Stress Perfusion Research Articles

New avenues for the assessment of stable ischemic heart disease.

Myocardial ischemia is a complex condition which may result from epicardial and/or microvascular causes involving functional and structural mechanisms. These mechanisms may overlap in a given patient illustrating the difficulties for appropriate management. Assessment of myocardial ischemia can be performed using noninvasive and invasive tools. However, despite living in the era of individualized precision medicine, these tools are not yet used in a broader fashion. Emerging noninvasive techniques such as quantitative perfusion cardiac magnetic resonance imaging (CMR) and stress perfusion computed tomography (CT) or photon-counting CT techniques may contribute to new standards in the assessment of stable angina patients. Invasive evaluation of myocardial ischemia should not only focus on hemodynamically relevant epicardial disease but also involve coronary vasomotor function testing (coronary spasm, coronary flow reserve, and microvascular resistance) where appropriate. Optimal patient management will depend on accurate and comprehensive diagnostic evaluation of myocardial ischemia and development of new treatment options in the future.

Prognostic Value of Stress Perfusion Cardiac MRI in Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Effects of the Scanner, Stress Agent, and Analysis Technique.

Purpose To perform a systematic review and meta-analysis to assess the prognostic value of stress perfusion cardiac MRI in predicting cardiovascular outcomes. Materials and Methods A systematic literature search from the inception of PubMed, Embase, Web of Science, and China National Knowledge Infrastructure until January 2023 was performed for articles that reported the prognosis of stress perfusion cardiac MRI in predicting cardiovascular outcomes. The quality of included studies was assessed using the Quality in Prognosis Studies tool. Reported hazard ratios (HRs) of univariable regression analyses with 95% CIs were pooled. Comparisons were performed across different analysis techniques (qualitative, semiquantitative, and fully quantitative), magnetic field strengths (1.5 T vs 3 T), and stress agents (dobutamine, adenosine, and dipyridamole). Results Thirty-eight studies with 58 774 patients with a mean follow-up time of 53 months were included. There were 1.9 all-cause deaths and 3.5 major adverse cardiovascular events (MACE) per 100 patient-years. Stress-inducible ischemia was associated with a higher risk of all-cause mortality (HR: 2.55 [95% CI: 1.89, 3.43]) and MACE (HR: 3.90 [95% CI: 2.69, 5.66]). For MACE, pooled HRs of qualitative, semiquantitative, and fully quantitative methods were 4.56 (95% CI: 2.88, 7.22), 3.22 (95% CI: 1.60, 6.48), and 1.78 (95% CI: 1.39, 2.28), respectively. For all-cause mortality, there was no evidence of a difference between qualitative and fully quantitative methods (P = .79). Abnormal stress perfusion cardiac MRI findings remained prognostic when subgrouped based on underlying disease, stress agent, and field strength, with HRs of 3.54, 2.20, and 3.38, respectively, for all-cause mortality and 3.98, 3.56, and 4.21, respectively, for MACE. There was no evidence of subgroup differences in prognosis between field strengths or stress agents. There was significant heterogeneity in effect size for MACE outcomes in the subgroups assessing qualitative versus quantitative stress perfusion analysis, underlying disease, and field strength. Conclusion Stress perfusion cardiac MRI is valuable for predicting cardiovascular outcomes, regardless of the analysis method, stress agent, or magnetic field strength used. Keywords: MR-Perfusion, MRI, Cardiac, Meta-Analysis, Stress Perfusion, Cardiac MR, Cardiovascular Disease, Prognosis, Quantitative © RSNA, 2024 Supplemental material is available for this article.

