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Supplemental Digital Content is available in the text., Background: In the WRAP-IT trial (Worldwide Randomized Antibiotic Envelope Infection Prevention), adjunctive use of an absorbable antibacterial envelope resulted in a 40% reduction of major cardiac implantable electronic device infection without increased risk of complication in 6983 patients undergoing cardiac implantable electronic device revision, replacement, upgrade, or initial cardiac resynchronization therapy defibrillator implant. There is limited information on the cost-effectiveness of this strategy. As a prespecified objective, we evaluated antibacterial envelope cost-effectiveness compared with standard-of-care infection prevention strategies in the US healthcare system. Methods: A decision tree model was used to compare costs and outcomes of antibacterial envelope (TYRX) use adjunctive to standard-of-care infection prevention versus standard-of-care alone over a lifelong time horizon. The analysis was performed from an integrated payer-provider network perspective. Infection rates, antibacterial envelope effectiveness, infection treatment costs and patterns, infection-related mortality, and utility estimates were obtained from the WRAP-IT trial. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality-adjusted life years were discounted at 3%. An upper willingness-to-pay threshold of $150 000 per quality-adjusted life year was used to determine cost-effectiveness, in alignment with the American College of Cardiology/American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. Results: The base case incremental cost-effectiveness ratio of the antibacterial envelope compared with standard-of-care was $112 603/quality-adjusted life year. The incremental cost-effectiveness ratio remained lower than the willingness-to-pay threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. Conclusions: The absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of cardiac implantable electronic device infection. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02277990.

Background Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis. Objectives The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry. Methods Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189). Results U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild-type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival. Conclusions In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745)

Importance: Heart failure (HF) is the leading cause of hospitalization among patients over the age of 65 in the United States and developed countries, posing a significant economic burden to the health care systems. More than half of the patients with HF will be readmitted to the hospital within 6 months from discharge, leading not only to increased health care related expenses but also functional decline, iatrogenic injuries and in-hospital infections. With the increasing prevalence of HF, there is a substantial need for innovative delivery care models that can provide hospital level of care at a patient’s home. Observations: Home hospitalization was originally used to safely manage chronically ill patients with general medical (stroke, chronic obstructive pulmonary disease, deep vein thrombosis, community acquired pneumonia) and surgical conditions and was associated with improved patient satisfaction and improvement in activity of daily living status. This had no clear effect on readmission or cost. When hospital at home care model was applied to HF patients it demonstrated increased time to readmission, reduced index costs and improved health related quality of life, with no significant differences in adverse events. Eligible patients should be selected based on multiple factors taking into consideration applicable limitations and comorbidities. Conclusions and Relevance: Providing in-hospital level care to the patient’s house presents a reliable alternative, yielding multiple benefits both for the patient, as well as the health care system. Formulating a well-defined model is necessary before wide implementation.

Hyperkalemia is defined as serum potassium concentrations elevated above the upper limit of normal (> 5.0 mEq/L). It has become more common in cardiovascular practice due to the growing population of patients with chronic kidney disease and the broad application of drugs that modulate renal elimination of potassium by reducing production of angiotensin II (angiotensin-converting enzyme inhibitors, direct renin inhibitors, β-adrenergic receptor antagonists), blocking angiotensin II receptors (angiotensin receptor blockers), or antagonizing the action of aldosterone on mineralocorticoid receptors (mineralocorticoid receptor antagonists). The risk of hyperkalemia is a major limiting factor for the use of these disease-modifying drugs in both acute and chronic cardiorenal syndromes. Thus, agents to control the plasma concentration of potassium are needed in the multidrug treatment of cardiorenal disease, including chronic kidney disease, heart failure, and acute kidney injury. Novel oral therapies in development for both acute and extended use in the management of hyperkalemia include patiromer sorbitex calcium and sodium zirconium cyclosilicate. Important biochemical differences between these compounds result in unique product profiles and electrolyte outcomes in patients treated for hyperkalemia. This review highlights the major mechanisms of hyperkalemia and key results from randomized trials in a range of clinical scenarios in patients with, and at risk for, hyperkalemia.

