Hirotoshi Watanabe

Impact of post-challenge hyperglycemia on clinical outcomes in japanese patients with stable angina undergoing percutaneous coronary intervention

BackgroundPost-challenge hyperglycemia (PH) is well-established as one of risk factors for coronary artery disease. However, it remains unclear whether PH affects clinical outcomes in patients with stable angina undergoing percutaneous coronary intervention (PCI).MethodsA total of 828 patients with stable angina undergoing PCI were retrospectively analyzed. Of these, 452 patients with previously diagnosed diabetes mellitus (DM) or fasting plasma glucose (PG) ≥126 mg/dl and HbA1c ≥6.5% were defined as known DM. The remaining 376 patients were divided into the two groups according to 2-h PG: PH (2-h PG ≥140 mg/dl, n=236) and normal glucose tolerance (NGT, 2-h PG <140 mg/dl, n=140). We assessed the rate of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, stroke, and clinically-driven revascularization.ResultsDuring the median follow-up of 4.3 years, the MACE rate was significantly higher in the DM and PH groups than the NGT group (39.3% vs. 20.7%, P <0.001; 31.4% vs. 20.7%, P=0.044, respectively). Compared with the NGT group, the cumulative incidence of revascularization was significantly higher in the DM group (35.1% vs. 18.5%, P <0.001) and tended to be higher in the PH group (27.1% vs. 18.5%, P=0.067). In the multivariate analysis, known DM (Hazard ratio [HR]: 2.16, 95% confidence interval (CI): 1.49-3.27, P < 0.001), PH (HR: 1.62, 95% CI: 1.07-2.53, P = 0.023), LDL-C >100 mg/dl (HR: 1.62, 95% CI: 1.26 to 2.10, P < 0.001), and previous stroke (HR: 1.47, 95% CI: 1.03-2.04, P = 0.034) were predictors of MACE.ConclusionPH is associated with future cardiovascular events in patients with stable angina undergoing PCI.

Influence of Sex on Long-Term Outcomes After Implantation of Bare-Metal Stent A Multicenter Report From the Coronary Revascularization Demonstrating Outcome Study-Kyoto (CREDO-Kyoto) Registry Cohort-1

Background— Female sex was reported to be associated with lower risk for midterm restenosis and repeat revascularization after bare-metal stent implantation. However, the influence of sex on very long-term outcomes after bare-metal stent implantation has not been yet reported. Methods and Results— Among the 9877 patients in the multicenter Coronary Revascularization Demonstrating Outcome study in Kyoto (CREDO-Kyoto) registry cohort-1, bare-metal stent implantation was performed in 5313 patients (men, n=3742 and women, n=1571). Follow-up was completed in 4515 patients (85.0%) at 10 years (duration, 10.3±3.1 [0.0–14.1] years). The cumulative incidence of target-lesion revascularization (TLR) was 27% at 1 year and 34% at 10 years (0.8%/y beyond 1 year). Non–target-lesion revascularization (non-TLR) was the dominant coronary revascularization beyond 1 year (13% at 1 year and 31% at 10 years [2.0%/y beyond 1 year]). Cumulative incidence of stent thrombosis was low (1.2% at 1 year and 1.9% at 10 years). Women were older and had greater prevalence of cardiovascular risk factors than men. The cumulative 10-year incidences of and adjusted risk for TLR were significantly higher in men than in women (36% versus 30%, P<0.001; adjusted hazard ratio, 1.29; 95% confidence interval, 1.15–1.46; P<0.001). The higher risk of men relative to women for TLR was consistent regardless of age (<75 years and ≥75 years). Men in comparison with women were also associated with significantly higher adjusted risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR. Conclusions— TLR and stent thrombosis continued to occur without attenuation up to 10 years after bare-metal stent implantation. Men in comparison with women were associated with higher adjusted 10-year risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR.

