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Microvascular dysfunction (MVD) is considered a form of cardiac allograft vasculopathy (CAV), independently associated with poor prognosis after heart transplantation (HTX). It is unknown whether traditional risk factors for CAV are also applicable to MVD. We retrospectively analyzed factors associated with MVD in 94 HTX recipients who completed a PET scan after a normal baseline left heart catheterization excluding epicardial CAV. MVD was defined by abnormal PET blood flow. The mean age was 52 ± 14 and MVD was found in 49 patients (53%). No donor risk factors were significantly associated with recipient MVD. Recipients risk factors for MVD included-diabetes mellitus (51% vs. 27%, p = 0.016) and hypertension (78% vs. 49%, p = 0.004) in patients with and without MVD, respectively. In a multivariate model, recipient hypertension and diabetes were the only significant determinants of MVD development (OR = 2.63, 95% CI [1.69-36.98], p = 0.009 and OR 2.1, 95% CI [1.10-15.38], p = 0.035, respectively). In conclusion, MVD was more associated with metabolic risk determinants rather than traditional CAV risk factors., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite a record setting number of heart transplants performed annually, the national donor shortage continues to plague transplant teams across the United States. Here we describe the barriers to adaptation of numerous "non-traditional" orthotopic heart transplant donor characteristics including donors with hepatitis C virus, those meeting criteria for donation after cardiac death, donors with coronavirus disease 19 infection, donors with the human immunodeficiency virus, and grafts with left ventricular systolic dysfunction. Our center's objective was to increase our transplant volume by expanding our donor pool from "traditional" donors to these "non-traditional" donors. We detail how medical advances such as certain laboratory studies, pharmacologic interventions, and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study investigates concentrations of toxic and potentially toxic elements (PTEs) in organic and conventional wheat flour and grains marketed in Las Vegas. Geographic origins of the samples were evaluated using Linear Discriminant Analysis (LDA). Monte Carlo Simulation technique was also employed to evaluate non-carcinogenic risk in four life stages. Concentrations of Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, Sr, and Zn were determined using inductively coupled plasma mass spectrometry (ICP-MS) following hot block-assisted digestion. Obtained results showed non-significant differences in contents of toxic and PTEs between conventional and organic wheat grains/flour. Using LDA, metal (loid)s were found to be indicative of geographical origin. The LDA produced a total correct classification rate of 95.8% and 100% for US and West Pacific Region samples, respectively. The results of the present study indicate that the estimated non-carcinogenic risk associated with toxic element intakes across the four life stages were far lower than the threshold value (Target Hazard Quotient (THQ) > 1). However, the probability of exceeding the threshold value for Mn is approximately 32% in children aged between 5 and 8 years. The findings of this study can aid in understanding dietary Mn exposure in children in Las Vegas., Competing Interests: Declaration of competing interest 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., (Published by Elsevier Ltd.)

Introduction: Donation after circulatory death (DCD) donors are becoming an important source of organs for heart-transplantation (HT), but there are limited data regarding their use in multiorgan-HT., Methods: Between January 2020 and June 2023, we identified 87 adult multiorgan-HTs performed using DCD-donors [77 heart-kidney, 6 heart-lung, 4 heart-liver] and 1494 multiorgan-HTs using donation after brain death (DBD) donors (1141 heart-kidney, 165 heart-lung, 188 heart-liver) in UNOS. For heart-kidney transplantations (the most common multiorgan-HT combination from DCD-donors), we also compared donor/recipient characteristics, and early outcomes, including 6-month mortality using Kaplan-Meier (KM) and Cox hazards-ratio (Cox-HR)., Results: Use of DCD-donors for multiorgan-HTs in the United States increased from 1% in January to June 2020 to 12% in January-June 2023 (p < 0.001); but there was a wide variation across UNOS regions and center volumes. Compared to recipients of DBD heart-kidney transplantations, recipients of DCD heart-kidney transplantations were less likely to be of UNOS Status 1/2 at transplant (35.06% vs. 69.59%) and had lower inotrope use (22.08% vs. 43.30%), lower IABP use (2.60% vs. 26.29%), but higher durable CF-LVAD use (19.48% vs. 12.97%), all p < 0.01. Compared to DBD-donors, DCD-donors used for heart-kidney transplantations were younger [28(22-34) vs. 32(25-39) years, p = 0.004]. Recipients of heart-kidney transplantations from DCD-donors and DBD-donors had similar 6-month survival using both KM analysis, and unadjusted and adjusted Cox-HR models, including in propensity matched cohorts. Rates of PGF and in-hospital outcomes were also similar., Conclusions: Use of DCD-donors for multiorgan-HTs has increased rapidly in the United States and early outcomes of DCD heart-kidney transplantations are promising., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Concentrations of metal(loid)s, Ag, Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Se, Sr, V and Zn, were determined in rice on sale in Las Vegas. The rice samples were grown in five different countries, the USA, Thailand, India, Pakistan, and Bangladesh. The elemental concentrations in rice grain were determined using inductively coupled plasma mass spectrometry (ICP-MS) following hot block-assisted digestion. The accuracy of the laboratory procedure was verified by the analysis of rice flour standard reference material (NIST SRM 1568b). The mean metal(loid) contents in rice of various geographic origins were 3.18-5.91 mg kg -1 for Al, 0.05-0.12 mg kg -1 for As, 3.64-41 μg kg -1 for Cd, 5.11-12 μg kg -1 for Co, 0.12-0.14 mg kg -1 for Cr, 1.5-1.91 mg kg -1 for Cu, 3.04-4.98 mg kg -1 for Fe, 4.2-10.4 mg kg -1 for Mn, 0.21-0.41 mg kg -1 for Ni, 0.02-0.07 mg kg -1 for Se, 0.68-0.88 mg kg -1 for Sr, 3.64-5.26 μg kg -1 for V, and 16.6-19.9 mg kg -1 for Zn. respectively. The mean concentration of As in US rice was significantly higher than in Indian, Pakistani, and Bangladeshi rice. On the other hand, it was found a significantly low mean level of Cd in US-grown rice. It was also found that the concentrations of metal(loid)s in black and brown rice on sale in Las Vegas were statistically similar, except for Mn and Se. The geographic origin traceability of rice grain involved the use of ICP-MS analysis coupled with chemometrics that allowed their differentiation based on the rice metal(loid) profile, thus confirming their origins. Data were processed by linear discriminant analysis, and US and Thai rice samples were cross-validated with higher accuracy (100%). This authentication quickly discriminates US rice from the other regions and adds verifiable food safety measures for consumers., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Orthotopic heart transplant is the gold standard therapeutic intervention for patients with end-stage heart failure. Conventionally, heart transplant has relied on donation after brain death for organ recovery. Donation after circulatory death (DCD) is the donation of the heart after confirming that circulatory function has irreversibly ceased. DCD-orthotopic heart transplant differs from donation after brain death-orthotopic heart transplant in ways that carry implications for widespread adoption, including differences in organ recovery, storage and ethical considerations surrounding normothermic regional perfusion with DCD. Despite these differences, DCD has shown promising early outcomes, augmenting the donor pool and allowing more individuals to benefit from orthotopic heart transplant. This review aims to present the current state and future trajectory of DCD-heart transplant, examine key differences between DCD and donation after brain death, including clinical experiences and innovations in methodologies, and address the ongoing ethical challenges surrounding the new frontier in heart transplant with DCD donors., Competing Interests: Dr Jorde is a consultant for Abbott. Dr Goldstein is a consultant for Abbott Inc and a consultant and speaker for Abiomed Inc.

