Tricks and tracks of prevalence, occurrences, treatment technologies, and challenges of mixtures of emerging contaminants in the environment: With special emphasis on microplastic.

This paper aims to emphasize the occurrence of various emerging contaminant (EC) mixtures in natural ecosystems and highlights the primary concern arising from the unregulated release into soil and water, along with their impacts on human health. Emerging contaminant mixtures, including pharmaceuticals, personal care products, dioxins, polychlorinated biphenyls, pesticides, antibiotics, biocides, surfactants, phthalates, enteric viruses, and microplastics (MPs), are considered toxic contaminants with grave implications. MPs play a crucial role in transporting pollutants to aquatic and terrestrial ecosystems as they interact with the various components of the soil and water environments. This review summarizes that major emerging contaminants (ECs), like trimethoprim, diclofenac, sulfamethoxazole, and 17α-Ethinylestradiol, pose serious threats to public health and contribute to antimicrobial resistance. In addressing human health concerns and remediation techniques, this review critically evaluates conventional methods for removing ECs from complex matrices. The diverse physiochemical properties of surrounding environments facilitate the partitioning of ECs into sediments and other organic phases, resulting in carcinogenic, teratogenic, and estrogenic effects through active catalytic interactions and mechanisms mediated by aryl hydrocarbon receptors. The proactive toxicity of ECs mixture complexation and, in part, the yet-to-be-identified environmental mixtures of ECs represent a blind spot in current literature, necessitating conceptual frameworks for assessing the toxicity and risks with individual components and mixtures. Lastly, this review concludes with an in-depth exploration of future scopes, knowledge gaps, and challenges, emphasizing the need for a concerted effort in managing ECs and other organic pollutants.

Surveillance with dual noninvasive testing for acute cellular rejection after heart transplantation: Outcomes from the Surveillance HeartCare Outcomes Registry.

BACKGROUND: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated. METHODS: We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed. RESULTS: The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction. CONCLUSIONS: Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction.

Adsorptive removal of ciprofloxacin and sulfamethoxazole from aqueous matrices using sawdust and plastic waste-derived biochar: A sustainable fight against antibiotic resistance.

We produced carbon-negative biochar from the pyrolysis of sawdust biomass alone (SB) and from the co-pyrolysis of sawdust and plastic waste (SPB). The co-pyrolysis approach in this study was driven by several hypothetical factors, such as increased porosity, surface chemistry, stability, as well as waste management. We applied pyrolyzed and co-pyrolyzed biochars for the removal of ciprofloxacin (CFX) and sulfamethoxazole (SMX). Due to its more alkaline and amorphous nature, SB showed better removal efficiencies compared to SPB. The maximum removals of CFX and SMX with SB were observed as ∼95% and >95%, respectively whereas with SPB were 58.8%, and 34.9%, respectively. The primary mechanisms involved in the adsorption process were H-bonding, electrostatic and π-π electron donor-acceptor interactions. Homogenously and heterogeneously driven adsorption of both antibiotics followed the pseudo-second-order kinetic model, implying electron sharing/transfer (chemisorption) mediated adsorption. The work is highly pertinent in the context of emerging concerns related to drivers that promote antimicrobial resistance.

Pulmonary Artery Pressure-Guided Heart Failure Management Reduces Hospitalizations in Patients With Chronic Kidney Disease.

