Angina Patients Research Articles

Ranolazine: a better understanding of its pathophysiology and patient profile to guide treatment of chronic stable angina.

Chronic stable angina pectoris, the most prevalent symptomatic manifestation of coronary artery disease, greatly impairs quality of life and is associated with an increased risk for adverse cardiovascular outcomes. Better understanding of the pathophysiologic mechanisms of myocardial ischemia permitted new therapeutic strategies to optimize the management of angina patients. Ideally, antianginal drug treatment should be tailored to individual patient's profile and chosen according to the pathophysiology, hemodynamic profile, adverse effects, potential drug interactions and comorbidities. In this respect, and because of its peculiar mechanism of action, ranolazine represents an alternative therapeutic approach in patients with chronic stable angina and may be considered the first choice in presenceof comorbiditiesthat difficult the use of traditional therapies.

Safety and effectiveness of enhanced external counterpulsation (EECP) in refractory angina patients: A systematic reviews and meta-analysis.

Enhanced external counterpulsation (EECP) is believed to be a non-invasive treatment for coronary artery disease and angina. The aim of this study was to determine the safety and effectiveness of EECP in refractory angina patients through a systematic reviews and meta-analysis. We conducted a comprehensive search of the literature published on PubMed, Cochrane library, Scopus, ScienceDirect, Trip Database and Google Scholar databases using appropriate keywords and specific strategy with no time limit. Having selected and screened the studies based on the defined inclusion and exclusion criteria and evaluating their quality based on the Cochrane checklist. For the meta-analysis,the Mantel-Haenszel method or the generic Inverse Variance was used. Analyses were done with Review Manager 5.2 software. A number of 299 studies were initially reviewed and finally, seventeen studies were included in the meta-analysis based on the inclusion and exclusion criteria. Also, thirteen outcomes were analyzed and the results of meta-analysis in twelve outcomes including (Systolic Blood Pressure (7 studies), Diastolic Blood Pressure (7 studies), Pulse Pressure (4 studies), Mean Arterial Pressures (4 studies), Heart Rate (6 studies), Angina episodes (7 studies), Walking distance (2 studies),Canadian Cardiovascular Society classification (6 studies), Flow-Mediated Dilation (3 studies), Daily Nitrate Usage (4 studies), Exercise Treadmill Test-Time (2 studies), ST-segment depression (2 studies)demonstrated a significant clinical advantage in the EECP treatment effectiveness in patients with angina. No significant difference was observed regarding EECP usefulness (P = 0.18) in the outcome of brachial artery diameter (2 studies). Based on the meta-analysis, the results indicate the safety and effectiveness of EECP in patients with angina pectoris and indicate the usefulness of this treatment in these patients. In general, the authors believe that the general conclusion in this regard requires some studies with a large sample size and a control group assignment.

OR35. Exercise Effect on Global Myocardial Function Score in Patients with Refractory Angina Undergoing Extracorporeal Shockwave Myocardial Revascularization (ESMR): A Study focusing on Speckle Tracking and Exercise Stress Echocardiography

Abstract Aims Refractory angina pectoris (RAP) is defined as the occurrence of frequent angina attacks uncontrolled by optimal drug therapy. Extracorporeal shockwave myocardial revascularization (ESMR) is one of the alternative therapies that can be performed to treat RAP. Stress echocardiography is necessary to determine the inducible myocardial segments. To date, study evaluating the effect of exercise on myocardial function using WMSI and GLS was still limited. The aim of this study was to show the effect of exercise on global myocardial function evaluated using GLS and WMSI from echocardiography. Methods and Results This is a cross sectional and single center study of 9 Refractory Angina Pectoris patients underwent stress echocardiography from April - June 2021 in Mohammad Hoesin General Hospital, Palembang. Pre and post exercise WMSI and GLS were obtained and analyzed using McNemar non-parametric test. There were no significant differences between both pre and post GLS (p = 0.500) and WMSI (p = 0.250) through exercise stress echocardiography. Conclusion Our study showed no significant difference of global myocardial function evaluated by GLS and WMSI, pre and post exercise. Segmental myocardial function analysis seems to be more potential as useful assessment for RAP undergoing ESMR procedure.

Clinical outcomes of percutaneous coronary intervention for chronic total occlusion by treated segment length.

