Anginal Symptoms Research Articles

Abstract 10839: Two-year Follow-up Of Patients With Chronic Ischemic Heart Disease In A Specialized Center In Brazil

Introduction: Incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly between regions. Although populous, Brazil is often underrepresented in international registries. Objective: This study aimed to describe the quality of care and 2-year incidence of cardiovascular events and prognostic factors in CIHD patients in a tertiary public health care center in Brazil. Methods: Patients with CIHD, denoted as previous revascularization, myocardial infarction (MI) or stenosis > 50% in at least one epicardial coronary artery, were enrolled and followed for at least 2 years. Main endpoint was the composite of MI, stroke or death. We also evaluated prescription, symptoms and laboratory records. Results: 625 patients with mean age 65 (±9.6) years, 33.3% women, were included. Previous MI was present in 59.8%, CABG in 26.8%, and percutaneous coronary intervention in 40.6%. Diabetes was prevalent in 48.6%, high blood pressure in 83.1%, and chronic kidney disease (creatinine clearance < 60 mL/min) in 34.7%. Residual coronary anatomy was known in 266 patients, of whom 29.3% had multivessel disease, and 11.7% had lesion in the left main artery. At a median follow-up (FU) of 881 days, we recorded 37 events of primary composite endpoint, with 2-year estimate event incidence of 7.05%. Age (HR per 10 years 1.61, 95%CI 1.32-1.97), stroke (3.65, 1.48-9.00) and LDL-cholesterol (1.23, 1.14-1.33) were the main prognostic factors in multivariate analysis. The participants experienced relief of angina symptoms based on Canadian Cardiovascular Society (CCS) scale (baseline vs. FU respectively): 65.7% vs. 81.7% were asymptomatic, 13 vs. 7.2% CCS1, 17.1 vs. 8.3% CCS2, 4.2 vs. 2.9% CCS3 or 4 (p < 0.001). Analysis of therapeutic goals identified better quality of medication prescription, defined as the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker plus statin and any antithrombotic agent: 65.8% vs. 73.6% (p<0.001) comparing baseline with FU. On the other hand, there was no improvement in LDL or blood pressure control. Conclusion: This study shows that CIHD patients had a 2-year incidence of the primary composite endpoint of 7.05%, LDL was the main modifiable risk factor of worse prognosis.

Non-obstructive Coronary Artery Disease in Chinese Patients with Angina Diagnosed by Coronary Angiography: A Retrospective Study

Abstract Objective: This study aimed to estimate the proportion of non-obstructive coronary artery disease (CAD) patients in large percutaneous coronary intervention (PCI) centers in China. Methods: The study was conducted at 6 large PCI centers in China from January 1, 2013 to December 31, 2015. Demographic and clinical data were collected from medical records, prescription records, and laboratory reports of patients with symptoms of angina who underwent coronary angiography (CAG). Results: A total of 1713 patients were consecutively screened, 1600 of whom were included in the study. CAG showed that 300 patients had non-obstructive CAD while 1300 had obstructive CAD. Among the 300 patients with non-obstructive CAD, 203 displayed mild coronary stenosis (20%–49%) and 91 had normal coronary status (ie, <20% stenosis). Of the 1300 patients with obstructive CAD, 61.6% (801/1300) had typical symptoms of angina, compared with 49.3% (148/300) for patients with non-obstructive CAD. In addition, there were more women than men in the non-obstructive CAD group, whereas the reverse was observed among obstructive CAD patients. Conclusion: The prevalence of non-obstructive CAD in the Chinese population with coronary heart disease was estimated to be approximately 20%. Additionally, typical angina symptoms were correlated with obstructive CAD, whereas female gender was identified as a risk factor for non-obstructive CAD.

Optimal Medical Therapy as First-Line Therapy for Chronic Coronary Syndromes: Lessons from COURAGE, BARI 2D, FAME 2, and ISCHEMIA.

The chronic coronary syndromes (CCS) include patients with a classic history of angina pectoris in the presence of either risk factors for or known atherosclerotic coronary artery disease. Randomized, controlled trials conducted in the optimal medical therapy (OMT) era have convincingly demonstrated that adherence to the outdated paradigm focused on treatment of obstructive coronary disease with initial revascularization fails to reduce death or myocardial infarction and inconsistently reduces angina symptoms. Rather, OMT reduces events and improves symptoms and should be considered first-line treatment for patients with CCS.

