Positive Predictive Value of Computerized Tomography Coronary Angiography versus Computerized Tomography Fractional Flow Reserve in a Real-world Population.

Background: Computed Tomography coronary angiography and fractional flow reserve (CTCA and CT-FFR) are noninvasive 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 computerized tomography coronary angiography (CTCA) against the gold standard of ICA in different real-world patient groups. Methods: A retrospective analysis of 477 patients referred for CTCA or CT-FFR for investigation of possible coronary ischemia. 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 the scan was also performed. Patients who underwent invasive nonhyperemic pressure wire measurements had their instant wave-free ratio or resting full-cycle ratio 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.

Predictors of in-hospital mortality in critically ill patients with COVID-19: a large dual tertiary centre study.

OBJECTIVES: The aim of this study was to investigate the relationship of echocardiographic parameters, laboratory findings and clinical characteristics with in-hospital mortality in adult patients with COVID-19 admitted to the intensive care units (ICU) in two large collaborating tertiary UK centres. DESIGN: Observational retrospective study. SETTING: The study was conducted in patients admitted to the ICU in two large tertiary centres in London, UK. PARTICIPANTS: Inclusion criteria were: (1) patients admitted to the ICU with a COVID-19 diagnosis over a period of 16 weeks. and (2) underwent a transthoracic echocardiogram on the first day of ICU admission as clinically indicated.No exclusion criteria applied.Three hundred patients were enrolled and completed the follow-up. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure in this study was in-hospital mortality in patients admitted to the ICU with COVID-19 infection. RESULTS: Older age (HR: 1.027, 95% CI 1.007 to 1.047; p=0.008), left ventricular (LV) ejection fraction<35% (HR: 5.908, 95% CI 2.609 to 13.376; p<0.001), and peak C reactive protein (CRP) (HR: 1.002, 95% CI 1.001 to 1.004, p=0.001) were independently correlated with mortality in a multivariable Cox regression model. Following multiple imputation of variables with more than 5% missing values, random forest analysis was applied to the imputed data. Right ventricular (RV) basal diameter (RVD1), RV mid-cavity diameter (RVD2), tricuspid annular plane systolic excursion, RV systolic pressure, hypertension, RV dysfunction, troponin level on admission, peak CRP, creatinine level on ICU admission, body mass index and age were found to have a high relative importance (> 0.7). CONCLUSIONS: In patients with COVID-19 in the ICU, both severely impaired LV function and impaired RV function may have adverse prognostic implications, but older age and inflammatory markers appear to have a greater impact. A combination of echocardiographic and laboratory investigations as well as demographic and clinical characteristics appears appropriate for risk stratification in patients with COVID-19 who are admitted to the ICU.

Bullying in UK cardiology: a systemic problem requiring systemic solutions.

OBJECTIVES: Bullying of trainee doctors has been shown to be associated with detrimental outcomes for both doctors and patients. However, there is limited evidence regarding the level of bullying of trainees within medical specialties. METHODS: An annual survey of UK cardiology trainees was conducted through the British Junior Cardiologists' Association between 2017 and 2020 and asked questions about experiencing and witnessing bullying, and exposure to inappropriate language/behaviour in cardiology departments. Fisher's exact tests and univariable logistic regression models were used to describe associations between trainee characteristics, and reports of bullying and inappropriate language/behaviour. RESULTS: Of 1358 trainees, bullying was reported by 152 (11%). Women had 55% higher odds of reporting being bullied (OR: 1.55 95% CI (1.08 to 2.21)). Non-UK medical school graduates were substantially more likely to be bullied (European Economic Area (EEA) OR: 2.22 (1.31 to 3.76), non-EEA/UK OR: 3.16 (2.13 to 4.68)) compared with those graduating from UK-based medical schools. Women were more likely than men to report sexist language (14% vs 4%, p<0.001). Non-UK medical school graduates were more likely to experience racist language (UK 1.5%, EEA 6%, other locations 7%, p=0.006). One-third of trainees (33%) reported at least one inappropriate behaviour with 8% reporting being shouted at or targeted with spontaneous anger. Consultants in cardiology (82%) and other specialties (70%) were most commonly implicated by those reporting bullying. DISCUSSION: Bullying and inappropriate language are commonly experienced by cardiology trainees and disproportionately affect women and those who attended non-UK medical schools. Consultants both in cardiology and other specialties are the most commonly reported perpetrators.

Intravascular imaging-guided intracoronary lithotripsy: First real-world experience.

