The impact of tissue-tracking strain on the left atrial dysfunction in the patients with left ventricular dysfunction.

BACKGROUND: The extracellular volume (ECV) calculated by T1 mapping, and tissue-tracking strain using cardiac magnetic resonance (CMR) are useful for assessing the left ventricular (LV) function. However, those parameters are controversial for assessing left atrial (LA) function. This study aimed to investigate the usefulness of CMR to evaluate the LA function using those parameters. Furthermore, those LA function parameters were compared in each LV function. METHODS: A total of 65 consecutive patients who underwent contrast CMR were prospectively enrolled (age 55.7 ± 14. 6 years, males 67.7%). Among the 65 patients, there were 15 without hypertension, diabetes, or atrial fibrillation (Healthy group). The remaining 50 patients were divided into two groups according to a left ventricular ejection fraction (LVEF) of 50%. We assessed the correlations between the LV- and LA-CMR parameters among the three groups (LVEF < 50%; n = 20, LVEF ≥ 50%; n = 30, and Healthy; n = 15). RESULTS: The LA-longitudinal strain for an LVEF < 50% was lower than that for the others (LVEF < 50%; 13.6 ± 7.9%, LVEF ≥ 50%; 24. 5 ± 13.5%, Healthy; 24.5 ± 9.8%, p = 0.003). However, the LA-ECV did not significantly differ among the three groups (LVEF < 50%; 50.3 ± 3.6%, LVEF ≥ 50%; 53.1 ± 4.9%, Healthy; 53.2 ± 6.5%, p = 0.12). A multiple regression model after adjusting for the patient background revealed that a worse LA-longitudinal strain was correlated with a low LVEF and large LA-volume, but the LA-ECV was not associated with those. CONCLUSIONS: The LA-strain in LV dysfunction patients was significantly lower. However, the LA-ECV did not significantly differ from that in those without LV dysfunction. Tissue-tracking strain is more useful for evaluating the LA dysfunction than T1 mapping.

Diabetes mellitus and insulin resistance associate with left ventricular shape and torsion by cardiovascular magnetic resonance imaging in asymptomatic individuals from the multi-ethnic study of atherosclerosis.

BACKGROUND: Although diabetes mellitus (DM) and insulin resistance associate with adverse cardiac events, the associations of left ventricular (LV) remodeling and function with compromised glucose metabolism have not been fully evaluated in a general population. We used cardiovascular magnetic resonance (CMR) to evaluate how CMR indices are associated with DM or insulin resistance among participants before developing cardiac events. METHODS: We studied 1476 participants who were free of clinical cardiovascular disease and who underwent tagged CMR in the Multi-Ethnic Study of Atherosclerosis (MESA). LV shape and longitudinal myocardial shortening and torsion were assessed by CMR. A higher sphericity index represents a more spherical LV shape. Multivariable linear regression was used to evaluate the associations of DM or homeostasis model assessment-estimated insulin resistance (HOMA-IR) with CMR indices. RESULTS: In multiple linear regression, longitudinal shortening was lower in impaired fasting glucose than normal fasting glucose (NFG) (0.36% lower vs. NFG, p < 0.05); torsion was greater in treated DM (0.24 °/cm greater vs. NFG, p < 0.05) after full adjustments. Among participants without DM, greater log-HOMA-IR was correlated with greater LV mass (3.92 g/index, p < 0.05) and LV mass-to-volume ratio (0.05 /index, p < 0.01), and lower sphericity index (- 1.26/index, p < 0.01). Greater log-HOMA IR was associated with lower longitudinal shortening (- 0.26%/index, p < 0.05) and circumferential shortening (- 0.30%/index, p < 0.05). Torsion was positively correlated with log-HOMA-IR until 1.5 of log-HOMA-IR (0.16 °/cm/index, p = 0.030).), and tended to fall once above 1.5 of log-HOMA-IR (- 0.50 °/cm/index, p = 0.203). The sphericity index was associated negatively with LV mass-to-volume ratio (- 0.02/%, p < 0.001) and torsion (- 0.03°/cm/%, p < 0.001). CONCLUSIONS: Glucose metabolism disorders are associated with LV concentric remodeling, less spherical shape, and reduced systolic myocardial shortening in the general population. Although torsion is higher in participants who are treated for DM and impaired insulin resistance, myocardial shortening was progressively decreased with higher HOMA-IR and torsion was increased only with less severe insulin resistance. CLINICAL TRIAL REGISTRATION: Multi-Ethnic Study of Atherosclerosis (MESA): A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org/ . Study Start Date: January 1999 ( NCT00005487 ).