Associations between galectin-1, left ventricular diastolic dysfunction, and heart failure with preserved ejection fraction

Background: Galectin-1 is a glycan-binding protein with broad anti-inflammatory properties. Left ventricular diastolic dysfunction (DD) is associated with heart failure and mortality. The pathophysiology of DD is complex and our study aimed to investigate the associations between serum galectin-1 level, DD, and heart failure with preserved ejection fraction (HFpEF). Methods: Patients with symptoms of angina pectoris were enrolled. Serum galectin-1 levels and echocardiography were assessed. The study endpoint was a composite of all-cause mortality or new-onset HFpEF. Results: In total, 258 patients were enrolled (63% male; mean age 68±12 years) and grouped into tertiles based on galectin-1 levels. Patients in the highest galectin-1 group had increased left ventricular mass indexes, left atrial diameters, and prevalence of DD compared to those in the lower tertiles (all p<0.05). Moreover, elevated galectin-1 levels were significantly associated with the composite endpoint (p=0.039). After adjusting for confounding factors, high galectin-1 levels remained significantly associated with DD (odds ratio 2.44, p=0.005). The Kaplan-Meier analysis revealed patients in the highest galectin-1 group had lowest cumulative survival of composite endpoint (log rank p=0.043). Conclusions: Elevated serum galectin-1 levels were associated with DD and the composite endpoint of all-cause mortality and incident HFpEF.

СРАВНИТЕЛЬНОЕ ИЗУЧЕНИЕ ВЛИЯНИЯ ИНСУЛИНОЗАВИСИМОГО САХАРНОГО ДИАБЕТА 2-ГО ТИПА, ОТЯГОЩЕННОЙ НАСЛЕДСТВЕННОСТИ И КУРЕНИЯ НА ТЯЖЕСТЬ ИШЕМИЧЕСКОЙ БОЛЕЗНИ СЕРДЦА

Introduction. The presence of high-risk factors such as hereditary burdening, tobacco smoking, and diabetes mellitus significantly worsen the prognosis in potentially healthy individuals by increasing the incidence of coronary heart disease. Aim. To study the separate influence of insulin-dependent diabetes mellitus type 2, heredity and smoking on the severity and course of coronary heart disease. Material and methods. One hundred patients with coronary heart disease were enrolled in the study. The patients were divided according to the presence of the following high-risk factors: heredity, tobacco smoking, and insulin-dependent type 2 diabetes mellitus. The patients were examined at the beginning and 1 year after treatment. The results of echocardiography and electrocardiography were analyzed at the beginning of follow-up and one year later. The severity of coronary artery lesions was assessed using SYNTAX score analysis of coronarography protocols. The number of Q and QS waves on electrocardiogram, increased size and decreased left ventricular ejection fraction were also considered as criteria of coronary heart disease severity. The obtained data were processed using IBM Statistics SPSS-26 program. The differences were considered statistically significant at p&lt;0,05. Results and discussion. Patients with diabetes mellitus were more susceptible to aortocoronary bypass grafting, whereas coronary angioplasty was performed more frequently in patients with heredity (p&lt;0,05). Coronary vessels were more affected in diabetic patients and in tobacco smokers compared with patients with a burdened heredity [(20,4±2,7) points (21,9±1,39) and (12,9±1,8) points, respectively]. Severe heart failure prevailed among patients with concomitant diabetes mellitus. After one year, all patients had a reduction of clinical symptoms of angina and heart failure. The efficacy of medical treatment of angina in patients with heredity was lower compared to other groups. Conclusion. In patients with a history of diabetes mellitus development of coronary heart disease is manifested by severe myocardial and coronary lesions, which increases the risk of coronary artery bypass grafting. Despite this, patients with diabetes mellitus lend themselves well to drug treatment. The tobacco smoking group is not inferior to the diabetes mellitus group by the severity of heart and coronary artery lesions and is well amenable to drug therapy. The last place in the severity of coronary heart disease is occupied by patients with a hereditary burden, although they are more prone to acute coronary syndrome.

Difference between Acyclovir and Ganciclovir in the Treatment of Children with Epstein-Barr Virus-Associated Infectious Mononucleosis.

