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هدفت الدراسة إلى تحليل التناقص في مساحة الأراضي الزراعية بالوحدات الإدارية في موقع الشيخ سعد ومحيطه مكانياً خلال الفترة (2013-2023)، حيث تم اختيار مجموعة من الوحدات الإدارية القريبة والبعيدة نسبياً عن مركز المدينة (القريبة من الطريق العام والبعيدة عنه) ، كما تم ربط تناقص مساحة الأراضي الزراعية بالتوسع العمراني وبالزيادة السكانية لتحديد العوامل التي ساهمت بشكل أكبر في تناقص مساحة الأراضي الزراعية في منطقة الدراسة. اعتمدت الدراسة على استخدام أهم المؤشرات الحديثة لتحديد معدل التناقص في مساحة الأراضي الزراعية ومن هذه المؤشرات مؤشر اختلاف الغطاء النباتي NDVI. ومؤشرتمييز المناطق العمرانية NDBI لتحديد الأراضي العمرانية بالاعتماد على مرئيتين للقمر الصناعي لاندسات (Landsat8) الملتقطة في التاريخين 2013، 2023. توصلت الدراسة إلى مجموعة من النتائج أهمها: تراجع مساحة الأراضي الزراعية على مستوى منطقة الدراسة من 3855.8 هكتار عام 2013 إلى 3727.4 هكتار عام 2023، وأظهرت وجود علاقة عكسية قوية بين النمو العمراني ومساحة الأراضي الزراعية وعلاقة عكسية متوسطة بين النمو السكاني ومساحة الأراضي الزراعية. وأوصت الدراسة بضرورة المحافظة على الأراضي الزراعية ومنع الزحف العمراني نحوها وحددت مناطق مؤهلة للنمو العمراني السريع وأكدت على ضرورة مراقبتها والحفاظ على الأراضي الزراعية فيها.

Objective To explore the coping strategies of caregivers of children who have survived paediatric cancer in Jordan.Materials and methods This study used a cross-sectional survey design and convenient sampling. The sample included 102 caregivers of children who have survived cancer, and outcome measures included the Arabic-translated Brief COPE, and caregiver and child demographic and condition questionnaire. Data analyses included descriptive statistics, analysis of frequencies, Spearman-rank order correlations and linear regression.Results Caregivers most frequently used religion coping (mean=6.42, SD=1.85), followed by acceptance (mean=5.95, SD=1.96) and planning (mean=5.05, SD=1.94). The least used coping strategies were humour (mean=2.98, SD=1.24) and behavioural disengagement as coping strategies (mean=3.01, SD=1.42). Having a female child predicted more self-distraction utilisation (β=0.265, p=0.007).Conclusion Caregivers of children who have survived cancer in Jordan frequently use passive coping strategies like religion and acceptance coping to overcome daily life stressors. Caregivers might benefit from psychosocial occupational therapy interventions to support their engagement in more active or problem-focused coping strategies.

Chemical additives to perovskite precursors constitute a predominant route to passivate defects in perovskite films and improve carrier charge dynamics. In this work, ionic liquids (ILs) with chloride and iodide anions are used as additives for bulk passivation of perovskite films. The ionic liquids in the form of 1‑butyl‑4-methylpyradinium iodide (IL-I) and 1-ethylimidazolium chloride (IL-Cl) are mixed individually with a precursor of Cesium Formamidinium Lead Triiodide and Methylammonium Chloride (CsFAPbI3−MACl). The decay of charge carriers within the perovskite film before and after passivation with ILs was measured by Time Resolved Photoluminescence Spectroscopy (TRPL). The effect of added ILs on the recombination rate of the photocarriers was investigated by analyzing the decay of the TRPL signal in all samples. The average lifetimes obtained within one day of preparations were 79 ns, 73 ns and 275 ns for pristine perovskite, IL-I passivated perovskite and IL-Cl passivated perovskite films, respectively. These values show that the presence of the IL with chloride anion greatly improves the average lifetime of the charge carrier by around 250%, while IL with iodide anion decreased the lifetime by 32% as compared with the pristine perovskite sample. This finding renders the IL-Cl passivated perovskite films as a valuable resource in applications ranging from photoelectric to hydrogen generation devices.

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Pediatric Differentiated Thyroid Cancer (pedDTC) is a rare pediatric malignancy with an increasing incidence over time. To date, there is a paucity of literature specifically addressing pedDTC within the context of Middle Eastern ethnicity. This retrospective study aimed to assess the risk-stratifying factors for overall survival (OS) and event-free survival (EFS) in pediatric DTC patients from Iraq and Jordan. The medical records of 81 patients from two tertiary cancer institutes were retrieved. Kaplan–Meier analysis was employed to investigate OS and EFS, and the Cox proportional hazards model was employed to estimate hazard ratios. All patients underwent surgery and radioactive iodine therapy, with a median age of 14 and an interquartile range of 12–15. Lymph node involvement was observed in 55% of cases, while distant metastases were present in 13.5%. After a median follow-up period of 68 months, the 10-year survival rate was determined to be 94%, while the 10-year EFS rate was 58%. EFS was negatively impacted by cervical lymph node metastases and early age of diagnosis (p ≤ 0.01, each). Therefore, pediatrics with initial cervical lymph node metastases and those diagnosed before puberty tend to experience poorer EFS, which may justify the need for more aggressive management plans.

