Absence Of Obstructive Coronary Artery Disease Research Articles

Abstract 4113147: Global Longitudinal Strain in Patients with Coronary Microvascular Dysfunction

Background: Angina in the absence of obstructive coronary artery disease (ANOCA) is a common but undertreated condition due to poorly understood pathophysiologic mechanisms. This study investigates the potential link between ANOCA and left ventricular (LV) dysfunction, specifically focusing on coronary microvascular dysfunction (CMD) as a contributing factor. Methods: Registry patients diagnosed with CMD, were compared with those without CMD. Echocardiographic analysis, including global longitudinal strain (GLS), was conducted using advanced software aided by human expertise. Out of 281 patients, 121 had echocardiograms accessible in our systems for review. After excluding patients with echocardiograms of low technical quality, those with cardiomyopathies, or a history of myocardial ischemia, we identified 21 patients with CMD and 38 without CMD. Results: The mean age of the entire cohort was 59.5±11.5 years, with 76.7% being female. The prevalence of hypertension and hyperlipidemia was 71.2% and 67.8%, respectively, while 23.7% had diabetes. More than half of the patients had a CCS angina score of 2 (59.3%). There were no differences in medication usage during catheterization between the two groups concerning beta-blockers, nitrates, calcium channel blockers, and diuretics. No discrepancies were observed between the two groups in LVEF (overall mean of 62±8), LV mass, ventricle and atrium sizes and measurements, diastolic function, and other commonly used and reported echocardiographic variables. Despite initial hypotheses suggesting CMD-related alterations in LV mechanical function, no significant differences in GLS were observed between CMD-positive and CMD-negative groups. Conclusion: Our findings, although inconclusive, underscore the need for further large-scale investigations integrating comprehensive echocardiographic assessments to elucidate the complex interplay between CMD and LV mechanical function.

Coronary inflammation stratifies risk in patients undergoing coronary CT angiography: the Oxford Risk Factors and Non-Invasive Imaging (ORFAN) study

Abstract Background Patients with chest pain symptoms often undergo coronary CT angiography (CCTA) for the diagnosis of obstructive coronary artery disease (CAD) to guide revascularisation. However, acute cardiac events could occur in the absence of obstructive CAD. Further risk stratification of patients could potentially be useful by quantifying coronary inflammation using the Fat Attenuation Index (FAI) Score, and an artificial intelligence (AI)-assisted prognostic model that captures the inflammatory risk by integrating CCTA-derived metrics (including FAI Score and plaque burden) and the patient’s clinical risk factors. Purpose To evaluate the risk of cardiac events among patients without obstructive CAD, and the prognostic value of integrating coronary inflammation in risk stratifying this patient group. Methods From the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, patients undergoing CCTA in 7 UK Hospitals (n=40,091) were followed up for the incidence of cardiac mortality over a median(IQR) of 2.7(1.4-5.3) years. In a nested cohort of 3,393 patients with long-term follow up, we evaluated the long-term prognostic value of FAI Score and the performance of AI-Risk algorithm over a median(IQR) follow up of 7.7(6.4-9.1) years. Reclassification of risk category from AI-Risk was compared with contemporary clinical risk score (QRISK3). Results Patients without obstructive CAD (n=32,533, 81.1%) accounted for 63.7% of all cardiac deaths (n=1,754) during follow up, highlighting the substantial proportion of cardiac events in absolute terms given a large proportion of patients without obstructive CAD. In the nested cohort with long-term follow up, FAI Score in any of the 3 epicardial coronary arteries was significantly associated with cardiac mortality with or without obstructive CAD. In the whole cohort, the highest quartile of FAI Score in LAD showed 20-times higher risk of cardiac death compared with the lowest quartile (Panel A). Integrating coronary inflammation with clinical risk factors and plaque burden, patients with very-high AI-Risk classification showed 6-fold higher risk of cardiac mortality compared to low/medium risk, with good alignment of the incident predicted events from AI-Risk and observed events. (Panel B) The predicted cardiac mortality from AI-Risk also demonstrated good calibration with the observed events in the whole population. (Panel C) Finally, AI-Risk significantly reclassify the risk above clinical risk factor-based prediction (QRISK3) (Panel D). Conclusion Patients with high coronary inflammation measured by FAI Score showed significantly elevated risk for cardiac mortality. The AI-enabled absolute risk prediction algorithm leads to significant reclassification of patients undergoing routine CCTA, and can be used as a precision medicine tool.