Few proven treatment options exist for patients with heart failure with preserved ejection fraction (HFpEF). One of the few interventions shown to improve functional capacity in patients with HFpEF is exercise training, likely predominantly driven by peripheral mechanisms such as improved

The objective was to evaluate 6 commonly used heart failure (HF) prognostic models in an elderly, fatal HF population. Predictive models have been established to quantify risk among HF patients. The validation of these models has not been adequately studied, especially in an elderly cohort. Applying a single-center, retrospective study of serially admitted HF patients who died while in the hospital or within 30 days of discharge, the authors evaluated 6 prognostic models: the Seattle Heart Failure Model (SHFM), Heywood's model, Classification and Regression Tree (CART) Analysis, the Heart Failure Survival Score (HFSS), Heart Failure Risk Scoring System, and Pocock's score. Eighty patients were included (mean age, 82.7 ± 8.2 years). Twenty-three patients (28.75%) died in the hospital. The remainder died within 30 days of discharge. The models' predictions varied considerably from one another and underestimated the patients' actual mortality. This study demonstrates that these models underestimate the mortality risk in an elderly cohort at or approaching the end of life. Moreover, the predictions made by each model vary greatly from one another. Many of the models used were not intended for calculation during hospitalization. Development of improved models for the range of patients with HF syndromes is needed.

Depression is prevalent in patients with heart failure, and the two conditions share underlying physiologic mechanisms. The prevalence of depression increases sharply with the severity of heart failure symptoms, an important consideration when confronting patients with worsening heart failure. Depression leads to poorer outcomes in patients with heart failure, including increased risk of poor functional status, hospital readmission, and death. Although beta-blockers are often implicated in the development and exacerbation of depression, evidence for this association is lacking, so withholding beta-blocker therapy is not recommended for patients with heart failure and depression. Evidence on whether therapy for depression also improves cardiac outcomes in heart failure patients is inconclusive, and further research on this question is needed. Nevertheless, early identification of depression in heart failure patients is imperative, as it can facilitate intervention attempts.

Background— More than 400 patients with end-stage heart failure underwent left ventricular assist device (LVAD) implantation of LVAD as destination therapy (DT) after the US Food and Drug Administration approval of DT in 2002. Because most of these patients had surgeries at hospitals that were newly accredited, we sought to examine the impact of LVAD center volume on the outcomes of DT. Methods and Results— From July 1998 through December 2005, a total of 377 patients underwent implantation of HeartMate I LVAD as DT at 68 centers in the United States. Using data from the Thoratec DT Registry, we examined the association between LVAD center volume at the time of surgery and 1-year survival with DT. Of the studied 377 DT recipients, 53% underwent device implantation at centers that performed ≤4 DT implants at the time of surgery. Center experience with DT seemed to significantly correlate with the 1-year survival (47.8% versus 67.4% in recipients of ≤4th DT versus >9th DT implant; P =0.009). However, the DT center volume was not an independent predictor of 1-year survival with DT when adjusted for the preoperative DT Risk Score, suggesting that other factors, such as improved candidate selection, may have accounted for the institutional learning curve. Conclusions— The institutional experience with DT may have a significant impact on outcomes of this therapy. Better selection of candidates, systemic approach to surgical and postoperative care, as well as the long-term medical management most likely all contribute to these improvements.

Background— Prior investigations suggest that superimposing continuous flow on aortic flow (continuous aortic flow augmentation) produces vasodilation, cardiac unloading, and improved cardiac performance. Methods and Results— We compared percutaneous continuous aortic flow augmentation (flow ≤1.5 L/min for up to 96 hours) plus medical therapy versus medical therapy alone by randomizing 168 patients (device, n=109; control, n=59) hospitalized with heart failure, reduced left ventricular ejection fraction and cardiac index, elevated pulmonary capillary wedge pressure, and renal impairment or substantial diuretic requirement despite intravenous inotropes/vasodilators. The primary composite efficacy end point included pulmonary capillary wedge pressure (72 to 96 hours) and days alive out of hospital off mechanical support over 35 days. The population’s illness severity posed unique challenges. Enrollment ended early because of an inability to demonstrate significant benefit on the primary composite end point (device, 17.4%; control, 13.6%; P =0.45) in the face of excess device group bleeding. Pulmonary capillary wedge pressure decreased from 28.8±6.3 mm Hg (mean±SD) to 24.9±7.2 mm Hg (average, 72 to 96 hours) and 28.9±7.1 to 26.5±6.2 mm Hg in the device and control groups, respectively (between-group P =0.074). Cardiac index progressively increased in the device (2.05±0.53 to 2.44±0.52 L · min −1 · m −2 ) but not the control (between-group P P =0.10). Through 65 days, device-to-control hazard ratios were as follows: all-cause mortality, 1.05 (95% confidence interval, 0.60 to 1.82); death or heart failure hospitalization, 0.87 (95% confidence interval, 0.57 to 1.33); and heart failure hospitalization, 0.66 (95% confidence interval, 0.38 to 1.13). Major bleeds occurred in 16.5% in the device (7.3% treatment related) and 5.1% in the control ( P =0.05) group. Conclusions— Continuous aortic flow augmentation improved cardiac performance, improving cardiac index and pulmonary capillary wedge pressure, but statistical significance for the primary efficacy end point was not attained. Hemodynamic and clinical observations provide direction toward additional studies to further investigate the clinical effects of this treatment.

