Rikuta Hamaya

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.

Diagnostic and Prognostic Efficacy of Coronary Flow Capacity Obtained Using Pressure-Temperature Sensor–Tipped Wire–Derived Physiological Indices

OBJECTIVES This study aimed to evaluate the feasibility and efficacy of pressure-temperature sensor-tipped wire-derived coronary flow capacity (PTW-CFC) for assessing flow impairment and prognosis. BACKGROUND CFC provides an integrated coronary physiological assessment in which coronary flow reserve and coronary flow during hyperemia are organized. METHODS A total of 643 native de novo lesions for which physiological assessments were performed using a PressureWire (St. Jude Medical, St. Paul, Minnesota) in patients with stable coronary artery disease were identified. The entire cohort was stratified by PTW-CFC according to the well-validated thresholds of coronary flow reserve and the corresponding inverse of thermodilution-derived mean transit time under hyperemia. Coronary physiological indices and the prevalence of major adverse cardiac events (MACE) were assessed according to PTW-CFC categories. Furthermore, in patients who underwent percutaneous coronary intervention (PCI), post-PCI PTW-CFC categorization was performed and clinical outcomes were evaluated. RESULTS PTW-CFC categorization efficiently discriminated previously validated coronary physiological parameters for functional stenosis severity and microvascular dysfunction. MACE rates during follow-up (2.4 years) were significantly associated with advanced impairment of PTW-CFC except for severely reduced PTW-CFC. In the subgroup analysis of patients with severely reduced pre-PCI PTW-CFC who underwent successful PCI, MACE incidence was significantly frequent in patients with post-PCI non-normal PTW-CFC compared with those with post-PCI normal PTW-CFC. CONCLUSIONS PTW-CFC mapping was feasible, provided accurate stratifications of coronary flow impairment, and may predict MACE. Combined analysis involving PTW-CFC and fractional flow reserve may enrich the clinical implication of integrated coronary physiology and may help predict prognosis.

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.

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.

Interventricular Septal Hematoma after Retrograde Intervention for a Chronic Total Occlusion of a Right Coronary Artery: Echocardiographic and Magnetic Resonance Imaging—Diagnosis and Follow-Up

The reverse CART technique provides the potential to modify the retrograde procedure by improving the controlled movement of the retrograde wire and improve the success rates of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). Development of interventricular hematoma is a rare complication of CTO PCI. A 63-year-old man with effort angina with a right coronary artery CTO lesion underwent PCI by retrograde approach from the LAD to a septal branch. A contrast “stain” was demonstrated surrounding the septal collateral channel used for the retrograde approach at the end of the procedure without symptom. Echocardiography indicated an increased interventricular septum thickness with low echo signals region and decreased contractility. Cardiac magnetic resonance (CMR) imaging using gadolinium showed a diffusely thickened septum with a low signal fusiform neocavitation delimited by an enhanced-signal ring suggesting intraventricular septal dissecting hematoma. After conservative treatment, follow-up echocardiogram and CMR showed the resolution of the hematoma without clinical events. This case highlights the potentially lethal complication of septal perforator dissection and hematoma that may cause severe myocardial injury caused by retrograde approach for CTO PCI.

A selective peroxisome proliferator-activated receptor-β/δ agonist attenuates neointimal hyperplasia after wire-mediated arterial injury.

Background: Neointimal hyperplasia after the percutaneous coronary intervention is still a clinically serious problem, associated with the risk of thrombosis due to delayed reendothelization. Peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) belongs to a family of ligand-activated transcription factors. Objectives: In this study, we investigated the effects of GW-0742, a synthetic high-affinity PPAR-β/δ agonist, on neointimal hyperplasia after arterial injury. Using C57BL/6J mice, we made a wire-injury model and intraperitoneally injected GW-0742 or vehicle once a day. The arteries were harvested for pathological and molecular analysis on day 14 after injury. In vitro, vascular smooth muscle cells (VSMCs), macrophages and human umbilical vein endothelial cells (HUVECs) were cultured, and GW-0742 effects on the cells proliferation were measured. Results: The vehicle-treated injured arteries showed significantly thickened intima, while GW-0742 suppressed it. GW-0742 significantly suppressed IL-6 protein production, the expression of proliferating cell nuclear antigen in the neointima and enhanced CD31 expression. In vitro, GW-0742 attenuated VSMC proliferation triggered by cytokines or macrophages. The drug also induced endothelial regeneration after denudation injury. Conclusion: The data suggest that the PPAR-β/δ agonist is effective for atten- uation of neointimal hyperplasia by suppressing VSMC proliferation and accelerating reendothelization.

Coronary physiological assessment combining fractional flow reserve and index of microcirculatory resistance in patients undergoing elective percutaneous coronary intervention with grey zone fractional flow reserve

The aim of this study is to investigate the association between fractional flow reserve (FFR) values and change in coronary physiological indices after elective percutaneous coronary intervention (PCI).