Rest and stress aortic flow analysis by CMR in MyoFit46

Abstract Background Aortic stiffness is a strong predictor of future cardiovascular events and all-cause mortality. Aortic stiffness has never been measured during adenosine stress perfusion before, and may provide valuable relationship about this relationship. Aim To investigate if there are differences between aortic stiffness and conditions of rest and stress perfusion, in an older age-homogenous population-based cohort. Methods 203 participants from the longitudinal 1946 Medical Research Council National Survey of Health and Development British birth cohort were included. Cardiovascular Magnetic Resonance (CMR) imaging was performed at rest and during adenosine stress perfusion. 3 established and validated biomarkers of aortic stiffness were reported - pulse wave velocity, distensibility and beta stiffness, at rest and stress perfusion. All variables were non-normally distributed, therefore the Wilcoxon signed-rank test was used to look for significant differences between rest and stress. Results Aortic stiffness increased significantly during adenosine stress perfusion, shown by all biomarkers of aortic stiffness used: pulse wave velocity (p = <0.001), distensibility (p = <0.001), and beta stiffness (p = <0.001). However, the aortas of participants with a higher resting aortic stiffness at baseline were less dynamic (little if any aortic stiffness change with stress) when compared to those with low resting aortic stiffness. Conclusion It is feasible to measure aortic stiffness during adenosine stress perfusion. In healthy aortas, aortic stiffness increases in the acute phase of adenosine stress suggesting a new potential mechanism for the body response to adenosine – peripheral chemoreceptor reflex activation. Stiffer arteries at baseline are less modifiable and stress aortic flow CMR has the potential to identify these persons permitting early targeted therapy. Change in aortic stiffness, measured by stress aortic flow CMR is therefore a potential non-invasive biomarker of aortic health.

Non-invasive electrocardiographic assessment of arrhythmic risk in ischaemic cardiomyopathy patients undergoing revasularisation

Abstract Background Ventricular arrhythmias are a leading cause of death in patients with ischaemic cardiomyopathy (ICM). Ischaemia is thought to increase arrhythmic risk and coronary revascularisation is frequently undertaken to reduce this risk, although the recent REVIVED-BCIS2 trial did not show a difference in the incidence of death, device therapies or sustained arrhythmias in patients assigned to have percutaneous coronary intervention (PCI) compared to optimal medical therapy alone(1). Purpose We assessed the mechanistic effects of revascularisation on arrhythmic risk in patients with ICM using non-invasive electrocardiographic imaging (ECGi). Methods Patients were eligible if they had a left ventricular ejection fraction (LVEF) <40%, extensive coronary disease (BCIS Jeopardy Score≥6) and were scheduled to undergo revascularisation with coronary artery bypass grafting or PCI. ECGi assessment was performed using a 252-electrode vest with anatomical co-registration using a CT thorax. Patients underwent stress perfusion cardiac magnetic resonance (CMR) imaging; both ECGi and CMR were conducted at baseline and 3 months post revascularisation(Figure 1). The primary outcome measure was dispersion of repolarisation measured using global activation recovery interval (ARI) dispersion. Secondary outcome measures included repolarisation time (RT) dispersion, mean ARI and LV ARI dispersion. We also assessed the relationship between ARI dispersion, revascularisation and left ventricular scar burden. Data are presented as mean ± SD or median [IQR]. Results Thirty patients were recruited between 2020-2023; age 67±11 years, 90% male, BMI 28±5 and baseline LVEF was 29±8%. Twelve patients underwent CABG, 18 (60%) had PCI. The BCIS jeopardy score was 10 [9-11] at enrolment and decreased to 2 [0-4] after revascularisation. The LV scar burden at baseline was 15.1±6.5% and the change at 3 months was -0.5±5% (p=0.70). ARI dispersion and LV ARI dispersion were correlated with LV scar burden (r=0.62,p=0.01 and 0.71,p=0.002 respectively). No differences were seen in ARI dispersion (44.5 vs 44.1, p=0.86) or secondary outcome measures before and after revascularisation (RT dispersion: 45.5 vs 44.7, p=0.49; Mean ARI: 281.3 vs 282.6, p=0.74; ARI dispersion: 44.5 vs 44.1, p=0.86; LV ARI dispersion: 38.4 vs 36.7, p=0.39)(Figure 2). The LVEF change on CMR at 3 months was +6.9±10%; no relationship was seen between change in LVEF and ARI dispersion. Conclusion Arrhythmic risk assessed by non-invasive ECGi was not altered by coronary revascularisation. LV ARI dispersion was highly correlated with scar burden, which is not altered by revascularisation. Future work includes analysis of perfusion data. Our results support the findings of the REVIVED arrhythmia study that revascularisation does not reduce arrhythmic risk in patients with ICM(1). ECGi derived LV ARI dispersion correlates with scar and may represent a non-invasive arrhythmic risk assessment tool.Figure 1Figure 2

