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Percutaneous balloon mitral valvuloplasty (PBMV) is a safe alternative to management of a pregnant woman with mitral stenosis. We report the first successful PBMV in a 27-year-old pregnant patient in Tanzania at 32 weeks gestation with NYHA functional class III symptoms. PBMV yielded excellent results., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Despite cardiovascular disease being the leading cause of death in India, limited data exist regarding the factors associated with outcomes in patients with diabetes who suffer acute myocardial infarction (AMI)., Methods: We examined 21,374 patients with AMI enrolled in the ACS QUIK trial. We compared in-hospital and 30-day major adverse cardiac events including death, re-infarction, stroke, or major bleeding in those with and without diabetes. The associations between diabetes and cardiac outcomes were adjusted for presentation and in-hospital management using logistic regression., Results: Mean ± SD age was 60.1 ± 12.0 years, 24.3% were females, and 44.4% had diabetes. Those with diabetes were more likely to be older, female, hypertensive, and have higher Killip class but less likely to present with STEMI. Patients with diabetes had longer symptoms onset-to-arrival (median 225 vs 290 min; P < 0.001) and, in case of STEMI, longer door-to-balloon times (median, 75 vs 91 min; P < 0.001). Diabetes was independently associated with higher in-hospital death (adjusted odds ratio [aOR], 1.46; 95% CI, 1.12-1.89), in-hospital reinfarction (aOR, 1.52; 95% CI, 1.15-2.02), 30-day MACE (aOR, 1.33; 95% CI, 1.14-1.55) and 30-day death (aOR, 1.40; 95%CI, 1.16-1.69) but not 30-day stroke or 30-day major bleeding., Conclusion: Among patients presenting with AMI in Kerala, India, a considerable proportion has diabetes and are at increased risk for in-hospital and 30-day adverse cardiovascular outcomes. Increased awareness of the increased cardiovascular risk and attention to the implementation of established cardiovascular therapies are indicated for patients with diabetes in lower-middle-income countries who develop AMI., Clinical Trial Registration: ClinicalTrials.gov Unique identifier: NCT02256658., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: For rheumatic mitral stenosis (MS), a multidisciplinary evaluation is mandatory to determine the optimal treatment: medical, percutaneous balloon mitral valvuloplasty (PBMV) or valve surgery. Clinical and imaging evaluations are essential for procedural risk assessment and outcomes. PBMV interventions are increasingly available in Africa and are feasible options for selected candidates. Enhancing PBMV training/skills transfer across most of African countries is possible., Objectives: The aim of this study was to provide insight into the clinical practice of patients with rheumatic MS evaluated for PBMV in a Tanzanian teaching hospital and to define the role of imaging, and evaluate the heart team and training/skills transfer in PBMV interventions., Methods: From August 2019 to May 2022, 290 patients with rheumatic MS were recruited consecutively in the Tanzania Mitral Stenosis study. In total, 43 (14.8%) patients were initially evaluated for eligibility for PBMV by a heart team. We carried out the clinical assessment, laboratory investigations, transthoracic/oesophageal echocardiography (TTE/TEE) and electrocardiography., Results: The median age was 31 years (range 11-68), and two-thirds of the patients were female (four diagnosed during pregnancy). Two patients had symptomatic MS at six and eight years. Nine patients had atrial fibrillation with left atrial thrombus in three, and two were detected by TEE. Nine patients in normal sinus rhythm had spontaneous echo contrast. The mean Wilkins score was 8.6 (range 8-12). With re-evaluation by the local and visiting team, 17 patients were found to have unfavourable characteristics: Bi-commissural calcification (four), ≥ grade 2/4 mitral regurgitation (six), high scores and left atrial thrombus (three), left atrial thrombus (two), and severe pulmonary hypertension (two). Three patients died before the planned PBMV. Eleven patients were on a waiting list. We performed PBMV in 12 patients, with success in 10 of these, and good short-term outcomes [mean pre-PBMV (16.03 ± 5.52 mmHg) and post-PBMV gradients (3.08 ± 0.44 mmHg, p < 0.001)]. There were no complications., Conclusions: PBMV had good outcomes for selected candidates. TEE is mandatory in pre-PBMV screening and for procedural guidance. In our cohort, patients with Wilkins score of up to 11 underwent successful PBMV. We encourage PBMV skills expansion in low- and middle-income countries, concentrating on expertise centres.