BACKGROUND: Hemodynamic-guided heart failure management is a superior strategy to prevent decompensation leading to hospitalization compared with traditional clinical methods. It remains unstudied if hemodynamic-guided care is effective across severities of comorbid renal insufficiency or if this strategy impacts renal function over time. METHODS: In the CardioMEMS US PAS (Post-Approval Study), heart failure hospitalizations were compared from 1 year before and after pulmonary artery sensor implantation in 1200 patients with New York Heart Association class III symptoms and a previous hospitalization. Hospitalization rates were evaluated in all patients grouped into baseline estimated glomerular filtration rate (eGFR) quartiles. Chronic kidney disease progression was evaluated in patients with renal function follow-up data (n=911). RESULTS: Patients with stage 2 or greater chronic kidney disease at baseline exceeded 80%. Heart failure hospitalization risk was lower in all eGFR quartiles ranging from a hazard ratio of 0.35 (0.27-0.46; P<0.0001) in patients with eGFR >65 mL/min per 1.73 m2 to 0.53 (0.45-0.62; P<0.0001) in patients with eGFR ≤37 mL/min per 1.73 m2. Renal function was preserved or improved in most patients. Survival was different between quartiles and lower in quartiles with more advanced chronic kidney disease. CONCLUSIONS: Hemodynamic-guided heart failure management using remotely obtained pulmonary artery pressures is associated with lower hospitalization rates and general preservation of renal function in all eGFR quartiles or chronic kidney disease stages.

Aggregation behaviour of black carbon in aquatic solution: Effect of ionic strength and coexisting metals.

Black Carbon (BC) is an important constituent of both aquatic and terrestrial environment, but also has several adverse effects on human health, aquatic life, and contributes to the global climate change. Thus, to understand the fate and transport of BC nanoparticles (NPs) in the environment, it's important to understand the colloidal stability or aggregation behaviour and factors affecting it, under various environmental conditions, including both aquatic and atmospheric. This study investigated the individual influence of ionic strengths, valence (Na+, Ca2+ and Mg2+), metals (Zn2+, Cu2+, Ni2+ and Cd2+), and organic substances (PO43- and Humic Acid: HA) on the effective diameter or hydrodynamic diameter and zeta potential of BC-NPs in aquatic systems. A dynamic light scattering (DLS) principle-based 90 Plus Particle Size Analyzer was used for measurements of BC particle size and zeta potential at varying ionic chemistry. The results showed that strong ionic strength promotes aggregation of BC-NPs till the repulsion forces become dominant due to more negative zeta potential. The Aggregation of BC-NPs was observed to be significantly dependent on the ionic valence, where divalent ions caused more aggregation than monovalent ions. Metal ions at higher concentration (around 1 mM) promoted the aggregation rate of BC-NPs, and Cu+2 dominated among all selected metals. Conversely, organic matter (PO43- and HA) tends to promote stabilisation of BC-NPs instead of aggregation. Though this study investigated individual effect of substances, influence of possible environmental combination of substances will help to get more clear idea.

Sustained Reduction in Pulmonary Artery Pressures and Hospitalizations During 2 Years of Ambulatory Monitoring.

BACKGROUND: Therapy guided by pulmonary artery (PA) pressure monitoring reduces PA pressures and heart failure hospitalizations (HFH) during the first year, but the durability of efficacy and safety through 2 years is not known. METHODS AND RESULTS: The CardioMEMS Post-Approval Study investigated whether benefit and safety were generalized and sustained. Enrollment at 104 centers in the United States included 1200 patients with NYHA Class III symptoms on recommended HF therapies with prior HFH. Therapy was adjusted toward PA diastolic pressure 8-20 mmHg. Intervention frequency and PA pressure reduction were most intense during first 90 days, with sustained reduction of PA diastolic pressure from baseline 24.7 mmHg to 21.0 at 1 year and 20.8 at 2 years for all patients. Patients completing two year follow-up (n = 710) showed similar 2-year reduction (23.9 to 20.8 mmHg), with reduction in PA mean pressure (33.7 to 29.4 mmHg) in patients with reduced left ventricular ejection. The HFH rate was 1.25 events/patient/year prior to sensor implant, 0.54 at 1 year, and 0.37 at 2 years, with 59% of patients free of HFH during follow-up. CONCLUSIONS: Reduction in PA pressures and hospitalizations were early and sustained during 2 years of PA pressure-guided management, with no signal of safety concerns regarding the implanted sensor.

Development of novel Core-shell impregnated polyuronate composite beads for an eco-efficient removal of arsenic.

