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BACKGROUND Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available. METHODS We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up. The annualized rate ofall hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, were assessed through 5 years. RESULTS Of the 614 patients enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of hospitalization for heart failure through 5 years was 33.1% per year in the device group and 5Z2°/o per year in the control group (hazard ratio, 0.53; 95% confidence interval ICI],0.41 to 0.68). Allcause mortality through 5 years was 5Z3°6 in the device group and 67.2% in the control group (hazard ratio, 0.72; 95% CI, 0.58 to 0.89). Death or hospitalization for heart failure within 5 years occurred in 73.690 of the patients in the device group and in 91.5°6 ofthose in the control group (hazard ratio, 0.53; 95°6 CI, 0.44 to 0.64). Device-specific safety events within 5 years occurred in 4 of 293 treated patients (1.4°/o), with all the events occurring within 30 days after the procedure. CONCLUSIONS Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite guideline-directed medical therapy, transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality through 5 years of follow-up than medical therapy alone. [ABSTRACT FROM AUTHOR]

Aims: Heart failure with reduced ejection fraction (HFrEF) remains associated with high morbidity and mortality, poor quality of life (QoL) and significant exercise limitation. Sympatho‐vagal imbalance has been shown to predict adverse prognosis and symptoms in HFrEF, yet it has not been specifically targeted by any guideline‐recommended device therapy to date. Barostim™, which directly addresses this imbalance, is the first Food and Drug Administration approved neuromodulation technology for HFrEF. We aimed to analyse all randomized trial evidence to evaluate the effect of baroreflex activation therapy (BAT) on heart failure symptoms, QoL and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in HFrEF. Methods and results: An individual patient data (IPD) meta‐analysis was performed on all eligible trials that randomized HFrEF patients to BAT + guideline‐directed medical therapy (GDMT) or GDMT alone (open label). Endpoints included 6‐month changes in 6‐min hall walk (6MHW) distance, Minnesota Living With Heart Failure (MLWHF) QoL score, NT‐proBNP, and New York Heart Association (NYHA) class in all patients and three subgroups. A total of 554 randomized patients were included. In all patients, BAT provided significant improvement in 6MHW distance of 49 m (95% confidence interval [CI] 33, 64), MLWHF QoL of −13 points (95% CI −17, −10), and 3.4 higher odds of improving at least one NYHA class (95% CI 2.3, 4.9) when comparing from baseline to 6 months. These improvements were similar, or better, in patients who had baseline NT‐proBNP <1600 pg/ml, regardless of the cardiac resynchronization therapy indication status. Conclusion: An IPD meta‐analysis suggests that BAT improves exercise capacity, NYHA class, and QoL in HFrEF patients receiving GDMT. These clinically meaningful improvements were consistent across the range of patients studies. BAT was also associated with an improvement in NT‐proBNP in subjects with a lower baseline NT‐proBNP. [ABSTRACT FROM AUTHOR]

The regulatory landscape for device-based heart failure (HF) therapies has seen a major shift in the last 7 years. In 2013, the U.S. Food and Drug Administration released guidance for early feasibility and first-in-human studies, thereby encouraging device innovation, and in 2016 the U.S. Congress authorized the Breakthrough Devices Program to expedite access for Americans to innovative devices indicated for diagnosis and treatment of serious illnesses, such as HF. Since December 2016, there has been an increase in the number of HF devices for which manufacturers are seeking approval through the breakthrough designation pathway. This has led to a rapid uptake in the development and evaluation of device-based HF therapies. This article reviews the current and future landscape of device therapies for chronic HF and associated comorbidities and the regulatory environment that is driving current and future innovation. [ABSTRACT FROM AUTHOR]

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation. [ABSTRACT FROM AUTHOR]

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) outcomes remain poor despite optimal guideline‐directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during the 12 months after Ventura shunt implantation in the RELIEVE‐HF open‐label roll‐in cohort. Methods and results: Eligibility required symptomatic HF despite optimal GDMT with ≥1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device‐related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 ± 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) ≤40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12–16 points at all follow‐up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end‐systolic and end‐diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end‐systolic and end‐diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved. Conclusion: Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF. [ABSTRACT FROM AUTHOR]

Interatrial shunting for the treatment of heart failure: an on-demand, self-regulating left atrial pressure lowering system Patients with severe pulmonary hypertension or advanced right heart failure were excluded, as was one patient who had a transseptal complication and two who had transseptal puncture failure prior to the device implant attempt. B This article refers to 'One-year results of the first-in-man study investigating the Atrial Flow Regulator for left atrial shunting in symptomatic heart failure patients: the PRELIEVE study' by C. Paitazoglou I et al i ., published in this issue on pages 800-810. b Two-time U.S. Open Title winner Curtis Strange said, 'Under pressure, one of the most important things I have to remember to do is breathe'. [Extracted from the article]

Aims: Heart failure (HF) is associated with considerable symptom burden and impairment in physical functioning and quality of life. The sodium-glucose co-transporter 2 inhibitor empagliflozin reduced the risk of HF hospitalisation and cardiovascular death in patients with type 2 diabetes and established cardiovascular disease in the EMPA-REG OUTCOME trial, and could potentially improve congestion symptoms and exercise capacity in patients with HF. We describe the designs of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic stable HF, with or without type 2 diabetes.Methods: EMPERIAL-Preserved and EMPERIAL-Reduced are randomised, placebo-controlled trials designed to investigate the effects of empagliflozin on exercise capacity and patient-reported outcomes in patients with chronic stable HF with preserved ejection fraction [HFpEF; left ventricular ejection fraction (LVEF) > 40%] and HF with reduced ejection fraction (HFrEF; LVEF ≤ 40%), respectively. In each trial, approximately 300 patients will be randomised 1:1 to receive empagliflozin 10 mg or placebo once daily for 12 weeks. In both trials, the primary endpoint is the change from baseline in 6-min walk test distance at week 12. Key secondary endpoints are the change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score and change from baseline in dyspnoea score of the Chronic Heart Failure Questionnaire at week 12.Conclusion: The EMPERIAL-Preserved and EMPERIAL-Reduced trials will determine the effects of empagliflozin on exercise capacity and patient-reported outcomes in patients with HFpEF and HFrEF, respectively, and provide insight into the potential of empagliflozin in the treatment of patients with HF.Clinical Trial Registration: ClinicalTrials.gov ID: NCT03448406 (EMPERIAL-Preserved), NCT03448419 (EMPERIAL-Reduced). [ABSTRACT FROM AUTHOR]

