Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly different from heart failure with reduced EF in terms of etiology and natural history (Graziani et al., 2018). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (Crea et al., 2017). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (Paulus and Tschope, 2013). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (Ohanyan et al., 2018). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-β) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (Graziani et al., 2018;Lam et al., 2018). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart

Nonspecific chest pain and 30-day unplanned readmissions in the United States (From the Nationwide Readmission Database)

Chest pain is a common reason for admission to hospital and little is known regarding 30-day unplanned readmissions after an admission with a primary discharge diagnosis of nonspecific chest pain. We analyzed patients with a primary diagnosis of nonspecific chest pain in the Nationwide Readmission Database who were admitted in 2010 to 2014. Rates, causes, and predictors of 30-day unplanned readmissions were determined. A total of 1,842,270 patients had a diagnosis of nonspecific chest pain. The 30-day unplanned readmission rate was 8.6%. From 2010 to 2014, there was an increase in 30-day unplanned readmissions from 8.1% to 9.5%. The majority of 30-day unplanned readmissions were for noncardiac reasons (73.4%). The 3 most prevalent noncardiac causes for readmissions were neuropsychiatric (10.9%), gastrointestinal (10.5%), and infections (9.9%), while the 3 most prevalent cardiac causes were coronary artery disease including angina (8.4%), arrhythmias (6.6%), and heart failure 5.5%. The strongest predictors of readmission were alcohol misuse ([OR] odds ratio 1.74 95% [CI] confidence interval 1.66-1.81), renal failure (OR 1.82 95%CI 1.76-1.87), cancer (OR 2.40 95%CI 2.27-2.53), discharge to a nursing home (OR 2.26 95%CI 2.18-2.34), and discharge against medical advice (OR 1.94 95%CI 1.86-2.02). The rate of 30-day unplanned readmission was 6.1% among those who received any test compared to 9.3% in those who did not receive any test. Rates of early unplanned readmissions occur following 1 in 12 admissions for nonspecific chest pain with noncardiac causes being the most common reason. Patients who receive a cardiovascular investigation appear to have fewer unplanned readmissions

Cervical length varies considering different populations and gestational outcomes : Results from a systematic review and meta-analysis

Funding: This work was supported by the Bill & Melinda Gates Foundation, Seattle, WA [OPP1107597], the Brazilian Ministry of Health and the Brazilian National Council for Scientific and Technological Development (CNPq) [401615/20138]. RCP and BM received funds for the study. No author received salary from any funders and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Coronary microvascular dysfunction in heart failure with preserved ejection fraction: not the end but the end of the beginning

This article refers to 'Coronary microvascular dysfunction is associated with exertional haemodynamic abnormalities in patients with heart failure with preserved ejection fraction' by A. Ahmad et al., published in this issue on page

Catestatin in acutely decompensated heart failure patients: Insights from the CATSTAT-HF study

The role of catestatin (CST) in acutely decompensated heart failure (ADHF) and myocardial infarction (MI) is poorly elucidated. Due to the implicated role of CST in the regulation of neurohumoral activity, the goals of the study were to determine CST serum levels among ninety consecutively enrolled ADHF patients, with respect to the MI history and left ventricular ejection fraction (LVEF) and to examine its association with clinical, echocardiographic, and laboratory parameters. CST levels were higher among ADHF patients with MI history, compared to those without (8.94 ± 6.39 vs. 4.90 ± 2.74 ng/mL, p = 0.001). CST serum levels did not differ among patients with reduced, midrange, and preserved LVEF (7.74 ± 5.64 vs. 5.75 ± 4.19 vs. 5.35 ± 2.77 ng/mL, p = 0.143, respectively). In the multivariable linear regression analysis, CST independently correlated with the NYHA class (β = 0.491, p < 0.001), waist-to-hip ratio (WHR) (β = −0.237, p = 0.026), HbA1c (β = −0.235, p = 0.027), LDL (β = −0.231, p = 0.029), non-HDL cholesterol (β = −0.237, p = 0.026), hs-cTnI (β = −0.221, p = 0.030), and the admission and resting heart rate (β = −0.201, p = 0.036 and β = −0.242, p = 0.030), and was in positive association with most echocardiographic parameters. In conclusion, CST levels were increased in ADHF patients with MI and were overall associated with a favorable cardiometabolic profile but at the same time reflected advanced symptomatic burden (CATSTAT-HF ClinicalTrials.gov number, NCT03389386)

Catestatin in acutely decompensated heart failure patients: Insights from the CATSTAT-HF study

The role of catestatin (CST) in acutely decompensated heart failure (ADHF) and myocardial infarction (MI) is poorly elucidated. Due to the implicated role of CST in the regulation of neurohumoral activity, the goals of the study were to determine CST serum levels among ninety consecutively enrolled ADHF patients, with respect to the MI history and left ventricular ejection fraction (LVEF) and to examine its association with clinical, echocardiographic, and laboratory parameters. CST levels were higher among ADHF patients with MI history, compared to those without (8.94 ± 6.39 vs. 4.90 ± 2.74 ng/mL, p = 0.001). CST serum levels did not differ among patients with reduced, midrange, and preserved LVEF (7.74 ± 5.64 vs. 5.75 ± 4.19 vs. 5.35 ± 2.77 ng/mL, p = 0.143, respectively). In the multivariable linear regression analysis, CST independently correlated with the NYHA class (β = 0.491, p < 0.001), waist-to-hip ratio (WHR) (β = −0.237, p = 0.026), HbA1c (β = −0.235, p = 0.027), LDL (β = −0.231, p = 0.029), non-HDL cholesterol (β = −0.237, p = 0.026), hs-cTnI (β = −0.221, p = 0.030), and the admission and resting heart rate (β = −0.201, p = 0.036 and β = −0.242, p = 0.030), and was in positive association with most echocardiographic parameters. In conclusion, CST levels were increased in ADHF patients with MI and were overall associated with a favorable cardiometabolic profile but at the same time reflected advanced symptomatic burden (CATSTAT-HF ClinicalTrials.gov number, NCT03389386)