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In heart failure, specific target doses for each drug are recommended, but some patients receive suboptimal dosing, others are undertreated or remain chronically in a titration phase, despite having no apparent contraindication or intolerance. We assessed the association of different levels of adherence to guidelines with outcomes in patients with heart failure and reduced ejection fraction (HFrEF).Medical records of patients with HFrEF followed at our heart failure (HF) clinic for at least 6 months (n = 511) were reviewed and patients categorized as: 1) optimized (25.4%); 2) in-titration (29.0%); 3) undertreated (32.7%); and 4) intolerant/contraindicated (12.9%). Risk of mortality or HF events (hospitalization, emergency visit or ambulatory administration of intravenous diuretics) within one year was assessed using Cox regression models and Kaplan-Meier curves.Compared to optimized patients, those intolerant (HR: 4.60 [95%CI: 2.23-9.48]; p 0.0001) had the highest risk of outcomes, followed by those undertreated (3.45 [1.78-6.67]; p = 0.0002) and in-titration (1.99 [0.97-4.06]; p = 0.0588). Overall predictors of outcomes included loop diuretics' use (4.54 [2.39-8.60]), undertreatment (2.38 [1.22-4.67]), intolerance/ contraindication to triple therapy (3.08 [1.47-6.42]), peripheral vascular disease (2.13 [1.29-3.50]) and NYHA class III-IV (1.89 [1.25-2.85]); all p 0.05.Level of adherence to guidelines is associated with outcomes, with intolerant/contraindicated patients having the worst prognosis and those undertreated and in-titration at intermediate risk compared to those optimized. Up-titration of therapy should be attempted whenever possible, considering patients' limitations, to potentially improve outcomes.

Background: In Lamin A/C ( LMNA ) cardiomyopathy, atrial fibrillation (AF) commonly occurs before dilated cardiomyopathy, and the ability to predict its incidence is limited. We hypothesized that left atrial (LA) echocardiographic phenotyping can identify atrial myopathy and harbingers of AF. Methods: Echocardiograms from patients with pathogenic or likely pathogenic variants in LMNA (n=77) with and without reduced left ventricular ejection fraction (LVEF, (TTNtv ) (n=35) with similar LVEF, sex, and age distributions. Echocardiographic analysis, blinded to genotype, included strain and volumetric measures of left ventricular and atrial function. The primary outcome was incident AF. Results: At baseline, 43% of the patients with pathogenic or likely pathogenic LMNA variants had a history of AF, including 26% of those with LVEF ≥50%. Compared with healthy subjects, the patients with pathogenic or likely pathogenic LMNA variants and LVEF ≥50% had reduced LA contractile strain ( LMNA , 11.8±6.1% versus control, 15.0±4.2%; P =0.003). Compared to LVEF-matched ( TTNtv ) patients, the patients with pathogenic or likely pathogenic LMNA variants and LVEF P =0.02). Over a median follow-up of 2.8 (1.2–5.7) years, LA contractile strain was the only significant predictor of AF in multivariable Cox regression (hazard ratio, 4.0 [95% CI, 1.04–15.2]). Conclusions: LMNA cardiomyopathy is associated with early intrinsic atrial myopathy reflected by high AF prevalence and reduced LA contractile strain, even in the absence of LV dysfunction and LA dilation. Whether LA strain can be used as a monitoring strategy to detect and mitigate AF complications requires validation.

In Lamin A/C (Echocardiograms from patients with pathogenic or likely pathogenic variants inAt baseline, 43% of the patients with pathogenic or likely pathogenic

Cet article se veut un survol des réseaux de tenseurs et s’adresse aux débutants en la matière. Nous y mettons l’accent sur les outils nécessaires à l’implémentation concrète d’algorithmes. Quatre opérations de base (remodelage, permutation d’indices, contraction et décomposition) qui sont couramment utilisées dans les algorithmes de réseaux de tenseurs y sont décrites. Y seront aussi couverts la notation diagrammatique, intrication, les états en produit de matrices (MPS), les opérateurs en produit de matrices (MPO), état projeté de paires intriquées (PEPS), l’approche par renormalisation d’enchevêtrement multi-échelle (MERA), la décimation par bloc d’évolution temporelle (TEBD) et le groupe de renormalisation de tenseurs (TRG).

