Short-Term Clinical Outcomes of Transcatheter Aortic Valve Replacement in a Developing Country.

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) is an effective alternative to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis in all surgical risk groups. Reports of clinical outcomes post-TAVR in developing countries are scarce. We aimed to address the clinical outcomes and safety profile of TAVR in a developing country. METHODS: We conducted a single-center, retrospective study on patients undergoing TAVR at the American University of Beirut Medical Center (AUBMC) from January 2016 to April 2023. We included a total of 399 patients. Our primary endpoint was to assess the rate of TAVR in-hospital and 30-day mortality, neurologic events, and new permanent pacemaker implantation (PPI) in patients, stratified by the Society of Thoracic Surgeons (STS) risk of mortality score. RESULTS: Survival rates were 98.7% (394) at discharge vs. 97.5% (389) at 30 days post-procedure. The technical success rate was 95% (379) at the end of the procedure. Device success and early safety rates were 93.5% (373) and 83% (331), respectively at 30 days post-procedure. The all-cause mortality rate increased from 1.3% (5) at discharge to 2.5% (10) at 30-day intervals. The rate of ischemic stroke was 1.3% (five) at discharge and increased to 2% (eight) at 30 days post-procedure. PPI was needed in 5.8% (23) of patients at discharge with an increase to 7% (28) at one-month interval. Overall, the rates of TAVR outcomes among the three risk groups were comparable including neurologic events, valve-related complications, bleeding problems, vascular and access-related complications, and myocardial infarction. CONCLUSION: This study at AUBMC highlights the successful implementation of the TAVR program in a developing country, showcasing its efficacy and safety within 30 days post-operation, despite challenges such as financial constraints and limited access to specialized training. Larger cohorts and longer follow-up periods are needed to accurately represent clinical outcomes in developing countries.

Percutaneous Coronary Intervention with Procedural Unfractionated Heparin without Activated Clotting Time Guidance: A Unique Opportunity to Assess Thrombotic and Bleeding Events.

Background: Rates of major bleeding and intraprocedural thrombotic events (IPTE) in the setting of percutaneous coronary intervention (PCI) using weight-adjusted unfractionated heparin (UFH) without activated clotting time (ACT) monitoring are not known. Methods: We reviewed 2,748 consecutive patients who underwent coronary angiography at our tertiary care university hospital between January 2017 and December 2020. All patients who underwent PCI with weight-adjusted UFH without ACT guidance were considered for further analysis. Major bleeding complications occurring within 48 hours of PCI were collected from patients' medical records. IPTE were collected independently by two interventional cardiologists after review of coronary angiograms. Results: There were 718 patients included in the analysis (65.4 ± 12.2 years old; 81.3% male). In total, 45 patients (7.8%) experienced a major bleed or IPTE. The most common IPTE were slow/no reflow (1.5%) and coronary artery dissection with decreased flow (1.1%). Other IPTE occurred in <1% of cases. Major bleeding occurred in 11 patients (1.5%), of whom 8 required blood transfusion and 3 required vascular intervention. Bleeding complications were more common with femoral compared with radial access (6.6% vs. 0.2%, P < 0.001). Conclusion: Weight-adjusted UFH use during PCI without ACT monitoring was related to low rates of major bleeding or IPTE.

Donor Age, Sex, and Cause of Death and Their Relationship to Heart Transplant Recipient Cardiac Death.

BACKGROUND: Recent studies indicate that donor innate immune responses participate in initiating and accelerating innate responses and allorecognition in the recipient. These immune responses negatively affect recipient outcomes and predispose recipients to cardiovascular death (CV death). We hypothesized that a donor cause of death (COD) associated with higher levels of innate immune response would predispose recipients to more adverse outcomes post-transplant, including CV death. METHODS: We performed a single-institution retrospective analysis comparing donor characteristics and COD to recipient adverse cardiovascular outcomes. We analyzed the medical records of local adult donors (age 18-64) in a database of donors where adequate data was available. Donor age was available on 706 donors; donor sex was available on 730 donors. We linked donor characteristics (age and sex) and COD to recipient CV death. The data were analyzed using logistic regression, the log-rank test of differences, and Tukey contrast. RESULTS: Donor age, female sex, and COD of intracranial hemorrhage were significantly associated with a higher incidence of recipient CV death. CONCLUSIONS: In this single institution study, we found that recipients with hearts from donors over 40 years, donors who were female, or donors who died with a COD of intracranial hemorrhage had a higher frequency of CV death. Donor monitoring and potential treatment of innate immune activation may decrease subsequent recipient innate responses and allorecognition stimulated by donor-derived inflammatory signaling, which leads to adverse outcomes.

