Professional Education

  • Doctor of Medicine, Osaka University (2008)

Stanford Advisors


All Publications

  • The Prognostic Value of Residual Coronary Stenoses After Functionally Complete Revascularization JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kobayashi, Y., Nam, C., Tonino, P. A., Kimura, T., De Bruyne, B., Pijls, N. H., Fearon, W. F. 2016; 67 (14): 1701-1711


    The residual SYNTAX score (RSS) and SYNTAX revascularization index (SRI) quantitatively assess angiographic completeness of revascularization for patients with multivessel coronary artery disease. Whether residual angiographic disease remains of prognostic importance after "functionally" complete revascularization with fractional flow reserve (FFR) guidance is unknown.This study sought to investigate the prognostic value of the RSS and SRI after FFR-guided functionally complete revascularization.From the FFR-guided percutaneous coronary intervention (PCI) cohort of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial, the RSS and SRI were calculated in 427 patients after functionally complete revascularization. The RSS was defined as the SYNTAX score (SS) recalculated after PCI. The SRI was calculated as: 100 × (1 - RSS/baseline SS) (%). We compared differences in 1- and 2-year outcomes among patients with RSS of 0, >0 to 4, >4 to 8, and >8, and with SRI of 100%, 50% to <100%, and 0 to <50%.The mean baseline SS, RSS, and SRI were 14.4 ± 7.2, 6.5 ± 5.8, and 55.1 ± 32.5%, respectively. Major adverse cardiac events (MACE) at 1 year occurred in 53 patients (12.4%). Patients with MACE had higher SS than those without (18.0 [interquartile range (IQR): 11.0 to 21.0] vs. 12.0 [IQR: 9.0 to 18.0], p = 0.001), but had similar RSS and SRI after PCI (RSS: 6.0 [IQR: 3.0 to 10.0] vs. 5.0 [IQR: 2.0 to 9.5], p = 0.51 and SRI: 60.0% [IQR: 40.9% to 78.9%] vs. 58.8% [IQR: 26.7% to 81.8%], p = 0.24, respectively). Kaplan-Meier analysis showed similar 1-year incidence of MACE with RSS/SRI stratifications (log-rank p = 0.55 and p = 0.54, respectively). Results were similar with 2-year outcome data analysis.After functionally complete revascularization with FFR guidance, residual angiographic lesions that are not functionally significant do not reflect residual ischemia or predict a worse outcome, supporting functionally complete, rather than angiographically complete, revascularization. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774).

    View details for DOI 10.1016/j.jacc.2016.01.056

    View details for Web of Science ID 000373400500007

    View details for PubMedID 27056776

  • The impact of left ventricular ejection fraction on fractional flow reserve: Insights from the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial INTERNATIONAL JOURNAL OF CARDIOLOGY Kobayashi, Y., Tonino, P. A., De Bruyne, B., Yang, H., Lim, H., Pijls, N. H., Fearon, W. F. 2016; 204: 206-210


    Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) significantly improves outcomes compared with angio-guided PCI in patients with multivessel coronary artery disease. However, there is a theoretical concern that in patients with reduced left ventricular ejection fraction (EF) FFR may be less accurate and FFR-guided PCI less beneficial.From the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) trial database, we compared FFR values between patients with reduced EF (both ≤40%, n=90 and ≤50%, n=252) and preserved EF (>40%, n=825 and >50%, n=663) according to the angiographic stenosis severity. We also compared differences in 1year outcomes between FFR- vs. angio-guided PCI in patients with reduced and preserved EF.Both groups had similar FFR values in lesions with 50-70% stenosis (p=0.49) and with 71-90% stenosis (p=0.89). The reduced EF group had a higher mean FFR compared to the preserved EF group across lesions with 91-99% stenosis (0.55 vs. 0.50, p=0.02), although the vast majority of FFR values remained ≤0.80. There was a similar reduction in the composite end point of death, nonfatal myocardial infarction, and repeat revascularization with FFR-guided compared to angio-guided PCI for both the reduced (14.5% vs. 19.0%, relative risk=0.76, p=0.34) and the preserved EF group (13.8 vs. 17.0%, relative risk=0.81, p=0.25). The results were similar with an EF cutoff of 40%.Reduced EF has no influence on the FFR value unless the stenosis is very tight, in which case a theoretically explainable, but clinically irrelevant overestimation might occur. As a result, FFR-guided PCI remains beneficial regardless of EF.

