Lower BSA Research Articles

Small Left Ventricular Chamber Size And Mortality In A Large General Population

Enlargement of the left ventricle (LV) is an important marker of adverse cardiac remodeling and poor prognosis. Previous studies demonstrated increased cardiovascular risk in small subsets of patients with small LV chamber size, however, the prognostic implications of small chamber size in a general population remains unclear. The objective of this study was to examine the prognosis of a small LV chamber in a large general cohort. All consecutive subjects that underwent echocardiography examinations from 2011 to 2023 were retrieved for analysis. Small chamber size was defined as end-diastolic diameter less than 42 mm for men and 37.8 mm for women as per ASE guidelines. The primary endpoint for the study was all-cause mortality. 46,529 subjects (mean age 60 ± 19 years, 56% males) were included of whom 3,787 had small LV chamber size. Clinical variables associated with small chamber included increasing age and lower BSA. Echocardiographic variables included higher relative wall thickness, and E/e' ratio. On multivariable analysis, the presence of a small LV was significantly associated with mortality (HR 1.34 with 95% CI 1.22-1.46; p <0.001). This finding was significant in both older (over 65 years) (HR 1.30 95% CI 1.19-1.41; p <0.001) and younger (HR 2.09 95% CI 1.81-2.41; p <0.001) subjects and in both males and females. In conclusion, in this retrospective large cohort study, small LV chamber size was significantly associated with mortality in a broad range of patients. Further study is necessary to elucidate mechanisms and design preventive strategies.

The cardiovascular exercise response in children with overweight or obesity measured by cardiovascular magnetic resonance imaging.

Overweight and obesity are among the main causes of cardiovascular diseases. Exercise testing can aid in the early detection of subtle cardiac dysfunction not present in rest. We hypothesized that the cardiovascular response to exercise is impaired among children with overweight or obesity, characterized by the inability of the cardiovascular system to adapt to exercise by increasing cardiac volumes and blood pressure. We performed a cardiovascular stress test to investigate whether the cardiovascular exercise response is altered in children with overweight and obesity, as compared to children with a normal weight. A subgroup of the Generation R population-based prospective cohort study, consisting of 41 children with overweight or obesity and 166 children with a normal weight with a mean age of 16 years, performed an isometric exercise. Continuous heart rate and blood pressure were measured during rest, exercise and recovery. Cardiovascular magnetic resonance (CMR) measurements were performed during rest and exercise. Higher BMI was associated with a higher resting systolic and diastolic blood pressure (difference: 0.24 SDS (95% CI 0.10, 0.37) and 0.20 SDS (95% CI 0.06, 0.33)) and lower systolic and diastolic blood pressure increases from rest to peak exercise (-0.11 SDS (95% CI -0.20, -0.03) and -0.07 SDS (95% CI -0.07, -0.01)). BMI was also associated with a slower decrease in systolic and diastolic blood pressure during recovery (p values < 0.05). Higher childhood BMI was associated with lower BSA corrected left ventricular mass, end-diastolic volume and stroke volume (p values < 0.05). There were no associations of childhood BMI with the cardiac response to exercise measured by heart rate and CMR measurements. Childhood BMI is, across the full range, associated with a blunted blood pressure response to static exercise but there were no differences in cardiac response to exercise. Our findings suggest that adiposity may especially affect the vascular exercise reaction without affecting cardiac response.

Investigating the impact of the sulfonation degree in sulfonated polyphenylsulfone (sPPSU) on PES/sPPSU polymer blend membranes

Polyethersulfone (PES) has widespread applications due to its excellent processability, mechanical strength, and chemical resistance. Nevertheless, its hydrophobic nature often leads to severe fouling and permeance decline. To improve the hydrophilicity of PES membranes, polymer blending is one of the most common methods. In this work, a series of sulfonated polyphenylene sulfones (sPPSU) with 1.9, 4.5, 8.2, 12.7, 19 degrees of sulfonation (DS) were synthesized and used to blend with PES. The PES/sPPSU blends were found to be compatible by calculating their theoretical enthalpy of mixing and measuring their glass transition temperatures (Tg's) at a blend weight ratio of 1:1. Ultrafiltration (UF) membranes were cast using the nonsolvent-induced phase separation (NIPS) method. It was found that 50/50 PES/sPPSU blend membranes with a DS equaling to or exceeding 8.2 eliminated finger-like macrovoids, resulting in a thinner and tight cross-sectional structure. A higher DS of sPPSU rendered the blend membranes with more hydrophilicity and oleophobicity as well as a more negatively charged surface. The unmodified PES membrane had rejections of 87.47 % and 91.5 % in ultrafiltration tests using feed solutions containing BSA and oil/water emulsion, respectively. The rejections could be further increased to 99.37 % and 97.17 % respectively by the blend membranes. The blend membranes consisting of a higher DS of sPPSU also exhibited a higher permeance, lower BSA absorption and better anti-fouling properties than the PES membrane.

