Luis Eduardo Juárez-Orozco

Quantitative myocardial perfusion evaluation with positron emission tomography and the risk of cardiovascular events in patients with coronary artery disease: A systematic review of prognostic studies

Abstract Aims To evaluate the prognostic value of quantitative myocardial perfusion imaging with positron emission tomography (PET) for adverse cardiovascular outcomes in patients with known or suspected coronary artery disease (CAD). Methods and results A search in MEDLINE and Embase was conducted for studies that evaluated (i) myocardial perfusion in absolute terms with PET, (ii) prognostic value for the development of major adverse cardiovascular events (MACE), cardiac death, and/or all-cause mortality, and (iii) patients with known or suspected CAD. Studies were divided according to the radiotracer utilized and their included population (patients with and without previous infarction). Comprehensive description and a selected instance of pooling were performed. Eight studies (n = 6804) were analysed and documented clear variability in population, quantitative PET variables operationalization [stress myocardial blood flow (sMBF) and flow reserve (MFR)], statistical covariate structure, follow-up, and radiotracer utilized. MFR was independently associated with MACE in eight studies [range of adjusted hazard ratios (HRs): 1.19–2.93]. The pooling instance demonstrated that MFR significantly associates with the development of MACEs (HR: 1.92 [1.29, 2.84]; P = 0.001). sMBF was only associated with MACE in two studies that evaluated it, and only one study documented sMBF as a better predictor than MFR. Conclusion This systematic review demonstrates the prognostic value of quantitative myocardial perfusion evaluated with PET, in the form of MFR and sMBF, for the development of major adverse cardiovascular outcomes in populations with known or suspected CAD. In the qualitative comparison, MFR seems to outperform sMBF as an independent prognostic factor. Evidence is still lacking for assessing quantitative PET for the occurrence of cardiac death and all-cause mortality. There is clear heterogeneity in predictor operationalization and study performances.

Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy:

Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants.

Stress myocardial blood flow correlates with ventricular function and synchrony better than myocardial perfusion reserve: A Nitrogen-13 ammonia PET study

BackgroundCardiac PET quantifies stress myocardial blood flow (MBF) and perfusion reserve (MPR), while ECG-gated datasets can measure components of ventricular function simultaneously. Stress MBF seems to outperform MPR in the detection of significant CAD. However, it is uncertain which perfusion measurement is more related to ventricular function. We hypothesized that stress MBF correlates with ventricular function better than MPR in patients studied for suspected myocardial ischemia.MethodsWe studied 248 patients referred to a rest and adenosine-stress Nitrogen-13 ammonia PET. We performed a multivariate analysis using systolic function (left ventricular ejection fraction, LVEF), diastolic function (mean filling rate in diastole, MFR/3), and synchrony (Entropy) as the outcome variables, and stress MBF, MPR, and relevant covariates as the predictors. Secondarily, we repeated the analysis for the subgroup of patients with and without a previous myocardial infarction (MI).Results166 male and 82 female patients (mean age 63 ± 11 and 67 ± 11 year, respectively) were included. 60% of the patients presented hypertension, 57% dyslipidemia, 21% type 2 diabetes mellitus, 45% smoking, and 34.7% a previous MI. Mean stress MBF was 1.99 ± 0.75 mL/g/min, MPR = 2.55 ± 0.89, LVEF = 61.6 ± 15%, MFR/3 = 1.12 ± 0.38 EDV/s, and Entropy = 45.6 ± 11.3%. There was a significant correlation between stress MBF (P < .001) and ventricular function. This was stronger than the one for MPR (P = .063). Sex, age, diabetes, and extent of previous MI were also significant predictors. Results were similar for the analyses of the 2 subgroups.ConclusionStress MBF is better correlated with ventricular function than MPR, as evaluated by Nitrogen-13 ammonia PET, independently from other relevant cardiovascular risk factors and clinical covariates. This relationship between coronary vasodilatory capacity and ventricular function is sustained across groups with and without a previous MI.

