Association of HIV and HCV Infection With Carotid Artery Plaque Echomorphology in the MACS/WIHS Combined Cohort Study.

BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.

Presence of Intracardiac Thrombus at the Time of Left Ventricular Assist Device Implantation Is Associated With an Increased Risk of Stroke and Death.

BACKGROUND: Heart failure predisposes to intracardiac thrombus (ICT) formation. There are limited data on the prevalence and impact of preexisting ICT on postoperative outcomes in left ventricular assist device patients. We examined the risk for stroke and death in this patient population. METHODS AND RESULTS: We retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between February 2009 and March 2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT. There were 525 patients with a left ventricular assist device (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) included in this analysis. An ICT was identified in 44 patients (8.4%). During the follow-up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.00-3.33, P = .049). Patients with ICT were also at higher risk for stroke (HR 2.45, 95% CI 1.14-5.28, P = .021) and death (HR 2.36, 95% CI 1.17-4.79 P = .016) at 6 months of follow-up. CONCLUSIONS: The presence of ICT is an independent predictor of stroke and death at 6 months after left ventricular assist device implantation. Additional studies are needed to help risk stratify and optimize the perioperative management of this patient population.

Bivalirudin versus heparin in patients undergoing percutaneous peripheral interventions: A systematic review and meta-analysis.

BACKGROUND: Bivalirudin may be an effective alternative anticoagulant to heparin for use in percutaneous peripheral interventions. We aimed to compare the safety and efficacy of bivalirudin versus heparin as the procedural anticoagulant agent in patients undergoing percutaneous peripheral intervention. METHODS: For this meta-analysis and systematic review, we conducted a search in PubMed, Medline, Embase, and Cochrane for all the clinical studies in which bivalirudin was compared to heparin as the procedural anticoagulant in percutaneous peripheral interventions. Outcomes studied included all-cause mortality, all-bleeding, major and minor bleeding, and access site complications. RESULTS: Eleven studies were included in the analysis, totaling 20,137 patients. There was a significant difference favoring bivalirudin over heparin for all-cause mortality (risk ratio 0.58, 95% CI 0.39-0.87), all-bleeding (risk ratio 0.62, 95% CI 0.50-0.78), major bleeding (risk ratio 0.61, 95% CI 0.39-0.96), minor bleeding (risk ratio 0.66, 95% CI 0.47-0.92), and access site complications (risk ratio 0.66, 95% CI 0.51-0.84). There was no significant difference in peri-procedural need for blood transfusions (risk ratio 0.79, 95% CI 0.57-1.08), myocardial infarction (risk ratio 0.87, 95% CI 0.59-1.28), stroke (risk ratio 0.77, 95% CI 0.59-1.01), intracranial bleeding (risk ratio 0.77, 95% CI 0.29-2.02), or amputations (OR 0.75, 95% CI 0.53-1.05). CONCLUSION: Our meta-analysis suggests that bivalirudin use for percutaneous peripheral interventions is associated with lower all-cause mortality, bleeding, and access site complications as compared to heparin. Further large randomized trials are needed to confirm the current results.

A novel adenylyl cyclase type 5 inhibitor that reduces myocardial infarct size even when administered after coronary artery reperfusion.

We developed a novel adenylyl cyclase type 5 (AC5) inhibitor, C90, that reduces myocardial infarct size even when administered after coronary reperfusion. This is key, since it is not practical to administer a drug to a patient with myocardial infarction before revascularization, and is one reason why so many prior drugs, which reduced infarct in experimental animals, failed in clinical trials. C90 is the most potent AC5 inhibitor, as exhibited by its IC50 value for AC5 inhibition, which was 5 times lower than the next most potent AC5 inhibitor. C90 reduced cAMP in response to forskolin in wild type mice by 42%, but no longer reduced cAMP in response to forskolin in mice with disruption of AC5, indicating that the mechanism of C90 was specific for AC5 inhibition. Compared with vehicle treatment, C90 reduced infarct size by 64% at a dose of 0.6 mg/kg. Thus, C90 is a novel, selective and potent AC5 inhibitor that reduces infarct size, when delivered after coronary artery reperfusion, rendering it potentially clinically useful. It also reduces beta-adrenergic receptor signaling, which will provide additional benefit to patients with coronary artery disease or heart failure.

Complete versus culprit-only revascularisation in ST elevation myocardial infarction with multi-vessel disease.

