Heart failure subtype after acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) is associated with increased risk of heart failure (HF). Determining the type of HF experienced by AKI survivors (heart failure with preserved or reduced ejection fraction, HFpEF or HFrEF) could suggest potential mechanisms underlying the association and opportunities for improving post-AKI care. METHODS: In this retrospective study of adults within the Vanderbilt University health system with a diagnosis of HF, we tested whether AKI events in the two years preceding incident HF associated more with HFpEF or HFrEF while controlling for known predictors. HF outcomes were defined by administrative codes and classified as HFpEF or HFrEF by echocardiogram data. We used multivariable logistic regression models to estimate the effects of AKI on the odds of incident HFpEF versus HFrEF. RESULTS: AKI (all stages) trended towards a preferential association with HFpEF in adjusted analyses (adjusted OR 0.80, 95% CI 0.63 - 1.01). Stage 1 AKI was associated with higher odds of HFpEF that was statistically significant (adjusted OR 0.62, 95% CI 0.43 - 0.88), whereas stages 2-3 AKI showed a trend toward HFrEF that did not reach statistical significance (adjusted OR 1.11, 95% CI 0.76 - 1.63). CONCLUSIONS: AKI as a binary outcome trended towards a preferential association with HFpEF. Stage 1 AKI was associated with higher odds of HFpEF, whereas stage 2-3 trended towards an association with HFrEF that did not meet statistical significance. Different mechanisms may predominate in incident HF following mild versus more severe AKI. Close follow-up with particular attention to volume status and cardiac function after discharge is warranted after even mild AKI.

Physical Activity and Incident Obesity Across the Spectrum of Genetic Risk for Obesity.

Importance: Despite consistent public health recommendations, obesity rates in the US continue to increase. Physical activity recommendations do not account for individual genetic variability, increasing risk of obesity. Objective: To use activity, clinical, and genetic data from the All of Us Research Program (AoURP) to explore the association of genetic risk of higher body mass index (BMI) with the level of physical activity needed to reduce incident obesity. Design, Setting, and Participants: In this US population-based retrospective cohort study, participants were enrolled in the AoURP between May 1, 2018, and July 1, 2022. Enrollees in the AoURP who were of European ancestry, owned a personal activity tracking device, and did not have obesity up to 6 months into activity tracking were included in the analysis. Exposure: Physical activity expressed as daily step counts and a polygenic risk score (PRS) for BMI, calculated as weight in kilograms divided by height in meters squared. Main Outcome and Measures: Incident obesity (BMI ≥30). Results: A total of 3124 participants met inclusion criteria. Among 3051 participants with available data, 2216 (73%) were women, and the median age was 52.7 (IQR, 36.4-62.8) years. The total cohort of 3124 participants walked a median of 8326 (IQR, 6499-10 389) steps/d over a median of 5.4 (IQR, 3.4-7.0) years of personal activity tracking. The incidence of obesity over the study period increased from 13% (101 of 781) to 43% (335 of 781) in the lowest and highest PRS quartiles, respectively (P = 1.0 × 10-20). The BMI PRS demonstrated an 81% increase in obesity risk (P = 3.57 × 10-20) while mean step count demonstrated a 43% reduction (P = 5.30 × 10-12) when comparing the 75th and 25th percentiles, respectively. Individuals with a PRS in the 75th percentile would need to walk a mean of 2280 (95% CI, 1680-3310) more steps per day (11 020 total) than those at the 50th percentile to have a comparable risk of obesity. To have a comparable risk of obesity to individuals at the 25th percentile of PRS, those at the 75th percentile with a baseline BMI of 22 would need to walk an additional 3460 steps/d; with a baseline BMI of 24, an additional 4430 steps/d; with a baseline BMI of 26, an additional 5380 steps/d; and with a baseline BMI of 28, an additional 6350 steps/d. Conclusions and Relevance: In this cohort study, the association between daily step count and obesity risk across genetic background and baseline BMI were quantified. Population-based recommendations may underestimate physical activity needed to prevent obesity among those at high genetic risk.

Comparison of Contemporary Risk Scores in All Groups of Pulmonary Hypertension: A Pulmonary Vascular Research Institute GoDeep Meta-Registry Analysis.

