Basal Coronary Microvascular Resistance Predicting Death and Heart Failure in Patients Without Functional Coronary Stenosis.

BACKGROUND: Abnormal coronary microcirculation is linked to poor patient prognosis, so the aim of the present study was to assess the prognostic relevance of basal microvascular resistance (b-IMR) in patients without functional coronary stenosis.Methods and Results: Analyses of 226 patients who underwent intracoronary physiological assessment of the left anterior descending artery included primary endpoints of all-cause death and heart failure, as well as secondary endpoints of cardiovascular death and atherosclerotic vascular events. During a median follow-up of 2 years, there were 12 (5.3%) primary and 21 (9.3 %) secondary endpoints. The optimal b-IMR cutoff for the primary endpoints was 47.1 U. Kaplan-Meier curve analysis demonstrated worse event-free survival of the primary endpoints in patients with a b-IMR below the cutoff (χ2=21.178, P<0.001). b-IMR was not significantly associated with the secondary endpoints (P=0.35). A low coronary flow reserve (CFR; <2.5) had prognostic value for both endpoints (primary endpoints: χ2=11.401, P=0.001; secondary endpoints: (χ2=6.015; P=0.014), and high hyperemic microvascular resistance (≥25) was associated only with the secondary endpoints (χ2=4.420; P=0.036). Incorporating b-IMR into a clinical model that included CFR improved the Net Reclassification Index and Integrated Discrimination Improvement for predicting the primary endpoints (P<0.001 and P=0.034, respectively). CONCLUSIONS: b-IMR may be a specific marker of the risk of death and heart failure in patients without functional coronary stenosis.

Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry.

AIMS: The microvascular resistance reserve (MRR) was introduced as a means to characterize the vasodilator reserve capacity of the coronary microcirculation while accounting for the influence of concomitant epicardial disease and the impact of administration of potent vasodilators on aortic pressure. This study aimed to evaluate the diagnostic and prognostic performance of MRR. METHODS AND RESULTS: A total of 1481 patients with stable symptoms and a clinical indication for coronary angiography were included from the global ILIAS Registry. MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressure. The median MRR was 2.97 [Q1-Q3: 2.32-3.86] and the overall relationship between MRR and CFR was good [correlation coefficient (Rs) = 0.88, P < 0.005]. The difference between CFR and MRR increased with decreasing FFR [coefficient of determination (R2) = 0.34; Coef.-2.88, 95% confidence interval (CI): -3.05--2.73; P < 0.005]. MRR was independently associated with major adverse cardiac events (MACE) at 5-year follow-up [hazard ratio (HR) 0.78; 95% CI 0.63-0.95; P = 0.024] and with target vessel failure (TVF) at 5-year follow-up (HR 0.83; 95% CI 0.76-0.97; P = 0.047). The optimal cut-off value of MRR was 3.0. Based on this cut-off value, only abnormal MRR was significantly associated with MACE and TVF at 5-year follow-up in vessels with functionally significant epicardial disease (FFR <0.75). CONCLUSION: MRR seems a robust indicator of the microvascular vasodilator reserve capacity. Moreover, in line with its theoretical background, this study suggests a diagnostic advantage of MRR over other indices of vasodilatory capacity in patients with hemodynamically significant epicardial coronary artery disease.

Angiographic flow velocity predicts lower limb outcomes after endovascular therapy: Application of the frame count method.

INTRODUCTION: Several factors related to lesion characteristics and endovascular therapy (EVT) procedures have been reported to affect primary patency after EVT. However, it is unknown why these factors were associated with primary patency. We hypothesized patency failure was related to poor blood flow in affected arteries. METHODS: This retrospective study included 131 consecutive patients who had received EVT with bare metal stents for peripheral artery disease caused by femoropopliteal artery lesions. Based on the tertile post-EVT flow velocity of the superficial femoral artery (SFA), patients were divided into high (n = 43), middle (n = 44), and low (n = 44) flow velocity groups. Flow velocity was measured using the frame count method. We measured incidence of major adverse limb events (MALE), composed of target lesion revascularization (TLR), non-TLR, and major amputation. RESULTS: At a median follow-up period of 22.7 months, MALE had occurred in 7 (16.3%), 10 (22.7%), and 29 (65.9%) of patients from the high, middle, and low SFA flow velocity groups, respectively (p < 0.001). Kaplan-Meier analysis showed incidence of MALE was significantly higher in the patients of low SFA flow velocity (log-rank test χ2 = 38.8, p < 0.001). Multivariate analysis found low SFA flow velocity to be an independent predictor for MALE (hazard ratio: 4.42; 95% CI: 2.27 to 8.60; p < 0.001) as was ankle-brachial index. CONCLUSION: Post-EVT SFA flow velocity for femoropopliteal artery lesions treated with bare metal stents is an independent predictor of limb patency. The frame count method for assessing arterial flow velocity is convenient and has potential for wide applications in EVT.

