Search

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.

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. A kirigami-inspired stent-based system has been developed for extended local drug delivery to the gastrointestinal and respiratory tracts as well as the vascular system.

Ascertainment bias is a well-recognized source of bias in research, but few studies have systematically analyzed sources of ascertainment bias in randomized trials in which blinding is not possible and endpoint assessment is not protocolized. In the current study, we sought to evaluate differences in the clinical practice patterns of trial investigators with respect to bias in the ascertainment of pre-revascularization patient risk and the incidence of secondary endpoints post-revascularization. We conducted a cross-sectional survey of active investigators ( n = 936) from the Best Endovascular Versus Best Surgical Therapy for Patients with Critical Limb Ischemia (BEST-CLI) trial. The total survey response rate was 19.6% (183/936). Vascular surgeons were more likely than nonsurgical interventionalists to order tests for cardiac complications after both surgical bypass ( p < 0.001) and endovascular revascularization ( p = 0.038). Post-procedure, investigators were more likely to order additional testing for cardiac complications in open surgery versus endovascular cases (7% vs 16% never, 41% vs 65% rarely, 43% vs 17% sometimes, 9% vs 2% always, respectively; p < 0.0001). Significant variation in practice patterns exist in the pre- and post-procedure assessment of cardiac risk and events for patients with CLI undergoing revascularization. Variation in the ascertainment of risk and outcomes according to the type of revascularization procedure and physician specialty should be considered when interpreting the results of clinical studies, such as the BEST-CLI trial. ClinicalTrials.gov Identifier: NCT02060630

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.

Purpose To examine nationwide variations in inpatient use of drug-coated balloons (DCBs) for treating femoropopliteal segment occlusive disease and whether DCBs are associated with reduced early out-of-hospital health care utilization. Materials and Methods The study included 24,022 patients who survived hospitalization for femoropopliteal revascularization using DCB angioplasty (n=7850) or uncoated balloon angioplasty (n=16,172) in the 2016–2017 Nationwide Readmissions Database. Differences in patient, hospitalization, and institutional characteristics were compared between treatment strategies. Adjusted logistic regression models were used to examine differences in 6-month rates of readmission, amputation, and repeat intervention. Results are presented as the odds ratio (OR) and 95% confidence interval (CI). Results Patients treated with DCBs had a higher prevalence of chronic limb-threatening ischemia, diabetes, hypertension, and tobacco use. Revascularization with a DCB was associated with shorter hospitalizations, lower median hospitalization costs, and fewer inpatient lower extremity amputations. Readmissions at 6 months were decreased in patients treated with DCBs compared with uncoated balloon angioplasty (OR 0.90, 95% CI 0.83 to 0.98, p=0.014). The most common reasons for readmission were complications related to procedures (15.4%) and diabetes (15.4%). Compared to patients treated with DCBs, patients treated with uncoated balloon angioplasty were more often readmitted with early procedure-related complications (13.3% vs 17.5%). There were no between-group differences in readmission for sepsis, myocardial infarction, or congestive heart failure. Conclusion DCBs are less often used compared to uncoated balloons during inpatient femoropopliteal procedures. While DCB utilization is associated with more severe comorbidities and advanced peripheral artery disease, readmission rates are decreased through the first 6 months.

Oral anticoagulation reduces the ischemic stroke risk in patients with nonvalvular atrial fibrillation (NVAF) but inherently increases the bleeding risk. Percutaneous left atrial appendage occlusio...

Visual Abstract, Highlights • Restenosis limits the efficacy of PTA or stent treatment of atherosclerosis in peripheral and coronary artery disease. • Paclitaxel DCBs effectively reduce restenosis; however, recently, their overall safety profile has been called into question. • In an in vivo molecular-structural imaging study of 25 rabbits with experimental atherosclerosis, DCB-PTA, plain PTA, or sham-PTA was investigated using serial intravascular NIRF-OCT and IVUS. • DCB-PTA reduced lesion inflammation on NIRF-OCT and halted lesion progression on IVUS, compared with PTA or sham-PTA. • These findings indicated the potential for DCBs to serve effectively and safely as a regional anti-atherosclerosis therapy., Summary Paclitaxel drug-coated balloons (DCBs) reduce restenosis, but their overall safety has recently raised concerns. This study hypothesized that DCBs could lessen inflammation and reduce plaque progression. Using 25 rabbits with cholesterol feeding- and balloon injury-induced lesions, DCB-percutaneous transluminal angioplasty (PTA), plain PTA, or sham-PTA (balloon insertion without inflation) was investigated using serial intravascular near-infrared fluorescence−optical coherence tomography and serial intravascular ultrasound. In these experiments, DCB-PTA reduced inflammation and plaque burden in nonobstructive lesions compared with PTA or sham-PTA. These findings indicated the potential for DCBs to serve safely as regional anti-atherosclerosis therapy.

