Lack of Association Between Donor-Derived Cell-Free DNA and Cardiac Allograft Vasculopathy.

Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT). We evaluated donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker of CAV development after HT. The INSPIRE registry at the Intermountain Medical Center was queried for stored plasma samples from HT patients with and without CAV. At Stanford University, HT patients with CAV (cases) and without CAV (controls) were enrolled prospectively, and blood samples were collected. All the samples were analyzed for dd-cfDNA using the AlloSure assay (CareDx, Inc.). CAV was defined per the ISHLT 2010 standardized classification system. Univariate associations between patient demographics and clinical characteristics and their CAV grade were tested using chi-square and Wilcoxon rank sum tests. Associations between their dd-cfDNA levels and CAV grades were examined using a nonparametric Kruskal-Wallis test. A total of 69 pts were included, and 101 samples were analyzed for dd-cfDNA. The mean age at sample collection was 58.6 ± 13.7 years; 66.7% of the patients were male, and 81% were White. CAV 0, 1, 2, and 3 were present in 37.6%, 22.8%, 22.8%, and 16.8% of included samples, respectively. The median dd-cfDNA level was 0.13% (0.06, 0.33). The median dd-cfDNA level was not significantly different between CAV (-) and CAV (+): 0.09% (0.05%-0.32%) and 0.15% (0.07%-0.33%), respectively, p = 0.25 and with similar results across all CAV grades. In our study, dd-cfDNA levels did not correlate with the presence of CAV and did not differ across CAV grades. As such, dd-cfDNA does not appear to be a reliable noninvasive biomarker for CAV surveillance.

A highly predictive cardiac positron emission tomography (PET) risk score for 90-day and one-year major adverse cardiac events and revascularization.

BACKGROUND: With the increase in cardiac PET/CT availability and utilization, the development of a PET/CT-based major adverse cardiovascular events, including death, myocardial infarction (MI), and revascularization (MACE-Revasc) risk assessment score is needed. Here we develop a highly predictive PET/CT-based risk score for 90-day and one-year MACE-Revasc. METHODS AND RESULTS: 11,552 patients had a PET/CT from 2015 to 2017 and were studied for the training and development set. PET/CT from 2018 was used to validate the derived scores (n = 5049). Patients were on average 65 years old, half were male, and a quarter had a prior MI or revascularization. Baseline characteristics and PET/CT results were used to derive the MACE-Revasc risk models, resulting in models with 5 and 8 weighted factors. The PET/CT 90-day MACE-Revasc risk score trended toward outperforming ischemic burden alone [P = .07 with an area under the curve (AUC) 0.85 vs 0.83]. The PET/CT one-year MACE-Revasc score was better than the use of ischemic burden alone (P < .0001, AUC 0.80 vs 0.76). Both PET/CT MACE-Revasc risk scores outperformed risk prediction by cardiologists. CONCLUSION: The derived PET/CT 90-day and one-year MACE-Revasc risk scores were highly predictive and outperformed ischemic burden and cardiologist assessment. These scores are easy to calculate, lending to straightforward clinical implementation and should be further tested for clinical usefulness.

Reported history of childhood trauma and stress-related vulnerability: Associations with emotion regulation, executive functioning, daily hassles and pre-sleep arousal.

Childhood trauma is associated with poor health outcomes in adulthood. Mechanisms for these associations are not well understood because past studies have focused predominantly on populations that have already developed physical and mental health problems. The present study examined the association between childhood trauma and stress-related vulnerability factors in a healthy adult sample (n = 79; 68% female, mean age = 27.5, SD = 6.5). Emotion regulation difficulties were examined as a potential mediator. Participants completed baseline laboratory assessments of reported childhood trauma, emotion regulation difficulties, prior month sleep quality, baseline impedance cardiography and behavioural tests of executive functioning (EF) and a three-day experience sampling assessment protocol that included sleep diary, reported and objective pre-sleep arousal, daily hassles and reported EF difficulties. Reported history of childhood abuse was significantly associated with difficulties in emotion regulation, self-report and objective pre-sleep arousal, diary-assessed sleep quality, daily hassles and reported EF difficulties. Reported history of childhood neglect was associated with greater pre-sleep arousal and poorer EF-behavioural control. Emotion regulation difficulties mediated the relationship between childhood abuse and reported pre-sleep arousal, daily hassles and reported EF difficulties. In conclusion, history of childhood trauma is associated with a variety of stress-related vulnerability factors in healthy adults that may be viable early intervention targets.