Among the most renowned Ethiopian food crops, teff (Eragrostis tef (Zucc.)Trotter) is the most nutritious and gluten-free cereal. Because of the increase in demand for teff, it is necessary to establish geographic origin authentication of traditional teff brands based on multi-element fingerprint. For this purpose, a total of 60 teff samples were analysed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Accuracy of the laboratory procedure was verified by the analysis of rice flour standard reference material (NIST SRM 1568b). In this context, four traditional teff brands (Ada'a, Ginchi, Gojam and Tulu Bolo) were analytically characterized using multi-element fingerprint and further treated statistically using linear discriminant analysis (LDA). Due to obvious extrinsic Fe, Al and V contamination, these elements were excluded from the discriminant model. Five elements (Cu, Mo, Se, Sr, and Zn) significantly contributed to discriminate the geographical origin of white teff. On the other hand, Mn, Mo, Se and Sr were used as discriminant variables for brown teff. LDA revealed 90 and 100% correct classifications for white and brown teff, respectively. Overall, multi-element fingerprint coupled with LDA can be considered a suitable tool for geographic origin discrimination of traditional teff brands., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The dam failure of the Córrego do Feijão Mine (CFM) located in Minas Gerais State, Brazil, killed at least 278 people. In addition, large extensions of aquatic and terrestrial ecosystems were destroyed, directly compromising the environmental and socioeconomic quality of the region. This study assessed the pollution and human health risks of soils impacted by the tailing spill of the CFM dam, along a sample perimeter of approximately 200 km. Based on potential ecological risk and pollution load indices, the enrichments of Cd, As, Hg, Cu, Pb and Ni in soils indicated that the Brumadinho, Mário Campos, Betim and São Joaquim de Bicas municipalities were the most affected areas by the broken dam. Restorative and reparative actions must be urgently carried out in these areas. For all contaminated areas, the children's group indicated an exacerbated propensity to the development of carcinogenic and non-carcinogenic diseases, mainly through the ingestion pathway. Toxicological risk assessments, including acute, chronic and genotoxic effects, on people living and working in mining areas should be a priority for public management and mining companies to ensure effective environmental measures that do not harm human health and well-being over time., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Primary graft dysfunction (PGD) after cardiac transplantation is a devastating complication with increasing frequency lately in the setting of donation after circulatory death (DCD). Severe PGD is commonly treated with extracorporeal membrane oxygenation (ECMO) using central or peripheral cannulation. We retrospectively reviewed the outcomes of PGD after cardiac transplantation requiring ECMO support at our center from 2015 to 2020, focused on our now preferential approach using peripheral cannulation without a priori venting. During the study period, 255 patients underwent heart transplantation at our center and 26 (10.2%) of them required ECMO for PGD. Of 24 patients cannulated peripherally 19 (79%) were alive at 30 days and 17 (71%) 1 year after transplant; two additional patients underwent central ECMO cannulation due to unfavorable size of femoral vessels and concern for limb ischemia. Successful decannulation with full graft function recovery occurred in 22 of 24 (92%) patients cannulated peripherally. Six of them had an indwelling intra-aortic balloon pump placed before the transplantation. None of the other 18 patients received a ventricular vent. In conclusion, the use of an a priori peripheral and ventless ECMO approach in patients with PGD after heart transplant is an effective strategy associated with high rates of graft recovery and survival., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Fungal infective endocarditis, although rare, carries a high mortality risk. We present a case of successful multidisciplinary management of Exophiala dermatitidis infective endocarditis in an immunocompetent male with a bio-prosthetic mitral valve. This case highlights the clinical presentation and provides valuable treatment insights into this rare fungal entity. Prompt consideration of fungal pathogens in predisposed patients, expedited detection through non-culture-based tests, and a combined surgical and prolonged antifungal approach are pivotal., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The use of intra-aortic balloon pump (IABP) has decreased in recent years due to negative outcome studies in cardiogenic shock complicating acute myocardial infarction, despite its favorable adverse-event profile. Acute hemodynamic response studies have identified potential super-responders with immediate improvements in cardiac index (CI) in heart failure patients. This single-center retrospective study aimed to predict CI and mean arterial pressure (MAP) changes throughout the entire duration of IABP support. The study analyzed 336 patients who received IABP between 2016 and 2022. Linear mixed-effect regression models were used to predict CI and MAP improvement during IABP support. The results showed that CI and MAP increases during the first days of support, and changes during IABP support varied with time and were associated with baseline parameters. Longitudinal CI change was associated with body surface area, baseline CI, baseline pulmonary artery pulsatility index, baseline need for pressors, and diabetes. Longitudinal MAP change was associated with baseline MAP, baseline heart rate, need for pressors, or inotropes. The study recommends considering these parameters when deciding if IABP is the most appropriate form of support for a specific patient. Further prospective studies are needed to validate the findings., Competing Interests: Disclosure: F.C. is supported by a grant from the National Institute for Health (T32HL144456) and by the National Center for Advancing Translational Science (NCATS) Clinical and Translational Science Award at Einstein-Montefiore (UL1TR001073). U.P.J. is supported by the McAdam Family Foundation. The other authors have no conflicts of interest to report., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Non-ST-segment myocardial infarction (NSTEMI) occurs frequently in a growing population of patients with chronic heart failure (HF) and end-stage renal disease (ESRD) but outcomes with invasive management approaches are unknown. We sought to determine in-hospital outcomes with percutaneous coronary intervention (PCI) in comparison with medical management only. The National Inpatient Sample was used to capture hospitalizations in the United States from 2006 to 2019. Admissions for NSTEMI in patients with chronic HF and ESRD were identified by International Classification of Diseases codes. The cohort was divided into those that received PCI or medical management only. In-hospital outcomes were compared by multivariable logistic regression and propensity matching. In 27,433 hospitalizations, 8,004 patients (29%) underwent PCI, and 19,429 (71%) were managed with medications only. PCI was associated with lower adjusted odds of death during hospitalization (adjusted odds ratio 0.59, 95% confidence interval 0.52 to 0.66, p <0.01). This association remained consistent after propensity matching (adjusted odds ratio 0.56, 95% confidence interval 0.49 to 0.64, p <0.01) and was apparent across all subtypes of HF. Patients with PCI had greater duration (5, 3, to 9 vs, 5, 3 to 8 days, p <0.01) and cost of hospitalization ($107,942, 70,230 to $173,182 vs, $44,156, 24,409 to $80,810, p <0.01). In conclusion, patients with HF and ESRD admitted for NSTEMI experienced lower in-hospital mortality with PCI in comparison with medical therapy only. Invasive percutaneous revascularization may be reasonable for appropriately selected patients with HF and ESRD but randomized controlled trials are needed to determine its safety and efficacy in this