Circulating troponin and further left ventricular ejection fraction improvement in patients with previously recovered left ventricular ejection fraction.

AIMS: The aim of this study is to determine factors associated with long-term recovery of left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF) and if further recovery also occurs in this group. METHODS AND RESULTS: Among 621 participants enrolled in the Alberta Heart Failure Etiology and Analysis Team (HEART) Study, 316 with Stage C HF underwent comprehensive imaging and biomarker testing at enrolment and at 1-year follow up. Using pre-enrolment data, HF with recovered EF (HFrecEF) was defined as an absolute improvement ≥5% in LVEF from the prior lowest LVEF value, with a final LVEF value > 35% at or prior to study baseline. Participants with all LVEF > 40% were included for comparison. Hospitalization-free survival to 5 years was performed. The median cohort age was 66 years, and time from diagnosis was 4 years; 82% were male patients. Of the 316 patients, 95 (30%) patients had HFrecEF and 56 (18%) patients pHFrEF. On multivariate analysis, only shorter duration of HF was predictive of HFrecEF status. Over 1 year, LVEF increased in the HFrecEF group 4.0% (0.15-7.90, P = 0.042) as compared with persistent HFrEF, who in turn demonstrated higher baseline serum high sensitivity Troponin-T with further increase at follow up 0.55(0.33-0.86, P = 0.011). No change in any parameter in the HFpEF/HFmrEF group at follow up was observed. CONCLUSIONS: Patients with HFrecEF demonstrate evidence of additional late improvement in LVEF and unchanged troponin levels, in contrast to those with persistent HFrEF, where LVEF does not improve and serum troponin rises over time. These data help to inform mechanisms relating to late LV remodelling.

Recombinant human erythropoietin in the treatment of acute ischemic stroke.

BACKGROUND AND PURPOSE: Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke. METHODS: This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40,000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for. RESULTS: Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke. CONCLUSIONS: Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.

Update on anemia management in nephrology, including current guidelines on the use of erythropoiesis-stimulating agents and implications of the introduction of "biosimilars".

Several million patients with chronic kidney disease (CKD) have benefited from the use of erythropoiesis-stimulating agents (ESAs) to correct severe anemia. However, mortality data now suggest that treating CKD patients to achieve a hemoglobin (Hb) level >13 g/dl can be harmful. For levels of 11.5-13 g/dl, there is no evidence of either harm or benefit compared with a lower Hb level. Quality of life studies are variable in quality but do suggest superior outcomes and functional status. In the 9 years following 1997, the target Hb level recommended by international guidelines tended to increase, especially for patients without accompanying cardiovascular disease. However, strangely enough, the most recent target level of the Kidney Disease Outcomes Quality Initiative is 11-12 g/dl, which is exactly the range advocated by the same group a decade earlier. The relative importance of quality of life compared with other outcomes, the use of iron, and the impact of venous thrombotic events continue to be debated. In addition, new issues have arisen from the introduction of "biosimilar" erythropoietins, biopharmaceuticals that refer to the existing agents and are submitted for marketing authorization after the existing agents' protection expires. Biosimilars can resemble the agents on which they are modeled but cannot fully copy their properties. The complexity in molecular structure, the possible presence of impurities (which may include bacterial endotoxins), and the inherent immunogenicity of such agents have required authorities to develop a sophisticated regulatory framework.