BACKGROUND AND AIMS: Coronary calcification remains a significant challenge for the contemporary interventional cardiologist. We aim to describe the use of intravascular lithotripsy (IVL) in a range of real-world settings. METHODS: A retrospective two-center analysis of patients treated with IVL between June 2018 and November 2019. Technical and procedural success, as well as procedural complications and 30-day outcomes (death, myocardial infarction, or repeat target vessel revascularization), was recorded. RESULTS: Sixty-five patients underwent IVL: 80% were male and the mean age was 70.1 ± 12.0 years. 54% of patients presented with acute coronary syndrome (ACS) and 68% of patients had intracoronary imaging. Twelve patients required IVL within pre-existing stents, and 12 underwent IVL in the left main stem. All balloons were successfully delivered with 98.5% procedural success. There was a significant gain in MLA post PCI of 261.9 ± 100% following IVL. There were two procedural complications. At 30-day follow-up, there was one death, and one patient required a repeat procedure due to stent underexpansion. CONCLUSIONS: In this largest real-world series of imaging-guided IVL for calcified lesions to date, we demonstrate that IVL is deliverable, safe, and effective at calcium modification especially when intracoronary imaging is used.

First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19.

Presence of heart failure is associated with a poor prognosis in patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of preclinical heart failure, is associated with survival in patients hospitalized with COVID-19. A retrospective outcome study was performed in patients hospitalized with COVID-19 who underwent echocardiography (n=380) at the West Branch of the Union Hospital, Wuhan, China and in patients admitted to King's Health Partners in South London, United Kingdom. Association of EF1 with survival was performed using Cox proportional hazards regression. EF1 was compared in patients with COVID-19 and in historical controls with similar comorbidities (n=266) who had undergone echocardiography before the COVID-19 pandemic. In patients with COVID-19, EF1 was a strong predictor of survival in each patient group (Wuhan and London). In the combined group, EF1 was a stronger predictor of survival than other clinical, laboratory, and echocardiographic characteristics including age, comorbidities, and biochemical markers. A cutoff value of 25% for EF1 gave a hazard ratio of 5.23 ([95% CI, 2.85-9.60]; P<0.001) unadjusted and 4.83 ([95% CI, 2.35-9.95], P<0.001) when adjusted for demographics, comorbidities, hs-cTnI (high-sensitive cardiac troponin), and CRP (C-reactive protein). EF1 was similar in patients with and without COVID-19 (23.2±7.3 versus 22.0±7.6%, P=0.092, adjusted for prevalence of risk factors and comorbidities). Impaired EF1 is strongly associated with mortality in COVID-19 and probably reflects preexisting, preclinical heart failure.

Impact and Determinants of High-Sensitivity Cardiac Troponin-T Concentration in Patients With COVID-19 Admitted to Critical Care.

Cardiac Troponin (hs-TnT) elevation has been reported in unselected patients hospitalized with COVID-19 however the mechanism and relationship with mortality remain unclear. Consecutive patients admitted to a high-volume intensive care unit (ICU) in London with severe COVID-19 pneumonitis were included if hs-TnT concentration at admission was known. Kaplan-Meier survival analysis performed, with cohorts classified a priori by multiples of the upper limit of normal (ULN). 277 patients were admitted during a 7-week period in 2020; 176 were included (90% received invasive ventilation). hs-TnT at admission was 16.5 (9.0 to 49.3) ng/L, 56% had concentrations >ULN. 56 patients (31.8%) died during the index admission. Admission hs-TnT level was lower in survivors (12.0 (8.0-27.8) vs 28.5 (14.0 to 81.0) ng/L, p = 0.001). Univariate predictors of mortality were age, APACHE-II Score and admission hs-TnT (HR 1.73, p = 0.007). By multivariate regression, only age (HR 1.33, CI: 1.16.to 1.51, p < 0.01) and admission hs-TnT (HR 1.94, CI: 1.22 to 3.10, p = 0.006) remained predictive. Survival was significantly lower when admission hs-TnT was >ULN (log-rank p-value<0.001). Peak hs-TnT was higher in those who died but was not predictive of death after adjustment for other factors. In conclusion, in critically ill patients with COVID-19 pneumonitis, the hs-TnT level at admission is a powerful independent predictor of the likelihood of surviving to discharge from ICU. In most cases, hs-TnT elevation does not represent major myocardial injury but acts as a sensitive integrated biomarker of global stress. Whether stratification based on admission Troponin level could be used to guide prognostication and management warrants further evaluation.

Coronary artery lesion phenotype in frail older patients with non-ST-elevation acute coronary syndrome undergoing invasive care.

