Influence of ejection fraction on cause‐specific mortality in heart failure with preserved ejection fraction

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143697/1/ejhf1040.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143697/2/ejhf1040_am.pd

B-Type Natriuretic Peptide and Cardiac Troponin I Are Associated With Adverse Outcomes in Stable Kidney Transplant Recipients

Approximately 200,000 kidney transplant recipients are living in the US; they are at increased risk for cardiovascular and other adverse outcomes. Biomarkers predicting these outcomes are needed. Using specimens collected during the FAVORIT (Folic Acid for Vascular Outcome Reduction In Transplantation) trial, we determined whether plasma levels of B-type natriuretic peptide (BNP) and cardiac troponin I are associated with adverse outcomes in stable kidney transplant recipients

Left Ventricular Systolic Dysfunction in Patients Diagnosed with Hypertrophic Cardiomyopathy during Childhood:Insights from the SHaRe Registry

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children. METHODS:Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction &lt;50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models. RESULTS: We studied 1010 patients diagnosed with HCM during childhood (&lt;18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age &lt;12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction &lt;35% (HR, 3.76 [2.16-6.52]). CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care.</p

Effect of dapagliflozin on cause-specific mortality in patients with heart failure across the spectrum of ejection fraction

Importance: In 2 trials enrolling patients with heart failure (HF) across the spectrum of ejection fraction (EF), dapagliflozin has been shown to reduce the rate of the composite of worsening HF events or death from cardiovascular (CV) causes. Objective: To examine the effects of dapagliflozin on cause-specific CV and non-CV mortality across the spectrum of EF. Design, Setting, and Participants: This was a participant-level, pooled, prespecified secondary analysis of data from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure, or DAPA-HF trial (participant left ventricular EF [LVEF] ≤40%), and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure, or DELIVER trial (participant LVEF &gt;40%), to assess the effects of randomized treatment on cause-specific mortality. The trials assigned adjacent populations of patients with chronic HF, New York Heart Association class II-IV symptoms, and elevated natriuretic peptides to treatment with dapagliflozin (10 mg, once daily) or placebo. The primary outcome for each study was a composite of worsening HF events (hospitalization or urgent heart failure visits) or CV death. Clinical outcomes, including all deaths, were adjudicated as to cause by clinical end points committees blinded to treatment assignment. Intervention: Dapagliflozin vs placebo. Main Outcomes and Measures: The mode of death in relation to baseline EF was examined, as well as the effect of randomized treatment on cause-specific death in Cox regression models. Relationships with continuous EF were modeled using Poisson regression. Results: Of 11 007 patients in the pooled data set, there were 1628 deaths during follow-up (mean [SD] age, 71.7 [10.3] years; 1139 male [70.0%]). Of those who died, 872 (53.5%) were ascribed to CV deaths, 487 (29.9%) to non-CV deaths, and 269 (16.5%) to undetermined causes. Of CV deaths, 289 (33.1%; this represented 17.8% of total deaths) were due to HF, 441 (50.6%; 27.1% of total deaths) were sudden, 69 (7.9%; 4.2% of total deaths) were due to stroke, 47 (5.4%; 2.9% of total deaths) to myocardial infarction, and 26 (3.0%; 1.6% of total deaths) were due to other CV causes. The proportion of non-CV deaths was higher in those with higher EF. In the pooled population, across the spectrum of EF, treatment with dapagliflozin was associated with lower rates of CV death (hazard ratio [HR], 0.86; 95% CI, 0.75-0.98; P = .02), principally due to lower rates of sudden death (HR, 0.84; 95% CI, 0.70-1.01; P = .07) and HF death (HR, 0.88; 95% CI, 0.70-1.11; P = .30), with little difference in rates of death from stroke or MI. Conclusions and Relevance: In a pooled analysis of patients with HF in the DAPA-HF and DELIVER randomized clinical trials, across the full spectrum of LVEF, dapagliflozin significantly reduced risks of CV death with contributions from lower rates of sudden death and death from progressive HF. Trial Registration: ClinicalTrials.gov Identifier: NCT03036124, NCT0361921

Integration of Land Use and Land Cover Models: Coupling Two Existing Models to Improve the Simulation of Location Choice