Objective To investigate the efficacy differences between acyclovir and ganciclovir in the treatment of children with Epstein–Barr virus (EBV)- associated infectious mononucleosis (IM). Methods A total of 128 children with EBV-IM who were admitted to our hospital from February 2019 to February 2021 were selected and randomly divided into the acyclovir group (n = 64) and the ganciclovir group (n = 64) according to the random number table method. All the children were given symptomatic treatments such as protecting the liver and reducing fever. On this basis, the acyclovir group was given an intravenous drip of acyclovir, while the ganciclovir group was given an intravenous drip of ganciclovir. The treatment was continued for 7 days. After the treatment, the clinical efficacy, disappearance time of symptoms and signs, related blood routine indexes, EBV-DNA negative conversion rate, and the incidence of adverse reactions during the treatment were compared between the two groups. Results After treatment, the total effective rate of the ganciclovir group (92.19%) was higher than that of the acyclovir group (73.44%) and the difference was statistically significant (P < 0.05). The disappearance time for the symptoms and signs of angina, fever, lymphadenopathy, hepatomegaly, and splenomegaly in the ganciclovir group was lower than that in the acyclovir group, and the difference was statistically significant (P < 0.05). After treatment, the levels of atypical lymphocyte proportion, lymphocyte proportion, and WBC count in the two groups were lower than those before treatment, the levels in the ganciclovir group were lower than those in the acyclovir group, and the difference was statistically significant (P < 0.05). After treatment, the EBV-DNA negative conversion rate (81.25%) in the ganciclovir group was higher than that in the acyclovir group (60.93%) and the difference was statistically significant (P < 0.05). During treatment, the incidence of adverse reactions in the ganciclovir group was significantly lower than that in the acyclovir group and the difference was statistically significant (P < 0.05). Conclusion In the treatment of children with EBV-IM, the therapeutic effect of ganciclovir is obviously superior to that of acyclovir. Ganciclovir can quickly eliminate the symptoms of angina, fever, enlarged lymph nodes, and other signs in children, can improve abnormal blood indicators, and has a higher negative conversion rate of EBV and less adverse reactions.

Quality of life in patients with long-standing persistent atrial fibrillation after surgical ablation and simultaneous coronary artery bypass grafting

Aim. To analyze quality of life (QOL) of patients with coronary artery disease (CAD) in combination with long-standing persistent atrial fibrillation (AF) in the long-term postoperative period, depending on chosen surgical strategy for concomitant pathology.Material and methods. The analysis of QOL changes in the long-term postoperative period (12 and 24 months) in 116 patients with CAD and concomitant long-term persistent AF who selectively underwent biatrial (BA) or isolated left atrial (LA) ablation with simultaneous on-pump coronary artery bypass grafting. To assess QOL, a non-specific Medical Outcomes Study 36-Item Form Health Status Survey (SF-36) questionnaire was used. Patients were questioned in preoperative and long-term postoperative periods (12 and 24 months).Results. All SF-36 parameters significantly improve after open surgical treatment in the long-term postoperative period (24 months) with both treatment strategies (BA and LA ablation) for AF. In the BA ablation group, 74% of patients did not have arrhythmia after 12 months, and only 38,5% of patients in the LA ablation group belonged to European Heart Rhythm Association (EHRA) score class 1 (p=0,001). After 24 months, a comparison revealed a significant diff erence between the two groups in arrhythmia symptoms (p=0,014), with maintaining the advantage of the BA ablation group. After 12 and 24 months, none of the patients in both compared groups had severe class IV angina.Conclusion. SF-36 parameters were improved 24 months after surgical treatment of CAD and long-standing persistent AF, regardless of the ablation strategy. Elimination of angina symptoms and long-term maintenance of sinus rhythm can improve the QOL of patients in the long-term postoperative period.

Troponin to risk stratify patients with suspected acute coronary syndrome for computed tomography coronary angiography

