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Patients with chronic coronary syndrome (CCS), even when they have complete revascularization and normal left ventricular (LV) systolic function, experience subsequent cardiovascular disease (CVD), highlighting the importance of surrogate markers to prevent adverse consequences. Speckle-tracking echocardiography-derived left atrial (LA) reservoir strain has emerged as a sensitive marker for CVD in various clinical settings. The present study investigated the prevalence, determinants, and prognostic value of LA dysfunction in CCS. We included 278 consecutive patients with CCS with completed percutaneous coronary intervention and preserved LV ejection fraction who underwent follow-up echocardiography. Speckle-tracking analysis was performed to assess LA reservoir strain, and LA dysfunction was defined as LA reservoir strain ≤24%. The primary outcome comprised new-onset atrial fibrillation, heart failure hospitalization, acute coronary syndrome, stroke, or all-cause death. At baseline, 28 patients (10.1%) had LA dysfunction. Multivariable analysis identified age, hypertension, LV ejection fraction, and multivessel disease as independent determinants of LA reservoir strain (all p0.05). During a median follow-up of 4.8 years, the primary outcome occurred in 60 patients (21.6%). LA dysfunction carried a significant risk for primary outcome independent of traditional risk factors, LV parameters, and LA size (adjusted hazard ratio 3.10, p = 0.003); the risk increase remained significant even after excluding atrial fibrillation from the primary outcome (adjusted hazard ratio 2.27, p = 0.043). In conclusion, approximately 10% of patients with CCS with normal LV ejection fraction had LA dysfunction associated with adverse cardiovascular outcomes. Further studies are needed to explore whether therapeutic interventions affecting LA remodeling may help prevent CVD events.

Aims Aortic valve sclerosis (AVS) without haemodynamically significant obstruction is related to cardiovascular morbidity and mortality independent of left ventricular (LV) hypertrophy, although the underlying mechanisms remain unknown. This study investigated the prevalence of AVS and its association with subclinical LV systolic and diastolic dysfunction in individuals with normal LV geometry free of cardiovascular disease. Methods and results We examined 962 participants with normal LV geometry and free from significant AV stenosis who underwent standard and speckle-tracking echocardiography. AVS was categorized into four groups as follows: no AVS, AV thickening, calcification on one leaflet, and calcification on ≥2 leaflets. Among the 962 participants, 767 (79.7%) individuals were classified as no AVS, 74 (7.7%) as AV thickening, 87 (9.0%) as calcification on one leaflet, and 34 (3.5%) as calcification on ≥2 leaflets. The prevalence of subclinical LV diastolic dysfunction (E/e′ ratio ≥13) and systolic dysfunction [LV global longitudinal strain (GLS) > −17.0% for men and > −18.0% for women] were greater in AVS groups than those in no AVS group. Subclinical LV diastolic impairment was evident from AV thickening and systolic dysfunction was observed at AV calcification. Multivariable logistic regression analysis demonstrated that AV thickening as well as calcification were independently associated with subclinical LV diastolic impairment (all P < 0.05), while only AV calcification on ≥2 leaflets conferred significant increased risk of impaired LVGLS. Conclusion AVS was observed in approximately 20% individuals without cardiac disease and was associated with subclinical LV diastolic and systolic function even in the absence of LV morphological change.

Arterial structural and functional remodeling is recognized as a key determinant of incident heart failure, although the contribution of arterial properties on left ventricular (LV) remodeling is not fully studied. Aortic dilatation is an early manifestation of arterial remodeling and estimated pulse wave velocity (ePWV) is emerging as a simple measure of arterial stiffness. This study aimed to characterize the association of aortic size and ePWV with LV morphology and function.The study cohort consisted of 539 participants without overt cardiac disease who underwent extensive cardiovascular examination. Aortic root diameter was measured by two-dimensional echocardiography and ePWV was calculated from a regression equation using age and mean blood pressure. LV global longitudinal strain (LVGLS) was obtained by speckle-tracking echocardiography.Aortic root diameter and ePWV were correlated with LV mass index and LVGLS, while only ePWV was related to E / e' ratio. In multivariable analysis, aortic root diameter and ePWV were significantly related to LV mass index and LVGLS (all P 0.05), and the association of aortic root size and ePWV with LVGLS was independent of LV mass index and E / e' ratio. Individuals with both aortic root enlargement and increased ePWV had significantly larger LV mass index and reduced LVGLS compared with those either or those with normal aortic size and ePWV (both P 0.05).Aortic root size and ePWV were independently associated with unfavorable LV remodeling in individuals free of cardiac disease, which might provide useful information into the pathogenesis-linking arterial remodeling and heart failure.

Valvular heart disease is an important contributor to cardiovascular morbidity and mortality and remains underdiagnosed. Deep learning analysis of electrocardiography (ECG) may be useful in detecting aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR).This study aimed to develop ECG deep learning algorithms to identify moderate or severe AS, AR, and MR alone and in combination.A total of 77,163 patients undergoing ECG within 1 year before echocardiography from 2005-2021 were identified and split into train (n = 43,165), validation (n = 12,950), and test sets (n = 21,048; 7.8% with any of AS, AR, or MR). Model performance was assessed using area under the receiver-operating characteristic (AU-ROC) and precision-recall curves. Outside validation was conducted on an independent data set. Test accuracy was modeled using different disease prevalence levels to simulate screening efficacy using the deep learning model.The deep learning algorithm model accuracy was as follows: AS (AU-ROC: 0.88), AR (AU-ROC: 0.77), MR (AU-ROC: 0.83), and any of AS, AR, or MR (AU-ROC: 0.84; sensitivity 78%, specificity 73%) with similar accuracy in external validation. In screening program modeling, test characteristics were dependent on underlying prevalence and selected sensitivity levels. At a prevalence of 7.8%, the positive and negative predictive values were 20% and 97.6%, respectively.Deep learning analysis of the ECG can accurately detect AS, AR, and MR in this multicenter cohort and may serve as the basis for the development of a valvular heart disease screening program.

Aims Heart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort. Methods and results Two-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>−14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation [hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47–4.92; P = 0.001]. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51–8.43; P = 0.004) but not other subtypes. Conclusion LV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain–heart interaction and may help improve stroke primary prevention strategies.

