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Background Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear. Objectives The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre–COVID-19 cohorts. Methods From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re–myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre–COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019). Results In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non–ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p, Central Illustration

Background Microvascular angina is caused by cardiac small vessel disease, and dysregulation of the endothelin system is implicated. The minor G allele of the non-coding single nucleotide polymorphism (SNP) rs9349379 enhances expression of the endothelin 1 gene in human vascular cells, increasing circulating concentrations of ET-1. The prevalence of this allele is higher in patients with ischemic heart disease. Zibotentan is a potent, selective inhibitor of the ETA receptor. We have identified zibotentan as a potential disease-modifying therapy for patients with microvascular angina. Methods We will assess the efficacy and safety of adjunctive treatment with oral zibotentan (10 mg daily) in patients with microvascular angina and assess whether rs9349379 (minor G allele; population prevalence ~36%) acts as a theragnostic biomarker of the response to treatment with zibotentan. The PRIZE trial is a prospective, randomized, double-blind, placebo-controlled, sequential cross-over trial. The study population will be enriched to ensure a G-allele frequency of 50% for the rs9349379 SNP. The participants will receive a single-blind placebo run-in followed by treatment with either 10 mg of zibotentan daily for 12 weeks then placebo for 12 weeks, or vice versa, in random order. The primary outcome is treadmill exercise duration using the Bruce protocol. The primary analysis will assess the within-subject difference in exercise duration following treatment with zibotentan versus placebo. Conclusion PRIZE invokes precision medicine in microvascular angina. Should our hypotheses be confirmed, this developmental trial will inform the rationale and design for undertaking a larger multicenter trial.

Background: The pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. Methods: A prospective, multicenter, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28-60 days post-discharge (visit 2). Multisystem investigations included chest computed tomography with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging, digital electrocardiography, and multisystem biomarkers. The primary outcome was the adjudicated likelihood of myocarditis.Results: 161 patients (mean age 55 years, 43% female) and 27 controls with similar age, sex, ethnicity, and vascular risk factors were enrolled from 22 May 2020 to 2 July 2021 and had a primary outcome evaluation. Compared to controls, at 28-60 days post-discharge, patients with COVID-19 had persisting evidence of cardio-renal involvement, systemic inflammation, and hemostasis pathway activation. Myocarditis was adjudicated as being not likely (n=17; 10%), unlikely (n=56; 35%), probable (n=67; 42%) or very likely (n=21; 13%). Acute kidney injury (odds ratio, 95% confidence interval: 3.40 (1.13, 11.84); p=0.038) and low hemoglobin A1c (0.26 (0.07, 0.87); p=0.035) were multivariable associates of adjudicated myocarditis. During convalescence, compared to controls, COVID-19 was associated with worse health-related quality of life (EQ5D-5L) (pConclusions: The illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung damage and hemostasis activation. Adjudicated myocarditis occurred in one in eight hospitalized patients and was associated with impairments in health status, physical and psychological wellbeing during community convalescence. Public registration: ClinicalTrials.gov identifier is NCT04403607.

Background Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA). Objectives Our research has 2 objectives. The first is to undertake a diagnostic study, and the second is to undertake a nested, clinical trial of stratified medicine. Design A prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03477890) will be performed. All-comers referred for clinically indicated CTCA for investigation of suspected coronary artery disease (CAD) will be screened in 3 regional centers. Following informed consent, eligible patients with angina symptoms are enrolled before CTCA and remain eligible if CTCA excludes obstructive CAD. Diagnostic study: Invasive coronary angiography involving an interventional diagnostic procedure (IDP) to assess for disease endotypes: (1) angina due to obstructive CAD (fractional flow reserve ≤0.80); (2) microvascular angina (coronary flow reserve 25); (3) microvascular angina due to small vessel spasm (acetylcholine); (4) vasospastic angina due to epicardial coronary spasm (acetylcholine); and (5) noncoronary etiology (normal coronary function). The IDP involves direct invasive measurements using a diagnostic coronary guidewire followed by provocation testing with intracoronary acetylcholine. The primary outcome of the diagnostic study is the reclassification of the initial CTCA diagnosis based on the IDP. Stratified medicine trial: Participants are immediately randomized 1:1 in the catheter laboratory to therapy stratified by endotype (intervention group) or not (control group). The primary outcome of the trial is the mean within-subject change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and certainty), and clinical utility (impact on treatment and investigations). Health status assessments include quality of life, illness perception, anxiety-depression score, treatment satisfaction, and physical activity. Participants who are not randomized will enter a follow-up registry. Health and economic outcomes in the longer term will be assessed using electronic patient record linkage. Value CorCTCA will prospectively characterize the prevalence of disease endotypes in INOCA and determine the clinical value of stratified medicine in this population., Graphical abstract Unlabelled Image

