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.

Coronary artery plaque volume and obesity in patients with diabetes: the factor-64 study.

PURPOSE: To determine the relationship between coronary plaque detected with coronary computed tomographic (CT) angiography and clinical parameters and cardiovascular risk factors in asymptomatic patients with diabetes. MATERIALS AND METHODS: All patients signed institutional review board-approved informed consent forms before enrollment. Two hundred twenty-four asymptomatic diabetic patients (121 men; mean patient age, 61.8 years; mean duration of diabetes, 10.4 years) underwent coronary CT angiography. Total coronary artery wall volume in all three vessels was measured by using semiautomated software. The coronary plaque volume index (PVI) was determined by dividing the wall volume by the coronary length. The relationship between the PVI and cardiovascular risk factors was determined with multivariable analysis. RESULTS: The mean PVI (±standard deviation) was 11.2 mm(2) ± 2.7. The mean coronary artery calcium (CAC) score (determined with the Agatston method) was 382; 67% of total plaque was noncalcified. The PVI was related to age (standardized ß = 0.32, P < .001), male sex (standardized ß = 0.36, P < .001), body mass index (BMI) (standardized ß = 0.26, P < .001), and duration of diabetes (standardized ß = 0.14, P = .03). A greater percentage of soft plaque was present in younger individuals with a shorter disease duration (P = .02). The soft plaque percentage was directly related to BMI (P = .002). Patients with discrepancies between CAC score and PVI rank quartiles had a higher percentage of soft and fibrous plaque (18.7% ± 3.3 vs 17.4% ± 3.5 [P = .008] and 52.2% ± 7.2 vs 47.2% ± 8.8 [P < .0001], respectively). CONCLUSION: In asymptomatic diabetic patients, BMI was the primary modifiable risk factor that was associated with total and soft coronary plaque as assessed with coronary CT angiography.

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.

Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial.

IMPORTANCE: Coronary artery disease (CAD) is a major cause of cardiovascular morbidity and mortality in patients with diabetes mellitus, yet CAD often is asymptomatic prior to myocardial infarction (MI) and coronary death. OBJECTIVE: To assess whether routine screening for CAD by coronary computed tomography angiography (CCTA) in patients with type 1 or type 2 diabetes deemed to be at high cardiac risk followed by CCTA-directed therapy would reduce the risk of death and nonfatal coronary outcomes. DESIGN, SETTING, AND PARTICIPANTS: The FACTOR-64 study was a randomized clinical trial in which 900 patients with type 1 or type 2 diabetes of at least 3 to 5 years' duration and without symptoms of CAD were recruited from 45 clinics and practices of a single health system (Intermountain Healthcare, Utah), enrolled at a single-site coordinating center, and randomly assigned to CAD screening with CCTA (n = 452) or to standard national guidelines-based optimal diabetes care (n = 448) (targets: glycated hemoglobin level <7.0%, low-density lipoprotein cholesterol level <100 mg/dL, systolic blood pressure <130 mm Hg). All CCTA imaging was performed at the coordinating center. Standard therapy or aggressive therapy (targets: glycated hemoglobin level <6.0%, low-density lipoprotein cholesterol level <70 mg/dL, high-density lipoprotein cholesterol level >50 mg/dL [women] or >40 mg/dL [men], triglycerides level <150 mg/dL, systolic blood pressure <120 mm Hg), or aggressive therapy with invasive coronary angiography, was recommended based on CCTA findings. Enrollment occurred between July 2007 and May 2013, and follow-up extended to August 2014. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization; the secondary outcome was ischemic major adverse cardiovascular events (composite of CAD death, nonfatal MI, or unstable angina). RESULTS: At a mean follow-up time of 4.0 (SD, 1.7) years, the primary outcome event rates were not significantly different between the CCTA and the control groups (6.2% [28 events] vs 7.6% [34 events]; hazard ratio, 0.80 [95% CI, 0.49-1.32]; P = .38). The incidence of the composite secondary end point of ischemic major adverse cardiovascular events also did not differ between groups (4.4% [20 events] vs 3.8% [17 events]; hazard ratio, 1.15 [95% CI, 0.60-2.19]; P = .68). CONCLUSIONS AND RELEVANCE: Among asymptomatic patients with type 1 or type 2 diabetes, use of CCTA to screen for CAD did not reduce the composite rate of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization at 4 years. These findings do not support CCTA screening in this population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00488033.

