Validation of a claims-based algorithm to identify patients with chronic thromboembolic pulmonary hypertension using electronic health record data.

This study aimed to validate an algorithm developed to identify chronic thromboembolic pulmonary hypertension (CTEPH) among patients with a history of pulmonary embolism. Validation was halted because too few patients had gold-standard evidence of CTEPH in the administrative claims/electronic health records database, suggesting that CTEPH is underdiagnosed.

The Three-Decade Long Journey in Heart Failure Drug Development.

Heart failure is a global disease with increasing prevalence due to an aging worldwide population with increasing co-morbidities. Despite several therapeutic options available to treat HFrEF, morbidity and mortality remain high. Importantly, no approved therapies are available to treat HFpEF. This paper will briefly summarize the burden of disease, HF classification and definitions and the landmark clinical trials in both HFrEF and HFpEF. Given the increasing incidence and prevalence of HF and the high morbidity and mortality associated with this disease, continued development efforts are essential to address the unmet needs of these patients.

Novel sGC Stimulators and sGC Activators for the Treatment of Heart Failure.

The burden of heart failure (HF) increases worldwide with an aging population, and there is a high unmet medical need in both, heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). The nitric oxide (NO) pathway is a key regulator in the cardiovascular system and modulates vascular tone and myocardial performance. Disruption of the NO-cyclic guanosine monophosphate (cGMP) signaling axis and impaired cGMP formation by endothelial dysfunction could lead to vasotone dysregulation, vascular and ventricular stiffening, fibrosis, and hypertrophy resulting in a decline of heart as well as kidney function. Therefore, the NO-cGMP pathway is a treatment target in heart failure. Exogenous NO donors such as nitrates have long been used for treatment of cardiovascular diseases but turned out to be limited by increased oxidative stress and tolerance. More recently, novel classes of drugs were discovered which enhance cGMP production by targeting the NO receptor soluble guanylate cyclase (sGC). These compounds, the so-called sGC stimulators and sGC activators, are able to increase the enzymatic activity of sGC to generate cGMP independently of NO and have been developed to target this important signaling cascade in the cardiovascular system.This review will focus on the role of sGC in cardiovascular (CV) physiology and disease and the pharmacological potential of sGC stimulators and sGC activators therein. Preclinical data will be reviewed and summarized, and available clinical data with riociguat and vericiguat, novel direct sGC stimulators, will be presented. Vericiguat is currently being studied in a Phase III clinical program for the treatment of heart failure with reduced ejection fraction (HFrEF).

Intensive insulin therapy for critically ill patients.

OBJECTIVE: To evaluate the clinical outcomes of glycemic control of intensive insulin therapy and recommend its place in the management of critically ill patients. DATA SOURCES: Searches of MEDLINE (1966-March 2004) and Cochrane Library, as well as an extensive manual review of abstracts were performed using the key search terms hyperglycemia, insulin, intensive care unit, critically ill, outcomes, and guidelines and algorithms. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and deemed relevant if they included and assessed clinical outcomes. DATA SYNTHESIS: Mortality among patients with prolonged critical illness exceeds 20%, and most deaths are attributable to sepsis and multisystem organ failure. Hyperglycemia is common in critically ill patients, even in those with no history of diabetes mellitus. Maintaining normoglycemia with insulin in critically ill patients has been shown to improve neurologic, cardiovascular, and infectious outcomes. Most importantly, morbidity and mortality are reduced with aggressive insulin therapy. This information can be implemented into protocols to maintain strict control of glucose. CONCLUSIONS: Use of insulin protocols in critically ill patients improves blood glucose control and reduces morbidity and mortality in critically ill populations. Glucose levels in critically ill patients should be controlled through implementation of insulin protocols with the goal to achieve normoglycemia, regardless of a history of diabetes. Frequent monitoring is imperative to avoid hypoglycemia.