Left Atrial Strain and Incident Atrial Fibrillation in Older Adults.

Atrial fibrillation (AF) is frequent in older adults and associated with left atrial (LA) dysfunction. LA strain (LAε) and LA strain rate (LASR) may detect subclinical LA disease. We investigated whether reduced LAε and LASR predict new-onset AF in older adults without history of AF or stroke. LAε and LASR were assessed by speckle-tracking echocardiography in 824 participants from the community-based Cardiovascular Abnormalities and Brain Lesions study. Positive longitudinal LAε and LASR during ventricular systole, LASR during early ventricular diastole, and LASR during LA contraction were measured. Cause-specific hazards regression model evaluated the association of LAε and LASR with incident AF, adjusting for pertinent covariates. The mean age was 71.1 ± 9.2 years (313 men, 511 women). During a mean follow-up of 10.9 years, new-onset AF occurred in 105 participants (12.7%). Lower LAε and LASR at baseline were observed in patients with new-onset AF (all p <0.01). In multivariable analysis, positive longitudinal LAε (adjusted hazard ratio [HR] per SD decrease 2.05, confidence interval [CI] 1.24 to 3.36) and LASR during LA contraction (HR per SD increase 2.24, CI 1.37 to 3.65) remained associated with new-onset AF, independently of LA volumes and left ventricular function. Along with positive longitudinal LAε, reduced LASR during ventricular systole predicted AF in participants with LA volume below the median value (HR 2.54, CI 1.10 to 6.09), whereas reduced LASR during LA contraction predicted AF in participants with larger LA (HR 2.35, CI 1.31 to 4.23). In conclusion, reduced positive longitudinal LAε and LASR predict new-onset AF in older adults regardless of LA size and may improve AF risk stratification.

Association of Left Atrial Strain With Ischemic Stroke Risk in Older Adults.

Importance: The 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. Objective: To investigate whether LAε and LASR are associated with new-onset ischemic stroke among older adults. Design: The 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. Exposures: Left 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 Measures: Risk 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. Results: The 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 Relevance: This 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.

Subclinical left ventricular systolic dysfunction and incident stroke in the elderly: long-term findings from Cardiovascular Abnormalities and Brain Lesions.

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.

Myocardial Microvascular Dysfunction in Rheumatoid ArthritisQuantitation by 13N-Ammonia Positron Emission Tomography/Computed Tomography.

BACKGROUND: The goal of this study was to assess the prevalence of myocardial microvascular dysfunction in rheumatoid arthritis (RA) patients without clinical cardiovascular disease and its association with RA characteristics and measures of cardiac structure and function. METHODS: Participants with RA underwent rest and vasodilator stress N-13 ammonia positron emission tomography and echocardiography. Global myocardial blood flow was quantified at rest and during peak hyperemia. Myocardial flow reserve (MFR) was calculated as peak stress myocardial blood flow/rest myocardial blood flow. A small number of asymptomatic and symptomatic non-RA controls were also evaluated. RESULTS: In RA patients, mean±SD MFR was 2.9±0.8, with 29% having reduced MFR (<2.5). Male sex and higher interleukin-6 were significantly associated with lower MFR, while the use of tumor necrosis factor inhibitors was associated with higher MFR. Lower MFR was associated with higher left ventricle mass index and higher left ventricle volumes but not with ejection fraction or diastolic dysfunction. RA and symptomatic controls had comparable MFR (mean±SD: 2.9±0.8 versus 2.55±0.6; P=0.48). In contrast, MFR was higher in the asymptomatic controls (mean±SD: 3.25±0.7) although not statistically different. CONCLUSIONS: Reduced MFR was observed in a third of RA patients without clinical cardiovascular disease and was associated with a measure of inflammation and with higher left ventricle mass and volumes. MFR in RA patients was similar to controls referred for clinical scans (symptomatic controls). Whether reduced MFR contributes to the increased risk for heart failure in RA remains unknown.

Myocardial Inflammation, Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography, Is Associated With Disease Activity in Rheumatoid Arthritis.

