Non-Invasive Assessment of Endothelial Shear Stress in Myocardial Bridges Using Coronary Computed Tomography Angiography.

Myocardial bridging (MB) is a segment of coronary arteries with an intramural course, typically spared from atherosclerosis, while the adjacent proximal segment is reported to be atherosclerosis-prone, a phenomenon contributed to local endothelial shear stress (ESS). We aimed to describe the ESS milieu in coronaries with MBs combining coronary computed tomography angiography with computational fluid dynamics and to investigate the association of atherosclerosis presence proximal to MBs with hemorheological characteristics. Patients (n = 36) were identified and 36 arteries with MBs (11 deep and 25 superficial) were analyzed. ESS did not fluctuate 5 mm proximally to MBs vs 5 mm within MBs (0.94 vs 1.06 Pa, p = .56). There was no difference when comparing ESS in the proximal versus mid versus distal MB segments (1.48 vs 1.37 vs 1.9 Pa, p = ns). In arteries with plaques (n = 12), no significant ESS variances were observed around the MB entrance, when analyzing all arteries (p = .81) and irrespective of morphological features of the bridged segment (deep MBs; p = .65, superficial MBs; p = .84). MBs are characterized by homogeneous, atheroprotective ESS, possibly explaining the absence of atherosclerosis within bridged segments. The interplay between ESS and atherosclerosis is potentially not different in arteries with MB compared with arteries without bridges.

Long-term impact of myocardial inflammation on quantitative myocardial perfusion-a descriptive PET/MR myocarditis study.

PURPOSE: Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. METHODS: Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18). RESULTS: Compared to remote segments, healed segments showed higher stress MBF (2.71 mL*min-1*g-1 [IQR 2.18-3.08] vs. 2.20 mL*min-1*g-1 [1.75-2.68], p < 0.0001), MFR (3.78 [2.83-4.79] vs. 3.36 [2.60-4.03], p < 0.0001), and washout (rest 0.24/min [0.18-0.31] and stress 0.53/min [0.40-0.67] vs. 0.22/min [0.16-0.27] and 0.46/min [0.32-0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE. CONCLUSION: In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation. CMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement.

Left ventricular function and volumes from gated [13N]-ammonia positron emission tomography myocardial perfusion imaging: A prospective head-to-head comparison against CMR using a hybrid PET/MR device.

BACKGROUND: Positron emission tomography (PET) myocardial perfusion imaging (MPI) can be used to evaluate left ventricular (LV) volumes and function. We performed a head-to-head comparison of LV function and volumes obtained simultaneously using [13N]-ammonia-PET and cardiac magnetic resonance (CMR), with the latter serving as the reference standard. METHODS AND RESULTS: In this prospective study, 51 patients underwent [13N]-ammonia-PET MPI and CMR using a hybrid PET/MR device. Left ventricular end-systolic volumes (LVESV), end-diastolic volumes (LVEDV), stroke volumes (LVSV), ejection fractions (LVEF), and segmental wall motion were analyzed for both methods and were compared using correlational and Bland-Altman (BA) analysis; segmental wall motion was compared using ANOVA. The agreement between [13N]-ammonia-PET and CMR for LVEF was good, with minimal bias (- .6%) and narrow BA limits of agreement (- 7.9% to 6.8%), but [13N]-ammonia-PET systematically underestimated LV volumes, with high bias in LVESV (- 11.2 ml), LVEDV (- 28.9 ml), and LVSV (- 17.5 ml). Mean segmental wall motion in [13N]-ammonia-PET differed significantly among the corresponding normokinetic (6.6 ± 2 mm), hypokinetic (5.1 ± 2 mm), and akinetic (3.3 ± 2 mm) segments in CMR (P < .01). CONCLUSION: LVEF and LV wall motion can be accurately assessed using [13N]-ammonia-PET MPI, although LV volumes are significantly underestimated compared to CMR.

Risk stratification using coronary artery calcium scoring based on low tube voltage computed tomography.