The impact of child-specific characteristics on warfarin dosing requirements

BackgroundThe influence of child characteristics on warfarin dosing has been reported; however, there is no consensus on the nature and extent of this effect. ObjectivesTo investigate the impacts of the demographic and clinical characteristics of children on the warfarin dose required to achieve a therapeutic international normalization ratio (INR). MethodsThis retrospective cohort study included children aged 3 months to 14 years old who were prescribed warfarin for 3 months or longer with a “stable INR.” The primary outcome was the total daily dose (TDD) and total weekly dose of warfarin required to achieve a therapeutic INR target. ResultsWe included 127 patients with a mean age of 7.7 ± 3.7 years and a median weight of 22 (IQR, 16-33) kg. Of the sample, 55 patients (43.3%) required a TDD of ≤0.1 mg/kg. The TDD for children younger than 5 years, 5 to 10 years, and older than 10 years were 0.14 ± 0.06 mg/kg, 0.12 ± 0.05 mg/kg, and 0.096 ± 0.04 mg/kg, respectively (P = .002). Overweight and obese children required a smaller TDD than normal-weight children: 0.09 ± 0.05 vs 0.13 ± 0.05 mg/kg (P = .004), which was similar for underweight children. A lower body surface area (<0.5 m2) required a higher dose. All the other variables did not affect warfarin doses. The incidence of a subtherapeutic or supratherapeutic INR was independent of demographic or clinical variables. ConclusionThe study confirmed that the patient demographics affect the daily warfarin dose required to achieve the INR target. However, they do not have any predictive value for the incidence of out-of-range-INR.

Sex-specific differences in bi-atrial strain in elite athletes: results from the ELITE cohort

Abstract Background Athletes frequently demonstrate increased atrial volumes as a result of physiological adaptation to sports. In the general population, atrial dilatation is associated with decreased atrial function, measured as atrial ejection fraction and strain. However, studies on bi-atrial function in athletes have been limited and have primarily focused on male endurance athletes. Purpose To determine sex-specific differences in left- and right atrial strain in elite athletes. Methods The study population consisted of elite athletes included in the ELITE-cohort older than 16 years of age and exercising ≥10 hours per week and competing at the highest national, international or Olympic level in the Netherlands. All included athletes underwent a standardised resting transthoracic echocardiogram. Left- and right atrial (LA/RA) reservoir-, conduit- and cntractile- strain were measured with grey-scale-based 2D Speckle tracking software in the four- and two-chamber views and bi-atrial volume and function parameters were collected. Results A total of 166 elite athletes were included (48.2% female, media age 25 years [22, 28]), with athletic disciplines road cycling 25.3%, hockey 16.9%, rowing 14.5%, soccer 12.7%, water polo 9.6%, sailing 6.0%, track cycling 3.6%, and other 11.6%. There were no sex differences in age and training hours (18 hours per week). Athletic disciplines were evenly distributed among female- and male athletes. Female athletes had a lower BSA than male athletes (1.8 cm2 [1.7, 1.9] vs 2.1 cm2 [1.9, 2.2], p &amp;lt;0.001). Female athletes had similar LAESVi (36.5 ml/cm2 [32.0, 42.0] vs 36.5 ml/cm2 [31.0, 47.8]) and LAESAi (11.2 cm2/m2 [9.5, 12.2] vs 10.6 cm2/m2 [9.0, 11.9]) compared with male athletes. Female athletes had a higher LAEF (63.2 ±6.2% vs 60.7 ±5.8%, p =0.007) and greater LA deformation than male elite athletes during the reservoir- (34.7 ±6.2% vs 31.4 ±4.9%, p &amp;lt;0.001) and conduit phase (-25.2 ±5.2% vs -22.6 ±3.7% p &amp;lt;0.001). LA deformation during the contractile phase (-9.0% [-12.0, -7.0] vs – 9.0% [-11,-7]) was similar (figure 1). Female athletes had a lower RAESVi (29.5 ml/m2 [25.2, 36.4] vs 35.3 ml/m2 [28.5, 41.9], p &amp;lt;0.01) but there were no differences in RAEF (42.6 ±10.3% vs 45.2 ±11.1%) and RAESAi (9.8cm2/m2 [8.8, 11.3] vs 10.1 cm2/m2 [8.8-11.3]). There were no differences in RA reservoir- (30.7 ±7.6% vs 29.4 ±8.0%), conduit (-21.4 ±6.6% vs -20 ±6.6%) and contractile strain (-9.0% [-11.0, -6.8] vs -9.0% [-11.8, -7.0]) (figure 2). Conclusion In both male and female elite athletes, the LA is of comparable area and volume. However, in female athletes LA deformation is greater during the reservoir and conduit phases, resulting in a greater LA ejection fraction in the presence of similar LA contractile deformation. Conversely, RA volumes were smaller in female athletes, but deformation was similar compared with male athletes. Our findings suggest the presence of sex-specific atrial exercised-induced adaptation.Figure 1.Figure 2.

