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OBJECTIVES The study sought to investigate the association between soluble growth stimulation expressed gene 2 (sST2) Level and adverse outcomes in acute heart failure (HF).BACKGROUND Several studies have demonstrated the prognostic utility of sST2 Levels in HF.METHODS sST2 levels were measured in sequential baseline and follow-up (48 to 72 h and 30 days) plasma samples from 858 acute HF subjects enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial biomarker substudy and were related to in-hospital and post-discharge clinical outcomes.RESULTS Higher sST2 levels were associated with increased death risk at 180 days (baseline hazard ratio [FIR]: 2.21; follow-up HR: 2.64; both p 60 ng/ml) sST2 Levels at follow-up had higher 180-day death rates than those with lower follow-up sST2 Levels (adjusted HR: 2.91, p = 0.004). Neither baseline nor follow-up sST2 levels were associated with dyspnea improvement. Changes in sST2 from baseline were less in the nesiritide versus placebo group at follow-up, but were similar at 30 days.CONCLUSIONS Elevated levels of sST2 were associated with an increased risk of adverse clinical events in acute HF, but prognostic value of baseline sST2 diminished after adjusting for clinical covariates and aminoterminal pro-B-type natriuretic peptide. In those with elevated baseline sST2 Levels, persistently elevated sST2 levels at follow-up were associated with increased mortality risk. In addition, nesiritide did not demonstrate an incremental impact on sST2 Levels over standard therapy. (C) 2016 by the American College of Cardiology Foundation.

Background The authors sought to estimate incremental economic impact of atrial fibrillation (AF) and the timing of its onset in myocardial infarction (MI) patients. Hypothesis Concurrent AF and its timing are associated with higher costs in MI patients. Methods This retrospective cohort study included incident MI patients from Olmsted County, Minnesota, treated between November 1, 2002, and December 31, 2010. We compared inflation-adjusted standardized costs accumulated between incident MI and end of follow-up among 3 groups by AF status and timing: no AF, new-onset AF (within 30 days after index MI), and prior AF. Multivariate adjustment of median costs accounted for right-censoring in costs. Results The final study cohort had 1389 patients, with 989 in no AF, 163 in new-onset AF, and 237 in prior AF categories. Median follow-up times were 3.98, 3.23, and 2.55 years, respectively. Mean age at index was 67 years, with significantly younger patients in the no AF group (64 years vs 76 and 77 years, respectively; P < 0.001). New-onset and prior AF patients had more comorbid conditions (hypertension, heart failure, and chronic obstructive pulmonary disease). After accounting for differences in baseline characteristics, we found adjusted median (95% confidence interval) costs of $73 000 ($69 000-$76 000) for no AF; $85 000 ($81 000-$89 000) for new-onset AF; and $97 000 ($94 000-$100 000) for prior AF. Inpatient costs composed the largest share of total median costs (no AF, 82%; new-onset AF, 84%; prior AF, 83%). Conclusions Atrial fibrillation frequently coexists with MI and imposes incremental costs, mainly attributable to inpatient care. Timing of AF matters, as prior AF was found to be associated with higher costs than new-onset AF.

Aims: \ud \ud Thrombin is a critical element of crosstalk between pathways contributing to worsening of established heart failure (HF). The aim of this study is to explore the efficacy and safety of rivaroxaban 2.5 mg bid compared with placebo (with standard care) after an exacerbation of HF in patients with reduced ejection fraction (HF-rEF) and documented coronary artery disease.\ud Methods: \ud \ud This is an international prospective, multicentre, randomized, double-blind, placebo-controlled, event-driven study of approximately 5000 patients for a targeted 984 events. Patients must have a recent symptomatic exacerbation of HF, increased plasma concentrations of natriuretic peptides (B-type natriuretic peptide ≥200 pg/mL or N-terminal pro–B-type natriuretic peptide ≥800 pg/mL), with left ventricular ejection fraction ≤40% and coronary artery disease. Patients requiring anticoagulation for atrial fibrillation or other conditions will be excluded. After an index event (overnight hospitalization, emergency department or observation unit admission, or unscheduled outpatient parenteral treatment for worsening HF), patients will be randomized 1:1 to rivaroxaban or placebo (with standard of care). The primary efficacy outcome event is a composite of all-cause mortality, myocardial infarction or stroke. The principal safety outcome events are the composite of fatal bleeding or bleeding into a critical space with potential permanent disability, bleeding events requiring hospitalization and major bleeding events according to International Society on Thrombosis and Haemostasis bleeding criteria.\ud Conclusion: \ud \ud COMMANDER HF is the first prospective study of a target-specific oral antithrombotic agent in HF. It will provide important information regarding rivaroxaban use following an HF event in an HF-rEF patient population with coronary artery disease.

Preview Inactivity adds to the decline of patients with congestive heart failure (CHF). However, in prescribing exercise in these patients, three principles must be understood: ejection fraction does not predict functional capacity, exercise can bring marked peripheral improvement without changing ejection fraction or hemodynamics, and benefits accrue slowly. The authors review the mechanisms of exercise intolerance in CHF and the factors to keep in mind when designing an exercise program.

Background Postoperative atrial fibrillation (POAF) is a well-recognized complication of cardiac surgery; however, its management remains a challenge, and the implementation and outcomes of various strategies in clinical practice remain unclear. Hypothesis We hypothesize that treatment for POAF is variable, and that it is associated with particular morbidity and mortality following cardiac surgery. Methods We compared patient characteristics, operative procedures, postoperative management, and outcomes between patients with and without POAF following coronary artery bypass grafting (CABG) in the Society of Thoracic Surgeons multicenter Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) registry (2004–2005). Results Of 2390 patients who underwent CABG, 676 (28%) had POAF. Compared with patients without POAF, those with POAF were older (median age 74 vs 71 years, P < 0.0001) and more likely to have hypertension (86% vs 83%, P = 0.04) and impaired renal function (median estimated glomerular filtration rate 56.9 vs 58.6 mL/min/1.73 m2, P = 0.0001). A majority of patients with POAF were treated with amiodarone (77%) and β-blockers (68%); few (9.9%) underwent cardioversion. Patients with POAF were more likely to experience complications (57% vs 41%, P < 0.0001), including acute limb ischemia (1.0% vs 0.4%, P = 0.03), stroke (4.0% vs 1.9%, P = 0.002), and reoperation (13% vs 7.9%, P < 0.0001). Length of stay (median 8 days vs 6 days, P < 0.0001), in-hospital mortality (6.8% vs 3.7%, P = 0.001), and 30-day mortality (7.8 vs 3.9, P < 0.0001) were all worse for patients with POAF. In adjusted analyses, POAF remained associated with increased length of stay following surgery (adjusted ratio of the mean: 1.27, 95% confidence interval: 1.2-1.34, P < 0.0001). Conclusions Postoperative AF is common following CABG, and such patients continue to have higher rates of postoperative complications. Postoperative AF is significantly associated with increased length of stay following surgery.