Background— Patients with American College of Cardiology/American Heart Association stage C/D heart failure experience substantial morbidity and mortality, but available interventions beyond standard medical and device therapies are limited. Nesiritide relieves dyspnea and reduces pulmonary congestion, but its risk profile is uncertain. Pilot data suggested a potential benefit of nesiritide given as serial outpatient infusions. Methods and Results— The Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial was a randomized, double-blind, placebo-controlled trial of outpatient serial nesiritide infusions for patients with American College of Cardiology/American Heart Association stage C/D heart failure. Patients with 2 recent heart failure hospitalizations, ejection fraction P =0.79). There were no statistically significant differences between groups in any of the secondary end points, including the number of cardiovascular or renal hospitalizations, the number of days alive and out of the hospital, change in Kansas City Cardiomyopathy Questionnaire score, or cardiovascular death. Adverse events were similar between groups; nesiritide was associated with more hypotension but less predefined worsening renal function. Conclusions— Serial outpatient nesiritide infusions do not provide a demonstrable clinical benefit over intensive outpatient management of patients with advanced American College of Cardiology/American Heart Association stage C/D heart failure.

Endothelial dysfunction has been recognized as a pathophysiologic mechanism in the progression of heart failure (HF). However, little attention has been given to the ability of dietary approaches to improve endothelial function. This study examined the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on endothelial function, exercise capacity, and quality of life in patients with chronic symptomatic (stage C) HF. Forty-eight patients were randomized to follow the DASH diet (n = 24) or the general HF dietary recommendations (n = 24). Endothelial function was assessed by measuring large and small arterial elasticity (LAE and SAE) at rest. Exercise capacity (measured with the 6-minute walk test) and quality of life (measured with the Minnesota Living with Heart Failure Questionnaire) at baseline and 3 months were also evaluated. Patients were older adults with an average HF duration of 5 years. LAE at 1 month improved significantly in the DASH diet group (P < 0.01). Overall LAE and SAE scores at 3 months also improved; however, the net changes were not statistically significant. The DASH group had better exercise capacity (292 m vs 197 m; P = 0.018) and quality of life scores (21 vs 39; P = 0.006) over time, while sodium intake levels at 1, 2, and 3 months were comparable between the groups. Adhering to the DASH diet improved arterial compliance initially and improved exercise capacity and quality of life scores at 3 months. The DASH diet may be an important adjunctive therapy for patients with symptomatic HF.

The uterus and the heart share a common structure and may remodel in a similar fashion, albeit temporally distinct. The authors investigated the prevalence of systemic hypertension in women with uterine leiomyomata (fibroids) and compared the prevalence in women undergoing hysterectomy for other reasons as well as in age‐matched women from the National Health and Nutrition Examination Survey III (NHANES III). A total of 584 women, 205 with leiomyomata in 1999 (group A) and 379 who underwent hysterectomy for a variety of reasons in 2000 (group B) at Advocate Christ Medical Center were included. Presence of leiomyomata was confirmed by pathology. Hypertension was defined as blood pressure ≥140/90 mm Hg or history of hypertension with or without medication use. The prevalence of hypertension in group A and B patients with leiomyomata compared with NHANES III overall was 48.6% vs. 24% (p

The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or full revision is needed. This process gives priority to areas where major changes in text, particularly recommendations

The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial demonstrated increased 1- and 2-year survival and improved quality of life for end-stage heart failure patients implanted with the HeartMate VE Left Ventricular Assist Device (LVAD) (Thoratec Corporation, Pleasanton, CA) compared with optimal medical management. This is the first report of Destination Therapy (DT) experience since REMATCH and incorporates improvements with the HeartMate XVE LVAD and patient management. Forty-two patients with end-stage heart failure at higher volume institutions were supported with the LVAD over a duration of 26.7 patient years (mean 232 days). Compared with REMATCH, DT patients had a 40% lower rate of death (0.49 vs. 0.84 deaths per patient year). Kaplan-Meier estimates of survival in the DT and REMATCH LVAD groups at 30 days were 90% and 81%, and at 1 year were 61% and 52%. The death rate due to sepsis was 8.3 times lower in DT patients (risk ratio, 0.12; 95% confidence interval, 0.02-0.90). DT patients were 2.1 times less likely to experience an adverse event (risk ratio, 0.47; 95% confidence interval, 0.35-0.63). These results demonstrate continued improvement with outcomes in long-term DT with LVADs. Given that these DT patients were similar to those in the REMATCH trial, the improved outcomes likely reflect improvements in the HeartMate XVE LVAD and experience with patient management.