Abstract 17910: Is Implantation of a Larger Edwards Sapien Transcatheter Pulmonary Valve Associated With Early Valve Failure? A Different Type of Patient-Prosthesis Mismatch

Introduction: Transcatheter pulmonary valve replacement (TPVR) is an alternative option to address failing native and bioprosthetic pulmonary valves (BPV). TPVR has expanded to implantation in native right ventricular outflow tracts (nRVOT) and progressively smaller patients. We aim to define the relationship between valve-to-patient size ratio and early development of pulmonary insufficiency (PI). Methods: This single-center retrospective cohort study identified patients who underwent TPVR with a Sapien valve between 2014 and 2021. We collected demographic, anatomic, and pre- and post-TPVR echo data. Echo data were collected at four post-TPVR time points: prior to discharge, short-term (1-9 months), mid-term (9-18 months), and most recent study. The primary outcome was development of moderate or severe PI by mid-term follow-up. Valve size-to-body surface area (BSA) ratio was evaluated for correlation with the development of moderate or severe PI. Results: The cohort consisted of 187 patients; 79 (42.2%) underwent TPVR within the nRVOT (Table). Compared to patients with TPVR in a conduit or BPV, patients with a nRVOT were younger, had lower weight, and lower BSA. Moderate or severe PI post-TPVR was more common in patients in the nRVOT group (P-value &lt; 0.001), occurring in 9 (11.5%) by mid-term follow-up, compared to 2 (1.9%) in a conduit or BPV. In the subset of patients with TPVR within the nRVOT, the development of moderate or severe PI was associated with a larger valve size-BSA ratio (OR=1.13, 95% CI: 1.03, 1.26, P-value=0.012). Conclusions: Development of moderate or severe PI following TPVR with a Sapien valve was rare in this cohort. Patients receiving a Sapien TPVR within the nRVOT with a large valve size-to-BSA ratio were more likely to develop early PI. The increased risk of early valve failure in these patients should inform counseling regarding expected longevity of the valve and may guide valve choice as more transcatheter valve options become available.

Use of Intracorporeal Durable LVAD Support in Children Using HVAD or HeartMate 3-A EUROMACS Analysis.

Purpose: The withdrawal of HVAD in 2021 created a concern for the pediatric population. The alternative implantable centrifugal blood pump HeartMate 3 has since been used more frequently in children. This paper analyses the outcome of children on LVAD support provided with an HVAD or HM3. Methods: A retrospective analysis of the EUROMACS database on children supported with VAD < 19 years of age from 1 January 2009 to 1 December 2021 was conducted. All patients with an LVAD and either an HVAD or HM3 were included. Patients with missing data on VAD status and/or missing baseline and/or follow up information were excluded. Kaplan-Meier survival analysis was performed to evaluate survival differences. Analyses were performed using Fisher's exact test. Results: The study included 150 implantations in 142 patients with 128 implants using an HVAD compared to 28 implants using an HM3. Nine patients (6%) needed temporary right ventricular mechanical support, which was significantly higher in the HM3 group, with 25% (p: 0.01). Patients in the HVAD group were significantly younger (12.7 vs. 14.5 years, p: 0.01), weighed less (45.7 vs. 60 kg, p: <0.000) and had lower BSA values (1.3 vs. 1.6 m2, p: <0.000). Median support time was 204 days. Overall, 98 patients (69%) were discharged and sent home, while 87% were discharged in group HM3 (p: ns). A total of 123 children (86%) survived to transplantation, recovery or are ongoing, without differences between groups. In the HVAD group, 10 patients (8%) died while on support, whereas in 12% of HM3 patients died (p: 0.7). Conclusions: Survival in children implanted with an HM3 was excellent. Almost 90% were discharged and sent home on the device.

PEDS5: VAD Discharge at Pediatric Centers- Why can’t we get home?

Background: The use of intra-corporeal continuous flow ventricular assist devices (CF-VAD) has allowed patients with advanced heart failure to be discharged home. Moreover, it has been shown that heart transplant (HTx)>30 days after VAD implant offers some survival benefit. Despite this, only about 50% of patients at pediatric centers are discharged, while others remain in hospital until HTx. We sought to characterize the cohort of patients who are transplanted during their index VAD admission as a means to identify potential barriers to discharge. Methods: Using the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry, individuals who underwent implant with a dischargeable VAD (HVAD and HM3) at a pediatric center were included. Data including patient demographics, characteristics and clinical course were compared between the discharged versus hospitalized cohorts. Patients who recovered or died during their VAD admission were excluded. Results: From December 2012 to June 2022, 220 patients underwent implant with HM3 (n=108) or HVAD (n=111) across 32 pediatric centers. Overall, 28% (62/220) of patients remained hospitalized until HTx. There was no significant difference in age, underlying diagnosis, days to extubation, INTERMACS profile, or history of ECMO in those who were discharged versus hospitalized. There was also no significant difference in adverse events including stroke, bleeding, infection, hepatic or renal dysfunction, or right heart failure between the two groups (See Table 1). Patients with HM3 were less likely to be discharged if lower BSA (p=0.05) or on BiVAD support (p=0.04). Conclusion: Although discharge in VAD patients at pediatric centers is improving, nearly one-third of patients undergoing implant with dischargeable VADs remain hospitalized until transplant. There was no significant difference in markers of severity of illness or adverse events in those who remain hospitalized versus discharged. Thus, perceived non-medical barriers by providers or families may be limiting discharge at pediatric centers and may be a potential target for further education.