Background Although atrial fibrillation (AF) occurs frequently in patients hospitalized with acute coronary syndrome (ACS), strategies for prevention of thromboembolic complications are poorly characterized. Hypothesis We sought to examine exposure to warfarin and P2Y12 inhibitors and clinical outcomes among patients with AF and ACS. Methods Patients age >65 years hospitalized with a primary diagnosis of ACS and a secondary diagnosis of AF between 2007 and 2010 were identified in the Medicare 5% sample. Medication exposure was ascertained during a 90-day period following the index discharge using Medicare drug claims. Among patients who were alive and not readmitted during the ascertainment period, we examined the cumulative incidence of all-cause mortality and all-cause readmission by medication exposure at 1 year. Results A total of 2509 Medicare beneficiaries met the inclusion criteria. Among the 1633 patients (65%) who were alive and not readmitted during the 90-day ascertainment period, 24.0% received warfarin, 38.9% received P2Y12 inhibitors, 10.2% received combination therapy, and 26.8% received neither therapy. Readmission rates were high in all groups at 1 year (warfarin, 47.5%; P2Y12 inhibitors, 46.6%; combination therapy, 38.0%; and neither therapy, 39.3%), and the overall 1-year mortality rate was 12.5%. Conclusions Among Medicare beneficiaries with AF and ACS, combination therapy with warfarin and P2Y12 inhibitor was uncommon during the 90-day ascertainment period, and more than one-quarter of patients had no claims for warfarin or P2Y12 inhibitors. Rates of all-cause readmission and mortality within 1 year of hospitalization for ACS were high.

Background Effective warfarin thromboprophylaxis requires maintaining anticoagulation within the recommended international normalized ratio (INR) range. INR testing rates and associations between testing and outcomes are not well understood. Hypothesis INR testing rates after hospitalization for acute decompensated heart failure are suboptimal, and testing is associated with lower risks of mortality and adverse clinical events. Methods We conducted a retrospective cohort study of patients who were long-term warfarin users and were hospitalized for heart failure, had a medical history of atrial fibrillation or valvular heart disease, and were enrolled in fee-for-service Medicare. INR testing was defined as ≥1 outpatient INR test within 45 days after discharge. Using Cox proportional hazards models, we examined associations between testing and all-cause mortality, all-cause readmission, and adverse clinical events at 1 year. Results Among 8558 patients, 7722 (90.2%) were tested. After 1 year, tested patients had lower all-cause mortality (23.5% vs 32.6%; P

Background Timing of initial treatment for acute decompensated heart failure (ADHF) varies across hospitals and its impact on outcomes remains poorly defined. We examined the association between time to first intravenous (IV) heart failure (HF) therapy and patient outcomes. Methods Using the ADHERE-EM linked to Medicare claims data, we identified patients ≥65 years old who were hospitalized for ADHF and received IV HF therapy during index admission. Cox proportional hazard model was used to assess the association of time to treatment with a composite of 30-day all-cause mortality or re-admission. Generalized linear mixed models were used to examine the association of time to treatment with in-hospital all-cause mortality, index hospitalization length of stay, and total days alive and out-of-hospital at 30 days. Results Of 6,971 patients, the median time to first IV HF therapy was 2.3-hours (interquartile range 1.1, 4.4). The cumulative incidence of 30-day all-cause mortality or readmission was 27.4%. After adjusting for covariates, time to treatment was not associated with increased risk of composite 30-day all-cause mortality or re-admission (HR 1.00; 95% CI 1.00-1.00; P = .221). However, every hour delay in treatment was associated with a modest increased risk of in-hospital mortality (adjusted OR 1.01; 95% CI 1.00-1.02; P = .001) and an approximately 1.4-hour increase in index admission length of stay ( P Conclusion Among older patients presenting with ADHF, delay in initiating IV HF therapy was associated with modestly higher risk for in-hospital mortality and longer length of stay, but was not associated with 30-day outcomes.

Objectives: Randomized acute coronary syndrome (ACS) trials testing various antithrombotic (AT) regimens have largely excluded patients with coexisting conditions and indications for anticoagulation (AC). The purpose of this study is to examine the 2-year clinical outcomes of patients with ACS with indication for AC due to venous thromboembolism (VTE) during hospitalization for the ACS event or a prior or new diagnosis of atrial fibrillation (AF) with a CHADS2 (Congestive heart failure; Hypertension; Age; Diabetes; previous ischemic Stroke) score ⩾2. Methods: ACS patients with AC indication from 2004 to 2009 were identified ( n = 619). A Cox proportional hazards model was used to examine the primary efficacy outcome of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) or stroke. The primary explanatory variable was at-discharge antithrombotic strategy [single antiplatelet ± AC, dual antiplatelet (DAP) ± AC or AC only; referent DAP + AC]. Results: A total of 261 (42.2%) patients had a MACE event. AT strategy was not a significant factor for MACE (all p > 0.09). The factors associated with MACE were high mortality risk score [hazard ratio (HR)=1.87, 95% confidence interval (CI): 1.39– 2.52; p < 0.001), prior MI (HR = 1.44, 95% CI: 1.03–2.01; p= 0.033) and presentation of ST elevation MI (HR = 2.70, 95% CI: 1.61–4.51; p < 0.001) or non-ST elevation MI (HR = 1.70, 95% CI: 1.15–2.49; p < 0.001) compared with angina. Conclusions: In this real world observational study, the at-discharge AT strategy was not significantly associated with the 2-year risk of MACE. These findings do not negate the need for randomized trials to generate evidence-based approaches to management of this important population.

Background: Warfarin use and associated outcomes in patients with heart failure and atrial fibrillation and a cardiovascular implantable electronic device have not been described previously. Hypothesis: We hypothesized that warfarin is underused and is associated with lower risks of mortality, thromboembolic events, and myocardial infarction. Methods: Using data from a clinical registry linked with Medicare claims, we examined warfarin use at discharge and 30-day and 1-year Kaplan-Meier estimates of all-cause mortality and cumulative incidence rates of mortality, thromboembolic events, myocardial infarction, and bleeding events in patients 65 years or older, with a history of atrial fibrillation and a cardiovascular implantable electronic device admitted with heart failure between 2001 and 2006, who were naive to anticoagulation therapy at admission. We compared outcomes between patients who were or were not prescribed warfarin at discharge and tested associations between treatment and outcomes. Results: Of 2586 eligible patients in 252 hospitals, 2049 were discharged without a prescription for warfarin. At 1 year, the group discharged without warfarin had a higher mortality rate after discharge (37.4% vs 28.8%; P < 0.001) but similar rates of thromboembolism, myocardial infarction, and bleeding events. After adjustment, treatment with warfarin was associated with lower risk of all-cause death 1 year after discharge (hazard ratio: 0.76, 95% confidence interval: 0.63–0.92). Conclusions: Among older patients with heart failure and atrial fibrillation and a cardiovascular implantable electronic device, 4 of 5 were discharged without a prescription for warfarin. Warfarin nonuse was associated with a higher risk of death 1 year after discharge. Clin. Cardiol. 2011 DOI: 10.1002/clc.22064 Damon M. Seils, MA, Duke University, assisted with manuscript preparation. Mr. Seils did not receive compensation for his assistance apart from his employment at the institution where the study was conducted. This study was supported by a research agreement between Duke University and Janssen Pharmaceuticals. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Background Patients hospitalized with heart failure (HF) have elevated B-type natriuretic peptide (BNP) levels and increased risk for thromboembolic events. Associations between BNP level and thromboembolic events in patients with HF without atrial fibrillation (AF) are not well studied. Methods We linked data from the ADHERE registry for 2003 through 2006 with Medicare claims to identify patients ≥65 years who were hospitalized with HF, did not have AF, and did not receive warfarin at discharge. We estimated rates of all-cause mortality, thromboembolic events, myocardial infarction (MI), and stroke using Kaplan-Meier methods and the cumulative incidence function. We used Cox models to assess associations between log BNP level and each outcome after adjustment for potential confounders. Results The study population included 11,679 patients from 146 sites. Patients in the highest quartile of BNP level were older and more often male and African American. They had higher rates of coronary artery disease, renal insufficiency, and peripheral vascular disease and lower rates of diabetes mellitus and chronic obstructive pulmonary disease. After multivariable adjustment, each 30% increase in BNP level was associated with increased risks of death (hazard ratio 1.07, 95% CI 1.05-1.08) and MI (1.07, 1.04-1.10) but not thromboembolism or stroke. Conclusion Higher BNP level upon admission with HF among older patients without AF was associated with increased risks of MI and mortality; however, higher BNP level was not associated with subsequent thromboembolism or stroke.