Background In a randomized trial, baroreflex activation therapy (BAT) improved exercise capacity, quality of life and NT-proBNP in patients with heart failure with reduced ejection fraction (HFrEF). In view of different mechanisms underlying HFrEF, we performed a post-hoc subgroup analysis of efficacy and safety of BAT in patients with and without coronary artery disease (CAD). Methods and results Patients with left ventricular ejection fraction <35% and NYHA Class III were randomized 1:1 to guideline-directed medical and device therapy alone or plus BAT. Patients with a history of CAD, prior myocardial infarction or coronary artery bypass graft were assigned to the CAD group with all others assigned to the no-CAD group. Of 71 BAT treated patients, 52 had CAD and 19 had no CAD. In the control group, 49 of 69 patients had CAD and 20 had no CAD. The system- or procedure-related major adverse neurological or cardiovascular event rate was 3.8% in the CAD group vs. 0% in the no-CAD group (p = 1.0). In the whole cohort, NYHA Class, Minnesota Living with Heart Failure score, 6-minute hall walk distance and NTproBNP were improved in BAT treated patients compared with controls. Statistical analyses revealed no interaction between the presence of CAD and effect of BAT (all p > 0.05). Conclusion No major differences were found in BAT efficacy or safety between patients with and without CAD, indicating that BAT improves exercise capacity, quality of life and NTproBNP in patients with ischemic and non-ischemic cardiomyopathy. ClinicalTrials.gov identifier NCT01471860 and NCT01720160 . [ABSTRACT FROM AUTHOR]

Aims Cardiac resynchronization therapy ( CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short-term clinical response. Methods and results In an individual patient meta-analysis of three double-blind, randomized trials, clinical composite score ( CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment-covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis ( n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction ( LVEF) as predictors of CRT clinical response ( P < 0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms. Conclusions In symptomatic chronic heart failure patients ( NYHA class II-IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT. [ABSTRACT FROM AUTHOR]

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short-term clinical response.Methods and Results: In an individual patient meta-analysis of three double-blind, randomized trials, clinical composite score (CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment-covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis (n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction (LVEF) as predictors of CRT clinical response (P < 0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms.Conclusions: In symptomatic chronic heart failure patients (NYHA class II-IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT. [ABSTRACT FROM AUTHOR]

Rates of heart failure hospitalization remain unacceptably high. Such hospitalizations are associated with substantial patient, caregiver, and economic costs. Randomized controlled trials of noninvasive telemedical systems have failed to demonstrate reduced rates of hospitalization. The failure of these technologies may be due to the limitations of the signals measured. Intracardiac and pulmonary artery pressure-guided management has become a focus of hospitalization reduction in heart failure. Early studies using implantable hemodynamic monitors demonstrated the potential of pressure-based heart failure management, whereas subsequent studies confirmed the clinical utility of this approach. One large pivotal trial proved the safety and efficacy of pulmonary artery pressure-guided heart failure management, showing a marked reduction in heart failure hospitalizations in patients randomized to active pressure-guided management. "Next-generation" implantable hemodynamic monitors are in development, and novel approaches for the use of this data promise to expand the use of pressure-guided heart failure management. [ABSTRACT FROM AUTHOR]

Background: In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group.Methods: The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661.Findings: Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55-0·80]; p<0·0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0·52 [95% CI 0·40-0·69]; p<0·0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported.Interpretation: Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure.Funding: St Jude Medical Inc. [ABSTRACT FROM AUTHOR]

Aims: Increased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Carotid baroreceptor stimulation (baroreflex activation therapy, BAT) results in centrally mediated reduction of sympathetic and increase in parasympathetic activity. Because patients treated with cardiac resynchronization therapy (CRT) may have less sympathetic/parasympathetic imbalance, we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT.Methods and Results: New York Heart Association (NYHA) Class III patients with an ejection fraction (EF) ≤35% were randomized (1 : 1) to ongoing guideline-directed medical and device therapy (GDMT, control) or ongoing GDMT plus BAT. Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events (MANCE). Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life (QoL), 6-min hall walk distance (6MHWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and HF hospitalization rate. In this sample, 146 patients were randomized (70 control; 76 BAT) and were 140 activated (45 with CRT and 95 without CRT). MANCE-free rate at 6 months was 100% in CRT and 96% in no-CRT group. At 6 months, in the no-CRT group, QoL score, 6MHWD, LVEF, NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls. Changes in efficacy endpoints in the CRT group favoured BAT; however, the improvements were less than in the no-CRT group and were not statistically different from control.Conclusions: BAT is safe and significantly improved QoL, exercise capacity, NTpro-BNP, EF, and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients. These effects were most pronounced in patients not treated with CRT. [ABSTRACT FROM AUTHOR]

