Invasive Evaluation Research Articles

Cardiac Involvement and Arrhythmias Associated with Myotonic Dystrophy.

Myotonic dystrophy is an autosomal dominant genetic disease of nucleotide expansion resulting in neuromuscular disease with two distinct subtypes. There are significant systemic manifestations of this condition including progressive muscular decline, neurologic abnormalities, and cardiac disease. Given the higher prevalence of cardiac dysfunction compared to the general population, there is significant interest in early diagnosis and prevention of cardiac morbidity and mortality. Cardiac dysfunction has an origin in abnormal and unstable nucleotide repeats in the DMPK and CNBP genes which have downstream effects leading to an increased propensity for arrhythmias and left ventricular systolic dysfunction. Current screening paradigms involve the use of routine screening electrocardiograms, ambulatory electrocardiographic monitors, and cardiac imaging to stratify risk and suggest further invasive evaluation. The most common cardiac abnormality is atrial arrhythmia, however there is significant mortality in this population from high-degree atrioventricular block and ventricular arrhythmia. In this review, we describe the cardiac manifestations of myotonic dystrophy with an emphasis on arrhythmia which is the second most common cause of death in this population after respiratory failure.

Tissue Engineering Scaffolds for Minimally-Invasive Immunosurveillance of Acute Cellular Graft Rejection

<h3>Purpose</h3> As there is no assay to predict the risk of acute cellular allograft rejection (ACAR), clinicians rely on protocol graft biopsy and aggressive, <i>one-size-fits-all</i> immunosuppression. Immunosuppression protects grafts from ACAR but increases systemic toxicities. Endomyocardial biopsy (EMB) histology suffers from variability and lags behind molecular biomarkers. <b>A minimally invasive surveillance method is urgently needed to quantify early risk of rejection for minimizing graft biopsy and personalizing treatment.</b> <h3>Methods</h3> Biomaterial scaffolds accumulate immune cells producing biomarkers of ACAR as an engineered immunological niche. We implanted subcutaneous poly-caprolactone scaffolds in murine heart or skin transplants to determine if they could identify ACAR. Rag2KO mice received full MHC mismatch allografts or syngeneic controls, and ACAR was initiated as a tunable event by C57BL/6 T cell transfer. Scaffolds were explanted and analyzed via histology and differential gene expression by RNA sequencing. <h3>Results</h3> The scaffolds provided a novel measure of graft health. We algorithmically identified <b>11 differentially-expressed genes as biomarkers</b> that distinguish mice with rejecting grafts from those with healthy grafts. <i>Importantly, the scoring system detects oncoming ACAR prior to clinical signs of rejection.</i> Also, histology of these niches identified changes associated with ACAR progression. <h3>Conclusion</h3> Gene expression in the cell-capture scaffold identified a biomarker signature of early ACAR, without invasive biopsy. <b>Scaffold cell capture technology provides a leading indicator of ACAR by monitoring tissue-specific immune responses associated with allograft rejection.</b> This implantable scaffold enables minimally invasive histological evaluation and molecular calculation of the early risk of rejection to reduce the frequency of routine EMB and personalize immune suppression that ultimately could prolong transplant life while minimizing risk.

Resistive reserve ratio and microvascular resistance reserve in patients with coronary vasospastic angina.

Patients with epicardial coronary vasospastic angina (VSA) may be likely to have coronary microvascular dysfunction, although mixed results have been reported. The aim of this study was to evaluate coronary microvascular function in detail using novel invasive physiologic indices, such as resistive reserve ratio (RRR) and microvascular resistance reserve (MRR). A total of 45 patients undergoing intracoronary acetylcholine (ACh) provocation test and invasive coronary circulatory evaluation using a thermodilution method were prospectively included. VSA was diagnosed as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes by intracoronary injection of ACh. Coronary circulation was assessed with physiologic indices including fractional flow reserve, resting and hyperemic mean transit time (Tmn), coronary flow reserve (CFR), basal resistance index, index of microcirculatory resistance (IMR), RRR, and MRR. Of 45 patients, 23 (51.1%) were diagnosed as having VSA. Patients with positive ACh test had longer resting Tmn (slower coronary flow velocity), higher basal resistance index, and greater RRR and MRR than those without, while fractional flow reserve, CFR, and IMR did not differ significantly between the two groups. In conclusion, although conventional measures such as CFR and IMR failed to show significant differences, RRR and MRR, novel invasive coronary physiologic indices, provided counterintuitive insights that coronary microvascular dilation function was better preserved in patients with VSA than those without.