high-risk population., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There is a paucity of data on heart transplantation (HT) using COVID-19 donors., Objectives: This study investigated COVID-19 donor use, donor and recipient characteristics, and early post-HT outcomes., Methods: Between May 2020 and June 2022, study investigators identified 27,862 donors in the United Network for Organ Sharing, with 60,699 COVID-19 nucleic acid amplification testing (NAT) performed before procurement and with available organ disposition. Donors were considered "COVID-19 donors" if they were NAT positive at any time during terminal hospitalization. These donors were subclassified as "active COVID-19" (aCOV) donors if they were NAT positive within 2 days of organ procurement, or "recently resolved COVID-19" (rrCOV) donors if they were NAT positive initially but became NAT negative before procurement. Donors with NAT-positive status >2 days before procurement were considered aCOV unless there was evidence of a subsequent NAT-negative result ≥48 hours after the last NAT-positive result. HT outcomes were compared., Results: During the study period, 1,445 "COVID-19 donors" (COVID-19 NAT positive) were identified; 1,017 of these were aCOV, and 428 were rrCOV. Overall, 309 HTs used COVID-19 donors, and 239 adult HTs from COVID-19 donors (150 aCOV, 89 rrCOV) met study criteria. Compared with non-COV, COVID-19 donors used for adult HT were younger and mostly male (∼80%). Compared with HTs from non-COV donors, recipients of HTs from aCOV donors had increased mortality at 6 months (Cox HR: 1.74; 95% CI: 1.02-2.96; P = 0.043) and 1 year (Cox HR: 1.98; 95% CI: 1.22-3.22; P = 0.006). Recipients of HTs from rrCOV and non-COV donors had similar 6-month and 1-year mortality. Results were similar in propensity-matched cohorts., Conclusions: In this early analysis, although HTs from aCOV donors had increased mortality at 6 months and 1 year, HTs from rrCOV donors had survival similar to that seen in recipients of HTs from non-COV donors. Continued evaluation and a more nuanced approach to this donor pool are needed., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure: The authors have no conflicts of interest to report.

The use of temporary mechanical circulatory support in cardiogenic shock has increased dramatically despite a lack of randomized controlled trials or evidence guiding clinical decision-making. Recommendations from professional societies on temporary mechanical circulatory support escalation and de-escalation are limited. This scientific statement provides pragmatic suggestions on temporary mechanical circulatory support device selection, escalation, and weaning strategies in patients with common cardiogenic shock causes such as acute decompensated heart failure and acute myocardial infarction. The goal of this scientific statement is to serve as a resource for clinicians making temporary mechanical circulatory support management decisions and to propose standardized approaches for their use until more robust randomized clinical data are available.

Aims: Pulmonary artery pressure (PAP)-guided therapy in patients with heart failure (HF) using the CardioMEMS (CMM) device, an implantable PAP sensor, has been shown to reduce HF hospitalizations in previous studies. We sought to evaluate the clinical benefit of the CMM device in regard to 30, 90, and 180 day readmission rates in real-world usage., Methods and Results: We queried the Nationwide Readmissions Database (NRD) to identify patients who underwent CMM implantation (International Classification of Diseases 9 and 10 codes) between the years 2014 and 2019 and studied their HF readmissions. Moreover, we compared CMM patients and their readmissions with a matched cohort of patients with HF but without CMM. Multivariable Cox regression analysis was performed to adjust for other predictors of readmissions. Prior to matching, we identified 5 326 530 weighted HF patients without CMM and 1842 patients with CMM. After propensity score matching for several patients and hospital-related characteristics, the cohort consisted of 1839 patients with CMM and 1924 with HF without CMM. Before matching, CMM patients were younger (67.0 ± 13.5 years vs. 72.3 ± 14.1 years, P < 0.001), more frequently male (62.7% vs. 51.5%, P < 0.001), with higher rates of prior percutaneous coronary intervention (16.9% vs. 13.2%, P = 0.002), peripheral vascular disease (29.6% vs. 17.8%, P < 0.001), pulmonary circulatory disorder (38.7% vs. 23.2%, P < 0.001), atrial fibrillation (51.2% vs. 45.3%, P = 0.002), prior left ventricular assist device (1.8% vs. 0.2%, P < 0.001), high income (32.2% vs. 16.4%, P < 0.001), and acute kidney disease (43.8% vs. 29.9%, P < 0.001). Readmission rates at 30 days were 17.3% vs. 20.9% for patients with vs. without CMM, respectively, and remained statistically significant after matching (17.3% vs. 21.5%, P = 0.002). The rates of 90 day (29.6% vs. 36.5%, P = 0.002) and 180 day (39.6% vs. 46.6%, P = 0.009) readmissions were lower in the CMM group. In a multivariable regression model, CMM was associated with lower risk of readmissions (hazard ratio 0.75, 95% confidence interval 0.63-0.89, P = 0.001)., Conclusions: The CMM device was associated with reduced HF rehospitalization rates in a nationally representative cohort of HF patients, validating the clinical trial that led to the approval of this device and its utilization in the treatment of HF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Cardiac injury has been reported in up to 20%-to-30% of patients with COVID-19, and severe disease can lead to cardiopulmonary failure. The role of mechanical circulatory support in these patients remains undetermined. The authors here aimed to determine the characteristics and outcomes of patients with COVID-19 requiring venoarterial extracorporeal membrane oxygenation (VA ECMO) or veno-arterial-venous (VAV) ECMO support., Design and Setting: A multicenter, retrospective case series., Participants: The cohort consisted of adult patients (18 years of age and older) with confirmed COVID-19 requiring VA ECMO or VAV ECMO support in the period from March 1, 2020, to April 30, 2021. Outcomes were recorded until July 31, 2021., Measurements and Main Results: To show factors related to death during hospitalization, patients were grouped as survivors and nonsurvivors. Kaplan-Meier analysis was used to estimate 90-day in-hospital mortality. Overall, 37 patients from 12 centers comprised the study cohort. The median patient age was 44 years old (interquartile range [IQR], 35-52), and 12 (32%) were female patients. The duration of ECMO support ranged from 2-to-132 days. At the end of the follow-up period, 13 patients (35%) were discharged or transferred alive, and 24 patients (65%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 64% (95% confidence interval: 47-81). During the time from intubation to VA ECMO or VAV ECMO initiation (1 day [IQR 0-7.5] v 6 days [IQR 2.5-14], p = 0.0383), body mass index (32 [IQR 26-36] v 37 [IQR 33-40], p = 0.009), and baseline C-reactive protein (7.15 v 38.9 mg/dL, p = 0.009) were higher in those who expired., Conclusion: Only one-third of the patients with COVID-19 requiring VA ECMO or VAV ECMO survived to discharge. Close monitoring of at-risk patients with early initiation of ECMO with circulatory support may further improve outcomes., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cardiac intensive care units (CICUs) serve medically complex patients with multiorgan dysfunction. Whether a CICU that is staffed full time by heart failure (HF) specialists is associated with decreased mortality is unclear., Methods and Results: A retrospective review of consecutive CICU admissions from January 1, 2012, to December 31, 2016, was performed. In January 2014, the CICU changed from an open unit staffed by any cardiologist to a closed unit managed by HF specialists. Patients' baseline characteristics were determined, and a multivariate regression analysis was performed to ascertain mortality rates in the CICU. Baseline severity of illness was higher in the closed/HF specialist CICU model (P< 0.001). Death occurred in 101 of 1185 patients admitted to