8th International Congress on Environmental Modelling and Software, Toulouse, France, 10-14 July 2016Single models do not usually provide all answers required for complex policy decisions, so an integrated modelling is often applied to inform policy makers and urban planners. Developing a fully integrated model is an expensive and time consuming task, thus, coupling existing models is often used for model integration. The paper provides an overview of potential model integration approaches, briefly describes the Simple Integrated Land Use Orchestrator (SILO) model and the Chesapeake Bay Land Change Model (CBLCM), and focuses on the integration method applied to link those models. Particularly, Python wrappers were developed to loosely couple SILO and CBLCM; while ArcGIS Model Builder was used to provide a graphical user interface. The suggested approach is especially efficient when the models are developed in different programming languages, their source code is not available or the licensing restrictions make other coupling approaches infeasible.European Commission - Seventh Framework Programme (FP7)GeoSInPoMarie Curie Fellowshi

Calcium channel blockade and survival in recipients of successful renal transplant: an analysis of the FAVORIT trial results

Introduction: Single-center and observational studies have suggested that calcium channel blocking agents may decrease the expression of sepsis in individual populations. In the renal transplant population, a role for calcium channel blockers in allograft protection and in prevention of sepsis has been postulated. We hypothesized that any important survival benefit or risk related to chronic use of calcium channel blocking agents should be discernable through an analysis of a large database of stable recipients of renal allografts who had enrolled in a large international trial. Methods: A retrospective analysis of 4,110 renal transplant recipients who enrolled in the international Folic Acid for Vascular Outcome Reduction in Transplantation trial between 2002 and 2007 and were followed until 2010 was undertaken comparing cohorts (FAVORIT) of patients either taking (n=1,436) or not taking (n=2,674) calcium channel blocking medications. The endpoint was all-cause mortality (cardiovascular, noncardiovascular mortality, or unknown). Results were adjusted for country, age, race, sex, smoker, systolic blood pressure, diabetes mellitus, low-density lipoprotein, and chronic kidney disease status. Results: There were no statistically significant differences in incidence rates of cardiovascular, noncardiovascular, and all-cause mortality between patients taking or not taking calcium channel blocking medications. Conclusion: Although physiologic reasoning and small series results suggest a benefit for calcium channel blocking agents for allograft protection and sepsis prevention in immunosuppressed patients, we find no clear survival benefit in a large international renal transplant trial

Significantly Improving Lossy Compression for HPC Datasets with Second-Order Prediction and Parameter Optimization

Today\u27s extreme-scale high-performance computing (HPC) applications are producing volumes of data too large to save or transfer because of limited storage space and I/O bandwidth. Error-bounded lossy compression has been commonly known as one of the best solutions to the big science data issue, because it can significantly reduce the data volume with strictly controlled data distortion based on user requirements. In this work, we develop an adaptive parameter optimization algorithm integrated with a series of optimization strategies for SZ, a state-of-the-art prediction-based compression model. Our contribution is threefold. (1) We exploit effective strategies by using 2nd-order regression and 2nd-order Lorenzo predictors to improve the prediction accuracy significantly for SZ, thus substantially improving the overall compression quality. (2) We design an efficient approach selecting the best-fit parameter setting, by conducting a comprehensive priori compression quality analysis and exploiting an efficient online controlling mechanism. (3) We evaluate the compression quality and performance on a supercomputer with 4,096 cores, as compared with other state-of-the-art error-bounded lossy compressors. Experiments with multiple real-world HPC simulations datasets show that our solution can improve the compression ratio up to 46% compared with the second-best compressor. Moreover, the parallel I/O performance is improved by up to 40% thanks to the significant reduction of data size

Smoking and outcomes in kidney transplant recipients: a post hoc survival analysis of the FAVORIT trial