AIMS: The association of frailty with coronary plaque phenotype among older patients with non-ST-elevation acute coronary syndrome (NSTEACS) is not known. The aim of this study was to evaluate the association of frailty with coronary plaque phenotype among older patients with NSTEACS. METHODS AND RESULTS: Older patients with NSTEACS who underwent invasive angiography were recruited. Frailty was measured using the Fried frailty score. Following angiography, patients underwent greyscale and virtual histology intravascular ultrasound (VH-IVUS) imaging. Of the 90 patients, 26 (28.9%) were robust, 49 (54.4%) patients were pre-frail, and 15 (16.7%) were frail. Mean age was 80.9±3.8 years; 59 (65.6%) were male. Compared to robust patients, the pre-frail group had a significantly greater presence of high-risk lesions including VH thin-cap fibroatheroma (TCFA, p=0.011), minimum lumen area (MLA) ≤4 mm2 (p=0.016), TCFA+MLA ≤4 mm2 (p=0.005), TCFA+plaque burden (PB) ≥70% (p=0.005) and TCFA+PB ≥70%+MLA ≤4 mm2 (p=0.003). By age- and sex-adjusted logistic regression analysis, frailty was found to be strongly and independently associated with the presence of TCFA (odds ratio [OR] 2.81, 95% confidence interval [CI]:1.06-7.48, p=0.039). CONCLUSIONS: This is the first study to report the relationship between frailty phenotype and coronary plaque morphology among frail older NSTEACS patients. ClinicalTrials.gov Identifier: NCT01933581.

One-year clinical outcomes in older patients with non-ST elevation acute coronary syndrome undergoing coronary angiography: An analysis of the ICON1 study.

AIMS: The aim of this prospective, observational study was to identify predictors of adverse outcome at one year, following invasive care of older patients with non-ST-elevation acute coronary syndrome (NSTEACS) according to frailty status. METHODS: Older patients (aged ≥ 75 years), presenting with NSTEACS, undergoing invasive coronary angiography with a view to revascularisation, underwent assessment of frailty, cognition, functional status and quality of life. Participants were categorised as robust, pre-frail or frail using the Fried criteria. The primary outcome comprised a composite of all-cause mortality, myocardial infarction, stroke, unplanned revascularisation and major bleeding, at one year. Cox proportional hazards regression was used to derive a multivariate risk score. RESULTS: Overall, the composite endpoint was observed in 81 participants (29%). There was a significant difference in the occurrence of the primary outcome in the 3 frailty groups (robust 18.0%, pre-frail 27.5% and frail 39%; p = 0.03; hazard ratio (HR) for frail vs. robust: 2.79, 95% Confidence Interval [CI] 1.28-6.08). Fried frailty classification, age (categorised as ≥85 years), raised Killip class, systolic blood pressure on admission, history of peripheral vascular disease (PVD), problems dressing self and implantation of a bare metal stent were identified as predictors of adverse events at one year, with a C-statistic of 0.77 (95% CI 0.71-0.83). A point-based clinical risk score (FRAIL-HEART) was defined, which had a C-statistic of 0.70 (95% CI 0.63-0.77) and significantly outperformed the GRACE 2 score. CONCLUSION: Frailty is associated with adverse clinical outcomes, following invasive management of older patients with NSTEACS. The derived risk models may enable improved risk stratification in practice.

Tris(2-pyridyl)phosphine as a versatile ligand for pnictogen acceptors.

We report cationic complexes of arsenic and antimony with the tris(2-pyridyl)phosphine ligand. Chloride ion abstraction from AsCl3 using TMSOTf in the presence of the ligand gives [P(Pyr)3As][OTf]3, in which the trication adopts a C3v symmetric cage structure. The reaction proceeds via the intermediate [P(Pyr)3AsCl][OTf]2, which undergoes chloride exchange to give [P(Pyr)3As][OTf]3 and [P(Pyr)3AsCl2][OTf]. The rearrangement reaction has been supported by the isolation of the antimony mono fluoride derivative [P(Pyr)3SbF][OTf]2. The asymmetric axial lone pairs in derivatives of [P(Pyr)3Pn]3+ are electronically separated. The HOMO-1 (for arsenic) and HOMO (for antimony) represent the major contribution to the phosphine lone pair indicating the possibility for nucleophilic behaviour despite the +3 charge. Less accessible is the HOMO-7, which represents the lone pair at arsenic or antimony, respectively.

Gender Differences in Outcomes and Predictors of All-Cause Mortality After Percutaneous Coronary Intervention (Data from United Kingdom and Sweden).

