Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled ...randomised trials to show its efficacy.
ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593.
ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI −8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group.
In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.
NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre.
In this trial involving 2492 patients, coronary revascularization guided by iFR, as compared with fractional flow reserve-guided revascularization, was within the prespecified margin for ...noninferiority with respect to major adverse cardiac events.
For the past 20 years, physiological measurements obtained during invasive procedures have been used to guide coronary revascularization. Pioneering work supported the use of flow measurements to make safe decisions about revascularization,
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but this approach was soon superseded by the use of fractional flow reserve (FFR), which measures pressure as a surrogate of flow to estimate the severity of stenosis.
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FFR was successful largely because of its technical simplicity and because clinical trials showed that it was associated with improved clinical outcomes after percutaneous coronary intervention (PCI).
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Consequently, FFR is now included in the appropriate-use criteria for . . .
The purpose of this study was to develop an adenosine-independent, pressure-derived index of coronary stenosis severity.
Assessment of stenosis severity with fractional flow reserve (FFR) requires ...that coronary resistance is stable and minimized. This is usually achieved by administration of pharmacological agents such as adenosine. In this 2-part study, we determine whether there is a time when resistance is naturally minimized at rest and assess the diagnostic efficiency, compared with FFR, of a new pressure-derived adenosine-free index of stenosis severity over that time.
A total of 157 stenoses were assessed. In part 1 (39 stenoses), intracoronary pressure and flow velocity were measured distal to the stenosis; in part 2 (118 stenoses), intracoronary pressure alone was measured. Measurements were made at baseline and under pharmacologic vasodilation with adenosine.
Wave-intensity analysis identified a wave-free period in which intracoronary resistance at rest is similar in variability and magnitude (coefficient of variation: 0.08 ± 0.06 and 284 ± 147 mm Hg s/m) to those during FFR (coefficient of variation: 0.08 ± 0.06 and 302 ± 315 mm Hg s/m; p = NS for both). The resting distal-to-proximal pressure ratio during this period, the instantaneous wave-free ratio (iFR), correlated closely with FFR (r = 0.9, p < 0.001) with excellent diagnostic efficiency (receiver-operating characteristic area under the curve of 93%, at FFR <0.8), specificity, sensitivity, negative and positive predictive values of 91%, 85%, 85%, and 91%, respectively.
Intracoronary resistance is naturally constant and minimized during the wave-free period. The instantaneous wave-free ratio calculated over this period produces a drug-free index of stenosis severity comparable to FFR. (Vasodilator Free Measure of Fractional Flow Reserve ADVISE; NCT01118481).
A large proportion of patients presenting with non–ST-segment elevation myocardial infarction (NSTEMI) present with multivessel disease (MVD). There is uncertainty in the role of complete coronary ...revascularization in this group of patients.
The aim of this study was to investigate the outcomes of complete revascularization compared with culprit vessel–only intervention in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI) for NSTEMI.
The authors undertook an observational cohort study of 37,491 NSTEMI patients treated between 2005 and 2015 at the 8 heart attack centers in London. Clinical details were recorded at the time of the procedure into local databases using the British Cardiac Intervention Society (BCIS) PCI dataset. A total of 21,857 patients (58.3%) presented with NSTEMI and MVD. Primary outcome was all-cause mortality at a median follow-up of 4.1 years (interquartile range: 2.2 to 5.8 years).
A total of 11,737 (53.7%) patients underwent single-stage complete revascularization during PCI for NSTEMI, rates that significantly increased during the study period (p = 0.006). Those patients undergoing complete revascularization were older and more likely to be male, diabetic, have renal disease and a history of previous myocardial infarction/revascularization compared with the culprit-only revascularization group. Although crude, in-hospital major adverse cardiac event rates were similar (5.2% vs. 4.8%; p = 0.462) between the 2 groups. Kaplan-Meier analysis demonstrated significant differences in mortality rates between the 2 groups (22.5% complete revascularization vs. 25.9% culprit vessel intervention; p = 0.0005) during the follow-up period. After multivariate Cox analysis (hazard ratio: 0.90; 95% confidence interval: 0.85 to 0.97) and the use of propensity matching (hazard ratio: 0.89; 95% confidence interval: 0.76 to 0.98) complete revascularization was associated with reduced mortality.
