Outcomes after fractional flow reserve-guided percutaneous coronary intervention versus coronary artery bypass grafting (FAME 3): 5-year follow-up of a multicentre, open-label, randomised trial.Lancet (London, England) • February 03, 2025
William Fearon, Frederik Zimmermann, Victoria Ding, Kuniaki Takahashi, Zsolt Piroth, Albert H Van Straten, Laszlo Szekely, Giedrius Davidavičius, Gintaras Kalinauskas, Samer Mansour, Rajesh Kharbanda, Nikolaos Östlund Papadogeorgos, Adel Aminian, Keith Oldroyd, Nawwar Al Attar, Nikola Jagic, Jan-henk Dambrink, Petr Kala, Oskar Angerås, Philip Maccarthy, Olaf Wendler, Filip Casselman, Nils Witt, Kreton Mavromatis, Steven E Miner, Jaydeep Sarma, Thomas Engstrøm, Evald Christiansen, Pim A Tonino, Michael Reardon, Hisao Otsuki, Yuhei Kobayashi, Mark Hlatky, Kenneth Mahaffey, Manisha Desai, Y Woo, Alan Yeung, Nico H Pijls, Bernard De Bruyne
Background: Long-term outcomes following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) might be changing because of improved techniques and better medical therapy. This final prespecified analysis of the Fractional Flow Reserve (FFR) versus Angiography for Multivessel Evaluation (FAME) 3 trial aimed to reassess their comparative effectiveness at 5 years.
Methods: FAME 3 was a multicentre, randomised trial comparing FFR-guided PCI using current-generation zotarolimus-eluting stents versus CABG in patients with three-vessel coronary artery disease not involving the left main coronary artery. 48 hospitals in Europe, USA and Canada, Australia, and Asia participated in the trial. Patients (aged ≥21 years with no cardiogenic shock, no recent ST segment elevation myocardial infarction, no severe left ventricular dysfunction, and no previous CABG) were randomly assigned to either PCI or CABG using a web-based system. At 1 year, FFR-guided PCI did not meet the prespecified threshold for non-inferiority for the outcome of death, stroke, myocardial infarction, or repeat revascularisation versus CABG. The primary endpoint for this intention-to-treat analysis was the 5-year incidence of the prespecified composite outcome of death, stroke, or myocardial infarction. The trial was registered at ClinicalTrials.gov, NCT02100722, and is completed; this is the final report. Findings: Between Aug 25, 2014 and Nov 28, 2019, 757 of 1500 participants were assigned to PCI and 743 to CABG. 5-year follow-up was achieved in 724 (96%) patients assigned to PCI and 696 (94%) assigned to CABG. At 5 years, there was no significant difference in the composite of death, stroke, or myocardial infarction between the two groups, with 119 (16%) events in the PCI group and 101 (14%) in the CABG group (hazard ratio 1·16 [95% CI 0·89-1·52]; p=0·27). There were no differences in the rates of death (53 [7%] vs 51 [7%]; 0·99 [0·67-1·46]) or stroke (14 [2%] vs 21 [3%], 0·65 [0·33-1·28]), but myocardial infarction was higher in the PCI group than in the CABG group (60 [8%] vs 38 [5%], 1·57 [1·04-2·36]), as was repeat revascularisation (112 [16%] vs 55 [8%], 2·02 [1·46-2·79]). Interpretation: At the 5-year follow-up, there was no significant difference in a composite outcome of death, stroke, or myocardial infarction after FFR-guided PCI versus CABG, although myocardial infarction and repeat revascularisation were higher with PCI. These results provide contemporary evidence to allow improved shared decision making between physicians and patients. Funding: Medtronic and Abbott Vascular.
Outcomes After CABG Compared With FFR-Guided PCI in Patients Presenting With Acute Coronary Syndrome.JACC. Cardiovascular Interventions • September 14, 2024
Kuniaki Takahashi, Hisao Otsuki, Frederik Zimmermann, Victoria Ding, Zsolt Piroth, Keith Oldroyd, Olaf Wendler, Michael Reardon, Manisha Desai, Y Woo, Alan Yeung, Bernard De Bruyne, Nico H Pijls, William Fearon
Background: There are limited data comparing coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) in patients presenting with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
Objective: The aim of this study was to evaluate differences in outcomes in patients presenting with or without NSTE-ACS after CABG compared with fractional flow reserve (FFR)-guided PCI using current generation drug-eluting stents.
