharge medication data were collected from 138 001 patients with acute myocardial infarction discharged from 1470 US hospitals participating in the National Registry of Myocardial Infarction 3 from July 1998 to June 1999. Lipid-lowering medications were part of the discharge regimen in 31. 7%. Among patients with prior history of CAD, revascularization, or diabetes, less than one half of the patients were discharged on treatment. In multivariate analysis, factors independently related to lipid-lowering use included history of hypercholesterolemia (odds ratio [OR] 4.93; 95% CI 4.79 to 5.07), cardiac catheterization during hospitalization (OR 1.29; 95% CI 1.24 to 1.34), care provided at a teaching hospital, (OR 1.26; 95% CI 1.22 to 1.32), use of ss-blocker (OR 1.43; 95% CI 1.39 to 1.48), and smoking cessation counseling (OR 1.51; 95% CI 1.44 to 1.59). Lipid-lowering medications were given less often to patients who were older (65 to 74 versus <55 years of age; OR 0.82; 95% CI 0.78 to 0.86), those with a history of hypertension (OR 0.92; 95% CI 0.89 to 0.95), and those undergoing coronary artery bypass graft surgery (OR 0.58; 95% CI 0.55 to 0.60)., Conclusions: Analysis of current practice patterns for the use of lipid-lowering medications in patients hospitalized with acute myocardial infarction reveals that a significant proportion of high-risk patients did not receive treatment at time of discharge.

The therapeutic goals for patients hospitalized with acute decompensated heart failure are to reverse acute hemodynamic abnormalities, relieve symptoms, and provide the ability to initiate early treatment, which will decrease disease progression and improve long-term survival. The use of nesiritide on top of standard care, such as diuretic therapy, has been proven to lead to meaningful clinical benefits in a broad range of acutely decompensated heart failure patients. Nesiritide is an attractive therapeutic option because of its more rapid and sustained hemodynamic profile with less adverse effects than alternative heart failure treatments, such as nitroglycerine or dobutamine. The use of nesiritide represents an entirely new treatment approach to reverse acutely decompensated heart failure and to facilitate optimization of the heart failure medical regimen.

Dilated cardiomyopathy is a disease of diverse causes. Untreated, this condition will likely progress to advanced heart failure, sudden death, or both. There have been a number of significant advances in the understanding of the mechanisms involved in the pathogenesis of this disease. Treatments that counteract ventricular remodeling with neurohumoral blockade have substantially improved the outcome for many patients. Although cardiac transplantation is of benefit to patients with advanced disease, the growing donor heart shortage limits this option. New treatments are clearly needed, and many are being actively investigated. As the genetic and cellular derangements that result in dilated cardiomyopathy are better understood, new therapeutic targets will be identified in the quest to restore normal cardiac structure and function.

Acute decompensated heart failure is characterized by hemodynamic abnormalities as well as neuroendocrine activation, which contribute to heart failure symptoms, progressive cardiac dysfunction, and sudden death. The therapeutic goals in patients hospitalized with decompensated heart failure are to reverse acute hemodynamic abnormalities, relieve symptoms, and initiate treatment that will slow disease progression and improve long-term survival. Traditional hemodynamic targets in acute heart failure have been reduction in left and right ventricular filling pressures, reduction in systemic vascular resistance, and increase in cardiac output. Treatments aimed at these targets in patients with acute decompensated heart failure include diuretics, vasodilators, and inotropic agents. In patients hospitalized with acute decompensated heart failure, persistently elevated left ventricular filling pressure has been shown to be highly predictive of an increased risk of fatal decompensation and sudden death. Measures of systemic perfusion, arterial pressure, and vascular resistance have not. Thus, there is a more compelling physiologic rationale for the use of vasodilators than for inotropic agents in these patients. An ideal agent for acute decompensated heart failure would be one that rapidly reduces pulmonary wedge pressure, results in balanced arterial and venous dilation, promotes natriuresis, lacks direct positive inotropic effects, and does not result in reflex neuroendocrine activation.

