Polypharmacy in cardiorenal syndrome patients.

Cardiorenal syndrome (CRS) is a term defined as complex interactions between concomitant cardiac and renal dysfunction in which disease of one organ initiates, perpetuates, and/or accelerates the decline in the other. It accounts for a third of presentations with heart failure and is associated with poor clinical outcomes. Polypharmacy (defined as using five or more medications) is common in CRS patients and is associated with worst clinical outcomes. The risk for polypharmacy increases to several fold with associated comorbidities, poses risks to the overall health of the patient, and enhances non-compliance to essential medications. Deprescribing non-essential medications, coordination between multiple specialties to mitigate the risk of polypharmacy, pharmacist- and nurse-led clinics to improve adherence to medications, use of polypills and telemonitoring are various methods to reduce polypharmacy. In this paper, we highlight different strategies to prevent polypharmacy and improve compliance and adherence to essential medications.

Anticoagulation practices and complications associated with Impella® support at an advanced cardiac center in the Middle East gulf region.

Anticoagulation during Impella® support is a challenge due to its complications and inconsistent practice across the globe. This observational, retrospective chart review included all patients with Impella® support at our advanced cardiac center at a quaternary care hospital in the Middle East gulf region. The study was conducted over six years (2016-2022), a time period during which manufacturer recommendations for purge solution, anticoagulation protocols as well as Impella® place in therapy and utilization were all evolving. We aimed to evaluate the efficacy of different anticoagulation practices and association with complications and outcomes. Forty-one patients underwent Impella® during the study period, including 25 patients with support for more than 12 h, and are the focus of our analysis. Cardiogenic shock (n = 25, 60.9%) was the primary indication for Impella®, followed by facilitating high-risk PCI (n = 15, 36.7%) and left ventricular afterload reduction in patients undergoing veno-arterial extracorporeal membrane oxygenation (n = 1, 2.4%). Our overall Impella® usage evolved over the years from a primary use to facilitate a high-risk PCI to the recent more common use of LV unloading in cardiogenic shock. No patients experienced device malfunction and the incidence of other complications including ischemic stroke and bleeding were comparable to those reported in the literature (12.2% and 24% respectively). The 30-day all-cause mortality of 41 patients was 53.6%. In line with the evolving recommendations and evidence, we observed an underutilization of non-heparin-based purge solutions and inconsistent management of anticoagulation in the setting of both Impella® and VA ECMO which necessitates more education and protocols.

Heart failure and COVID-19.

Heart failure is a common disease state that can be encountered at different stages in the course of a COVID-19 patient presentation. New or existing heart failure in the setting of COVID-19 can present a set of unique challenges that can complicate presentation, management, and prognosis. A careful understanding of the hemodynamic and diagnostic implications is essential for appropriate triage and management of these patients. Abnormal cardiac biomarkers are common in COVID-19 and can stem from a variety of mechanisms that involve the viral entry itself through the ACE2 receptors, direct cardiac injury, increased thrombotic activity, stress cardiomyopathy, and among others. The cytokine storm observed in this pandemic can be a culprit in many of the observed mechanisms and presentations. A correct understanding of the two-way interaction between heart failure medications and the infection as well as the proposed COVID-19 medications and heart failure can result in optimal management. Guideline-directed medical therapy for heart failure should not be interrupted for theoretical concerns but rather based on tolerance and clinical presentation. Initiating specific cardiac or heart failure medications to prevent the infection or mitigate the disease is also not an evidence-based practice at this time. Heart failure patients on advanced therapies including those with heart transplantation will particularly benefit from involving the advanced heart failure team members in the overall management if they contract the virus.

The role of renin-angiotensin system activated phagocytes in the SARS-CoV-2 coronavirus infection.