In NSTEMI patients with MVD, despite higher initial (in-hospital) mortality rates, single-stage complete coronary revascularization appears to be superior to culprit-only vessel PCI in terms of long-term mortality rates. This supports the need for further randomized study to confirm these findings.
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Objectives This study sought to determine if adenosine administration is required for the pressure-only assessment of coronary stenoses. Background The instantaneous wave-free ratio (iFR) is a ...vasodilator-free pressure-only measure of the hemodynamic severity of a coronary stenosis comparable to fractional flow reserve (FFR) in diagnostic categorization. In this study, we used hyperemic stenosis resistance (HSR), a combined pressure-and-flow index, as an arbiter to determine when iFR and FFR disagree which index is most representative of the hemodynamic significance of the stenosis. We then test whether administering adenosine significantly improves diagnostic performance of iFR. Methods In 51 vessels, intracoronary pressure and flow velocity was measured distal to the stenosis at rest and during adenosine-mediated hyperemia. The iFR (at rest and during adenosine administration iFRa), FFR, HSR, baseline, and hyperemic microvascular resistance were calculated using automated algorithms. Results When iFR and FFR disagreed (4 cases, or 7.7% of the study population), HSR agreed with iFR in 50% of cases and with FFR in 50% of cases. Differences in magnitude of microvascular resistance did not influence diagnostic categorization; iFR, iFRa, and FFR had equally good diagnostic agreement with HSR (receiver-operating characteristic area under the curve 0.93 iFR vs. 0.94 iFRa and 0.96 FFR, p = 0.48). Conclusions iFR and FFR had equivalent agreement with classification of coronary stenosis severity by HSR. Further reduction in resistance by the administration of adenosine did not improve diagnostic categorization, indicating that iFR can be used as an adenosine-free alternative to FFR. (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study CLARIFY; NCT01118481 )
Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.
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.
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).
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 < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 95% confidence interval: 2.04 to 5.42). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).
In this multicenter international registry, COVID-19–positive ACS patients presented later and had increased in-hospital mortality compared with a pre–COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.
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The purpose of this study was to compare the safety and efficacy of percutaneous coronary intervention (PCI) with stenting against coronary artery bypass grafting (CABG) in patients with diabetes and ...symptomatic multivessel coronary artery disease.
CABG is the established method of revascularization in patients with diabetes and multivessel coronary disease, but with advances in PCI, there is uncertainty whether CABG remains the preferred method of revascularization.
The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), and stroke, and the main secondary outcome included the addition of repeat revascularization to the primary outcome events. A total of 510 diabetic patients with multivessel or complex single-vessel coronary disease from 24 centers were randomized to PCI plus stenting (and routine abciximab) or CABG. The primary comparison used a noninferiority method with the upper boundary of the 95% confidence interval (CI) not to exceed 1.3 to declare PCI noninferior. Bare-metal stents were used initially, but a switch to Cypher (sirolimus drug-eluting) stents (Cordis, Johnson & Johnson, Bridgewater, New Jersey) was made when these became available.
At 1 year of follow-up, the composite rate of death, MI, and stroke was 10.5% in the CABG group and 13.0% in the PCI group (hazard ratio HR: 1.25, 95% CI: 0.75 to 2.09; p=0.39), all-cause mortality rates were 3.2% and 3.2%, and the rates of death, MI, stroke, or repeat revascularization were 11.3% and 19.3% (HR: 1.77, 95% CI: 1.11 to 2.82; p=0.02), respectively. When the patients who underwent CABG were compared with the subset of patients who received drug-eluting stents (69% of patients), the primary outcome rates were 12.4% and 11.6% (HR: 0.93, 95% CI: 0.51 to 1.71; p=0.82), respectively.
The CARDia (Coronary Artery Revascularization in Diabetes) trial is the first randomized trial of coronary revascularization in diabetic patients, but the 1-year results did not show that PCI is noninferior to CABG. However, the CARDia trial did show that multivessel PCI is feasible in patients with diabetes, but longer-term follow-up and data from other trials will be needed to provide a more precise comparison of the efficacy of these 2 revascularization strategies. (The Coronary Artery Revascularisation in Diabetes trial; ISRCTN19872154).