Background: Tobacco use remains an international health problem with between 10% and 40% of adults currently using tobacco. Given the rising number of patients either awaiting or having received a kidney transplant and the absence of smoking cessation as the criterion for transplantation in guidelines, we explored the association between smoking status and clinical outcomes in kidney transplant recipients. Patients and methods In this post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplant trial, the associations between smoking status, defined as never having smoked, formerly or currently smoking, and both all-cause mortality and graft survival were assessed using Cox proportional hazards models. Fatal events were centrally adjudicated into prespecified categories: all-cause, cardiovascular and non-cardiovascular causes. Graft loss was defined as return to dialysis or retransplantation. Clinical Trials URL: http://www.clinicaltrials.gov/show/NCT00064753. Results: Among 4110 transplant recipients, there were 451 current smokers and 1611 former smokers. The mortality rate per 100 patient-years was 4.0 (71 deaths) for smokers, 3.5 (226 deaths) for former smokers and 2.4 (116 deaths) for never smokers. Hazard ratio for mortality for current smokers was 1.70 (CI=1.26–2.29, p=0.001) and for former smokers was 1.21 (0.98–1.50, p=0.08) with 1.0 representing never smokers. As the number of cardiovascular deaths was similar in each group (all p>0.3), the differences between groups was driven by non-cardiovascular death rates. Current smokers (2.39; 1.62–3.61, p100% increased risk of non-cardiovascular death, 70% greater risk of all-cause mortality and a 50% greater risk of graft loss, a risk not seen in former smokers. These findings confirm previous non-adjudicated observations that smoking is associated with adverse clinical outcomes and suggest that more emphasis should be placed on smoking cessation prior to kidney transplantation

Does diabetes impact therapeutic immunomodulation therapy decisions for kidney transplant recipients? Data from the Folic Acid for Vascular Outcome Reduction in Transplant (FAVORIT) trial

Although survival has improved for kidney transplant recipients over the past several decades, long-term survival in diabetic cohorts still is significantly less than that of non-diabetic cohorts. We hypothesized that among stable kidney transplant recipients, there might be differences between subgroups with and without diabetes with respect to prevalence of prior cardiovascular events and post-transplant antihypertensive and immunosuppressive therapy. We performed a post hoc analysis of participants in the Folic Acid for Vascular Outcome Reduction in Transplant (FAVORIT) trial, a multicenter international trial of 4110 prevalent kidney transplant recipients enrolled from 2002 to 2007 evaluating the effect of homocysteine-lowering vitamin therapy on cardiovascular outcomes. There were 2447 participants without diabetes, 166 with type 1 diabetes, and 1447 with type 2 diabetes at study entry, which occurred on average 4 years post-transplant. Recipients with diabetes had a greater prevalence of prior cardiovascular events, were more likely to have required multiple medications to control hypertension, and were more likely to have received tacrolimus as opposed to cyclosporine than the non-diabetic transplant recipients (all p<0.001). The effect of differences in treatment of non-diabetic vs diabetic cohorts after stable renal transplantation upon outcomes has not yet been studied and could provide additional information that might lead to improved care

Changes in N-terminal pro-B-type natriuretic peptide levels and outcomes in heart failure with preserved ejection fraction: an analysis of the I-Preserve study

Aims: In patients with heart failure (HF) and reduced ejection fraction, decreases or increases in NT-proBNP levels are associated with better and worse outcomes, respectively. The association in HF and preserved ejection fraction (HF-PEF) is unknown. We examined the association between change in level of NT-proBNP and prognosis in patients with HF-PEF. Methods and results: We examined the association between change in NT-proBNP from baseline to 6 months and cardiovascular (CV) death or HF hospitalization in 2612 participants in the Irbesartan in Patients with Heart Failure and Preserved Systolic Function Study (I-Preserve). Change in NT-proBNP was modelled as a restricted cubic spline in a Cox model after adjusting for baseline NT-proBNP and known prognostic variables. Median change in NT-proBNP from baseline was −7 pg/mL (interquartile range −143 to +108). After adjustment, a 1000 pg/mL decrease in NT-proBNP from baseline was associated with a reduction in the risk of CV death or HF hospitalization [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.53–1.02]; a 1000 pg/mL increase was associated with an increase in risk (HR 2.01, 95% CI 1.50–2.69). Beyond a 1000 pg/mL rise or fall, there was little additional change in risk. Addition of change in NT-proBNP at 6 months to a model with only baseline NT-proBNP improved the C-statistic from 0.752 to 0.769 (P = 0.013). Conclusion: In HF-PEF, a rise in NT-proBNP was associated with an increase in risk of CV death or HF hospitalization and a fall was associated with a trend towards a decrease in risk. NT-proBNP may be a useful marker to monitor prognosis in this condition