Background: This study determined whether evidence of congestion after 4 to 6 weeks of heart failure management predicted outcome for patients hospitalized with chronic New York Heart Association class IV symptoms. Class IV symptoms predict high mortality rates, but outcome is not known for patients who improve to establish freedom from congestion. Revised estimates at 1 month could facilitate decisions regarding transplantation and other high-risk interventions., Methods: At 4 to 6 weeks after hospital discharge, 146 patients were evaluated for congestion by 5 criteria (orthopnea, jugular venous distention, edema, weight gain, and new increase in baseline diuretics). Heart failure management included inpatient therapy tailored to relieve congestion, followed by adjustments to maintain fluid balance during the next 4 weeks., Results: Freedom from congestion was demonstrated at 4 to 6 weeks in 80 (54%) patients, who had 87% subsequent 2-year survival compared with 67% in 40 patients with 1 or 2 criteria of congestion and 41% in 26 patients with 3 to 5 criteria. The Cox proportional hazards model identified left ventricular dimension, pulmonary wedge pressure on therapy, and freedom from congestion as independent predictors of survival. Persistence of orthopnea itself predicted 38% 2-year survival (without urgent transplantation) versus 77% in 113 without orthopnea. Serum sodium was lower and blood urea nitrogen and heart rate higher when orthopnea persisted., Conclusions: The ability to maintain freedom from congestion identifies a population with good survival despite previous class IV symptoms. At 4 to 6 weeks, patients with persistent congestion may be considered for high-risk intervention.

Background: Controversy surrounds the use of resistance exercise in patients with heart failure because of concerns that increases in rate-pressure product and systemic vascular resistance might lead to increased afterload and decreased cardiac output., Methods: Following pharmacologic left ventricular unloading therapy using a pulmonary artery catheter, 34 patients with advanced heart failure performed isotonic weightlifting exercise at 50%, 65%, and 80% of the calculated one repetition maximum. Measurements were made of hemodynamics, ST segment, rate-pressure product, serum norepinephrine, rating of perceived exertion, and dysrhythmias following each exercise set., Results: Repeated analysis of variance showed significant increases in systolic blood pressure (p = 0.0005), diastolic blood pressure (p = 0.01), rate-pressure product (p = 0.005); serum norepinephrine (p = 0.004), and rating of perceived exertion (p = 0.0005). However, systemic vascular resistance and cardiac output did not change significantly (p>0.05). Pulmonary capillary wedge pressures, the incidence of dysrhythmias, and ST segments did not significantly differ from baseline. No patients experienced angina or dyspnea during the study., Conclusions: Isotonic exercise using hand-held weights was well tolerated hemodynamically and clinically, and no patients experienced adverse outcomes during exercise.

Treatment of human artery wall cells with apolipoprotein A-I (apoA-I), but not apoA-II, with an apoA-I peptide mimetic, or with high density lipoprotein (HDL), or paraoxonase, rendered the cells unable to oxidize low density lipoprotein (LDL). Human aortic wall cells were found to contain 12-lipoxygenase (12-LO) protein. Transfection of the cells with antisense to 12-LO (but not sense) eliminated the 12-LO protein and prevented LDL-induced monocyte chemotactic activity. Addition of 13(S)-hydroperoxyoctadecadienoic acid [13(S)-HPODE] and 15(S)-hydroperoxyeicosatetraenoic acid [15(S)-HPETE] dramatically enhanced the nonenzymatic oxidation of both 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and cholesteryl linoleate. On a molar basis 13(S)-HPODE and 15(S)-HPETE were approximately two orders of magnitude greater in potency than hydrogen peroxide in causing the formation of biologically active oxidized phospholipids (m/z 594, 610, and 828) from PAPC. Purified paraoxonase inhibited the biologic activity of these oxidized phospholipids. HDL from 10 of 10 normolipidemic patients with coronary artery disease, who were neither diabetic nor receiving hypolipidemic medications, failed to inhibit LDL oxidation by artery wall cells and failed to inhibit the biologic activity of oxidized PAPC, whereas HDL from 10 of 10 age- and sex-matched control subjects did. We conclude that a) mildly oxidized LDL is formed in three steps, one of which involves 12-LO and each of which can be inhibited by normal HDL, and b) HDL from at least some coronary artery disease patients with normal blood lipid levels is defective both in its ability to prevent LDL oxidation by artery wall cells and in its ability to inhibit the biologic activity of oxidized PAPC.