Abstract Background Patients with suspected acute coronary syndrome in whom myocardial infarction has been ruled-out are at risk of future adverse cardiac events. However, the optimal approach to risk stratify and investigate these patients is uncertain. Methods We performed a prospective cohort study of 250 patients presenting to the Emergency Department with suspected acute coronary syndrome and troponin concentrations below the sex-specific 99th centile (16 ng/L for women and 34 ng/L for men). Patients were recruited in a 2:1 fashion stratified by peak high-sensitivity cardiac troponin I concentration above and below the early rule-out threshold of 5 ng/L (167 patients with intermediate troponin concentrations between 5 ng/L and the sex-specific 99th centile threshold and 83 patients with troponin concentrations &amp;lt;5 ng/L). All patients underwent computed tomography coronary angiography after they were discharged from hospital. Results Overall, 37.6% (94/250) of patients had normal coronary arteries whilst 36.0% (90/250) and 26.4% (66/250) had non-obstructive and obstructive coronary artery disease, respectively. Patients with intermediate troponin concentrations were more likely to have coronary artery disease than those with troponin concentrations &amp;lt;5 ng/L (71.9% [120/167] versus 43.4% [36/83]; odds ratio 3.33 [95% confidence interval 1.92–5.78]). This association persisted irrespective of whether patients had anginal symptoms. Conversely, there was no difference in the prevalence of coronary artery disease between those with and without anginal symptoms (63.2% [67/106] and versus 61.8% [89/144]; odds ratio 0.92 [0.48–1.76]). The majority of patients found to have coronary artery disease did not have a prior diagnosis and were not on optimal preventative medical therapy prior to undergoing computed tomography coronary angiography (50.8% [61/120] and 61.0% [22/36], versus 61.7% [74/120] and 69.4% [25/36] in patients with intermediate versus low troponin concentrations, respectively). Conclusions In patients with suspected acute coronary syndrome who have myocardial infarction ruled out, those with intermediate cardiac troponin concentrations are three-times more likely to have coronary artery disease than those with low troponin concentrations. Conversely anginal symptoms did not discriminate between those with and without coronary artery disease. Further studies are required to determine if targeting computed tomography coronary angiography to those with intermediate cardiac troponin concentrations can improve the use of preventative medical therapies and clinical outcomes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The British Heart Foundation Odds ratio of coronary artery diseaseCumulative proportion with CAD

Positive predictive value of CT coronary angiography vs. CT fractional flow reserve in a real-world population

Abstract Background Computerised tomography coronary angiography and fractional flow reserve (CTCA and CT-FFR) are non-invasive diagnostic tools for the detection of flow limiting coronary artery stenoses. Although their negative predictive values are well established, there is a concern that the high sensitivity of these tests may lead to overestimation of coronary artery disease (CAD) and unnecessary invasive coronary angiography (ICA). We compared the positive predictive value (PPV) of CT-FFR with computerised tomography coronary angiography (CTCA) against the gold standard of ICA in different real-world patient groups. Methods We conducted a retrospective study of 477 patients referred for CTCA or CT-FFR for investigation of possible coronary ischaemia. Patients were excluded if the image quality was poor or inconclusive. Patient-based PPV was calculated to detect or rule out significant CAD, defined as more than 70% stenosis on ICA. A sub-analysis of PPV by indication for scan was also performed. Patients that underwent invasive non-hyperaemic pressure wire measurements had their iFR or RFR compared with their CT-FFR values. Results In a patient-based analysis, the overall PPV was 59.3% for CTCA and 76.2% for CT-FFR. This increased to 81.0% and 86.7% respectively for patients with stable angina symptoms. In patients with atypical angina symptoms, CT-FFR considerably outperformed CTCA with a PPV of 61.3% vs. 37.5%. There was not a linear relationship between invasive pressure wire measurement and CT-FFR value (r=0.23, p=0.265). Conclusion The PPV of CTCA and CT-FFR is lower in the real-world than in previously published trials, partly due to the heterogeneity of indication for the scan. However, in patients with typical angina symptoms, both are reliable diagnostic tools to determine the presence of clinically significant coronary stenoses. CT-FFR significantly outperforms CTCA in patients with more atypical symptoms and the targeted use of CT-FFR in this group may help to avoid unnecessary invasive procedures. Funding Acknowledgement Type of funding sources: None.

Effect of revascularization on exercise-induced changes in cardiac and pro-thrombotic biomarkers in patients with coronary artery disease

