Absence Of Coronary Artery Disease Research Articles

Considering the Possible Role of Pharmacists According to the Presence or Absence of Lifestyle-Related Diseases at the Time of Coronary CT Examination and Trends of Medication Use for These Diseases by Medical Doctors.

Because patients often already have coronary artery disease (CAD) at the time of a coronary artery computed tomography angiography (CCTA) examination, we examined the medications prescribed by medical doctors for lifestyle-related diseases and investigated what possible role pharmacists can play in prescribing. Patients (n = 1357) who underwent CCTA examination were divided into two groups according to the presence or absence of lifestyle-related diseases [hypertension (HTN), dyslipidemia (DL) and diabetes mellitus (DM)], and the relationship between the presence or absence of CAD was examined. The rate of CAD was significantly higher in patients with HTN, DL or DM than in patients without these diseases. The blood pressure in the HTN group was 140 ± 20/79 ± 13 mmHg, the low-density lipoprotein cholesterol value in the DL group was 119 ± 35 mg/dL, and the hemoglobin A1c value in the DM group was 7.0 ± 1.1%, all of which were poorly controlled. Anti-hypertensive drugs were used at low rates in the HTN group, statins were used in 47% and ezetimibe was used in 4% of the DL group, and dipeptidyl peptidase-4 inhibitors were used in 41% of the DM group. Since the rate of CAD (+) was high and control of the three major lifestyle-related diseases was poor, pharmacists should advise medical doctors to use combinations of drugs.

Level of Perivascular Inflammation Is Significantly Lower Around the Left Internal Mammary Artery Than Around Native Coronary Arteries.

The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA insitu and native coronary arteries in patients with coronary artery disease. A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA insitu and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA insitu was significantly lower around the 3 coronary arteries (-82.9 [-87.3 to -78.0] versus -70.8 [-75.9 to -65.9]; P<0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16-7.59]; P=0.017). The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA insitu than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04523194.

SCARY ECG IN TAKOTSUBO CARDIOMYOPATHY

Abstract Takotsubo cardiomyopathy (TTC) is characterized by a transient ventricular wall motion abnormality and shares common features with acute coronary syndrome (ACS) with a wide spectrum of triggers, such as both emotional or physical, activating common toxic catecholamines–mediated pathways. TTC might be associated with severe clinical complications. We report a case of a 74–year female patient with circulatory shock with mixed phenotype, distributive due to sepsis and cardiogenic due to TTC. The patient presented to the emergency department with severe hypotension, pathological qSOFA score and clinical and laboratory findings consistent with severe sepsis. ECG showed diffuse lambda ST–segment elevation, also called “shark fin”(fig.1). According to hemodynamically unstable scenario and ECG pattern, emergency coronary angiography was performed, showing absence of coronary artery disease(fig. 2). Echocardiography revealed severe LV systolic disfunction (EF 20–25%) with apical ballooning and severe systolic anterior motion (SAM) of the anterior mitral leaflet eliciting dynamic LVOTO with peak gradient greater than 90 mmHg; fig. 3) and severe MR. Patient was treated with cautious fluid administration, hemotrasfusion and empiric large spectrum antibiotic therapy. According to TTC working diagnosis, even if septic state was thought to contribute to cardiogenic shock, norepinephrine was not administered due to concerns for LVOTO and SAM. After overcoming of dramatic first phase and after hemodynamic steadiness was achieved, beta blockade and ACEi were progressively administered. Seriate transthoracic echocardiogram revealed progressive improvement of LV systolic function, regression of apical ballooning, SAM and LVOTO. ECG monitoring showed regression of ischemic ST elevation. ST elevation has been described in about 56% of TTC cases, however with amplitude tipically lower than in STEMI. Lambda–wave ST elevation has been rarely reported. Vasospasm, local intermittent microvascular constriction, catecholamine–induced metabolic toxicity, transmural systolic wall tension and its the mechano–electric feedback can explain scaring ECG–pattern. Despite its rare prevalence in TTC “shark fin” pattern appears to relate to adverse outcome and it should be used as an early marker of potential further clinical deterioration, suggesting more intensive monitoring to avoid delays in possible therapy escalation.