Long lesions are known to have worse outcomes following percutaneous coronary intervention (PCI), but there are limited data assessing the association between lesion length and clinical outcomes in PCI procedures undertaken in chronic total occlusions (CTO). We formed a longitudinal cohort (2006-2018, n=27,205) of stable angina patients who underwent PCI to CTO in the British Cardiovascular Intervention Society (BCIS) database. Clinical, demographical, procedural, and outcome data were analyzed in three groups by treated segment length, < 30 mm (n=11,782), 30-59 mm (n=10,415), ≥ 60 mm (n=5008). Prevalence of previous myocardial infarction and PCI were higher in patients in 30-59 mm group or ≥ 60 mm group compared with < 30 mm group. Following multivariable analysis, no significant difference was observed in in-patient death (OR=30-59 mm group=1.10, CI:0.55-2.19, p=0.78) (OR ≥ 60 mm group=0.82, CI: 0.33-2.05, p=0.67), and 1-year death (OR=30-59 mm group=1.06, CI: 0.81-1.37, p=0.69) (OR ≥ 60 mm group =1.01, CI: 0.70-1.43, p=0.99) (< 30 mm group=reference) but in-patient MACE was higher in >=60 mm group (OR: 1.52, CI: 1.15-2.01, p=0.06) but similar in 30-59 mm group (OR: 1.16, CI: 0.91-1.48, p=0.22) compared with < 30 mm group. The adjusted rates of procedural complications were higher in ≥ 60 mm group (OR: 1.61, CI: 1.40-1.85, p < 0.001) but were similar in 30-59 mm group (OR: 1.06, CI: 0.94-1.20, p < 0.31) compared with < 30 mm group. For every 10 mm increase, there was an increased adjusted risk of in-patient procedural complications and coronary perforation but not in-patient MACE or death. Patients with very long CTO lesions have higher risk of procedural complications and in-patient MACE but similar risk of short or long-term mortality compared with short CTO lesions.

Economic Impact And SafetY of Same-Day Discharge Following Percutaneous Coronary Intervention: A Tertiary-Care Centre Experience From Northern India (EASY-SDD)

BackgroundThe literature about the safety and feasibility of same-day discharge (SDD) following complex percutaneous coronary intervention (PCI) and in acute coronary syndrome (ACS) is scarce. The economic impact of SDD has not been evaluated in this geographical region. We in the present study evaluated the safety, feasibility, and economic impact of SDD following PCI at a tertiary care centre of north India. MethodsIt was a single-centre, non-randomized, prospective study, in which all consecutive PCI patients during the study period of 15 months were evaluated for SDD using a “patient-centred” approach. The patients who were discharged on the next calendar day were included in the next day discharge (NDD) group. The baseline demographic data including coronary risk factors, clinical presentation, and management details were noted for all patients. All patients were followed up for 6 weeks. The Indian health system is only partially insured, hence most of the expendable costs are borne by patients. In the present study, we computed the total societal expenditure of each PCI which includes both the health system costs and the expenditure borne by the patients. A standardized tool and bottoms up costing method were used for recording out-of-pocket expenditure (OOPE) by the patients and health care expenditure respectively. ResultsOut of a total of 675 PCI patients, 617 patients were enrolled in the study, and 132/617 (21.39%) patients were discharged the same day. Sixty-five % of patients (86/132) in the SDD cohort and 70% of patients (337/485) in the NDD cohort presented with ACS. Baseline characteristics in the two cohorts were identical. A higher syntax score, greater number of stents, and longer stented segment predicted the NDD. The mean length of stay after PCI in patients with SDD and NDD was 8.71 ± 2.48 and 21.76 ± 2.42 h, respectively. In the SDD group, there were no readmissions or adverse events after discharge till 6 weeks of follow-up. The total mean cost of PCI (health care system and OOPE) for SDD and NDD was Indian Rupees (INR) 129,322.14 [United States dollar (US$) 1810.51] and INR 165500.71 [US$ 2317.01] respectively. An amount of INR 36178.57 (health system cost: INR 10242.76 and OOPE: INR 25935.71 was saved for each SDD. Besides 100 cardiac unit bed days including 85 intensive cardiac care bed days were saved with 21% SDD in the present cohort. ConclusionPost PCI SDD is safe and feasible in selected ACS/chronic stable angina patients using the “patient-centred” approach. Besides, decreasing OOPE for the patients, SDD also helps in the efficient use of scarce health system resources.

Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial

Compared with visual angiographic assessment, pressure wire-based physiological measurement more accurately identifies flow-limiting lesions in patients with coronary artery disease. Nonetheless, angiography remains the most widely used method to guide percutaneous coronary intervention (PCI). In FAVOR III China, we aimed to establish whether clinical outcomes might be improved by lesion selection for PCI using the quantitative flow ratio (QFR), a novel angiography-based approach to estimate the fractional flow reserve. FAVOR III China is a multicentre, blinded, randomised, sham-controlled trial done at 26 hospitals in China. Patients aged 18 years or older, with stable or unstable angina pectoris or patients who had a myocardial infarction at least 72 h before screening, who had at least one lesion with a diameter stenosis of 50-90% in a coronary artery with a reference vessel of at least 2·5 mm diameter by visual assessment were eligible. Patients were randomly assigned to a QFR-guided strategy (PCI performed only if QFR ≤0·80) or an angiography-guided strategy (PCI based on standard visual angiographic assessment). Participants and clinical assessors were masked to treatment allocation. The primary endpoint was the 1-year rate of major adverse cardiac events, a composite of death from any cause, myocardial infarction, or ischaemia-driven revascularisation. The primary analysis was done in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03656848). Between Dec 25, 2018, and Jan 19, 2020, 3847 patients were enrolled. After exclusion of 22 patients who elected not to undergo PCI or who were withdrawn by their physicians, 3825 participants were included in the intention-to-treat population (1913 in the QFR-guided group and 1912 in the angiography-guided group). The mean age was 62·7 years (SD 10·1), 2699 (70·6%) were men and 1126 (29·4%) were women, 1295 (33·9%) had diabetes, and 2428 (63·5%) presented with an acute coronary syndrome. The 1-year primary endpoint occurred in 110 (Kaplan-Meier estimated rate 5·8%) participants in the QFR-guided group and in 167 (8·8%) participants in the angiography-guided group (difference, -3·0% [95% CI -4·7 to -1·4]; hazard ratio 0·65 [95% CI 0·51 to 0·83]; p=0·0004), driven by fewer myocardial infarctions and ischaemia-driven revascularisations in the QFR-guided group than in the angiography-guided group. In FAVOR III China, among patients undergoing PCI, a QFR-guided strategy of lesion selection improved 1-year clinical outcomes compared with standard angiography guidance. Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Centre for Cardiovascular Diseases, Fuwai Hospital.

Correlation of Triglyceride with Coronary Artery Disease Severity in Pre-Diabetic Chronic Stable Angina Patients

Background: Individuals with prediabetes have multiple disturbances in lipoprotein metabolism resulting from multiple combinations of insulin deficiency, insulin resistance and hyperglycemia. Dyslipidemia is the commonest complication of prediabetes and diabetes, and it predispose to premature atherosclerosis causing cardiovascular complication. The aim of this study was to assess correlation of triglyceride (TG) with coronary artery disease (CAD) severity in pre-diabetic chronic stable angina patients.&#x0D; Methods: Our cross-sectional observational study was conducted on 100 pre-diabetic patients (HbA1c 5.7% to 6.4%) with different levels of TG and stable CAD, referred to Tanta university hospitals. Each patient had been subjected to adequate history taking, complete clinical examination and laboratory investigations and electrocardiogram with transthoracic echocardiography. SYNTAX score was calculated.&#x0D; Results: There were significant positive correlations between TG and LDL, ratio and TLC respectively while there was a significant negative correlation between TG and HDL. There was significant positive correlation between SYNTAX and LDL, ratio and urea respectively while there was high significant negative correlation between TG and HDL. TG level was significantly higher in male than female (p= 0.028). There was no significant difference in SYNTAX regarding gender. For the multivariate analysis, only LDL was a significant independent predictor for CAD.&#x0D; Conclusions: There was a positive correlation between the TG and the severity of coronary lesions in pre-diabetic stable angina pectoris patients.

Doppler Echocardiography Assessment of Coronary Microvascular Function in Patients With Angina and No Obstructive Coronary Artery Disease.

Echocardiographic evaluation is an essential part of the diagnostic work-up in patients with known or suspected cardiovascular disease. Transthoracic Doppler echocardiography (TTDE) enables straightforward and reliable visualization of flow in the left anterior descending artery. In the absence of obstructive coronary artery disease, low TTDE-derived coronary flow velocity reserve (CFVR) is considered a marker of coronary microvascular dysfunction (CMD). TTDE CFVR is free from ionizing radiation and widely available, utilizing high-frequency transducers, pharmacologic vasodilator stress, and pulsed-wave Doppler quantification of diastolic peak flow velocities. European Society of Cardiology guidelines recommend TTDE CFVR evaluation only following preceding anatomic invasive or non-invasive coronary imaging excluding obstructive CAD. Accordingly, clinical use of TTDE CFVR is limited and CMD frequently goes undiagnosed. An evolving body of evidence underlines that low CFVR is an important and robust predictor of adverse prognosis and continuing symptoms in angina patients both with and without obstructive CAD. The majority of angina patients have no obstructive CAD, particularly among women. This has led to the suggestion that there may be a gender-specific female atherosclerotic phenotype with less epicardial obstruction, and a low CFVR signifying CMD instead. Nevertheless, available evidence indicates low CFVR is an equally important prognostic marker in both men and women. In this review, TTDE CFVR was evaluated regarding indication, practical and technical aspects, and interpretation of results. Association with symptoms and prognosis, comparison with alternative invasive and non-invasive imaging modalities, and possible interventions in angina patients with low CFVR were discussed, and key research questions were proposed.