To determine gender differences and predictors of all-cause mortality (30 days and 1 year) after percutaneous coronary intervention (PCI) in patients with stable angina pectoris and acute coronary syndrome (non-ST-elevation myocardial infarction/unstable angina pectoris and ST-elevation myocardial infarction) in the British Cardiovascular Intervention Society (BCIS) and Swedish Coronary Angiography and Angioplasty Registry (SCAAR) data sets, an analysis of prospectively collected data from 2007 to 2011 was performed. In total, 458,261 patients (BCIS: n = 368,492 [25.9% women]; Sweden: n = 89,769 [27.2% women]) who underwent PCI were included in this analysis. Using multiple regression analysis, in the BCIS registry, female gender was an independent predictor of all-cause mortality at 30 days (odds ratio [OR] 1.15, 95% CI 1.10 to 1.22, p <0.0001) and at 1 year (OR 1.08, 95% CI 1.04 to 1.12, p <0.0001) after PCI for all patients. Likewise, in the SCAAR registry, female gender was an independent predictor of all-cause mortality at 30 days (OR 1.15, 95% CI 1.05 to 1.26, p = 0.002) and 1 year (OR 1.09, 95% CI 1.03 to 1.17, p = 0.006) after PCI for all patients. In both data sets, there was no statistically significant interaction between age and gender for all-cause mortality at 30 days (BCIS, p = 0.59; SCAAR, p = 0.40) and at 1 year (BCIS, p = 0.11; SCAAR, p = 0.83). In conclusion, despite advances in care, women compared with men continue to experience higher all-cause mortality after PCI for coronary artery disease. The patient's age at the time of PCI remains a strong predictive factor of mortality in this population. Strategies and further research are warranted to better address the management of coronary artery disease in women with possibly earlier diagnosis and more tailored treatments.

MicroRNAs in Ischemic Heart Disease: From Pathophysiology to Potential Clinical Applications.

Despite rapid advances in cardiovascular research and therapeutic strategies, ischemic heart disease (IHD) remains the leading cause of mortality worldwide. MicroRNAs (miRNAs) are small, noncoding RNAs which post transcriptionally regulate gene expression. In the past few years, miRNAs have emerged as key tools for the understanding of the pathophysiology of IHD, with potential uses as new biomarkers and therapeutic targets. Several studies report a regulatory role of miRNAs, with regard to fundamental components of IHD pathogenesis and progression, such as lipoprotein metabolism, atherogenesis, vascular calcification, platelet function, and angiogenesis. Due to their high stability in biofluids, circulating miRNAs have attracted attention as promising biomarkers of IHD, especially in cardiovascular risk prediction and the diagnosis of myocardial infarction. Furthermore, experimental studies have demonstrated the potential of miRNA-targeted therapy in improving hyperlipidemia, atherosclerosis, and angiogenesis. In this review, the current knowledge on the role of miRNAs in IHD and translational perspectives of their use is discussed.

Engaging older patients in cardiovascular research: observational analysis of the ICON-1 study.

BACKGROUND: As a consequence of population ageing, the number of older patients presenting with acute coronary syndrome (ACS) is increasing. The historical underrepresentation of older patients in many pivotal ACS clinical trials undermines the practice of evidence-based medicine in this high-risk cohort. This study evaluates the feasibility of recruitment of older patients to a longitudinal, clinical study. METHODS: The study to Improve Cardiovascular Outcomes in high-risk patieNts with ACS (ICON-1) is an observational, prospective cohort study investigating predictors of poor outcome in older patients with ACS. All patients aged ≥75 years, referred to a tertiary cardiovascular centre in the North East of England for coronary angiography with a view to urgent percutaneous coronary intervention, were screened for inclusion. A screening log was prospectively maintained, and a detailed analysis was performed to identify the factors associated with recruitment and non-recruitment to ICON-1. RESULTS: Of the 629 patients screened over 34 months, 457 (72.7%) satisfied the a priori-defined study inclusion/exclusion criteria. Of those eligible to participate, 300 (68.5%) provided informed consent and were recruited to the study; 59 (13.5%) were unable to consent due to a lack of capacity or limitations in communication, and 79 patients (18.0%) declined to participate in the study. Those lacking adequate capacity to consent were older than those able to provide informed consent (83.0±4.7 vs 81.0±4.7 years, p=0.002). Women were more likely to decline than men (25.1% vs 10.0%, p<0.001). CONCLUSIONS: The recruitment of patients was robust, comparing favourably to previous longitudinal studies within this age group. Although enrolling older people to research remains challenging, this cohort is enthusiastic to participate. The contribution of older patients must not be ignored, particularly in the setting of an ever-ageing population, in whom cardiovascular disease burden is high. TRIAL REGISTRATION NUMBER: NCT01933581; Pre-results.