Elevated Remnant Lipoprotein Related to Adverse Events in Patients with Chronic Limb-Threatening Ischemia after Endovascular Therapy for Below-the-Knee Lesions.

BACKGROUND: The prognosis of patients with chronic limb-threatening ischemia (CLTI) is unacceptably poor, and risk factors are unknown. Serum remnant lipoprotein has been associated with cardiovascular events. The aim of our study was to test the hypothesis that remnant lipoprotein is associated with the prognosis of patients with CLTI. METHODS: This retrospective study included 67 patients with CLTI who had received endovascular therapy (EVT) for de novo below-the-knee lesions. Patients were divided into 2 groups using fasting preoperative value of remnant-like particle cholesterol (RLP-C) with a cutoff value of 5.1 mg/dL into LOW RLP-C (n = 46) and HIGH RLP-C (n = 21). We assessed the differences between the 2 groups in the prevalence of major adverse limb events (MALE), composed of target lesion revascularization and major amputation. RESULTS: At a median follow-up period of 12 months, MALE had occurred in 11 LOW RLP-C patients (23.9%) and 11 HIGH RLP-C patients (52.4%; P = 0.03). Kaplan-Meier analysis showed the prevalence of MALE was significantly higher in HIGH RLP-C than LOW RLP-C (log-rank χ2 = 5.2, P = 0.02). Multivariate analysis found HIGH RLP-C to be an independent predictor for MALE (hazard ratio, 2.6; 95% confidence interval, 1.1-6.1; P = 0.02) along with history of coronary artery disease. CONCLUSIONS: Preoperative remnant lipoprotein was associated with the prognosis of patients with CLTI who had received EVT for de novo below-the-knee lesions.

Determinants of visual-functional mismatches as assessed by coronary angiography and quantitative flow ratio.

OBJECTIVE: We aimed to evaluate the determinants of visual-functional mismatches between quantitative coronary angiography (QCA) and the quantitative flow ratio (QFR). BACKGROUND: The fractional flow reserve (FFR) has been established as a method to estimate the functional stenosis severity of coronary artery disease and to optimize decision-making for revascularization. The QFR is a novel angiography-derived computational index that can estimate the FFR without pharmacologically induced hyperemia or the use of pressure wire. METHODS: A total of 504 de novo intermediate-to-severe stable lesions that underwent angiographic and physiological assessments were analyzed. All lesions were divided into four groups based on the significance of visual (QCA-diameter stenosis [DS] > 50% and ≤ 50%) and functional (QFR ≤ 0.80 and > 0.80) stenosis severity. Patient characteristics, angiographic findings, and physiological indices were compared. RESULTS: One-hundred seventy-eight lesions (35.3%) showed discordant visual-functional assessments; mismatch (QCA-DS > 50% and QFR > 0.80) in 75 lesions (14.9%) and reverse mismatch (QCA-DS ≤ 50% and QFR ≤ 0.80) in 103 lesions (20.4%), respectively. Reverse mismatch was associated with non-diabetes, lower ejection fraction, higher Duke jeopardy score, and lower coronary flow reserve (CFR). Mismatch was associated with smaller QCA-DS, larger reference diameter, shorter lesion length, lower Duke jeopardy score, and higher CFR. Lesion location and microcirculatory resistance was not associated with the prevalence of mismatches. Reverse mismatch group had the higher prevalence of discordant decision-makings between QFR and FFR than the other three groups. CONCLUSIONS: The CFR and subtended myocardial mass were predictors of visual-functional mismatches between QCA-DS and the QFR. Caution should be exercised in lesions showing QCA-DS/QFR reverse mismatch.