Relationship of interleukin-6 with regional and global left-ventricular function in asymptomatic individuals without clinical cardiovascular disease: insights from the Multi-Ethnic Study of Atherosclerosis.

AIMS: We sought to examine the relationship between circulating interleukin-6 (IL-6) level and regional left-ventricular (LV) function among apparently healthy individuals free of cardiovascular disease. METHODS AND RESULTS: Using magnetic resonance myocardial tagging, we determined peak systolic circumferential strain (Ecc) as a measure of regional systolic function in 894 asymptomatic participants in the Multi-Ethnic Study of Atherosclerosis. Ecc was analysed by harmonic phase imaging separately in the LV anterior wall, septum, lateral wall, and inferior wall. Global Ecc was calculated as the average of Ecc in all myocardial segments. We performed multivariable linear regression to evaluate the independent associations between log IL-6 and Ecc, after adjusting for demographic features, cardiovascular risk factors, and markers of subclinical atherosclerosis. The inverse relationships between IL-6 and absolute Ecc were similar in both genders. In multivariable analysis, higher IL-6 level was independently associated with reduced systolic function (less negative Ecc) in the septum [regression coefficient = 1.03 per unit higher log IL-6, 95% confidence interval (CI) 0.26-1.79, P = 0.008] and inferior wall (regression coefficient = 1.65, 95% CI 0.74-2.56, P < 0.001), but not in the anterior wall (P = 0.27) or lateral wall (P = 0.52). Overall, there was an independent inverse association between IL-6 and global Ecc (regression coefficient = 0.94, 95% CI 0.37-1.51, P = 0.001). Compared with C-reactive protein, higher IL-6 level demonstrates a stronger independent association with reduced regional systolic function. CONCLUSION: In asymptomatic men and women without documented cardiovascular disease, there is a strong, independent, inverse relationship between IL-6 and regional LV systolic function. These findings suggest that IL-6 may underlie the pathogenetic link between inflammation, LV dysfunction and incipient heart failure. The observed variable relationships between IL-6 and systolic function across different LV regions warrant further investigations.

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.

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.

Arterial stiffness is associated with regional ventricular systolic and diastolic dysfunction: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: The pathophysiology of left ventricular (LV) dysfunction, particularly in the setting of a preserved ejection fraction (EF), remains unclear. Few studies have investigated the relationship between arterial compliance and LV function in humans, and none used cardiovascular MRI. METHODS AND RESULTS: We sought to determine whether arterial compliance is related to regional myocardial function among participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Arterial compliance was assessed using carotid ultrasound measurements to calculate the distensibility coefficient (DC) and Young's modulus (YM). Circumferential systolic (SR(S)) and diastolic (SR(E)) strain rates were calculated by harmonic phase (HARP) from tagged MRI. Associations between arterial compliance and indices of ventricular function were adjusted for cardiovascular risk factors. We found a significant association between arterial compliance and SR(S) in all myocardial regions (P<0.05); arterial compliance was also associated with SR(E) in the lateral and septal wall regions (P<0.05). Multiple linear regression analyses demonstrated a direct linear relationship between the carotid artery DC and SR(S) across all LV segments and slices, even after adjustment for cardiovascular risk factors and LV mass. In regression analyses, a significant relationship between arterial compliance and SR(E) in the septal and antero-apical walls was also found and remained significant after multivariable adjustment. CONCLUSIONS: Arterial stiffness is associated with early and asymptomatic impairment of systolic as well as diastolic myocardial function. Further studies are needed to elucidate role of vascular compliance in the development of ventricular dysfunction and failure.