To determine if coronary artery calcium (CAC) scoring using computed tomography at 80 kilovolt-peak (kVp) and 70-kVp and tube voltage-adapted scoring-thresholds allow for accurate risk stratification as compared to the standard 120-kVp protocol. We prospectively included 170 patients who underwent standard CAC scanning at 120-kVp and 200 milliamperes and additional scans with 80-kVp and 70-kVp tube voltage with adapted tube current to normalize image noise across scans. Novel kVp-adapted thresholds were applied to calculate CAC scores from the low-kVp scans and were compared to those from standard 120-kVp scans by assessing risk reclassification rates and agreement using Kendall's rank correlation coefficients (Τb) for risk categories bounded by 0, 1, 100, and 400. Interreader reclassification rates for the 120-kVp scans were assessed. Agreement for risk classification obtained from 80-kVp and 70-kVp scans as compared to 120-kVp was good (Τb = 0.967 and 0.915, respectively; both p < 0.001) with reclassification rates of 7.1% and 17.2%, respectively, mostly towards a lower risk category. By comparison, the interreader reclassification rate was 4.1% (Τb = 0.980, p < 0.001). Reclassification rates were dependent on body mass index (BMI) with 7.1% and 13.6% reclassifications for the 80-kVp and 70-kVp scans, respectively, in patients with a BMI < 30 kg/m2 (n = 140), and 2.9% and 7.4%, respectively, in patients with a BMI < 25 kg/m2 (n = 68). Mean effective radiation dose from the 120-kVp, the 80-kVp, and 70-kVp scans was 0.54 ± 0.03, 0.42 ± 0.02, and 0.26 ± 0.02 millisieverts. CAC scoring with reduced tube voltage allows for accurate risk stratification if kVp-adapted thresholds for calculation of CAC scores are applied.ClinicalTrials.gov NCT03637231.

Transluminal attenuation gradient derived from coronary CT angiography to predict ischemia in SPECT myocardial perfusion imaging: Effect of coronary cross-sectional area.

BACKGROUND: Coronary computed tomography angiography (CCTA)-based transluminal attenuation gradient (TAG) was suggested to determine the functional significance of a stenosis. However, evidence that TAG acquired by wide-volume scanners can assess the hemodynamic significance of stenosis assessed by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is lacking. Moreover, coronary cross-sectional area may influence TAG. Hence, we aimed at assessing the diagnostic value of TAG to predict ischemia in SPECT-MPI and the correlation between TAG and the transluminal cross-sectional area gradient (TCG). METHODS: Patients undergoing CCTA and SPECT-MPI for suspected coronary artery disease were included. TAG and TCG were calculated measuring the mean vessel attenuation and the cross-sectional area along major coronary vessels at 5-mm intervals. RESULTS: A total of 255 coronary arteries of 87 patients were included. TAG and TCG did not discriminate between coronary arteries with or without ischemia as assessed by SPECT-MPI (p = .44 and p = .25, respectively). The area under the curve to predict ischemia was not increased by adding TAG (0.88, 95% CI 0.83-0.92) or TCG (0.87, 95% CI 0.81-0.90) to CCTA alone (0.85, 95% CI 0.80-0.89). There was a significant correlation between TAG and TCG (r = 0.43; p < .001). CONCLUSIONS: CCTA-derived TAG and TCG do not offer any value in predicting ischemia assessed by SPECT-MPI. TAG is partly affected by differences in the coronary luminal area.

Impact of Adaptive Statistical Iterative Reconstruction-V on Coronary Artery Calcium Scores Obtained From Low-Tube-Voltage Computed Tomography - A Patient Study.

OBJECTIVE: To evaluate the impact of adaptive statistical iterative reconstruction-V (ASIR-V) on the accuracy of ultra-low-dose coronary artery calcium (CAC) scoring. MATERIALS AND METHOD: One-hundred-and-three patients who underwent computed tomography (CT) for CAC scoring were prospectively included. All underwent standard scanning with 120-kilovolt-peak (kVp) and with 80- and 70-kVp tube voltage. ASiR-V was applied to the 80- and 70-kVp scans at different levels. The 120-kVp scans reconstructed with filtered back projection served as the standard of reference. Recently published novel kVp-adapted thresholds were used for calculation of CAC scores from 80- and 70-kVp scans and the resulting CAC scores were compared against the standard of reference. Patients were stratified into six CAC score risk categories: 0, 1-10, 11-100, 101-400, 401-1000, and >1000. RESULTS: Increasing levels of ASIR-V led to an increasing underestimation of CAC scores with bias ranging from -128 to -118 and from -205 to -198 for the 80- and 70-kVp scans, respectively, when compared with the standard of reference. Reconstruction with 20% and 40% ASIR-V for the 80- and 70-kVp scans, respectively, yielded noise levels comparable to the standard of reference. Nevertheless, a change in risk-class was observed in 29 (28.6%) and 46 (44.7%) patients, exclusively to a lower risk-class, when CAC scores were derived from these reconstructions. CONCLUSION: ASIR-V leads to noise reduction in CT scans acquired with low tube-voltages. However, ASIR-V introduces substantial inaccuracies and marked underestimation of ultra-low-dose CAC scoring as compared with standard-dose CAC scoring despite normalization of noise.

