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The 2020 guidelines of the European Society of Cardiology (ESC) recommend a novel ESC 0/2h-algorithm as the preferred alternative to the ESC 0/1h-algorithm in the early triage for rule-out and/or rule-in of Non-ST-segment-elevation myocardial infarction (NSTEMI). The aim was to prospectively validate the performance of the ESC 0/2h-algorithm using the high-sensitivity cardiac troponin I (hs-cTnI) assay (ARCHITECT) in an international, multicenter diagnostic study enrolling patients presenting with acute chest discomfort to the emergency department.

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 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.

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 P 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.

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 from13N-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.

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 b = 0.980, p 2 (n = 140), and 2.9% and 7.4%, respectively, in patients with a BMI 2 (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.

Background Trimethylamine N-oxide (TMAO) has been associated with cardiovascular outcomes. However, the diagnostic value of TMAO and its precursors have not been assessed for functionally relevant coronary artery disease (fCAD) and its prognostic potential in this setting needs to be evaluated. Methods Among 1726 patients with suspected fCAD serum TMAO, and its precursors betaine, choline and carnitine, were quantified using liquid chromatography tandem mass spectrometry. Diagnosis of fCAD was performed by myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography blinded to marker concentrations. Incident all-cause death, cardiovascular death (CVD) and myocardial infarction (MI) were assessed during 5-years follow-up. Results Concentrations of TMAO, betaine, choline and carnitine were significantly higher in patients with fCAD versus those without (TMAO 5.33 μM vs 4.66 μM, p p p p = 0.003; HR = 1.66 [1.07, 2.59], p = 0.025). Prognostic discriminative accuracy for TMAO was good and robust for death and CVD (2-years AUC for CVD 0.73, 95% CI [0.65–0.80]). Conclusion TMAO and its precursors, betaine, choline and carnitine were significantly associated with fCAD, but with limited diagnostic value. TMAO was a strong predictor for incident death and CVD in patients with suspected fCAD. Clinical trial registration NCT01838148. Graphical abstract

Background: The early non-invasive discrimination of Type 2 versus Type 1 Myocardial Infarction (T2MI, T1MI) is a major unmet clinical need. We aimed to externally validate a recently derived clinical score (Neumann) combing female sex, no radiating chest pain, and high-sensitivity cardiac troponin I (hs-cTnI) concentration ≤40.8 ng/L. Methods: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. The final diagnoses of T2MI and T1MI were centrally adjudicated by two independent cardiologists using all information including cardiac imaging and serial measurements of hs-cTnT/I according to the fourth universal definition of MI. Model performance for T2MI diagnosis was assessed by formal tests and graphical means of discrimination and calibration. Results: Among 6684 enrolled patients, MI was the adjudicated final diagnosis in 1079 (19%) patients, of which 242 (22%) had T2MI. External validation of the Neumann Score showed a moderate discrimination (C-statistic 0.67 (95%CI 0.64–0.71)). Model calibration showed underestimation of the predicted probabilities of having T2MI for low point scores. Model extension by adding the binary variable heart rate &gt, 120/min significantly improved model performance (C-statistic 0.73 (95% CI 0.70–0.76, p &lt, 0.001) and had good calibration. Patients with the highest score values of 3 (Neumann Score, 9.9%) and 5 (Extended Neumann Score, 3.3%) had a 53% and 91% predicted probability of T2MI, respectively. Conclusion: The Neumann Score provided moderate discrimination and suboptimal calibration. Extending the Neumann Score by adding heart rate &gt, 120/min improved the model’s performance.

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 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.