Elevated homocysteine is associated with reduced regional left ventricular function: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: An elevated homocysteine (Hcy) level has been reported to be a risk factor for the development of congestive heart failure in individuals free of myocardial infarction. In this study, we aim to investigate the relationship between Hcy levels and regional left ventricular function in an asymptomatic population. METHOD AND RESULTS: Regional peak systolic midwall circumferential strains were calculated from 1178 tagged magnetic resonance imaging studies in participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Left ventricular regions were defined by coronary territories (left anterior descending, left circumflex, right coronary artery). For the 1178 study participants (66+/-10 years of age, 58% males), the median (interquartile range) of Hcy was 9.1 (9.0 to 9.3). After adjustment for traditional risk factors, race, height, weight, left ventricular end-diastolic mass/volume, serum creatinine, and measures of atherosclerosis, reduced regional myocardial circumferential shortening across sex-specific quartiles of plasma Hcy in the left anterior descending (P=0.038) and left circumflex (P=0.009) regions persisted, which indicated an important association of reduced function with elevated Hcy. Multiple linear regression analyses confirmed that circumferential systolic dysfunction was associated with log transformed Hcy levels in the left anterior descending (P=0.004) and left circumflex (P=0.0002) regions. In the fully adjusted model, the odds ratio for left ventricular strains below the 10th percentile with 1 SD increases in log-transformed Hcy was 1.33 (95% confidence interval, 1.04 to 1.70; P=0.022) for the left anterior descending, 1.28 (95% confidence interval, 1.00 to 1.64; P=0.046) for the left circumflex, and 1.32 (95% confidence interval, 1.03 to 1.69; P=0.025) for the right coronary artery region. CONCLUSIONS: In this asymptomatic population, an elevated Hcy level is associated with reduced regional left ventricular systolic function detected by tagged magnetic resonance imaging.

Diastolic suction is impaired by bed rest: MRI tagging studies of diastolic untwisting.

Bed rest deconditioning leads to physiological cardiac atrophy, which may compromise left ventricular (LV) filling during orthostatic stress by reducing diastolic untwisting and suction. To test this hypothesis, myocardial-tagged magnetic resonance imaging (MRI) was performed, and maximal untwisting rates of the endocardium, midwall, and epicardium were calculated by Harmonic Phase Analysis (HARP) before and after -6 degrees head-down tilt bed rest for 18 days with (n = 14) and without exercise training (n = 10). LV mass and LV end-diastolic volume were measured using cine MRI. Exercise subjects cycled on a supine ergometer for 30 min, three times per day at 75% maximal heart rate (HR). After sedentary bed rest, there was a significant reduction in maximal untwisting rates of the midwall (-46.8 +/- 14.3 to -35.4 +/- 12.4 degrees /s; P = 0.04) where untwisting is most reliably measured, and to a lesser degree of certainty in the endocardium (-50.3 +/- 13.8 to -40.1 +/- 18.5 degrees /s; P = 0.09); the epicardium was unchanged. In contrast, when exercise was performed in bed, untwisting rates were enhanced at the endocardium (-48.4 +/- 20.8 to -72.3 +/- 22.3 degrees /ms; P = 0.05) and midwall (-39.2 +/- 12.2 to -59.0 +/- 19.6 degrees /s; P = 0.03). The differential response was significant between groups at the endocardium (interaction P = 0.02) and the midwall (interaction P = 0.004). LV mass decreased in the sedentary group (156.4 +/- 30.3 to 149.5 +/- 27.9 g; P = 0.07), but it increased slightly in the exercise-trained subjects (156.4 +/- 34.3 to 162.3 +/- 40.5 g; P = 0.16); (interaction P = 0.03). We conclude that diastolic untwisting is impaired following sedentary bed rest. However, exercise training in bed can prevent the physiological cardiac remodeling associated with bed rest and preserve or even enhance diastolic suction.

Lower myocardial perfusion reserve is associated with decreased regional left ventricular function in asymptomatic participants of the multi-ethnic study of atherosclerosis.

BACKGROUND: Myocardial ischemia is an important determinant of regional left ventricular systolic function. Myocardial blood flow reserve may be impaired by cardiovascular disease before alterations of myocardial perfusion at rest become manifest. Nevertheless, the relation between flow reserve and regional myocardial function has not been studied in individuals without a history of clinical heart disease. METHODS AND RESULTS: Seventy-four participants (66+/-9 years, mean+/-SD) of the Multi-Ethnic Study of Atherosclerosis (MESA) underwent myocardial magnetic resonance tagging and contrast-enhanced perfusion studies. Regional myocardial function was evaluated as peak systolic circumferential strain (Ecc) in the three main coronary territories (left anterior descending [LAD], left circumflex, and right coronary artery [RCA]). Myocardial blood flow at rest and during adenosine-induced hyperemia was quantified by contrast-enhanced magnetic resonance imaging, to study the relation between regional flow and function after multivariable adjustment for age, gender, body mass index, left ventricular mass, and traditional risk factors. Lower regional myocardial blood flow during hyperemia was associated with reduced regional left ventricular function expressed as lower Ecc in the RCA (P<0.01) and left circumflex regions (P<0.05) measured in the subendocardium, mid-wall, and subepicardium. In contrast, no significant association was seen in the LAD territory (P=0.16). In addition, segmental function in LAD and RCA regions was reduced when individuals in the lowest 10th percentile for regional myocardial flow reserve were compared with the other participants. Absolute decreases in mid-wall Ecc LAD and RCA and global Ecc were 3.0%, 3.4%, and 2.8%, respectively (P<0.05 for all regions). CONCLUSIONS: Lower myocardial flow reserve is related to reduced regional function in asymptomatic individuals.

