Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort : A Prospective Observational Cohort Study.

BACKGROUND: Coronary atherosclerosis may develop at an early age and remain latent for many years. OBJECTIVE: To define characteristics of subclinical coronary atherosclerosis associated with the development of myocardial infarction. DESIGN: Prospective observational cohort study. SETTING: Copenhagen General Population Study, Denmark. PARTICIPANTS: 9533 asymptomatic persons aged 40 years or older without known ischemic heart disease. MEASUREMENTS: Subclinical coronary atherosclerosis was assessed with coronary computed tomography angiography conducted blinded to treatment and outcomes. Coronary atherosclerosis was characterized according to luminal obstruction (nonobstructive or obstructive [≥50% luminal stenosis]) and extent (nonextensive or extensive [one third or more of the coronary tree]). The primary outcome was myocardial infarction, and the secondary outcome was a composite of death or myocardial infarction. RESULTS: A total of 5114 (54%) persons had no subclinical coronary atherosclerosis, 3483 (36%) had nonobstructive disease, and 936 (10%) had obstructive disease. Within a median follow-up of 3.5 years (range, 0.1 to 8.9 years), 193 persons died and 71 had myocardial infarction. The risk for myocardial infarction was increased in persons with obstructive (adjusted relative risk, 9.19 [95% CI, 4.49 to 18.11]) and extensive (7.65 [CI, 3.53 to 16.57]) disease. The highest risk for myocardial infarction was noted in persons with obstructive-extensive subclinical coronary atherosclerosis (adjusted relative risk, 12.48 [CI, 5.50 to 28.12]) or obstructive-nonextensive (adjusted relative risk, 8.28 [CI, 3.75 to 18.32]). The risk for the composite end point of death or myocardial infarction was increased in persons with extensive disease, regardless of degree of obstruction-for example, nonobstructive-extensive (adjusted relative risk, 2.70 [CI, 1.72 to 4.25]) and obstructive-extensive (adjusted relative risk, 3.15 [CI, 2.05 to 4.83]). LIMITATION: Mostly White persons were studied. CONCLUSION: In asymptomatic persons, subclinical, obstructive coronary atherosclerosis is associated with a more than 8-fold elevated risk for myocardial infarction. PRIMARY FUNDING SOURCE: AP Møller og Hustru Chastine Mc-Kinney Møllers Fond.

Left ventricular end-diastolic pressure is associated with left atrial functional measures by echocardiography.

Echocardiography guidelines recommend the assessment of maximal LA volume (LAVmax). Evidence, however, suggests additional value of functional LA measures. We investigated the association between functional LA measures and left ventricular end-diastolic pressure (LVEDP). Patients suspected of coronary artery disease referred for invasive coronary angiography (ICA) underwent, in addition to ICA, invasive pressure measurements. LVEDP > 12 mmHg was considered elevated. LA measurements by echocardiography included: LAVmax, minimal LA volume (LAVmin), total LA emptying fraction (LAEFtotal), passive LA emptying fraction (LAEFpassive), and active LA emptying fraction (LAEFactive). Of 43 patients, 28 (65%) had elevated LVEDP. These patients more frequently had coronary vessel disease (VD) and impaired LA mechanics for all measures except LAVmax. All LA measures except LAVmax were associated with LVEDP in unadjusted linear regression analyses. After adjustment for age and VD, only LA emptying fractions remained associated with LVEDP (2.6 (1.2-4.0) mmHg increase, p = 0.001, per 5% decrease in LAEFtotal; 1.4 (0.1-2.8) mmHg increase, p = 0.040, per 5% decrease in LAEFactive; 1.8 (0.1-3.4) mmHg increase, p = 0.038, per 5% decrease in LAEFpassive). In logistic regression, only LAEFpassive was significantly associated with elevated LVEDP after adjusting for age and VD (OR = 1.11 (1.01-1.21), p = 0.023, per 1% decrease). Similar findings were made in subgroup analyses among patients without dilated LA and patients without conventional indicators of elevated filling pressure. Left ventricular end-diastolic pressure is significantly associated with LA functional measures but not LA volumes. Additionally, LAEFpassive is associated with elevated LVEDP. Future studies examining LA function should include all components of LAEF.