BACKGROUND: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated. RESEARCH QUESTION: Are risk scores originally developed for PAH predictive in PH groups 1 through 4? STUDY DESIGN AND METHODS: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including REVEAL Lite 2, REVEAL 2.0, ESC/ERS 2022, COMPERA 3-strata, and COMPERA 4-strata. RESULTS: Eight thousand five hundred sixty-five patients were included in the study, of whom 3,537 patients were assigned to group 1 PH, whereas 1,807 patients, 1,635 patients, and 1,586 patients were assigned to group 2 PH, group 3 PH, and group 4 PH, respectively. Pulmonary hemodynamics were impaired with median mean pulmonary arterial pressure of 42 mm Hg (33-52 mm Hg) and pulmonary vascular resistance of 7 WU (4-11 WU). All risk scores were prognostic in the entire PH population and in each of the PH groups 1 through 4. The REVEAL scores, when used as continuous prediction models, demonstrated the highest statistical prognostic power and granularity; the COMPERA 4-strata risk score provided subdifferentiation of the intermediate-risk group. Similar results were obtained when separately analyzing various subgroups (PH subgroups 1.1, 1.4.1, and 1.4.4; PH subgroups 3.1 and 3.2; group 2 with isolated postcapillary PH vs combined precapillary and postcapillary PH; patients of all groups with concomitant cardiac comorbidities; and severe [> 5 WU] vs nonsevere PH). INTERPRETATION: This comprehensive study with real-world data from 15 PH centers showed that PAH-designed risk scores possess predictive power in a large PH cohort, whether considered as common to the group or calculated separately for each PH group (1-4) and various subgroups.

Cirrhosis-related sarcopenia may not resolve after liver transplantation.

Background & Aims: Sarcopenia has significant burden in cirrhosis and has been shown to worsen short-term post-liver transplantation (LT). This study aims to evaluate the long-term change in sarcopenia post-LT along with its associations and predictors. Methods: A retrospective study of adult patients who underwent LT at a tertiary centre between 1/1/2009 and 12/31/2018. Relevant demographic and clinical data were collected. Skeletal muscle index (SMI) was calculated using standard of care computerised tomography (CT) scans pre- and post-LT. Sarcopenia was defined using previously established cut-points. The primary outcome was SMI change post-LT and secondary outcome was post-LT mortality. Results: Out of 1165 patients, 401 met inclusion criteria (1,205 CT scans reviewed). The average age at transplant was 57 years; 63% were male. The average BMI was 28 kg/m2. Thirteen percent of females and 32% of males had sarcopenia pre-LT. Post-LT SMI declined by 4.7 cm2/m2 in the first year then by 0.39 cm2/m2 per year thereafter. Females had greater rate of decline in SMI after the first year compared with males (0.87 cm2/m2 per year vs. 0.17 cm2/m2 per year, respectively, p = 0.02). Post-LT physical rehabilitation, infection, and readmissions were not associated with SMI trajectory. At 3 years post-LT, 31% of females and 48% of males had sarcopenia. Baseline sarcopenia was the only predictor of long-term post-LT sarcopenia on multivariable analysis, but it was not associated with mortality. Conclusions: Sarcopenia does not appear to resolve post-LT and likely worsens leading to nearly doubling its prevalence in those with long-term follow-up. Immediate post-LT physical rehabilitation was not associated with SMI trajectory in our cohort. Impact and implications: The prevalence of sarcopenia is high among patients with cirrhosis; however, data are mixed on the impact of sarcopenia on post-liver transplant (LT) course and there have been no studies evaluating the long-term evolution of sarcopenia post-LT beyond 1 year. In this study, we analysed changes in muscle mass up to 3 years after transplant in 401 patients and found that sarcopenia did not resolve in most liver transplant recipients and skeletal muscle mass tended to worsen after transplant with the greatest decline in muscle mass in the first year post-LT. Interestingly, sarcopenia did not influence post-transplant outcomes. Future prospective studies are needed to further understand the natural course of sarcopenia post-LT to guide interventions aiming at reversing post-LT sarcopenia.