    View details for DOI 10.1016/j.ijcard.2015.11.169

    View details for Web of Science ID 000367008200058

  • Non-invasive FFRCT revealing severe inducible ischaemia in an anomalous right coronary artery. European heart journal Zimmermann, F. M., Kobayashi, Y., Mullen, W. L., Fearon, W. F. 2016

    View details for DOI 10.1093/eurheartj/ehw542

    View details for PubMedID 27941015

  • The Influence of Lesion Location on the Diagnostic Accuracy of Adenosine-Free Coronary Pressure Wire Measurements. JACC. Cardiovascular interventions Kobayashi, Y., Johnson, N. P., Berry, C., De Bruyne, B., Gould, K. L., Jeremias, A., Oldroyd, K. G., Pijls, N. H., Fearon, W. F. 2016; 9 (23): 2390–99


    This work compares the diagnostic performance of adenosine-free coronary pressure wire indices based on lesion location.Several adenosine-free coronary pressure wire indices have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that lesion location and the mass of perfused myocardium may affect diagnostic performance.A total of 763 patients were prospectively enrolled from 12 institutions. Fractional flow reserve (FFR) and contrast-based FFR (cFFR) were obtained during adenosine-induced maximal hyperemia and contrast-induced submaximal hyperemia respectively, whereas the instantaneous wave-free ratio (iFR) and distal pressure/aortic pressure (Pd/Pa) were obtained at rest. Using an FFR of ≤0.80 as a reference standard, the diagnostic accuracy of each index was compared based on lesion location (left main or proximal left anterior descending artery [LM/pLAD] compared with other lesion locations).The median FFR, cFFR, iFR, and Pd/Pa were 0.81 (interquartile range [IQR]: 0.74 to 0.87), 0.86 (IQR: 0.79 to 0.91), 0.90 (IQR: 0.85 to 0.94), and 0.92 (IQR: 0.88 to 0.95), respectively. The cFFR, iFR, and Pd/Pa were less accurate in LM/pLAD compared with other lesion locations (cFFR: 80.3% vs. 87.8%; iFR: 73.3% vs. 81.8%; Pd/Pa: 71.4% vs. 81.1%, respectively). By receiver-operating characteristics curve analysis, cFFR provided better diagnostic accuracy than resting indices regardless of lesion location (p ≤0.0001 vs. iFR and Pd/Pa for both groups).The cFFR, iFR, and Pd/Pa are less accurate in LM/pLAD compared with other lesion locations, likely related to the larger amount of myocardium supplied by LM/pLAD. Nevertheless, cFFR provides the best diagnostic accuracy among the adenosine-free indices, regardless of lesion location.

    View details for DOI 10.1016/j.jcin.2016.08.041

    View details for PubMedID 27838269

  • Invasive Assessment of the Coronary Microcirculation. JACC. Cardiovascular interventions Fearon, W. F., Kobayashi, Y. 2016

    View details for DOI 10.1016/j.jcin.2016.01.028

    View details for PubMedID 27017372

  • Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease JACC-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Fearon, W. F., Honda, Y., Tanaka, S., Pargaonkar, V., Fitzgerald, P. J., Lee, D. P., Stefanick, M., Yeung, A. C., Tremmel, J. A. 2015; 8 (11): 1433-1441


    This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

    View details for DOI 10.1016/j.jcin.2015.03.045

    View details for Web of Science ID 000361757600013

    View details for PubMedID 26404195

  • Impact of Target Lesion Coronary Calcification on Stent Expansion - An Optical Coherence Tomography Study CIRCULATION JOURNAL Kobayashi, Y., Okura, H., Kume, T., Yamada, R., Kobayashi, Y., Fukuhara, K., Koyama, T., Nezuo, S., Neishi, Y., Hayashida, A., Kawamoto, T., Yoshida, K. 2014; 78 (9): 2209-2214
  • Invasive Coronary Microcirculation Assessment - Current Status of Index of Microcirculatory Resistance CIRCULATION JOURNAL Kobayashi, Y., Fearon, W. F. 2014; 78 (5): 1021-1028
  • Left ventricular myocardial function assessed by three-dimensional speckle tracking echocardiography in Takotsubo cardiomyopathy. Echocardiography (Mount Kisco, N.Y.) Kobayashi, Y., Okura, H., Kobayashi, Y., Fukuda, S., Hirohata, A., Yoshida, K. 2017


    We aimed to investigate left ventricular (LV) functional recovery in Takotsubo cardiomyopathy (TC) using three-dimensional (3D) speckle tracking echocardiography.Twenty-one patients with TC who underwent routine and 3D echocardiography as well as electrocardiography were enrolled. 3D images were analyzed to measure 3D radial strain and area tracking (area change of each LV segment). Postsystolic shortening (PSS) or thickening (PST) was defined as a further shortening or thickening occurred after the end-systole. 3D echocardiography and ECG were repeated at 4 weeks and 6 months later.Mean age was 70.9±11.1 years, and 18 (86%) patients were female. All patients presented classical type of TC with apical ballooning. LV ejection fraction (EF) improved from 49.9±7.2 to 64.9±6.0% (P<.001) at 4 weeks without segmental wall-motion abnormality. However, PSS or PST still existed in 43% of LV segments, and electrocardiographic abnormality was also observed in 51% at 4 weeks and disappeared at 6 months. Mean 3D radial strain decreased from baseline to 6 months at base (36.1±19.6 vs 28.0±12.6%, P=.04), whereas it increased at mid (16.2±7.2 vs 28.7±9.1%, P=.03) and the apex (8.0±4.4 vs 21.2±7.9%, P<.001). Mean area tracking increased from baseline to 6 months at mid and apex (-28.5±9.5 vs -44.5±9.6%, P<.001 for mid, and -24.2±13.0 vs -42.9±16.8%, P=.002 for the apex), while it did not change at base (-37.0±8.9 vs -41.9±9.6%, P=NS).Patients with TC show abnormal wall motion during acute phase. Even after LV wall-motion recovery, subtle abnormalities of regional LV function appear to persist at 4 weeks followed by normalization at 6 months.