Background: There is a paucity of real-world data on the in-hospital (IH) and post-discharge outcomes in patients undergoing lower extremity peripheral vascular intervention (PVI) with adjunctive atherectomy., Aims: In this retrospective, registry-based study, we evaluated IH and post-discharge outcomes among patients undergoing PVI, treated with or without atherectomy, in the National Cardiovascular Data Registry PVI Registry., Methods: The IH composite endpoint included procedural complications, bleeding or thrombosis. The primary out-of-hospital endpoint was major amputation at 1 year. Secondary endpoints included repeat endovascular or surgical revascularisation and death. Multivariable regression was used to identify predictors of atherectomy use and its association with clinical endpoints., Results: A total of 30,847 patients underwent PVI from 2014 to 2019, including 10,971 (35.6%) treated with atherectomy. The unadjusted rate of the IH endpoint occurred in 524 (4.8%) of the procedures involving atherectomy and 1,041 (5.3%) of non-atherectomy procedures (p=0.07). After adjustment, the use of atherectomy was not associated with an increased risk of the combined IH endpoint (p=0.68). In the 6,889 (22.4%) patients with out-of-hospital data, atherectomy was associated with a reduced risk of amputation (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI]: 0.51-0.85; p<0.01) and surgical revascularisation (aHR 0.63, 95% CI: 0.44-0.89; p=0.017), no difference in death rates (p=0.10), but an increased risk of endovascular revascularisation (aHR 1.21, 95% CI: 1.06-1.39; p<0.01) at 1 year., Conclusions: The use of atherectomy during PVI is common and is not associated with an increase in IH adverse events. Longitudinally, patients treated with atherectomy undergo repeat endovascular reintervention more frequently but experience a reduced risk of amputation and surgical revascularisation.

Climate change is the greatest existential challenge to planetary and human health and is dictated by a shift in the Earth's weather and air conditions owing to anthropogenic activity. Climate change has resulted not only in extreme temperatures, but also in an increase in the frequency of droughts, wildfires, dust storms, coastal flooding, storm surges and hurricanes, as well as multiple compound and cascading events. The interactions between climate change and health outcomes are diverse and complex and include several exposure pathways that might promote the development of non-communicable diseases such as cardiovascular disease. A collaborative approach is needed to solve this climate crisis, whereby medical professionals, scientific researchers, public health officials and policymakers should work together to mitigate and limit the consequences of global warming. In this Review, we aim to provide an overview of the consequences of climate change on cardiovascular health, which result from direct exposure pathways, such as shifts in ambient temperature, air pollution, forest fires, desert (dust and sand) storms and extreme weather events. We also describe the populations that are most susceptible to the health effects caused by climate change and propose potential mitigation strategies, with an emphasis on collaboration at the scientific, governmental and policy levels., (© 2022. Springer Nature Limited.)

Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor (bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for the treatment of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from fruiting bodies of Laetiporus sulphureus and a mycelial culture of Antrodia sp. MUCL 56049. The structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution electrospray mass spectrometry (HR-ESIMS). The secondary metabolites were tested for neurotrophin (ngf and bdnf ) expression levels on human astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the expression of neurotrophic factors, namely, ngf (sulphurenic acid, 15α-dehydroxytrametenolic acid, fomefficinic acid D, and 16α-hydroxyeburicoic acid) and bdnf (sulphurenic acid and 15α-dehydroxytrametenolic acid), respectively. The triterpenes also potentiated ngf-induced neurite outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound class of lanostanes in direct relation to bdnf and ngf enhancement. These compounds are widespread in medicinal mushrooms; hence, they appear promising as a starting point for the development of drugs and mycopharmaceuticals to combat neurodegenerative diseases. Interestingly, they do not show any pronounced cytotoxicity and may, therefore, be better suited for therapy than many other neurotrophic compounds that were previously reported.

Data on skin manifestations associated with pediatric obesity are limited. We conducted a prospective study to evaluate the association of pediatric obesity with skin dermatoses and dermatologic quality of life. Our findings suggest that ongoing monitoring of skin problems is recommended for children with obesity., (© 2022 Wiley Periodicals LLC.)