Arsenic (As) can geogenically and anthropogenically contaminate the potable water resources and undoubtedly reduces its availability for human consumption. To circumvent this predicament, present study focuses on the development of a novel biosorbent by impregnating calcium cross-linked polyuronate (alginate) beads (CABs) with bilayer-oleic coated magnetite nanoparticles (CAB@BOFe) for As(V) removal. Initially, the system parameters (i.e., adsorbents dose (0.1- 3.0 g L-1), pH (4.0-13), reaction times (0-180 min) and sorbate concentrations (10-150 µg L-1)) were optimized to establish adsorbent at the lab-scale. CAB@BOFe had higher monolayer (ad)sorption capacity (∼62.5 µg g-1, 120 min) than CABs (∼17.9 µg g-1, 180 min). Electrostatic/Ion-dipole interactions and surface-complexation mechanisms mediated As(V) sorption onto CAB@BOFe mainly obeyed Langmuir isotherm (R2 âˆ¼ 0.9) and well described by intraparticle diffusion process. Furthermore, it demonstrated an excellent arsenate removal performance from the single/multiple anionic contaminants simulated water samples which supported its prospective field applicability.

Microwave-assisted synthesis of cross-linked chitosan-metal oxide nanocomposite for methyl orange dye removal from unary and complex effluent matrices.

Textile/Dyeing industries have been considered as one of the intense water-consuming units, resulting in the generation of a large volume of dye(s) contaminated effluent posing a heavy burden on the receiving water bodies. Therefore, the identification of methods to synthesize bulk quantity of adsorbent(s) and further their evaluation for the efficient treatment of effluent is one of the most prominent topics. Hence, microwave-assisted method was proposed for the rapid synthesis of nanocomposite (C-CS@ZnO) from natural biomolecule (chitosan-CS), a well-known crosslinker (tripolyphosphate) and metal-oxide (ZnO) nanoparticles. Detailed characterization was performed to identify the structure (SEM, XRD) and composition (FT-IR, XPS) of the sorbent. Sorption experiments with methyl orange (MO) dye solution were carried out under different pH (2.0-12.0), dye concentrations (150-350 mg L-1), reaction times (0-210 min) and temperature (25-45 °C) to establish the adsorbent at the lab-scale. The maximum sorption capacity (185.2 mg g-1) was obtained because of the ligand-exchange, Yoshida H-bonding and electrostatic interactions and was best elucidated by Freundlich (R2 ≥ 0.99) and pseudo-second-order (R2 ≥ 1) models. To simulate the field conditions, the effects of co-existing ions (anions/cations), cocktail dyes/ions mixture and regenerant were also studied. The obtained results suggest its promising applicability at a large scale for textile effluent treatment.

Aminoalkyl-organo-silane treated sand for the adsorptive removal of arsenic from the groundwater: Immobilizing the mobilized geogenic contaminants.

Arsenic (As), a geogenic legacy pollutant can be present in environmental matrices (water, soil, plants, or animal) in two redox states (As(III) or As(V)). In the present study, charged mono- and di-amino functionalized triethoxy and methoxyorganosilane (TT1 and TT2- 1% and 5%) were impregnated with quartz sand particles for the treatment of As polluted water. Spectroscopic characterization of organosilane treated sand (STS) indicated the co-existence of minerals (Mg, Mn, Ti), amide, and amidoalkyl groups, which implies the suitability of silanized materials as a metal(loids) immobilization agent from water. Changes in peaks were observed after As sorption in Fourier thermal infrared and EDS images indicating the involvement of chemisorption. Batch sorption studies were performed with the optimized experimental parameters, where an increased removal (>20% for TT2-1% and >60% for TT1-1%) of As was observed with sorbate concentration (50 µg L-1), temp. (25 ± 2 ºC) and sorbent dosages (of 10 g L-1) at 120 min contact time. Among the different adsorbent dosages, 10 g L-1 of both TT1 and TT2 was selected as an optimum dosage (maximum adsorption capacity ≈ 2.91 µg g-1). The sorption model parameters suggested the possibility of chemisorption, charge/ion-dipole interaction for the removal of arsenate.

Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury.

It has been established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocyte pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists in the current pandemic. ACE2 serves as a regulatory enzyme in maintaining homeostasis between proinflammatory angiotensin II and anti-inflammatory angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome. Augmentation of the ACE2/Ang 1,7 axis represents a critical target in the supportive management of coronavirus disease 2019-associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists, requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

Antidrug resistance in the Indian ambient waters of Ahmedabad during the COVID-19 pandemic.

The ongoing COVID-19 pandemic increases the consumption of antimicrobial substances (ABS) due to the unavailability of approved vaccine(s). To assess the effect of imprudent consumption of ABS during the COVID-19 pandemic, we compare the 2020 prevalence of antidrug resistance (ADR) of Escherichia coli (E. coli) with a similar survey carried out in 2018 in Ahmedabad, India using SARS-CoV-2 gene detection as a marker of ABS usage. We found a significant ADR increase in 2020 compared to 2018 in ambient water bodies, harbouring a higher incidence of ADR E.coli towards non-fluoroquinolone drugs. Effective SARS-CoV-2 genome copies were found to be associated with the ADR prevalence. The prevalence of ADR depends on the efficiency of WWTPs (Wastewater Treatment Plants) and the catchment area in its vicinity. In the year 2018 study, prevalence of ADR was discretely distributed, and the maximum ADR prevalence recorded was ~60%; against the current homogenous ADR increase, and up to 85% of maximum ADR among the incubated E.coli isolated from the river (Sabarmati) and lake (Chandola and Kankaria) samples. Furthermore, wastewater treatment plants showed less increase in comparison to the ambient waters, which eventually imply that although SARS-CoV-2 genes and faecal pollution may be diluted in the ambient waters, as indicated by low Ct-value and E.coli count, the danger of related aftermath like ADR increase cannot be nullified. Also, Non-fluoroquinolone drugs exhibited overall more resistance than quinolone drugs. Overall, this is probably the first-ever study that traces the COVID-19 pandemic imprints on the prevalence of antidrug resistance (ADR) through wastewater surveillance and hints at monitoring escalation of other environmental health parameters. This study will make the public and policyholders concerned about the optimum use of antibiotics during any kind of treatment.

Hexametaphosphate cross-linked chitosan beads for the eco-efficient removal of organic dyes: Tackling water quality.

There is an increasing trend of developing various low-cost grafted natural amino polysaccharides for the biosorptive removal of noxious dye effluents like Malachite green (MG) and anionic Reactive Red-195 (RR-195) dyes from aqueous solution. Chemically cross-linked chitosan microsphere (CTS-HMP), a promising non-toxic biosorbent possessing high charge density and thermal stability was prepared by using hexametaphosphate as ionic cross-linker. Batch biosorption experiments were carried out under different temperatures (298, 308 and 318 K), pH (2.0-10.0), initial concentrations (25-250 mg L-1), adsorbent dosage (0.01-0.1 g) and contact times (0-180 min) to understand the optimum experimental conditions and simultaneously evaluate the adsorption isotherms and kinetics of CTS-HMP. Biosorption equilibrium was established in 120 and 60 min for MG and RR-195 removal process. The pseudo-equilibrium process was best described by the pseudo-second-order kinetic (R2 ≥ 0.98), Freundlich and Temkin isotherm model (R2 ≥ 0.90). The removal rate of MG and RR-195 gradually increased (69.40 and 148 mg g-1) at 250 mg L-1 of initial concentration till 100 and 50 min of contact period in a single contaminant system, though the removal efficiency of acid dye was ~2 times higher compared to basic dye under optimum conditions (p < 0.05; t-test). Thermodynamic parameters indicated exothermic (MG) and endothermic (RR-195) nature of spontaneous dye removal. The activation energy of sorption (Ea) was <50 kJ mol-1 which highlighted the importance of physical adsorption process. Therefore, the obtained results clearly validate the sustainable utilization of CTS-HMP as a promising functionalized chitosan microparticles/agent for removing dye effluents from the contaminated aqueous phase.