Objective Type 2 diabetes disproportionately affects African American women, a population exposed to high levels of stress, including financial strain (Centers for Disease Control & Prevention, 2011, ). We tested a mediational model in which chronic financial strain among African American women contributes to elevated serum inflammation markers, which, in turn, lead to increased haemoglobin A1C (HbA1c) levels and risk for type 2 diabetes. Methods We assessed level of financial strain four times over a 10-year period and tested its effect on two serum inflammation markers, C-reactive protein ( CRP) and soluble interleukin-6 receptor (sIL-6R) in year 11 of the study. We tested the inflammation markers as mediators in the association between chronic financial strain and HbA1c, an index of average blood glucose level over several months. Design Data were from 312 non-diabetic African American women from the Family and Community Health Study (FACHS; Cutrona et al., 2000, J. Pers. Soc. Psychol., 79, 1088). Results Chronic financial strain predicted circulating sIL-6R after controlling for age, BMI, health behaviours, and physical health measures. In turn, sIL-6R significantly predicted HbA1c levels. The path between chronic financial strain and HbA1c was significantly mediated by sIL-6R. Contrary to prediction, CRP was not predicted by chronic financial strain. Conclusions Results support the role of inflammatory factors in mediating the effects of psychosocial stressors on risk for type 2 diabetes. Findings have implications for interventions that boost economic security and foster effective coping as well as medical interventions that reduce serum inflammation to prevent the onset of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background We conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients. Methods At CRT-D implant, patients were stratified based on detectable TnT (≥0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels. Patients were classified into three groups: high (both detectable TnT and high BNP), intermediate (either detectable TnT or high BNP), or low (nondetectable TnT and low BNP). Patients were followed for 12 months. Survival curves free from mortality or heart failure hospitalizations (HFH) were assessed. To assess the predictive value of biomarker category, we constructed a multivariate Cox regression model, including the covariates of age, New York Heart Association class, left ventricular ejection fraction (LVEF), and QRS duration. Results A total of 267 patients (age 66 ± 12 years, males 80%, LVEF 25% ± 8%, ischemic cardiomyopathy 52%, QRSd 155 ± 26 ms) were studied. After 1 year, there were 13 deaths and 25 HFH events. A significant difference in event-free survival among the three groups was observed, with high and intermediate categories having worse survival than low (log-rank test, P < 0.001). In the multivariate model, risk category was a significant predictor of outcome: hazard ratios were 7.34 (95% confidence interval [CI]: 2.48-21.69) and 2.50 (95% confidence interval [CI]: 1.04-6.04) for high-risk and intermediate-risk groups, respectively (P < 0.0001). Conclusion Among CRT-D recipients, baseline TnT and BNP values alone or in combination provide significant prognostic value for the outcome of mortality or HFH. [ABSTRACT FROM AUTHOR]

Background Although right heart catheterization (RHC) remains the gold standard for assessment of hemodynamics in patients with known or suspected pulmonary hypertension (PH), there are significant limitations to this type of assessment. The current study evaluates the limitations of RHC in the diagnosis of left heart–related PH (World Health Organization group II) among patients enrolled in the CHAMPION trial and discusses insights into patient risk from home implantable hemodynamic monitor (IHM) data that were not identified at the time of the RHC procedure. Methods The CHAMPION trial enrolled 550 New York Heart Association functional class III patients who had been hospitalized for heart failure (HF) in the previous year, regardless of left ventricular ejection fraction or etiology. Hemodynamic data obtained during baseline RHC were compared with IHM data obtained during the first week of home readings. HF hospitalization rates and mortality were analyzed to assess patient risk. Results The study population for this retrospective analysis comprised 537 patients with available IHM data. For 320 patients in the PH RHC group, home IHM data confirmed the RHC findings with similar mean pulmonary artery pressures obtained from both methods (36 mm Hg vs 36 mm Hg, p = 0.5066). However, of the 217 patients in the No PH RHC group, 106 patients (48.8%) exhibited PH based on the home IHM data (PH IHM group). The remaining 111 patients (51.2%) in the No PH RHC group had no evidence of PH on the IHM data (No PH IHM group). Patients in the No PH RHC /PH IHM group had significantly higher mean PA pressures on IHM than patients in the No PH RHC /No PH IHM group (31 mm Hg vs 18 mm Hg, p < 0.0001). Patients in the No PH RHC /No PH IHM group had significantly lower HF hospitalization rates than patients in the No PH RHC /PH IHM group (0.25 vs 0.49, incidence rate ratio = 0.51, 95% confidence interval = 0.33–0.77, p = 0.0007). Conclusions Using only RHC, World Health Organization group II PH may be significantly under-diagnosed. In patients with left-sided HF and resting mean PA pressure ≤25 mm Hg during RHC, more frequent PA pressure monitoring using an IHM device can provide additional data for improved diagnosis and patient risk stratification compared with a single RHC alone. [ABSTRACT FROM AUTHOR]

Implantable monitoring devices have been developed to detect early evidence of heart failure (HF) decompensation, with the hypothesis that early detection might enable clinicians to commence therapy sooner than would otherwise be possible, and potentially to reduce the rate of hospitalization. In addition to the usual challenges inherent to device trials (such as the difficulty of double-blinding and potential for bias), studies of implantable monitoring devices present unique difficulties because they involve assessment of therapeutic end points for diagnostic devices. Problems include the lack of uniform approaches to treatment in study protocols for device alerts or out-of-range values, and the requirement of levels of evidence traditionally associated with therapeutic devices to establish effectiveness and safety. In this Review, the approaches used to deal with these issues are discussed, including the use of objective primary end points with blinded adjudication, identical duration of follow-up and number of encounters for patients in active monitoring and control groups, and treatment recommendations between groups that are consistent with international guidelines. Remote monitoring devices hold promise for reducing the rate of hospitalization among patients with HF. However, optimization of regulatory approaches and clinical trial design is needed to facilitate further evaluation of the effectiveness of combining health information technology and medical devices. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to describe usage of the wearable cardioverter-defibrillator (WCD) during mandated waiting periods following myocardial infarction (MI) for patients perceived to be at high risk for sudden cardiac arrest (SCA). Background: Current device guidelines and insurance coverage require waiting periods of either 40 days or 3 months before implanting a cardioverter-defibrillator post-myocardial infarction (MI), depending on whether or not acute revascularization was undertaken. Methods: We assessed characteristics of and outcomes for patients who had a WCD prescribed in the first 3 months post-MI. The WCD medical order registry was searched for patients who were coded as having had a “recent MI with ejection fraction ≤35%” or given an International Classification of Diseases, Ninth Revision 410.xx diagnostic code (acute MI), and then matched to device-recorded data. Results: Between September 2005 and July 2011, 8,453 unique patients (age 62.7 ± 12.7 years, 73% male) matched study criteria. A total of 133 patients (1.6%) received 309 appropriate shocks. Of these patients, 91% were resuscitated from a ventricular arrhythmia. For shocked patients, the left ventricular ejection fraction (LVEF) was ≤30% in 106, 30% to 35% in 17, >36% in 8, and not reported in 2 patients. Of the 38% of patients not revascularized, 84% had a LVEF ≤30%; of the 62% of patients revascularized, 77% had a LVEF ≤30%. The median time from the index MI to WCD therapy was 16 days. Of the treated patients, 75% received treatment in the first month, and 96% within the first 3 months of use. Shock success resulting in survival was 84% in nonrevascularized and 95% in revascularized patients. Conclusions: During the 40-day and 3-month waiting periods in patients post-MI, the WCD successfully treated SCA in 1.4%, and the risk was highest in the first month of WCD use. The WCD may benefit individual patients selected for high risk of SCA early post-MI. [ABSTRACT FROM AUTHOR]