Clinical Significance of Increased Computed Tomography Attenuation of Periaortic Adipose Tissue in Patients With Abdominal Aortic Aneurysms.

BACKGROUND: Recent imaging studies reported an association between vascular inflammation and progression of abdominal aortic aneurysm (AAA). This study investigated the clinical significance of periaortic adipose tissue inflammation derived from multidetector computed tomography angiography (MDCTA).Methods and Results:Patients with asymptomatic AAA (n=77) who underwent an index and >6 months follow-up MDCTA examinations were retrospectively investigated. MDCTA analysis included AAA diameter and the periaortic adipose tissue attenuation index (PAAI). The PAAI was defined as the mean CT attenuation value within a predefined range from -190 to -30 Hounsfield units of adipose tissue surrounding the AAA. The growth rate of the AAA was calculated as the change in diameter. AAA progression (AP) was defined as an AAA growth rate ≥5 mm/year. Univariate and multivariate logistic regression analysis were performed to determine the predictors of AP. AP was observed in 19 patients (24.7%), the median baseline AAA diameter was 38.9 mm (interquartile range [IQR] 32.7-42.9 mm), and the median growth rate was 3.1 mm/year (IQR 1.5-4.9 mm/year). Baseline AAA diameter (odds ratio [OR] 1.16; 95% confidence interval [CI] 1.05-1.28; P=0.001) and PAAI (OR 1.12; 95% CI 1.05-1.20; P=0.004) were independent predictors of AP. CONCLUSIONS: PAAI was an independent and significant predictor of AP, supporting the notion that local adipose tissue inflammation may contribute to aortic remodeling.

Risk factors and prognostic impact of post-discharge bleeding after endovascular therapy for peripheral artery disease.

This study evaluated the incidence, predictors, and impact of bleeding requiring hospitalization following successful endovascular therapy (EVT) for peripheral artery disease. Platelet inhibition after EVT reduces the risk of major adverse limb events but increases the risk of bleeding. The incidence of post-discharge bleeding after EVT, its independent predictors, and its prognostic importance in clinical practice have not been fully addressed. We evaluated 779 consecutive patients who underwent EVT. We found that 77 patients (9.9%) were hospitalized for major bleeding during follow-up after EVT (median 39 months, range 22-66 months), with almost half (48.1%) of the bleeding categorized as gastrointestinal bleeding. Significant predictors of post-discharge bleeding were hemodialysis (hazard ratio (HR), 3.12; 95% CI: 1.93 to 5.05; p < 0.001) and dual antiplatelet therapy (DAPT) use (HR, 1.87; 95% CI: 1.03 to 3.41; p = 0.041). During follow-up, the all-cause mortality-free survival rate was significantly worse in patients who had experienced major bleeding than in those who had not (log-rank test χ2 = 54.6; p < 0.001). Cox proportional hazards analysis showed that major bleeding (HR, 2.78; 95% CI: 1.90 to 4.06; p < 0.001) was an independent predictor of all-cause death after EVT. Hospitalization for post-discharge bleeding after EVT is associated with a substantially increased risk of death, even after successful EVT. We concluded that patients' predicted bleeding risk should be considered when selecting patients likely to benefit from EVT, and that the risk should be considered especially thoroughly in hemodialysis patients.

Eicosapentaenoic acid levels predict prognosis of peripheral artery disease caused by aortoiliac artery lesions.

BACKGROUND AND AIM: Eicosapentaenoic acid (EPA) has been reported to improve clinical outcome of high-risk atherosclerotic patients. We investigated whether endogenous EPA values predict prognosis of peripheral artery disease (PAD) patients. METHODS AND RESULTS: This retrospective study included 166 consecutive patients who had received endovascular therapy (EVT) for PAD caused by aortoiliac artery lesions. Patients were divided into 2 groups using median preoperative EPA value (57 µg/ml): LOW EPA (n = 83) and HIGH EPA (n = 83). We compared differences between the 2 groups in prevalence of major adverse limb events (MALE) which included target lesion revascularization (TLR), non-TLR, and major amputation, and major adverse events (MAE) which included MALE and all cause death. At a median follow-up period of 20 months, MALE had occurred in 24 LOW EPA patients (28.9%) and in 12 HIGH EPA patients (14.5%) (p = 0.04), and MAE had occurred in 41 LOW EPA patients (49.4%) and in 21 HIGH EPA patients (25.3%) (p < 0.01). Kaplan-Meier analysis showed prevalence of MALE and MAE was significantly higher in LOW EPA than in HIGH EPA (long-rank test χ2 = 8.5, p < 0.01, log-rank test χ2 = 13.2, p < 0.01, respectively). Multivariate Cox regression revealed preoperative EPA value < 57 µg/ml was an independent predictor for MALE (hazard ratio [HR]: 2.70; 95% CI: 1.35 to 5.4; p < 0.01) and MAE (HR: 2.86; 95% CI: 1.67 to 4.91; p < 0.01). CONCLUSIONS: Endogenous EPA value seems to be associated with risk of MALE and MAE after EVT in patients with PAD caused by aortoiliac artery lesions.