Context The impact of galectin-3 inhibitors on nonalcoholic fatty liver diseases (NAFLD)-related outcomes is currently under investigation in randomized clinical trials. Whether there is a causal association between plasma galectin-3 levels and NAFLD is unknown. Objective To evaluate the causal effect of circulating galectin-3 levels on NAFLD as well as >800 other human diseases. Design Inverse variance-weighted (IVW) Mendelian randomization (MR) and phenome-wide MR. Setting Summary statistics of genome-wide association studies. Patients Participants of the UK Biobank, Electronic Medical Records and Genomics (eMERGE), FinnGen, Prevention of Renal and Vascular End-Stage Disease (PREVEND), and IMPROVE cohorts. Intervention Identification of independent single-nucleotide polymorphisms (SNPs) associated with galectin-3 levels (P Main outcome measures Presence of NAFLD in a meta-analysis of genome-wide association study of the eMERGE, UK Biobank, and FinnGen cohorts (3042 NAFLD cases and 504 853 controls), as well as >800 other human diseases in the UK Biobank and FinnGen. Results Using IVW-MR, we found no causal association between galectin-3 levels and NAFLD in the meta-analysis of the 3 cohorts or in each individual cohort. After correction for multiple testing, we found no causal association between galectin-3 levels and >800 human disease-related traits. Conclusions This MR study revealed no causal associations between circulating galectin-3 levels and NAFLD or any other disease traits, suggesting that plasma galectin-3 levels may not be directly implicated in the pathogenesis of NAFLD or other human diseases.

Cardiogenic shock is the most extreme cardiovascular disease state during pregnancy. Peripartum cardiomyopathy is the most common cause of cardiogenic shock toward the end of pregnancy and in the early postpartum period. Therapy for cardiogenic shock relies on appropriate phenotyping of shock etiology, severity and ventricular predominance, which are critical in the appropriate selection of medical and mechanical therapy. Mechanical circulatory support may be used as a bridge to recovery or as definitive therapy. Intra-aortic balloon pumps, percutaneous left ventricular assist devices and venoarterial extracorporeal circulatory devices have been successfully used in pregnancy and the postpartum period. The most commonly used mechanical therapy in the pregnant patient is extracorporeal membranous oxygenation circulatory support. The use of mechanical circulatory devices in peripartum cardiomyopathy has contributed to improved survival rates in recent years. Further efforts to identify the optimal mechanical circulatory support strategy for peripartum cardiomyopathy and cardiogenic shock in the peripartum period are needed.

Sleep apnea (SA) is potentially a modifiable risk factor for dementia. However, its associations to specific aetiologies of dementia remain uncertain. A systematic review and meta-analysis of cohort studies investigating the association between sleep apnea and specific aetiologies of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), vascular dementia (VaD), and frontotemporal dementia (FTD) was performed. The use of biomarkers to support clinical diagnoses in eligible studies was collected. Eleven studies were included, comprising 1,333,424 patients. Patients with sleep apnea had an increased risk of developing any type of neurocognitive disorder (HR: 1.43 [95% CI 1.26-1.62]), Alzheimer's disease (HR: 1.28 [95% CI 1.16-1.41]), and Parkinson's disease (HR: 1.54 [95% CI 1.30-1.84]). No statistically significant association was found for vascular dementia. One study reported a two-fold increased risk for Lewy body dementia (HR: 2.06 [95% CI 1.45-2.91]). No studies investigated the risk for frontotemporal dementia and none of the studies reported results pertaining to biomarkers. Sleep apnea is associated with a significantly increased risk of dementia, particularly for Alzheimer's disease and Parkinson's disease, but not for vascular dementia. Future studies should look at the impact of sleep apnea on specific dementia biomarkers.

Background Heart transplantation is a life-saving procedure that has seen improvements in transplant and patient outcomes due to advances in immunosuppression and prevention of posttransplantation infectious episodes (IEps). This study systematically evaluates IEps in the modern era of heart transplantation at Stanford University Medical Center. Methods This is a single-center retrospective review that includes 279 consecutive adult heart transplantation recipients from January 2008 to September 2017. Baseline demographic, clinical, serological, and outcomes information were collected. Kaplan-Meier estimator was used to assess survival stratified by IEp occurrence within the first year. Results A total of 600 IEps occurred in 279 patients (2.15 IEps per patient) during a median follow-up period of 3 years. Overall survival was 83.3% (95% confidence interval [CI], 76.2-88.4) at 1 year posttransplantation for those with any IEp compared with 93.0% (95% CI, 87.2-96.4) in those without IEp (P = 0.07). Bacterial IEps were the most common (n = 375; 62.5%), followed by viral (n = 180; 30.0%), fungal (n = 40; 6.7%), and parasitic (n = 5; 0.8%). IEps by Gram-negative bacteria (n = 210) outnumbered those by Gram-positive bacteria (n = 142). Compared with prior studies from our center, there was a decreased proportion of viral (including cytomegalovirus), fungal (including Aspergillus spp. and non-Aspergillus spp. molds), and Nocardia infections. There were no IEps due to Mycobacterium tuberculosis, Pneumocystis jirovecii, or Toxoplasma gondii. Conclusions A significant reduction in viral, fungal, and Nocardia IEps after heart transplantation was observed, most likely due to advancements in immunosuppression and preventive strategies, including pretransplant infectious diseases screening and antimicrobial prophylaxis.