OBJECTIVE: Management of the pandemic caused by the novel coronavirus SARS-CoV-2 challenges both scientists and physicians to rapidly develop, and urgently assess, effective diagnostic tests and therapeutic interventions. The initial presentation of the disease in symptomatic patients is invariably respiratory, with dry cough being the main symptom, but an increasing number of reports reveal multiple-organ involvement. The aim of this review is to summarize the potential role of the renin-angiotensin system activated phagocytes in the pathogenesis of COVID-19 disease. METHODS: Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "SARS," "COVID-19," "renin-angiotensin-system," "phagocyte," "reactive free radical," "antioxidant," "ARDS," "thrombosis," "myocardial," "ischaemia," "reperfusion," "microvascular," and "ACE2." Abstracts and reports from meetings were not included in this work. Only articles published in English between 1976 and 2020 were reviewed. RESULTS: The cellular target of SARS viruses is the angiotensin-converting enzyme 2, a critical regulating protein in the renin-angiotensin system. The elimination of this enzyme by the viral spike protein results in excessive activation of phagocytes, migration into the tissues via the high endothelial venules, and an oxidative burst. In the case of an overstimulated host immune response, not only devastating respiratory symptoms but even systemic or multiorgan involvement may be observed. CONCLUSIONS: Early-stage medical interventions may assist in returning the exaggerated immune response to a normal range; however, some therapeutic delay might result in excessive tissue damages, occasionally mimicking a systemic disease with a detrimental outcome.

Appropriateness of the Direct Oral Anticoagulants Dosing in the Middle East Gulf Region.

ABSTRACT: Direct oral anticoagulants (DOACs) have proven efficacy to prevent cardioembolic strokes. Data are scarce about the appropriateness of DOAC dosing in the Middle East. We investigated the prevalence of inappropriate DOAC dosing in the region. A cross-sectional study was conducted at our hospital between April 2015 and February 2019 of patients receiving 1 of the 3 available DOACs. Patients with incomplete data sets, those prescribed DOACs for indications other than atrial fibrillation, on DOACs for <30 days, and dialysis patients were excluded. A total of 608 met the inclusion criteria. The mean age was 65.2 ± 13.9 years, and most were men (58.6%). The mean CHA2DS2-VASc score was 3.8 ± 2.0. There were 346 (56.9%) on apixaban, 123 (20.2%) on dabigatran, and 139 (22.9%) on rivaroxaban. The logistic regression model showed that for the 3 agents together, age, eGFR, major bleeding history, and history of prior stroke were significantly associated with the decision to inappropriately underdose (P < 0.05). Fifteen patients had an ischemic stroke after apixaban initiation (5 underdosed and 3 overdosed). Among patients with at least one follow-up encounter, major bleeding occurred in 13 patients (11.7%) with inappropriate dosing compared with 29 patients (6.0%) with appropriate dosing (P = 0.04). Ischemic stroke occurred in 11 patients (9.9%) with inappropriate dosing compared with 15 patients (3.1%) with appropriate dosing (P < 0.01). We concluded that inappropriate DOAC underdosing is common in our region, particularly with apixaban and rivaroxaban. It is associated with increased risk of stroke and bleeding. More education targeting prescribers is needed to encourage adherence to standard dosing criteria.

COVID-19: breaking down a global health crisis.

Coronavirus disease 2019 (COVID-19) is the second pandemic of the twenty-first century, with over one-hundred million infections and over two million deaths to date. It is a novel strain from the Coronaviridae family, named Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2); the 7th known member of the coronavirus family to cause disease in humans, notably following the Middle East Respiratory syndrome (MERS), and Severe Acute Respiratory Distress Syndrome (SARS). The most characteristic feature of this single-stranded RNA molecule includes the spike glycoprotein on its surface. Most patients with COVID-19, of which the elderly and immunocompromised are most at risk, complain of flu-like symptoms, including dry cough and headache. The most common complications include pneumonia, acute respiratory distress syndrome, septic shock, and cardiovascular manifestations. Transmission of SARS-CoV-2 is mainly via respiratory droplets, either directly from the air when an infected patient coughs or sneezes, or in the form of fomites on surfaces. Maintaining hand-hygiene, social distancing, and personal protective equipment (i.e., masks) remain the most effective precautions. Patient management includes supportive care and anticoagulative measures, with a focus on maintaining respiratory function. Therapy with dexamethasone, remdesivir, and tocilizumab appear to be most promising to date, with hydroxychloroquine, lopinavir, ritonavir, and interferons falling out of favour. Additionally, accelerated vaccination efforts have taken place internationally, with several promising vaccinations being mass deployed. In response to the COVID-19 pandemic, countries and stakeholders have taken varying precautions to combat and contain the spread of the virus and dampen its collateral economic damage. This review paper aims to synthesize the impact of the virus on a global, micro to macro scale.

Thromboelastography findings in critically ill COVID-19 patients.

