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Background Coronary flow capacity (CFC), which is a categorical assessment based on the combination of hyperemic coronary flow and coronary flow reserve (CFR), has been introduced as a comprehensive assessment of the coronary circulation to overcome the limitations of CFR alone. The aim of this study was to quantify coronary flow changes after percutaneous coronary intervention in relation to the classification of CFC and the current physiological cutoff values of fractional flow reserve, instantaneous wave‐free ratio, and CFR. Methods and Results Using the combined data set from DEFINE FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect ‐Combined Pressure and Doppler FLOW Velocity Measurements) and IDEAL (Iberian‐Dutch‐English), a total of 133 vessels that underwent intracoronary Doppler flow measurement before and after percutaneous coronary intervention were analyzed. CFC classified prerevascularization lesions as normal (14), mildly reduced (40), moderately reduced (31), and severely reduced (48). Lesions with larger impairment of CFC showed greater increase in coronary flow and vice versa (median percent increase in coronary flow by revascularization: 4.2%, 25.9%, 50.1%, and 145.5%, respectively; P50% increase in coronary flow after percutaneous coronary intervention. Receiver operating characteristic curve analysis demonstrated that only CFC has a superior predictive efficacy to CFR (P

Background Although ischemic heart disease has a complex and multilevel origin, the diagnostic approach is mainly focused on focal obstructive disease as assessed by pressure‐derived indexes. The prognostic relevance of coronary flow over coronary pressure has been suggested and implies that identification of relevant perfusion abnormalities by invasive physiology techniques is critical for the correct identification of patients who benefit from coronary revascularization. The purpose of this study was to evaluate the diagnostic potential of a sequential approach using pressure‐derived indexes instantaneous wave‐free ratio (iFR), fractional flow reserve (FFR), and coronary flow reserve (CFR) measurements to determine the number of intermediate lesions associated with flow abnormalities after initial pressure measurements. Methods and Results A total of 366 intermediate lesions were assessed with simultaneous intracoronary pressure and flow velocity measurements. Contemporary clinical iFR, FFR, and CFR cut points for myocardial ischemia were applied. A total of 118 (32%) lesions were FFR+ and 136 (37%) lesions were iFR+. Subsequent CFR assessment resulted for FFR in a total of 91 (25%) FFR+/CFR+ and for iFR a total of 111 (30%) iFR+/CFR+ lesions. An iFR, FFR, and invasive flow velocity assessment approach would have yielded 20% of lesions (74 of 366) as ischemic. Conclusions Ultimately, 20% of intermediate lesions are associated with flow abnormalities after applying a pressure and flow velocity sequential approach. If iFR is borderline, FFR has limited additional value, in contrast with CFR. These results emphasize the use of coronary physiology in assessing stenosis severity but may also further question the contemporary reputation of a pressure‐based approach as a gold standard for the detection of myocardial ischemia in ischemic heart disease.

Objective Diastolic-systolic velocity ratio (DSVR) is a resting index to assess stenoses in the left anterior descending artery (LAD). DSVR can be measured by echocardiographic or intracoronary Doppler flow velocity. The objective of this cohort study was to elucidate the fundamental rationale underlying the decreased DSVR in coronary stenoses.Methods In cohort 1, simultaneous measurements of intracoronary Doppler flow velocity and pressure were acquired in the LAD of 228 stable patients. Phasic stenosis resistance, microvascular resistance and total vascular resistance (defined as stenosis and microvascular resistance combined) were studied during physiological resting conditions. Stenoses were classified according to severity by strata of 0.10 fractional flow reserve (FFR) units.Results DSVR was decreased in stenoses with lower FFR. Stenosis resistance was equal in systole and diastole for every FFR stratum. Microvascular resistance was consistently higher during systole than diastole. In lower FFR strata, stenosis resistance as a percentage of the total vascular resistance increases both during systole and diastole. The difference between the stenosis resistance as a percentage of total vascular resistance during systole and diastole increases for lower FFR strata, with an accompanying rise in diastolic-systolic resistance ratio. A significant inverse correlation was observed between DSVR and the diastolic-systolic resistance ratio (r=0.91, p

ObjectiveThe aim was threefold: 1) expound the independent physiological parameters that drive FFR, 2) elucidate contradictory conclusions between fractional flow reserve (FFR) and coronary flow reserve (CFR), and 3) highlight the need of both FFR and CFR in clinical decision making. Simple explicit theoretical models were supported by coronary data analyzed retrospectively.MethodologyFFR was expressed as a function of pressure loss coefficient, aortic pressure and hyperemic coronary microvascular resistance. The FFR-CFR relationship was also demonstrated mathematically and was shown to be exclusively dependent upon the coronary microvascular resistances. The equations were validated in a first series of 199 lesions whose pressures and distal velocities were monitored. A second dataset of 75 lesions with pre- and post-PCI measures of FFR and CFR was also analyzed to investigate the clinical impact of our hemodynamic reasoning.ResultsHyperemic coronary microvascular resistance and pressure loss coefficient had comparable impacts (45% and 49%) on FFR. There was a good concordance (y = 0.96 x - 0.02, r2 = 0.97) between measured CFR and CFR predicted by FFR and coronary resistances. In patients with CFR < 2 and CFR/FFR ≥ 2, post-PCI CFR was significantly >2 (p < 0.001), whereas it was not (p = 0.94) in patients with CFR < 2 and CFR/FFR < 2.ConclusionThe FFR behavior and FFR-CFR relationship are predictable from basic hemodynamics. Conflicting conclusions between FFR and CFR are explained from coronary vascular resistances. As confirmed by our results, FFR and CFR are complementary; they could jointly contribute to better PCI guidance through the CFR-to-FFR ratio in patients with coronary artery disease.