We introduce a methodology for generating random multi-qubit stabilizer codes based on solving a constraint satisfaction problem (CSP) on random bipartite graphs. This framework allows us to enforce stabilizer commutation, X/Z balancing, finite rate, sparsity, and maximum-degree constraints simultaneously in a CSP that we can then solve numerically. Using a state-of-the-art CSP solver, we obtain convincing evidence for the existence of a satisfiability threshold. Furthermore, the extent of the satisfiable phase increases with the number of qubits. In that phase, finding sparse codes becomes an easy problem. Moreover, we observe that the sparse codes found in the satisfiable phase practically achieve the channel capacity for erasure noise. Our results show that intermediate-size finite-rate sparse quantum codes are easy to find, while also demonstrating a flexible methodology for generating good codes with custom properties. We therefore establish a complete and customizable pipeline for random quantum code discovery.

AimTo investigate the effect of the new definition of pulmonary hypertension (PH) and new pulmonary vascular resistance (PVR) thresholds on the prevalence, clinical characteristics, and events following cardiac transplantation (CTx) over 30 years.MethodsPatients who underwent CTx between 1983 and 2014 for whom invasive hemodynamic data was available were analyzed (n = 342). Patients transplanted between 1983 and 1998 were classified as early era and those transplanted between 1999 and 2014 were classified as recent era. Group 2 PH was diagnosed in the presence of a mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. Isolated post capillary PH (Ipc-PH) was defined as PVR ≤ 2 wood units and combined pre and post capillary PH (Cpc-PH) was defined PVR > 2 wood units. Moderate to severe PH was defined as mPAP ≥ 35 mmHg. The primary outcome was 30-day mortality and long-term mortality according to type and severity of PH. Proportions were analyzed using the chi-square test, and survival analyses were performed using Kaplan-Meier curves and compared using the logrank test.ResultsThe prevalence of PH in patients transplanted in the early era was 89.1%, whilst 84.2% of patients transplanted in the recent era had PH (p = 0.3914). There was no difference in the prevalence of a pre-capillary component according to era (p = 0.4001), but severe PH was more common in the early era (51.1% [early] vs 38.0% [recent] p = 0.0151). Thirty-day and long-term mortality were not significantly associated with severity or type of PH. There was a trend toward increased 30-day mortality in mild PH (10.1%), compared to no PH (4.4%) and moderate to severe PH (6.6%; p = 0.0653). Long-term mortality did not differ according to the severity of PH (p = 0.1480). There were no significant differences in 30-day or long-term mortality in IpcPH compared to CpcPH (p = 0.3974 vs p = 0.5767, respectively).ConclusionOver 30 years, PH has remained very prevalent before CTx. The presence, severity, and type (pre- vs post-capillary) of PH is not significantly associated with short- or long-term mortality.

The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection.The primary aim was to assess the incidence and nature of IEp. The secondary aim was to evaluate the effect of potential risk factors, such as recipient age; sex; body mass index; panel-reactive antibodies; cytomegalovirus (CMV) primary mismatch; prednisone, tacrolimus, and sirolimus levels; and gene expression profile (GEP) score, in the development of IEp.The OAR comprises 1,504 patients, of whom 220 patients (14.6%) had an IEp during a median follow-up period of 382 days (interquartile range [IQR] 230 to 579 days). The cause-specific 5-year hazard ratio for any infection was 2.029 (p = 0.12). The pattern of early infection was consistent with nosocomial and opportunistic causes, whereas later infection was consistent with late-onset opportunistic and community-acquired etiologies. Sixty-two percent of the infections occurred early. In the time-dependent analysis, higher prednisone dose (log prednisone, hazard ratio [HR] 1.30, p = 0.022) was the most significant risk factor for all IEp.In the OAR cohort, the majority of infections occurred within 1 year after transplantation. Clinicians may consider more aggressive prednisone withdrawal in low-risk patients to reduce IEp.