Peak steps: Capacity for activity improves after adding approved therapy in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) patients have low activity. Activity intensity or duration could be a measure of clinical status or improvement. We aimed to determine whether standard or novel actigraphy measures could detect increases in activity after adding therapy. This was a prospective, single-center observational study evaluating activity after adding therapy in Group 1 PAH; we also report a validation cohort. For our study, two different accelerometers were used, a wrist (ActiGraph) and chest (MC10) device. Patients were analyzed in two groups, Treatment Intensification (TI, adding therapy) or Stable. Both groups had baseline monitoring periods of 7 days; the TI group had follow-up at 3 months, while Stables had follow-up within 4 weeks to assess stability. Activity time and steps were reported from both devices' proprietary algorithms. In ActiGraph only, steps in 1-min intervals throughout the day were ranked (not necessarily contiguous). Average values for each week were calculated and compared using nonparametric testing. Thirty patients had paired data (11 Stable and 19 TI). There was no between-group difference at baseline; we did not observe therapy-associated changes on average daily steps or activity time/intensity. The top 5 min of steps (capacity) increased after adding therapy; there was no difference in the stable group. This key finding was validated in a previously reported randomized trial studying a behavioral intervention to increase exercise. Total daily activity metrics are influenced by both disease and non-disease factors, making therapy-associated change difficult to detect. Peak minute steps were a treatment-responsive marker in both a pharmacologic and training intervention.

Genetics of Pulmonary Pressure and Right Ventricle Stress Identify Diabetes as a Causal Risk Factor.

Background Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary hypertension and right heart adaptation are not well known. We sought to leverage unbiased genetic approaches to determine clinical conditions that share genetic architecture with pulmonary pressure and right ventricular dysfunction. Methods and Results We leveraged Vanderbilt University's deidentified electronic health records and DNA biobank to identify 14 861 subjects of European ancestry who underwent at least 1 echocardiogram with available estimates of pulmonary pressure and right ventricular function. Analyses of the study were performed between 2020 and 2022. The final analytical sample included 14 861 participants (mean [SD] age, 63 [15] years and mean [SD] body mass index, 29 [7] kg/m2). An unbiased phenome-wide association study identified diabetes as the most statistically significant clinical International Classifications of Diseases, Ninth Revision (ICD-9) code associated with polygenic risk for increased pulmonary pressure. We validated this finding further by finding significant associations between genetic risk for diabetes and a related condition, obesity, with pulmonary pressure estimate. We then used 2-sample univariable Mendelian randomization and multivariable Mendelian randomization to show that diabetes, but not obesity, was independently associated with genetic risk for increased pulmonary pressure and decreased right ventricle load stress. Conclusions Our findings show that genetic risk for diabetes is the only significant independent causative driver of genetic risk for increased pulmonary pressure and decreased right ventricle load stress. These findings suggest that therapies targeting genetic risk for diabetes may also potentially be beneficial in treating pulmonary hypertension and right heart dysfunction.

Cardiometabolic Risk Factors Associated With Right Ventricular Function and Compensation in Patients Referred for Echocardiography.

Background Pulmonary hypertension and right ventricular (RV) dysfunction are drivers of adverse outcomes; however, modifiable risk factors for RV dysfunction are not well described. We investigated the association between clinical markers of metabolic syndrome and echocardiographic RV function in a large referral population. Methods and Results Using electronic health record data, we performed a retrospective cohort study of patients aged ≥18 years referred for transthoracic echocardiography between 2010 and 2020 with RV systolic pressure (RVSP) or tricuspid annular plane systolic excursion (TAPSE) values. Pulmonary hypertension was defined by RVSP >33 mm Hg and RV dysfunction by TAPSE ≤1.8 cm. Our sample included 37 203 patients of whom 19 495 (52%) were women, 29 752 (83%) were White, with a median age of 63 years (interquartile range, 51-73). Median (interquartile range) RVSP was 30.0 mm Hg (24.0-38.7), and median TAPSE was 2.1 cm (1.7-2.4). Within our sample, 40% had recorded RVSP >33 mm Hg, and 32% with TAPSE <1.8 cm. Increase in RVSP from normal (<33 mm Hg) to mildly elevated (33-39 mm Hg) or elevated (>39 mm Hg) was associated with lower low-density lipoprotein and high-density lipoprotein, and higher hemoglobin A1c and body mass index (P<0.001). A decrease in TAPSE between groups of TAPSE >1.8 cm, TAPSE 1.5-1.8 cm, and TAPSE <1.5 cm was associated with increased triglyceride:high-density lipoprotein ratio and hemoglobin A1c, and decreased body mass index, low-density lipoprotein, high-density lipoprotein, and systolic blood pressure (P<0.001). Most associations between cardiometabolic predictors and RVSP and TAPSE were nonlinear with clear inflection points associated with higher pulmonary pressure and lower RV function. Conclusions Clinical measures of cardiometabolic function were highly associated with echocardiographic measures of right ventricular function and pressure.

Clinical features do not identify risk of progression from isolated postcapillary pulmonary hypertension to combined pre- and postcapillary pulmonary hypertension.