the CICU (8.5%) in the open-unit model and in 139 of 2163 patients (6.4%) admitted to the closed/HF specialist model (absolute risk reduction 2.1%, 95% confidence interval [CI] 0.1-4.0%; P = 0.01). The transition from an open to a closed/HF specialist model was associated with a lower overall CICU mortality rate (odds ratio [OR] 0.63; 95% CI 0.43-0.93). Prespecified interaction with a mechanical circulatory support device and unit model showed that treatment with such a device was associated with lower mortality rates in the closed/HF specialist model of a CICU (OR 0.6; 95% CI 0.18-0.78; P for interaction <0.01)., Conclusion: Transition to a closed unit model staffed by a dedicated HF specialist is associated with lower CICU mortality rates., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Introduction: COVID-19 first struck New York City in the spring of 2020, resulting in an unprecedented strain on our healthcare system and triggering multiple changes in public health policy governing hospital operations as well as therapeutic approaches to COVID-19. We examined inpatient mortality at our centre throughout the course of the pandemic., Methods: This is a retrospective chart review of clinical characteristics, treatments and outcome data of all patients admitted with COVID-19 from 1 March 2020 to 28 February 2021. Patients were grouped into 3-month quartiles. Hospital strain was assessed as per cent of occupied beds based on a normal bed capacity of 1491., Results: Inpatient mortality decreased from 25.0% in spring to 10.8% over the course of the year. During this time, use of remdesivir, steroids and anticoagulants increased; use of hydroxychloroquine and other antibiotics decreased. Daily bed occupancy ranged from 62% to 118%. In a multivariate model with all year's data controlling for demographics, comorbidities and acuity of illness, percentage of bed occupancy was associated with increased 30-day in-hospital mortality of patients with COVID-19 (0.7% mortality increase for each 1% increase in bed occupancy; HR 1.007, CI 1.001 to 1.013, p=0.004) CONCLUSION: Inpatient mortality from COVID-19 was associated with bed occupancy. Early reduction in epicentre hospital bed occupancy to accommodate acutely ill and resource-intensive patients should be a critical component in the strategic planning for future pandemics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning., Methods: A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed. We identified 91 patients who had early RV AMCS on index admission. Cox proportional-hazards model was constructed to identify predictors of 1-year mortality post-RV AMCS implantation and competing risk modeling identified RV AMCS weaning predictors., Results: There were 91 of 826 patients (11%) who required RV AMCS after CF-LVAD implantation with 51 (56%) receiving a concomitant RV AMCS and 40 (44%) implanted with a postoperative RV AMCS during their ICU stay; 48 (53%) patients were weaned from RV AMCS support. Concomitant RV AMCS with CF-LVAD insertion was associated with lower mortality (HR 0.45 [95% CI 0.26-0.80], p = 0.01) in multivariable model (which included age, BMI, angiotensin-converting enzyme inhibitor use, and heart transplantation as a time-varying covariate). In the multivariate competing risk analysis, a TPG < 12 (SHR 2.19 [95% CI 1.02-4.70], p = 0.04) and concomitant RV AMCS insertion (SHR 3.35 [95% CI 1.73-6.48], p < 0.001) were associated with a successful wean., Conclusions: In patients with RVF after LVAD implantation, concomitant RV AMCS insertion at the time of LVAD was associated with improved 1-year survival and increased chances of RV support weaning compared to postoperative insertion., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The use of the HeartMate 3 (HM3) left ventricular assist device (LVAD) is expanding. Despite being associated with lower rates of adverse events and increased survival, outflow graft obstruction (OGO) has been reported in patients with HM3. The incidence and best management of this serious complication remain unclear., Methods: We describe six cases of HM3 OGO occurring in five patients in our institutional HM3 cohort. Four cases underwent computed tomography angiography and in two percutaneous angiography was directly performed to confirm the diagnosis. In four cases, percutaneous repair of the OG was performed using common interventional cardiology (IC) techniques., Results: Our institutional incidence of OGO was 7% (event rate of 0.05 per patient year); much higher than the previously reported incidence of 1.6%. All cases occurred in the bend relief covered segment. Only two patients had apparent OG twisting, and in two, OGO occurred despite placement of an anti-twist clip at the time of implant. External compression seems to play a role in most cases. Balloon "graftoplasty" and stent deployment via the femoral artery alleviated the obstruction and normalized LVAD flow in all patients who underwent percutaneous repair. The use of self-expanding stents allowed for downsizing of the procedural access site to 10 Fr. No serious procedure-related complications occurred., Conclusion: OGO is common in HM3 patients, external compression due to biomaterial accumulated surrounding the OG is a common etiology. Percutaneous repair using standard IC techniques is safe and feasible in cases of compression with or without partial twisting., (© 2021 Wiley Periodicals LLC.)

Aims: Prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implant remains a challenge. The EUROMACS right-sided heart failure (EUROMACS-RHF) risk score was proposed as a prediction tool for post-LVAD RHF but lacks from large external validation. The aim of our study was to externally validate the score., Methods and Results: From January 2007 to December 2017, 878 continuous-flow LVADs were implanted at three tertiary centres. We calculated the EUROMACS-RHF score in 662 patients with complete data. We evaluated its predictive performance for early RHF defined as either (i) need for short- or long-term right-sided circulatory support, (ii) continuous inotropic support for ≥14 days, or (iii) nitric oxide for ≥48 h post-operatively. Right heart failure occurred in 211 patients (32%). When compared with non-RHF patients, pre-operatively they had higher creatinine, bilirubin, right atrial pressure, and lower INTERMACS class (P < 0.05); length of stay and in-hospital mortality were higher. Area under the ROC curve for RHF prediction of the EUROMACS-RHF score was 0.64 [95% confidence interval (CI) 0.60-0.68]. Reclassification of patients with RHF was significantly better when applying the EUROMACS-RHF risk score on top of previous published scores. Patients in the high-risk category had significantly higher in-hospital and 2-year mortality [hazard ratio: 1.64 (95% CI 1.16-2.32) P = 0.005]., Conclusion: In an external cohort, the EUROMACS-RHF had limited discrimination predicting RHF. The clinical utility of this score remains to be determined., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Outcomes for cardiogenic shock (CS) patients remain relatively poor despite significant advancements in primary percutaneous coronary interventions (PCI) and temporary circulatory support (TCS) technologies. Mortality from CS shows great disparities that seem to reflect large variations in access to care and physician practice patterns. Recent reports of different models to standardize care in CS have shown considerable potential at improving outcomes. The creation of regional, integrated, 3-tiered systems, would facilitate standardized interventions and equitable access to care. Multidisciplinary CS teams at Level I centers would direct care in a hub-and-spoke model through jointly developed protocols and real-time shared decision making. Levels II and III centers would provide early access to life-saving therapies and safe transfer to designated hub centers. In regions with large geographical distances, the implementation of telemedicine-cardiac intensive care unit (CICU) care can be an important resource for the creation of effective systems of care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alvarez Villela, Clark, William, Sims and Jorde.)

