ST2 and Multimarker Testing in Acute Decompensated Heart Failure

Most data on heart failure biomarkers have been derived from patient cohorts with chronic disease. However, risk prediction in patients admitted with acute decompensated heart failure (ADHF) remains a challenge. ADHF is not a single disease: it presents in various manners, and different causes may underlie ADHF, which may be reflected by different biomarkers. Soluble suppression of tumorigenicity 2 (ST2) has been shown to be a strong independent predictor of short-, mid-, and long-term outcome in ADHF. Furthermore, combining biomarkers may help further improve the prognostic power of ST2. The ProBNP Investigation of Dyspnea in the Emergency Department study showed that elevated plasma levels of ST2 together with elevated levels of 4 other biomarkers have clear incremental values to predict outcome in ADHF. The Multinational Observational Cohort on Acute Heart Failure study is an international collaborative network that recruited 5,306 patients hospitalized for ADHF that demonstrated that ST2 and midregional pro-adrenomedulin had independently strong value to predict 30-day and 1-year outcome in patients with ADHF. The Multinational Observational Cohort on Acute Heart Failure study also showed that C-reactive protein plus ST2 better classified risk in patients with ADHFs than ST2 alone. Combining biomarkers for risk prediction or risk stratification might have clinical and more importantly pathophysiological meaning

Overlapping Effects of miR-21 Inhibition and Drugs for Idiopathic Pulmonary Fibrosis: Rationale for Repurposing Nintedanib as a Novel Treatment for Ischemia/Reperfusion Injury

ABSTRACT: A specific anti-miR-21 has emerged as an effective treatment for ischemia/reperfusion injury in a pig model of myocardial infarction (MI), but the perspectives for clinical translation are limited. Anti-miR-21 blunts profibrotic pathways, whose excessive activation is detrimental in the post-MI setting. Repurposing antifibrotic drugs approved for other indications is a possible strategy. We compared the molecular effects of anti-miR-21 and the 2 drugs approved for idiopathic pulmonary fibrosis (nintedanib and pirfenidone) through a bioinformatic approach. We report that nintedanib and anti-miR-21 share many targets, including the proto-oncogene Rous sarcoma oncogene cellular homolog. Conversely, pirfenidone and anti-miR-21 do not have common mechanisms of action. In summary, the molecular mechanisms activated by nintedanib are partially overlapping with those elicited by anti-miR-21. Nintedanib could be evaluated in animal studies or clinical trials on MI

Idiopathic Dilated Cardiomyopathy: Molecular Basis and Distilling Complexity to Advance

Cardiomyopathies are heterogeneous diseases of the myocardium associated with abnormal findings of chamber size, wall thickness, and/or functional contractility. In particular, dilated cardiomyopathy (DCM) is mainly characterized by ventricular chamber enlargement with systolic dysfunction and normal left ventricular (LV) wall thickness. Although DCM is thought to be induced mainly by genetic or environmental factors, in the majority of cases, the cause is unknown. With an estimated prevalence of 1:2500 and an incidence of 1:18,000 per year in adults, DCM is the most frequent indication for heart transplantation, which represents an enormous cost burden on healthcare systems. These figures warrant greater accuracy in patient diagnosis and prognosis and further insight into the underlying basis of DCM. Here, we discuss past and recent findings on the molecular mechanisms involved in DCM. Dilated cardiomyopathy has been linked to the overactivation of extracellular signal-regulated kinase (ERK1/2), which in turn is related to activation of low-density lipoprotein receptor–related protein-1 (LRP-1). Moreover, a redistribution of LRP-1 into cholesterol-enriched plasma membrane domains (lipid rafts) and alterations in cardiac DNA methylation have been reported in failing hearts. In conclusion, more comprehensive analyses of myocardial lipid rafts and epigenetic mechanisms may advance our understanding of DCM causes and progression. In turn, this understanding may promote the development of innovative treatments

Potential role for clinical calibration to increase engagement with and application of home telemonitoring: a report from the HeartCycle programme

Aims: There is a need for alternative strategies that might avoid recurrent admissions in patients with heart failure. home telemonitoring (HTM) to monitor patient's symptoms from a distance may be useful. This study attempts to assess changes in HTM vital signs in response to daily life activities (variations in medication, salt intake, exercise, and stress) and to establish which variations affect weight, blood pressure, and heart rate. Methods and results: We assessed 76 patients with heart failure (mean age 76 ± 10.8 years, 75% male, mainly in NYHA class II/III and from ischaemic aetiology cause). Patients were given a calendar of interventions scheduling activities approximately twice a week before measuring their vital signs. Eating salty food or a large meal were the activities that had a significant impact on weight gain (+0.3 kg; P < 0.001 and P = 0.006, respectively). Exercise and skipping a dose of medication other than diuretics increased heart rate (+3 bpm, P = 0.001 and almost +2 bpm, P = 0.016, respectively). Conclusions: Our HTM system was able to detect small changes in vital signs related to these activities. Further studies should assess if providing such a schedule of activities might be useful for patient education and could improve long-term adherence to recommended lifestyle changes