Association of epicardial adipose tissue with different stages of coronary artery disease: A cross-sectional UK Biobank cardiovascular magnetic resonance imaging substudy.

Objective: Increased epicardial adipose tissue (EAT) has been identified as a risk factor for the development of coronary artery disease (CAD). However, the exact role of EAT in the development of CAD is unclear. This study aims to compare EAT volumes between healthy controls and individuals with stable CAD and a history of myocardial infarction (MI). Furthermore, associations between clinical and biochemical parameters with EAT volumes are examined. Methods: This retrospective cross-sectional study included 171 participants from the United Kingdom Biobank (56 healthy controls; 60 stable CAD; 55 post MI), whom were balanced for age, sex and body mass index (BMI). EAT volumes were quantified on end-diastolic cardiac magnetic resonance (CMR) imaging short-axis slices along the left and right ventricle and indexed for body surface area (iEAT) and iEAT volumes were compared between groups. Results: iEAT volumes were comparable between control, CAD and MI cases (median [IQR]: 66.1[54.4-77.0] vs. 70.9[55.8-85.5] vs. 67.6[58.6-82.3] mL/m2, respectively (p > 0.005 for all). Increased HDL-cholesterol was associated with decreased iEAT volume (ß = -14.8, CI = -24.6 to -4.97, p = 0.003) and suggestive associations (P-value < 0.05 and ≥ 0.005) were observed between iEAT and triglycerides (ß = 3.26, CI = 0.42 to 6.09, p = 0.02), Apo-lipoprotein A (ß = -16.3, CI = -30.3 to -2.24, p = 0.02) and LDL-cholesterol (ß = 3.99, CI = -7.15 to -0.84, p = 0.01). Conclusions: No significant differences in iEAT volumes were observed between patients with CAD, MI and healthy controls. Our results indicate the importance of correcting for confounding by CVD risk factors, including circulating lipid levels, when studying the relationship between EAT volume and CAD. Further mechanistic studies on causal pathways and the role of EAT composition are warranted.

Focal pericoronary adipose tissue attenuation is related to plaque presence, plaque type, and stenosis severity in coronary CTA.

OBJECTIVES: To investigate the association of pericoronary adipose tissue mean attenuation (PCATMA) with coronary artery disease (CAD) characteristics on coronary computed tomography angiography (CCTA). METHODS: We retrospectively investigated 165 symptomatic patients who underwent third-generation dual-source CCTA at 70kVp: 93 with and 72 without CAD (204 arteries with plaque, 291 without plaque). CCTA was evaluated for presence and characteristics of CAD per artery. PCATMA was measured proximally and across the most severe stenosis. Patient-level, proximal PCATMA was defined as the mean of the proximal PCATMA of the three main coronary arteries. Analyses were performed on patient and vessel level. RESULTS: Mean proximal PCATMA was -96.2 ± 7.1 HU and -95.6 ± 7.8HU for patients with and without CAD (p = 0.644). In arteries with plaque, proximal and lesion-specific PCATMA was similar (-96.1 ± 9.6 HU, -95.9 ± 11.2 HU, p = 0.608). Lesion-specific PCATMA of arteries with plaque (-94.7 HU) differed from proximal PCATMA of arteries without plaque (-97.2 HU, p = 0.015). Minimal stenosis showed higher lesion-specific PCATMA (-94.0 HU) than severe stenosis (-98.5 HU, p = 0.030). Lesion-specific PCATMA of non-calcified, mixed, and calcified plaque was -96.5 HU, -94.6 HU, and -89.9 HU (p = 0.004). Vessel-based total plaque, lipid-rich necrotic core, and calcified plaque burden showed a very weak to moderate correlation with proximal PCATMA. CONCLUSIONS: Lesion-specific PCATMA was higher in arteries with plaque than proximal PCATMA in arteries without plaque. Lesion-specific PCATMA was higher in non-calcified and mixed plaques compared to calcified plaques, and in minimal stenosis compared to severe; proximal PCATMA did not show these relationships. This suggests that lesion-specific PCATMA is related to plaque development and vulnerability. KEY POINTS: • In symptomatic patients undergoing CCTA at 70 kVp, PCATMA was higher in coronary arteries with plaque than those without plaque. • PCATMA was higher for non-calcified and mixed plaques compared to calcified plaques, and for minimal stenosis compared to severe stenosis. • In contrast to PCATMA measurement of the proximal vessels, lesion-specific PCATMA showed clear relationships with plaque presence and stenosis degree.

Towards reference values of pericoronary adipose tissue attenuation: impact of coronary artery and tube voltage in coronary computed tomography angiography.