Background: Limited data exist on the risk profile and outcomes among young patients with acute myocardial infarction(AMI) in low-and middle-income countries(LMICs). This study explored differences in the clinical characteristics, medical care, and outcomes of AMI in young adults in India with a subanalysis focusing on sex disparities amongst the young., Methods: Using the Acute Coronary Syndrome Quality Improvement in Kerala trial database, we compared baseline characteristics, management, and outcomes amongst the young patients(≤50 years) and their older counterparts. The primary outcomes were the rates of in-hospital and 30-day composite of in-hospital major adverse cardiovascular events(MACE)., Results: Of the 21,374 adults enrolled, 4762(22%) were young, of which 614 (12.9%) were females. Young patients with AMI were more likely to be smokers(41.9% vs. 27.8%; P  < 0.001) and undergo coronary angiography (66.3%vs.57.3%; P < 0.001) and percutaneous coronary intervention (PCI)(57.5% vs. 47.0%; P  < 0.001), compared to older patients. After adjustment for potential confounders, younger patients had a lower likelihood of in-hospital (RR = 0.49; 95%CI 0.40-0.61; P  < 0.001) and 30-day MACE (RR = 0.54; 95%CI 0.46-0.64; P  < 0.001). Subgroup analysis comparing young males and females revealed worse cardiovascular risk profile among young women except for smoking. In-hospital MACE(RR = 1.60; 95%CI, 1.0-2.45; P  = 0.048) were higher for young women compared to men., Conclusion: Young AMI patients had higher prevalence of modifiable risk factors, were more likely to receive reperfusion therapy, and had better short and intermediate outcomes, compared to older patients. Compared to young men with AMI, young women had worse cardiovascular risk profile, were less likely to be treated with diagnostic angiography or PCI and experienced higher in-hospital death and MACE., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Public acceptance of governmental measures are key to controlling the spread of infectious diseases. The COVID-19 pandemic has placed a significant burden on healthcare systems for high-income countries as well as low- and middle-income countries (LMICs). The ability of LMICs to respond to the challenge of the COVID-19 pandemic has been limited and may have affected the impact of governmental strategies to control the spread of COVID-19. This study aimed to evaluate and compare public opinion on the governmental COVID-19 response of high and LMICs in the Middle East and benchmark it to international countries., Methods: An online, self-administered questionnaire was distributed among different Middle Eastern Arab countries. Participants' demographics and level of satisfaction with governmental responses to COVID-19 were analyzed and reported. Scores were benchmarked against 19 international values., Results: A total of 7395 responses were included. Bahrain scored highest for satisfaction with the governmental response with 38.29 ± 2.93 on a scale of 40, followed by the Kingdom of Saudi Arabia (37.13 ± 3.27), United Arab Emirates (36.56 ± 3.44), Kuwait (35.74 ± 4.85), Jordan (23.08 ± 6.41), and Lebanon (15.39 ± 5.28). Participants' country of residence was a significant predictor of the satisfaction score (P < 0.001), and participants who suffered income reduction due to the pandemic, had a history of SARS-CoV-2 infection, and held higher educational degrees had significantly lower satisfaction scores (P < 0.001). When benchmarked with other international publics, countries from the Gulf Cooperation Council had the highest satisfaction level, Jordan had an average score, and Lebanon had one of the lowest satisfaction scores., Conclusion: The political crisis in Lebanon merged with the existing corruption were associated with the lowest public satisfaction score whereas the economical instability of Jordan placed the country just before the lowest position. On the other hand, the solid economy plus good planning and public trust in the government placed the other countries of the Gulf Cooperation Council on top of the scale. Further investigation is necessary to find out how the governments of other low-income countries may have handled the situation wisely and gained the trust of their publics. This may help convey a clearer picture to Arab governments that have suffered during the pandemic., (© 2022. The Author(s).)

Background/objectives: Café-au-lait macules (CALMs) are a characteristic feature of neurofibromatosis type 1 (NF1), but also occur in other genetic disorders. Differential diagnosis of CALMs remains challenging and can be stressful for families. We sought to examine the role of an established CALMs screening clinic in diagnosing CALMs-related disorders., Method: We retrospectively reviewed patients seen between July 2012 and January 2019 in a CALMs screening clinic at The Hospital for Sick Children, a tertiary pediatric hospital in Toronto, Canada. Pediatric patients were referred because of multiple CALMs or suspected NF1. Selection was based on a chronological referral sample with no exclusions. A pediatric dermatologist examined all patients for CALMs and NF1 manifestations. Genetic testing was offered to confirm a clinical diagnosis or when clinical findings were inconclusive., Results: Three hundred patients, of which 152 (50.7%) were female and had a mean age of 5.6 ± 4.8 years were seen during the study period. NF1 was diagnosed in 76 (25.3%) patients, mosaic NF1 in 38 (12.7%) patients, and 8 (2.7%) patients received other genetic diagnoses. One hundred and twelve (37.3%) patients were diagnosed with isolated CALMs not associated with an underlying genetic disease. Furthermore, 36 (12%) of our patients did not have CALMs., Conclusions: The CALMs screening clinic aided in the early diagnosis of genetic disorders such as NF1 and distinguished CALMs from other hyperpigmented lesions. We encourage the adoption of this clinic model in referral centers to streamline and optimize care of patients with presumptive diagnosis of CALMs., (© 2022 Wiley Periodicals LLC.)