The impact of blood pressure (BP) levels on subclinical left ventricular (LV) dysfunction and possible sex-specific difference remains unclarified. This study investigated the relationship between BP categories given in the new 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and subclinical LV dysfunction in subjects free of cardiac disease.We examined antihypertensive medication-naive 858 individuals who underwent extensive cardiovascular health check-up. LV global longitudinal (LVGLS) and circumferential strain (LVGCS) were assessed by two-dimensional speckle-tracking echocardiography. Participants were categorized into four groups: normal BP, elevated BP, isolated diastolic hypertension (IDH), and systolic hypertension (SH). Among the 858 participants, 422 individuals had normal BP, 113 had elevated BP, 160 had IDH, and 163 had SH. Prevalence of abnormal LVGLS (-18.6%) was greatest in SH (19.0%), followed by IDH (17.5%), elevated BP (14.2%), and normal BP (7.1%, P 0.001); no significant differences were observed for LVGCS (P = 0.671). In the multivariable analyses, IDH and SH were associated with impaired LVGLS [adjusted odds ratio (OR) 2.69 and 2.66, P 0.001], and borderline significance was observed for elevated BP (adjusted OR 1.90, P = 0.060); there was no significant association between any of the BP groups and LVGCS. In sex-stratified analysis, IDH and SH carried the significant risk of abnormal LVGLS in both sexes, while elevated BP was associated with LVGLS only in women.Isolated diastolic hypertension and SH redefined by ACC/AHA guideline carried significant risk for LVGLS, but not LVGCS. Elevated BP was associated with LVGLS only in women. Our findings provide information on cardiac correlates of the newly established BP categories.

Aims There is limited information on the association between left ventricular (LV) dimensions and cardiovascular (CV) outcomes in patients with heart failure (HF) with reduced LV ejection fraction (HFrEF) receiving recommended HF treatment. We investigated the association between LV dimensions and CV outcomes in HFrEF patients receiving recommended HF treatment. Methods and results We investigated the association between LV echocardiographic dimensions and CV outcomes using conventional Cox models in 1138 HFrEF patients in sinus rhythm randomized to warfarin or aspirin treatment in the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. LV enlargement, whether by diameter [LV end‐diastolic diameter index (LVEDDI) and LV end‐systolic diameter index (LVESDI)] or volume [LV end‐diastolic volume index (LVEDVI) and LV end‐systolic volume index (LVESVI)], was independently associated with all‐cause death [LVEDDI: hazard ratio (HR) per cm/m2 1.53, LVESDI: HR per cm/m2 1.65, LVEDVI: HR per 10 mL/m2 1.07, and LVESVI: HR per 10 mL/m2 1.10; all P values

Volatiles from herbivore-infested plants function as a chemical warning of future herbivory for neighboring plants. (Z)-3-Hexenol emitted from tomato plants infested by common cutworms is taken up by uninfested plants and converted to (Z)-3-hexenyl β-vicianoside (HexVic). Here we show that a wild tomato species (Solanum pennellii) shows limited HexVic accumulation compared to a domesticated tomato species (Solanum lycopersicum) after (Z)-3-hexenol exposure. Common cutworms grow better on an introgression line containing an S. pennellii chromosome 11 segment that impairs HexVic accumulation, suggesting that (Z)-3-hexenol diglycosylation is involved in the defense of tomato against herbivory. We finally reveal that HexVic accumulation is genetically associated with a uridine diphosphate-glycosyltransferase (UGT) gene cluster that harbors UGT91R1 on chromosome 11. Biochemical and transgenic analyses of UGT91R1 show that it preferentially catalyzes (Z)-3-hexenyl β-D-glucopyranoside arabinosylation to produce HexVic in planta., 植物間コミュニケーションの仕組みを解明 --受容した香りを防御物質に変える遺伝子発見--. 京都大学プレスリリース. 2023-02-28.

AimsPatients with chronic coronary syndrome (CCS) suffer from subsequent cardiovascular events, even after complete revascularization; thus, elucidation of the underlying pathophysiological mechanisms is required. Epicardial adipose tissue (EAT) is increasingly recognized as a metabolically active organ with a key role in the pathogenesis of metabolic-related cardiac diseases. The present study investigated the association between EAT burden and left heart remodelling in patients with CCS.Methods and resultsWe studied 267 CCS patients (210 men; 71 ± 9 years) with complete revascularization and normal left ventricular (LV) ejection fraction who underwent follow-up echocardiography. All patients underwent the measurement of EAT thickness and speckle-tracking analysis to evaluate LV global longitudinal strain (LVGLS) and left atrial (LA) phasic strain. The mean EAT thickness was 5.0 ± 1.8 mm. Age, sex, body mass index, and diabetes mellitus were independently associated with EAT thickness (all P < 0.05). Multivariable linear regression analysis demonstrated that EAT thickness was significantly associated with LV mass index, early diastolic mitral annular velocity, and LA conduit strain independent of age, sex, and cardiovascular risk factors (all P < 0.05). On the other hand, there was no relationship between EAT thickness and LV systolic parameters including LV ejection fraction and LVGLS.ConclusionCCS patients with increased EAT thickness had unfavourable left heart remodelling. The assessment of EAT thickness by echocardiography may have clinical utility as a simple surrogate to aid in risk stratification for impaired left heart function in CCS patients.

UNSTRUCTURED Introduction Atrial fibrillation (AF) and heart failure (HF) commonly coexist due to shared pathophysiological mechanisms. Prompt identification of patients with HF at risk of developing AF would allow clinicians the opportunity to implement appropriate monitoring strategy and timely treatment, reducing the impact of AF on patient’s health. Methods Four machine learning (ML) models combined with logistic regression and cluster analysis were applied to patient level data from the Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial to identify factors which predict development of AF in patients with HF. Out of the (n = 2219) patients included for analysis, (n = 215, 9.7%) presented AF as an adjudicated adverse event during the 6 years (mean [±SD], 3.5±1.8) follow up period. Results Logistic regression applied to patients of a white racial ethnicity shows that white divorced patients have a 1.75-fold higher risk of AF than white patients reporting other marital statuses (95% CI 1.19–2.57, p-value = 0.002). By contrast, similar analysis for the non-white racial ethnicity patients suggests that non-white patients who live alone have a 2.58-fold higher risk of AF than those not living alone (95% CI 1.45–4.59, p-value < 0.001). ML analysis also identified “marital status” and “line alone” as relevant predictors of AF. Apart from previously well-recognised factors (e.g., age, heart failure), the ML algorithms and cluster analysis identified 2 clearly distinct clusters, namely white and non-white ethnicities. This should serve as reminder of the impact of social factors on health. The findings indicate the need to explore the impact of social factors on the under-represented non-white ethnicity group of patients and the potential impact that social interventions, or the lack thereof, have on them. Conclusion The use of ML can prove useful in identifying novel cardiac risk factors. Our analysis has highlighted that “social factors”, such as living alone, may disproportionately increase the risk of AF in the under-represented non-white patient group with HF. The study also highlights the need for more studies focusing on stratification of multiracial cohorts to better uncover the heterogeneity of AF mechanisms across different racial groups.