Chalcogen bonding in copper(II)-mediated synthesis.

The chalcogen bond (ChB) is a noncovalent attraction between an electrophilic chalcogen atom and a nucleophilic (Nu) region in the same (intramolecular) or another (intermolecular) molecular entity: R-Ch⋯Nu (Ch = O, S, Se or Te; R = substituents; Nu = nucleophile). ChB is comparable to the hydrogen and halogen bonds both in terms of strengths and directionality. However, in contrast to the monovalent halogen atoms, usually the divalent or tetravalent chalcogen atoms are able to display more than one electrophilic centre (on account of the existence of two or three species bonded to the chalcogen atom), which provides an additional opportunity in the use of this type of noncovalent binding in synthetic operations. In this work, the role of ChB at the secondary coordination sphere of metal complexes through copper(II)-mediated activation of dioxygen or of one nitrile group of a 1,2,5-selenadiazole-3,4-dicarbonitrile ligand to form a carbimidate or an imino-carboxylic acid is demonstrated. DFT calculations allowed evaluation of the strength of the ChBs and proved their relevant structure directing role in the solid state architectures. The effect of metal-coordination on the σ-hole opposite to the coordinated SeO bond has been analysed using molecular electrostatic potential (MEP) surfaces and explains the greater ability of the coordinated selenoxide derivatives to form strong ChBs.

Self-gated, dynamic contrast-enhanced magnetic resonance imaging with compressed-sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice.

High-risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self-gated, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe-/- atherosclerotic mice during natural disease progression. Twenty-four, 8-week-old, female Apoe-/- mice were divided into four groups (n = 6 each) and imaged with self-gated DCE-MRI at 4, 8, 12, and 16 weeks after high-fat diet initiation, and then euthanized for CD68 immunohistochemistry for macrophages. Eight additional mice were kept on a high-fat diet and imaged longitudinally at the same time points. Aortic-root pseudo-concentration curves were analyzed using a validated piecewise linear model. Contrast agent wash-in and washout slopes (b1 and b2 ) were measured as surrogates of aortic root endothelial permeability and compared with macrophage density by immunohistochemistry. b2 , indicating contrast agent washout, was significantly higher in mice kept on an high-fat diet for longer periods of time (p = 0.03). Group comparison revealed significant differences between mice on a high-fat diet for 4 versus 16 weeks (p = 0.03). Macrophage density also significantly increased with diet duration (p = 0.009). Spearman correlation between b2 from DCE-MRI and macrophage density indicated a weak relationship between the two parameters (r = 0.28, p = 0.20). Validated piecewise linear modeling of the DCE-MRI data showed that the aortic root contrast agent washout rate is significantly different during disease progression. Further development of this technique from a single-slice to a 3D acquisition may enable better investigation of the relationship between in vivo imaging of endothelial permeability and atherosclerotic plaques' genetic, molecular, and cellular makeup in this important model of disease.

Right Heart Failure Following Left Ventricular Device Implantation: Natural History, Risk Factors, and Outcomes: An Analysis of the STS INTERMACS Database.

BACKGROUND: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF. METHODS: Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes. RESULTS: Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03-1.09 per 5 mg/dL increase; P<0.0001), previous tricuspid valve repair/replacement (ORs, 2.01-10.09; P<0.001), severely depressed right ventricular systolic function (ORs,1.17-2.20; P=0.004); and centrifugal versus axial LVAD (ORs,1.15-1.78; P=0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P<0.001). CONCLUSIONS: RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.

Synthesis of a Novel Series of Cu(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane as Homogeneous and Carbon-Supported Catalysts for the Synthesis of 1- and 2-Substituted-1,2,3-triazoles.