Invasive Hemodynamic Evaluation of the Fontan Circulation: Current Day Practice and Limitations.

Establishing the Fontan circulation has led to improved survival in patients born with complex congenital heart diseases. Despite early success, the long-term course of Fontan patients is complicated by multi-organ dysfunction, mainly due to a combination of low resting and blunted exercise-augmented cardiac output as well as elevated central venous (Fontan) pressure. Similarly, despite absolute hemodynamic differences compared to the normal population with biventricular circulation, the "normal" ranges of hemodynamic parameters specific to age-appropriate Fontan circulation have not been well defined. With the ever-increasing population of patients requiring Fontan correction, it is of utmost importance that an acceptable range of hemodynamics in this highly complex patient cohort is better defined. Multiple publications have described hemodynamic limitations and potential management options in patients with Fontan circulation; however, an acceptable range of hemodynamic parameters in this patient population has not been well defined. Identification of "normal" hemodynamic parameters among patients with Fontan circulation will allow physicians to more objectively define indications for intervention, which is a necessary first step to eliminate institutional and regional heterogeneity in Fontan management and potentially improve long-term clinical outcomes.

Bleeding Episodes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Very Early Versus Standard Care Invasive Examination (from the Very EaRly vs Deferred Invasive Evaluation Using Computerised Tomography [VERDICT] Trial)

Bleeding is known to influence the prognosis in patients with acute coronary syndromes. In this predefined secondary outcome analysis of the Very EaRly vs Deferred Invasive evaluation using Computerized Tomography (VERDICT) trial, we investigated whether a very early invasive coronary angiography (ICA), compared with one performed within 48 to 72hours (standard care), was associated with fewer serious bleedings. Furthermore, we tested the association between demographic data including GRACE score and serious bleedings as well as bleedings and mortality. In the 2,147 patients included in the main study, bleedings within 30days of admission were assessed based on Thrombolysis In Myocardial Infarction and Bleeding Academic Research Consortium criteria. Differences were calculated by cumulative incidence methods and Grays test. Variables associated with bleeding and mortality were estimated by Cox proportional hazard models. Serious (Bleeding Academic Research Consortium 3abc) bleeding rates were low (15 [1.4%, standard] vs 12 [1.2%, early], p=0.56). There were no fatal bleedings or serious bleedings before ICA in either group. By multivariate analysis, there was no difference in bleedings between the 2 groups. Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.2 to 6.4; p=0.02), anemia (HR 7.0, 95% CI 2.8 to 17.0; p <0.001), and increasing blood pressure (HR 1.3, 95% CI 1.1 to 1.5; p=0.01) were individually associated with serious bleeding, whereas GRACE score >140 was not (HR 1.03, 95% CI 0.4 to 2.9; p=0.96). In conclusion, serious bleedings were few, and there were none before ICA in either group. A very early invasive strategy did not reduce serious bleedings within 30days, which was associated with female gender, increasing blood pressure, and anemia.

Diagnostic performance of deep learning algorithm for analysis of computed tomography myocardial perfusion.

To evaluate the diagnostic accuracy of a deep learning (DL) algorithm predicting hemodynamically significant coronary artery disease (CAD) by using a rest dataset of myocardial computed tomography perfusion (CTP) as compared to invasive evaluation. One hundred and twelve consecutive symptomatic patients scheduled for clinically indicated invasive coronary angiography (ICA) underwent CCTA plus static stress CTP and ICA with invasive fractional flow reserve (FFR) for stenoses ranging between 30 and 80%. Subsequently, a DL algorithm for the prediction of significant CAD by using the rest dataset (CTP-DLrest) and stress dataset (CTP-DLstress) was developed. The diagnostic accuracy for identification of significant CAD using CCTA, CCTA + CTP stress, CCTA + CTP-DLrest, and CCTA + CTP-DLstress was measured and compared. The time of analysis for CTP stress, CTP-DLrest, and CTP-DLStress was recorded. Patient-specific sensitivity, specificity, NPV, PPV, accuracy, and area under the curve (AUC) of CCTA alone and CCTA + CTPStress were 100%, 33%, 100%, 54%, 63%, 67% and 86%, 89%, 89%, 86%, 88%, 87%, respectively. Patient-specific sensitivity, specificity, NPV, PPV, accuracy, and AUC of CCTA + DLrest and CCTA + DLstress were 100%, 72%, 100%, 74%, 84%, 96% and 93%, 83%, 94%, 81%, 88%, 98%, respectively. All CCTA + CTP stress, CCTA + CTP-DLRest, and CCTA + CTP-DLStress significantly improved detection of hemodynamically significant CAD compared to CCTA alone (p < 0.01). Time of CTP-DL was significantly lower as compared to human analysis (39.2 ± 3.2 vs. 379.6 ± 68.0 s, p < 0.001). Evaluation of myocardial ischemia using a DL approach on rest CTP datasets is feasible and accurate. This approach may be a useful gatekeeper prior to CTP stress..