Enhanced infarct border zone function and altered mechanical activation predict inducibility of monomorphic ventricular tachycardia in patients with ischemic cardiomyopathy.

PURPOSE: To prospectively determine whether mechanical behavior of left ventricular wall segments that contain different degrees of scar tissue and are located at different distances from the interface between infarcted and noninfarcted myocardial tissue can help predict inducibility of monomorphic ventricular tachycardia (VT) in patients with ischemic cardiomyopathy. MATERIALS AND METHODS: This HIPAA-compliant study was institutional review board approved; written informed consent was obtained from all patients. Forty-six patients (36 men, 10 women; mean age +/- standard deviation, 61.6 years +/- 11.9) with prior myocardial infarction (MI) and left ventricular dysfunction were referred for defibrillator implantation and underwent an electrophysiologic examination and tagged contrast-enhanced magnetic resonance (MR) imaging. Peak circumferential shortening strain (Ecc) and time to peak Ecc were measured in 12 segments from short-axis sections. Remote, adjacent, and border zones were defined according to increasing proximity to the MI. Patients in whom monomorphic VT could be induced (ie, inducible patients) were considered positive for inducibility. Relationships between inducibility of monomorphic VT, peak Ecc, and time to peak Ecc were analyzed with one-way analysis of variance and Bonferroni test. RESULTS: Inducible patients had more infarcted and border zone sectors and a shorter time to peak Ecc than did noninducible patients in the border zone and adjacent and infarcted regions (P < .001). Peak Ecc in the border zone of inducible patients (-11.42% +/- 0.46 [standard error]) was greater than that in noninducible patients (-10.18% +/- 0.38; P < .05). Ratio of Ecc in border zone and in remote regions was greater (P < .05) in inducible patients than in noninducible patients (1.31 +/- 0.27 vs 0.64 +/- 0.13, respectively). CONCLUSION: Enhanced border zone function defined as greater Ecc and earlier time to peak Ecc showed positive correlation to VT inducibility in patients with prior MI and left ventricular dysfunction.

Regional left ventricular function in individuals with mild to moderate renal insufficiency: the Multi-Ethnic Study of Atherosclerosis.

INTRODUCTION: Asymptomatic individuals with moderate reduction in renal function are at increased risk for congestive heart failure. In this study we investigate the relationship between mild-moderate renal insufficiency and regional left ventricle function in a population free of cardiovascular disease. METHOD: This is a cross-sectional study in 500 individuals > or = 45 years of age without known cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis. Regional systolic and diastolic strain rate as well as peak systolic midwall circumferential strain were calculated from tagged magnetic resonance imaging studies in these participants. Regions were defined by coronary territories (left anterior descending, left circumflex, right coronary artery). Creatinine clearance (CrCl) was estimated by using the Cockcroft-Gault equation and categorized as > or = 90 mL/min (normal CrCl), 60 to 89 mL/min (mildly reduced CrCl), and < 60 mL/min (moderately reduced CrCl). RESULTS: The mean participant age was 66 +/- 10 years (58% men). The mean CrCl was 80 +/- 25 mL/min. Multiple linear regression analyses indicated that circumferential systolic strain as well as systolic strain rate were significantly lower in participants with moderately reduced CrCl compared with those with normal CrCl in all coronary territories. Lower diastolic strain rates was observed in mild-moderate renal territories compared with those with normal CrCl. CONCLUSIONS: Impaired regional systolic and diastolic function was observed with mild-moderate reduction of renal function without evidence of clinical heart disease. The results strengthen the usefulness of routine determination of renal function in potentially identify individuals with early myocardial dysfunction.