Cardiovascular magnetic resonance in an adult human population: serial observations from the multi-ethnic study of atherosclerosis.

The Multi-Ethnic Study of Atherosclerosis (MESA) is the first large-scale multi-ethnic population study in the U.S. to use advanced cardiovascular magnetic resonance (CMR) imaging. MESA participants were free of cardiovascular disease at baseline between 2000 and 2002, and were followed up between 2009 and 2011 with repeated CMR examinations as part of MESA. CMR allows the clinician to visualize and accurately quantify volume and dimensions of all four cardiac chambers; measure systolic and diastolic ventricular function; assess myocardial fibrosis; assess vessel lumen size, vessel wall morphology, and vessel stiffness. CMR has a number of advantages over other imaging modalities such as echocardiography, computed tomography, and invasive angiography, and has been proposed as a diagnostic strategy for high-risk populations. MESA has been extensively evaluating CMR imaging biomarkers, as markers of subclinical disease, in the last 15 years for low-risk populations. On a more practical level, some of the imaging biomarkers developed and studied are translatable to at-risk populations. In this review, we discuss the progression of subclinical cardiovascular disease and the mechanisms responsible for the transition to symptomatic clinical outcomes based on our findings from MESA.

Association of Insulin Resistance and Glycemic Metabolic Abnormalities With LV Structure and Function in Middle Age: The CARDIA Study.

OBJECTIVES: This study sought to investigate how cumulative exposure to glycemic abnormalities and trajectories of insulin resistance (IR) relate to left ventricular (LV) remodeling and function during young to middle adulthood. BACKGROUND: Cumulative exposure to glycemic abnormalities and trajectories of IR may adversely influence LV remodeling and function over a 25-year period in subjects who were young adults, predisposing individuals to heart failure later in life. METHODS: In the CARDIA (Coronary Artery Risk Development in Young Adults) Year 25 examination, 3,179 participants were identified with information on glucose metabolism; these participants were stratified into 4 subgroups: group 1 normal glucose tolerance (NGT), group 2 impaired glucose tolerance (IGT) or impaired fasting glucose, group 3 late diabetes mellitus (DM) (DM diagnosed at year 15 or later), and group 4 early DM (DM diagnosed at year 0 to year 15). Among the subgroup without DM, 3 trajectory groups of change in the homeostasis model assessment of IR were identified: low IR, moderate IR, and high IR. LV mass, relative wall thickness, LV ejection fraction (LVEF), longitudinal systolic strain (Ell), and early diastolic strain rate (Ell_SRe) at year 25 were assessed by echocardiography. Clinically relevant systolic and diastolic dysfunction were defined as LVEF <50% for systolic dysfunction, and E/e' ≥13 for diastolic dysfunction. RESULTS: The early DM group had less favorable LV mass (coefficient = 11.04; p < 0.001), LVEF (coefficient = -2.72; p < 0.05), Ell (coefficient = 1.53; p < 0.001), and Ell_SRe (coefficient = -0.09; p < 0.05) than did the NGT group. Being in the early DM group and having high hemoglobin A1c were independently associated with greater odds of having systolic dysfunction (odds ratio = 5.44; p < 0.005) compared with the NGT group. High IR was associated with worse relative wall thickness (coefficient = 0.019; p < 0.0001) and worse Ell, E', and Ell_SRe, depending on obesity level. CONCLUSIONS: Cumulative exposure to DM or higher IR beginning in early adulthood adversely impacts LV remodeling and function at middle age.

Transitions in Metabolic Risk and Long-Term Cardiovascular Health: Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: Despite evidence suggesting that early metabolic dysfunction impacts cardiovascular disease risk, current guidelines focus on risk assessments later in life, missing early transitions in metabolic risk that may represent opportunities for averting the development of cardiovascular disease. METHODS AND RESULTS: In 4420 young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we defined a "metabolic" risk score based on components of the Third Report of the Adult Treatment Panel's definition of metabolic syndrome. Using latent class trajectory analysis adjusted for sex, race, and time-dependent body mass index, we identified 6 distinct metabolic trajectories over time, specified by initial and final risk: low-stable, low-worsening, high-stable, intermediate-worsening, intermediate-stable, and high-worsening. Overall, individuals gained weight over time in CARDIA with statistically but not clinically different body mass index trend over time. Dysglycemia and dyslipidemia over time were highest in initially high or worsening trajectory groups. Divergence in metabolic trajectories occurred in early adulthood (before age 40), with 2 of 3 individuals experiencing an increase in metabolic risk over time. Membership in a higher-risk trajectory (defined as initially high or worsening over time) was associated with greater prevalence and extent of coronary artery calcification, left ventricular mass, and decreased left ventricular strain at year 25. Importantly, despite similar rise in body mass index across trajectories over 25 years, coronary artery calcification and left ventricular structure and function more closely tracked risk factor trajectories. CONCLUSIONS: Transitions in metabolic risk occur early in life. Obesity-related metabolic dysfunction is related to subclinical cardiovascular phenotypes independent of evolution in body mass index, including coronary artery calcification and myocardial hypertrophy and dysfunction.