A1082 - Serum total cell-free DNA as a marker for invasive evaluation in total cystectomy

A1082 - Serum total cell-free DNA as a marker for invasive evaluation in total cystectomy

Future perspective in diabetic patients with pre- and post-capillary pulmonary hypertension.

Pulmonary hypertension is a clinical syndrome that may include multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. Pulmonary hypertension secondary to left heart disease is the prevalent clinical condition and accounts for two-thirds of all cases. Type 2 diabetes mellitus, which affects about 422 million adults worldwide, has emerged as an independent risk factor for the development of pulmonary hypertension in patients with left heart failure.While a correct diagnosis of pulmonary hypertension secondary to left heart disease requires invasive hemodynamic evaluation through right heart catheterization, several scores integrating clinical and echocardiographic parameters have been proposed to discriminate pre- and post-capillary types of pulmonary hypertension.Despite new emerging evidence on the pathophysiological mechanisms behind the effects of diabetes in patients with pre- and/or post-capillary pulmonary hypertension, no specific drug has been yet approved for this group of patients. In the last few years, the attention has been focused on the role of antidiabetic drugs in patients with pulmonary hypertension secondary to left heart failure, both in animal models and in clinical trials.The aim of the present review is to highlight the links emerged in the recent years between diabetes and pre- and/or post-capillary pulmonary hypertension and new perspectives for antidiabetic drugs in this setting.

Hematopoiesis, Inflammation and Aging-The Biological Background and Clinical Impact of Anemia and Increased C-Reactive Protein Levels on Elderly Individuals.

Anemia and systemic signs of inflammation are common in elderly individuals and are associated with decreased survival. The common biological context for these two states is then the hallmarks of aging, i.e., genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Such aging-associated alterations of hematopoietic stem cells are probably caused by complex mechanisms and depend on both the aging of hematopoietic (stem) cells and on the supporting stromal cells. The function of inflammatory or immunocompetent cells is also altered by aging. The intracellular signaling initiated by soluble proinflammatory mediators (e.g., IL1, IL6 and TNFα) is altered during aging and contributes to the development of both the inhibition of erythropoiesis with anemia as well as to the development of the acute-phase reaction as a systemic sign of inflammation with increased CRP levels. Both anemia and increased CRP levels are associated with decreased overall survival and increased cardiovascular mortality. The handling of elderly patients with inflammation and/or anemia should in our opinion be individualized; all of them should have a limited evaluation with regard to the cause of the abnormalities, but the extent of additional and especially invasive diagnostic evaluation should be based on an overall clinical evaluation and the possible therapeutic consequences.

Mortality in Stable Coronary Disease in Patients With Intermediate- or High-Risk Myocardial Perfusion Imaging