Concerns regarding risk versus benefit, that is, the possible impact of surgical-site bleeding on post-operative joint infections, have contributed to a continuing debate over recommendations for venous thromboembolism (VTE) prophylaxis in post-surgical orthopedic patients undergoing total hip and knee arthroplasty (THA/TKA).A comprehensive literature search using MEDLINE covering the period 2004-2009 was conducted, and published studies that focused on THA and TKA and contained data applicable to thromboprophylaxis, post-surgical wound infection and bleeding are reviewed in this paper. The search strategy included various combinations of terms related to lower limb joint arthroplasty, anticoagulant drugs, post-operative bleeding and prosthetic joint infection (wound infection). Methodological constraints included failure in some studies to define an infection, variations among the studies in the definitions of bleeding and differences in the follow-up time for capturing infection and bleeding events. Despite this, this comprehensive review identified observational, 'real-world' data that can contribute in important ways to the existing evidence base.There are insufficient data to either confirm or refute the hypothesis that post-operative bleeding is a mediating pathophysiologic factor linking pharmacologic VTE prophylaxis to an increased risk for wound infection. Studies specifically designed to examine the interrelationship between thromboprophylaxis, bleeding and wound infections following THA/TKA are warranted.

The aim of this study was to evaluate the mode of death and hospitalizations in advanced heart failure (HF) patients with renal dysfunction and to examine the rate of concordance between events reported by the clinical events committee and site investigators (using case report forms) in the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Little is known about the cause of death and hospitalization in patients with advanced HF. FUSION II was a randomized, double-blind, placebo-controlled trial evaluating outpatient nesiritide infusions versus placebo, with 911 patients with advanced HF (New York Heart Association class III or IV) and renal dysfunction enrolled. There were 151 deaths and 1,041 hospitalizations at 24 weeks. The clinical events committee classified events as cardiac, renal, cardiorenal, other or noncardiovascular, or unknown. Kappa statistics and McNemar tests were used to assess agreement (overall and by individual modes of death and hospitalization indications). In conclusion, the most common cause of death or hospitalization was cardiac related, with 70% of deaths and 60% of hospitalizations due to cardiac causes. There was 74% agreement (26% disagreement) on cardiac cause of death (κ = 0.40, McNemar p = 0.001) and 75% agreement (25% disagreement) between the investigators and the clinical events committee on cardiac classification for hospitalization (κ = 0.49, McNemar p

Background: Many individuals with atrial fibrillation (AF) do not receive recommended anticoagulant prophylaxis for stroke prevention. The study investigators attempted to assess whether the presence of relative contraindications (RCIs) to anticoagulation with warfarin might contribute to this, and to assess the risks and benefits of prophylaxis in patients with RCIs. Methods: Study investigators identified patients with established non-valvular AF and flutter in a claims database. Operationally defined RCIs included, in order of clinical severity: (1) prior intracranial hemorrhage; (2) gastrointestinal bleeding or esophageal varices; (3) neurological disorder; and (4) dizziness. Nonfatal events were attributed to warfarin if patients had an appropriate claim in the previous month. Results: A total of 67,082 AF patients were eligible for analysis, including 50,485 (75.3%) in the prevalent cohort. Warfarin exposure during the study period was 68% in the prevalent cohort. At baseline, 50.5% of prevalent cohort patients had one or more RCIs. Patients with RCI had higher prevalence of stroke risk factors (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and prior stroke or transient ischemic attack) compared to those without RCI. Patients with RCIs often received warfarin and had lower rates of ischemic stroke than those who did not. Conclusions: These results suggest that RCIs do not account for underutilization of anticoagulant prophylaxis in AF patients. Further, the benefit/risk aspects of anticoagulation for stroke prophylaxis may be favorable for many patients with RCIs.

Our understanding of the natriuretic peptide system continues to evolve rapidly. B-type natriuretic peptide (BNP), originally thought to be a simple volume-regulating hormone that is produced in response to cardiac stretch, has been shown to also play important roles in modulating bronchodilation, endothelial function, and cardiac remodeling. Recent data demonstrate that elevated levels of BNP in patients with heart failure do not represent a simple ratcheting up of normal production in response to increased stimulus. Instead, we now know that chronic stimulation of BNP synthesis induces a reversion to fetal gene expression, resulting in production of high molecular weight forms of BNP that are functionally deficient. Standard point-of-care BNP assays are immunoassays that will detect any molecule containing the target epitopes. Consequently, these assays cannot distinguish between defective, high molecular weight forms of BNP and normal, physiologically active BNP. In 2 separate evaluations, mass spectroscopy detected little, if any, normal BNP in patients with heart failure, despite the appearance of high circulating levels of immunoreactive BNP (iBNP) using commercial assays. Therefore, these commercial assays should be considered to be only an indication of myocardial stress. They do not measure physiologic BNP activity. This accounts for the "BNP paradox," namely, that administration of exogenous recombinant human BNP (rhBNP, nesiritide) has substantial clinical and hemodynamic impact in the presence of high levels of circulating iBNP using commercial assays. In addition to its short-term hemodynamic impact, rhBNP may have other important effects in this setting, and further investigation is warranted.

Background We assessed the effect of increases in serum creatinine on mortality in nesiritide-treated versus control subjects with acute decompensated heart failure (ADHF). Hypothesis Mortality effect of nesiritide-related increases in serum creatinine differs from that of standard therapies. Methods Scios Inc., granted unrestricted access to data from all 5 randomized, controlled nesiritide infusion trials completed to date in patients hospitalized with ADHF. We used 2 different definitions of acute serum creatinine increase: >0.3 mg/dL and > 0.5mg/dL within 30 days of study enrollment and determined 30-day mortality risk for nesiritide-treated versus control subjects utilizing each definition. Results A total of 1,270 subjects participated in the 5 trials. A >0.3 mg/dL increase in serum creatinine was associated with a significant increase in mortality risk in control subjects, (hazard ratio [HR]: 3.47, 95% confidence interval [CI]: 1.49–8.09) but not in nesiritide-treated subjects (HR: 1.65, 95% CI: 0.90–3.05). Results were similar for a >0.5 mg/dL increase (control HR: 5.12, 95% CI: 2.09–12.57 and nesiritide HR: 1.77, 95% CI: 0.90–3.51). In subjects with >0.3 mg/dL and >0.5 mg/dL increases in serum creatinine, respectively, the 30-day mortality odds ratios for nesiritide relative to control were 0.73 (95% CI: 0.29–1.93) and 0.52 (95% CI: 0.17–1.63) using a stratified Mantel-Haenszel analysis. Conclusions The impact of increased serum creatinine on mortality was attenuated in nesiritide-treated patients compared to control, suggesting that the mechanism and clinical significance of increases in serum creatinine associated with nesiritide treatment may differ from those associated with standard therapies. Further investigation is warranted. Copyright © 2009 Wiley Periodicals, Inc.