BackgroundCoronary microcirculatory dysfunction portends a poor cardiovascular outcome. Invasive assessment of microcirculatory dysfunction by coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) is affected by coronary artery disease (CAD). In this study we propose minimal microvascular resistance (mMR) as a new measure of microcirculatory dysfunction and aim to determine whether mMR is influenced by CAD. Methods and ResultsWe obtained 482 simultaneous measurements of intracoronary Doppler flow velocity and pressure. The mMR is defined as the ratio between distal coronary pressure and flow velocity during the hyperemic wave‐free period. Measurements were divided into 2 cohorts. Cohort 1 was a paired analysis involving 81 pairs with a vessel with and without CAD to investigate whether HMR, CFR, and mMR are modulated by CAD. CFR was lower, and HMR was higher, in vessels with CAD than in vessels without CAD: 2.12±0.79 versus 2.56±0.63 mm Hg·cm−1·s, P

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.)

Background: The pressure-derived parameters fractional flow reserve (FFR) and the emerging instantaneous wave-free ratio (iFR) are the most widely applied invasive coronary physiology indices to guide revascularisation. However, approximately 15-20% of intermediate stenoses show discordant FFR and iFR, and therapeutical consensus is lacking., Aims: We sought to associate hyperaemic stenosis resistance index, coronary flow reserve (CFR) and coronary flow capacity (CFC) to FFR/iFR discordance., Methods: We assessed pressure and flow measurements of 647 intermediate lesions (593 patients) of two multi-centre international studies., Results: FFR and iFR were discordant in 15% of all lesions (97 out of 647). FFR+/iFR- lesions had similar hyperaemic average peak velocity (hAPV), CFR and CFC as FFR-/iFR- lesions, whereas FFR-/iFR+ lesions had similar hAPV, CFR and CFC as FFR+/iFR+ lesions (p > 0.05 for all). FFR+/iFR- lesions were associated with lower baseline stenosis resistance, but not hyperaemic stenosis resistance, compared with FFR-/iFR+ lesions (p < 0.001)., Conclusions: Discordance with FFR+/iFR- is characterised by maximal flow values, CFR, and CFC patterns similar to FFR-/iFR- concordance that justifies conservative therapy. Discordance with FFR-/iFR+ on the other hand, is characterised by low flow values, CFR, and CFC patterns similar to iFR+/FFR+ concordance that may benefit from percutaneous coronary intervention., (© 2023. The Author(s).)

