Junji Matsuda

Relationship Between Subclinical Cardiac Troponin I Elevation and Culprit Lesion Characteristics Assessed by Optical Coherence Tomography in Patients Undergoing Elective Percutaneous Coronary Intervention

Background—The prevalence of subclinical, cardiac troponin I (cTnI) elevation in stable patients undergoing elective percutaneous coronary intervention and its relationship to culprit lesion characteristics assessed by optical coherence tomography (OCT) are unknown. Methods and Results—We studied 206 native de novo culprit coronary lesions from 206 patients with stable angina pectoris who underwent OCT before elective percutaneous coronary intervention. Patients were divided into 2 groups according to the presence (cTnI group; n=47; 22.8%) or absence (non-cTnI group; n=159; 77.2%) of cTnI ≥0.03 ng/mL at admission. The clinical and OCT findings were compared between these 2 groups. No significant difference was found in the clinical presentation between the groups except for the serum C-reactive protein levels and presence of multivessel disease. By OCT, cTnI elevation was associated with the presence of thin-cap fibroatheromas, a greater lipid arc, and a longer lipid length. In a multivariable analysis, the presence of positive C-reactive protein levels (odds ratio, 4.38; 95% confidence interval, 1.90–10.08; P=0.001) and OCT-derived thin-cap fibroatheromas (odds ratio, 2.89; 95% confidence interval, 1.22–6.86; P=0.016) were independent predictors of cTnI elevation. Periprocedural myocardial injury, defined as postpercutaneous coronary intervention peak cTnI levels >1.0 ng/mL (5× the upper reference limit), occurred more often in patients with cTnI elevation at admission (cTnI group: 41% versus non-cTnI group: 18%; P=0.001). Conclusions—The presence of subclinical cTnI elevation at admission was not uncommon and was associated with OCT-derived unstable plaque morphology in patients undergoing elective percutaneous coronary intervention, and may help to identify patients with stable angina pectoris at high risk for periprocedural myocardial injury.

Preprocedural fractional flow reserve and microvascular resistance predict increased hyperaemic coronary flow after elective percutaneous coronary intervention.

Epicardial focal coronary artery stenosis, diffuse coronary disease, and microvascular resistance (MR) may limit coronary flow. The purpose of percutaneous coronary intervention (PCI) is to increase coronary flow by targeting epicardial lesions. After PCI, MR might change and affect coronary flow. We investigated whether PCI influences MR using the index of microcirculatory resistance (IMR) and if pre‐PCI fractional flow reserve (FFR) or MR predicts the post‐PCI change in hyperaemic coronary flow.

Efficacy of pressure parameters obtained during contrast medium-induced submaximal hyperemia in the functional assessment of intermediate coronary stenosis

BACKGROUND Despite evidence demonstrating the superiority of percutaneous coronary intervention guided by fractional flow reserve (FFR), FFR evaluation has not been widely adopted. We sought to determine the diagnostic performance of baseline conditions and contrast medium-induced pressure indices in predicting FFR. We hypothesized that the contrast medium-induced end-diastolic pressure parameter would offer superior diagnostic agreement with FFR, compared to other indices. METHODS & RESULTS Ninety-one intermediate stenoses in 75 patients were studied prospectively. The baseline distal coronary pressure to aortic pressure ratio (Pd/Pa) and end-diastolic instantaneous Pd/Pa 60 ms before the electrocardiographic R-wave (ED-Pd/Pa) were measured; then, after intracoronary injection of 6 mL contrast medium at 3 mL/s, Pd/Pa (C-Pd/Pa) and end-diastolic Pd/Pa (C-ED-Pd/Pa) were obtained. Subsequently, conventional FFR was measured as a reference standard. Of the 91 lesions, 11 (12.1%) were excluded because of suboptimal data acquisition, leaving 80 for final analysis. C-ED-Pd/Pa values (median 0.80 [interquartile range 0.70-0.88]) were significantly lower than conventional FFR (0.83 [0.75-0.89], P<0.01), whereas Pd/Pa (0.93 [0.90-0.96], P<0.01), ED-Pd/Pa (0.91 [0.87-0.93], P<0.01), and C-Pd/Pa (0.85 [0.79-0.90], P<0.05) were significantly higher. Correlation coefficients (R) with conventional FFR were 0.74 (standard error of the estimate [SEE] 0.067, P<0.0001), 0.78 (SEE 0.062, P<0.0001), 0.85 (SEE 0.052, P<0.0001), and 0.93 (SEE 0.037, P<0.0001) for Pd/Pa, ED-Pd/Pa, C-Pd/Pa, and C-ED-Pd/Pa, respectively. Diagnostic accuracy was 81.2%, 83.8%, 87.5% and 93.8% for Pd/Pa, ED-Pd/Pa, C-Pd/Pa, and C-ED-Pd/Pa, respectively. CONCLUSIONS Among baseline indices and contrast-induced pressure parameters, C-ED-Pd/Pa is a novel, feasible, and high-performance measure for the physiological assessment of intermediate coronary stenosis.