Café au lait macules (CALMs) are a normal and frequent finding in the general population, but multiple CALMs raise the possibility of an underlying neurocutaneous disease like neurofibromatosis type I. Certain features of CALMs like number, size, shape, and distribution are important in identifying children at higher risk of having a neurocutaneous disorder or another genetic disorder. Genetic testing can be especially helpful in establishing a diagnosis in atypical presentations, or when the child is young and other features of the disease aside from CALMs have not manifested., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Rheumatic heart disease (RHD) is the most common acquired heart disease occurring in children and adolescents. RHD is associated with significant morbidity and mortality particularly in low and middle- income countries (LMICs) where the burden is estimated to be higher compared to high income countries. Subclinical RHD is the presence of valvular lesion diagnosed by echocardiography in a person with no clinical manifestation of RHD. This study aimed at determining the prevalence, types and factors associated with subclinical RHD among primary school children in Dar Es Salaam, Tanzania., Methods: A descriptive community-based cross-sectional study was conducted in primary school children from February to May 2019. A standardized structured questionnaire was used to collect demographic characteristics, history of upper respiratory tract infections (URTIs), anthropometric measurements, and chest auscultation findings. Moreover echocardiographic screening was done to all children recruited into the study. World Heart Federation echocardiographic classification was used to define the types and prevalence of subclinical RHD., Results: A total of 949 primary school children were enrolled with females being predominant (57.1%). The prevalence of subclinical RHD was 34 per 1000. All the participants had mitral valve disease only whereby 17 had definite disease and 15 had a borderline disease. The associated factors for subclinical RHD were older age of more than 9 years (OR 10.8, 95% CI 1.4-82.2, P = 0.02) having three or more episodes of URTI in previous six months (OR 21, 95% CI 9.6-46, P = 0.00) and poor hygiene (OR 3, 95% CI 1.3-6.8, P = 0.009)., Conclusion: Subclinical RHD as detected by echocardiographic screening is prevalent in primary school children, uniformly affects the mitral valve, and is associated with potentially modifiable risk factors. Children with a history of more than three episodes of URTI in six months represents a high-risk population that should be targeted for RHD screening., (© 2021. The Author(s).)

Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly, estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV-2 thereby blocking its entry into cells. In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.

Coronary artery disease (CAD) remains a leading cause of mortality and warrants new imaging approaches to better guide clinical care. We report on a miniaturized, hybrid intravascular catheter and imaging system for comprehensive coronary artery imaging in vivo. Our catheter exhibits a total diameter of 1.0 mm (3.0 French), equivalent to standalone clinical intravascular ultrasound (IVUS) catheters but enables simultaneous near-infrared fluorescence (NIRF) and IVUS molecular-structural imaging. We demonstrate NIRF-IVUS imaging in vitro in coronary stents using NIR fluorophores, and compare NIRF signal strengths for prism and ball lens sensor designs in both low and high scattering media. Next, in vivo intravascular imaging in pig coronary arteries demonstrates simultaneous, co-registered molecular-structural imaging of experimental CAD inflammation on IVUS and distance-corrected NIRF images. The obtained results suggest substantial potential for the NIRF-IVUS catheter to advance standalone IVUS, and enable comprehensive phenotyping of vascular disease to better assess and treat patients with CAD., (© 2021 Wiley-VCH GmbH.)