The N-alkylation of 1,3,5-triaza-7-phosphaadamantane (PTA) with ortho-, meta- and para-substituted nitrobenzyl bromide under mild conditions afforded three hydrophilic PTA ammonium salts, which were used to obtain a new set of seven water-soluble copper(I) complexes. The new compounds were fully characterized and their catalytic activity was investigated for the low power microwave assisted one-pot azide-alkyne cycloaddition reaction in homogeneous aqueous medium to obtain disubstituted 1,2,3-triazoles. The most active catalysts were immobilized on activated carbon (AC), multi-walled carbon nanotubes (CNT), as well as surface functionalized AC and CNT, with the most efficient support being the CNT treated with nitric acid and NaOH. In the presence of the immobilized catalyst, several 1,4-disubstituted-1,2,3-triazoles were obtained from the reaction of terminal alkynes, organic halides and sodium azide in moderate yields up to 80%. Furthermore, the catalyzed reaction of terminal alkynes, formaldehyde and sodium azide afforded 2-hydroxymethyl-2H-1,2,3-triazoles in high yields up to 99%. The immobilized catalyst can be recovered and recycled through simple workup steps and reused up to five consecutive cycles without a marked loss in activity. The described catalytic systems proceed with a broad substrate scope, under microwave irradiation in aqueous medium and according to "click rules".

Framework to Classify Reverse Cardiac Remodeling With Mechanical Circulatory Support: The Utah-Inova Stages.

BACKGROUND: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD. METHODS: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF <40% were termed partial responders, and the remaining patients with no significant improvement in LVEF were termed nonresponders. RESULTS: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was -0.6 cm (interquartile range [IQR], -1.1 to -0.1 cm; nonresponders), -1.1 cm (IQR, -1.8 to -0.4 cm; partial responders), and -1.9 cm (IQR, -2.9 to -1.1 cm; responders). Similarly, the median change in LVEF was -2% (IQR, -6% to 1%), 9% (IQR, 6%-14%), and 27% (IQR, 23%-33%), respectively. CONCLUSIONS: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.

A new amido-phosphane as ligand for copper and silver complexes. Synthesis, characterization and catalytic application for azide-alkyne cycloaddition in glycerol.

The new sterically hindered amido-phosphane 1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-3,7-diylbis(phenylmethanone), DBPTA (1), has been obtained via an open-cage double N-acylation of 1,3,5-triaza-7-phosphadamantane (PTA) using benzoic anhydride. DBPTA is the only acyl derivative of PTA that contains an aromatic appendage. Due to the bulky nature of the benzoyl C(O)Ph groups, they exhibit mutual anti configuration as confirmed by solution NMR and single crystal X-ray diffraction. Compound 1 is readily soluble in common polar organic and green solvents, making it a very versatile ligand that could be used in a variety of reaction systems. To assess the coordination characteristics of the new phosphane, seven copper complexes of formulas [Cu(DBPTA)4]BF4 (2), [CuX(DBPTA)3] {X = Br (3) and I (4)}, [Cu(µ-X)(DBPTA)2]2 {X = Br (5) and I (6)}, [Cu(bpy)(DBPTA)2]Y {Y = BF4 (7) and BPh4 (8)} {bpy = 2,2'-bipyridine}, and three silver complexes with formulas [Ag(DBPTA)4]NO3 (9), [Ag(Tpm*)(DBPTA)]NO3 (10) and [Ag(Tpms)(DBPTA)] (11) {Tpm* = tris(3,5-dimethyl-1-pyrazolyl)methane, Tpms = tris(pyrazol-1-yl)methanesulfonate} have been synthesised. Compounds 1-11 were characterized by elemental analyses and electrospray ionization mass spectrometry (ESI-MS), as well as by FT-IR and NMR (1H, 13C, 31P, COSY and HSQC) spectroscopic techniques. The catalytic activity of the complexes has been investigated for 1,3-dipolar azide-alkyne cycloaddition reaction using glycerol as a reaction medium to afford 1,4-disubstituted-1,2,3-triazoles. Complex 7 was found to be the most efficient catalyst, affording triazoles in yields up to 97% after 18 h under standard bench experimental conditions (at 23 °C, aerobic conditions and in the absence of any additional bases) and up to 98% after 15 minutes under microwave irradiation (125 °C, 30 W). The catalysis proceeds with a broad substrate scope according to "Click" rules providing a significant contribution to "Green Chemistry".

Bias in Medicine: Lessons Learned and Mitigation Strategies.