The Influence of Elective Percutaneous Coronary Intervention on Microvascular Resistance: a Serial Assessment Using the Index of Microcirculatory Resistance

This study investigates whether hyperemic microvascular resistance (MR) is influenced by elective percutaneous coronary intervention (PCI) by using the index of microcirculatory resistance (IMR). Seventy-one consecutive patients with stable angina pectoris undergoing elective PCI were prospectively studied. The IMR was measured before and after PCI and at the 10-mo follow-up. The IMR significantly decreased until follow-up; the pre-PCI, post-PCI, and follow-up IMRs had a median of 19.8 (interquartile range, 14.6-28.9), 16.2 (11.8-22.1), and 14.8 (11.8-18.7), respectively (P < 0.001). The pre-PCI IMR was significantly correlated with the change in IMR between pre- and post-PCI (r = 0.84, P < 0.001) and between pre-PCI and follow-up (r = 0.93, P < 0.001). Pre-PCI IMR values were significantly higher in territories with decreases in IMR than in those with increases in IMR [pre-PCI IMR: 25.4 (18.4-35.5) vs. 12.5 (9.4-16.8), P < 0.001]. At follow-up, IMR values in territories showing decreases in IMR were significantly lower than those with increases in IMR [IMR at follow-up: 13.9 (10.9-17.6) vs. 16.6 (14.0-21.4), P = 0.013]. The IMR decrease was significantly associated with a greater shortening of mean transit time, indicating increases in coronary flow (P < 0.001). The optimal cut-off values of pre-PCI IMR to predict a decrease in IMR after PCI and at follow-up were 16.8 and 17.0, respectively. In conclusion, elective PCI affected hyperemic MR and its change was associated with pre-PCI MR, resulting in showing a wide distribution. Overall hyperemic MR significantly decreased until follow-up. The modified hyperemic MR introduced by PCI may affect post-PCI coronary flow.

Prevalence and Clinical Significance of Discordant Changes in Fractional and Coronary Flow Reserve After Elective Percutaneous Coronary Intervention.

Background Fractional flow reserve (FFR) and coronary flow reserve (CFR) are well‐validated physiological indices; however, changes in FFR and CFR after percutaneous coronary intervention (PCI) remain elusive. We sought to evaluate these changes and to investigate whether physiological indices predict cardiac event‐free survival after PCI. Methods and Results Physiological assessment of 220 stenoses from 220 patients was performed before and after PCI. The changes in FFR and CFR were studied, and factors associated with CFR change were investigated. Follow‐up data were collected to determine the predictor of cardiac events. CFR increase was found in 158 (71.8%) territories, and 62 (28.2%) presented a decrease, whereas FFR increased in all 220 (100%) territories. Pre‐ and post‐PCI percentage diameter stenoses were 57.7±11.2% and 7.48±4.79%, respectively. Post‐PCI CFR increase was associated with pre‐PCI indices including low FFR, low CFR and high microvascular resistance, and post‐PCI hyperemic coronary flow increase. Post‐PCI CFR decrease was not associated with significant post‐PCI hyperemic coronary flow increase. At a median follow‐up of 24.3 months, adverse event–free survival was significantly worse in patients with lower pre‐PCI CFR (log‐rank test λ2=7.26; P=0.007). Cox proportional hazards analysis showed that lower pre‐PCI CFR (hazard ratio 0.73; 95% CI 0.55–0.97; P=0.028) was an independent predictor of adverse cardiovascular events after PCI. Conclusions CFR decrease after PCI was not uncommon, and discordant change in FFR and CFR was associated with high pre‐PCI CFR, low pre‐PCI microvascular resistance, and no significant post‐PCI hyperemic coronary flow increase. Pre‐PCI CFR, not post‐PCI physiological indices, may help identify patients who require adjunctive management strategy after successful PCI.