    View details for DOI 10.1111/echo.13492

    View details for PubMedID 28266731

  • Left atrial function and phenotypes in asymmetric hypertrophic cardiomyopathy. Echocardiography (Mount Kisco, N.Y.) Kobayashi, Y., Wheeler, M., Finocchiaro, G., Ariyama, M., Kobayashi, Y., Perez, M. V., Liang, D., Kuznetsova, T., Schnittger, I., Ashley, E., Haddad, F. 2017


    Few studies have analyzed changes in left atrial (LA) function associated with different phenotypes of asymmetric hypertrophic cardiomyopathy (HCM). We sought to demonstrate the association of impairments in LA function with disease phenotype in patients with obstructive and nonobstructive HCM.From Stanford Cardiomyopathy Registry, we randomly selected 50 age-/sex-matched healthy controls, 35 patients with nonobstructive HCM (HCM 1), 35 patients with obstructive HCM (HCM 2), and 35 patients with obstructive HCM requiring septal reduction therapy (HCM 3). Echocardiography was performed to evaluate left ventricular (LV) strain as well as LA function including LA emptying fraction and LA strain.The mean age was 51±14 years and 57% were male. LA volume index differed among all four predefined groups (25.6±6.7 mL/m(2) in controls, 32.2±13.3 mL/m(2) in HCM 1, 42.0±12.9 mL/m(2) in HCM 2, 52.4±15.2 mL/m(2) for HCM 3, and P<.05 all between groups). All measurement of LA function was impaired in patients with HCM than controls. Total and passive LA function was further impaired in HCM 2 or 3 compared with HCM 1, while active LA function was not different among the three groups. Among LV strains, only septal longitudinal strain differed among all groups (-18.5±1.9% in controls, -14.5±1.9% in HCM 1, -13.3±1.8% in HCM 2, -11.6±2.3% in HCM 3, and P<.05 all between groups).LA function was impaired in patients with HCM even in minimally symptomatic nonobstructive phenotype. Total and passive LA function was further impaired in patients with obstructive HCM.

    View details for DOI 10.1111/echo.13533

    View details for PubMedID 28370331

  • Coronary Endothelial Dysfunction and the Index of Microcirculatory Resistance as a Marker of Subsequent Development of Cardiac Allograft Vasculopathy. Circulation Lee, J. H., Okada, K., Khush, K., Kobayashi, Y., Sinha, S., Luikart, H., Valantine, H., Yeung, A. C., Honda, Y., Fearon, W. F. 2017; 135 (11): 1093–95

    View details for DOI 10.1161/CIRCULATIONAHA.116.025268

    View details for PubMedID 28289008

  • Acute stent recoil and optimal balloon inflation strategy: an experimental study using real-time optical coherence tomography. EuroIntervention Kitahara, H., Waseda, K., Yamada, R., Otagiri, K., Tanaka, S., Kobayashi, Y., Okada, K., Kume, T., Nakagawa, K., Teramoto, T., Ikeno, F., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2016; 12 (2): e190-8


    Our aim was to evaluate stent expansion and acute recoil at deployment and post-dilatation, and the impact of post-dilatation strategies on final stent dimensions.Optical coherence tomography (OCT) was performed on eight bare metal platforms of drug-eluting stents (3.0 mm diameter, n=6 for each) during and after balloon inflation in a silicone mock vessel. After nominal-pressure deployment, a single long (30 sec) vs. multiple short (10 sec x3) post-dilatations were performed using a non-compliant balloon (3.25 mm, 20 atm). Stent areas during deployment with original delivery systems were smaller in stainless steel stents than in cobalt-chromium and platinum-chromium stents (p<0.001), whereas subsequent acute recoil was comparable among the three materials. At post-dilatation, acute recoil was greater in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001), resulting in smaller final stent areas in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001). In comparison between conventional and latest-generation cobalt-chromium stents, stent areas were not significantly different after both deployment and post-dilatation. With multiple short post-dilatations, acute recoil was significantly improved from first to third short inflation (p<0.001), achieving larger final area than a single long inflation, despite stent materials/designs (p<0.001).Real-time OCT revealed significant acute recoil in all stent types. Both stent materials/designs and post-dilatation strategies showed a significant impact on final stent expansion.

    View details for DOI 10.4244/EIJV12I2A32

    View details for PubMedID 27290678

  • Association of periarterial neovascularization with progression of cardiac allograft vasculopathy and long-term clinical outcomes in heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Kitahara, H., Okada, K., Tanaka, S., Yang, H., Miki, K., Kobayashi, Y., Kimura, T., Luikart, H., Yock, P. G., Yeung, A. C., Fitzgerald, P. J., Khush, K. K., Fearon, W. F., Honda, Y. 2016; 35 (6): 752-759


    This study investigated the relationship between periarterial neovascularization, development of cardiac allograft vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested.Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures <1 mm in diameter, located ≤2 mm outside of the external elastic membrane. The signal void structures were excluded when they connected to the coronary lumen (considered as side branches) or could not be followed in ≥3 contiguous frames. The number of PSV was counted at 1-mm intervals throughout the first 50 mm of the left anterior descending artery, and the PSV score was calculated as the sum of cross-sectional values. Patients with a PSV score increase of ≥ 4 between baseline and 1-year post-transplant were classified as the "proliferative" group. Maximum intimal thickness was measured for the entire analysis segment.During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p < 0.001) and had a higher incidence of acute cellular rejection (50.0% vs 23.9%, p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036).The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation.