Background Positron emission tomography myocardial perfusion imaging (PET MPI) is a robust and excellent tool for assessing ischemia. So far, however, no methodology has been established to distinguish truly reduced MFR due to microvascular dysfunction or three-vessel coronary disease (CAD) from seemingly impaired MFR due to inadequate adenosine response. Conversely, for cardiac stress magnetic resonance (CMR) the adenosine induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response. Purpose We assessed the feasibility of detecting SSO in adenosine stress 13N-ammonia PET MPI using SSO in CMR as the standard of reference. Methods 50 patients underwent simultaneous PET MPI and CMR on a hybrid PET/MR device with co-injection of 13N-ammonia and a gadolinium-based contrast agent during rest and adenosine-induced stress. In CMR, SSO was assessed qualitatively and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). Similarly, in PET MPI the splenic signal activity ratio (SAR) was calculated as the proportion of the maximal standard uptake value of the spleen in stress and rest. Additionally, MFR was quantified in PET MPI. Results Visual SSO in CMR was present in 37 (74%) patients, whereas 13 patients had no SSO. The median SIR in CMR was significantly lower in patients with visual SSO compared to patients without visual SSO (0.57 [IQR 0.49–0.62] vs. 0.89 [IQR 0.76–0.98]; p Conclusion Similarly to CMR, SSO can be detected in 13N-ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel CAD. Figure 1. Splenic switch off (*) illustrated on transaxial 13N-ammonia PET MPI stress (A) compared to rest perfusion images (B) and similarly in stress (C) and rest (D) short axis CMR (**) in the same patient during adenosine induced stress and co-injection of 13N-ammonia and a gadolinium based contrast agent, acquired on a hybrid PET/MR device. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF)

Background: Many patients with non-alcoholic fatty liver disease (NAFLD) simultaneously suffer from cardiovascular (CV) disease and often carry multiple CV risk factors. Several CV risk factors are known to drive the progression of fibrosis in patients with NAFLD. Objectives: To investigate whether an established CV risk score, the Framingham risk score (FRS), is associated with the diagnosis of NAFLD and the degree of fibrosis in an Austrian screening cohort for colorectal cancer. Material and Methods: In total, 1965 asymptomatic subjects (59 &plusmn, 10 years, 52% females, BMI 27.2 &plusmn, 4.9 kg/m2) were included in this study. The diagnosis of NAFLD was present if (1) significantly increased echogenicity in relation to the renal parenchyma was present in ultrasound and (2) viral, autoimmune or hereditary liver disease and excess alcohol consumption were excluded. The FRS (ten-year risk of coronary heart disease) and NAFLD Fibrosis Score (NFS) were calculated for all patients. High CV risk was defined as the highest FRS quartile (&gt, 10%). Both univariable and multivariable logistic regression models were used to calculate associations of FRS with NAFLD and NFS. Results: Compared to patients without NAFLD (n = 990), patients with NAFLD (n = 975) were older (60 &plusmn, 9 vs. 58 &plusmn, 10 years, p &lt, 0.001), had higher BMI (29.6 &plusmn, 4.9 vs. 24.9 &plusmn, 3.6 kg/m2, 0.001) and suffered from metabolic syndrome more frequently (33% vs. 7%, 0.001). Cardiovascular risk as assessed by FRS was higher in the NAFLD-group (8.7 &plusmn, 6.4 vs. 5.4 &plusmn, 5.2%, 0.001). A one-percentage-point increase of FRS was independently associated with NAFLD (OR 1.04, 95%CI 1.02&ndash, 1.07, 0.001) after correction for relevant confounders in multivariable logistic regression. In patients with NAFLD, NFS correlated with FRS (r = 0.29, 0.001), and FRS was highest in patients with significant fibrosis (F3-4, 11.7 &plusmn, 5.4) compared to patients with intermediate results (10.9 &plusmn, 6.3) and those in which advanced fibrosis could be ruled-out (F0-2, 7.8 &plusmn, 5.9, p &lt, 0.001). A one-point-increase of NFS was an independent predictor of high-risk FRS after correction for sex, age, and concomitant diagnosis of metabolic syndrome (OR 1.30, 95%CI 1.09&ndash, 1.54, p = 0.003). Conclusion: The presence of NAFLD might independently improve prediction of long-term risk for CV disease and the diagnosis of NAFLD might be a clinically relevant piece in the puzzle of predicting long-term CV outcomes. Due to the significant overlap of advanced NAFLD and high CV risk, aggressive treatment of established CV risk factors could improve prognosis in these patients.

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.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.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.DLIR significantly reduces noise in CCTA compared to ASiR-V, while yielding superior image quality at equal diagnostic accuracy.