BACKGROUND: Multi-vessel coronary disease in people with ST elevation myocardial infarction (STEMI) is common and is associated with worse prognosis after STEMI. Based on limited evidence, international guidelines recommend intervention on only the culprit vessel during STEMI. This, in turn, leaves other significantly stenosed coronary arteries for medical therapy or revascularisation based on inducible ischaemia on provocative testing. Newer data suggest that intervention on both the culprit and non-culprit stenotic coronary arteries (complete intervention) may yield better results compared with culprit-only intervention. OBJECTIVES: To assess the effects of early complete revascularisation compared with culprit vessel only intervention strategy in people with STEMI and multi-vessel coronary disease. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, World Health Organization International Clinical Trials Registry Platform Search Portal, and ClinicalTrials.gov. The date of the last search was 4 January 2017. We applied no language restrictions. We handsearched conference proceedings to December 2016, and contacted authors and companies related to the field. SELECTION CRITERIA: We included only randomised controlled trials (RCTs), wherein complete revascularisation strategy was compared with a culprit-only percutaneous coronary intervention (PCI) for the treatment of people with STEMI and multi-vessel coronary disease. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of each trial using the Cochrane 'Risk of bias' tool. We resolved the disagreements by discussion among review authors. We followed standard methodological approaches recommended by Cochrane. The primary outcomes were long-term (one year or greater after the index intervention) all-cause mortality, long-term cardiovascular mortality, long-term non-fatal myocardial infarction, and adverse events. The secondary outcomes were short-term (within the first 30 days after the index intervention) all-cause mortality, short-term cardiovascular mortality, short-term non-fatal myocardial infarction, revascularisation, health-related quality of life, and cost. We analysed data using fixed-effect models, and expressed results as risk ratios (RR) with 95% confidence intervals (CI). We used GRADE criteria to assess the quality of evidence and we conducted Trial Sequential Analysis (TSA) to control risks of random errors. MAIN RESULTS: We included nine RCTs, that involved 2633 people with STEMI and multi-vessel coronary disease randomly assigned to either a complete (n = 1381) versus culprit-only (n = 1252) revascularisation strategy. The complete and the culprit-only revascularisation strategies did not differ for long-term all-cause mortality (65/1274 (5.1%) in complete group versus 72/1143 (6.3%) in culprit-only group; RR 0.80, 95% CI 0.58 to 1.11; participants = 2417; studies = 8; I2 = 0%; very low quality evidence). Compared with culprit-only intervention, the complete revascularisation strategy was associated with a lower proportion of long-term cardiovascular mortality (28/1143 (2.4%) in complete group versus 51/1086 (4.7%) in culprit-only group; RR 0.50, 95% CI 0.32 to 0.79; participants = 2229; studies = 6; I2 = 0%; very low quality evidence) and long-term non-fatal myocardial infarction (47/1095 (4.3%) in complete group versus 70/1004 (7.0%) in culprit-only group; RR 0.62, 95% CI 0.44 to 0.89; participants = 2099; studies = 6; I2 = 0%; very low quality evidence). The complete and the culprit-only revascularisation strategies did not differ in combined adverse events (51/2096 (2.4%) in complete group versus 57/1990 (2.9%) in culprit-only group; RR 0.84, 95% CI 0.58 to 1.21; participants = 4086; I2 = 0%; very low quality evidence). Complete revascularisation was associated with lower proportion of long-term revascularisation (145/1374 (10.6%) in complete group versus 258/1242 (20.8%) in culprit-only group; RR 0.47, 95% CI 0.39 to 0.57; participants = 2616; studies = 9; I2 = 31%; very low quality evidence). TSA of long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction showed that more RCTs are needed to reach more conclusive results on these outcomes. Regarding long-term repeat revascularisation more RCTs may not change our present result. The quality of the evidence was judged to be very low for all primary and the majority of the secondary outcomes mainly due to risk of bias, imprecision, and indirectness. AUTHORS' CONCLUSIONS: Compared with culprit-only intervention, the complete revascularisation strategy may be superior due to lower proportions of long-term cardiovascular mortality, long-term revascularisation, and long-term non-fatal myocardial infarction, but these findings are based on evidence of very low quality. TSA also supports the need for more RCTs in order to draw stronger conclusions regarding the effects of complete revascularisation on long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction.