Effect of history of atrial arrhythmias on the rate of recurrent stroke in patients after PFO closure

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Although the importance of persistent foramen ovale (PFO) closure is well established, it is far from complete its role in patients with atrial arrhythmias. Patients with a history of atrial arrhythmias, especially younger and healthy persons with PFO after a stroke, are indicated for PFO closure. This is despite the uncertainty of whether atrial arrhythmia (it means silent atrial fibrillation) is the actual cause of the stroke. Objectives To describe prospective observations comparing cohort PFO closure patients with and without atrial arrhythmias. Method A retrospective analysis of the real world of a prospective registry of patients after PFO closure. This is a set of patients from one cardiac center over 19 years; each patient was followed up once a year for seven years. The recurrence of ischemic stroke was monitored. Results A total of 712, 378 females (53.1%) and 334 males, aged 50 (+/-12) years, were indicated for PFO closure mostly due to stroke (436 i.e. 61.4%) and systemic embolization (56 i.e. 7.9%). DM was present in 55 patients ( i.e. 7.7%), and arterial hypertension was also in 306 patients (i.e. 43%). See other demographic data in Table 1. A history of atrial arrhythmias ( salvage SVES or intrinsic atrial fibrillation) before PFO closure was described in 50 patients ( 7.1%). During the 7-year follow-up, recurrent stroke was detected in a total of 14 cases, 13 in the group without previous arrhythmic history (4.3%) and 1 with previous arrhythmic history (3.8%, p=0.912). A surprising finding was the statistically higher representation of women in the cohort with previous arrhythmic history (p=0.001), in the cohort of shorter (p=0.012) and thinner (p=0.022) women, and thus in the cohort with lower BSA (p=0.006). On the other hand, unsurprisingly, there was a statistically higher proportion of diabetics (p0.024) and patients with coronary artery disease (p=0.013) in the cohort with atrial arrhythmias in the pre-hospital period. Detailed results are in table 1. Conclusion There was no difference in the incidence of recurrent stroke between the cohorts of patients with and without a prior history of atrial arrhythmias in the seven-year follow-up after PFO closure. The cohort of patients with a previous history of atrial arrhythmias was, unsurprisingly, statistically larger in patients with diabetes and coronary artery disease.

Sepsis in postcardiotomy cardiogenic shock patients supported with veno- arterial extracorporeal membrane oxygenation.

Sepsis could affect the outcomes of patients with postcardiotomy cardiogenic shock supported with extracorporeal membrane oxygenation (ECMO). Our objectives were to characterize sepsis patients with ECMO support for postcardiotomy cardiogenic shock and assess its predictors and effect on patients' outcomes. This retrospective study included 103 patients with ECMO for postcardiotomy cardiogenic shock from 2009 to 2020. Patients were divided according to the occurrence and timing of sepsis into three groups. Group 1 included patients with no sepsis (n = 67), Group 2 included patients with ECMO-related sepsis (n = 10), and Group 3 included patients with non-ECMO-related sepsis (n = 26). Lactate level before ECMO was highest in the ECMO-associated sepsis group (Group 1 and 2 p = 0.003 and Group 2 and 3 p = 0.003). Dialysis and gastrointestinal bleeding were highest in ECMO-associated sepsis (p = 0.03 and 0.04, respectively). Blood transfusion was higher in ECMO-associated sepsis than in patients with no sepsis (p = 0.01). Mortality was nonsignificantly higher in patients with ECMO-associated sepsis. High BMI (OR: 1.11; p = 0.004), preoperative dialysis (OR: 7.35; p = 0.02), preoperative IABP (OR: 9.9.61; p = 0.01) and CABG (OR: 6.29; p = 0.01) were significantly associated with sepsis. Older age (OR: 1.08; p = 0.004), lower BSA (OR: 0.004; p = 0.003), peripheral cannulation (OR: 29.82; p = 0.03), and high pre ECMO lactate level (OR: 1.24; p = 0.001) were associated with increased mortality. Sepsis did not predict mortality (OR: 1.83; p = 0.21). Sepsis is a dreaded complication in patients with postcardiotomy cardiogenic shock, especially ECMO-associated sepsis. Preoperative risk factors could predict postoperative sepsis in ECMO patients.