Splenic switch-off as a novel marker for adenosine response in nitrogen-13 ammonia PET myocardial perfusion imaging: Cross-validation against CMR using a hybrid PET/MR device.

BACKGROUND: No methodology is available to distinguish truly reduced myocardial flow reserve (MFR) in positron emission tomography myocardial perfusion imaging (PET MPI) from seemingly impaired MFR due to inadequate adenosine response. The adenosine-induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response in cardiac magnetic resonance (CMR). We assessed the feasibility of detecting SSO in nitrogen-13 ammonia PET MPI using SSO in CMR as the standard of reference. METHODS AND RESULTS: Fifty patients underwent simultaneous CMR and PET MPI on a hybrid PET/MR device with co-injection of a gadolinium-based contrast agent and nitrogen-13 ammonia during rest and adenosine-induced stress. In CMR, SSO was assessed visually (positive vs negative SSO) and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). In PET MPI, the splenic signal activity ratio (SAR) was calculated as the maximal standard uptake value of the spleen during stress over rest. The median SIR was significantly lower in patients with positive versus negative SSO in CMR (0.57 [IQR 0.49 to 0.62] vs 0.89 [IQR 0.76 to 0.98]; P < .001). Similarly, median SAR in PET MPI was significantly lower in patients with positive versus negative SSO (0.40 [IQR 0.32 to 0.45] vs 0.80 [IQR 0.47 to 0.98]; P < .001). CONCLUSION: Similarly to CMR, SSO can be detected in nitrogen-13 ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel coronary artery disease.

Prognostic value of regional myocardial flow reserve derived from 13N-ammonia positron emission tomography in patients with suspected coronary artery disease.

PURPOSE: To assess the prognostic value of regional quantitative myocardial flow measures as assessed by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD). METHODS: We retrospectively included 150 consecutive patients with suspected CAD who underwent clinically indicated 13 N-ammonia PET-MPI and who did not undergo revascularization within 90 days of PET-MPI. The presence or absence of a decreased global myocardial flow reserve (i.e., MFR < 2) as well as decreased regional MFR (i.e., ≥ 2 adjacent segments with MFR < 2) was recorded, and patients were classified as having preserved global and regional MFR (MFR group 1), preserved global but decreased regional MFR (MFR group 2), or decreased global and regional MFR (MFR group 3). We obtained follow-up regarding major adverse cardiac events (MACE, i.e., a combined endpoint including all-cause death, non-fatal myocardial infarction, and late revascularization) and all-cause death. RESULTS: Over a median follow-up of 50 months (IQR 38-103), 30 events occurred in 29 patients. Kaplan-Meier analysis showed significantly reduced event-free and overall survival in MFR groups 2 and 3 compared to MFR group 1 (log-rank: p = 0.015 and p = 0.013). In a multivariable Cox regression analysis, decreased regional MFR was an independent predictor for MACE (adjusted HR 3.44, 95% CI 1.17-10.11, p = 0.024) and all-cause death (adjusted HR 4.72, 95% CI 1.07-20.7, p = 0.04). CONCLUSIONS: A decreased regional MFR as assessed by 13 N-ammonia PET-MPI confers prognostic value by identifying patients at increased risk for future adverse cardiac outcomes and all-cause death.

Coronary artery lumen volume index as a marker of flow-limiting atherosclerosis-validation against 13N-ammonia positron emission tomography.