High Titer of Circulating Antiglutamic Acid Decarboxylase Antibodies in a Patient with Cerebellar Ataxia and Type 1 Diabetes.

A 24-year-old female who was recently diagnosed with Type 1 diabetes mellitus (TiD) presented with a five-year history of visible gait disturbance and slurred speech. Her neurologic examination was remarkable for dysarthria, bilateral nystagmus, dysdiadochokinesia, finger-nose incoordination, heel-knee incoordination, and ataxic gait. A brain MRI disclosed diffuse cerebellar atrophy. Her serum antiglutamic acid decarboxylase (GAD) antibody titer was elevated. Antinuclear antibody (ANA) test was positive with atiterofl:2560 and a speckledpattern. Genetictests for inherited ataxia, including Friedreich ataxia, were negative for mutations. Her cerebrospinal fluid (CSF) analysis revealed oligoclonal bands and she had a positive CSF GAD65 antibody. A diag- nosis of GAD antibody-induced cerebellar ataxia was considered. She developed GAD autoimmune antibody positive TiD during the course ofher dis- ease. GAD antibody-associated cerebellar ataxia is a rare entity, however it should be considered as a possibility in patients with associated autoimmune disease and positive anti-GAD antibody.

A Food and Drug Administration-Approved Antiviral Agent that Inhibits Adenylyl Cyclase Type 5 Protects the Ischemic Heart Even When Administered after Reperfusion.

A Food and Drug Administration-approved antiviral agent, known as vidarabine or adenine 9-ß-D-arabinofuranoside (AraA), has features of inhibiting adenylyl cyclase type 5 (AC5) and protects against chronic coronary artery occlusion (CAO). The goal of this investigation was to determine whether AraA protects against myocardial ischemia, even when delivered after coronary artery reperfusion (CAR). AraA, delivered after CAR in wild-type mice, reduced infarct size by 55% compared with vehicle-treated controls, whereas an equal dose of adenosine reduced infarct size only when administered before CAR. A 5-fold greater dose of adenosine was required to reduce infarct size when delivered after CAR, which also reduced arterial pressure by 15%, whereas AraA did not affect pressure. The reduction in infarct size with AraA was prevented by a MEK/extracellular signal-regulated kinase blocker, a pathway also involved in the mechanism of protection of the AC5 knockout (KO) model. Infarct size was also reduced in cardiac-specific AC5 KO mice similarly in the presence and absence of AraA, further suggesting that AraA protection involves the AC5 pathway. AraA reduced infarct size in chronically instrumented conscious pigs when delivered after CAR, and in this model, it also reduced post-CAR coronary hyperemia, which could be another mechanism for cardioprotection (i.e., by reducing oxidative stress during CAR). Thus, AraA inhibits AC5 and exhibits unique cardioprotection when delivered after CAR, which is critical for clinical translation.

Type 5 adenylyl cyclase increases oxidative stress by transcriptional regulation of manganese superoxide dismutase via the SIRT1/FoxO3a pathway.

BACKGROUND: For reasons that remain unclear, whether type 5 adenylyl cyclase (AC5), 1 of 2 major AC isoforms in heart, is protective or deleterious in response to cardiac stress is controversial. To reconcile this controversy we examined the cardiomyopathy induced by chronic isoproterenol in AC5 transgenic (Tg) mice and the signaling mechanisms involved. METHODS AND RESULTS: Chronic isoproterenol increased oxidative stress and induced more severe cardiomyopathy in AC5 Tg, as left ventricular ejection fraction fell 1.9-fold more than wild type, along with greater left ventricular dilation and increased fibrosis, apoptosis, and hypertrophy. Oxidative stress induced by chronic isoproterenol, detected by 8-OhDG was 15% greater, P=0.007, in AC5 Tg hearts, whereas protein expression of manganese superoxide dismutase (MnSOD) was reduced by 38%, indicating that the susceptibility of AC5 Tg to cardiomyopathy may be attributable to decreased MnSOD expression. Consistent with this, susceptibility of the AC5 Tg to cardiomyopathy was suppressed by overexpression of MnSOD, whereas protection afforded by the AC5 knockout (KO) was lost in AC5 KO×MnSOD heterozyous KO mice. Elevation of MnSOD was eliminated by both sirtuin and MEK inhibitors, suggesting both the SIRT1/FoxO3a and MEK/ERK pathway are involved in MnSOD regulation by AC5. CONCLUSIONS: Overexpression of AC5 exacerbates the cardiomyopathy induced by chronic catecholamine stress by altering regulation of SIRT1/FoxO3a, MEK/ERK, and MnSOD, resulting in oxidative stress intolerance, thereby shedding light on new approaches for treatment of heart failure.