QLTI-07. IDENTIFYING RISK FACTORS FOR PROLONGED TRANSFUSION-DEPENDENT TEMOZOLOMIDE-INDUCED THROMBOCYTOPAENIA IN PATIENTS RECEIVING CONCURRENT CHEMO-RADIOTHERAPY FOR GLIOBLASTOMA (GBM)

Abstract BACKGROUND Temozolomide-induced thrombocytopaenia is a well-recognised clinical issue with significant inter-patient variation. However, knowledge of the extent of the problem and its potential risk factors remains limited. Our aim was to determine the incidence of patients requiring platelet transfusion and ascertain associated risk factors using real-world data. METHODS Data from patients with GBM receiving concurrent temozolomide-chemo-radiotherapy (CRT) from 01/01/18-31/12/2019 retrospectively reviewed. Patients receiving platelet transfusion identified (Local policy: transfusion for platelet count ≤ 30x109/L). Logistic regression and chi-squared tests used to compare variables in patients requiring platelet transfusion and those not. RESULTS 111 patients with GBM received TMZ-CRT (60Gy/30#; 75mg/m2 temozolomide). 12/111 patients received platelet transfusion: 10 during concurrent-CRT and 2 during adjuvant-treatment. Numbers of transfusions: 1-2: 7 patients; 3-4: 2 patients; ≥ 5 transfusions: 3 patients. Median time from platelet count ≥ G3 to ≥ 100 in 11/12 patients: 38 days (range 6-72). 1 did not recover, patient died 84 days following start of TMZ-CRT with thrombocytopaenia. Comparison of the transfused vs the non-transfused cohort shows: transfused: 50% female; non-transfused: 36% female. Mean BSA: transfused: 1.73, SD0.21; non-transfused:1.96, SD0.22 (OR 0.01; 95% CI:0.0003 – 0.16). Mean age: transfused: 57, SD15.8; non-transfused: 58, SD10.7 . Mean baseline platelet count: transfused: 329, SD185; non-transfused: 319, SD117. Mean PTV: transfused: 400, SD115; non-transfused: 414, SD123. There were no statistically significant associations with demographics, age, blood parameters or planning target volume. CONCLUSION This study demonstrates a subset of patients who experience severe and prolonged thrombocytopaenia. Risk factors elucidated are female sex and lower BSA. Large-scale prospective trials evaluating a panel of predictors including concomitant medications, patient MGMT variants and temozolomide-metabolite concentrations would be valuable. Precise stratification of this vulnerable subgroup may permit consideration of temozolomide dose-capping in the future. Careful informed consent with all patients and caution with intensifying treatment under trials is vital presently.

Nivolumab in squamous cell carcinomas of the head and neck (SCCHN): A real-world outcome study in Ontario, Canada.

e18017 Background: The CheckMate-141 trial led to the approval of nivolumab in platinum-resistant metastatic squamous cell carcinomas of the head and neck (SCCHN). We evaluated outcomes of SCCHN patients in Ontario, Canada treated with nivolumab since its funding through the New Drug Funding Program (NDFP) of Cancer Care Ontario (CCO). Methods: Retrospective review using the provincial treatment registry (CCO NDFP) was undertaken. Patient characteristics, reason for treatment, treatment length, and date of death were collected. Kaplan-Meier method was used to estimate overall survival and Cox regression to evaluate prognostic effect of selected factors. Results: 134 patients with SCCHN received nivolumab between March 2017 and March 2019. Median patient age was 63 years with 80.6% male. Nivolumab was used as second-line therapy after disease relapse within 6 months of curative-intent platinum chemotherapy (PC) in 39.6% of patients (Indication 1 – I1), used as second-line therapy post PC in non-curative intent in 42.6% of patients (Indication 2 – I2), and used as first-line therapy in non-curative intent due to contraindication for PC in 17.2% of patients (Indication 3 – I3). Median overall survival (mOS) was 5.8 months (95% confidence intervals (CI) 4.5-7.3), and one-year OS was 28.4% (CI 2.10-36.1). HPV status had no statistically significant impact on OS (p = 0.12). Patients with a lower BSA (&lt; 1.81) had median OS of 3.9 months (CI 3.1-6.7) versus 9.0 months (CI 6.5-14.8) in those with higher BSA, HR = 0.12 (CI 0.04-0.39, p &lt; 0.001). Differences between indications was statistically significant (p &lt; 0.001). Patients who received nivolumab for I1 had mOS 7.2 months (CI 3.8-9.8) versus 11.9 months (CI 6.2-not reached) for I3, HR = 1.73(CI 0.94-3.16). Patients who received nivolumab for I2 had mOS 3.9 months (CI 2.9-5.4) as compared to I3, HR = 3.27(CI 1.80-5.94). Patients who received nivolumab for I2 had poorer mOS as compared to I1 HR = 1.90(CI 1.23-2.92). Conclusions: Real world data in Ontario demonstrates poorer mOS, but similar 1-year survival compared to CheckMate-141 trial. HPV status had no significant impact on mOS. Patients who received nivolumab as first-line therapy in the non-curative setting appeared to have longer mOS than those who received initial PC for non-curative intent followed by nivolumab. Patients who received nivolumab as second-line therapy post PC in non-curative intent setting as compared to within 6 months of curative-intent therapy had poorer mOS.