Implantable drug depots have the capacity to locally meet therapeutic requirements by maximizing local drug efficacy and minimizing potential systemic side effects. Tubular organs including the gastrointestinal tract, respiratory tract and vasculature all manifest with endoluminal disease. The anatomic distribution of localized drug delivery for these organs using existing therapeutic modalities is limited. Application of local depots in a circumferential and extended longitudinal fashion could transform our capacity to offer effective treatment across a range of conditions. Here we report the development and application of a kirigami-based stent platform to achieve this. The stents comprise a stretchable snake-skin-inspired kirigami shell integrated with a fluidically driven linear soft actuator. They have the capacity to deposit drug depots circumferentially and longitudinally in the tubular mucosa of the gastrointestinal tract across millimetre to multi-centimetre length scales, as well as in the vasculature and large airways. We characterize the mechanics of kirigami stents for injection, and their capacity to engage tissue in a controlled manner and deposit degradable microparticles loaded with therapeutics by evaluating these systems ex vivo and in vivo in swine. We anticipate such systems could be applied for a range of endoluminal diseases by simplifying dosing regimens while maximizing drug on-target effects through the sustained release of therapeutics and minimizing systemic side effects., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Peri-device leak (PDL) following left atrial appendage occlusion (LAAO) may lead to an increased risk of thrombosis. However, current modalities for PDL detection, such as trans-esophageal echo (TEE) and cardiac CT do not provide quantitative measures of PDL., Objective: to use dielectric imaging (DI) to measure PDL from a Watchman (WM) LAAO device., Methods: A conductivity contrast agent is injected into the left atrium (LA) through the WM delivery system, while making DI measurements. Recordings are analyzed with a two-compartment model and the flow from the left atrial appendage (LAA) characterized by a "% clearance / beat" (CPB) parameter. With ethics approval, four dogs (26 ± 1.8  kg) were anesthetized and ventilated. Body-surface electrodes were placed and impedance data continuously acquired. WM devices (0-35% oversized) were introduced and placed into the LAA. During the study, the WM was either fully or partial deployed. At each deployment level, 10 mL of conductivity contrast was injected through the WM delivery sheath. At twenty-two deployment conditions, Doppler-flow TEE measurements were made, and compared to the DI-based value., Results: In all cases, CPB values correctly predicted the TEE-based assessment of PDL (100% sensitivity/specificity). The TEE leak size also corresponded to CPB values with a correlation of r = 0.914 (p 0.001)., Conclusion: Using DI signals, the leak flow from the WM LAAO can be measured and yields comparative results to TEE for detection of PDL. The DI method requires no other imaging modality or ionizing radiation and iodine contrast agent injection.

Aims: Our aim was to explore sex differences and inequalities in terms of medical management and cardiovascular disease (CVD) outcomes in a low/middle-income country (LMIC), where reports are scarce., Methods: We examined sex differences in presentation, management and clinical outcomes in 21 374 patients presenting with acute coronary syndrome (ACS) in Kerala, India enrolled in the Acute Coronary Syndrome Quality Improvement in Kerala trial. The main outcomes were the rates of in-hospital and 30-day major adverse cardiovascular events (MACEs) defined as composite of death, reinfarction, stroke and major bleeding. We fitted log Poisson multivariate random effects models to obtain the relative risks comparing women with men, and adjusted for clustering by centre and for age, CVD risk factors and cardiac presentation., Results: A total of 5191 (24.3%) patients were women. Compared with men, women presenting with ACS were older (65±12 vs 58±12 years; p<0.001), more likely to have hypertension and diabetes. They also had longer symptom onset to hospital presentation time (median, 300 vs 238 min; p<0.001) and were less likely to receive primary percutaneous coronary intervention for ST-elevation myocardial infarction (45.9% vs 49.8% of men, p<0.001). After adjustment, women were more likely to experience in-hospital (adjusted relative risk (RR)=1.53; 95% CI 1.32 to 1.77; p<0.001) and 30-day MACE (adjusted RR=1.39; 95% CI 1.23 to 1.57, p<0.001)., Conclusion: Women presenting with ACS in Kerala, India had greater burden of CVD risk factors, including hypertension and diabetes mellitus, longer delays in presentation, and were less likely to receive guideline-directed management. Women also had worse in-hospital and 30-day outcomes. Further efforts are needed to understand and reduce cardiovascular care disparities between men and women in LMICs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Improvements in spatial and temporal resolution now permit robust high quality characterization of presence, morphology and composition of coronary atherosclerosis in computed tomography (CT). These characteristics include high risk features such as large plaque volume, low CT attenuation, napkin-ring sign, spotty calcification and positive remodeling. Because of the high image quality, principles of patient-specific computational fluid dynamics modeling of blood flow through the coronary arteries can now be applied to CT and allow the calculation of local lesion-specific hemodynamics such as endothelial shear stress, fractional flow reserve and axial plaque stress. This review examines recent advances in coronary CT image-based computational modeling and discusses the opportunity to identify lesions at risk for rupture much earlier than today through the combination of anatomic and hemodynamic information.