Metabolomic analysis of two different models of delayed preconditioning.

Recently we described an ischemic preconditioning induced by repetitive coronary stenosis, which is induced by 6 episodes of non-lethal ischemia over 3 days, and which also resembles the hibernating myocardium phenotype. When compared with traditional second window of ischemic preconditioning using cDNA microarrays, many genes which differed in the repetitive coronary stenosis appeared targeted to metabolism. Accordingly, the goal of this study was to provide a more in depth analysis of changes in metabolism in the different models of delayed preconditioning, i.e., second window and repetitive coronary stenosis. This was accomplished using a metabolomic approach based on liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques. Myocardial samples from the ischemic section of porcine hearts subjected to both models of late preconditioning were compared against sham controls. Interestingly, although both models involve delayed preconditioning, their metabolic signatures were radically different; of the total number of metabolites that changed in both models (135 metabolites) only 7 changed in both models, and significantly more, p<0.01, were altered in the repetitive coronary stenosis (40%) than in the second window (8.1%). The most significant changes observed were in energy metabolism, e.g., phosphocreatine was increased 4 fold and creatine kinase activity increased by 27.2%, a pattern opposite from heart failure, suggesting that the repetitive coronary stenosis and potentially hibernating myocardium have enhanced stress resistance capabilities. The improved energy metabolism could also be a key mechanism contributing to the cardioprotection observed in the repetitive coronary stenosis and in hibernating myocardium. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".

Explainable Machine Learning Analysis of Right Heart Failure After Left Ventricular Assist Device Implantation.

Right heart failure (RHF) remains a common and serious complication after durable left ventricular assist device (LVAD) implantation. We used explainable machine learning (ML) methods to derive novel insights into preimplant patient factors associated with RHF. Continuous-flow LVAD implantations from 2008 to 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) were included. A total of 186 preimplant patient factors were analyzed and the primary outcome was 30 days of severe RHF. A boosted decision tree ML algorithm and an explainable ML method were applied to identify the most important factors associated with RHF, nonlinear relationships and interactions, and risk inflection points. Out of 19,595 patients, 19.1% developed severe RHF at 30 days. Thirty top predictors of RHF were identified with the top five being INTERMACS profile, Model for End-stage Liver Disease score, the number of inotropic infusions, hemoglobin, and race. Many top factors exhibited nonlinear relationships with key risk inflection points such as INTERMACS profile between 2 and 3, right atrial pressure of 15 mmHg, pulmonary artery pressure index of 3, and prealbumin of 23 mg/dl. Finally, the most important variable interactions involved INTERMACS profile and the number of inotropes. These insights could help formulate patient optimization strategies prior to LVAD implantation.

Natural language processing analysis of the psychosocial stressors of mental health disorders during the pandemic.

Over the past few years, the COVID-19 pandemic has exerted various impacts on the world, notably concerning mental health. Nevertheless, the precise influence of psychosocial stressors on this mental health crisis remains largely unexplored. In this study, we employ natural language processing to examine chat text from a mental health helpline. The data was obtained from a chat helpline called Safe Hour from the "It Gets Better" project in Chile. This dataset encompass 10,986 conversations between trained professional volunteers from the foundation and platform users from 2018 to 2020. Our analysis shows a significant increase in conversations covering issues of self-image and interpersonal relations, as well as a decrease in performance themes. Also, we observe that conversations involving themes like self-image and emotional crisis played a role in explaining both suicidal behavior and depressive symptoms. However, anxious symptoms can only be explained by emotional crisis themes. These findings shed light on the intricate connections between psychosocial stressors and various mental health aspects in the context of the COVID-19 pandemic.

Prevention of heart failure in mice by an antiviral agent that inhibits type 5 cardiac adenylyl cyclase.