Enhanced hydrophilicity and anticoagulation of polysulfone materials modified via dihydroxypropyl, sulfonic groups and chitosan

A novel modified polysulfone (PSF) is successfully prepared for hemodialysis by grafting with a well-defined heparin-like polymer, sulfonated dihydroxypropyl chitosan (SDHPCS), which is obtained in proper sequence via alkalization of chitosan, etherification and sulfonation. PSF is modified via chloroacetyl chloride, and then, the chloroacylated polysulfone (CAPSF) with pristine PSF is transformed into CAPSF/PSF blend membrane via the phase inversion, followed introducing amino group into CAPSF on the surface and taking glutaraldehyde as bridge between modified PSF membrane and SDHPCS. The result of 1H NMR spectrum of prepared CAPSF indicates that the degree of the substitution of chloroacetyl group. The SEM, EDS mapping, FTIR and XPS show that SDHPCS-g-PSF membranes are successfully prepared. The hydrophilicity of the membrane modified by SDHPCS is improved obviously, and the contact angle remarkably reduced from 87 ° to below 45°, exhibiting much better hydrophilicity. The hemocompatibility characterizations including BSA adsorption, Plasma recalcification time (PRT), hemolysis ratio (HR), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) also certificates that SDHPCS-g-PSF possesses lower BSA adsorption and enhanced blood compatibility.

Tetrapeptide ligands screening for antibody separation and purification by molecular simulation and experimental verification

Short peptide resin has a great advantage in the separation and purification of antibodies due to its high selectivity and stable ligand binding ability. In this study, a peptide library containing 480 tetrapeptides was established with six critical residues (Phe, Tyr, Leu, Glu, Ile, Lys) of Protein A binding to Fc part of the antibody and one Histidine. Then the library was screened by LibDock and five tetrapeptide ligands with high LibDock scores were selected. Subsequently, the electrostatic interaction energies and van der Waals interaction energies between the screened ligands and the Fc-A fragment of IgG were further calculated by molecular dynamics simulation to research the binding ability between ligands and target proteins. The simulation results showed that YEHF was the optimal ligand with higher van der Waals interaction energies. Then, four tetrapeptides (YFLH, FYHI, FYKH and YEHF) were selected as ligands for preparing adsorption resins, and the resins were used to bind hIgG and BSA by static adsorption experiments. The results showed that Ac-YEHF-4FF resin had higher hIgG binding ability and lower BSA binding ability, also indicating that YEHF was the optimal screened ligand. Therefore, molecular simulation was verified as a well use technology for antibody separation and purification.

U.S. budget impactanalysis of body surface area (BSA)dosing for a rituximab biosimilar vsflat-fixed-dosing for subcutaneous rituximab in non-Hodgkin lymphoma (NHL)and chronic lymphocytic leukemia (CLL).

e18822 Background: The first rituximab biosimilar approved in the US, rituximab-abbs, is a CD20-directed monoclonal antibody that is expected to significantly reduce drug acquisition costs. This economic analysis evaluated budgetary impact of BSA-based rituximab-abbs (IV-R-BIOSIM) vs flat-fixed rituximab/hyaluronidase human subcutaneous injection (SC-R) dosing in NHL (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL]) and CLL. The objective was to project incremental cost differences per patient between IV-R-BIOSIM and SC-R from a US healthcare insured (Medicare) population. Methods: An illustrative BIM estimated 1-year costs for IV-R-BIOSIM and SC-R. The model assumed equal efficacy and safety between products. Values for epidemiology, market share distribution, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Costs for the first infused rituximab (IV-R) dose were excluded for appropriate comparison. IV-R-BIOSIM doses used BSAs of 1.6 m2, 1.8 m2, infusion duration was 3 hours. Annual dose counts of IV-R-BIOSIM or SC-R were: 9 untreated FL with maintenance; 7 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 5 CLL. Drug acquisition and administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. Patient cost share was 2020 Medicare Part B 20% cost-share for office visits and drugs. A scenario analysis was also performed to estimate FL maintenance costs for 2-year dosing. Results: Estimated 1-year savings with IV-R-BIOSIM for 1.8 m2 BSA dosing were $1,067–$6,893 with variability between indications (Table). For 1.6 m2 BSA dosing, estimated 1-year savings with IV-R-BIOSIM were $3,819–$10,856. Estimated 2-year savings with IV-R-BIOSIM for FL maintenance dosing were $9,191 for 1.8 m2 BSA dosing and $14,475 for 1.6 m2 BSA dosing. Savings of up to $1,900 were seen for higher-than-average BSA dosing, regardless of regimen. Conclusions: These findings demonstrate the potential economic benefits of replacing a proportion of SC-R use with BSA-based IV-R-BIOSIM from a US payer perspective, especially when lower BSA dosing is used. Savings are driven by drug costs and may increase with IV-R-BIOSIM as patient BSA decreases due to static costs with SC-R doses. These data also suggest that drug wastage may occur with SC-R in lower BSA patients.[Table: see text]

The Use of Cardiopulmonary Stress Testing to Predict Poor Outcomes Post-Heart Transplantation

