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Background: Placebo-controlled evidence from ORBITA-2 (Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina-2) found that percutaneous coronary intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many patients. The reason for this was unclear., Objectives: This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, noninvasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI., Methods: Prerandomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the World Health Organization Rose angina questionnaire (Rose). Disease severity was assessed using quantitative coronary angiography, stress echocardiography, fractional flow reserve, and instantaneous wave-free ratio. Bayesian ordinal regression was used., Results: At prerandomization, the median number of daily angina episodes was 0.8 (Q1-Q3: 0.4-1.6), 64% had Rose angina, quantitative coronary angiography diameter stenosis was 61% (Q1-Q3: 49%-74%), stress echocardiography score was 1.0 (Q1-Q3: 0.0-2.7), fractional flow reserve was 0.63 (Q1-Q3: 0.49-0.75), and instantaneous wave-free ratio was 0.78 (Q1-Q3: 0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with quantitative coronary angiography ordinal correlation coefficient: 0.06 (95% credible interval [CrI]: 0.00-0.08); stress echocardiography: 0.09 (95% CrI: 0.02-0.10); fractional flow reserve: 0.04 (95% CrI: -0.03 to 0.07); and instantaneous wave-free ratio: 0.04 (95% CrI: -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR: 1.9; 95% CrI: 1.6-2.1; probability of interaction [Pr Interaction ] = 99.9%; and OR: 1.8; 95% CrI: 1.6-2.1; Pr Interaction  = 99.9%, respectively)., Conclusions: Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI., Competing Interests: Funding Support and Author Disclosures ORBITA-2 was an investigator-initiated trial sponsored by Imperial College London. The trial was funded by grants from National Institute for Health and Care Research Imperial Biomedical Research Centre, Medical Research Council, British Heart Foundation, National Institute for Health and Care Research, and the Imperial Coronary Flow Trust. Philips Volcano supplied the coronary pressure wires. Dr Simader has received a sponsorship from Servier Pharmaceuticals. Dr Rajkumar has received speaker fees from Menarini; and has received consulting fees from Philips. Dr Foley has received speaker fees from Menarini and Philips. Dr Khokhar has received speaker fees and travel support from Boston Scientific and Abbott. Dr Davies has received grants from Medtronic and Abbott; has received sponsorship from Vascular Perspectives, Boston Scientific, Medtronic and Abbott; and has received speaker fees from AstraZeneca, Pfizer, Bristol Myers Squibb, and Novartis. Dr Keeble has served on advisory boards for Abbott Vascular and SMT; and has received institutional research funding from Terumo, Medtronic, Boston Scientific, Abbott Vascular, Philips Volcano, and Cardionovum. Dr O’Kane has received speaker fees from Abbott Vascular, Biosensors, Boston Scientific, Heartflow, Medtronic, Philips, Shockwave, and Terumo. Dr Kotecha has received honoraria from Bayer and Janssen. Dr Nijjer has received speaker fees from Philips Volcano, Pfizer, Bayer, AstraZeneca, Boehringer Ingelheim, and Amarin. Dr Spratt has received speaker fees from Boston Scientific Corporation and Shockwave Medical, Inc. Dr Sen has received speaker and consulting fees from Philips, Medtronic, Recor, and AstraZeneca. Dr Curzen has received grants from Beckman Coulter, Inc, Boston Scientific Corporation, Haemonetics Corporation, and HeartFlow Inc; and has received speaker fees from Heartflow. Dr Howard has received shares in Mycardium AI; and has received a grant from the British Heart Foundation. Dr Cole has received shares in Mycardium AI. Dr Al-Lamee has served on advisory boards for Janssen Pharmaceuticals, Abbott, and Philips; and has received speaker fees from Abbott, Philips, Medtronic, Servier, Omniprex, and Menarini. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement., Methods: ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed., Findings: Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group., Interpretation: ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease., Funding: Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation., Competing Interests: Declaration of interests MJF reports speaker's fees from Menarini and Philips. CAR reports consulting fees from Philips and speaker's fees from Menarini. FAS reports speaker's fees and travel support from Servier pharmaceuticals. JRD reports grants from Medtronic and Abbott; sponsorship from Vascular Perspectives, Boston Scientific, Medtronic, and Abbott; and speaker's honoraria from AstraZeneca, Pfizer, Bristol Myers Squibb, and Novartis. TRK reports being on an advisory board for Abbott Vascular and SMT; institutional research funding from Terumo, Medtronic, Boston Scientific, Abbott Vascular, Philips Volcano, and Cardionovum; and travel support from Neovasc. CC reports grant support, honoraria, and travel support from Shockwave and Boston Scientific. JCS reports speaker's fees from Boston Scientific, Shockwave, and Medtronic; and institutional research funding from Boston Scientific and Shockwave. PDO’K reports speaker's fees from Abbott Vascular, Biosensors, Boston