Clinical outcomes of intravenous iron therapy in patients with heart failure and iron deficiency: Meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Iron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF. METHODOLOGY: We conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH. RESULTS: Nine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75-0.93; I2 = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85-0.99; I2 = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit. CONCLUSION: In patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.

Differences in Social Hardships in Women and Men with Acute Myocardial Infarction: Impact on 30-Day Readmission.

Background: Studies have shown that women with acute myocardial infarction (AMI) have a higher prevalence of unfavorable social variables then men and have a worse outcome. Less is known regarding the impact of these social variables on 30-day readmission after AMI. Materials and Methods: We analyzed adult patients with AMI enrolled in a Quality Improvement Program intended to improve the peri-discharge care of patients with an AMI, and decrease all-cause 30-day unplanned readmissions. We compared clinical and social variables by gender. Multivariate logistic regression, with separate adjustment for clinical and for social variable, was used to measure adjusted odds for readmission by gender. Results: Among 208 patients included in our project 68 (32.7%) were women. Only 30.9% of women were married or had domestic partner at the time of the interview and only 16.2% were employed. Nearly half of women (48.5%) needed help with medical care, and 39.7% of women did not speak English as their first language. These variables were significantly different by gender. Rates of 30-day readmissions were higher in women than men (22.1% vs. 7.8%, p = 0.024). After adjusting for clinical variables this difference by gender in 30-day readmissions remained significant (odds ratio [OR] 3.34 95% confidence interval [CI] 1.1-11.1, p = 0.049). However, when adjusting for social variables, this difference was no longer noted (OR 0.87 95% CI 0.27-2.78, p = 0.822). Conclusion: Women with AMI are more likely than men to have unfavorable social factors that can impact recovery from AMI and women have a higher 30-day readmission rate. The higher 30-day readmissions in women appears to be influenced by these social factors. Health care interventions aimed at reducing 30-day readmission after AMI should focus on eliciting a detailed social history and providing aid for those requiring additional social support at home.

Unsupervised clustering for phenotypic stratification of clinical, demographic, and stress attributes of cardiac risk in patients with nonischemic exercise stress echocardiography.

INTRODUCTION AND AIM: Patients undergoing exercise echocardiography with no evidence of myocardial ischemia are considered a low-risk group; however, this group is likely heterogeneous in terms of short-term adverse events and subsequent cardiac testing. We hypothesized that unsupervised cluster modeling using clinical and stress characteristics can detect heterogeneity in cardiovascular risk and need for subsequent cardiac testing among these patients. METHODS: We retrospectively studied 445 patients who had exercise echocardiography results negative for myocardial ischemia. All patients were followed for adverse cardiovascular events, subsequent cardiac testing, and nonacute coronary syndrome (ACS) revascularization. The heterogeneity of the study subjects was tested using computational clustering, an exploratory statistical method designed to uncover invisible natural groups within data. Clinical and stress predictors of adverse events were extracted and used to construct 3 unsupervised cluster models: clinical, stress, and combined. The study population was split into training (357 patients) and testing sets (88 patients). RESULTS: In the training set, the clinical, stress, and combined cluster models yielded 5, 4, and 3 clusters, respectively. Each model had 1 high-risk and 1 low-risk cluster while other clusters were intermediate. The combined model showed a better predictive ability compared to the clinical or stress models alone. The need for future testing mirrored the pattern of adverse cardiovascular events. A risk score derived from the combined cluster model predicted end points with acceptable accuracy. The patterns of risk and the calculated risk scores were preserved in the testing set. CONCLUSIONS: Patients with no evidence of ischemia on exercise stress echocardiography represent a heterogeneous group. Cluster-based modeling using combined clinical and stress characteristics can expose this heterogeneity. The findings can help better risk-stratify this group of patients and aid cost-effective healthcare utilization toward better diagnostics and therapeutics.

Manipulation of ACE2 expression in COVID-19.

SARS-CoV-2 is the virus responsible for the ongoing COVID-19 outbreak. The virus uses ACE2 receptor for viral entry. ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium. There is, however, significant controversy regarding the role of ACE2 expression in COVID-19 pathogenesis. Some have argued that decreasing ACE2 expression would result in decreased susceptibility to the virus by decreasing available binding sites for SARS-CoV-2 and restricting viral entry into the cells. Others have argued that, like the pathogenesis of other viral pneumonias, including those stemming from previous severe acute respiratory syndrome (SARS) viruses, once SARS-CoV-2 binds to ACE2, it downregulates ACE2 expression. Lack of the favourable effects of ACE2 might exaggerate lung injury by a variety of mechanisms. In order to help address this controversy, we conducted a literature search and review of relevant preclinical and clinical publications pertaining to SARS-CoV-2, COVID-19, ACE2, viral pneumonia, SARS, acute respiratory distress syndrome and lung injury. Our review suggests, although controversial, that patients at increased susceptibility to COVID-19 complications may have reduced baseline ACE2, and by modulating ACE2 expression one can possibly improve COVID-19 outcomes. Herein, we elucidate why and how this potential mechanism might work.