Myocardial Blood Flow by Magnetic Resonance in Patients With Suspected Coronary Stenosis: Comparison to PET and Invasive Physiology.

BACKGROUND: Despite recent guideline recommendations, quantitative perfusion (QP) estimates of myocardial blood flow from cardiac magnetic resonance (CMR) have only been sparsely validated. Furthermore, the additional diagnostic value of utilizing QP in addition to the traditional visual expert interpretation of stress-perfusion CMR remains unknown. The aim was to investigate the correlation between myocardial blood flow measurements estimated by CMR, positron emission tomography, and invasive coronary thermodilution. The second aim is to investigate the diagnostic performance of CMR-QP to identify obstructive coronary artery disease (CAD). METHODS: Prospectively enrolled symptomatic patients with >50% diameter stenosis on computed tomography angiography underwent dual-bolus CMR and positron emission tomography with rest and adenosine-stress myocardial blood flow measurements. Subsequently, an invasive coronary angiography (ICA) with fractional flow reserve and thermodilution-based coronary flow reserve was performed. Obstructive CAD was defined as both anatomically severe (>70% diameter stenosis on quantitative coronary angiography) or hemodynamically obstructive (ICA with fractional flow reserve ≤0.80). RESULTS: About 359 patients completed all investigations. Myocardial blood flow and reserve measurements correlated weakly between estimates from CMR-QP, positron emission tomography, and ICA-coronary flow reserve (r<0.40 for all comparisons). In the diagnosis of anatomically severe CAD, the interpretation of CMR-QP by an expert reader improved the sensitivity in comparison to visual analysis alone (82% versus 88% [P=0.03]) without compromising specificity (77% versus 74% [P=0.28]). In the diagnosis of hemodynamically obstructive CAD, the accuracy was only moderate for a visual expert read and remained unchanged when additional CMR-QP measurements were interpreted. CONCLUSIONS: CMR-QP correlates weakly to myocardial blood flow measurements by other modalities but improves diagnosis of anatomically severe CAD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.

Unlocking the path to environmental sustainability: navigating economic policy uncertainty, ICT, and environmental taxes for a sustainable future.

The study aims to gauge the impact of economic policy uncertainty, ICT, and environmental tax on environmental sustainability, which is measured by carbon emission and ecological footprint in a panel of 22 nations from 1997 to 2021. The present study has implemented the advanced panel data estimation techniques, including continuously updated fully modified (CUP-FM) and continuously updated bias-corrected (CUP-BC), dynamic seemingly unrelated regressions (DSUR), and nonlinear autoregressive distributed lagged (NARDL) in documenting the elasticities of target variables. Moreover, the directional causality has been tested through the D-H causality test. Study findings documented a positive and statistically significant linkage between EPU and environmental degradation. That is, EPU amplifies the emission of CO2 and ecological instability. The effects of ET and ICT are positively associated with environmental sustainability; that is, ET and ICT control the emission of CO2 and bring ecological improvement. This study contributes to the existing body of literature by conducting a thorough analysis of the relationship between various factors and their impact on environmental degradation. The study emphasizes the significance of every factor in influencing environmental outcomes. It provides policy suggestions to reduce CO2 emissions and promote ecological sustainability. The findings add valuable insights to the ongoing conversation about how to tackle environmental challenges in our constantly evolving world.

Unveiling the power of education, political stability and ICT in shaping technological innovation in BRI nations.

Technological innovation is a critical element of economic and environmental sustainability; thus, the promotion of technological innovation in the economy has gained an apex among policy makers. The study's impetus is to measure the effect of investments in information and communication technology (ICT), education, and political stability on technical innovation in BRI countries for 2004-2020. In the process of documenting the empirical nexus through the implementation of novel panel techniques commonly known as Dynamic Seemingly Unrelated Regressions (SUR), continuously updated fully modified" (Cup-FM) and continuously updated bias-corrected (Cup-BC). The results of the slope of heterogeneity, cross-sectional dependency test, and panel cointegration test have revealed the presence of heterogeneity, all the research variables possessed certain common dynamics, and, most importantly presence of long-run association. The study documented the coefficients of ICT, education and Political stability are positive and statistically significant, indicating a contributory effect in fostering technological innovation in BRI nations. The findings emphasize the importance of upholding political stability, directing resources toward education, and fostering an environment that encourages innovation through the integration of information and communication technology (ICT). The study also highlights how critical it is to bring in FDI and use it to your advantage in order to boost tech development and the economy.