In this work, the corrosion resistance of mild steel surface nanostructured with a femtosecond laser and coated with high corrosion resistant CrCoNi (CCN) medium entropy alloy through magnetron sputtering is studied. Substantial improvement in corrosion protection was achieved by applying a combination of high-power femtosecond laser surface nano-structuring at ambient conditions and thin-film coating with (CCN) medium entropy alloy. XRD analysis revealed that femtosecond laser structuring increases the susceptibility of the surfaces to Fe2O3 nucleation through oxidation. The surface wettability measurements and electrochemical polarization tests revealed that the combined approach of femtosecond laser structuring and magnetron sputter coating is the best for desired high corrosion resistance. Through this novel method, the resulting corrosion resistance of mild steel was improved by more than one-fold. The results are explained considering the detailed microstructural analysis. The presented findings open new possibilities for corrosion prevention using a combination of new powerful technologies that yield to unprecedented corrosion-inhibition efficacy.

Herein, we utilized several deep eutectic solvents (DES) that were based on hydrogen donors and hydrogen acceptors for their antibacterial application. These DES were tested for their bactericidal activities against Gram-positive (Streptococcus pyogenes, Bacillus cereus, Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli K1, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens) bacteria. Using lactate dehydrogenase assays, DES were evaluated for their cytopathic effects towards human cells. Results from antibacterial tests revealed that DES prepared from the combination of methyl-trioctylammonium chloride and glycerol (DES-4) and DES prepared form methyl-trioctylammonium chloride and fructose (DES-11) at a 2 µL dose showed broad-spectrum antibacterial behavior and had the highest bactericidal activity. Moreover, DES-4 showed 40% and 68% antibacterial activity against P. aeruginosa and E. coli K1, respectively. Similarly, DES-11 eliminated 65% and 61% E. coli K1 and P. aeruginosa, respectively. Among Gram-positive bacteria, DES-4 showed important antibacterial activity, inhibiting 75% of B. cereus and 51% of S. pneumoniae. Likewise, DES-11 depicted 70% B. cereus and 50% S. pneumoniae bactericidal effects. Finally, the DES showed limited cytotoxic properties against human cell lines with the exception of the DES prepared from Methyltrioctylammonium chloride and Citric acid (DES-10), which had 88% cytotoxic effects. These findings suggest that DES depict potent antibacterial efficacies and cause minimal damage to human cells. It can be concluded that the selected DES in this study could be utilized as valuable and novel antibacterial drugs against bacterial infections. In future work, the mechanisms for bactericides and the cytotoxicity effects of these DES will be investigated.

Although significant cardiac reverse remodeling is a prerequisite for a left ventricular (LV) assist device (LVAD) patient to be considered for device weaning, multiple factors including patient goals, physician comfort, and center experience, weigh in on this complex decision. Existing predictive models defining recovery as device withdrawal, entail the above-mentioned confounders, and may under detect patients that could benefit from a targeted bridge to recovery strategy. We sought to derive and validate a predictive tool to identify patients prone to reverse remodel, independent of the complex decision to remove a durable, surgically deployed device. Heart failure patients (N=782) requiring LVAD were enrolled at one (n=537) and five US programs (n=245). Baseline characteristics were recorded. The primary outcome was responder incidence, defined as follow-up LV ejection fraction ≥40% and LV end-diastolic diameter ≤6 cm within one year on LVAD support. Bootstrap imputation and lasso variable selection techniques were used to derive a predictive model which was then validated using our multicenter dataset. A predictive calculator was developed, and patients were classified into groups with varying potential for reverse remodeling. Patients were predominantly white (84%), male (82%), aged 56±1 years. Overall, 14.8% patients were identified as responders. Nine preoperative variables associated with reverse remodeling were included in the multivariate model achieving an optimism corrected C-statistic of 0.77 (95% CI: 0.71-0.82) (Figure). The UCAR calculator is a machine learning-based multicenter and validated risk tool, implementing routine clinical data, that effectively stratifies patients into groups with varying potential for reverse remodeling. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols that can promote reverse remodeling and myocardial recovery. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (DM) and poor glycemic control portend a higher risk for cardiovascular morbidity and mortality. We sought to assess their impact on left ventricular assist device (LVAD)-mediated cardiac recovery in chronic advanced heart failure (HF). Consecutive patients (N=477) receiving a durable continuous-flow LVAD were prospectively evaluated. After excluding patients with acute HF etiologies or inadequate follow-up after LVAD (<3 months), 396 patients were stratified based on pre-LVAD DM status into non-diabetics (n=121; no history of DM and HbA1c <5.7) and diabetics/prediabetics (n=275; history of DM or HbA1c ≥5.7). Diabetics/prediabetics were further divided into 3 groups: prediabetics, n=106; well-controlled DM (HbA1c <7%), n=90; or not well-controlled DM, n=79. The absolute left ventricular ejection fraction (LVEF) change (ΔLVEF = LVEF post-LVAD - LVEF pre-LVAD) within one year on LVAD support was compared between groups with linear regression. DM is frequently associated with ischemic cardiomyopathy (ICM), so patients were stratified a priori into ICM and non-ICM (NICM). Compared to non-diabetics, diabetics/prediabetics were older, more likely male, with a higher BMI, and more commonly had an ICM, remote history of hypertension, and a longer HF symptoms duration. The Figure depicts the ΔLVEF between the study groups stratified into ICM or NICM. After adjusting for age, sex, BMI, HF symptoms duration, and history of hypertension, patients with well-controlled DM responded more favorably compared to patients with poor glycemic control. Overall, NICM patients responded more favorably than ICM patients. DM appears to negatively affect functional cardiac improvement on LVAD support and effective glycemic control seems to be beneficial in enhancing the favorable myocardial functional response. Further research is warranted to investigate the underlying mechanisms driving the differential responses. [ABSTRACT FROM AUTHOR]

We propose the use of novel adsorbents, namely, micelle?clay complexes, made up of cetyl-pyridinium chloride (CPC) and clay for the eradication of keratitis-causing Acanthamoeba. The possibility of adding CPC, approved by the FDA for human use, in a contact lens disinfectant to formulate effective disinfectants is discussed further.