BACKGROUND: Prolonged monitoring of cardiac rhythm has been used to screen for subclinical atrial fibrillation (AF); little is known about other arrhythmias in the general population, especially in the elderly, who are at higher risk of arrhythmias. METHODS: We evaluated the frequency of arrhythmias in the tri-ethnic (white, Black, Hispanic), community-based Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study using a patch-based recorder for up to 14 days in 527 participants free of AF, congestive heart failure (CHF) or history of stroke. Differences according to gender, age, ethnicity and presence of hypertension, diabetes and pertinent ECG and echocardiographic variables were examined. RESULTS: Mean age was 77.2±6.8 years (37.2% men, 62.8% women). AF was present in 10 participants (1.9%), only 2 of them symptomatic. Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) episodes were observed in 84.4% and 25.0% but only 13.5% and 10.6% of participants reported symptoms, respectively. Severe bradycardia (75 years; ventricular arrhythmias and severe bradycardia were more common in men. Whites had significantly more episodes of AF than Hispanics, SVT than Blacks and VT≥10 beats than Hispanics and Blacks. Hypertensives had more episodes of severe bradycardia. LV hypertrophy or LVEF

Although higher body mass index (BMI) is associated with adverse left ventricular morphology and functional remodeling, its possible association with right ventricular (RV) dysfunction has not been extensively evaluated. RV free wall longitudinal strain (RVLS) is emerging as an important tool to detect early RV dysfunction. This study aimed to investigate the independent effect of increased BMI on RVLS in a large sample of the general population without overt cardiac disease. We examined 1,085 participants (603 men, mean age 62 years) who voluntarily underwent an extensive cardiovascular health check-up. This included laboratory tests and speckle-tracking echocardiography to assess RVLS. The association between BMI and RVLS was determined by logistic regression analyses. The prevalence of abnormal RVLS (-19.2%) was greatest in obese individuals (29.7%), followed by overweight (16.3%), and normal weight (10.6%, p0.001). In multivariable analyses, BMI was significantly associated with abnormal RVLS (adjusted odds ratio [OR] = 1.07 per 1 kg/m

Aims This study aimed to investigate the impact of baseline 6 min walk test distance (6MWTD) on time to major cardiovascular (CV) events in heart failure with reduced ejection fraction (HFrEF) and its impact in clinically relevant subgroups. Methods and results In the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial, 6MWTD at baseline was available in 2102 HFrEF patients. Median follow‐up was 3.4 years. All‐cause death and heart failure hospitalization (HFH) exhibited a significant non‐linear relationship with 6MWTD (P = 0.023 and 0.032, respectively), whereas a significant association between 6MWTD and CV death was shown in a linear model [hazard ratio (HR) per 10 m increase, 0.989; P = 0.011]. In linear splines with the best cut‐off point at 200 m, the positive effect of a longer 6MWTD on all‐cause death and HFH was only observed for 6MWTD > 200 m (HR per 10 m increase, 0.987; P = 0.0036 and 0.986; P = 0.0022, respectively). The associations between 6MWTD and CV outcomes were consistent across clinical subgroups; for age, a significant relationship between 6MWTD and HFH was observed in patients ≥60 years (HR per 10 m increase, 0.98; P

Aortic valve sclerosis (AVS) without hemodynamically significant obstruction is related to cardiovascular morbidity and mortality independent of left ventricular (LV) hypertrophy, although the underlying mechanisms remain unknown. This study investigated the prevalence of AVS and its association with subclinical LV systolic and diastolic dysfunction in individuals with normal LV geometry free of cardiovascular disease.We examined 962 participants with normal LV geometry and free from significant AV stenosis who underwent standard and speckle-tracking echocardiography. AVS was categorized into 4 groups as follows: no AVS, AV thickening, calcification on one leaflet and calcification on ≥2 leaflets.Among the 962 participants, 767 (79.7%) individuals were classified as no AVS, 74 (7.7%) as AV thickening, 87 (9.0%) as calcification on one leaflet, and 34 (3.5%) as calcification on ≥2 leaflets. The prevalence of subclinical LV diastolic dysfunction (E/e' ratio ≥13) and systolic dysfunction (LV global longitudinal strain (GLS) -17.0% for men and -18.0% for women) were greater in AVS groups than those in no AVS group. Subclinical LV diastolic impairment was evident from AV thickening and systolic dysfunction was observed at AV calcification. Multivariable logistic regression analysis demonstrated that AV thickening as well as calcification were independently associated with subclinical LV diastolic impairment (all p 0.05), while only AV calcification on ≥2 leaflets conferred significant increased risk of impaired LVGLS.AVS was observed in approximately 20% individuals without cardiac disease and was associated with subclinical LV diastolic and systolic function even in the absence of LV morphological change.We investigated the prevalence of aortic valve sclerosis (AVS) and its association with subclinical left ventricular (LV) systolic and diastolic dysfunction in 962individuals with normal LV geometry free of cardiac disease. In this study population, AVS characterized by thickening or calcification was present in 20% of individuals. Subclinical LV diastolic dysfunction appeared from AV thickening and systolic dysfunction by LV global longitudinal strain was observed at calcification on ≥2 leaflets; these associations were independent of age, sex and cardiovascular risk factors.

Purpose Although subclinical hypothyroidism (SCH) is a common clinical entity and carries independent risk for incident heart failure (HF), its possible association with subclinical cardiac dysfunction is unclear. Left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic strain can unmask subclinical left heart abnormalities and are excellent predictors for HF. This study aimed to investigate the association between the presence of SCH and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease. Methods We examined 1078 participants who voluntarily underwent extensive cardiovascular health check-ups, including laboratory tests and 2-dimensional speckle-tracking echocardiography to assess LVGLS and LA reservoir, conduit, and pump strain. SCH was defined as an elevated serum thyroid-stimulating hormone level with normal concentration of free thyroxine. Results Mean age was 62 ± 12 years, and 56% were men. Seventy-eight (7.2%) participants exhibited SCH. Individuals with SCH had significantly reduced LA reservoir (37.1 ± 6.6% vs 39.1 ± 6.6%; P = 0.011) and conduit strain (17.3 ± 6.3% vs 19.3 ± 6.6%; P = 0.012) compared with those with euthyroidism, whereas there was no significant difference in left ventricular ejection fraction, LA volume index, LVGLS, and LA pump strain between the 2 groups. In multivariable analyses, SCH remained associated with impaired LA reservoir strain, independent of age, traditional cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters. including LVGLS (standardized β −0.054; P = 0.032). Conclusions In an unselected community-based cohort, individuals with SCH had significantly impaired LA phasic function. This association may be involved in the higher incidence of HF in subjects with SCH.