Objectives This study determined whether in vivo positron emission tomography (PET) of arterial inflammation (18F-fluorodeoxyglucose [18F-FDG]) or microcalcification (18F-sodium fluoride [18F-NaF]) could predict restenosis following PTA. Background Restenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty. Methods In this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent 18F-FDG and 18F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months. Results Forty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (18F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p, Central Illustration

Introduction: Patients with diabetes are more likely to experience an acute myocardial infarction (AMI), heart failure, or death from cardiovascular (CV) causes than patients without diabetes. Despite cardiovascular disease being the leading cause of death in India, limited data exists on the outcome of patients with diabetes who suffer acute cardiovascular events. Hypothesis: Diabetes is common in patients with acute myocardial infarction (AMI) in India and is associated with worse in-hospital and 30-day cardiovascular outcomes. Methods: We examined 21374 patients with AMI enrolled in the Acute Coronary Syndrome Quality Improvement in Kerala trial. We compared those with and without diabetes with regards to the development of in-hospital and 30-day major adverse cardiac events including death, re-infarction, stroke, or major bleeding. 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 and 24.3% were females. A total of 44.4% of AMI patients had diabetes. Those with diabetes were more likely to be older, female, with hypertension and have higher Killip class on presentation but less likely to present with STEMI. Patients with diabetes had longer symptoms onset-to-arrival (median 225 vs 290 min; P 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 CV risk and attention to the implementation of established cardiovascular therapies are indicated for patients with diabetes in lower-middle income countries who develop AMI.

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.

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 observed 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-CoV2 thereby blocking its entry into cells. In a mouse model, 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. Funding: Dr. Lino Cardenas is supported by the MGH Physician-Scientist Development Award and the MGH Department of Medicine Pilot Translational Research Grant. Dr. Malhotra is supported by a COVID-19 Fast Grant (fastgrants.org), NHLBI R01 HL142809, the American Heart Association grant 18TPA34230025, and the Wild Family Foundation. Dr. Lindsay is supported by the Fredman Fellowship, the Toomey Fund for Aortic Dissection Research, the Hassenfeld Fellowship and NIH/NHLBI R01HL130113. Dr. Davila-Del Carpio, Dr. Aguilar Pineda and Dr. Vera Lopez are supported by the COVID-19 Fast Grant (0371-VRINV-2020) from the Vicerrectorado de Investigacion de la Universidad Catolica de Santa Maria, Arequipa, Peru. Conflict of Interest: Authors declare no competing interests. Ethical Approval: All experiments involving mice were approved by the Partners Subcommittee on Research Animal Care. Personnel from the laboratory carried out all experimental protocols under strict guidelines to insure careful and consistent handling of the mice.

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 naive 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.

Objective: Near-infrared autofluorescence (NIRAF) of atherosclerosis associates with intraplaque hemorrhage and is detectable in living patients with coronary artery disease. However, further mechanisms underlying NIRAF generation have not been fully characterized. Here, we investigated the role of lipids and oxidative stress in NIRAF generation in atherosclerosis and in vitro in human macrophages. Approach and Results: In N=15 human carotid endarterectomy specimens, we investigated the spatial distribution of lipid, intraplaque hemorrhage, and NIRAF (ex/em 630/650 nm). Plaque NIRAF associated with both Sudan black-positive lipids ( r =0.53, P =0.023) and GPA (glycophorin A)-positive intraplaque hemorrhage ( r =0.48, P =0.043). Plaque NIRAF also localized with lipid and specifically insoluble lipid (ceroid) and iron. Intriguingly, some NIRAF-positive areas were Sudan black-positive but GPA-negative. Studies on human macrophages investigated further the role of lipids in NIRAF generation. OxLDL (Oxidized low-density lipoprotein) and hemoglobin, but not LDL, generated NIRAF in both THP-1 cells and monocyte-derived macrophages. In oxLDL-treated THP-1 cells, higher NIRAF, lipid peroxidation products, and intracellular oxidative stress markers evolved ( P Conclusions: In human atherosclerosis and human macrophages in vitro, NIRAF colocalizes with lipid and specifically insoluble lipid or ceroid. In vitro studies further show that oxidized LDL generates NIRAF, oxidative stress, and lipid peroxidation products. These results demonstrate a new pathway for NIRAF generation through oxidized lipid-driven oxidative stress and support ceroid as a source of NIRAF in human atherosclerosis. These findings may inform future clinical intracoronary NIRAF imaging studies of patients with coronary artery disease.