Diabetes mellitus (DM) is prevalent among advanced heart failure (HF) patients, however its effect on the potential of left ventricular assist device (LVAD)-mediated cardiac recovery has not been described. Consecutive advanced chronic HF patients (N=425) requiring durable continuous-flow LVAD were prospectively evaluated. After excluding patients with acute HF etiologies or post-LVAD follow up <3 months, 336 patients were included. Patients with history of DM and/or pre-LVAD HbA1c ≥6.5 comprised the DM group (n=142), while those with no history of DM and a pre-LVAD HbA1c <6.5 comprised the non-DM group (n=194). Diabetics with a pre-LVAD HbA1c <7 were considered well-controlled (n=72) and those with a pre-LVAD HbA1c ≥7 not well-controlled (n=70). Relative changes between pre- and post-LVAD LVEF and LVEDD, were calculated. Cardiac recovery was defined as post-LVAD LVEF ≥40% and LVEDD <6.0cm. Baseline characteristics of the 2 groups are shown in the Table. Cardiac functional and structural improvement, as evidenced by relative LVEF and LVEDD changes, was more prominent in non-DM compared to DM patients, and in well- compared to not well-controlled DM patients (Figure). Overall, DM patients were less likely to experience cardiac recovery (8.4% vs 17.5%; p=0.032), while on LVAD support. This remained significant in a multivariate logistic regression after controlling for potential confounders. The presence of DM, and notably not well-controlled DM, appears to negatively affect the potential for LVAD-induced myocardial recovery. Further research is needed to investigate the dynamic cardiac metabolism in HF with DM. [ABSTRACT FROM AUTHOR]

Meaning is so intangible that one group of linguists, the structuralists, preferred not to deal with it or rely on it at all . It is a variable and not to be taken for granted. Nevertheless, many theories have been interested in the study of meaning. Because of the limited scope of this paper, the discussion will cover some of the well-known theories of meaning formulated in the last century. Mainly referential theory of meaning, non-referential theory of meaning and generative grammarian theory of meaning are discussed. Some assumptions, merits and limitations for each theory are also described. The researcher hopes that many people can benefit from this article since meaning is a complex concept and difficult to understand. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. The development of novel diagnostic methods is needed to detect tumours at an early stage when patients are eligible for curative treatments. The purpose of this proof-of-concept study was to determine if micro-Raman spectroscopy applied to the sera of cirrhotic patients may be an alternative method for rapidly discriminating patients with and without HCC. Serum samples were collected from 2 groups of patients: cirrhotic patients with HCC (n = 37) and without HCC (n = 34). Two different approaches were used, dried serum drops and freeze-dried serum, and micro-Raman spectra were acquired in the point-mode with a 785 nm laser excitation in the spectral range of 600–1800 cm−1. Spectra were quality-tested and pre-processed (smoothing, baseline subtraction, vector normalization). Using principal component analysis, the 2 classes, corresponding to cirrhotic patients with and without HCC, could not be differentiated. In contrast, the support vector machine method using the leave-one-out cross validation procedure was able to correctly classify the two groups of patients with an overall rate of accuracy of 84.5% to 90.2% for dried serum drops and 86% to 91.5% for freeze-dried serum. These results are promising and support the concept that serum micro-Raman spectroscopy may become a useful diagnostic tool to detect biomarkers in the field of cancer, as described here for distinguishing between cirrhotic patients with and without HCC. [ABSTRACT FROM AUTHOR]

Although significant reverse cardiac remodeling is required for an LVAD-supported patient to be considered for device weaning, multiple factors including patient willingness, physician expertise, and center experience influence this complex decision. Existing predictive models defining cardiac recovery as device removal might underestimate reverse remodeling rates and lack accuracy in identifying patients prone to improve cardiac structure and function. We sought to develop a predictive tool to identify patients with such potential, independent of the decision to deactivate a durable, surgically deployed device. Chronic HF patients (N=703) requiring continuous-flow LVADs were evaluated. After excluding patients with acute HF and/or <3 months post-LVAD follow up, 3 US programs contributed 390 patients (derivation cohort), while 5 US programs formed the validation cohort (n=245). We defined responders as patients with an LVEF ≥40% and LVEDD ≤6.0 cm within a year on LVAD support. Multivariable logistic regression on the derivation set yielded a predictive model, which was externally tested; a predictive score was developed. Overall, 18.5% of the patients were responders. Compared to the validation, patients in the derivation cohort were more likely white (83 vs 69%; p<0.001), with ischemic HF (42 vs 33%; p=0.04), and longer HF duration (88 vs 66 months; p<0.001). Multivariable predictors of responders and the derived scoring system are shown in the Figure (c-statistic 0.74 [95% CI: 0.66-0.83] and 0.71 [95% CI: 0.59-0.77] in the derivation and validation set). We propose a novel score to predict significant cardiac improvement on LVAD support achieving good discriminative performance in distinct, heterogeneous, contemporary cohorts. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols to promote reverse remodeling and myocardial recovery. [ABSTRACT FROM AUTHOR]