Impact of pericoronary adipose tissue inflammation on left ventricular hypertrophy and regional physiological indices in stable coronary artery disease patients with preserved systolic function.

Systemic low-grade inflammation has been shown to be associated with left ventricular hypertrophy (LVH). However, the relationship between pericoronary adipose tissue attenuation (PCATA) and both LVH and regional physiological indices remains unknown. This study aimed to evaluate the association of PCATA with LVH and regional physiological indices in stable coronary artery disease (CAD) patients with preserved systolic function. A total of 114 CAD patients who underwent coronary CT angiography (CTA) and invasive physiological tests showing ischemia due to a single de novo lesion were included in the study. On proximal 40-mm segments of all three major coronary vessels on CTA, PCATA was assessed by the crude analysis of the mean CT attenuation value [- 190 to - 30 Hounsfield units [HU)] and the culprit vessel PCATA was used for the analysis. Regional physiological indices were invasively obtained by pressure-temperature sensor-tipped wire. The patients were divided into three groups by culprit vessel PCATA tertiles, and clinical, CTA-derived, and physiological indices were compared. Univariable and multivariable analyses were further performed to determine the predictors of LVH. Angiographic stenosis severity, culprit lesion locations, culprit vessel fractional flow reserve, coronary flow reserve, index of microcirculatory resistance, total and target vessel coronary calcium score, and biomarkers including high-sensitivity C-reactive protein were not different among the groups. The left ventricular (LV) mass, LV mass index (LVMI), and LV mass at risk were all significantly different in the three groups with the greatest values in the highest tertile group (all, P < 0.05). On multivariable analysis, male gender, NT-proBNP, and PCATA were independent predictors of LVMI. Culprit vessel PCATA was significantly associated with LVMI, but not with regional physiology in CAD patients with functionally significant lesions and preserved systolic function. Our results may offer insight into the pathophysiological mechanisms linking pericoronary inflammation and LVH to worse prognosis.

Clinical Outcomes after Endovascular Therapy Among Hemodialysis Patients with Peripheral Artery Disease Stratified by the Primary Kidney Disease.

OBJECTIVES: The objective of this study was to investigate the clinical characteristics of hemodialysis patients with peripheral artery disease (PAD) and the outcomes after endovascular therapy (EVT) in such patients stratified by the primary kidney disease. METHODS: This retrospective observational study evaluated 142 consecutive hemodialysis patients with symptomatic PAD who underwent EVT (men: n = 103, age: 74 ± 8 years). Patients were divided into 3 groups in accordance with the reason for hemodialysis: hypertensive nephrosclerosis (HTN [n = 26]), diabetic nephropathy (DN [n = 85]), and chronic glomerulosclerosis (CGN [n = 31]). The primary outcome was major adverse event(s) (MAEs), including target lesion revascularization, major amputation, and all-cause death. Clinical characteristics and outcomes were compared among the 3 groups. RESULTS: Patients with HTN were older (81 ± 6 years vs. 72 ± 8 years vs. 74 ± 8 years; P < 0.001) and had a shorter hemodialysis vintage (2.4 years vs. 6.8 years vs. 11.2 years; P < 0.001) than those with DN and CGN. Critical limb ischemia (CLI) affected 15 (58%) patients in the HTN group, 52 (61%) in the DN group, and 10 (32%) in the CGN group. Target lesion length was longer in patients with HTN than in those in the other groups (155 ± 101 mm vs. 108 ± 77 mm [DN] vs. 98 ± 76 mm [CGN]; P = 0.020). During a median follow-up period of 372 days (interquartile range, 198-730 days), Kaplan-Meier curve analysis revealed that HTN was associated with an increased risk for MAEs (χ2 11.6; P = 0.003). Furthermore, multivariate Cox regression analysis revealed that CLI, HTN, and B-type natriuretic peptide levels were independent predictors of MAE (hazard ratio 3.91, 2.88, and 1.00; P < 0.001, P < 0.001, and P = 0.001, respectively). CONCLUSIONS: Among hemodialysis patients with PAD, HTN was associated with an increased risk for MAEs after EVT.

