Despite the availability of technologies and guidelines recommendations, invasive coronary function testing (IFT) remains underperformed in patients with ischemia with no obstructive coronary artery disease (INOCA), but the current state of IFT in Canadian cardiac catheterization laboratories (CCL) remained unknown. Therefore, we conducted an survey among Canadian CCL directors(n=46). While most CCL directors believed that IFT should be performed in INOCA patients experience persisting symptoms or adverse clinical outcomes, only 19.6% (n=9) and 30.4% (n=14) of responding centers performed invasive assessment of the microvasculature and vasomotor function, respectively. Despite the availability of technologies and guidelines recommendations, invasive coronary function testing (IFT) remains underperformed in patients with ischemia with no obstructive coronary artery disease (INOCA), but the current state of IFT in Canadian cardiac catheterization laboratories (CCL) remained unknown. Therefore, we conducted an survey among Canadian CCL directors(n=46). While most CCL directors believed that IFT should be performed in INOCA patients experience persisting symptoms or adverse clinical outcomes, only 19.6% (n=9) and 30.4% (n=14) of responding centers performed invasive assessment of the microvasculature and vasomotor function, respectively. Around 40% of all patients with demonstrated ischemia non-invasive testing undergoing elective coronary angiography for the investigation of chronic coronary syndromes have no obstructive coronary artery disease (CAD),1Patel M.R. Peterson E.D. Dai D. et al.Low Diagnostic Yield of Elective Coronary Angiography.New England Journal of Medicine. 2010; 362: 886-895https://doi.org/10.1056/NEJMoa0907272Crossref PubMed Scopus (1305) Google Scholar commonly known as INOCA. Despite the absence of obstructive CAD, INOCA is associated with a higher risk of mortality and morbidity,2Gulati M. Cooper-DeHoff R.M. McClure C. et al.Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project.Arch Intern Med. 2009; 169 (In eng): 843-850https://doi.org/10.1001/archinternmed.2009.50Crossref PubMed Scopus (467) Google Scholar and impaired quality of life.3Tavella R. Cutri N. Tucker G. Adams R. Spertus J. Beltrame J.F. Natural history of patients with insignificant coronary artery disease.European Heart Journal - Quality of Care and Clinical Outcomes. 2016; 2: 117-124https://doi.org/10.1093/ehjqcco/qcv034Crossref Scopus (44) Google Scholar The two main key endotypes of INOCA are structural coronary microvascular disorder (CMD) and coronary vasomotor disorders, the latter only diagnosable through invasive means. In the CORonary MICrovascular Angina (CorMicA) trial that included 151 patients with INOCA randomized to stratified medical therapy (guided by IFT) or standard care, only 17 (13,2%) patients had a normal coronary endothelial function : structural CMD, vasomotor disorders or both were identified in 78 (51.7%), 25 (16.6%) and 31 (20.5%) of patients, respectively.4Ford T.J. Stanley B. Good R. et al.Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial.J Am Coll Cardiol. 2018; 72 (In eng): 2841-2855https://doi.org/10.1016/j.jacc.2018.09.006Crossref PubMed Scopus (454) Google Scholar Guidewire-based coronary flow reserve (CFR) and/or microcirculatory resistance measurement (Class 2a, level of evidence B) and acetylcholine provocation testing (Class 2b, level of evidence B) is currently recommended in INOCA patients with persisting anginal symptoms to assess the presence of structural CMD and coronary vasomotor disorder.5Knuuti J. Wijns W. Saraste A. et al.2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC).European Heart Journal. 2020; 41: 407-477https://doi.org/10.1093/eurheartj/ehz425Crossref PubMed Scopus (4396) Google Scholar Despite the availability of technologies and guidelines recommendations, invasive coronary function testing (IFT), including guidewire-based CFR and/or microcirculatory resistance measurement and spasm provocation testing, remains underperformed in INOCA patients, but the current state of IFT in Canadian cardiac catheterization laboratories (CCL) remains unknown. Therefore, we conducted a survey among CCL directors to assess the state of IFT in Canadian CCL. We conducted an online survey among Canadian CCL directors from January 11th to May 5th, 2024. All CCL directors responded to the survey (n=46). Respondents were from Ontario (n=18; 39.1%), Quebec (n=15; 32.6%), British Columbia (n=5; 10.8%), Alberta (n=3; 6.5%), Saskatchewan (n=2; 4.4%), Manitoba (n=1; 