<h3>Purpose</h3> Cardiopulmonary stress testing (CPX) has been used as a reliable marker for poor outcomes among patients with chronic heart failure. The utility of pre-transplant CPX to predict post heart transplant (HT) outcomes has not been evaluated. <h3>Methods</h3> We conducted an observational, retrospective, cohort study of all HT recipients who underwent a pre-HT CPX at a single center from 2013 to 2019. Measures of cardiovascular performance were evaluated including METs achieved, peak VO2, %-predicted peak VO2, VE/VCO2 slope, RER, and VO2/heart rate (HR). These were correlated to post-HT clinical outcomes including hospital length of stay (LOS), ICU LOS, need for mechanical circulatory support (MCS) (e.g. intra-aortic balloon pump or VA-ECMO), and death. <h3>Results</h3> 52 HT recipients were included (mean age 57 years, 67% male). All subjects underwent a CPX and subsequently received a HT within 139 ± 122 days. Subjects exhibited poor cardiovascular performance with 57% achieving a VE/VCO2 greater than 35 (average 37± 8), only 35% able to demonstrate greater than 6 METs, 58% with %-predicted peak VO2 less than 50, and 60% with VO2/HR of less than 11. Subjects with VE/VCO2 greater than 35 were older (60 years vs 49 years, p = 0.013) and had lower BSA (1.9 m2 vs 2.1 m2, p = 0.04). Ability to achieve greater than 6 METs was associated with less than 5-day ICU LOS (25% vs 10%, p=0.03) and a reduced need for MCS (2% vs 33%, p<0.001) (Fig. 1). A peak VO2 of greater than 14 ml/kg/min also was associated with a lesser need for MCS support (14% vs 43%, p=0.06). Patients with a VE/VCO2 slope of less than 35 were more likely to have a total LOS of less than 24 days (43% vs 25%, p=0.02). None of the CPX measures were associated with post-HT death. <h3>Conclusion</h3> Ability to achieve greater than 6 METs and a VE/VCO2 less than 35 were associated with positive post-HT clinical outcomes of reduced ICU LOS, reduced need for MCS, and reduced total hospital LOS. Pre-operative CPX measures may provide clinical utility in identifying subjects at risk for adverse post-HT outcomes.

Early Postoperative Arrhythmias after Paediatric Cardiac Surgery

Pediatric arrhythmias represent around 55.1 per 100,000 patients assessed in pediatric crisis divisions. Patients with intrinsic coronary illness are at deep rooted hazard for the advancement of arrhythmias. The point of this investigation is to assess the rate and kinds of early postoperative arrhythmias after pediatric cardiovascular medical procedure. Strategies: The current investigation included 227 pediatric patients with intrinsic heart maladies made arrangements for careful repair.All patients will be exposed to Demographic information, Complete cardiovascular conclusion, Preoperative treatment,Operative system, Post-usable boundaries (electrolyte levels, oxygen immersion, blood pH, serum calcium, sodium, and potassium levels), and Electrocardiogram (ECG) , Echocardiography (ECHO). Results: there was slight female power in which female patients represented 52.9% of the complete accomplice, yet rate of arrhythmia was higher in male patients. the examination between the arrhythmic and non-arrhythmic gathering of patients uncovered a measurably critical distinction as respect of sexual orientation, with higher danger of arrythmia in male patients. There was a marginal relationship between more youthful age at activity and arrythmia too (p =0.055). In like manner, the examination between the arrhythmic and non-arrhythmic gathering of patients uncovered a measurably critical distinction as respect of BSA, with lower BSA in arrythmia gathering. End: Lower age, male sexual orientation, lower body weight, longer ACC time, longer mechanical ventilation, longer ICU remain, electrolyte irregularities, and biventricular physiology all are hazard factors for postoperative arrhythmias.Thus, specialists must consider these components preoperatively to have the option to recognize in danger populace and plan the postoperative consideration as needs be.

Correlation between QRS duration and cardiac output measured by left ventricular outflow tract velocity in patient with cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy (CRT) is proved as an effective treatment for moderate to severe heart failure. It reduces all-cause mortality in patients with advanced heart failure. There is strong evidence that CRT reduces mortality and hospitalization, improves cardiac function and structure in symptomatic chronic heart failure patients with optimal medical treatment, severely depressed LVEF (i.e. &amp;lt;35%) and complete LBBB. However 30% of patients may show negative response to CRT therapy. Therefore, optimization of CRT therapy in patients with heart failure seems to be a main subject for study in our researches. Methods of optimization includes optimization of medical therapy, control of risk factors and comorbidities, and optimization of device implantation and programming. Overall, studying the correlation between QRS duration and cardiac output will improve CRT programming optimization techniques. Aim To study the correlation between QRS duration and cardiac output measured by left ventricular outflow tract (LVOT) VTI in patients with CRT implantation. Methods Study included 100 CRT already implanted patients, they are requested to do a simple electrocardiographic and echocardiographic study. The relation between post implant QRS and cardiac output are studied among the patients. Results There was negative significant correlation between QRS duration and LVOT VTI and SVi. The optimal cut off values for optimal response to CRT using ROC curves were 130msec for post implant QRS duration and 17.1 cm for LVOT VTI. Conclusion CRT response is more in female patients with lower BSA, and without previous history of IHD or smoking. There is a significant negative correlation between QRS duration and LVOT VTI. Post implantation cut off value of QRS duration (&amp;lt;130) predict higher LVOT VTI and also the post implantation benefit for the patient with CRT implanted.