Methods: The FAME 3 trial (Fractional flow reserve versus Angiography for Multivessel Evaluation; NCT02100722) was an investigator-initiated, randomized controlled trial to attest noninferiority of FFR-guided PCI using the current-generation drug-eluting stents to CABG with respect to the primary endpoint, defined as a composite of death, myocardial infarction (MI), stroke, or repeat revascularization at 1 year, in 1,500 patients with 3-vessel coronary artery disease. The prespecified key secondary endpoint was a composite of death, MI, or stroke at 3 years.
Results: Of 1,500 patients enrolled, 587 (39.2%) presented with NSTE-ACS. Patients were followed up for a median of 1,080 days (Q1-Q3: 1,080-1,080 days). At 3 years, the risk of the composite of death, MI, or stroke was similar between patients presenting with NSTE-ACS and with chronic coronary syndrome (CCS) (11.8% vs 10.0%; adjusted HR [aHR]: 1.20; 95% CI: 0.81-1.77; P = 0.37). Patients presenting with NSTE-ACS had a similar risk of death, MI, or stroke at 3 years after CABG as compared with PCI (aHR: 0.98; 95% CI: 0.60-1.60; P = 0.94), whereas patients presenting with CCS had a significantly reduced risk after CABG compared with PCI (aHR: 0.58; 95% CI: 0.38-0.90; P = 0.02; Pinteraction = 0.11), which was driven by a lower risk of MI (aHR: 0.32; 95% CI: 0.15-0.64; P = 0.002; Pinteraction = 0.01).
Conclusions: The risk of death, MI, or stroke at 3 years was similar after CABG compared with FFR-guided PCI in patients presenting with NSTE-ACS, but reduced by CABG in patients presenting with CCS. (Fractional flow reserve versus Angiography for Multivessel Evaluation [FAME 3]; NCT02100722).
First-In-Human Experience of the New Fully Repositionable IMPERIA Delivery System to Implant the ALLEGRA Transcatheter Heart Valve in Patients With Severe Calcific Aortic Stenosis or Degenerated Surgical Bioprosthesis: Thirty-Day Results of the EMPIRE I Study.Structural Heart : The Journal Of The Heart Team • September 03, 2024
José Antonio Baz, Christof Burgdorf, Christian Frerker, Ignacio Cruz González, Joan Antoni Gômez, Joseph Graham, José Maria Hernândez, Pilar Jimenez, Claire Ren, Ernest Spitzer, Pim Tonino, Pieter Vriesendorp, Nicolas Van Mieghem, Samuel Copt, Anders Jönsson, Keith Oldroyd, Nicolas Doll
The ALLEGRA (Biosensors International) transcatheter heart valve is a self-expanding supra-annular bovine pericardial aortic valve. A new delivery system (IMPERIA™, Biosensors International) has been designed which allows the valve to be fully resheathed and repositioned in situ. The aim of this premarket study was to assess the safety and efficacy of transcatheter aortic valve implantation using the combination of the CE (Conformite Europeenne) marked ALLEGRA valve and the new IMPERIA delivery system. One hundred thirty-seven patients were enrolled in 11 centers from January to November 2023. There were 30 roll-in patients, 91 in the intention-to-treat (ITT) population and 16 with degenerated surgical aortic bioprostheses. The primary outcome was device success according to the Valve Academic Research Consortium-2 from discharge up to 7 days in the ITT cohort. Implantation of the ALLEGRA valve was successful in 136 patients (99.3%). There were no device embolizations and no patient required a second valve. Device success was achieved in 91.9% of the ITT cohort. At 30 days, all-cause mortality was 2.2% in the native aortic stenosis (AS) cohort and 0% in the valve-in-valve cohort. New pacemaker implantation was required in 12.4% (17/137). There was no patient prosthesis mismatch (PPM) in the 121 patients with native AS and moderate PPM in 2/16 valve-in-valve patients. This study confirms the safety and efficacy of transcatheter aortic valve implantation using the IMPERIA delivery system to implant the CE marked ALLEGRA transcatheter heart valve in patients with severe calcific native AS or a degenerated surgical aortic bioprostheses.