Testicular germ cell tumours are the most common malignancy in men aged 20 to 40 years. They are subdivided into seminoma and non-seminomatous germ cell tumours (NSGCTs). Both seminoma and NSGCT occur at about the same rate, however some tumours contain a combination of both. Cisplatin-based chemotherapy is used adjuvantly in high-risk stage 1 mixed and NSGCT patients and contributes towards oncological cure in almost all metastatic cases, regardless of histology. However, cardiovascular toxicity is a major concern. In addition to acute endothelial toxicity and associated risk of arterial thrombosis, accelerated atherosclerosis may be the result of chemotherapy-associated latent cardio-metabolic dysfunction. A 45-year-old man began treatment with cisplatin-based chemotherapy for testicular cancer. On day 9, he suffered an anterior ST segment elevation myocardial infarction (STEMI). There was proximal occlusion of the left anterior descending (LAD) artery but otherwise normal coronary arteries. Ten months following chemotherapy, he had another STEMI. There was a fresh obstructive lesion in the previously angiographically normal mid LAD, new diffuse coronary atheroma elsewhere and a deterioration in lipid profile despite statin therapy. Acute and longer-term cardiovascular risks of cisplatin-based chemotherapy may have different underlying pathophysiological mechanisms. These issues are of growing relevance in a population of patients expected to have excellent cancer-related outcomes.

No abstract available.

MI with non-obstructive coronary arteries (MINOCA) is caused by a heterogeneous group of vascular or myocardial disorders. MINOCA occurs in 5–15% of patients presenting with acute ST-segment elevation MI or non-ST segment elevation MI and prognosis is impaired. The diagnosis of MINOCA is made during coronary angiography following acute MI, where there is no stenosis ≥50% present in an infarct-related epicardial artery and no overt systemic aetiology for the presentation. Accurate diagnosis and subsequent management require the appropriate utilisation of intravascular imaging, coronary function testing and subsequent imaging to assess for myocardial disorders without coronary involvement. Although plaque-related MINOCA is currently managed with empirical secondary prevention strategies, there remains an unmet therapeutic need for targeted and evidence-based therapy for MINOCA patients and increased awareness of the recommended diagnostic pathway.

Ischemic heart disease (IHD) is a leading global cause of ill-health and premature death. Clinical research into IHD is providing new insights into the pathophysiology, epidemiology and treatment of this condition. The major endotypes of IHD include coronary heart disease (CHD) and vasomotor disorders, including microvascular angina and vasospastic angina. Considering unselected patients presenting with stable chest pain, the pre-test probability of CHD is higher in men whereas the pre-test probability of a vasomotor disorder is higher in women. The diagnostic accuracy of diagnostic tests designed to assess coronary anatomy and disease and/or coronary vascular function (functional tests) differ for coronary endotypes. Clinical management should therefore be personalized and take account of sex-related factors. In this review, we consider the definitions of angina and myocardial ischemia. We then appraise the mechanistic links between myocardial ischemia and anginal symptoms and the relative merits of non-invasive and invasive diagnostic tests and related clinical management. Finally, we describe the rationale and importance of stratified medicine of IHD.