Predicting cardiac structural and functional improvement in advanced heart failure (HF) patients before durable left ventricular assist device (LVAD) implantation remains challenging. Identifying clinical predictors could improve patient selection and impact clinical management. Advanced chronic HF patients (N=652) supported with continuous-flow LVADs were evaluated. After excluding patients with acute HF etiologies or without adequate post-LVAD follow up (<3 months), they were divided into an internal Derivation cohort (n=339, UTAH program) and an external Validation cohort (n=227, 4 US programs). Patients with post-LVAD LVEF ≥40% and LVIDd ≤6.0cm within the 1st year post-implant, were defined as Responders (R). Multivariate Cox regression was used to predict R, in the Derivation cohort, and the fit of the model was tested in the Validation cohort. In total, 10% of the LVAD patients were R. Univariate analysis showed that R were younger, had shorter HF symptoms duration, less need for diuretics and their LV were less dilated pre-LVAD. Further, R had higher acuity disease as evidenced by the higher vasoactive agents need, higher BNP and higher incidence of abnormal liver enzymes. The multivariate Cox regression (AUC=0.74; p<0.001) predicted R using 3 clinical parameters: LVIDd<6.9 cm, age<50 years, and HF duration<36 months (Table). The model's predictive accuracy was validated in the external Validation cohort (AUC=0.78; p<0.001). Younger patients with less LV dilation and shorter duration of HF are more likely to improve their cardiac function during LVAD support. Whether these characteristics also predict sustainability of improved cardiac function after LVAD weaning warrants further investigation. [ABSTRACT FROM AUTHOR]

LVAD therapy has been primarily studied in patients with elevated pulmonary capillary wedge pressure (PCW) and low cardiac index (CI), "cold and wet". In daily practice, LVADs are often also offered to patients with low PCW and low CI, "cold and dry". The efficacy of LVAD therapy in this population is not well studied. Patients implanted with LVAD with a baseline CI <2.0 Lpm were categorized as "wet" (PCW>18mmHg) or "dry" (PCW<18mmHg). These values were derived from serial pre-LVAD right heart catheterization studies in order to reflect a sustainable hemodynamic profile. Variables of interest and 3-year survival were compared between groups. Independent predictors of mortality were identified using multivariate Cox regression analysis. Serial invasive hemodynamics data was available for 92 pts (cold-dry group, n=34 and cold-wet group, n=58) (Table). Diuretic and vasodilator use pre-LVAD was comparable in both groups. Cold-dry patients had no change in CVP or PCW with a smaller increase in CI after LVAD. Adjusted 3-year mortality was higher for cold-dry patients (Figure). Age (HR=1.09, 95%CI 1.02-1.2; p=006) and cold-dry profile (HR=5.4, 95%CI 1.4-21; p=0.016) were identified as independent predictors of mortality. "Cold and dry" patients with advanced heart failure may not derive equal benefit from LVAD therapy as those who are "cold and wet". This observation warrants further investigation. [ABSTRACT FROM AUTHOR]

Despite several models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support, poor performance when externally validated has limited their widespread use. We sought to derive a predictive model for RVF after LVAD implantation, and ascertain its performance in an independent cohort. End-stage heart failure (HF) patients requiring continuous-flow LVAD were prospectively enrolled at one US program (n=477, derivation cohort), with two other US medical centers forming the validation cohort (n=321). The primary outcome was RVF incidence, defined as the need for right ventricular assist device or inotropes for >14 days. Multivariable logistic regression in the derivation set yielded a RVF predictive model, which was subsequently applied to the validation cohort, and a risk score was ultimately developed. Derivation cohort included patients less likely to be African-Americans (7% vs 37%; p<0.001), Hispanics (7% vs 30%; p<0.001), have a remote history of hypertension (49% vs 60%; p=0.002) or be bridged with short-term MCS (8% vs 16%; p=0.001), compared to the validation set. RVF incidence was 16% in the derivation and 36% in the validation cohort (p<0.001). Multivariable analysis identified 7 variables (Figure) as predictive of RVF, with the model achieving a C statistic of 0.734 (95% CI=0.674-0.794) in the derivation and 0.709 (95% CI=0.651-0.767) in the heterogeneous validation cohort. Patients were stratified into 3 RVF risk groups (all comparisons; p<0.001) (Figure). We propose a novel scoring system to predict post-LVAD RVF, achieving high discriminative performance in distinct, heterogeneous LVAD cohorts. [ABSTRACT FROM AUTHOR]

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is a serious complication with poor prognosis. Improved selection of patients with greater risk of developing the condition is crucial, considering the growing need for destination therapy patients. However, predicting RVF remains a vexing clinical problem. From 2008 to 2019, 478 consecutive chronic heart failure (HF) patients supported with continuous-flow LVADs were prospectively evaluated. RVF was defined by the need for intravenous inotropes for >14 days and/or right ventricular assist device implantation. Data was analyzed based on the presence or absence of RVF in the early post-operative period and their baseline clinical, hemodynamic, imaging and laboratory data were compared. Multivariable logistic regression was used to develop a clinical model for RVF prediction. Overall, 77 (16.1%) patients developed RVF. Univariate analysis showed that the RVF was associated with higher acuity disease before LVAD implantation reflected by low INTERMACS profile, high vasoactive medication requirement, presence of IABP support, hyponatremia, thrombocytopenia, low serum albumin, and renal dysfunction. Additionally, RVF was associated with increased heart rate, right atrial (RA) and right atrial to wedge pressure (RA/PCWP) ratio, along with decreased systolic pulmonary artery pressure (PAP), right ventricular stroke work index (RVSWi) and pulmonary artery pulsatility index (PAPi), at baseline. Interestingly, patients who developed RVF had decreased left ventricular end-diastolic diameter at baseline, when compared to the no RVF group. The multivariate model (AUC=0.77; p<0.0001) predicted RVF using 7 clinical parameters: 1) Remote history of systemic hypertension, 2) Preoperative need for IABP, 3) Systolic PAP <60 mmHg, 4) RA/PCWP ≥0.66, 5) PAPi <1.44, 6) Na <135 mEq/L, & 7) PLT <100 × 103/microL Our model seems capable of distinguishing patients prone to develop RVF post-LVAD implantation. The identified pre-LVAD predictors include markers of globally advanced HF syndrome and higher acuity as well as markers specific to severity of RVF. [ABSTRACT FROM AUTHOR]

