Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (May 2022)

Clinical Relevance of Ischemia with Nonobstructive Coronary Arteries According to Coronary Microvascular Dysfunction

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

DOI
https://doi.org/10.1161/JAHA.121.025171
Journal volume & issue
Vol. 11, no. 9

Abstract

Read online

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.

Keywords