Introduction: LMNA cardiomyopathy is characterized by a high incidence of atrial fibrillation (AF) and an increased risk for AF-related stroke. AF commonly occurs before apparent cardiomyopathy, and the ability to predict its incidence in asymptomatic LMNA mutation carriers is limited. We sought to evaluate the presence of echocardiographic features specific to LMNA and whether they predict AF incidence. Methods: Patients harboring LMNA mutations (n=77) from two referrals centers between 2000 and 2017 were retrospectively included. Comparator groups included patients with TTN cardiomyopathy (n=35) and healthy subjects (n=36). Echocardiograms at first clinical contact were analyzed for routine metrics and LA strain and related to incident AF. Results: Patients with LMNA mutations were assessed at median age 47 years (IQR, 32-62) with median LVEF 51% (41-61). In LMNA patients with LVEF ≥55% (n=20) and healthy subjects matched for LVEF, LA contractile strain was lower in LMNA patients (-10% vs -16%, respectively; P = 0.047), whereas other parameters did not significantly differ (Figure, panel A). Comparison of LVEF-matched LMNA and TTN cardiomyopathy patients showed LA contractile strain as the only distinguishing feature (-5.8% vs -12.8%, respectively; P = 0.01) (Figure, panel B). LMNA patients without previous AF (n=35) were followed for a total of 133 patient-years during which 11 (31%) developed AF. In Cox regressions adjusted for clinical and echocardiographic variables, decreased LA contractile strain (<

Rain fills the atmosphere with water particles, which breaks the common assumption that light travels unaltered from the scene to the camera. While it is well-known that rain affects computer vision algorithms, quantifying its impact is difficult. In this context, we present a rain rendering pipeline that enables the systematic evaluation of common computer vision algorithms to controlled amounts of rain. We present three different ways to add synthetic rain to existing images datasets: completely physic-based; completely data-driven; and a combination of both. The physic-based rain augmentation combines a physical particle simulator and accurate rain photometric modeling. We validate our rendering methods with a user study, demonstrating our rain is judged as much as 73% more realistic than the state-of-theart. Using our generated rain-augmented KITTI, Cityscapes, and nuScenes datasets, we conduct a thorough evaluation of object detection, semantic segmentation, and depth estimation algorithms and show that their performance decreases in degraded weather, on the order of 15% for object detection, 60% for semantic segmentation, and 6-fold increase in depth estimation error. Finetuning on our augmented synthetic data results in improvements of 21% on object detection, 37% on semantic segmentation, and 8% on depth estimation., 19 pages, 19 figures, IJCV 2020 preprint. arXiv admin note: text overlap with arXiv:1908.10335

The purpose of this paper is to investigate the relationship between three antecedents, namely, work self-determination, managerial support (i.e. interpersonal motivation style) and person-organization fit (P-O) (i.e. shared values among employees and the overall organization) on employee work satisfaction in a French Canadian health care context. Assessing the relationships between such intrapersonal, interpersonal and macro-level variables will help to better comprehend work satisfaction in health care and shed light on applicable transformations for management.The study tested a judicious model grounded in self-determination theory in order to capture and construe the three levels of influence. Participants were recruited from four health centers in the Suroît (Quèbec, Canada) region. Management was provided with the questionnaire and asked to distribute to all employees including nurses and allied health. A serial multiple mediation analysis was used to test the proposed model.The findings revealed that nearly 60 percent of the participants from each of the professional groups reported feeling moderately to not at all satisfied with their job (follow-up ANOVA revealed that nurses were the least satisfied). Through closer examination, the findings revealed that 46 percent of the variance in reported job satisfaction was explained by the three focal antecedents from the hypothesized model (work self-determination, managerial support and P-O fit). Therefore the model, in its entirety, represents a comprehensive perspective for influencing employee work satisfaction in particularly demanding health care work contexts.The study is the first to indicate the prevailing factors necessary to pursue and support employee satisfaction within a health care context among French Canadians.

The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world., It is unclear whether plant trait relationships found at the global scale extend to climatic extremes. Here the authors analyse six major aboveground traits to show that known plant trait relationships extend to the tundra biomes and exhibit the same two dimensions of variation detected at the global scale.

AIMS Bromocriptine is thought to facilitate left ventricular (LV) recovery in peripartum cardiomyopathy (PPCM) through inhibition of prolactin secretion. However, this potential therapeutic effect remains controversial and was incompletely studied in diverse populations. METHODS AND RESULTS Consecutive women with new-onset PPCM (n = 76) between 1994 and 2015 in Quebec, Canada, were classified according to treatment (n = 8, 11%) vs. no treatment (n = 68, 89%) with bromocriptine. We assessed LV functional recovery at mid-term (6 months) and long-term (last follow-up) and compared outcomes among groups. Women treated with bromocriptine experienced better mid-term left ventricular ejection fraction (LVEF) recovery from 23 ± 10% at baseline to 55 ± 12% at 6 months, compared with a change from 30 ± 12% at baseline to 45 ± 13% at 6 months in women treated with standard medical therapy (P interaction

