A Prospective Observational Study of Physical Activity Levels and Physical Fitness of People at High Risk for Lung Cancer.

Introduction: Physical activity (PA) is a potentially modifiable risk factor for lung cancer, with previous research revealing that people who engage in more PA have lower risk of developing lung cancer. PA levels of lung cancer screening participants have not previously been explored. Methods: Participants at a single Australian International Lung Screen Trial site were eligible for assessment of self-reported PA levels (International Physical Activity Questionnaire and Physical Activity Scale for the Elderly) and physical assessments (6-min walk distance, hand grip muscle strength, daily step count, and body composition) at a single time point during lung cancer screening. Statistics were predominantly descriptive, with parametric data presented as mean and SD and nonparametric data presented as median and interquartile range (IQR). Results: A total of 178 participants were enrolled in this study, with a median age of 61 years. Of the participants, 61% were men and 51% were people who currently smoke. The median total International Physical Activity Questionnaire score was 1756 MET/min/wk (IQR 689, 4049). Mean total Physical Activity Scale for the Elderly score was 160 (SD 72), higher than described in healthy sedentary adults. The median daily step count was 7237 steps (IQR 5353, 10,038) and mean 6-minute walk distance was 545 m (SD 92). Median grip strengths were within predicted normal range, with an elevated median percentage body fat and low skeletal muscle mass found on body composition. Conclusion: Almost a quarter of International Lung Screen Trial participants assessed reported low levels of PA and have a potentially modifiable risk factor to improve health outcomes. Larger studies are needed to characterize the burden of inactivity among high-risk lung cancer screening populations.

Validation of the psychosocial consequences of screening in lung cancer questionnaire in the international lung screen trial Australian cohort.

BACKGROUND: Evaluation of psychosocial consequences of lung cancer screening with LDCT in high-risk populations has generally been performed using generic psychometric instruments. Such generic instruments have low coverage and low power to detect screening impacts. This study aims to validate an established lung cancer screening-specific questionnaire, Consequences Of Screening Lung Cancer (COS-LC), in Australian-English and describe early results from the baseline LDCT round of the International Lung Screen Trial (ILST). METHODS: The Danish-version COS-LC was translated to Australian-English using the double panel method and field tested in Australian-ILST participants to examine content validity. A random sample of 200 participants were used to assess construct validity using Rasch item response theory models. Reliability was assessed using classical test theory. The COS-LC was administered to ILST participants at prespecified timepoints including at enrolment, dependent of screening results. RESULTS: Minor linguistic alterations were made after initial translation of COS-LC to English. The COS-LC demonstrated good content validity and adequate construct validity using psychometric analysis. The four core scales fit the Rasch model, with only minor issues in five non-core scales which resolved with modification. 1129 Australian-ILST participants were included in the analysis, with minimal psychosocial impact observed shortly after baseline LDCT results. CONCLUSION: COS-LC is the first lung cancer screening-specific questionnaire to be validated in Australia and has demonstrated excellent psychometric properties. Early results did not demonstrate significant psychosocial impacts of screening. Longer-term follow-up is awaited and will be particularly pertinent given the announcement of an Australian National Lung Cancer Screening Program. TRIAL REGISTRATION: NCT02871856.

Factors predicting the progression from paroxysmal to persistent atrial fibrillation despite an index catheter ablation.

INTRODUCTION: Despite undergoing an index ablation, some patients progress from paroxysmal atrial fibrillation (PAF) to persistent AF (PersAF), and the mechanism behind this is unclear. The aim of this study was to investigate the predictors of progression to PersAF after catheter ablation in patients with PAF. METHODS: This study included 400 PAF patients who underwent an index ablation between 2015 and 2019. The patients were classified into three groups based on their outcomes: Group 1 (PAF to sinus rhythm, n = 226), Group 2 (PAF to PAF, n = 146), and Group 3 (PAF to PersAF, n = 28). Baseline and procedural characteristics were collected, and predictors for AF recurrence and progression were evaluated. RESULTS: The mean age of the patients was 58.4 ± 11.1 years, with 272 males. After 3 years of follow-up, 7% of the PAF cases recurred and progressed to PersAF despite undergoing an index catheter ablation. In the multivariable analysis, a larger left atrial (LA) diameter and the presence of non-pulmonary vein (PV) triggers during the index procedure independently predicted recurrence. Moreover, a larger LA diameter, the presence of non-PV triggers, and a history of thyroid disease independently predicted AF progression. CONCLUSION: The progression from PAF to PersAF after catheter ablation is associated with a larger LA diameter, history of thyroid disease, and the presence of non-PV triggers. Meticulous preprocedural evaluation, patient selection, and comprehensive provocation tests during catheter ablation are recommended.