Pulmonary hypertension is a common sequelae of left heart failure and may present as isolated postcapillary pulmonary hypertension (Ipc-PH) or combined pre- and postcapillary pulmonary hypertension (Cpc-PH). Clinical features associated with progression from Ipc-PH to Cpc-PH have not yet been described. We extracted clinical data from patients who underwent right heart catheterizations (RHC) on two separate occasions. Ipc-PH was defined as mean pulmonary pressure >20 mmHg, pulmonary capillary wedge pressure >15 mmHg, and pulmonary vascular resistance (PVR) < 3 WU. Progression to Cpc-PH required an increase in PVR to ≥3 WU. We performed a retrospective cohort study with repeated assessments comparing subjects that progressed to Cpc-PH to subjects that remained with Ipc-PH. Of 153 patients with Ipc-PH at baseline who underwent a repeat RHC after a median of 0.7 years (IQR 0.2, 2.1), 33% (50/153) had developed Cpc-PH. In univariate analysis comparing the two groups at baseline, body mass index (BMI) and right atrial pressure were lower, while the prevalence of moderate or worse mitral regurgitation (MR) was higher among those who progressed. In age- and sex-adjusted multivariable analysis, only BMI (OR 0.94, 95% CI 0.90-0.99, p = 0.017, C = 0.655) and moderate or worse MR (OR 3.00, 95% CI 1.37-6.60, p = 0.006, C = 0.654) predicted progression, but with poor discriminatory power. This study suggests that clinical features alone cannot distinguish patients at risk for development of Cpc-PH and support the need for molecular and genetic studies to identify biomarkers of progression.

Quantifying physical activity needed to mitigate genetic risk for obesity.

Despite consistent public health recommendations, obesity rates continue to increase. Physical activity (e.g. daily steps) is a well-established modifier of body weight. Genetic background is an important, but typically uncaptured, contributor to obesity risk. Leveraging physical activity, clinical, and genetic data from the All of Us Research Program, we measured the impact of genetic risk of obesity on the level of physical activity needed to reduce incident obesity. For example, we show that an additional 3,310 steps per day (11,910 steps total) would be needed to mitigate a 25% higher than average genetic risk of obesity. We quantify the number of daily steps needed to mitigate obesity risk across the spectrum of genetic risk. This work quantifies the relationship between physical activity and genetic risk showing significant independent effects and provides a first step towards personalized activity recommendations that incorporate genetic information to reduce incident obesity risk.

Daily Step Counts Before and After the COVID-19 Pandemic Among All of Us Research Participants.

This cohort study of US adults examines changes in physical activity following the onset of the COVID-19 pandemic.

Ferroptosis Promotes Pulmonary Hypertension.

Background: Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species (ROS) generation, results in lipid peroxidation-induced ferroptosis. Ferroptosis is an inflammatory mode of cell death as it both promotes complement activation and recruits macrophages. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells exhibit disrupted lipid metabolism and increased ROS production, and there is ectopic complement deposition and inflammatory macrophage accrual in the surrounding vasculature. However, the integrative effects of ferroptosis on metabolism, cellular landscape changes in the lung, complement induction, and pulmonary vascular remodeling are unknown. Methods: Multi-omics analyses in rodents and a genetic association study in humans evaluated the role of ferroptosis in PAH. Results: Ferrostatin-1, a small-molecule ferroptosis inhibitor, mitigated PAH severity and improved right ventricular function in monocrotaline rats. RNA-seq and proteomics analyses demonstrated ferroptosis was induced with increasingly severe PAH. Metabolomics and proteomics data showed ferroptosis inhibition restructured lung metabolism and altered phosphatidylcholine and phosphatidylethanolamine levels. RNA-seq, proteomics, and confocal microscopy revealed complement activation and pro-inflammatory cytokines/chemokines were suppressed by ferrostatin-1. Additionally, ferrostatin-1 combatted changes in endothelial, smooth muscle, and interstitial macrophage abundances and gene activation patterns in the lungs as revealed by deconvolution RNA-seq. Finally, the presence of six single-nucleotide polymorphisms in ferroptosis genes were independently associated with pulmonary hypertension severity in the Vanderbilt BioVU repository. Conclusions: Rodent and human data nominate ferroptosis as a PAH regulating pathway via its ability to modulate lung lipid metabolism, repress pathogenic complement activation, dampen interstitial macrophage infiltration, and restore the lung cellular environment.