OBJECTIVE: To determine the prevalence and correlates of subclinical myocardial inflammation in patients with rheumatoid arthritis (RA). METHODS: RA patients (n = 119) without known cardiovascular disease underwent cardiac 18-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT). Myocardial FDG uptake was assessed visually and measured quantitatively as the standardized uptake value (SUV). Multivariable linear regression was used to assess the associations of patient characteristics with myocardial SUVs. A subset of RA patients who had to escalate their disease-modifying antirheumatic drug (DMARD) therapy (n = 8) underwent a second FDG PET-CT scan after 6 months, to assess treatment-associated changes in myocardial FDG uptake. RESULTS: Visually assessed FDG uptake was observed in 46 (39%) of the 119 RA patients, and 21 patients (18%) had abnormal quantitatively assessed myocardial FDG uptake (i.e., mean of the mean SUV [SUVmean ] ≥3.10 units; defined as 2 SD above the value in a reference group of 27 non-RA subjects). The SUVmean was 31% higher in patients with a Clinical Disease Activity Index (CDAI) score of ≥10 (moderate-to-high disease activity) as compared with those with lower CDAI scores (low disease activity or remission) (P = 0.005), after adjustment for potential confounders. The adjusted SUVmean was 26% lower among those treated with a non-tumor necrosis factor-targeted biologic agent compared with those treated with conventional (nonbiologic) DMARDs (P = 0.029). In the longitudinal substudy, the myocardial SUVmean decreased from 4.50 units to 2.30 units over 6 months, which paralleled the decrease in the mean CDAI from a score of 23 to a score of 12. CONCLUSION: Subclinical myocardial inflammation is frequent in patients with RA, is associated with RA disease activity, and may decrease with RA therapy. Future longitudinal studies will be required to assess whether reduction in myocardial inflammation will reduce heart failure risk in RA.

First-in-human study to assess the safety, pharmacokinetics and pharmacodynamics of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non-Japanese and Japanese healthy subjects.

AIMS: The aims of the present study were to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a randomized, placebo-controlled, double-blind, sequential, ascending-dose study of 2-h (part A) and 5-day (part B) intravenous (IV) infusions of BMS-962212. Part A used four doses (1.5, 4, 10 and 25 mg h-1 ) of BMS-962212 or placebo in a 6:2 ratio per dose. Part B used four doses (1, 3, 9 and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese (n = 4 active, n = 1 placebo) subjects per dose. The PK, PD, safety and tolerability were assessed throughout the study. RESULTS: BMS-962212 was well tolerated; there were no signs of bleeding, and adverse events were mild. In parts A and B, BMS-962212 demonstrated dose proportionality. The mean half-life in parts A and B ranged from 2.04 to 4.94 h and 6.22 to 8.65 h, respectively. Exposure-dependent changes were observed in the PD parameters, activated partial thromboplastin time (aPTT) and factor XI clotting activity (FXI:C). The maximum mean aPTT and FXI:C change from baseline at 20 mg h-1 in part B was 92% and 90%, respectively. No difference was observed in weight-corrected steady-state concentrations, aPTT or FXI:C between Japanese and non-Japanese subjects (P > 0.05). CONCLUSION: BMS-962212 has tolerability, PK and PD properties suitable for investigational use as an acute antithrombotic agent in Japanese or non-Japanese subjects.

Association of body size metrics with left atrial phasic volumes and reservoir function in the elderly.

Aims: General obesity, defined by increased body mass index (BMI), is associated with left atrial (LA) enlargement, a marker of cardiovascular risk in the general population. The association between abdominal adiposity, defined by increased waist circumference (WC) or waist-to-hip ratio (WHR), and LA phasic volumes and reservoir function is not well known. The aim of this study was to evaluate the association between different body size metrics and LA phasic volumes and reservoir function in the elderly. Methods and results: Participants from the CABL (Cardiovascular Abnormalities and Brain Lesions) study underwent measurement of BMI, WC, and WHR. The LA maximum (LAVmax) and minimum (LAVmin) volumes, and LA reservoir function, measured as total emptying volume index (LAEVI), total emptying fraction (LAEF), and expansion index (LAEI), were assessed by real-time 3D echocardiography. The study population included 629 participants (mean age 71 ± 9 years, 61% women). Mean BMI was 27.9 ± 4.6 kg/m2, WC was 95.0 ± 11.7 cm, WHR was 0.91 ± 0.08. After adjusting for multiple potential confounders (demographics, cardiovascular risk factors, left ventricular mass index, and diastolic function), higher WC was significantly associated with higher LA phasic volumes (LAVmax, ß = 0.10, P = 0.007 and LAVmin, ß = 0.12, P = 0.002) and reduced reservoir function (LAEVI, ß = -0.15, P = 0.001 and LAEI, ß = -0.09, P = 0.027). WHR was significantly associated only with reduced reservoir function (LAEVI, ß = -0.11, P = 0.012), whereas BMI was not associated with either LA phasic volumes or reservoir function. Conclusion: In the elderly, WC may have more impact on LA phasic volumes and reservoir function, and therefore risk for cardiovascular events, than WHR and BMI.