Optical coherence tomography-defined plaque vulnerability in relation to functional stenosis severity stratified by fractional flow reserve and quantitative flow ratio.

OBJECTIVES: We sought to investigate that the quantitative flow ratio (QFR) might be associated with optical coherence tomography (OCT)-defined plaque vulnerability. BACKGROUND: Both functional stenosis severity and plaque instability are related to adverse clinical outcomes in patients with coronary artery disease. Recent studies have shown an association between physiological stenosis severity and the presence of thin-cap fibroatheroma (TCFA). Measurement of QFR is a novel method for rapid computational estimation of fractional flow reserve (FFR). METHODS: We investigated 327 de novo intermediate-to-severe coronary lesions in 295 stable patients who underwent OCT, FFR, and QFR computation. The lesions were divided into tertiles based on either the FFR or QFR. The OCT findings were compared among these tertiles of FFR and QFR. Each tertile was defined as follows: FFR-T1 (FFR < 0.72), FFR-T2 (0.72 ≤ FFR ≤ 0.79), and FFR-T3 (FFR > 0.79) and QFR-T1 (QFR < 0.73), QFR-T2 (0.73 ≤ QFR ≤ 0.78), and QFR-T3 (QFR > 0.78). RESULTS: The prevalence of OCT-defined TCFA showed graded differences in proportion to the QFR tertiles (25.0% vs. 12.8% vs. 6.6%, p = .003). An overall significant difference in the prevalence of TCFA was found among FFR tertiles (p = .048), although pairwise comparison did not show statistical significance. Compared with FFR-based classifications, the model that integrated the FFR and QFR categorization improved the incremental reclassification efficacy (relative integrated discrimination improvement, 0.069; p = .002; continuous net reclassification improvement, 0.356; p = .022) for predicting the presence of TCFA. CONCLUSIONS: OCT-defined plaque instability was associated with the QFR in angiographically intermediate-to-severe lesions. Compared with the FFR alone, the QFR can provide incremental efficacy in predicting the presence of TCFA.

Clinical significance of the presence of puff-chandelier ruptures detected by nonobstructive aortic angioscopy.

OBJECTIVE: This study aimed to investigate the prevalence and prognostic significance of atherosclerotic aortic plaques (AAPs) or specific AAP types detected by nonobstructive angioscopy (NOA) in patients who underwent percutaneous coronary intervention (PCI). BACKGROUND: Although recent studies have reported the presence of various patterns of AAPs, identified by NOA, the clinical significance of the presence of AAPs remains elusive. METHODS: In this retrospective, multicenter cohort study, a total of 167 patients who underwent PCI and intra-aortic scans with NOA were studied. The association between AAPs and the incidence of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, stroke, and clinically driven unplanned revascularizations, was assessed. RESULTS: AAPs were detected in 126 patients (75%) who underwent NOA. MACEs occurred in 28 (17%) patients during the follow-up (median 2.9 years [range 2.1-3.8]). Among all types of AAPs, only puff-chandelier rupture (PCR) showed a significant difference in frequency between patients with and those without MACEs: 21 (75%) and 49 (35%), respectively (p < .001). Multivariable Cox proportional hazard analysis revealed that PCR (hazard ratio [HR] 3.73, 95% confidence interval [CI] 1.57-8.87, p = .004) and chronic kidney disease (HR 2.97, 95% CI 1.37-6.44, p = .010) were independent predictors of MACEs. Kaplan-Meier analysis revealed that PCR was significantly associated with more frequent MACEs. CONCLUSION: The detection of PCR in the aorta using NOA was significantly associated with an increased risk of subsequent adverse events after PCI.

All Resting Physiological Indices May Not Be Equivalent　- Comparison Between the Diastolic Pressure Ratio and Resting Full-Cycle Ratio.

