LAUSR

Vasospastic angina (VSA), which is one of the important functional cardiac disorders, may also play a role in the pathogenesis of atherosclerosis. Conversely, organic coronary stenosis is also known as an independent predictor for poor clinical outcomes in VSA patients. Although VSA patients have a variable degree of organic coronary stenosis in clinical setting, the functional importance of organic stenosis in those patients remains to be elucidated. The aim of this study was to examine the clinical importance and prognostic impact of fractional flow reserve (FFR) in patients with VSA and organic coronary stenosis. We enrolled 236 consecutive patients with suspected vasospastic angina who underwent acetylcholine provocation test for coronary spasm (M/F 148/88, 63.6±12.0 [SD] yrs.). Among them, 175 patients (74.1%) were diagnosed as having VSA, while the remaining non-VSA patients were regarded as controls (Group-C, n=61). We divided the VSA patients into 3 groups based on angiographical findings and FFR values; VSA with no organic stenosis (>50% luminal stenosis) (Group-N, n=110), organic stenosis and high FFR (≥0.80) (Group-H, FFR 0.87±0.05, n=36), and organic stenosis and low FFR (<0.80) (Group-L, FFR 0.71±0.07, n=29). We evaluated the incidence of major adverse cardiovascular events (MACE), including cardiovascular death (CVD), non-fatal myocardial infarction (MI), urgent percutaneous coronary intervention (PCI), and hospitalization due to unstable angina pectoris (UAP) during the median follow-up period of 656 days. The groups with organic stenosis (Groups H and L) were characterized by higher prevalence of diabetes mellitus (Group-C/N/H/L, 23.0/20.9/44.4/34.5%, P=0.03) and dyslipidemia (Group-C/N/H/L, 37.7/39.1/50.0/65.5%, P=0.03) as compared with Group-C. After provocation test, all VSA patients received calcium channel blockers (CCBs). In addition, 20 days (median) after provocation test, 26 patients (92.9%) in Group-L underwent elective PCI with coronary stents, while no patient underwent PCI in Groups N or H. The incidence of MACE during follow-up was significantly higher in Group-L (Group-C/N/H/L; 1.6/3.6/5.6/27.6%, log-rank P<0.001), whereas clinical outcomes were comparable among the remaining 3 groups (Figure). Importantly, all 8 patients with MACE in Group-L had poor outcomes (CVD/MI/urgent PCI/UAP; 2/1/3/2) despite complete revascularization and the prevention of coronary spasm with CCBs, indicating that they might be resistant to standard contemporary therapies. They were characterized by less frequent use of angiotensin convert enzyme inhibitor (0 vs. 47.6%, P=0.02) and higher prevalence of multi-vessel organic lesions (37.5 vs. 4.8%, P=0.052) compared with those without MACE. Figure 1 These results provide the first evidence that evaluation of coronary functional abnormalities with FFR is useful for making therapeutic strategies in VSA patients with organic coronary stenosis.