Autoimmune Disorders in Heart Failure With Preserved Ejection Fraction

BackgroundInflammation plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of an underlying systemic inflammatory disease such as rheumatoid arthritis or systemic lupus erythematosus. ObjectivesThis study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and autoimmune or primary inflammatory disorders. MethodsOf 982 consecutively evaluated patients with HFpEF diagnosed, 79 (8.0%) had autoimmune disorders. HFpEF was defined by invasive cardiopulmonary hemodynamic exercise testing. ResultsFemale sex, higher heart rate, lower hemoglobin, absence of atrial fibrillation, and absence of coronary artery disease were independently associated with autoimmune disorders. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with autoimmune disorders, reflected by lower arterial-venous oxygen content difference at rest (4.2 ± 0.7 mL/dL vs 4.6 ± 1.0 mL/dL; P < 0.001) and during exercise (9.3 ± 2.2 mL/dL vs 10.4 ± 2.2 mL/dL; P < 0.001), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCo2 slope, regression slope relating minute ventilation to carbon dioxide output) was also more impaired (38.0 ± 7.9 vs 36.2 ± 7.3; P = 0.043). Patients with autoimmune disorders had a higher risk of death or heart failure (HF) hospitalization compared with those without in adjusted analyses (HR: 1.95 [95% CI: 1.17-3.27]; P = 0.011) over a median follow-up of 3.0 years, which was primarily attributable to higher risk of HF hospitalization (HR: 2.87 [95% CI: 1.09-7.57]; P = 0.033). ConclusionsPatients with HFpEF and autoimmune disorders have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared with those without.

Impact of coronary artery disease and revascularization on outcomes of transcatheter aortic valve replacement for severe aortic stenosis

Background/purposeTo evaluate the impact of coronary artery disease (CAD), percutaneous coronary intervention (PCI), and coronary lesion complexity on outcomes of transcatheter aortic valve replacement (TAVR) for aortic stenosis. Methods/materialsThis retrospective study included 1042 patients divided into two groups by the presence or absence of CAD (SYNTAX score 0, no history of revascularization). Propensity score matching was used to compare the two groups. The effect of PCI, SYNTAX score, and residual SYNTAX score was also analyzed. ResultsThe median age of the cohort was 82 years, and 641 patients had CAD. After propensity score matching, 346 pairs were analyzed. During 5 years of follow-up (median: 25, range 0–72 months), the rate of coronary intervention was significantly higher in CAD patients (p = 0.018). However, all-cause mortality, composite of all-cause mortality, stroke, and coronary intervention, and overt bleeding defined by VARC-3 were comparable. After stratification, in patients with creatinine ≥1.5 mg/dl, CAD was associated with a worse composite outcome (p = 0.016). Neither PCI nor SYNTAX score was associated with all-cause mortality in CAD patients. Similarly, residual SYNTAX score showed no association with mortality in patients undergoing PCI (all p values >0.7). PCI did not reach a significant difference in overt bleeding in CAD patients (adjusted p = 0.06). ConclusionsDespite a higher incidence of coronary interventions, major clinical outcomes were similar between patients with and without CAD after TAVR. In patients with chronic kidney disease, CAD may be associated with an adverse composite outcome. Neither PCI nor SYNTAX/residual SYNTAX score influenced all-cause mortality.

The Role of Magnetic Resonance Imaging in Cardiomyopathies in the Light of New Guidelines: A Focus on Tissue Mapping.

Cardiomyopathies (CMPs) are a group of myocardial disorders that are characterized by structural and functional abnormalities of the heart muscle. These abnormalities occur in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease. CMPs are an increasingly important topic in the field of cardiovascular diseases due to the complexity of their diagnosis and management. In 2023, the ESC guidelines on cardiomyopathies were first published, marking significant progress in the field. The growth of techniques such as cardiac magnetic resonance imaging (CMR) and genetics has been fueled by the development of multimodal imaging approaches. For the diagnosis of CMPs, a multimodal imaging approach, including CMR, is recommended. CMR has become the standard for non-invasive analysis of cardiac morphology and myocardial function. This document provides an overview of the role of CMR in CMPs, with a focus on tissue mapping. CMR enables the characterization of myocardial tissues and the assessment of cardiac functions. CMR sequences and techniques, such as late gadolinium enhancement (LGE) and parametric mapping, provide detailed information on tissue composition, fibrosis, edema, and myocardial perfusion. These techniques offer valuable insights for early diagnosis, prognostic evaluation, and therapeutic guidance of CMPs. The use of quantitative CMR markers enables personalized treatment plans, improving overall patient outcomes. This review aims to serve as a guide for the use of these new tools in clinical practice.

