Cardiac magnetic resonance biomarkers as surrogate endpoints in cardiovascular trials for myocardial diseases.

Cardiac magnetic resonance offers multiple facets in the diagnosis, risk stratification, and management of patients with myocardial diseases. Particularly, its feature to precisely monitor disease activity lends itself to quantify response to novel therapeutics. This review critically appraises the value of cardiac magnetic resonance imaging biomarkers as surrogate endpoints for prospective clinical trials. The primary focus is to comprehensively outline the value of established cardiac magnetic resonance parameters in myocardial diseases. These include heart failure, cardiac amyloidosis, iron overload cardiomyopathy, hypertrophic cardiomyopathy, cardio-oncology, and inflammatory cardiomyopathies like myocarditis and sarcoidosis.

Coronary microvascular function in male physicians with burnout and job stress: an observational study.

BACKGROUND: As a professional group, physicians are at increased risk of burnout and job stress, both of which are associated with an increased risk of coronary heart disease that is at least as high as that of other professionals. This study aimed to examine the association of burnout and job stress with coronary microvascular function, a predictor of major adverse cardiovascular events. METHODS: Thirty male physicians with clinical burnout and 30 controls without burnout were included. Burnout was assessed with the Maslach Burnout Inventory and job stress with the effort-reward imbalance and overcommitment questionnaire. All participants underwent myocardial perfusion positron emission tomography to quantify endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular function. Burnout and job stress were regressed on coronary flow reserve (primary outcome) and two additional measures of coronary microvascular function in the same model while adjusting for age and body mass index. RESULTS: Burnout and job stress were significantly and independently associated with endothelium-dependent microvascular function. Burnout was positively associated with coronary flow reserve, myocardial blood flow response, and hyperemic myocardial blood flow (r partial = 0.28 to 0.35; p-value = 0.008 to 0.035). Effort-reward ratio (r partial = - 0.32 to - 0.38; p-value = 0.004 to 0.015) and overcommitment (r partial = - 0.30 to - 0.37; p-value = 0.005 to 0.022) showed inverse associations with these measures. CONCLUSIONS: In male physicians, burnout and high job stress showed opposite associations with coronary microvascular endothelial function. Longitudinal studies are needed to show potential clinical implications and temporal relationships between work-related variables and coronary microvascular function. Future studies should include burnout and job stress for a more nuanced understanding of their potential role in cardiovascular health.

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.

Impact of deep learning image reconstructions (DLIR) on coronary artery calcium quantification.

BACKGROUND: Deep learning image reconstructions (DLIR) have been recently introduced as an alternative to filtered back projection (FBP) and iterative reconstruction (IR) algorithms for computed tomography (CT) image reconstruction. The aim of this study was to evaluate the effect of DLIR on image quality and quantification of coronary artery calcium (CAC) in comparison to FBP. METHODS: One hundred patients were consecutively enrolled. Image quality-associated variables (noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR)) as well as CAC-derived parameters (Agatston score, mass, and volume) were calculated from images reconstructed by using FBP and three different strengths of DLIR (low (DLIR_L), medium (DLIR_M), and high (DLIR_H)). Patients were stratified into 4 risk categories according to the Coronary Artery Calcium - Data and Reporting System (CAC-DRS) classification: 0 Agatston score (very low risk), 1-99 Agatston score (mildly increased risk), Agatston 100-299 (moderately increased risk), and ≥ 300 Agatston score (moderately-to-severely increased risk). RESULTS: In comparison to standard FBP, increasing strength of DLIR was associated with a significant and progressive decrease of image noise (p < 0.001) alongside a significant and progressive increase of both SNR and CNR (p < 0.001). The use of incremental levels of DLIR was associated with a significant decrease of Agatston CAC score and CAC volume (p < 0.001), while mass score remained unchanged when compared to FBP (p = 0.232). The underestimation of Agatston CAC led to a CAC-DRS misclassification rate of 8%. CONCLUSION: DLIR systematically underestimates Agatston CAC score. Therefore, DLIR should be used cautiously for cardiovascular risk assessment. KEY POINTS: • In coronary artery calcium imaging, the implementation of deep learning image reconstructions improves image quality, by decreasing the level of image noise. • Deep learning image reconstructions systematically underestimate Agatston coronary artery calcium score. • Deep learning image reconstructions should be used cautiously in clinical routine to measure Agatston coronary artery calcium score for cardiovascular risk assessment.