We examined 1) contractile properties and the intracellular Ca(2+) concentration ([Ca(2+)](i)) transient in cardiac myocytes and 2) sarcoplasmic reticulum (SR) Ca(2+) uptake and release function in myocardium from patients with end-stage heart failure caused by ischemic (ICM) vs. idiopathic dilated cardiomyopathy (DCM). The amplitude of cell motion was decreased 43 +/- 6% in ICM and 68 +/- 7% in DCM compared with that in normal organ donors (DN). Time to peak of shortening was increased 43 +/- 15% in DCM, but not in ICM. Prolongation of the relaxation time was more predominant in ICM. In DCM the systolic [Ca(2+)](i) was decreased 27 +/- 9% and diastolic [Ca(2+)](i) was increased 36 +/- 11%. In ICM the diastolic [Ca(2+)](i) was increased 59 +/- 12% but the systolic [Ca(2+)](i) was unchanged. A significant decrease of the ATP-dependent SR Ca(2+) uptake rate associated with the reduction of the SR Ca(2+)-ATPase protein level was found in ICM. In contrast, the significant decrease in SR Ca(2+) release rate was distinct in DCM. The large amount of Ca(2+) retained in the SR associated with a significant decrease in the maximum reaction velocity and increase in the Michaelis-Menten constant in the caffeine concentration-response curve suggests a fundamental abnormality in the SR Ca(2+) release channel gating property in DCM. We conclude that potentially important differences exist in the intracellular Ca(2+) homeostasis and excitation-contraction coupling in ICM vs. DCM. The SR Ca(2+) release dysfunction may play an important pathogenetic role in the abnormal Ca(2+) homeostasis in DCM, and the SR Ca(2+) uptake dysfunction may be responsible for the contractile dysfunction in ICM.

Background: The BVS 5000i external pulsatile assist device is used to support patients with reversible cardiogenic shock. Its low cost and potential for insertion without cardiopulmonary bypass make it an attractive option., Methods: Nineteen status I patients failing inotropic support were treated with the BVS 5000i with the intention of short-term bridge to transplant. Fourteen patients received left ventricular support whereas 5 received biventricular support. Cardiopulmonary bypass was used in less than 50% of patients., Results: Median support time was 7 days. The 2 myocarditis patients were weaned from support. Twelve patients were transplanted and there were 5 deaths on support. Overall 14 of 19 were transplanted or weaned. One-year survival was 79%. Median hospital stay was 31 days., Conclusions: The BVS 5000i can be used for short-term mechanical assist toward transplantation in selected patients for whom a donor can be expected soon. The device may provide a cost-effective, short-term strategy to optimize end-organ function before orthotopic heart transplant, particularly for patients who are predictably not ideal to be discharged with implantable left ventricular assist device treatment.

The most important advance in heart failure during the past decade has been the recognition that medications inhibiting neurohormonal activation relieve symptoms, reduce hospitalizations, and prolong survival in patients with heart failure from left ventricular systolic dysfunction. Recent trials with angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, aldosterone antagonists, and beta blockers have provided valuable information regarding the uses, dosing, and extent of therapeutic benefits of neurohormonal inhibition.

Objective: We evaluated interscan variation in coronary artery calcium scores in a large screening population as determined by electron beam CT., Materials and Methods: One thousand patients (average age, 53 years; age range, 18-85 years) who were asymptomatic for coronary artery disease underwent two consecutive scans of the heart on an electron beam CT scanner. Scans were performed with ECG gating, breath-hold, 3-mm collimation, and 100-msec exposure. Two contiguous pixels with density values greater than 130 H were used as the minimum criterion for a calcific lesion. The calcium score was determined on a vessel-by-vessel basis for both scans of each patient. Interscan variation in calcium and vessels involved with calcification was evaluated on the basis of age, sex, and average calcium score., Results: The percentage of difference between calcium scores in scans was 28.4% and 43.0% for women and men, respectively. For the individual epicardial arteries (left main, left anterior descending, circumflex, and right coronary), the percentage of difference for calcium scores was 20.2-24.2% for women and 30.5-44.9% for men. A difference between the two scans in at least one vessel of the total coronary arteries identified with calcium was noted in 31% of patients., Conclusion: Interscan variability in calcium scores may be important in the determination of risk stratification. Subjects with a nonzero calcium score may benefit from undergoing two scans at the time of initial imaging.