Supplemental Digital Content is available in the text., Background: Current guidance from International Society for Heart and Lung Transplantation recommends using body weight for donor-recipient size matching for heart transplantation. However, recent studies have shown that predicted heart mass, using body weight, height, age, and sex, may represent a better method of size matching. We aim to validate a cardiovascular magnetic resonance (CMR)–derived equation for predicted left ventricular mass (LVM) in a cohort of normal individuals in the United Kingdom. Methods: This observational study was conducted in 5065 middle-aged (44–77 years old) UK Biobank participants who underwent CMR imaging in 2014 to 2015. Individuals with cancer diagnosis in the previous 12 months or history of cardiovascular disease were excluded. Predicted LVM was calculated based on participants’ sex, height, and weight recorded at the time of imaging. Correlation analyses were performed between the predicted LVM and the LVM obtained from manual contouring of CMR cine images. The analysis included 3398 participants (age 61.5±7.5 years, 47.8% males). RESULTS: Predicted LVM was considerably higher than CMR-derived LVM (mean±SD of 138.8±28.9 g versus 86.3±20.9 g). However, there was a strong correlation between the 2 measurements (Spearman correlation coefficient 0.802, P

Objectives This study investigated temporal changes in the demographics and the prognosis of cardiac allograft vasculopathy (CAV) over 30 years following heart transplantation (HTx). Background Effects of the changing HTx demographics on CAV outcomes, based on International Society for Heart and Lung Transplantation (ISHLT) classification of CAV, have been incompletely investigated. Methods Patients who underwent HTx at the Montreal Heart Institute were classified according to the severity of CAV (CAV 0 is no presence of CAV; CAV 1 is mild, CAV 2 to 3 is moderate to severe) and era of HTx (early: 1983 to 1998; recent: 1999 to 2011). We compared the risk of progression, survival, and independent predictors of outcomes among the groups. Results A total of 298 patients were followed for 11.6 ± 6.6 years. Patients who received transplants in the early era exhibited a higher risk for progression from CAV 1 to a higher grade (adjusted odds ratio: 8.0; 95% confidence interval [CI]: 1.01 to 62.6). The presence of CAV was associated with a significantly increased risk for all-cause mortality in the early era (hazard ratio [HR]: 1.6; 95% CI: 1.1 to 2.5) but not in the recent era (HR: 1.1; 95% CI: 0.2 to 4.9). Regardless of the era, CAV classes 2 to 3 and CAV 1 were associated with a significantly increased risk for all-cause mortality compared to CAV 0 (HR: 6.5; 95% CI: 2.7 to 15.7; and HR: 1.750; 95% CI: 1.001 to 3.046, respectively). Conclusions The progression and prognosis of CAV have improved over 30 years. The ISHLT CAV classification accurately and independently predicts long-term outcome following HTx.

Purpose Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality following heart transplantation (HTx). The purpose of this study was to determine the mortality risk and incidence of PGD pre- and post-implementation of the new UNOS heart allocation policy. Methods A total of 426 consecutive adult patients underwent HTx from 1/2010 to 5/2019. Recipients of combined organ transplants were excluded. Definition of severe PGD was based on the 2014 ISHLT consensus statement which includes dependence on mechanical circulatory support, excluding requirement for intra-aortic balloon pump (IABP). The primary outcome was the incidence of PGD and overall 1-year survival. Results The cohort studied was predominantly male (70.8%), with a mean age of 53.4±12.8 years; 31.6% were supported with a left ventricular assist device as a bridge to HTx, and 38.4% were blood type O. There were 17 (4.0%) cases of severe PGD, all of which required extracorporeal membrane oxygenation support. Baseline characteristics pre-HTx were similar in those with and without PGD (Figure 1). There was no difference in the incidence of severe PGD following the introduction of the new allocation policy in October 18, 2018 (5.9 vs. 4.5%, p=0.70), but there was a significant increase in the use of post-transplant IABP (23.5 vs. 9.1%, p=0.009). There was no correlation between RADIAL score and incidence of severe PGD (p=0.41). Severe PGD was associated with reduced 30-day survival (97.6% [95% CI: 95.5-98.8] vs. 68.7% [40.5-85.6], p Conclusion Incidence of severe PGD has not increased in the contemporary era with the new UNOS heart allocation policy. PGD is associated with poor 1-year survival and is not predicted by the RADIAL score, which underscores the need for a new risk prediction model.