    View details for DOI 10.1016/j.healun.2016.02.002

    View details for Web of Science ID 000379367700008

    View details for PubMedID 27068036

  • Invasive Assessment of Coronary Physiology Predicts Late Mortality After Heart Transplantation CIRCULATION Yang, H., Khush, K., Luikart, H., Okada, K., Lim, H., Kobayashi, Y., Honda, Y., Yeung, A. C., Valantine, H., Fearon, W. F. 2016; 133 (20): 1945-1950


    -The aim of this study is to determine the prognostic value of invasively assessing coronary physiology early after heart transplantation.-Seventy-four cardiac transplant recipients had fractional flow reserve (FFR), coronary flow reserve (CFR), the index of microcirculatory resistance (IMR) and intravascular ultrasound (IVUS) performed down the left anterior descending coronary artery soon after (baseline) and 1 year after heart transplantation. The primary endpoint was the cumulative survival free of death or retransplantation at a mean follow-up of 4.5±3.5 years. The cumulative event-free survival was significantly lower in patients with an FFR<0.90 at baseline (42 vs 79%, p=0.01) or an IMR≥20 measured one year after heart transplantation (39 vs. 69%, p=0.03). Patients in whom IMR decreased or did not change from baseline to 1 year had higher event-free survival compared to those patients with an increase in IMR (66 vs. 36%, p=0.03). FFR<0.90 at baseline (hazards ratio [HR] 0.13, 95% confidence interval [CI] 0.02-0.81, p=0.03), IMR ≥20 at 1 year (HR 3.93, 95% CI 1.08-14.27, p=0.04) and rejection during the first year (HR 6.00, 95% CI 1.56-23.09, p=0.009) were independent predictors of death/retransplantation, while IVUS parameters were not.-Invasive measures of coronary physiology (FFR and IMR) determined early after heart transplantation are significant predictors of late death or retransplantation.

    View details for DOI 10.1161/CIRCULATIONAHA.115.018741

    View details for Web of Science ID 000376618600009

    View details for PubMedID 27143679

  • Quantitative precision of optical frequency domain imaging: direct comparison with frequency domain optical coherence tomography and intravascular ultrasound. Cardiovascular intervention and therapeutics Kobayashi, Y., Kitahara, H., Tanaka, S., Okada, K., Kimura, T., Ikeno, F., Yock, P. G., Fitzgerald, P. J., Honda, Y. 2016; 31 (2): 79-88


    No systematic validation study is available with optical frequency domain imaging (OFDI), directly compared with frequency domain optical coherence tomography (FD-OCT) and intravascular ultrasound (IVUS). Controversy also remains about the impact of different stent contour tracing methods by OFDI/FD-OCT. In vitro: coronary phantom models (1.51-5.04 mm) were imaged with OFDI, FD-OCT, and IVUS, demonstrating excellent quantitative precision with a slight overestimation of mean lumen diameter (difference 0.01-0.02 mm). In vivo: corresponding 64 OFDI/IVUS images of stented coronary segments from 20 swines were analyzed. Minimum lumen area by OFDI was larger than IVUS at baseline (P < 0.001), whereas it was smaller than IVUS at follow-up. When stent was traced at leading edges of struts by OFDI, minimum stent area was similar between OFDI and IVUS (P = 0.60). When traced at the highest intensity points of struts by OFDI, it was significantly larger in OFDI than in IVUS (P < 0.001). Three modalities have clinically acceptable precision across the wide range of lumen diameters. In vivo measurements by OFDI and IVUS could slightly be discrepant depending on the parameters and time points. In stent assessment by OFDI, the 2 methods led to a small but systematic difference; therefore, consistency in methodology is advised for comparative studies.

    View details for DOI 10.1007/s12928-015-0349-x

    View details for PubMedID 26271203

  • Functional Versus Anatomic Assessment of Myocardial Bridging by Intravascular Ultrasound: Impact of Arterial Compression on Proximal Atherosclerotic Plaque. Journal of the American Heart Association Yamada, R., Tremmel, J. A., Tanaka, S., Lin, S., Kobayashi, Y., Hollak, M. B., Yock, P. G., Fitzgerald, P. J., Schnittger, I., Honda, Y. 2016; 5 (4)