Purpose A subset of end-stage heart failure (HF) patients on left ventricular assist device (LVAD) can significantly improve their native heart structure and function. Long-term stability of this cardiac improvement (CI) after LVAD weaning has not been well investigated. Methods We included chronic advanced non-ischemic cardiomyopathy patients (acute HF excluded) who were weaned from LVAD support based on predefined myocardial structural, functional and hemodynamic criteria. We defined "sustainable CI" after LVAD weaning as LVEF≥ 40% & LVEDD< 57mm. Regression analysis evaluated trends. Results Our cohort included 6 males and 6 females, mean age 33±12. Patients achieved LVAD weaning criteria after 532 [196, 2304] days of support. LVEF improved from 18±6 pre-implant to 46±10 % at LVAD explant (p<0.0001), LVEDD decreased from 65±7 to 46±6 mm (p<0.0001) and BNP decreased from 1438±1585 to 90±77 pg/ml (p<0.02). During a follow up post LVAD removal of 844 [15, 1241] days, we identified 2 groups, patients with sustainable (n=7) and with declining (n=5) CI (Figure). At the latest follow-up, the stable and declining groups differed with respect to LVEF (52 vs 17 %; p<0.0001), LVEDD (52 vs 65 mm; p=0.003) and BNP (58 vs 677 pg/ml; p=0.04). Quality of life assessment matched well with improvements in LV remodeling (Figure). The degree of CI pre-LVAD removal did not differ between the 2 groups and hence was not identified as a predictor of post weaning stability of CI. After LVAD weaning, 4/5 patients in the declining group had chronic systemic infection, drug abuse and HF medications therapy non-adherence, which likely affected negatively the stability of CI. A patient from this group was deceased due to HF recurrence. Conclusion In this single center report the long-term stability of CI after LVAD weaning appears to be encouraging. Larger and longer follow up clinical and translational studies are warranted to provide further clinical and mechanistic insights regarding factors associated with sustainable CI. [ABSTRACT FROM AUTHOR]

Purpose The identification of clinical and molecular predictors of Left Ventricular Assist Device (LVAD) induced myocardial recovery before device implantation could significantly impact the management of patients with advanced heart failure (HF). Inflammation plays a central role in the pathophysiology of HF. We sought to investigate whether cardiac or systemic inflammation could be associated with the myocardial structural and functional response after LVAD support. Methods We prospectively enrolled 152 patients with chronic HF supported with durable LVAD as bridge to transplant or as destination therapy (acute HF patients were excluded). Serum and cardiac tissue was collected at the time of LVAD implantation for measurement of fourteen inflammatory markers (cytokines and transcription factors). Cardiac recovery was prospectively assessed via serial turn down echocardiography studies. Results Thirteen percent of the study population showed significant improvement of the cardiac function (i.e. "responders") after LVAD unloading (final LVEF>40%). At LVAD implant, serum TNFα, IL6 and IL10 was lower in responders compared to non-responders (p<0.05 for all comparisons). STAT3, a transcription factor activated by cytokines that regulates inflammatory response was less activated in the cardiac tissue of responders compared to non-responders (0.87±0.2 vs 2.4±0.7 AU, p=0.037). To further investigate the lower inflammatory burden noted in the cardiac tissue and serum of responders, we performed multivariate dichotomous regression analysis of the serum cytokines and we identified that low levels of INFg (OR 0.06, CI 0.01-0.35) and TNFα (OR 0.05, CI 0.00-0.43) were independent predictors of cardiac recovery. A multivariable model combining IFNg and TNFα was identified as a significant predictor of LVAD-induced recovery (AUC 0.93, p<0.001). Conclusion Reduced cardiac and systemic inflammatory burden correlates with the recovery of the failing human heart after LVAD unloading. We identified a two-cytokine model with high sensitivity and specificity for pre-LVAD prediction of cardiac recovery that could serve as a decision tool in the clinical management of advanced HF patients. Further investigations to elucidate the underlying molecular mechanisms are warranted. [ABSTRACT FROM AUTHOR]

