The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

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.

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Stress myocardial perfusion with qualitative magnetic resonance and quantitative dynamic computed tomography: comparison of diagnostic performance and incremental value over coronary computed tomography angiography.

AIMS: Assessment of haemodynamically significant coronary artery disease (CAD) using cardiovascular magnetic resonance (CMR) imaging perfusion or dynamic stress myocardial perfusion imaging by computed tomography (CT perfusion) may aid patient selection for invasive coronary angiography (ICA). We evaluated the diagnostic performance and incremental value of qualitative CMR perfusion and quantitative CT perfusion complementary to cardiac computed tomography angiography (CCTA) for the diagnosis of haemodynamically significant CAD using fractional flow reserve (FFR) and quantitative coronary angiography (QCA) as reference standard. METHODS AND RESULTS: CCTA, qualitative visual CMR perfusion, visual CT perfusion, and quantitative relative myocardial blood flow (CT-MBF) were performed in patients with stable angina pectoris. FFR was measured in coronary vessels with stenosis visually estimated between 30% and 90% diameter reduction on ICA. Haemodynamically significant CAD was defined as FFR <0.80, or QCA ≥80% in those cases where FFR could not be performed. A total of 218 vessels from 93 patients were assessed. An optimal cut-off of 0.72 for relative CT-MBF was determined. The diagnostic performances (area under the receiver-operating characteristics curves, 95% CI) of visual CMR perfusion (0.84, 0.77-0.90) and relative CT-MBF (0.86, 0.81-0.92) were comparable and outperformed visual CT perfusion (0.64, 0.57-0.71). In combination with CCTA ≥50%, CCTA + visual CMR perfusion (0.91, 0.86-0.96), CCTA + relative CT-MBF (0.92, 0.88-0.96), and CCTA + visual CT perfusion (0.82, 0.75-0.90) improved discrimination compared with CCTA alone (all P < 0.05). CONCLUSION: Visual CMR perfusion and relative CT-MBF outperformed visual CT perfusion and provided incremental discrimination compared with CCTA alone for the diagnosis of haemodynamically significant CAD.

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

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.

Changes in Cardiac Morphology and Function in Individuals With Diabetes Mellitus: The UK Biobank Cardiovascular Magnetic Resonance Substudy.

BACKGROUND: Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease. Detection of early cardiac changes before manifest disease develops is important. We investigated early alterations in cardiac structure and function associated with DM using cardiovascular magnetic resonance imaging. METHODS: Participants from the UK Biobank Cardiovascular Magnetic Resonance Substudy, a community cohort study, without known cardiovascular disease and left ventricular ejection fraction ≥50% were included. Multivariable linear regression models were performed. The investigators were blinded to DM status. RESULTS: A total of 3984 individuals, 45% men, (mean [SD]) age 61.3 (7.5) years, hereof 143 individuals (3.6%) with DM. There was no difference in left ventricular (LV) ejection fraction (DM versus no DM; coefficient [95% CI]: -0.86% [-1.8 to 0.5]; P=0.065), LV mass (-0.13 g/m2 [-1.6 to 1.3], P=0.86), or right ventricular ejection fraction (-0.23% [-1.2 to 0.8], P=0.65). However, both LV and right ventricular volumes were significantly smaller in DM, (LV end-diastolic volume/m2: -3.46 mL/m2 [-5.8 to -1.2], P=0.003, right ventricular end-diastolic volume/m2: -4.2 mL/m2 [-6.8 to -1.7], P=0.001, LV stroke volume/m2: -3.0 mL/m2 [-4.5 to -1.5], P<0.001; right ventricular stroke volume/m2: -3.8 mL/m2 [-6.5 to -1.1], P=0.005), LV mass/volume: 0.026 (0.01 to 0.04) g/mL, P=0.006. Both left atrial and right atrial emptying fraction were lower in DM (right atrial emptying fraction: -6.2% [-10.2 to -2.1], P=0.003; left atrial emptying fraction:-3.5% [-6.9 to -0.1], P=0.043). LV global circumferential strain was impaired in DM (coefficient [95% CI]: 0.38% [0.01 to 0.7], P=0.045). CONCLUSIONS: In a low-risk general population without known cardiovascular disease and with preserved LV ejection fraction, DM is associated with early changes in all 4 cardiac chambers. These findings suggest that diabetic cardiomyopathy is not a regional condition of the LV but affects the heart globally.

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.

Normal values of aortic dimensions assessed by multidetector computed tomography in the Copenhagen General Population Study.