    The presence of a myocardial bridge (MB) has been shown to promote atherosclerotic plaque formation proximal to the MB, presumably because of hemodynamic disturbances provoked by retrograde blood flow toward this segment in cardiac systole. We aimed to determine the anatomic and functional properties of an MB related to the extent of atherosclerosis assessed by intravascular ultrasound.We enrolled 100 patients with angina but no significant obstructive coronary artery disease who had an intravascular ultrasound-detected MB in the left anterior descending artery (median age 54 years, 36% male). The MB was identified with intravascular ultrasound by the presence of an echolucent band (halo). Anatomically, the MB length was 22±13 mm, and halo thickness was 0.7±0.6 mm. Functionally, systolic arterial compression was 23±12%. The maximum plaque burden up to 20 mm proximal to the MB entrance was significantly greater than the maximum plaque burden within the MB segment. Among the intravascular ultrasound-defined MB properties, arterial compression was the sole MB parameter that demonstrated a significant positive correlation with maximum plaque burden up to 20 mm proximal to the MB entrance (r=0.254, P=0.011 overall; r=0.545, P<0.001 low coronary risk). In multivariate analysis, adjusting for clinical characteristics and coronary risk factors, arterial compression was independently associated with maximum plaque burden up to 20 mm proximal to the MB entrance.In patients with an MB in the left anterior descending artery, the percentage of arterial compression is related directly to the burden of atherosclerotic plaque located proximally to the MB, particularly in patients who otherwise have low coronary risk. This may prove helpful in identifying high-risk MB patients.

    View details for DOI 10.1161/JAHA.114.001735

    View details for PubMedID 27098967

  • Comparison of left ventricular manual versus automated derived longitudinal strain: implications for clinical practice and research INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING Kobayashi, Y., Ariyama, M., Kobayashi, Y., Giraldeau, G., Fleischman, D., Kozelj, M., Vrtovec, B., Ashley, E., Kuznetsova, T., Schnittger, I., Liang, D., Haddad, F. 2016; 32 (3): 429-437


    Systolic global longitudinal strain (GLS) is emerging as a useful metric of ventricular function in heart failure and usually assessed using post-processing software. The purpose of this study was to investigate whether longitudinal strain (LS) derived using manual-tracings of ventricular lengths (manual-LS) can be reliable and time efficient when compared to LS obtained by post-processing software (software-LS). Apical 4-chamber view images were retrospectively examined in 50 healthy controls, 100 patients with dilated cardiomyopathy (DCM), and 100 with hypertrophic cardiomyopathy (HCM). We measured endocardial and mid-wall manual-LS and software-LS, using peak of average regional curve [software-LS(a)] and global ventricular lengths [software-LS(l)] according to definition of Lagragian strain. We compared manual-LS and software-LS by using Bland-Altman plot and coefficient of variation (COV). In addition, test-retest was also performed for further assessment of variability in measurements. While manual-LS was obtained in all subjects, software-LS could be obtained in 238 subjects (95 %). The time spent for obtaining manual-LS was significantly shorter than for the software-LS (94 ± 39 s vs. 141 ± 79 s, P < 0.001). Overall, manual-LS had an excellent correlation with both software-LS (a) (R(2) = 0.93, P < 0.001) and software-LS(l) (R(2) = 0.84, P < 0.001). The bias (95 %CI) between endocardial manual-LS and software-LS(a) was 0.4 % [-2.8, 3.6 %] in absolute and 3.5 % [-17.0, 24.0 %] in relative difference while it was 0.4 % [-2.5, 3.3 %] and 3.4 % [-16.2, 23.1 %], respectively with software-LS(l). Mid-wall manual-LS and mid-wall software-LS(a) also had good agreement [a bias (95 % CI) for absolute value of 0.1 % [-2.1, 2.5 %] in HCM, and 0.2 % [-2.2, 2.6 %] in controls]. The COV for manual and software derived LS were below 6 %. Test-retest showed good variability for both methods (COVs were 5.8 and 4.7 for endocardial and mid-wall manual-LS, and 4.6 and 4.9 for endocardial and mid-wall software-LS(a), respectively. Manual-LS appears to be as reproducible as software-LS; this may be of value especially when global strain is the metric of interest.

    View details for DOI 10.1007/s10554-015-0804-x

    View details for Web of Science ID 000370166100008

    View details for PubMedID 26578468

  • Impact of analysis interval size on the quality of optical frequency domain imaging assessments of stent implantation for lesions of the superficial femoral artery. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions Miki, K., Fujii, K., Kawasaki, D., Shibuya, M., Fukunaga, M., Imanaka, T., Tamaru, H., Sumiyoshi, A., Nishimura, M., Horimatsu, T., Saita, T., Kobayashi, Y., Honda, Y., Fitzgerald, P. J., Masuyama, T., Ishihara, M. 2016


    This study aimed to investigate the influence of analysis interval size on optical frequency domain imaging (OFDI) assessment of stent therapy for lesions of the superficial femoral artery (SFA).No consensus or validating data are available with respect to the methodology of intravascular imaging analysis for the peripheral arteries.OFDI was performed for 30 SFA lesions, during endovascular therapy and at the 6-month follow-up. Initially, lumen and stent borders were traced at 1-mm axial intervals. Volumes were calculated using a PC-based software, and the volume index (VI) was defined as the volume divided by the stent length. Two additional OFDI analyses were performed using 2-mm and 5-mm intervals, thereby reducing the number of cross-sectional image frames analyzed.The mean stent length was 89.7 ± 35.2 mm. The mean difference in baseline minimum lumen area (MLA) was 0.4 mm(2) between MLA values from the 1-mm and 2-mm interval analyses, and 2.2 mm(2) between MLA values from the 1-mm and 5-mm interval analyses. In volumetric analysis, there were excellent correlations and good agreements for stent, lumen, and neointimal VI measurements obtained on the basis of different analysis intervals.Using large intervals in OFDI analyses of SFA lesions resulted in few differences in measurement variability of volumetric parameters. However, planar analysis for MLA assessment can be susceptible to high variability when large intervals are applied. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/ccd.26673