The new 2023 ESC guidelines for the management of cardiomyopathies: a guiding path for cardiologist decisions.

In the ESC 2023 guidelines, cardiomyopathies are conservatively defined as 'myocardial disorders in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease sufficient to cause the observed myocardial abnormality'. They are morpho-functionally classified as hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathy with the addition of the left ventricular non-dilated cardiomyopathy that describes intermediate phenotypes not fulfilling standard disease definitions despite the presence of myocardial disease on cardiac imaging or tissue analysis. The new ESC guidelines provide 'a guide to the diagnostic approach to cardiomyopathies, highlight general evaluation and management issues, and signpost the reader to the relevant evidence base for the recommendations'. The recommendations and suggestions included in the document provide the tools to build up pathways tailored to specific cardiomyopathy (phenotype and cause) and define therapeutic indications, including target therapies where possible. The impact is on clinical cardiology, where disease-specific care paths can be assisted by the guidelines, and on genetics, both clinics and testing, where deep phenotyping and participated multi-disciplinary evaluation provide a unique tool for validating the pathogenicity of variants. The role of endomyocardial biopsy remains underexploited and confined to particular forms of restrictive cardiomyopathy, myocarditis, and amyloidosis. New research and development will be needed to cover the gaps between science and clinics. Finally, the opening up to disciplines such as bioinformatics, bioengineering, mathematics, and physics will support clinical cardiologists in the best governance of the novel artificial intelligence-assisted resources.

Screening for dilated cardiomyopathy in immediate family members: to whom, how, when (and where).

Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilation and systolic dysfunction in the absence of coronary artery disease, valvular disease, congenital heart disease, or altered haemodynamic conditions. Dilated cardiomyopathy can recognize multiple aetiologies, including infectious processes, effect of toxic substances, immunological mechanisms, and genetic causes. In recent years, many genes coding for proteins involved in the structure and function of the cardiomyocytes have been associated with the development of DCM, making the identification of familial forms increasingly frequent. At the same time, an ever-increasing use of cardiac magnetic resonance imaging has made it possible to identify early morpho-functional alterations in subjects with initial forms of the disease, or carriers of pathogenic genetic variants. The increasingly in-depth understanding of the genetic and molecular mechanisms operating in DCM has also favoured the development of new therapeutic strategies including drugs with molecular targets and gene therapies. In this panorama, screening of family members of patients affected by DCM represents an important tool for early diagnosis, treatment, and prognostic stratification. In relation to its clinical relevance and its complexity, it is important that family screening and follow-up of identified patients are carried out in units dedicated to the treatment and study of cardiomyopathies.

Endovascular Therapy for Thoracic Aortic Mobile Thrombus

Thoracic aortic mobile thrombus (TAMT) in the absence of atherosclerosis, traumatic injury, or thrombophilia represents an uncommon but well-acknowledged form of a non-cardiogenic thromboembolic source. The morbidity and mortality of acute visceral thromboembolism from an aortic thrombus remains elevated, though delay in diagnosis is common given its underappreciated source as a potentially catastrophic aetiology. Nomenclature to describe any thromboembolism to abdominal viscera remains varied throughout the literature with a cardiac source from arrhythmias most prevalent. Computerized tomographic angiogram (CTA) of chest and abdomen is the modality that most commonly diagnoses TAMT. Trans-esophageal echocardiography (TEE), however, has been the imaging modality of choice in defining the specific thrombus morphology of TAMT. Patient morbidity and mortality of TAMT may entail devastating thromboembolism to myriad sites: cerebrum, mesentery, renal and upper and/or lower extremity peripheral vasculatures. Risks factors of developing aortic mural thrombus are explored within each case. Herein are two illustrative cases of TAMT presenting with acute peritoneal signs and symptoms of visceral ischemia, respectively involving spleen and kidney in the first, and spleen and intestine, the second case. Both cases were successfully managed by physical examination, CTA-diagnosis, intravascular ultrasound (IVUS) to define the morphology of the aortic thrombus, and subsequent thoracic endovascular aortic repair (TEVAR) graft deployment.