Among the most exciting developments in the field of heart failure in recent times has been the rediscovery of the natriuretic peptide system and its pleuripotent effects on cardiac structure and function. This is particularly true of its natriuretic and hemodynamic effects. There has been an explosion of the knowledge base seeking to understand the wide range of homeostatic, regulatory, and counter-regulatory functions in which the natriuretic peptide system participates. Additional interest has been stimulated by advances in technology such as point-of-care and core laboratory BNP assays and the use of the recombinant B-type natriuretic peptide nesiritide as a treatment option. Despite this recent interest, the available literature lacks a comprehensive expert review of the current science and roles of natriuretic peptides for diagnostic, prognostic, screening, treatment monitoring, and therapeutic purposes. More importantly, a summary updating and guiding the clinician on most of these advances was lacking. An expert Consensus Panel with basic, methodological, and clinical expertise was convened to summarize current knowledge in these areas and the findings and consensus statements are contained herein.

Heart failure (HF) management has seen enormous advances in the past two decades, including publication of HF management guidelines targeted at further reduction of morbidity and mortality. Nonetheless, the morbidity of HF has steadily increased and now represents one of the largest health care expenditures in this country. Because hospitalization for HF is most likely for patients with more advanced HF, they share a disproportionate burden of the hospitalization costs and will require treatment regimens beyond the current guidelines, if this burden is to be alleviated. In June 2004, a group of investigators who helped establish the natriuretic peptide treatment paradigm, met to discuss the potential role of nesiritide as an outpatient treatment option for patients with symptomatic HF who were at high risk for repeated admissions, a syndrome now described as "chronic decompensated HF." This report presents their considerations on the contribution of natriuretic peptide physiology to the amelioration of progressive left ventricular dysfunction, the therapeutic use of B-type natriuretic peptide, and its potential application to the outpatient management of acute and chronic decompensated HF. The use of outpatient IV nesiritide was considered a promising treatment option for symptomatic chronic decompensated HF patients that merits further investigation. Such an approach, once validated, should be integrated into an evidence-based HF disease management program.

Heart failure is a chronic disease marked by variable acute exacerbations. Once hospitalized the decompensated patient may have signs and symptoms only partially reversed, medical therapy only partially optimized and deranged physiology only partially restored. Therefore, the post-acute care period is one of unique vulnerability and merits efforts of careful and comprehensive assessment of patients at risk of recurrent decompensation and rehospitalization. Natriuretic peptide (NP) assessment which has the ability to monitor dynamic changes in a patient's physiology, may play an important role as part of a post-acute care algorithm focused on early detection and prevention of further decompensation and rehospitalization.

ObjectivesThis study was designed to determine whether nesiritide, administered for acute decompensated congestive heart failure (CHF), affects healthcare costs by hospital length of stay (LOS), readmissions and short-term mortality, compared to dobutamine.BackgroundDobutamine is a commonly used inotropic treatment for CHF. Although dobutamine may have favorable hemodynamic and symptomatic effects, its use may be associated with side effects such as tachycardia, cardiac arrhythmias and myocardial ischemia. Nesiritide (B-type natriuretic peptide) is a new intravenous (IV) drug that produces hemodynamic and symptomatic improvement through balanced vasodilatory effects, neurohormonal suppression and enhanced natriuresis and diuresis.MethodsFrom an open-label randomized study of nesiritide versus standard care (SC) in patients with CHF requiring hospitalization, we compared short-term outcome data from patients given nesiritide (0.015 or 0.03 μg/kg per min) with a subgroup of SC patients given dobutamine. A total of 261 patients are included in this analysis.ResultsCompared to dobutamine, both nesiritide doses were administered for a shorter total duration (p < 0.001), and the total duration of all IV vasoactive therapy (including study drug) was also shorter (p ≤ 0.012). Although there was no difference in LOS, there was a trend toward decreased readmissions in the two nesiritide groups (8% and 11%, respectively, vs. 20% in the dobutamine group). Six-month mortality was lower in the nesiritide groups.ConclusionsTreatment of decompensated CHF with nesiritide may lead to lower healthcare costs and reduced mortality compared to treatment with dobutamine.

n his teachings, Hippocrates inferred the importance of dynamic circulatory factors in mediating illness. The search for these “intense and strong juices” has led to the discovery of biomarkers in cardiovascular medicine. To-day, in patients with known or suspected cardiovascular disease, biomarkers are reported to be associated with the risk, presence, and severity of disease. Additionally, they have prognostic implications and serve as guides for po-tential therapeutic interventions. The cardiac natriuretic peptides, atrial (ANP) and B-type (BNP), are secreted in response to various signals, including myocardial stretch and volume overload. Both ANP and BNP are produced with their inactive amino-terminal fragments NT-proANP and NT-proBNP.