BACKGROUND: Differences between resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have not been sufficiently discussed. This study aimed to investigate if there is a difference in diagnostic performance between RFR and dPR for the functional lesion assessment and to assess if there are specific characteristics for discordant revascularization decision-makings between RFR and dPR.Methods and Results:A total of 936 intermediate lesions in 776 patients who underwent measurements of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) were retrospectively studied. Physiological indices were measured from anonymized pressure recordings at an independent core laboratory. Both RFR and dPR measures were highly correlated (r=0.997, P<0.001), with equivalent diagnostic performance relative to FFR-based decision-makings measured by using a dichotomous threshold of 0.80 (accuracy, 79.7% vs. 80.1%, respectively, P=0.960). The rate of diagnostic discordance was 4.7% (44/936), with no RFR-/dPR+ lesions observed. An overall significant difference in FFR and CFR values were detected among RFR/dPR-based classifications. The prevalence of positive studies was significantly higher for RFR than dPR (54.3% vs. 49.6%, respectively, P=0.047) when using the cut-off value of 0.89. CONCLUSIONS: Both RFR and dPR were highly correlated, but the prevalence of positive studies was significantly different. The revascularization rate may differ significantly according to the resting index used.

Ventricular Fibrillation During Optical Coherence Tomography/Optical Frequency Domain Imaging　- A Large Single-Center Experience.

BACKGROUND: The risks of ventricular fibrillation (Vfib) associated with frequency-domain optical coherence tomography (OCT)/optical frequency domain imaging (OFDI) remain undetermined.Methods and Results:We retrospectively studied the occurrence of Vfib during OCT/OFDI for unselected indications. The frequency of Vfib and patient and procedural characteristics were investigated. A total of 4,467 OCT/OFDI pullback examinations were performed in 1,754 patients (median of 2.0 [2.0-3.0] pullbacks for 1.0 [1.0-1.3] vessels). OCT/OFDI was performed during PCI in 899 patients (51.3%). The contrast injection volume per pullback was 14.4 (11.7-17.2) mL with a flow rate of 3.4 (3.2-3.5) mL/s. Vfib occurred in 31 pullbacks (0.69%) in 30 patients (1.7%). No cases of Vfib occurred when using low-molecular-weight dextran. On multivariate analysis, contrast volume was the only independent factor for predicting Vfib (odds ratio, 1.080; 95% confidence interval, 1.008-1.158, P=0.029). The best cutoff value of contrast volume for predicting Vfib was 19.2 mL (area under the curve, 0.713, P<0.001; diagnostic accuracy, 87.1%). CONCLUSIONS: The present large, single-center registry study indicated that Vfib during OCT/OFDI was rare for unselected indications. Contrast injection volume used to displace blood should be limited to avoid Vfib.

Prognostic Value of Phase-Contrast Cine-Magnetic Resonance Imaging-Derived Global Coronary Flow Reserve in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Treated With Urgent Percutaneous Coronary Intervention.

BACKGROUND: Phase-contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying coronary sinus flow (CSF) and global coronary flow reserve (G-CFR). We evaluated the prognostic value of G-CFR using PC-CMR in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).Methods and Results:The study prospectively enrolled 116 NSTE-ACS patients who underwent uncomplicated urgent PCI within 48 h of symptom onset. Post-PCI (median, 20 days) PC-CMR images of the CS were acquired to assess absolute CSF at rest and during maximum hyperemia. The association of G-CFR with major adverse cardiac events (cardiac death, nonfatal myocardial infarction, late revascularization, or hospitalization for congestive heart failure) was investigated. Rest and maximal hyperemic CSF and corrected G-CFR were 1.27 [interquartile range, 0.79-1.73] mL/min/g, 2.95 [2.02-3.84] mL/min/g, and 2.42 [1.69-3.34], respectively. At a median follow-up of 17 months, cardiac event-free survival was significantly worse in patients with a corrected G-CFR <2.33 (log-rank χ2=19.5, P<0.001). Cox proportional-hazards analysis showed that corrected G-CFR (hazard ratio, 0.434, 95% CI, 0.270-0.699, P<0.001) and NT-pro BNP at admission (hazard ratio, 1.0001, 95% CI, 1.0000-1.0001, P=0.007) were independent predictors of adverse cardiac events during follow-up. CONCLUSIONS: In NSTE-ACS patients successfully revascularized within 48 h of onset, post-PCI PC-CMR-derived G-CFR provided significant prognostic information independent of infarct size and conventional risk scores.

