TY - JOUR
T1 - Clinical Relevance of Ischemia with Nonobstructive Coronary Arteries According to Coronary Microvascular Dysfunction
AU - Lee, Seung Hun
AU - Shin, Doosup
AU - Lee, Joo Myung
AU - van de Hoef, Tim P.
AU - Hong, David
AU - Choi, Ki Hong
AU - Hwang, Doyeon
AU - Boerhout, Coen K. M.
AU - de Waard, Guus A.
AU - Jung, Ji-Hyun
AU - Mejia-Renteria, Hernan
AU - Hoshino, Masahiro
AU - Echavarria-Pinto, Mauro
AU - Meuwissen, Martijn
AU - Matsuo, Hitoshi
AU - Madera-Cambero, Maribel
AU - Eftekhari, Ashkan
AU - Effat, Mohamed A.
AU - Murai, Tadashi
AU - Marques, Koen
AU - Doh, Joon-Hyung
AU - Christiansen, Evald H.
AU - Banerjee, Rupak
AU - Kim, Hyun Kuk
AU - Nam, Chang-Wook
AU - Niccoli, Giampaolo
AU - Nakayama, Masafumi
AU - Tanaka, Nobuhiro
AU - Shin, Eun-Seok
AU - Chamuleau, Steven A. J.
AU - ILIAS Registry Investigators †
AU - van Royen, Niels
AU - Knaapen, Paul
AU - Koo, Bon Kwon
AU - Kakuta, Tsunekazu
AU - Escaned, Javier
AU - Piek, Jan J.
N1 - Publisher Copyright: © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2022/5/3
Y1 - 2022/5/3
N2 - BACKGROUND: In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. METHODS AND RESULTS: From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all-cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD (P<0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HRadjusted ], 2.88; 95% CI, 1.52–7.19; P=0.024; group 4: HRadjusted, 4.00; 95% CI, 1.41–11.35; P=0.009). CONCLUSIONS: In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long-term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4-fold difference in long-term cardiovascular events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04485234.
AB - BACKGROUND: In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. METHODS AND RESULTS: From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all-cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD (P<0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HRadjusted ], 2.88; 95% CI, 1.52–7.19; P=0.024; group 4: HRadjusted, 4.00; 95% CI, 1.41–11.35; P=0.009). CONCLUSIONS: In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long-term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4-fold difference in long-term cardiovascular events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04485234.
KW - Coronary Artery Disease/diagnosis
KW - Coronary Stenosis/diagnostic imaging
KW - Coronary Vessels/diagnostic imaging
KW - Fractional Flow Reserve, Myocardial/physiology
KW - Humans
KW - Ischemia
KW - Microcirculation/physiology
KW - Myocardial Ischemia/diagnosis
KW - Syndrome
KW - coronary flow reserve
KW - coronary microvascular disease
KW - ischemia with nonobstructive coronary arteries
KW - myocardial ischemia
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=85129781221&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/JAHA.121.025171
DO - https://doi.org/10.1161/JAHA.121.025171
M3 - Article
C2 - 35475358
SN - 2047-9980
VL - 11
SP - e025171
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 9
M1 - e025171
ER -