    View details for PubMedID 27515475

  • Additive value of nicorandil on ATP for further inducing hyperemia in patients with an intermediate coronary artery stenosis. Coronary artery disease Kobayashi, Y., Okura, H., Neishi, Y., Higa, T., Kobayashi, Y., Uemura, S., Yoshida, K. 2016


    The induction of hyperemia is of importance to precisely assess the functional significance of coronary artery lesions with fractional flow reserve (FFR). Adenosine or ATP alone is used widely in this setting; however, little is known about the additive value of nicorandil, which acts as a nitrate and a K-ATP channel opener, to induce further hyperemia.A total of 183 intermediate native coronary artery lesions from 112 patients were prospectively enrolled into this study. FFR was measured using a coronary pressure wire during an intravenous ATP infusion alone (150 mcg/kg/min) (FFRATP) and repeated after an adjunctive intracoronary nicorandil injection (2.0 mg) (FFRATP+Nico).Physiologic measurements were completed without any severe adverse effects from ATP and nicorandil in all patients. FFRATP and FFRATP+Nico had a strong linear correlation (R=0.79, P<0.001). The FFR value became significantly lower with an adjunctive intracoronary nicorandil injection compared with ATP alone [FFRATP vs. FFRATP+Nico, 0.87 (interquartile range: 0.81-0.92) vs. 0.85 (0.79-0.90), P<0.001]. A total of 18 lesions out of 183 (9.8%) were reclassified after a nicorandil injection (12 from FFR>0.80 to ≤0.80 vs. six from FFR≤0.80 to >0.80, P=0.26). The adjunctive effect of nicorandil was accentuated with each increment of FFRATP strata (per 0.05 increase, P for trend<0.001), but with minimal effect around the borderline FFR zone.An adjunctive intracoronary nicorandil injection is safe, but appears to have little effect in inducing further hyperemia. Therefore, its effect on the clinical scenario is limited.

    View details for DOI 10.1097/MCA.0000000000000433

    View details for PubMedID 27611876

  • Paradoxical Vessel Remodeling of the Proximal Segment of the Left Anterior Descending Artery Predicts Long-Term Mortality After Heart Transplantation JACC-HEART FAILURE Okada, K., Kitahara, H., Yang, H., Tanaka, S., Kobayashi, Y., Kimura, T., Luikart, H., Yock, P. G., Yeung, A. C., Valantine, H. A., Fitzgerald, P. J., Khush, K. K., Honda, Y., Fearon, W. F. 2015; 3 (12): 942-952
  • Exercise Strain Echocardiography in Patients With a Hemodynamically Significant Myocardial Bridge Assessed by Physiological Study. Journal of the American Heart Association Kobayashi, Y., Tremmel, J. A., Kobayashi, Y., Amsallem, M., Tanaka, S., Yamada, R., Rogers, I. S., Haddad, F., Schnittger, I. 2015; 4 (11)


    Although a myocardial bridge (MB) is often regarded as a benign coronary variant, recent studies have associated MB with focal myocardial ischemia. The physiological consequences of MB on ventricular function during stress have not been well established.We enrolled 58 patients with MB of the left anterior descending artery, diagnosed by intravascular ultrasound. Patients underwent invasive physiological evaluation of the MB by diastolic fractional flow reserve during dobutamine challenge and exercise echocardiography. Septal and lateral longitudinal strain (LS) were assessed at rest and immediately after exercise and compared with strain of matched controls. Absolute and relative changes in strain were also calculated. The mean age was 42.5±16.0 years. Fifty-five patients had a diastolic fractional flow reserve ≤0.76. At rest, there was no significant difference between the 2 groups in septal LS (19.0±1.8% for patients with MB versus 19.2±1.5% for control, P=0.53) and lateral LS (20.1±2.0% versus 20.0±1.6%, P=0.83). With stress, compared with controls, patients with MB had a lower peak septal LS (18.9±2.6% versus 21.7±1.6%, P<0.001) and lower absolute (-0.1±2.1% versus 2.5±1.3%, P<0.001) and relative change (-0.6±11.2% versus 13.1±7.8%, P<0.001) in septal LS, whereas there was no significant difference in lateral LS. In multivariate analysis, diastolic fractional flow reserve and length were independent determinants of lower changes in septal LS.Patients with a hemodynamically significant MB, determined by invasive diastolic fractional flow reserve, have significantly lower change in septal LS on exercise echocardiography, suggesting that septal LS may be useful for noninvasively assessing the hemodynamic significance of an MB.

