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Concept: Heart failure

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Background Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function. Methods We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96 hours after random assignment. Patients were followed for 60 days. Results Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96 hours after enrollment (P=0.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96 hours, the mean change in the creatinine level was -0.04±0.53 mg per deciliter (-3.5±46.9 μmol per liter) in the pharmacologic-therapy group, as compared with +0.23±0.70 mg per deciliter (20.3±61.9 μmol per liter) in the ultrafiltration group (P=0.003). There was no significant difference in weight loss 96 hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5±5.1 kg [12.1±11.3 lb] and 5.7±3.9 kg [12.6±8.5 lb], respectively; P=0.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs. 57%, P=0.03). Conclusions In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00608491 .).

Concepts: Clinical trial, Heart failure, Renal physiology, Blood urea nitrogen, Creatinine, Adverse event, Kilogram, Acute decompensated heart failure

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 To determine the impact of the Hospital Value-Based Purchasing (HVBP) program-the US pay for performance program introduced by Medicare to incentivize higher quality care-on 30 day mortality for three incentivized conditions: acute myocardial infarction, heart failure, and pneumonia.

Concepts: Myocardial infarction, Atherosclerosis, Hospital, Cardiology, Heart failure, Percutaneous coronary intervention, Necrosis, Emergency department

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Aggressive diuretic therapy in a patient who is hospitalized for acute decompensated heart failure often leads to progressive renal dysfunction despite persistent congestion. The underlying mechanisms of this so-called acute cardiorenal syndrome are complex and not fully understood.(1),(2) As initial therapy in this setting, ultrafiltration as compared with diuretic therapy may result in a higher rate of sodium and volume removal, with greater weight loss and less frequent rehospitalizations.(3),(4) These findings have suggested that ultrafiltration can provide more effective relief of congestion than pharmacologic therapy can, particularly in the setting of cardiorenal compromise. Ultrafiltration may also reduce diuretic-induced . . .

Concepts: Medicine, Hospital, Heart failure, Diuretic, Acute accent, Acute decompensated heart failure

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BACKGROUND: A high index of suspicion is required to make this diagnosis of constrictive pericarditis (CP) in patients presenting with cirrhosis and volume overload, as they can otherwise go misdiagnosed for years. METHODS: Case report. FINDINGS: A 51 year-old man with a history of presumed alcoholic cirrhosis presented to the emergency department with anasarca. Abdominal ultrasound with Doppler demonstrated a nodular cirrhotic liver, but no evidence of portal hypertension or ascites. The chest x-ray, however, was significant for a right-sided pleural effusion and pericardial calcification, suggestive of (CP). Transthoracic echocardiogram and ECG-gated computerized tomography scan of the chest without IV contrast confirmed the diagnosis. The patient was referred to thoracic surgery for definitive pericardiectomy. CONCLUSION: The diagnosis of CP is often neglected by admitting physicians, who usually attribute the symptoms to another disease process. Although a multimodality approach is necessary for the diagnosis of CP, this case highlights the utility of chest x-ray, a relatively non-invasive and inexpensive test, in expediting the diagnosis.

Concepts: Heart failure, Echocardiography, Medical imaging, Cirrhosis, Ascites, Pleural effusion, Hepatorenal syndrome, Wilson's disease

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BACKGROUND: Heart failure (HF) patients have a high risk of death, and implantable cardioverter defibrillators (ICDs) are effective in preventing sudden cardiac death (SCD). However, a certain percentage of patients may not be immediate candidates for ICDs, particularly those having a short duration of risk or an uncertain amount of risk. This includes the newly diagnosed patients, as well as those on the cardiac transplant list or NYHA class IV heart failure patients who do not already have an ICD. In these patients, a wearable cardioverter defibrillator (WCD) may be used until long term risk of SCD is defined. The purpose of this study was to determine the incidence of SCD in this population, and the efficacy of early defibrillation by a WCD. METHODS: Ten enrolling centers identified 89 eligible HF patients who were either listed for cardiac transplantation, diagnosed with dilated cardiomyopathy, or receiving inotropic medications. Data collected included medical history, device records, and outcomes (including 90 day mortality). RESULTS: Out of 89 patients, final data on 82 patients has been collected. Patients wore the device for 75+/-58 days. Mean age was 56.8+/-13.2, and 72% were male. Most patients (98.8%) were diagnosed with dilated cardiomyopathy with a low ejection fraction (<40%) and twelve were listed for cardiac transplantation. Four patients were on inotropes. There were no sudden cardiac arrests or deaths during the study. Interestingly, 41.5% of patients were much improved after WCD use, while 34.1% went on to receive an ICD. CONCLUSIONS: In conclusion, the WCD monitored HF patients until further assessment of risk. The leading reasons for end of WCD use were improvement in left ventricular ejection fraction (LVEF) or ICD implantation if there was no significant improvement in LVEF.

Concepts: Myocardial infarction, Cardiology, Cardiomyopathy, Heart failure, Ejection fraction, Implantable cardioverter-defibrillator, Cardiac arrest, Ventricular fibrillation

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Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth mediators but its contribution to tumour biology has not been investigated. We aimed to examine the potential effects of MPE in promoting growth, migration and chemo-resistance of mesothelioma.

Concepts: Cancer, Biology, Pneumonia, Heart failure, Pleural effusion, Pleurodesis, Thoracentesis

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In acute decompensated heart failure (ADHF) the risk of acute kidney injury (AKI) is high. Early detection of patients at risk for AKI is important. We tested urinary [TIMP-2] × [IGFBP7], a new US Food and Drug Administration-cleared test to assess AKI risk, in a cohort of hospitalized ADHF patients.

Concepts: Kidney, Hospital, Heart failure, Acute kidney injury, Cardiovascular diseases, Andrew Martin, Acute decompensated heart failure

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Background Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia. Methods In this randomized, double-blind trial, we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter) to receive either darbepoetin alfa (to achieve a hemoglobin target of 13 g per deciliter) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure. Results The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin alfa group and 565 of 1142 patients (49.5%) in the placebo group (hazard ratio in the darbepoetin alfa group, 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes. The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups. Fatal or nonfatal stroke occurred in 42 patients (3.7%) in the darbepoetin alfa group and 31 patients (2.7%) in the placebo group (P=0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the darbepoetin alfa group and 114 patients (10.0%) in the placebo group (P=0.01). Cancer-related adverse events were similar in the two study groups. Conclusions Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Our findings do not support the use of darbepoetin alfa in these patients. (Funded by Amgen; RED-HF ClinicalTrials.gov number, NCT00358215 .).

Concepts: Hemoglobin, Clinical trial, Red blood cell, Heart failure, Anemia, Clinical research, Darbepoetin alfa, Amgen

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Background Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. Methods In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). Results In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. Conclusions Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493 .).

Concepts: Clinical trial, Myocardial infarction, Medical terms, Cardiology, Heart failure, Ejection fraction, Atrial natriuretic peptide, Isosorbide mononitrate

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Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

Concepts: Protein, Genetics, Cardiology, Cardiomyopathy, Heart failure, Variant type, Dilated cardiomyopathy, Peripartum cardiomyopathy