Purpose Occasionally new onset cardiomyopathy patients (pts) present late, in such advanced disease stage that they cannot tolerate heart failure (HF) drug therapy. We investigated the cardiac recovery (CR) potential following a combination of left ventricular assist device (LVAD) and guideline-directed HF drug therapy in this medication-naive population. Methods Chronic advanced HF pts requiring durable continuous-flow LVAD were prospectively evaluated. Pts with acute HF (myocarditis etc) or post LVAD follow up <3 months were excluded. The "meds-treated" group (n=203) comprised pts treated adequately with at least one neurohormonal blocking agent during their HF history (b-blocker, ACEI/ARB, Aldosterone antagonist) and "meds-naive" group (n=8) comprised pts who were never before treated adequately with any HF medication. A great variety of baseline and follow up data were analyzed. LVAD pts were phenotyped as CR responders or non responders, based on published predefined criteria. Results Univariate analysis showed that "med-naive" pts were younger, more likely to be on intravenous vasoactive agents, temporary MCS and with lower INTERMACS profile before LVAD implantation. Interestingly, no differences were seen in HF symptoms duration or other comorbidities. Baseline and follow up hemodynamics were similar in both groups, besides higher right atrial pressure pre-LVAD in the "meds-naive" group (16 vs 11 mmHg; p=0.04). Baseline echocardiographic (including LV dilation) and biochemical parameters revealed no differences between the groups, besides lower LVEF and higher BNP in the "meds-naive" group (14 vs 19 %; p=0.03 and 2352 vs 1270; p=0.03, respectively). CR rates were significantly higher on "meds-naive" versus "meds-failed" group (50.0 vs 13.8 %; p=0.005). Despite higher cardiac recovery rates in the "meds-naive" group the time course and magnitude of the favorable functional and structural response was similar among the CR responders of each of the 2 groups. Conclusion Young pts with new onset dilated cardiomyopathy sometimes present late, with advanced disease stage, unable to tolerate HF medications and requiring durable LVAD support. This patient population appears to have a potential for CR up to 50% and this could be factored in decisions surrounding their long-term therapeutic options. [ABSTRACT FROM AUTHOR]

Purpose Predicting cardiac recovery (CR) in advanced heart failure (HF) patients before left ventricular assist device (LVAD) implantation remains challenging. This study sought to investigate whether CR after LVAD unloading can be predicted by cardiac functional and structural parameters together with clinical characteristics. Methods From 2008 to 2016, consecutive advanced chronic HF patients (N=347) supported with durable continuous-flow LVADs were prospectively evaluated. Patients with acute HF etiologies or without adequate post-LVAD follow up (<3 months) were excluded. A great variety of clinical characteristics were evaluated in the remaining 285 subjects. LVAD patients were phenotyped while on support, as CR Responders or Non Responders, based on published predefined echocardiographic criteria. Multivariable logistic regression was used to form the model and the Utah Cardiac Recovery (UCAR) score was created from the regression beta coefficients of the final model. Results CR occurred in 13.7% of patients. Univariate analysis showed that responders were more likely to be young, female, non-ischemic cardiomyopathy, with shorter HF symptoms duration and no prior heart surgery. They had lower blood urea nitrogen and were less likely to be on temporary mechanical support before LVAD. The multivariable UCAR model (AUC=0.755; p<0.001) predicted CR using 3 clinical parameters - Table. Conclusion Univariate and multivariable predictors of CR include both modifiable and non-modifiable patient characteristics that are known prior to LVAD implantation. The UCAR score can serve as a practical tool for targeted patient selection to implement protocols that facilitate CR in the advanced HF patient subpopulation that is most likely to respond. [ABSTRACT FROM AUTHOR]

There is limited information on regional variation in rates of cardiac recovery and left ventricular assist device (LVAD) explantation at a global level. We aimed to compare the rates of cardiac recovery and LVAD explantation across several world regions. LVAD recipients registered in the International Registry for Mechanically Assisted Circulatory Support (IMACS) were analyzed. Cardiac recovery was defined as follow-up LVEF >40% and a pre-LVAD LVEF <30%. Cardiac recovery and LVAD explantation/deactivation due to recovery were evaluated in bridge-to-recovery (BTR) and non-BTR designation patients in the Americas, Asia-Pacific and Europe. A total of 16,029 patients met our inclusion criteria and were included in the analysis. Of these, 9,381 patients had at least one follow-up echocardiogram and a minimum of 3 months of LVAD support. Cardiac recovery was achieved in 13.3% (n=1,249) of patients, with a rate of 55.3% (n=21) in BTR compared with 13.1% (n=1,228) in non-BTR patients. Rates of cardiac recovery varied significantly by region: 12.7% (n=1,079) in the Americas, 15.9% (n=94) in Asia-Pacific and 29.5% (n=76) in Europe (p<0.001) (Figure 1A). Rates of LVAD explantation/deactivation were similar between the Americas (5.7%) and Asia-Pacific (4.6%) and lower in Europe (2.0%) (p<0.001) (Figure 1B). Global rates of both cardiac recovery and LVAD explantation are higher in patients implanted with a priori BTR strategy. Rates of cardiac recovery appear to be higher in Europe for reasons that warrant further investigation. The global rates of LVAD explantation are much lower compared to the corresponding cardiac recovery rates. This observation invites future investigations to identify the challenges in regards to LVAD weaning when recovery is identified, which could result in higher rates of LVAD explantation. [ABSTRACT FROM AUTHOR]

The variability of left ventricular structural and functional improvement following continuous flow left ventricular assist device (LVAD) implantation is poorly understood. The study consecutively enrolled 358 patients with confirmed chronic heart failure who required a durable LVAD across four study sites. Echocardiograms were performed preceding LVAD implantation and serially up to a year after. Patients were categorized by the degree of structural (left ventricular internal diastolic diameter, LVIDd) and functional (left ventricular ejection fraction, LVEF) change after LVAD. In the cohort, 34 patients (10%) experienced improvement of the LVEF ≥40% and LVIDd ≤6.0cm and were termed responders. The rest of the patients were distinguished in 3 groups based on the absolute change (Δ) in LVEF during follow up: Partial Responders had Δ-LVEF ≥10% (n=57, 16%), Borderline Responders Δ-LVEF 5-10% (n=55, 15%), Non-Responders Δ-LVEF <5% (n=212, 59%, Figure). The LVEF absolute change following mechanical unloading was: -3.2±5.9%, 6.3±1.4%, 15.5±5.4%, 27.7±9.7% in Non-Responders, Borderline Responders, Partial Responders and Responders, respectively (p<0.001). Structural changes in terms of LV dimensions followed a different pattern with significant improvements even in patients that had minimal systolic functional improvement. Multivariate logistic regression identified the following clinical characteristics as predictive of favorable reverse myocardial remodeling: smaller pre-LVAD implantation LVIDd, use of an axial flow device, and shorter heart failure duration preceding LVAD implant. Reverse left ventricular remodeling associated with durable LVAD support is not an all or none phenomenon and manifests in a continuous spectrum. Defining four stages across this continuum can inform clinical management and facilitate advancing the field of myocardial plasticity by informing the design of future investigations. [ABSTRACT FROM AUTHOR]

