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.

Trends, burden, and impact of arrhythmia on cardiac amyloid patients: A 16-year nationwide study from 1999 to 2014.

BACKGROUND: Patients with cardiac amyloidosis (CA) have increased mortality, which can be explained in part by an increased risk of arrhythmias. The burden of arrhythmias in CA, their predictors, and impact on in-hospital outcomes remains unclear. The role of implantable cardioverter-defibrillators (ICD) in this population is also uncertain. METHODS: We queried the National Inpatient Sample (NIS) using ICD-9-CM codes 277.39 and 425.7 to identify CA. Twelve common arrhythmias were extracted using appropriate, validated ICD-9-CM codes. ICD implantation was identified using procedure ICD-9 codes 37.94 to 37.98, 00.51 and 00.54. RESULTS: There were a total of 145,920 CA hospitalizations between 1999 and 2014 in the United States and 56,199 (38.5%) of them were associated with arrhythmias. The prevalence of arrhythmias remained relatively constant from 41.5% in 1999 to 40.2% in 2014. The most common arrhythmia was atrial fibrillation (25.4%). In-patient mortality was significantly higher in CA patients with arrhythmias (10.4% vs 6.5%, P < .001). ICD implantation was performed in 1,381 (0.94%) patients with CA and analysis revealed an incremental trend in implantation over the study period (0.48% in 1999 to 0.65% in 2014). In-hospital mortality was significantly lower in patients who underwent ICD implantation (3.7% vs 8%; P = .0078). CA patients with arrhythmias also had an increased cost of hospitalization and length of stay ($65,046 ± 1,079 vs $53,322 ± 687 and 8.3 ± 0.1 vs 7.4 ± 0.1 days, respectively; P < .0001). CONCLUSION: Cardiac arrhythmias are common in patients with CA and are associated with worse in-hospital outcomes, increased length of stay, and cost of hospitalization.

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.

Pharmacological management of hypertension in the elderly and frail populations.

INTRODUCTION: Cardiovascular disease is a leading cause of mortality in the elderly. Hypertension is an important modifiable risk factor that contributes to cardiovascular morbidity and mortality. The prevalence of hypertension is known to increase with age, and hypertension has been associated with an increase in risk for cardiovascular disease in the elderly. There is a wealth of evidence that supports aggressive control of blood pressure to lower cardiovascular risk in the general population. However, there are limited data to guide management of hypertension in the elderly and frail patient subgroups. These subgroups are inadequately treated due to lack of clarity regarding blood pressure thresholds, treatment targets, comorbidities, frailty, drug interactions from polypharmacy, and high cost of care. Areas covered: We review the current evidence behind the definition, goals, and treatments for hypertension in the elderly and frail and outline a strategy that can be used to guide antihypertensive pharmacotherapy in this population. Expert commentary: Lower blood pressure to < 130/80 mm Hg in elderly patients if tolerated and promote use of combination therapy if the blood pressure is > 20/10 mm Hg over the goal blood pressure. Antihypertensive treatment regimens must be tailored to each individual based on their comorbidities, risk for adverse effects, and potential drug interactions ( Figure 1 ).

Nationwide Trends in Hospital Outcomes and Utilization After Lower Limb Revascularization in Patients on Hemodialysis.

OBJECTIVES: This study aimed to describe the temporal trends and outcomes of endovascular and surgical revascularization in a large, nationally representative sample of patients with end-stage renal disease on hemodialysis hospitalized for peripheral artery disease (PAD). BACKGROUND: PAD is prevalent among patients with end-stage renal disease on hemodialysis and is associated with significant morbidity and mortality. There is a paucity of information on trends in endovascular and surgical revascularization and post-procedure outcomes in this population. METHODS: We used the Nationwide Inpatient Sample (2002 to 2012) to identify hemodialysis patients undergoing endovascular or surgical procedures for PAD using diagnostic and procedural codes. We compared trends in amputation, post-procedure complications, mortality, length of stay, and costs between the 2 groups using trend tests and logistic regression. RESULTS: There were 77,049 endovascular and 29,556 surgical procedures for PAD in hemodialysis patients. Trend analysis showed that endovascular procedures increased by nearly 3-fold, whereas there was a reciprocal decrease in surgical revascularization. Post-procedure complication rates were relatively stable in persons undergoing endovascular procedures but nearly doubled in those undergoing surgery. Surgery was associated with 1.8 times adjusted odds (95% confidence interval: 1.60 to 2.02) for complications and 1.6 times the adjusted odds for amputations (95% confidence interval: 1.40 to 1.75) but had similar mortality (adjusted odds ratio: 1.05; 95% confidence interval: 0.85 to 1.29) compared with endovascular procedures. Length of stay for endovascular procedures remained stable, whereas a decrease was seen for surgical procedures. Overall costs increased marginally for both procedures. CONCLUSIONS: Rates of endovascular procedures have increased, whereas those of surgeries have decreased. Surgical revascularization is associated with higher odds of overall complications. Further prospective studies and clinical trials are required to analyze the relationship between the severity of PAD and the revascularization strategy chosen.