Geogenic arsenic removal through core-shell based functionalized nanoparticles: Groundwater in-situ treatment perspective in the post-COVID anthropocene.

Groundwater, one of the significant potable water resources of the geological epoch is certainly contaminated with class I human carcinogenic metalloid of pnictogen family which delimiting its usability for human consumption. Hence, this study concerns with the elimination of arsenate (As(V)) from groundwater using bilayer-oleic coated iron-oxide nanoparticles (bilayer-OA@FeO NPs). The functionalized (with high-affinity carboxyl groups) adsorbent was characterized using the state-of-the-art techniques in order to understand the structural arrangement. The major emphasis was to examine the effects of pH (5.0-13), contact times (0-120 min), initial concentrations (10-150 µg L-1), adsorbent dosages (0.1-3 g L-1), and co-existing anions in order to understand the optimal experimental conditions for the effective removal process. The adsorbent had better adsorption efficiency (∼ 32.8 µg g-1, after 2 h) for As(V) at neutral pH. Adsorption process mainly followed pseudo-second-order kinetics and Freundlich isotherm models (R2∼0.90) and was facilitated by coulombic, charge-dipole and surface complexation interactions. The regeneration (upto five cycles with 0.1 M NaOH) and competition studies (with binary and cocktail mixture of co-anions) supported the potential field application of the proposed adsorbent.

Lower Rates of Heart Failure and All-Cause Hospitalizations During Pulmonary Artery Pressure-Guided Therapy for Ambulatory Heart Failure: One-Year Outcomes From the CardioMEMS Post-Approval Study.

BACKGROUND: Ambulatory hemodynamic monitoring with an implantable pulmonary artery (PA) sensor is approved for patients with New York Heart Association Class III heart failure (HF) and a prior HF hospitalization (HFH) within 12 months. The objective of this study was to assess the efficacy and safety of PA pressure-guided therapy in routine clinical practice with special focus on subgroups defined by sex, race, and ejection fraction. METHODS: This multi-center, prospective, open-label, observational, single-arm trial of 1200 patients across 104 centers within the United States with New York Heart Association class III HF and a prior HFH within 12 months evaluated patients undergoing PA pressure sensor implantation between September 1, 2014, and October 11, 2017. The primary efficacy outcome was the difference between rates of adjudicated HFH 1 year after compared with the 1 year before sensor implantation. Safety end points were freedom from device- or system-related complications at 2 years and freedom from pressure sensor failure at 2 years. RESULTS: Mean age for the population was 69 years, 37.7% were women, 17.2% were non-White, and 46.8% had preserved ejection fraction. During the year after sensor implantation, the mean rate of daily pressure transmission was 76±24% and PA pressures declined significantly. The rate of HFH was significantly lower at 1 year compared with the year before implantation (0.54 versus 1.25 events/patient-years, hazard ratio 0.43 [95% CI, 0.39-0.47], P<0.0001). The rate of all-cause hospitalization was also lower following sensor implantation (1.67 versus 2.28 events/patient-years, hazard ratio 0.73 [95% CI, 0.68-0.78], P<0.0001). Results were consistent across subgroups defined by ejection fraction, sex, race, cause of cardiomyopathy, presence/absence of implantable cardiac defibrillator or cardiac resynchronization therapy and ejection fraction. Freedom from device- or system-related complications was 99.6%, and freedom from pressure sensor failure was 99.9% at 1 year. CONCLUSIONS: In routine clinical practice as in clinical trials, PA pressure-guided therapy for HF was associated with lower PA pressures, lower rates of HFH and all-cause hospitalization, and low rates of adverse events across a broad range of patients with symptomatic HF and prior HFH. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02279888.

