小林 欣夫

Purpose Ventricular outflow tract arrhythmias (VOTAs) can be successfully treated by catheter ablation. However, it is sometimes difficult to differentiate the origin of VOTAs between the right ventricular outflow tract (RVOT) and the other sites, leading to a long fluoroscopy time and unnecessary radiofrequency applications. This study aimed to clarify distinguishable characteristics of the propagation pattern obtained from non-contact mapping (NCM) for VOTA ablation. Methods Consecutive 45 patients with VOTAs who underwent catheter ablation using the NCM system were included in this study. We analyzed an isopotential map on three-dimensional geometry of the RVOT obtained from the virtual unipolar electrograms (VUEs) and assessed mapping data of the isopotential area with an initial negative VUE of -1 mV. Results Successful ablation was achieved from the endocardial RVOT in 34 patients (RVOT group) and the non-RVOT in 11 (non-RVOT group). Major and minor axis diameters of the isopotential area did not significantly differ between the two groups. However, a ratio of major/minor axis diameter was greater in the RVOT group (1.9 +/- 0.1 versus 1.3 +/- 0.1; P < 0.001). In addition, the propagation velocity defined as an increase of the isopotential area per millisecond was significantly slower in the RVOT group (2.2 +/- 0.4 versus 4.2 +/- 0.7 mm(2)/ms; P = 0.02). Conclusions The isopotential area of VOTAs originating from the RVOT, as compared to the other sites, spread more elliptically and slowly. The propagation pattern obtained from NCM can provide useful information and efficient strategy for VOTA ablation.

Background: Direct oral anticoagulants (DOACs) have been developed as alternatives to conventional therapy with warfarin for the treatment of acute venous thromboembolism (VTE) events. The safety and efficacy of DOACs in Japanese patients with acute VTE has been investigated in small trials or subgroups from global randomized controlled trials (RCTs). Methods and Results: We conducted a systematic review and meta-analysis of RCTs, to compare the safety and efficacy of DOACs to those of conventional therapy in Japanese patients with acute VTE. Published research was systematically searched for RCTs that compared DOAC to conventional therapy in Japanese patients with acute VTE. Random-effects models were used to pool safety and efficacy data across RCTs. Three studies, including 386 patients, were identified. Patients randomized to DOAC had a decreased risk for all bleeding [risk ratio (RR) 0.69, 95% confidential interval (CI) 0.50-0.95], without any significant differences in recurrent VTE (RR 0.84, 95% CI 0.29-2.43) and recurrent VTE/all-cause death (RR 0.60, 95% CI 0.23-1.56). Conclusion: DOACs offer clinical benefit over conventional therapy in Japanese patients with acute VTE, showing a significant difference in their bleeding profile. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Background: The impact of chronic kidney disease (CKD) on the antiplatelet effect of clopidogrel and low dose (3.75 mg) prasugrel in Japanese patients is largely unknown. Methods: A total of 53 consecutive Japanese patients with stable coronary artery disease who received aspirin and clopidogrel were enrolled, and categorized by estimated glomerular filtration rate (eGFR): CKD group (n = 15, eGFR < 60 int/min/1.73 m(2)) and non-CKD group (n = 38, eGFR >= 60 ml/min/1.73 m2). Clopidogrel was switched to 3.75 mg prasugrel. Platelet reactivity measurement using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA) was performed at baseline (on clopidogrel) and day 14 (on prasugrel). Results: The VerifyNow P2Y12 reaction units (PRU) during clopidogrel therapy was significantly higher in the CKD group than that in the non-CKD group (185.2 +/- 51.1 PRU vs. 224.3 +/- 57.0 PRU, p = 0.02), whereas, the PRU with the prasugrel therapy in the CKD group and non-CKD group were not significantly different (149.9 +/- 51.1 PRU vs. 165.3 +/- 61.8 PRU, p = 0.36). The PRU was significantly lower with the prasugrel therapy compared to that with the clopidogrel therapy both in the CKD group and in the non-CKD group. Conclusions: Antiplatelet effect of clopidogrel but not prasugrel is attenuated in patients with CKD. Prasugrel achieves a consistently lower platelet reactivity compared with clopidogrel regardless of the presence of mild to moderate CKD. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Deployment of polytetrafluoroethylene (PTFE)-covered stent is a useful technique to seal coronary perforation. However, the high profile and low flexibility compromise its deliverability. To facilitate stent delivery, a guide extension catheter (GuideLiner™ catheter) through a 6 Fr guiding catheter has been used. This case report describes a successful deployment of a PTFE-covered stent using a 6 Fr GuideLiner catheter to seal coronary perforation.