The article presents the randomized trial which assessed the impact of cardiac-resynchronization therapy (CRT) in patients with New York Heart Association class III or IV heart failure. It claims that the study was supported by the firms Biotronik and GE Healthcare. The results were analyzed at the University of Glasgow's Robertson Centre for Biostatistics in Scotland.

Heart failure (HF) is a global phenomenon, and the overall incidence and prevalence of the condition are steadily increasing. Medical therapies have proven efficacious, but only a small number of pharmacological options are in development. When patients cease to respond adequately to optimal medical therapy, cardiac resynchronization therapy has been shown to improve symptoms, reduce hospitalizations, promote reverse remodelling, and decrease mortality. However, chalienges remain in identifying the ideal recipients for this therapy. The field of mechanical circulatory support has seen immense growth since the early 200Os, and left ventricular assist devices (LVADs) have transitioned over the past decade from large, pulsatile devices to smaller, more-compact, continuous41ow devices. Infections and haematological issues are still important areas that need to be addressed. Whereas LVADs were once approved only for 'bridge to transplantation', these devices are now used as destination therapy for critically ill patients with HF, allowing these individuals to return to the community. A host of novel strategies, including cardiac contractility modulation, implantable haemodynamic-monitoring devices, and phrenic and vagus nerve stimulation, are under investigation and might have an impact on the future care of patients with chronic HF. [ABSTRACT FROM AUTHOR]

Hyponatremia is a common electrolyte disorder associated with increased morbidity and mortality, particularly in the elderly. Lixivaptan, a new selective vasopressin V2-receptor antagonist, safely corrected serum sodium concentrations in phase II studies of patients with euvolemic hyponatremia. Here our multinational, double-blind, placebo-controlled, phase III study assessed the effect of lixivaptan on serum sodium concentrations in 106 initially hospitalized patients with euvolemic hyponatremia (serum sodium less than 130 mmol/l). Of them, 52 were randomized to receive placebo and 54 received 50 mg lixivaptan once daily and were then titrated to receive 25-100 mg once daily depending on serum sodium concentration. Fluid restriction was at the investigator's discretion. Initial titration occurred in a monitored inpatient setting; patients were then treated as outpatients for a total of 30 days. The primary end point was the change in serum sodium concentration from baseline to day 7. Lixivaptan significantly increased the serum sodium concentration from baseline to day 7 (the primary end point) by 6.7 mmol/l compared with placebo (4.5 mmol/l; P=0.034). Importantly, the serum sodium concentration was normalized safely and more rapidly in patients receiving lixivaptan than placebo (P=0.004) and was well tolerated. After drug discontinuation, serum sodium concentrations decreased to near-baseline levels within 7 days. Thus, lixivaptan safely and effectively corrects serum sodium concentrations in patients with euvolemic hyponatremia. [ABSTRACT FROM AUTHOR]

Hyponatremia is the most common electrolyte disorder in clinical practice. Its incidence increases with age and it is associated with increased morbidity and mortality. Recently, the vaptans, antagonists of the arginine vasopressin pathway, have shown promise for safe treatment of hyponatremia. Here we evaluated the efficacy, safety, and tolerability of oral lixivaptan, a selective vasopressin V2-receptor antagonist, for treatment of nonhospitalized individuals with euvolemic hyponatremia (sodium less than 135 mmol/l) in a multicenter, randomized, double-blind, placebo-controlled, phase III study. About half of the 206 patients were elderly in a chronic care setting. Of these patients, 52 were given a placebo and 154 were given 25-100 mg per day lixivaptan, titrated based on the daily serum sodium measurements. Compared with placebo (0.8 mmol/l), the serum sodium concentration significantly increased by 3.2 mmol/l from baseline to day 7 (primary efficacy endpoint) with lixivaptan treatment. A significantly greater proportion of patients that received lixivaptan achieved normal serum sodium (39.4%) by day 7 relative to placebo (12.2%). Overall, lixivaptan was considered safe and well-tolerated. Thus, oral lixivaptan can be safely initiated in the outpatient setting and effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia. [ABSTRACT FROM AUTHOR]

The article discusses a study on the monitoring of chronic heart failure with the use of wireless pulmonary artery haemodynamics. Under the study, patients with a history of heart failure have been subjected to an implantation of a pulmonary artery sensor that serves as a part of the wireless implantable haemodynamic monitoring (W-IHM) system. Results indicate that the treatment group exhibited greater reduction in pulmonary artery mean pressure and hospitalization due to heart failure. The safeness of the W-IHM system is also emphasized.