OBJECTIVES: Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), has been proposed as an indicator of diffuse atherosclerosis. We investigated the association of CAVi with quantitative flow parameters and its ability to predict ischemia as derived from 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI). METHODS: Sixty patients who underwent hybrid CCTA/PET-MPI due to suspected CAD were retrospectively included. CAVi was defined as total coronary artery lumen volume over myocardial mass, both derived from CCTA. From PET-MPI, quantitative stress and rest myocardial blood flow (MBF) and myocardial flow reserve (MFR) were obtained and correlated with CAVi, and semi-quantitative perfusion images were analyzed for the presence of ischemia. Harrell's c-statistic and net reclassification improvement (NRI) analysis were performed to evaluate the incremental value of CAVi over the CCTA model (i.e., stenosis > 50% and > 70%). RESULTS: CAVi correlated moderately with stress MBF and MFR (R = 0.50, p < 0.001, and R = 0.39, p = 0.002). Mean stress MBF and MFR were lower in patients with low (i.e., ≤ 20.2 mm3/g, n = 24) versus high (i.e., > 20.2 mm3/g, n = 36) CAVi (p < 0.001 for both comparisons). CAVi was independently associated with abnormal stress MBF (OR 0.90, 95% CI 0.82-0.998, p = 0.045). CAVi increased the predictive ability of the CCTA model for abnormal stress MBF and ischemia (c-statistic 0.763 versus 0.596, pdiff < 0.05 and 0.770 versus 0.645, pdiff < 0.05, NRI 0.84, p = 0.001 and 0.96, p < 0.001, respectively). CONCLUSIONS: CAVi exhibits incremental value to predict both abnormal stress MBF and ischemia over CCTA alone. KEY POINTS: • Coronary artery volume indexed to left myocardial mass (CAVi), derived from coronary computed tomography angiography (CCTA), is correlated with myocardial blood flow indices derived from 13N-ammonia positron emission tomography myocardial perfusion imaging. • CAVi is independently associated with abnormal stress myocardial blood flow. • CAVi provides incremental diagnostic value over CCTA for both abnormal stress MBF and ischemia.

Splenic switch-off as a predictor for coronary adenosine response: validation against 13N-ammonia during co-injection myocardial perfusion imaging on a hybrid PET/CMR scanner.

BACKGROUND: Inadequate coronary adenosine response is a potential cause for false negative ischemia testing. Recently, the splenic switch-off (SSO) sign has been identified as a promising tool to ascertain the efficacy of adenosine during vasodilator stress cardiovascular magnetic resonance imaging (CMR). We assessed the value of SSO to predict adenosine response, defined as an increase in myocardial blood flow (MBF) during quantitative stress myocardial perfusion 13 N-ammonia positron emission tomography (PET). METHODS: We prospectively enrolled 64 patients who underwent simultaneous CMR and PET myocardial perfusion imaging on a hybrid PET/CMR scanner with co-injection of gadolinium based contrast agent (GBCA) and 13N-ammonia during rest and adenosine-induced stress. A myocardial flow reserve (MFR) of  > 1.5 or ischemia as assessed by PET were defined as markers for adequate coronary adenosine response. The presence or absence of SSO was visually assessed. The stress-to-rest intensity ratio (SIR) was calculated as the ratio of stress over rest peak signal intensity for splenic tissue. Additionally, the spleen-to-myocardium ratio, defined as the relative change of spleen to myocardial signal, was calculated for stress (SMRstress) and rest. RESULTS: Sixty-one (95%) patients were coronary adenosine responders, but SSO was absent in 18 (28%) patients. SIR and SMRstress were significantly lower in patients with SSO (SIR: 0.56 ± 0.13 vs. 0.93 ± 0.23; p < 0.001 and SMRstress: 1.09 ± 0.47 vs. 1.68 ± 0.62; p < 0.001). Mean hyperemic and rest MBF were 2.12 ± 0.68 ml/min/g and 0.78 ± 0.26 ml/min/g, respectively. MFR was significantly higher in patients with vs. patients without presence of SSO (3.07 ± 1.03 vs. 2.48 ± 0.96; p = 0.038), but there was only a weak inverse correlation between SMRstress and MFR (R = -0.378; p = 0.02) as well as between SIR and MFR (R = -0.356; p = 0.004). CONCLUSIONS: The presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation.

Role of quantitative myocardial blood flow and 13N-ammonia washout for viability assessment in ischemic cardiomyopathy.

