Clinical Relevance of Ischemia with Nonobstructive Coronary Arteries According to Coronary Microvascular Dysfunction
Authors: Lee Seung Hun , Shin Doosup , Lee Joo Myung , van de Hoef Tim P. , Hong David , Choi Ki Hong , Hwang Doyeon , Boerhout Coen K. M. , de Waard Guus A. , Jung Ji‐Hyun , Mejia‐Renteria Hernan , Hoshino Masahiro , Echavarria‐Pinto Mauro , Meuwissen Martijn , Matsuo Hitoshi , Madera‐Cambero Maribel , Eftekhari Ashkan , Effat Mohamed A. , Murai Tadashi , Marques Koen , Doh Joon‐Hyung , Christiansen Evald H. , Banerjee Rupak , Kim Hyun Kuk , Nam Chang‐Wook , Niccoli Giampaolo , Nakayama Masafumi , Tanaka Nobuhiro , Shin Eun‐Seok , Chamuleau Steven A. J. , van Royen Niels , Knaapen Paul , Koo Bon Kwon , Kakuta Tsunekazu , Escaned Javier , Piek Jan J. , van de Hoef Tim P. , Lee Joo Myung , Choi Ki Hong , Hong David , Lee Seung Hun , Shin Doosup , Hoshino Masahiro , Murai Tadashi , Kakuta Tsunekazu , Koo Bon Kwon , Hwang Doyeon , Boerhout Coen K. M. , Piek Jan J , de Waard Guus A. , Chamuleau Steven A. J. , Marques Koen , Knaapen Paul , Jung Ji‐Hyun , Mejia‐Renteria Hernan , Escaned Javier , Echavarria‐Pinto Mauro , Meuwissen Martijn , Matsuo Hitoshi , Madera‐Cambero Maribel , Eftekhari Ashkan , Christiansen Evald H , Effat Mohamed A , Doh Joon‐Hyung , Banerjee Rupak , Kim Hyun Kuk , Nam Chang‐Wook , Niccoli Giampaolo , Nakayama Masafumi , Tanaka Nobuhiro , Shin Eun‐Seok , Royen Niels 
Published: April 2022

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 [HR
adjusted
], 2.88; 95% CI, 1.52–7.19;
P
=0.024; group 4: HR
adjusted
, 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.