Heart failure (HF) is a major public health problem in the United States. Nearly 5 million patients in this country have HF, and nearly 500,000 patients are diagnosed with HF for the first time each year. The disorder is the underlying reason for 12 to 15 million office visits and 6.5 million hospital days each year (1). During the last 10 years, the annual number of hospitalizations has increased from approximately 550,000 to nearly 900,000 for HF as a primary diagnosis and from 1.7 to 2.6 million for HF as a primary or secondary diagnosis (2). Nearly 300,000 patients die of HF as a primary or contributory cause each year, and the number of deaths has increased steadily despite advances in treatment. HFs primarily a disease of the elderly (3). Approximately 6% to 10% of people older than 65 years have HF (4), and approximately 80% of patients hospitalized with HF are more than 65 years old (2). HF is the most common Medicare diagnosis-related group, and more Medicare dollars are spent for the diagnosis and treatment of HF than for any other diagnosis (5). The total inpatient and outpatient costs for HF in 1991 were approximately $38.1 billion, which was approximately 5.4% of the healthcare budget that year (1). In the United States, approximately $500 million annually is spent on drugs for the treatment of HF. The American College of Cardiology (ACC) and the American Heart Association (AHA) first published guidelines for the evaluation and management of HF in 1995 (6). Since that time, a great deal of progress has been made in the development of both pharmacological and nonpharmacological approaches to treatment for this common, costly, disabling, and generally fatal disorder. For this reason, the 2 organizations believed that the time was right to reassess and update these …

Background . Recent scientific and clinical data suggest that chronic mechanical ventricular unloading may lead to myocardial recovery. Evaluating and monitoring patients for myocardial recovery and the optimal methods of weaning the left ventricular assist device are not well defined. Methods . Six patients with advanced heart failure and severe mitral regurgitation have undergone successful bridge to recovery using a Thoratec left ventricular assist device. Data that details their monitoring for myocardial recovery and weaning from the left ventricular assist device were prospectively collected. Results . Clinical data collected during the recovery phase included chest roentgenogram, echocardiography, plasma norepinephrine, tumor necrosis factor-α, bioimpedance, and cardiopulmonary exercise testing (peak oxygen consumption). Normalization of these variables with a 10% increase in the peak oxygen consumption was obtained before weaning. The Thoratec device rate and percent systole were manipulated to allow gradual reloading of the ventricle. The weaning process occurred for more than 5 to 10 days to allow time for observation of the ventricle and its response to the increasing workload. Conclusions . Select patients with advanced congestive heart failure and severe mitral insufficiency can benefit from mechanical device support. We describe our technique of monitoring for myocardial recovery using clinical variables. Our technique of weaning allows for gradual reloading of the ventricle and a longer period of observation before device removal. Additional research is needed to determine which variables will accurately predict long-term myocardial recovery and the optimal weaning method.

OBJECTIVES The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 μg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo. BACKGROUND Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied. METHODS This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction ≤35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion. RESULTS One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion. CONCLUSIONS The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.

The failing heart is not just an enlarged version of the normal heart. Louis N. Katz ([1][1]) In 1981, de Bold et al. ([2][2]) described a potent diuretic and natriuretic factor derived from the atrial extracts of rats. Subsequent research has led to the characterization of a family of peptides

A brief panel discussion was held on March 23, 2005, in New York City following a live symposium for primary care physicians discussing the roles of B-type natriuretic peptide in a variety of cardiovascular diseases. The participants were Dr. Marc A. Silver, Advocate Christ Medical Center, Oak Lawn, IL; Dr. Clive Rosendorff, Mount Sinai School of Medicine, New York, NY and VA Medical Center, Bronx, NY; Dr. Robert Berkowitz, Hackensack University Medical Center, Hackensack, NJ; and Dr. W. Franklin Peacock IV, The Cleveland Clinic Department of Emergency Medicine, Cleveland, OH. Dr. Silver moderated the discussion. The panel gathered to review some of the questions that emerged from the symposium and the questions raised by the attendees. These are of interest and importance to all interested in heart failure and B-type natriuretic peptide.