Transcatheter procedures offer an alternative to cardiac surgery in select patients with structural heart disease (SHD). Unfortunately, inadvertent disruption of electrical pathways and subsequent development of new onset conduction disturbances can occur in up to 5–70% of percutaneous interventions, result in pacemaker implantation, and confer a worse prognosis. The physical proximity between the conduction system (atrioventricular node, bundle of His, and bundle branches) and the site of percutaneous repair is increasingly recognized as a key factor influencing new onset conduction disturbance development in procedures located near the conduction system. This review covers the incidence, clinical significance, and mechanisms of new onset conduction disturbances and discusses current and emerging strategies to address this complication in these populations.

We present our next generation clinical dual-modality OCT and near infrared autofluorescence/fluorescence (NIRAF/NIRF) imaging platform. This platform allows combined tissue microstructure visualization (OCT) and obtaining molecular information either by intrinsic tissue near infrared autofluorescence (NIRAF) or by exogenous near infrared fluorescence contrast agents (NIRF). Components of this platform, OCT-NIRAF/NIRF imaging system, rotary junction and catheters, were developed using an industry standard design control processes to enable quality clinical translation. We have identified sources of image degradation in dual-modality catheter-based imaging (e.g. core-cladding crosstalk in OCT, background noise in fluorescence) and present methods to mitigate their effects. We also show catheter fabrication and validation, as well as automated fluorescence sensitivity and distance calibration methods that ensure robust and repeatable system performance.

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.

Introduction: Endothelial shear stress (ESS) identifies coronary plaques at high risk for progression and rupture leading to a future acute coronary syndrome. We developed an optimized methodology to derive ESS using computational fluid dynamics (CFD) in 3D models of coronaries from noninvasive computed tomography angiography (CTA). We hypothesized that ESS based on CTA has a high correlation with ESS based on the gold standard fusion of intravascular ultrasound (IVUS)/optimical coherence tomography (OCT) and CTA. Methods: In 14 patients, paired patient-specific CFD models based on invasive and CTA imaging of the left anterior descending (LAD) coronaries were created. 10 were used to optimize, and 4 patients to test the methodology. Time averaged ESS (TAESS) was calculated for both coronary models applying physiological data at the time of imaging. Each 3D reconstructed coronary was divided into 2 mm segments and further subdivided into 8 arcs (45 o ). TAESS was averaged per segment and arc. The paired segment and arc averaged TAESS were categorized into patient-specific tertiles (low, medium and high). Results: In the 10 LADs, used for optimization of the methodology, we found high correlations between invasively- and noninvasively-derived TAESS averaged over segments (n=263, r=0.86) and arcs (n=2104,r= 0.85,p Conclusions: We showed that we can accurately assess the TAESS distribution noninvasively from CTA and demonstrated a high correlation with TAESS using IVUS/OCT 3D models. Future studies should prove the prognostic value of CTA-based TAESS for plaque progression and clinical events.

Introduction: Despite the increasing interest in sex differences in acute coronary syndrome (ACS) presentation, management, and outcomes in high-income countries, reports on such differences from low- and middle-income countries (LMICs) are limited. Limited resources in LMICs may worsen health disparities experienced by women and vulnerable populations. Methods: Using ACS QUIK trial database, we examined sex-differences in terms of baseline characteristics, management received, and relevant clinical outcomes of 21,374 patients presenting with ACS. The main outcomes were the rates of in-hospital and 30-day composite of death, reinfarction, stroke, and major bleeding. We fitted log Poisson multivariate random effects models to obtain the relative risks comparing females to males. We used random intercepts for different hospitals and centers as the clustering variable. Effect measure modification by baseline variables was examined by restricting the analysis to each category and comparing the effect estimates for females to males. Results: A total of 5,191 (24.3%) patients were women. Compared to men, women presenting with ACS were older (65±12 vs 58±12 years; p < 0.001), more likely to have hypertension (61.2% vs 42.4%; p < 0.001), and diabetes mellitus (53.5% vs 41.4%; p < 0.001). After symptom onset, women tended to present later to the hospital (medians, 300 vs 238 mins; p < 0.001) and had higher Killip class on presentation (17.8% vs 12.3%; p < 0.001). Women presenting with STEMI were less likely to receive primary PCI (45.9% vs 49.8% of men, p Conclusion: In summary, our study confirms a higher CVD risk profile, delayed presentation, suboptimal medical care in women presenting with ACS in Kerala, India. Women were also found to have higher in-hospital and 30-day MACE, even after adjustment for potential confounders.