2.1%), Nova Scotia (n=1; 2.2%) and New-Brunswick (n=1; 2.2%). The authors confirm that patient consent is not applicable to this article, as no patient was directly involved in this survey. A summary of the findings of the survey is represented in Figure 1. Guidewire-based CFR and microcirculatory resistance measurement is performed in 19.6% (n=9) of responding centers, with 88.9% (n=8) using a thermodilution-based technique and 11.1% (n=1) using a doppler-based technique. Sixty-five percent (64.9%;n=24) of responding centers who did not performed invasive assessment of the coronary microvasculature could refer to a nearby institution for guidewire-based CFR and microcirculatory resistance measurement: 37.5% (n=9), 50.0 % (n=12) and 12.5 % (n=3) reported a waiting time at the referral institution of less than 3 months, 3 to 6 months and more than 6 months, respectively. Among centers who did not perform invasive assessment of the coronary microvasculature, 19 (51.4%) responding centers were planning to do so in the future, while 18 (48.6%) responding centers did not. Twenty-eight percent (28.3%;n=13) of responding centers had access to non-invasive modalities for the assessment of the microvasculature at their institution, which were stress cardiac positron emission tomography with myocardial blood flow reserve (MBFR), cardiac magnetic resonance with MBFR and stress transthoracic echography with coronary flow velocity reserve in 61.5% (n=8), 30.8% (n=4) and 7.7% (n=1) of the cases, respectively. Forty-six percent (46.2%;n=6), thirty-eight percent (38.4%;n=5) and fifteen percent (15.4 %;n=2) reported a waiting time for non-invasive assessment of the microvasculature of less than 3 months, 3 to 6 months and more than 6 months, respectively. Fifty-nine percent (58.7%; n=27) of respondents believed that invasive assessment of the microvasculature should be offered initially to patients with INOCA, while 41.3% (n=19) did not. If empiric therapy was chosen as the initial strategy, respondents believed that invasive assessment of the microvasculature should be considered if the patients experiences daily (n=12; 26.1%) or weekly (n=30; 65.2%) symptoms or major cardiac adverse events (n=4; 8.7%). Invasive assessment of coronary vasomotor disorders is performed in 30.4% (n=14) of responding centers, with 71.4% (n=10) using acetylcholine and 28.6% (n=4) using ergonovine as provocation agents. Two percent (2.2%;n=1) and thirteen percent (13.0%; n=6) stopped performing invasive assessment of coronary vasomotor disorders because of an adverse event and the acetylcholine shortage, respectively. Sixty-three percent (62.5%; n=20) of responding centers who did not performed invasive assessment of coronary vasomotor disorders could refer to a nearby institution for provocation testing: 35.0% (n=7), 45.0% (n=9) and 2.0 % (n=4) reported a waiting time at the referral institution of less than 3 months, 3 to 6 months and more than 6 months, respectively. Among centers who did not performed invasive assessment of coronary vasomotor disorders, 12 (37.5 %) responding centers were planning to do so in the future, while 20 (62.5%) responding centers did not. Seventy-eight percent (78.3%;n=36) of respondents believed that invasive assessment of the vasomotor function should be offered initially to patients with INOCA, while 21.7% (n=10) did not. If empiric therapy was chosen as the initial strategy, respondents believed that invasive assessment of the microvasculature should be considered if the patients experiences daily (n=9; 19.6%) or weekly (n=29; 63.0%) symptoms or major cardiac adverse events (n=7; 15.2%). The indication for performing invasive coronary function testing, which may include invasive assessment of the microvasculature and vasomotor function, is set by an interventional cardiologist in the majority of cases (84.1%; n=37) or by a clinical cardiologist alternatively (15.9%; n=7). This survey is the first to examine the current state of IFT among Canadian CCL and it identified important findings. First, only 19.6% and 30.4% of responding centers perform invasive assessment of the microvasculature and vasomotor function, respectively. While non-invasive diagnostic modality is currently available for coronary vasomotor disorders, only 28.3% of responding centers had access to a non-invasive alternative for the assessment of the microvascular function. Second, despite the low performance of IFT, most responders believed that IFT should be offered to INOCA patients if they experience daily or weekly symptoms, or an adverse event. Third, responders believed in majority that the indication for IFT in INOCA patient should be set by the interventional cardiologist, underlying the importance of the involvement of interventional cardiologist in the care of INOCA patients. It has been well established that the majority patients with angina in the absence of coronary artery disease have an abnormal coronary function, and that performing IFT to explore microcirculatory and vasomotor disorders increases the diagnostic yield in this population.4Ford T.J. Stanley B. Good R. et al.Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial.J Am Coll Cardiol. 2018; 72 (In eng): 2841-2855https://doi.org/10.1016/j.jacc.2018.09.006Crossref PubMed Scopus (454) Google Scholar Recently, the CORonary MICrovascular Angina (CorMicA) trial demonstrated that tailored treatment guided by the results of IFT leads to a significant reduction in anginal symptoms and an amelioration in the quality of life, compared with conventional, non-guided medical therapy.4Ford T.J. Stanley B. Good R. et al.Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial.J Am Coll Cardiol. 2018; 72 (In eng): 2841-2855https://doi.org/10.1016/j.jacc.2018.09.006Crossref PubMed Scopus (454) Google Scholar The CorMicA trial also reinforced the fact most INOCA patients have an abnormal coronary function, with structural CMD, vasomotor disorders or both identified in 78 (51.7%), 25 (16.6%) and 31 (20.5%) of patients, respectively, as well as the safety of IFT, with no major adverse event reported in the trial.4Ford T.J. Stanley B. Good R. et al.Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial.J Am Coll Cardiol. 2018; 72 (In eng): 2841-2855https://doi.org/10.1016/j.jacc.2018.09.006Crossref PubMed Scopus (454) Google Scholar The improvement in patient well-being associated with stratified medicine including IFT with linked medical therapy is reflected in the current guidelines who recommend guidewire-based CFR and/or microcirculatory resistance measurement (Class 2a, level of evidence B) and acetylcholine provocation testing (Class 2b, level of evidence B) in INOCA patients with persisting anginal symptoms.5Knuuti J. Wijns W. Saraste A. et al.2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC).European Heart Journal. 2020; 41: 407-477https://doi.org/10.1093/eurheartj/ehz425Crossref PubMed Scopus (4396) Google Scholar While performing IFT in INOCA patients may positively impact symptoms, quality of life, and healthcare costs by reducing repeated testing as a result of symptoms persistence, it has not been showed to impact major adverse cardiac events, as no therapy is currently proven to mitigate the increased mortality and morbidity observed in this population.2Gulati M. Cooper-DeHoff R.M. McClure C. et al.Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project.Arch Intern Med. 2009; 169 (In eng): 843-850https://doi.org/10.1001/archinternmed.2009.50Crossref PubMed Scopus (467) Google Scholar Low implantationof invasive diagnostic pathways to investigate microcirculatory or vasomotor disorders is often cited in the literature, but no other country has assessed the state of IFT in their CCLs. Therefore, this survey is one of the first to prove that performance of IFT remains low across CCL, despite that CCL directors believe that IFT should be performed in INOCA patients experiencing persisting symptoms or and adverse event. While the reasons behind the low adaptation of IFT are unexplored, one can hypothesize that several factors can contribute to the relatively low performance of IFTs, such as insufficient CCL time, the absence of billing codes for IFT, budgetary constraints in Canadian CCL, the recent approval of Coroflow (Coroventis Research, Sweden) by Health Canada, concerns regarding the safety of IFT, the absence of evidence that proves that diagnostic strategy linked to therapy improves patients morbidity and mortality, etc. Future research should focus on investigating the factors that may explain poor uptake of IFT among INOCA patients, in order to identify potential solutions that favor the performance of IFT in Canadian CCL and the development of efficient referral pathways for INOCA patients. In conclusion, despite that most CCL directors believed that IFT should be performed in INOCA patients experience persisting symptoms or adverse clinical outcomes, a small proportion of Canadian CCLs is currently performing IFT, with little access to non-invasive assessment of the microvasculature. None.
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