[15O]H2O myocardial perfusion positron emission tomography: Added value of relative stress perfusion deficit in the prediction of significant coronary artery stenosis in a mixedpopulation

BackgroundIt remains unknown whether estimation of the relative stress perfusion deficit offers added value in the prediction of significant coronary artery stenosis in myocardial perfusion imaging with [15O]H2O positron emission tomography (PET) in a population with high prevalence of established cardiac disease. MethodsDuring eight months, we consecutively included all patients undergoing [15O]H2O PET and subsequent invasive coronary angiography (ICA). Significant stenosis was defined from ICA as fractional flow reserve ≤.8 or coronary artery narrowing of ≥70%. We calculated absolute and relative total perfusion deficits (aTPD and rTPD, respectively) as semiquantitative measures of the extent and severity of reduced stress perfusion. A multivariate logistic regression analysis was performed to test the adjusted associations (odds ratio (OR) with 95% CI) with significant coronary artery stenosis. ResultsOf 800 patients undergoing [15O]H2O PET, 144 underwent ICA, where 142 patients had aTPD of ≥3% and 79 (55%) of these had at least one significant stenosis. In an adjusted analysis, rTPD (OR10% increase = 2.12 (1.44-3.12), P < .001), previous coronary artery bypass grafting (CABG) (OR = .11 (.03-.36), P < .001) and reduced left ventricular ejection fraction (LVEF) (OR = .25 (.08-.84), P = .02) were independently associated with significant stenosis, whereas the association with aTPD (OR10% increase = 1.14 (.98-1.32), P = .08) was modest. ConclusionsIn the presence of an absolute perfusion deficit (aTPD of ≥3%), rTPD may improve the prediction of significant stenosis in a heterogeneous population of patients examined with [15O]H2O PET. Furthermore, previous CABG and reduced LVEF are associated with nonstenotic perfusion deficiencies, suggesting caution when interpreting myocardial perfusion imaging in such patients.

Predicting red blood cell traffcking and capillary hemodynamics in angiogenic and tumor microcirculation in silico

Objective: Angiogenic and tumor microvasculatures are known to have abnormal topology due to the presence of frequent vessel junctions, irregular and deflated blood vessels, multi-furcations, and tessellated vessel organization. Although recent advances in imaging techniques in vivo have enabled mapping such vasculatures at high spatial resolution, simultaneous measurements of hemodynamic parameters, such as the wall shear stress (WSS) with full 3D details, remain a challenge. Theoretical network flow models, often used for hemodynamic predictions in such experimentally acquired images, cannot provide the full 3D hemodynamic details either, as these models treat each blood vessel as 1D segment and do not explicitly model red blood cells (RBCs). To overcome this limitation, we have developed a high-fidelity, 3D Computational Fluid Dynamics modeling to predict the flow of a large number of deformable RBCs through physiologically realistic tumor/angiogenic microvascular networks in silico. Methods: We use in vivo images to create such vascular networks in silico and then predict RBC traffcking and capillary hemodynamics. Deformation of every flowing RBC is considered with high accuracy, and 3D geometry of each vessel is accurately modeled. Flow is driven by specifying physiological pressure boundary conditions. Model predictions have been validated against in vivo data. This in-house predictive tool is versatile, can be applied to any microvascular network image obtained in vivo in any organ, and can predict trajectories of diverse cell types including leukocytes, platelets and circulating tumor cells, drug and molecular transport in capillary blood, and cell-vessel adhesion. Results: We provide quantitative differences between healthy microvascular networks and tumor/angiogenic networks in terms of RBC distribution, perfusion, and wall shear stress. Our model shows increased heterogeneity in RBC and flow distribution in both tumor and angiogenic vasculatures than the healthy one. Also, we predict reduced flow and hematocrit in several vessels in both tumor and angiogenic vasculatures. Interestingly, several vessels in the angiogenic vasculature are predicted to have higher flow than the healthy one, while most vessels in the tumor vasculature show flow reduction. This in silico prediction is consistent with a recent in vivo study which showed higher flow in peri-tumor region and reduced flow in tumor. We further predict a significant heterogeneity in WSS and WSS gradient, blood velocity profiles, and near-wall RBC-depleted region. Conclusion: In conclusion, we have developed a versatile, in silico model that allows high-fidelity prediction of capillary hemodynamics in tumor microcirculation and provide information on hemodynamic variables that are not readily measurable in vivo but have physiological significance in tumor progression and treatment. NIH (R01EY033003) and NSF (CBET1804591). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Quantitative myocardial perfusion in liver transplantation candidates: Poorly metabolized caffeine inhibition of vasodilatory stress