Translation and validation of a Chinese version of the body talk scale for women and men.

Body talk has received increasing research attention in recent years, with accumulating evidence supporting the link between body talk and eating and body image disturbances. However, research on body talk in China is still relatively scarce and generally focused on fat talk, especially in women, and much remains unknown about muscle talk and positive body talk for both Chinese women and men. To promote a better understanding of body talk in the Chinese context, the present study adapted the Body Talk Scale (BTS) into Chinese Mandarin (i.e., C-BTS) and evaluated the factor structure and psychometric properties of the C-BTS in Chinese adult women and men. The English version of the BTS was translated into Chinese Mandarin with standard procedures. With 300 Chinese women (Mage = 29.48 years, SD = 7.26) and 300 men (Mage = 29.36 years, SD = 6.81), we examined the factor structure and gender invariance of the C-BTS, as well as internal consistency reliability, test-retest reliability, and construct validity, including convergent, concurrent, and incremental validity of the C-BTS. The results indicated that, consistent with the development study of the BTS, the C-BTS had three subscales (i.e., Negative Fat Talk, Negative Muscle Talk, and Positive Body Talk) and good reliability and validity. The findings demonstrate that the C-BTS can be a useful measure of body talk in both Chinese women and men.

The Body Talk Scale (BTS) measures three types of body talk, including negative fat talk, negative muscle talk, and positive body talk. The present study adapted the English version of the BTS into Chinese Mandarin and examined its psychometric properties in Chinese adult women and men. Results showed that the BTS had adequate reliability and validity in Chinese adults and could be used to assess body talk in Chinese women and men.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for ß-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here we compared combined CRISPR-Cas9 endonuclease editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. We found that combined targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two sgRNAs resulted in superior HbF induction, including in engrafting erythroid cells from sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers. We corroborated prior observations that double strand breaks (DSBs) could produce unintended on- target outcomes in hematopoietic stem and progenitor cells (HSPCs) such as long deletions and centromere-distal chromosome fragment loss. We show these unintended outcomes are a byproduct of cellular proliferation stimulated by ex vivo culture. Editing HSPCs without cytokine culture bypassed long deletion and micronuclei formation while preserving efficient on-target editing and engraftment function. These results indicate that nuclease editing of quiescent hematopoietic stem cells (HSCs) limits DSB genotoxicity while maintaining therapeutic potency and encourages efforts for in vivo delivery of nucleases to HSCs.

Oral Cladribine Impairs Intermediate, but Not Conventional, Monocyte Transmigration in Multiple Sclerosis Patients across a Model Blood-Brain Barrier.

Multiple sclerosis (MS) is a disease in which the immune system damages components of the central nervous system (CNS), leading to the destruction of myelin and the formation of demyelinating plaques. This often occurs in episodic "attacks" precipitated by the transmigration of leukocytes across the blood-brain barrier (BBB), and repeated episodes of demyelination lead to substantial losses of axons within and removed from plaques, ultimately leading to progressive neurological dysfunction. Within leukocyte populations, macrophages and T and B lymphocytes are the predominant effectors. Among current immunotherapies, oral cladribine's impact on lymphocytes is well characterised, but little is known about its impact on other leukocytes such as monocytes and dendritic cells (DCs). The aim of this study was to determine the transmigratory ability of monocyte and DC subsets in healthy subjects and untreated and cladribine-treated relapse-remitting MS (RRMS) patients using a well-characterised model of the BBB. Peripheral blood mononuclear cells from subjects were added to an in vitro transmigration assay to assess cell migration. Our findings show that while prior treatment with oral cladribine inhibits the migration of intermediate monocytes, it has no impact on the transmigration of DC subsets. Overall, our data indicate a previously unrecognised role of cladribine on intermediate monocytes, known to accumulate in the brain active MS lesions.

Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.