A man in his 60s presented to the emergency department with two hours of gradually worsening right-sided chest pain that occurred at rest. During the week before presentation he had also experienced a coryzal illness, including rhinorrhoea, non-productive cough, fever, and lethargy. He described shorter episodes of chest pain, lasting less than 15 minutes, for four weeks before this attendance, but he had not sought medical advice. His vital signs were stable, he was apyrexial, and had normal heart sounds and no pericardial rub. His right chest wall was tender to palpation, particularly at the costochondral margins. The patient was a smoker, had a history of hypertension and dyslipidaemia, and a family history of angina. …

Background Angina is associated with impaired quality of life and an adverse prognosis. Purpose Prospectively evaluate quality of life and clinical outcomes in patients with angina undergoing invasive coronary angiography according to endotype: symptoms and/or signs of ischaemia and no obstructive coronary artery disease (INOCA) compared to obstructive coronary artery disease subjects managed by medical therapy, revascularization with percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery, respectively. Methods We conducted a prospective clinical evaluation of patients with angina undergoing clinically indicated invasive management (NCT03193294). Symptom severity and quality of life were assessed at baseline and repeated after 6 months. Comparisons between treatment groups were based on analysis of covariance general linear models adjusting for baseline score, sex, and cardiovascular risk. INOCA subjects were considered as one diagnostic group and not all subjects had invasive vasoreactivity testing. Results 391 patients (mean age 62±10 years, 52% female) were enrolled over 12 months and classified into one of four groups: INOCA (N=185; 47%), obstructive CAD treated by PCI (N=126; 32%), obstructive CAD treated by CABG (N=48; 12%) and obstructive CAD managed with medical therapy (N=32; 8%). After adjusting for between group differences and overall risk, INOCA subjects had worse angina and worse treatment response at follow up (21% and 27% reduction in angina score compared to CAD patients revascularized with PCI and CABG respectively). INOCA subjects had numerically lower treatment response than CAD patients managed with medications (6.4 units, −12%; P=0.181). Population baseline mean Seattle Angina Questionnaire (SAQ) frequency score (60±26) and SAQ summary score (52.5±19) were similar between groups. The absolute difference was 6.4 units versus medically managed CAD (95% CI: −3.0 to 15.9; P=0.181), 11.3 units versus the CAD group undergoing PCI (6.1 to 16.5; P Conclusion(s) Patients with INOCA had more severe angina symptoms reflecting worse quality of life and treatment response at 6 months with similar MACE as CAD subjects even after adjustment for confounding factors. This study highlights the need for evidence-based antianginal therapies and disease-modifying treatments for angina patients regardless of the presence of obstructive coronary disease. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): This work was funded by the British Heart Foundation (PG/17/2532884; RE/13/5/30177; RE/18/6134217)

Background COVID-19 is typically a primary respiratory illness with multisystem involvement. The prevalence and clinical significance of cardiovascular and multisystem involvement in COVID-19 remain unclear. Methods This is a prospective, observational, multicentre, longitudinal, cohort study with minimal selection criteria and a near-consecutive approach to screening. Patients who have received hospital care for COVID-19 will be enrolled within 28 days of discharge. Myocardial injury will be diagnosed according to the peak troponin I in relation to the upper reference limit (URL, 99th centile) (Abbott Architect troponin I assay; sex-specific URL, male: >34 ng/L; female: >16 ng/L). Multisystem, multimodality imaging will be undertaken during the convalescent phase at 28 days post-discharge (Visit 2). Imaging of the heart, lung, and kidneys will include multiparametric, stress perfusion, cardiovascular magnetic resonance imaging, and computed tomography coronary angiography. Health and well-being will be assessed in the longer term. The primary outcome is the proportion of patients with a diagnosis of myocardial inflammation. Conclusion CISCO-19 will provide detailed insights into cardiovascular and multisystem involvement of COVID-19. Our study will inform the rationale and design of novel therapeutic and management strategies for affected patients. Clinical trial registration ClinicalTrials.gov identifier NCT04403607.