Predictive value of cardiac magnetic resonance right ventricular longitudinal strain in patients with suspected myocarditis.

BACKGROUND: Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR. METHODS: Patients referred for CMR, meeting clinical criteria for suspected myocarditis and no other cardiomyopathy were enrolled in a dual-center register cohort study. Ejection fraction (EF), GLS and tissue characteristics were assessed in both ventricles to assess their association to first major adverse cardiovascular events (MACE) including hospitalization for heart failure (HF), ventricular tachycardia (VT), recurrent myocarditis and death. RESULTS: Among 659 patients (62.8% male; 48.1 ± 16.1 years), RV GLS was impaired (> - 15.4%) in 144 (21.9%) individuals, of whom 76 (58%), 108 (77.1%), 27 (18.8%) and 40 (32.8%) had impaired right ventricular ejection fraction (RVEF), impaired left ventricular ejection fraction (LVEF), RV late gadolinium enhancement (LGE) or RV edema, respectively. After a median observation time of 3.7 years, 45 (6.8%) patients were hospitalized for HF, 42 (6.4%) patients died, 33 (5%) developed VT and 16 (2.4%) had recurrent myocarditis. Impaired RV GLS was associated with MACE (HR = 1.07, 95% CI 1.04-1.10; p < 0.001), HF hospitalization (HR = 1.17, 95% CI 1.12-1.23; p < 0.001), and death (HR = 1.07, 95% CI 1.02-1.12; p = 0.004), but not with VT and recurrent myocarditis in univariate analysis. RV GLS lost its association with outcomes, when adjusted for RVEF, LVEF, LV GLS and LV LGE extent. CONCLUSION: RV strain is associated with MACE, HF hospitalization and death but has neither independent nor incremental prognostic value after adjustment for RV and LV function and tissue characteristics. Therefore, assessing RV GLS in the setting of myocarditis has only limited value.

Radiation dose reduction with deep-learning image reconstruction for coronary computed tomography angiography.

OBJECTIVES: Deep-learning image reconstruction (DLIR) offers unique opportunities for reducing image noise without degrading image quality or diagnostic accuracy in coronary CT angiography (CCTA). The present study aimed at exploiting the capabilities of DLIR to reduce radiation dose and assess its impact on stenosis severity, plaque composition analysis, and plaque volume quantification. METHODS: This prospective study includes 50 patients who underwent two sequential CCTA scans at normal-dose (ND) and lower-dose (LD). ND scans were reconstructed with Adaptive Statistical Iterative Reconstruction-Veo (ASiR-V) 100%, and LD scans with DLIR. Image noise (in Hounsfield units, HU) and quantitative plaque volumes (in mm3) were assessed quantitatively. Stenosis severity was visually categorized into no stenosis (0%), stenosis (< 20%, 20-50%, 51-70%, 71-90%, 91-99%), and occlusion (100%). Plaque composition was classified as calcified, non-calcified, or mixed. RESULTS: Reduction of radiation dose from ND scans with ASiR-V 100% to LD scans with DLIR at the highest level (DLIR-H; 1.4 mSv vs. 0.8 mSv, p < 0.001) had no impact on image noise (28 vs. 27 HU, p = 0.598). Reliability of stenosis severity and plaque composition was excellent between ND scans with ASiR-V 100% and LD scans with DLIR-H (intraclass correlation coefficients of 0.995 and 0.974, respectively). Comparison of plaque volumes using Bland-Altman analysis revealed a mean difference of - 0.8 mm3 (± 2.5 mm3) and limits of agreement between - 5.8 and + 4.1 mm3. CONCLUSION: DLIR enables a reduction in radiation dose from CCTA by 43% without significant impact on image noise, stenosis severity, plaque composition, and quantitative plaque volume. KEY POINTS: •Deep-learning image reconstruction (DLIR) enables radiation dose reduction by over 40% for coronary computed tomography angiography (CCTA). •Image noise remains unchanged between a normal-dose CCTA reconstructed by ASiR-V and a lower-dose CCTA reconstructed by DLIR. •There is no impact on the assessment of stenosis severity, plaque composition, and quantitative plaque volume between the two scans.

Low-dose CT from myocardial perfusion SPECT/CT allows the detection of anemia in preoperative patients.