The rate of venous and arterial thrombotic events among patients infected with severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) is high. This may be due to a hypercoagulable state induced by the severe inflammation that results from the SAR-CoV-2 infection. We aimed to determine hypercoagulable states' incidence based on thromboelastography study and its association with thrombotic events in critically ill patients with coronavirus disease 2019 (COVID-19). Fifty-two COVID-19 patients who had thromboelastography study were retrospectively included. All patients received pharmacologic thromboprophylaxis. The hypercoagulable state was observed in 16 patients (30.8%). Among them, maximum amplitude and a-angle were elevated in 75% and 25%, respectively. Reaction time and K were low in only 12.5% for both of them. Inflammatory and coagulation markers, as well as thromboprophylaxis regimens, were not associated with a hypercoagulable state. Fourteen patients (27%) experienced a total of 16 thrombotic events, including 8 (57%) deep venous thrombosis, 6 (43%) pulmonary embolism, and 2 (14.3%) arterial thrombosis. The hypercoagulable state was not significantly associated with thrombotic events. In summary, we observed a lower rate of hypercoagulable state on thromboelastography study in critically ill COVID-19 patients. Also, the hypercoagulable state was not associated with the occurrence of thrombotic events.

Traveling for heart transplantation and returning with COVID-19: a logistical, clinical, and pharmacotherapeutic challenge from the Middle East.

Heart transplantation (HT) has become a standard option for patients with end-stage heart failure (HF). However, the scarcity of donor availability remains a major hurdle for receiving this novel therapy, especially in the context of the rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic. We report the case of a patient in the United Arab Emirates (UAE) with advanced HF who was glucose-6-phosphate dehydrogenase deficient and had a history of type 2 diabetes mellitus with diabetic retinopathy and nephropathy, chronic kidney disease stage II, and hyperlipidemia. He was referred for HT abroad and was subsequently caught in the midst of the COVID-19 pandemic in New York, the US state most affected by the crisis at the time. Despite limited experience with favipiravir, we judged it to be the most appropriate agent with this patient's complex history given the lower risk for QT prolongation, no need for renal-dose adjustment, and no reported drug-drug interactions. Given the limited clinical experience with this agent, particularly for our patient, we decided to adopt strategies to mitigate and monitor the potential for QT prolongation. We outline the logistical, clinical, and pharmacological challenges that the poly-morbid patient and our HT program in the Middle-East faced under those novel circumstances.

Choosing the best antithrombotic regimen in patients with ventricular assist devices.

PURPOSE OF REVIEW: Two major complications compromise the outcomes and quality of life for left ventricular assist device (LVAD) patients. This review aims to discuss the mechanisms of thrombosis and bleeding, recent literature on the optimal approaches for antithrombotic therapy, and novel approaches to prevent bleeding. RECENT FINDINGS: Recent studies with the newly designed LVAD, the fully magnetically levitated rotor, show lower thrombotic risk but sustain similar bleeding risk. Small studies present options for less intense antithrombotic regimens with the newer devices. Bridging anticoagulation when needed in this patient population might require modified regimens and close monitoring to avoid anticoagulation overlap during the bridged periods. The necessity to add an antiplatelet to anticoagulation is particularly being challenged with the recent data. Antiplatelet responsiveness testing is an intriguing approach to customize regimens. In addition, novel approaches that target activation of the angiotensin II receptors and inflammatory responses might offer further protection against bleeding in implanted patients. SUMMARY: Close monitoring, novel, and patient-tailored approaches may offer the best antithrombotic strategies for LVAD patients. More clinical and long-term data are needed to establish the potential for less intense regimens particularly with the newly designed devices.

Thrombotic events following tocilizumab therapy in critically ill COVID-19 patients: a Façade for prognostic markers.

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

Equalizing excitation-inhibition ratios across visual cortical neurons.