Background: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease., Objectives: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors., Methods: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death)., Results: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse)., Conclusion: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality., Competing Interests: Declaration of competing interests P.K. receives research grants and consulting fees from Biosense-Webster, Abbott-Medical, Medtronic, and Boston Scientific. A patent for Ripple Mapping is licensed to Biosense-Webster, and royalties are paid to Imperial College. C.C. is the recipient of a British Heart Foundation Clinical Research Training Fellowship (number FS/20/14/34917). A.A. has had support to attend conferences from Bayer. A.N. received a research grant from the NIHR Academy. S.N. received payment or honoraria for speaker events/presentations from Bayer, Pfizer, and Philips and participates on an Advisory Board for Astra Zeneca. G.Y.H.L. is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. No fees are received personally. N.M. is supported by a Chair Award, Program Grant, and Research Excellence Award (CH/F/21/90010, RG/20/10/34966, and RE/18/5/34216, respectively) from the British Heart Foundation. A.J.C. reports personal fees/consulting fees from Bayer, Pfizer, BMS, Daiichi Sankyo, and Boehringer Ingelheim; reports royalties and/or editorial fees from Oxford University Press, Wiley, and Springer Verlag; and participates on DSMBs/Advisory Boards at Biotronik, Johnson and Johnson, and Allergan. G.S.C. receives grants from the NIHR, participates on DSMBs, and is a nonexecutive director at the MHRA. W.G. reports fees for participation in Advisory Board from Amgen, Novartis, Pfizer, Principia Biopharma Inc—a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, and Hutchmed; lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, and Sanofi; and research grants from Bayer and BMS/Pfizer. M.T. reports Scientific Advisory Board personal fees from MorphogenIX and personal fees/honoraria from J&J/Actelion. R.A.-L. receives speaker’s honoraria from Philips Volcano, Medtronic, and Menarini. M.S.-S. has received honoraria from Pfizer (<£500). D.P.F., D.C., A.M., G.K., P.P., M.S., G.C., D.d.A.N., J.H., R.E., M.K., R.M., G.B., R.M.M., A.K., M.M., K.M., J.S., S.J.C., M.J.L., N.P., R.P., A.S.M.B., M.D., I.M., N.P., V.C. have no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Coronary flow reserve (CFR) assessment has proven clinical utility, but Doppler-based methods are sensitive to noise and operator bias, limiting their clinical applicability. The objective of the study is to expand the adoption of invasive Doppler CFR, through the development of artificial intelligence (AI) algorithms to automatically quantify coronary Doppler quality and track flow velocity., Methods and Results: A neural network was trained on images extracted from coronary Doppler flow recordings to score signal quality and derive values for coronary flow velocity and CFR. The outputs were independently validated against expert consensus. Artificial intelligence successfully quantified Doppler signal quality, with high agreement with expert consensus (Spearman's rho: 0.94), and within individual experts. Artificial intelligence automatically tracked flow velocity with superior numerical agreement against experts, when compared with the current console algorithm [AI flow vs. expert flow bias -1.68 cm/s, 95% confidence interval (CI) -2.13 to -1.23 cm/s, P < 0.001 with limits of agreement (LOA) -4.03 to 0.68 cm/s; console flow vs. expert flow bias -2.63 cm/s, 95% CI -3.74 to -1.52, P < 0.001, 95% LOA -8.45 to -3.19 cm/s]. Artificial intelligence yielded more precise CFR values [median absolute difference (MAD) against expert CFR: 4.0% for AI and 7.4% for console]. Artificial intelligence tracked lower-quality Doppler signals with lower variability (MAD against expert CFR 8.3% for AI and 16.7% for console)., Conclusion: An AI-based system, trained by experts and independently validated, could assign a quality score to Doppler traces and derive coronary flow velocity and CFR. By making Doppler CFR more automated, precise, and operator-independent, AI could expand the clinical applicability of coronary microvascular assessment., Competing Interests: Conflict of interest: C.M.C. has received grants or research support from Edwards Lifesciences, honoraria or consultation fees from Boston Scientific, Philips, Viz.ai, and Medtronic and is a shareholder of Cerebria.ai and Viz.ai. S.N. has received honoraria for speaking on Coronary Physiology from Phillips. H.S. has received educational funding from Amgen. R.A.-L. has received speaking fees from Philips Volcano. R.P. has acted as consultant to Philips. T.P.v.d.H. has served as a speaker at educational events organized by Philips Volcano, St Jude Medical (now Abbott), and Boston Scientific. S.S. reports speaking fees for Philips, Pfizer, and Astra Zenenca and an Educational Grant from Medtronic. N.V.R. reports grants from Philips, Abbott, and Biotronik, and personal fees from Medtronic. All other authors have no conflicts to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Oxygen-pulse morphology and gas exchange analysis measured during cardiopulmonary exercise testing (CPET) has been associated with myocardial ischaemia. The aim of this analysis was to examine the relationship between CPET parameters, myocardial ischaemia and anginal symptoms in patients with chronic coronary syndrome and to determine the ability of these parameters to predict the placebo-controlled response to percutaneous coronary intervention (PCI)., Methods and Results: Patients with severe single-vessel coronary artery disease (CAD) were randomized 1:1 to PCI or placebo in the ORBITA trial. Subjects underwent pre-randomization treadmill CPET, dobutamine stress echocardiography (DSE) and symptom assessment. These assessments were repeated at the end of a 6-week blinded follow-up period.A total of 195 patients with CPET data were randomized (102 PCI, 93 placebo). Patients in whom an oxygen-pulse plateau was observed during CPET had higher (more ischaemic) DSE score [+0.82 segments; 95% confidence interval (CI): 0.40 to 1.25, P = 0.0068] and lower fractional flow reserve (-0.07; 95% CI: -0.12 to -0.02, P = 0.011) compared with those without. At lower (more abnormal) oxygen-pulse slopes, there was a larger improvement of the placebo-controlled effect of PCI on DSE score [oxygen-pulse plateau presence (Pinteraction = 0.026) and oxygen-pulse gradient (Pinteraction = 0.023)] and Seattle angina physical-limitation score [oxygen-pulse plateau presence (Pinteraction = 0.037)]. Impaired peak VO2, VE/VCO2 slope, peak oxygen-pulse, and oxygen uptake efficacy slope was significantly associated with higher symptom burden but did not relate to severity of ischaemia or predict response to PCI., Conclusion: Although selected CPET parameters relate to severity of angina symptoms and quality of life, only an oxygen-pulse plateau detects the severity of myocardial ischaemia and predicts the placebo-controlled efficacy of PCI in patients with single-vessel CAD., Competing Interests: Conflict of interest: S.G., C.A.R., M.F., D.T., R.W., D.F., and R.P. have nothing to disclose. A.N.N. reports receiving support for a Doctoral Fellowship by the NIHR Academy which was paid to her institution. H.S. reports research funding from the Imperial College COVID research fund and the Foundation for Circulatory Support. S.S. reports individual grants from Medtronic and Phillips and speaker’s honoraria from Medtronic, Phillips and Pfizer. S.N. reports consulting and speaking fees from Phillips Volcano. S.A.T. reports an unpaid leadership role with the UK National Institute for Health Research cardiovascular advisory panel. J.D. reports receipt of consulting fees (from Boston Scientific, Abbott and Medtronic), speaker’s honoraria (from Pfizer, Bayer and Novartis), and equipment support (from Abbott and Terumo). M.S.-S. reports speaker’s honoraria from Pfizer. J.H. reports a small cardiac MRI project grant from the Academy of Medical Sciences. R.A.-L. reports speaker’s honoraria from Philips Volcano, Abbott Vascular, and Menarini Pharmaceuticals., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

[Figure: see text].

Competing Interests: Disclosure: The authors have no conflicts of interest to declare.

Introduction: During viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject's face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p<0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/., Conclusion: Full-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks., Competing Interests: No authors have competing interests.

Objectives: The clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK., Methods: We retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention., Results: Mean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, p<0.001). Only four COVID-19 patients had invasive coronary angiography, two underwent percutaneous coronary intervention and one required a permanent pacemaker implantation. 7.0% (n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39, 95% CI 1.31 to 4.40, p=0.005) and history of hypertension (OR 1.88, 95% CI 1.01 to 3.55, p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for., Conclusion: Hypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention., Competing Interests: Competing interests: GWM is director of annual Imperial Valve and Cardiovascular Course (IVCC) which receives support from industry companies. She is also a director of an international fellowship supported by Abbott Vascular between Imperial Healthcare NHS trust, Villa Maria Cecilia Hospital GVM and Columbus Hospital Italy. RA-L has received speaker honorarium from Phillips Volcano., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo-controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline-directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results After enrollment into the ORBITA trial, all 200 patients entered a 6-week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2-4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0-1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions In the 12-week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this into longer-term clinical practice should be a focus of future study. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02062593.

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff., Competing Interests: Disclosure: HS has received research funding from Amgen. SS has received speaking fees from AstraZeneca, Pfizer and Philips Volcano, and an educational grant from Medtronic. SN has received speaking fees from Philips Volcano. RAL has received speaking fees from Philips Volcano. RP has acted as a consultant for Philips. All other authors have no conflicts of interest to declare., (Copyright © 2020, Radcliffe Cardiology.)