Cognitive bias consists of systematic errors in thinking due to human processing limitations or inappropriate mental models. Cognitive bias occurs when intuitive thinking is used to reach conclusions about information rather than analytic (mindful) thinking. Scientific progress is delayed when bias influences the dissemination of new scientific knowledge, as it has with the role of human leucocyte antigen antibodies and antibody-mediated rejection in cardiac transplantation. Mitigating strategies can be successful but involve concerted action by investigators, peer reviewers, and editors to consider how we think as well as what we think.

Water-Soluble O-, S- and Se-Functionalized Cyclic Acetyl-triaza-phosphines. Synthesis, Characterization and Application in Catalytic Azide-alkyne Cycloaddition.

The 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) derivatives, viz. the already reported 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane 5-oxide (DAPTA=O, 1), the novel 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-sulfide (DAPTA=S, 2), and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-selenide (DAPTA=Se, 3), have been synthesized under mild conditions. They are soluble in water and most common organic solvents and have been characterized using 1H and 31P NMR spectroscopy and, for 2 and 3, also by single crystal X-ray diffraction. The effect of O, S, or Se at the phosphorus atom on the structural features of the compounds has been investigated, also through the analyses of Hirshfeld surfaces. The presence of 1-3 enhances the activity of copper for the catalytic azide-alkyne cycloaddition reaction in an aqueous medium. The combination of cheaply available copper (II) acetate and compound 1 has been used as a catalyst for the one-pot and 1,4-regioselective procedure to obtain 1,2,3-triazoles with high yields and according to 'click rules'.

The Role of Nonglycolytic Glucose Metabolism in Myocardial Recovery Upon Mechanical Unloading and Circulatory Support in Chronic Heart Failure.

BACKGROUND: Significant improvements in myocardial structure and function have been reported in some patients with advanced heart failure (termed responders [R]) following left ventricular assist device (LVAD)-induced mechanical unloading. This therapeutic strategy may alter myocardial energy metabolism in a manner that reverses the deleterious metabolic adaptations of the failing heart. Specifically, our previous work demonstrated a post-LVAD dissociation of glycolysis and oxidative-phosphorylation characterized by induction of glycolysis without subsequent increase in pyruvate oxidation through the tricarboxylic acid cycle. The underlying mechanisms responsible for this dissociation are not well understood. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose-phosphate pathway and 1-carbon metabolism, which may mediate myocardial recovery in R. METHODS: We prospectively obtained paired left ventricular apical myocardial tissue from nonfailing donor hearts as well as R and nonresponders at LVAD implantation (pre-LVAD) and transplantation (post-LVAD). We conducted protein expression and metabolite profiling and evaluated mitochondrial structure using electron microscopy. RESULTS: Western blot analysis shows significant increase in rate-limiting enzymes of pentose-phosphate pathway and 1-carbon metabolism in post-LVAD R (post-R) as compared with post-LVAD nonresponders (post-NR). The metabolite levels of these enzyme substrates, such as sedoheptulose-6-phosphate (pentose phosphate pathway) and serine and glycine (1-carbon metabolism) were also decreased in Post-R. Furthermore, post-R had significantly higher reduced nicotinamide adenine dinucleotide phosphate levels, reduced reactive oxygen species levels, improved mitochondrial density, and enhanced glycosylation of the extracellular matrix protein, α-dystroglycan, all consistent with enhanced pentose-phosphate pathway and 1-carbon metabolism that correlated with the observed myocardial recovery. CONCLUSIONS: The recovering heart appears to direct glycolytic metabolites into pentose-phosphate pathway and 1-carbon metabolism, which could contribute to cardioprotection by generating reduced nicotinamide adenine dinucleotide phosphate to enhance biosynthesis and by reducing oxidative stress. These findings provide further insights into mechanisms responsible for the beneficial effect of glycolysis induction during the recovery of failing human hearts after mechanical unloading.

Provider Perspectives on the Feasibility and Utility of Routine Patient-Reported Outcomes Assessment in Heart Failure: A Qualitative Analysis.