Purpose Acute rejection is an important complication following Heart Transplant (HT). The widespread use of peripheral blood markers can reduce the burden of biopsies. We assessed whether the rate of surveillance biopsies decreased after the introduction of gene expression profiling (GEP) in March 2013 and donor-derived cell-free DNA (cfDNA) in October 2018. Methods We analyzed the monthly biopsy time series after the introduction of GEP and cfDNA using an interrupted time series model for the 12 months prior to and after their introduction: GEP 02/12-02/13 v. 03/13-02/14 and for cfDNA 10/17-09/18 vs 10/18-09/19. For both models, an autoregressive regression model was applied to quantify the impact of the introduction of each intervention on the number of biopsies per patient-month. A Durban-Watson test was used to detect the presence of autocorrelation. Results Before the introduction of GEP, biopsies per patient-month were decreasing at a rate of 0.21 (95% CI = [-0.64, 0.23], p=0.35) per month. After the introduction of GEP there was a significant drop in per-patient monthly biopsies of 4.97 (95% CI = [-9.20, -0.74], p=0.021) (Fig1A) but rising at a rate of 0.34 per-patient-month after the initial drop. Similar to GEP, monthly biopsies per patient were already decreasing, at a monthly rate of 0.23 (95% CI = [-0.50, 0.04], p =0.095), before cfDNA was introduced. This introduction further steepened the downward trend in the per-patient-month biopsies at rate of 0.45 per month (Fig IB) despite a steady increase in the number of patients followed over the last 10 years (Fig 1D). Conclusion In a high-volume transplant center, the application of non-invasive testing with cfDNA and GEP has resulted in a considerable reduction in routine surveillance biopsies. Should these tests become widely accessible, GEP and cfDNA will likely provide a sustainable reduction in the biopsy burden across all programs.

BACKGROUND Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor-derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS). METHODS Retrospective single-center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5 mm, and CAV development was defined as MIT ≥1 mm or an increase in MIT ≥0.5 mm at year 1 compared with baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV. RESULTS Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51 ± 11 years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA- vs. 59% in DA + (p = .012). Donor age was a strong predictor of DA (p = .016). Significant risk factors for CAV included male sex (HR = 4.141, p = .001), non-Caucasian race (HR = 1.98, p = .011), BMI

Background Despite significant advances in durable mechanical support survival, infectious complications remain the most common adverse event after ventricular assist device (VAD) implantation and the leading cause of early death after transplantation. In this study, we aim to describe our local infectious epidemiology and review short-term survival and infectious incidence rates in the post-transplantation period and assess risk factors for infectious episodes after transplantation. Methods Retrospective single-center study of all consecutive adult heart transplant patients from 2008 to 2017. Survival data were estimated and summarized using the Kaplan-Meier method. We quantified and evaluated the difference in the incidence rate between patients with and without infection using a Fine-Gray model. The outcome of interest is the time to first infection diagnosis with post-transplant death as the competing event. Results Among 278 heart transplant patients, 74 (26.5%) underwent LVAD implantation. Twenty-one patients (28.3%) developed an infection while supported by an LVAD. When compared to patients supported by an LVAD without a preceding infection, BMI was significantly greater (31.2 vs 27.8 kg/m2 , P = .03). Median follow-up post-transplantation was 3.01 years. Significant risk factors for the competing risk regression for infection after heart transplantation include LVAD infection (HR 1.94, [95% CI] 1.11-3.39, P = .020) and recipient COPD (HR 2.14, [95% CI] 1.39-3.32, P = .001) when adjusted for recipient age, gender, hypertension, diabetes mellitus, and body mass index. Conclusions Patients with LVAD-related infection had a significantly increased risk of infectious complications after heart transplantation. Further research on the avoidance of induction agents and reduced maintenance immunosuppression in this patient population is warranted.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality, accounting for the majority of heart failure (HF) hospitalization. To identify the most complementary predictors of mortality among clinical, laboratory and echocardiographic data, we used cluster based hierarchical modeling. Using Stanford Translational Research Database, we identified patients hospitalized with HFpEF between 2005 and 2016 in whom echocardiogram and NT-proBNP were both available at the time of admission. Comprehensive echocardiographic assessment including left ventricular longitudinal strain (LVLS), right ventricular function and right ventricular systolic pressure (RVSP) was performed. The outcome was defined as all-cause mortality. Among patients identified, 186 patients with complete echocardiographic assessment were included in the analysis. The cohort included 58% female, with a mean age of 78.7 ± 13.5 years, LVLS of -13.3 ± 2.5%, an estimated RVSP of 38 ± 13 mmHg. Unsupervised cluster analyses identified six clusters including ventricular systolic-function cluster, diastolic-hemodynamic cluster, end-organ function cluster, vital-sign cluster, complete blood count and sodium clusters. Using a stepwise hierarchical selection from each cluster, we identified NT-proBNP (standard hazard ratio [95%CI] = 1.56 [1.17-2.08]) and RVSP (1.37 [1.09-1.78]) as independent correlates of outcome. When adding these parameters to the well validated Get with the Guideline Heart Failure risk score, the Chi-square was significantly improved (p = 0.01). In conclusion, NT-proBNP and RVSP were independently predictive in HFpEF among clinical, imaging, and biomarker parameters. Cluster-based hierarchical modeling may help identify the complementally predictive parameters in small cohorts with higher dimensional clinical data. ispartof: SCIENTIFIC REPORTS vol:9 issue:1 ispartof: location:England status: published