Natural History of Myocardial Function in an Adult Human Population: Serial Longitudinal Observations From MESA.

OBJECTIVES: The aim of this longitudinal study was to define the determinants of aging-related left ventricular (LV) remodeling and function in a large multiethnic population. BACKGROUND: The influence of risk factor exposure on myocardial remodeling and function in humans across adult life remains incompletely understood. MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal population-based cohort of asymptomatic adults at baseline. METHODS: We examined 757 participants who were free of clinical cardiovascular disease and underwent tagged cardiac magnetic resonance both at baseline and at the 10-year follow-up as part of the MESA study. LV remodeling, circumferential shortening (CS), and torsion were assessed by tagged cardiac magnetic resonance. Multivariable linear regression was used to determine the association of changes in risk factors with changes in cardiac geometry and function. RESULTS: The mean age of participants was 63 ± 9 years at baseline; 50% were women. Overall, the LV mass-to-volume ratio increased by 10% over 10 years (p < 0.01). CS was unchanged (17.8% to 17.9%, p = 0.246), whereas torsion increased by 13% (3.8°/cm to 4.3°/cm, p < 0.001). Increased systolic blood pressure was associated with reduced CS (-0.02%/mm Hg, p < 0.01). Participants who remained on antihypertensive therapy during the whole study had a greater decrease in LV mass-to-volume ratio (-0.045 vs. no medication, p < 0.05) with a greater increase in CS (0.78% vs. no medication, p < 0.01). Moreover, greater LV mass at baseline was significantly associated with reduced CS (-0.02%/g, p < 0.01) and torsion (-0.02°/cm/g, p < 0.01) independently of risk factors. CONCLUSIONS: Longitudinal observation demonstrates that LV mass and worsening risk factors are fundamental determinants of reduced regional myocardial shortening over 10 years. Increased torsion of the myocardial wall is seen with progressive concentric remodeling and may explain why systolic function is maintained with aging.

Emphysema Quantification on Cardiac CT Scans Using Hidden Markov Measure Field Model: The MESA Lung Study.

Cardiac computed tomography (CT) scans include approximately 2/3 of the lung and can be obtained with low radiation exposure. Large cohorts of population-based research studies reported high correlations of emphysema quantification between full-lung (FL) and cardiac CT scans, using thresholding-based measurements. This work extends a hidden Markov measure field (HMMF) model-based segmentation method for automated emphysema quantification on cardiac CT scans. We show that the HMMF-based method, when compared with several types of thresholding, provides more reproducible emphysema segmentation on repeated cardiac scans, and more consistent measurements between longitudinal cardiac and FL scans from a diverse pool of scanner types and thousands of subjects with ten thousands of scans.

Quantitative tissue-tracking cardiac magnetic resonance (CMR) of left atrial deformation and the risk of stroke in patients with atrial fibrillation.

BACKGROUND: Recent evidence suggests that left atrial (LA) dysfunction may be mechanistically contributing to cerebrovascular events in patients with atrial fibrillation (AF). We investigated the association between regional LA function and a prior history of stroke during sinus rhythm in patients referred for catheter ablation of AF. METHODS AND RESULTS: A total of 169 patients (59 ± 10 years, 74% male, 29% persistent AF) with a history of AF in sinus rhythm at the time of pre-ablation cardiac magnetic resonance (CMR) were analyzed. The LA volume, emptying fraction, strain (S), and strain rate (SR) were assessed by tissue-tracking cardiac magnetic resonance. The patients with a history of stroke or transient ischemic attack (n=18) had greater LA volumes (Vmax and Vmin; P=0.02 and P<0.001, respectively), lower LA total emptying fraction (P<0.001), lower LA maximum and pre-atrial contraction strains (Smax and SpreA; P<0.001 and P=0.01, respectively), and lower absolute values of LA SR during left ventricular (LV) systole and early diastole (SRs and SRe; P=0.005 and 0.03, respectively) than those without stroke/transient ischemic attack (n=151). Multivariable analysis demonstrated that the LA reservoir function, including total emptying fraction, Smax, and SRs, was associated with stroke/transient ischemic attack (odds ratio 0.94, 0.91, and 0.17; P=0.03, 0.02, and 0.04, respectively) after adjusting for the CHA2DS2-VASc score and LA Vmin. CONCLUSIONS: Depressed LA reservoir function assessed by tissue-tracking cardiac magnetic resonance is significantly associated with a prior history of stroke/transient ischemic attack in patients with AF. Our findings suggest that assessment of LA reservoir function can improve the risk stratification of cerebrovascular events in AF patients.