AIMS: Accurate assessment of aortic dimensions can be achieved using contrast-enhanced computed tomography. The aim of this study was to define normal values and determinants of aortic dimensions throughout multiple key anatomical landmarks of the aorta in healthy individuals from the Copenhagen General Population Study. METHODS AND RESULTS: The study group consisted of 902 healthy subjects selected from 3000 adults undergoing cardiovascular thoracic and abdominal computed tomography-angiography (CTA), where systematic measurements of aortic dimensions were performed retrospectively. Individuals included were without any of the following predefined cardiovascular risk factors: (i) self-reported angina pectoris; (ii) hypertension; (iii) hypercholesterolaemia; (iv) taking cardiovascular prescribed medication including diuretics, statins, or aspirin; (v) overweight (defined as body mass index ≥30 kg/m2); (vi) diabetes mellitus (self-reported or blood glucose >8 mmol/L); and (vii) chronic obstructive pulmonary disease. Maximal aortic diameters were measured at seven aortic regions: sinuses of Valsalva, sinotubular junction, ascending aorta, mid-descending aorta, abdominal aorta at the diaphragm, abdominal aorta at the coeliac trunk, and infrarenal abdominal aorta. Median age was 52 years, and 396 (40%) were men. Men had significantly larger aortic diameters at all levels compared with women (P < 0.001). Multivariable analysis revealed that sex, age, and body surface area were associated with increasing aortic dimensions. CONCLUSION: Normal values of maximal aortic dimensions at key aortic anatomical locations by contrast-enhanced CTA have been defined. Age, sex, and body surface area were significantly associated with these measures at all levels of aorta. Aortic dimensions follow an almost identical pattern throughout the vessel regardless of sex.

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.

Relationship between patient presentation and morphology of coronary atherosclerosis by quantitative multidetector computed tomography.

AIMS: Quantitative computed tomography (QCT) allows assessment of morphological features of coronary atherosclerosis. We aimed to test the hypothesis that clinical patient presentation is associated with distinct morphological features of coronary atherosclerosis. METHODS AND RESULTS: A total of 1652 participants, representing a spectrum of clinical risk profiles [787 asymptomatic individuals from the general population, 468 patients with acute chest pain without acute coronary syndrome (ACS), and 397 patients with acute chest pain and ACS], underwent multidetector computed tomography. Of these, 274 asymptomatic individuals, 254 patients with acute chest pain without ACS, and 327 patients with acute chest pain and ACS underwent QCT to assess coronary plaque volumes and proportions of dense calcium (DC), fibrous, fibro fatty (FF), and necrotic core (NC) tissue. Furthermore, the presence of vulnerable plaques, defined by plaque volume and tissue composition, was examined. Coronary plaque volume increased significantly with worsening clinical risk profile [geometric mean (95% confidence interval): 148 (129-166) mm3, 257 (224-295) mm3, and 407 (363-457) mm3, respectively, P < 0.001]. Plaque composition differed significantly across cohorts, P < 0.0001. The proportion of DC decreased, whereas FF and NC increased with worsening clinical risk profile (mean proportions DC: 33%, 23%, 23%; FF: 50%, 61%, 57%; and NC: 17%, 17%, 20%, respectively). Significant differences in plaque composition persisted after multivariable adjustment for age, gender, body surface area, hypertension, statin use at baseline, diabetes, smoking, family history of ischaemic heart disease, total plaque volume, and tube voltage, P < 0.01. CONCLUSION: Coronary atherosclerotic plaque volume and composition are strongly associated to clinical presentation.

Reproducibility of quantitative coronary computed tomography angiography in asymptomatic individuals and patients with acute chest pain.

PURPOSE: Quantitative computed tomography (QCT) provides important prognostic information of coronary atherosclerosis. We investigated intraobserver and interobserver QCT reproducibility in asymptomatic individuals, patients with acute chest pain without acute coronary syndrome (ACS), and patients with acute chest pain and ACS. METHODS: Fifty patients from each cohort, scanned between 01/02/2010-14/11/2013 and matched according to age and gender, were retrospectively assessed for inclusion. Patients with no coronary artery disease, previous coronary artery bypass graft surgery, and poor image quality were excluded. Coronary atherosclerosis was measured semi-automatically by 2 readers. Reproducibility of minimal lumen area (MLA), minimal lumen diameter (MLD), area stenosis, diameter stenosis, vessel remodeling, plaque eccentricity, plaque burden, and plaque volumes was assessed using concordance correlation coefficient (CCC), Bland-Altman, coefficient of variation, and Cohen's kappa. RESULTS: A total of 84 patients (63 matched) were included. Intraobserver and interobserver reproducibility estimates were acceptable for MLA (CCC = 0.94 and CCC = 0.91, respectively), MLD (CCC = 0.92 and CCC = 0.86, respectively), plaque burden (CCC = 0.86 and CCC = 0.80, respectively), and plaque volume (CCC = 0.97 and CCC = 0.95, respectively). QCT detected area and diameter stenosis ≥50%, positive remodeling, and eccentric plaque with moderate-good intraobserver and interobserver reproducibility (kappa: 0.64-0.66, 0.69-0.76, 0.46-0.48, and 0.41-0.62, respectively). Reproducibility of plaque composition decreased with decreasing plaque density (intraobserver and interobserver CCC for dense calcium (>0.99; 0.98), fibrotic (0.96; 0.93), fibro-fatty (0.95; 0.91), and necrotic core tissue (0.89; 0.84). Reproducibility generally decreased with worsening clinical risk profile. CONCLUSIONS: Semi-automated QCT of coronary plaque morphology is reproducible, albeit with some decline in reproducibility with worsening patient risk profile.

