Refractory bradycardia and hypotension in patients with autonomic dysfunction treated with pseudoephedrine.

We describe a man in his 40s with a history of chronic intranasal cocaine use and C5-C7 incomplete quadriplegia complicated by neurogenic orthostatic hypotension, admitted to the intensive care unit for worsening bradycardia and hypotension requiring initiation of dopamine and an increase of his home midodrine dose. The patient experienced refractory bradycardia and hypotension with weaning of dopamine, and therefore a recommendation was made to add pseudoephedrine to his current regimen. This case describes the addition of pseudoephedrine to facilitate weaning off intravenous vasopressors within 24 hours in a patient with refractory bradycardia and hypotension secondary to autonomic dysfunction.

Clinical impact of pulmonary artery catheter in patients with cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: The clinical utility of the pulmonary artery catheter (PAC) for the management of cardiogenic shock (CS) remains controversial. We performed a systematic review and meta-analysis exploring the association between PAC use and mortality among patients with CS. METHODS: Published studies of patients with CS treated with or without PAC hemodynamic guidance were retrieved from MEDLINE and PubMed databases from January 1, 2000, to December 31, 2021. The primary outcome was mortality, which was defined as a combination of in-hospital mortality and 30-day mortality. Secondary outcomes assessed 30-day and in-hospital mortality separately. To assess the quality of nonrandomized studies, the Newcastle-Ottawa Scale (NOS), a well-established scoring system was used. We analyzed outcomes for each study using NOS with a threshold value of >6, indicating high quality. We also performed analyses based on the countries of the studies conducted. RESULTS: Six studies with a total of 930,530 patients with CS were analyzed. Of these, 85,769 patients were in the PAC-treated group, and 844,761 patients did not receive a PAC. PAC use was associated with a significantly lower risk of mortality (PAC: 4.6 % to 41.5 % vs control: 18.8 % to 51.0 %) (OR 0.63, 95 % CI: 0.41-0.97, I2 = 0.96). Subgroup analyses demonstrated no difference in the risk of mortality between NOS ≥ 6 studies and NOS < 6 studies (p-interaction = 0.57), 30-day and in-hospital mortality (p-interaction = 0.83), or the country of origin of studies (p-interaction = 0.08). CONCLUSIONS: The use of PAC in patients with CS may be associated with decreased mortality. These data support the need for a randomized controlled trial testing the utility of PAC use in CS.

Virtual Care Team Guided Management of Patients With Heart Failure During Hospitalization.

BACKGROUND: Scalable and safe approaches for heart failure guideline-directed medical therapy (GDMT) optimization are needed. OBJECTIVES: The authors assessed the safety and effectiveness of a virtual care team guided strategy on GDMT optimization in hospitalized patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In a multicenter implementation trial, we allocated 252 hospital encounters in patients with left ventricular ejection fraction ≤40% to a virtual care team guided strategy (107 encounters among 83 patients) or usual care (145 encounters among 115 patients) across 3 centers in an integrated health system. In the virtual care team group, clinicians received up to 1 daily GDMT optimization suggestion from a physician-pharmacist team. The primary effectiveness outcome was in-hospital change in GDMT optimization score (+2 initiations, +1 dose up-titrations, -1 dose down-titrations, -2 discontinuations summed across classes). In-hospital safety outcomes were adjudicated by an independent clinical events committee. RESULTS: Among 252 encounters, the mean age was 69 ± 14 years, 85 (34%) were women, 35 (14%) were Black, and 43 (17%) were Hispanic. The virtual care team strategy significantly improved GDMT optimization scores vs usual care (adjusted difference: +1.2; 95% CI: 0.7-1.8; P < 0.001). New initiations (44% vs 23%; absolute difference: +21%; P = 0.001) and net intensifications (44% vs 24%; absolute difference: +20%; P = 0.002) during hospitalization were higher in the virtual care team group, translating to a number needed to intervene of 5 encounters. Overall, 23 (21%) in the virtual care team group and 40 (28%) in usual care experienced 1 or more adverse events (P = 0.30). Acute kidney injury, bradycardia, hypotension, hyperkalemia, and hospital length of stay were similar between groups. CONCLUSIONS: Among patients hospitalized with HFrEF, a virtual care team guided strategy for GDMT optimization was safe and improved GDMT across multiple hospitals in an integrated health system. Virtual teams represent a centralized and scalable approach to optimize GDMT.