Vascular dysfunction and its recovery after transradial coronary angioplasty- A serial observational study

ObjectiveTo serially evaluate the effect of trans-radial coronary angioplasty (TRA) on the vascular function of radial artery (RA) and upstream brachial artery (BA) and to find out the relative contribution of endothelial dependent flow-mediated vasodilatation (FMD) and endothelial independent nitrate mediated dilatation (NMD). MethodsForty patients of chronic stable angina with successful TRA were studied. FMD and NMD of bilateral RA and BA were measured with high-resolution ultrasound, before and at 24 h and at 3 months, after catheterization. ResultsFMD as well as NMD were significantly decreased in right RA (16.3 ± 3.6% to 5.7 ± 1.8%; p = 0.001, and 24.1 ± 5.3% to 9.7 ± 2.8%; p = 0.001, respectively) as well as in upstream BA (17.0 ± 1.6% to 9.4 ± 0.5%; p = 0.001,and 26.5 ± 6.8% to 20.5 ± 3.7%; p = 0.001, respectively) at 24 h. FMD/NMD ratio was also decreased in RA (70 ± 10% to 60 ± 10%; p = 0.04) and as well as in BA (70 ± 20% to 50 ± 10%; p = 0.03). The endothelial dysfunctions returned to normal at 3 months. Control arm did not show any change in vascular function at any point of time. Radial artery diameter/sheath ratio <1 and catheter exchanges >2 were the independent predictors for >50% decrease in FMD. ConclusionsTRA results in reversible depression in FMD as well as NMD in the radial artery as well as upstream brachial artery. These vascular dysfunctions are limited to the catheterized arm only and return to normal after 3 months.

A nationwide questionnaire-based survey on practice patterns and management of chronic stable angina with a controlled release formulation of trimetazidine

Background: There is lack of real-world evidence on various aspects of chronic stable angina (CSA). Hence, a questionnaire-based survey was conducted to garner real-world data about the prevalence of CSA among Indian patients; the associated comorbidities among these patients; management practices for CSA in India; and factors affecting compliance in patients with CSA with a special focus on day and night pack for trimetazidine controlled release (CR) 35 mg BD tablets.Methods: In all, 100 health care practitioners (HCPs) who each observed 15 patients with CSA in their clinical practice participated in this quantitative, cross-sectional, questionnaire-based study. The data were collected using a structured questionnaire with 30 questions grouped into 5 sections. Data were analyzed using percentages.Results: The results from the survey showed that 52.7% HCPs had observed 31-50% of angina patients with diabetes mellitus as comorbidity. As per the questionnaire survey, 77.4% HCPs preferred trimetazidine as a second-line agent when an angina patient was not responding to beta-blockers, calcium channel blockers (CCBs), and nitrates. Furthermore, 30.1% of HCPs preferred trimetazidine CR 35 mg BD as it improved exercise tolerance as well. Results from the survey reported that 65.6% HCPs agreed with the statement that day and night packs of trimetazidine tablets help in improving patient compliance and adherence to therapy.Conclusions: Trimetazidine CR 35 mg BD appears to have a safety profile suitable for various conditions and for patients with multiple comorbidities. Trimetazidine day and night packs of tablets help in improving patient compliance and adherence to therapy.

Assessment of ECG variables in patients with CRO revascularization: comparison of patients with evidence of ischemia versus patients with angina only

Abstract Objective Recent studies have shown that CTO intervention improves ECG depolarization. however, its effect on mortality and left ventricular function is uncertain. Therefore, decision to revascularisation in CTO patients remains challenging. In this study, we aimed to evaluate the electrical changes in CTO patients according to the ischemia status detected by myocardial perfusion scintigraphy (MPS). Method The study population consisted of two groups. CTO patients with angina were included in the first group and CTO patients with ischemia detected by MPS were included in the second group. Only symptomatic patients were included. CTO patients without angina were excluded from the study. After successful percutaneous CTO recanalization, ECG variables were measured before the procedure and 12–18 months after the procedure. Results After pre-assessment, 94 patients met study criteria. 49 patients without MPS. 45 patients were included in the MPS group. Three studies showed a significant decrease in mean QT dispersion of 17.46 ms [95% CI 10.62–24.30] after successful CTO PCI. In both groups, post-PCI QT dispersion did not differ between groups. All groups were similar in terms of ventricular arrhythmia. There was no sudden cardiac death in either group. However, more symptomatic improvement was observed in the group with ischemia with MPS. Conclusion According to our findings, CTO intervention has reduced proarrhythmic ECG findings. But similar electrical changes were observed between symptomatic (with angina) patients and patients with evidence of ischemia. In this context, CTO PCI should be considered in terms of electrical stability and improvement in symptoms in all patients presenting with anginal symptoms, with or without evidence of ischemia. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Ondokuz Mayis University Scientific Research Office

