Defining heterogeneity of epicardial functional stenosis with low coronary flow reserve by unsupervised machine learning
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ORIGINAL ARTICLE
Defining heterogeneity of epicardial functional stenosis with low coronary flow reserve by unsupervised machine learning Rikuta Hamaya1,2 · Masahiro Hoshino1 · Taishi Yonetsu3 · Joo Myung Lee4 · Bon‑Kwon Koo5,6 · Javier Escaned7,8 · Tsunekazu Kakuta1,9 Received: 2 April 2020 / Accepted: 29 May 2020 © Springer Japan KK, part of Springer Nature 2020
Abstract Low CFR is associated with poor prognosis, whereas it is a heterogeneous condition according to the actual coronary flow, such as high resting or low hyperemic coronary flow, which should have different physiological traits and clinical implications. This study aimed to detect and define the sub-phenotypes of vessels with low coronary flow reserve (CFR) epicardial disease by unsupervised machine-learning methods. Hierarchical clustering was applied to 376 vessels from 364 patients with CFR less than the median and fractional flow reserve ≤ 0.8 from a global, multicenter registry. Detailed features of coronary flow physiology and survivals from vessel-oriented composite outcomes (VOCO) were assessed according to the clusters. Clustering defined three distinct physiological subgroups (PS). PS1 (n = 151) were characterized by high resting coronary flow, dominantly left anterior descending artery (LAD) lesions. PS2 (n = 131) were, in contrast, low hyperemic coronary flow, mainly LAD lesions. PS3 (n = 82) mostly consisted of non-LAD lesions with similar flow status to PS1 except for the low hyperemic Pd. Survivals from VOCO were significantly different according to the clusters (p = 0.005) and PS3 had the highest rate of VOCO. In a COX proportional model predicting VOCO, there was a significant interaction between PCI and PSs, suggesting potentially different effects of PCI on outcome between PS1 and PS2. The unsupervised machine-learning approaches provided unique insights into low CFR condition. Among low CFR epicardial lesions, high resting flow with low hyperemic Pd might be related to poor prognosis, and low hyperemic flow in LAD could benefit from elective PCI. Clinical Trial Registration Information https://clinicaltrials.gov/ct2/show/NCT03690713, NCT03690713. Keywords Stable angina · Fractional flow reserve · Clinical research
Introduction A list of study collaborators can be found in the “Appendix”. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00380-020-01640-x) contains supplementary material, which is available to authorized users. * Tsunekazu Kakuta [email protected] 1
Division of Cardiovascular Medicine, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
2
Harvard T.H. Chan School of Public Health, Boston, MA, USA
3
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
4
Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Low coronary flow reserve (CFR), a ratio of hyperemic and resting coronary blood
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