OBJECTIVE: Positron emission tomography (PET) integrating assessment of perfusion with 13N-ammonia (NH3) and viability with 18F-fluorodeoxyglucose (FDG) has high accuracy to identify viable, hibernating myocardium. We tested whether quantification of myocardial blood flow (MBF) and washout (k2) can predict myocardial viability using FDG as standard of reference. METHODS: In 180 consecutive patients with ischemic cardiomyopathy, myocardium was categorized on a segment-level into normal, ischemic, hibernating, and scar. From dynamic images, stress MBF, rest MBF, and k2 were derived and myocardial flow reserve (MFR) and volume of distribution (VD) were calculated. RESULTS: Across myocardial tissues, all parameters differed significantly. The area under the curve (AUC) was 0.564 (95% CI 0.527-0.601), 0.635 (0.599-0.671), 0.553 (0.516-0.591), 0.520 (0.482-0.559), and 0.560 (0.522-0.597) for stress MBF, rest MBF, MFR, k2, and VD. The generalized linear mixed model correctly classified 81% of scar as viable, hibernating myocardium. If the threshold of rest MBF to predict viability was set to 0.45 mL·min-1·g-1, sensitivity and specificity were 96% and 12%, respectively. CONCLUSION: Quantitative NH3 PET parameters have low to moderate diagnostic performance to predict viability in ischemic cardiomyopathy. However, if rest MBF falls below 0.45 mL·min-1·g-1, viability testing by FDG-PET may be safely deferred.

Prognostic Value of Quantitative Metrics From Positron Emission Tomography in Ischemic Heart Failure.

OBJECTIVES: The aim of this study was to investigate the prognostic and clinical value of quantitative positron emission tomographic (PET) metrics in patients with ischemic heart failure. BACKGROUND: Although myocardial flow reserve (MFR) is a strong predictor of cardiac risk in patients without heart failure, it is unknown whether quantitative PET metrics improve risk stratification in patients with ischemic heart failure. METHODS: The study included 254 patients referred for stress and rest myocardial perfusion imaging and viability testing using PET. Major adverse cardiac event(s) (MACE) consisted of death, resuscitated sudden cardiac death, heart transplantation, acute coronary syndrome, hospitalization for heart failure, and late revascularization. RESULTS: MACE occurred in 170 patients (67%) during a median follow-up of 3.3 years. In a multivariate Cox proportional hazards model including multiple quantitative PET metrics, only MFR predicted MACE significantly (p = 0.013). Beyond age, symptom severity, diabetes mellitus, previous myocardial infarction or revascularization, 3-vessel disease, renal insufficiency, ejection fraction, as well as presence and burden of ischemia, scar, and hibernating myocardium, MFR was strongly associated with MACE (adjusted hazard ratio per increase in MFR by 1: 0.63; 95% confidence interval: 0.45 to 0.91). Incorporation of MFR into a risk assessment model incrementally improved the prediction of MACE (likelihood ratio chi-square test [16] = 48.61 vs. chi-square test [15] = 39.20; p = 0.002). CONCLUSIONS: In this retrospective analysis of a single-center cohort, quantitative PET metrics of myocardial blood flow all improved risk stratification in patients with ischemic heart failure. However, in a hypothesis-generating analysis, MFR appears modestly superior to the other metrics as a prognostic index.

Myocardial creep-induced misalignment artifacts in PET/MR myocardial perfusion imaging.

PURPOSE: Misalignment between positron emission tomography (PET) datasets and attenuation correction (AC) maps is a potential source of artifacts in myocardial perfusion imaging (MPI). We assessed the impact of adenosine on the alignment of AC maps derived from magnetic resonance (MR) and PET datasets during MPI on a hybrid PET/MR scanner. METHODS: Twenty-eight volunteers underwent adenosine stress and rest 13N-ammonia MPI on a PET/MR. We acquired Dixon sequences for the creation of MRAC maps. After reconstruction of the original non-shifted PET images, we examined MRAC and PET datasets for cardiac spatial misalignment and, if necessary, reconstructed a second set of shifted PET images after manually adjusting co-registration. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were compared between shifted and non-shifted PET images. Additionally, we measured the amount of cranial movement of the heart (i.e., myocardial creep) after termination of adenosine infusion. RESULTS: Realignment was necessary for 25 (89.3%) stress and 12 (42.9%) rest PET datasets. Median SRS, SSS, and SDS of the non-shifted images were 6 (IQR = 4-7), 12 (IQR = 7-18), and 8 (IQR = 2-11), respectively, and of the shifted images 2 (IQR = 1-6), 4 (IQR = 7-18), and 1 (IQR = 0-2), respectively. All three scores were significantly higher in non-shifted versus shifted images (all p < 0.05). The difference in SDS correlated moderately but significantly with the amount of myocardial creep (r = 0.541, p = 0.005). CONCLUSION: Misalignment of MRAC and PET datasets commonly occurs during adenosine stress MPI on a hybrid PET/MR device, potentially leading to an increase in false-positive findings. Our results suggest that myocardial creep may substantially account for this and prompt for a careful review and correction of PET/MRAC data.