Coronary artery atherosclerosis is related to reduced regional left ventricular function in individuals without history of clinical cardiovascular disease: the Multiethnic Study of Atherosclerosis.

OBJECTIVE: We investigated whether regional coronary calcium score by computed tomography is related to regional left ventricular systolic function measured by MRI tagging in participants of the Multiethnic Study of Atherosclerosis. METHODS AND RESULTS: The Multiethnic Study of Atherosclerosis is a prospective observational study of men and women without a history of previous heart disease from 4 ethnic groups. Calcium scores were measured separately for the left anterior descendent (LAD), left circumflex (LCX), and right (RCA) coronary arteries. Left ventricular strain and strain rate were determined by tagged MRI in the corresponding vascular territories of the coronary vessels in 509 participants. Greater coronary calcification in the LAD, LCX, and right RCA coronary arteries were related to worse function in their respective perfusion. Anterior wall strain rate was -1.37+/-0.41 when LAD calcium was zero versus -1.17+/-0.24 1/s in the highest quartile of calcium score (P<0.001). Similar relationships were evident in the LCX and RCA regions. Participants with 1- and 2-vessel coronary artery calcium had better myocardial function in the remote area compared with the territory supplied by the diseased artery. CONCLUSIONS: High-local calcium score is related to regional dysfunction in the corresponding coronary territory among individuals without a history of previous heart disease. These results indicate a link between atherosclerosis and subclinical regional left ventricular dysfunction.

New noninvasive method for assessment of left ventricular rotation: speckle tracking echocardiography.

BACKGROUND: Left ventricular (LV) torsion is due to oppositely directed apical and basal rotation and has been proposed as a sensitive marker of LV function. In the present study, we introduce and validate speckle tracking echocardiography (STE) as a method for assessment of LV rotation and torsion. METHODS AND RESULTS: Apical and basal rotation by STE was measured from short-axis images by automatic frame-to-frame tracking of gray-scale speckle patterns. Rotation was calculated as the average angular displacement of 9 regions relative to the center of a best-fit circle through the same regions. As reference methods we used sonomicrometry in anesthetized dogs during baseline, dobutamine infusion, and apical ischemia, and magnetic resonance imaging (MRI) tagging in healthy humans. In dogs, the mean peak apical rotation was -3.7+/-1.2 degrees (+/-SD) and -4.1+/-1.2 degrees, and basal rotation was 1.9+/-1.5 degrees and 2.0+/-1.2 degrees by sonomicrometry and STE, respectively. Rotations by both methods increased (P<0.001) during dobutamine infusion. Apical rotation by both methods decreased during left anterior descending coronary artery occlusion (P<0.007), whereas basal rotation was unchanged. In healthy humans, apical rotation was -11.6+/-3.8 degrees and -10.9+/-3.3 degrees, and basal rotation was 4.8+/-1.7 degrees and 4.6+/-1.3 degrees by MRI tagging and STE, respectively. Torsion measurement by STE showed good correlation and agreement with sonomicrometry (r=0.94, P<0.001) and MRI (r=0.85, P<0.001). CONCLUSIONS: The present study demonstrates that regional LV rotation and torsion can be measured accurately by STE, suggesting a new echocardiographic approach for quantification of LV systolic function.

Left ventricular concentric remodeling is associated with decreased global and regional systolic function: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The transition from compensatory concentric remodeling to myocardial failure is not completely understood in humans. To investigate determinants of incipient myocardial dysfunction, we examined the association between concentric remodeling and regional LV function in asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Myocardial tagged MRI was performed. Regional myocardial function expressed as peak systolic midwall circumferential strain (Ecc) was analyzed in 441 consecutive studies by HARP (Harmonic Phase) tool. Peak Ecc was correlated with the extent of concentric remodeling determined by the ratio of left ventricular mass to end-diastolic volume (M/V ratio). In men, a gradual decline in peak global Ecc was seen with increasing M/V ratio (test for trend, P<0.001). Among women, however, Ecc tended to be lower only in the fifth compared with the first quintile of M/V ratio (P=0.1). The association of lower Ecc with increasing M/V ratio was regionally heterogeneous but was particularly prominent in the LAD region in men (test for trend, P<0.001) and in women (test for trend, P=0.02). In the right coronary and left circumflex artery territories, these associations were less marked in both genders. CONCLUSIONS: In this cross-sectional study of asymptomatic individuals, concentric left ventricular remodeling was related to decreased regional systolic function. The reduction in regional function, which was more pronounced in the left anterior descending coronary artery territory, may reflect the local transition from compensatory remodeling to myocardial dysfunction.