Role of diffusion-weighted imaging in response prediction and evaluation after high dose rate brachytherapy in patients with colorectal liver metastases.

BACKGROUND: The aim of the study was to assess the role of diffusion-weighted imaging (DWI) to evaluate treatment response in patients with liver metastases of colorectal cancer. PATIENTS AND METHODS: In this retrospective, observational cohort study, we included 19 patients with 18 responding metastases (R-Mets; follow-up at least one year) and 11 non-responding metastases (NR-Mets; local tumor recurrence within one year) who were treated with high-dose-rate brachytherapy (HDR-BT) and underwent pre- and post-interventional MRI. DWI (qualitatively, mean apparent diffusion coefficient [ADCmean], ADCmin, intraindividual change of ADCmean and ADCmin) were evaluated and compared between pre-interventional MRI, first follow-up after 3 months and second follow-up at the time of the local tumor recurrence (in NR-Mets, mean: 284 ± 122 d) or after 12 months (in R-Mets, mean: 387+/-64 d). Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for detection of local tumor recurrence were calculated on second follow up, evaluating (1) DWI images only, and (2) DWI with Gd-enhanced T1-weighted images on hepatobiliary phase (contrast-enhanced [CE] T1-weight [T1w] hepatobiliary phase [hb]). RESULTS: ADCmean significantly increased 3 months after HDR-BT in both groups (R-Mets: 1.48 ± 0.44 and NR-Mets: 1.49 ± 0.19 x 10-3 mm2;/s, p < 0.0001 and p = 0.01), however, intraindividual change of ADCmean (175% vs.127%, p = 0.03) and ADCmin values (0.44 ± 0.24 to 0.82 ± 0.58 x 10-3 mm2/s) significantly increased only in R-Mets (p < 0.0001 and p < 0.001). ADCmin was significant higher in R-Mets compared to NR-Mets on first follow-up (p = 0.04). Sensitivity (1 vs. 0.72), specificity (0.94 vs. 0.72), PPV (0.91 vs. 0.61) and NPV (1 vs. 0.81) could be improved by combining DWI with CE T1w hb compared to DWI only. CONCLUSIONS: DW-MRI seems to be helpful in the qualitative and quantitative evaluation of treatment response after HDR-BT of colorectal metastases in the liver.

Impact of Absolute Myocardial Blood Flow Quantification on the Diagnostic Performance of PET-Based Perfusion Scans Using 82Rubidium.

BACKGROUND: Guidelines propose the inclusion of quantitative measurements from 82Rubidium positron emission tomography (RbPET) to discriminate obstructive coronary artery disease (CAD). However, the effect on diagnostic accuracy is unknown. The aim was to investigate the optimal RbPET reading algorithm for improved identification of obstructive CAD. METHODS: Prospectively enrolled patients (N=400) underwent RbPET and invasive coronary angiography with fractional flow reserve and quantitative coronary angiography. Quantitative measurements (myocardial blood flow (MBF), MBF reserve, transient ischemic dilatation) by RbPET were step-wisely added to a qualitative assessment by the summed stress score based on their diagnostic accuracy of obstructive CAD by invasive coronary angiography-fractional flow reserve. Prespecified cutoffs were summed stress score ≥4, hyperemic MBF 2.00 mL/g per min, and MBF reserve 1.80, respectively. Hemodynamically obstructive CAD was defined as >90% diameter stenosis or invasive coronary angiography-fractional flow reserve ≤0.80, and sensitivity analyses included a clinically relevant reference of anatomically severe CAD (>70% diameter stenosis by invasive coronary angiography-quantitative coronary angiography). RESULTS: Hemodynamically obstructive CAD was present in 170/400 (42.5%) patients. Stand-alone summed stress score showed a sensitivity and specificity of 57% and 93%, respectively, while hyperemic MBF showed similar sensitivity (61%, P=0.57) but lower specificity (85%, P=0.008). With increased discrimination by receiver-operating characteristic curves (0.78 versus 0.85; P<0.001), combining summed stress score, MBF and MBF reserve showed the highest sensitivity of 77% but lower specificity of 74% (P<0.001 for both comparisons). Against anatomically severe CAD, all measures independently yielded high discrimination ≥0.90 with increased sensitivity and lower specificity by additional quantification. CONCLUSIONS: The inclusion of quantitative measurements to a RbPET read increases in the identification of obstructive CAD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481712.