An i-motif is a non-canonical DNA structure implicated in gene regulation and linked to cancers. The C-rich strand of the HRAS oncogene, 5'-CGCCCGTGCCCTGCGCCCGCAACCCGA-3' (herein referred to as iHRAS), forms an i-motif in vitro but its exact structure was unknown. HRAS is a member of the RAS proto-oncogene family. About 19 % of US cancer patients carry mutations in RAS genes. We solved the structure of iHRAS at 1.77 Šresolution. The structure reveals that iHRAS folds into a double hairpin. The two double hairpins associate in an antiparallel fashion, forming an i-motif dimer capped by two loops on each end and linked by a connecting region. Six C-C+ base pairs form each i-motif core, and the core regions are extended by a G-G base pair and a cytosine stacking. Extensive canonical and non-canonical base pairing and stacking stabilizes the connecting region and loops. The iHRAS structure is the first atomic resolution structure of an i-motif from a human oncogene. This structure sheds light on i-motifs folding and function in the cell.

Effects of multicomponent exercise training on muscle oxygenation in young and older adults.

Objective: Though multicomponent exercise training was found beneficial in improving the physical functionality, the effects of multicomponent exercise training on muscle oxygenation are still unclear. The purpose of this study was to investigate the effects of multicomponent exercise training on muscle oxygenation in young and older participants. Methods: In this study, 17 young adults (Y) and 18 healthy older adults (E) were recruited to receive a multicomponent exercise training for 12 weeks, 2-3 sessions per week. Muscle oxygenation, muscle strength, and electromyography data were collected and compared pre- and post-training. Muscle oxygen saturation (SpO2) during isometric knee extension tests involving voluntary contraction (VOL) and electrical stimulation (ES) was measured by near-infrared spectroscopy. The SpO2 kinetics in the contraction and recovery phases were calculated using a tangential model to extract ΔSpO2 and inflection time (IF). Results: Muscle strength significantly increased in the post-training (234.31 ± 83.2 N·m, p < 0.05). The post-training ΔSpO2 of the ES in the Y (8.43 ± 5.35%) significantly increased and was higher than that in the E (2.78 ± 3.03%, p < 0.05). In the recovery phase, the post-training IF of VOL (7.07 ± 3.31s) was significantly shorter than that of the pre-training period (8.73 ± 4.46s, p < 0.05). Additionally, the median frequency of electromyography significantly decreased in the post-training period (103.84 ± 21.75 Hz, p < 0.05). Conclusion: The multicomponent exercise training improved the muscle strength, neuromuscular performance, and muscle aerobic function irrespective of age. The primary adaptation of the muscles to the multicomponent exercise training between the two groups varied.

Human genetic diversity alters off-target outcomes of therapeutic gene editing.

CRISPR gene editing holds great promise to modify DNA sequences in somatic cells to treat disease. However, standard computational and biochemical methods to predict off-target potential focus on reference genomes. We developed an efficient tool called CRISPRme that considers single-nucleotide polymorphism (SNP) and indel genetic variants to nominate and prioritize off-target sites. We tested the software with a BCL11A enhancer targeting guide RNA (gRNA) showing promise in clinical trials for sickle cell disease and ß-thalassemia and found that the top candidate off-target is produced by an allele common in African-ancestry populations (MAF 4.5%) that introduces a protospacer adjacent motif (PAM) sequence. We validated that SpCas9 generates strictly allele-specific indels and pericentric inversions in CD34+ hematopoietic stem and progenitor cells (HSPCs), although high-fidelity Cas9 mitigates this off-target. This report illustrates how genetic variants should be considered as modifiers of gene editing outcomes. We expect that variant-aware off-target assessment will become integral to therapeutic genome editing evaluation and provide a powerful approach for comprehensive off-target nomination.

Effects of Resistance Training Intensity on Heart Rate Variability at Rest and in Response to Orthostasis in Middle-Aged and Older Adults.