Despite numerous discoveries from genetically engineered mice, relatively few have been translated to the bedside, mainly because it is difficult to translate from genes to drugs. This investigation examines an antiviral drug, which also has an action to selectively inhibit type 5 adenylyl cyclase (AC5), a pharmaceutical correlate of the AC5 knockout (KO) model, which exhibits longevity and stress resistance. Our objective was to examine the extent to which pretreatment with this drug, adenine 9-ß-d-arabinofuranoside (Ara-A), favorably ameliorates the development of heart failure (HF). Ara-A exhibited selective inhibition for AC5 compared with the other major cardiac AC isoform, AC6, i.e., it reduced AC activity significantly in AC5 transgenic (Tg) mice, but not in AC5KO mice and had little effect in either wild-type or AC6Tg mice. Permanent coronary artery occlusion for 3 wk in C57Bl/6 mice increased mortality and induced HF in survivors, as reflected by reduced cardiac function, while increasing cardiac fibrosis. The AC5 inhibitor Ara-A significantly improved all of these end points and also ameliorated chronic isoproterenol-induced cardiomyopathy. As with the AC5KO mice, Ara-A increased mitogen/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation. A MEK inhibitor abolished the beneficial effects of the AC5 inhibitor in the HF model, indicating the involvement of the downstream MEK-ERK pathway of AC5. Our data suggest that pharmacological AC5 inhibition may serve as a new therapeutic approach for HF.

The History of Durable Left Ventricular Assist Devices and Comparison of Outcomes: HeartWare, HeartMate II, HeartMate 3, and the Future of Mechanical Circulatory Support.

The utilization of left ventricular assist devices (LVADs) in end-stage heart failure has doubled in the past ten years and is bound to continue to increase. Since the first of these devices was approved in 1994, the technology has changed tremendously, and so has the medical and surgical management of these patients. In this review, we discuss the history of LVADs, evaluating survival and complications over time. We also aim to discuss practical aspects of the medical and surgical management of LVAD patients and future directions for outcome improvement in this population.

Anthropogenic influence on surface changes at the Olivares glaciers; Central Chile.

We have investigated the source and role of light-absorbing impurities (LAIs) deposited on the glaciers of the Olivares catchment, in Central Chile. LAIs can considerably darken (lowered albedo) the glacier surface, enhancing their melt. We combined chemical and mineralogical laboratory analyses of surface and ice core samples with field-based spectral reflectance measurements to investigate the nature and properties of such LAIs. Using remote sensing-based albedo maps, we upscaled local information to glacier-wide coverage. We then used a model to evaluate the sensitivity of surface mass balance to a change in ice and snow albedo. The across-scale surface observations in combination with ice core analysis revealed a history of over half a century of LAIs deposition. We found traces of mining residuals in glacier surface samples. The glaciers with highest mass loss in the catchment present enhanced concentrations of surface dust particles with low reflectance properties. Our results indicate that dust particles with strong light-absorbing capacity have been mobilized from mine tailings and deposited on the nearby glacier surfaces. Large-scale assessment from satellite-based observations revealed darkening (ice albedo lowering) at most investigated glacier tongues from 1989 to 2018. Glacier melt is sensitive to ice albedo. We believe that an accelerated winter and spring snow albedo decrease, partially triggered by surface impurities, might be responsible for the above-average mass loss encountered in this catchment.

Right heart failure after left ventricular assist device: From mechanisms to treatments.

Left ventricular assist device (LVAD) therapy is a lifesaving option for patients with medical therapy-refractory advanced heart failure. Depending on the definition, 5-44% of people supported with an LVAD develop right heart failure (RHF), which is associated with worse outcomes. The mechanisms related to RHF include patient, surgical, and hemodynamic factors. Despite significant progress in understanding the roles of these factors and improvements in surgical techniques and LVAD technology, this complication is still a substantial cause of morbidity and mortality among LVAD patients. Additionally, specific medical therapies for this complication still are lacking, leaving cardiac transplantation or supportive management as the only options for LVAD patients who develop RHF. While significant effort has been made to create algorithms aimed at stratifying risk for RHF in patients undergoing LVAD implantation, the predictive value of these algorithms has been limited, especially when attempts at external validation have been undertaken. Perhaps one of the reasons for poor performance in external validation is related to differing definitions of RHF in external cohorts. Additionally, most research in this field has focused on RHF occurring in the early phase (i.e., ≤1 month) post LVAD implantation. However, there is emerging recognition of late-onset RHF (i.e., > 1 month post-surgery) as a significant cause of morbidity and mortality. Late-onset RHF, which likely has a unique physiology and pathogenic mechanisms, remains poorly characterized. In this review of the literature, we will describe the unique right ventricular physiology and changes elicited by LVADs that might cause both early- and late-onset RHF. Finally, we will analyze the currently available treatments for RHF, including mechanical circulatory support options and medical therapies.