The management of patients with stable coronary disease and intermediate- or high-risk features on single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) continues to be controversial as to whether they should be treated with an initial invasive strategy (catheterization and revascularization when feasible) or medical therapy alone to improve mortality. We performed a retrospective observational study of 1,946 patients with intermediate- or high-risk SPECT MPI scans performed over a 6-year period (from 2014 to 2019). Each patient was followed from the time of SPECT MPI to 16 months after the last patient was enrolled. The primary end point was all-cause mortality and the secondary end point cardiovascular mortality. Of the eligible 1,697 patients, 1,144 had an intermediate-risk scan, 553 a high-risk scan, 915 had medical therapy alone, and 782 went on an initial invasive strategy. All patients were divided into the following three groups: combined SPECT MPI (both intermediate- and high-risk), high-risk SPECT MPI, and intermediate-risk SPECT MPI groups. After propensity score matching, there was a statistically significant difference in cardiovascular death (5.9% vs 2.7%; p=0.038) in the medical therapy cohort compared with initial invasive cohort in the combined SPECT MPI group, but no difference in all-cause death (15.7% vs 13%; p=0.318). On subgroup analysis, in intermediate-risk SPECT MPI group, there was no significant difference in either all-cause death (13.8 vs 11.7%; p=0.583) or cardiac death (5.4% vs 2.5%; p=0.16) in conservative cohort compared with invasive strategy cohort. In high-risk SPECT MPI group, conservative therapy cohort had higher cardiac death (11.7% vs 2.5%; p=0.002) compared with initial invasive strategy cohort, but there was no significant difference in all-cause death (24.5% vs 15.3%; p=0.052). In conclusion, this study supports that patients with intermediate- or high-risk SPECT MPI scans when considered together or only with high-risk features, derive a cardiovascular mortality benefit with an initial invasive strategy. Patients who had undergone intermediate-risk SPECT MPI had similar outcomes with either medical therapy alone or initial invasive evaluation.

Development of a biosensor for phosphorylated Tau 181 protein detection in Early-Stage Alzheimer’s disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly, and there are still no reliable methods for its early detection. Recently, the phosphorylated protein Tau181 (p-Tau181) was identified as a highly specific biomarker for AD. Therefore, in this work, a new strategy for the development of an electrochemical-based immunosensor for the detection of p-Tau181 is described. For this purpose, a carbon screen-printed electrode (C-SPE) was modified with platinum nanoparticles decorated with multi-walled carbon nanotubes (MWCNTs- PAH /Pt) to enable antibody binding. Scanning electron microscopy, transmission electron microscopy, Raman and X-ray photoelectron spectroscopy were used to study the morphology and crystallinity of the nanomaterials. Cyclic voltammetry and square-wave voltammetry were performed to compare the electrochemical properties of these electrodes. Under optimal conditions, the developed immunosensor exhibited a linear range from 8.6 to 1100 pg/mL, and the detection limit was estimated to be 0.24 pg/mL. This device showed excellent reproducibility and stability with remarkable selectivity for p-Tau181 in serum samples. Overall, this device enables minimally invasive clinical evaluation of p-Tau181 level with high sensitivity through simple operation, which makes this device a promising tool for future point-of-care purposes that will contribute to the technological development of clinical diagnostics.

Role of fractional flow reserve for invasive functional evaluation in surgical myocardial revascularization: available evidence and state of the art

Fractional flow reserve (FFR) is the ratio of distal to proximal pressure during maximal hyperemia and indirectly estimates the blood flow across a stenotic coronary artery and the related degree of myocardial ischemia. Several studies have investigated the role of FFR in the setting of percutaneous myocardial revascularization and further research is ongoing. However, current evidence on FFR-guided surgical myocardial revascularization is controversial and limited. The main scientific interest is to clarify whether FFR-guided coronary artery bypass surgery is associated with clinical benefits in terms of mortality, myocardial infarction, major adverse cardiovascular events, minimally invasive surgical access compared with sternotomy and off-pump surgery. Furthermore some data suggest that conduit selection for coronary artery bypass grafting and surgical technique might be affected by FFR value. The aim of this article is to review the most recent available evidence about FFR-guided coronary artery bypass grafting and to discuss clinical implications and future perspectives.

Ventricular arrhythmias in athletes: Role of a comprehensive diagnostic workup.