Aims: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established., Methods and Results: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction., Conclusions: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19.

Aims: Patients with left ventricular assist device (LVAD) suffer from persistent exercise limitation despite improvement of their heart failure syndrome. Exercise training (ET) programmes to improve aerobic capacity have shown modest efficacy. High-intensity interval training (HIIT), as an alternative to moderate continuous training, has not been systematically tested in this population. We examine the feasibility of a short, personalized HIIT programme in patients with LVAD and describe its effects on aerobic capacity and left ventricular remodelling., Methods and Results: Patients on durable LVAD support were prospectively enrolled in a 15-session, 5 week HIIT programme. Turndown echocardiogram, Kansas City Cardiomyopathy Questionnaire, and cardiopulmonary exercise test were performed before and after HIIT. Training workloads for each subject were based on pretraining peak cardiopulmonary exercise test work rate (W). Percentage of prescribed training workload completed and adverse events were recorded for each subject. Fifteen subjects were enrolled [10 men, age = 51 (29-71) years, HeartMate II = 12, HeartMate 3 = 3, and time on LVAD = 18 (3-64) months]. Twelve completed post-training testing. HIIT was well tolerated, and 90% (inter-quartile range: 78, 99%) of the prescribed workload (W) was completed with no major adverse events. Improvements were seen in aV̇O 2 at ventilatory threshold [7.1 (6.5, 9.1) to 8.5 (7.7, 9.3) mL/kg/min, P = 0.04], work rate at ventilatory threshold [44 (14, 54) to 55 (21, 66) W, P = 0.05], and left ventricular end-diastolic volume [168 (144, 216) to 159 (124, 212) mL, n = 7, P = 0.02]. HIIT had no effect on maximal oxygen consumption (V̇O 2peak ) or Kansas City Cardiomyopathy Questionnaire score., Conclusions: Cardiopulmonary exercise test-guided HIIT is feasible and can improve submaximal aerobic capacity in stable patients with chronic LVAD support. Further studies are needed on its effects on the myocardium and its potential role in cardiac rehabilitation programmes., (©2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Peripheral venous pressure (PVP) monitoring is a noninvasive method to assess volume status. We investigated the correlation between PVP and central venous pressure (CVP) in heart failure (HF), heart transplant (HTx), and left ventricular assist device (LVAD) patients undergoing right heart catheterization (RHC). A prospective, cross-sectional study examining PVP in 100 patients from October 2018 to January 2020 was conducted. The analysis included patients undergoing RHC admitted for HF, post-HTx monitoring, or LVAD hemodynamic testing. Sixty percent of patients had HF, 30% were HTx patients, and 10% were LVAD patients. The mean PVP was 9.4 ± 5.3 mm Hg, and the mean CVP was 9.2 ± 5.8 mm Hg. The PVP and CVP were found to be highly correlated (r = 0.93, p < 0.00001). High correlation was also noted when broken down by HF (r = 0.93, p < 0.00001), HTx (r = 0.93, p < 0.00001), and LVAD groups (r = 0.94, p < 0.00005). In conclusion, there is a high degree of correlation between PVP and CVP in HF, HTx, and LVAD patients. PVP measurements can be used as a rapid, reliable, noninvasive estimate of volume status in these patient populations., Competing Interests: Conflicts of 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background Severe coronavirus disease 2019 (COVID-19) is characterized by a proinflammatory state with high mortality. Statins have anti-inflammatory effects and may attenuate the severity of COVID-19. Methods and Results An observational study of all consecutive adult patients with COVID-19 admitted to a single center located in Bronx, New York, was conducted from March 1, 2020, to May 2, 2020. Patients were grouped as those who did and those who did not receive a statin, and in-hospital mortality was compared by competing events regression. In addition, propensity score matching and inverse probability treatment weighting were used in survival models to examine the association between statin use and death during hospitalization. A total of 4252 patients were admitted with COVID-19. Diabetes mellitus modified the association between statin use and in-hospital mortality. Patients with diabetes mellitus on a statin (n=983) were older (69±11 versus 67±14 years; P <0.01), had lower inflammatory markers (C-reactive protein, 10.2; interquartile range, 4.5-18.4 versus 12.9; interquartile range, 5.9-21.4 mg/dL; P <0.01) and reduced cumulative in-hospital mortality (24% versus 39%; P <0.01) than those not on a statin (n=1283). No difference in hospital mortality was noted in patients without diabetes mellitus on or off statin (20% versus 21%; P =0.82). Propensity score matching (hazard ratio, 0.88; 95% CI, 0.83-0.94; P <0.01) and inverse probability treatment weighting (HR, 0.88; 95% CI, 0.84-0.92; P <0.01) showed a 12% lower risk of death during hospitalization for statin users than for nonusers. Conclusions Statin use was associated with reduced in-hospital mortality from COVID-19 in patients with diabetes mellitus. These findings, if validated, may further reemphasize administration of statins to patients with diabetes mellitus during the COVID-19 era.

Contemporary cardiac intensive care units (CICUs) have an increasing prevalence of noncardiovascular comorbidities and multisystem organ dysfunction. However, little guidance exists to support the development of best-practice principles specific to the CICU. This scientific statement evaluates strategies to avoid the potentially preventable complications encountered within contemporary CICUs, focusing on those that are most applicable to the CICU environment. This scientific statement reviews evidence-based practices derived in non-CICU populations, assesses their relevance to CICU practice, and highlights key knowledge gaps warranting further investigation to attenuate patient risk.