Objectives: The aim of this study was to assess the long-term clinical outcomes of patients with left main coronary artery (LM) stenosis in whom treatment strategy was based on the instantaneous wave-free ratio (iFR)., Background: The overall safety of iFR to guide revascularization decision making in patients with stable coronary artery disease has been established. However, no study has examined the safety of deferral of revascularization of LM disease on the basis of iFR., Methods: This multicenter observational study included 314 patients in whom LM stenosis was deferred (n = 163 [51.9%]) or revascularized (n = 151 [48.1%]) according to the iFR cutoff ≤0.89. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were each individual component of the primary endpoint and also cardiac death., Results: At a median follow-up period of 30 months, the primary endpoint occurred in 15 patients (9.2%) in the deferred group and 22 patients (14.6%) in the revascularized group (hazard ratio: 1.45; 95% confidence interval: 0.75 to 2.81; p = 0.26), indicating no evidence of a significant difference between the 2 groups. For the secondary endpoints, findings in the iFR-based deferral and revascularization groups were as follows: all-cause death, 3.7% versus 4.6%; cardiac death, 1.2% versus 2.0%; nonfatal myocardial infarction, 2.5% versus 5.3%; and target lesion revascularization, 4.3% versus 5.3% (p > 0.05 for all)., Conclusions: Deferral of revascularization of LM stenosis on the basis of iFR appears to be safe, with similar long-term outcomes to those in patients in whom LM revascularization was performed according to iFR values., (Copyright © 2020. Published by Elsevier Inc.)

Background: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina)., Methods: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling., Results: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score ( P interaction =0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina ( P interaction =0.116), physical limitation ( P interaction =0.461), quality of life ( P interaction =0.689), EuroQOL 5 quality-of-life score ( P interaction =0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class ( P interaction =0.693), and treadmill exercise time ( P interaction =0.426)., Conclusions: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.

Background: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation., Methods: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2)., Results: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s -1 versus post-TAVI 3.04±1.6 mm Hg·cm·s -1 [ P =0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [ P =0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74., Conclusions: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease.

Background: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) disagree on the hemodynamic significance of a coronary lesion in ≈20% of cases. It is unknown whether the physiological pattern of disease is an influencing factor for this. This study assessed whether the physiological pattern of coronary artery disease influences discordance between FFR and iFR measurement., Methods and Results: Three-hundred and sixty intermediate coronary lesions (345 patients; mean age, 64.4±10.3 years; 76% men) with combined FFR, iFR, and iFR pressure-wire pullback were included for analysis from an international multicenter registry. Cut points for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89, respectively. Lesions were classified into FFR+/iFR+ (n=154; 42.7%), FFR-/iFR+ (n=38; 10.6%), FFR+/iFR- (n=41; 11.4%), and FFR-/iFR- (n=127; 35.3%) groups. The physiological pattern of disease was classified according to the iFR pullback recordings as predominantly physiologically focal (n=171; 47.5%) or predominantly physiologically diffuse (n=189; 52.5%). Median FFR and iFR were 0.80 (interquartile range, 0.75-0.85) and 0.89 (interquartile range, 0.86-0.92), respectively. FFR disagreed with iFR in 22% (79 of 360). The physiological pattern of disease was the only influencing factor relating to FFR/iFR discordance: predominantly physiologically focal was significantly associated with FFR+/iFR- (58.5% [24 of 41]), and predominantly physiologically diffuse was significantly associated with FFR-/iFR+ (81.6% [31 of 38]; P<0.001 for pattern of disease between FFR+/iFR- and FFR-/iFR+ groups)., Conclusions: The physiological pattern of coronary artery disease was an important influencing factor for FFR/iFR discordance.

Aims: To determine the agreement between sensor-tipped microcatheter (MC) and pressure wire (PW)-derived fractional flow reserve (FFR)., Methods and Results: Studies comparing FFR obtained from MC (FFR MC , Navvus Microcatheter System, ACIST Medical Systems, Eden Prairie, Minnesota, USA) versus standard PW (FFR PW ) were identified, and a meta-analysis of numerical and categorical agreement was performed. The relative levels of drift and device failure of MC and PW systems from each study were assessed. Six studies with 440 lesions (413 patients) were included. The mean overall bias between FFR MC and FFR PW was -0.029 (FFR MC lower). Bias and variance were greater for lesions with lower FFR PW (p<0.001). Using a cut-off of 0.80, 18 % of lesions were reclassified by FFR MC versus FFR PW (with 15 % being false positives). The difference in reported drift between FFR PW and FFR MC was small. Device failure was more common with MC than PW (7.1% vs 2%)., Conclusion: FFR MC systematically overestimates lesion severity, with increased bias in more severe lesions. Using FFR MC changes revascularisation guidance in approximately one out of every five cases. PW drift was similar between systems. Device failure was higher with MC., Competing Interests: Competing interests: Drs Cook, Al-Lamee and Nijjer have conducted teaching sessions supported by Volcano Corporation. Dr Petraco is a consultant for Philips Volcano. Dr Davies is a consultant for and has received research funding from Philips Volcano. Dr Sen has attended and conducted teaching sessions supported by Volcano Corporation, St. Jude Medical, Medtronic, Pfizer and AstraZeneca. Dr Chamie has acted as a consultant to Abott Vascular inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR)., Objectives: The purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial., Methods: MACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex., Results: A total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06)., Conclusions: iFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Severe aortic stenosis frequently involves the development of left ventricular hypertrophy (LVH) creating a dichotomous haemodynamic state within the coronary circulation. Whilst the increased force of ventricular contraction enhances its resultant relaxation and thus increases the distal diastolic coronary "suction" force, the presence of LVH has a potentially opposing effect on ventricular-coronary interplay. The aim of this study was to use non-invasive coronary wave intensity analysis (WIA) to separate and measure the sequential effects of outflow tract obstruction relief and then LVH regression following intervention for aortic stenosis., Methods: Fifteen patients with unobstructed coronary arteries undergoing aortic valve intervention (11 surgical aortic valve replacement [SAVR], 4 TAVI) were successfully assessed before and after intervention, and at 6 and 12 months post-procedure. Coronary WIA was constructed from simultaneously acquired coronary flow from transthoracic echo and pressure from an oscillometric brachial cuff system., Results: Immediately following intervention, a decline in the backward decompression wave (BDW) was noted (9.7 ± 5.7 vs 5.1 ± 3.6 × 10 3  W/m 2 /s, P < 0.01). Over 12 months, LV mass index fell from 114 ± 19 to 82 ± 17 kg/m 2 . Accompanying this, the BDW fraction increased to 32.8 ± 7.2% at 6 months (P = 0.01 vs post-procedure) and 34.7 ± 6.7% at 12 months (P < 0.001 vs post-procedure)., Conclusion: In aortic stenosis, both the outflow tract gradient and the presence of LVH impact significantly on coronary haemodynamics that cannot be appreciated by examining resting coronary flow rates alone. An immediate change in coronary wave intensity occurs following intervention with further effects appreciable with hypertrophy regression. The improvement in prognosis with treatment is likely to be attributable to both features., (© 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Background: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease., Methods: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling., Results: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR ( P interaction =0.318) or iFR ( P interaction =0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR ( P interaction <0.00001) and decreasing iFR ( P interaction <0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR ( P interaction =0.849) or iFR ( P interaction =0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR ( P interaction =0.693) nor iFR ( P interaction =0.761) modified this effect., Conclusions: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