Ventricular arrhythmias (VAs) represent a critical issue with regard to sports eligibility assessment in athletes. The ideal diagnostic evaluation of competitive and leisure-time athletes with complex VAs has not been clearly defined. The purpose of this study was to assess the clinical implications of invasive electrophysiological assessments and endomyocardial biopsy (EMB) among athletes with VAs. We evaluated 227 consecutive athletes who presented to our institutions after being disqualified from participating in sports because of VAs. After noninvasive tests, electrophysiological study (EPS), electroanatomic mapping (EAM), and EAM- or cardiac magnetic resonance imaging-guided EMB was performed, following a prespecified protocol. Sports eligibility status was redefined at 6-month follow-up. From our sample, 188 athletes (82.8%) underwent EAM and EPS, and 42 (15.2%) underwent EMB. A diagnosis ofheart disease could be formulated in 30% of the study population (67/227; 95% confidence interval [CI] 0.24-0.36) after noninvasive tests; in 37% (83/227; 95% CI 31%-43%) after EPS and EAM; and in 45% (102/227; 95% CI 39%-51%) after EMB. In the subset of athletes undergoing EMB, invasive diagnostic workup allowed diagnostic reclassification of half of the athletes (n = 21 [50%]). Reclassification was particularly common among subjects without definitive findings after noninvasive evaluation (n = 23; 87% reclassified). History of syncope, abnormal echocardiogram, presence of late gadolinium enhancement, and abnormal EAM were linked to sports ineligibility at 6-month follow-up. A comprehensive invasive workup provided additional diagnostic elements and could improve the sports eligibility assessment of athletes presenting with VAs. The extensive invasive evaluation presented could be especially helpful when noninvasive tests show unclear findings.

Blood pressure-lowering and cardiovascular effects of plumbagin in rats: An insight into the underlying mechanisms

BackgroundPlumbagin, a natural phenolic compound is investigated for response against blood pressure and vascular reactivity. MethodologyBlood pressure lowering effects were observed by in-vivo invasive evaluation in normotensive rats, and in-vitro experimentation to measure changes of tension in isolated rat aorta and contractility in atria. ResultsThe percentage decrease in mean arterial pressure (MAP) observed with plumbagin intravenously at doses of 0.1, 0.5, 1, 5, 10 ​μg/kg in normotensive rats was 7.16 ​± ​2.35, 15.5 ​± ​5.62, 19.5 ​± ​5.27, 26 ​± ​6.67, 34.33 ​± ​8.80, respectively. Plumbagin exerted vasorelaxant effects in rat aorta, unaffected by the removal of vascular endothelium, and L-NAME and methylene blue pretreatment. Plumbagin completely inhibited phenylephrine (1 ​μM) and High K+ (80 ​mM) induced contractions. Similar to a Ca+2 channel antagonist, plumbagin caused a rightward shift in the Ca+2 concentration-response-curves (CRCs), resembling nifedipine. Pre-incubation with plumbagin, significantly suppressed contractions induced by phenylephrine in Ca+2-free medium via disrupting Ca+2 release from intracellular stores. No change in vasorelaxant response was observed with the addition of potassium channel blockers, TEA and BaCl2. In rat atrial strips, plumbagin exerted significant negative inotropic and chronotropic effects. No significant change was observed with atropine and atenolol pretreatment, so the effect appeared independent of muscarinic and beta-adrenergic receptors. ConclusionThis study suggests the blood pressure lowering effects of plumbagin. That could be contributed by a decrease in vascular resistance via calcium antagonism, interferences in calcium efflux, and depressive effects on the rate and force of cardiac contraction. Further studies would be necessary to probe deeper into the underlying mechanisms.

Diagnostic and Therapeutic Values of Angiogenic Factors in Endometrial Cancer.

Endometrial cancer (EC) is the most frequent gynecological malignancy in developed countries and requires a relatively invasive diagnostic evaluation and operative therapy as the primary therapeutic approach. Angiogenesis is one of the main processes needed for cancer growth and spread. The production of angiogenic factors (AFs) appears early in the process of carcinogenesis. The detection of AFs in plasma and tissue and a better understanding of the angiogenic properties of EC may contribute not only to earlier but also more specific diagnosis and consequently tailored and individual therapeutic approaches. AFs and their receptors also have high potential as binding sites for targeted cancer therapy. In this review, we discuss angiogenesis in EC and the characteristics of the AFs that most contribute to angiogenesis in EC. We also highlight therapeutic strategies that target angiogenesis as potential EC therapy.