Background Patient-reported outcomes (PROs) objectively measure health-related quality of life and provide prognostic information. Advances in technology now allow for rapid, patient-friendly PRO assessment and scoring, yet the adoption of PROs in clinic has been slow. We conducted a multicenter qualitative study of diverse providers to describe the barriers and facilitators of routine PRO use in heart failure clinics. Methods and Results Sixty heart failure providers from 5 institutions participated in 8 focus groups to explore provider perspectives on the use of heart failure-specific and generic PROs in clinical practice. A qualitative editing approach was used to analyze the data, whereby a coding dictionary was iteratively developed and applied using the qualitative software program Altas.ti. Three main themes, supporting and impeding PRO use, emerged: (1) data collection; (2) presentation and interpretation; and (3) utility and value. For each construct, we identified perspectives that highlighted both barriers and facilitators. Providers identified burden, survey fatigue, and language/health literacy barriers as potentially impeding data collection. Optimal workflow, PRO frequency and length, use of PRO translations, and assistance of a patient's proxy were suggested as facilitators. Focus group discussions provided insight on how to display PROs to support its interpretability and sharing. Furthermore, the need to educate providers on the utility and value PROs over and above current clinical approaches emerged. Conclusions Overcoming the barriers and supporting facilitators of PRO adoption could potentially lead to more successful adoption of PROs in heart failure clinics.

Change in cardiac troponin T level after intravitreal anti-vascular endothelial growth factor treatment: Prospective pilot study.

BACKGROUND: Evaluate subclinical myocardial injury associated with intravitreal anti-vascular endothelial growth factor therapy by measuring serum high-sensitivity cardiac troponin T. METHODS: This is a prospective pilot comparative study conducted at American University of Beirut Medical Center, Beirut, Lebanon. In total, 40 consecutive patients were randomized to receive either intravitreal bevacizumab or ranibizumab. Patients received three consecutive monthly injections of the assigned drug, then continued treatment as needed. Systemic concentrations of high-sensitivity cardiac troponin T and vascular endothelial growth factor were obtained at baseline, week 9, and week 24. Primary endpoint measure was change in high-sensitivity cardiac troponin T levels compared to baseline. Secondary endpoint measure was change in systemic vascular endothelial growth factor levels. RESULTS: There was no significant difference in high-sensitivity cardiac troponin T levels over time (p = 0.227) within each treatment group and no significant difference between treatments at any time point (p = 0.276). There was a significant decrease in plasma vascular endothelial growth factor levels at week 9 (p = 0.001) and week 24 (p < 0.001) compared to baseline. In the ranibizumab group, vascular endothelial growth factor levels were not significantly different at weeks 9 and 24 compared to baseline (p = 0.708 and p = 0.117, respectively). There was a significant association between the number of bevacizumab injections from weeks 8 to 24 and the decrease in vascular endothelial growth factor levels at week 24 (R = -0.67, p = 0.032). This correlation was not observed in the ranibizumab group (R = -0.341, p = 0.141). CONCLUSION: Repeated intravitreal bevacizumab or ranibizumab did not influence serum high-sensitivity cardiac troponin levels. Intravitreal bevacizumab but not ranibizumab lowered free-systemic vascular endothelial growth factor levels, which was observed in this study to be inversely related to the number of bevacizumab injections.

Risk score-guided multidisciplinary team-based Care for Heart Failure Inpatients is associated with lower 30-day readmission and lower 30-day mortality.

OBJECTIVE: Using augmented intelligence clinical decision tools and a risk score-guided multidisciplinary team-based care process (MTCP), this study evaluated the MTCP for heart failure (HF) patients' 30-day readmission and 30-day mortality across 20 Intermountain Healthcare hospitals. BACKGROUND: HF inpatient care and 30-day post-discharge management require quality improvement to impact patient health, optimize utilization, and avoid readmissions. METHODS: HF inpatients (N = 6182) were studied from January 2013 to November 2016. In February 2014, patients began receiving care via the MTCP based on a phased implementation in which the 8 largest Intermountain hospitals (accounting for 89.8% of HF inpatients) were crossed over sequentially in a stepped manner from control to MTCP over 2.5 years. After implementation, patient risk scores were calculated within 24 hours of admission and delivered electronically to clinicians. High-risk patients received MTCP care (n = 1221), while lower-risk patients received standard HF care (n = 1220). Controls had their readmission and mortality scores calculated retrospectively (high risk: n = 1791; lower risk: n = 1950). RESULTS: High-risk MTCP recipients had 21% lower 30-day readmission compared to high-risk controls (adjusted P = .013, HR = 0.79, CI = 0.66, 0.95) and 52% lower 30-day mortality (adjusted P < .001, HR = 0.48, CI = 0.33, 0.69). Lower-risk patients did not experience increased readmission (adjusted HR = 0.88, P = .19) or mortality (adjusted HR = 0.88, P = .61). Some utilization was higher, such as prescription of home health, for MTCP recipients, with no changes in length of stay or overall costs. CONCLUSIONS: A risk score-guided MTCP was associated with lower 30-day readmission and 30-day mortality in high-risk HF inpatients. Further evaluation of this clinical management approach is required.