Objectives: The study sought to determine the coronary flow characteristics of angiographically intermediate stenoses classified as discordant by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR)., Background: Discordance between FFR and iFR occurs in up to 20% of cases. No comparisons have been reported between the coronary flow characteristics of FFR/iFR discordant and angiographically unobstructed vessels., Methods: Baseline and hyperemic coronary flow velocity and coronary flow reserve (CFR) were compared across 5 vessel groups: FFR+/iFR+ (108 vessels, n = 91), FFR-/iFR+ (28 vessels, n = 24), FFR+/iFR- (22 vessels, n = 22), FFR-/iFR- (208 vessels, n = 154), and an unobstructed vessel group (201 vessels, n = 153), in a post hoc analysis of the largest combined pressure and Doppler flow velocity registry (IDEAL [Iberian-Dutch-English] collaborators study)., Results: FFR disagreed with iFR in 14% (50 of 366). Baseline flow velocity was similar across all 5 vessel groups, including the unobstructed vessel group (p = 0.34 for variance). In FFR+/iFR- discordants, hyperemic flow velocity and CFR were similar to both FFR-/iFR- and unobstructed groups; 37.6 (interquartile range [IQR]: 26.1 to 50.4) cm/s vs. 40.0 [IQR: 29.7 to 52.3] cm/s and 42.2 [IQR: 33.8 to 53.2] cm/s and CFR 2.36 [IQR: 1.93 to 2.81] vs. 2.41 [IQR: 1.84 to 2.94] and 2.50 [IQR: 2.11 to 3.17], respectively (p > 0.05 for all). In FFR-/iFR+ discordants, hyperemic flow velocity, and CFR were similar to the FFR+/iFR+ group; 28.2 (IQR: 20.5 to 39.7) cm/s versus 23.5 (IQR: 16.4 to 34.9) cm/s and CFR 1.44 (IQR: 1.29 to 1.85) versus 1.39 (IQR: 1.06 to 1.88), respectively (p > 0.05 for all)., Conclusions: FFR/iFR disagreement was explained by differences in hyperemic coronary flow velocity. Furthermore, coronary stenoses classified as FFR+/iFR- demonstrated similar coronary flow characteristics to angiographically unobstructed vessels., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The index of microcirculatory resistance (IMR) is increasingly used to quantify microcirculatory function. However, in normal coronary arteries, resistance increases with the branching structure of the coronary tree, which suggests that IMR could be influenced by the amount of downstream myocardial mass (MM). We aimed to evaluate the influence of the amount of MM subtended to an intermediate stenosis on the IMR., Methods and Results: IMR, fractional flow reserve and coronary flow reserve (CFR) were measured in 123 coronary arteries (102 patients) with intermediate stenosis. Jeopardised MM was estimated with the Myocardial Jeopardy Index (MJI). MM was inversely associated with IMR (R.