Scientific, Philips, Shockwave, and Terumo; and advisory boards for Shockwave Medical, Abbott Vascular, and Philips. RDS reports consulting and advisory fees, institutional research support, and speaking fees for Shockwave; and speaking fees and institutional research support from Abbott Vascular. JMH reports speaker's fees, honoraria, and research support from Abbott Vascular, Abiomed, Boston Scientific, Medtronic, and Shockwave; and equity in Shockwave. SSN reports speaker fees from Philips, Pfizer, Bayer, AstraZeneca, Boehringer Ingelheim, and Amarin; and leadership or board roles in the British Cardiac Intervention Society and the Royal Society of Medicine. SS reports speaker's and consultancy fees from Philips, Medtronic, Recor, and AstraZeneca. RP reports consultant fees from Philips and Abbott. GWM reports honoraria from Medtronic and directorship of the Imperial Valve and Cardiovascular Course. RK reports speaker's fees from Medtronic; and consultancy for Novartis, Amgen, and Cryotherapeutics. TK reports honoraria from Bayer and Jansen and travel support from Jansen. GDC reports shares in Mycardium AI. JPH reports shares in Mycardium AI and grant support from the British Heart Foundation. MJS-S reports consulting fees from Mycardium AI and Medtronic. RKA-L reports being on a trial steering committee for Janssen Pharmaceuticals; being on an advisory board for Abbot and Philips; speaker's honoraria for Abbott, Philips, Medtronic, Servier, Omniprex, and Menarini; and grant support from the British Heart Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The coronary sinus Reducer (CSR) is an hourglass-shaped device which creates an artificial stenosis in the coronary sinus. Whilst placebo-controlled data show an improvement in angina, these results are unreplicated and are the subject of further confirmatory research. The mechanism of action of this unintuitive therapy is unknown. The Coronary Sinus Reducer Objective Impact on Symptoms, MRI Ischaemia, and Microvascular Resistance (ORBITA-COSMIC) trial is a randomised, placebo-controlled, double-blind trial investigating the efficacy of the CSR. Patients with (i) established epicardial coronary artery disease, (ii) angina on maximally tolerated antianginal medication, (iii) evidence of myocardial ischaemia and (iv) no further options for percutaneous coronary intervention or coronary artery bypass grafting will be enrolled. Upon enrolment, angina and quality-of-life questionnaires, treadmill exercise testing and quantitative stress perfusion cardiac magnetic resonance (CMR) imaging will be performed. Participants will record their symptoms daily on a smartphone application throughout the trial. After a 2-week symptom assessment phase, participants will be randomised in the cardiac catheterisation laboratory to CSR or a placebo procedure. After 6 months of blinded follow-up, all prerandomisation tests will be repeated. A prespecified subgroup will undergo invasive coronary physiology assessment at prerandomisation and follow-up. The primary outcome is stress myocardial blood flow on CMR. Secondary outcomes include angina frequency, quality of life and treadmill exercise time. (ClinicalTrials.gov: NCT04892537).

Background: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics., Aims: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology., Methods: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting., Results: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR., Conclusion: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rasha Al-Lamee reports a relationship with A Menarini International Pharmaceutics that includes: speaking and lecture fees. Michael Foley reports a relationship with A Menarini International Pharmaceutics that includes: speaking and lecture fees. Christopher Rajkumar reports a relationship with A Menarini International Pharmaceutics that includes: speaking and lecture fees. Rasha Al-Lamee reports a relationship with Philips Healthcare that includes: speaking and lecture fees. Michael Foley reports a relationship with Philips Healthcare that includes: speaking and lecture fees. Christopher Rajkumar reports a relationship with Philips Healthcare that includes: speaking and lecture fees. Sayan Sen reports a relationship with Philips Healthcare that includes: speaking and lecture fees. Ricardo Petraco reports a relationship with Philips Healthcare that includes: speaking and lecture fees. Sukhjinder Nijjer reports a relationship with Philips Healthcare that includes: speaking and lecture fees. Takayuki Warisawa reports a relationship with Abbott Vascular Japan Co Ltd. that includes: consulting or advisory. Takayuki Warisawa reports a relationship with Philips Healthcare that includes:. Hitoshi Matsuo reports a relationship with Philips Healthcare that includes: speaking and lecture fees. Hitoshi Matsuo reports a relationship with Abbott Vascular Japan Co Ltd. that includes: speaking and lecture fees. Hitoshi Matsuo reports a relationship with Boston Scientific Japan that includes: speaking and lecture fees. Hitoshi Matsuo reports a relationship with Zeon Medical that includes: speaking and lecture fees. Shingo Kuwata reports a relationship with Abbott Vascular Japan Co Ltd. that includes: consulting or advisory., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)