David Erlinge, Akiko Maehara, Ori Ben-Yehuda, Hans Erik Bøtker, Michael Maeng, Lars Kjøller-Hansen, Thomas Engstrøm, Mitsuaki Matsumura, Aaron Crowley, Ovidiu Dressler, Gary S Mintz, Ole Fröbert, Jonas Persson, Rune Wiseth, Alf Inge Larsen, Lisette Okkels Jensen, Jan Erik Nordrehaug, Øyvind Bleie, Elmir Omerovic, Claes Held, Stefan K James, Ziad A Ali, James E Muller, Gregg W Stone, Ole Ahlehoff, Azad Amin, Oskar Angerås, Praveen Appikonda, Saranya Balachandran, Ståle Barvik, Kristoffer Bendix, Maria Bertilsson, Ulrika Boden, Nigussie Bogale, Vernon Bonarjee, Fredrik Calais, Jörg Carlsson, Steen Carstensen, Christina Christersson, Evald Høj Christiansen, Maria Corral, Ole De Backer, Usama Dhaha, Christian Dworeck, Kai Eggers, Charlotta Elfström, Julia Ellert, Erlend Eriksen, Christian Fallesen, Margareta Forsman, Helena Fransson, Mohsen Gaballa, Marek Gacki, Matthias Götberg, Lars Hagström, Theresa Hallberg, Kristina Hambraeus, Inger Haraldsson, Jan Harnek, Ole Havndrup, Knut Hegbom, Matthias Heigert, Steffen Helqvist, Jon Herstad, Ziad Hijazi, Lene Holmvang, Dan Ioanes, Amjid Iqbal, Allan Iversen, Jaclyn Jacobson, Lars Jakobsen, Ivana Jankovic, Ulf Jensen, Karin Jensevik, Nina Johnston, Torfi Fjalar Jonasson, Erik Jørgensen, Francis Joshi, Ulf Kajermo, Frida Kåver, Henning Kelbæk, Thomas Kellerth, Mitra Kish, Wolfgang Koenig, Sasha Koul, Bo Lagerqvist, Bertil Larsson, Jens Flensted Lassen, Olav Leiren, Zhe Li, Christer Lidell, Rikard Linder, Michael Lindstaedt, Gunilla Lindström, Shen Liu, Kjetil Halvorsen Løland, Jacob Lønborg, László Márton, Habib Mir-Akbari, Shameema Mohamed, Jacob Odenstedt, Christer Ogne, Jonas Oldgren, Göran Olivecrona, Nikolas Östlund-Papadogeorgos, Michael Ottesen, Erik Packer, Åsa Michelgård Palmquist, Quratulain Paracha, Frans Pedersen, Petur Petursson, Truls Råmunddal, Svein Rotevatn, Raquel Sanchez, Giovanna Sarno, Kari I Saunamäki, Fredrik Scherstén, Patrick W Serruys, Iwar Sjögren, Rikke Sørensen, Iva Srdanovic, Zuka Subhani, Eva Svensson, Anne Thuesen, Jan Tijssen, Hans-Henrik Tilsted, Tim Tödt, Thor Trovik, Bjørn Inge Våga, Christoph Varenhorst, Karsten Veien, Emma Vestman, Sebastian Völz, Lars Wallentin, Joanna Wykrzykowska, Leszek Zagozdzon, Manuela Zamfir, Crister Zedigh, Hang Zhong, Zhipeng Zhou, Cardiology, ACS - Atherosclerosis & ischemic syndromes, and ACS - Heart failure & arrhythmias
Background Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). Methods PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Findings Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17 women, 745 [83 men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2 951.0-15.6) of 898 patients, with 66 (8.0 95.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9[SD 15.9]). Highly lipidic lesions (851 [24 of 3500 lesions, present in 520 [59 of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22 of 3629 lesions, present in 530 [59 of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.095.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.295.4-17.6). Interpretation Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Copyright (C) 2021 Elsevier Ltd. All rights reserved. BackgroundNear-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).MethodsPROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.FindingsBetween June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55–70] years). Median follow-up was 3·7 (IQR 3·0–4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0–15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2–10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25–4·13) and non-culprit lesion-specific MACEs (7·83, 4·12–14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0–10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4–17·6).InterpretationCombined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.FundingAbbott Vascular, Infraredx, and The Medicines Company.