The optimal use of diuretics in decompensated heart failure remains uncertain. We analyzed data from the ADHERE registry to look at the impact of diuretic dosing. 62,866 patients receiving

Objectives We undertook this analysis to determine whether there is a relationship between the time to measurement of immunoreactive B-type natriuretic peptide (iBNP) and early intervention for acutely decompensated heart failure (ADHF) and whether these variables are associated with morbidity and mortality in ADHF patients. Background Although natriuretic peptides (NPs) can aid emergency department (ED) physicians in the diagnosis of ADHF, the relationship between the time to measurement of NP levels and time to treatment is not clear. In addition, the impact of time to treatment on clinical outcomes has not been demonstrated. Methods Patients from ADHERE (Acute Decompensated Heart Failure National Registry) who were admitted to the ED and who received intravenous diuretics were included. Recordings of iBNP levels and the timing of intravenous diuretic therapy were documented. Patients were divided by quartiles of time to treatment and iBNP levels, creating 16 categories. Results In 58,465 ADHF episodes from 209 hospitals, patients with the longest average time to iBNP draw also had the longest time to treatment. Mean ED time increased with increased time-to-treatment quartiles. Rales on initial examination were associated with early recognition of HF and earlier institution of therapy. The later the treatment took place, the fewer patients were asymptomatic at the time of hospital discharge. Within the time-to-treatment quartiles, mortality increased with increasing iBNP. Treatment delay was independently, but modestly, associated with increased in-hospital mortality with a risk-adjusted odds ratio 1.021, 95% confidence interval 1.010 to 1.033, and p Conclusions In the ED setting, delayed measurement of iBNP levels and delay in treatment for ADHF were strongly associated. These delays were linked with modestly increased in-hospital mortality, independent of other prognostic variables. The adverse impact of delay was most notable in patients with greater iBNP levels (Registry for Acute Decompensated Heart Failure Patients; NCT00366639).

Background An improved understanding of the characteristics, treatment, and outcome of patients with “Stage D” heart failure (HF) may improve patient outcomes. We conducted an analysis of the ADHERE LM to enhance this understanding. Methods ADHERE LM is a multicenter registry designed specifically to prospectively collect observational data on chronic Stage D HF. The findings were analyzed and compared to data from ADHERE CM, a multicenter registry designed to prospectively collect data on the entire spectrum of acute decompensated HF. Descriptive statistics and Kaplan-Meier analysis were used to evaluate data from all 1433 patients in ADHERE LM. Results Compared to patients with acute decompensated HF, patients with chronic Stage D HF tended to be younger (69.6 vs 72.8 years), males (65% vs 49%), with hyperlipidemia/dyslipidemia (65% vs 41%), and with coronary artery disease (73% vs 57%). In Stage D patients, use of intravenous diuretics (73%) and vasoactive agents (84%) was common. Kaplan-Meier–estimated 1-year survival was 71.9% (95% CI 69.3%-74.5%) and estimated 1-year freedom from hospitalization or death was 32.9% (95% CI 30.2%-35.6%). Conclusions Patients with Stage D HF are frequently males with dyslipidemia and coronary artery disease. Morbidity and mortality are high. Therapeutic decisions based on studies in HF patients with different characteristics may not be applicable; additional research is needed to determine optimal therapeutic regimens for these patients.

SummaryConflicting evidence exists regarding predictors of and antithrombotic benefit on mortality in hospitalised acutely-ill medical patients. We compared mortality risk within 90 days post-discharge among medically ill patients who did and did not receive antithrombotics. This retrospective claims analysis included patients40 years with nonsurgical hospitalisation2 days between 2005 and 2009 using the HealthCore Integrated Research Database. Antithrombotic use (i.e. anticoagulants and antiplatelets) post-discharge was captured from pharmacy claims. All-cause mortality was determined from Social Security Death Index; cause of death was identified from National Death Index database. Kaplan-Meier survival curves were generated and hazard ratios (HR) for mortality risk were estimated using Cox proportional hazards models. Patients prescribed anticoagulants or antiplatelets post-discharge had lower risk of short-term mortality. For the anticoagulant model, the most significant predictors of mortality were malignant/benign neoplasms (hazard ratio [HR] 1.6, 95 % confidence interval [CI] 1.5–1.7), liver disease (HR 1.6, 95 % CI 1.5–1.7), anticoagulant omission (HR 1.6, 95 % CI 1.4–1.8), gastrointestinal or respiratory tract intubations (HR 1.5, 95 % CI 1.3–1.7), and blood dyscrasias (HR 1.4, 95 % CI 1.4–1.5). For the antiplatelet model, the most significant predictors of mortality were antiplatelet omission (HR 3.7, 95 % CI 3.3–4.1), liver disease (HR 1.6, 95 % CI 1.4–1.7), malignant/benign neoplasms (HR 1.6, 95 % CI 1.5–1.6), gastrointestinal or respiratory tract intubations (HR 1.5, 95 % CI 1.3–1.7), and blood dyscrasias (HR 1.4, 95 % CI 1.4–1.5). These mortality risk factors may guide future studies assessing potential benefits of antithrombotics in specific subsets of patients.

background Vasodilators are considered to be contraindicated in patients with severe aortic stenosis because of concern that they may precipitate life-threatening hypotension. However, vasodilators such as nitroprusside may improve myocardial performance if peripheral vasoconstriction is contributing to afterload. methods We determined the response to intravenous nitroprusside in 25 patients with severe aortic stenosis and left ventricular systolic dysfunction. Patients were included in the study if they had been admitted to the intensive care unit for invasive hemodynamic monitoring of heart failure and if they had a depressed ejection fraction (≤0.35), severe aortic stenosis (aortic-valve area, ≤1 cm 2 ), and a depressed cardiac index (≤2.2 liters per minute per square meter). Patients were excluded if they had hypotension, defined as either the need for intravenous inotropic or pressor agents or a low mean systemic arterial pressure (

B-type natriuretic peptide, or nesiritide, recently gained US Food and Drug Administration approval as the first new parenteral agent approved for heart failure therapy in more than a decade. Nesiritide refers to a peptide identical to endogenous B-type natriuretic peptide, currently manufactured by recombinant DNA technology. Nesiritide has been evaluated in clinical trials involving more than 700 subjects. The drug produces a prompt fall in systemic vascular resistance and pulmonary capillary wedge pressure, associated with rapid clinical improvement in decompensated heart failure. Nesiritide represents an attractive choice for “first-line therapy” of acutely decompensated heart failure patients. In this review, the authors summarize the currently available data regarding the use of nesiritide, and offer recommendations for its use based on our experience with the compound in clinical trials.

Background— Outcomes associated with episodes of hypotension while hospitalized with acute decompensated heart failure are not well understood. Methods and Results— Using data from Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF), we assessed factors associated with in-hospital hypotension and subsequent 30-day outcomes. Patients were classified as having symptomatic or asymptomatic hypotension. Multivariable logistic regression was used to determine factors associated with in-hospital hypotension, and Cox proportional hazards models were used to assess the association between hypotension and 30-day outcomes. We also tested for treatment interaction with nesiritide on 30-day outcomes and the association between in-hospital hypotension and renal function at hospital discharge. Overall, 1555 of 7141 (21.8%) patients had an episode of hypotension, of which 73.1% were asymptomatic and 26.9% were symptomatic. Factors strongly associated with in-hospital hypotension included randomization to nesiritide (odds ratio, 1.98; 95% confidence interval [CI], 1.76–2.23; P P P =0.001) or S3 gallop (odds ratio, 1.21; 95% CI, 1.06–1.40; P =0.006). In-hospital hypotension was associated with increased hazard of 30-day mortality (hazard ratio, 2.03; 95% CI, 1.57–2.61; P P P P =0.874 for death, P =0.908 for death/heart failure hospitalization, P =0.238 death/all-cause hospitalization). Conclusions— Hypotension while hospitalized for acute decompensated heart failure is an independent risk factor for adverse 30-day outcomes, and its occurrence highlights the need for modified treatment strategies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00475852.