The role of markers of endothelial dysfunction in the pathogenesis of coronary microvascular dysfunction in patients with non-obstructive coronary artery disease

Aim. To study the potential of non-invasive biomarkers in the diagnosis of coronary microvascular dysfunction (CMD) and prediction of the course of heart failure with preserved ejection fraction (HFpEF) in non-obstructive coronary artery disease.Materials and methods. The 12-month observational study included 118 consecutive patients (6 patients dropped out of the study due to contact loss) with non-obstructive coronary artery disease (CAD) and HFpEF (62 [59; 64]%). At the beginning of the study, serum levels of several biomarkers were assessed using the enzyme immunoassay: N-terminal pro-B-type natriuretic peptide (NT-proBNP), vascular endothelial growth factor (VEGF), and endothelin-1. Coronary flow reserve (CFR) was examined using dynamic single photon emission computed tomography. In the absence of obstructive CAD, CMD was defined as a global decrease in CFR ≤ 2. Echocardiography was used to determine parameters of hemodynamics, LV diastolic dysfunction, and myocardial stress. LV global longitudinal strain (GLS) was assessed using 2D speckle tracking.Results. The patients were divided into groups depending on the presence of CMD: group 1 included patients with CMD (n = 43), group 2 included those without it (n = 75). In patients in group 1, serum levels of endothelin-1 were 1.9 times higher (p = 0.012), levels of VEGF were 2.16 times higher (p = 0.008), and the concentration of NT-proBNP was 2.6 times higher (p = 0.004) than in patients in group 2. According to the ROC analysis, the concentrations of endothelin-1 ≥ 6.9 pg / ml (AUC = 0.711; p = 0.040) and VEGF ≥ 346.7 pg / ml (AUC = 0.756; p = 0.002) were considered as markers associated with the presence of CMD in patients with non-obstructive CAD. The multivariate regression analysis showed that only the presence of CMD (odds ratio (OR) 2.42; 95% confidence interval (95% CI) 1.26–5.85; p < 0.001) and an increase in NT-proBNP ≥ 760.5 pg / ml (OR 1.33; 95% CI 1.08–3.19; p = 0.023) were factors associated with adverse events, and their combination increased the risk of HFpEF progression by more than 3 times (OR 3.18; 95% CI 2.76–7.98; p < 0.001), whereas markers of endothelial dysfunction were not independent predictors. Conclusion. Endothelin-1 ≥ 6.9 pg / ml and VEGF ≥ 346.7 pg / ml can be used as non-invasive markers for the diagnosis of CMD. However, markers of endothelial dysfunction were not independent predictors of HFpEF progression in patients with non-obstructive CAD during 12-month follow-up.

Cost-effectiveness of a novel AI technology to quantify coronary inflammation and cardiovascular risk in patients undergoing routine Coronary Computed Tomography Angiography.

Coronary Computed Tomography Angiography (CCTA) is a first line investigation for chest pain in patients with suspected obstructive coronary artery disease (CAD). However, many acute cardiac events occur in the absence of obstructive CAD. We assessed the lifetime cost-effectiveness of integrating a novel artificial intelligence-enhanced image analysis algorithm (AI-Risk) that stratifies the risk of cardiac events by quantifying coronary inflammation, combined with the extent of coronary artery plaque and clinical risk factors, by analysing images from routine CCTA. A hybrid decision-tree with population cohort Markov model was developed from 3,393 consecutive patients who underwent routine CCTA for suspected obstructive CAD and followed up for major adverse cardiac events over a median(IQR) of 7.7(6.4-9.1) years. In a prospective real-world evaluation survey of 744 consecutive patients undergoing CCTA for chest pain investigation, the availability of AI-Risk assessment led to treatment initiation or intensification in 45% of patients. In a further prospective study of 1,214 consecutive patients with extensive guideline recommended cardiovascular risk profiling, AI-Risk stratification led to treatment initiation or intensification in 39% of patients beyond the current clinical guideline recommendations. Treatment guided by AI-Risk modelled over a lifetime horizon could lead to fewer cardiac events (relative reductions of 4%, 4%, 11%, and 12% for myocardial infarction, ischaemic stroke, heart failure and cardiac death, respectively). Implementing AI-Risk classification in routine interpretation of CCTA is highly likely to be cost-effective (Incremental cost-effectiveness ratio £1,371-3,244), both in scenarios of current guideline compliance or when applied only to patients without obstructive CAD. Compared with standard care, the addition of AI-Risk assessment in routine CCTA interpretation is cost effective, by refining risk guided medical management.

Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study

Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

Validation and potential usefulness of the updated PROMISE minimal risk tool in patients with suspected coronary artery disease undergoing coronary CT angiography