Significance of Microvascular Function in Visual—Functional Mismatch Between Invasive Coronary Angiography and Fractional Flow Reserve

Background Despite a moderate correlation between angiographical stenosis and physiological significance, the mechanism of discordance has not been fully elucidated, particularly regarding the significance of microvascular function. This study sought to clarify whether microvascular function affects visual‐functional mismatch between quantitative coronary angiography (QCA) and fractional flow reserve (FFR). Methods and Results We assessed QCA, FFR, coronary flow reserve, and the index of microcirculatory resistance in 849 non‐left‐main coronary lesions with visually estimated intermediate stenoses from 532 patients. Clinical and lesion‐specific characteristics and physiological parameters associated with mismatch and reverse mismatch were studied. Coronary flow reserve and index of microcirculatory resistance showed a weak, but significant, correlation with FFR (R=0.306, P<0.001 and R=0.158, P<0.001, respectively). Four hundred twenty‐two lesions were visually nonsignificant (diameter stenosis assessed by QCA [QCA‐DS] ≤50%) and 427 lesions were visually significant (QCA‐DS >50%). Among visually nonsignificant lesions, FFR ≤0.80 (reverse mismatch) was observed in 129 lesions (30.6%). Among visually significant lesions, FFR >0.80 (mismatch) were observed in 179 lesions (41.9%). The significant predictors of reverse mismatch were male sex, nonculprit lesions of acute coronary syndrome, left anterior descending artery location, smaller QCA reference diameter, greater QCA‐DS, lower coronary flow reserve, and lower index of microcirculatory resistance. Mismatch was associated with right coronary artery location, greater QCA reference diameter, smaller QCA‐DS, lesion length, higher coronary flow reserve, and higher index of microcirculatory resistance. Conclusions There was a high prevalence of visual‐functional mismatches between QCA and FFR. The discrepancy was related to clinical characteristics, lesion‐specific factors, and microvascular resistance that was undistinguishable by coronary angiography, thus suggesting the importance of physiological lesion assessment.

Efficacy of Multidetector Computed Tomography to Predict Periprocedural Myocardial Injury After Percutaneous Coronary Intervention for Chronic Total Occlusion

Specific signatures of culprit lesions detected on multidetector computed tomography (MDCT) were identified as predictors of periprocedural myocardial injury (PMI) after percutaneous coronary intervention (PCI) in patients with stable angina; PMI has been shown to be associated with a worse prognosis. We investigated the association between preprocedural culprit lesion characteristics, assessed by MDCT, and PMI after PCI for chronic total occlusion (CTO). From three medical centers, 81 patients who underwent pre-PCI MDCT and CTO PCI, and systematic cardiac troponin (cTn) sampling before and after PCI, were included. Patients were divided into two groups according to the presence or absence of post-PCI cTn elevation. Patient characteristics, MDCT findings, and procedural variables were compared between the two groups. Procedure success was observed in 65 patients (80.2%) and was not associated with PMI. The incidence of PMI was higher in patients treated with the retrograde versus the antegrade approach. On MDCT, lesion length and the presence of the napkin-ring sign were significantly associated with PMI. Multivariate analysis revealed that the lesion length (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.01-1.08; P < 0.05), napkin-ring sign (OR: 5.41; 95% CI: 1.01-29.0; P < 0.05), and retrograde approach (OR: 4.78; 95% CI: 1.28-15.4; P < 0.05) were significant predictors of PMI. PMI is not uncommon in patients undergoing elective CTO PCI, regardless of procedure success or failure. Pre-PCI MDCT may help identify patients at high risk for PMI after CTO PCI.

Effect of Elective Percutaneous Coronary Intervention on Hyperemic Absolute Coronary Blood Flow Volume and Microvascular Resistance

