Association of Pro-B-Type Natriuretic Peptide With Cardiac Magnetic Resonance-Measured Global and Regional Cardiac Function and Structure Over 10 Years: The MESA Study.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is widely used to diagnose and manage patients with heart failure. We aimed to investigate associations between NT-proBNP levels and development of global and regional myocardial impairment, dyssynchrony, and risk of developing myocardial scar over time. Methods and Results We included 2416 adults (45-84 years) without baseline clinical cardiovascular disease from MESA (Multi-Ethnic Study of Atherosclerosis). NT-proBNP was assessed at baseline (2000-2002). Cardiac magnetic resonance-measured left ventricular parameters were assessed at baseline and year 10 (2010-2012). Tagged cardiac magnetic resonance and myocardial dyssynchrony were assessed. We used linear and logistic regression models to study the relationships between quartiles of NT-proBNP levels and outcome variables. Left ventricular parameters decreased over time. After 10-year follow-up and adjusting for cardiovascular disease risk factors, people in the highest quartile had significantly greater decline in left ventricular ejection fraction (-1.60%; 95% CI, -2.26 to -0.94; P<0.01) and smaller decline in left ventricular end systolic volume index (-0.47 mL/m2; 95% CI, -1.18 to 0.23; P<0.01) compared with those in the lowest quartile. Individuals in the highest quartile had more severe risk factor adjusted global, mid, and apical regional dyssynchrony compared with those in the lowest, second, and third quartiles (all P-trend<0.05). Compared with the lowest-quartile group, the adjusted odds ratios for having myocardial scar was 1.3 (95% CI, 0.7-2.2) for quartile 2; 1.2 (95% CI, 0.6-2.3) for quartile 3; and 2.7 (95% CI, 1.4-5.5) for quartile 4 (P-trend=0.012) for the total sample. Conclusions Among participants without baseline clinical cardiovascular disease, higher baseline NT-proBNP concentration was significantly associated with subclinical changes in developing myocardial dysfunction, more severe cardiac dyssynchrony, and higher odds of having myocardial scar over a 10-year period independent of traditional cardiovascular disease risk factors.

Regional myocardial functional patterns: Quantitative tagged magnetic resonance imaging in an adult population free of cardiovascular risk factors: The multi-ethnic study of atherosclerosis (MESA).

PURPOSE: To characterize the left ventricular (LV) regional deformation patterns and identify normal values of left ventricular strains from tagged magnetic resonance imaging (MRI) in a population with low-risk-factor (LRF) exposure. MATERIALS AND METHODS: Tagged CMR on three LV short axis slices was performed in participants of the MESA study who were free of cardiovascular disease at baseline. Images were analyzed by the harmonic phase imaging method to obtain: peak torsion, circumferential (Ecc) and radial (Err) strains, and systolic (SRs) and early-diastolic (SRe) strain rates. An LRF group was created from the overall population based on strict exclusion criteria (n = 129) based on risk factors and events observed over a 10-year follow-up. RESULTS: The normative prediction intervals for the averaged peak Ecc (%) and torsion (deg/cm) measures were: in 45-59-year-old women: (-20.8, -13.2) and (2.1, 6.3); 60-84-year-old women: (-20.6, -12.8) and (2.2, 6.9); 45-59-year-old men: (-21.3, -13.5) and (1.9, 5.7); 60-84-year-old men: (-20.5, -12.5) and (1.5, 5.2). In general, African-Americans (Ecc = -15.9, torsion = 3.3) had lower strains as compared to Chinese (Ecc = -17.1, torsion = 3.9), while Caucasians and Hispanics were intermediate and not significantly different. Circumferential shortening increased spatially from the epicardium to the endocardium (-16.9 to -18.2 at the mid-ventricle) and from the base to the apex (-15.1 to -17.5 at the midwall). CONCLUSION: The present study provides reference ranges and deformation patterns of deformation values from a large healthy population free of cardiovascular disease at baseline.

Metabolic syndrome, strain, and reduced myocardial function: multi-ethnic study of atherosclerosis.

BACKGROUND: Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (εCC) and longitudinal strain (εLL), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders. OBJECTIVE: We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE. METHODS: We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components. RESULTS: Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower εCC and lower εLL than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative εCC (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative εLL after adjustment for ethnicity, LVEF, and creatinine. CONCLUSION: Left ventricular εCC and εLL, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%.