Abstract Introduction The steady decline in test positivity among patients with suspected coronary artery disease (CAD) has raised interest in developing strategies to identify patients who may not require testing. The updated PROMISE minimal-risk tool (PMRT) was developed specifically for this purpose, but never tested in our population. The aim of this study was to assess the diagnostic performance of this new tool, and to compare it with the guideline-recommended pre-test probability (PTP) and with the risk factor-weighted clinical likelihood (RF-CL) model in a Portuguese cohort of symptomatic patients undergoing coronary computed tomography angiography (CCTA). Methods We conducted a two-centre cross-sectional study of symptomatic patients undergoing CCTA for suspected CAD. Key exclusion criteria were age &amp;lt;30 years, known CAD, suspected acute coronary syndrome or symptoms other than chest pain or dyspnoea. A simplified version of the updated PMRT (without HDL-C), the guideline PTP, and RF-CL score were calculated for each patient. Obstructive CAD was defined as any luminal stenosis ≥ 50% on CCTA. ‘Low risk’ was defined as absence of obstructive CAD and coronary artery calcium (CAC) score &amp;lt; 100 (both conditions present, where CCTA results are unlikely to change patient management). The cut-off value of the PMRT with 95% positive predictive value for identifying patients with ‘Low risk’ was identified in ROC curve analysis. Results A total of 2162 patients (mean age 60±11years, 59% female) were included. Overall, 14.9% (N=323) of patients had obstructive CAD, and 73.5% (N=1589) fulfilled the criteria for ‘Low risk’. Patients with ‘Low risk’ were more frequently female, had higher prevalence of non-anginal chest pain and had fewer cardiovascular risk factors. For obstructive CAD, the discriminative power of the updated PMRT was similar to the one provided by the guideline PTP and RF-CL models (Figure 1A). However, for identifying patients with ‘Low risk’, the updated PMRT showed greater discriminative power than the guideline PTP and RF-CL models (Figure1B). The PMRT cut-off value with 95% positive predictive value for detecting patients at "Low risk" was identified as &amp;gt;46%. A total of 458 patients (21.2%) had a PMRT &amp;gt;46%. Conclusion In this cohort of symptomatic patients undergoing CCTA, the updated PMRT showed similar discriminative power for obstructive CAD, but greater discriminative power to identify "Low risk" than the guideline-recommended PTP and the RF-CL models. The criterion that identified "Low Risk" with 95% positive predictive value was present in roughly one fifth of patients undergoing CCTA, who would derive less benefit from testing.

Validation and potential usefulness of the updated PROMISE Minimal Risk Tool in patients with suspected coronary artery disease undergoing coronary CT angiography

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The steady decline in test positivity among patients with suspected coronary artery disease (CAD) has raised interest in developing strategies to identify patients who may not require testing. The updated PROMISE minimal-risk tool (PMRT) was developed specifically for this purpose, but never tested in our population. The aim of this study was to assess the diagnostic performance of this new tool, and to compare it with the guideline-recommended pre-test probability (PTP) and with the risk factor-weighted clinical likelihood (RF-CL) model in a Portuguese cohort of symptomatic patients undergoing coronary computed tomography angiography (CCTA). Methods We conducted a two-centre cross-sectional study of symptomatic patients undergoing CCTA for suspected CAD. Key exclusion criteria were age &amp;lt;30 years, known CAD, suspected acute coronary syndrome or symptoms other than chest pain or dyspnoea. A simplified version of the updated PMRT (without HDL-C), the guideline PTP, and RF-CL score were calculated for each patient. Obstructive CAD was defined as any luminal stenosis ≥ 50% on CCTA. ‘Low risk’ was defined as absence of obstructive CAD and coronary artery calcium (CAC) score &amp;lt; 100 (both conditions present, where CCTA results are unlikely to change patient management). The cut-off value of the PMRT with 95% positive predictive value for identifying patients with ‘Low risk’ was identified in ROC curve analysis. Results A total of 2162 patients (mean age 60±11years, 59% female) were included. Overall, 14.9% (N=323) of patients had obstructive CAD, and 73.5% (N=1589) fulfilled the criteria for ‘Low risk’. Patients with ‘Low risk’ were more frequently female, had higher prevalence of non-anginal chest pain and had fewer cardiovascular risk factors. For obstructive CAD, the discriminative power of the updated PMRT was similar to the one provided by the guideline PTP and RF-CL models (Figure 1A). However, for identifying patients with ‘Low risk’, the updated PMRT showed greater discriminative power than the guideline PTP and RF-CL models (Figure1B). The PMRT cut-off value with 95% positive predictive value for detecting patients at "Low risk" was identified as &amp;gt;46%. A total of 458 patients (21.2%) had a PMRT &amp;gt;46%. Conclusion In this cohort of symptomatic patients undergoing CCTA, the updated PMRT showed similar discriminative power for obstructive CAD, but greater discriminative power to identify "Low risk" than the guideline-recommended PTP and the RF-CL models. The criterion that identified "Low Risk" with 95% positive predictive value was present in roughly one fifth of patients undergoing CCTA, who would be less likely to derive benefit from testing.