The relationship between synaptic excitation and inhibition (E/I ratio), two opposing forces in the mammalian cerebral cortex, affects many cortical functions such as feature selectivity and gain. Individual pyramidal cells show stable E/I ratios in time despite fluctuating cortical activity levels. This is because when excitation increases, inhibition increases proportionally through the increased recruitment of inhibitory neurons, a phenomenon referred to as excitation-inhibition balance. However, little is known about the distribution of E/I ratios across pyramidal cells. Through their highly divergent axons, inhibitory neurons indiscriminately contact most neighbouring pyramidal cells. Is inhibition homogeneously distributed or is it individually matched to the different amounts of excitation received by distinct pyramidal cells? Here we discover that pyramidal cells in layer 2/3 of mouse primary visual cortex each receive inhibition in a similar proportion to their excitation. As a consequence, E/I ratios are equalized across pyramidal cells. This matched inhibition is mediated by parvalbumin-expressing but not somatostatin-expressing inhibitory cells and results from the independent adjustment of synapses originating from individual parvalbumin-expressing cells targeting different pyramidal cells. Furthermore, this match is activity-dependent as it is disrupted by perturbing pyramidal cell activity. Thus, the equalization of E/I ratios across pyramidal cells reveals an unexpected degree of order in the spatial distribution of synaptic strengths and indicates that the relationship between the cortex's two opposing forces is stabilized not only in time but also in space.

Nurse-led education for heart failure patients in developing countries.

Heart failure readmissions are associated with significant morbidity and mortality. Adequate education on adherence and self-care behaviours can affect readmission rates positively and nurses are at the frontline of patient education. Such education is valuable when establishing heart failure programmes in developing countries, in light of the challenging socioeconomic circumstances in these. This study aimed to evaluate nurses' heart failure knowledge, to assess patients' baseline knowledge, and to evaluate the effectiveness of structured nurse-driven education. METHODS: a total of 131 cardiac centre-based nurses and 30 chronic heart failure patients participated in the study in Kuwait. Patients were surveyed a second time 3 to 6 months later, while being followed at an advanced heart failure clinic by dedicated heart failure nurses. RESULTS: the majority of the nurses (80%) had not received heart failure education previously, although they were able to recognise most heart failure symptoms. Significant improvement in patients' knowledge was noted between the initial and follow-up surveys. CONCLUSION: establishing a dedicated advanced heart failure programme to care for patients in a developing country can result in significant improvement in disease awareness and self-care behaviours when led by well-trained heart failure nurses. More research is needed to determine if these findings are shared by other countries in the Middle-East and other developing countries.

Heart failure in the elderly: ten peculiar management considerations.

Chronic heart failure (HF) is a disease with significantly higher prevalence in the elderly or patients older than 65 years old. Typically, older patients have more risk factors for HF, more comorbidities, and are more likely to have recurrent admissions for acute decompensations. With HF burden on health care systems primarily related to hospital and nursing home costs, it is critical that elderly patients are approached with a clear understanding of certain unique clinical, laboratory, imaging, and pharmacokinetic differences that can alter their management and outcomes. Psychosocial factors have major implications on adherence to therapy as well as decisions on advanced care for elderly HF patients. In this article, we highlight ten peculiar management considerations when approaching older patients with HF. We discuss issues related to epidemiology, diagnostic challenges, pharmacotherapy, and palliative care; all of which can impact this unique population and, more importantly, the disease burden as a whole.

The Safety and Effectiveness of Apixaban in Patients with End-Stage Kidney Disease on Dialysis: A Retrospective Observational Study.

Background: Apixaban has been increasingly utilized for various FDA-approved indications, including stroke prevention and venous thromboembolism (VTE) treatment in patients with end stage kidney disease (ESKD) on hemodialysis. However, the safety and efficacy of its use in this population is not well established. Hence, the purpose of this study is to evaluate the safety and effectiveness of apixaban by examining outcomes in this population. Methods: This was a retrospective observational study that involved adults with ESKD who were on hemodialysis and prescribed apixaban from our hospital's outpatient pharmacy between 1 May 2015, and 31 March 2022. Demographics, apixaban indications, dose appropriateness, concomitant antiplatelet use, and comorbidities data were collected. Bleeding and thromboembolic events were also collected. Results: Sixty-six patients fulfilled the inclusion criteria, 50% of them males. Median age was 71 (63.5-82) years, and the median BMI 28.2 (59.5-86.25) kg/m2. The median follow-up time was 5 (1.9-12.3) months. Concomitant antiplatelet use (39.4%) and high medication adherence (84.8%) were observed. During follow-up, major bleeding events occurred in 15.2% of cases, with minor bleeding being more common (36.4%), and VTE and stroke events occurred in 4.5% of cases; appropriate dosing was prevalent (62.1%), and there was an overall all-cause mortality rate of 34.8%. Most patients received a 2.5 mg BID apixaban dose (56.1%), including both NVAF and VTE groups. Notably, the multivariate logistic regression analysis indicated that weight, and daily dose were insignificant predictors of bleeding events (p = 0.104, 0.591), however, the BMI was the main independent risk factor for bleeding in this population [OR = 0.9, 95% CI: 0.8-0.99; p = 0.023]. Conclusions: Our analysis of apixaban-treated ESKD patients highlights that the risk of bleeding is significant, and BMI was the main independent risk factor. A larger prospective study is needed to confirm our findings.