An investigation of financial openness, trade openness, gross capital formation, urbanization, financial development, education and energy nexus in BRI: Evidence from the symmetric and asymmetric framework.

Clean energy development can bring numerous benefits, such as decreased greenhouse gas emissions, improved air quality, and increased job opportunities in the green industry. These advantages can be achieved through the collaborative efforts of all stakeholders involved. Ultimately, adopting clean energy can lead to a healthier planet and economy. Energy availability and scarcity influence the aggregated economy. The present study explores the interrelationships between financial openness, trade openness, gross capital formation, urbanization, financial development, education, and energy within the Belt and Road Initiative (BRI) nations. A panel of 56 nations has considered empirical investigation for 2002-2020. The coefficients extracted from CS-ARDL revealed a catalyst role of openness in the energy mix, especially the inclusion of clean energy both in the long run and short. The asymmetric evaluation revealed that positive negative shocks in openness lead to a positive association with energy consumption. Moreover, the asymmetric association was also exposed through the execution of a standard Wald test. The study findings show that FO, TO, and GCF are critical in energy sustainability in BRI nations. It implies that clean energy inclusion in the energy mix might be amplified, and energy sustainability may be ensured. The energy transition of Belt and Road Initiative (BRI) nations is significantly affected by financial, trade, and domestic capital adequacy. The success of sustainable energy policies is determined by several factors, which play a crucial role in countries participating in BRI projects; the findings provide insight into the complex interdependencies among the variables above and their effects on the energy dynamics within the BRI region. Furthermore, the research findings hold considerable significance for policymakers as they offer valuable insights into the possible synergies and trade-offs among these factors that can facilitate sustainable energy transitions in the BRI economies.

Clarifying the relationship between green investment, technological innovation, financial openness, and renewable energy consumption in MINT.

The importance of Renewable energy has been well documented in the literature, especially in the nexus of renewable energy-led environmental sustainability. The purpose of the study is to gauge the effects of green investment (GI), technological innovation (TI), and financial Openness (FO) on Renewable Energy Consumption (REC) in MINT for the period 1996-2019. Several econometric tools have been considered in documenting the target nexus, including the panel unit root test following CADF and CIPS, Error correction Cointegration test, CS-ARDL, nonlinear ARDL, and directional causality test by employing the D-H Causality test. The panel unit root test revealed that all the variables become stationary after the first difference. The long-run association in the target model is unveiled with the panel cointegration test. A positive and statistically significant connection regarding FO, TI, and GI coefficients on REC has been exposed. It suggests that the progress in RE development and inclusion in economic activities could be amplified through FO, TI, and GI. Inferring the results of asymmetric valuation, the test statistics of a standard Wald test document asymmetric association in the long run and short run. Furthermore, the coefficients of positive and negative innovation in explanatory variables, i.e., TI, GI, & FO, divulge a positive statistically significant tie to REC, which is valid in long-run and short-run assessment.

Coronary Artery Stenosis Evaluation by Angiography-Derived FFR: Validation by Positron Emission Tomography and Invasive Thermodilution.