The impact of cardiac SPECT in risk stratification for women with suspected coronary artery disease in a very high cardiovascular risk country

Abstract Funding Acknowledgements Type of funding sources: None. Background Risk stratification has become increasingly important in the management of women with coronary artery disease (CAD). Population based cross-sectional study of cardiovascular risk (CVR) factors in Latvia revealed that women in age 25 -74 are in a very high CVR group: more than 60% of women have dyslipidemia, 30% have arterial hypertension (AH) and are overweight. Purpose To evaluate CVR factor profile in women with suspected CAD and performed cardiac single photon emission computed tomography (SPECT) and to prove the need of perfusion imaging for women in a very high cardiovascular risk population. Methods Cardiac SPECT for women with suspected CAD and positive or non-informative exercise test was performed in a single center from 2018 till 2022. The patients were analyzed by risk factors and perfusion test result, divided into 2 groups: normal myocardial perfusion or true myocardial perfusion defect. Results 466 patients without known CAD were analyzed. The mean age of cohort patients was 59.3±10.9 years. 28 (6.0%) patients had no CVR factors, 90 (19.3%) women had only 1, but the rest of them (348, 74.7%) had 2 or more CVR factors. Dyslipidemia was present in 358 (76.8%), AH in 282 (60.5%) and type 2 Diabetes mellitus (T2DM) in 27 (5.8%) patients. More than half of patients (n=303, 65.0%) were overweight (BMI&amp;gt;25.0 kg/m2). 65 (13.9%) women were current or ex-smokers. True myocardial perfusion defect was detected in 96 patients (20.6%). There was no statistically significant difference between CVR risk factor count and cardiac SPECT result (p=0.229), although there were patients with significant perfusion defect without any risk factor present. However, significant correlation between risk factors and detection of obstructive coronary artery disease (CAD) after positive cardiac SPECT was found (p&amp;lt;0.001). Totally in study was detected 71 patients with suspected ischemia with non-obstructive CAD (INOCA), but further investigation with intracoronary physiology measurements – coronary flow reserve (CFR), index of microvascular resistance (IMR) and acetylcholine provocation test is required to define INOCA endotype. Conclusions The cardiac SPECT is an appropriate diagnostic method for women patients with suspected CAD. Even in patients with no CVR factors, but with positive or non-informative exercise test, the CAD is present, therefore they should be referred to cardiac SPECT in a very high CVR country. In patients with significant perfusion defect and absence of obstructive CAD, the performance of intracoronary physiology measurements is required.

Significance of Beta-Blocker in Patients with Hypertensive Left Ventricular Hypertrophy and Myocardial Ischemia.

Arterial Hypertension (HTN) is a key risk factor for left ventricular hypertrophy (LVH) and a cause of ischemic heart disease (IHD). The association between myocardial ischemia and HTN LVH is strong because myocardial ischemia can occur in HTN LVH even in the absence of significant stenoses of epicardial coronary arteries. To analyze pathophysiological characteristics/co-morbidities precipitating myocardial ischemia in patients with HTN LVH and provide a rationale for recommending beta-blockers (BBs) to prevent/treat ischemia in LVH. We searched PubMed, SCOPUS, PubMed, Elsevier, Springer Verlag, and Google Scholar for review articles and guidelines on hypertension from 01/01/2000 until 01/05/2022. The search was limited to publications written in English. HTN LVH worsens ischemia in coronary artery disease (CAD) patients. Even without obstructive CAD, several pathophysiological mechanisms in HTN LVH can lead to myocardial ischemia. In the same guidelines that recommend BBs for patients with HTN and CAD, we could not find a single recommendation for BBs in patients with HTN LVH but without proven CAD. There are several reasons for the proposal of using some BBs to control ischemia in patients with HTN and LVH (even in the absence of obstructive CAD). Some BBs ought to be considered to prevent/treat ischemia in patients with HTN LVH (even in the absence of obstructive CAD). Furthermore, LVH and ischemic events are important causes of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death; these events are another reason for recommending certain BBs for HTN LVH.

Asymmetric Dimethylarginine as a Biomarker in Coronary Artery Disease.

As atherosclerosis remains a leading cause of morbidity and mortality worldwide despite the advances in its medical and interventional management, the identification of markers associated with its incidence and prognosis constitutes an appealing prospect. In this regard, asymmetric dimethylarginine (ADMA), a well-studied endogenous endothelial nitric oxide synthase inhibitor, represents a core mediator of endothelial dysfunction in atherosclerotic diseases. Given the pathophysiologic background of this molecule, its importance in the most frequent atherosclerotic manifestation, coronary artery disease (CAD), has been extensively studied in the past decades. The available evidence suggests elevation of ADMA in the presence of common cardiovascular risk factors, namely diabetes mellitus, arterial hypertension, and hypertriglyceridemia, being related to endothelial dysfunction and incident major adverse cardiovascular events in these groups of patients. Moreover, ADMA is associated with CAD occurrence and severity, as well as its prognosis, especially in populations with renal impairment. Interestingly, even in the absence of obstructive CAD, increased ADMA may indicate coronary endothelial dysfunction and epicardial vasomotor dysfunction, which are prognostication markers for incident cardiovascular events. In the case of acute coronary syndromes, high ADMA levels signify an augmented risk of incomplete ST-segment elevation resolution and poorer prognosis. Abnormal ADMA elevations may indicate adverse outcomes following percutaneous or surgical coronary revascularization, such as in-stent restenosis, graft patency, and hard cardiovascular endpoints. Finally, since its association with inflammation is significant, chronic inflammatory conditions may present with coronary endothelial dysfunction and subclinical coronary atherosclerosis by means of increased coronary artery calcium, with augmented ADMA acting as a biomarker.