This study aimed to determine the effect on long-term survival of using optical coherence tomography (OCT) during percutaneous coronary intervention (PCI).
Angiographic guidance for PCI has ...substantial limitations. The superior spatial resolution of OCT could translate into meaningful clinical benefits, although limited data exist to date about their effect on clinical endpoints.
This was a cohort study based on the Pan-London (United Kingdom) PCI registry, which includes 123,764 patients who underwent PCI in National Health Service hospitals in London between 2005 and 2015. Patients undergoing primary PCI or pressure wire use were excluded leaving 87,166 patients in the study. The primary endpoint was all-cause mortality at a median of 4.8 years.
OCT was used in 1,149 (1.3%) patients, intravascular ultrasound (IVUS) was used in 10,971 (12.6%) patients, and angiography alone in the remaining 75,046 patients. Overall OCT rates increased over time (p < 0.0001), with variation in rates between centers (p = 0.002). The mean stent length was shortest in the angiography-guided group, longer in the IVUS-guided group, and longest in the OCT-guided group. OCT-guided procedures were associated with greater procedural success rates and reduced in-hospital MACE rates. A significant difference in mortality was observed between patients who underwent OCT-guided PCI (7.7%) compared with patients who underwent either IVUS-guided (12.2%) or angiography-guided (15.7%; p < 0.0001) PCI, with differences seen for both elective (p < 0.0001) and acute coronary syndrome subgroups (p = 0.0024). Overall this difference persisted after multivariate Cox analysis (hazard ratio HR: 0.48; 95% confidence interval CI: 0.26 to 0.81; p = 0.001) and propensity matching (hazard ratio: 0.39; 95% CI: 0.21 to 0.77; p = 0.0008; OCT vs. angiography-alone cohort), with no difference in matched OCT and IVUS cohorts (HR: 0.88; 95% CI: 0.61 to 1.38; p = 0.43).
In this large observational study, OCT-guided PCI was associated with improved procedural outcomes, in-hospital events, and long-term survival compared with standard angiography-guided PCI.
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 (Pinteraction=0.318) or iFR (Pinteraction=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 (Pinteraction<0.00001) and decreasing iFR (Pinteraction<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 (Pinteraction=0.849) or iFR (Pinteraction=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 (Pinteraction=0.693) nor iFR (Pinteraction=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:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02062593.
The Evolut PRO self-expanding transcatheter aortic valve has been designed to feature an outer pericardial wrap that aims to reduce paravalvular regurgitation (PVR) rates. Medium-term clinical ...outcomes, compared to its predecessor Evolut R, in a real-world setting, have not been investigated. The aim of the present study was to compare the two valves with regards to peri-procedural complications, early outcomes and mid-term survival.
Consecutive patients, undergoing TAVI with either the Evolut PRO or Evolut R device, from the multicenter ATLAS registry were retrospectively studied. Outcomes studied included periprocedural complications, PVR at discharge, need for new pacemaker implantation and Kaplan-Meier estimated 1-year all-cause mortality.
Analysis included 673 patients (498 treated with Evolut R and 175 treated with Evolut PRO). At least moderate PVR was numerically lower amongst patients treated with Evolut PRO (7.4% vs 3.8% for Evolut R and Evolut PRO respectively, p = .108). Rates of new permanent pacemaker (PPM) implantation (21.1% vs. 11.9%, p = .023), and bail-out valve-in-valve (2.4% vs. 0%, p = .049) were significantly lower amongst the Evolut PRO group. No differences were demonstrated regarding bleeding, stroke or acute kidney injury. One-year Kaplan-Meier estimated survival was similar between groups (93% for Evolut R vs. 91.2% for Evolut PRO, plog-rank = 0.806).
The Evolut PRO self-expanding valve demonstrates similar mid-term survival rates and numerically, yet not significant, lower incidence of PVR compared to its predecessor. Interestingly this new generation valve is associated with a significantly reduced rate for new PPM implantation. Future studies are required to confirm this finding.
•Last generation Evolut PRO features an outer pericardial wrap aiming to reduced PVR•It demonstrates similar mid-term survival rates compared to its predecessor.•Last generation device demonstrates, yet not significant, lower incidence of PVR.•Significantly reduced rate of new PPM implantation has been recorded.
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