Abstract Introduction Exercise-induced increase in cardiac and pro-thrombotic biomarkers have previously been shown in patients with coronary artery disease (CAD) before revascularization, which may be due to myocardial ischemia. Purpose We aimed to examine whether resting levels and exercise-induced changes of high sensitive cardiac Troponin T (cTnT), NT-proBNP, pro-thrombin fragment (F) 1+2, D-dimer, tissue factor pathway inhibitor (TFPI) and endogenous thrombin potential (ETP) were affected by revascularization in patients with CAD. We hypothesized that resting and exercise-induced levels of the biomarkers would be reduced after revascularization. Methods Patients presenting with symptoms of CAD were included. A maximal exercise ECG stress test (EST) (EST1) was performed, and venous blood samples were drawn at rest and within five min after termination. All patients underwent coronary angiography. Patients (n=20) with confirmed CAD, fully revascularized with percutaneous coronary intervention (PCI) and without symptoms of angina, were invited to perform a second EST (EST2), at the same workload (median 145W), at a median of 66 days after revascularization. Mean exercise duration at both time points were 11:30 min:sec. Of the total population 15 patients were treated with PCI on stenosis located on LAD and 5 patients with stenosis on RCA. Results Significant increase in cTnT and NT-proBNP from resting to post exercise levels at EST1 was found as expected (p&amp;lt;0.001, both). Also at EST2, increased levels were observed (p&amp;lt;0.01, both), however, not significantly different from the changes at EST1. Resting levels of cTnT at EST2 compared to EST1 were significantly higher (median 8.1 vs 7.1 ng/L, p=0.02). At both visits significant increase in D-dimer (p=0.008 and &amp;lt;0.001), F1+2 (p=0.009 and 0.001) and TFPI (p&amp;lt;0.001 and 0.001) during exercise were demonstrated, with no difference in these changes. There were no significant changes in ETP during exercise at any visit, but resting levels were reduced at EST2 vs EST1 (p&amp;lt;0.01). Also resting levels of TFPI were reduced at EST2 (p&amp;lt;0.01). Conclusion After revascularization there was still significant increase in exercise-induced release of cardiac and pro-thrombotic biomarkers, thus revascularization does not affect the ability to release these biomarkers. Also, the higher resting levels of cTnT after revascularization indicate that revascularization per se does not affect secretion of cardiac biomarkers, probably due to the disease state. The lower resting levels of ETP and TFPI after revascularization may, however, be indicative of reduced thrombin generation potential and endothelial activation. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Stein Erik Hagens Foundation for Clinical Heart Research, Oslo, Norway

The impact of non-pharmacological therapies on cardiovascular outcomes in patients with refractory angina: a systematic review and meta-analysis of randomized controlled trials

Abstract Despite advances in revascularization techniques and optimal medical management, refractory angina (RFA) represents an essential group of patients where progress has stalled, and in which therapeutic approaches remain uncertain. Numerous randomized control trials have reported clinical outcomes on a variety of treatments but to date no direct outcome comparison has been made. Our aim is to investigate and compare the outcomes of these different non-pharmacological technologies in RFA, centring on major adverse cardiac events and all-cause mortality. We performed a systematic review and meta-analysis of randomized controlled trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive search was performed of PubMed, EMBASE (Excerpta Medica database),Cochrane, ClinicalTrials.gov, Google Scholar databases of randomized controlled trials, and scientific session abstracts. Studies were deemed eligible if they met the following criteria: (1) full-length publications in peer-reviewed journals; (2) evaluated non-pharmacological therapies use in patients with no further revascularization options while on optimal medical treatment; (3) patients had ongoing angina, Canadian Cardiovascular Society class II–IV; and (4) included a placebo/control arm. We calculated risk ratios for all-cause mortality, combined MACE events. We assessed heterogeneity using χ2 and I2 tests. We analysed 3292 citations with 51 randomized control trials testing 9 therapies including angiogenic proteins, stem-cell therapy, lipoprotein apheresis, coronary sinus reducer, spinal cord stimulator, percutaneous laser revascularization, shock-wave therapy, transmyocardial laser revascularization and enhanced external counter pulsation all meeting the inclusion criteria (table 1). Our analysis identified stem cell therapy as the only therapy with a reduction in all-cause mortality (Odds ratio, 0.45; CI, 0.21–1.00) (figure 1). A corresponding reduction in major adverse cardiac events (MACE) was also seen with stem cell therapy (OR 0.48: CI 0.30–0.75) alongside patients who received angiogenic proteins (OR 0.72: CI 0.55–0.93) and cardiac shockwave therapy (OR, 0.21: CI 0.10–0.46) Improvements in secondary measures of angina symptoms or frequency were seen with stem cell therapy, angiogenic proteins, coronary sinus reducer, spinal cord stimulator, shock-wave therapy, transmyocardial laser revascularization and enhanced external counterpulsation. This is the largest meta-analysis comparing outcomes of novel technologies used in refractory angina. This suggests that stem cell therapy is the only non-pharmacological therapy for RFA associated with a reduction in mortality, MACE and anginal symptoms. We propose further larger randomized control trials, to support these findings. Funding Acknowledgement Type of funding sources: None. Table 1. Randomized control trials and outcomesFigure 1. All-cause mortality forest plot

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

External validation of prediction models for obstructive coronary artery disease in patients with suspected stable coronary artery disease