Myocardial performance index by tissue Doppler echocardiography predicts adverse events in patients with atrial fibrillation.

AIMS: The prognostic value of myocardial performance index (MPI) has not yet been assessed in patients with atrial fibrillation (AF). The aim of this study was to evaluate the prognostic value of MPI by tissue Doppler imaging (TDI) M-mode in AF patients. METHODS AND RESULTS: Echocardiograms from 210 patients with AF during examination were analysed offline. Patients with known heart failure (HF) were excluded. Time intervals were measured using an M-mode line through the mitral valve leaflets to provide a colour diagram of the mitral leaflet movement so all time intervals could be measured from one cardiac cycle. MPI was calculated as the sum of isovolumic relaxation time and isovolumic contraction time divided by the ejection time [(IVRT+IVCT)/ET]. During a median follow-up of 2.4 years, 84 patients (40%) reached the combined endpoint of major adverse cardiovascular events (MACE), being all-cause mortality, HF, myocardial infarction, or stroke. Increasing MPI was significantly associated with an increased risk of MACE, and the risk increased with 20% per 0.1 increase in MPI [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.10-1.32; P < 0.001]. Increasing MPI was also significantly associated with a lower left ventricular ejection fraction (LVEF) (P < 0.001). Nevertheless, MPI remained an independent predictor even after adjustment for age, sex, diabetes mellitus, left atrial volume, and LVEF (HR 1.12, 95% CI 1.01-1.25; P = 0.038). CONCLUSION: Increasing MPI was significantly associated with increased risk of MACE and remained an independent predictor after multivariable adjustment. This demonstrates that the MPI obtained by TDI M-mode might be useful in assessing cardiac function in AF patients with ongoing arrhythmia during examination.

Coronary plaque composition assessed by cardiac computed tomography using adaptive Hounsfield unit thresholds.

PURPOSE: Quantitative computed tomography (QCT) may be useful in detecting high-risk patients with coronary atherosclerosis. Assessment of plaque composition using fixed Hounsfield unit (HU) thresholds is influenced by luminal contrast density. A method using adaptive HU thresholds has therefore been developed. This study investigates agreement between plaque volumes derived using fixed and adaptive HU thresholds and the influence of luminal contrast density on the determination of plaque composition. METHODS: We performed QCT in 260 patients with recent acute-onset chest pain without acute coronary syndrome. Plaque volumes of necrotic core (NC), fibrous fatty (FF), fibrous (FI) and dense calcium (DC) tissue were measured in 1161 coronary segments. Agreement between plaque volumes using fixed and adaptive HU thresholds was tested using the Bland-Altman method. Additionally, patients were stratified into tertiles of ascending aortic luminal contrast density and plaque volumes were compared. RESULTS: Bland-Altman plots revealed that fixed HU thresholds underestimated FI and FF plaque volumes and overestimated NC and DC plaque volumes compared to adaptive HU thresholds. Volumes of dense calcium plaque differed with increasing tertiles of luminal contrast density when using fixed HU thresholds but not when using adaptive HU thresholds: DC for fixed HU thresholds (mm3, median (95%CI)): 7.73 (5.17;12.31), 9.83 (6.55;13.57), 12.02 (8.26;16.24); DC for adaptive HU thresholds (mm3, median (95%CI)): 7.34 (5.12;12.03), 7.78 (5.40;12.61), 8.56 (5.22;12.69). CONCLUSIONS: Plaque volumes by fixed and adaptive HU thresholds differed. Plaque volumes by adaptive HU thresholds were more independent of luminal contrast density for higher attenuation tissues compared to fixed HU thresholds.

Post-systolic shortening: normal values and association with validated echocardiographic and invasive measures of cardiac function.