In this review, the authors reflect upon the role of coronary physiology in the modern management of coronary artery disease. They critically appraise the scientific background of the instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR), from early experimental studies to validation studies against indexes of ischemia, to clinical trials assessing outcome. At this important juncture for the field, the authors make predictions for the future of physiological stenosis assessment, outlining developments for both iFR and FFR in new clinical domains beyond the confines of stable angina. With a focus on the evolving future of iFR and FFR, the authors describe how physiological assessment with iFR may advance its application from simply justifying to guiding revascularization., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Computed tomography-derived fractional flow reserve (FFR-CT) is a novel, noninvasive test for myocardial ischemia. Clinicians using FFR-CT must be able to interpret individual FFR-CT results to determine subsequent patient care., Objective: To provide clinicians a means of interpreting individual FFR-CT results with respect to the range of invasive FFRs that this interpretation might likely represent., Evidence Review: We performed a systematic review in accordance with guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic search of MEDLINE (January 1, 2011, to 2016, week 2) and EMBASE (January 1, 2011, to 2016, week 2) was performed for studies assessing the diagnostic accuracy of FFR-CT. Title words used were computed tomography or computed tomographic and fractional flow reserve or FFR. Results were limited to publications in peer-reviewed journals. Duplicate studies and abstracts from scientific meetings were removed. All of the retrieved studies, including references, were reviewed., Findings: There were 908 vessels from 536 patients in 5 studies included in the analysis. A total of 365 (68.1%) were male, and the mean (SD) age was 63.2 (9.5) years. The overall per-vessel diagnostic accuracy of FFR-CT was 81.9% (95% CI, 79.4%-84.4%). For vessels with FFR-CT values below 0.60, 0.60 to 0.70, 0.70 to 0.80, 0.80 to 0.90, and above 0.90, diagnostic accuracy of FFR-CT was 86.4% (95% CI, 78.0%-94.0%), 74.7% (95% CI, 71.9%-77.5%), 46.1% (95% CI, 42.9%-49.3%), 87.3% (95% CI, 85.1%-89.5%), and 97.9% (95% CI, 97.9%-98.8%), respectively. The 82% (overall) diagnostic accuracy threshold was met for FFR-CT values lower than 0.63 or above 0.83. More stringent 95% and 98% diagnostic accuracy thresholds were met for FFR-CT values lower than 0.53 or above 0.93 and lower than 0.47 or above 0.99, respectively., Conclusions and Relevance: The diagnostic accuracy of FFR-CT varies markedly across the spectrum of disease. This analysis allows clinicians to interpret the diagnostic accuracy of individual FFR-CT results. In combination with patient-specific factors, clinicians can use FFR-CT to judge when the cost and risk of an invasive angiogram may safely be avoided.

Background: Patients presenting with ST-elevation myocardial infarction commonly have multi-vessel coronary artery disease. After the culprit artery is treated, the optimal treatment strategy for the residual disease is not yet defined. Large observational studies suggest that treatment of residual disease should be deferred but smaller randomised controlled trials (RCTs) suggest multi-vessel primary percutaneous coronary intervention (MV-PPCI) at the time of STEMI is safe. We examine if allocation bias of high-risk patients could explain the conflicting results between observational studies and RCTs and aim to resolve the paradox between the two., Methods: A meta-analysis of registries comparing culprit-only PPCI to MV-PPCI was performed. We then determined if high-risk patients were more likely to be allocated to MV-PPCI. A meta-regression was performed to determine if any allocation bias of high-risk patients could explain the difference in outcomes between therapies., Results: 47,717 patients (19 studies) were eligible. MV-PPCI had higher mortality than culprit-only PPCI (OR 1.59, 95% CI 1.12 to 2.24, p=0.03). However, higher risk patients were more likely to be allocated to MV-PPCI (OR 1.45, 95% CI 1.18 to 1.78, p=0.0005). When this was accounted for, there was no difference in mortality between culprit-only PPCI and MV-PPCI (OR 0.99, 95% CI 0.69 to 1.41, p=0.94)., Discussion: Clinicians preferentially allocate higher-risk patients to MV-PPCI at the time of STEMI, resulting in observational studies reporting higher mortality with this strategy. When this is accounted for, these large observational studies in 'real world' patients support the conclusion of the smaller RCTs in the field: MV-PPCI has equivalent mortality to a culprit-only approach., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: Previously, we examined the difference in stent designs across different sizes for six widely used Drug Eluting Stents (DESs). Although stent post-dilatation to larger diameter is commonly done, typically in the setting of long tapering segment or left-main PCI, there is an increasing recognition that information with regard to the different stent model designs has a critical impact on overexpansion results. This study aims to provide an update on stent model designs for contemporary DES platforms as well as test overexpansion results under with oversized post-dilatation., Methods and Results: We studied 6 different contemporary commercially available DES platforms: Synergy, Xience Xpedition, Ultimaster, Orsiro, Resolute Onyx and Biomatrix Alpha. We investigated for each platform the difference in stent designs across different sizes and results obtained after post-expansion with larger balloon sizes. The stents were deployed at nominal diameter and subsequently over expanded using increasingly large post dilatation balloon sizes (4.0, 5.0 and 6.0mm at 14ATM). Light microscopy was used to measure the changes in stent geometry and lumen diameter after over-expansion. For each respective DES platform, the MLD observed after overexpansion of the largest stent size available with a 6.0mm balloon was 5.7mm for Synergy, 5.6mm for Xience, 5.2mm for Orsiro, 5.8mm for Ultimaster, 5.5mm for 4mm Onyx (5.9mm for the 5mm XL size) and 5.8mm for BioMatrix Chroma., Conclusion: This update presents valuable novel insights that may be helpful for careful selection of stent size for contemporary DES based on model designs. Such information is especially critical in left main bifurcation stenosis treatment where overexpansion to larger oversized diameter may be required to ensure full stent apposition., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Aims: Vasodilator-free basal stenosis resistance (BSR) equals fractional flow reserve (FFR) accuracy for ischaemia-inducing stenoses. Nonetheless, basal haemodynamic variability may impair BSR accuracy compared with hyperaemic stenosis resistance (HSR). We evaluated the influence of basal haemodynamic variability, as encountered in practice, on BSR accuracy versus HSR when derived from simultaneous pressure and flow velocity measurements, and determined its diagnostic performance for HSR-defined significant stenoses., Methods and Results: Simultaneous coronary pressure and flow velocity were obtained in 131 stenoses. The impact of basal haemodynamic conditions on BSR was evaluated by means of their relationship with the relative difference between BSR and HSR. Diagnostic performance of BSR, FFR, iFR, and resting Pd/Pa was assessed by comparing the area under the curve (AUC), using HSR as reference standard. The relative difference between BSR and HSR was not associated with basal heart rate, aortic pressure or rate pressure product. Among all stenoses, as well as within the 0.6-0.9 FFR range, BSR AUC was significantly greater than resting Pd/Pa and iFR AUC; all other AUCs were equivalent., Conclusions: With simultaneous pressure and flow velocity measurements, basal conditions do not systematically limit BSR accuracy compared with HSR. Consequently, diagnostic performance of BSR is equivalent to FFR, and closely approximates HSR.