There is little evidence of beta-blocker treatment benefit in patients with heart failure and reduced left ventricular ejection fraction (HFREF) and atrial fibrillation (AF). We investigated the effects of bucindolol in HFREF patients with AF enrolled in the Beta-blocker Evaluation of Survival Trial (BEST).A post-hoc analysis of patients in BEST with and without AF was performed to estimate the effect of bucindolol on mortality and hospitalization. Patients were also evaluated for treatment effects on heart rate and the influence of beta1-adrenergic receptor position 389 (β(1)389) arginine (Arg) vs. glycine (Gly) genotypes. In the 303/2708 patients in AF, patients receiving bucindolol were more likely to achieve a resting heart rate ≤ 80 b.p.m. at 3 months (P0.005) in the absence of treatment-limiting bradycardia. In AF patients and sinus rhythm (SR) patients who achieved a resting heart rate ≤ 80 b.p.m., there were beneficial treatment effects on cardiovascular mortality/cardiovascular hospitalization [hazard ratio (HR) 0.61, P = 0.025, and 0.79, P = 0.002]. Without achieving a resting heart rate ≤ 80 b.p.m., there were no treatment effects on events in either group. β(1)389-Arg/Arg AF patients had nominally significant reductions in all-cause mortality/HF hospitalization and cardiovascular mortality/hospitalization with bucindolol (HR 0.23, P = 0.037 and 0.28, P = 0.039), whereas Gly carriers did not. There was no evidence of diminished heart rate response in β(1)389-Arg homozygotes.In HFREF patients with AF, bucindolol was associated with reductions in composite HF endpoints in those who achieved a resting heart rate ≤ 80 b.p.m. and nominally in those with the β(1)389-Arg homozygous genotype.

Right ventricular (RV) infarction is a well-recognized complication of some acute inferior myocardial infarctions. Recently, there have been numerous case reports of RV infarctions complicated by severe refractory hypoxemia secondary to right-to-left shunting through a patent foramen ovale. An additional case missed by transthoracic echocardiography and cardiac catheterization is reported and the English literature on the subject is reviewed.

Inflammatory heart diseases are characterized as a focal, diffuse, or sparse inflammatory process of the myocardium and its adjacent structures. In adults, inflammatory heart disease often progresses to symptomatic dilated cardiomyopathy and heart failure. We report the case of a 42-year-old woman who was diagnosed with right-sided heart failure, presumably secondary to inflammatory heart disease, after the acute onset of exercise intolerance. Nine years after the initial diagnosis, she developed clinical symptoms of calcified constrictive pericarditis. Pericardiectomy was performed and the patient resumed normal functional capacity. In conclusion, close monitoring and careful evaluation of patients with presumed inflammatory heart disease is warranted because of the potential for late-occurring chronic constrictive sequelae.

Familial dilated cardiomyopathy (F-DCM) describes a clinically and genetically heterogeneous group of diseases, mostly inherited as autosomal dominant traits, having idiopathic left ventricular dilatation and dysfunction as a common phenotype. The age of onset, rate of progression, disease complications, as well as overall prognosis and outcome vary both amongst and within families. Clinical traits, both cardiac and extracardiac, may recur in association with the DCM phenotype. The former include conduction defects, structural abnormalities such as left ventricular noncompaction, of right ventricular involvement, and recurrence of atrial or ventricular arrhythmias; the latter commonly affect the musculoskeletal (myopathies/dystrophies, both clinically overt and subclinical), ocular, auditory, nervous, and integument systems. These traits may help guide genetic testing. In parallel to the clinical heterogeneity, F-DCM also shows genetic heterogeneity: more than 40 genes have been causally linked to F-DCM, with mutations recurring more commonly in a few known genes, and less frequently in rare, less commonly known genes. Based on the known prevalence of mutations in disease genes, more than 50% of F-DCM cases can be regarded as still genetically orphan, implying that further disease genes have to be discovered. Family screening and genetic testing are now established as the gold standard for diagnosis, care, and prevention in F-DCM. Diagnostic tests are performed using Sanger-based sequencing. Furthermore, new biotechnology tools, based on next-generation sequencing, are now being implemented in the research setting and will dramatically modify the future of the nosology of F-DCM.

Mariell Jessup, MD, FACC, FAHA, Chair [*][1] William T. Abraham, MD, FACC, FAHA[†][2] Donald E. Casey, MD, MPH, MBA[‡][3] Arthur M. Feldman, MD, PhD, FACC, FAHA[§][4] Gary S. Francis, MD, FACC, FAHA[§][4] Theodore G. Ganiats, MD[∥][5] Marvin A. Konstam, MD, FACC[¶][6] Donna M.