OBJECTIVES: To determine normal pericoronary adipose tissue mean attenuation (PCATMA) values for left the anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) in patients without plaques on coronary CT angiography (cCTA), taking into account tube voltage influence. METHODS: This retrospective study included 192 patients (76 (39.6%) men; median age 49 years (range, 19-79)) who underwent cCTA with third-generation dual-source CT for the suspicion of CAD between 2015 and 2017. We selected patients without plaque on cCTA. PCATMA was measured semi-automatically on cCTA images in the proximal segment of the three main coronary arteries with 10 mm length. Paired t-testing was used to compare PCATMA between combinations of two coronary arteries within each patient, and one-way ANOVA testing was used to compare PCATMA in different kV groups. RESULTS: The overall mean ± standard deviation (SD) PCATMA was - 90.3 ± 11.1 HU. PCATMA in men was higher than that in women: - 88.5 ± 10.5 HU versus - 91.5 ± 11.3 HU (p = 0.001). PCATMA of LAD, LCX, and RCA was - 92.4 ± 11.6 HU, - 88.4 ± 9.9 HU, and - 90.2 ± 11.4 HU, respectively. Pairwise comparison of the arteries showed significant difference in PCATMA: LAD and LCX (p < 0.001), LAD and RCA (p = 0.009), LCX and RCA (p = 0.033). PCATMA of the 70 kV, 80 kV, 90 kV, 100 kV, and 120 kV groups was - 95.6 ± 9.6 HU, - 90.2 ± 11.5 HU, - 87.3 ± 9.9 HU, - 82.7 ± 6.2 HU, and - 79.3 ± 6.8 HU, respectively (p < 0.001). CONCLUSIONS: In patients without plaque on cCTA, PCATMA varied by tube voltage, with minor differences in PCATMA between coronary arteries (LAD, LCX, RCA). PCATMA values need to be interpreted taking into account tube voltage setting. KEY POINTS: • In patients without plaque on cCTA, PCATMA differs slightly by coronary artery (LAD, LCX, RCA). • Tube voltage of cCTA affects PCATMA measurement, with mean PCATMA increasing linearly with increasing kV. • For longitudinal cCTA analysis of PCATMA , the use of equal kV setting is strongly recommended.

Active Tobacco Smoking Impairs Cardiac Systolic Function.

Tobacco smoking is a well-established risk factor for cardiovascular disease, but its direct effect on myocardial structure and function remains unclear. This study investigated the effects of smoking using a nested matched case-control study design. 5,668 participants of the UK Biobank study who underwent cardiovascular magnetic resonance imaging were screened for inclusion. 102 smokers (56 males) with a median age of 56 years were matched to non-smokers based on sex, age, and body surface area. Manual post-processing and feature tracking analyses were performed to determine left ventricular (LV) and right ventricular (RV) structure and function measures. Linear regression analyses were performed to determine the effect of tobacco smoking on imaging measures. Tobacco smoking was associated with increased LV and RV end-systolic volume (4.98 ± 2.08 mL, 5.19 ± 2.62 mL, P = 0.018, 0.049 respectively), reduced LV and RV ejection fraction (ß: -2.21 ± 0.82%, -2.06 ± 0.87%, P = 0.007, 0.019 respectively), and reduced absolute measures of LV peak global longitudinal, radial, and circumferential strain (ß: 0.86 ± 0.30%, -2.52 ± 0.99%, 1.05 ± 0.32%, P = 0.004, 0.011, 0.001 respectively). Effect sizes were larger in daily smokers compared to occasional smokers. In a general Caucasian population without known clinical cardiovascular disease, active tobacco smoking was dose dependently associated with impaired cardiac systolic function.

T1 reactivity as an imaging biomarker in myocardial tissue characterization discriminating normal, ischemic and infarcted myocardium.

To demonstrate the potential for differentiating normal and diseased myocardium without Gadolinium using rest and stress T1-mapping. Patients undergoing 1.5T magnetic resonance imaging (MRI) as part of clinical work-up due to suspicion of coronary artery disease (CAD) were included. Adenosine stress perfusion MRI and late gadolinium enhancement (LGE) imaging were performed to identify ischemic and infarcted myocardium. Patients were retrospectively categorized into an ischemic, infarct and control group based on conventional acquisitions. Patient with both ischemic and infarcted myocardium were excluded. A total of 64 patients were included: ten with myocardial ischemia, 15 with myocardial infarction, and 39 controls. A native Modified Look-Locker Inversion Recovery (MOLLI) T1-mapping acquisition was performed at rest and stress. Pixel-wise myocardial T1-maps were acquired in short-axis view with inline motion-correction. Short-axis T1-maps were manually contoured using conservative septal sampling. Regions of interest were sampled in ischemic and infarcted areas detected on perfusion and LGE images. T1 reactivity was calculated as the percentage difference in T1 values between rest and stress. Remote myocardium was defined as myocardium without defects in the ischemic and infarcted group whereas normal myocardium is found in the control group only. Native T1-values were significantly higher in infarcted myocardium in rest and stress [median 1044 ms (interquartile range (IQR) 985-1076) and 1053 ms (IQR 989-1088)] compared to ischemic myocardium [median 961 ms (IQR 939-988) and 958 ms (IQR 945-988)]. T1-reactivity was significantly lower in ischemic and infarcted myocardium [median 0.00% (IQR - 0.18 to 0.16) and 0.41% (IQR 0.09-0.86)] compared to remote myocardium [median 3.54% (IQR 1.48-5.78) and 3.21% (IQR 1.95-4.79)]. Rest-stress T1-mapping is able to distinguish between normal, ischemic, infarcted and remote myocardium using native T1-values and T1-reactivity, and holds potential as an imaging biomarker for tissue characterization in MRI.