Coronary microvascular function and atherosclerotic plaque burden in ischaemia and no obstructive coronary arteries: a secondary analysis of the CorMicA trial.Heart (British Cardiac Society) • July 01, 2024
Daniel T Ang, Jaclyn Carberry, Thomas Ford, Anna Kamdar, Robert Sykes, Novalia Sidik, David Carrick, Peter Mccartney, Damien Collison, Keith Robertson, Aadil Shaukat, J Rocchiccioli, R Mcgeoch, Stuart Watkins, Stuart Hood, Margaret Mcentegart, Mitchell Lindsay, Hany Eteiba, Keith Oldroyd, Richard Good, Alex Mcconnachie, Colin Berry
Background: The relationship between atherosclerosis and endotypes of myocardial ischaemia with no obstructive coronary artery disease (INOCA) is unclear. We investigated potential associations between cumulative atherosclerotic plaque burden quantified using the Gensini score, novel invasive indices of coronary microvascular function (microvascular resistance reserve (MRR); resistive reserve ratio (RRR)) and related INOCA endotypes.
Methods: Coronary angiography and invasive coronary function tests were simultaneously acquired in the CorMicA cohort. A comprehensive physiological assessment was performed using both a thermodilution-based diagnostic guidewire and intracoronary acetylcholine provocation testing. Angiograms were examined for luminal stenosis in each segment of the SYNTAX coronary model. Cumulative plaque burden was quantified using the Gensini score, which incorporated both the number of diseased coronary segments and stenosis severity. Results were compared with indices of microvascular function and INOCA endotypes. Angiographic analyses were performed blind to coronary physiology findings.
Results: In 151 participants (median age 61 years; 73.5% female) without flow-limiting coronary artery disease, medical history included 41.7% smoking, 63.6% hypertension and 19.2% diabetes mellitus. The left anterior descending artery underwent diagnostic guidewire testing in 85.4%, and 55.0% of participants had abnormal coronary flow reserve (CFR) and/or Index of Microcirculatory Resistance (IMR). The median Gensini score was 6.0 (IQR 2.5-11.0). CFR (p=0.012), MRR (p=0.026) and RRR (p=0.026), but not IMR (p=0.445), were univariably associated with raised Gensini scores. These significant effects persisted in multivariable models controlling for potential confounders. Considering INOCA endotypes, Gensini scores differed among participants with microvascular angina (MVA) (7.0 (2.5-11.0)), vasospastic angina (VSA) (4.5 (2.0-10.0)), mixed MVA/VSA (9.0 (5.0-11.5)) and non-cardiac symptoms (3.5 (1.5-8.0)); Kruskal-Wallis p=0.030.
Conclusions: Reduced CFR, MRR and RRR, and MVA were associated with increased coronary atherosclerotic plaque burden, as evidenced by higher Gensini scores. These novel findings provide a mechanistic link between INOCA and cardiovascular events, reinforcing the importance of antiatherosclerosis therapy in patients with MVA.
A randomised trial of selective intracoronary hypothermia during primary PCI.EuroIntervention : Journal Of EuroPCR In Collaboration With The Working Group On Interventional Cardiology Of The European Society Of Cardiology • June 18, 2024
Mohamed El Farissi, Nico H Pijls, Richard Good, Thomas Engström, Thomas Keeble, Branko Beleslin, Bernard De Bruyne, Ole Fröbert, David Erlinge, Koen Teeuwen, Rob Eerdekens, Jesse P Demandt, Kenneth Mangion, Jakob Lonborg, Wikke Setz Pels, Grigoris Karamasis, Inge Wijnbergen, Pieter Vlaar, Annemiek De Vos, Guus Brueren, Keith Oldroyd, Colin Berry, Pim A Tonino, Marcel Van't Veer, Luuk Otterspoor
Background: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking.
Objective: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI.
Methods: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months.
Results: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53).
Conclusions: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).