Do Patients With Non-Viable Myocardium From Ischemic Cardiomyopathy Benefit From Revascularization? A Systematic Review And Meta-Analysis.

BACKGROUND: Myocardial viability assessment is used to select patients who will derive the greatest benefit from revascularization. It remains controversial whether revascularization only benefits patients with ischemic cardiomyopathy who have viable myocardium. The objective of this meta-analysis was to compare mortality between patients with ischemic cardiomyopathy and non-viable myocardium who underwent revascularization and those who underwent medical therapy alone. METHODS: The MEDLINE database was searched using PubMed to retrieve studies published up to December 2021. Inclusion criteria were 1. studies that evaluated the impact of revascularization (revascularization group) versus medical therapy alone (control group) following myocardial viability assessment; 2. patients who had coronary artery disease that was amenable to coronary artery bypass grafting or percutaneous coronary intervention; and 3. patients who had non-viable myocardium. The main outcome measure was all-cause mortality. RESULTS: A total of 12 studies were included, evaluating 1363 patients with non-viable myocardium, of whom 501 patients underwent revascularization and 862 patients received medical therapy alone. There was a significant reduction in all-cause mortality (RR 0.76, 95 % CI: 0.62-0.93, I2 = 0) in the revascularization group compared to the control group. There was no association between the type of viability imaging modality and the risk of all-cause mortality (P-interaction = 0.58). CONCLUSIONS: The findings of this meta-analysis suggest a benefit from revascularization compared to medical therapy in patients with ischemic cardiomyopathy despite the lack of myocardial viability.

An Insight Into Pathophysiology, Epidemiology, and Management of Cardiovascular Complications of SARS-CoV-2 Infection, Post-acute COVID Syndrome, and COVID Vaccine.

Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic health emergency in March 2020. Elderly patients and those with pre-existing medical conditions including cardiovascular disease are at increased risk of developing severe disease. Not only is the viral infection with SARS-CoV-2 associated with higher mortality in patients with underlying cardiovascular disease, but development of cardiovascular complications is also common in patients with COVID-19. Even after recovery from the acute illness, post-acute COVID syndrome with cardiopulmonary manifestations can occur in some patients. Additionally, there are rare but increasingly recognized adverse events, including cardiovascular side effects, reported with currently available COVID-19 vaccines. In this review, we discuss the most common cardiovascular complications of SARS-CoV-2 and COVID-19 vaccines, cardiopulmonary manifestations of post-acute COVID syndrome and the current evidence-based guidance on the management of such complications.

Alginate-based 3D cancer cell culture for therapeutic response modeling.

Two-dimensional (2D) culture of tumor cells fails to recapitulate some important aspects of cellular organization seen in in vivo experiments. In addition, cell cultures traditionally use non-physiological concentration of nutrients. Here, we describe a protocol for a facile three-dimensional (3D) culture format for cancer cells. This 3D platform helps overcome the 2D culture limitations. In addition, it allows for longitudinal modeling of responses to cancer therapeutics. For complete details on the use and execution of this protocol, please refer to Lhuissier et al. (2017), Lehmann et al. (2016), Liu et al. (2016), and Duval et al. (2011).

Safety of ticagrelor in patients with baseline conduction abnormalities: A PLATO (Study of Platelet Inhibition and Patient Outcomes) analysis.

