The instantaneous wave-free ratio (iFR) is an index used to assess the severity of coronary-artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the ...two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events.
We conducted a multicenter, randomized, controlled, open-label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary-artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 12 months after the procedure.
A primary end-point event occurred in 68 of 1012 patients (6.7%) in the iFR group and in 61 of 1007 (6.1%) in the FFR group (difference in event rates, 0.7 percentage points; 95% confidence interval CI, -1.5 to 2.8; P=0.007 for noninferiority; hazard ratio, 1.12; 95% CI, 0.79 to 1.58; P=0.53); the upper limit of the 95% confidence interval for the difference in event rates fell within the prespecified noninferiority margin of 3.2 percentage points. The results were similar among major subgroups. The rates of myocardial infarction, target-lesion revascularization, restenosis, and stent thrombosis did not differ significantly between the two groups. A significantly higher proportion of patients in the FFR group than in the iFR group reported chest discomfort during the procedure.
Among patients with stable angina or an acute coronary syndrome, an iFR-guided revascularization strategy was noninferior to an FFR-guided revascularization strategy with respect to the rate of major adverse cardiac events at 12 months. (Funded by Philips Volcano; iFR SWEDEHEART ClinicalTrials.gov number, NCT02166736 .).
Summary Background Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to ...compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. Methods In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age <75 years vs ≥75 years and presence of cardiogenic shock yes vs no) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3–5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov , number NCT01519518. Findings Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients 13% in the bivalirudin group and 140 patients 15% in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk RR 1·52, 95% CI 1·09–2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70–1·89, p=0·59). Interpretation Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. Funding Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).
The BASILICA (Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction during TAVR) investigational device exemption trial was a prospective, ...multicenter, single-arm safety and feasibility study.
Coronary artery obstruction is a rare but devastating complication of transcatheter aortic valve replacement (TAVR). Current stent-based preventative strategies are suboptimal. Bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction during TAVR (BASILICA) is a novel transcatheter technique performed immediately before TAVR to prevent coronary artery obstruction.
Subjects with severe native or bioprosthetic aortic valve disease at high or extreme risk for surgery, and at high risk of coronary artery obstruction, were included. The primary success endpoint was successful BASILICA and TAVR without coronary obstruction or reintervention. The primary safety endpoint was freedom from major adverse cardiovascular events. Data were independently monitored. Endpoints were independently adjudicated. A core laboratory analyzed computed tomography images.
Between February 2018 and July 2018, 30 subjects were enrolled. Primary success was met in 28 (93%) subjects. BASILICA traversal and laceration was successful in 35 of 37 (95%) attempted leaflets. There was 100% freedom from coronary obstruction and reintervention. Primary safety was met in 21 (70%), driven by 6 (20%) major vascular complications related to TAVR but not BASILICA. There was 1 death at 30 days. There was 1 (3%) disabling stroke and 2 (7%) nondisabling strokes. Transient hemodynamic compromise was rare (7%) and resolved promptly with TAVR.
BASILICA was feasible in both native and bioprosthetic valves. Hemodynamic compromise was uncommon. Safety was acceptable and needs confirmation in larger studies. BASILICA appears effective in preventing coronary artery obstruction from TAVR in subjects at high risk.
We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery ...disease.
Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.
A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval CI, 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy.
In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).
Coronary artery obstruction is an uncommon but devastating complication of transcatheter aortic valve replacement (TAVR). Computed tomography appears to be a sensitive but nonspecific predictor of ...coronary artery obstruction. Transcatheter approaches to prevent and treat coronary artery obstruction, such as "snorkel" stenting, are unsatisfactory because of serious early and late ischemic complications. Bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction during TAVR (BASILICA) is an early-stage transcatheter procedure to prevent coronary artery obstruction. It works by splitting the native or bioprosthetic leaflets so that they splay after TAVR and preserve coronary artery inflow. Because of the paucity of suitable alternatives, there is interest in the BASILICA technique despite its infancy. This tutorial review summarizes current thinking about how to predict and prevent coronary artery obstruction using BASILICA. First, the authors depict the main pathophysiological mechanisms of TAVR-associated coronary artery obstruction, along with the factors thought to contribute to coronary obstruction. Next, the authors provide a step-by-step guide to analyzing pre-procedural computed tomographic findings to assess obstruction risk and, if desirable, to plan BASILICA. Next, the authors describe the mechanisms underlying transcatheter electrosurgery. Finally, they provide step-by-step guidance on how to perform the procedure, along with a required equipment list.