Objectives Recently, more sophisticated blood pressure (BP) measurements, such as central and ambulatory BP (ABP), have proven to be stronger predictors of future cardiovascular disease than conventional office BP. Their predictive value for atrial fibrillation development is not established. We investigated the prognostic impact for incident atrial fibrillation of office, central and ambulatory BP measurements in a predominantly older population-based cohort. Methods Of 1004 participants in the Cardiovascular Abnormalities and Brain Lesions (CABL) study, 769 in sinus rhythm with no history of atrial fibrillation or stroke (mean age 70.5 years) underwent ABP and arterial wave reflection analysis for central BP determination. Fine and Gray's proportional subdistribution hazards models were used to assess the association of BP parameters with incident atrial fibrillation. Results During 9.5 years, atrial fibrillation occurred in 83 participants. No office BP variable showed a significant association with incident atrial fibrillation. Central SBP and central pulse pressure were marginally associated with incident atrial fibrillation in multivariate analysis. Among ABP variables, 24-h SBP [adjusted hazard ratio per 10 mmHg, 1.24; 95% confidence interval (CI) 1.07--1.44; P = 0.004], daytime SBP (adjusted hazard ratio per 10 mmHg, 1.21; 95% CI 1.04--1.40; P = 0.011) and night-time SBP (adjusted hazard ratio per 10 mmHg, 1.22; 95% CI 1.07--1.39; P = 0.002) were significantly associated with incident atrial fibillation. Conclusion In a predominantly older, stroke-free community-based cohort, ABP was a better independent predictor of incident atrial fibrillation than central BP, whereas office BP was inadequate for this purpose.

Background Mitochondrial permeability transition pore (mPTP) closure triggers cardiomyocyte differentiation during development while pathological opening causes cell death during myocardial ischemia-reperfusion and heart failure. Ubiquinone modulates the mPTP; however, little is known about its mechanistic role in health and disease. We previously found excessive proton leak in newborn Fmr1 KO mouse forebrain caused by ubiquinone deficiency and increased open mPTP probability. Because of the physiological differences between the heart and brain during maturation, we hypothesized that developing Fmr1 KO cardiomyocyte mitochondria would demonstrate dissimilar features. Methods Newborn male Fmr1 KO mice and controls were assessed. Respiratory chain enzyme activity, ubiquinone content, proton leak, and oxygen consumption were measured in cardiomyocyte mitochondria. Cardiac function was evaluated via echocardiography. Results In contrast to controls, Fmr1 KO cardiomyocyte mitochondria demonstrated increased ubiquinone content and decreased proton leak. Leak was cyclosporine (CsA)-sensitive in controls and CsA-insensitive in Fmr1 KOs. There was no difference in absolute mitochondrial respiration or cardiac function between strains. Conclusion These findings establish the newborn Fmr1 KO mouse as a novel model of excess ubiquinone and closed mPTP in the developing heart. Such a model may help provide insight into the biology of cardiac development and pathophysiology of neonatal heart failure. Impact Ubiquinone is in excess and the mPTP is closed in the developing FXS heart. Strengthens evidence of open mPTP probability in the normally developing postnatal murine heart and provides new evidence for premature closure of the mPTP in Fmr1 mutants. Establishes a novel model of excess CoQ and a closed pore in the developing heart. Such a model will be a valuable tool used to better understand the role of ubiquinone and the mPTP in the neonatal heart in health and disease.

Background Although carotid intima-media thickness (IMT) is an established marker of atherosclerosis and carries independent risk for cardiovascular disease, its possible association with subclinical cardiac dysfunction has not been extensively evaluated. Left ventricular global longitudinal strain (LVGLS) and peak left atrial longitudinal systolic strain (PALS) can detect subclinical left heart dysfunction. Purpose This study aimed to investigate the association between carotid IMT and subclinical left heart dysfunction in a large sample of the general population without overt cardiac disease. Methods We examined 1,161 participants who underwent extensive cardiovascular examination. Ultrasonography of common carotid artery was performed for the measurement of maximal carotid IMT. LVGLS and PALS were assessed by 2-dimensional speckle-tracking echocardiography. Results Mean age was 62±12 years, and 56% were male. The prevalence of abnormal LVGLS (>−18.6%) and PALS ( Conclusion Participants with increased IMT had significantly impaired LV and LA function in an unselected community-based cohort. This association may be involved in the higher incidence of cardiovascular disease in individuals with increased carotid IMT. Funding Acknowledgement Type of funding source: None

Background Increased arterial stiffness has been proposed as one of the key mechanisms of incident heart failure with preserved ejection fraction (HFpEF). However, the possible association between arterial stiffness and subclinical left ventricular (LV) dysfunction and possible sex-specific differences remain unclarified. LV strain is emerging as a highly sensitive tool to unmask early LV abnormalities. Purpose We investigated whether increased arterial stiffness is independently associated with subclinical LV dysfunction in a large community-based cohort without overt cardiovascular disease. Methods We examined 1,155 participants who underwent extensive cardiovascular examination. Speckle-tracking echocardiography was employed to assess LV global longitudinal strain (LVGLS) and circumferential strain (GCS), and arterial stiffness was assessed by cardio-ankle vascular index (CAVI). Results Mean age was 62±12 years, and 56% were male. CAVI as continuous variable was associated with abnormal LVGLS (>−18.6%), independent of cardiovascular risk factors and pertinent laboratory and echocardiographic parameters (adjusted odds ratio [OR] 1.23, p=0.034), whereas there was no relationship with LVGCS. In sex-stratified analysis, more pronounced association between quartiles of CAVI and abnormal LVGLS was observed in women than in men (unadjusted OR = 6.43 in women and 2.46 in men for upper quartile vs. lower quartile, both p Conclusion Increased arterial stiffness was independently associated with decreased LVGLS even in the absence of overt cardiovascular disease; a sex-specific pattern exists in the alteration of vascular-ventricular coupling, which might partially explain the greater susceptibility to HFpEF in women. Funding Acknowledgement Type of funding source: None

Aims Although serum uric acid (SUA) level is correlated with oxidative stress and serves as a marker of poor prognosis in heart failure patients, its possible association with subclinical left ventricular (LV) dysfunction has not been evaluated. This study aimed to investigate the association between SUA and subclinical LV dysfunction in a sample of a general population without overt cardiac disease. Methods and results We examined 1175 participants who underwent extensive cardiovascular health check‐up including laboratory tests and speckle‐tracking echocardiography to assess LV global longitudinal strain (GLS). The association of SUA concentration, as a continuous variable and a categorical variable using quartiles, with the presence of abnormal LVGLS was assessed. Mean age was 62 ± 12 years, and 656 (56%) were male participants. Mean SUA was 5.6 ± 1.3 mg/dL (25th–75th percentile, 4.6–6.5 mg/dL). The prevalence of abnormal LVGLS (greater than –18.6%) was greatest in the upper quartile of SUA. In multivariable analysis, SUA as a continuous variable was significantly associated with abnormal LVGLS [adjusted odds ratio (OR), 1.26 per 1 mg/dL; P = 0.008] independent of traditional cardiovascular risk factors, pertinent laboratory parameters and echocardiographic measures, and medications. In the categorical analysis, the upper quartile of SUA was independently associated with abnormal LVGLS in a fully adjusted model (adjusted OR, 2.28 vs. lowest quartile; P = 0.020). Conclusions In a sample of the general population, an elevated SUA was independently associated with subclinical LV dysfunction. Assessment of LVGLS may add important prognostic information in individuals with elevated SUA, even in the absence of overt cardiac disease.