Race-ethnic and sex differences in left ventricular structure and function: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: We investigated race-ethnic and sex-specific relationships of left ventricular (LV) structure and LV function in African American and white men and women at 43 to 55 years of age. METHODS AND RESULTS: The Coronary Artery Risk Development in Young Adults (CARDIA) Study enrolled African American and white adults, age 18 to 30 years, from 4 US field centers in 1985-1986 (Year-0) who have been followed prospectively. We included participants with echocardiographic assessment at the Year-25 examination (n=3320; 44% men, 46% African American). The end points of LV structure and function were assessed using conventional echocardiography and speckle-tracking echocardiography. In the multivariable models, we used, in addition to race-ethnic and gender terms, demographic (age, physical activity, and educational level) and cardiovascular risk variables (body mass index, systolic blood pressure, diastolic blood pressure, heart rate, presence of diabetes, use of antihypertensive medications, number of cigarettes/day) at Year-0 and -25 examinations as independent predictors of echocardiographic outcomes at the Year-25 examination (LV end-diastolic volume [LVEDV]/height, LV end-systolic volume [LVESV]/height, LV mass [LVM]/height, and LVM/LVEDV ratio for LV structural indices; LV ejection fraction [LVEF], Ell, and Ecc for systolic indices; and early diastolic and atrial ratio, mitral annulus early peak velocity, ratio of mitral early peak velocity/mitral annulus early peak velocity; ratio, left atrial volume/height, longitudinal peak early diastolic strain rate, and circumferential peak early diastolic strain rate for diastolic indices). Compared with women, African American and white men had greater LV volume and LV mass (P<0.05). For LV systolic function, African American men had the lowest LVEF as well as longitudinal (Ell) and circumferential (Ecc) strain indices among the 4 sex/race-ethnic groups (P<0.05). For LV diastolic function, African American men and women had larger left atrial volumes; African American men had the lowest values of Ell and Ecc for diastolic strain rate (P<0.05). These race/sex differences in LV structure and LV function persisted after adjustment. CONCLUSIONS: African American men have greater LV size and lower LV systolic and diastolic function compared to African American women and to white men and women. The reasons for these racial-ethnic differences are partially but not completely explained by established cardiovascular risk factors.

Association of obesity in early adulthood and middle age with incipient left ventricular dysfunction and structural remodeling: the CARDIA study (Coronary Artery Risk Development in Young Adults).

OBJECTIVES: The goal of this study was to investigate the relationship of body mass index (BMI) and its 25-year change to left ventricular (LV) structure and function. BACKGROUND: Longstanding obesity may be associated with clinical cardiac dysfunction and heart failure. Whether obesity relates to cardiac dysfunction during young adulthood and middle age has not been investigated. METHODS: The CARDIA (Coronary Artery Risk Development in Young Adult) study enrolled white and black adults ages 18 to 30 years in 1985 to 1986 (Year-0). At Year-25, cardiac function was assessed by conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE). Twenty-five-year change in BMI (classified as low: <27 kg/m(2) and high: ≥27 kg/m(2)) was categorized into 4 groups (Low-Low, High-Low, Low-High, and High-High). Multiple linear regression was used to quantify the association between categorical changes in BMI (Low-Low as reference) with LV structural and functional parameters obtained in middle age, adjusting for baseline and 25-year change in risk factors. RESULTS: The mean BMI was 24.4 kg/m(2) in 3,265 participants included at Year-0. Change in BMI adjusted for risk factors was directly associated with incipient myocardial systolic dysfunction assessed by STE (High-High: ß-coefficient = 0.67; Low-High: ß-coefficient = 0.35 for longitudinal peak systolic strain) and diastolic dysfunction assessed by TDI (High-High: ß-coefficient = -074; Low-High: ß-coefficient = -0.45 for e') and STE (High-High: ß-coefficient = -0.06 for circumferential early diastolic strain rate). Greater BMI was also significantly associated with increased LV mass/height (High-High: ß-coefficient = 26.11; Low-High: ß-coefficient = 11.87). CONCLUSIONS: Longstanding obesity from young adulthood to middle age is associated with impaired LV systolic and diastolic function assessed by conventional echocardiography, TDI, and STE in a large biracial cohort of adults age 43 to 55 years.