Background: Small drifts in intracoronary pressure measurements (±2 mm Hg) can affect stenosis categorization using pressure indices. This has not previously been assessed for fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and whole-cycle distal pressure/proximal pressure (Pd/Pa) indices., Methods and Results: Four hundred forty-seven stenoses were assessed with FFR, iFR, and whole-cycle Pd/Pa. Cut point values for significance were predefined as ≤0.8, <0.90, and <0.93, respectively. Pressure wire drift was simulated by offsetting the distal coronary pressure trace by ±2 mm Hg. FFR, iFR, and whole-cycle Pd/Pa indices were recalculated and stenosis misclassification quantified. Median (±median absolute deviation) values for FFR, iFR, and whole-cycle Pd/Pa were 0.81 (±0.11), 0.90 (±0.07), and 0.93 (±0.06), respectively. For the cut point of FFR, iFR, and whole-cycle Pd/Pa, 34.6% (155), 50.1% (224), and 62.2% (278) of values, respectively, lay within ±0.05 U. With ±2 mm Hg pressure wire drift, 21% (94), 25% (110), and 33% (148) of the study population were misclassified with FFR, iFR, and whole-cycle Pd/Pa, respectively. Both FFR and iFR had significantly lower misclassification than whole-cycle Pd/Pa (P<0.001). There was no statistically significant difference between the diagnostic performance of FFR and iFR (P=0.125)., Conclusions: In a substantial proportion of cases, small amounts of pressure wire drift are enough to cause stenoses to change classification. Whole-cycle Pd/Pa is more vulnerable to such reclassification than FFR and iFR., (© 2016 The Authors.)

Wave intensity analysis (WIA) has found particular applicability in the coronary circulation where it can quantify traveling waves that accelerate and decelerate blood flow. The most important wave for the regulation of flow is the backward-traveling decompression wave (BDW). Coronary WIA has hitherto always been calculated from invasive measures of pressure and flow. However, recently it has become feasible to obtain estimates of these waveforms noninvasively. In this study we set out to assess the agreement between invasive and noninvasive coronary WIA at rest and measure the effect of exercise. Twenty-two patients (mean age 60) with unobstructed coronaries underwent invasive WIA in the left anterior descending artery (LAD). Immediately afterwards, noninvasive LAD flow and pressure were recorded and WIA calculated from pulsed-wave Doppler coronary flow velocity and central blood pressure waveforms measured using a cuff-based technique. Nine of these patients underwent noninvasive coronary WIA assessment during exercise. A pattern of six waves were observed in both modalities. The BDW was similar between invasive and noninvasive measures [peak: 14.9 ± 7.8 vs. -13.8 ± 7.1 × 10(4) W·m(-2)·s(-2), concordance correlation coefficient (CCC): 0.73, P < 0.01; cumulative: -64.4 ± 32.8 vs. -59.4 ± 34.2 × 10(2) W·m(-2)·s(-1), CCC: 0.66, P < 0.01], but smaller waves were underestimated noninvasively. Increased left ventricular mass correlated with a decreased noninvasive BDW fraction (r = -0.48, P = 0.02). Exercise increased the BDW: at maximum exercise peak BDW was -47.0 ± 29.5 × 10(4) W·m(-2)·s(-2) (P < 0.01 vs. rest) and cumulative BDW -19.2 ± 12.6 × 10(3) W·m(-2)·s(-1) (P < 0.01 vs. rest). The BDW can be measured noninvasively with acceptable reliably potentially simplifying assessments and increasing the applicability of coronary WIA., (Copyright © 2016 the American Physiological Society.)

Aims: Maximum and stable hyperaemia are critical prerequisites for the accurate measurement of fractional flow reserve (FFR). However, in some patients in whom hyperaemia is induced through a central vein (IV) the minimum distal coronary pressure to aortic pressure ratio (Pd/Pa ratio) develops before the stabilisation of hyperaemia. We sought to describe the prevalence, magnitude and clinical implications of this phenomenon., Methods and Results: The FFR tracing archive of a single institution was reviewed and a total of 104 high-quality IV-FFR recordings from 90 patients were identified. Whenever the minimum Pd/Pa ratio was found before the onset of stable hyperaemia, a search for the lowest Pd/Pa ratio within the steady-state hyperaemic plateau was performed and labelled as FFRstable. Whilst in most cases the minimum Pd/Pa ratio developed during stable hyperaemia, in 19 cases (prevalence of 18.3% [95% CI: 12.0% to 26.8%]) this value was found before the stabilisation of the hyperaemic state. In such cases, the minimum Pd/Pa ratio stabilised later at a higher level (0.77±0.09 vs. 0.81±0.08, p<0.001) (mean difference, 0.03±0.02, range, 0.01 to 0.10). In terms of dichotomous classification of stenosis severity and if FFRstable had been used to decide on revascularisation, reclassification would have occurred in three (2.9%) cases, all presenting a minimum Pd/Pa ratio ≤0.80 with FFRstable >0.80., Conclusions: During IV adenosine infusion, the minimum Pd/Pa ratio occurs before the stabilisation of hyperaemia in a significant proportion of cases. While the overall difference between the minimum Pd/Pa ratio and its FFRstable counterpart is small, reclassification of stenosis severity might occur, if choosing between the minimum and stable values of FFR within the same trace.