BACKGROUND: Fractional flow reserve (FFR) derived from invasive coronary angiography (QFR) is promising for evaluation of intermediate coronary artery stenosis. OBJECTIVES: The authors aimed to compare the diagnostic performance of QFR and the guideline-recommended invasive FFR using 82Rubidium positron emission tomography (82Rb-PET) myocardial perfusion imaging as reference standard. METHODS: This is a prospective, observational study of symptomatic patients with suspected obstructive coronary artery disease on coronary computed tomography angiography (≥50% diameter stenosis in ≥1 vessel). All patients were referred to 82Rb-PET and invasive coronary angiography with FFR and QFR assessment of all intermediate (30%-90% diameter stenosis) stenoses. Main analyses included a comparison of the ability of QFR and FFR to identify reduced myocardial blood flow (<2 mL/g/min) during vasodilation and/or relative perfusion abnormalities (summed stress score ≥4 in ≥2 adjacent segments). RESULTS: A total of 250 patients (320 vessels) with indication for invasive physiological assessment were included. The continuous relationship of 82Rb-PET stress myocardial blood flow per 0.10 increase in FFR was +0.14 mL/g/min (95% CI: 0.07-0.21 mL/g/min) and +0.08 mL/g/min (95% CI: 0.02-0.14 mL/g/min) per 0.10 QFR increase. Using 82Rb-PET as reference, QFR and FFR had similar diagnostic performance on both a per-patient level (accuracy: 73%; 95% CI: 67%-79%; vs accuracy: 71%; 95% CI: 64%-78%) and per-vessel level (accuracy: 70%; 95% CI: 64%-75%; vs accuracy: 68%; 95% CI: 62%-73%). The per-vessel feasibility was 84% (95% CI: 80%-88%) for QFR and 88% (95% CI: 85%-92%) for FFR by intention-to-diagnose analysis. CONCLUSIONS: With 82Rb-PET as reference modality, the wire-free QFR solution showed similar diagnostic accuracy as invasive FFR in evaluation of intermediate coronary stenosis. (DAN-NICAD - Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease; NCT02264717).

Likelihood reclassification by an acoustic-based score in suspected coronary artery disease.

OBJECTIVE: Validation studies of the 2019 European Society of Cardiology pretest probability model (ESC-PTP) for coronary artery disease (CAD) report that 35%-40% of patients have low pretest probability (ESC-PTP 5% to <15%). Acoustic detection of coronary stenoses could potentially improve clinical likelihood stratification. Aims were to (1) investigate the diagnostic performance of an acoustic-based CAD score and (2) study the reclassification potential of a dual likelihood strategy by the ESC-PTP and a CAD score. METHODS: Consecutive patients (n=1683) with stable angina symptoms referred for coronary CT angiography (CTA) underwent heart sound analyses by an acoustic CAD-score device. All patients with ≥50% luminal stenosis in any coronary segment at coronary CTA were referred to investigation with invasive coronary angiography (ICA) with fractional flow reserve (FFR).A predefined CAD-score cut-off ≤20 was used to rule out obstructive CAD. RESULTS: In total, 439 patients (26%) had ≥50% luminal stenosis on coronary CTA. The subsequent ICA with FFR showed obstructive CAD in 199 patients (11.8%). Using the ≤20 CAD-score cut-off for obstructive CAD rule-out, sensitivity was 85.4% (95% CI 79.7 to 90.0), specificity 40.4% (95% CI 37.9 to 42.9), positive predictive value 16.1% (95% CI 13.9 to 18.5) and negative predictive value 95.4% (95% CI 93.4 to 96.9) in all patients. Applying the cut-off in ESC-PTP 5% to <15% patients, 316 patients (48%) were down-classified to very-low likelihood. The obstructive CAD prevalence was 3.5% in this group. CONCLUSION: In a large contemporary cohort of patients with low CAD likelihood, the additional use of an acoustic rule-out device showed a clear potential to downgrade likelihood and could supplement current strategies for likelihood assessment to avoid unnecessary testing. TRIAL REGISTRATION NUMBER: NCT03481712.

Second-Line Myocardial Perfusion Imaging to Detect Obstructive Stenosis: Head-to-Head Comparison of CMR and PET.