Interstitial fibrosis, left ventricular remodeling, and myocardial mechanical behavior in a population-based multiethnic cohort: the Multi-Ethnic Study of Atherosclerosis (MESA) study.

BACKGROUND: Tagged cardiac magnetic resonance provides detailed information on regional myocardial function and mechanical behavior. T1 mapping by cardiac magnetic resonance allows noninvasive quantification of myocardial extracellular expansion (ECE), which has been related to interstitial fibrosis in previous clinical and subclinical studies. We assessed sex-associated differences in the relation of ECE to left ventricular (LV) remodeling and myocardial systolic and diastolic deformation in a large community-based multiethnic population. METHODS AND RESULTS: Midventricular midwall peak circumferential shortening and early diastolic strain rate and LV torsion and torsional recoil rate were determined using cardiac magnetic resonance tagging. Midventricular short-axis T1 maps were acquired in the same examination pre- and postcontrast injection using Modified Look-Locker Inversion-Recovery sequence. Multivariable linear regression (estimated regression coefficient, B) was used to adjust for risk factors and subclinical disease measures. Of 1230 participants, 114 had a visible myocardial scar by late gadolinium enhancement. Participants without a visible myocardial scar (n=1116) had no history of previous clinical events. In the latter group, multivariable linear regression demonstrated that lower postcontrast T1 times, reflecting greater ECE, were associated with lower circumferential shortening (B=-0.1; P=0.0001), lower LV end-diastolic volume index (B=0.6; P=0.0001), and lower LV end-diastolic mass index (B=0.4; P=0.0001). In addition, lower postcontrast T1 times were associated with lower early diastolic strain rate (B=0.01; P=0.03) in women only and lower LV torsion (B=0.005; P=0.03) and lower LV ejection fraction (B=0.2, P=0.01) in men only. CONCLUSIONS: Greater ECE is associated with reduced LV end-diastolic volume index and LV end-diastolic mass index in a large multiethnic population without history of previous cardiovascular events. In addition, greater ECE is associated with reduced circumferential shortening, lower early diastolic strain rate, and a preserved ejection fraction in women, whereas in men, greater ECE is associated with greater LV dysfunction manifested as reduced circumferential shortening, reduced LV torsion, and reduced ejection fraction.

Relation of torsion and myocardial strains to LV ejection fraction in hypertension.

OBJECTIVES: The goal of this study was to define the mechanism of preserved ejection fraction (EF) despite depressed myocardial strains in hypertension (HTN). BACKGROUND: Concentric left ventricular (LV) remodeling in HTN may have normal or supranormal EF despite depressed myocardial strains. The reason for such discordance is not clear. The aim of this study was to comprehensively evaluate the LV mechanics in a well-defined HTN population to define underlying reasons for such a paradox. METHODS: Sixty-seven patients with resistant HTN and 45 healthy control subjects were studied by cardiac magnetic resonance imaging and tissue tagging with 3-dimensional analysis. Amplitude and directional vector of longitudinal (Ell), circumferential (Ecc), and principal strain for maximal shortening (E3) were computed at basal, mid, and distal LV levels, respectively. LV torsion, defined as the rotation angle of apex relative to base, and LV twist, which accounts for the effects of differential LV remodeling on torsion for comparison among the 2 groups, were also calculated. RESULTS: LV mass index and LV mass/LV end-diastolic volume ratio were significantly higher in the HTN group compared with controls, consistent with concentric LV remodeling. Ell and Ecc were significantly decreased in amplitude with altered directional vector in HTN compared with controls. However, the amplitude of E3 was similar in the 2 groups. Torsion and twist were significantly higher in HTN, which was mainly due to increase in apical rotation. The HTN group demonstrated significantly increased LV wall thickening compared with controls that resulted in greater LVEF in the HTN group compared with controls (70% vs. 65%, p < 0.001, respectively). CONCLUSIONS: In compensated LV remodeling secondary to HTN, there is increased LV wall thickening with preserved E3 and increased torsion compared with normal controls. This, therefore, contributes to supranormal LVEF in HTN despite depressed longitudinal and circumferential strains.