Paclitaxel coated balloon catheters (PCB) were developed as a polymer-free non-implantable alternative to drug eluting stents, delivering similar drug payloads in a matter of minutes. While PCB have shown efficacy in treating peripheral arterial disease in certain patient groups, restenosis rates remain high and there is no class effect. To help further optimize these devices, we developed a scanning electron microscopy (SEM) imaging technique and computational modeling approach that provide insights into the coating micromorphology dependence of in vivo drug transfer and retention. PCBs coated with amorphous/flaky or microneedle coatings were inflated for 60 sec in porcine femoral arteries. Animals were euthanized at 0.5, 24 and 72 h and treated arteries processed for SEM to image endoluminal coating distribution followed by paclitaxel quantification by mass spectrometry (MS). Endoluminal surfaces exhibited sparse coating patches at 0.5 h, predominantly protruding (13.71 vs 0.59%, P < 0.001), with similar micro-morphologies to nominal PCB surfaces. Microneedle coating covered a 1.5-fold endoluminal area (16.1 vs 10.7%, P = 0.0035) owing to higher proximal and distal delivery, and achieved 1.5-fold tissue concentrations by MS (1933 vs 1298 μg/g, P = 0.1745) compared to amorphous/flaky coating. Acute longitudinal coating distribution tracked computationally predicted microindentation pressure gradients (r = 0.9, P < 0.001), with superior transfer of the microneedle coatings attributed to their amplification of angioplasty contact pressures. By 24 h, paclitaxel concentration and coated tissue areas both declined by >93% even as nonprotruding coating levels were stable between 0.5 and 72 h, and 2.7-fold higher for microneedle vs flaky coating (0.64 vs 0.24%, P = 0.0195). Tissue retained paclitaxel concentrations at 24-72 h trended 1.7-fold higher post treatment with microneedle coating compared to the amorphous/flaky coating (69.9 vs 39.9 μg/g, P = 0.066). Thus, balloon based drug delivery is critically dependent on coating micromorphologies, with superior performance exhibited by micromorphologies that amplify angioplasty pressures., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The optimal treatment strategy for treating ST-segment-elevation myocardial infarction (STEMI) in context of the coronavirus disease 2019 (COVID-19) pandemic is unclear given the potential risk of occupational exposure during primary percutaneous coronary intervention (PPCI). We quantified the impact of different STEMI treatment strategies on patient outcomes and provider risk in context of the COVID-19 pandemic., Methods: Using a decision-analytic framework, we evaluated the effect of PPCI versus the pharmaco-invasive strategy for managing STEMI on 30-day patient mortality and individual provider infection risk based on presence of cardiogenic shock, suspected coronary territory, and presence of known or presumptive COVID-19 infection., Results: For patients with low suspicion for COVID-19, PPCI had mortality benefit over the pharmaco-invasive strategy, and the risk of cardiac catheterization laboratory provider infection remained very low (<0.25%) across all subgroups. For patients with presumptive COVID-19 with cardiogenic shock, PPCI offered substantial mortality benefit to patients relative to the pharmaco-invasive strategy (7.9% absolute decrease in 30-day mortality), but also greater risk of provider infection (2.3% absolute increase in risk of provider infection). For patients with presumptive COVID-19 with nonanterior STEMI without cardiogenic shock, PPCI offered a 0.4% absolute mortality benefit over the pharmaco-invasive strategy with a 0.2% greater absolute risk of provider infection, and the tradeoff between patient and provider risk with PPCI became more apparent in sensitivity analysis with more severe COVID-19 infections., Conclusions: Usual care with PPCI remains the appropriate treatment strategy in the majority of cases presenting with STEMI in the setting of the COVID-19 pandemic. However, utilization of a pharmaco-invasive strategy in selected patients with STEMI with presumptive COVID-19 and low likelihood of mortality from STEMI and use of preventive strategies such as preprocedural intubation in high risk patients when PPCI is the preferred strategy may be reasonable to reduce provider risk of COVID-19 infection.