The extent to which abnormal endothelium-dependent vasodilator mechanisms contribute to abnormal resting vasoconstriction and blunted reflex vasodilation seen in heart failure is unknown. The purpose of this study was to test the hypothesis that the resting and reflex abnormalities in vascular tone that characterize heart failure are mediated by abnormal endothelium-mediated mechanisms. Thirteen advanced heart-failure patients (New York Heart Association III-IV) and 13 age-matched normal controls were studied. Saline, acetylcholine (20 microg/min), or L-arginine (10 mg/min) was infused into the brachial artery, and forearm blood flow was measured by venous plethysmography at rest and during mental stress. At rest, acetylcholine decreased forearm vascular resistance in normal subjects, but this response was blunted in heart failure. During mental stress with intra-arterial acetylcholine or L-arginine, the decrease in forearm vascular resistance was not greater than during saline control in heart failure [saline control vs. acetylcholine (7 +/- 3 vs. 6 +/- 3, P = NS) or vs. L-arginine (9 +/- 2 units, P = NS)]. The increase in forearm blood flow was not greater than during saline control in heart failure [saline control vs. acetylcholine (1. 2 +/- 0.3 vs. 1.3 +/- 0.3, P = NS), or vs. L-arginine (1.2 +/- 0.2 ml x min(-1) x 100 ml(-1), P = NS)]. Furthermore, during mental stress with nitroprusside, the decrease in forearm vascular resistance was not greater than during saline control [saline control vs. nitroprusside (7 +/- 3 vs. 5 +/- 4 ml x min(-1) x 100 g(-1), P = NS)], and the increase in forearm blood flow was not greater than during saline control [saline control vs. nitroprusside (1.2 +/- 0.3 vs. 1.3 +/- 0.5 ml x min(-1) x 100 g(-1), P = NS)]. Because the endothelial-independent agent nitroprusside was unable to restore resting and reflex vasodilation to normal in heart failure, we conclude that impaired endothelium-mediated vasodilation with acetylholine-nitric oxide cannot be the principal cause of the attenuated resting- or reflex-mediated vasodilation in heart failure.

1. The consecutive pre- and post-1994 eras have demonstrated improved survival for all age groups. This is linked to improved preservation methods, surgical technique and immunosuppression agents. 2. The use of marginal donor hearts for Status I and alternate elderly patients has followed the model of matching donor and recipient risk without affecting patient outcome and minimized the use of implantable assist devices. 3. A donor history of systemic gram-negative infection, hypertension, or traumatic intracranial bleeds was an important marker for risk. Younger age and shorter ischemia time could compensate for other hazards. 4. Heart transplantation in carefully selected elderly recipients yielded clinical results similar to those of younger patients with less rejection. 5. An adult alternate recipient list proved useful to prevent diversion of standard donors away from younger recipients. 6. Retransplantation for TCAD is acceptable but much less satisfactory for acute graft failure. 7. Trends show an increase in the use of implantable devices; refinement in technology for mechanical assist and replacement is forthcoming.

Enzymes associated with circulating HDL include lecithin: cholesterol acyl transferase, phospholipid transfer protein, cholesterol ester transfer protein, paraoxonase 1 and platelet activating factor acetylhydrolase. Together with lipoprotein lipase and hepatic lipase these enzymes produce important lipoprotein remodeling and modulate their structure and function and therefore their role in artery wall metabolism.

Paraoxonase (PON1) hydrolyses organophosphate insecticides and nerve gases and is responsible for determining the selective toxicity of these compounds in mammals. Human PON1 has two genetic polymorphisms giving rise to amino-acid substitutions at positions 55 and 192. The 192 polymorphism is the major determinant of the PON1 activity polymorphism towards organophosphates. However, the 55 polymorphism also modulates activity. Ex vivo, the PON1 polymorphisms are important in determining the capacity of HDL to protect LDL against oxidative modification in vitro and this may explain the relationship between the PON1 alleles and coronary heart disease in case-control studies. In recent case-control studies serum PON1 concentration and activity were also found to be decreased in coronary heart disease (CHD) independent of the PON1 polymorphism, and in diabetes serum PON1 specific activity decrease is also independent of the PON1 genetic polymorphism. HDL from transgenic mice lacking PON1 fails to protect LDL against oxidative modification. Thus PON1 may be a determinant of resistance to the development of atherosclerosis by protecting lipoproteins against oxidative modification, perhaps by hydrolysing phospholipid and cholesteryl-ester hydroperoxides.