Clinical significance of microRNA-126 in Coronary artery disease patients

Abstract Background Coronary artery disease (CAD) is major public health problem and the leading cause of premature death all over the world. Early diagnosis with adequate management of CAD patients can significantly reduce morbidity and mortality rate. Purpose The purpose of this study was to explore the clinical significance of plasma miR-126 as a biomarker of stable angina pectoris patients and investigated the protective effects of hypoxic exposed HUVEC cell injury. Methods Angiographically confirmed 127 stable coronary artery (CAD) patients, 55 healthy subjects and 18hours hypoxic (1% O2) HUVEC cells were included in this study. Results The expression of miR-126 levels were remarkably down-regulated in stable CAD patients and hypoxic exposed HUVEC cells as compared with controls (p&amp;lt;0.001). Circulating plasma miR-126 was able to accurately differentiated stable CAD patients from healthy subjects with high sensitivity and specificity (AUC 0.928). The caspase-3 activity, apoptosis rate, LDH levels and intracellular ROS generation were significantly increased in 24hours hypoxic exposed HUVEC cells than normal control cells (p&amp;lt;0.001). On the contrary, over expressions of miR-126 were evidently reduced caspase-3 activity, apoptosis rate, LDH levels, intracellular ROS production and significantly improved HUVEC cellular viability (p&amp;lt;0.001). Moreover, TNF receptor-associated factor 6 (TRAF6) expressions were markedly increased in Hypoxic induced HUVEC cells, whereas mimic expression of miR-126 significantly decreased TRAF6 expression. Conclusion Down-regulated miR-126 may consider as a potential risk factor for stable CAD patients and it may used as a possible biomarker for early evaluation of CAD patients. Mimic expression of miR-126 remarkably decreased caspase-3 activity, LDH secretions, ROS levels and markedly improved HUVEC cellular viability by down-regulating TRAF6 expression, suggesting a newer therapeutic target for CAD patients. Funding Acknowledgement Type of funding sources: None.

Priority of non-HDL-C assessment to predict occurrence of new lesions after percutaneous coronary intervention in stable angina patients with diabetes mellitus prescribed strong statins

Abstract Background Diabetes mellitus (DM) patients are known to suffer from a higher risk of adverse outcomes following percutaneous coronary intervention (PCI) despite of low-density lipoprotein cholesterol (LDL-C)-lowering therapy with statins. Thus, identification of factors that may occurrence of new lesions following PCI in DM patients treated with strong statin is clinically important. Although LDL-C is generally calculated using the Friedewald equation method [LDL-C (F)], the effects of LDL-C measured by the Martin method [LDL-C (M)] or non-high-density lipoprotein cholesterol (non-HDL-C) on the occurrence of new lesions on coronary angiography after PCI among stable angina patients with DM receiving treatment with strong statins are unknown. Purpose The aim of the present study was to investigate the clinical factor on the occurrence of new lesions in stable angina patients with DM at 9-month follow-up coronary angiography and within 2 years after PCI. Methods The subject was 313 consecutive stable angina patients with DM who were admitted to undergo PCI. All patients had undergone successfully elective PCI using second-generation drug-eluting stents and intravascular ultrasound, and had been prescribed strong statins regardless dyslipidemia more than 2 week before PCI. We investigated the clinical factor on the occurrence of new lesions with myocardial ischemia. We estimated LDL-C (F), LDL-C (M), and non-HDL-C in this study. Acute coronary syndrome and hemodialysis patients were excluded from this study. Results Median of age and level of glycosylated hemoglobin (HbA1c) were 69 years (62–76) and 6.8% (6.3–7.3). New lesions appeared 9-month follow-up coronary angiography [New lesion(+) 9-month] and within 2 years [New lesion(+) 2-year] after PCI in 19 (6%) and 62 (20%) patients, respectively. The rate of history of smoking, using of β-blocker, and non-HDL-C ≥100 mg/dL and level of HbA1c were significantly higher in the New lesion(+) 9-month group than those in the New lesion(−) 9-month group after PCI. Age, level of high-sensitivity C-reactive protein and triglyceride, frequencies of LDL-C (F) ≥70 mg/dL, LDL-C (M) ≥70 mg/dL and non-HDL-C ≥100 mg/dL were significantly higher in the New lesion(+) 2-year group than those in the New lesion(−) 2-year group after PCI. Multivariate logistic regression analysis demonstrated only non-HDL-C ≥100 mg/dL was associated with the occurrence of new lesions both 9-month and within 2 years [9-month: hazard ratio (HR) 4.25, 95% confidence interval (CI) 1.30–19.23, p=0.014 and 2-year: HR 2.30, 95% CI 1.24–4.45, p=0.010]. Conclusion Only non-HDL-C ≥100 mg/dL was an independently associated with the occurrence of new lesions both 9-month and within 2 years after PCI in stable angina patients with DM treated with strong statins. Residual risk after PCI in DM patients should be considered by assessing non-HDL-C beyond the scope of LDL-C-lowering therapy with strong statins. Funding Acknowledgement Type of funding sources: None.