This study sought to evaluate perisplenic artery nerve distribution and the feasibility of splenic artery denervation (SDN). The NEXION radiofrequency catheter was used to perform SDN in healthy and inflammatory arthritis pigs. Splenic artery anatomy, nerve distribution, and splenic norepinephrine (NEPI) levels were evaluated before and after SDN. Perisplenic artery nerves were primarily distributed within 2.5 mm of the arterial lumen and were largely sympathetic on the basis of tyrosine hydroxylase expression. The pancreas, tended to be circumferentially positioned around the proximal splenic artery, typically >2.5 mm from the lumen, ensuring that most of the nerves could be targeted without affecting this sensitive organ. The mid segment of the splenic artery was relatively free of contact with the adjacent pancreas. Splenic NEPI levels and nerve abundance followed a decreasing gradient from the proximal to distal splenic artery. SDN resulted in significant reductions in splenic NEPI levels at day 14 (60.7%, P = 0.024) in naïve pigs and day 45 (100%, P = 0.001) in inflammatory arthritis pigs. There was no significant effect of SDN on joint soft tissue injury or circulating inflammatory markers in the inflammatory arthritis model. The majority of perisplenic arterial nerves are within close proximity of the lumen and are primarily sympathetic efferent fibers. Nerves in the mid-segment may be the preferred SDN target given their proximity to the artery and paucity of periarterial off-target organs. SDN appears safe and effective at reducing splenic NEPI levels., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inferior vena cava filters (IVCF) are associated with complications which may be due to delayed retrieval. Initiation of an automated reminder system may improve retrieval rates and reduce complications. A computerized reminder system, which provides interactive email reminders after implantation while collecting IVCF use data, was implemented. IVCF retrieval was compared before ("reminder not provided" group) and after ("reminder provided" group) implementation. Data regarding implantation, retrieval, and complications were collected. The primary efficacy outcome was retrieval rate, and the primary safety outcome was indwelling complication rate. Secondary outcomes were time to retrieval and a composite adverse outcome defined as IVCF thrombosis, deep venous thrombosis (DVT), pulmonary embolism, and death. A total of 1,070 IVCF insertions were included, 715 in the "reminder not provided" group and 355 in the "reminder provided" group. Patient age (61 vs 64 years, p = 0.95) and gender (42% vs 40% female, p = 0.55) were similar in the "reminder not provided" and "reminder provided" groups, respectively. In the "reminder provided" group, the retrieval rate was higher (148/297 [49.8%] vs 223/715 [31.2%], p = 0.0001), the indwelling complication rate was lower (30/319 [9.4%] vs 115/715 [16.1%], p = 0.005), and the time to retrieval was shorter (112 days vs 146 days, p = 0.02). The composite adverse outcome occurred less frequently in the "reminder provided" group: (85/355 [23.9%] vs 297/715 [41.5%], p = 0.0001). The system was associated with increased odds of IVCF retrieval (odds ratio 2.56; 95% confidence interval: 1.82 to 3.59; p <0.0001) and reduced odds of the composite adverse outcome (odds ratio 0.72; 95% confidence interval: 0.60 to 0.80; p <0.0001). In conclusion, implementing a computerized email reminder system was associated with higher IVCF retrieval rates, fewer indwelling complications, and shorter dwell times., (Copyright © 2018. Published by Elsevier Inc.)

Background: Extracorporeal membrane oxygenation (ECMO) has been used to stabilize patients with massive pulmonary embolism though few reports describe this approach. We describe the presentation, management and outcomes of patients who received ECMO for massive pulmonary embolism (PE) in our pulmonary embolism response team (PERT) registry., Methods: We enrolled a consecutive cohort of patients with confirmed PE for whom PERT was activated and selected patients treated with ECMO. We prospectively captured clinical, therapeutic and outcome data at the time of PERT activation and during the follow-up period for up to 365 days., Results: Thirteen patients who had PERT activation with confirmed PE diagnosis have undergone ECMO since the initiation of our PERT program in 2012. The mean age was 49 ± 19 years. Six (46%) patients were female. All the patients had cardiac arrest, either as an initial presentation or in-hospital cardiac arrest after presentation. All the patients exhibited right ventricular (RV) dilation on echocardiogram with RV hypokinesis. Eight (62%) patients received systemic thrombolysis with intravenous tissue plasminogen activator (tPA) and three (23%) patients underwent catheter-directed thrombolysis therapy using the EKOS system (EKOS Corporation, Bothell, WA, USA). Four (31%) patients underwent surgical embolectomy. Mean ECMO duration was 5.5 days, ranging from 2-18 days. Thirty-day mortality was 31% and one-year mortality was 54%., Conclusions: Patients with massive pulmonary embolism who suffer a cardiac arrest have high morbidity and mortality. ECMO can be used in conjunction with systemic thrombolysis, catheter-directed therapy or as a bridge to surgical embolectomy.

Successful motor performance relies on our ability to adapt to changes in the environment by learning novel mappings between motor commands and sensory outcomes. Such adaptation is thought to involve two distinct mechanisms: an implicit, error-based component linked to slow learning and an explicit, strategic component linked to fast learning and savings (i.e., faster relearning). Because behavior, at any given moment, is the resultant combination of these two processes, it has remained a challenge to parcellate their relative contributions to performance. The explicit component to visuomotor rotation (VMR) learning has recently been measured by having participants verbally report their aiming strategy used to counteract the rotation. However, this procedure has been shown to magnify the explicit component. Here we tested whether task-specific eye movements, a natural component of reach planning, but poorly studied in motor learning tasks, can provide a direct readout of the state of the explicit component during VMR learning. We show, by placing targets on a visible ring and including a delay between target presentation and reach onset, that individual differences in gaze patterns during sensorimotor learning are linked to participants' rates of learning and their expression of savings. Specifically, we find that participants who, during reach planning, naturally fixate an aimpoint rotated away from the target location, show faster initial adaptation and readaptation 24 h later. Our results demonstrate that gaze behavior cannot only uniquely identify individuals who implement cognitive strategies during learning but also how their implementation is linked to differences in learning. NEW & NOTEWORTHY Although it is increasingly well appreciated that sensorimotor learning is driven by two separate components, an error-based process and a strategic process, it has remained a challenge to identify their relative contributions to performance. Here we demonstrate that task-specific eye movements provide a direct read-out of explicit strategies during sensorimotor learning in the presence of visual landmarks. We further show that individual differences in gaze behavior are linked to learning rate and savings.