Background: Evidence is accumulating that specific "triggers," such as intense psychological stress, may precipitate myocardial infarction and sudden death. Patients with advanced heart failure have increased resting sympathoexcitation, which has been directly related to increased mortality. The impact of triggers on sympathetic nerve activity and regional blood flow in heart failure has not been examined in patients with heart failure., Methods and Results: Twenty-seven patients with heart failure (NYHA functional class III or IV) and 26 age-matched normal control subjects were studied. Muscle sympathetic nerve activity, heart rate, mean arterial pressure, forearm blood flow, and renal blood flow were measured during mental stress testing with mental arithmetic and Stroop color word test. Patients with heart failure had elevated levels of resting muscle sympathetic nerve activity and heart rate. Mental stress significantly increased muscle sympathetic nerve activity and heart rate in both patients with heart failure and control subjects, although the magnitude of increases tended to be blunted in patients with heart failure. Nevertheless, absolute levels of sympathetic activity in patients with heart failure remained significantly higher than levels in control subjects during mental stress. The decrease in renal blood flow in patients with heart failure was similar to that of control subjects, despite greater resting renal vasoconstriction. The increase in forearm blood flow during mental stress testing in patients with heart failure was blunted compared with that of control subjects., Conclusions: Patients with heart failure do not have augmented muscle sympathetic nerve activity responses to mental stress, despite elevated resting levels of sympathetic activity, but they do have markedly higher absolute levels of sympathetic nerve activity during mental stress as well as at rest.

Objectives: To assess the impact of a comprehensive heart failure management program, functional status, hospital readmission rate and estimated hospital costs were determined and compared for the 6 months before and the 6 months after referral., Background: The course of advanced heart failure is characterized by progressive clinical deterioration reflected in frequent hospital admissions, which comprise the major financial cost., Methods: Over a 3-year period, 214 patients were accepted for heart transplantation and discharged after evaluation, which included adjustments in medical therapy and intensive patient education. Patients were in New York Heart Association functional class III or IV (94 and 120 patients, respectively), with a mean left ventricular ejection fraction of 0.21, peak oxygen consumption of 11 ml/kg per min and a total of 429 hospital admissions in the previous 6 months (average 2.0 per patient). Changes in the medical regimen included a 98% increase in angiotensin-converting enzyme inhibitor dose and a flexible diuretic regimen after 4.2-liter net diuresis, with counseling also regarding diet and progressive exercise., Results: During the 6 months after referral, there were only 63 hospital readmissions (85% reduction), with 0.29/patient (p < 0.0001). Functional status improved as assessed by functional class (p < 0.0001) and peak oxygen consumption (15.2 vs. 11.0 ml/kg per min, p < 0.001). The same results were seen after excluding the 35 patients without full 6-month follow-up (9 deaths, 14 urgent transplant procedures during hospital readmission, 12 elective transplant procedures from home); 34 hospital admissions occurred after referral, compared with 344 before referral. Even when adding in the initial hospital admission after referral for these 179 patients, there was a 35% decrease in total hospital admissions in the 6-month period. The estimated savings in hospital readmission costs after subtracting the initial hospital costs for management was $9,800 per patient., Conclusions: Comprehensive heart failure management led to improved functional status and an 85% decrease in the hospital admission rate for transplant candidates discharged after evaluation. The potential to reduce both symptoms and costs suggests that referral to a heart failure program may be appropriate not only for potential heart transplantation, but also for medical management of persistent functional class III and IV heart failure.