Proteomic biomarker profiles and vascular dysfunction in angina with no obstructive coronary artery disease

Abstract Background Coronary vascular dysfunction is a common cause of symptoms in patients with angina and no obstructed coronary arteries (ANOCA). Several endotypes have been defined but there are big gaps in our understanding of the underlying pathophysiology. Proteomic analyses may improve the understanding of the pathophysiology. Purpose Exploratory approach to 1) compare the proteomic biomarker profile across different types of vascular dysfunction in ANOCA and 2) assess the value of prediction models with protein biomarkers for vascular dysfunction in ANOCA. Methods We included 107 angina patients without previous coronary artery disease, left ventricular ejection fraction &amp;gt;45% and no obstructive coronary artery disease (CAD) (&amp;lt;50% stenosis of epicardial vessels) on coronary angiography. Three types of vascular dysfunction were assessed: 1) Vasomotor dysfunction (VMD) defined as epicardial or microvascular vasospasm on acetylcholine provocation, 2) Coronary microvascular dysfunction (CMD) defined as coronary flow velocity reserve (CFVR) ≤2.5 on echocardiography of the LAD on adenosine stimulation and 3) Reactive Hyperaemia Index (RHI) ≤1.67 as a measure of peripheral endothelial dysfunction. Blood samples were analysed for 184 protein biomarkers related to cardiovascular disease. Correlations between biomarkers and results of vascular function assessments were analysed with Pearson's correlation coefficient and visualized with volcano plots. Significantly correlated biomarkers (p&amp;lt;0.05) were tested in prediction models for their incremental value over age and gender with C-statistics. Results CFVR was correlated to 24 biomarkers before (figure 1a) and 2 biomarkers after adjustment for age and gender. The basic prediction model had AUC of 0.68 and was not significantly improved by adding biomarkers (figure 2a). RHI was correlated to 27 biomarkers before (figure 1b) and 10 biomarkers after adjustment for age and gender. The clinical prediction model was significantly improved (p=0.037) by adding TRAIL R2 and IL-18, in addition to age and gender, with an AUC of 84.4 (figure 2b). VMD was correlated to 14 biomarkers before (figure 1c) and 6 biomarkers after adjustment for age and gender. The prediction model was significantly improved (p=0.011) by adding HSP-27, RARRES-2 and SERPINA-12 in addition to age and gender in prediction of VMD with an AUC of 85.4 (figure 2c). Conclusion Several biomarkers were associated with vascular dysfunction in ANOCA patients with little overlap between different endotypes. We identified biomarkers that may contribute to the understanding of the underlying pathophysiology and have applications for screening. Results need to be confirmed in larger studies. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark.Department of Cardiology and Angiology, Robert Bosch Krankenhaus, Stuttgart, Germany

A novel flow and pressure catheter for complete interventional cardiology physiology management

Abstract Ischemia with No Obstructive Coronary Artery (INOCA) in angina patients increases the risk of major cardiac events, with a 1.5x increased mortality rate. There is a link between COVID-19 infection and impairment in the myocardial micro-vasculation which may cause an increase of INOCA patients. Fractional Flow Reserve (FFR), is the standard of care in cardiology but its diagnostic function is only related to Obstructive Coronary Artery disease (or epicardial) and it is ineffective with INOCA. The lack of effective and accurate tools for timely evaluation of coronary impairments creates a clinical unmet need. The PhysioCath catheter was developed within the Eurostars project “FP-Catheter, E!113577” aims to resolve this need a provide an effective tool to interventional cardiologists. The main project outcome is a catheter prototype equipped with a blood flow velocity sensor based on a thermo-convection principle, and a fiber optic pressure sensor (based on Fabry-Perot principle). While the use of Fabry-Perot type of sensor is already standard in the industry, the use of a thermo-convection sensor represents a progress with respect the state of the art. The sensor creates an overheat of 7°C above the physiological blood's temperature (considered as being within the safety limits), and it exchanges thermal power with the blood stream. The power is then measured and converted to velocity by means of a calibration curve. The project encompassed interviews with 14 clinical experts, the summary of the interviews indicated that the preferred form of the device is an over the wire microcatheter, with rapid exchange. Within the project then, it was developed a 3Fr microcatheter, with a rapid exchange section of 24cm. Both pressure sensor and flow velocity sensor were integrated in this embodiment. Finally, the PhysioCath prototype was evaluated in a bench test study. The test setup was composed by an anatomical silicone phantom of the aortic root and the coronaries (Elastrat, Geneva, Switzerland), perfused with a peristaltic pump (Harvard Apparatus, Holliston MA, US). The measurements performed by the flow velocity sensor were compared against and external doppler flow velocity sensor. While the pressure measurement was assessed for stability and presence of drift. The data processing revealed and extreme accuracy in the measurement of flow based indexes like CFR (±6% variability), accuracy of the blood flow velocity measurement (±10%), and extreme stability in the measurement of both pressure and flow velocity. In the second part of the project (that is currently ongoing), it will be studied the performance of the device within an animal setting. In conclusion, the PhysioCath device is a microcatheter integrating bot pressure measurement and blood flow velocity measurement. Its performance is of very high accuracy and stability, that represent a main step ahead with respect the current state of the art, based mainly on thermodilution. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Eureka-Eurostars Test benchMicrocatheter prototype

Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DΔNΔC gene therapy eight-year follow-up of phase I KAT301 study

In phase I KAT301 trial, intramyocardial adenovirus-mediated vascular endothelial growth factor -DΔNΔC (AdVEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved symptoms in refractory angina patients at 1-year follow-up without major safety concerns. We investigated the long-term safety and efficacy of AdVEGF-D GT. 30 patients (24 in VEGF-D group and 6 blinded, randomized controls) were followed for 8.2 years (range 6.3–10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse event (MACE) and other predefined safety endpoints. MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.97; 95% confidence interval 0.36–2.63; P = 0.95). Mortality and new-onset comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P = 0.006) but not in control group (2.2 vs. 2.6; P = 0.414). Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up.

Comparison of Lp-PLA2 Activity, Lp-PLA2 Mass and Lp-PLA2 mRNA in Acute Coronary Syndrome Patients

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk predictor for cardiovascular diseases (CVD). Generally, plasma Lp-PLA2 was thought to be secreted by circulatory inflammatory cells. Lp-PLA2 mRNA expression of PBMC may also be a risk predictor. Methods: A total of 104 subjects angiographically verified ACS patients were enrolled, including 73 unstable angina pectoris (UAP) patients and 31 acute myocardial infarction (AMI) patients. Plasma lipids, Lp-PLA2 activity and Lp-PLA2 mass were measured. Lp-PLA2 mRNA expression of PBMC was relatively quantified by real-time fluorescence PCR. Results: Plasma Lp-PLA2 activity was increased in AMI patients compared to UAP patients (395.21±145.91 vs. 328.53±127.03 U/L, p=0.024). Lp-PLA2 mass of AMI patients was also higher than UAP patients (136.43±45.46 vs. 119.16±44.19 ng/mL, p=0.093), while PBMC mRNA expression was not statistically different [1.07 (0.74, 1.57) vs. 0.88(0.49, 1.99), p=0.453]. Comparing Lp-PLA2 mRNA by groups, Lp-PLA2 mRNA level was higher in male ACS patients and smoking ACS patients (p=0.008, p=0.048, respectively). Multivariate logistic regression analysis showed that Lp-PLA2 activity was an AMI risk predictor (OR=5.224, 95% CI 1.687-16.181, p=0.004), after smoking, systolic blood pressure, diabetes and hyperlipidemia were adjusted. Recurrent ACS patients were older (p=0.035), but they showed lower levels of Lp-PLA2 mass and Lp-PLA2 activity (p=0.014, p=0.045, respectively), compared to primary ACS patients. Conclusion: Smoking may be an important regulatory factor for Lp-PLA2 mRNA expression in PBMC. Among three Lp-PLA2 indexes, Lp-PLA2 activity was the best marker indicating AMI risk, while Lp-PLA2 mass maybe play better role as a predictor in avoiding ACS recurrence.

Qi-Regulating and Blood Circulation-Promoting Therapy Improves Health Status of Stable Angina Pectoris Patients with Depressive Symptoms