BACKGROUND: Guidelines recommend verification of myocardial ischemia by selective second-line myocardial perfusion imaging (MPI) following a coronary computed tomography angiography (CTA) with suspected obstructive coronary artery disease (CAD). Head-to-head data on the diagnostic performance of different MPI modalities in this setting are sparse. OBJECTIVES: The authors sought to compare, head-to-head, the diagnostic performance of selective MPI by 3.0-T cardiac magnetic resonance (CMR) and 82rubidium positron emission tomography (RbPET) in patients with suspected obstructive stenosis at coronary CTA using invasive coronary angiography (ICA) with fractional flow reserve (FFR) as reference. METHODS: Consecutive patients (n = 1,732, mean age: 59.1 ± 9.5 years, 57.2% men) referred for coronary CTA with symptoms suggestive of obstructive CAD were included. Patients with suspected stenosis were referred for both CMR and RbPET and subsequently ICA. Obstructive CAD was defined as FFR ≤0.80 or >90% diameter stenosis by visual assessment. RESULTS: In total, 445 patients had suspected stenosis on coronary CTA. Of these, 372 patients completed both CMR, RbPET and subsequent ICA with FFR. Hemodynamically obstructive CAD was identified in 164 of 372 (44.1%) patients. Sensitivities for CMR and RbPET were 59% (95% CI: 51%-67%) and 64% (95% CI: 56%-71%); P = 0.21, respectively, and specificities 84% (95% CI: 78%-89%) and 89% (95% CI: 84%-93%]); P = 0.08, respectively. Overall accuracy was higher for RbPET compared with CMR (73% vs 78%; P = 0.03). CONCLUSIONS: In patients with suspected obstructive stenosis at coronary CTA, CMR, and RbPET show similar and moderate sensitivities but high specificities compared with ICA with FFR. This patient group represents a diagnostic challenge with frequent mismatch between advanced MPI tests and invasive measurements. (Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2 [Dan-NICAD 2]; NCT03481712).

Does environmental degradation matter for poverty? Clarifying the nexus between FDI, environmental degradation, renewable energy, education, and poverty in Morocco and Tunisia.

Poverty is the curse for sustainable and equitable development worldwide by detreating environmental sustainability, economic instability, and inequality. However, as a remedy for poverty reduction, researchers over the past decade have examined the key macro determinants and established positive associations, implying the contributory role in poverty reduction. The study explores the environmental, energy, education, and foreign direct investment (FDI) effects on poverty reduction in Morocco and Tunisia from 1991 to 2020. We employed autoregressive distributed lagged (ARDL) and nonlinear ARDL frameworks to document the explanatory variables' elasticity on poverty reduction in both the long- and short-run horizons. According to linear assessment, the study documented that education, energy, and FDI support poverty reduction. At the same time, the cost of environmental degradation has a detrimental effect on poverty augmentation. Referring to asymmetric assessment, the study established a long-run asymmetric association between asymmetric shocks of education, FDI, and energy with poverty. For directional association, the study has implemented a casualty test with the Fourier TY causality test and revealed a bidirectional association between education and poverty, and energy and poverty. Moreover, the unidirectional casualty was unveiled between FDI and poverty, and poverty and environment.

International randomized trial on the effect of revascularization or optimal medical therapy of chronic total coronary occlusions with myocardial ischemia - ISCHEMIA-CTO trial - rationale and design.

BACKGROUND: Chronic total occlusions (CTO) are frequent among patients with coronary artery disease. Revascularization with percutaneous coronary intervention (PCI) is safe and feasible in experienced hands. However, randomized data are needed to demonstrate symptomatic as well as prognostic effect of CTO-PCI compared to optimal medical therapy alone. METHODS: This trial aims to evaluate the effect of CTO PCI in patients with a CTO lesion and target vessel diameter ≥ 2.5 mm, and myocardial ischemia in the relevant territory. First, all patients are subjected to optimal medical therapy (OMT) for at least for 3 months and non-CTO lesions are managed according to guidelines. Subsequently, prior to randomization myocardial ischemia and quality of life (Seattle Questionnaire (SAQ)) is assessed. Patients are divided into two cohorts based on their SAQ score and randomized to either OMT alone or OMT and CTO-PCI. Cohort A is defined as Low- or asymptomatic patients with a quality-of-life score > 60 and/or CCS class < 2, and more than 10 % ischemia in the left ventricle (LV). Cohort B is symptomatic patients with a quality-of-life score < 60 or CCS class angina > 1 and at least ischemia in 5% of the LV. The primary end-point in cohort A is a composite of major adverse cardiac and cerebral events, hospitalization for heart failure and malignant ventricular arrhythmias. The primary endpoint in cohort B is difference in quality of life 6 months after randomization. IMPLICATIONS: This trial is designed to investigate if CTO-PCI improves QoL and MACCE. Both positive and negative outcome of the trial will affect future guidelines and recommendations on how to treat patients with CTO.