Effects of Caffeine on Myocardial Blood Flow: A Systematic Review.

BACKGROUND: Caffeine is one of the most widely consumed stimulants worldwide. It is a well-recognized antagonist of adenosine and a potential cause of false-negative functional measurements during vasodilator myocardial perfusion. The aim of this systematic review is to summarize the evidence regarding the effects of caffeine intake on functional measurements of myocardial perfusion in patients with suspected coronary artery disease. Pubmed, Web of Science, and Embase were searched using a predefined electronic search strategy. Participants-healthy subjects or patients with known or suspected CAD. Comparisons-recent caffeine intake versus no caffeine intake. Outcomes-measurements of functional myocardial perfusion. Study design-observational. Fourteen studies were deemed eligible for this systematic review. There was a wide range of variability in study design with varying imaging modalities, vasodilator agents, serum concentrations of caffeine, and primary outcome measurements. The available data indicate a significant influence of recent caffeine intake on cardiac perfusion measurements during adenosine and dipyridamole induced hyperemia. These effects have the potential to affect the clinical decision making by re-classification to different risk-categories.

Computational quantitative flow ratio to assess functional severity of coronary artery stenosis.

Background Computational quantitative flow ratio (QFR) based on 3-dimensional quantitative coronary angiography (3D QCA) analysis offers the opportunity to assess the significance of coronary artery disease (CAD) without using an invasive pressure wire or inducing hyperemia. This study aimed to evaluate the diagnostic performance of QFR compared to wire-based fractional flow reserve (FFR) and to validate the previously reported QFR cut-off value of >0.90 to safely rule out functionally significant CAD. Methods QFR was retrospectively derived from standard-care coronary angiograms. Correlation and agreement of fixed-flow QFR (fQFR) and contrast-flow QFR (cQFR) models with invasive wire-based FFR was calculated. Diagnostic performance of QFR was evaluated at different QFR cut-off values defining significant CAD (FFR ≤ 0.80). Results 101 vessels in 96 patients who underwent FFR were studied. Mean FFR was 0.87 ±â€¯0.08 and 21 of 101 (21%) vessels had an FFR ≤ 0.80. Correlation of fQFR and cQFR with FFR was r = 0.71 (p < 0.001) and r = 0.70 (p < 0.001), respectively. Sensitivity and specificity were 57% and 93% for fQFR and 67% and 96% for cQFR at a QFR cut-off value >0.80 defining non-significant CAD, respectively. fQFR > 0.90 was present in 34 (34%) and cQFR > 0.90 in 39 (39%) vessels. For both QFR models, none of the vessels with QFR > 0.90 had an FFR ≤ 0.80. Conclusions QFR appears to be a safe and effective gatekeeper to wire-based FFR when applying a QFR threshold of >0.90 to rule out significant CAD. Further prospective research is required to establish QFR in the real-life setting of functional CAD assessment in the catheterization laboratory.

Accurate late gadolinium enhancement prediction by early T1- based quantitative synthetic mapping.

OBJECTIVES: Early synthetic gadolinium enhancement (ESGE) imaging from post-contrast T1 mapping after adenosine stress-perfusion cardiac magnetic resonance (CMR) was compared to conventional late gadolinium enhancement (LGE) imaging for assessing myocardial scar. METHODS: Two hundred fourteen consecutive patients suspected of myocardial ischaemia were referred for stress-perfusion CMR. Myocardial infarct volume was quantified on a per-subsegment basis in both synthetic (2-3 min post-gadolinium) and conventional (9 min post-gadolinium) images by two independent observers. Sensitivity, specificity, PPV and NPV were calculated on a per-patient and per-subsegment basis. RESULTS: Both techniques detected 39 gadolinium enhancement areas in 23 patients. The median amount of scar was 2.0 (1.0-3.1) g in ESGE imaging and 2.2 (1.1-3.1) g in LGE imaging (p=0.39). Excellent correlation (r=0.997) and agreement (mean absolute difference: -0.028±0.289 ml) were found between ESGE and LGE images. Sensitivity, specificity, PPV and NPV of ESGE imaging were 96 (78.9-99.9), 99 (97.1-100.0)%, 96 (76.5-99.4) and 99.5 (96.6-99.9) in patient-based and 99 (94.5-100.0), 100 (99.9-100.0)%, 97.0 (91.3-99.0) and 100.0 (99.8-100.0) in subsegment-based analysis. CONCLUSION: ESGE based on post-contrast T1 mapping after adenosine stress-perfusion CMR imaging shows excellent agreement with conventional LGE imaging for assessing myocardial scar, and can substantially shorten clinical acquisition time. KEY POINTS: • Synthetic gadolinium enhancement images can be used for detection of myocardial scar. • Early synthetic gadolinium enhancement images can substantially shorten clinical acquisition time. • ESGE has high diagnostic accuracy as compared to conventional late gadolinium enhancement. • Quantification of myocardial scar with ESGE closely correlates with conventional LGE. • ESGE after stress perfusion CMR avoids need for additional gadolinium administration.