Effects of Age and Sex on Clinical Outcomes after Percutaneous Coronary Intervention Relative to Coronary Artery Bypass Grafting in Patients with Triple Vessel Coronary Artery Disease

Background— Age and sex are important considerations in the choice between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in daily clinical practice. Methods and Results— Of 25 816 patients enrolled in the multicenter Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto; Cohort-1, n=9877; Cohort-2, n=15 939), the present study population consisted of 5651 patients (men, n=3998; women, n=1653) with triple-vessel coronary artery disease who were considered to be pertinent in comparisons of PCI with CABG (PCI, n=3165; CABG, n=2486). Patients were divided into 3 groups according to the tertiles of age: ⩽65 years (n=1972), 66 to 73 years (n=1820), and ≥74 years (n=1859). The excess adjusted mortality risk of PCI relative to CABG was significant in patients ≥74 years of age (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.10–1.79; P=0.006), whereas the risks were neutral in patients ⩽65 years of age (HR, 1.05; 95% CI, 0.73–1.53; P=0.78) and in patients 66 to 73 years of age (HR, 1.03; 95% CI, 0.78–1.36; P=0.85; interaction P=0.003). The excess mortality risk of PCI relative to CABG was significant in men (HR, 1.24; 95% CI, 1.03–1.50; P=0.02) and trended to be significant in women (HR, 1.34; 95% CI, 0.98–1.84; P=0.07) without significant interaction between sex and the mortality risk of PCI relative to CABG (interaction P=0.40). Conclusions— There was a significant association between age and the mortality risk of PCI relative to CABG with excess risk in patients ≥74 years of age and neutral risk in younger patients. There was no significant sex-related difference in the mortality risk of PCI relative to CABG.

Feasibility and diagnostic performance of fractional flow reserve measurement derived from coronary computed tomography angiography in real clinical practice

Non-invasive fractional flow reserve measured by coronary computed tomography angiography (FFRCT) has demonstrated a high diagnostic accuracy for detecting coronary artery disease (CAD) in selected patients in prior clinical trials. However, feasibility of FFRCT in unselected population have not been fully evaluated. Among 60 consecutive patients who had suspected significant CAD by coronary computed tomography angiography (CCTA) and were planned to undergo invasive coronary angiography, 48 patients were enrolled in this study comparing FFRCT with invasive fractional flow reserve (FFR) without any exclusion criteria for the quality of CCTA image. FFRCT was measured in a blinded fashion by an independent core laboratory. FFRCT value was evaluable in 43 out of 48 (89.6 %) patients with high prevalence of severe calcification in CCTA images [calcium score (CS) >400: 40 %, and CS > 1000: 19 %). Per-vessel FFRCT value showed good correlation with invasive FFR value (Spearman’s rank correlation = 0.69, P < 0.001). The area under the receiver operator characteristics curve (AUC) of FFRCT was 0.87. Per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 68.6, 92.9, 52.4, 56.5, and 91.7 %, respectively. Even in eight patients (13 vessels) with extremely severely calcified lesions (CS > 1000), per-vessel FFRCT value showed a diagnostic performance similar to that in patients with CS ≤ 1000 (Spearman’s rank correlation = 0.81, P < 0.001). FFRCT could be measured in the majority of consecutive patients who had suspected significant CAD by CCTA in real clinical practice and demonstrated good diagnostic performance for detecting hemodynamically significant CAD even in patients with extremely severe calcified vessels.

Validating Utility of Dual Antiplatelet Therapy Score in a Large Pooled Cohort From 3 Japanese Percutaneous Coronary Intervention Studies