Endothelial progenitor cells and major adverse cardiovascular events in patients receiving elective coronary angiography

Background and purpose: The association of circulating endothelial progenitor cells (EPCs) with different cardiovascular diseases and their related major adverse cardiovascular events (MACE) remained inconclusive. We aimed to clarify associations between the circulating EPC levels and the risk of MACE concerning different atherosclerosis-related diseases. Methods: This prospective cohort study was conducted from December 2009 to March 2015. Patients who underwent non-emergent coronary angiography (CAG) were included. The circulating EPC levels were measured using flow cytometry prior to the CAG procedure. The study evaluation of circulating EPC levels among patients with obstructive coronary artery disease (CAD) and other comorbidities. Patients were then assigned to tertiles by circulating EPC levels to evaluate the predictive values of the development of MACEs. Results: The study enrolled 1099 patients, of whom, 736 (67%) were men, with a mean age of 66.7 ± 12.5 years old. Overall, 637 (58%) patients were diagnosed with obstructive CAD according to CAG. MACE occurred in 268 (24.4%) patients. Circulating EPC levels were lower in patients with peripheral artery disease (PAD) but not associated with the presence of obstructive CAD, atrial fibrillation, chronic kidney disease (CKD), heart failure, and diabetes mellitus. Higher circulating EPC levels are linked with higher MACE among patients with suspected CAD, regardless of the presence or absence of obstructive CAD or CKD. The association did not present in patients with PAD. Conclusions: Higher circulating EPC levels are associated with a greater risk of MACE, regardless of the presence of obstructive CAD or CKD. This association was not apparent in the patients with PAD, suggesting impaired endothelial repair in these patients.

26 CORONARY MICROVASCULAR DYSFUNCTION: IT COULD BE (ALSO) A MAN'S WORLD!

Abstract Introduction Coronary microvascular dysfunction (CMD) is one of the possible manifestation of ischaemic heart disease with signs and symptoms of myocardial ischaemia, but no obstructive coronary artery disease (CAD). CMD is defined by an impaired coronary flow reserve owing to functional and/or structural abnormalities of the microcirculation and it is associated with adverse cardiovascular prognosis. Women are known to be more likely than men to have angina in the absence of obstructive CAD and CMD has been proposed as one of the major reasons for this presentation. However, also in men, CMD should be recognized, in order to give the best treatment to relieve symptoms and improve patient prognosis. Index of microvascular resistance (IMR) and coronary flow reserve (CFR) are needed to diagnose CMD and are now easily obtained with pressure wires measurement. Methods Since the adoption in our Cath Lab of the PressureWire™ X Guidewire with the Coroventis CoroFlow Cardiovascular System (Abbott) we started to study IMR and CFR in patients with no obstructive CAD and typical angina. No acute coronary syndromes have been studied in our Cath Lab so far. In this brief study we report a descriptive analysis of the first patients studied and of the first period of follow-up, focusing on men. Results From January 2022 (date when we received the new software) to April 2022 we studied 24 patients and 8 (33%) were men. Among men, mean age was 58±5 yo and two have been already treated with PCI during the previous 6 months. Mean ejection fraction was 57±2% and mean GFR was 76±20 ml/min/mq. 7 out of 8 patients were affected by dyslipidemia, 5 were smoker, 50% were affected by arterial hypertension and only 1 by diabetes. Mean RFR and FFR in left anterior descending artery were 0.92±0.02 and 0.92±0.03, respectively. In 6/8 (75%) patients IMR derived was &amp;gt;25 and, among them 4 (66%) had CFR&amp;lt;2. After coronary study we tried to optimize medical therapy in all these patients, adding or changing to Zofenopril previous ACE inhibitor therapy, adding or titrating Ranolazine and adding or titrating negative chronotropic therapy (beta blockers or calcium channel blockers). After therapy optimization none of the patients had resumption of symptoms (follow-up from 3 to 7 months). Conclusions Even if historically considered a women's disease, we should remember that CMD also affects men. New widespread technologies should be used systematically to rule out CMD and to define patients’ symptoms mechanisms. This would lead to targeted therapy that could improve patient's lives.