BACKGROUND: Although bradyarrhythmias have been observed with ticagrelor and its use with advanced atrioventricular block is not recommended, questions arise regarding its use in patients with mild conduction abnormalities. The objectives were to compare rates of clinically relevant arrhythmias in relation to any mild baseline conduction abnormality in patients with acute coronary syndrome randomized to ticagrelor versus clopidogrel. METHODS: We included all subjects in the electrocardiographic (ECG) substudy of the Platelet Inhibition and Patient Outcomes trial, excluding those with missing baseline ECG or with a pacemaker at baseline (N = 15,460). Conduction abnormality was defined as sinus bradycardia, first-degree atrioventricular block, hemiblock, or bundle-branch block. The primary arrhythmic outcome was the composite of any symptomatic brady- or tachyarrhythmia, permanent pacemaker placement, or cardiac arrest through 12 months. RESULTS: Patients with baseline conduction abnormalities (n = 4,256, 27.5%) were older and more likely to experience the primary arrhythmic outcome. There were no differences by ticagrelor versus clopidogrel in the composite arrhythmic end point in those with baseline conduction disease (1-year cumulative incidence rate: 17% for both study arms; hazard ratio: 0.99 [0.86-1.15]) or without baseline conduction disease (1-year cumulative incidence rate: clopidogrel 12.8% vs ticagrelor 12.4%; hazard ratio: 0.98 (0.88-1.09). There were also no statistically significant differences between ticagrelor and clopidogrel in the rates of bradycardic (or any individual arrhythmic) events in patients with baseline conduction abnormalities. CONCLUSIONS: Ticagrelor compared to clopidogrel did not increase arrhythmic events even in subjects with acute coronary syndrome who present with mild conduction abnormalities on their baseline ECG.

Relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non-ST-segment elevation acute coronary syndrome in the PLATO trial.

BACKGROUND: Guidelines suggest that "upstream" P2Y12 receptor antagonists should be considered in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). HYPOTHESIS: Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. METHODS: In the PLATO trial, 6792 NSTE-ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of "early" (<3h) vs "late" (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. RESULTS: Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. CONCLUSIONS: The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.

Surface acoustic waves induced micropatterning of cells in gelatin methacryloyl (GelMA) hydrogels.

Acoustic force patterning is an emerging technology that provides a platform to control the spatial location of cells in a rapid, accurate, yet contactless manner. However, very few studies have been reported on the usage of acoustic force patterning for the rapid arrangement of biological objects, such as cells, in a three-dimensional (3D) environment. In this study, we report on a bio-acoustic force patterning technique, which uses surface acoustic waves (SAWs) for the rapid arrangement of cells within an extracellular matrix-based hydrogel such as gelatin methacryloyl (GelMA). A proof-of-principle was achieved through both simulations and experiments based on the in-house fabricated piezoelectric SAW transducers, which enabled us to explore the effects of various parameters on the performance of the built construct. The SAWs were applied in a fashion that generated standing SAWs (SSAWs) on the substrate, the energy of which subsequently was transferred into the gel, creating a rapid, and contactless alignment of the cells (<10 s, based on the experimental conditions). Following ultraviolet radiation induced photo-crosslinking of the cell encapsulated GelMA pre-polymer solution, the patterned cardiac cells readily spread after alignment in the GelMA hydrogel and demonstrated beating activity in 5-7 days. The described acoustic force assembly method can be utilized not only to control the spatial distribution of the cells inside a 3D construct, but can also preserve the viability and functionality of the patterned cells (e.g. beating rates of cardiac cells). This platform can be potentially employed in a diverse range of applications, whether it is for tissue engineering, in vitro cell studies, or creating 3D biomimetic tissue structures.

Bioprinted thrombosis-on-a-chip.

Pathologic thrombosis kills more people than cancer and trauma combined; it is associated with significant disability and morbidity, and represents a major healthcare burden. Despite advancements in medical therapies and imaging, there is often incomplete resolution of the thrombus. The residual thrombus can undergo fibrotic changes over time through infiltration of fibroblasts from the surrounding tissues and eventually transform into a permanent clot often associated with post-thrombotic syndrome. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an in vitro platform using human cells and blood components would be beneficial. Towards achieving this aim, there have been studies utilizing the capabilities of microdevices to study the hemodynamics associated with thrombosis. In this work, we further exploited the utilization of 3D bioprinting technology, for the construction of a highly biomimetic thrombosis-on-a-chip model. The model consisted of microchannels coated with a layer of confluent human endothelium embedded in a gelatin methacryloyl (GelMA) hydrogel, where human whole blood was infused and induced to form thrombi. Continuous perfusion with tissue plasmin activator led to dissolution of non-fibrotic clots, revealing clinical relevance of the model. Further encapsulating fibroblasts in the GelMA matrix demonstrated the potential migration of these cells into the clot and subsequent deposition of collagen type I over time, facilitating fibrosis remodeling that resembled the in vivo scenario. Our study suggests that in vitro 3D bioprinted blood coagulation models can be used to study the pathology of fibrosis, and particularly, in thrombosis. This versatile platform may be conveniently extended to other vascularized fibrotic disease models.