Potential of Radiation Dose Reduction by Optimizing Z-Axis Coverage in Coronary Computed Tomography Angiography on a Latest-Generation 256-Slice Scanner.

OBJECTIVE: The purpose of this study was to quantify the reduction in radiation dose achievable by using the optimal z-axis coverage in coronary computed tomography (CT) angiography (CCTA) on a latest-generation 256-slice scanner. METHODS: A total of 408 scans were reviewed that were performed on a wide-range detector scanner allowing up to 16-cm z-axis coverage (adjustable in 2-cm increments). For each CCTA study, we assessed the radiation dose (ie, dose-length product and volume CT dose index) and measured the minimum z-axis coverage necessary to cover the complete cardiac anatomy. We calculated the potential radiation dose savings achievable through reduction of the z-axis coverage to the minimum necessary. RESULTS: The majority of the CCTA scans were performed with a z-axis coverage of 16 cm (n = 285, 69.9%), followed by 14 cm (n = 121, 29.7%) and 12 cm (n = 2, 0.5%). In the group that was scanned with a collimation of 16 cm, radiation dose could have been reduced by 12.5% in 55 patients, 25% in 195 patients, and 37.5% in 33 patients when using optimal z-axis coverage for CCTA. In the group that was scanned with a collimation of 14 cm, radiation dose could have been reduced by 14.3% in 90 patients, and 28.6% in 30 patients, whereas in the group that was scanned with a collimation of 12 cm, dose could have been reduced by 16.7% in 2 patients. CONCLUSIONS: Using correct z-axis coverage in CCTA on a latest-generation 256-slice scanner yields average dose reductions of 22.0% but may be as high as 37.5%.

Coronary artery volume index: a novel CCTA-derived predictor for cardiovascular events.

Coronary computed tomography angiography (CCTA) provides critical prognostic information on plaque burden and stenosis severity of coronary arteries. We aimed to investigate the long-term prognostic value of coronary artery volume per myocardial mass as a potential new imaging parameter. Consecutive patients with suspected coronary artery disease (CAD) were included. Coronary artery volume index (CAVi) was defined as volume over myocardial mass. Additionally, obstructive CAD (≥ 70% stenosis) and segment severity score (SSS: sum of all segments scored according to lesion severity with 0 = no lesion, 1 = narrowing < 50%, 2 = stenosis 50-69% and 3 = stenosis ≥ 70%) were evaluated. Major adverse cardiovascular events (MACE) were defined as cardiac death, non-fatal myocardial infarction or revascularization. The association of CAVi with MACE was evaluated using Cox regression hazards ratios (HR) and Kaplan Meier curves. In a total of 325 patients, 36 (11.1%) patients experienced MACE during the mean follow-up of 5.4 ± 1.7 years. Patients with low-CAVi (< 27.9 mm3/g) experienced more MACE than patients with high-CAVI (17.2% versus 4.5%, p < 0.001, Kaplan Meier curve p = 0.001). SSS, obstructive CAD and low-CAVi were all significant predictors of MACE in univariable analysis (HR 1.14, 95% CI 1.09-1.19, p < 0.001; HR 5.51, 95% CI 2.86-10.60, p < 0.001; and HR 3.79, 95% CI 1.66-8.65, p = 0.002, respectively). CAVi maintained significant association with MACE when adjusted to SSS (CAVi HR 2.43, 95% CI 1.02-5.75, p = 0.04) or obstructive CAD (CAVi HR 2.4, 95% CI 1.002-5.75, p = 0.049). CAVi could further risk stratify patients without obstructive CAD when stratifying patients according to obstructive CAD (Kaplan-Meier curve p = 0.049). CAVi is a novel CCTA-derived imaging parameter, yielding independent prognostic value over stenosis and plaque burden.