Background: The impact of different types of regional wall motion abnormalities (RWMAs), including the Takotsubo syndrome-like (TTS-like) phenotype, on posttransplant outcomes when using donor hearts with transient left ventricular systolic dysfunction (LVSD) is unknown. We evaluated the prevalence, clinical characteristics, and prognostic association of different RWMAs including TTS-like hypokinesis and posttransplant outcomes when using donor hearts with transient LVSD., Methods: From all adult (≥18 years) heart transplants in United Network of Organ Sharing between January 2007 and September 2015, we identified 472 donor hearts with improving or transient LVSD, defined as left ventricular ejection fraction ≤ 40% on initial transthoracic echocardiogram (TTE) that improved to ≥50% on follow-up TTE during donor evaluation. These improved LVSD donors were then subdivided into 3 groups based on RWMAs on the initial TTE, TTS-like (49, 10.38%), non-TTS RWMAs (74, 15.68%), and diffuse global hypokinesis (349, 73.94%), and compared for baseline characteristics and posttransplant outcomes with follow up until June 2018., Results: Donors with TTS-like LVSD were older and more likely to be female. The type of RWMA on initial TTE (including TTS-like) of transient LVSD donor hearts was not associated with 1-year or 5-year posttransplant mortality. Posttransplant functional status scores of recipients (at 1 year) and donor left ventricular ejection fraction (at median follow-up of 3.6 years) improved in all 3 subgroups. Rates of stroke or pacemaker predischarge were also similar., Conclusions: In the largest analysis of transplanted donor hearts with transient LVSD, 1 in 4 had RWMAs on the initial TTE, but this was not associated with adverse posttransplant outcomes. Donor hearts with initial LVSD should be pursued irrespective of TTS-like hypokinesis or other RWMAs., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of evidence to guide appropriate donor sizing in recipients with moderate pulmonary hypertension (pHTN) awaiting heart transplantation (HTx). It is common practice to oversize donor hearts for such recipients to prevent post-operative right ventricular failure. Therefore, our objective was to determine if oversizing in pre-transplant moderate pHTN provides a survival advantage., Methods: The United Network for Organ Sharing database was analyzed to include HTx recipients from 1994 to 2016. Recipients were considered as having moderate pHTN if the pulmonary vascular resistance (PVR) was 2.5 to 5 Wood units (WU) or transpulmonary gradient (TPG) was 10 to 18 mm Hg. Heart size mismatch was determined using the predicted heart mass equations. A size mismatch of ≥15% in either direction was considered undersized or oversized, respectively. Ninety-day and 1-year survival were analyzed based on size matching via univariate and Cox regression analysis. Propensity matching was performed to specifically evaluate the effect of donor sex among male transplant recipients., Results: Among 29,441 HTx recipients, 10,666 had moderate pHTN by PVR criteria and 12,624 HTx patients had moderate pHTN according to TPG criteria. Among patients with a PVR of 2.5 to 5 WU, oversizing was not associated with lower mortality compared with matched hearts at 90 days (7.6% vs 7.4%; p = 0.75) and 1 year (12.1% vs 11.3%; p = 0.26). Conversely, undersizing the donor was associated with a higher 90-day (10.6% vs 7.6% vs 7.4%; p < 0.01) and 1-year (15.3% vs 12.1% vs 11.3%; p < 0.01) mortality than recipients receiving oversized or matched hearts, respectively. On Cox regression analysis, there was no benefit with oversizing at 90 days (hazard ratio [HR] 0.88; p = 0.23) and 1 year (HR 0.99; p = 0.90), whereas undersizing was associated with higher 90-day (HR 1.32; p = 0.02) and 1-year mortality (HR 1.23; p = 0.03) compared to size-matched controls. Among patients with moderate pHTN based on TPG of 10 to 18 mm Hg, neither undersizing nor oversizing was predictive of mortality at 90 days and 1 year according to Cox regression analysis. Propensity matching revealed that female-to-male transplantation had similar 1-year mortality to male-to-male transplantation, and there was no advantage to oversizing female donors for male recipients., Conclusions: In this registry-based analysis, there was no benefit to oversizing donors for cardiac transplant recipients with moderate pHTN. Elimination of this restriction could increase the donor pool and reduce wait times for such recipients., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices, transplantation capabilities, and specialists in advanced heart failure, cardiothoracic surgery, cardiac pathology, immunology, and infectious disease. Education of frontline providers who are most likely to encounter FM first is essential to increase timely access to appropriately resourced facilities, to prevent multiorgan system failure, and to tailor disease-specific therapy as early as possible in the disease process.

Aim: Preoperatively elevated pulmonary vascular resistance (PVR) is a contraindication to heart transplantation (HT). Transpulmonary pressure gradient (TPG) is one of the main variables used in PVR determination (ie, PVR = TPG/cardiac output). Unlike PVR, which is subject to the shortcoming of cardiac output estimation, TPG is directly measured. We aimed to evaluate the relationship of TPG obtained before left ventricular assist device (LVAD) implantation on post-HT survival., Methods and Results: A total of 490 patients were implanted with Heartmate II LVADs in the multicenter Heartmate II Bridge-to-Transplantation clinical trial, and 416/490 had pre-LVAD TPG data available. Outcomes during LVAD support and after HT stratified by both PVR and TPG were studied. The median pre-LVAD TPG was 10 mm Hg. Baseline demographic and clinical characteristics were similar for patients with and without TPG >10 mm Hg. Outcomes during LVAD support (ie, recovery to LVAD explantation, HT, or ongoing device support) for patients below and above the median TPG were similar. However, post-HT 1-year survival rate was significantly higher for patients with TPG ≤10 mm Hg compared with those with TPG >10 mm Hg (91% vs 80%; P = .016). Analysis based on the median PVR of 2.68 Wood units did not stratify post-HTx 1-year survival rates between the groups (89% vs 83%; P = .25)., Conclusions: Elevated TPG, rather than high PVR, before LVAD implantation was associated with increased mortality following HT. Pre-LVAD TPG may be useful to identify a cohort that requires close follow-up with serial hemodynamic monitoring before HT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hepatitis C virus (HCV) donors should be categorized as HCV-viremic (antibody [Ab] negative or positive/Nucleic Acid testing [NAT] positive) or HCV Ab + nonviremic (Ab + /NAT - ). Whereas recipients of hearts from HCV-viremic donors will develop viremia but can be cured of HCV shortly after transplant with direct-acting antivirals (DAAs), recipients of hearts from HCV Ab + nonviremic donors are highly unlikely to become viremic or require DAAs. Given this important difference in risk, we assessed the utilization trends and post-heart-transplantation outcomes of HCV-naive (Ab - /NAT - ), HCV-viremic, and HCV Ab + nonviremic donor hearts., Methods: A total of 26,572 adult donors (≥18 years) with information on HCV Ab and NAT status were identified in the United Network for Organ Sharing registry between August 2015 and June 2018 for utilization rates. Adult heart transplant recipients of these donors were compared for primary graft failure (PGF) at 90 days and 1-year recipient survival., Results: A total of 96 HCV Ab + nonviremic and 135 HCV-viremic adult donor hearts were transplanted during the study period. The utilization rates of both HCV Ab + nonviremic (1.4%-23.4%) and HCV-viremic (0.7%-25.4%) donor hearts increased significantly approaching HCV-naive rates (29.04%). There was no significant difference in rates of PGF and 1-year survival between recipients in the 3 donor HCV groups. We also used (1:3) propensity score matching and found similar 1-year survival in different donor HCV groups (HCV-naive vs HCV Ab + nonviremic, p = 0.59, and HCV-naive vs HCV-viremic, p = 0.98)., Conclusions: Recipients of HCV-viremic and HCV Ab + nonviremic donor hearts had equivalent risk of PGF and 1-year mortality compared with recipients of HCV-naive donor hearts. Although only HCV-viremic organs require DAAs and the risk of coronary artery vasculopathy after treated HCV infection has not been defined, the utilization rates of both HCV Ab + nonviremic and HCV-viremic adult donor hearts have increased at an equal pace now approaching HCV-naive rates., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Hemolysis, even at low levels, activates platelets to create a prothrombotic state and is common during mechanical circulatory support. We examined the association of low-level hemolysis (LLH) and nonhemorrhagic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support., Methods: A single-center retrospective review of all adult patients placed on VA ECMO from January 2012 to September 2017 was conducted. To determine the association between LLH and nonhemorrhagic stroke, patients were categorized as those with and without LLH. LLH was defined by 48-hour plasma free hemoglobin (PFHb) of 11 to 50 mg/dL after VA ECMO implantation., Results: Of 201 patients who underwent VA ECMO placement, 150 (75%) met inclusion criteria and comprised the study population. They were 55 ± 14 years of age and 50 (33%) were women. Sixty-two (41%) patients had LLH. Patients with LLH had a higher likelihood of incident nonhemorrhagic stroke during VA ECMO support (20 [32%] versus 4 [5%]; adjusted hazard ratio [HR], 7.6; 95% confidence interval [CI], 2.2 to 25.9; p = 0.001). The severity of LLH was associated with an incrementally higher likelihood of a nonhemorrhagic stroke (PFHb 26 to 50 mg/dL: HR, 11.3; 95% CI, 3.6 to 35.1; p = 0.001; PFHb 11 to 25 mg/dL: HR, 4.4; 95% CI, 1.36 to 14.85; p = 0.014) in comparison with no LLH. Those with LLH had a 2-fold greater increase in mean platelet volume after VA ECMO placement (0.98 ± 1.1 fL versus 0.49 ± 0.96 fL; p = 0.03). Patients with a nonhemorrhagic stroke had a higher operative mortality (20 [83%] versus 57 [45%]; adjusted HR, 3.1; 95% CI, 1.8 to 5.3; p < 0.001)., Conclusions: Hemolysis at low levels during VA ECMO support is associated with subsequent nonhemorrhagic stroke., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Significant improvements have been achieved in cardiac arrest resuscitation and postarrest resuscitation care, but mortality remains high. Most of the poor outcomes and deaths of cardiac arrest survivors have been attributed to widespread brain injury. This brain injury, commonly manifested as a comatose state, is a marker of poor outcome and a major basis for unfavorable neurological prognostication. Accurate prognostication is important to avoid pursuing futile treatments when poor outcome is inevitable but also to avoid an inappropriate withdrawal of life-sustaining treatment in patients who may otherwise have a chance of achieving meaningful neurological recovery. Inaccurate neurological prognostication leading to withdrawal of life-sustaining treatment and deaths may significantly bias clinical studies, leading to failure in detecting the true study outcomes. The American Heart Association Emergency Cardiovascular Care Science Subcommittee organized a writing group composed of adult and pediatric experts from neurology, cardiology, emergency medicine, intensive care medicine, and nursing to review existing neurological prognostication studies, the practice of neurological prognostication, and withdrawal of life-sustaining treatment. The writing group determined that the overall quality of existing neurological prognostication studies is low. As a consequence, the degree of confidence in the predictors and the subsequent outcomes is also low. Therefore, the writing group suggests that neurological prognostication parameters need to be approached as index tests based on relevant neurological functions that are directly related to the functional outcome and contribute to the quality of life of cardiac arrest survivors. Suggestions to improve the quality of adult and pediatric neurological prognostication studies are provided.

Background: Continuous-flow left ventricular assist devices have revolutionized the management of advanced heart failure. Device complications continue to limit survival, but enhanced management strategies have shown promise. This study compared outcomes for HeartMate II recipients before and after implementation of a multidisciplinary continuous support heart team (HTMCS) strategy., Methods: Between January 2012 and December 2016, 124 consecutive patients underwent primary HeartMate II implantation at our institution. In January 2015, we instituted a HTMCS approach consisting of (1) daily simultaneous cardiology/cardiac surgery/critical care/pharmacy/coordinator rounds, (2) pharmacist-directed anticoagulation, (3) speed optimization echocardiogram before discharge, (4) comprehensive device thrombosis screening and early intervention, (5) blood pressure clinic with pulsatility-adjusted goals, (6) early follow-up after discharge and individual long-term coordinator/cardiologist assignment, and (7) systematic basic/advanced/expert training and credentialing of ancillary in-hospital providers. All patients completed 1-year of follow-up., Results: Demographic characteristics for pre-HTMCS (n = 71) and HTMCS (n = 53) groups, including age (55.8 ± 12.1 versus 52.5 ± 14.1 years, p = not significant), percentage of men (77.5% versus 71.7%, p = not significant), and Interagency Registry for Mechanically Assisted Circulatory Support class 3 (84.5% versus 83.0%, p = not significant), were comparable. One-year survival was 74.6% versus 100% for the pre-HTMCS and HTMCS groups, respectively (p = 0.0002). One-year survival free of serious adverse events (reoperation to replace device or disabling stroke) was 70.4% versus 84.9% for the pre-HTMCS and HTMCS groups, respectively (p = 0.059). Event per patient-year rates for disabling stroke (0.15 versus 0, p = 0.019), gastrointestinal bleeding (0.87 versus 0.51, p = 0.11), and driveline infection (0.24 versus 0.10, p = 0.18) were lower for the HTMCS group, whereas pump thrombosis requiring device exchange was higher (0.09 versus 0.18, p = 0.14)., Conclusions: Implementing a comprehensive multidisciplinary approach substantially improved outcomes for recipients of continuous-flow left ventricular assist devices., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The clinical significance of positive anti-hepatitis C virus (anti-HCV) antibody tests in recipients of left ventricular assist devices remains unclear. In light of emerging evidence suggesting the possibility of persistent low-level HCV infection in patients with positive anti-HCV antibody test but negative HCV ribonucleic acid, it is very important to distinguish the truly false positive HCV antibodies, in recipients of continuous flow left ventricular assist devices, from those suggestive of a prior clinically resolved infection or one where a low-level viremia may have persisted. We conducted a retrospective analysis of left ventricular assist device recipients at our institution. While the total incidence of positive HCV antibody with concomitantly negative HCV ribonucleic acid test (19.2%) was in keeping with the incidences reported in prior cross-sectional studies, we longitudinally followed our patients and observed a 100% seroreversion. Seroreversion, which has not been reported in other studies, occurred either during continued left ventricular assist device support (10 out of 26) or after heart transplant (7 out of 26). Hundred percent seroreversion strongly suggested that the anti-HCV antibodies were truly false positive., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Human immunodeficiency virus-positive (HIV+) patients are not routinely offered heart transplantation (HT) due to lack of adequate outcomes data. Between January 2004 and March 2017, we identified 41 adult (≥18 years) HT recipients with known HIV+ serostatus at the time of transplant in UNOS and evaluated post-HT outcomes. Overall, Kaplan-Meier (KM) estimates of survival at 1 and 5 years were 85.9% and 77.3%, respectively, with no significant difference in bridge-to-transplant ventricular-assist device (BTT-VAD, n = 22) and no-BTT-VAD (n = 19). KM estimates of cardiac allograft vasculopathy (CAV) and malignancy at 5 years were 32% and 19%, respectively. Using propensity scores, 41 HIV+ HT recipients were matched to 41 HIV- HT recipients for idiopathic dilated-cardiomyopathy; and there was no significant difference in post-HT survival up to 5 years. Furthermore, only 24 centers in the United States had performed HIV+ HT during the study period, indicating that >80% of HT centers in the United States had not performed any HIV+ HT. In a cohort representative of the current status of HIV+ HTs in the United States, we found that the posttransplant survival was excellent and rates of CAV and malignancy were comparable to the overall HT population. These results should encourage greater number of centers to offer HT to suitable HIV+ candidates and help reduce unequal access to HT for HIV+ patients., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The popularity of gluten-free foods has been increasing across the United States and abroad. A significant reason for this trend involves marketing efforts targeted towards individuals seeking to avoid the consequences of celiac disease or a perceived gluten intolerance. Many gluten-free food products originate in regions of the world where irrigation with metal-contaminated waters is common. Calcium, Fe, Mg, Ti and Zn were detected at various levels across all foods products. Cadmium was detected in 96.8% of U.S. and 54.5% of Asian gluten-free foods with gluten containing foods above reported averages (216 μg kg -1 Cd); as was Co (140μg kg -1 ) in 48.4 % of U.S., 72.7% of Asian gluten-free foods, and 40% of the gluten containing foods; Cr was in 54.8% of the U.S., 72.5% of Asian gluten-free foods, and 100% of gluten containing food products; while Ca, Fe, Mg, Ti and Zn were greater than 10,000 μg kg -1 with Ba, Cd, Co, Mo, and Ni above reported averages. Finally, trace metals were more commonly detected in the gluten containing foods overall. It was found that trace elements were more commonly found in the gluten containing products; however, none of the higher than expected levels pose a significant health risk to consumers., Competing Interests: Conflicts of Interest The authors declare no conflict of interest.