OBJECTIVE: Aging and deficits related to decreased physical activity can lead to higher risks of autonomic nervous system (ANS) dysfunction. The aim of this study was to evaluate the effects of 24 weeks of resistance training (RT) at various intensities on hemodynamics as well as heart rate variability (HRV) at rest and in response to orthostatic tests in middle-aged and older adults. METHODS: Forty adults were randomized into three groups: high-intensity (HEX) (80% 1-RM) (11 female, 4 male; 60 ± 4 years); low-moderate-intensity (LEX) (50% 1-RM) (nine female, four male; 61 ± 5 years); and a control group (CON) (eight female, four male; 60 ± 4 years). The RT program consisted of nine exercises, with two sets performed of each exercise two times per week for 24 weeks. Data collected included 1-RM, heart rate, and blood pressure and HRV at rest and in response to orthostasis. RESULTS: Both the HEX (42-94%) and LEX (31.3-51.7%) groups showed increases in 1-RM (p < 0.01). The HEX group showed decreases in resting heart rate (-4.0%), diastolic blood pressure (-3.2 mmHg (-4.2%)), and low frequency/high frequency (LF/HF) (Ln ratio) (p < 0.05). Post-study, the HEX group had higher HF (Ln ms2) than the CON, adjusted for pre-study value and age (p < 0.05). Post-study, the supine-standing ratio (SSR) of LFn (normalized unit) in the HEX group was greater than that in the LEX and CON groups, while the SSR of LF/HF in the HEX group was greater than the CON (p < 0.05). In conclusion, high-intensity RT can improve resting heart rate and HRV by enhancing cardiac vagal control. High-intensity RT might also improve the orthostatic response in terms of HRV. High intensity RT might assist ANS modification and could perhaps decrease the risks of cardiovascular disease and orthostatic intolerance.

Psychometric Validation of Senior Perceived Physical Literacy Instrument.

Aim: To validate the Senior Perceived Physical Literacy Instrument (SPPLI). Methods: In the pilot study, we refined the Perceived Physical Literacy Instrument (PPLI, Cronbach's α = 0.94, initially designed for adults) into SPPLI using internal reliability, content validity, and construct validity results. A total of 341 older adults recruited from community centers in Southern Taiwan participated in the study. A principle component analysis (PCA) identified three components of SPPLI. Results: Eleven items were captured from the 18-item PPLI as the SPPLI (Cronbach's α = 0.90). SPPLI exhibits three components: attitude toward physical activity, physical activity ability, and sociality around physical activity. Significant differences were discovered in physical activity ability by educational attainment (p < 0.05) and in all three components by stage of exercise (maintenance vs. non-maintenance) (p < 0.05). The SPPLI possesses proper reliability and validity to assess physical literacy among older adults. Conclusions: This instrument is suggested for physical literacy assessments in physical activity programs to assess the needs of older adults and/or the effectiveness of an intervention program that aims to improve the attitude, ability, and sociality of physical activity.

Operationally defining physical literacy in Chinese culture: Results of a meta-narrative synthesis and the Panel's recommendations.

Purpose: The definition of physical literacy (PL) needs to be explored by researchers from educational, public health, and sports organisations in Chinese culture; an adequate definition and theoretical framework of PL can then be embraced within different contexts and according to cultural influences. Methods: This meta-narrative synthesis of literature in this area included a series of planning, search, mapping, appraisal, synthesis, and recommendation phases. The literature was translated into English and circulated among international experts to seek suggestions. A total of 74 articles were included in the PL definition synthesis and 28 were included for philosophical synthesis in this study. Results: Based on three rounds of discussions, the final agreement was reached among panel members regarding the defining statements and practical and theoretical models of PL in Chinese culture. According to consensus, PL is the integration of physical, perceptual, cognitive, psychological, and behavioural capabilities, echoing with the need for an active, healthy, and fulfilling lifestyle, which involves continuous positive interactions with the environment and embodied engagement in physical activities for life. The framework addressed five domains (physical, sensory-perceptual, cognitive, psychological, and behavioural) and one important overlapping factor (dynamic environment). A further explanation was provided in the defining statement to assist in understanding the concept. Conclusion: It is suggested that the cultural interpretation and historical background of PL in Chinese discourse should be addressed and respected. The development of a specific cultural definition statement of PL in one country could provide implications for PL researchers worldwide.

Application of dynamic display technology to identify gaps after pulmonary vein isolation in catheter ablation of atrial fibrillation.