Objectives: The purpose of this study was to determine the effects of cardiac resynchronization therapy (CRT) with respect to heart failure etiology among patients in the REVERSE (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction) study. Background: CRT improves outcomes in New York Heart Association functional class III/IV heart failure with wide QRS with a more pronounced effect on left ventricular (LV) reverse remodeling in nonischemic patients. Methods: A total of 277 patients with nonischemic heart disease (IHD) and 333 with IHD etiology in New York Heart Association functional class I or II with QRS ≥120 ms and left ventricular ejection fraction ≤40% received a CRT (± implantable cardioverter-defibrillator) and were randomized to CRT-ON or CRT-OFF for 12 months. The primary end point was the percentage of patients worsened by the HF clinical composite response, and multiple prespecified secondary end points were evaluated regarding etiology using univariable and multivariable analysis. Results: At baseline, IHD patients were significantly older and had more comorbidities and less dyssynchrony than non-IHD patients. In non-IHD patients, 10% worsened in CRT-ON compared with 19% in CRT-OFF (p = 0.01). In IHD patients, 20% worsened in the CRT-ON compared with 24% in the CRT-OFF group (p = 0.10). Non-IHD patients assigned to CRT-ON improved more in left ventricular end-systolic volume index than IHD patients. Randomization to CRT, left bundle branch block, and wider QRS duration independently predicted response to both end points, whereas non-IHD etiology was an independent predictor only for left ventricular end-systolic volume index. Conclusions: This substudy of REVERSE shows that CRT reverses left ventricular remodeling with a more extensive effect on nonischemic patients. Etiology was, however, not an independent predictor of clinical response. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154) [Copyright &y& Elsevier]

Hyponatremia is a common electrolyte disorder in patients with heart failure (HF) associated with cognitive dysfunction and increased mortality and rehospitalization rates. Loop diuretics worsen renal function, produce neurohormonal activation, and induce electrolyte imbalances. Lixivaptan is a selective, oral vasopressin V-receptor antagonist that improves hyponatremia by promoting electrolyte-free aquaresis without significant side effects. The Treatment of Hyponatremia Based on Lixivaptan in NYHA Class III/IV Cardiac Patient Evaluation (BALANCE) study is a randomized, double-blind, placebo-controlled, phase 3 trial designed to evaluate the effects of lixivaptan on serum sodium in patients hospitalized with worsening heart failure (target N= 650), signs of congestion and serum sodium concentrations <135 mEq/L. Other endpoints include assessment of dyspnea, body weight, cognitive function, and days of hospital-free survival. Patients are randomized 1:1 to lixivaptan or matching placebo for 60 days, with a 30-day safety follow-up. Doses of lixivaptan or placebo are adjusted based on serum sodium and volume status. Lixivaptan was shown to increase serum sodium and reduce body weight, without renal dysfunction or hypokalemia. BALANCE seeks to address unmet questions regarding the use of vasopressin antagonists including their effects on cognitive function and clinical outcomes in patients with hyponatremia and worsening heart failure. Clin Trans Sci 2010; Volume 3: 249-253. [ABSTRACT FROM AUTHOR]

Aims: To assess the safety and tolerability of darbepoetin alfa (DA) in the treatment of anaemia in heart failure (HF). [ABSTRACT FROM PUBLISHER]

Background: Cardiac resynchronization therapy (CRT) has proven to be a valuable therapy addition for patients with drug-refractory heart failure and a ventricular conduction delay. Delivery of CRT is dependent upon the successful implantation and chronic performance of a left ventricular (LV) pacing lead. This study assessed the long-term electrical performance and safety of a steroid-eluting, transvenous, over-the-wire, cardiac vein pacing lead. Methods: The Attain Model 4193 LV lead (Medtronic, Inc, Minneapolis MN, USA) was successfully implanted in 1,070 patients with 286 patients completing 3 years of follow-up. Clinical data were collected at pre-implant, implant, and at 6-month intervals for 3 years. Results: Over 3 years, the mean chronic pacing threshold ranged from 1.9 V to 2.1 V, the mean R-wave sensing amplitudes ranged between 13.6 mV and 15.0 mV, and the mean pacing impedance ranged between 562 ohms and 590 ohms. Additionally, the observed freedom from first post-implant LV-lead-related complications was 90.4%. Of 1,070 total patients, 82 experienced 89 LV-lead-related adverse events requiring invasive interventions or resulting in the termination of the CRT therapy. The LV lead was repositioned in 31 patients, replaced in 21 patients, and explanted/capped in four patients. There were no deaths related to the LV lead during implantation or during the follow-up period. Conclusions: The data suggest that the 4193 LV lead is safe and effective over time. The LV lead electrical measurements remained stable through follow-up, demonstrating reliable long-term performance within the recommended value range at 36 months and had an acceptable complication rate. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that female and elderly patients with heart failure (HF) are less likely to receive guideline-recommended therapies, but these studies have involved select patient populations. We evaluated the differences in medical care and patient outcomes by age and gender among a broad cohort of hospitalized patients with HF. The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) is a registry and performance-improvement program involving 48,612 patients with HF from 259 hospitals. The data were analyzed by gender, age <75 years, and age ≥75 years. Appropriate angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and β-blocker use were similar between women and men (p = 0.244 and p = 0.237, respectively). However, compared with men, fewer women received hospital discharge instructions (p <0.001) and the length of stay was longer (p <0.001). Risk-adjusted in-hospital and postdischarge mortality were similar. All guideline-recommended cardiac medications were prescribed less frequently at discharge to eligible patients ≥75 than to those <75 years (all p <0.001). Older age was independently associated with in-hospital and postdischarge mortality risk increases (76% and 62%, respectively; p <0.001 for both). In conclusion, among the OPTIMIZE-HF hospitals, female patients with HF generally received similar medical care and had similar risks of adverse clinical outcomes compared with male patients. Older patients with HF were less likely to receive guideline-recommended therapies and remained at greater risk of adverse outcomes. [Copyright &y& Elsevier]

The article discusses heart failure, its epidemiology, prevalence, pathophysiology, diagnosis, treatment, and surgical approaches. The authors explain that the prevalence and incidence of heart failure vary due to a lack of uniformity in the definition of the syndrome. The mechanisms through which coronary artery disease leads to heart failure are discussed. Diagnosis with echocardiography, magnetic resonance imagining, and measurement of amounts of plasma of either B-type natriuretic peptide (BNP) or N terminal-proBNP is examined. Preventive treatment with drugs such as angiotensin-converting enzyme (ACE) inhibitors is also discussed. The role of the renin-angiotensis-aldosterone system (RAAS) is also addressed.