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 ( 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.

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.

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 $\pm$ 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.

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 by93% 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.

Objective To evaluate the impact of COVID‐19 pandemic migitation measures on of ST‐elevation myocardial infarction (STEMI) care. Background We previously reported a 38% decline in cardiac catheterization activations during the early phase of the COVID‐19 pandemic mitigation measures. This study extends our early observations using a larger sample of STEMI programs representative of different US regions with the inclusion of more contemporary data. Methods Data from 18 hospitals or healthcare systems in the US from January 2019 to April 2020 were collecting including number activations for STEMI, the number of activations leading to angiography and primary percutaneous coronary intervention (PPCI), and average door to balloon (D2B) times. Two periods, January 2019–February 2020 and March–April 2020, were defined to represent periods before (BC) and after (AC) initiation of pandemic mitigation measures, respectively. A generalized estimating equations approach was used to estimate the change in response variables at AC from BC. Results Compared to BC, the AC period was characterized by a marked reduction in the number of activations for STEMI (29%, 95% CI:18–38, p

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; p0.0001) and reduced odds of the composite adverse outcome (odds ratio 0.72; 95% confidence interval: 0.60 to 0.80; p0.0001). In conclusion, implementing a computerized email reminder system was associated with higher IVCF retrieval rates, fewer indwelling complications, and shorter dwell times.

Cardiovascular disease (CVD) represents a major public health problem in low- and middle-income countries. Global health partnerships emphasizing training and sustainability have begun to emerge in an effort to stem the tide of CVD [(1)][1]. As has been described by other fellows-in-training (FITs

The COVID-19 pandemic has significantly affected the U.S. health care system. To preserve resources, including personal protective equipment and hospital beds to care for COVID-19 patients, the Centers for Disease Control and Prevention recommended deferral of elective cardiac procedures ([1][1])

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.

Introduction: Substantial heterogeneity exists in reperfusion strategies for patients with ST-segment myocardial infarction (STEMI) in low- and middle-income countries (LMICs). We sought to compare outcomes associated with primary percutaneous coronary intervention (PPCI) and non-primary percutaneous coronary intervention (nPPCI) reperfusion strategies in patients with STEMI in Kerala, India.Methods: We performed a retrospective analysis of patients with STEMI (n = 8665) from the Acute Coronary Syndrome Quality Improvement in Kerala (ACS QUIK) randomized trial receiving either PPCI (n = 6623) or nPPCI (n = 2042). nPPCI included all PCI strategies implemented when PPCI was not available including all post-fibrinolysis PCI strategies and PCI without fibrinolysis. Clinical outcomes among patients undergoing PPCI and nPPCI were compared after propensity-score matching. The main outcomes were the rates of in-hospital and 30-day major adverse cardiovascular events (MACE), defined as the composite of death, reinfarction, stroke, and major bleeding.Results: In the propensity-score matched cohort (n = 1266 in each group), nPPCI had longer symptom onset to hospital arrival time (347.5 vs. 195.0 minutes, p < 0.001), door to balloon time (108 minutes vs. 75 minutes, p < 0.001), and were less likely to receive a coronary stent (89.4% vs. 95%, p < 0.001), including drug-eluting stents (89.5% vs. 94.4%, p < 0.001). There were no clinically meaningful differences in discharge medical therapy. However, patients treated with nPPCI were less commonly referred for cardiac rehabilitation (20.2% vs. 24.2%; p = 0.019). In-hospital (3.6% vs. 3.3%, p = 0.74%) and 30-day (4.4% vs. 4.6%, p = 0.77) MACE did not differ between nPPCI and PPCI matched groups.Conclusion: In a large, contemporary population of STEMI patients from a LMIC, patients treated with a nPPCI reperfusion strategy had comparable short- and intermediate-term outcomes compared to PPCI despite differences in hospital presentation time and coronary stent use. These findings are reassuring but highlight the need for continued quality improvement in the delivery of STEMI care in resource-limited settings.