A comprehensive individual patient data meta-analysis of the effects of cardiac contractility modulation on functional capacity and heart failure-related quality of life.

AIMS: Cardiac contractility modulation, also referred to as CCM™, has emerged as a promising device treatment for heart failure (HF) in patients not indicated for cardiac resynchronization therapy. We performed a comprehensive individual patient data meta-analysis of all non-confounded prospective randomized controlled trials of CCM vs. control that have measured functional capacity and/or quality of life questionnaires in patients with HF. METHODS AND RESULTS: The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in January 2020 to identify eligible randomized controlled trials. We also asked the sole manufacturer of the device for their list of known trials. Primary outcomes of interest were peak oxygen consumption (peak VO2 ), 6 min walk test distance, and quality of life measured by Minnesota Living with Heart Failure Questionnaire (MLWHFQ), and all data were received as individual patient and individual time point data-points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed-effects model. Five trials were identified, four randomized studies enrolling 801 participants for all endpoints of interest, and for peak VO2 alone (n = 60), there was an additional single arm non-randomized trial (FIX-HF-5C2) with a prospective comparison of its 24 week peak VO2 data compared with the control group of the FIX-HF-5C control patients. Pooled analysis showed that, compared with control, CCM significantly improved peak VO2 (mean difference +0.93, 95% CI 0.56 to 1.30 mL/kg/min, P < 0.00001), 6 min walk test distance (mean difference +17.97, 95% CI 5.48 to 30.46 m, P = 0.005), and quality of life measured by MLWHFQ (mean difference -7.85, 95% CI -10.76 to -4.94, P < 0.00001). As a sensitivity analysis, we excluded the FIX-HF-5C2 trial (only relevant for peak VO2 ), and the result was similar, mean difference +0.65, 95% CI 0.21 to 1.08 mL/kg/min, P = 0.004. CONCLUSIONS: This comprehensive meta-analysis of individual patient data from all known randomized trials has shown that CCM provides statistically significant and clinically meaningful benefits in measures of functional capacity and HF-related quality of life.

Clinical Outcomes and Quality of Life With an Ambulatory Counterpulsation Pump in Advanced Heart Failure Patients: Results of the Multicenter Feasibility Trial.

BACKGROUND: The NuPulseCV intravascular ventricular assist system (iVAS) provides extended duration ambulatory counterpulsation via a durable pump placed through the distal subclavian artery. METHODS: We performed a prospective, single-arm, multicenter, US Food and Drug Administration-approved feasibility trial of iVAS therapy as a bridge to transplant or decision following the FIH (First-In-Human) trial. RESULTS: Forty-seven patients were enrolled, and 45 patients (median 61 years old, 37 males, and 30 listed on United Network of Organ Sharing) received iVAS support for median 44 (25-87) days. There were no intraoperative complications. Success was defined as survival or transplant on iVAS therapy free from disabling stroke. Outcome success at 30 days (the primary end point of this study) and at 6 months was 89% and 80%, respectively. During 6 months of iVAS support, 2 patients died and 2 patients experienced disabling neurological dysfunction. Six-minute walk distance, 2-minute step test, and Kansas City Cardiomyopathy Questionnaire score improved during 4-week iVAS support. CONCLUSIONS: This feasibility trial demonstrated promising short-term outcomes of iVAS therapy with improved functional capacity and quality of life during the therapy. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02645539.

Association of Clinical Outcomes With Left Ventricular Assist Device Use by Bridge to Transplant or Destination Therapy Intent: The Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) Randomized Clinical Trial.