Relationship between body mass and ambulatory blood pressure: comparison with office blood pressure measurement and effect of treatment.

Epidemiologic studies assessing the relationship between blood pressure (BP), body mass, and cardiovascular events have primarily been based on office BP measurements, and few data are available in the elderly. The aim of the present study was to evaluate the relationship between body mass index (BMI) and BP values obtained by ambulatory blood pressure monitoring (ABPM) as compared to office BP measurements, and the effect of anti-hypertensive treatment on the relationship. The study population consisted of 813 subjects participating in the cardiovascular abnormalities and brain lesions (CABL) study who underwent 24-h ABPM. Office BP (mean of two measurements) was found to be associated with increasing BMI, for both SBP (p ≤ 0.05) and DBP (p ≤ 0.001). In contrast, there was no association seen of increasing BMI with ABPM parameters in the overall cohort, even after adjusting for age and gender. However, among subjects not on anti-hypertensive treatment, office SBP and DBP measurements were significantly correlated with increasing BMI (p ≤ 0.01) as were daytime SBP and 24-h SBP, although with a smaller spread across BMI subgroups compared with office readings. In treated hypertensives, there was only a trend toward increasing office DBP and increasing DBP variability with higher BMI. Our results suggest that body mass may have a less significant influence on BP values in the elderly when ABPM rather than office measurements are considered, particularly in patients receiving anti-hypertensive treatment.

Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations.

The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue on the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17, 2016, represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions.

Association of anti-citrullinated protein or peptide antibodies with left ventricular structure and function in rheumatoid arthritis.

Objective: High levels of ACPAs in RA are associated with more severe arthritis and worse prognosis. However, the role of ACPAs in mediating the increased risk of heart failure in RA remains undefined. We examined whether specific ACPAs were associated with subclinical left ventricular (LV) phenotypes that presage heart failure. Methods: Sera from RA patients without clinical cardiovascular disease were assayed for specific ACPAs using a custom Bio-Plex bead assay, and their cross-sectional associations with cardiac magnetic resonance-derived LV measures were evaluated. High ACPA level was defined as ⩾ 75th percentile. Findings were assessed in a second independent RA cohort with an expanded panel of ACPAs and LV measures assessed by 3D-echocardiography. Results: In cohort 1 (n = 76), higher levels of anti-citrullinated fibrinogen 41-60 and anti-citrullinated vimentin antibodies were associated with a 10 and 6% higher adjusted mean LV mass index (LVMI), respectively, compared with lower antibody levels (P < 0.05). In contrast, higher levels of anti-citrullinated biglycan 247-266 were associated with a 13% lower adjusted mean LVMI compared with lower levels (P < 0.001). In cohort 2 (n = 74), the association between ACPAs targeting citrullinated fibrinogen and citrullinated vimentin peptides or protein and LVMI was confirmed: higher anti-citrullinated fibrinogen 556-575 and anti-citrullinated vimentin 58-77 antibody levels were associated with a higher adjusted mean LVMI (19 and 15%, respectively; P < 0.05), but no association with biglycan was found. Conclusion: Higher levels of antibodies targeting citrullinated fibrinogen and vimentin peptides or protein were associated with a higher mean LVMI in both RA cohorts, potentially implicating autoimmune targeting of citrullinated proteins in myocardial remodelling in RA.

Coronary atherosclerosis burden by coronary computed tomography in type II diabetes with preclinical non-obstructive carotid atherosclerosis and without inducible myocardial ischemia.