ImportanceThe risk of ischemic stroke is higher among patients with left atrial (LA) enlargement. Left atrial strain (LAε) and LA strain rate (LASR) may indicate LA dysfunction when LA volumes are still normal. The association of LAε with incident ischemic stroke in the general population is not well established.ObjectiveTo investigate whether LAε and LASR are associated with new-onset ischemic stroke among older adults.DesignThe Cardiovascular Abnormalities and Brain Lesions study was conducted from September 29, 2005, to July 6, 2010, to investigate cardiovascular factors associated with subclinical cerebrovascular disease. A total of 806 participants in the Northern Manhattan Study who were aged 55 years or older without history of prior stroke or atrial fibrillation (AF) were included, and annual follow-up telephone interviews were completed May 22, 2022. Statistical analysis was performed from June through November 2022.ExposuresLeft atrial strain and LASR were assessed by speckle-tracking echocardiography. Global peak positive longitudinal LAε and positive longitudinal LASR during ventricular systole, global peak negative longitudinal LASR during early ventricular diastole, and global peak negative longitudinal LASR during LA contraction were measured. Brain magnetic resonance imaging was used to detect silent brain infarcts and white matter hyperintensities at baseline.Main Outcomes and MeasuresRisk analysis with cause-specific Cox proportional hazards regression modeling was used to assess the association of positive longitudinal LAε and positive longitudinal LASR with incident ischemic stroke, adjusting for other stroke risk factors, including incident AF.ResultsThe study included 806 participants (501 women [62.2%]) with a mean (SD) age of 71.0 (9.2) years; 119 participants (14.8%) were Black, 567 (70.3%) were Hispanic, and 105 (13.0%) were White. During a mean (SD) follow-up of 10.9 (3.7) years, new-onset ischemic stroke occurred in 53 participants (6.6%); incident AF was observed in 103 participants (12.8%). Compared with individuals who did not develop ischemic stroke, participants with ischemic stroke had lower positive longitudinal LAε and negative longitudinal LASR at baseline. In multivariable analysis, the lowest (ie, closest to zero) vs all other quintiles of positive longitudinal LAε (adjusted hazard ratio [HR], 3.12; 95% CI, 1.56-6.24) and negative longitudinal LASR during LA contraction (HR, 2.89; 95% CI, 1.44-5.80) were associated with incident ischemic stroke, independent of left ventricular global longitudinal strain and incident AF. Among participants with a normal LA size, the lowest vs all other quintiles of positive longitudinal LAε (HR, 4.64; 95% CI, 1.55-13.89) and negative longitudinal LASR during LA contraction (HR, 11.02; 95% CI 3.51-34.62) remained independently associated with incident ischemic stroke.Conclusions and RelevanceThis cohort study suggests that reduced positive longitudinal LAε and negative longitudinal LASR are independently associated with ischemic stroke in older adults. Assessment of LAε and LASR by speckle-tracking echocardiography may improve stroke risk stratification in elderly individuals.

Introduction The global pandemic caused by coronavirus (COVID-19) sped up the adoption of telemedicine. We aimed to assess whether factors associated with no-show differed between in-person and telemedicine visits. The focus is on understanding how social economic factors affect patient no-show for the two modalities of visits. Methods We utilized electronic health records data for outpatient internal medicine visits at a large urban academic medical center, from February 1, 2020 to December 31, 2020. A mixed-effect logistic regression was used. We performed stratified analysis for each modality of visit and a combined analysis with interaction terms between exposure variables and visit modality. Results A total of 111,725 visits for 72,603 patients were identified. Patient demographics (age, gender, race, income, partner), lead days, and primary insurance were significantly different between the two visit modalities. Our multivariable regression analyses showed that the impact of sociodemographic factors, such as Medicaid insurance (OR 1.23, p < 0.01 for in-person; OR 1.03, p = 0.57 for telemedicine; p < 0.01 for interaction), Medicare insurance (OR 1.11, p = 0.04 for in-person; OR 0.95, p = 0.32 for telemedicine; p = 0.03 for interaction) and Black race (OR 1.36, p < 0.01 for in-person; OR 1.20, p < 0.01 for telemedicine; p = 0.03 for interaction), on increased odds of no-show was less for telemedicine visits than for in-person visits. In addition, inclement weather and younger age had less impact on no-show for telemedicine visits. Discussion Our findings indicated that if adopted successfully, telemedicine had the potential to reduce no-show rate for vulnerable patient groups and reduce the disparity between patients from different socioeconomic backgrounds.

We examined the age-related differences in cardiovascular health (CVH) metrics for incident cardiovascular disease (CVD). Analyses were conducted using data from the JMDC Claims Database from 2005 to 2020 (n = 2,728,427; mean age 44.9 ± 11.0 years; 56.2% men). Participants were categorized on the basis of age: 20 to 49 years (n = 1,800,161), 50 to 59 years (n = 644,703), and 60 to 75 years (n = 283,563). Ideal CVH metrics included nonsmoking, body mass index25 kg/m

Background Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure. We hypothesized that subclinical left ventricular dysfunction adversely affects LA/RV geometry and function even in a preclinical setting. This study aimed to investigate the atrioventricular and ventricular functional interdependence in a community‐based cohort without overt cardiovascular disease. Methods and Results Left ventricular global longitudinal strain (LVGLS), RV free‐wall longitudinal strain and LA phasic strain were assessed by speckle‐tracking echocardiography in 1080 participants (600 men; 62±12 years) between 2014 and 2018. One hundred and forty‐three participants (13.2%) had an abnormal LVGLS (>−18.6%). LA reservoir strain, conduit strain, and RV free‐wall longitudinal strain were significantly decreased in abnormal LVGLS group compared with normal LVGLS group (all P −19.2%) were present in 18.9% and 19.6% of participants with abnormal LVGLS. Decreased LVGLS was associated with worse LA reservoir strain, conduit strain and RV free‐wall longitudinal strain (standardized β=−0.20, −0.19 and 0.11 respectively, all P 28.6 pg/mL for men and >44.4 pg/mL for women) compared with normal LVGLS (odds ratio, 2.01; P =0.030). Conclusions LA/RV dysfunction was present in 20% individuals with abnormal LVGLS and multi‐chamber impairment was associated with elevated B‐type natriuretic peptide level, which may provide valuable insights for a better understanding of atrioventricular and ventricular interdependence and possibly heart failure preventive strategies.