BACKGROUND: To assess whether low-dose CT for attenuation correction of myocardial perfusion single-photon emission computed tomography (SPECT) allows for identification of anemic patients and grading anemia severity. METHODS AND RESULTS: Patients who underwent a preoperative blood-test and low-dose CT scan, as a part of a cardiac SPECT exam, between 01 January 2015 and 31 December 2017 were enrolled in this retrospective study. Hemoglobin (Hb) levels and hematocrit were derived from clinical records. CT images were visually assessed (qualitative analysis) for the detection of inter-ventricular septum sign (IVSS) and aortic rim sign (ARS) and quantitative analysis were performed. The diagnostic accuracy for detecting anemia was compared using Hb values as the standard of reference. A total of 229 patients were included (110 with anemia; 57 mild; 46 moderate; 7 severe). The AUC of IVSS and ARS were 0.830 and 0.669, respectively (p<0.0001). The quantitative analysis outperformed ARS and IVSS; (AUC of 0.893, p=0.29). The optimal anemia cut-off using Youden index was 4.5 HU. CONCLUSION: Quantitative analysis derived from low-dose CT images, as a part of cardiac SPECT exams, have a diagnostic accuracy similar to that of hematocrit for the detection of anemia and may allow discriminating different anemia severities.

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.

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.

Quantification of perivascular inflammation does not provide incremental prognostic value over myocardial perfusion imaging and calcium scoring.

AIMS: Perivascular fat attenuation index (FAI) has emerged as a novel coronary computed tomography angiography (CCTA)-based biomarker predicting cardiovascular outcomes by capturing early coronary inflammation. It is currently unknown whether FAI adds prognostic value beyond that provided by single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) and CCTA findings including coronary artery calcium scoring (CACS). METHODS AND RESULTS: A total of 492 patients (mean age 62.5 ± 10.8 years) underwent clinically indicated multimodality CCTA and electrocardiography (ECG)-gated 99mTc-tetrofosmin SPECT-MPI between May 2005 and December 2008 at our institution, and follow-up data on major adverse cardiovascular events (MACE) was obtained for 314 patients. FAI was obtained from CCTA images and was measured around the right coronary artery (FAI[RCA]), the left anterior descending artery (FAI[LAD]), and the left main coronary artery (FAI[LMCA]). During a median follow-up of 2.7 years, FAI[RCA] > - 70.1 was associated with an increased rate of MACE (log rank p = 0.049), while no such association was seen for FAI[LAD] or FAI[LMCA] (p = NS). A multivariate Cox regression model accounting for cardiovascular risk factors, CCTA and SPECT-MPI findings identified FAI[RCA] as an independent predictor of MACE (HR 2.733, 95% CI: 1.220-6.123, p = 0.015). However, FAI[RCA] was no longer a significant predictor of MACE after adding CACS (p = 0.279). A first-order interaction term consisting of sex and FAI[RCA] was significant in both models (HR 2.119, 95% CI: 1.218-3.686, p = 0.008; and HR 2.071, 95% CI: 1.111-3.861, p = 0.022). CONCLUSION: FAI does not add incremental prognostic value beyond multimodality MPI/CCTA findings including CACS. The diagnostic value of FAI[RCA] is significantly biased by sex.

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.

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.

Value of 12-lead electrocardiogram to predict myocardial scar on FDG PET in heart failure patients.

PURPOSE: A surface 12-lead electrocardiogram (ECG) is widely available, fast, inexpensive, and safe. However, its value to predict a true myocardial scar in patients with ischemic cardiomyopathy (ICM) has not been studied extensively yet. This study was conducted to assess whether Q waves on resting surface 12-lead ECG are predictive of non-viable myocardium in patients with ICM. METHODS: We analyzed resting ECGs of 149 patients with ICM undergoing cardiac positron emission tomography (PET) with 13N-ammonia (NH3) and 18F-fluorodeoxyglucose (FDG) at our institution. Pathological Q waves and QS complexes were assigned to one of three coronary artery territories and compared to the PET findings. Myocardial scar was defined as 2 or more contiguous myocardial segments with an average (matched) reduction of NH3 and FDG uptake <50% of the maximum value. RESULTS: Pathological Q waves had a sensitivity and specificity of 70% and 40%, respectively, and a PPV and NPV of 37% and 73%, respectively, to detect myocardial scar on FDG PET. For QS complexes, sensitivity and specificity were 46% and 59%, respectively, and PPV and NPV were 36% and 68%, respectively. Sensitivity was lower, but specificity was significantly higher in both the LCX and RCA compared to the LAD territory (p<0.001), particularly for QS complexes. CONCLUSION: Pathological Q waves on resting 12-lead ECG have poor or at best moderate sensitivity and specificity to detect myocardial scar on FDG PET. These findings support the use of more advanced imaging techniques to assess myocardial viability in ICM.