2009;53;1343-1382; originally published online Mar 26, 2009; J. Am. Coll. Cardiol. Rahko, Marc A. Silver, Lynne Warner Stevenson, and Clyde W. Yancy Francis, Theodore G. Ganiats, Marvin A. Konstam, Donna M. Mancini, Peter S. Mariell Jessup, William T. Abraham, Donald E. Casey, Arthur M. Feldman, Gary S. Heart and Lung Transplantation Developed in Collaboration With the International Society for Guidelines Cardiology Foundation/American Heart Association Task Force on Practice Management of Heart Failure in Adults: A Report of the American College of 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and This information is current as of August 30, 2010 http://content.onlinejacc.org/cgi/content/full/53/15/1343 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Neurologic events during left ventricular assist device (LVAD) support are associated with significant morbidity and death. To evaluate this problem, we analyzed neurocognitive function and the frequency and incidence of neurologic events in 21 consecutive patients who were undergoing long-term support with the HeartMate® XVE LVAD (Thoratec Corporation; Pleasanton, Calif). The mean duration of LVAD support was 531 days (range, 55–1,309 d); the cumulative support time was 11,188 days (30.7 yr). No patients received anticoagulant therapy, and most received aspirin. None experienced strokes or transient ischemic attacks. Twenty patients were discharged from the hospital; 2 were later readmitted because of transient changes in neurologic status (metabolic encephalopathy) that ultimately resolved. Neurologic function, as measured by the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Score (MRS), was abnormal before LVAD implantation but normal 6 and 12 months after (mean NIHSS, 23.6 before vs 0 after; mean MRS, 0.68 before vs 0.18 after). Neurocognitive function, as evaluated by the Boston Naming Test, Trail Making Test part B, and Block Design Test, also improved during LVAD support. Together, these findings indicate that few neurologic events occur during long-term HeartMate XVE LVAD support in the absence of anticoagulation therapy. They also suggest that modifications made to the HeartMate LVAD since the REMATCH trial have resulted in fewer complications, and that better patient selection and supportive care have improved outcomes.

The aim of this work was to review and provide a summary of published literature on the clinical impact of thermal therapy (ie, warm water immersion, traditional sauna bathing, and dry infrared sauna) in patients with heart failure. Medline and Embase database literature searches were conducted, and studies that included measurement of heart failure-related clinical parameters were reviewed. Thermal therapy was found to have a positive impact on key heart failure-related parameters across multiple studies. Significant improvements were noted across a wide scope of heart failure-related parameters in the areas of (1) endothelial function, (2) hemodynamics, (3) cardiac geometry, (4) neurohormonal markers, and (5) quality of life. Of special note, thermal therapy also conveyed a strong antiarrhythmic effect in heart failure patients. The clinical evidence highlights repeatable and compelling data showing that thermal therapy may provide an important and viable adjunct in the treatment of heart failure.

The organization of work in the construction industry often has been presented as the exemplar of “craft administration” wherein managerial positions are of relatively low significance. Occupational control of employment and work structure in this context presumably is manifest through the craft union. On the other hand, research on other industries has shown the managerial position in the firm to be a source of extrinsic and intrinsic reward. This results from the manager's pivotal position in the bureaucratized labor process. This paper seeks to reconcile these perspectives. Data from a survey of 246 unionized construction workers and 14 local union officers from nine building trades are used to assess the impact of the managerial position and union involvement on work autonomy (self-direction and freedom from supervision) and employment security (unemployment and trade agreement infringements). In general, the results indicate that managerial affiliations to employers' firms are associated with greater autonomy and more employment security. Union involvement has contradictory consequences for individual tradespeople.

Introduction: Bucindolol is a nonselective beta-adrenergic blocker with potent sympatholytic properties. The Beta-blocker Evaluation of Survival Trial (BEST) reported that the administration of bucindolol resulted in a nonsignificant decrease in total mortality (HR = 0.89 (0.78, 1.02), unadjusted p=0.10) in patients with advanced, NYHA Class III-IV heart failure (HF). Recent observations from that trial also reported that the amino acid arginine (Arg/Arg) or glycine (any Gly) in position 389 of the beta-1 receptor plays a significant role on the clinical response to bucindolol. The impact of bucindolol on cardiovascular mortality and morbidity (cardiovascular hospitalizations) has been incompletely investigated, because hospitalizations had been evaluated from case report forms (CRFs) only, and never adjudicated by the endpoints committee (EPC). Methods: The BEST data base consists of 2708 patients with a mean follow-up of 2.0 years. Cardiovascular (CV) mortality and hospitalizations have now been evaluated by EPC, which further subclassified total hospitalizations into cardiovascular (CV) and those due to worsening heart failure (HF). The impacts of Arg or Gly encoded at amino acid position 389 on endpoints were further investigated in the 1040 patient substudy. Results: Time to event results for adjudicated CV endpoints are presented below. Conclusions: Chronic administration of bucindolol results in a significant reduction in cardiovascular hospitalizations and mortality. Effects on either are strikingly beta-1 389 Arg/Gly specific, with the higher functioning, Arg/Arg version of the receptor associated with large treatment effects and Gly carriers exhibiting little or no evidence of efficacy. Genetic targeting of the β 1 -ΑR 389 polymorphism may improve the clinical responses to bucindolol for CV mortality and morbidity.