Pericoronary adipose tissue attenuation in patients with acute aortic dissection based on coronary computed tomography angiography.

Periaortic fat is associated with coronary disease. Thus, it was hypothesized that the inflammation associated with acute aortic dissection (AAD) spreads to pericoronary adipose tissue (PCAT) via thoracic periaortic fat. Pericoronary adipose tissue attenuation (PCATa) serves as a marker for inflammation of perivascular adipose tissue (PVAT). This study sought to examine PCATa in individuals diagnosed with AAD. Consecutive patients with chest pain from May 2020 to September 2022 were prospectively enrolled in this study and underwent coronary computed tomography angiography (CCTA) and/or aorta computed tomography angiography (CTA). Based on the results of the CTA, the patients were divided into the following two groups: (I) the AAD group; and (II) the non-AAD group. PCATa of the right coronary angiography (RCA), left anterior descending (LAD), and left circumflex (LCx) was quantified for each patient using semi-automated software. The PCATa values were compared between the AAD and non-AAD patients according to the atherosclerosis of the coronary arteries. Similarly, the PCATa values of the AAD patients were compared between the preoperative and postoperative steady states. A total of 136 patients (42 female, 94 male; mean age: 63.3±11.9 years) were divided into the two groups according to the presence of aortic dissection on CTA. The RCAPCATa, LADPCATa, and LCxPCATa values were significantly higher in the AAD subjects than the non-AAD subjects, regardless of the presence or absence of atherosclerosis in the coronary arteries [-85.1±9.3 vs. -92.9±10.0 Hounsfield unit (HU); -83.2±7.4 vs. -89.9±9.1 HU; -77.5±8.4 vs. -85.6±7.9 HU, all P<0.001). The preoperative RCAPCATa, LADPCATa, and LCxPCATa values were higher in the AAD patients than the postoperative steady-state patients (-82.9±8.7 vs. -97.6±8.8 HU; -79.8±7.6 vs. -92.8±6.8 HU; -74.6±7.1 vs. -87.7±6.9 HU, all P<0.001). According to the multivariable logistic regression analysis, high RCAPCATa and LADPCATa values were associated with AAD regardless of the degree of stenosis [odds ratio (OR) =0.014; 95% confidence interval (CI): 0.001-0.177; P=0.001 and OR =0.010; 95% CI: 0.001-0.189; P=0.002]. PCATa on computed tomography was increased in patients with AAD regardless of the presence or absence of coronary artery disease (CAD). This suggests that vascular inflammation is present in AAD independent of CAD. Further research should be conducted to investigate the potential of this imaging biomarker to predict AAD and monitor patients' responses to therapies for AAD.

Ferroptosis: A New Mechanism in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DC) is a pathophysiologic condition caused by diabetes mellitus (DM) in the absence of coronary artery disease, valvular heart disease, and hypertension that can lead to heart failure (HF), manifesting itself in the early stages with left ventricular hypertrophy and diastolic dysfunction, with marked HF and decreased systolic function in the later stages. There is still a lack of direct evidence to prove the exact existence of DC. Ferroptosis is a novel form of cell death characterized by reactive oxygen species (ROS) accumulation and lipid peroxidation. Several cell and animal studies have shown that ferroptosis is closely related to DC progression. This review systematically summarizes the related pathogenic mechanisms of ferroptosis in DC, including the reduction of cardiac RDH10 induced ferroptosis in DC cardiomyocytes which mediated by retinol metabolism disorders; CD36 overexpression caused lipid deposition and decreased GPX4 expression in DC cardiomyocytes, leading to the development of ferroptosis; Nrf2 mediated iron overload and lipid peroxidation in DC cardiomyocytes and promoted ferroptosis; lncRNA-ZFAS1 as a ceRNA, combined with miR-150-5p to inhibit CCND2 expression in DC cardiomyocytes, thereby triggering ferroptosis.