Disagreement between splenic switch-off and myocardial T1-mapping after caffeine intake.

Caffeine is an adenosine receptor antagonist and a possible cause of inadequate stress perfusion. Splenic switch-off (SSO) and splenic rest-stress T1-mapping have been proposed as indicators of stress adequacy during perfusion cardiac magnetic resonance (CMR). We compared myocardial rest-stress T1-mapping with SSO and splenic rest-stress T1-mapping in patients with and without recent coffee intake. We analyzed 344 consecutive patients suspected of myocardial ischemia with adenosine perfusion CMR. All 146 normal CMR studies with a normal T1-rest of the myocardium, used as standard of reference, were included and divided in two groups. 22 patients accidentally ingested coffee < 4 h before CMR, compared to control group of 124 patients without self-reported coffee intake. Two independent readers graded SSO visually. T1-reactivity (ΔT1) was defined as percentual difference in T1-rest and T1-stress. Follow-up data were extracted from electronic patients records. In patients with recent coffee intake SSO was identified in 96%, which showed no significant difference with SSO in controls (94%, p = 0.835), however event rates were significantly different (13.6 and 0.8%, respectively (p < 0.001), median FU 17 months). Myocardial ΔT1 in the coffee group (- 5.2%) was significantly lower compared to control (+ 4.0%, p < 0.001), in contrast to the splenic ΔT1 (- 3.7 and - 4.0%, p = 0.789). The splenic T1-mapping results failed to predict false negative results. SSO and splenic rest-stress T1-mapping are not reliable indicators of stress adequacy in patients with recent coffee intake. Therefore, the dark spleen sign does not indicate adequate myocardial stress in patients with recent caffeine intake. Myocardial rest-stress T1-mapping is an excellent indicator of stress adequacy during adenosine perfusion CMR.

Influence of hydrostatic pressure on intracoronary indices of stenosis severity in vivo.

BACKGROUND: An influence of hydrostatic pressure on intracoronary indices of stenosis severity in vitro was recently reported. We sought to analyze the influence of hydrostatic pressure, caused by the height difference between the distal and proximal pressure sensor after guidewire positioning in the interrogated vessel, on intracoronary pressure measurements in vivo. METHODS AND RESULTS: In 30 coronary stenoses, intracoronary pressure measurements were performed in supine, left, and right lateral patient position. Height differences between the distal and proximal pressure sensor were measured by blinded observers. Measurement results of the position with the highest ("high") and lowest height difference ("low") were compared. In group "high", all measured indices were higher: mean difference of fractional flow reserve (FFR) 0.045 (SD 0.033, 95% CI 0.033-0.057, p < 0.0001), of instantaneous wave-free ratio (iFR) 0.043 (SD 0.04, 95% CI 0.029-0.057, p < 0.0001), and of resting Pd/Pa 0.037 (SD 0.034, 95% CI 0.025-0.049, p < 0.0001). Addition of the physically expectable hydrostatic pressure to the distal coronary pressures of the control group abolished the differences: corrected ∆FFR - 0.006 (SD 0.027, 95% CI - 0.015 to 0.004, p = 0.26), corrected ∆Pd/Pa - 0.008 (SD 0.03, 95% CI - 0.019 to 0.003, p = 0.18). Adjustment for hydrostatic pressure of FFR values in a standard supine position increased all values in anterior vessels and decreased all values in posterior vessels. The mean changes of FFR due to adjustment were: LAD - 0.048 (SD 0.016), CX 0.02 (SD 0.009), RCA 0.02 (SD 0.021). Dichotomous severity classification changed in 12.9% of stenoses. CONCLUSIONS: The study demonstrates a relevant influence of hydrostatic pressure on intracoronary indices of stenosis severity in vivo, caused by the height differences between distal and proximal pressure sensor.