Abstract Background Pre-test probability (PTP) is an important tool in the diagnostic work-up for obstructive coronary artery disease (CAD) but must be calibrated to the declining disease prevalence in patients referred to diagnostic testing. Purpose To externally validate the published basic and clinical PTP models in a contemporary angina cohort with low prevalence of CAD and to compare with the reference European Society of Cardiology 2019 PTP (ESC 2019 PTP). Methods The validation cohort consisted of 42.328 patients (54% women, age ≥30 years, no previous CAD) with symptoms of CAD referred for cardiac computed tomography angiography in the western region of Denmark from 2008–2017 (3.3 million inhabitants). Obstructive CAD was defined from either invasive angiography as stenosis &amp;gt;50%, or when performed, from FFR &amp;lt;0.8 in coronary arteries with diameters &amp;gt;2 mm. The basic prediction model included type of angina, sex, and age, and the clinical model added diabetes, family history of CAD, and dyslipidemia. The ESC 2019 PTP was calculated from age, sex, and angina symptoms. Discrimination, calibration, and negative predictive value (NPV) were measured for all three models. Results Obstructive CAD was present in 3718 (8.8%). In the ESC 2019 PTP model, the basic model, and the clinical model 19.5%, 48.5%, and 55.7% were classified as very low risk and only 1.6%, 3.7%, and 3.5% of these had obstructive CAD, respectively (figure 1). Discrimination was similar for the three models with AUC of 0.76 (95% CI 0.75–0.77), 0.74 [0.73–0.75], and 0.76 [0.75–0.76], for the ESC 2019 PTP, basic, and clinical model, respectively. At the clinically relevant very low predicted probability (≤5%) of CAD, the clinical and basic model were very well calibrated, whereas the ESC 2019 PTP model overestimated the CAD prevalence. NPV at cut-off ≤5% were 98.4% [98.1–98.7] for the ESC 2019 PTP model, 96.3% [96.1–96.6] for the basic model, and 96.5% [96.3–96.7] for the clinical model. At cut-off &amp;lt;15%, NPVs were 96.1% [95.8–96.3] for the ESC 2019 PTP model, 94.5% [94.2–94.7] for the basic model, and 94.2% [94.0–94.5] for the clinical model. Conclusion In a population with a prevalence of 8.8% obstructive CAD, a clinical prediction model including diabetes, family history of CAD, and dyslipidemia in addition to the variables of the ESC 2019 PTP model ruled out 36.2% more patients than the ESC 2019 PTP model (23.592 vs. 8245 patients) while only overlooking 1.9% more cases of obstructive CAD when choosing a cut-off ≤5%. Use of this model is therefore potentially cost saving. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DΔNΔC gene therapy: eight-year follow-up of phase 1 KAT301 study

Abstract Backgound/Introduction In phase I KAT301 trial, adenovirus-mediated intramyocardial vascular endothelial growth factor-DΔNΔC (VEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved angina at 1-year follow-up without major safety concerns. Purpose Our objective was to investigate the long-term safety and efficacy of AdVEGF-D GT. A total of 30 patients (24 VEGF-D and 6 randomized and blinded controls) participated in KAT301 trial. Methods The mean follow-up time was 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 events (MACEs) and other predefined endpoints including cancer. Results 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 0.90; 95% confidence interval 0.09–9.32; P=0.95). Mortality and 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). Conclusion(s) 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. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Kuopio University Hospital Heart Center Figure 1. The incidence of MACEFigure 2. CCS class

Myocardial ischaemia of non-obstructive origin as a cause of new onset anginal chest pain in the long COVID syndrome

Abstract Background New-onset chest pain occurs in around 20% of patients with long COVID syndrome (LCS). Being the vascular endothelium one of the targets of the SARS-CoV-2 virus, we hypothesized that new onset anginal symptoms in LCS could be due to endothelium dysfunction and other non-obstructive causes of myocardial ischaemia. Methods We investigated 11 consecutive patients who developed new onset anginal chest pain, suggestive of myocardial ischaemia, after documented SARS-CoV-2 infection. Intracoronary assessment included endothelium-dependent evaluation with acetylcholine testing (Ach), and endothelium-independent assessment with coronary flow reserve (CFR) and microcirculatory resistance (MR). Criteria for positiveness of these tests and medical treatment recommendation were obtained from 2019 ESC guidelines and 2020 EAPCI consensus document on ischaemia with non-obstructive coronary arteries (INOCA). Results Mean patient age was 56 years (SD ± 15); 10 (91%) were female. In the acute COVID-19 phase, 4 patients (36%) had had pulmonary infiltrates and 2 (18%) required hospitalization. Conclusive non-invasive tests were obtained in 7 (64%), showing exercise-related myocardial ischaemia in 6 (86%). Coronary angiography ruled out obstructive epicardial stenoses in all the patients. Ach testing revealed abnormal endothelium-dependent responses in 9 (82%) patients: 5 (56%) had epicardial vessel and 4 (44%) microvascular spasm. Endothelium-independent assessment was abnormal in 6 (54%) cases, with abnormal CFR in 2 (33%), abnormal MR in 2 (33) and both abnormal CFR and MR in 2 (33%) patients. The most frequent endotype was combined endothelium dependent- and independent abnormalities (6/9, 67%). Stratified medical treatment according to endotype led to significant improvement in Seattle Angina Scores for angina frequency (+22 points, p=0.013) and a notable trend towards angina stability (+25 points, p=0.093) at a mean follow-up time of 222 days. Conclusions Myocardial ischaemia of non-obstructive origin is common in patients with chest pain and LCS. Vasomotor abnormalities related to endothelial dysfunction occurred in 82% of patients, frequently associated to impaired microvascular vasodilation or high microvascular resistance. Stratified medical treatment led to significant improvement in angina stability and frequency. Funding Acknowledgement Type of funding sources: None.

