Peter van der Meer

Anemia and Mortality in Heart Failure Patients: A Systematic Review and Meta-Analysis

OBJECTIVES The aim of this study was to assess the effect of anemia on mortality in chronic heart failure (CHF). BACKGROUND Anemia is frequently observed in patients with CHF, and evidence suggests that anemia might be associated with an increased mortality. METHODS A systematic literature search in MEDLINE (through November 2007) for English language articles was performed. In addition, a manual search was performed. We included cohort studies and retrospective secondary analyses of randomized controlled trials whose primary objective was to analyze the association between anemia and mortality in CHF. Of a total of 1,327 initial studies, we included 34 studies, comprising 153,180 patients. Information on study design, patient characteristics, outcome, and potential confounders were extracted. RESULTS Anemia was defined by criteria used in the original articles. Of the 153,180 CHF patients, 37.2% were anemic. After a minimal follow-up of 6 months, 46.8% of anemic patients died compared with 29.5% of nonanemic patients. Crude mortality risk of anemia was odds ratio 1.96 (95% confidence interval: 1.74 to 2.21, p < 0.001). Lower baseline hemoglobin values were associated with increased crude mortality rates (r = -0.396, p = 0.025). Adjusted hazard ratios showed an increased adjusted risk for anemia (hazard ratio 1.46 [95% confidence interval: 1.26 to 1.69, p < 0.001]). Subgroup analysis showed no significant difference between mortality risk of anemia in diastolic or systolic CHF. CONCLUSIONS Anemia is associated with an increased risk of mortality in both systolic and diastolic CHF. Anemia should, therefore, be considered as a useful prognosticator, and therapeutic strategies aimed to increase hemoglobin levels in CHF should be investigated.

Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction

Abstract Aims. Galectin-3 is an emerging biomarker which has been studied in relatively small heart failure (HF) cohorts with predominantly systolic HF. We studied the prognostic value of base-line galectin-3 in a large HF cohort, with preserved and reduced left ventricular ejection fraction (LVEF), and compared this to other biomarkers. Methods. We studied 592 HF patients who had been hospitalized for HF and were followed for 18 months. The primary end-point was a composite of all-cause mortality and HF hospitalization. Results. A doubling of galectin-3 levels was associated with a hazard ratio (HR) of 1.97 (1.62–2.42) for the primary outcome (P < 0.001). After correction for age, gender, BNP, eGFR, and diabetes the HR was 1.38 (1.07–1.78; P = 0.015). Galectin-3 levels were correlated with higher IL-6 and CRP levels (P < 0.002). Changes of galectin-3 levels after 6 months did not add prognostic information to the base-line value (n = 291); however, combining plasma galectin-3 and BNP levels increased prognostic value over either biomarker alone (ROC analysis, P < 0.05). The predictive value of galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to patients with reduced LVEF (P < 0.001). Conclusions. Galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF.

Red blood cell distribution width and 1-year mortality in acute heart failure.

Red blood cell distribution width (RDW) predicts mortality in chronic heart failure (HF) and stable coronary artery disease. The prognostic value of RDW in more acute settings such as acute HF, and its relative prognostic value compared with more established measures such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), remains unknown.

Generation of Functional Ventricular Heart Muscle from Mouse Ventricular Progenitor Cells

A Fix to the Heart Regenerative cardiovascular medicine is a promising avenue for therapeutic application in advanced heart failure. Although clinical trials have suggested some limited benefits in cell transplantation therapy, robust cardiac muscle formation is lacking. Domian et al. (p. 426) examined the developmental processes in normal mature cardiac muscle. A two-color murine reporter system was used to isolate committed ventricular progenitors, which were then used to build functional force-generating cardiac tissue. Such combinations of tissue engineering and stem cell biology may eventually lead to cardiac regenerative therapy. A combination of tissue engineering and stem cell biology is used to build functional force-generating mouse cardiac tissue. The mammalian heart is formed from distinct sets of first and second heart field (FHF and SHF, respectively) progenitors. Although multipotent progenitors have previously been shown to give rise to cardiomyocytes, smooth muscle, and endothelial cells, the mechanism governing the generation of large numbers of differentiated progeny remains poorly understood. We have employed a two-colored fluorescent reporter system to isolate FHF and SHF progenitors from developing mouse embryos and embryonic stem cells. Genome-wide profiling of coding and noncoding transcripts revealed distinct molecular signatures of these progenitor populations. We further identify a committed ventricular progenitor cell in the Islet 1 lineage that is capable of limited in vitro expansion, differentiation, and assembly into functional ventricular muscle tissue, representing a combination of tissue engineering and stem cell biology.

Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients

AIMS We examined the adequacy of endogenous erythropoietin (EPO) levels for the degree of anaemia in patients with chronic heart failure (CHF) and its relation to prognosis. METHODS AND RESULTS We studied 74 anaemic CHF patients from a cohort of 240 patients. The adequacy of endogenous EPO levels was assessed by derived observed/predicted (O/P) ratio. A ratio value < 0.92 indicates EPO levels lower than expected, whereas a value > 1.09 indicates EPO levels higher than expected. The primary endpoint was mortality. During a median follow up of 4.9 years, 35 of the 74 (47.3%) anaemic patients died. EPO levels lower than expected were observed in 29 patients (39%), whereas EPO levels higher than expected were present in 22 anaemic patients (29%). The Kaplan-Meier analysis revealed that anaemic patients with EPO levels higher than expected had a significantly higher mortality rate compared to patients with EPO levels as expected or EPO levels lower than expected (log-rank: P = 0.024). A higher O/P ratio was an independent predictor of increased mortality risk adjusted for variables including age, sex, haemoglobin, NT-proBNP, and renal function; hazard ratio (HR): 1.020 95%CI (1.004-1.036), P = 0.012. CONCLUSION EPO levels higher than expected, suggesting resistance to the hormone, are common in CHF patients and are associated with a higher mortality.

Functional Differences in Engineered Myocardium from Embryonic Stem Cell-Derived versus Neonatal Cardiomyocytes

Summary Stem cell-derived cardiomyocytes represent unique tools for cell- and tissue-based regenerative therapies, drug discovery and safety, and studies of fundamental heart-failure mechanisms. However, the degree to which stem cell-derived cardiomyocytes compare to mature cardiomyocytes is often debated. We reasoned that physiological metrics of engineered cardiac tissues offer a means of comparison. We built laminar myocardium engineered from cardiomyocytes that were differentiated from mouse embryonic stem cell-derived cardiac progenitors or harvested directly from neonatal mouse ventricles, and compared their anatomy and physiology in vitro. Tissues assembled from progenitor-derived myocytes and neonate myocytes demonstrated similar cytoskeletal architectures but different gap junction organization and electromechanical properties. Progenitor-derived myocardium had significantly less contractile stress and slower longitudinal conduction velocity than neonate-derived myocardium, indicating that the developmental state of the cardiomyocytes affects the electromechanical function of the resultant engineered tissue. These data suggest a need to establish performance metrics for future stem cell applications.

Erythropoietin in cardiovascular diseases: exploring new avenues.

Cardiovascular disease is an important burden in the Western world, with a prevalence that is increasing exponentially. Indeed, the lifetime risk of coronary artery disease at 40 years of age is 1 in 2 for men and 1 in 3 for women, and it is estimated that one-third of the population worldwide will die of cardiovascular disease, with a majority of these deaths related to MI (myocardial infarction) or the complications of MI. Recent research has suggested that EPO (erythropoietin), an endogenous erythropoietic hormone, may have pleiotropic effects well beyond the maintenance of red blood cells, and may have a cardiovascular role as well, including a potentially salutary effect on reperfusion injury. Although findings supportive of a role of EPO as a cardioprotective agent appear promising, the mechanisms behind the observed benefits remain elusive. In the present issue of Clinical Science, Piuhola and co-workers provide an interesting study that may shed light on the effects of EPO (and possibly related compounds) in the context of acute MI.

РЕКОМЕНДАЦИИ ESC ПО ДИАГНОСТИКЕ И ЛЕЧЕНИЮ ОСТРОЙ И ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ 2016

2016 ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HEART FAILURE. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.