Background: The dual antiplatelet therapy (DAPT) score was developed to estimate ischemic and bleeding risks from the DAPT study. However, few studies validated its utility externally. We sought to validate the utility of the DAPT score in the Japanese population. Methods: In a pooled cohort of 3 studies conducted in Japan (the CREDO-Kyoto [Coronary Revascularization Demonstrating Outcome Study in Kyoto] Registry Cohort-2, RESET [Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial], and NEXT [NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial]), we compared risks for ischemic and bleeding events from 13 to 36 months after percutaneous coronary intervention among patients with a DAPT score ≥2 (high DS) and a DAPT score <2 (low DS). Results: Among 12 223 patients receiving drug-eluting stents who were free from ischemic or bleeding events at 13 months after percutaneous coronary intervention, 3944 patients had high DS and 8279 had low DS. The cumulative incidence of primary ischemic end point (myocardial infarction/stent thrombosis) was significantly higher in high DS than in low DS (1.5% versus 0.9%, P=0.002), whereas the cumulative incidence of primary bleeding end point (GUSTO moderate/severe) tended to be lower in high DS than in low DS (2.1% versus 2.7%, P=0.07). The cumulative incidences of cardiac death, myocardial infarction, and stent thrombosis were also significantly higher in high DS than in low DS (2.0% versus 1.4%, P=0.03; 1.5% versus 0.8%, P=0.002; 0.7% versus 0.3%, P<0.001, respectively), whereas the cumulative incidences of noncardiac death and GUSTO severe bleeding were significantly lower in high DS than in low DS (2.4% versus 3.9%, P<0.001; 1.0% versus 1.6%, P=0.03, respectively). Conclusions: In the current population, the DAPT score successfully stratified ischemic and bleeding risks, although the ischemic event rate was remarkably low even in high DS. Further studies would be warranted to evaluate the utility of prolonged DAPT guided by the DAPT score.

Long-Term Outcomes After Coronary Stent Implantation in Patients Presenting With Versus Without Acute Myocardial Infarction (an Observation from Coronary Revascularization Demonstrating Outcome Study-Kyoto Registry Cohort-2)

It has not been adequately addressed yet how long the excess cardiovascular event risk persists after acute myocardial infarction (AMI) compared with stable coronary artery disease. Of 10,470 consecutive patients who underwent percutaneous coronary intervention either with sirolimus-eluting stent (SES) only or with bare-metal stent (BMS) only in the Coronary Revascularization Demonstrating Outcome Study-Kyoto Registry Cohort-2, 3,710 (SES: n = 820 and BMS: n = 2,890) and 6,760 patients (SES: n = 4,258 and BMS: n = 2,502) presented with AMI (AMI group) and without AMI (non-AMI group), respectively. During the median 5-year follow-up, the excess adjusted risk of the AMI group relative to the non-AMI group for the primary outcome measure (cardiac death or myocardial infarction) was significant (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.30 to 1.80, p <0.001). However, the excess event risk was limited to the early period within 3 months. Late adjusted risk beyond 3 months was similar between the AMI and non-AMI groups (HR 1.16, 95% CI 0.95 to 1.41, p = 0.15). The higher risk of the AMI group relative to the non-AMI group for stent thrombosis (ST) was significant within 3 months (HR 3.38, 95% CI 2.04 to 5.60, p <0.001), whereas the risk for ST was not different between the 2 groups beyond 3 months (HR 1.11, 95% CI 0.65 to 1.90, p = 0.70). There were no interactions between the types of stents implanted and the risk of the AMI group relative to the non-AMI groups for all the outcome measures including ST. In conclusion, patients with AMI compared with those without AMI were associated with similar late cardiovascular event risk beyond 3 months after percutaneous coronary intervention despite their higher early risk within 3 months.

Antiplatelet Therapy Discontinuation and the Risk of Serious Cardiovascular Events after Coronary Stenting: Observations from the CREDO-Kyoto Registry Cohort-2

Relation of antiplatelet therapy (APT) discontinuation with the risk of serious cardiovascular events has not been fully addressed yet. This study is aimed to evaluate the risk of ischemic event after APT discontinuation based on long-term APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939 consecutive patients undergoing first coronary revascularization, 10470 patients underwent percutaneous coronary intervention either with bare-metal stents (BMS) only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus 24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT status (dual-, single- and no-APT) and linked the adverse events to the APT status just 1-day before the events. No-APT as compared with dual- or single-APT was associated with significantly higher risk for stent thrombosis (ST) beyond 1-month after SES implantation (cumulative incidence rates beyond 1-month: 1.23 versus 0.15/0.29, P<0.001/P<0.001), while higher risk of no-APT for ST was evident only until 6-month after BMS implantation (incidence rates between 1- and 6-month: 8.43 versus 0.71/1.20, P<0.001/P<0.001, and cumulative incidence rates beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/P=0.08). No-APT as compared with dual- or single-APT was also associated with significantly higher risk for spontaneous myocardial infarction (MI) and stroke regardless of the types of stents implanted. Single-APT as compared with dual-APT was not associated with higher risk for serious adverse events, except for the marginally higher risk for ST in the SES stratum. In conclusion, discontinuation of both aspirin and thienopyridines was associated with increased risk for serious cardiovascular events including ST, spontaneous MI and stroke beyond 1-month after coronary stenting.