BackgroundData on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion. MethodConsecutive LT candidates (n = 114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n = 41) initially used was changed to dobutamine (n = 73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure severity were evaluated. Coronary flow data of LT candidates were compared to non-LT control group (n = 102 for dipyridamole, n = 29 for dobutamine). ResultsPrevalence of patients with detectable blood caffeine was 63.3%, 36.7% and 33.3% after 2-, 5- and 7-day of caffeine abstinence, respectively. MELD score was associated with detectable caffeine (odd ratio 1.18,P < 0.001). CFR was higher during dipyridamole stress without-caffeine versus with-caffeine (2.22 ± 0.80 vs 1.55 ± 0.37,P = 0.048) but lower than dobutamine stress (2.22 ± 0.80 vs 2.82 ± 1.02,P = 0.026). Mediation analysis suggested that the dominant association between CFR and MELD score in dipyridamole group derived from caffeine-impaired CFR and liver failure/caffeine interaction. CFR in LT candidates was lower than non-LT control population in both dipyridamole and dobutamine group. ConclusionWe demonstrate exceptionally high prevalence of detectable blood caffeine in LT candidates undergoing stress PET myocardial perfusion imaging resulting in reduced CFR with dipyridamole compared to dobutamine. The delayed caffeine clearance in LT candidates makes dobutamine a preferred stress agent in this population.

Clinical implementation of a fully automated quantitative perfusion cardiovascular magnetic resonance imaging workflow with a simplified dual-bolus contrast administration scheme

This study clinically implemented a ready-to-use quantitative perfusion (QP) cardiovascular magnetic resonance (QP CMR) workflow, encompassing a simplified dual-bolus gadolinium-based contrast agent (GBCA) administration scheme and fully automated QP image post-processing. Twenty-five patients with suspected obstructive coronary artery disease (CAD) underwent both adenosine stress perfusion CMR and an invasive coronary angiography or coronary computed tomography angiography. The dual-bolus protocol consisted of a pre-bolus (0.0075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) and a main bolus (0.075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) at an infusion rate of 3 ml/s. The arterial input function curves showed excellent quality. Stress MBF ≤ 1.84 ml/g/min accurately detected obstructive CAD (area under the curve 0.79; 95% Confidence Interval: 0.66 to 0.89). Combined visual assessment of color pixel QP maps and conventional perfusion images yielded a diagnostic accuracy of 84%, sensitivity of 70% and specificity of 93%. The proposed easy-to-use dual-bolus QP CMR workflow provides good image quality and holds promise for high accuracy in diagnosis of obstructive CAD. Implementation of this approach has the potential to serve as an alternative to current methods thus increasing the accessibility to offer high-quality QP CMR imaging by a wide range of CMR laboratories.