691 RELATION BETWEEN HIGH-SENSITIVITY TROPONIN I SERUM LEVELS AND MYOCARDIAL ISCHEMIA IN PATIENTS WITH SUSPECTED CHRONIC CORONARY SYNDROME: THE RESET-MI STUDY

Abstract Background Although the detection of a rise and/or fall pattern of cardiac troponin (cTn) serum levels in presence of a clinical context of acute myocardial ischemia, represents the main criterion for the diagnosis of acute myocardial infarction (AMI), troponins may increase in various conditions of myocardial injury different from ischemic myocardial necrosis or simply following myocardial ischemia, in the absence of cell necrosis. Some studies found that troponins also increase after physical exertion and other types of stressful stimuli in the absence of obstructive CAD and myocardial ischemia. No previous study, however, investigated the relation between cTn serum levels and the extent of myocardial ischemia in patients with a suspect of CCS. Methods We prospectively enrolled consecutive patients undergoing an elective stress myocardial perfusion scintigraphy (MPS) because of a clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups based on the evidence and degree of stress-induced MI at MPS: 1) group 1, no MI (≤4%); 2) group 2, mild MI (5-10%); 3) group 3, moderate-to-severe MI (≥10%). High sensitivity (hs)-cTnI was measured immediately before (T0) and 1 hour (T1) and 4 hours (T2) after the stress test. A successive evaluation of patients was performed at 24 months. Results One-hundred consecutive patients (64 males; age 65.5±9.5 years) were enrolled in the study. Serum hs-cTnI concentrations significantly increased after MPS, compared to baseline, in the whole population, from (median, interquartile range) 3.9 (2.5-6.1) ng/L at T0, to 4.2 (2.8-7.3) ng/L at T1 (p&amp;lt;0.001) and 6.7 (3.8-14.1) ng/L at T2 (p&amp;lt;0.001 vs. both T0 and T1). The increase in hs-cTnI did not significantly differ between the 3 groups (p=0.35). Heart rate achieved during the test was the strongest determinant of cTnI increase (p &amp;lt; 0.001). No major adverse cardiac event occurred during follow-up. Only 12 patients (12%) underwent coronary revascularization, whereas angina episodes were reported by 23 patients (23%). There were no significant differences in hs-cTnI increase after the stress test between patients with clinical events at follow-up compared with those who did not report myocardial revascularization or angina recurrence (p=0.21). Conclusions In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and the extent of myocardial ischemia and is mainly related to myocardial work, as indicated by HR achieved during the test.

Abstract 14553: Clonal Hematopoiesis of Indeterminate Potential is Associated With Atrial Fibrillation in Patients With Early Coronary Artery Disease

Introduction: The mechanistic link between early coronary artery disease (CAD) and atrial fibrillation (AF) continues to be explored. Clonal hematopoiesis of indeterminate potential (CHIP) is increasingly recognized as a risk factor for cardiovascular disease. We hypothesize CHIP further increases the risk for AF in early CAD. Methods: 184 participants underwent invasive coronary angiogram with endothelial function testing. Buffy coat was used for whole exosome sequencing to identify CHIP (variant allele frequency &gt; 2% and minor allele frequency ≤ 0.1%). Early CAD was defined by the presence of coronary endothelial dysfunction (CED) in the absence of obstructive CAD. Invasive coronary angiography with endothelial function testing characterized CED as ≥ 20% increase in coronary artery diameter or ≤ 50% increase in coronary blood flow in response to acetylcholine. AF was identified by ICD-10 code or patient survey and confirmed by an independent investigator by chart review. Cox proportional hazard regression was adjusted for age, sex, and conventional cardiovascular comorbidities (hypertension, diabetes, and total cholesterol). Results: Of the 184 participants, we identified 23 cases with both early CAD and CHIP and 62 normal controls without CHIP or CAD. Case patients were significantly older (mean 60 ±9 vs 52 ±10 years, p = 0.004 years) and predominantly female (74% vs 81%, p = 0.506). AF was more likely among case participants when compared to normal controls (29% vs 10%, p = 0.036). Mean time to AF or last follow-up was 11 ±7 years. Case patients with both early CAD and CHIP were nearly 10 times more likely to develop AF when compared to normal controls in a Cox regression model adjusted for age, sex, and conventional cardiovascular comorbidities (HR 9.52, 95% CI 1.93 - 47.02, p = 0.006). The risk for AF was not significant if we defined cases by only the presence of CHIP (n = 30) or early CAD (n = 122). Conclusions: Patients with both CHIP and early CAD may have greater risk for developing AF beyond the presence of CHIP or CAD alone. Our findings suggest an added mechanistic role of CHIP that further increases the risk for AF in early CAD.

Time-resolved fluorescence based direct two-site apoA-I immunoassays and their clinical application in patients with suspected obstructive coronary artery disease.