No abstract available.

Background and aims Anti-platelet and anti-thrombotic therapy are well-established treatments in acute coronary syndromes. Highly sensitive assays have diminished the positive predictive value of troponin in acute coronary syndromes and increased the importance of the clinical assessment in interpreting positive results. This cohort study sought to investigate over-treatment of non-coronary troponin rises and associated adverse outcomes. Methods and results We reviewed 223 consecutive patients presenting to Queen Elizabeth University Hospital, Glasgow, with suspected acute coronary syndromes over a six-week period. Of these, 27 (12%) met our ‘inappropriate therapy’ criteria. This group had a low ischaemic risk (HEART score: 4.2 ± 1.4) (GRACE score: 117 ± 30.8) but an intermediate-high bleeding risk (CRUSADE score: 34 ± 14.5). Approximately half of the patients (14/27, 52%) reported chest pain, with only 4/27 (15%) having ischaemic ECG changes. There were three intracranial haemorrhages, each after the patient had received a single dose of aspirin, ticagrelor and fondaparinux. Conclusion The combination of injudicious high-sensitivity troponin testing with potent anti-platelet and anti-thrombotic therapy was associated with possible over-treatment of patients and associated harm. Emphasis on interpretation of troponin in the context of clinical presentation and improved awareness of type 2 myocardial infarction are essential to limit iatrogenic pharmacological harm.

Background Adenosine is frequently used during coronary angiography to induce hyperaemia and allow operators to perform quantitative measurements of lesion severity. Acute bronchospasm is a recognised side effect relating to the activation of ‘off target’ A2B receptors. The true incidence of severe bronchospasm relating to adenosine administration is not known. Methods Using an electronic patient database, we analysed 100,253 consecutive coronary angiograms over almost 19 years. Fractional flow reserve (FFR) was measured under systemic adenosine in 9,440 cases. Results Adenosine-related bronchospasm was reported in only five cases (0.05%). One case resulted in a life-threatening respiratory arrest. Conclusions This study reveals the incidence of acute bronchospasm during FFR testing to be extremely low. Although rare, these reactions can be severe and are not simply limited to patients with brittle airways disease. Physicians should be aware of the utility of bolus intravenous aminophylline providing targeted therapy to reverse and treat adenosine-related bronchospasm.

Background Patients with mildly abnormal or equivocal myocardial perfusion imaging (MPI) scans undergo diagnostic angiography or receive medical management. However, current guidelines mandate different treatment goals for patients with known coronary artery disease (CAD), and catheterization is often required. Coronary computed tomography angiography (CCTA) may be an effective alternative to catheterization for patients at intermediate risk for CAD. Objectives The purpose of this study was to analyze the cost implications of CCTA before catheterization in patients with mildly abnormal or equivocal MPI scans. Methods Patients (n = 206) with mildly abnormal or equivocal MPI scans underwent 64-detector CCTA instead of catheterization at the discretion of a treating physician. Studies were evaluated by a trained reader, and results were classified as “no evident CAD,” “nonobstructive CAD,” or “potentially obstructive CAD.” Cost data were analyzed based on actual reimbursements for CT angiography and cardiac catheterization. We modeled the costs of two clinical approaches. “Selective catheterization” involved catheterization only if CCTA showed potentially obstructive CAD. “Immediate catheterization” considered catheterization for all patients in the cohort. Sensitivity analysis was performed on multiple variables. Results Thirty-two percent of patients had potentially obstructive plaque on CTA. Selective catheterization saves $1454 per patient. Sensitivity analysis revealed cost savings to be preserved even if up to 81.5% of the patient cohort undergoes catheterization, as well as across wide ranges of procedural costs. Conclusion A strategy that uses CCTA as a gatekeeper to catheterization is cost saving as opposed to initial catheterization for patients with equivocal or mildly abnormal myocardial perfusion scans.