Structural characterization and biological properties of silver(I) tris(pyrazolyl)methane sulfonate.

The water-soluble 1D helical coordination polymer [Ag(Tpms)]n (1) [Tpms = tris(pyrazolyl)methane sulfonate, -O3SC(pz)3; pz = pyrazolyl] was synthesized and fully characterized, its single-crystal X-ray diffraction analysis revealing the ligand acting as a bridging chelate N3-donor ligand. The antiproliferative potential of 1 was performed on two human tumour cell lines, A2780 and HCT116, and in normal fibroblasts, with a much higher effect in the former cell line (IC50 of 0.04 µM) as compared to the latter cell line and to normal fibroblasts. Compound 1 does not alter cell cycle progression but interferes with the adherence of A2780 cells triggering cell apoptosis. Apoptosis appears to occur via the extrinsic pathway (no changes in mitochondria membrane potential, reactive oxygen species (ROS) and pro-apoptotic (B-cell lymphoma 2 (BCL-2) associated protein (BAX))/anti-apoptotic (BCL-2) ratio) being this hypothesis also supported by the presence of silver mainly in the supernatants of A2780 cells. Results also indicated that cell death via autophagy was triggered. Proteomic analysis allowed us to confirm that compound 1 is able to induce a stress response in A2780 cells that is related with its antiproliferative activity and the trigger of apoptosis.

Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation.

BACKGROUND: The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. OBJECTIVES: The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. METHODS: A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. RESULTS: There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19- cell population in the rituximab-treated group. CONCLUSIONS: A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745).

Post-transplant outcome in patients bridged to transplant with temporary mechanical circulatory support devices.

BACKGROUND: The new heart allocation system in the United States prioritizes patients supported by temporary mechanical circulatory support (TMCS) devices over those with uncomplicated durable continuous-flow left ventricular assist devices (CF-LVADs), which may increase the number of patients bridged to transplant with TMCS. Limited data are available in guiding post-transplant outcomes with various TMCS devices. We sought to describe post-transplant outcome and identify clinical variables associated with post-transplant outcome in patients bridged to transplant with TMCS. METHODS: Using data from the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, we included subjects who underwent transplantation between 2005 and 2016 with known use of mechanical circulatory support. Pre-transplant recipient, donor, and transplant-specific variables were abstracted. The primary outcome was patient survival at 1-year post-transplant. Outcomes of patients bridged to transplant with TMCS were compared with those of patients bridged with CF-LVADs. Cox regression analyses were performed to identify clinical variables associated with the outcomes. RESULTS: There were 6,528 patients bridged to transplant with the following types of mechanical circulatory support: durable CF-LVADs (n = 6,206), extracorporeal membrane oxygenation (ECMO, n = 134), percutaneous temporary CF-LVADs (n = 75), surgically implanted temporary CF-LVADs (n = 38) or surgically implanted temporary BiVAD (n = 75). Bridging with ECMO (hazard ratio 3.79, 95% confidence interval [CI] 2.69-5.34, p < 0.001) or percutaneous temporary CF-LVADs (hazard ratio 1.83, 95% CI 1.09-3.08, p = 0.02) was independently associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index, higher recipient creatinine, and prolonged ischemic time. CONCLUSIONS: This analysis of a large international cohort of patients bridged to transplant with mechanical circulatory support identified ECMO and percutaneous temporary CF-LVADs as predictors of mortality after transplant, along with additional donor and recipient clinical characteristics. These findings may provide guidance to clinicians in decisions on mechanical circulatory support device selection, transplant eligibility, and timing of transplant.