Association of Longitudinal Activity Measures and Diabetes Risk: An Analysis From the National Institutes of Health All of Us Research Program.

CONTEXT: Prior studies of the relationship between physical activity and incident type 2 diabetes mellitus (T2DM) relied primarily on questionnaires at a single time point. OBJECTIVE: We sought to investigate the relationship between physical activity and incident T2DM with an innovative approach using data from commercial wearable devices linked to electronic health records in a real-world population. METHODS: Using All of Us participants' accelerometer data from their personal Fitbit devices, we used a time-varying Cox proportional hazards models with repeated measures of physical activity for the outcome of incident T2DM. We evaluated for effect modification with age, sex, body mass index (BMI), and sedentary time using multiplicative interaction terms. RESULTS: From 5677 participants in the All of Us Research Program (median age 51 years; 74% female; 89% White), there were 97 (2%) cases of incident T2DM over a median follow-up period of 3.8 years between 2010 to 2021. In models adjusted for age, sex, and race, the hazard of incident diabetes was reduced by 44% (95% CI, 15%-63%; P = 0.01) when comparing those with an average daily step count of 10 700 to those with 6000. Similar benefits were seen comparing groups based on average duration of various intensities of activity (eg, lightly active, fairly active, very active). There was no evidence for effect modification by age, sex, BMI, or sedentary time. CONCLUSION: Greater time in any type of physical activity intensity was associated with lower risk of T2DM irrespective of age, sex, BMI, or sedentary time.

Association of step counts over time with the risk of chronic disease in the All of Us Research Program.

The association between physical activity and human disease has not been examined using commercial devices linked to electronic health records. Using the electronic health records data from the All of Us Research Program, we show that step count volumes as captured by participants' own Fitbit devices were associated with risk of chronic disease across the entire human phenome. Of the 6,042 participants included in the study, 73% were female, 84% were white and 71% had a college degree, and participants had a median age of 56.7 (interquartile range 41.5-67.6) years and body mass index of 28.1 (24.3-32.9) kg m-2. Participants walked a median of 7,731.3 (5,866.8-9,826.8) steps per day over the median activity monitoring period of 4.0 (2.2-5.6) years with a total of 5.9 million person-days of monitoring. The relationship between steps per day and incident disease was inverse and linear for obesity (n = 368), sleep apnea (n = 348), gastroesophageal reflux disease (n = 432) and major depressive disorder (n = 467), with values above 8,200 daily steps associated with protection from incident disease. The relationships with incident diabetes (n = 156) and hypertension (n = 482) were nonlinear with no further risk reduction above 8,000-9,000 steps. Although validation in a more diverse sample is needed, these findings provide a real-world evidence-base for clinical guidance regarding activity levels that are necessary to reduce disease risk.

An algorithm to identify cases of pulmonary arterial hypertension from the electronic medical record.

BACKGROUND: Study of pulmonary arterial hypertension (PAH) in claims-based (CB) cohorts may facilitate understanding of disease epidemiology, however previous CB algorithms to identify PAH have had limited test characteristics. We hypothesized that machine learning algorithms (MLA) could accurately identify PAH in an CB cohort. METHODS: ICD-9/10 codes, CPT codes or PAH medications were used to screen an electronic medical record (EMR) for possible PAH. A subset (Development Cohort) was manually reviewed and adjudicated as PAH or "not PAH" and used to train and test MLAs. A second subset (Refinement Cohort) was manually reviewed and combined with the Development Cohort to make The Final Cohort, again divided into training and testing sets, with MLA characteristics defined on test set. The MLA was validated using an independent EMR cohort. RESULTS: 194 PAH and 786 "not PAH" in the Development Cohort trained and tested the initial MLA. In the Final Cohort test set, the final MLA sensitivity was 0.88, specificity was 0.93, positive predictive value was 0.89, and negative predictive value was 0.92. Persistence and strength of PAH medication use and CPT code for right heart catheterization were principal MLA features. Applying the MLA to the EMR cohort using a split cohort internal validation approach, we found 265 additional non-confirmed cases of suspected PAH that exhibited typical PAH demographics, comorbidities, hemodynamics. CONCLUSIONS: We developed and validated a MLA using only CB features that identified PAH in the EMR with strong test characteristics. When deployed across an entire EMR, the MLA identified cases with known features of PAH.

Clinical insights into pulmonary hypertension in chronic obstructive pulmonary disease.