Objective. To determine factors associated with single antiplatelet (SAP) or dual antiplatelet (DAP) therapy and anticoagulants (AC) use in hospital and after discharge among patients with acute coronary syndrome (ACS).Methods. We evaluated 5,294 ACS patients in the Intermountain Heart Collaborative Study from 2004 to 2009. Multivariable logistic regressions were used to determine predictors of AC or AP use.Results. In hospital, 99% received an AC, 79% DAP, and 19% SAP; 78% had DAP + AC. Coronary stents were the strongest predictors of DAP use in hospital compared to SAP (P<0.001). After discharge, 77% received DAP, 20% SAP, and 9% AC; 5% had DAP + AC. DAP compared to SAP was less likely for patients on AC (odds ratio [OR] = 0.30,P<0.0001) after discharge. Placement of a stent increased the likelihood of DAP (bare metal: OR = 54.8,P<0.0001; drug eluting: OR = 59.4,P<0.0001). 923 had atrial fibrillation and 337 had a history of venous thromboembolism; these patients had increased use of AC (29% and 40%, resp.).Conclusion. While in-hospital use of AC was nearly universal, postdischarge AC use was rare. Concern for providing the best antithrombotic therapy, while maintaining an acceptable bleeding risk, may explain the selection decisions.

BACKGROUND Chronotropic incompetence is one cause of diminished exercise capacity in heart transplant recipients. If reinnervation occurs, it often is late after transplantation and is not always accompanied by functional improvements in peak heart rate and appropriate tachycardia during exercise. To determine the efficacy of rate-responsive pacing on peak heart rate and exercise capacity, the authors studied eight male heart transplant recipients (age 57 +/- 12 years; 23 +/- 9 months after transplantation) that had either atrial or dual-chambered pacemakers. METHODS All subjects completed two maximal graded exercise tests (GXT) using the Naughton treadmill protocol. During the first GXT, pacemakers were programmed for bradycardia support only and without rate responsiveness (unpaced). After a 14-day regimen of beta blockade with metoprolol to nullify the influence of circulating catecholamines on heart rate, subjects performed the second GXT with pacemakers programmed to respond optimally in the rate-responsive mode (paced). RESULTS Peak heart rate (149 versus 129 bpm), peak oxygen uptake (18.9 versus 15.4 mL/kg/min), treadmill time to exhaustion (14.6 versus 12.4 min), and minute ventilation (76.7 versus 66.2 L/min) were significantly increased (P < or = 0.05) during the paced versus unpaced GXT. CONCLUSIONS The results of this study demonstrate that chronotropic support of the transplanted heart using a rate-responsive pacemaker, with activity-based sensors programmed for maximal sensitivity, improves both peak heart rate and exercise capacity in heart transplant recipients significantly more than circulating catecholamines alone.

OBJECTIVESWe sought to test the hypothesis that plasma volume (PV) expansion in heart transplant recipients (HTRs) is caused by failure to reflexively suppress the renin-angiotensin-aldosterone (RAA) axis.BACKGROUNDExtracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs.METHODSPlasma volume and fluid regulatory hormones were measured in eight HTRs (57 ± 6 years old) both before and after treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na+, PV was measured by using the modified Evans blue dye dilution technique. After approximately four months (16 ± 5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was repeated.RESULTSCaptopril pharmacologically suppressed (p < 0.05) supine rest levels of angiotensin II (−65%) and aldosterone (−75%). The reductions in vasopressin and atrial natriuretic peptide levels after captopril did not reach statistical significance. The PV, normalized for body weight (ml/kg), was significantly reduced by 12% when the HTRs received captopril.CONCLUSIONSExtracellular fluid volume is expanded (12%) in clinically stable HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that fluid retention is partly engendered by a failure to reflexively suppress the RAA axis when HTRs become hypervolemic.

R research interest has focused on the effects of heparin on allograft survival. In addition to anticoagulant properties, heparin has immunosuppressive effects and inhibitory effects on smooth muscle cell proliferation.1 Animal studies1–4 have shown that low doses of heparin devoid of anticoagulant activity extend the survival of skin allografts as well as heterotopic and xenographic cardiac allografts. The addition of low molecular weight heparin (LMWH) to cyclosporine immunosuppression reduced the frequency and severity of accelerated graft coronary disease and the extent of acute parenchymal rejection in a rat model of heterotopic heart transplantation.5 Because endothelial dysfunction has been proposed as a surrogate end point for the subsequent development of cardiac allograft vasculopathy,6 we undertook a pilot study to evaluate the effect of LMWH in addition to enhanced antirejection therapy on endothelium-dependent vasomotor responses in acute cardiac allograft rejection. • • • Thirteen orthotopic heart transplant recipients who had International Society for Heart and Lung Transplant grade III or IV acute allograft rejection7 confirmed by endomyocardial biopsy between July 1, 1995, and March 1, 1997, were screened for this randomized, parallel-design pilot study comparing the effects of standard therapy and LMWH with standard therapy alone on endothelium-dependent vasomotor responses. Exclusion criteria included age ,18 years, angiographically significant coronary stenosis (.50% luminal diameter narrowing), hemodynamically compromising rejection with systolic blood pressure ,90 mm Hg and/or cardiac index ,2.0 L/min/m, a major contraindication to anticoagulation such as life-threatening bleed in the previous 6 months, platelet count ,50,000 or prior allergic reaction to heparin. One patient was excluded from the study because of early hemodynamic complications from the rejection episode. Three patients refused consent. The remaining 9 patients with acute cellular allograft rejection underwent cardiac catheterization and vasomotor function testing within 18 hours of the histologic diagnosis of rejection, before initiation of any antirejection therapy. After vasomotor function testing, patients were randomized into 2 groups. All patients received enhanced immunosuppression with intravenous methylprednisolone 1,000 mg/day for 3 days. Four patients in group 1 received LMWH (Enoxaparin, Rhone-Poulenc Rorer, Collegeville, Pennsylvania) 2 mg/kg/day in 2 divided subcutaneous doses for 3 days in addition to methylprednisolone. Five patients in group 2 were treated with methylprednisolone alone. At the time of the next endomyocardial biopsy (10 6 3 days), all but 1 patient underwent repeat vasomotor function assessment. All study patients had received 3-drug (prednisone, cyclosporine, and azathioprine) immunosuppression with therapeutic drug levels and 1 in each group had received diltiazem for hypertension before the acute episode. All vasoactive medications were discontinued $12 hours before the study procedure. After coronary angiography from the femoral approach, all patients received 5,000 U of unfractionated heparin intravenously. Using an 8Fr wide lumen guiding catheter, a steerable 0.014-inch, 12-MHz Doppler guidewire (Flowire, Cardiometrics, Inc., Mountainview, California) and a 3.2Fr, 30-MHz intravascular ultrasound catheter (IVUS; Cardiovascular Imaging Systems, Inc., Sunnyvale, California) were positioned in the middle left anterior descending artery for simultaneous assessment of vascular structure and function in relation to coronary blood flow. Use of these 2 systems together has been previously reported.8,9 The Doppler transducer at the tip of the Flowire was positioned 5 to 10 mm distal to the tip of the imaging transducer to avoid interference with Doppler velocity signals caused by the IVUS catheter. Identical catheter positions on serial studies were confirmed by reference to branch vessels in 2 views. Simultaneous IVUS and Doppler recordings were made during intracoronary infusions of adenosine 16 mg, acetylcholine 60 mg, and nitroglycerin 200 mg as boluses. Time was allowed for coronary blood flow (CBF) and luminal diameter to return to baseline before administration of each agent. Doppler and IVUS signals were recorded on 1/2-inch videotape for off-line analysis. The interventional cardiologists that performed these studies were not blinded. Quantitative measurements of average peak velocity were made and CBF reserve was defined as the ratio of hyperemic to resting baseline average peak velocities. Vessel cross-sectional area was measured directly by tracing the lumen-wall interface from a single diastolic frame using the Cardiovascular ImagFrom the University of Florida College of Medicine, Division of Cardiovascular Medicine, Gainesville, Florida. This research was supported in part by the American College of Cardiology/Merck Research Fellowship Award, Bethesda, Maryland; the American Heart Association, St. Petersburg, Florida; Florida Affiliate Research Fellowship Award, and the Bracco Diagnostics/Society for Cardiac Angiography and Interventions Research Fellowship Award, Breckenridge, Colorado; and a grant from Rhone-Poulenc Rorer, Collegeville, Pennsylvania. Dr. Mills’ address is: Division of Cardiology, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195. Manuscript received September 13, 1999; revised manuscript received and accepted January 7, 2000.