Repeated social defeat induces transient glial activation and brain hypometabolism: A positron emission tomography imaging study

Psychosocial stress is a risk factor for the development of depression. Recent evidence suggests that glial activation could contribute to the development of depressive-like behaviour. This study aimed to evaluate in vivo whether repeated social defeat (RSD) induces short- and long-term inflammatory and metabolic alterations in the brain through positron emission tomography (PET). Male Wistar rats (n = 40) were exposed to RSD by dominant Long-Evans rats on five consecutive days. Behavioural and biochemical alterations were assessed at baseline, day 5/6 and day 24/25 after the RSD protocol. Glial activation (11C-PK11195 PET) and changes in brain metabolism (18F-FDG PET) were evaluated on day 6, 11 and 25 (short-term), and at 3 and 6 months (long-term). Defeated rats showed transient depressive- and anxiety-like behaviour, increased corticosterone and brain IL-1β levels, as well as glial activation and brain hypometabolism in the first month after RSD. During the third- and six-month follow-up, no between-group differences in any investigated parameter were found. Therefore, non-invasive PET imaging demonstrated that RSD induces transient glial activation and reduces brain glucose metabolism in rats. These imaging findings were associated with stress-induced behavioural changes and support the hypothesis that neuroinflammation could be a contributing factor in the development of depression.

Residual Activity Correction in Quantitative Myocardial Perfusion N-13-Ammonia PET Imaging: A Study in Post-MI Patients

BACKGROUND/INTRODUCTION/AIM Positron emission tomography (PET) is the gold standard for the quantification of myocardial blood flow (MBF). A standard PET scan is acquired in two phases (rest and pharmacological stress). 13N-ammonia is a perfusion radiotracer that may show residual activity, which may affect MBF estimation during the second phase of the scan. An algorithm for residual activity correction (RAC) is available when reconstruction is performed using Syngo MBF (by Siemens). The aim of this study was to evaluate differences in MBF estimation with and without RAC by Syngo MBF in patients with a previous MI using 13N-ammonia PET. METHODS MBF was evaluated by 13N-ammonia PET in a group of 25 patients with a history of MI. Dynamic MBF measurements were analyzed with Syngo Dynamic PET, with and without RAC, and the results were evaluated with statistical methods. RESULTS Significant differences in stress phase MBF after RAC were identified in the left anterior descending coronary artery (LAD) territory (p=0.0425) and the right coronary artery (RCA) territory (p=0.004). A trend towards significance was identified in the global polar plot (p=0.049). No statistically significant difference was found in the left circumflex artery (LCx) territory (p=0.333). CONCLUSION Syngo Dynamic PET, through its RAC function, can be a useful adjunct in assessing second-phase MBF of primarily the RCA territory and secondarily the global polar plot and LAD territory but not the LCx territory.

Current and future trends in multimodality imaging of coronary artery disease

Nowadays, there is a wide array of imaging studies available for the evaluation of coronary artery disease, each with its particular indications and strengths. Cardiac single photon emission tomography is mostly used to evaluate myocardial perfusion, having experienced recent marked improvements in image acquisition. Cardiac PET has its main utility in perfusion imaging, atherosclerosis and endothelial function evaluation, and viability assessment. Cardiovascular computed tomography has long been used as a reference test for non-invasive evaluation of coronary lesions and anatomic characterization. Cardiovascular magnetic resonance is currently the reference standard for non-invasive ventricular function evaluation and myocardial scarring delineation. These specific strengths have been enhanced with the advent of hybrid equipment, offering a true integration of different imaging modalities into a single, simultaneous and comprehensive study.

The machine learning horizon in cardiac hybrid imaging

BackgroundMachine learning (ML) represents a family of algorithms that has rapidly developed within the last years in a wide variety of knowledge areas. ML is able to elucidate and grasp complex patterns from data in order to approach prediction and classification problems. The present narrative review summarizes fundamental notions in ML as well as the evidence of its application in standard cardiac imaging and the potential for implementation in cardiac hybrid imaging.ResultsML, and in particular Deep Learning, has begun to revolutionize medical imaging though the optimization of diagnostic and prognostic estimations at the individual-patient level. On the other hand, the spread and availability of high quality non-invasive imaging has provided growing amounts of data in the characterization of suspected cardiovascular diseases. At the same time, modern combined imaging equipment has set the ground for the concept of hybrid imaging to develop. Cardiac hybrid imaging refers to the combination of diagnostic images and offers the possibility to comprehensively characterize the heart and great vessels when a pathology is suspected or clinically known. Analysis and integration of large amounts of cardiac hybrid imaging data (and corresponding clinical profiles) constitutes a highly complex process and ML will likely be able to enhance it in the near future.ConclusionML conveys novel and powerful approaches in the processing of large and complex datasets that may include images as well as imaging-derived data. Given the growing amount of data in the realm of cardiac hybrid imaging and the rapid development of ML, it is highly desirable to implement and test ML in the optimization of our multimodality imaging diagnostic and prognostic evaluations in cardiovascular disease.