Aims: This study was conducted to detect the presence of cyanide in popular fruit and vegetable smoothies and juices marketed as raw and natural., Study Design: Eleven (11) popular varieties of drinks were analyzed for total cyanide ( T CN). Drinks contained raw vegetables and fruits, flax seeds, whole apples with seeds, raw almond milk, and pasteurized almond milk as ingredients., Place and Study Duration: Samples were collected from health food eateries located within Las Vegas, Nevada (USA) during the summer of 2017., Methodology: Fifty milliliters (mL) of a homogenized smoothie and juice drink and 1 gram of flax seeds were subjected to the above-referenced methods for sample preparation per USEPA Methods 9012B (digestion) followed by USEPA method 9014 (colorimetry)., Results: The highest T CN was detected in drinks containing raw flax seed followed by unpasteurized raw almond milk, then fresh whole apple juice. No T CN was observed in drinks that contained none of the above mentioned items (e.g. flax seed, raw almond milk) or those utilizing pasteurized ingredients., Conclusion: This study observed that T CN is present in smoothies and juices containing raw flax seeds, fresh whole apples, and/or unpasteurized almond milk. Concentrations were detected as high as 341 μg L -1 in commercially available smoothies containing vegetables, raw flax seeds, almond milk and fruits. Smoothies with vegetables, fruits, unpasteurized almond milk, and no flax seeds contained 41 ug L -1 T CN, while similar smoothies with pasteurized almond milk contained negligible to 9.6 ug L -1 CN - . Unpasteurized almond milk and raw flax seeds were the major sources of T CN in drinks. With the increased demand for raw and natural foods, there is a potential sublethal exposure of T CN by consumers.

Background: Hepatitis C (HCV) donors are rarely used for cardiac transplantation due to historically poor outcomes. In 2015, nucleic acid testing (NAT) for viral load was added to the routine work-up of organ donors, allowing for the distinction between subjects who remain viremic (HCV Ab + /NAT + ) and those who have cleared HCV and are no longer viremic (HCV Ab + /NAT - ). The American Society of Transplantation recently recommended that HCV Ab + /NAT - donors be considered non-infectious and safe for transplantation. We present our initial experience with such donors., Methods: All patients were counseled regarding donor HCV antibody (Ab) and NAT. Transplant recipients were tested post-transplant at 1 week and at 1, 3, and 6 months for HCV seropositivity and viremia. We also analyzed the UNOS database to determine the potential impact of widespread acceptance of HCV Ab + /NAT - organs., Results: Fourteen HCV Ab ‒ subjects received hearts from HCV Ab + /NAT - donors in 2017. Over a median follow-up of 256 (192 to 377) days, 3 patients developed a reactive HCV Ab, yet none had a detectable HCV viral load during prospective monitoring at any time. Analysis of the UNOS database for the calendar year 2016 revealed that only 7 (3%) of 220 HCV Ab + /NAT - donors were accepted for heart transplantation., Conclusions: We have demonstrated the feasibility of utilizing HCV Ab + /NAT - donors for cardiac transplantation without recipient infection. A small percentage of recipients developed HCV Ab without evidence of viremia, possibly consistent with a biological false reactive test, as has been seen in other settings. Large-scale validation of our data may have a significant impact on transplantation rates., (Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Gastrointestinal bleeding (GIB) is one of the principal adverse events affecting patients with continuous-flow left ventricular assist devices (CF-LVADs). Despite the early recognition that GIB is commonly because of gastrointestinal angiodysplasia (GIAD), the exact pathophysiology of this process remains elusive. It has been postulated that the abnormal hemodynamic profile in CF-LVAD patients may activate the angiogenesis signaling cascade via the HIF (hypoxia-inducible factor)-1α/angiopoietin-2 pathway leading to formation of GIADs. Digoxin is a potent inhibitor of HIF-1α synthesis, and we hypothesized that its use reduces the incidence of GIAD and GIB in patients with CF-LVAD., Methods and Results: Charts of all adult patients implanted with CF-LVAD between February 2006 and February 2017 were reviewed with particular emphasis on occurrence and cause of GIB. Fifty-four of 199 patients (27%) experienced a GIB. Overall frequency of GIB was lower in the 64 patients receiving digoxin compared with the 135 patients not receiving digoxin (16% versus 33%, P=0.01). Multivariable-adjusted Cox regression analysis confirmed that digoxin use was independently associated with a reduced risk for overall GIB (hazard ratio, 0.49; 95% CI, 0.24-0.98; P=0.045). GIBs were then categorized as non-GIAD, GIAD, or likely GIAD. Although the incidence of non-GIAD was similar in both groups (11% versus 7%, P=0.41), the frequency of GIAD/likely GIAD bleeding was significantly reduced in the digoxin group (5% versus 25%, P=0.0003). Multivariable-adjusted analysis confirmed that digoxin use was independently associated with a reduced risk for GIAD/likely GIAD bleeding (hazard ratio, 0.18; 95% CI, 0.06-0.6; P=0.005). However, digoxin use was not associated with reduced risk for non-GIAD GIB (hazard ratio, 1.54; 95% CI, 0.58-4.08; P=0.39)., Conclusions: Use of digoxin was associated with a significant reduction in GIAD-related GIB in patients with CF-LVAD.