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.

This review outlines the chemical properties, pharmacology and clinical trials data which support the development of nesiritide (synthetic human B-type natriuretic peptide, or hBNP) as a therapeutic agent for patients with decompensated congestive heart failure. Nesiritide is a 32-amino acid peptide, structurally identical to endogenous hBNP. Clinical trials with single bolus, repeated boluses and sustained infusions of nesiritide have demonstrated prompt, significant and sustained reductions in pulmonary capillary wedge pressure and increases in cardiac output, consistent with a direct vasodilator effect. Nesiritide has a short half-life, approximately 18 min, which is not dependent upon renal function. It not associated with tachyphylaxis through 24 h of therapy. Nesiritide is not an inotrope, and its action is not dependent upon beta adrenergic receptors. The safety profile has been excellent; the major adverse effect is hypotension. The frequency of ventricular arrhythmia is not increased in patients treated with nesiritide. In our opinion, nesiritide has many attributes of an ideal first-line therapeutic agent for decompensated heart failure.

“Human beings, who are almost unique in having the ability to learn from the experience of others, are also remarkable for their apparent disinclination to do so.” Douglas Adams, Last Chance to See ([1][1]) Learning to interpret immunoreactive B-type natriuretic peptide (iBNP) levels in heart

The mechanisms responsible for immediate adjustments in cardiac output at onset of exercise, in the absence of neural drive, are not well defined in heart transplant (HT) recipients. Seven male HT recipients (mean ± SD 57 ± 6 years) and 7 age-matched sedentary normal control subjects (mean age 57 ± 5 years) performed constant load cycle exercise at 40% of peak power output (Watts). Cardiac output and plasma norepinephrine were determined at rest and every 30 seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All subjects were admitted to the General Clinical Research Center for determination of plasma volume. After 3 days of equilibration to a controlled and standardized diet, plasma volume was measured using a modified Evans Blue Dye (T-1824) dilution technique. Heart rate at rest was higher in the HT group (105 ± 12 vs 74 ± 6 beats/min), but during submaximum exercise, heart rates in the control group increased more rapidly (p ≤0.05) and to a greater magnitude (54 ± 7% vs 17 ± 4% above rest). Stroke volume at rest was lower in HT recipients (45 ± 4 vs 68 ± 9 ml) but was significantly augmented immediately after onset of exercise (30 seconds) and the relative increase was greater than controls at peak exercise (61% vs 38% greater than baseline). Cardiac output at rest was within the normal range in both groups (4.58 ± 0.27 vs 4.94 ± 0.40 L/min). Relative increases in cardiac output were similar (p ≥0.05) for the HT (106 ± 12%) and control groups (97 ± 10%). Plasma norepinephrine did not become significantly greater than resting values until approximately 4 minutes after onset of exercise in both groups. Blood volume, normalized for body weight, was 12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%) augment stroke volume immediately after the onset of exercise. Plasma norepinephrine levels contribute negligibly to the rapid adjustment in cardiac output. Rather, we speculate that abrupt on-transit increases in stroke volume are due to augmented venous return, secondary to expanded blood volume.

To determine the effect of resistance exercise training (ET) on glucocorticoid-induced myopathy in heart transplant recipients (HTR), 14 male HTR were randomly assigned to a ET group that trained for 6 months (54 +/- 3 yr old; mean +/- SD) or a control group (51 +/- 8 yr old; mean +/- SD).Fat mass, fat-free mass, and total body mass were measured by dual-energy x-ray absorptiometry before and 2 months after transplantation (Tx), and after 3 and 6 months of ET or control period. The exercise regimen consisted of lumbar extension (MedX) performed 1 d.wk-1 and variable resistance exercises (Nautilus) performed 2 d.wk-1. PreTx body composition did not differ between groups.At 2 months after Tx, fat-free mass was significantly decreased below baseline in both control (-3.4 +/- 2.1%) and ET groups (-4.3 +/- 2.4%). Fat mass was significantly increased at 2 months after Tx in both the control (+8.3 +/- 2.8%) and ET groups (+7.3 +/- 4.0%). Six months of ET restored fat-free mass to levels 3.9 +/- 2.1% greater (Por = 0.05) than before Tx. Fat-free mass of the control group decreased progressively to levels that were 7 +/- 4.4% lower than preTx values (Por = 0.05). Both groups increased knee extension, chest press, and lumbar extensor strength, but improvements in the ET group were four- to six-fold greater (Por = 0.05).Our results demonstrate that glucocorticoid-induced changes in body composition in HTR occur early after Tx. However, 6 months of specific ET restores fat-free mass to levels greater than before Tx and dramatically increases skeletal muscle strength. Resistance exercise, as part of a strategy to prevent steroid-induced myopathy, appears to be safe and should be initiated early after heart Tx.

Thirteen out of 223 consecutive cardiac transplant patients required permanent pacemaker implantation; 11 for sinus node dysfunction and 2 for complete AV block. Patients with sinus node dysfunction were considered for AAIR mode pacemakers if they had intact AV conduction defined as a Wenckebach point of > 120 beats/min. Ten of 11 patients with sinus node dysfunction had a single atrial lead placed. Atrial lead placement was most easily accomplished with a straight, active fixation lead and the use of manually curved stylets to find an optimal position in the donor atrium, although active fixation leads with a preformed atrial J were used as well. Two leads dislodged requiring revision. In contrast, only 1 of 250 atrial leads implanted in nontransplanted hearts dislodged (P < 0.0001). Transvenous endomyocardial biopsies have not caused atrial lead dislodgment. Most transplant recipients requiring permanent pacing have intact AV nodal function and require only atrial pacing. Atrial lead dislodgment requiring lead revision occurs more frequently in heart transplant recipients than in native hearts. Use of a straight active fixation lead with a manually formed curve in the stylet is useful in order to find the optimal position for pacing.

Previous research has established the existence of homogeneous religious coping profiles in cardiac-transplantation candidates labeled as the deferring/collaborators, self-directors, and the eclectic religious copers. However, their prospective impact on outcome has not yet been established. This paper examines potential differences between pre-cardiac transplantation religious coping cluster groups on post-cardiac transplantation quality of life (physical functioning, mental health, and general health). Results indicated that the religious coping profiles of deferring/collaborators and self-directors had significantly better scores on mental health and general health than did the eclectics. Implications for religious-coping research and clinical practice are discussed.

This study provides descriptive data on the prevalence of symptoms and quality of life of cardiac transplantation recipients and tests the predictive validity of a pre-cardiac transplantation psychological assessment battery on posttransplantation quality of life. Following the formation of four cluster groups of pretransplantation MMPI profiles based on previous research, frequency analysis found that the cluster groups were not equally represented among cardiac recipients, such that the “Distressed/Confused” cluster had only one recipient member. Tests of significance among the three remaining cluster groups on the posttransplantation quality of life variables found no significant differences. Regression analyses to test the predictive validity of other pretransplantation medical and psychological variables indicated that trait anxiety was a significant predictor of increased symptom frequency and symptom problems and decreased mental health among recipients. Collectively, modest support was found for the use of pretransplantation psychological variables as predictors of posttransplantation quality of life. Interpretation of psychological test data in the context of other psychosocial variables is discussed.