    View details for DOI 10.1161/JAHA.115.002496

    View details for PubMedID 26581225

  • Direct relationship of local C-reactive protein production and lipid pool characterized by integrated backscatter intravascular ultrasound: a preliminary observation CORONARY ARTERY DISEASE Kobayashi, Y., Okura, H., Kume, T., Miyamoto, Y., Yamada, R., Kobayashi, Y., Fukuhara, K., Koyama, T., Neishi, Y., Yoshida, K. 2015; 26 (5): 425-431


    Local production of C-reactive protein (CRP) in human coronary arterial plaque was reported as a possible marker for local inflammation and vulnerable plaque. Integrated backscatter intravascular ultrasound (IB-IVUS) plaque tissue characterization may detect vulnerable plaque with high local plaque inflammation. Thus, the aim of this study was to clarify the relationship between IB-IVUS-based plaque characteristics and local high-sensitivity C-reactive protein (hs-CRP) production in stable and unstable plaque.Eighteen patients (nine unstable angina/non-ST-segment elevation myocardial infarction and nine stable angina) were prospectively enrolled. Using the microcatheter, blood samples from the proximal and distal sites of the culprit lesion were obtained to measure local CRP production. Translesional hs-CRP was defined as distal hs-CRP minus proximal hs-CRP of the culprit lesion. Gray-scale and IB-IVUS analyses were carried out at the target lesion. The translesional hs-CRP level tended to be higher in the unstable angina group than in the stable angina group (0.026±0.033 vs. 0.003±0.007 mg/dl, P=0.050). Gray-scale IVUS-derived indices did not correlate with translesional hs-CRP. However, % lipid pool area by IB-IVUS correlated positively (r=0.54, P=0.02) and % fibrosis area correlated negatively with the translesional hs-CRP level (r=-0.52, P=0.03).Lipid pool area detected by IB-IVUS is correlated positively with the translesional hs-CRP level.

    View details for DOI 10.1097/MCA.0000000000000250

    View details for Web of Science ID 000357641400010

    View details for PubMedID 25886998

  • The relationship between fractional flow reserve and index of microcirculatory resistance: be careful with whom you associate. Catheterization and cardiovascular interventions Kobayashi, Y., Tremmel, J. A. 2015; 85 (4): 593-594

    View details for DOI 10.1002/ccd.25850

    View details for PubMedID 25702909

  • Assessment of Atrial Synchrony in Paroxysmal Atrial Fibrillation and Impact of Pulmonary Vein Isolation for Atrial Dyssynchrony and Global Strain by Three-Dimensional Strain Echocardiography JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Kobayashi, Y., Okura, H., Kobayashi, Y., Okawa, K., Banba, K., Hirohata, A., Tamada, T., Obase, K., Hayashida, A., Yoshida, K. 2014; 27 (11): 1193-1199
  • Acute myocardial infarction after Kawasaki disease. JACC. Cardiovascular interventions Kobayashi, Y., Kobayashi, Y., Hirohata, A. 2014; 7 (7): e77-8

    View details for DOI 10.1016/j.jcin.2013.10.030

    View details for PubMedID 25060031

  • Pheochromocytoma found in takotsubo cardiomyopathy patients. journal of invasive cardiology Kobayashi, Y., Kobayashi, Y., Hirohata, A. 2014; 26 (6): E76-7


    Increased level of serum catecholamines in the acute phase was reported to be a feature of takotsubo cardiomyopathy (TC). We report a TC case with pheochromocytoma, which caused a stir in the diagnosis of TC and suggests the importance of screening for a catecholamine-producing tumor. A female patient was referred to our emergency department due to ongoing chest pain. Coronary angiography showed no abnormality; however, subsequent left ventriculography showed basal hyperkinesis and apical ballooning, which completely recovered in 2 weeks. She experienced significant emotional stress on the eve of her admission, to which the diagnosis of TC was attributed. Although serum catecholamine levels on admission in our case were higher than on day 14, the value on day 14 was much higher than the normal range in our patient. The screening abdominal computed tomography scan revealed a left adrenal mass, which was diagnosed as pheochromocytoma by 24-hour urinary excretion of catecholamine and (131)I-MIBG scintigraphy. The mass was successfully resected and pathological findings supported the diagnosis. In our case, emotional stress was thought to be the direct trigger to develop TC by exceeding the threshold of catecholamine-induced cardiomyopathy. Screening for a catecholamine-producing tumor through careful history-taking and measuring catecholamines at a follow-up stage were important clinical aspects in this case and may well be for others.

