This is a retrospective study evaluating consecutive patients with ANOCA who underwent comprehensive FCA between 2013 and 2022 at 2 tertiary hospital sites, including the use of a dual sensor-tipped pressure and doppler-flow wire (ComboWire, Philips, CA) with intravenous adenosine (140mg/kg over 2 minutes) to induce hyperemia. Patients underwent FCA and were included in the study if they had (1) a clinical diagnosis of persistent angina, and (2) coronary angiography demonstrating no obstructive coronary artery disease (≤50% diameter stenosis in major coronary arteries). Persistent angina was defined as ongoing angina episodes despite prior/current use of calcium channel blockers and nitrates, with beta-blockers not routinely initiated until coronary artery spasm had been excluded by FCA. Exclusion criteria were: (1) acute coronary syndrome admission within the past month, (2) prior coronary artery bypass surgery, (3) impaired left ventricular systolic function (EF <50%), (4) severe renal or liver impairment, (5) known intolerance to adenosine or acetylcholine (ACh), (6) known cardiomyopathy. The referring cardiologist endorsed the temporary suspension of calcium channel blockers and/or nitrates for at least 24 hours prior to diagnostic angiography thereby minimizing drug effects on the physiological test results. Baseline patient demographic and clinical characteristics data were collected through hospital administrative records. The study was approved by the Central Adelaide Local Health Network Ethics Committee, and written informed consent was obtained from all patients.

Routine coronary angiography was performed via radial or femoral artery access, with intravenous heparin (50-70 U/kg) anticoagulation during coronary instrumentation. Diagnostic angiography confirmed the absence of obstructive coronary artery disease, whereafter FCA was performed utilizing a previously described protocol In brief, the left coronary artery (LCA) was engaged and a ComboWire (dual pressure-Doppler blood flow velocity sensory guide wide) was calibrated and advanced to the mid-segment of the left anterior descending artery (LAD). Continuous measurements of distal coronary pressure and average peak flow velocity (APV) were recorded using the ComboMap system (Volcano Corporation San Diego, CA, USA) during intravenous adenosine-induced hyperemia (140μg/kg/min), for the assessment of coronary microvascular function. CFR was defined as the ratio of maximal hyperemic coronary blood flow (hyperemic APV; hAPV) to resting coronary blood flow (basal APV; bAPV). Basal microvascular resistance (bMR) was calculated as distal coronary pressure/bAPV, whereas hMR was calculated as the distal coronary pressure/hAPV. For the purposes of this study, impaired coronary microvascular function was defined as an abnormal CFR (i.e. ≤ 2) and/or hMR (i.e. ≥1.9mmHg/cm/s), acknowledging that alternative thresholds have been used in other studies. ^,

Following this, all patients underwent provocative spasm testing involving administration of intracoronary bolus doses of ACh into the LCA (25, 50, 100μg). Coronary artery spasm (CAS) was defined as epicardial spasm where occlusive/sub-occlusive spasm (≥90% vasoconstriction) occurred in response to intracoronary ACh associated with ischemic ECG changes and reproducible chest pain symptoms, and microvascular spasm where reproducible chest pain symptoms and ECG changes occurred in the absence of epicardial constriction.

Diagnostic angiograms were retrospectively analyzed by 2 independent observers blinded to patient details, diagnoses, and physiological data to calculate cTFC as previously described In brief, the number of frames were counted (at the cine acquired speed of 7.5 or 15 frames/second) for contrast transit between standardized proximal and distal landmarks in the LAD artery. This value was multiplied by 4- or 2-fold (respectively) to obtain cTFC equivalent to 30 frames/second acquisition speed described in the original paper. Furthermore, the LAD TIMI frame count (cTFC-LAD) was corrected for the length of the LAD by a factor of 1.7. As per international guidelines, ^, the CSFP was defined as a cTFC ≥ 25 frames.

Continuous variables are reported as mean ± SD and analyzed using independent samples t-test. Categorical variables are reported as n (%) and analyzed using Chi-squared test. Pearson’s correlation was used to assess the relationship between cTFC-LAD and coronary hemodynamic parameters, as continuous variables. P values were calculated as 2-tailed, with <0.05 considered statistically significant. Data analysis was undertaken using SPSS Software Version 23 (IBM, NY).

Comprehensive FCA, including microcirculatory assessment and provocative spasm testing, was undertaken in 103 patients with ANOCA included in the final analysis. Baseline demographics, physiological and angiographic characteristics are shown in Table 1 . The patient cohort was predominantly females (77%) aged 57 ± 11 years with significant cardiovascular risk factors (hypertension in 54%, hypercholesterolemia in 61% and active smoking in 17%). At the time of procedure, 95% of patients had angina symptoms within the past month, with 70% experiencing episodes at least once a week despite anti-anginal therapy.

Of 103 patients, 69 (67%) met the cTFC criteria for the CSFP (mean cTFC 37 ± 10 frames). Clinically, cardiovascular risk factors were similar in those with/without the CSFP, although there was a reduced prevalence amongst women ( Table 2 ). Comparison of FCA findings ( Table 2 ) revealed that those with the CSFP were (1) more likely to have a lower basal coronary blood flow velocity (bAPV) and thus correspondingly higher basal microvascular resistance (bMR), (2) more likely to have a higher hMR, which was abnormal in almost two-thirds of patients, and (3) had a high prevalence of an impaired coronary microvascular function marker (i.e. abnormal CFR, hMR or microvascular spasm in almost 3-quarters of CSFP patients), but (4) there was no difference in mean CFR between groups nor ACh-inducible epicardial/microvascular spasm. Overall, 63 of the 69 (91%) patients with the CSFP had evidence of a coronary vasomotor disorder (ACh-induced spasm or abnormal hyperemic microvascular index) on FCA.

Considering cTFC as a continuous measure, this study confirms an inverse relationship between cTFC and resting blood flow velocity (bAPV) ( r =−0.289, P =. 004; Figure 1A ). Furthermore, there is a modest correlation between cTFC and microvascular resistance, both at rest (bMR: r = 0.384, P =. 002; Figure 1B ) and during hyperemia (hMR: r = 0.258, P =. 008; Figure 1C ). Not surprisingly, the cTFC was poorly associated with CFR ( r = 0.058, P =. 564; Figure 1D ).

Correlation of corrected thrombolysis in myocardial infarction frame count (cTFC) with resting blood flow velocity (bAPV) and microvascular resistance (bMR) (B), and hyperemic microvascular resistance (hMR) (C) and coronary flow reserve (CFR) (D).

Corrected thrombolysis in myocardial infarction frame (cTFC) count had a moderately strong, positive correlation with both resting microvascular resistance and coronary blood flow velocity ( n = 65, r = 0.384, P =. 002; n = 97 r = −0.289, P =. 004, respectively) as well as hyperemic microvascular resistance ( r = 0.258, P =.008). cTFC was not associated with coronary flow reserve ( r = −0.058, P =.564). Patients with coronary slow flow phenomenon (corrected thrombolysis in myocardial infarction frame count ≥25) are within the red box. bMR indicates resting microvascular resistance (calculated as distal coronary pressure/APV); bAPV, resting average coronary blood flow velocity; hMR, hyperemic microvascular resistance measured in the left anterior descending artery; CFR, coronary flow reserve measured in the left anterior descending artery; cTFC, corrected thrombolysis in myocardial infarction frame count.

Stay updated, free articles. Join our Telegram channel

Join