Objectives: We sought to determine the effects of cardiac resynchronization therapy (CRT) in New York Heart Association (NYHA) functional class II heart failure (HF) and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. Background: Cardiac resynchronization therapy improves left ventricular (LV) structure and function and clinical outcomes in NYHA functional class III and IV HF with prolonged QRS. Methods: Six hundred ten patients with NYHA functional class I or II heart failure with a QRS ≥120 ms and a LV ejection fraction ≤40% received a CRT device (±defibrillator) and were randomly assigned to active CRT (CRT-ON; n = 419) or control (CRT-OFF; n = 191) for 12 months. The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The prospectively powered secondary end point was LV end-systolic volume index. Hospitalization for worsening HF was evaluated in a prospective secondary analysis of health care use. Results: The HF clinical composite response end point, which compared only the percent worsened, indicated 16% worsened in CRT-ON compared with 21% in CRT-OFF (p = 0.10). Patients assigned to CRT-ON experienced a greater improvement in LV end-systolic volume index (−18.4 ± 29.5 ml/m2 vs. −1.3 ± 23.4 ml/m2, p < 0.0001) and other measures of LV remodeling. Time-to-first HF hospitalization was significantly delayed in CRT-ON (hazard ratio: 0.47, p = 0.03). Conclusions: The REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) trial demonstrates that CRT, in combination with optimal medical therapy (±defibrillator), reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154). [Copyright &y& Elsevier]

The article investigates the cardiac effects of continuous and bilevel positive airway pressure (PAP) for patients with heart failure and obstructive sleep apnea (OSA). Results suggest that randomized and controlled trial indicates that bilevel PAP is superior to continuous PAP (CPAP) in improving left ventricular ejection fraction (LVEF) in patients with systolic dysfunction and OSA. Bilevel PAP increased LVEF 7.9% more than CPAP.

Heart failure (HF) guidelines recommend that β blockers be titrated to achieve the target doses shown to be effective in major clinical trials, if tolerated. Little is known, however, regarding the doses of β blockers used in patients with HF in routine clinical practice before, during, and after hospitalization for HF. The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) enrolled 5,791 patients admitted with HF in a registry with prespecified 60- to 90-day follow-up at 91 academic and community hospitals throughout the United States. Among 2,373 patients with systolic HF eligible for β blockers at discharge, 1,350 (56.9%) were receiving β-blocker therapy before admission and continued on therapy, and 632 (26.6%) were newly started. The mean total daily dose for β blockers before hospital admission was <1/2 the recommended target dose (carvedilol 21.5 ± 17.8 mg and metoprolol succinate 69.2 ± 51.9 mg), with infrequent up- or down-titration during the HF hospitalization. More than 2/3 of patients had no change in their β-blocker doses in the first 60 to 90 days after hospital discharge. At 60- to 90-day postdischarge follow-up, only 17.5% and 7.9% of patients were being treated with recommended target doses of carvedilol and metoprolol succinate, respectively. In conclusion, these data reveal that the doses of β blockers applied in clinical practice are substantially less that the doses achieved in randomized clinical trials in HF and recommended in national guidelines. In the first 60 to 90 days after hospital discharge, little up-titration in β-blocker dosing occurs. Further efforts are needed to help understand and overcome this β-blocker titration gap. [Copyright &y& Elsevier]

Objectives: The aim of this study was to develop a clinical model predictive of in-hospital mortality in a broad hospitalized heart failure (HF) patient population. Background: Heart failure patients experience high rates of hospital stays and poor outcomes. Although predictors of mortality have been identified in HF clinical trials, hospitalized patients might differ greatly from trial populations, and such predictors might underestimate mortality in a real-world population. Methods: The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) is a registry/performance improvement program for patients hospitalized with HF in 259 U.S. hospitals. Forty-five potential predictor variables were used in a stepwise logistic regression model for in-hospital mortality. Continuous variables that did not meet linearity assumptions were transformed. All significant variables (p < 0.05) were entered into multivariate analysis. Generalized estimating equations were used to account for the correlation of data within the same hospital in the adjusted models. Results: Of 48,612 patients enrolled, mean age was 73.1 years, 52% were women, 74% were Caucasian, and 46% had ischemic etiology. Mean left ventricular ejection fraction was 0.39 ± 0.18. In-hospital mortality occurred in 1,834 (3.8%). Multivariable predictors of mortality included age, heart rate, systolic blood pressure (SBP), sodium, creatinine, HF as primary cause of hospitalization, and presence/absence of left ventricular systolic dysfunction. A scoring system was developed to predict mortality. Conclusions: Risk of in-hospital mortality for patients hospitalized with HF remains high and is increased in patients who are older and have low SBP or sodium levels and elevated heart rate or creatinine at admission. Application of this risk-prediction algorithm might help identify patients at high risk for in-hospital mortality who might benefit from aggressive monitoring and intervention. (Organized Program to Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513) [Copyright &y& Elsevier]

Objectives: This study ascertains the relationship between continuation or withdrawal of beta-blocker therapy and clinical outcomes in patients hospitalized with systolic heart failure (HF). Background: Whether beta-blocker therapy should be continued or withdrawn during hospitalization for decompensated HF has not been well studied in a broad cohort of patients. Methods: The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) program enrolled 5,791 patients admitted with HF in a registry with pre-specified 60- to 90-day follow-up at 91 academic and community hospitals throughout the U.S. Outcomes data were prospectively collected and analyzed according to whether beta-blocker therapy was continued, withdrawn, or not started. Results: Among 2,373 patients eligible for beta-blockers at discharge, there were 1,350 (56.9%) who were receiving beta-blockers before admission and continued on therapy, 632 (26.6%) newly started, 79 (3.3%) in which therapy was withdrawn, and 303 (12.8%) eligible but not treated. Continuation of beta-blockers was associated with a significantly lower risk and propensity adjusted post-discharge death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.37 to 0.99, p = 0.044) and death/rehospitalization (odds ratio: 0.69; 95% CI: 0.52 to 0.92, p = 0.012) compared with no beta-blocker. In contrast, withdrawal of beta-blocker was associated with a substantially higher adjusted risk for mortality compared with those continued on beta-blockers (HR: 2.3; 95% CI: 1.2 to 4.6, p = 0.013), but with similar risk as HF patients eligible but not treated with beta-blockers. Conclusions: The continuation of beta-blocker therapy in patients hospitalized with decompensated HF is associated with lower post-discharge mortality risk and improved treatment rates. In contrast, withdrawal of beta-blocker therapy is associated with worse risk and propensity-adjusted mortality. (Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513) [Copyright &y& Elsevier]

