Cardiovascular medications and regulation of COVID-19 receptors expression

INTRODUCTION: Emerging epidemiological studies suggested that Renin–Angiotensin–Aldosterone system (RAAS) inhibitors may increase infectivity and severity of COVID-19 by modulating the expression of ACE2. METHODS: In silico analysis was conducted to compare the blood expression levels of SARS-CoV-2 entry genes between age and gender matched cohort of hypertensive patients versus control, and to determine the effect of common cardiovascular medications on the expression of COVID-19 receptors in vitro using primary human hepatocytes. RESULTS: The transcriptomic analysis revealed a significant increase of ACE2 and TMPRSS2 in the blood of patients with hypertension. Treatment of primary human hepatocytes with captopril, but not enalapril, significantly increased ACE2 expression. A similar pattern of ACE2 expression was found following the in vitro treatments of rat primary cells with captopril and enalapril. Telmisartan, a second class RAAS inhibitors, did not affect ACE2 levels. We have also tested other cardiovascular medications that may be used alone, or in combination with RAAS inhibitors. Some of these medications increased TMPRSS2, while others, like furosemide, significantly reduced COVID-19 receptors. CONCLUSIONS: The increase in ACE2 expression levels could be due to chronic use of RAAS inhibitors or alternatively caused by other hypertension-related factors or presence of other comorbidities. Treatment of common co-morbidities often require chronic use of multiple medications, which may result in an additive increase in the expression of ACE2 and TMPRSS2. Our data suggest that more research is needed to determine the effect of different medications, as well as medication combinations, on COVID-19 receptors

Effect of Common Medications on the Expression of SARS-CoV-2 Entry Receptors in Kidney Tissue

Besides the respiratory system, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection was shown to affect other essential organs such as the kidneys. Early kidney involvement during the course of infection was associated with worse outcomes, which could be attributed to the direct SARS-CoV-2 infection of kidney cells. In this study, the effect of commonly used medications on the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme (ACE)2, and TMPRSS2 protein in kidney tissues was evaluated. This was done by in silico analyses of publicly available transcriptomic databases of kidney tissues of rats treated with multiple doses of commonly used medications. Of 59 tested medications, 56% modified ACE2 expression, whereas 24% modified TMPRSS2 expression. ACE2 was increased with only a few of the tested medication groups, namely the renin-angiotensin inhibitors, such as enalapril, antibacterial agents, such as nitrofurantoin, and the proton pump inhibitor, omeprazole. The majority of the other medications decreased ACE2 expression to variable degrees with allopurinol and cisplatin causing the most noticeable downregulation. The expression level of TMPRSS2 was increased with a number of medications, such as diclofenac, furosemide, and dexamethasone, whereas other medications, such as allopurinol, suppressed the expression of this gene. The prolonged exposure to combinations of these medications could regulate the expression of ACE2 and TMPRSS2 in a way that may affect kidney susceptibility to SARS-CoV-2 infection. Data presented here suggest that we should be vigilant about the potential effects of commonly used medications on kidney tissue expression of ACE2 and TMPRSS2

18. Effect of standardized catheterization lab order forms on peri-procedural prescription errors, patient care and staff satisfaction

Medication errors are the most common cause of iatrogenic adverse events. They can lead to severe complications, including prolonged hospitalization, unnecessary diagnostic tests and treatments, and even death. Objective:We set to explore the impact of introducing standardized cath lab order forms on medication errors, quality of patient care and staff satisfaction. This was a single center observational study conducted in a tertiary cardiac center in Saudi Arabia. We enrolled a total of 100 consecutive patients who underwent diagnostic or interventional cardiac catheterization before or after the introduction of standardized order forms. The cohort was divided into two equal groups. We compared medication prescription errors (as defined by hospital formulary) between the two groups. We also studies the impact of the standardized order forms on peri-procedural care including laboratory tests order completion, peri-procedural fluid and diabetes management, anticoagulant, diuretic and analgesia management. We have also employed a structured questionnaire to assess staff satisfaction with the use of these forms implementation of standardized order forms resulted in significant reduction of prescription errors from 32.0% to 0.0% (p = 0.025). There was also a significant improvement in patient care as indicated by improvement in the rates of completion of laboratory orders that improved from 76.0% to 96.0% after the implementation of order forms (p = 0.004), proper fluid management (100% vs. 86.0%, p = 0.023) and better peri-procedural diabetic management (see attached table). There was also improvement in the monitoring of the vascular access site (80% vs. 100%, p = 0.004) that resulted in reduction in access site related complications (6% vs. 0%). We administered a satisfaction questionnaire to 61 participants (nurses, physicians and pharmacists). The mean total satisfaction score was 62.8 for pharmacists, 50.4 for nurses and 48.6 for physicians indicating that the pharmacists were most satisfied with the implementation of these order forms and the physicians were the least satisfied (p = 0.052). Our study shows that standardized order forms have the potential to decrease medication-prescribing errors and improve quality of patient care among patients undergoing diagnostic and interventional cardiac procedures

Interrupted versus uninterrupted anticoagulation therapy for catheter ablation in adults with arrhythmias

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. The objective of this review is to systematically compare the efficacy and harms of interrupted versus uninterrupted anticoagulation therapy for catheter ablation (CA) in adults with arrhythmias. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