A Case of Hemorrhagic Cholecystitis in a Patient on Apixaban After COVID-19 Infection.

BACKGROUND Hemorrhagic cholecystitis is a rare cause of abdominal pain, which can result from malignancy, bleeding, or trauma. The presentation, which includes right upper-quadrant pain, nausea, and vomiting, can overlap with other disease states, thereby rendering the diagnosis challenging. CASE REPORT We describe a patient taking apixaban wo had paroxysmal atrial fibrillation with history of joint pain on long-term steroids who developed hemorrhagic cholecystitis following an episode of pneumonia secondary to SARS-CoV-2 virus (COVID-19) infection. The hospital COVID-19 pneumonia protocol included the administration of steroids and symptomatic care. Following discharge, he presented to our hospital with a sudden onset of severe abdominal pain and distention accompanied by elevated liver enzymes and a low hemoglobin level of 78 g/L. Magnetic resonance cholangiopancreatography revealed a distended gallbladder and intraluminal layering, early subacute blood products, and increased wall thickness, which was thought to represent non-calcular hemorrhagic cholecystitis. Furthermore, a stable 18×16×20 mm cyst in the tail of the pancreas was also located posteriorly, with indentation to the splenic vein. The patient was managed conservatively, and the pain subsided on day 3 after admission. CONCLUSIONS Hemorrhagic cholecystitis is rarely reported with the use of the direct oral anticoagulants (DOACs). In our case the combination of a recent COVID-19 hospitalization, steroid use, and possible pancreatic cancer (CA 19-9 288.4 kU/L) may have contributed to such incidence in the setting of apixaban utilization; however, it is not possible to make definitive correlations. Investigating hemorrhagic cholecystitis in the setting of DOAC use in patients with multiple risk factors such as those that existed in our patient is imperative for proper diagnosis and management.

Sustaining Life versus Altering Life-Saving Drugs: Insights to Explain the Paradoxical Effect of Extracorporeal Membrane Oxygenation on Drugs.

There has been a substantial increase in the use of extracorporeal membrane oxygenation (ECMO) support in critically ill adults. Understanding the complex changes that could affect drugs' pharmacokinetics (PK) and pharmacodynamics (PD) is of suitable need. Therefore, critically ill patients on ECMO represent a challenging clinical situation to manage pharmacotherapy. Thus, clinicians' ability to predict PK and PD alterations within this complex clinical context is fundamental to ensure further optimal and, sometimes, individualized therapeutic plans that balance clinical outcomes with the minimum drug adverse events. Although ECMO remains an irreplaceable extracorporeal technology, and despite the resurgence in its use for respiratory and cardiac failures, especially in the era of the COVID-19 pandemic, scarce data exist on both its effect on the most commonly used drugs and their relative management to achieve the best therapeutic outcomes. The goal of this review is to provide key information about some evidence-based PK alterations of the drugs used in an ECMO setting and their monitoring.

Efficient coding of cognitive variables underlies dopamine response and choice behavior.

Reward expectations based on internal knowledge of the external environment are a core component of adaptive behavior. However, internal knowledge may be inaccurate or incomplete due to errors in sensory measurements. Some features of the environment may also be encoded inaccurately to minimize representational costs associated with their processing. In this study, we investigated how reward expectations are affected by features of internal representations by studying behavior and dopaminergic activity while mice make time-based decisions. We show that several possible representations allow a reinforcement learning agent to model animals' overall performance during the task. However, only a small subset of highly compressed representations simultaneously reproduced the co-variability in animals' choice behavior and dopaminergic activity. Strikingly, these representations predict an unusual distribution of response times that closely match animals' behavior. These results inform how constraints of representational efficiency may be expressed in encoding representations of dynamic cognitive variables used for reward-based computations.

QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection.

BACKGROUND: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population. METHODS: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms). RESULTS: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (P = .004 for the likelihood-ratio test). CONCLUSION: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.