Prognostic value of a novel artificial intelligence-based coronary CTA-derived ischemia algorithm among patients with normal or abnormal myocardial perfusion

BackgroundAmong patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCTischemia) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCTischemia among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion. MethodsAI-QCTischemia was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream 15O-H2O-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCTischemia. Absolute stress myocardial blood flow ≤2.3 ​ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4–8.3] years. Results662 of 768 (86%) patients had conclusive AI-QCTischemia result. In patients with normal 15O-H2O-PET perfusion, an abnormal AI-QCTischemia result (n ​= ​147/331) vs. normal AI-QCTischemia result (n ​= ​184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17–5.21, p ​= ​0.018). This did not pertain to patients with abnormal 15O-H2O-PET perfusion (abnormal AI-QCTischemia result (n ​= ​269/331) vs. normal AI-QCTischemia result (n ​= ​62/331); adjusted HR 1.09, 95% CI 0.58–2.02, p ​= ​0.794) (p-interaction ​= ​0.039). ConclusionAmong patients with obstructive CAD on coronary CTA referred for downstream 15O-H2O-PET perfusion imaging, AI-QCTischemia showed incremental prognostic value among patients with preserved perfusion by 15O-H2O-PET imaging, but not among those with reduced perfusion.

DEep LearnIng-based QuaNtification of epicardial adipose tissue predicts MACE in patients undergoing stress CMR

Background and aimsThis study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging. Methods730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created. ResultsIn the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903–10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765–7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822–10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045–1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336–1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort. ConclusionsIn patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.

Impact of sex on myocardial perfusion following percutaneous coronary intervention of chronic total coronary occlusions

ObjectivesWe sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H2O positron-emission tomography (PET) perfusion imaging. BackgroundCTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. MethodsA total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H2O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min−1·g−1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. ResultsThis study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). ConclusionsThe present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H2O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. Clinical perspectiveWhat is new?•CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization.•We found a greater recovery of stress perfusion in females compared to males after CTO PCI as measured by serial [15O]H2O PET imaging, whereas coronary flow reserve was comparable between sexes.•The present study adds to the limited body of evidence on the impact of sex on myocardial perfusion following CTO PCI.What are the clinical implications?•Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients.•These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes.•Future studies with standardized preprocedural imaging are warranted to increase our understanding of the impact of sex on changes in myocardial perfusion following CTO PCI.

Endoplasmic Reticulum Stress Induces Vasodilation in Liver Vessels That Is Not Mediated by Unfolded Protein Response.

There is a growing body of evidence that ER stress and the unfolded protein response (UPR) play a key role in numerous diseases. Impaired liver perfusion and ER stress often accompany each other in liver diseases. However, the exact impact of ER stress and UPR on the hepatic perfusion is not fully understood. The aim of this study was to disclose the effect of ER stress and UPR on the size of liver vessels and on the levels of Ca2+ and nitric oxide (NO), critical regulators of vascular tonus. This study was carried out in precisely cut liver tissue slices. Confocal microscopy was used to create 3D images of vessels. NO levels were determined either using either laser scan microscopy (LSM) in cells or by NO-analyser in medium. Ca2+ levels were analysed by LSM. We show that tunicamycin, an inducer of ER stress, acts similarly with vasodilator acetylcholine. Both exert a similar effect on the NO and Ca2+ levels; both induce significant vasodilation. Notably, this vasodilative effect persisted despite individual inhibition of UPR pathways-ATF-6, PERK, and IRE1-despite confirming the activation of UPR. Experiments with HUVEC cells showed that elevated NO levels did not result from endothelial NO synthase (eNOS) activation. Our study suggests that tunicamycin-mediated ER stress induces liver vessel vasodilation in an NO-dependent manner, which is mediated by intracellular nitrodilator-activatable NO store (NANOS) in smooth muscle cells rather than by eNOS.

High-Resolution Free-Breathing Automated Quantitative Myocardial Perfusion by Cardiovascular Magnetic Resonance for the Detection of Functionally Significant Coronary Artery Disease.