Risk scores for predicting incident heart failure admission in patients with chronic coronary syndromes: validation in a prospective, monocentric, long-term, cohort study

Abstract Background Heart failure (HF) admission is a serious event in the follow up of patients with chronic coronary syndromes (CCS). Stratification schemes have been described for predicting this end-point but none of them has been externally validated. Purpose To develop point-scores for predicting incident HF admission with data from previous studies, to perform an external validation in an independent prospective cohort study, and to compare their discriminative ability for this event. Methods We performed a literature review searching for prospective studies including patients with CCS, excluding patients with HF at baseline, with data on HF admission incidence in follow up and predictive variables. If undescribed previously, scores were developed including those variables independently associated with this outcome, and score points were assigned based in the relative magnitude of the coefficients of Cox regression models. The resulting scores were validated and their discriminative ability compared in a prospective, monocentric, 17-years cohort study, that included consecutive outpatients with CCS. Results Four studies were included: two post-hoc analysis of clinical trials (CARE and PEACE) and two observational registries (CORONOR and CLARIFY). The validation cohort included 1212 patients (mean age 67±11 years, 74% male) followed for up to 17 years (median 12 years, p25–75 5–15 years), with 171 patients suffering at least one HF admission in follow-up. The proportions of the variables needed for scores calculation available in the database of the study were 75% (6/8), 88% (15/17), 100% (8/8) and 85% (17/20) respectively, for each of these study-derived scores. Discriminative ability for predicting HF admission was statistically significant for all (C-statistic 0.72, 95% CI 0.68–0.75, p&amp;lt;0.0005; 0.72, 95% CI 0.68–0.76, p&amp;lt;0.0005; 0.73, 95% CI 0.69–0.76, p&amp;lt;0.0005; and 0.69, 95% CI 0.65–0.73, p&amp;lt;0.0005 for CARE, PEACE, CORONOR and CLARIFY scores, figure 1) and paired comparison among them were all non-significant except for CORONOR and CLARIFY scores (p=0.03). The CORONOR score (Age [each year] 2 points, ejection fraction [each percentage point] −1 point, hypertension 11 points, diabetes 10 points, atrial fibrillation 14 points, body mass index [each kg/m2 unit] 1 point, symptomatic angina 11 points and multivessel disease 7 points) identified subgroups of patients with 12 years-HF admission free survival probabilities of 97%, 87 and 62% (p&amp;lt;0.0005, first, second and third tertile of the score, figure 2). Conclusions All tested scores showed significant discriminative ability for predicting incident HF admission in this independent validation study. Their discriminative ability was similar, except that CORONOR score performed significantly better than CLARIFY score. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The work for this paper was funded by the Andalusian Society of Cardiology through anunconditional grant from Astra Zeneca. ROC curves for HF predictive scoresHF free survival by CORONOR score

Correlation of Seattle Angina Questionnaire score and post-procedural outcomes in patients undergoing multi-vessel coronary intervention