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.

Artificial intelligence for detecting small FDG-positive lung nodules in digital PET/CT: impact of image reconstructions on diagnostic performance.

OBJECTIVES: To evaluate the diagnostic performance of a deep learning algorithm for automated detection of small 18F-FDG-avid pulmonary nodules in PET scans, and to assess whether novel block sequential regularized expectation maximization (BSREM) reconstruction affects detection accuracy as compared to ordered subset expectation maximization (OSEM) reconstruction. METHODS: Fifty-seven patients with 92 18F-FDG-avid pulmonary nodules (all ≤ 2 cm) undergoing PET/CT for oncological (re-)staging were retrospectively included and a total of 8824 PET images of the lungs were extracted using OSEM and BSREM reconstruction. Per-slice and per-nodule sensitivity of a deep learning algorithm was assessed, with an expert readout by a radiologist/nuclear medicine physician serving as standard of reference. Receiver-operator characteristic (ROC) curve of OSEM and BSREM were assessed and the areas under the ROC curve (AUC) were compared. A maximum standardized uptake value (SUVmax)-based sensitivity analysis and a size-based sensitivity analysis with subgroups defined by nodule size was performed. RESULTS: The AUC of the deep learning algorithm for nodule detection using OSEM reconstruction was 0.796 (CI 95%; 0.772-0.869), and 0.848 (CI 95%; 0.828-0.869) using BSREM reconstruction. The AUC was significantly higher for BSREM compared to OSEM (p = 0.001). On a per-slice analysis, sensitivity and specificity were 66.7% and 79.0% for OSEM, and 69.2% and 84.5% for BSREM. On a per-nodule analysis, the overall sensitivity of OSEM was 81.5% compared to 87.0% for BSREM. CONCLUSIONS: Our results suggest that machine learning algorithms may aid detection of small 18F-FDG-avid pulmonary nodules in clinical PET/CT. AI performed significantly better on images with BSREM than OSEM. KEY POINTS: • The diagnostic value of deep learning for detecting small lung nodules (≤ 2 cm) in PET images using BSREM and OSEM reconstruction was assessed. • BSREM yields higher SUVmaxof small pulmonary nodules as compared to OSEM reconstruction. • The use of BSREM translates into a higher detectability of small pulmonary nodules in PET images as assessed with artificial intelligence.

Ultra-low-dose computed tomography for attenuation correction of cadmium-zinc-telluride single photon emission computed tomography myocardial perfusion imaging.

BACKGROUND: The applicability of ultra-low-dose computed tomography (CT) for attenuation correction (AC) of single-photon-emission computed tomography myocardial perfusion imaging (SPECT-MPI) remains elusive. METHODS AND RESULTS: One-hundred patients underwent one-day 99mTc-tetrofosmin stress-rest MPI and non-contrast enhanced cardiac CT with 120, 80, and 70 kilovolt peak (kVp) tube voltage and tube current of 200 milliamperes for creation of AC maps. Normalized percent myocardial uptake from SPECT-MPI using 80 kVp scans for AC showed excellent correlation vs AC from 120 kVp scans for stress [intraclass correlation (ICC) = 0.988, 95% CI = 0.986-0.989, P < .001] and rest (ICC = 0.985, 95% CI = 0.983-0.987, P < .001) with narrow Bland-Altman limits of agreement (BA-LA) (- 5.3% to 4.5% and - 5.4% to 4.4%, respectively) and minimal bias (- 0.4% and - 0.5%, respectively). Correlation of AC SPECT-MPI based on 70 vs 120 kVp scans was excellent for stress (ICC = 0.988, 95% CI = 0.986-0.989, P < .001) and rest (ICC = 0.986, 95% CI = 0.984-0.987, P < .001) with narrow BA-LA (- 5.3% to 4.4% and - 5.2% to 4.5%, respectively) and small bias (- 0.4% and - 0.3%, respectively). Mean effective radiation dose for the 120, 80 and 70 kVp scans were 0.58 ± 0.07, 0.19 ± 0.02, and 0.12 ± 0.01 mSv, respectively. CONCLUSIONS: Attenuation maps for MPI obtained from ultra-low radiation dose CT scans are interchangeable with attenuation maps from standard-dose CT while offering a substantial reduction in radiation dose exposure.

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.

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.