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Little is known about the prevalence and clinical profiles of patients with COPD-PH. We report the clinical characteristics, hemodynamic profiles, and prognosis in a large population of patients with COPD referred for right heart catheterization (RHC). We extracted data from all patients referred for RHC between 1997 and 2017 in Vanderbilt's deidentified medical record. PH was defined as mean pulmonary artery pressure >20 mmHg. Pre- and postcapillary PH were defined according to contemporary guidelines. COPD was identified using a validated rules-based algorithm requiring international classification of diseases codes relevant to COPD. We identified 6065 patients referred for RHC, of whom 1509 (24.9%) had COPD and 1213 had COPD and PH. Patients with COPD-PH had a higher prevalence of diabetes, atrial fibrillation, and heart failure compared with COPD without PH. Approximately 55% of patients with COPD-PH had elevated left ventricle (LV) filling pressure. Pulmonary function testing data from individuals with COPD-PH revealed subtype differences, with precapillary COPD-PH having lower diffusion capacity of the lungs for carbon monoxide (DLCO) values than the other COPD-PH subtypes. Patients with COPD-PH had significantly increased mortality compared with COPD alone (hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.28-2.26) with the highest mortality among the combined pre- and postcapillary COPD-PH subgroup (HR: 2.39; 95% CI: 1.64-3.47). PH is common among patients with COPD referred for RHC. The etiology of PH in patients with COPD is often mixed due to multimorbidity and is associated with high mortality, which may have implications for risk factor management.

Cirrhotic cardiomyopathy: Appraisal of the original and revised criteria in predicting posttransplant cardiac outcomes.

Cardiovascular disease (CVD) significantly contributes to morbidity and mortality after liver transplantation (LT). Cirrhotic cardiomyopathy (CCM) is a risk factor for CVD after transplant. CCM criteria were originally introduced in 2005 with a revision proposed in 2020 reflecting echocardiographic technology advancements. This study assesses the two criteria sets in predicting major adverse cardiac events (MACE) after transplant. This single-center retrospective study reviewed adult LT recipients between January 1, 2009, and December 31, 2018. Patients with insufficient pre-LT echocardiographic data, prior ischemic heart disease, portopulmonary hypertension, or longitudinal care elsewhere were excluded. The primary composite outcome was MACE (arrhythmia, heart failure, cardiac arrest, and/or cardiac death) after transplant. Of 1165 patients, 210 met the eligibility criteria. CCM was present in 162 patients (77%) per the original criteria and 64 patients (30%) per the revised criteria. There were 44 MACE and 31 deaths in the study period. Of the deaths, 38.7% occurred secondary to CVD. CCM defined by the original criteria was not associated with MACE after LT (p = 0.21), but the revised definition was significantly associated with MACE (hazard ratio [HR], 1.93; 95% confidence interval, 1.05-3.56; p = 0.04) on multivariable analysis. Echocardiographic variable analysis demonstrated low septal e' as the most predictive variable for MACE after LT (HR, 3.45; p < 0.001). CCM, only when defined by the revised criteria, was associated with increased risk for MACE after LT, validating the recently revised CCM definition. Abnormal septal e', reflecting impaired relaxation, appears to be the most predictive echocardiographic criterion for MACE after LT.

The episodic flanker effect: Memory retrieval as attention turned inward.

This article tests the conjecture that memory retrieval is attention turned inward by developing an episodic flanker task that is analogous to the well-known perceptual flanker task and by developing models of the spotlight of attention focused on a memory list. Participants were presented with a list to remember (ABCDEF) followed by a probe in which one letter was cued (# # C # # #). The task was to indicate whether the cued letter matched the letter in the cued position in the memory list. The data showed classic results from the perceptual flanker task. Response time and accuracy were affected by the distance between the cued letter in the probe and the memory list (# # D # # # was worse than # # E # # #) and by the compatibility of the uncued letters in the probe and the memory list (ABCDEF was better than STCRVX). There were six experiments. The first four established distance and compatibility effects. The fifth generalized the results to sequential presentation of memory lists, and the sixth tested the boundary conditions of distance and flanker effects with an item recognition task. The data were fitted with three families of models that apply space-based, object-based, and template-based theories of attention to the problem of focusing attention on the cued item in memory. The models accounted for the distance and compatibility effects, providing measures of the sharpness of the focus of attention on memory and the ability to ignore distraction from uncued items. Together, the data and theory support the conjecture that memory retrieval is attention turned inward and motivate further research on the topic. (PsycInfo Database Record (c) 2021 APA, all rights reserved).