    View details for PubMedID 24907091

  • Nicorandil prevents microvascular dysfunction resulting from PCI in patients with stable angina pectoris: a randomised study. EuroIntervention Hirohata, A., Yamamoto, K., Hirose, E., Kobayashi, Y., Takafuji, H., Sano, F., Matsumoto, K., Ohara, M., Yoshioka, R., Takinami, H., Ohe, T. 2014; 9 (9): 1050-1056


    Nicorandil, an ATP sensitive potassium channel opener, may reduce the incidence of microvascular dysfunction after percutaneous coronary intervention (PCI) by dilating coronary resistance vessels. The aim of the study was evaluation of the impact of the administration of intravenous nicorandil on measuring the index of microcirculatory resistance (IMR) in PCI to patients with stable angina pectoris (SAP).Intravascular ultrasound (IVUS), fractional flow reserve (FFR), IMR and blood examination (CK-MB), cardiac troponin I (cTnI) immediately post-PCI (and 24 hours later) were performed in 62 consecutive patients with SAP undergoing PCI. FFR and IMR were measured simultaneously with a single coronary pressure wire. IMR was defined as Pd/coronary flow (or Pd* mean transit time) at peak hyperaemia. Patients were randomised to the control (n=29), or nicorandil group (n=33). In the nicorandil group, nicorandil was intravenously administered as a 6 mg bolus injection just before PCI and as a constant infusion at 6 mg/hour for 24 hours thereafter. All volumetric IVUS parameters and FFR were similar between the two groups both pre- and post-PCI. However, IMR immediately post-PCI and cTnI 24 hours post-PCI were significantly higher in the control group compared to the nicorandil group (IMR: 25.4±12.1 vs. 17.9±9.1 units, and cTnI: 0.21±0.13 vs. 0.12±0.08 ng/mL, for control vs. nicorandil). The incidence for cTnI elevation more than fivefold the normal range (>0.20 ng/mL) was significantly larger in the control group than in the nicorandil group (41% vs. 12%, p<0.01). Additionally, the control group showed a closer correlation between plaque volume reduction during stenting as assessed by volumetric IVUS, and cTnI elevation than the nicorandil group (r=0.55 vs. 0.42, p<0.001 for control vs. nicorandil).In patients undergoing successful coronary stenting for stable angina, administration of nicorandil is associated with reduced microvascular dysfunction induced by PCI.

    View details for DOI 10.4244/EIJV9I9A178

    View details for PubMedID 24457276

  • Conference Scene: A congress report from the American Heart Association Scientific Sessions 2013 Interventional Cardiology Kobayashi, Y., Hollak, M. B., Honda, Y. 2014; 6 (1): 21-23

    View details for DOI 10.2217/ica.13.88

  • Left Main Coronary Thrombotic Occlusion Due to Secondary Polycythemia in a Normal Sinus of Valsalva JOURNAL OF INVASIVE CARDIOLOGY Kobayashi, Y., Kobayashi, Y., Hirohata, A. 2013; 25 (8): 421-422


    A case of acute myocardial infarction (AMI) due to thrombus in the left coronary cusp to the ascending aorta is described. There was no clinical evidence of coagulopathy, immunodisability, or local erosive lesion of the aortic and sinus of Valsalva wall macroscopically. Secondary polycythemia, induced by heavy smoking, was the likely cause of the myocardial infarction. Although this may be a rare case, intraaortic thrombus should be considered in the differential diagnosis of the causes of AMI.

    View details for Web of Science ID 000324872700018

    View details for PubMedID 23913610

  • Four-year clinical outcomes of the OLIVUS-Ex (impact of Olmesartan on progression of coronary atherosclerosis: Evaluation by intravascular ultrasound) extension trial ATHEROSCLEROSIS Hirohata, A., Yamamoto, K., Miyoshi, T., Hatanaka, K., Hirohata, S., Yamawaki, H., Komatsubara, I., Hirose, E., Kobayashi, Y., Ohkawa, K., Ohara, M., Takafuji, H., Sano, F., Toyama, Y., Kusachi, S., Ohe, T., Ito, H. 2012; 220 (1): 134-138


    The previous OLIVUS trial reported a positive role in achieving a lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent (ARB), for stable angina pectoris (SAP) patients requiring percutaneous coronary intervention (PCI). However, the benefits between ARB administration on long-term clinical outcomes and serial atheroma changes by IVUS remain unclear. Thus, we examined the 4-year clinical outcomes from OLIVUS according to treatment strategy with olmesartan.Serial volumetric IVUS examinations (baseline and 14 months) were performed in 247 patients with hypertension and SAP. When these patients underwent PCI for culprit lesions, IVUS was performed in their non-culprit vessels. Patients were randomly assigned to receive 20-40mg of olmesartan or control, and treated with a combination of β-blockers, calcium channel blockers, glycemic control agents and/or statins per physician's guidance. Four-year clinical outcomes and annual progression rate of atherosclerosis, assessed by serial IVUS, were compared with major adverse cardio- and cerebrovascular events (MACCE).Cumulative event-free survival was significantly higher in the olmesartan group than in the control group (p=0.04; log-rank test). By adjusting for validated prognosticators, olmesartan administration was identified as a good predictor of MACCE (p=0.041). On the other hand, patients with adverse events (n=31) had larger annual atheroma progression than the rest of the population (23.8% vs. 2.1%, p<0.001).Olmesartan therapy appears to confer improved long-term clinical outcomes. Atheroma volume changes, assessed by IVUS, seem to be a reliable surrogate for future major adverse cardio- and cerebrovascular events in this study cohort.

    View details for DOI 10.1016/j.atherosclerosis.2011.10.013

    View details for Web of Science ID 000298374800022

    View details for PubMedID 22119063

  • Clinical benefit and patient selection of Endeavor stent. Coronary Intervention Kobayashi, Y., Hirose, E., Hirohata, A. 2011; 7: 85-88