BACKGROUND: The identification of post pulmonary vein isolation (PVI) gaps by activation and voltage maps is time-consuming. This study aimed to investigate the characteristics, efficiency and accuracy of LiveView dynamic display module (EnSite™ Dynamic Display; Abbott, Abbott Park, IL, USA) in unmasking post PVI gaps and conduction block line. METHOD: Twenty four patients with paroxysmal atrial fibrillation (PAF) who failed to achieve first-pass PVI or with recurrent PAF were enrolled. Ninety-six pulmonary veins (PVs) were evaluated, and gaps were identified in 25 (26.0%) PVs. The gap location was confirmed by activation and propagation maps; 110 frames on gaps and 118 frames on block lines were analyzed by using LiveView module. We defined isochronal crowding in the local activation time (LAT) mode as three colors between two adjacent electrodes. Each frame was classified as with or without isochronal crowding in LAT mode and one/continuous color or isochronal discontinuity in reentrant mode. The gray color inside the PVs was considered to represent conduction block. RESULT: The isochronal crowding could be found on both gap and block line in LAT mode, whereas isochronal discontinuity only presented on the block line in reentrant mode. The sensitivity and specificity of isochronal discontinuity or gray color in reentrant mode to identify block line were 61.0% and 100%, respectively. The sensitivity and specificity of isochronal crowding or gray color in LAT mode to identify block line were 71.2% and 71.8%, respectively. CONCLUSION: Reentrant mode in LiveView module is very specific in identifying block lines. We proposed an efficient, practical algorithm to differentiate the block line from PV gaps.

Application of Ensite™ LiveView function for identification of scar-related ventricular tachycardia isthmus.

INTRODUCTION: Dynamic display of real-time wavefront activation pattern may facilitate the recognition of reentrant circuits, particularly the diastolic path of ventricular tachycardia (VT). OBJECTIVE: We aimed to evaluate the feasibility of LiveView Dynamic Display for mapping the critical isthmus of scar-related reentrant VT. METHODS: Patients with mappable scar-related reentrant VT were selected. The characteristics of the underlying substrates and VT circuits were assessed using HD grid multielectrode catheter. The VT isthmuses were identified based on the activation map, entrainment, and ablation results. The accuracy of the LiveView findings in detecting potential VT isthmus was assessed. RESULTS: We studied 18 scar-related reentrant VTs in 10 patients (median age: 59.5 years, 100% male) including 6 and 4 patients with ischemic and nonischemic cardiomyopathy, respectively. The median VT cycle length was 426 ms (interquartile range: 386-466 ms). Among 590 regional mapping displays, 92.0% of the VT isthmus sites were identified by LiveView Dynamic Display. The accuracy of LiveView for isthmus identification was 84%, with positive and negative predictive values of 54.8% and 97.8%, respectively. The area with abnormal electrograms was negatively correlated with the accuracy of LiveView Dynamic Display (r = -.506, p = .027). The median time interval to identify a VT isthmus using LiveView was significantly shorter than that using conventional activation maps (50.5 [29.8-120] vs. 219 [157.5-400.8] s, p = .015). CONCLUSION: This study demonstrated the feasibility of LiveView Dynamic Display in identifying the critical isthmus of scar-related VT with modest accuracy.

How effective are campus-wide smoking bans? A comparison of two small colleges.

Objective The current study tracked attitudinal and behavioral changes related to a campus-wide smoking ban. Participants: Students from 2 colleges in Massachusetts (N = 418; April 2014; N = 640 April 2018). Methods: Surveys tracked students' smoking habits, beliefs about smoking, and attitudes before and four years after the implementation of a campus-wide smoking ban. Results: While student smoking rates and secondhand exposure did drop following the campus-wide ban, they did not drop at a significantly higher rate than the control. However, attitudes toward smoking, perceived smoking, and attitudes toward a campus-wide smoking ban did improve at rates significantly above any improvements shown at the control campus. Conclusions: Campus-wide smoking bans may lower the frequency of smoking on small college campuses, but not necessarily more than other smoking cessation efforts. They do appear to uniquely influence general attitudes and the visibility of smoking on campus.

Predictors of COVID-19 vaccine intentions in the United States: the role of psychosocial health constructs and demographic factors.