Síndrome Metabólica, Strain e Redução da Função Miocárdica: Multi-Ethnic Study of Atherosclerosis / Metabolic Syndrome, Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis

Fundamento: A doença cardiovascular subclínica é prevalente em pacientes com síndrome metabólica (SM). O strain circunferencial (εCC) e o strain longitudinal (εLL) do ventriculo esquerdo (VE), avaliados pelo ecocardiograma com speckle tracking (STE), são índices de função sistólica: o encurtamento das fibras circunferenciais e longitudinais do VE é indicado por um valor negativo do strain. Portanto, quanto mais negativo o strain, melhor a função sistólica do VE. O εCC e o εLL têm sido usados para demonstrar disfunção ventricular subclínica em vários distúrbios clínicos. Objetivo: Levantamos a hipótese de que a SM está associada com comprometimento da função miocárdica, quando avaliada pelo STE. Métodos: Este estudo analisou participantes do Multi-Ethnic Study of Atherosclerosis (MESA) que realizaram o STE e foram avaliados para todos os componentes da SM. Resultados: Entre os 133 participantes incluídos (mulheres: 63%; idade: 65 ± 9 anos), a prevalência de SM foi de 31% (41/133). Indivíduos com SM apresentaram valores menores do εCC e do εLL que aqueles sem SM (-16,3% ± 3,5% vs. -18,4% ± 3,7%, p < 0,01; e -12,1% ± 2,5% vs. -13,9% ± 2,3%, p < 0,01, respectivamente). A fração de ejeção do VE (FEVE) foi semelhante nos dois grupos (p = 0,09). Na análise multivariada, a SM associou-se a um valor mais baixo do strain circunferencial (B = 2,1%, IC 95%: 0,6-3,5; p < 0,01), mesmo após ajuste para idade, etnia, massa VE e FEVE. De maneira semelhante, a presença de SM (B = 1,3%, IC 95%: 0,3-2,2; p < 0,01) e a massa do VE (B = 0,02%, IC 95%: 0,01 0,03; p = 0,02) associaram-se a um valor menor do strain longitudinal após ajuste para etnia, FEVE e creatinina. Conclusão: O εCC ...

Background: Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (εCC) and longitudinal strain (εLL), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders. Objective: We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE. Methods: We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components. Results: Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower εCC and lower εLL than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative εCC (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative εLL after adjustment for ethnicity, LVEF, and creatinine. Conclusion: Left ventricular εCC and εLL, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%. .

Resting heart rate as predictor for left ventricular dysfunction and heart failure: MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES: The objective of this study was to investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND: The association of resting heart rate to HF and LV function has not been well described in an asymptomatic multi-ethnic population. METHODS: Resting heart rate was measured in participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial at inclusion. Incident HF was registered (n = 176) during follow-up (median 7 years) in those who underwent cardiac magnetic resonance imaging (n = 5,000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1,056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume, and mass in addition to resting heart rate. RESULTS: Cox analysis demonstrated that for 1 beat/min increase in resting heart rate, there was a 4% greater adjusted relative risk for incident HF (hazard ratio: 1.04; 95% CI: 1.02 to 1.06; p < 0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even when all coronary heart disease events were excluded from the model. CONCLUSIONS: Elevated resting heart rate was associated with increased risk for incident HF in asymptomatic participants in the MESA trial. Higher heart rate was related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Prognostic value of myocardial circumferential strain for incident heart failure and cardiovascular events in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis.

AIMS: Left ventricular (LV) circumferential strain (Ecc) is a sensitive index of regional myocardial function. Currently, no studies have assessed its prognostic value in general population. We sought to investigate whether Ecc has a prognostic value for predicting incident heart failure (HF) and other major cardiovascular events in asymptomatic individuals without a history of previous cardiovascular diseases. METHODS AND RESULTS: We, prospectively, assessed incident HF and atherosclerotic events during a 5.5 ± 1.3-year period in 1768 asymptomatic individuals aged 45-84 (mean age 65 years; 47% female) who underwent tagged magnetic resonance imaging for strain determination. During the follow-up period, 39 (2.2%) participants experienced incident HF and 108 (6.1%) participants had atherosclerotic cardiovascular events. Average of peak Ecc of 12-LV segments (Ecc-global) and mid-slice (Ecc-mid) was -17.0 ± 2.4 and -17.5 ± 2.7%, respectively. Participants with average absolute Ecc-mid lower than -16.9% had a higher cumulative hazard of incident HF (log-rank test, P = 0.001). In cox regression analysis, Ecc-mid predicted incident HF independent of age, diabetes status, hypertension, interim myocardial infarction, LV mass index, and LV ejection fraction (hazard ratio 1.15 per 1%, 95% CI: 1.01-1.31, P = 0.03). This relationship remained significant after adjustment for LV-end-systolic wall stress into covariates. In addition, by adding Ecc-mid to risk factors, LV ejection fraction, and the LV mass index, both the global χ(2) value (76.6 vs. 82.4, P = 0.04) and category-less net-reclassification index (P = 0.01, SE = 0.18, z = 2.53) were augmented for predicting HF. Circumferential strain was also significantly related to the composite atherosclerotic cardiovascular events, but its relationship was attenuated after introducing the LV mass index. CONCLUSION: Circumferential shortening provides robust, independent, and incremental predictive value for incident HF in asymptomatic subjects without any history of previous clinical cardiovascular disease. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