Current assessment of myocardial ischaemia from stress perfusion cardiovascular magnetic resonance (SP-CMR) largely relies on visual interpretation. This study investigated the use of high-resolution free-breathing SP-CMR with automated quantitative mapping in the diagnosis of coronary artery disease (CAD). Diagnostic performance was evaluated against invasive coronary angiography (ICA) with fractional flow reserve (FFR) measurement. Seven-hundred and three patients were recruited for SP-CMR using the research sequence at 3 Tesla. Of those receiving ICA within 6 months, 80 patients either had FFR measurement, or identification of a chronic total occlusion (CTO) with inducible perfusion defects seen on SP-CMR. Myocardial blood flow (MBF) maps were automatically generated in-line on the scanner following image acquisition at hyperaemic stress and rest, allowing myocardial perfusion reserve (MPR) calculation. 75 coronary vessels assessed by FFR, and 28 vessels with CTO were evaluated at both segmental and coronary territory level. Coronary territory stress MBF and MPR were reduced in FFR-positive (≤ 0.80) regions (median stress MBF: 1.74 [0.90-2.17] ml/min/g; MPR: 1.67 [1.10-1.89]) compared with FFR-negative regions (stress MBF: 2.50 [2.15-2.95] ml/min/g; MPR 2.35 [2.06-2.54] p < 0.001 for both). Stress MBF ≤ 1.94 ml/min/g and MPR ≤ 1.97 accurately detected FFR-positive CAD on a per-vessel basis (area under the curve: 0.85 and 0.96 respectively; p < 0.001 for both). A novel scanner-integrated high-resolution free-breathing SP-CMR sequence with automated in-line perfusion mapping is presented which accurately detects functionally significant CAD.

Hybrid artificial intelligence outcome prediction using features extraction from stress perfusion cardiac magnetic resonance images and electronic health records.

Prediction of clinical outcomes in coronary artery disease (CAD) has been conventionally achieved using clinical risk factors. The relationship between imaging features and outcome is still not well understood. This study aims to use artificial intelligence to link image features with mortality outcome. A retrospective study was performed on patients who had stress perfusion cardiac magnetic resonance (SP-CMR) between 2011 and 2021. The endpoint was all-cause mortality. Convolutional neural network (CNN) was used to extract features from stress perfusion images, and multilayer perceptron (MLP) to extract features from electronic health records (EHRs), both networks were concatenated in a hybrid neural network (HNN) to predict study endpoint. Image CNN was trained to predict study endpoint directly from images. HNN and image CNN were compared with a linear clinical model using area under the curve (AUC), F1 scores, and McNemar's test. Total of 1,286 cases were identified, with 201 death events (16%). The clinical model had good performance (AUC =80%, F1 score =37%). Best Image CNN model showed AUC =72% and F1 score =38%. HNN outperformed the other two models (AUC =82%, F1 score =43%). McNemar's test showed statistical difference between image CNN and both clinical model (P<0.01) and HNN (P<0.01). There was no significant difference between HNN and clinical model (P=0.15). Death in patients with suspected or known CAD can be predicted directly from stress perfusion images without clinical knowledge. Prediction can be improved by HNN that combines clinical and SP-CMR images.

Coronary microvascular dysfunction: prevalence and aetiology in patients with suspected myocardial ischaemia

To evaluate the prevalence, aetiology, and corresponding morbidity of coronary microvascular dysfunction (CMD) in patients with suspected myocardial ischaemia. The present study included 115 patients with suspected myocardial ischaemia who underwent stress perfusion cardiac magnetic resonance imaging. CMD was assessed visually based on the myocardial perfusion results. The CMR-derived myocardial perfusion reserve index (MPRI) and left ventricular (LV) strain parameters obtained using the post-processing software CVI42 were employed to evaluate LV myocardial perfusion and deformation. LV strain parameters included global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS), global systolic/diastolic longitudinal, circumferential, and radial strain rates (SLSR, SCSR, SRSR, DLSR, DCSR, and DRSR). Of the 115 patients, 12 patients were excluded and 103 patients were finally included in the study. CMD was observed in 79 % (81 patients, aged 53±12 years) of patients. Regarding aetiology, 91 (88 %) patients had non-obstructive coronary artery disease (CAD), eight (8 %) had obstructive CAD, and four (4 %) had hypertrophic cardiomyopathy (HCM). The incidence of CMD was highest (100 %) in patients with HCM, followed by those with non-obstructive CAD (up to 79 %). There were no statistical differences between CMD and non-CMD groups in GCS, GRS, GLS, SRSR, SCSR, SLSR, DCSR, DRSR and DLSR. The incidence of CMD was higher in patients with signs and symptoms of ischaemia. CMD occurred with non-obstructive CAD, obstructive CAD, and HCM, with the highest prevalence of CMD in HCM.