African Americans (AAs) have lower survival rates after heart transplantation (HTx) than Caucasians. The aim of this analysis was to evaluate racial differences in gene expression and their associations with survival and the composite outcome of death, retransplant, rejection with hemodynamic compromise, and graft dysfunction in the Outcomes AlloMap Registry.Registry participants included low-risk Caucasian and AA heart transplant recipients with a baseline and at least 1 follow-up gene expression test (AlloMap(C)) within the first year after HTx. The Kaplan-Meier method with delayed entry was used to describe differences in outcomes. Multivariable Cox hazard regression was used to evaluate the associations of overall gene expression profiling score, MARCH8 and FLT3 expression, and tacrolimus levels with each outcome, and stratified Cox models were developed to quantify race-specific associations.Among 933 eligible recipients, 737 (79%) were Caucasian and 196 (21%) were AA. Compared with Caucasians, AAs were significantly younger (55 vs 59 years, p0.001), with higher rates of non-ischemic cardiomyopathy (68% vs 50%, p0.001), sensitization (10% panel reactive antibody, 16% vs 9.1%, p = 0.009), and human leukocyte antigen mismatches (7 vs 7, p = 0.01), but less frequent primary cytomegalovirus serostatus mismatch (14.31% vs 27.3%, p0.001). Overall, AAs had an increased adjusted mortality risk (hazard ratio [HR] 4.13, p = 0.007). Higher tacrolimus levels were associated with decreased mortality in AAs (HR 0.62, p = 0.009). Overall gene expression profiling score was associated with increased mortality among Caucasians (HR 1.21, p = 0.048). In Caucasians, but not AAs, overexpression of MARCH8 was associated with increased mortality (HR 2.90, p = 0.001). FLT3 upregulation was associated with increased mortality (HR 2.42, p = 0.033) in AAs. There was an inverse relationship between FLT3 expression and tacrolimus levels (-0.029 and -0.176, respectively) in Caucasians and AAs.AAs have a significantly higher mortality risk after HTx than Caucasians, even in the low-risk Outcomes AlloMap Registry population. AAs and Caucasians had differential outcomes based upon the varying expression of MARCH8 and FLT3 genes following HTx.

Defects in fatty acid (FA) utilization have been well described in group 1 pulmonary hypertension (PH) and in heart failure (HF), yet poorly studied in group 2 PH. This study was to assess whether the metabolomic profile of patients with pulmonary hypertension (PH) due HF, classified as group 2 PH, differs from those without PH. We conducted a proof-of-principle cross-sectional analysis of 60 patients with chronic HF with reduced ejection fraction and 72 healthy controls in which the circulating level of 71 energy-related metabolites was measured using various methods. Echocardiography was used to classify HF patients as noPH-HF (n = 27, mean pulmonary artery pressure [mPAP] 21 mmHg) and PH-HF (n = 33, mPAP 35 mmHg). The profile of circulating metabolites among groups was compared using principal component analysis (PCA), analysis of covariance (ANCOVA), and Pearson’s correlation tests. Patients with noPH-HF and PH-HF were aged 64 ± 11 and 68 ± 10 years, respectively, with baseline left ventricular ejection fractions of 27 ± 7% and 26 ± 7%. Principal component analysis segregated groups, more markedly for PH-HF, with long-chain acylcarnitines, acetylcarnitine, and monounsaturated FA carrying the highest loading scores. After adjustment for age, sex, kidney function, insulin resistance, and N-terminal pro-brain natriuretic peptide (NT-proBNP), 5/15 and 8/15 lipid-related metabolite levels were significantly different from controls in noPH-HF and PH-HF subjects, respectively. All metabolites for which circulating levels interacted between group and NT-proBNP significantly correlated with NT-proBNP in HF-PH, but none with HF-noPH. FA-related metabolites were differently affected in HF with or without PH, and may convey adverse outcomes given their distinct correlation with NT-proBNP in the setting of PH.