Pathogenetic and clinical rationale for syntropic pathology based on metabolic syndrome, coronary heart disease and type 2 diabetes mellitus

Pathogenetic and clinical rationale for syntropic pathology based on metabolic syndrome, coronary heart disease and type 2 diabetes mellitus

Differential Impact of Blood Pressure Control Targets on Epicardial Coronary Flow After Transcatheter Aortic Valve Replacement

BackgroundThe cause for the association between increased cardiovascular mortality rates and lower blood pressure (BP) after aortic valve replacement (AVR) is unclear. This study aims to assess how the epicardial coronary flow (ECF) after AVR varies as BP levels are changed in the presence of a right coronary lesion. MethodsThe hemodynamics of a 3D printed aortic root model with a SAPIEN 3 26 deployed were evaluated in an in vitro left heart simulator under a range of varying systolic blood pressure (SBP) and diastolic blood pressure (DBP). ECF and the flow ratio index were calculated. Flow index value <0.8 was considered a threshold for ischemia. ResultsAs SBP decreased, the average ECF decreased below the physiological coronary minimum at 120 mmHg. As DBP decreased, the average ECF was still maintained above the physiological minimum. The flow ratio index was >0.9 for SBP ≥130 mmHg. However, at an SBP of 120 mmHg, the flow ratio was 0.63 (p ≤ 0.0055). With decreasing DBP, no BP condition yielded a flow ratio index that was less than 0.91. ConclusionsReducing BP to the current recommended levels assigned for the general population after AVR in the presence of coronary artery disease may require reconsideration of levels and treatment priority. Additional studies are needed to fully understand the changes in ECF dynamics after AVR in the presence and absence of coronary artery disease.

Fifteen-year follow-up and impact of age and sex on cardiovascular outcomes in diabetes and non-diabetes patients without CAD

Abstract Background In the absence of angiographically-detectable coronary artery disease (CAD), patients with diabetes have a risk of myocardial infarction that is comparable to patients without diabetes, while still having higher risks of ischemic stroke and all-cause mortality when followed for up to 10 years. In the current study we extended follow-up to 15 years and, additionally, examined the impact of age and sex on cardiovascular risk in diabetes and non-diabetes patients without CAD. Purpose To examine the cardiovascular risk and mortality associated with age and sex in diabetes and non-diabetes patients without CAD. Methods We included every patient with no or mild CAD when examined by coronary angiography in Western Denmark from 2003-2021 with and without diabetes. We performed age-stratified (&amp;lt;65 year, 65-74 years, and ≥75 years) and sex-stratified analyses. Patients were followed for up to 15 years. Outcomes were myocardial infarction, ischemic stroke, and all-cause death. We estimated adjusted hazard ratios (aHR) using Cox regression. Results We included 60,712 patients without angiographically detectable CAD, of whom 7,690 (12.6%) had diabetes. Median age was 62 years and 51% were men. Median follow-up was 9 years ((inter-quartile range 6-13)). Diabetes was associated with an increased 15-year risk of myocardial infarction (5.8% versus 4.1% aHR 1.30, 95% CI 1.13-1.50), ischemic stroke (8.1% vs 4.0%, aHR 1.87, 95% CI 1.66-2.10), and all-cause death (46.2% vs 33.1%, aHR 1.66, 95% CI 1.58-1.73) compared to patients without diabetes. The relative risk associated with diabetes declined by age (Figure 1), while there was no sex-dependent difference associated with diabetes (Figure 2). Conclusions At 15-year follow-up, diabetes patients without angiographically-detectable CAD at baseline had a relatively small increased risk of myocardial infarction but a substantial increased risk of ischemic stroke and all-cause mortality. Furthermore, the relative importance of diabetes decreased with age, while being independent of sex. These results support that aggressive multifactorial cardiovascular risk management, even in the absence of CAD and independently of age and sex, should be initiated when diabetes is diagnosed.Figure 1Figure 2