BACKGROUND: On December 21, 2020, a study was conducted to investigate a range of psychosocial health constructs and demographic variables potentially associated with intentions toward accepting or forgoing the coronavirus (COVID-19) vaccine. PURPOSE: The goal of the study was to identify predictors of forgoing COVID-19 vaccination at the time of the initial rollout. METHODS: A cross-sectional, representative online survey of 350 U.S. residents was conducted using the online crowdsourcing site Prolific to assess vaccine intentions, health attitudes, and demographic information. Variables examined included demographic factors and health constructs corresponding to each of the elements of the health belief model (perceived severity, susceptibility, benefits, barriers, and cues to action), the theory of planned behavior (attitudes, subjective norms, and perceived behavioral control), attitudes toward vaccines in general, and trust in the COVID-19 vaccine approval process. RESULTS: After using hierarchical linear regression to control for demographics, the health constructs uniquely associated with the likelihood to forgo vaccination were perceived barriers, general attitudes toward the COVID-19 vaccine, subjective norms, and trust in the vaccine approval process. Significant demographic predictors of vaccine reluctance included being female, politically conservative, and more religious. CONCLUSIONS: The current research identified three demographic factors and four health constructs uniquely associated with vaccine acceptance. These findings reveal that the constructs contained within the health belief model and theory of planned behavior can be used to predict COVID-19 vaccination intentions, and can be supplemented with an assessment of general vaccine attitudes and attitudes toward the vaccine approval process.

Measuring positive and negative body talk in men and women: The development and validation of the Body Talk Scale.

Research suggests that positive and negative body talk are important factors in people's body image, however, the instruments designed to measure body talk are generally designed for use with a specific gender and primarily measure negative body talk. To address the shortcomings in the existing measures, the Body Talk Scale (BTS) was designed to measure both positive and negative body talk in men and women. The current study examines the development and psychometric properties of this new scale in two samples of adults, both including men and women. Study 1 focused on the development and examined the factor structure of the original scale items. Study 2 confirmed the factor structure and examined the concurrent validity, incremental validity, test-retest reliability of the scale, and also gender differences. The results indicated that the BTS is a 14-item scale that contains three subscales (Negative Fat Talk, Negative Muscle Talk, and Positive Body Talk) and demonstrates good concurrent validity, incremental validity, and test-retest reliability. Gender comparisons on all three subscales indicated that men engage in more positive body talk than women. The findings demonstrate that the BTS is a useful measure of positive and negative body talk in both men and women.

The myocardial phenotype of Fabry disease pre-hypertrophy and pre-detectable storage.

AIMS: Cardiac involvement in Fabry disease (FD) occurs prior to left ventricular hypertrophy (LVH) and is characterized by low myocardial native T1 with sphingolipid storage reflected by cardiovascular magnetic resonance (CMR) and electrocardiogram (ECG) changes. We hypothesize that a pre-storage myocardial phenotype might occur even earlier, prior to T1 lowering. METHODS AND RESULTS: FD patients and age-, sex-, and heart rate-matched healthy controls underwent same-day ECG with advanced analysis and multiparametric CMR [cines, global longitudinal strain (GLS), T1 and T2 mapping, stress perfusion (myocardial blood flow, MBF), and late gadolinium enhancement (LGE)]. One hundred and fourteen Fabry patients (46 ± 13 years, 61% female) and 76 controls (49 ± 15 years, 50% female) were included. In pre-LVH FD (n = 72, 63%), a low T1 (n = 32/72, 44%) was associated with a constellation of ECG and functional abnormalities compared to normal T1 FD patients and controls. However, pre-LVH FD with normal T1 (n = 40/72, 56%) also had abnormalities compared to controls: reduced GLS (-18 ± 2 vs. -20 ± 2%, P < 0.001), microvascular changes (lower MBF 2.5 ± 0.7 vs. 3.0 ± 0.8 mL/g/min, P = 0.028), subtle T2 elevation (50 ± 4 vs. 48 ± 2 ms, P = 0.027), and limited LGE (%LGE 0.3 ± 1.1 vs. 0%, P = 0.004). ECG abnormalities included shorter P-wave duration (88 ± 12 vs. 94 ± 15 ms, P = 0.010) and T-wave peak time (Tonset - Tpeak; 104 ± 28 vs. 115 ± 20 ms, P = 0.015), resulting in a more symmetric T wave with lower T-wave time ratio (Tonset - Tpeak)/(Tpeak - Tend) (1.5 ± 0.4 vs. 1.8 ± 0.4, P < 0.001) compared to controls. CONCLUSION: FD has a measurable myocardial phenotype pre-LVH and pre-detectable myocyte storage with microvascular dysfunction, subtly impaired GLS and altered atrial depolarization and ventricular repolarization intervals.