Background Peripartum cardiomyopathy (PPCM) is a rare disorder with potentially fatal consequences, which occurs mainly in previously healthy women. The aetiology of PPCM remains unknown and various pathologic mechanisms have been proposed, including immune-mediated injuries and impaired response to oxidative stress and inflammatory cytokines. Several therapies have been studied, but few have been validated in a well-designed randomized controlled trial. Methods In the present study we sought to review the medical treatment intended for acute PPCM. To this end, we performed a systematic review of the literature of randomized and nonrandomized prospective clinical studies. Results We identified 2 randomized controlled trials that evaluated the dopamine agonist bromocriptine and the inotrope levosimendan, respectively, and 1 nonrandomized study that evaluated the nonselective phosphodiesterase inhibitor pentoxifylline. We reviewed the pathophysiological, pharmacological, and clinical properties for each treatment option identified. Bromocriptine and pentoxifylline both improved left ventricular systolic function and patient-oriented clinical end points and levosimendan did not improve mortality or echocardiographic findings of PPCM. Conclusions In this review we identified bromocriptine and pentoxifylline, but not levosimendan, as potentially useful agents to improve left ventricle function and outcomes in PPCM.

Research is a core aspect of training in academic medicine, but fellows face many challenges thwarting their ability to perform clinically meaningful projects. The concept of a multicentre clinical trial collectively operated by fellows, and integrated longitudinally into training, has never been described. In this article, the authors expose the key principles of Collectively Operated Fellow-Initiated Research (COFIR) that they put in place. The aim of COFIR is to introduce a cohort of fellows to the career of clinician-scientists by conducting a longitudinal research project integrated into the curriculum of their clinical fellowship at a level they would not have access to as single individuals. First, fellows must formulate the research hypothesis to generate a patient-oriented research idea that resonates with a large group of trainees. Second, fellows must be actively involved in the multifaceted aspects of research under the mentorship of clinical scientists. Third, fellows must document and disseminate the newly acquired methodological know-how. Finally, fellows must put the safety of patients above any other consideration. Examples of how these principles were applied in a research project are provided in this article; it represents a call to action for fellows to collectively contribute to the production of significant medical research.

Polar codes were introduced in 2009 by Arikan as the first efficient encoding and decoding scheme that is capacity achieving for symmetric binary-input memoryless channels. Recently, this code family was extended by replacing the block-structured polarization step of polar codes by a convolutional structure. This article presents a numerical exploration of this so-called convolutional polar codes family to find efficient generalizations of polar codes, both in terms of decoding speed and decoding error probability. The main conclusion drawn from our study is that increasing the convolution depth is more efficient than increasing the polarization kernel’s breadth as previously explored.

BACKGROUND Gene expression profiling (GEP) was developed for non-invasive surveillance of acute cellular rejection . Despite its widespread use, there has been a paucity in outcome data for patients managed with GEP outside of clinical trials. METHODS The Outcomes AlloMap Registry (OAR) is an observational, prospective, multicenter study including patients aged ≥ 15 years and ≥ 55 days post-cardiac transplant. Primary outcome was death and a composite outcome of hemodynamically significant rejection, graft dysfunction , retransplantation , or death. Secondary outcomes included readmission rates and development of coronary allograft vasculopathy and malignancies. RESULTS The study included 1,504 patients, who were predominantly Caucasian (69%), male (74%), and aged 54.1 ± 12.9 years. The prevalence of moderate to severe acute cellular rejection (≥2R) was 2.0% from 2 to 6 months and 2.2% after 6 months. In the OAR there was no association between higher GEP scores and coronary allograft vasculopathy (p = 0.25), cancer (p = 0.16), or non-cytomegalovirus infection (p = 0.10). Survival at 1, 2, and 5 years post-transplant was 99%, 98%, and 94%, respectively. The composite outcome occurred in 103 patients during the follow-up period. GEP scores in dual-organ recipients (heart-kidney and heart-liver) were comparable to heart-alone recipients. CONCLUSIONS This registry comprises the largest contemporary cohort of patients undergoing GEP for surveillance. Among patients selected for GEP surveillance, survival is excellent, and rates of acute rejection, graft dysfunction, readmission, and death are low.

Altres ajuts europeus: P.A.W. was additionally supported by the European Union Fourth Environment and Climate Framework Programme (Project Number ENV4-CT970586)P.A.W. was additionally supported by the European Union Fourth Environment and Climate Framework Programme (Project Number ENV4-CT970586). The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature-trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.