Mortality associated with high-risk pulmonary embolism (PE) remains high. Extra-corporeal membrane oxygenation (ECMO) allows for acute hemodynamic stabilization and potentially for administration of other disease process altering therapies. We sought to compare two eras: pre-ECMO and post-ECMO in relation to high-risk PE treatment and mortality. A single-center retrospective chart review was conducted of high-risk PE patients. High-risk PE was defined as acute PE and cardiac arrest or shock. A total of 60 patients were identified, 31 in the pre-ECMO era and 29 in the post-ECMO era. Mean age was 56.1±21.1 years and 51.7% were women. More patients in the post-ECMO era were identified with computed tomography (82.8% vs 51.6%, p=0.011) and more patients in the post-ECMO era had right ventricular dysfunction on echocardiography (96.4% vs 78.3%, p=0.045). No other differences were noted in baseline characteristics or clinical, laboratory and imaging data between the two groups. In total, ECMO was used in 13 (44.8%) patients in the post-ECMO era. There was greater utilization of catheter-directed therapies in the post-ECMO era compared to the pre-ECMO era ( n = 7 (24.1%) vs n = 1 (3.2%), p=0.024). Thirty-day survival increased from 17.2% in patients who presented in the pre-ECMO era to 41.4% in the post-ECMO era ( p=0.043). While more work is necessary to better identify those PE patients who stand to benefit from mechanical circulatory support, our findings have important implications for the management of such patients.

Dual-antiplatelet therapy (DAPT) is considered mandatory after new-generation drug-eluting coronary stent implantation to reduce ischemic complications such as stent thrombosis, but the need for DAPT makes the timing of elective surgery difficult. Interrupting DAPT places patients at risk for stent thrombosis, and surgery in the setting of DAPT may lead to bleeding. The 2016 American College of Cardiology/American Heart Association guideline recommends delaying elective noncardiac surgery for a minimum 6-month period to reduce ischemic risks after the implantation of a second-generation metallic drug-eluting stent (DES). However, the guideline fails to appropriately stratify surgical patients based on the indication for second-generation metallic DES implantation and other patient characteristics. The Absorb bioresorbable vascular scaffold (Abbott Vascular, Abbott Park, IL), which has a higher propensity for stent thrombosis compared with second-generation metallic DES, also produces DAPT management challenges in patients presenting for elective noncardiac surgery. Due to the novelty of bioresorbable vascular scaffold therapy, there are no guidelines available for the management of patients undergoing elective noncardiac surgery. This review addresses DAPT management in patients undergoing noncardiac surgery less than 12 months after new-generation metallic DES or bioresorbable vascular scaffold implantation and provides further guidance for anesthesiologists who encounter these challenging cases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To present a theoretical basis for noninvasively characterizing in vivo fluid-mechanical energy losses and to apply it in a pilot study of patients known to express abnormal aortic flow patterns., Methods: Four-dimensional flow MRI was used to characterize laminar viscous energy losses in the aorta of normal controls (n = 12, age = 37 ± 10 yr), patients with aortic dilation (n = 16, age = 52 ± 8 yr), and patients with aortic valve stenosis matched for age and aortic size (n = 14, age = 46 ± 15 yr), using a relationship between the three-dimensional velocity field and viscous energy dissipation., Results: Viscous energy loss was elevated significantly in the thoracic aorta in patients with dilated aorta (3.6 ± 1.3 mW, P = 0.024) and patients with aortic stenosis (14.3 ± 8.2 mW, P < 0.001) compared with healthy volunteers (2.3 ± 0.9 mW). The same pattern of significant differences was seen in the ascending aorta, where viscous energy losses in patients with dilated aortas (2.2 ± 1.1 mW, P = 0.021) and patients with aortic stenosis (10.9 ± 6.8 mW, P < 0.001) were elevated compared with healthy volunteers (1.2 ± 0.6 mW)., Conclusion: This technique provides a capability to quantify the contribution of abnormal laminar blood flow to increased ventricular afterload. In this pilot study, viscous energy loss in patient cohorts was significantly elevated and indicates that cardiac afterload is increased due to abnormal flow., (Copyright © 2013 Wiley Periodicals, Inc.)