ABO Incompatible Heart Transplantation in Young Children: Less Rejection and Infection

Purpose Transplantation (Tx) of young children with ABO incompatible (ABOi) hearts has evolved from an experimental approach to a routine procedure in many centers. Prior studies have shown equal survival after ABOi and ABO compatible (ABOc)-Tx, but also revealed altered B-cell response and less HLA sensitization following ABOi-Tx with yet unknown clinical impact. Using a large registry cohort, we investigated outcomes of ABOi recipients in comparison to all and directly matched ABOc recipients. Methods Data from the Pediatric Heart Transplant Society was analyzed comparing children < 2 years of age undergoing ABOi or ABOc-Tx as identified by donor and recipient blood groups between 1999 and 2017. Given significantly different demographics, each ABOi recipient was directly matched to 2 ABOc recipients by age ± 1 month, diagnosis, and use of mechanical circulatory support. Results ABOi-Tx was performed in 337 (16%) of children < 2 years. These recipients were younger, had lower BSA, were transplanted more recently, and had a higher proportion of mechanical circulatory support than ABOc recipients. After matching, only expected differences in blood group persisted with more O in the ABOi and AB in the ABOc group. Post-Tx graft survival, coronary allograft graft vasculopathy (CAV), and malignancy were similar between groups. ABOi recipients had significantly longer time to first rejection (p=0.03), hemodynamically compromising rejection (p=0.01) and first severe infection (p=0.005). These outcome differences remained when comparing ABOi-Tx to all 1801 ABOc-Tx <2 years despite lower acuity profile of the latter. Conclusion In this large cohort of young children receiving ABOi-Tx in a clinical routine setting rates of graft survival, CAV and malignancy were equivalent to matched ABOc recipients. ABOi-Tx was associated with longer time to rejection, suggesting better graft acceptance associated with acquired blood group tolerance. ABOi-Tx was also associated with longer time to severe infection, potentially secondary to less rejection treatment. The benefits of ABOi-Tx seen in the matched cohort analysis persisted when analyzed against all ABOc-Tx children. Transplantation (Tx) of young children with ABO incompatible (ABOi) hearts has evolved from an experimental approach to a routine procedure in many centers. Prior studies have shown equal survival after ABOi and ABO compatible (ABOc)-Tx, but also revealed altered B-cell response and less HLA sensitization following ABOi-Tx with yet unknown clinical impact. Using a large registry cohort, we investigated outcomes of ABOi recipients in comparison to all and directly matched ABOc recipients. Data from the Pediatric Heart Transplant Society was analyzed comparing children < 2 years of age undergoing ABOi or ABOc-Tx as identified by donor and recipient blood groups between 1999 and 2017. Given significantly different demographics, each ABOi recipient was directly matched to 2 ABOc recipients by age ± 1 month, diagnosis, and use of mechanical circulatory support. ABOi-Tx was performed in 337 (16%) of children < 2 years. These recipients were younger, had lower BSA, were transplanted more recently, and had a higher proportion of mechanical circulatory support than ABOc recipients. After matching, only expected differences in blood group persisted with more O in the ABOi and AB in the ABOc group. Post-Tx graft survival, coronary allograft graft vasculopathy (CAV), and malignancy were similar between groups. ABOi recipients had significantly longer time to first rejection (p=0.03), hemodynamically compromising rejection (p=0.01) and first severe infection (p=0.005). These outcome differences remained when comparing ABOi-Tx to all 1801 ABOc-Tx <2 years despite lower acuity profile of the latter. In this large cohort of young children receiving ABOi-Tx in a clinical routine setting rates of graft survival, CAV and malignancy were equivalent to matched ABOc recipients. ABOi-Tx was associated with longer time to rejection, suggesting better graft acceptance associated with acquired blood group tolerance. ABOi-Tx was also associated with longer time to severe infection, potentially secondary to less rejection treatment. The benefits of ABOi-Tx seen in the matched cohort analysis persisted when analyzed against all ABOc-Tx children.

Effectiveness of Peritoneal Dialysis in Management of Acute Hyperthermia after On-Pump Heart Surgery in Infants

Introduction: Acute hyperthermia is a common complication in the first 24 hours after open heart surgery with the incidence of 12% to 73%. The aim of this study was to evaluate the efficiency of postoperative peritoneal dialysis for controlling acute hyperthermia in pediatrics undergoing on-pump heart surgery. Methods: We reviewed clinical outcomes of 40 infants who underwent congenital surgery from August 2016 to August 2017. Patients were divided into two groups in terms of peritoneal dialysis requirement as group A and B. Demographic data, intraoperative and postoperative variables were compared between the patients. Results: Among the 40 high risk infants who underwent cardiac surgery, 20 patients were treated with peritoneal dialysis (group A). Mean rectal temperature and incidence of acute hyperthermia in 24h after surgery were higher in group A compared to group B (p ˂ 0.05). Infants in group A were younger, lighter and showed lower BSA compare to group B (p Conclusion: Peritoneal dialysis performance was effective in treatment of induced hyperthermia in the first 24 h after operation. Indeed, younger age and lighter weight children are more prone to postoperative complication related to cardiopulmonary bypass surgery.