Nonrestorative sleep in healthy, young adults without insomnia: associations with executive functioning, fatigue, and pre-sleep arousal.

OBJECTIVES: Previous research suggests that nonrestorative sleep (NRS), even in the absence of insomnia symptoms or other sleep disorders, may be associated with daytime dysfunction. This study examined the association between NRS and daytime dysfunction in healthy adults screened for insomnia and sleep apnea. DESIGN: Multi-day assessment approach. SETTING: Community-based adults and college students. PARTICIPANTS: Healthy young adults without insomnia and sleep apnea (n = 79; 68% female, mean age = 27.5, SD = 6.5). MEASUREMENTS: Laboratory protocol included a behavioral assessment of executive functioning (EF), self-report of prior month sleep-related daytime dysfunction, and depressive symptoms in the prior two weeks. Subsequently, participants completed an experience sampling assessment that included morning ratings of NRS, repeat affect ratings throughout the day via palm-pilot, nighttime ratings of pre-sleep arousal and EF disturbances, ambulatory cardiac impedence monitoring, and wrist actigraphy. RESULTS: NRS was significantly associated with poorer performance on behaviorally-assessed EF, perceived EF difficulties, daily ratings of fatigue, and past-month reported daytime dysfunction. These associations remained significant after controlling for age and sleep duration (measured by actigraphy). NRS was also associated with increased sympathetic nervous system activation prior to bedtime. Further, reported pre-sleep arousal was associated with NRS, and this association was mediated by perceived EF difficulties. CONCLUSIONS: Findings indicate that, even among healthy, young adults without insomnia or sleep apnea, NRS is associated with poorer cognitive functioning and may be a precursor to insomnia.

Examining the relation between respiratory sinus arrhythmia and depressive symptoms in emerging adults: A longitudinal study.

Major depressive disorder (MDD) is a debilitating and prevalent disorder associated with lower quality of life and substantial economic burden. Recently, there has been strong interest in respiratory sinus arrhythmia (RSA) as a biological predictor of later depression. Theoretical work suggests that higher resting RSA indexes physiological flexibility and better emotion regulation whereas lower RSA may mark vulnerability for psychopathology. However, empirical findings have varied. This study examined whether lower resting RSA predicted later depressive symptoms in a sample of healthy young adults across one year (n=185). Results indicate that year one (Y1) resting RSA predicted Y2 depressive symptoms. This finding remained significant when accounting for the stability of RSA and depressive symptoms across both time points and when including trait anxiety, body mass index, and medication use in statistical models. Findings provide further support for RSA as a promising biological marker for understanding and predicting depressive symptoms.

Testing the effectiveness of 3D film for laboratory-based studies of emotion.

Research in psychology and affective neuroscience often relies on film as a standardized and reliable method for evoking emotion. However, clip validation is not undertaken regularly. This presents a challenge for research with adolescent and young adult samples who are exposed routinely to high-definition (HD) three-dimensional (3D) stimuli and may not respond to older, validated film clips. Studies with young people inform understanding of emotional development, dysregulated affect, and psychopathology, making it critical to assess whether technological advances improve the study of emotion. In the present study, we examine whether 3D film is more evocative than 2D using a tightly controlled within-subjects design. Participants (n  =  408) viewed clips during a concurrent psychophysiological assessment. Results indicate that both 2D and 3D technology are highly effective tools for emotion elicitation. However, 3D does not add incremental benefit over 2D, even when individual differences in anxiety, emotion dysregulation, and novelty seeking are considered.