Interrelationship in the prognostic efficacy of regional coronary flow reserve, fractional flow reserve, high-sensitivity cardiac troponin-I and NT-proBNP in patients with stable coronary artery disease.

This study aimed to investigate the combined efficacy in prediction of major adverse cardiac events (MACE) by coronary regional physiological indices including coronary flow reserve (CFR) or fractional flow reserve (FFR) and high-sensitivity cardiac troponin-I (hs-cTnI) or N-terminal pro brain natriuretic peptide (NT-proBNP). Impaired CFR, decreased FFR, elevated cardiac troponin, and NT-proBNP are all associated with increased MACE, while these interaction or collinearity remains uncertain. The study included 429 patients with stable coronary artery disease (CAD) evaluated hs-cTnI and NT-proBNP levels before regional physiological measurement during coronary angiography. Patients were followed up for MACE including all-cause death, myocardial infarction, hospital admission for heart failure and target vessel remote revascularization. Median hs-cTnI and NT-proBNP values were 4 ng/L and 85 ng/L, respectively. Regional CFR was significantly albeit weakly correlated with hs-cTnI and NT-proBNP, while fractional flow reserve (FFR) was only linked to hs-cTnI. The addition of hs-cTnI and NT-proBNP on clinical backgrounds and angiographic score significantly improved predictive accuracy for MACE incidence, and further consideration of FFR and CFR could refine the model. The combined stratification using hs-cTnI, NT-proBNP, FFR and CFR could efficiently stratify patient risk for MACE. In patients with stable CAD, integrated assessment of cardiac biomarkers and physiological indices could be useful for predicting future cardiovascular events.

Impact of Transradial Catheterization on Vascular Function of the Brachial Artery Assessed by Flow-Mediated Dilatation.

BACKGROUND: Few studies have evaluated long-term vascular function after radial access catheterization. Furthermore, the impact of repeated catheterization remains unknown. We investigated flow-mediated dilatation (FMD) of the brachial artery after transradial catheterization. METHODS: We prospectively enrolled 50 patients with suspected coronary artery disease referred for diagnostic coronary angiography. No ad-hoc percutaneous coronary interventions (PCI) had been performed at the time of the index procedure. In 30 patients (63.8%), PCI and/or repeated follow-up diagnostic catheterization were subsequently performed via the radial artery used at the index catheterization. FMD was successfully measured before catheterization, at 24 h after catheterization, and after long-term follow-up (mean, 32 months; range, 24-43) in 47 patients. FMD at follow-up was compared between patients receiving only one procedure and those receiving multiple procedures via the same arteries. RESULTS: FMD was significantly decreased after catheterization and recovered well in long-term follow-up (3.7 ± 1.6%, 3.0 ± 1.7%, and 3.9 ± 1.6%). There was no significant difference in follow-up FMD between the patients undergoing single catheterization and those with multiple procedures (3.4 ± 1.3 vs. 4.3 ± 1.7, p = 0.06). When the patients were divided into two groups according to the median follow-up FMD value, no significant predictive factor was identified for worse FMD. CONCLUSIONS: After transradial catheterization, FMD of the brachial artery temporarily decreased but recovered in long-term follow-up. Recovery of FMD was not jeopardized by repeated catheterization, which suggests the potential of the brachial artery to recover endothelial function after repeated transradial procedures.