Objectives: We sought to examine the characteristics, quality of care, and clinical outcomes for a large cohort of African-American patients hospitalized with heart failure (HF) in centers participating in a quality improvement initiative. Background: Heart failure in African Americans is characterized by variations in natural history, lesser response to evidence-based therapies, and disparate health care. We hypothesized that a performance improvement program will achieve similar adherence to quality measures in African Americans admitted with HF compared with non–African Americans. Methods: The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) registry-based performance-improvement program includes a pre-specified 10% subgroup with 60- to 90-day follow-up. Data on quality of care measures and outcomes were analyzed for 8,608 African-American patients compared with 38,501 non–African-American patients. Results: African Americans were significantly younger and more likely to receive evidence-based medications but less likely to receive discharge instructions and smoking cessation counseling. In multivariable analyses, African-American race was an independent predictor of lower in-hospital mortality (odds ratio 0.71; 95% confidence interval 0.57 to 0.87; p < 0.001) but similar hospital length of stay. After multivariable adjustment, post-discharge outcomes were similar for American-American and non–African-American patients, but African-American race was associated with higher angiotensin-converting enzyme inhibitor prescription and left ventricular function assessment; no other HF quality indicators were influenced by race. Conclusions: In the context of a performance-improvement program, African Americans with HF received similar or better treatment with evidence-based medications, less discharge counseling, had better in-hospital survival, and similar adjusted risk of follow-up death/repeat hospital stay. (Organized Program to Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513) [Copyright &y& Elsevier]

The article reports that heart failure (HF) is the leading cause of hospitalization of older people in the U.S. According to the authors, American adults older than 65 years have been hospitalized because of heart failure. They add that there are 3.6 million hospitalizations with HF as the primary or secondary cause each year in the country. HF cases are also associated with significant morbidity and mortality. The authors identified several factors that worsen HF and contribute for its hospitalization. It includes arrhythmias, myocardial ischemia, respiratory infection, uncontrolled hypertension, and nonadherence to medications and diet.

Objectives: The purpose of this study was to determine whether a heart failure (HF) management strategy using continuous intracardiac pressure monitoring could decrease HF morbidity. Background: Patients with HF may experience frequent decompensations that require hospitalization despite intensive treatment and follow-up. Methods: The COMPASS-HF (Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure) study was a prospective, multicenter, randomized, single-blind, parallel-controlled trial of 274 New York Heart Association functional class III or IV HF patients who received an implantable continuous hemodynamic monitor. Patients were randomized to a Chronicle (Medtronic Inc., Minneapolis, Minnesota) (n = 134) or control (n = 140) group. All patients received optimal medical therapy, but the hemodynamic information from the monitor was used to guide patient management only in the Chronicle group. Primary end points included freedom from system-related complications, freedom from pressure-sensor failure, and reduction in the rate of HF-related events (hospitalizations and emergency or urgent care visits requiring intravenous therapy). Results: The 2 safety end points were met with no pressure-sensor failures and system-related complications in only 8% of the 277 patients who underwent implantation (all but 4 complications were successfully resolved). The primary efficacy end point was not met because the Chronicle group had a nonsignificant 21% lower rate of all HF-related events compared with the control group (p = 0.33). A retrospective analysis of the time to first HF hospitalization showed a 36% reduction (p = 0.03) in the relative risk of a HF-related hospitalization in the Chronicle group. Conclusions: The implantable continuous hemodynamic monitor-guided care did not significantly reduce total HF-related events compared with optimal medical management. Additional trials will be necessary to establish the clinical benefit of implantable continuous hemodynamic monitor-guided care in patients with advanced HF. [Copyright &y& Elsevier]

Anemia in heart failure (HF) is increasingly recognized and treated, but little is known about the prevalence and its relation to outcomes in patients hospitalized for decompensated HF in a situation of both reduced and preserved systolic function. We hypothesized that lower hemoglobin is correlated with death during hospitalization and 60 to 90 days postdischarge in patients with HF. The Organized Program to Initiate Lifesaving Treatment in Patients with Heart Failure is a registry and performance improvement program for hospitalized patients with HF. Study cohorts were defined by admission hemoglobin quartile. Data from 48,612 patients at 259 hospitals showed that half of the total cohort had low hemoglobin (<12.1 g/dl) and that 25% were moderately to severely anemic (lowest hemoglobin quartile, 5 to 10.7 g/dl). Patients with low hemoglobin were older, were more often women and Caucasian, and had preserved systolic function and elevated creatinine. They were also less likely to receive angiotensin-converting enzyme inhibitors and β blockers at discharge. Anemic patients had higher in-hospital mortality (4.8% vs 3.0%, lowest vs highest quartile), longer hospital length of stay (6.5 vs 5.3 days), and more readmissions by 90 days (33.1% vs 24.2%) (all p <0.0001). In conclusion, these data reveal a higher prevalence of low hemoglobin in hospitalized patients than noted in randomized HF trials and outpatient registries. Lower hemoglobin is associated with higher morbidity and mortality in hospitalized patients with HF. [Copyright &y& Elsevier]

This study evaluates the effect of the U.S. hospital-based initiative called "Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure" (OPTIMIZE-HF) on the quality of care received by patients hospitalized with heart failure. Study concludes that OPTIMIZE-HF resulted to shorter lengths of stay of patients hospitalized with HF while hospital's use of process-of-care improvement tools resulted to further improvements in quality of care.