Importance: Left ventricular assist devices (LVADs) are well established in the treatment of advanced heart failure, but it is unclear whether outcomes are different based on the intended goal of therapy in patients who are eligible vs ineligible for heart transplant. Objective: To determine whether clinical outcomes in the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) trial differed by preoperative categories of bridge to transplant (BTT) or bridge to transplant candidacy (BTC) vs destination therapy (DT). Design, Setting, and Participants: This study was a prespecified secondary analysis of the MOMENTUM 3 trial, a multicenter randomized clinical trial comparing the magnetically levitated centrifugal-flow HeartMate 3 (HM3) LVAD to the axial-flow HeartMate II (HMII) pump. It was conducted in 69 centers with expertise in managing patients with advanced heart failure in the United States. Patients with advanced heart failure were randomized to an LVAD, irrespective of the intended goal of therapy (BTT/BTC or DT). Main Outcomes and Measures: The primary end point was survival free of disabling stroke or reoperation to remove or replace a malfunctioning device at 2 years. Secondary end points included adverse events, functional status, and quality of life. Results: Of the 1020 patients with implants (515 with HM3 devices [50.5%] and 505 with HMII devices [49.5%]), 396 (38.8%) were in the BTT/BTC group (mean [SD] age, 55 [12] years; 310 men [78.3%]) and 624 (61.2%) in the DT group (mean [SD] age, 63 [12] years; 513 men [82.2%]). Of the patients initially deemed as transplant ineligible, 84 of 624 patients (13.5%) underwent heart transplant within 2 years of LVAD implant. In the primary end point analysis, HM3 use was superior to HMII use in patients in the BTT/BTC group (76.8% vs 67.3% for survival free of disabling stroke and reoperation; hazard ratio, 0.62 [95% CI, 0.40-0.94]; log-rank P = .02) and patients in the DT group (73.2% vs 58.7%; hazard ratio, 0.61 [95% CI, 0.46-0.81]; log-rank P < .001). For patients in both BTT/BTC and DT groups, there were not significantly different reductions in rates of pump thrombosis, stroke, and gastrointestinal bleeding with HM3 use relative to HMII use. Improvements in quality of life and functional capacity for either pump were not significantly different regardless of preimplant strategy. Conclusions and Relevance: In this trial, the superior treatment effect of HM3 over HMII was similar for patients in the BTT/BTC or DT groups. It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure. Trial Registration: ClinicalTrials.gov identifier: NCT02224755.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

The Utility of a Wireless Implantable Hemodynamic Monitoring System in Patients Requiring Mechanical Circulatory Support.

Proper timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients is not well established and is an area of intense interest. In addition, optimizing LVAD performance after implantation remains difficult and represents a significant clinical need. Implantable hemodynamic monitoring systems may provide physicians with the physiologic information necessary to improve the timing of LVAD implantation as well as LVAD performance when compared with current methods. The CardioMEMS Heart sensor Allows for Monitoirng of Pressures to Improve Outcomes in NYHA Class III heart failure patients (CHAMPION) Trial enrolled 550 previously hospitalized patients with New York Heart Association (NYHA) class III heart failure. All patients were implanted with a pulmonary artery (PA) pressure monitoring system and randomized to a treatment and control groups. In the treatment group, physicians used the hemodynamic information to make heart failure management decisions. This information was not available to physicians for the control group. During an average of 18 month randomized follow-up, 27 patients required LVAD implantation. At the time of PA pressure sensor implantation, patients ultimately requiring advanced therapy had higher PA pressures, lower systemic pressure, and similar cardiac output measurements. Treatment and control patients in the LVAD subgroup had similar clinical profiles at the time of enrollment. There was a trend toward a shorter length of time to LVAD implantation in the treatment group when hemodynamic information was available. After LVAD implantation, most treatment group patients continued to provide physicians with physiologic information from the hemodynamic monitoring system. As expected PA pressures declined significantly post LVAD implant in all patients, but the magnitude of decline was higher in patients with PA pressure monitoring. Implantable hemodynamic monitoring appeared to improve the timing of LVAD implantation as well as optimize LVAD performance when compared with current methods. Further studies are necessary to evaluate these findings in a prospective manner.