Prognostic value of the index of microcirculatory resistance after percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: The prognostic value of physiological indices in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing percutaneous coronary intervention (PCI) is unknown. We investigated the prognostic efficacy of physiological indices obtained after PCI in patients with NSTE-ACS. METHODS: Eighty-three patients (men: n = 70, age: 63.7 ± 9.7 years) undergoing PCI for NSTE-ACS within 48 hr postadmission were investigated. Fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) of the culprit vessels were measured after the completion of PCI. The patients were clinically followed up to determine major cardiac adverse events (MACE), including death, congestive heart failure requiring hospitalization, and remote coronary revascularization. RESULTS: The median FFR, CFR, and IMR values were 0.90 (interquartile range [IQR] 0.86-0.95), 2.38 (IQR 1.75-4.17), and 22.9 (IQR 11.2-31.5), respectively. During a median follow-up of 20.7 months, 19 MACEs (22.9%) were documented. No significant difference in baseline patient characteristics, except for age, was detected between patients with and without MACE. Patients with MACE showed higher IMR and lower CFR than those without (IMR: 27.2 vs. 16.3; P = 0.001, CFR: 1.82 vs. 2.55; P = 0.04), whereas FFR was not significantly different (0.92 vs. 0.89; P = 0.72), irrespective of the MACE occurrence. Post-PCI IMR was the only independent predictor of MACE (hazard ratio 1.033, 95% confidence interval 1.013-1.052, P = 0.001). The MACE-free survival was significantly worse in patients with high post-PCI IMR (χ2 7.12; P = 0.008). CONCLUSION: Post-PCI IMR may help identify patients at high risk for subsequent adverse coronary events who require adjunctive therapeutic strategies.

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.

OBJECTIVES: 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). BACKGROUND: Decision making for revascularization when FFR is 0.75-0.80 is controversial. METHODS: A retrospective analysis was performed of 296 patients with stable angina pectoris who underwent physiological examinations before and after PCI. To investigate the differences of coronary flow improvement between territories with low-FFR (<0.75) and grey-zone FFR (0.75-0.80), serial changes in physiological indices including mean transit time (Tmn), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were compared between these two groups. RESULTS: Compared to low-FFR territories, grey-zone FFR territories showed significantly lower prevalence of Tmn shortening, CFR improvement, and decrease in IMR (Tmn shorting, 63.9% vs. 87.0%, P < .001; CFR improvement, 63.0% vs. 75.7%, P = .019; IMR decrease, 51.3% vs. 63.3%, P = .040) and lower extent of their absolute changes (Tmn shorting, 0.06 (-0.03 to 0.16) vs. 0.22 (0.07-0.45), P < .001; CFR improvement, 0.45 (-0.32 to 1.87) vs. 1.08 (0.02-2.44), P < .01; IMR decrease, 0.2 (-44.0 to 31.3) vs. 2.9 (-2.9 to 11.8), P = .022). Multivariate analysis showed that pre-PCI IMR predicted improved coronary flow profile in both groups, whereas pre-PCI FFR predicted increased coronary flow indices in low-FFR territories. CONCLUSIONS: Worsening of physiological indices after PCI was not uncommon in territories showing grey-zone FFR. Physiological assessment combining FFR and IMR may help identify patients who may benefit by PCI, particularly those in the grey zone.

Absolute Myocardial Blood Flow After Elective Percutaneous Coronary Intervention Evaluated on Phase-Contrast Cine Cardiovascular Magnetic Resonance Imaging.

BACKGROUND: Few studies have documented changes in myocardial blood flow (MBF) after percutaneous coronary intervention (PCI). Phase-contrast cine cardiovascular MRI (PC-CCMR) of the coronary sinus (CS) is a promising approach to quantify MBF. The aim of this study was to quantify CS flow (CSF) on PC-CCMR as a measure of volumetric MBF before and after elective PCI.Methods and Results:We prospectively studied 34 patients with stable angina undergoing elective PCI for a single de novo lesion. Breath-hold PC-CCMR of CS was acquired to assess CSF and coronary flow reserve (CFR) at rest and during maximum hyperemia both before and after PCI (median, 3 days before PCI and 10 days after PCI, respectively). In total, hyperemic CSF increased significantly after PCI (before PCI, median, 2.3 mL/min/g [IQR, 1.5-3.2 mL/min/g] after PCI, 3.0 [1.8-3.7] mL/min/g), although 13 patients (38.2%) had a decrease despite successful PCI and fractional flow reserve (FFR) improvement. Global CFR also significantly increased from a median of 2.5 (IQR, 1.5-3.5) to 3.4 (IQR, 2.1-4.2), whereas 12 patients had decreased CFR after PCI. Pre-PCI hyperemic CSF was the only independent factor of change in CSF following PCI. CONCLUSIONS: Serial PC-CCMR of CS as a measure of change in absolute MBF is feasible. Uncomplicated PCI does not necessarily increase hyperemic global MBF, despite regional FFR improvement.