ObjectiveHigh-density lipoprotein (HDL) is a heterogeneous group of subpopulations differing in protein/lipid composition and in their anti-atherogenic function. There is a lack of assays that can target the functionality of HDL particles related to atherosclerosis. The objective of this study was to construct two-site apolipoprotein A-I (apoA-I) assays and to evaluate their clinical performance in patients with suspected obstructive coronary artery disease (CAD).Approach and resultsDirect two-site apoA-I assays (named 109–121 and 110–525) were developed to identify the presence of apoA-I in the HDL of patients with CAD using apoA-I antibodies as a single-chain variable fragment fused with alkaline phosphatase. ApoA-I109−121 and apoA-I110−525 were measured in 197 patients undergoing coronary computed tomography angiography (CTA) and myocardial positron emission tomography perfusion imaging due to suspected obstructive CAD. Among patients not using lipid-lowering medication (LLM, n = 125), the level of apoA-I110−525 was higher in the presence than in the absence of coronary atherosclerosis [21.88 (15.89–27.44) mg/dl vs. 17.66 (13.38–24.48) mg/dl, P = 0.01)], whereas there was no difference in apoA-I109−121, HDL cholesterol, and apoA-I determined using a polyclonal apoA-I antibody. The levels of apoA-I109−121 and apoA-I110−525 were similar in the presence or absence of obstructive CAD. Among patients not using LLM, apoA-I110−525 adjusted for age and sex identified individuals with coronary atherosclerosis with a similar accuracy to traditional risk factors [area under the curve [AUC] (95% CI): 0.75(0.66–0.84) 0.71 (0.62–0.81)]. However, a combination of apoA-I110−525 with risk factors did not improve the accuracy [AUC (95% CI): 0.73 (0.64–0.82)].ConclusionDirect two-site apoA-I assays recognizing heterogeneity in reactivity with apoA-I could provide a potential approach to identify individuals at a risk of coronary atherosclerosis. However, their clinical value remains to be studied in larger cohorts.

Coronary Artery Ectasia in the Pathophysiology of Myocardial Infarction With Nonobstructive Coronary Arteries

Coronary artery ectasia (CAE) is associated with an increased risk for acute myocardial infarction (AMI). A significant proportion of patients with AMI have no obstructive coronary artery disease (CAD), however, the underlying mechanism of myocardial infarction with nonobstructive coronary arteries (MINOCA) is poorly understood. Therefore, the present study aimed to investigate whether CAE has a role in the pathogenesis of MINOCA. A total of 1,284 patients who were admitted with a diagnosis of non-ST-segment elevation myocardial infarction were included in the study. Patients were divided into 2 groups according to the presence or absence of obstructive CAD (≥50% stenosis). Patients without obstructive CAD (MINOCA group) and patients with obstructive CAD (no-MINOCA group) were compared regarding the frequency of CAE. Additionally, the association between CAE and MINOCA was investigated. In the study participants, 101 patients (7.9%) were diagnosed with MINOCA, whereas 1,183 (92.1%) had AMI with obstructive CAD. Importantly, the frequency of patients with CAE was significantly higher in patients with MINOCA compared with those with obstructive CAD (22.8% vs 3.5%, p <0.001). Moreover, CAE was observed in 64 patients (4.9%). The frequency of MINOCA was found to be significantly higher in patients with CAE compared with patients without CAE (35.9% vs 6.4%, p <0.001). Furthermore, multivariate analysis demonstrated that the presence of CAE was an independent predictor of MINOCA in patients presented with a diagnosis of non-ST-segment elevation myocardial infarction (odds ratio 1.812, 95% confidence interval 1.376 to 2.581, p <0.001). In conclusion, CAE may be considered as a risk factor for MINOCA and may have a role in the pathophysiology of MINOCA.

Coronary angiography in acute ischemic stroke patients: frequency and determinants of pathological findings in a multicenter cohort study

BackgroundMyocardial injury as indicated by cardiac troponin elevation is associated with poor prognosis in acute stroke patients. Coronary angiography (CAG) is the diagnostic gold-standard to rule-out underlying obstructive coronary artery disease (CAD) in these patients. However, weighing risks and benefits of coronary angiography (CAG) against each other is particularly challenging, because stroke patients undergoing CAG may have a higher risk for secondary intracranial bleeding. Current guidelines remain vague. Thus, the aim of this study was to analyze frequency of pathological findings of CAG and associated clinical factors.MethodsWe analyzed indications and frequency of CAG performed in acute ischemic stroke patients in clinical routine in two European tertiary care hospitals from 2011 to 2018. All data were obtained retrospectively. Multiple logistic regression analyses were performed to identify variables associated with absence of obstructive coronary artery disease defined as presence of at least one coronary vessel stenosis ≥ 50%.ResultsA total of 139 AIS patients underwent CAG. Frequent indications for CAG were suspected acute coronary syndrome (N = 114) or scheduled cardiac surgery (N = 25). Acute coronary stenting was applied in 51/139 patients. Among patients with suspected acute coronary syndrome, no obstructive CAD was found in 27/114 patients. Absence of obstructive CAD was associated with insular cortex lesions, no clinical symptoms for ACS, less than three cardiovascular risk factors, younger age and normal wall motion.ConclusionSeveral variables suggest absence of CAD in AIS patients and may help in clinical decision making in stroke patients with myocardial injury.