Aims: We sought to compare the diagnostic accuracy of basal stenosis resistance index (BSR), instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) for stenosis-specific myocardial ischaemia identified by means of a combined reference standard of myocardial perfusion scintigraphy and the hyperaemic stenosis resistance index., Methods and Results: BSR and FFR were determined for 299 coronary stenoses, iFR was determined for 85 coronary stenoses (iFR cohort). The discriminative value for stenosis-specific myocardial ischaemia was compared by means of the area under the receiver operating characteristic (ROC) curves (AUC). Classification agreement with the reference standard was determined according to ROC curve-derived ischaemic cut-off values, as well as according to clinical cut-off values, equivalent to the 0.80 FFR cut-off. Across all stenoses, the discriminative value of BSR and FFR was equivalent (AUC: 0.90 and 0.91, respectively, p=0.46). In the iFR cohort, the discriminative value was equivalent for BSR, iFR, and FFR (AUC: 0.88, 0.84, and 0.88, respectively; p≥0.20 for all). At both ischaemic as well as clinical cut-off values, classification agreement with the reference standard was equivalent for BSR and FFR across all stenoses, as well as for BSR, iFR, and FFR in the iFR cohort., Conclusions: BSR, iFR, and FFR have equivalent diagnostic accuracy for the detection of ischaemia-generating coronary stenoses.

Objectives: This study sought to understand the physiological basis of baseline distal-to-aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) agreement and discordance, using coronary flow reserve (CFR), stenosis resistance, and microcirculatory resistance measurements, and form there, to investigate the potential value of combining Pd/Pa with FFR in the diagnostic rationale., Background: Pd/Pa is always available before FFR assessment, and emerging data supports the notion that baseline indices can determine the ischemic potential of coronary stenosis in selected subsets., Methods: A total of 467 stenosed vessels from 363 patients were investigated with pressure and flow sensors during baseline and hyperemia: 168 vessels (135 patients) with thermodilution-derived flow, and 299 vessels (228 patients) with Doppler-derived flow., Results: Pd/Pa correlated more strongly with CFR than FFR (ρ difference = 0.129; p for ρ comparison <0.001). Although Pd/Pa and FFR were closely correlated (ρ = 0.798; 95% confidence interval: 0.767 to 0.828), categorical discordance was observed in 19.3% of total vessels. Such discordance was associated with the patients' clinical profile and was characterized by contrastive changes in stenosis resistance, microcirculatory resistance, and the underlying CFR. Notably, all stenosis with Pd/Pa ≤0.83 (n = 74, 15.8%) progressed to FFR ≤0.80, and although no Pd/Pa cutoff was able to exclude the development of FFR ≤0.80 in the high end of values, only 15 (10.1%) vessels with Pd/Pa ≥0.96 (n = 149, 31.9%) developed FFR ≤0.80, from which none had definite ischemia, as defined by CFR ≤1.74., Conclusions: Combining baseline Pd/Pa with FFR seems to provide a more comprehensive physiological examination of stenosed coronary arteries and a closer pressure-based appraisal of the flow reserve of the downstream myocardial bed., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This article assesses the data from contemporary human studies to address some of the common assumptions regarding hyperemic and baseline physiology in the context of the baseline pressure-derived index of instant wave-free ratio and the hyperemic index of fractional flow reserve. The article aims to determine if the available evidence supports the continued investigation, development, and use of baseline indices., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Modern randomised controlled trials typically use composite endpoints. This is only valid if each endpoint is equally important to patients but few trials document patient preference and seek the relative importance of components of combined endpoints. If patients weigh endpoints differentially, our interpretation of trial data needs to be refined., Methods and Results: We derive a quantitative, structured tool to determine the relative importance of each endpoint to patients. We then apply this tool to data comparing angioplasty with drug-eluting stents to bypass surgery. The survey was administered to patients undergoing cardiac catheterisation. A meta-analysis comparing coronary artery bypass grafting (CABG) to percutaneous coronary interventuin (PCI) was then performed using (a) standard MACE and (b) patient-centred MACE. Patients considered stroke worse than death (stroke 102.3 ± 19.6%, p < 0.01), and MI and repeat revascularisation less severe than death (61.9 ± 26.8% and 41.9 ± 25.4% respectively p < 0.01 for both). 7 RCTs (5251 patients) were eligible. Meta-analysis demonstrated that standard MACE occurs more frequently with PCI than surgery (OR 1.44; 95% CI 1.10 to 1.87; p = 0.007). Re-analysis using patient-centred MACE found no significant difference between PCI and CABG (OR 1.22, 95% CI 0.97 to 1.53; p = 0.10)., Conclusions: Patients do not consider the constituent endpoints of MACE equal. We derive a novel patient-centred metric that recognises and quantifies the differences attributed to each endpoint. When patient preference data are applied to contemporary trial results, there is no significant difference between PCI and CABG. Responses from individual patients in clinic could be used to give individual patients a recommendation that is truly personalised., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Advances in the understanding of healing mechanisms after stent implantation have led to the recognition of stent strut thickness as an essential factor affecting re-endothelialization and overall long term vessel healing response after Percutaneous Coronary Interventions (PCI). Emergence of Drug-eluting stents (DESs) with anti-proliferative coating has contributed to reducing the incidence of restenosis and Target Lesion Revascularization (TVR), while progress and innovations in stent materials have in the meantime facilitated the design of newer platforms with more conformability and thinner struts, producing lesser injury and improving integration into the vessel wall. Recent advances in biodegradable metal and polymer materials now also allow for the design of fully biodegradable platforms, which are aimed at scaffolding the vessel only temporarily to prevent recoil and constrictive remodeling of the vessel during the initial period required, and are then progressively resorbed thereby avoiding the drawback of leaving an unnecessary implant permanently in the vessel. The aim of this article is to review recent evolution in stent material and stent strut design while understanding their impact on PCI outcomes. The article describes the different metallic alloys and biodegradable material properties and how these have impacted the evolution of stent strut thickness and ultimately outcomes in patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)