Introduction: There is limited information on the association between left ventricular (LV) dimensions and cardiovascular (CV) outcomes in patients with heart failure with reduced LV ejection fraction (HFrEF) receiving recommended HF treatment. We investigated the association between LV dimensions and CV outcomes in HFrEF patients receiving recommended HF treatment. Methods: We investigated the association between LV echocardiographic dimensions and CV outcomes using conventional Cox models in 1138 HFrEF patients in sinus rhythm randomized to warfarin or aspirin treatment in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial. Results: LV enlargement, whether by diameter (LV end-diastolic diameter index: LVEDDI, and LV end-systolic diameter index: LVESDI) or volume (LV end-diastolic volume index: LVEDVI, and LV end-systolic volume index: LVESVI), was independently associated with all-cause death [LVEDDI: hazard ratio (HR) per cm/m 2 1.53, LVESDI: HR per cm/m 2 1.65, LVEDVI: HR per 10 ml/m 2 1.07 and LVESVI: HR per 10 ml/m 2 1.10; all p-values < 0.001], CV death (HR 1.68, 1.79, 1.09 and 1.12, respectively; all p-values < 0.001) and HF hospitalization (HR 1.59, 1.79, 1.06 and 1.08, respectively; all p-values < 0.001). No association was observed with myocardial infarction or stroke. The associations were independent of LV ejection fraction values, and incremental to them. LV volumes conferred additional predictive value over LV diameters. Conclusions: LV enlargement is an independent predictor of CV events in patients with HFrEF and recommended HF treatment. LV dimensions should be considered in the risk assessment.

RATIONALE AND OBJECTIVE: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD. STUDY DESIGN: Neuroimaging substudy of a randomized trial. SETTING & PARTICIPANTS: A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). INTERVENTION: Participants were randomly assigned to intensive (systolic BP 30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI −3.01, 6.82), 0.003 cm(3) (asinh transformed, 95% CI −0.13, 0.13), and −7.0 cm(3) (95% CI −13.3, −0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04). LIMITATIONS: Measurement variability due to multi-site design. CONCLUSIONS: Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease. FUNDING: The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: SPRINT was registered at ClinicalTrials.gov with the study number NCT01206062.

BACKGROUND: LV hypertrophy is an independent risk factor for cardiovascular outcomes. There are limited data about modifiable factors associated with progression of LV hypertrophy in the older adults. Our objective is to describe the changes in left ventricular (LV) mass and geometry over time in a predominantly older multi-ethnic cohort and to identify possible predictors of changes over time. METHODS: We analyzed data from participants in the Northern Manhattan Study (NOMAS) who underwent serial echocardiographic studies, comparing the baseline and the most recent echocardiograms. We recorded changes in LV mass and geometry and correlated them with baseline characteristics using linear regression models. RESULTS: There were 826 participants (mean age 64.2 ± 8.0 years) included in the analysis (time between measurements: 8.5 ± 2.7 years). Overall, LV mass index increased from 45.0 ± 12.7 to 50.3 ± 14.6 g/m(2.7) (p < 0.001). There were 548 participants (66.3%) with LV mass increase; 258 subjects (31.2%) showed worsening LV geometry. Multivariable analysis showed that change in LV mass index was independently associated with baseline LV mass index (β estimate: −17.000, [standard error: 1.508], p < 0.001), hypertension (2.094 [0.816], p=0.011), body mass index (0.503 [0.088], p < 0.001) and waist-to-hip ratio (1.031 [0.385], p=0.008).Both waist-to-hip ratio or waist-to-height ratio remained significantly associated with LV mass increase even after adjusting for body mass index (p= 0.008 and p=0.036, respectively) CONCLUSIONS: Regardless of race/ethnicity, LV mass progressed over time in the older adults. We also observed worsening geometry was frequent. Assessment of central obesity in the older population is important because indicators of central obesity add prognostic value over body mass index for the risk of LV mass increase.

Hypertension is the most prevalent modifiable risk factor for stroke. Office blood pressure (BP) measurements may have limitations in defining the impact of hypertension on stroke. Our aim was to compare the stroke risk for office, central, and ambulatory BP measurements in a predominantly older population-based prospective cohort. Participants in the CABL study (Cardiovascular Abnormalities and Brain Lesions; n=816; mean age, 70.8±9.0 years; 39.8% men) underwent applanation tonometry of the radial artery for central BP and 24-hour ambulatory BP monitoring. During a follow-up of 9.6±3.1 years, stroke occurred in 76 participants (9.3%). Among office BP variables, only diastolic BP was associated with stroke in multivariable competing risk model ( P =0.016). None of the central BP variables showed a significant association with stroke. Conversely, all ambulatory systolic and diastolic BP variables were significantly associated with stroke after adjustment for clinical confounders (all P P

Obesity increases the risk for atrial fibrillation (AF), although the impact of abdominal fat distribution on left atrial (LA) morphology and functional remodeling remains unclear. This study aimed to investigate whether increased abdominal adiposity is independently associated with impaired LA function and/or LA enlargement in a sample of the general population and to evaluate the role of adipokines in this association.The study cohort consisted of 527 participants (362 men; 57 ± 10 years) without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination and echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess LA phasic function including reservoir, conduit and pump strain. LA reservoir and conduit strain decreased with increasing VFA quartiles (both p 0.05), whereas no significant differences were observed in LA volume index and pump strain. When stratified by SFA, there were no significant differences in LA size and function across the quartiles. In multivariable analysis, VFA was significantly associated with LA conduit strain independent of cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters (standardized β = -0.136, p = 0.019). VFA was correlated with serum adiponectin level (r = -0.51, p 0.001), but there was no association between adiponectin level and three LA phasic strains.In a sample of the general population, VFA accumulation was independently associated with worse LA conduit strain, which may be involved in the pathophysiological mechanism of obesity-related AF.

Summary Lactate metabolism has been shown to have increasingly important implications in cellular functions as well as in the development and pathophysiology of disease. The various roles as a signaling molecule and metabolite have led to interest in establishing a new method to detect lactate changes in live cells. Here we report our development of a genetically encoded metabolic indicator specifically for probing lactate (GEM-IL) based on superfolder fluorescent proteins and mutagenesis. With improvements in its design, specificity, and sensitivity, GEM-IL allows new applications compared with the previous lactate indicators, Laconic and Green Lindoblum. We demonstrate the functionality of GEM-IL to detect differences in lactate changes in human oncogenic neural progenitor cells and mouse primary ventricular myocytes. The development and application of GEM-IL show promise for enhancing our understanding of lactate dynamics and roles.