Following left ventricular assist device (LVAD) mechanical unloading significant improvements in myocardial structure and function have been reported in some advanced heart failure (HF) patients, termed as Responders (R). Our prior work demonstrated a post-LVAD mismatch of glycolysis and oxidative phosphorylation characterized by upregulation of glycolysis without subsequent increase in pyruvate oxidation via the Krebs cycle. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose phosphate pathway (PPP) and one-carbon metabolism (OCM), which may mediate myocardial structural and functional improvement in Responders. We prospectively obtained myocardial tissue from Non-Failing Donor hearts (n=15) and from Responders (n=11) and Non-Responders (n=30) at LVAD implant (Pre-LVAD) and later at transplantation (Post-LVAD). Responders and Non-Responders were defined based on prior published criteria. We conducted protein expression and metabolite profiling and evaluated mitochondrial structure using electron microscopy. Western blot analysis of key PPP and OCM rate-limiting enzymes, glucose-6-phosphate dehydrogenase and phosphoglycerate dehydrogenase were significantly increased in Post-LVAD Responders (Post-R). In agreement with these findings the metabolite levels of these enzyme substrates such as sedoheptulose-6-phosphate (PPP) and serine and glycine (OCM) were decreased in Post-R. Furthermore, Post-R had significantly higher NADPH levels, reduced ROS levels, improved mitochondrial dynamics and enhanced glycosylation of the extracellular matrix (ECM) protein, α-dystroglycan, indicating increased flux of glucose into the PPP and OCM pathways and all together these findings correlated with the observed myocardial structural and functional improvement. The recovering human heart appears to direct glycolytic metabolites into the PPP and OCM pathways which could contribute to cardioprotection and improved myocardial function by generating NADPH to enhance biosynthesis for repair and by reducing oxidative stress. [ABSTRACT FROM AUTHOR]

Although left ventricular (LV) reverse remodeling has been described in patients with left ventricular assist devices (LVADs), little is known about left atrial (LA) structural and functional changes. Echocardiographic parameters were obtained at pre-LVAD implant and following 1, 3, and 6 months of LVAD support. Favorable LV structural and functional response following LVAD support (i.e. Responders) was defined using previously published criteria. Structural and functional indices specific to LA such as LA volume index (LAVI) and LA total emptying fraction (LATEF) were compared in eighteen Responders versus twenty Non-Responders. Statistical comparison of quantitative data was performed using 2-tailed Wilcoxon signed-rank test for paired samples and categorical data were compared using Fisher's exact test. The magnitude and time course of functional changes as reflected by the LVEF and LATEF in Responders and Non-Responders are depicted in Figure 1A and 1B. LA remodeling structural changes over time in Responders and Non-Responders are depicted in Figure 1C. Patients experiencing post-LVAD favorable LV functional response had significantly better LA remodeling structural and functional indices before LVAD implantation and further improved those early after the initiation of LV mechanical support. LA reverse remodeling studies with longer follow-up and correlation with post LVAD-weaning patient outcomes are warranted. [ABSTRACT FROM AUTHOR]

Recent studies have shown enhanced survival and reduced morbidity with centrifugal (HeartMate 3-HM3) left ventricular assist device (LVAD) compared with axial-flow (HeartMate II-HMII) LVAD. However, differences in LVAD-induced left ventricular (LV) reverse remodeling between the two devices remain uninvestigated. The aim of our study was to compare the LV structural and functional changes between these two types of mechanical unloading. Echocardiographic parameters of LV structure and function were obtained pre-implant and at 1, 3, 6, and 12 month of LVAD support. Statistical comparison of quantitative data was performed using 2-tailed Wilcoxon signed-rank test for paired samples and categorical data were compared using Fisher's exact test. A total of 32 consecutive patients (median age 62.5 [IQR 52-68] years, 15.6% female) received axial-flow LVAD (HMII) and 31 consecutive patients (median age 58 [IQR 47-71] years, 16.1% female) received centrifugal LVADs (HM3). There were no significant differences in the baseline characteristics between the study groups. Following LVAD support there were no differences in the LV ejection fraction or LV mass index between the two types of mechanical unloading across all time points (figure 1A and 1B). In centrifugal LVAD patients, LV end diastolic volume index was lower at 1 and 3 months and LV end systolic volume index was lower at 1 month. No differences were identified after 3 months of mechanical unloading (figure 1C and 1D). Both centrifugal and axial-flow LVADs resulted in improved LV function and structure. Although LV volumes were found to be lower at 1 and 3 months in centrifugal pump patients, long-term (> 3month) mechanical unloading seem to exert similar effects on LV structural and functional parameters. [ABSTRACT FROM AUTHOR]