PET myocardial perfusion quantification: anatomy of a spreading functional technique

Purpose To summarize the physical principles, imaging method, available tools for and the clinical value of quantitative perfusion evaluation with cardiac PET as well as future aims in the field in a narrative review.Results Cardiac positron-emission tomography (PET) currently constitutes the reference standard for non-invasive quantitative evaluation of myocardial blood flow. This added modality provides useful information beyond standard semi-quantitative myocardial perfusion evaluation. A description of how the different phases of PET studies are interpreted is provided, as well as a short depiction of the most commonly used radiotracers and the main characteristics affecting their clinical utility. The diagnostic and prognostic utility concerning myocardial perfusion quantified in absolute terms is discussed and the additional contribution of the increasingly spread hybrid equipment is summarized.ConclusionPET myocardial perfusion represents an excellent noninvasive technique for the evaluation of known or suspected ischemic heart disease, and its clinical application should widen in the near future. The clinical value of PET quantitative perfusion is expected to improve patient outcomes and optimize therapeutic decisions, which constitute key elements for the future of cardiovascular medicine.

RIGHT VENTRICLE FREE WALL STRAIN PREDICTS POST-SURGICAL LOW CARDIAC OUTPUT SYNDROME IN PATIENTS UNDERGOING AORTIC VALVE REPLACEMENT

Background: Severe aortic stenosis (AoS) represents a common entity for which surgical aortic valve replacement (SAVR) remains the treatment of choice. Low cardiac output syndrome after SAVR is related with increased mortality and treatment related costs. Recently strain imaging has been shown to be

13N-Ammonia pet-derived ventricular synchrony correlates with myocardial perfusion reserve better than left ventricular ejection fraction: A study in infarcted patients

Background: PET myocardial perfusion allows myocardial perfusion reserve (MPR) quantification as well as left ventricular ejection fraction (LVEF) and synchrony estimation through phase analysis. There is a relationship between MPR and LVEF and both have proven prognostic value in coronary artery disease (CAD). A relation between angiographic CAD extent and post-stress synchrony has been proposed with SPECT. We used 13N-ammonia PET to evaluate the relationship between MPR and ventricular synchrony in patients with a previous infarction and secondarily, to compare it to the relation MPR-LVEF. Methods: We studied 63 patients (64.4±11.1years) with a previous myocardial infarction with a rest/adenosine-stress 13N-ammoniaPET. Demographics and cardiovascular history were retrieved. MPR was calculated dividing the stress by the rest blood flow. Synchrony was evaluated through Entropy, systolic function through LVEF and the area of previous infarction through the resting total perfusion defect (TPD). Two multiple regressions were done: the first used Entropy as dependent variable and MPR, TPD and clinical variables as predictors; in the second LVEF replaced the dependent variable. The standardized regression coefficients were compared. Results: There were 49 males and 14 females, 39% with diabetes, 54% with hypertension, 54% with dyslipidemia, 42% of smokers and 44% with chest pain. Mean MPR=2.14±0.79, mean TPD=15.8%±11.2, mean LVEF=49%±17 and mean Entropy=53.4%±11.8. The first regression showed a significant independent relation between MPR and Entropy (β=-.384, p=0.006). This relation was greater than the one between MPR and LVEF (β=.292, p=0.013) in the second regression. In both, TPD (p=0.021, p=0.001) and gender (p=0.041, p=0.001) showed a significant correlation with the dependent variables. Conclusions: In patients with a previous myocardial infarction, PET-measured MPR significantly correlates to ventricular synchrony independently from the area of infarction. This correlation is stronger than the one between MPR and LVEF. Our results warrant further research into the added prognostic value of PET-measured ventricular synchrony and entropy in the setting of CAD.