Circulating large Extracellular Vesicles (EV-L) from STEMI patients contribute to post-injury adverse myocardial remodeling

Abstract Background While primary percutaneous coronary intervention (PCI) is the treatment of choice in patients with ST-segment elevation myocardial infarction (STEMI), this treatment does not fully prevent late adverse cardiac remodeling. Infarcted myocardial tissue releases damage-associated extracellular vesicles (EV) that mediate tissue inflammation and may regulate myocardial remodeling. Here, we investigated the role of circulating EV in STEMI patients, with a focus on endothelial cell (EC) injury and myocardial fibrosis. Methods Peripheral blood samples were obtained from STEMI patients (n=30) within 4 hrs of onset of pain before PCI and from age- and gender-matched healthy control (CTRL; n=30) with documented absence of coronary artery disease. Raw serum was characterized by atomic force microscopy (AFM) single-particle morphometry. Large EV (EV-L) were isolated by differential centrifugation and used for in vitro experiments on human aortic endothelial cells (hAEC), and human cardiac fibroblast (hCF). Results AFM analysis showed a 7.5-fold increase in EV-L in STEMI vs. CTRL serum. In vitro treatment of hAEC with EV-L from STEMI patients, but not CTRL-EV-L, induced an increase in reactive oxygen species (ROS; 1.15-Fold increase), p66SHC and oxidized low-density lipoprotein receptor 1 (LOX-1) expression (1.34 and 20-Fold increase, respectively), and cell death (1.40-Fold increase). Interestingly, ELISA analysis on EV-L showed an enrichment of LOX-1 in STEMI-EV-L compared to CTRL-EV-L (3.01-Fold increase). Moreover, STEMI-EV-L, but not CTRL-EV-L, stimulated in vitro proliferation (1.4-Fold increase) of hCF and their activation in myofibroblasts, as assessed by alpha smooth muscle actin (αSMA) expression (1.8-fold increase), resulting in increased extracellular matrix (ECM) secretion (1.5-Fold increase). Conclusions Our preliminary data showed a pathological role of circulating EV-L derived from STEMI patients. In particular, results from in vitro experiments evidence their function in inducing endothelial damage and activation of cardiac fibroblast into myofibroblast; two important features in the progression of pathological myocardial remodeling.Graphical abstract

Rethinking the false positive exercise stress test in the context of coronary microvascular dysfunction

Abstract Background Exercise stress testing (EST) was the traditional tool to detect myocardial ischaemia, but its use has declined due to its perceived high false positive rate. However, EST was historically validated against the reference standard of obstructive coronary artery disease (CAD). It is now well recognised that myocardial ischaemia can occur in the absence of CAD and this cohort, termed angina with non-obstructive coronary arteries (ANOCA), comprises nearly 50% of all patients presenting with stable angina. Purpose Our study assesses the accuracy of EST in detecting a substrate for myocardial ischaemia, with the reference standard being comprehensive coronary physiology assessment in patients with ANOCA. Methods Patients with typical angina and non-obstructive coronary arteries underwent physiological characterisation of the coronary circulation using a dual sensor-tipped intracoronary guidewire in the left anterior descending artery. The epicardial vessel was assessed by Fractional Flow Reserve (FFR) and the microcirculation by both endothelium-independent function (coronary flow reserve, CFR, using intravenous adenosine) and endothelium-dependent function (acetylcholine flow reserve, AChFR, using intracoronary acetylcholine infusion). Those with FFR≤0.80 were excluded per protocol. Coronary microvascular dysfunction was defined a priori as impaired CFR (&amp;lt;2.5) or impaired AChFR (≤1.5). All patients underwent a treadmill EST, using a standard Bruce protocol, with ischaemic electrocardiographic (ECG) changes defined as the appearance of 0.1mV ST-segment depression 80 milliseconds from the J-point. Patients, physiologists, and researchers were all blinded to the coronary physiology data. All data are presented as mean±SD or median (IQR). Results Ninety-one patients [67% female, 62±9 years, CCS 3 (2 to 3)] were recruited into this study. EST was performed 27 (15 to 139) days after angiography. Twenty-seven patients (30%) developed ischaemic ECG changes during their EST (Ischaemic group), whereas 64 patients (70%) did not (Control group). Both groups were phenotypically similar for demographics, risk factors, exercise time and FFR (Figure 1). 100% of the Ischaemic group and 69% of the control group had CMD. Conversely, 38% of patients with CMD developed ischaemic ECG changes on exercise but none (0%) of those with normal microvascular function did (p=0.001) (Figure 2A). The false positive rates with progressively granular reference standards are depicted in Figure 2B; there were no false positive ESTs using a comprehensive physiological reference standard. Angina reported during EST was less specific for CMD than induced ECG changes (70% vs 100%, p&amp;lt;0.001). Conclusions In patients with ANOCA a positive EST is always indicative of CMD. The potential utility of EST as a rule-in test for CMD makes it an attractive non-invasive widely available test that could be re-integrated into clinical pathways for assessing new onset angina.Patient characteristicsEST versus coronary physiology