Pathophysiology and management of valvular disease in patients with destination left ventricular assist devices.

Over the last two decades, implantable continuous flow left ventricular assist devices (LVAD) have proven to be invaluable tools for the management of selected advanced heart failure patients, improving patient longevity and quality of life. The presence of concomitant valvular pathology, including that involving the tricuspid, mitral, and aortic valve, has important implications relating to the decision to move forward with LVAD implantation. Furthermore, the presence of concomitant valvular pathology often influences the surgical strategy for LVAD implantation. Concomitant valve repair or replacement is not uncommonly required in such circumstances, which increases surgical complexity and has demonstrated prognostic implications both short and longer term following LVAD implantation. Beyond the index operation, it is also well established that certain valvular pathologies may develop or worsen over time following LVAD support. The presence of pre-existing valvular pathology or that which develops following LVAD implant is of particular importance to the destination therapy LVAD patient population. As these patients are not expected to have the opportunity for heart transplantation in the future, optimization of LVAD support including ameliorating valvular disease is critical for the maximization of patient longevity and quality of life. As collective experience has grown over time, the ability of clinicians to effectively address concomitant valvular pathology in LVAD patients has improved in the pre-implant, implant, and post-implant phase, through both medical management and procedural optimization. Nevertheless, there remains uncertainty over many facets of concomitant valvular pathology in advanced heart failure patients, and the understanding of how to best approach these conditions in the LVAD patient population continues to evolve. Herein, we present a comprehensive review of the current state of the field relating to the pathophysiology and management of valvular disease in destination LVAD patients.

Citizens at the forefront of the constitutional debate: Voluntary citizen participation determinants and emergent content in Chile.

In the past few decades, constitution-making processes have shifted from being undertakings performed by elites and closed off from the public to ones incorporating democratic mechanisms. Little is known, however, about the determinants of voluntary public participation and how they affect the outcomes of the deliberative process in terms of content and quality. Here, we study the process of constituent involvement in the rewriting of Chile's constitution in 2016. A total of 106, 412 citizens in 8, 113 different local encounters voluntarily congregated in groups of ten or more to collectively determine what social rights should be considered for inclusion in the new constitution, deliberating and then articulating in the written word why should be included. We brought our data to statistical regression models at the municipality level, the results show that the main determinants associated with increasing citizen participation are educational level, engagement in politics, support for the government, and Internet access. In contrast, population density and the share of Evangelical Christians in the general population decrease citizen participation. Then, we further analyze the written arguments for each collectively-selected constitutional rights. The findings suggest that groups from socioeconomically developed municipalities (with higher educational levels and where the main economic activities are more distant from natural resources), on average, deliberate consistently more about themes, concepts, and ideas compared to groups from less developed municipalities. These results provide an empirical ground on the driver factors of voluntary citizen participation and on the benefits and disadvantages of deliberative democracy. Hence, results can inform the organization of new deliberative processes.

Projected increases in surface melt and ice loss for the Northern and Southern Patagonian Icefields.

The Northern Patagonian Icefield (NPI) and the Southern Patagonian Icefield (SPI) have increased their ice mass loss in recent decades. In view of the impacts of glacier shrinkage in Patagonia, an assessment of the potential future surface mass balance (SMB) of the icefields is critical. We seek to provide this assessment by modelling the SMB between 1976 and 2050 for both icefields, using regional climate model data (RegCM4.6) and a range of emission scenarios. For the NPI, reductions between 1.5 m w.e. (RCP2.6) and 1.9 m w.e. (RCP8.5) were estimated in the mean SMB during the period 2005-2050 compared to the historical period (1976-2005). For the SPI, the estimated reductions were between 1.1 m w.e. (RCP2.6) and 1.5 m w.e. (RCP8.5). Recently frontal ablation estimates suggest that mean SMB in the SPI is positively biased by 1.5 m w.e., probably due to accumulation overestimation. If it is assumed that frontal ablation rates of the recent past will continue, ice loss and sea-level rise contribution will increase. The trend towards lower SMB is mostly explained by an increase in surface melt. Positive ice loss feedbacks linked to increasing in meltwater availability are expected for calving glaciers.