Background and Purpose: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. Methods: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS ( Results: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P =0.78), death (4.9% versus 8.5%, P =0.68), fatal strokes (2.4% versus 8.5%, P =0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P =0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. Conclusions: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT02283294.

Background Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease. Methods We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR − 16.65%). Results Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e′ ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (− 17.6 ± 2.6% vs. − 19.7 ± 3.1%, p Conclusions In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals.

Background and ObjectiveThe Food and Drug Administration (FDA) relies on advice from scientific and medical experts to make approval decisions about new prescription medications and medical devices. Therefore, it is crucial that FDA Advisory Committees (ACs) include the most knowledgeable scientists and clinicians in the decision-making process. However, to ensure that the advice is free from biases, current FDA policy often excludes those most qualified from participating in ACs due to perceived conflicts of interest (COI). The objective of the present study is to elicit opinion among subject matter experts regarding current FDA COI rules and regulations.MethodsWe conducted a cross-sectional study using formal, self-administered online survey consisting of 14 questions, 3 of which addressed perceived implications of current FDA COI policy. We send a formal online survey to study subjects via Qualtrics. Study subjects were 1) individuals who participated in FDA ACs and 2) those who were interested in participating in ACs and had completed FDA COI paperwork but rejected by the FDA due to COI. The outcome measure is response to the 3 questions about the perceived implications of current FDA COI policy. Responses were scored on a 5-point Likert-type scale.ResultsAmong 403 study subjects (200 AC members and 203 individuals who were rejected due to COI), 145 (36%) responded to the survey including 90 AC members and 55 rejected individuals. Respondents included 41 (28%) females. 97% were holding MD or PhD degrees. 88% were age 46 and over, and 66% had more than 25 years in practice. The primary findings were that 49% of respondents agreed that the current FDA regulations lead to a lower quality of experts on ACs, 72% agreed that current policies exclude qualified experts from serving on ACs, and 48% agreed that FDA policy lowers the overall quality of AC input, to at least a “moderate” extent (19%-37% to a “high” or “very high” extent).ConclusionsThe prevailing opinion among respondents to the formal survey is that current FDA COI policy has the potential effects to lowering quality of experts, excluding qualified experts, and lowering overall quality of AC input. The present report elucidates a potential need for the FDA to discuss the benefit and risk of the current AC COI policies.

Introduction: Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure (HF). However, the alteration of atrioventricular and ventricular functional interdependence in a preclinical setting is unclear. We aimed to investigate the association between LA/RV functional remodeling and subclinical left ventricular (LV) dysfunction. Methods: LV global longitudinal strain (LVGLS), RV free wall longitudinal strain (RVLS) and LA reservoir strain were assessed by speckle-tracking echocardiography in 1,080 participants (600 men; 62±12 years) without cardiac disease. Results: A hundred and forty-three participants (13.2%) had an abnormal LVGLS (>-18.6%). LA reservoir strain and RVLS were significantly decreased in abnormal LVGLS group compared with normal LVGLS group (both p -19.2%) were present in 18.9% and 19.6% of participants with abnormal LVGLS, respectively (Figure). Decreased LVGLS was significantly associated with worse LA reservoir strain and RVLS (standardized β=-0.20 and 0.11 respectively, both p Conclusions: In the general population without overt cardiac disease, approximately 20% subjects with impaired LVGLS exhibited LA/RV dysfunction, and LVGLS was independently associated with both LA and RV strain. Our findings may provide valuable insights for a better understanding of HF pathophysiology and possibly preventive strategies.

Background: Although subclinical hypothyroidism (SCH) is a common clinical entity and carries independent risk for incident heart failure (HF), its possible association with subclinical cardiac dysfunction has not been extensively evaluated. Left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic strain can unmask subclinical left heart dysfunction and are excellent predictors for HF. This study aimed to investigate the association between the presence of SCH and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease. Methods: We examined 1,078 participants who underwent extensive cardiovascular health check-up including laboratory tests and 2-dimensional speckle-tracking echocardiography to assess LVGLS and LA reservoir, conduit and pump strain. SCH was defined as an elevated serum thyroid stimulating hormone level with normal concentration of free thyroxine. Results: Mean age was 62±12 years, and 56% were men. Seventy-eight (7.2%) participants exhibited SCH. Individuals with SCH had significantly reduced LA reservoir and conduit strain (both p Conclusions: In an unselected community-based cohort, individuals with SCH had significantly impaired LA function. This association may be involved in the higher incidence of HF in subjects with SCH.

Background Obesity carries independent risk for incident atrial fibrillation (AF), although the impact of abdominal fat distribution on LA morphological and functional remodeling is not fully elucidated. Speckle-tracking echocardiography is a novel and sensitive tool that allows quantification and detection of subtle alterations in left atrial (LA) phasic function. Purpose This study aimed to investigate whether increased visceral adiposity is independently associated with impaired LA phasic function in a community-based cohort. Methods We included 527 participants without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination and speckle-tracking echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess LA phasic function including reservoir, conduit and pump strain as well as left ventricular global longitudinal strain (LVGLS). Results Mean age was 57±10 years and 362 of the participants (69%) were men. LA reservoir and conduit strain were decreased according to the VFA quartiles (both p Conclusion In a sample of the general population, VFA accumulation was independently associated with worse LA conduit strain, which may be involved in the pathophysiological mechanism of obesity-related AF. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Yamauchi Susumu Scholarship for Cardiovascular Research

Background Prolonged monitoring of cardiac rhythm has been used in patients with symptomatic arrhythmias and to assess for atrial fibrillation (AF) after cryptogenic stroke, but not in the general population and especially in older adults. Purpose To evaluate the frequency of arrhythmias in a community-based cohort of older adults through 14-days continuous cardiac monitoring using a patch-based device. Methods Cardiac rhythm was analyzed in 533 participants free of AF and congestive heart failure (CHF) from the tri-ethnic (white, black, Hispanic) Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study. AF, supraventricular tachycardia (SVT, defined as 4 beats or more), premature atrial (PACs) and ventricular (PVCs) contractions, ventricular tachycardia (VT, defined as 4 beats or more), sinus pauses (SP) and atrio-ventricular blocks (AVB) were analyzed. Gender, age and race-ethnic differences were examined. Results Mean age was 77.2±6.8 years (198 men, 335 women). Recording duration was over 10 days in 91%, and over 13 days in 84%. AF was present in 10 participants (1.9%), atrial flutter in 1 (0.2%). Other arrhythmias are reported in the Table. SP (1.9%) and high-degree AVB (Mobitz II: 0.6%; 3rd degree: 0.9%) were rare. No significant race-ethnic differences were observed. Conclusion In older adults without history of stroke or CHF, prolonged rhythm monitoring revealed moderate frequency of AF, but higher than expected frequencies of AF-predisposing conditions such as SVT and frequent PACs. VT episodes were relatively frequent, whereas SP and AVB were less frequent than commonly believed. Most arrhythmias were more frequent in the oldest; ventricular arrhythmias were more common in men than in women. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NINDS R01 NS083874