Early and long-term prognosis in patients with remaining chronic total occlusions after revascularization attempt. A cohort study from the SKEJ-CTO registry.

OBJECTIVES: The present study aimed to compare safety and long-term prognosis of patients with chronic total coronary occlusions (CTO) stratified for remaining CTOs after percutaneous coronary intervention (PCI). DESIGN: The study cohort consisted of patients with coronary artery disease who underwent CTO PCI in a high volume tertiary center from 2009 to 2019 and were registered in Danish high-quality registers. Patients with successful PCI of all CTOs were compared to patients with ≥1 remaining CTO post-procedural. Primary endpoints were analysed using Cox-regression and Kaplan-Meier estimates, and included all-cause mortality, major adverse cardio- and cerebrovascular events (MACCE) and a 30-day safety endpoint. RESULTS: Procedural success rate was 87.7%, and 76.5% of patients had all CTO(s) opened post-PCI. Safety endpoint occurred in 4.6% of patients, and more frequently in patients with remaining CTO(s) (RD 4.9, 95%CI 0.1, 9.8). All-cause mortality was higher in patients with remaining CTO(s) (Unadjusted HR 1.65, 95% CI 1.03, 2.47, p = .015. Adjusted HR 1.32, 95%CI 0.88-1.99, p = .18) after eight years of follow-up. Risk of MACCE was significantly higher in patients with remaining CTO(s) (Unadjusted HR 1.79, 95% CI 1.34-2.41, p < .001. Adjusted HR 1.51, 95% CI 1.11-2.05, p = .009). CONCLUSIONS: In our centre, CTO PCI was associated with high success rate and low risk of 30-days complications. Presence of remaining CTO(s) after final revascularization attempt was associated with higher but statistically insignificant long-term mortality but was an independent predictor of MACCE.

68Ga-DOTATATE PET/CT and MRI with Diffusion-Weighted Imaging (DWI) in Short- and Long-Term Assessment of Tumor Response of Neuroendocrine Liver Metastases (NELM) Following Transarterial Radioembolization (TARE).

The aim of this study was to evaluate the role of SUV and ADC in assessing early response in patients with NELM following TARE. Thirty-two patients with pre- and postinterventional MRI with DWI and 68Ga-DOTATATE PET/CT were included. ADC and SUV of three target lesions and of tumor-free spleen and liver tissue were determined on baseline and first follow-up imaging, and tumor to spleen (T/S) and tumor to liver (T/L) ratios were calculated. Response was assessed by RECIST 1.1 and mRECIST on first follow-up, and long-term response was defined as hepatic progression-free survival (HPFS) over 6, 12, and <24 months. In responders, intralesional ADC values increased and SUV decreased significantly regardless of standard of reference for response assessment (mRECIST/RECIST/HPFS > 6/12/24 m). Using ROC analysis, ΔSUV T/S ratio (max/max) and ΔSUV T/L ratio (max/mean) were found to be the best and most robust metrics to correlate with longer HPFS and were superior to ΔADC. ΔT/S ratio (max/max) < 23% was identified as an optimal cut-off to discriminate patients with longer HPFS (30.2 m vs. 13.4 m; p = 0.0002). In conclusion, early percentage changes in SUV tumor-to-organ ratios on first follow-up seem to represent a prognostic marker for longer HPFS and may help in assessing therapeutic strategies.