Abstract 12097: Genetics of Cardiac Troponin

Introduction: In the absence of coronary artery disease, observational studies suggest that myocardial injury may occurs because of drugs/toxins, infection, inflammatory disease, and malignancy, alongside commonly associated conditions such as heart failure, kidney disease, and hypertension, among others. The causes and optimal treatment for myocardial injury without ischemic heart disease remains an unmet need in cardiovascular medicine. We aimed to leverage genome-wide association studies (GWAS) to identify previously unreported risk loci for circulating troponin levels in the absence of ischemia, and Mendelian randomization (MR) to highlight causes of myocardial injury and identify potential targets for intervention. Methods: We performed a GWAS meta-analysis of circulating cardiac troponin I (cTnI) and T (cTnT) among up to 46,267 healthy ambulatory individuals using METAL. Using publicly-available GWAS of ~40 common cardiovascular risk factors such as lipids, blood pressure, and kidney function available from the IEU Open GWAS Project, we used Mendelian randomization (MR) to identify their potential causal association with circulating troponin. We primarily employed inverse-variance weighted MR; weighted median and weighted mode methods were applied as sensitivity analyses. Results: Our meta-analysis revealed three risk loci each for cTnI and cTnT, including a previously unreported signal on chromosome 3 (rs1706435) for cTnT. After accounting for multiple testing by controlling the false discovery rate (q &lt; 0.05), MR identified 8 and 10 cardiovascular risk factors associated with elevated cTnI and cTnT, respectively. These factors included blood pressure, creatinine, classes of obesity, and waist circumference. Conclusions: This analysis identified a new risk locus for circulating troponin in the absence of ischemia. Our MR results provide human genetic evidence to support obesity and hypertension as important contributors to elevated circulating troponin, highlighting their potential role in myocardial injury.

Abstract 14000: Elevated Galectin-3 Levels Are Associated With Higher Mortality in Patients With Atrial Fibrillation

Introduction: Atrial fibrillation (Afib) is associated with structural and electrical atrial remodeling. Galectin-3 (Gal-3) is a mediator of atrial fibrosis and higher levels have been associated with new onset Afib. Whether Gal-3 levels are prognostic in Afib remains unknown. Research Question: Investigate whether higher Gal-3 levels are associated with higher mortality in Afib. Methods: Patients with a history of Afib, enrolled in the Emory Cardiovascular Biobank of patients undergoing coronary angiography for suspected or confirmed CAD were included. Primary outcomes were all-cause and cardiovascular (CV) mortality. Kaplan-Meier and Cox regression analyses were used to compare survival between different Gal-3 levels. Results: We included 767 patients (mean age 68 years, 69.8% males) who were followed for a mean of 4.4 years. There were 234 (30%) all cause and 149 (19%) CV deaths. Third and fourth quartiles of Gal-3, were associated with higher hazard, when compared to the first quartile, with hazard ratios (HR) of 2.1 (1.4, 3.3) (Q3) and 3.5 (2.3, 5.3) (Q4) for all-cause mortality and 2.8 (1.5, 5.2) (Q3) and 4.9 (2.7, 8.7) (Q4) for cardiovascular mortality respectively. A one unit increase in Gal-3 was associated with HR of 1.4% and 1.8% for all-cause and CV mortality respectively, after adjusting for age, NT-proBNP, hypertension, stroke, MI, PVD, absence of coronary artery disease on left heart catheterization, history of HF and anti-coagulation therapy. Conclusions: Higher levels of Gal-3 are associated with higher incidence of all-cause and cardiovascular mortality in patients with Afib. Gal-3 can be used to identify high risk patients with Afib.