Intravascular Ultrasound Observation of an Obstruction of the Left Main Coronary Artery Caused by Displaced Leaflet Calcification and Hematoma After Transcatheter Aortic Valve Implantation

An 89-year-old woman underwent transcatheter aortic valve implantation (TAVI) using a transapical approach for severe senile calcific aortic stenosis (area = 0.39 cm2; peak and mean gradients = 176 mm Hg and 103 mm Hg, respectively; ejection fraction = 62%). Preprocedural computed tomography imaging revealed severe calcification of the left coronary cusp and a small sinus of Valsalva (Figure 1A). The patient was considered high-risk for coronary obstruction after TAVI. Figure 1. Computed tomography (CT) imaging before and after transcatheter aortic valve implantation (TAVI). A , CT imaging before TAVI showing a severe calcification of the left coronary cusp and a small sinus of valsalva. B , CT imaging after TAVI showing the displaced leaflet calcification and …

Prediction of Thrombotic and Bleeding Events After Percutaneous Coronary Intervention: CREDO‐Kyoto Thrombotic and Bleeding Risk Scores

Background Prediction of thrombotic and bleeding risk is important to optimize antithrombotic therapy after percutaneous coronary intervention. Methods and Results We developed the prediction rules for thrombotic and bleeding events separately in Japanese patients. Derivation and validation cohorts consisted of 4778 patients from CREDO‐Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort 2 and 4669 patients from RESET (Randomized Evaluation of Sirolimus‐Eluting Versus Everolimus‐Eluting Stent Trial) and NEXT (Nobori Biolimus‐Eluting Versus Xience/Promus Everolimus‐Eluting Stent Trial). Primary thrombotic and bleeding events were a composite of myocardial infarction, definite or probable stent thrombosis or ischemic stroke, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate or severe bleeding. The prediction rule for thrombosis assigned 2 points for severe chronic kidney disease, atrial fibrillation, peripheral vascular disease, and anemia and 1 point for age ≥75 years, heart failure, diabetes mellitus, and chronic total occlusion. The prediction rule for bleeding assigned 2 points for thrombocytopenia, severe chronic kidney disease, peripheral vascular disease, and heart failure and 1 point for prior myocardial infarction, malignancy, and atrial fibrillation. In derivation and validation cohorts, area under the curve was 0.68 and 0.64, respectively, for thrombosis and 0.66 and 0.66, respectively, for bleeding. In the validation cohort, a high thrombosis risk score (≥4, n=682) was associated with higher 3‐year incidence of thrombotic events than a score that was intermediate (2–3, n=1178) or low (0–1, n=2809) (7.6%, 3.7%, versus 2.4%, respectively; P<0.0001). A high bleeding risk score (≥3, n=666) was associated with higher incidence of bleeding than scores that were intermediate (1–2, n=1802) or low (0, n=2201) (8.8%, 4.1%, versus 2.3%, respectively; P<0.0001). Among 682 patients at high thrombotic risk, only 39 (5.7%) had low bleeding risk, whereas 401 (58.8%) had high bleeding risk with very high incidence of bleeding (11.6%). Conclusions CREDO‐Kyoto thrombotic and bleeding risk scores demonstrated modest accuracy in stratifying thrombotic and bleeding risks; however, a large proportion of patients at high thrombotic risk also had high bleeding risk.

A Case of Successful Reopening of Left Main Coronary Artery Occlusion After Transcatheter Aortic Valve Replacement

An 86-year-old woman with severe aortic stenosis was referred for transcatheter aortic valve replacement (TAVR). The transfemoral TAVR procedure was conducted under general anesthesia. Aortography during pre-dilatation with a 20-mm balloon demonstrated reduced blood flow through the left main