Post-systolic shortening (PSS) does not contribute to the ejection of blood and may inhibit diastolic filling. We determined normal values of PSS in healthy subjects and investigated associations with echocardiographic and invasive measures of systolic and diastolic function. We prospectively analyzed participants from the general population (n = 620, mean age 47 ± 14 years) with no cardiovascular disease. Participants underwent echocardiography, including speckle tracking assessment of the post-systolic index (PSI), strain and time. We defined the PSI as: 100 × [(peak global longitudinal strain - peak systolic longitudinal strain)/(peak global longitudinal strain)]. We also included stable patients (n = 44) referred for left ventricle (LV) catheterization and echocardiography. Normal values: median PSI 2.0% (IQR 0.7, 4.8), post-systolic strain 0.4% (IQR 0.2, 0.8) and post-systolic time 22.6 ms (IQR 10.7, 40.8). Sex modified the relationship between PSI and age (P interaction = 0.037), such that PSI increased with age in women but not in men. PSI was associated with diastolic function (e', E/e' and E/A) (P < 0.05 for all), but not with LV ejection fraction (P = 0.08). PSI was associated with invasively measured LV pressure decline in early diastole, dP/dt min ([Formula: see text] = 0.12, P = 0.010), but not with LV pressure rise in early systole, dP/dt max ([Formula: see text]= - 0.05, P = 0.30). A PSI > 5% had 82% specificity and 99% sensitivity for identifying impaired LV systolic and/or diastolic function. Normal values of PSS are modified by sex. The PSI is associated with most validated echocardiographic and invasive measures of cardiac systolic and diastolic function.

Global longitudinal strain corrected by RR-interval is a superior echocardiographic predictor of outcome in patients with atrial fibrillation.

BACKGROUND: Echocardiographic assessment of systolic and diastolic function during atrial fibrillation (AF) is challenging. This study evaluates the prognostic value of strain in patients with AF and suggests a novel approach on how to take into account the varying heart cycle lengths in AF. METHODS: Echocardiograms from 204 patients with AF during examination were analyzed offline. Patients with known heart failure (HF) were excluded. Peak global longitudinal strain (GLS) was averaged from 18 myocardial segments. To adjust for the varying heart cycle lengths, we indexed GLS with the square root of the RR-interval, (GLS/√(RR)). The composite endpoint included incident HF, stroke, myocardial infarction and all-cause mortality. RESULTS: During a median follow-up of 2.4 years, 82 patients (40%) reached the composite endpoint. Decreasing GLS/√(RR) was significantly associated with the composite endpoint, and the risk of reaching the endpoint increased significantly per 1%/sec1/2 decrease in strain (HR 1.13, 95% CI 1.07-1.20, p < 0.001). GLS/√(RR) remained an independent predictor even after adjustment for various risk factors and conventional echocardiography (LVEF and E/e') (HR 1.10, 95% CI: 1.02-1.19, p = 0.017). In contrast, GLS did not remain a significant predictor after adjusting for the same variables (p = 0.07), neither did LVEF (p = 0.11). CONCLUSION: Decreasing GLS/√(RR) was significantly associated with increased risk of an adverse outcome and remained an independent predictor after multivariable adjustment. Indexing GLS with the square root of the RR-interval can counteract the variable cycle length in AF patients and GLS/√(RR) offers a more convincing risk-stratification assessment in AF patients compared with GLS.

Multimodality Cardiac Imaging for the Assessment of Left Atrial Function and the Association With Atrial Arrhythmias.

Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the current moment. Numerous studies, however, have shown that functional measures may be superior to the maximal LA volume in several aspects and to possess clinical value even in the absence of structural abnormalities. Such functional measures could prove particularly useful in the setting of predicting atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing evidence has supported the use of functional measures and proven its superiority to the maximal LA volume, they have still not been adopted in clinical guidelines. The reason for this discrepancy may rely on the fact that there is little to no agreement on how to technically perform deformation analysis of the LA. Such technical considerations, limitations, and alternate imaging prospects will be addressed in this review.

Total average diastolic longitudinal displacement by colour tissue doppler imaging as an assessment of diastolic function.