Angiographic profile and outcomes in persistent non-valvular atrial fibrillation: A study from tertiary care center in North India

BackgroundThe relationship of atrial fibrillation (AF) with coronary artery disease (CAD) is well established, yet it is often missed. There is evidence of myocardial ischemia on stress imaging in AF patients in the absence of obstructive CAD. In this prospective cohort, we studied the angiographic profiles of non-valvular AF patients. MethodsThe study was a nonrandomized, prospective, single-center observational study of consecutive patients of persistent non-valvular AF. Patients symptomatic for AF despite optimal medical therapy for 3 months were recruited and all underwent coronary angiograms (CAG). Patients with prior history of CAD were excluded. ResultsA total of 70 patients were followed for a mean duration of 12 ± 1.4 months. The mean age of the study group was 66.07 (±11.49) years. Hypertension was the commonest comorbidity seen in 74% patients. Obstructive CAD was present in 32 (46%) patients, non-obstructive (<50% stenosis) CAD in 17 (24%) patients and normal coronaries in 21 (30%) patients. Overall 49 (70%) patients had evidence of CAD. Amongst patients without obstructive CAD, slow flow was seen in 16 (42%) patients. Lower baseline ejection fraction, lower haemoglobin & albumin levels and higher creatinine levels was associated with increased mortality. In patients without obstructive CAD, hospitalizations for fast ventricular rate were significantly increased in those having slow flow on CAG (p = 0.005). ConclusionsMajority (70%) of our patients had evidence of atherosclerotic CAD on CAG. A large proportion of patients without obstructive CAD had slow flow on CAG.

Role of Exercise Treadmill Testing in the Assessment of Coronary Microvascular Disease

ObjectivesThe authors aimed to study the sensitivity and specificity of exercise treadmill testing (ETT) in the diagnosis of coronary microvascular disease (CMD), as well as the prognostic implications of ETT results in patients with CMD. BackgroundETT is validated to evaluate for flow-limiting coronary artery disease (CAD), however, little is known about its use for evaluating CMD. MethodsWe retrospectively studied 249 consecutive patients between 2006 and 2016 who underwent ETT and positron emission tomography within 12 months. Patients with obstructive CAD or left ventricular systolic dysfunction were excluded. CMD was defined as a coronary flow reserve <2. Patients were followed for the occurrence of a first major adverse event (composite of death or hospitalization for myocardial infarction or heart failure). ResultsThe sensitivity and specificity of a positive ETT to detect CMD were 34.7% (95% CI: 25.4%-45.0%) and 64.9% (95% CI: 56.7%-72.5%), respectively. The specificity of a positive ETT to detect CMD increased to 86.8% (95% CI: 80.3%-91.7%) when only classifying studies with ischemic electrocardiogram changes that lasted at least 1 minute into recovery as positive, although at a cost of lower sensitivity (15.3%; 95% CI: 8.8%-24.0%). Over a median follow-up of 6.9 years (IQR: 5.1-8.2 years), 30 (12.1%) patients met the composite endpoint, including 13 (13.3%) with CMD (n = 98). In patients with CMD, ETT result was not associated with the composite endpoint (P = 0.076). ConclusionsOur data suggest limited sensitivity of ETT to detect CMD. However, a positive ETT with ischemic changes that persist at least 1 minute into recovery in the absence of obstructive CAD should raise suspicion for the presence of CMD given a high specificity. Further study is needed with larger patient sample sizes to assess the association between ETT results and outcomes in patients with CMD.

Diagnostic accuracy of SPECT and PET myocardial perfusion imaging in patients with left bundle branch block or ventricular-paced rhythm

BackgroundThe difference in diagnostic accuracy of coronary artery disease (CAD) between vasodilator SPECT and PET myocardial perfusion imaging (MPI) in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR) is unknown. MethodsWe identified patients with LBBB or VPR who underwent either vasodilator SPECT or PET MPI and subsequent coronary angiography. LBBB/VPR-related septal and anteroseptal defects were defined as perfusion defects involving those regions in the absence of obstructive CAD in the left anterior descending artery or left main coronary artery. ResultsOf the 55 patients who underwent coronary angiography, 38 (69%) underwent SPECT and 17 patients (31%) underwent PET. PET compared to SPECT demonstrated higher sensitivity (88% vs 60%), specificity (56% vs 14%), positive predictive value (64% vs 20%), negative predictive value (83% vs 50%), and overall superior diagnostic accuracy (AUC .72 (95% CI .50-.93) vs .37 (95% CI .20-.54), P = .01) to detect obstructive CAD. LBBB/VPR-related septal and anteroseptal defects were more common with SPECT compared to PET (septal: 72% vs 17%, P = .001; anteroseptal: 47% vs 8%, P = .02). ConclusionsPET has higher diagnostic accuracy when compared to SPECT for the detection of obstructive CAD in patients with LBBB or VPR.