Validation of deep-learning image reconstruction for coronary computed tomography angiography: Impact on noise, image quality and diagnostic accuracy.

BACKGROUND: Advances in image reconstruction are necessary to decrease radiation exposure from coronary CT angiography (CCTA) further, but iterative reconstruction has been shown to degrade image quality at high levels. Deep-learning image reconstruction (DLIR) offers unique opportunities to overcome these limitations. The present study compared the impact of DLIR and adaptive statistical iterative reconstruction-Veo (ASiR-V) on quantitative and qualitative image parameters and the diagnostic accuracy of CCTA using invasive coronary angiography (ICA) as the standard of reference. METHODS: This retrospective study includes 43 patients who underwent clinically indicated CCTA and ICA. Datasets were reconstructed with ASiR-V 70% (using standard [SD] and high-definition [HD] kernels) and with DLIR at different levels (i.e., medium [M] and high [H]). Image noise, image quality, and coronary luminal narrowing were evaluated by three blinded readers. Diagnostic accuracy was compared against ICA. RESULTS: Noise did not significantly differ between ASiR-V SD and DLIR-M (37 vs. 37 HU, p = 1.000), but was significantly lower in DLIR-H (30 HU, p < 0.001) and higher in ASiR-V HD (53 HU, p < 0.001). Image quality was higher for DLIR-M and DLIR-H (3.4-3.8 and 4.2-4.6) compared to ASiR-V SD and HD (2.1-2.7 and 1.8-2.2; p < 0.001), with DLIR-H yielding the highest image quality. Consistently across readers, no significant differences in sensitivity (88% vs. 92%; p = 0.453), specificity (73% vs. 73%; p = 0.583) and diagnostic accuracy (80% vs. 82%; p = 0.366) were found between ASiR-V HD and DLIR-H. CONCLUSION: DLIR significantly reduces noise in CCTA compared to ASiR-V, while yielding superior image quality at equal diagnostic accuracy.

Sex and age differences in the association of heart rate responses to adenosine and myocardial ischemia in patients undergoing myocardial perfusion imaging.

BACKGROUND: In light of growing cardiovascular mortality rates observed in young women, sexual dimorphism in cardiac autonomic nervous control is gaining increasing attention. Heart rate responses to adenosine mirror autonomic activity and may carry important prognostic information. METHODS AND RESULTS: Hemodynamic changes during adenosine stress were retrospectively analysed in a propensity-matched cohort of 1932 consecutive patients undergoing myocardial perfusion single-photon-emission computed tomography (MPI-SPECT). Heart rate (HR) and systolic blood pressure (SBP) increased during adenosine infusion (P < 0.001). The increase in SBP and HR (heart rate reserve, HRR), was significantly more pronounced in women compared with men (P < 0.05). Patients ≤ 55 years had a higher HRR compared with patients > 55 years (46.8% vs 37.5%, P = 0.015). Women ≤ 55 years with a reversible perfusion defect on MPI-SPECT exhibited the highest HRR (89.2%), while age-matched men showed a blunted HR response to adenosine (26.4%, P = 0.01). Accordingly, age and an interaction term of female sex and increased HRR were identified as significant predictors of myocardial ischemia in a multiple regression analysis (OR 1.4, 95% CI 1.02-1.9, P = 0.038). CONCLUSION: HRR during adenosine infusion is influenced by age and sex. Our data suggest a stronger, sympathetic-driven, hemodynamic response to adenosine in younger women with myocardial ischemia.

Association between vertebral bone mineral density, myocardial perfusion, and long-term cardiovascular outcomes: A sex-specific analysis.

BACKGROUND: Sexual dimorphism in the manifestation of coronary artery disease (CAD) has unleashed a call to reconsider cardiovascular risk assessment. Alterations of bone mineral density (BMD) have been associated with congestive heart failure and appear to be modified by sex. However, the sex-specific association between BMD, myocardial perfusion, and cardiovascular outcomes is currently unknown. METHODS: A total number of 491 patients (65.9 ± 10.7 years, 32.4% women) underwent 13N-ammonia positron emission tomography/computed tomography for evaluation of CAD, and were tracked for major adverse cardiac events (MACEs). RESULTS: Event-free survival (median follow-up time of 4.3 ± 2.0 years) was significantly reduced in patients with low (≤ 100 Hounsfield units) compared to those with higher BMD (log-rank P = .037). Accordingly, reduced BMD was chosen as significant predictor of MACE in a fully adjusted proportional hazards regression model (P = .015). Further, a first-order interaction term consisting of sex and BMD was statistically significant (P = .007). BMD was significantly lower in patients with abnormal myocardial perfusion or impaired left ventricular ejection fraction (P < .05). This difference, however, was noticed in men, but not in women. CONCLUSIONS: The association between low BMD and cardiovascular disease is sex dependent. Our data suggest that quantification of BMD during myocardial perfusion imaging for evaluation of CAD may be particularly useful in men.