Background: During therapy to relieve congestion in advanced heart failure, cardiac filling pressures can frequently be reduced to near-normal levels with improved cardiac output. It is not known whether the early hemodynamic improvement and drug response can be maintained long term., Methods and Results: After referral for cardiac transplantation with initially severe hemodynamic decompensation, 25 patients survived without transplantation to undergo hemodynamic reassessment after 8+/-6 months of treatment tailored to early hemodynamic response. Initial changes included net diuresis, increased ACE inhibitor doses, and frequent addition of nitrates. After 8 months of therapy, early reductions were sustained for pulmonary wedge pressure (24+/-9 to 15+/-5 mm Hg early; 12+/-6 mm Hg late) and systemic vascular resistance (1651+/-369 to 1207+/-281 dynes x s(-1) x cm(-5) early; 1003+/-193 dynes x s(-1) x cm(-5) late). Acute response to doses persisted at reevaluation. Sustained reduction in filling pressures was accompanied by a progressive increase in stroke volume (42+/-10 to 56+/-13 mL early; 79+/-20 mL late), improved functional class, and freedom from resting symptoms. Study design did not control for amiodarone, which was initiated for arrhythmias in 12 patients and associated with greater improvement in cardiac index (1.8 to 3.2 L min(-1) x m(-2) late on amiodarone versus 2.0 to 2.6 L x min(-1) x m(-2), P<.05)., Conclusions: During chronic therapy tailored to early hemodynamic response in advanced heart failure, acute vasodilator response persists, and near-normal filling pressures can be maintained in patients who survive without transplantation. Stroke volumes at low filling pressures increase further over time. Chronic hemodynamic improvement was accompanied by symptomatic improvement, but the contributions of the monitored hemodynamic approach, increased vasodilator doses, and comprehensive outpatient management have not yet been established.

The effect of psychologic variables (situational emotional state and psychiatric diagnosis) and physiologic variables (plasma norepinephrine, decreased cardiac exercise capacity, and elevated pulmonary capillary wedge pressure) on natural killer cell activity was evaluated in 19 patients with advanced heart failure of ischemic or idiopathic origin. Only peak exercise capacity was independently predictive of natural killer cell deficiency.

We have examined the effects of mildly oxidized LDL and atherosclerosis on the levels of two proteins associated with HDL; apolipoprotein J (apoJ), and paraoxonase (PON). On an atherogenic diet, PON activity decreased by 52%, and apoJ levels increased 2.8-fold in fatty streak susceptible mice, C57BL/6J (BL/6), but not in fatty streak resistant mice, C3H/HeJ (C3H). Plasma PON activity was also significantly decreased, and apoJ levels were markedly increased in apolipoprotein E knockout mice on the chow diet, resulting in a 9.2-fold increase in the apoJ/PON ratio as compared to controls. Furthermore, a dramatic increase in the apoJ/PON ratio (over 100-fold) was observed in LDL receptor knockout mice when they were fed a 0.15%-cholesterol-enriched diet. Injection of mildly oxidized LDL (but not native LDL) into BL/6 mice (but not in C3H mice) on a chow diet resulted in a 59% decrease in PON activity (P < 0.01) and a 3.6-fold increase in apoJ levels (P < 0.01). When an acute phase reaction was induced in rabbits, or the rabbits were placed on an atherogenic diet, hepatic mRNA for apoJ was increased by 2.7-fold and 2.8-fold, respectively. Treatment of HepG2 cells in culture with mildly oxidized LDL (but not native LDL) resulted in reduced mRNA levels for PON (3.0-fold decrease) and increased mRNA levels for apoJ (2.0-fold increase). In normolipidemic patients with angiographically documented coronary artery disease who did not have diabetes and were not on lipid-lowering medication (n = 14), the total cholesterol/HDL cholesterol ratio was 3.1+/-0.9 as compared to 2.9+/-0.4 in the controls (n = 19). This difference was not statistically significant. In contrast, the apoJ/PON ratio was 3.0+/-0.4 in the patients compared to 0.72+/-0.2 in the controls (P < 0.009). In a subset of these normolipidemic patients (n = 5), the PON activity was low (48+/-6.6 versus 98+/-17 U/ml for controls; P < 0.009), despite similar normal HDL levels, and the HDL from these patients failed to protect against LDL oxidation in co-cultures of human artery wall cells. We conclude that: (a) mildly oxidized LDL can induce an increased apoJ/PON ratio, and (b) the apoJ/PON ratio may prove to be a better predictor of atherosclerosis than the total cholesterol/HDL cholesterol ratio.