AIMS: To quantify cardiovascular risk in persons with type-2 diabetes (DM) and established carotid atherosclerosis, without inducible myocardial ischemia by stress imaging. METHODS: We selected clinically healthy DM and subjects without DM (nonDM, controls) with non-obstructive carotid atherosclerosis and without significant coronary artery disease (CAD) by stress echocardiography. Coronary flow velocity reserve (CFR) was assessed during stress echocardiography. In those with negative stress imaging, coronary artery calcium (CAC) assessment by computed tomography (CT) was proposed. Outcome at 180-day follow-up was performed by visits or telephone interview. RESULTS: Total CAC was greater in DM (n=19) than in nonDM (n=19, CAC: 225±158 vs 78±65Agatston units, 156±161 vs 53±51 in the left anterior descendent artery, both p<0.05). Coronary stenosis burden was greater in DM than in nonDM, albeit <75% in all cases; CFR was lower in DM than nonDM (p<0.05). Mean age was slightly higher (69±6 vs 64±12, p>0.2), and male gender tended to be less frequent (63 vs 79%) with DM than with nonDM; all subjects showed dyslipidemia, and almost all had arterial hypertension. Based on CAC, a 10-year cardiovascular risk was 10-20% in 78% of the DM and in 28% of the non-DM, and was >20% in 11% of the DM but in none of the nonDM. A single non-fatal myocardial infarction was recorded within 180days from test, among DM. CONCLUSIONS: Based on CAC, in the presence of non-obstructive carotid atherosclerosis, asymptomatic DM may show significantly higher CAD burden than nonDM even in the absence of inducible myocardial ischemia.

LA Phasic Volumes and Reservoir Function in the Elderly by Real-Time 3D Echocardiography: Normal Values, Prognostic Significance, and Clinical Correlates.

OBJECTIVES: This study sought to assess the prevalence and prognostic value of abnormalities in left atrial (LA) phasic volumes and reservoir function in a community cohort. BACKGROUND: LA enlargement is associated with adverse cardiovascular outcomes. Real-time 3-dimensional (RT3D) echocardiography allows assessment of LA phasic volumes and reservoir function. However, there is a paucity of data regarding normal values, clinical correlates, and prognostic value of RT3D echocardiography-derived LA phasic volumes and reservoir function, especially in the elderly, a subgroup at high risk for cardiovascular events. METHODS: Left atrial maximum volume (LAVimax), minimum volume (LAVimin), and reservoir function assessed as emptying volume (LAEV), emptying fraction (LAEF), and expansion index (LAEI), were measured by RT3D echocardiography in participants from a community-based cohort study. Cut-off values for LA phasic volumes were derived from a healthy subgroup of participants free of cardiovascular disease and risk factors (n = 142; 66 ± 9 years of age; 55% women). Annual follow-up examinations were performed for cardiovascular outcomes (myocardial infarction, ischemic stroke, and vascular death). RESULTS: The cohort included 706 participants (71 ± 9 years of age; 59% women). LAVimax and LAVimin were not associated with age in the healthy subgroup but progressively increased with age in the entire cohort (p < 0.001). During a median follow-up of 7 years (minimum 0.06, maximum 9.5 years), 78 cardiovascular events occurred. In univariate analysis, LAVimax, LAVimin, and reservoir function parameters were significantly associated with outcome. In multivariate analysis, LAVimin ≥20.5 ml/m2 (adjusted hazard ratio [aHR]: 1.79; 95% confidence interval [CI]:1.02 to 3.16) and LAEV ≤5.7 ml/m2 (aHR: 1.98; 95% CI: 1.02 to 3.85) remained significantly associated with events. LAVimin and LA reservoir function showed incremental prognostic value over that of LAVimax. CONCLUSIONS: LA phasic volumes and reservoir functions assessed by RT3D echocardiography were strong independent predictors of cardiovascular events in a community-based elderly cohort. LAVimin and reservoir function assessment may improve cardiovascular outcome prediction over LAVimax.

Association of chronic kidney disease with impaired left atrial reservoir function: A community-based cohort study.