Myocardial perfusion in cardiac amyloidosis.

Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Retrospectively gated ultrashort-echo-time MRI T1 mapping reveals compromised pulmonary microvascular NO-dependent function in a murine model of acute lung injury.

This study sought to develop noninvasive, in vivo imaging schemes that allow for quantitative assessment of pulmonary microvascular functional status based on the combination of pulmonary T1 mapping and dynamic contrast-enhanced (DynCE) imaging. Ultrashort-echo-time (UTE) imaging at 9.4 T of lung parenchyma was performed. Retrospective gating was based on modulation of the first point in each recorded spoke. T1 maps were obtained using a series of five consecutive images with varying RF angles and analyzed with the variable flip angle approach. The obtained mean T1 lung value of 1078 ± 38 ms correlated well with previous reports. Improved intersession variability was observed, as evident from a decreased standard deviation of motion-resolved T1 mapping (F-test = 0.051). Animals received lipopolysaccharide (LPS) and were imaged at t= 2, 6, and 12 h after administration. The nitric oxide (NO)-dependent function was assessed according to changes in lung T1 after L-NAME injection, while microvascular perfusion and oxidant stress were assessed with contrast-enhanced imaging after injection of gadolinium or 3-carbamoyl-proxyl nitroxide radical, respectively. Retrospectivel gated UTE allowed robust, motion-compensated imaging that could be used for T1 mapping of lung parenchyma. Changes in lung T1 after L-NAME injection indicated that LPS induced overproduction of NO at t= 2 and 6 h after LPS, but NO-dependent microvascular function was impaired at t= 12 h after LPS. DynCE imaging at t= 6 h after LPS injection revealed decreased microvascular perfusion, with increased vascular permeability and oxidant stress. MRI allows to visualize and quantify lung microvascular NO-dependent function and its concomitant impairment during acute respiratory distress syndrome development with high sensitivity. UTE T1 mapping appears to be sensitive and useful in probing pulmonary microvascular functional status.

High-resolution quantification of stress perfusion defects by cardiac magnetic resonance.

Quantitative stress perfusion cardiac magnetic resonance (CMR) is becoming more widely available, but it is still unclear how to integrate this information into clinical decision-making. Typically, pixel-wise perfusion maps are generated, but diagnostic and prognostic studies have summarized perfusion as just one value per patient or in 16 myocardial segments. In this study, the reporting of quantitative perfusion maps is extended from the standard 16 segments to a high-resolution bullseye. Cut-off thresholds are established for the high-resolution bullseye, and the identified perfusion defects are compared with visual assessment. Thirty-four patients with known or suspected coronary artery disease were retrospectively analysed. Visual perfusion defects were contoured on the CMR images and pixel-wise quantitative perfusion maps were generated. Cut-off values were established on the high-resolution bullseye consisting of 1800 points and compared with the per-segment, per-coronary, and per-patient resolution thresholds. Quantitative stress perfusion was significantly lower in visually abnormal pixels, 1.11 (0.75-1.57) vs. 2.35 (1.82-2.9) mL/min/g (Mann-Whitney U test P < 0.001), with an optimal cut-off of 1.72 mL/min/g. This was lower than the segment-wise optimal threshold of 1.92 mL/min/g. The Bland-Altman analysis showed that visual assessment underestimated large perfusion defects compared with the quantification with good agreement for smaller defect burdens. A Dice overlap of 0.68 (0.57-0.78) was found. This study introduces a high-resolution bullseye consisting of 1800 points, rather than 16, per patient for reporting quantitative stress perfusion, which may improve sensitivity. Using this representation, the threshold required to identify areas of reduced perfusion is lower than for segmental analysis.