Study to Improve Cardiovascular Outcomes in high-risk older patieNts (ICON1) with acute coronary syndrome: study design and protocol of a prospective observational study.

INTRODUCTION: The ICON1 study (a study to Improve Cardiovascular Outcomes in high-risk older patieNts with acute coronary syndrome) is a prospective observational study of older patients (≥75 years old) with non-ST-elevation acute coronary syndrome managed by contemporary treatment (pharmacological and invasive). The aim of the study was to determine the predictors of poor cardiovascular outcomes in this age group and to generate a risk prediction tool. METHODS AND ANALYSIS: Participants are recruited from 2 tertiary hospitals in the UK. Baseline evaluation includes frailty, comorbidity, cognition and quality-of-life measures, inflammatory status assessed by a biomarker panel, including microRNAs, senescence assessed by telomere length and telomerase activity, cardiovascular status assessed by arterial stiffness, endothelial function, carotid intima media thickness and left ventricular systolic and diastolic function, and coronary plaque assessed by virtual histology intravascular ultrasound and optical coherence tomography. The patients are followed-up at 30 days and at 1 year for primary outcome measures of death, myocardial infarction, stroke, unplanned revascularisation, bleeding and rehospitalisation. ETHICS AND DISSEMINATION: The study has been approved by the regional ethics committee (REC 12/NE/016). Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT01933581: Pre-results.

Coronary artery disease in patients with dementia.

Our population is ageing. The prevalence of dementia is increasing as the population ages. Dementia is known to share many common risk factors with coronary artery disease including age, genetics, smoking, the components of the metabolic syndrome and inflammation. Despite the growing ageing population with dementia, there is underutilization of optimal care (pharmacotherapy and interventional procedures) in this cohort. Given common risk factors and potential benefit, patients with cognitive impairment and dementia should be offered contemporary care. However, further research evaluating optimal care in this patient cohort is warranted.

Intracoronary Imaging in the Detection of Vulnerable Plaques.

Coronary artery disease is the result of atherosclerotic changes to the coronary arterial wall, comprising endothelial dysfunction, vascular inflammation and deposition of lipid-rich macrophage foam cells. Certain high-risk atherosclerotic plaques are vulnerable to disruption, leading to rupture, thrombosis and the clinical sequelae of acute coronary syndrome. Though recognised as the gold standard for evaluating the presence, distribution and severity of atherosclerotic lesions, invasive coronary angiography is incapable of identifying non-stenotic, vulnerable plaques that are responsible for adverse cardiovascular events. The recognition of such limitations has impelled the development of intracoronary imaging technologies, including intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy, which enable the detailed evaluation of the coronary wall and atherosclerotic plaques in clinical practice. This review discusses the present status of invasive imaging technologies; summarises up-to-date, evidence-based clinical guidelines; and addresses questions that remain unanswered with regard to the future of intracoronary plaque imaging.

The Role of Virtual Histology Intravascular Ultrasound in the Identification of Coronary Artery Plaque Vulnerability in Acute Coronary Syndromes.

Markers of coronary plaque vulnerability, such as a high lipid burden, increased inflammatory activity, and a thin fibrous cap, have been identified in histological studies. In vivo, grayscale intravascular ultrasound (IVUS) provides more in-depth information on coronary artery plaque burden than conventional angiography but is unable to accurately distinguish between noncalcific tissue types within the plaque. An analysis of IVUS radiofrequency backscatter based on spectral pattern recognition, such as virtual histology IVUS, allows detailed scrutiny of plaque composition and classification of coronary lesions. This review discusses the virtual histology IVUS technology and its accuracy in identifying vulnerable plaque features, focusing on its use in predicting patient outcomes after acute coronary syndrome, and its limitations in clinical practice.

Carotid Intima Media Thickness and Its Utility as a Predictor of Cardiovascular Disease: A Review of Evidence.

Cardiovascular (CV) disease is still the leading cause of death in the developed world, despite the considerable progress in CV medical and surgical therapeutics. Many risk factors are associated with the development of future adverse CV events, such as age, hypertension, body mass index, and other comorbidities. Carotid intima media thickness (CIMT) is one method of calculating plaque burden by assessing the level of arterial thickening present. CIMT can be used as a noninvasive marker of atherosclerotic disease with increasing CIMT linked to an increased risk of subsequent CV events. In this review, the association of CIMT with CV disease is explored. Current literature on the role of CIMT in predicting CV outcomes is reviewed to determine whether it is a predictor of CV events, both in the general population and in the high-risk groups, such as those with hypertension, diabetes mellitus, and chronic kidney disease.