Background Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation, although the pathophysiological mechanisms remain unclear. This study investigated the relationship between CKD and left atrial (LA) volume and function in a sample of the general population without overt cardiac disease. Design and methods We examined 358 participants from the Cardiovascular Abnormalities and Brain Lesions study. The LA minimum volume index (LAVImin), LA maximum volume index (LAVImax), and LA emptying fraction (LAEF) were assessed by real-time three-dimensional echocardiography. Based on their estimated glomerular filtration rate (eGFR), the participants were divided into a CKD group (eGFR <60 ml/min/1.73 m2) and a non-CKD group (eGFR ≥60 ml/min/1.73 m2). Results Of the 358 participants, 69 (19%) were classified as having CKD and 289 (81%) as non-CKD. Participants with CKD were older, had a greater prevalence of hypertension and use of antihypertensive drugs, a larger left ventricular (LV) mass index, and a higher prevalence of diastolic dysfunction than those without CKD (all p < 0.05). There was no significant difference in LAVImax between the CKD and non-CKD groups (23.4 ± 7.1 vs. 22.8 ± 5.8 ml/m2, p = 0.47), whereas significant differences were observed for LAVImin (13.6 ± 5.5 vs. 12.0 ± 4.6 ml/m2, p = 0.01) and LAEF (42.7 ± 11.4 vs. 47.8 ± 11.5%, p = 0.001). Multivariate regression analysis revealed that the eGFR was significantly associated with LAEF independent of age, LV mass index, and diastolic dysfunction (all p < 0.05). Conclusions Participants with CKD in an unselected community-based cohort had significantly impaired LA reservoir function. Assessment of LA function may add important information in the prognostic assessment of patients with CKD even in the absence of overt cardiac disease.

Abdominal adiposity, general obesity, and subclinical systolic dysfunction in the elderly: A population-based cohort study.

AIMS: General obesity, measured by body mass index (BMI), and abdominal adiposity, measured as waist circumference (WC) and waist-to-hip ratio (WHR), are associated with heart failure and cardiovascular events. However, the relationship of general and abdominal obesity with subclinical left ventricular (LV) dysfunction is unknown. We assessed the association of general and abdominal obesity with subclinical LV systolic dysfunction in a population-based elderly cohort. METHODS AND RESULTS: Participants from the Cardiovascular Abnormalities and Brain Lesions study underwent measurement of BMI, WC, and WHR. Left ventricular systolic function was assessed by two-dimensional echocardiographic LV ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS). The study population included 729 participants (mean age 71 ± 9 years, 60% women). In multivariate analysis, higher BMI (but not WC and WHR) was associated with higher LVEF (ß = 0.11, P = 0.003). Higher WC (ß = 0.08, P = 0.038) and higher WHR (ß = 0.15, P < 0.001) were associated with lower GLS, whereas BMI was not (P = 0.720). Compared with normal WHR, high WHR was associated with lower GLS in all BMI categories (normal, overweight, and obese), and was associated with subclinical LV dysfunction by GLS both in participants without [adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.6, P = 0.020] and with general obesity (adjusted OR 5.4, 95% CI 1.1-25.9, P = 0.034). WHR was incremental to BMI and risk factors in predicting LV dysfunction. CONCLUSION: Abdominal adiposity was independently associated with subclinical LV systolic dysfunction by GLS in all BMI categories. BMI was not associated with LV dysfunction. Increased abdominal adiposity may be a risk factor for LV dysfunction regardless of the presence of general obesity.

Relationship of Office and Ambulatory Blood Pressure With Left Ventricular Global Longitudinal Strain.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) is an early indicator of subclinical cardiac dysfunction, even when LV ejection fraction (LVEF) is normal, and is an independent predictor of cardiovascular events. Ambulatory blood pressure (BP) is a better predictor of cardiovascular events, including heart failure, than office BP. We investigated the association of office and ambulatory BP measurements with subclinical LV systolic dysfunction in a community-based cohort with normal LVEF. METHODS: Two-dimensional speckle-tracking echocardiography and 24-hour ambulatory BP monitoring were performed in 577 participants (mean age 70±9 years; 60% women) with LVEF ≥50% from the Cardiovascular Abnormalities and Brain Lesions (CABL) study. Univariable and multivariable linear regression analyses were used to assess the associations of BP measures with GLS. RESULTS: Higher ambulatory and office BP values were consistently associated with impaired GLS. After adjustment for pertinent covariates (age, sex, race/ethnicity, body mass index, diabetes mellitus, coronary artery disease, LV mass index, and antihypertensive medication), office diastolic BP and ambulatory systolic and diastolic BPs (24-hour, daytime and nighttime) were independently associated with GLS (P = 0.003 for office DBP, P ≤ 0.001 for all ambulatory BPs). When ambulatory and office BP values were included in the same model, all ambulatory BP measures remained significantly associated with GLS (all P < 0.01), whereas office BP values were not. CONCLUSIONS: Ambulatory BP values are significantly associated with impaired GLS and the association is stronger than for office BP. Ambulatory BP monitoring might have a role in the risk stratification of hypertensive patients for early LV dysfunction.