Metabolic Activity in Central Neural Structures of Patients With Myocardial Injury.

Background Increasing evidence suggests a psychosomatic link between neural systems and the heart. In light of the growing burden of ischemic cardiovascular disease across the globe, a better understanding of heart-brain interactions and their implications for cardiovascular treatment strategies is needed. Thus, we sought to investigate the interaction between myocardial injury and metabolic alterations in central neural areas in patients with suspected or known coronary artery disease. Methods and Results The association between resting metabolic activity in distinct neural structures and cardiac function was analyzed in 302 patients (aged 66.8±10.2 years; 70.9% men) undergoing fluor-18-deoxyglucose positron emission tomography and 99mTc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging. There was evidence for reduction of callosal, caudate, and brainstem fluor-18-deoxyglucose uptake in patients with impaired left ventricular ejection fraction (<55% versus ≥55%: P=0.047, P=0.022, and P=0.013, respectively) and/or in the presence of myocardial ischemia (versus normal perfusion: P=0.010, P=0.013, and P=0.016, respectively). In a sex-stratified analysis, these differences were observed in men, but not in women. A first-order interaction term consisting of sex and impaired left ventricular ejection fraction or myocardial ischemia was identified as predictor of metabolic activity in these neural regions (left ventricular ejection fraction: P=0.015 for brainstem; myocardial ischemia: P=0.004, P=0.018, and P=0.003 for callosal, caudate, or brainstem metabolism, respectively). Conclusions Myocardial dysfunction and injury are associated with reduced resting metabolic activity of central neural structures, including the corpus callosum, the caudate nucleus, and the brainstem. These associations differ in women and men, suggesting sex differences in the pathophysiological interplay of the nervous and cardiovascular systems.

No differences in rest myocardial blood flow in stunned and hibernating myocardium: insights into the pathophysiology of ischemic cardiomyopathy.

PURPOSE: The human pathophysiology of stunned, hibernating and scarred myocardium in ischemic cardiomyopathy is a subject of controversy. While the "smart heart" theory postulates that reduced myocardial blood flow (MBF) at rest is responsible for myocytes switching to a state of hibernation, other theories suggest that a reduced myocardial flow reserve (MFR) may be the cause. METHODS: We included 110 patients with ischemic cardiomyopathy. Based on quantitative myocardial perfusion assessment and viability imaging with 13N-NH3 and 18F-FDG positron emission tomography, respectively, as well as wall motion assessment from echocardiography, myocardial tissue was characterized as remote (i.e., normal myocardium), stunned (i.e., dysfunctional but viable myocardium with normal rest perfusion), hibernating (i.e., dysfunctional but viable myocardium with impaired rest perfusion), or scarred myocardium (i.e., non-viable myocardium). RESULTS: Compared to remote myocardium, dysfunctional but viable myocardium (including stunned and hibernating) had reduced rest MBF (0.89 mL/min/g vs. 0.79 and 0.76 mL/min/g, respectively; p < 0.001) and MFR (1.53 vs. 1.27 and 1.17; p < 0.001). Between stunned and hibernating myocardium, however, rest MBF and MFR did not differ (p = 0.40). In scarred myocardium, rest MBF was lowest (0.66 mL/min/g; p < 0.001) but, in contrast to the other myocardial states, k2 (i.e., tracer washout) was increased (0.199/min vs. 0.178/min to 0.181/min; all p < 0.05 in pairwise comparison). CONCLUSIONS: In patients with ischemic cardiomyopathy, impaired MFR is associated with stunning and hibernation. These states of dysfunctional but viable myocardium have lower rest MBF compared to remote myocardium. At the end of the continuum, rest MBF is lowest in scar tissue and linked to increased rate of tracer washout.