The risks and benefits of anticoagulation for patients with both heart failure and atrial fibrillation are unclear. We hypothesized that anticoagulation was associated with improved clinical outcomes of heart failure patients with atrial fibrillation independent of other risk factors. We conducted a retrospective cohort study of clinical registry data linked to Medicare claims for new users of oral anticoagulation (warfarin) without contraindications, discharged home alive, and stratified by CHADS2 score. Outcomes of interest were propensity score-adjusted estimates of the effects of warfarin at discharge on all-cause mortality, thromboembolic events, major adverse cardiovascular events, and bleeding events. Among 10,494 patients with heart failure and atrial fibrillation, the 2249 patients newly treated with warfarin had lower 1-year mortality (27.7% vs 39.3% for CHADS2 score ≤ 3 [P > .001]; 31.6% vs 41.8% for CHADS2 score > 3 [P > .001]) than patients not treated with warfarin. There was no significant difference in thromboembolic events, major adverse cardiovascular events, or bleeding events at 1 year. After multivariate adjustment, exposed individuals in both CHADS2 subgroups had lower adjusted 1-year mortality (CHADS2 ≤ 3: hazard ratio, 0.78 [95% confidence interval, 0.69-0.89]; CHADS2 >3: 0.78 [0.66-0.93]). In conclusion, warfarin use in heart failure patients with atrial fibrillation was associated with improved survival at 1 year independent of baseline CHADS2 score. However, there was no significant reduction in clinical events, such as thromboembolic or major adverse cardiovascular events at 1 year that might simply explain the survival benefit associated with warfarin.

Background The relative impact of atrial fibrillation on early outcomes of patients with heart failure with reduced or preserved ejection fraction (EF) is unknown. Methods We conducted a retrospective cohort study of clinical registry data linked to Medicare claims for patients with heart failure with reduced or preserved EF stratified by presence of atrial fibrillation at admission. Outcomes of interest were all-cause mortality and readmission at 30days. We used Kaplan-Meier methods to estimate mortality and calculated cumulative incidence estimates of readmission. We used Cox proportional hazards models to examine associations between atrial fibrillation and 30-day outcomes. Results Among 66,357 patients admitted to 283 hospitals between January 2001 and March 2006, 46% had atrial fibrillation (44% of patients with reduced EF and 48% of patients with preserved EF). After adjustment for other patient characteristics, atrial fibrillation was associated with a modestly higher risk of 30-day mortality (HR, 1.08; 95% CI, 1.03-1.14) and readmission (HR, 1.06; 95% CI, 1.02-1.11). In subgroup analyses, atrial fibrillation was associated with a higher risk of 30-day mortality (HR, 1.16; 95% CI, 1.08-1.25) among patients with preserved EF but not among patients with reduced EF. The association of atrial fibrillation with readmission did not differ by heart failure type ( P =.37 for the interaction). Conclusions Atrial fibrillation was associated with higher 30-day mortality among patients with heart failure with preserved EF but not reduced EF. The association of atrial fibrillation with 30-day readmission was modest and did not differ by heart failure type.

Background The prevalence of atrial fibrillation ( AF ) continues to increase; however, there are limited data describing the division of care among practitioners in the community and whether care differs depending on provider specialty. Methods and Results Using the Outcomes Registry for Better Informed Treatment of AF ( ORBIT ‐ AF ) Registry, we described patient characteristics and AF management strategies in ambulatory clinic practice settings, including electrophysiology ( EP ), general cardiology, and primary care. A total of 10 097 patients were included; of these, 1544 (15.3%) were cared for by an EP provider, 6584 (65.2%) by a cardiology provider, and 1969 (19.5%) by an internal medicine/primary care provider. Compared with those patients who were cared for by cardiologists or internal medicine/primary care providers, patients cared for by EP providers were younger (median age, 73 years [interquartile range, IQR , 64, 80 years, Q1, Q3] versus 75 years [ IQR , 67, 82 years] for cardiology and versus 76 years [ IQR , 68, 82 years] for primary care). Compared with cardiology and internal medicine/primary care providers, EP providers used rhythm control (versus rate control) management more often (44.2% versus 29.7% and 28.8%, respectively, P OR ] EP versus cardiology, 1.66 [95% confidence interval, CI , 1.05 to 2.61]; adjusted OR for internal medicine/primary care versus cardiology, 0.91 [95% CI , 0.65 to 1.26]). Use of oral anticoagulant therapy was high across all providers, although it was higher for cardiology and EP providers (overall, 76.1%; P =0.02 for difference between groups). Conclusions Our data demonstrate important differences between provider specialties, the demographics of the AF patient population treated, and treatment strategies—particularly for rhythm control and anticoagulation therapy.

BACKGROUND: Effective warfarin thromboprophylaxis requires maintaining anticoagulation within the recommended international normalized ratio (INR) range. INR testing rates and associations between testing and outcomes are not well understood. HYPOTHESIS: INR testing rates after hospitalization for acute decompensated heart failure are suboptimal, and testing is associated with lower risks of mortality and adverse clinical events. METHODS: We conducted a retrospective cohort study of patients who were long‐term warfarin users and were hospitalized for heart failure, had a medical history of atrial fibrillation or valvular heart disease, and were enrolled in fee‐for‐service Medicare. INR testing was defined as ≥1 outpatient INR test within 45 days after discharge. Using Cox proportional hazards models, we examined associations between testing and all‐cause mortality, all‐cause readmission, and adverse clinical events at 1 year. RESULTS: Among 8558 patients, 7722 (90.2%) were tested. After 1 year, tested patients had lower all‐cause mortality (23.5% vs 32.6%; P

Introduction Medically ill, hospitalized patients are at increased risk for venous thromboembolism (VTE) after discharge. This study aimed to examine thromboprophylaxis patterns, risk factors, and post-discharge outcomes. Methods This was a retrospective claims analysis involving administrative claims data and in-patient data abstracted from a sample of hospital charts. Patients aged ≥ 40 years hospitalized for ≥ 2 days for nonsurgical reasons between 2005 and 2009 were included. Hospital chart data were abstracted for a random sample of patients without evidence of anticoagulant use at 30 days post-discharge. The combined data determined whether in-patient thromboprophylaxis (anticoagulant or mechanical prophylaxis) reduces risk of VTE at 90 days post-discharge. Hazard ratios (HR) and odds ratios (OR) were calculated using Cox proportional hazard models and logistic regression. Results Of 141,628 patients in the claims analysis, 3.9% received anticoagulants (3.6% warfarin). VTE, rehospitalization, and mortality rates were 1.9%, 17.2%, and 6.2%, respectively. The strongest predictors of post-discharge VTE were history of VTE (HR = 4.0, 95% confidence interval [CI]: 3.3-4.8), and rehospitalization (HR = 3.9, 95% CI: 3.6-4.3). Of 504 medical charts, 209 (41.5%) reported in-patient thromboprophylaxis. There was no statistically significant difference in post-discharge VTE rates between patients who did and did not receive in-patient thromboprophylaxis. All-cause mortality was greater among patients without use of VTE prophylaxis. Conclusion Utilization rates of in-hospital and post-discharge VTE prophylaxis were low. In-hospital VTE prophylaxis did not reduce the risk of post-discharge VTE in the absence of post-discharge anticoagulation. Combined in-patient and post-discharge thromboprophylaxis lowered the odds of short-term, all-cause post-discharge mortality.