Background— The hemodynamics involved in the relationship between absolute coronary blood flow (ABF) volume and myocardial resistance (MR) are complex, and the effect of percutaneous coronary intervention (PCI) on their changes remains unclear. The aim of this study was to investigate the differences in hyperemic ABF and MR before and after elective PCI using a thermodilution method. Methods and Results— We investigated 28 vessels (right coronary artery, 9; left anterior descending coronary artery, 18; left circumflex coronary artery, 1) from 28 patients with stable angina pectoris undergoing elective PCI. ABF was measured pre- and post-PCI using a pressure–temperature sensor-equipped wire, based on a thermodilution method with a continuous saline infusion of 20 mL/min through a proximally located microcatheter with an end-hole in the target vessel. MR equals distal coronary perfusion pressure divided by ABF at maximal hyperemia. Conventional fractional flow reserve was also measured pre- and post-PCI. Fractional flow reserve increased significantly after PCI (from 0.70 [0.65–0.75] to 0.88 [0.85–0.95]) in all examined territories. ABF also increased significantly (from 137.8 mL/min [86.3–180.8 mL/min] to 173.3 mL/min [137.9–234.3 mL/min] ; increase: 52.8 mL/min [9.7–80.8 mL/min]) while MR decreased in 11 vessels and increased in 17. No significant relationship was detected between these increases in fractional flow reserve and ABF. Both pre- and post-PCI MR distributed in a wide range, and there was a significant relationship between pre-PCI MR and the increase in ABF (r=0.44; P=0.02) although no significant change in MR was observed between pre- and post-PCI (P=0.37). Conclusions— Direct measurement of ABF and MR using thermodilution method offers a feasible approach that could shed a light on previously unclear aspects of coronary hemodynamics.

Prevalence of Thin-Cap Fibroatheroma in Relation to the Severity of Anatomical and Physiological Stenosis

BACKGROUND The relationship between the features of morphologically unstable plaque and physiological lesion severity remains elusive. We aimed to investigate this relationship using optical coherence tomography (OCT)-derived high-risk plaque characteristics and fractional flow reserve (FFR) as the degree of anatomical and physiological stenosis severity.Methods and Results:We investigated 286 de novo intermediate and severe coronary lesions in 248 patients who underwent OCT and FFR examinations. Lesions were divided into tertiles based on either FFR or quantitative coronary angiographic diameter stenosis (QCA-%DS). The OCT findings were compared among the tertiles of FFR and QCA-%DS. FFR and QCA tertiles were defined as follows: FFR-T1 (FFR <0.74), FFR-T2 (0.74≤FFR≤0.81), and FFR-T3 (FFR >0.81); and QCA-T1 (%DS ≥61%), QCA-T2 (51%≤%DS<61%), and QCA-T3 (%DS <51%). The prevalence of thin-cap fibroatheroma (TCFA) was significantly greater in FFR-T1 (20.0%) than in FFR-T2 and FFR-T3 (7.0%, P=0.03 and 7.7%, P=0.04, respectively), although no significant differences were observed among the QCA tertiles. CONCLUSIONS Physiological severity of coronary stenosis evaluated by FFR correlated with plaque instability in terms of TCFA. Preferable clinical outcomes for lesions with negative FFR based on the existing clinical evidence might be attributable to less likelihood of TCFA.

Efficacy of pressure parameters obtained during contrast medium-induced submaximal hyperemia in the functional assessment of intermediate coronary stenosis in comparison with instantaneous wave-free ratio.

BACKGROUND Despite evidence demonstrating the benefits of percutaneous coronary intervention guided by fractional flow reserve (FFR), FFR evaluation has not been widely adopted. We sought to compare the diagnostic performances of instantaneous wave-free ratio (iFR) to a novel contrast medium-induced index in FFR prediction, hypothesizing that the latter parameter would offer superior diagnostic agreement with FFR. METHODS & RESULTS We studied 132 intermediate stenoses in 97 patients prospectively. iFR was measured first, followed by intracoronary injection of 6 mL contrast medium at 3 mL/s to obtain end-diastolic instantaneous distal coronary pressure/aortic pressure ratio (Pd/Pa) 60 ms before the electrocardiographic R-wave (C-ED-Pd/Pa). Subsequently, conventional hyperemic FFR was measured as a reference standard. Of the 132 lesions, 120 were available for final analysis. The FFR values of 95/120 lesions (79.2%) were between 0.60 and 0.90. C-ED-Pd/Pa values (median 0.79 [interquartile range 0.69-0.87]) were significantly lower than FFR values (0.81 [0.75-0.88], P<0.01), whereas iFR values (0.91 [0.86-0.94], P<0.01) were significantly higher. Correlation coefficients with FFR were 0.78 (standard error of the estimate [SEE] 0.067, P<0.0001) and 0.93 (SEE 0.052, P<0.0001) for iFR and C-ED-Pd/Pa, respectively (P<0.001). The areas under the receiver operating characteristic curves were 0.88 and 0.96 for iFR and C-ED-Pd/Pa, respectively (P<0.01). Diagnostic accuracy was 85.0% and 92.5% for iFR and C-ED-Pd/Pa, respectively (P=0.06). CONCLUSIONS C-ED-Pd/Pa is a novel, practical, and accurate measure for the physiological assessment of intermediate coronary stenosis compared to iFR.