High-sensitivity C-reactive protein as an independent predictor of progressive myocardial functional deterioration: the multiethnic study of atherosclerosis.

BACKGROUND: Systemic inflammation has been linked to the development of heart failure in population studies including Multi-Ethnic Study of Atherosclerosis (MESA), but little evidence exists regarding potential mechanism of this relationship. In this study, we used longitudinal magnetic resonance imaging follow-up analysis to examine whether C-reactive protein (CRP) levels relate to progressive myocardial functional deterioration as a potential mechanism of incident heart failure. METHODS: Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac magnetic resonance imaging both at baseline and at 5-year follow-up were analyzed. Left ventricular midwall and midslice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Circumferential strain change was calculated as the difference between baseline and follow-up Ecc. RESULTS: During the follow-up period, participants (n = 785) with elevated CRP experienced a decrease in strain, independent of age, gender, and ethnicity (B = 0.081, ∆Ecc change per 1 mg/L CRP change, 95% CI 0.036-0.126, P < .001, model 1) and, additionally, beyond systolic blood pressure, heart rate, diabetes, smoking status, body mass index, current medication, and glomerular filtration rate (B = 0.099, 0.052-0.145, P < .001, model 2). The relationship remained statistically significant after further adjustment for left ventricular mass, coronary calcium score, and interim clinical coronary events (B = 0.098, 0.049-0.147, P < .001, model 3). CONCLUSION: Higher CRP levels are related to progressive myocardial functional deterioration independent of subclinical atherosclerosis and clinical coronary events in asymptomatic individuals without previous history of heart disease.

Usefulness of radial strain mapping by multidetector computer tomography to quantify regional myocardial function in patients with healed myocardial infarction.

We introduce and evaluate strain mapping by multidetector computer tomography as a new noninvasive method for assessment of myocardial function. In patients (n = 16) with healed myocardial infarction, peak systolic radial strain was measured by automated pixel pattern matching analysis of multiple left ventricular 64-slice multidetector computer tomographic short-axis recordings. For comparison, radial strain and myocardial infarct extent were measured by tagged magnetic resonance imaging (MRI) and late enhancement MRI, respectively. In a linear mixed model analysis, myocardial infarct extent was a strong predictor of segmental strain by multidetector computer tomography (beta = -0.44, p <0.0001). Strain was significantly different among noninfarcted (0%), nontransmurally infarcted (0% to 50%), and transmurally infarcted (>50%) segments (p <0.001) and between infarcted and noninfarcted border zone segments (p <0.001). There was a close relation between strain by multidetector computer tomography and by tagged MRI (mean difference -7.4 +/- 11.7%, r = 0.68, p <0.0001). Mean time-to-peak systolic strain was 324 +/- 42 ms by multidetector computer tomography and 335 +/- 56 ms by tagged MRI (mean difference 11 +/- 40 ms). In conclusion, to our knowledge this is the first study to demonstrate that regional myocardial function can be quantified by multidetector computer tomographic imaging, indicating that assessment of radial strain by multidetector computer tomography might be a useful tool in the evaluation of patients with cardiovascular diseases.

Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Age-related alterations of left ventricular (LV) structure and function that may predispose to cardiovascular events are not well understood. METHODS AND RESULTS: We used cardiac MRI to examine age-related differences in LV structure and function in 5004 participants without overt cardiovascular disease when enrolled in the Multi-Ethnic Study of Atherosclerosis; 1099 participants received additional strain analyses by MRI tagging. We also assessed the relation of age-associated remodeling with cardiovascular outcomes using Cox proportional hazard models adjusting for cardiovascular risk factors. Although LV mass decreased with age (-0.3 g per year), the mass-to-volume ratio markedly increased (+5 mg/mL per year, P<0.0001), driven by a substantial reduction in end-diastolic volume (-0.8 mL per year, P<0.0001). Age was also associated with a significant fall in stroke volume (-0.4 mL per year, P<0.0001), along with strain patterns reflecting systolic (P<0.0001) as well as diastolic (P<0.01) myocardial dysfunction-despite a modestly enhanced ejection fraction (+0.1% per year, P<0.0001). Increased mass-to-volume ratio conferred a significant risk for total cardiovascular events; this trend was strongest among younger (<65 years; hazard ratio, 3.69 [CI, 1.34 to 10.10]) versus older (> or =65 years; hazard ratio, 1.68 [CI 0.77 to 3.68]) individuals with the highest compared to lowest mass-to-volume ratio quintile (P(interaction)=0.013). CONCLUSIONS: Age is associated with a phenotype of LV remodeling marked by increased mass-to-volume ratio and accompanied by systolic as well as diastolic myocardial dysfunction that is not reflected by preserved ejection fraction. This pattern of ventricular remodeling confers significant cardiovascular risk, particularly when present earlier in life.

Age, increased left ventricular mass, and lower regional myocardial perfusion are related to greater extent of myocardial dyssynchrony in asymptomatic individuals: the multi-ethnic study of atherosclerosis.

BACKGROUND: Age and left ventricular (LV) hypertrophy are risk factors for the development of LV dysfunction and congestive heart failure. Our goal was to study the relationships of LV mass and age with myocardial dyssynchrony among asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis. METHODS AND RESULTS: A total of 1100 individuals underwent tagged magnetic resonance imaging. Regional LV function was analyzed with the use of harmonic phase imaging. Time to peak systolic circumferential strain and strain rate were measured in 12 segments, and myocardial dyssynchrony was expressed as the SD of time to peak strain and strain rate. Relationships of age, LV mass, and myocardial perfusion with timing of strain, strain rate, and dyssynchrony were studied. There was a positive relationship between age and time to peak strain before (regression coefficient=0.37 ms/year of age; 95% confidence interval, 0.05 to 0.70; P=0.025) and after adjustment for demographic characteristics and risk factors (P=0.007). Positive associations between age and SD of time to peak strain (regression coefficient=0.33 ms/year of age; P=0.002) and SD of time to peak systolic strain rate were documented (P=0.045). Importantly, we found that LV mass index is directly related to time to peak strain (P<0.001), time to peak strain rate, and the SD of time to strain rate (P=0.001 for all). Finally, decreased myocardial perfusion at rest was associated with delayed contraction and increased extent of dyssynchrony. CONCLUSIONS: In asymptomatic individuals, age, increased LV mass, and decreased myocardial perfusion are related to delayed myocardial contraction and greater extent of dyssynchrony. Increased dyssynchrony may mediate the association of myocardial dysfunction with age and LV hypertrophy.

Subclinical atherosclerosis and incipient regional myocardial dysfunction in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVES: This study sought to determine whether increased carotid intima-media thickness (IMT) is related to reduced regional myocardial function in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). BACKGROUND: Carotid artery IMT is an established index of subclinical atherosclerosis, and tagged magnetic resonance imaging (MRI) can detect incipient alterations of segmental function that precede overt myocardial failure. METHODS: The MESA study is a prospective observational study including four ethnic groups free from clinical cardiovascular disease. Peak midwall systolic circumferential strain (ECC) and regional strain rates were calculated by harmonic phase from tagged MRI data of 500 participants. Systolic ECC and diastolic strain rate were regressed on IMT of the common carotid artery defined by ultrasound, with adjustments for body mass index, blood pressure, cholesterol, diabetes, smoking, left ventricular hypertrophy, C-reactive protein, age, and gender. RESULTS: The mean participant age was 66 +/- 10 years (mean +/- SD). Among the 58 participants, 4% were male and the interquartile (25th to 75th percentile) range for IMT was 0.25 mm. Multiple linear regression analyses showed that increased IMT was related to reduced systolic regional function (less shortening ECC) in all myocardial regions (p < 0.05), except in the inferior wall. The analyses also showed that greater IMT was associated with a lower diastolic strain rate (diastolic reduced function) in all regions (p < 0.01), except in the anterior wall. CONCLUSIONS: Greater carotid IMT is associated with alterations of myocardial strain parameters reflecting reduced systolic and diastolic myocardial function. These observations indicate a relationship between subclinical atherosclerosis and incipient myocardial dysfunction in a population free of clinical heart disease.