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.

Subclinical leaflet thickening and stent frame geometry in self-expanding transcatheter heart valves.

AIMS: This study aimed to assess the potential relationship between subclinical leaflet thickening and stent frame geometry in patients who underwent aortic valve replacement with a self-expanding transcatheter heart valve (THV). METHODS AND RESULTS: Seventy-five patients with a self-expanding THV were studied with 4D-computed tomography and analysed for leaflet thickening. There was no difference in THV size, overall THV expansion, eccentricity or implantation depth between patients with and those without leaflet thickening. Moderate-to-severe regional THV underexpansion (≤90°) more frequently occurred at the non-coronary and right coronary cusps with a significantly higher incidence of leaflet thickening than in cases of full regional THV expansion (24% vs. 3%, p<0.01). Regional THV underexpansion at the inflow level more often translated into the same issue at the valvular level in THV with intra-annular as compared to supra-annular valve position (54% vs. 17%; p=0.04). In case of post-dilatation, regional THV underexpansion occurred less frequently as compared to THV that were not post-dilated (18% vs. 43%, p=0.028). A similar but non-significant trend was found for leaflet thickening. CONCLUSIONS: Regional THV stent frame underexpansion is associated with an increased risk of leaflet thickening. Post-dilatation of self-expanding THV as well as a supra-annular valve position seem to reduce the occurrence of this phenomenon.

Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study.

BACKGROUND: Subclinical leaflet thrombosis of bioprosthetic aortic valves after transcatheter valve replacement (TAVR) and surgical aortic valve replacement (SAVR) has been found with CT imaging. The objective of this study was to report the prevalence of subclinical leaflet thrombosis in surgical and transcatheter aortic valves and the effect of novel oral anticoagulants (NOACs) on the subclinical leaflet thrombosis and subsequent valve haemodynamics and clinical outcomes on the basis of two registries of patients who had CT imaging done after TAVR or SAVR. METHODS: Patients enrolled between Dec 22, 2014, and Jan 18, 2017, in the RESOLVE registry, and between June 2, 2014, and Sept 28, 2016, in the SAVORY registry, had CT imaging done with a dedicated four-dimensional volume-rendered imaging protocol at varying intervals after TAVR and SAVR. We defined subclinical leaflet thrombosis as the presence of reduced leaflet motion, along with corresponding hypoattenuating lesions shown with CT. We collected data for baseline demographics, antithrombotic therapy, and clinical outcomes. We analysed all CT scans, echocardiograms, and neurological events in a masked fashion. FINDINGS: Of the 931 patients who had CT imaging done (657 [71%] in the RESOLVE registry and 274 [29%] in the SAVORY registry), 890 [96%] had interpretable CT scans (626 [70%] in the RESOLVE registry and 264 [30%] in the SAVORY registry). 106 (12%) of 890 patients had subclinical leaflet thrombosis, including five (4%) of 138 with thrombosis of surgical valves versus 101 (13%) of 752 with thrombosis of transcatheter valves (p=0·001). The median time from aortic valve replacement to CT for the entire cohort was 83 days (IQR 33-281). Subclinical leaflet thrombosis was less frequent among patients receiving anticoagulants (eight [4%] of 224) than among those receiving dual antiplatelet therapy (31 [15%] of 208; p<0·0001); NOACs were equally as effective as warfarin (three [3%] of 107 vs five [4%] of 117; p=0·72). Subclinical leaflet thrombosis resolved in 36 (100%) of 36 patients (warfarin 24 [67%]; NOACs 12 [33%]) receiving anticoagulants, whereas it persisted in 20 (91%) of 22 patients not receiving anticoagulants (p<0·0001). A greater proportion of patients with subclinical leaflet thrombosis had aortic valve gradients of more than 20 mm Hg and increases in aortic valve gradients of more than 10 mm Hg (12 [14%] of 88) than did those with normal leaflet motion (seven [1%] of 632; p<0·0001). Although stroke rates were not different between those with (4·12 strokes per 100 person-years) or without (1·92 strokes per 100 person-years) reduced leaflet motion (p=0·10), subclinical leaflet thrombosis was associated with increased rates of transient ischaemic attacks (TIAs; 4·18 TIAs per 100 person-years vs 0·60 TIAs per 100 person-years; p=0·0005) and all strokes or TIAs (7·85 vs 2·36 per 100 person-years; p=0·001). INTERPRETATION: Subclinical leaflet thrombosis occurred frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. Anticoagulation (both NOACs and warfarin), but not dual antiplatelet therapy, was effective in prevention or treatment of subclinical leaflet thrombosis. Subclinical leaflet thrombosis was associated with increased rates of TIAs and strokes or TIAs. Despite excellent outcomes after TAVR with the new-generation valves, prevention and treatment of subclinical leaflet thrombosis might offer a potential opportunity for further improvement in valve haemodynamics and clinical outcomes. FUNDING: RESOLVE (Cedars-Sinai Heart Institute) and SAVORY (Rigshospitalet).

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.