Objective The mental health toll of COVID-19 on healthcare workers (HCW) is not yet fully described. We characterized distress, coping, and preferences for support among NYC HCWs during the COVID-19 pandemic. Methods This was a cross-sectional web survey of physicians, advanced practice providers, residents/fellows, and nurses, conducted during a peak of inpatient admissions for COVID-19 in NYC (April 9th–April 24th 2020) at a large medical center in NYC (n = 657). Results Positive screens for psychological symptoms were common; 57% for acute stress, 48% for depressive, and 33% for anxiety symptoms. For each, a higher percent of nurses/advanced practice providers screened positive vs. attending physicians, though housestaff's rates for acute stress and depression did not differ from either. Sixty-one percent of participants reported increased sense of meaning/purpose since the COVID-19 outbreak. Physical activity/exercise was the most common coping behavior (59%), and access to an individual therapist with online self-guided counseling (33%) garnered the most interest. Conclusions NYC HCWs, especially nurses and advanced practice providers, are experiencing COVID-19-related psychological distress. Participants reported using empirically-supported coping behaviors, and endorsed indicators of resilience, but they also reported interest in additional wellness resources. Programs developed to mitigate stress among HCWs during the COVID-19 pandemic should integrate HCW preferences.

Silent brain infarctions (SBI) and white matter hyperintensities (WMH) are associated with increased risk for stroke ([1][1]). Left atrial (LA) functional impairment is associated with increased cardiovascular events including stroke ([2][2]). Although LA volume measurement is the gold standard for

Background Despite growing evidence of cardiovascular complications associated with novel 2019 coronavirus disease (COVID-19), there is little data regarding the performance of transthoracic echocardiography (TTE) and spectrum of echocardiographic findings in this disease. Methods We performed a retrospective analysis of adult patients admitted to a quaternary care center in New York City between March 1st and April 3rd, 2020. Patients were included if they had a TTE performed during the hospitalization after a known positive diagnosis for COVID-19. Demographic and clinical data were obtained using chart abstraction from the electronic medical record. Results Of 749 patients, 72 (9.6%) had a TTE following a positive SARS-CoV-2 PCR test. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). While most patients had preserved biventricular function, 34.7% were found to have a left ventricular ejection fraction (LVEF) ≤ 50% and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation there was an inverse relationship between high sensitivity Troponin T and LVEF (rho = -0.34, p=0.006). Among 20 patients with prior echocardiograms, only two (10%) patients had a new reduction in LVEF of more than 10%. Clinical management was changed in eight (24.2%) of individuals who had a TTE ordered for concern for acute major cardiovascular event; and three (14.3%) in whom TTE was ordered for hemodynamic evaluation. Conclusions This study describes the clinical indications for usage and diagnostic performance, as well as findings seen on TTE in hospitalized patients with COVID-19. In appropriately selected patients TTE can be an invaluable tool for guiding COVID-19 clinical management., Highlights • TTEs are performed in a minority of COVID-19 patients • Focused studies could be performed quickly and the majority of tests were diagnostic • Patients with elevated cardiac biomarkers were more likely to exhibit reduced LV function • In appropriately selected patients TTE can guide COVID-19 clinical management

OBJECTIVES Increased arterial stiffness is currently recognized as an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. This study aimed to investigate the association of arterial stiffness with left atrial (LA) volume and phasic function in a community-based cohort. METHODS We included 1156 participants without overt cardiovascular disease who underwent extensive cardiovascular examination. Arterial stiffness was evaluated by cardio-ankle vascular index (CAVI). Speckle-tracking echocardiography was employed to evaluate LA phasic function including reservoir, conduit, and pump strain as well as left ventricular global longitudinal strain (LVGLS). RESULTS CAVI was negatively correlated with reservoir and conduit strain (r = -0.37 and -0.45, both P

X-linked scapuloperoneal myopathy (X-SM), one of Four-and-a-half LIM 1 (FHL1) related diseases, is an adult-onset slowly progressive myopathy, often associated with cardiomyopathy. We previously generated a knock-in mouse model that has the same mutation (c.365 G > C, p.W122S) as human X-SM patients. The mutant male mouse developed late-onset slowly progressive myopathy without cardiomyopathy. In this study, we observed that heterozygous (Het) and homozygous (Homo) female mice did not show alterations of skeletal muscle function or histology. In contrast, 20-month-old mutant female mice showed signs of cardiomyopathy on echocardiograms with increased systolic diameter [wild-type (WT): 2.74 ± 0.22 mm, mean ± standard deviation (SD); Het: 3.13 ± 0.11 mm, P

Previous studies in patients with atrial fibrillation showed that a history of heart failure (HF) could negatively impact anticoagulation quality, as measured by the average time in therapeutic range (TTR). Whether additional markers of HF severity are associated with TTR has not been investigated thoroughly. We aimed to examine the potential role of HF severity in the quality of warfarin control in patients with HF with reduced ejection fraction. Data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial were used to investigate the association between TTR and HF severity. Multivariable logistic regression models were used to examine the association of markers of HF severity, including New York Heart Association (NYHA) class, Minnesota Living with HF (MLWHF) score, and frequency of HF hospitalization, with TTR ≥70% (high TTR). We included 1,067 participants (high TTR, N = 413; low TTR, N = 654) in the analysis. In unadjusted analysis, patients with a high TTR were older and less likely to have had strokes or receive other antiplatelet agents. Those patients also had lower NYHA class, better MLWHF scores, greater 6-minute walk distance, and lower frequency of HF hospitalizations. Multivariable analysis showed that NYHA class III and/or IV (Odds ratio [OR] 0.68 [95% confidence intervals [CIs] 0.49 to 0.94]), each 10-point increase in MLWHF score (i.e., worse health-related quality of life) (OR 0.92 [0.86 to 0.99]), and higher number of HF hospitalization per year (OR0.45 [0.30 to 0.67]) were associated with decreased likelihood of having high TTR. In HF patients with systolic dysfunction, NYHA class III and/or IV, poor health-related quality of life, and a higher rate of HF hospitalization were independently associated with suboptimal quality of warfarin anticoagulation control. These results affirm the need to assess the new approaches, such as direct oral anticoagulants, to prevent thromboembolism in this patient population.