Background We sought to determine the risk of readmission for bleeding and major cardiac events in stented non–ST-segment elevation myocardial infarction (NSTEMI) atrial fibrillation (AF) patients. Methods For this patient population, selection of an antithrombotic strategy poses a unique challenge in clinical practice, and comparative outcome data are sparse. We linked NSTEMI patients aged ≥65 years in the CRUSADE Registry (2003-2006) to Medicare claims data. We examined patients with AF who received coronary stenting and either dual antiplatelet therapy (DAPT, aspirin + clopidogrel) or triple therapy (DAPT + warfarin) upon discharge. Multivariable Cox analysis was used to compare the 1-year risks of major cardiac events and readmission for bleeding. Results We identified 1,648 stented NSTEMI AF patients. Of these, 1,200 (73%) received DAPT, and 448 (27%) received triple therapy at hospital discharge. Predicted thromboembolic and bleeding risks did not appear to influence the decision to receive DAPT or triple therapy. At 1 year, 20.4% had a major cardiac event, and 13.5% were admitted for bleeding. Use of triple therapy relative to DAPT at discharge was associated with a similar adjusted risk of major cardiac events (adjusted hazard ratio 0.94, CI 0.73-1.21) but a trend toward increased risk of readmission for bleeding (hazard ratio 1.29, CI 0.96-1.74, P = .09). Conclusions In routine practice and in contrast with practice recommendations, most elderly NSTEMI patients with AF who undergo percutaneous coronary intervention with stent placement receive DAPT rather than triple therapy at discharge. Those receiving triple therapy versus DAPT had a similar risk of an ischemic event but a trend toward increased bleeding.

Objectives.We attempted to demonstrate that theophylline, an adenosine receptor antagonist, can reverse bradyarrhythmias after orthotopic heart transplantation.Background.Sinus node dysfunction, primarily sinus bradycardia, frequently occurs after orthotopic heart transplantation and may lead to permanent pacemaker implantation. Endogenous adenosine has been implicated as a cause of such posttransplantation bradyarrhythmia.Methods.Twenty-nine transplant recipients (group 1) were given theophylline after bradyarrhythmias developed after transplantation. Data in these patients were compared with those in a control group of 18 patients without bradyarrhythmias (group 2) who were not given theophylline.Results.The mean heart rate in group 1 increased from 62 ± 7 to 89 ± 10 beats/min after administration of theophylline (p < 0.0001); the mean heart rate in group 2 was 88 ± 12 beats/min. Patients in group 1 required more days of temporary atrial pacing (3.5 ± 1 vs. 1.5 ± 3, p < 0.04) before the administration of theophylline than did patients in group 2. The length of hospital stay after transplantation did not differ significantly between groups 1 and 2 (17 ± 7.5 vs. 20 ± 16 days, p = NS). Age, gender, underlying disease, preoperative use of amiodarone, graft ischemia time or the incidence of moderate to severe rejection were not different between patient groups.Conclusions.The use of theophylline for posttransplantation bradyarrhythmias increased heart rate and facilitated the withdrawal of chronotropic support. We conclude that theophylline offers effective and specific therapy for heart transplant patients with early bradyarrhythmias, reducing the need for implantation of a permanent pacemaker.

Measures of disease severity used in the evaluation of patients with heart failure include survival data, the New York Heart Association classification, ejection fraction, functional assessments, exercise protocols, rest and exercise hemodynamic data, and biochemical parameters including catecholamine levels and serum sodium. Clinicians must integrate these multiple variables into an overall assessment. An overview of the clinical application of these techniques in the evaluation and treatment of patients with heart failure is presented.

The recent wave of enthusiasm for including inflammation as one of the primary pathophysiologic processes in cardiovascular disease has substantial merit [(1)][1]. Arterial inflammation is central to plaque progression and plaque rupture. Among clinical markers of inflammation, C-reactive protein (

Background: Hospitalized medically ill patients receiving antithrombotic medications experience increased risk of bleeding. We examined antithrombotic use, bleeding rates, and associated risk factors at 30 days post discharge. Methods: This retrospective database analysis included nonsurgical patients aged ≥40 years hospitalized for ≥2 days during 2005 to 2009. Previously cited, validated International Classification of Diseases, Ninth Revision, Clinical Modification codes for major bleeding were used to define clinically relevant bleeding. Results: Of the 327,578 patients, 9.1% received antithrombotic medications, of which 3.7% were anticoagulants. Rates of major and minor bleeding were 1.8% and 7.1%, respectively. Preindex gastroduodenal ulcer, thromboembolic stroke, blood dyscrasias, liver disease, and rehospitalization were the strongest predictors of major bleeding. Other risk factors included increasing age, male gender, and hospital stay of ≥3 days. Conclusions: Careful consideration of these demonstrated bleed-associated comorbidities before initiating anticoagulation or combining antithrombotic medications in medically ill patients may improve strategies for prevention of postdischarge thromboembolism.

Risk of atrial fibrillation (AF) after coronary artery bypass grafting (CABG) is high, yet the effectiveness of guideline-recommended preoperative prophylaxis in clinical practice remains uncertain. We determined the utilization and variation of preoperative AF prevention and assessed the comparative effectiveness of alternative drugs using the Society of Thoracic Surgeons multicenter Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) registry. Among 2,177 patients who underwent high-risk CABG and/or valve surgery, the mean age was 71 ± 9, 66% were men, 26% had chronic lung disease, and 21% had cerebrovascular disease. Overall use of AF prophylaxis was 84% and varied across sites (range 52% to 100%). The most common preventive agents were beta blockers (72%), followed by calcium antagonists (17%). Postoperatively, 30% (n = 646) developed AF at a median of 2 (25th to 75th percentiles: 1 to 3) days after surgery. Increasing age, height, white race, body mass index35, New York Heart Association class IV heart failure, preoperative dialysis, and concomitant aortic valve replacement were associated with greater odds of postoperative AF (p0.05 for all). Preoperative amiodarone use was associated with a trend to reduction of postoperative AF (26%, adjusted odds ratio 0.72 [95% confidence interval 0.51 to 1.00], p = 0.052). After adjustment, the odds of postoperative AF were not statistically different across agents. In conclusion, use of AF prophylaxis before surgery varied significantly. In this high-risk population, we were unable to demonstrate that any of the commonly used preventive agents were associated with lower rates of AF compared with alternatives or no treatment.

As major prescribers of oral anticoagulants, cardiologists must be familiar with strategies to manage bleeding, the principal complication associated with all anticoagulants, and to reverse anticoagulant effects in acute‐care settings. The purpose of this manuscript is to review currently available information regarding dabigatran and rivaroxaban, the 2 novel oral anticoagulants approved to date in the United States. Further, we suggest reasonable interventions for the clinician faced with a patient who suffers a major bleeding event while receiving one of these agents. Data sources were peer‐reviewed publications, US Food and Drug Administration documents in the public domain, and approved US prescribing information for dabigatran (Pradaxa) and rivaroxaban (Xarelto). Strategies for management of bleeding and reversal of anticoagulant effects from warfarin include vitamin K, fresh frozen plasma, and prothrombin complex concentrates. For rivaroxaban and dabigatran, appropriate therapies include support and observation, which are likely to be effective for the majority of patients because of the short half‐lives of these agents. In severe life‐threatening hemorrhage, clotting‐factor substitutes may be appropriate in certain situations. Validated protocols specific to each agent remain to be developed. Clin. Cardiol. 2012 doi: 10.1002/clc.22037 Editorial support for this paper was provided by Janssen Scientific Affairs, LLC. W.F.P. has received research grants (>$10 000) from Abbott, Alere, Baxter, Brahms, Novartis, and The Medicines Company. He has been a consultant (