Cardiac resynchronization therapy (CRT) is well established as a treatment for patients with moderate to severe heart failure on optimal medical therapy. Early studies demonstrated improved functional capacity and evidence of reverse remodeling; more recently, CRT has been associated with a survival benefit in advanced heart failure both with and without a defibrillator. We review the eight landmark trials in CRT To date, criteria have focused on electrical delay, but echocardiographic parameters emphasize the importance of mechanical delay or ventricular dyssynchrony. With the exponential rise in implants, new issues have emerged, such as optimal device programming, identifying appropriate candidates, and accounting for cases without clinical benefit from CRT. [ABSTRACT FROM AUTHOR]

The authors present the results of a study that determined that heart failure performance measures, with the exception of the prescription of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at hospital discharge, have little relationship to patient mortality and the combination of mortality or rehospitalization in the first 60 to 90 days after hospital discharge. Performance measures studied included discharge instructions, evaluation of left ventricular systolic function, smoking cessation, anticoagulant administration and the use of angiotensin-converting enzyme inhibitors.

Objectives: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). Background: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. Methods: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. Results: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. Conclusions: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to examine the renal effects of a V2 receptor arginine vasopressin (AVP) antagonist in heart failure. Background: Arginine vasopressin has been implicated in the renal water retention and dilutional hyponatremia associated with chronic heart failure. Methods: We examined the effects of the oral, non-peptide, selective V2 receptor antagonist lixivaptan in 42 diuretic-requiring patients with mild-to-moderate heart failure in a randomized, double-blind, placebo-controlled, ascending single-dose study. After overnight fluid deprivation, patients received single-blind placebo on day −1 (baseline) and double-blind study medication (placebo [n = 12] or lixivaptan 10, 30, 75, 150, 250, or 400 mg [n = 5 per dose group]) on day 1, followed by 4 h of continued fluid restriction and additional 20 h with ad libitum fluid intake. Results: At all but the 10-mg dose, lixivaptan produced a significant and dose-related increase in urine volume over 4 h, compared with placebo. During 24 h, increases in urine volume ranged from 1.8 l with placebo to 3.9 l after the 400-mg lixivaptan dose (p < 0.01). These increases in urine volumes were accompanied by significant increases in solute-free water excretion. At higher doses, serum sodium was significantly increased; AVP antagonism was well tolerated in these patients. Conclusions: These observations confirm a role for AVP in the renal water retention associated with heart failure and suggest that the V2 receptor antagonist lixivaptan may be a promising therapeutic agent for the treatment of heart failure. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to evaluate the safety of implanting a cardiac resynchronization therapy (CRT) system. Background: Clinicians and patients require data on the safety of the CRT implant procedure to estimate procedural risk. Methods: We evaluated outcomes of transvenous CRT system implantation in 2,078 patients from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study, the MIRACLE Implantable Cardioverter-Defibrillator (ICD) study, and the InSync III study. We compared the MIRACLE study to the InSync III study and the MIRACLE ICD study randomized phase to its general phase to evaluate the effect of new technologies. Results: The implant attempt succeeded in 1,903 of 2,078 (91.6%) patients. Implant time decreased from 2.7 h in the MIRACLE study to 2.3 h in the InSync III study (p < 0.001), and from 2.8 h in the MIRACLE ICD study randomized phase to 2.4 h in the general phase (p < 0.001). The implant procedure produced 62 perioperative complications in 53 (9.3%) MIRACLE trial patients; 159 in 135 (21.1%) MIRACLE ICD study randomized phase patients and 71 in 62 (13.9%) general phase patients (p < 0.05 vs. randomized); and 41 in 37 (8.8%) InSync III study patients (p = NS vs. the MIRACLE study). We observed 73 postoperative complications in 62 (11.7%) MIRACLE trial patients, 77 in 68 (11.9%) MIRACLE ICD study randomized phase patients and 56 in 45 (11.0%) general phase patients (p = NS), and 37 in 34 (8.6%) InSync III study patients (p = NS). A total of 8% of patients required reoperation to treat lead dislodgement, extracardiac stimulation, or infection during follow-up. Conclusions: Transvenous CRT system implantation appears safe, well-tolerated, has a high success rate, and improves with operator experience and the addition of new technologies. [Copyright &y& Elsevier]

Objectives: The InSync III study evaluated sequential cardiac resynchronization therapy (CRT) in patients with moderate-to-severe heart failure and prolonged QRS. Background: Simultaneous CRT improves hemodynamic and clinical performance in patients with moderate-to-severe heart failure (HF) and a wide QRS. Recent evidence suggests that sequentially stimulating the ventricles might provide additional benefit. Methods: This multicenter, prospective, nonrandomized, six-month trial enrolled a total of 422 patients to determine the effectiveness of sequential CRT in patients with New York Heart Association (NYHA) functional class III or IV HF and a prolonged QRS. The study evaluated: whether patients receiving sequential CRT for six months experienced improvement in 6-min hall walk (6MHW) distance, NYHA functional class, and quality of life (QoL) over control group patients from the reported Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial; whether sequential CRT increased stroke volume compared to simultaneous CRT; and whether an increase in stroke volume translated into greater clinical improvements compared to patients receiving simultaneous CRT. Results: InSync III patients experienced greater improvement in 6MHW, NYHA functional class, and QoL at six months compared to control (all p < 0.0001). Optimization of the sequential pacing increased (median 7.3%) stroke volume in 77% of patients. No additional improvement in NYHA functional class or QoL was seen compared to the simultaneous CRT group; however, InSync III patients demonstrated greater exercise capacity. Conclusions: Sequential CRT provided most patients with a modest increase in stroke volume above that achieved during simultaneous CRT. Patients receiving sequential CRT had improved exercise capacity, but no change in functional status or QoL. [Copyright &y& Elsevier]