Myocardial bridges in a pediatric population: Outcomes following a standardized approach

ObjectiveTo describe clinical, functional, surgical, and outcomes data in pediatric patients with a myocardial bridge (MB) evaluated and managed following a standardized approach. MethodsProspective observational study included patients evaluated in the Coronary Artery Anomalies Program. Anatomy was determined by computed tomography angiography, myocardial perfusion by stress perfusion imaging, and coronary hemodynamic assessment by cardiac catheterization. ResultsIn total, 39 of 42 patients with a complete evaluation for MB were included (December 2012 to June 2022) at a median age of 14.1 years (interquartile range, 12.2-16.4). Sudden cardiac arrest occurred in 3 of 39 (8%), exertional symptoms in 14 (36%), and no/nonspecific symptoms in 7 (18%) patients. Exercise stress test was abnormal in 3 of 34 (9%), stress perfusion imaging in 8 of 34 (24%), and resting instantaneous wave-free ratio ≤0.89 or diastolic dobutamine fractional flow reserve ≤0.80 in 11 of 21 (52%) patients. As a result, 15 of 39 (38%) patients were determined to have hemodynamically significant MB, 1 of 15 patients started beta-blocker, and 14 of 15 were referred for surgery. Myotomy (n = 11) and coronary bypass (n = 1) were performed successfully, resulting in improved symptoms and stress testing results. One patient required pericardiocentesis postoperatively, and all were discharged without other complications. At median follow-up time of 2.9 (1.8-5.8) years, all (except 2 pending surgery) were doing well without exercise restriction. ConclusionsPediatric patients with MB can present with myocardial ischemia and sudden cardiac arrest. Provocative stress test and intracoronary hemodynamic tests helped risk-stratify symptomatic patients with MB and concern for ischemia. Surgical repair was safe and effective in mitigating exertional symptoms and stress test results, allowing patients to return to exercise without restriction.

Prognostic value of stress perfusion cardiac magnetic resonance in patients with prediabetes and suspected coronary artery disease.

Stress perfusion cardiac magnetic resonance (CMR) is an accurate and comprehensive modality for evaluating patients with suspected coronary artery disease (CAD), but its prognostic value in prediabetic patients is uncertain. This retrospective study included 452 consecutive prediabetic patients without prior diagnoses of CAD who underwent adenosine stress perfusion CMR. The primary endpoint was major adverse cardiovascular events (MACE), defined as cardiovascular death, nonfatal myocardial infarction (MI), hospitalization for heart failure, ischemic stroke, and late coronary revascularization (>90 days post-CMR). The secondary endpoint was a composite of cardiovascular death, nonfatal MI, and hospitalization for heart failure. The mean age was 68±11 years (49% male). Over a median follow-up time of 8.1 (IQR 5.7, 10.4) years, 55 patients experienced MACE, and 24 met the secondary endpoint. Patients with inducible ischemia had significantly greater annualized event rates for MACE (5.7% vs. 0.7%, p<0.001) and for the secondary endpoint (2.0% vs. 0.3%, p<0.001) than those without ischemia. Multivariable analysis revealed inducible ischemia as a consistent predictor for MACE (HR 3.36, 95%CI 1.90-5.94, p<0.001) and for the secondary endpoint (HR 2.89, 95%CI 1.22-6.80, p = 0.01). Late gadolinium enhancement (LGE) was an independent predictor of the secondary endpoint (HR 3.56, 95%CI 1.25-10.13; p = 0.02). Incorporating inducible ischemia and LGE data significantly improved the model's ability to discriminate MACE risk (C-statistic increase from 0.77 to 0.83; net reclassification improvement 0.42; integrated discrimination improvement 0.05). Stress perfusion CMR offers substantial independent prognostic value and effectively aids in reclassifying cardiovascular risk among prediabetic patients with suspected CAD.