185 Diagnostic accuracy of dynamic stress myocardial CT perfusion as compared with invasive coronary physiology metrics in stented patients: preliminary results of the advantage II study

Abstract Aims To compare the diagnostic performance of adenosine-stress dynamic myocardial perfusion assessed by CT (CTP) as compared with that of coronary CT angiography (CCTA) alone by using invasive fractional flow reserve (FFR) and index of microvascular resistance (IMR) as standard of reference. Diagnostic performance of CCTA for in-stent restenosis (ISR) detection is still challenging. Recently, CTP demonstrated additional specificity and diagnostic accuracy over CCTA alone in patients with previous stent implantation and suspected IRS or progression of coronary artery disease (CAD). However, no data are available in this clinical setting on the performance of CTP by using a new technique allowing for a non-invasive adjudication of regional myocardial blood flow (dynamic CTP) and to assess both macrovascular and microvascular disease status. Moreover, dynamic CTP was never compared vs. a comprehensive assessment of invasive coronary physiology (FFR and IMR). Methods and results We enrolled consecutive stable patients with previous coronary stenting referred for invasive coronary angiography (ICA) for clinical indication. All patients underwent dynamic stress myocardial CTP and rest CTP+CCTA by using a last generation scanner characterized by a 16-cm Z-axis coverage and fast (0.28 s) gantry rotation time. Invasive FFR and IMR were performed during ICA according to the standard practice. The diagnostic rate and diagnostic accuracy of CCTA and CTP were evaluated in a territory-based analyses vs. quantitative coronary angiography (QCA), FFR, and IMR. In 67 enrolled patients (55 men, mean age: 63.1 ± 8.2 years), the diagnostic rate (number of territories interpretable/number of territories evaluated) of CTP was significantly higher than that of CCTA (302/307 = 98.4% vs. 290/307 = 94.4%, P = 0.009). The interpretability of the combined CCTA/CTP approach was 99.7% (306/307 territories). When QCA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of CCTA (84.4% vs. 80.1%, P = 0.01). When coronary physiology metrics were used as gold standard, CTP diagnostic accuracy was significantly higher than that of CCTA vs. both FFR (84.3% vs. 72.2%, P = 0.02) and IMR (83.3% vs. 70.2%, P = 0.02). The radiation exposure of CCTA+CTP was 8.7 ± 2.5 mSv. Conclusions In patients with coronary stents, dynamic CTP significantly improves diagnostic rate and accuracy of CCTA alone in comparison with both FFR and IMR. The non-invasive assessment of ISR is still challenging. The comprehensive assessment by cardiac CT provides anatomical combined to functional evaluation of coronary arteries in revascularized patients with good agreement with invasive physiological evaluation.

Sevoflurane-based enhancement of phase-amplitude coupling and localization of the epileptogenic zone

ObjectivePhase-amplitude coupling between high-frequency (≥150 Hz) and delta (3–4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone. MethodsThis is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified ‘removed’ and ‘retained’ brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites. ResultsMI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2.0 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2.0 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1.0 MI. ConclusionsIntraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2.0 MAC in this small cohort of patients. SignificanceProspective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation.

Cortical regions and networks of hyperkinetic seizures: Electrocorticography and diffusion tensor imaging study

ObjectiveThe present study investigated the cortical areas and networks responsible for hyperkinetic seizures by analyzing invasive recordings and diffusion tensor imaging (DTI) tractography. MethodsSeven patients with intractable focal epilepsy in whom hyperkinetic seizures were recorded during an invasive evaluation at Sapporo Medical University between January 2012 and March 2020 were enrolled in the present study. Intracranial recordings were analyzed to localize seizure-onset zones (SOZs) and symptomatogenic zones (spread areas at clinical onset). DTI was used to identify the subcortical fibers originating from SOZs. ResultsTen SOZs were located in four areas: (1) the inferior parietal lobule (two SOZs in two patients), (2) temporo-occipital junction (three SOZs in two patients), (3) medial temporal area (three SOZs in three patients) and (4) medial/lateral frontal lobe (two SOZs in two patients). Symptomatogenic zones appeared to be the premotor area, basal temporal area, temporo-occipital junction, and the postcentral gyrus/supramarginal gyrus. The tractographic analysis revealed that the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MLF), arcuate fasciculus (AF)/superior longitudinal fasciculus (SLF) II, III, and cingulum bundle may be associated with hyperkinetic seizures. ConclusionThe present results suggest the cortical areas (the inferior parietal lobule, temporo-occipital junction, medial temporal area, and medial/lateral frontal lobe) and subcortical fibers (IFOF, ILF, MLF, AF/SLFII, III, and the cingulum bundle) responsible for generating hyperkinetic seizures.