31. Differential effects of intravenous bolus furosemide and continuous furosemide infusion on in-hospital management and outcomes among patients admitted with acute decompensated heart failure

Loop diuretics are a cornerstone in the management of Acute Decompensated Heart Failure (ADHF). However, the best therapeutic strategy in terms of intermittent boluses versus continuous infusion is still unclear.We set to examine the differences in hospital management and short-term and long-term mortality of patient receiving furosemide bolus or infusion treatment for ADHF.This is a retrospective cohort study of 207 patients admitted to KKUH with ADHF. Clinical data, labs, in-hospital outcomes and long-term mortality data were collected through review of medical records and HEARTS registry database. We stratified our cohort into two groups; furosemide infusion and bolus groups.The Mean age was 61.5 ± 13.87 years, and 66.2% were males. Approximately 42% had left ventricular ejection fraction LVEF <40%. Use of intravenous infusions furosemide and boluses during admission was 42.86% and 57.14%, respectively. Compared to patient received bolus therapy, patients on infusion therapy had more renal impairment at presentation (26.4% vs. 12.5%, p = 0.033) and anemia (18.1% vs. 4.25, P = 0.006). They had less diabetes (30.6% vs. 38.5%, p = 0.006) and prior MI (18.1% vs. 32.3%, p = 0.006). Infusion group received higher total daily diuretic dose (p < 0.001), more Metolazone (19.4% vs. 3.1%, p = 0.002) and mechanical ventilation (11.1% vs. 3.1, p = 0.038). There was no difference in total urine output and renal outcomes between the two groups. The infusion group had longer hospital stay (15.40 ± 12.14 vs. 10.26 ± 6.74 days, p < 0.001). The long-term mortality up to 3 years was significantly higher among patient who received infusion therapy (27.78% vs. 9.38%, p = 0.002). ADHF patients who received furosemide infusion needed higher diuretic dose, had significantly longer hospital stay and higher long-term mortality

Association between preoperative statin therapy and postoperative infectious complications in patients undergoing cardiac surgery: a systematic review and meta-analysis.

Infectious complications of cardiac surgery are often severe and life threatening. Statins having both immunomodulatory and anti-inflammatory effects were intuitively thought to influence the development of postsurgical infections. We sought to systematically examine whether any association exists between statin use and risk of infectious complications in patients undergoing cardiac surgery. We searched Ovid MEDLINE, Ovid EMBASE, Thomson Scientific Web of Science, and Elsevier Scopus from inception through February 2011 for comparative studies examining the association between statin use and risk of postoperative infections in patients undergoing cardiac surgery. We contacted a study's author for missing information. We conducted a random-effects meta-analysis of individual studies' odds ratios (adjusted for potential confounders). We identified 6 cohort studies for inclusion, 3 of which were conducted in Canada and 3 of which were conducted in the United States. Four were single-center studies, and 2 were population based. Exposure ascertainment was based on a review of admission medication list or prescription databases. Infectious outcomes were heterogeneous and included surgical site infections within 30 days, serious infections (sepsis), or any other postoperative infection. Statin use in the preoperative period was associated with a trend toward reduction in the incidence of postoperative infections in patients who underwent cardiac surgery (odds ratio, 0.81 [95% confidence interval, 0.64–1.01]; P = .06; I2 = 75%). Heterogeneity was explained by country effect. Studies performed in Canada showed weaker associations than studies performed in the United States. This difference could not be attributed to study quality alone. We did not find good evidence to support an association between statin use and postoperative infectious complications. However, the trend toward statistical significance for this association indicates that further investigation is warranted

27. The impact of introduction of code-stemi program on clinical outcomes of acute st-elevation myocardial infarction (stemi) patients undergoing primary pci: Single center study in Saudi Arabia

This study was conducted to evaluate the effect of direct Emergency Department activation of the Catheterization Lab on door to balloon (D2B) time and outcomes of acute ST-elevation myocardial infarction (STEMI) patients in King Khalid University Hospital (KKUH). Establishing dedicated comprehensive STEMI programs aiming at reducing door to balloon time will impact favourably the outcomes of patients presenting with acute STEMI. This was a retrospective cohort study that involved 100 patients in KKUH who presented with acute STEMI and underwent primary percutaneous intervention (PPCI), between June 2010 and January 2015. The cohort was divided into two groups, the first group consisted of 50 patients who were treated before establishing the Code-STEMI protocol, whereas the second group were 50 patients who were treated according to the protocol, which was implemented in June 2013. Code-STEMI program is a comprehensive program that includes direct activation of the cath lab team using a single call system, data monitoring and feedback, and standardized order forms. The mean age in both groups was 54 ± 12 years and 86% (43) and 94% (47) of the patients in the two groups were males, respectively. 90% (90) of patients in both groups had one or more comorbidities.Code-STEMI group had a significantly lower D2BT with 70% of patients treated within the recommended 90 minutes (median = 76.5 min, IQR: 63–90 min) compared to only 26% of pre code-STEMI patients (median = 107 min, IQR: 74–149 min) In-hospital complications were lower in the Code-STEMI group; however, the only statistically significant reduction was in non-fatal re-infarction, (8% vs. 0%, p = 0.043). In addition, the number of patients with more than one in-hospital complications was also reduced by 20%.Implementation of direct ER-Catheterization lab activation protocol was associated with a significant reduction in D2B time, and an overall improvement of in-hospital outcomes