Abstract Introduction The Seattle Angina Questionnaire (SAQ) score has been used to assess angina severity in patients undergoing coronary intervention. However, assessment of clinical outcomes using the SAQ score in those with multi-vessel disease (MVD) requiring multiple interventions has not been determined. Purpose To analyse patient-reported outcomes over time among individuals undergoing multiple staged interventions using serial SAQ scores. Methods We performed a retrospective analysis of 531 consecutive elective patients who underwent multi-vessel coronary intervention from January 1, 2015, to December 31, 2018, at a single academic centre. We used a short-form version of the SAQ score calculator that is built into our hospital electronic medical record. Trained clinical staff administered the SAQ at the point of care before each procedure. We divided the baseline SAQ scores into three groups [Group 1: &amp;lt;50, Group 2: 50–66, Group 3: ≥67] and analysed the correlation between the scores and patient-reported angina symptoms before the final staged intervention. Post index procedural outcomes, including myocardial infarction, congestive heart failure, post-procedural bleeding, and blood transfusion were reported. Results In all, 531 patients met inclusion and exclusion criteria. Patients' mean age was 65.66±10.30 years, and 78.3% of patients were males. Group 1 had an increased prevalence of diabetes (59.3% vs. 49.4% and 44%), prior coronary artery bypass surgery (CABG) (24.7% vs. 17.2% and 11.4%), a lower haemoglobin value (12.88±1.56 vs. 13.06±1.7 and 13.33±1.56) compared with group 2 and group 3. The rate of in-stent restenosis (ISR) was 18.7%, 11.5% and 8.6% in group 1, 2, and 3, respectively. Summary SAQ-7 values between interventions had improved significantly in group 1 (22.30±21.35) and group 2 (10.45±17.77), while group 3 failed to show any meaningful change (−1.09±14.79) (P&amp;lt;0.0001). [Table 1] The post-index-procedural outcomes were not statistically different among the three groups. In group 1, women (adjusted odds ratio [aOR]: 3.96; 95% confidence interval [CI]: 2.44 to 6.45; p&amp;lt;0.0001) and prior CABG patients (aOR: 2.03; 95% CI: 1.27 to 3.24; p=0.0031) had higher odds of SAQ-7 improvement between index and staged intervention. Conclusion The lowest baseline SAQ group had a significant improvement of SAQ score between the index and a staged intervention. The study demonstrated that serial SAQ scores could be used as a surrogate to measure patient-reported outcomes in those with MVD undergoing multiple interventions. Funding Acknowledgement Type of funding sources: None.

Device profile of the VEST for external support of SVG Coronary artery bypass grafting: historical development, current status, and future directions

ABSTRACT Introduction : A search for strategies to address saphenous vein graft (SVG) failure – the main factor limiting the long-term success of coronary bypass grafting – has led to trialing of external stenting technologies. Areas covered : The manuscript covers historical development and current status of external scaffolding for the treatment of SVG intimal hyperplasia. Comprehensive literature review and personal communication with VGS leadership, the developer of the VEST device, served as the sources. Expert opinion : If the external scaffolding concept proves to be successful in mitigating the intimal hyperplasia inherent to arterialized saphenous vein conduits, it could have a dramatic impact on the recurrence of anginal symptoms, the need for repeat revascularization, and the incidence of myocardial infarction following CABG surgery. These laudable sequelae could ultimately convey significant public health repercussions by reducing healthcare resource use and improving the long-term survival and quality of life of CABG recipients.

Pretest models for predicting abnormal stress single-photon emission computed tomography myocardial perfusion imaging

BackgroundThe frequency of abnormal stress SPECT myocardial perfusion imaging (MPS) decreased over the past decades despite an increase in the prevalence of cardiovascular risk factors. These findings strengthen the need to develop more effective strategies for appropriately referring patients with suspected coronary artery disease (CAD) to cardiac imaging. The aim of this study was to develop pretest assessment models for predicting abnormal stress MPS. MethodsWe included 5,601 consecutive patients with suspected CAD, who underwent stress MPS at our academic center. Two different models were considered: a basic model including age, gender, and anginal symptoms; and a clinical model including also diabetes, hypertension, hypercholesterolemia, smoking, and family history of CAD. ResultsIn patients with abnormal MPS, the basic model classified more than 75% of patients as intermediate risk, whereas only 23% were incorrectly classified as low risk. In patients with normal MPS, 45% were correctly classified as low risk and none as high risk. Basic and clinical models had a limited discriminating capacity (area under the receiver operating characteristic curve 0.644 for basic model and 0.647 for clinical model) between individuals with and without abnormal stress MPS. The decision curve analysis demonstrates a high net benefit across a range of threshold probabilities from ~ 15% to ~30% for both models. ConclusionsA pretest risk stratification based on traditional cardiovascular risk factors has a limited value for predicting an abnormal stress MPS in patients with suspected CAD. However, selecting a proper threshold probability enhances the appropriateness of referral to stress MPS.

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.