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.
Fractional flow reserve (FFR)-guided coronary artery bypass graft (CABG) surgery has been associated with lower number of graft anastomoses, lower rate of on-pump surgery, and higher graft patency ...rate as compared with angiography-guided CABG surgery. However, no clinical benefit has been reported to date.
Consecutive patients (n=627) treated by CABG between 2006 and 2010 were retrospectively included. In 198 patients, at least 1 stenosis was grafted according to FFR (FFR-guided group), whereas in 429 patients all stenoses were grafted based on angiography (angiography-guided group). The 2 coprimary end points were overall death or myocardial infarction and major adverse cardiovascular events (composite of overall death, myocardial infarction, and target vessel revascularization) up to 6-year follow-up. In the FFR-guided group, patients were significantly younger (66 57-73 versus 70 63-76;
<0.001), more often male (82% versus 72%;
=0.008), and less often diabetic (21% versus 30%;
=0.023). Clinical follow-up (median, 85 66-104 months) was analyzed in 396 patients after 1:1 propensity-score matching for these 3 variables. The rate of overall death or myocardial infarction was significantly lower in the FFR-guided (n=31 16% versus n=49 25%; hazard ratio, 0.59 95% confidence interval, 0.38-0.93;
=0.020) as compared with the angiography-guided group. Major adverse cardiovascular events rate was also numerically lower in the FFR-guided than in the angiography-guided group (n=42 21% versus n=52 26%; hazard ratio, 0.77 95% confidence interval, 0.51-1.16;
=0.21).
FFR-guided CABG is associated with a significant reduction in the rate of overall death or myocardial infarction at 6-year follow-up as compared with angiography-guided CABG.
Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown ...whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR.
We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk.
At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval CI, -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients 3.1% vs. 385 patients 30.8%, P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001).
Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .).
The purpose of this study was to investigate the relationship between angiographic and functional severity of coronary artery stenoses in the FAME (Fractional Flow Reserve Versus Angiography in ...Multivessel Evaluation) study.
It can be difficult to determine on the coronary angiogram which lesions cause ischemia. Revascularization of coronary stenoses that induce ischemia improves a patient's functional status and outcome. For stenoses that do not induce ischemia, however, the benefit of revascularization is less clear.
In the FAME study, routine measurement of the fractional flow reserve (FFR) was compared with angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease. The use of the FFR in addition to angiography significantly reduced the rate of all major adverse cardiac events at 1 year. Of the 1,414 lesions (509 patients) in the FFR-guided arm of the FAME study, 1,329 were successfully assessed by the FFR and are included in this analysis.
Before FFR measurement, these lesions were categorized into 50% to 70% (47% of all lesions), 71% to 90% (39% of all lesions), and 91% to 99% (15% of all lesions) diameter stenosis by visual assessment. In the category 50% to 70% stenosis, 35% were functionally significant (FFR <or=0.80) and 65% were not (FFR >0.80). In the category 71% to 90% stenosis, 80% were functionally significant and 20% were not. In the category of subtotal stenoses, 96% were functionally significant. Of all 509 patients with angiographically defined multivessel disease, only 235 (46%) had functional multivessel disease (>or=2 coronary arteries with an FFR <or=0.80).
Angiography is inaccurate in assessing the functional significance of a coronary stenosis when compared with the FFR, not only in the 50% to 70% category but also in the 70% to 90% angiographic severity category.
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