Absence of Coronary Artery Disease is a Strong Negative Predictor of Major Adverse Cardiovascular Events in Patients with Chronic Kidney Disease.

To investigate the interplay between chronic kidney disease (CKD) and coronary artery disease (CAD) on the incidence of cardiovascular events in patients with suspected chronic coronary syndrome (CCS). Patients with suspected CCS who underwent first-time coronary angiography in Western Denmark between 2003 and 2016 were included in this cohort study. Moreover, an age- and sex-matched general population cohort was established. Patients were stratified according to estimated glomerular filtration rate (eGFR). Presence of CAD was defined as ≥1 obstructive stenosis or non-obstructive diffuse disease. Major adverse cardiovascular events (MACE) were defined as a composite of myocardial infarction, ischemic stroke, and cardiac death. A total of 42,611 patients were included with a median follow-up of 7.3 years. Patients without and with CAD had MACE rates per 100 person-years that were 0.52 and 1.67 for eGFR ≥90 mL/min/1.73 m2, 0.68 and 2.09 for eGFR 60-89 mL/min/1.73 m2, 1.27 and 3.85 for eGFR 30-59 mL/min/1.73 m2, and 2.27 and 6.92 for eGFR <30 mL/min/1.73 m2. Comparing to eGFR ≥90 mL/min/1.73 m2, the adjusted incidence rate ratios for MACE were 1.29 (1.10-1.51) for eGFR 60-89 mL/min/1.73 m2, 1.86 (1.49-2.33) for eGFR 30-59 mL/min/1.73 m2, and 3.57 (1.92-6.67) for eGFR <30 mL/min/1.73 m2 in patients without CAD, and 1.11 (1.03-1.20), 1.71 (1.55-1.90), and 2.46 (1.96-3.09) in patients with CAD. The inverse relationship between kidney function and risk of MACE was confirmed when comparing patients with and without CAD to matched individuals in the general population. Absence of CAD is a strong negative predictor of major adverse cardiovascular events in patients with CKD.

Five-Year Follow-Up After Transcatheter Aortic Valve Implantation in Patients with Severe Aortic Stenosis and Concomitant Coronary Artery Disease: A Single-Center Experience.

There is no consensus on the impact of coronary artery disease in patients undergoing transcatheter aortic valve implantation. Therefore, the objective of this study was, in a single-center setting, to evaluate the five-year outcome of transcatheter aortic valve implantation patients with or without coronary artery disease. All transcatheter aortic valve implantation patients between 2009 and 2019 were included and grouped according to the presence or absence of coronary artery disease. The primary endpoint, five-year all-cause mortality, was evaluated using Cox regression adjusted for age, sex, procedure years, and comorbidities. Comorbidities interacting with coronary artery disease were evaluated with interaction tests. In-hospital complications was the secondary endpoint. In total, 176 patients had aortic stenosis and concomitant coronary artery disease, while 170 patients had aortic stenosis only. Mean follow-up was 2.2±1.6 years. There was no difference in the adjusted five-year all-cause mortality between transcatheter aortic valve implantation patients with and without coronary artery disease (hazard ratio 1.00, 95% confidence interval 0.59-1.70, P=0.99). In coronary artery disease patients, impaired renal function, peripheral arterial disease, or ejection fraction < 50% showed a significant interaction effect with higher five-year all-cause mortality. No significant differences in complications between the groups were found. Five-year mortality did not differ between transcatheter aortic valve implantation patients with or without coronary artery disease. However, in patients with coronary artery disease and impaired renal function, peripheral arterial disease, or ejection fraction < 50%, we found significantly higher five-year all-cause mortality.