Abstract 14441: Anemia is Associated With Coronary Microvascular Dysfunction and Future Adverse Outcomes in Patients With Non-Obstructive Coronary Artery Disease

Introduction: Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality. Anemia is an important predictor of outcomes in several cardiovascular diseases, such as heart failure and coronary artery disease (CAD), however its significance in patients with non-obstructive CAD is not fully elucidated. Hypothesis: We hypothesized that anemia would be associated with CMD and future adverse outcomes. Methods: We enrolled 1334 patients with signs and/or symptoms of ischemia and with non-obstructive CAD (&lt;50% angiographic stenosis) who underwent invasive CMD evaluation and had follow-up data. CMD was defined as coronary flow reserve (CFR) (hyperemic flow/baseline flow as measured by the doppler wire) of ≤2 in response to intracoronary adenosine injection. Anemia was defined as a Hgb &lt; 13.0 g/L in males and &lt;12.0 g/L in females. MACE was defined as any incidence of myocardial infarction, cardiac revascularization (PCI, CABG) and all-cause mortality. Results: Overall mean age was 51.3±12.4 years, 66% were female. Patients with anemia were more likely to be female and have diabetes mellitus. Anemics were more likely to be diagnosed with CMD (Odds Ratio 2.01, 95% Confidence Interval [1.14-3.54]; P = 0.02). This relationship remained significant even after adjusting for cardiovascular risk factors like age, sex, hypertension, diabetes mellitus and dyslipidemia (OR 1.84, 95% CI [1.03-3.29], P = 0.04). Furthermore, patients with anemia were more likely to experience MACE (OR 1.86, 95% CI [1.30-2.66], P = 0.001), independent of possible confounders (OR 1.84, 95% CI [1.27-2.69], P = 0.002). Conclusions: Anemia is an independent predictor of CMD and future adverse cardiovascular events in patients with NOCAD. Moreover, it was associated with an increased risk of future adverse events. Further studies are needed to elucidate whether treatment of anemia in this population translates into outcomes.

Abstract 10568: The Impact of Gender: Rates of Significant Coronary Artery Disease in Women and Men Undergoing Non-Invasive and Invasive Ischemic Evaluation for Acute Coronary Syndromes

Introduction: Key differences in the presentation and pathophysiology of cardiovascular disease (CVD) between men and women exacerbate diagnostic challenges when evaluating patients with acute coronary syndromes (ACS). Hypothesis: We aimed to better understand the impact of gender on diagnostic approaches and findings in similar cohorts of men and women who presented to rule out ACS and were evaluated with non-invasive cardiac imaging (NI) including Computed Tomography Coronary Angiography (CTCA) or Nuclear Stress Test (NST) prior to coronary angiography (CA). Methods: We performed a retrospective chart review to evaluate all patients referred to our catheterization laboratory for ACS over 1 year. Patients with a history of CVD, end stage renal disease or who underwent CA without NI were excluded. Statistical analysis was performed with Paired-T and Mann Whitney U Testing, and CHI-Square analysis. Results: 150 patients (45 women and 105 men) met our study criteria. There were no significant differences between men and women in age, BMI, GFR, Troponin, BNP, rates of hypertension, diabetes mellitus, hyperlipidemia, obesity, smoking history or utilization of aspirin, or statins. Grace Scores and Diamond Forrester Risk were similar. Women were less likely than men to have significant coronary disease on CA (M:66% W:34% p=0.00) or require intervention (M:73% W:34% p=0.00). There were no significant differences in rates of reported coronary disease on NI testing (M:53%, W:55% p=0.81), however, rates of artifact in NI testing were significantly higher in women (M:26% W:55% p=0.00). Women were significantly more likely to undergo NST rather than CTCA (M:22%, W:45% p=0.00). Conclusions: Our study found that women were far less likely to have significant coronary disease on CA after a NI workup, were more likely to have NI studies with reported artifact and were more likely to undergo NST than CTCA. We highlight differences between genders in significant CAD and need for intervention that may be related to higher rates artifact in NI results in women. Furthermore, we demonstrate the correlation with gender and physician decision making when selecting NI imaging, a finding which warrants further study.