Prior reports have suggested that an improved left ventricular (LV) function on LV assist device (LVAD) support might contribute to the development of device thrombosis. We investigated in a large multicenter dataset the association of LV function after LVAD with device thrombosis, cerebrovascular accident or transient ischemic attack (CVA/TIA), and hemolysis. The INTERMACS data were obtained via the NHLBI. We excluded patients with pulsatile-flow LVADs, right VAD only, total artificial heart, congenital heart disease, hypertrophic or restrictive cardiomyopathy, prior LVAD or heart transplantation, and baseline LV ejection fraction (LVEF) ≥40%. Patients were stratified by maximum LVEF after at least six months on LVAD support: <20%, 20-29%, 30-39%, 40-49%, and ≥50%. We assessed device thrombosis, CVA/TIA, and hemolysis rates across LVEF categories. Our study cohort comprised 9,556 patients. Baseline clinical characteristics are presented in the Table. Twelve percent of patients (n=1,136) achieved a post-LVAD LVEF higher than 40%. Patients in the post-LVAD LVEF ≥50%, 40-49%, 30-39% categories had a lower risk of developing device thrombosis compared to patients in the <20% LVEF group (adjusted hazard ratios [aHRs]: 0.75, 0.58, 0.83, respectively; p<0.05), while patients in the 20-29% group had a similar risk (aHR: 0.88; p=0.06). Overall, patients with post-LVAD LVEF ≥40% vs <40% had a lower risk of developing device thrombosis (aHR: 0.72; p<0.001). The risk of developing CVA/TIA was comparable across post-LVAD LVEF categories, while the risk of developing hemolysis was lower in patients comprising the 30-39% and 40-49% post-LVAD LVEF categories when compared to patients in the <20% post-LVAD LVEF group (aHRs: 0.81 and 0.72, respectively; p<0.001). Our findings from a large multicenter patient cohort indicate that an improved LV function on LVAD support is associated with a lower risk of device thrombosis. [ABSTRACT FROM AUTHOR]

Our understanding of how hemodynamics affect liver function in chronic heart failure (HF) is limited. A long-standing notion is that elevated right atrial pressure (RAP) predisposes to elevated liver enzymes and bilirubin, while decreased cardiac index (CI) increases aminotransferases. We sought to examine how liver function tests (LFTs) relate to hemodynamics in patients with advanced HF (AdvHF). Prospectively enrolled AdvHF patients who were evaluated in our program for advanced therapies and received a left ventricular assist device were studied (n=530). Univariate and multivariable logistic regression analyses were used to assess associations between abnormal LFTs (value >ULN) and non-invasive (mean arterial pressure [MAP], heart rate) and invasive (RAP, mean pulmonary artery pressure, wedge pressure, CI and systemic vascular resistance) hemodynamics. Variables identified as significant (P<0.05) in univariate analyses were included in the multivariable models together with use of inotropes and temporary mechanical circulatory support (tMCS). Mean age was 57±13 years, ejection fraction 18±8%, MAP 80±12 mmHg, RAP 11±6 mmHg and CI 1.8±0.5 L/min/m2, with 370 patients (70%) having NYHA class IV symptoms. Ninety-two (17%) patients were supported with tMCS and 374 (71%) were on inotropes. Prevalence of LFT abnormalities was 20% for alanine transaminase (ALT), 30% for aspartate transaminase (AST), 23% for alkaline phosphatase (ALP), 31% for bilirubin and 27% for albumin. Lower MAP was an independent predictor of abnormal ALT (OR: 1.03; 95% CI: 1.00-1.06, P=0.02), ALP (1.03; 1.00-1.06, P=0.008) and bilirubin (1.03; 1.00-1.05, P=0.01), while higher RAP was independently associated with abnormal ALT (1.05; 1.01-1.10, P=0.05) and bilirubin (1.09; 1.05-1.14, P<0.001). No association between LFTs and CI was demonstrated. In AdvHF patients RAP and MAP seem to be the most significant hemodynamic drivers of hepatic derangements. Given that LFT abnormalities negatively affect the prognosis of AdvHF patients, a pre- and post-advanced therapies strategy which prioritizes maintaining normal RAP and adequate MAP warrants further investigation [ABSTRACT FROM AUTHOR]

Purpose Systolic heart failure (HF) is a progressive disease characterized by adverse remodeling from ischemia (ischemic cardiomyopathy, ICM) or a multitude of other causes termed non-ischemic cardiomyopathy (NICM). To accurately characterize the myocardial transcriptome in advanced HF using RNA-sequencing (RNAseq) and identify gene signatures that predict HF phenotypes. Methods RNAseq was performed in myocardial tissue samples obtained at time of left ventricular assist device implant for advanced HF at two sites: the Inova Heart and Vascular Institute (n=39) and University of Utah (n=106). A large number of non-failing (NF) donor hearts (n=35) were also sequenced. Results RNAseq generated ∼26 million reads per sample. The proportion of cardiomyocytes in HF and NF tissues was 81% and 84%. In comparing HF and NF myocardium, there were 105 dysregulated genes (false-discovery rate <5%, log2 fold-change >1 or <-1) that were common to both datasets and highly concordant (r=0.95, p<0.001). There were no messenger or long non-coding RNAs that were differentially regulated between ICM and NICM. Transcriptome analysis identified two HF phenotypes: those with mild (n=102) and severe (n=42) quantitative adverse remodeling, not explained by patient characteristics (Figure). Conclusion Advanced HF transcriptomic analysis confirmed that myocardium in ICM and NICM converges to a final common adverse cardiac remodeling pathway. However, within this homogenously ill advanced HF population, two distinct phenotypes were identified with respect to the degree of aberrant gene expression. This differential myocardial transcriptomic signature may identify a HF phenotype that may benefit from targeted therapy to promote reverse remodeling and myocardial recovery. [ABSTRACT FROM AUTHOR]