Background— The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial first demonstrated that implantation of left ventricular assist devices (LVADs) as destination therapy (DT) can provide survival superior to any known medical treatment in patients with end-stage heart failure who are ineligible for transplantation. In the present study, we describe outcomes of DT in the post-REMATCH era in the United States. Methods and Results— The present study included 280 patients who underwent HeartMate XVE LVAD implantation between November 2001 and December 2005. A preoperative risk score for in-hospital mortality after LVAD implantation was established in 222 patients with complete data. All patients were followed up until death or December 2006. The 1-year survival after LVAD implantation was 56%. The in-hospital mortality after LVAD surgery was 27%. The main causes of death included sepsis, right heart failure, and multiorgan failure. The most important determinants of in-hospital mortality were poor nutrition, hematological abnormalities, markers of end-organ or right ventricular dysfunction, and lack of inotropic support. Stratification of DT candidates into low (n=65), medium (n=111), high (n=28), and very high (n=18) risk on the basis of the risk score calculated from these predictors corresponded with 1-year survival rates of 81%, 62%, 28%, and 11%, respectively. Conclusions— Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Patients with advanced heart failure who are referred for DT before major complications of heart failure develop have the best chance of achieving an excellent 1-year survival with LVAD therapy.

Heart failure remains a health care epidemic, and additional complementary therapies beyond pharmaceuticals and devices are needed. Using heat therapy or topical thermal therapy is an ancient therapeutic approach for the treatment of heart failure. Currently, there are several studies reporting salutary effects of heat therapy in patients with heart failure using either dry heat or water immersion therapies. The authors describe an additional theoretic construct using topically applied heat pads that might be a simple and economic approach to affect heat therapy as an adjunct for many patients. Hopefully future studies will continue to explore heat therapy as adjunctive care for heart failure patients.

The Prospective Evaluation of Enhanced External Counterpulsation in Congestive Heart Failure (PEECH) trial demonstrated that enhanced external counterpulsation (EECP) therapy increased exercise duration and improved functional status and quality of life without affecting peak oxygen consumption. The authors present data from a prespecified subgroup of elderly patients (65 years or older) enrolled in the PEECH trial. The 2 co-primary end points were the percentage of subjects with a >60-second increase in exercise duration and the percentage of subjects with a >1.25-mL/kg/min increase in peak volume of oxygen consumption. At 6-month follow-up, the exercise responder rate was significantly higher in EECP patients compared with controls (P=.008). Further, in contrast to the overall PEECH study, the EECP group demonstrated a significantly higher responder rate for peak oxygen consumption (P=.017). The authors conclude that an older subgroup of PEECH subjects confirms the beneficial effect of EECP in patients with chronic, stable, mild-to-moderate heart failure.

Endothelial dysfunction is an important pathophysiologic mechanism in the progression of heart failure. The objective of the present study was to determine the effects of acute and chronic oral magnesium supplementation on endothelial function in patients with symptomatic heart failure. Twenty-two symptomatic chronic heart failure patients were randomized to receive 800 mg oral magnesium oxide daily or placebo for 3 months. Data collected included large and small arterial elasticity/compliance, hemodynamic parameters, exercise capacity, and quality-of-life score at baseline, 1 week, and 3 months. Patients who received magnesium had improved small arterial compliance at 3 months from baseline compared with placebo. This study suggests that chronic supplementation with oral magnesium is well tolerated and could improve endothelial function in symptomatic heart failure patients.

Nonadherence to medical treatment among heart failure patients is high and results in frequent exacerbations and premature death. This treatment-only pilot study examined whether a year-long group-based self-management intervention is feasible and improves self-management skills in patients with mild-to-moderate heart failure (ejection fraction < or =40% and New York Heart Association functional class I, II, or III). A total of 31 of 100 recruited patients (31%) agreed to participate. Twenty-six (84%) completed the year-long self-management program. Compared with baseline, the intervention was associated with an increase in overall self-efficacy in practicing self-management skills (p