The rising prevalence of cardiovascular disease worldwide necessitates novel therapeutic approaches to manage atherosclerosis. Intravenously administered nanostructures are a promising noninvasive approach to deliver therapeutics that reduce plaque burden. The drug Liver X Receptor agonist GW3965 (LXR) can reduce atherosclerosis by promoting cholesterol efflux from plaque but causes liver toxicity when administered systemically at effective doses, thus preventing its clinical use. We investigated here the ability of peptide amphiphile nanofibers containing apolipoprotein A1-derived targeting peptide 4F to serve as nanocarriers for LXR delivery (ApoA1-LXR PA) in vivo. These nanostructures were found to successfully target atherosclerotic lesions in a mouse model within 24 hours of injection. After eight weeks of intravenous administration, the nanostructures significantly reduced plaque burden in both male and female mice to a similar extent as LXR alone in comparison to saline-treated controls. Furthermore, they did not cause increased liver toxicity in comparison to LXR treatments, which may be related to more controlled release by the nanostructure. These findings demonstrate the potential of supramolecular nanostructures as safe, effective drug nanocarriers to manage atherosclerosis.

Outcomes associated with different reperfusion strategies among STEMI patients in low- and middle-income countries are evolving but are not well described. STEMI patients (n=8665) from the ACS QUIK trial underwent either primary PCI (PPCI) or non-primary PCI (nPPCI). PPCI was defined as PCI within

Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Healthcare systems in low- and middle-income countries are developing the infrastructure to address the rising epidemic of cardiovascular disease. In the current study, we describe the prevalence, patterns, and

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.

Objective: Atherosclerosis is the leading cause of death and disability in the United States. We hypothesize that systemic administration of a novel nanofiber will target areas of atherosclerosis and regress atherosclerotic lesions. Methods: Self assembling peptide amphiphile (PA) nanofibers were synthesized. An 18 amino acid sequence which retains the cholesterol efflux actions of apolipoprotein-A1 (apoA1) along with a Liver X Receptor (LXR) agonist, known to enhance cholesterol efflux, were incorporated into the nanofiber to both target and treat atherosclerosis. To assess the ability of the nanofiber to target and treat atherosclerosis in vivo , LDL receptor knockout mouse (LDLR KO) mice were fed a high fat diet (HFD) for 14 weeks after which they received bi-weekly injections of the therapeutic or control for 8 weeks. Optimum dose, concentration, binding duration, and biodistribution was determined using fluorescent microscopy and pixel quantification. Treatment groups included: PBS control, PA nanofiber with a scrambled targeting sequence, LXR agonist alone, targeted PA nanofiber (ApoA PA), and targeted PA nanofiber incorporating LXR agonist (ApoA-LXR PA). n=10/treatment group. Results: ApoA PA and ApoA-LXR PA nanofibers effectively targeted atherosclerotic plaque in the aortic root. Optimum concentration of nanofiber was 2mg/mL, and optimum dose was 6mg/kg. There was no difference in optimum dosing or concentration between males and female mice. ApoA PA nanofiber localized to the aortic root for approximately 2-3 days, and was cleared from the aortic root by 7-10 days. Concentrations of ApoA PA in the aortic root was 5-fold higher than in the lung, liver, and kidney one day post injection. After only 8 weeks of treatment, male and female mice treated with ApoA-LXR PA had 11 and 9% plaque area reduction compared to PBS treated controls, respectively. Differences in treatment conditions vs. controls showed sex dependence, with only male mice demonstrating significantly higher plaque reduction from ApoA1-LXR PA treatment in comparison to scrambled PA treatment. Conclusions: Our results demonstrate that a novel targeted nanofiber binds specifically to atherosclerotic lesions and reduce plaque burden after a short treatment duration.

Biodegradable vascular scaffolds (BVS) are novel treatments for obstructive atherosclerotic cardiovascular disease that have been developed to overcome the limitations of traditional metallic drug-eluting stents (DES). The mechanical properties of bioabsorbable polymers used for the production of novel BVS are a key consideration for the clinical translation of this emerging technology. Herein, we describe the engineering of an in situ light-activated vascular scaffold (ILVS) comprised of a biodegradable citric acid-based elastomeric polymer, referred to as methacrylated poly-diol citrate (mPDC), and a diazeniumdiolate chitosan nitric oxide donor (chitoNO). In vitro studies demonstrate that the mechanical properties of the ILVS can be tailored to meet or exceed those of commercially available self-expanding bare metal stents (BMS). The radial compression strength of the ILVS is higher than that of a BMS despite undergoing degradation at physiologic conditions for 7 months. ILVS containing chitoNO provides sustained supraphysiologic levels of NO release. Lastly, ILVS were successfully cast in porcine arteries ex vivo using a custom designed triple balloon catheter, demonstrating translational potential. In conclusion, these data demonstrate the ability of an ILVS to provide tunable mechanical properties and drug-delivery capabilities for the vasculature, and thereby support mPDC as a promising material for the development of novel BVS platforms.