Left Ventricular Systolic Dysfunction by Longitudinal Strain Is an Independent Predictor of Incident Atrial Fibrillation: A Community-Based Cohort Study.

BACKGROUND: The increasing prevalence of atrial fibrillation (AF) represents a public health issue. Identifying new predictors of AF is therefore necessary to plan preventive strategies. We investigated whether left ventricular (LV) systolic dysfunction by global longitudinal strain (GLS), a predictor of cardiovascular events, may predict new-onset AF in a population setting. METHODS AND RESULTS: Participants (n=675; mean age, 71±9 years; 60% women) in sinus rhythm from the population-based Northern Manhattan Study (NOMAS) underwent 2- and 3-dimensional echocardiography as part of the Cardiac Abnormalities and Brain Lesions (CABL) study. LV systolic function was assessed by LV ejection fraction and speckle-tracking GLS. During a mean follow-up of 63.6±18.7 months, 32 (4.7%) new confirmed cases of AF occurred. Lower GLS (adjusted hazard ratio/unit decrease, 1.22; 95% confidence interval, 1.04-1.43; P=0.015) and increased left atrial volume index (LAVi; adjusted hazard ratio/unit increase, 1.12; 95% confidence interval, 1.07-1.17; P<0.001) were significantly associated with incident AF, whereas LV ejection fraction was not (P=0.176). Abnormal GLS (>-14.7%) was associated with risk of new-onset AF with an adjusted hazard ratio of 3.2 (95% confidence interval, 1.4-7.5; P=0.007). The coexistence of abnormal GLS/abnormal LAVi was associated with a 28.6% incidence of AF (adjusted hazard ratio, 12.1; 95% confidence interval, 3.3-44.8; P<0.001) compared with participants with normal GLS/normal LAVi (AF incidence, 2.0%). AF incidence was intermediate in those with either abnormal GLS or abnormal LAVi (9.3% and 11.1%, respectively). GLS prognostic value for incident AF was incremental over risk factors and LAVi. CONCLUSIONS: LV systolic dysfunction by GLS was a powerful and independent predictor of incident AF. GLS assessment may improve AF risk stratification in addition to established parameters.

Race-ethnic differences in subclinical left ventricular systolic dysfunction by global longitudinal strain: A community-based cohort study.

BACKGROUND: Race-ethnic differences exist in the epidemiology of heart failure, with blacks experiencing higher incidence and worse prognosis. Left ventricular (LV) systolic dysfunction (LVSD) detected by speckle-tracking global longitudinal strain (GLS) is a predictor of cardiovascular events including heart failure. It is not known whether race-ethnic differences in GLS-LVSD exist in subjects without overt LV dysfunction. METHODS: Participants from a triethnic community-based study underwent 2-dimensional echocardiography with assessment of LV ejection fraction (LVEF) and GLS by speckle-tracking. Participants with LVEF <50% were excluded. Left ventricular systolic dysfunction by GLS was defined as GLS >95% percentile in a healthy sample (-14.7%). RESULTS: Of the 678 study participants (mean age 71 ± 9 years, 61% women), 114 were blacks; 464, Hispanics; and 100, whites. Global longitudinal strain was significantly lower in blacks (-16.5% ± 3.5%) than in whites (-17.5% ± 3.0%) and Hispanics (-17.3% ± 2.9%) in both univariate (P = .015) and multivariate analyses (P = .011), whereas LVEF was not significantly different between the 3 groups (64.3% ± 4.6%, 63.4% ± 4.9%, 64.7% ± 4.9%, respectively, univariate P = .064, multivariate P = .291). Left ventricular systolic dysfunction by GLS was more frequent in blacks (27.2%) than in whites (19.0%) and Hispanics (14.9%, P = .008). In multivariate analysis adjusted for confounders and cardiovascular risk factors, blacks were significantly more likely to have GLS-LVSD (adjusted odds ratio 2.6, 95% CIs 1.4-4.7, P = .002) compared to the other groups. CONCLUSIONS: Among participants from a triethnic community cohort, black race was associated with greater degree of subclinical LVSD by GLS than other race-ethnic groups. This difference was independent of confounders and cardiovascular risk factors.