BACKGROUND: The current method for a non-invasive assessment of diastolic dysfunction is complex with the use of algorithms of many different echocardiographic parameters. Total average diastolic longitudinal displacement (LD), determined by colour tissue Doppler imaging (TDI) via the measurement of LD during early diastole and atrial contraction, can potentially be used as a simple and reliable alternative. METHODS: In 206 patients, using GE Healthcare Vivid E7 and 9 and Echopac BT11 software, we determined both diastolic LD, measured in the septal and lateral walls in the apical 4-chamber view by TDI, and the degree of diastolic dysfunction, based on current guidelines. Of these 206 patients, 157 had cardiac anomalies that could potentially affect diastolic LD such as severe systolic heart failure (n = 45), LV hypertrophy (n = 49), left ventricular (LV) dilation (n = 30), and mitral regurgitation (n = 33). Intra and interobserver variability of diastolic LD measures was tested in 125 patients. RESULTS: A linear relationship between total average diastolic LD and the degree of diastolic dysfunction was found. A total average diastolic LD of 10 mm was found to be a consistent threshold for the general discrimination of patients with or without diastolic dysfunction. Using linear regression, total average diastolic LD was estimated to fall by 2.4 mm for every increase in graded severity of diastolic dysfunction (ß = -0.61, p-value <0.001). Patients with LV hypertrophy had preserved total average diastolic LD despite being classified as having diastolic dysfunction. Reproducibility of LD measures was acceptable. CONCLUSIONS: There is strong evidence suggesting that patients with a total average diastolic LD under 10 mm have diastolic dysfunction.

Optimisation of coronary vascular territorial 3D echocardiographic strain imaging using computed tomography: a feasibility study using image fusion.

Current echocardiographic assessments of coronary vascular territories use the 17-segment model and are based on general assumptions of coronary vascular distribution. Fusion of 3D echocardiography (3DE) with multidetector computed tomography (MDCT) derived coronary anatomy may provide a more accurate assessment of left ventricular (LV) territorial function. We aimed to test the feasibility of MDCT and 3DE fusion and to compare territorial longitudinal strain (LS) using the 17-segment model and a MDCT-guided vascular model. 28 patients underwent 320-slice MDCT and transthoracic 3DE on the same day followed by invasive coronary angiography. MDCT (Aquilion ONE, ViSION Edition, Toshiba Medical Systems) and 3DE apical full-volume images (Artida, Toshiba Medical Systems) were fused offline using a dedicated workstation (prototype fusion software, Toshiba Medical Systems). 3DE/MDCT image alignment was assessed by 3 readers using a 4-point scale. Territorial LS was assessed using the 17-segment model and the MDCT-guided vascular model in territories supplied by significantly stenotic and non-significantly stenotic vessels. Successful 3DE/MDCT image alignment was obtained in 86 and 93 % of cases for reader one, and reader two and three, respectively. Fair agreement on the quality of automatic image alignment (intra-class correlation = 0.40) and the success of manual image alignment (Fleiss' Kappa = 0.40) among the readers was found. In territories supplied by non-significantly stenotic left circumflex arteries, LS was significantly higher in the MDCT-guided vascular model compared to the 17-segment model: -15.00 ± 7.17 (mean ± standard deviation) versus -11.87 ± 4.09 (p < 0.05). Fusion of MDCT and 3DE is feasible and provides physiologically meaningful displays of myocardial function.

Cardiac Time Intervals by Tissue Doppler Imaging M-Mode: Normal Values and Association with Established Echocardiographic and Invasive Measures of Systolic and Diastolic Function.