Depressive symptoms have been found to be highly prevalent among patients with coronary heart disease (CHD) and seriously affect the patients' quality of life. However, most psychotropic drugs have warnings about potential side effects. Accordingly, safer effective alternatives are urgently demanded. Angina pectoris of CHD is considered as “chest stuffiness and heartache syndrome” in traditional Chinese medicine, with the major syndrome type named Qi stagnation and blood stasis. Qi-regulating and blood circulation-promoting therapy has increasingly shown unique advantages in CHD patients. This study investigated the efficacy of Xuefu Zhuyu decoction, a representative prescription of Qi-regulating and blood circulation-promoting therapy, on angina pectoris patients with depressive symptoms. Depressive symptoms were stratified at baseline in 30 patients with stable angina pectoris who participated in both baseline and 12-week follow-up studies. After performing a stratified analysis, the angina pectoris-specific health status and traditional Chinese medicine “chest stuffiness and heartache syndrome” were evaluated by self-reports using the associated questionnaire scales, respectively. We measured serum concentrations of serotonin, brain-derived neurotrophic factor, and ATP, which are associated with the development of depression. We found that the Xuefu Zhuyu granule significantly improved the angina pectoris-specific health status in patients after 12 weeks of treatment; specifically, it had a better curative effect on patients with depressive symptoms. Xuefu Zhuyu granule also significantly improved the chest stuffiness and heartache syndrome in patients with depressive symptoms (efficacy index is 61.24%, P < 0.05 versus baseline). Interestingly, Xuefu Zhuyu granule has been found to be more susceptible to improving ATP levels in patients with depressive symptoms, indicating that the improvement in serum ATP levels might account for the better efficacy of Xuefu Zhuyu granule in patients with depressive symptoms. Our data provide prospective evidence that Xuefu Zhuyu granule improves angina pectoris-specific health status through regulating Qi and promoting blood circulation. This trial is registered with ChiCTR-IOR-15006989.

Combination of Activating Blood Circulation and Detoxifying Chinese Medicines Played an Anti-Inflammatory Role in Unstable Angina Patients after Percutaneous Coronary Intervention: A Multicenter, Open-Labeled, Randomized Controlled Trial.

To investigate the combined anti-inflammatory effect of activating blood circulation and detoxifying Chinese medicines in unstable angina (UA) patients. This study was an open-labeled, randomized controlled trial conducted in 5 centers in Beijing. A total of 154 patients were randomized into two groups at a 1:1 ratio by random numbers. Based on the conventional treatment, patients in the activating blood circulation (ABC) group were treated with Guanxin Danshen Droping Pill (, 0.4 g, thrice daily), and patients in the activating blood circulation and detoxifying (ABCD) group were treated with Guanxin Danshen Droping Pill (0.4 g, thrice daily) and Andrographis tablet (0.2 g, thrice daily) for 4 weeks. The primary outcome was the serum level of high sensitive C reaction protein (hs-CRP), and the secondary outcome index included the serum levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble CD40 ligand (sCD40L), thrombomodulin (TM), the score of angina pectoris, the score of blood stasis syndrome, and the score of Chinese medicine symptoms, observed at week 0 and week 4. A total of 144 patients completed the trial (ABC group, n=70; ABCD group, n=74). There were no significant differences in the clinical baseline characteristics between the two groups. When compared with the ABC group, ABCD group showed better performance in reducing the level of inflammatory factors, especially hs-CRP (P<0.05), IL-6 (P<0.01) and TNF-α (P<0.01). In term of clinical symptoms, ABCD group played a better role in improving the scores of angina pectoris and blood stasis syndrome than ABC group (all P<0.05). The combination of Guanxin Danshen Dropping Pill and Andrographis tablet exert significant anti-inflammatory effect on UA patients, which is superior to single Guanxin Danshen Dropping Pill. (Registration No. ChiCTR-TRC-13004072).

Intravascular ultrasound insights into the unstable features of the coronary atherosclerotic plaques: A systematic review and meta‐analysis

There is a lack of a comprehensive picture of plaque geometry and composition of unstable atherosclerotic lesions as observed with intravascular ultrasound techniques. We analysed through a systematic review with meta-analysis 39 characteristics of atherosclerotic plaques in three scenarios involving culprit and non-culprit lesions from acute coronary syndromes vs stable angina pectoris patients, and culprit vs non-culprit lesions in acute coronary syndromes patients. A systematic search of PubMed and EMBASE, from inception to April 2020 was performed. The combined odds ratios or mean differences of all IVUS characteristics were calculated with random-effects models. Twenty-eight studies involving 5434 subjects, and 5618 lesions were included. Culprit lesions in acute coronary syndromes have larger plaque areas and remodeling indexes (MD=0.13 [0.08; 0.17], p<0.001) and contained larger necrotic cores (MD=0.67 (95% CI 0.19;1.15), p=0.006) that stable angina culprit lesions. In acute patients, culprit plaques were also more remodeled, had larger necrotic cores and had more frequently a Thin-Cap Fibroatheroma morphology (OR=1.79 (95% CI 1.21; 2.65), p=0.004) than non-culprit lesions. Non-culprit lesions in acute syndromes were more often ruptured (OR=2.25 (95% CI:1.05; 4.82), p=0.037) or Thin-Cap Fibroatheromas than in stable angina. Culprit lesions from acute coronary patients are larger, more positively remodeled and contained more lipids as compared to stable angina lesions or non-culprit in acute patients. Non culprit lesions are also more often complicated or vulnerable in acute than stable patients.