Regional diastolic dysfunction in individuals with left ventricular hypertrophy measured by tagged magnetic resonance imaging--the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Impairment of global diastolic function is considered to be the mechanism of congestive heart failure in individuals with preserved systolic left ventricular (LV) function. Left ventricular hypertrophy (LVH) is known to be a risk factor for congestive heart failure with preserved systolic function, and this process may begin as a regional process. We investigated whether regional LV diastolic function measured by magnetic resonance tagging is altered in asymptomatic participants of the MESA with LVH and preserved systolic LV function. METHODS: Regional systolic and diastolic strain rates were calculated from strain data in 218 participants of the MESA study. Circumferential strain was calculated from the midwall layer of the septum, anterior, lateral, and inferior walls at mid-LV level. Global LV function measures were studied by magnetic resonance imaging in 4291 MESA participants. Left ventricular hypertrophy for men and women was defined from the MESA population using previously established Framingham criteria. RESULTS: Global systolic function was slightly less in the LVH (ejection fraction = 0.66 +/- 0.10) versus the non-LVH group (ejection fraction = 0.69 +/- 0.07, P < .001). Stepwise regression analyses showed a direct relationship between regional diastolic dysfunction and increasing LV mass. Regional systolic strain and strain rate measures from participants with LVH were not significantly different from those without LVH. However, regional diastolic strain rate was significantly reduced in participants with LVH (1.5 +/- 1.1 s(-1)) compared with the non-LVH group (2.2 +/- 1.1 s(-1), P < .001) regardless of age or sex. CONCLUSIONS: Left ventricular hypertrophy is associated with regional diastolic dysfunction in individuals without evidence of clinical cardiovascular disease and preserved systolic function. Magnetic resonance imaging tagging provides detailed quantification of regional diastolic function noninvasively.

Association between Obstructive Sleep Apnea and Left Ventricular Structure by Age and Gender: the Multi-Ethnic Study of Atherosclerosis.

STUDY OBJECTIVES: The presence and severity of obstructive sleep apnea (OSA) are associated with impaired left ventricular (LV) structure and function. Our goal was to quantify the associations between LV systolic function and mass with severity of OSA in an ethnically diverse cohort, assessing variations by age and sex. METHODS: We conducted a cross-sectional analysis of data from 1,412 racially/ethnically diverse participants across 6 US communities from the Multi-Ethnic Study of Atherosclerosis who underwent both overnight polysomnography and cardiac magnetic resonance imaging from 2010-2012. We evaluated the association between the obstructive apnea-hypopnea index (AHI) by clinical category (< 5, 5-15, 15-30, 30-50, > 50) and secondary measures of sleep apnea with the outcomes left ventricular (LV) mass adjusted for height, LV mass/volume ratio, and LV ejection fraction. RESULTS: After adjusting for potential confounders and mediators, LV mass was significantly increased with increasing AHI category for subjects age 65 y or younger (ß = 1.84 ± 0.47 g/m, P = 0.0001). The association between the AHI and LV mass appeared stronger in whites and Chinese compared to blacks and Hispanics, although interaction terms were not statistically significant. Additionally, while both LV mass and LV mass/volume ratio were significantly associated with hypoxia, ejection fraction was not associated with any OSA severity index. Comparable associations were observed in men and women. CONCLUSIONS: Independent of confounders, higher levels of AHI are significantly associated with increased LV mass in both men and women younger than 65 y from a community-based cohort.

Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

BACKGROUND: The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. METHODS AND RESULTS: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min. CONCLUSION: In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block.

Diagnosis of left ventricular pseudoaneurysm by cardiac CT angiography.

We present a case of a patient with left ventricular pseudoaneurysm which was not noted on transthoracic echocardiography but incidentally detected by CT angiography in preparation of ablation therapy for ventricular tachycardia. The patient underwent successful surgical repair of the pseudoaneurysm. The case illustrates the utility of CT angiography for the diagnosis of this rare, but hazardous condition.