PURPOSE: To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI) and the conventional method of obtaining MPI (MPIConv), with established echocardiographic and invasive measures of systolic and diastolic function. METHODS: In a large community based population study (n = 974), where all are free of any cardiovascular disease and cardiovascular risk factors, cardiac time intervals, including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI M-mode through the MV. IVCT/ET, IVRT/ET and the MPI ((IVRT+IVCT)/ET) were calculated. We also included a validation population (n = 44) of patients who underwent left heart catheterization and had the MPITDI and MPIConv measured. RESULTS: IVRT, IVRT/ET and MPI all increased significantly with increasing age in both genders (p<0.001 for all). IVCT, ET, IVRT/ET, and MPI differed significantly between males and females, displaying that women, in general exhibit better cardiac function. MPITDI was significantly associated with invasive (dP/dt max) and echocardiographic measures of systolic (LVEF, global longitudinal strain and global strainrate s) and diastolic function (e', global strainrate e)(p<0.05 for all), whereas MPIConv was significantly associated with LVEF, e' and global strainrate e (p<0.05 for all). CONCLUSION: Normal values of cardiac time intervals differed between genders and deteriorated with increasing age. The MPITDI (but not MPIConv) is associated with most invasive and established echocardiographic measures of systolic and diastolic function.

Systolic and Diastolic Function by Tissue Doppler Imaging Predicts Mortality in Patients with Atrial Fibrillation.

AIM: Tissue Doppler Imaging (TDI) detects early signs of left ventricular dysfunction. The prognostic potential of TDI in patients with atrial fibrillation (AF) has, however, not yet been clarified. This study evaluates the prognostic value of TDI in patients with atrial fibrillation. METHODS AND RESULTS: In total, echocardiograms from 313 patients with AF during examination were analyzed offline. Longitudinal systolic velocity (s'), early diastolic velocity (e') and longitudinal displacement (LD) were measured by color TDI. During a median follow-up of 891 days, 64 patients (20%) died. TDI was significantly associated with all-cause mortality, and the risk of dying increased significantly per 1 cm/s decrease in s' (HR of 1.31, 95% CI 1.05-1.63; p=0.018) and e' (HR of 1.17, 95% CI 1.01-1.35; p=0.038) respectively, even after adjustment for age, gender, heart rate, aortic stenosis, DM and LVEF quartiles. LD also proved to be a significant predictor of outcome after multivariate adjustment (HR 1.23; 95% CI 1.05-1.44; p=0.012). The population was stratified according to high or low s' and e'. Patients with low s' and e' had more than three times the risk of mortality compared to the patients with high s' and e' (HR 3.64; 95% CI 1.83-7.26; p<0.001) and remained in significantly higher risk after adjustment for various risk factors. CONCLUSIONS: Both systolic and diastolic performance, as assessed by TDI, are strong predictors of mortality in patients with atrial fibrillation, and especially the combination of systolic and diastolic dysfunction is a significant prognostic marker.

Concordance and reproducibility between M-mode, tissue Doppler imaging, and two-dimensional strain imaging in the assessment of mitral annular displacement and velocity in patients with various heart conditions.

AIMS: Mitral annular (MA) displacement reflects longitudinal left ventricular (LV) deformation and systolic velocity measurements reflect the rate of contraction; both are valuable in the diagnosis and prognosis of cardiac disease. The aim of this study was to test the agreement and reproducibility between motion mode (M-mode), colour tissue Doppler imaging (TDI), and two-dimensional strain imaging (2DSI) when measuring MA displacement and systolic velocity. METHODS AND RESULTS: Using GE Healthcare Vivid 7 and E9 and Echopac BT11 software, MA displacement and velocity measurements by 2DSI, TDI, and M-mode determined in the septal and lateral walls in the apical four-chamber view were assessed in 50 control subjects and in 168 patients with various cardiac anomalies known to affect longitudinal displacement such as heart failure, mitral regurgitation, LV hypertrophy, and LV dilation. Intra- and inter-observer variability were tested using the Bland-Altman method in 125 patients. A relatively low bias between M-mode and TDI with respect to MA displacement (mean difference ± 1.96 standard deviation: 0.08 ± 0.35 cm) and a low bias between TDI and 2DSI with respect to MA peak systolic velocity (-0.13 ± 1.87 cm/s) were found. Reproducibility was acceptable for all methods with TDI having the lowest intra- and inter-observer variability. CONCLUSION: LV function could be assessed in terms of MA displacement and systolic velocity using M-mode, TDI, and 2DSI. None of the measurement techniques are, however, interchangeable. Overall, TDI seems to be the most robust method, having the lowest observer variability.