We report a case of structural valve deterioration, which occurred 7 years after aortic valve replacement in a 78-year-old male with cardiac sarcoidosis. His echocardiography showed low transprosthetic valve gradient and depressed left ventricular function. A dobutamine stress echocardiography was performed to identify his pathophysiology, and it revealed that his depressed left ventricular function was not due to cardiac sarcoidosis but to structural valve deterioration. Reoperation for structural valve deterioration was performed, and his left ventricular function recovered.

冠動脈疾患を対象とする心臓CTの臨床的有用性について述べた。心電図同期撮像法の開発や検出器の多列化を中心としたCTの技術的革新により、近年は造影CTで冠動脈狭窄の診断が可能となった。CTによる冠動脈疾患評価は狭窄度評価のみならず、FFR-CTや心筋灌流CTなどによる冠動脈機能評価の面でもさらなる臨床応用が進むと思われる。また、画像再構成法の進歩による検査時の被曝低減や撮像時間短縮による造影剤減量も進み、今後心臓CTはさらに低侵襲で身近な検査になることが予想される。本稿では以下の項目で概説した。1)心臓CTによる冠動脈疾患診断の現状。2)心臓CTによる冠動脈機能評価の展望。3)心臓CTによる症例予後予測の有用性。4)遅延造影CTによる心筋梗塞(線維化)評価。5)三次元CT心筋ストレインの開発。

Our aim was to assess the discrepancy in the blood pressure amplification (BPA) value defined as the aortic-to-brachial increase in systolic BP (SBP) between invasive and noninvasive brachial cuff-based methods. In 45 patients undergoing cardiac catheterization, BP in the brachial artery and ascending aorta were measured with an invasive catheter and a brachial cuff-based oscillometric device. To calculate aortic SBP, brachial waveforms were calibrated by the brachial systolic and diastolic BP (DBP) (C1 calibration) or by the brachial mean BP and DBP (C2 calibration). C1 calibration underestimated aortic SBP (-17.7 mm Hg (95% confidence interval: -21.9 to -13.5)), whereas C2 calibration generated an approximately accurate aortic SBP (1.8 mm Hg (-2.4 to 5.9)). Regarding brachial SBP, noninvasively measured values were markedly underestimated (22.2 mm Hg (-26.4 to -18.0)), resulting in a slightly low BPA value in C1 calibration (11.9 +/- 6.3 mm Hg) and a paradoxical negative BPA value in C2 calibration (-7.6 +/- 6.7 mm Hg). Multiple linear regression analysis showed that the cuff-catheter difference of BPA was positively correlated with the cuff-catheter difference of brachial SBP in both calibrations (C1 calibration: beta=0.51; C2 calibration: beta=0.50; both P < 0.01). Although noninvasively measured BPA was associated with invasively measured BPA only in C1 calibration (r=0.33, P=0.03), when using invasively measured brachial SBP instead of a cuff-based measurement, the BPA was well associated with invasively measured BPA in both calibrations (C1 calibration: r=0.57; C2 calibration: r=0.52; both P < 0.001). In conclusion, there was a trade-off in accuracy between brachial cuff-based noninvasive aortic SBP and BPA because of the inherent inaccuracies in the cuff-based method. This finding should be fully considered in establishing standardized reference values for aortic BP.

Objectives The difference in intraluminal intensity of blood speckle (IBS) on integrated backscatter intravascular ultrasound (IVUS) across the coronary stenosis was reportedly correlated with fractional flow reserve (FFR) in the left descending coronary artery. The aim of this study was to investigate the novel physiological assessment using IVUS in all coronary arteries. Patients and methods Fifty-four patients with 57 coronary lesions underwent both FFR and IVUS. Intraluminal IBS was analyzed using integrated backscatter IVUS in crosssections at the ostium and the distal site of the target vessel Delta IBS was calculated as: (distal IBS)-(ostium IBS). Results Both.IBS (r=-0.50, P< 0.01) and minimum lumen area (MLA) (r= 0.55, P< 0.01) showed significant correlations with FFR. There were significant correlations between FFR and.IBS in the right and left descending coronary arteries (r=-0.60, P= 0.02, and r=-0.58, P< 0.01), but not in the left circumflex (r= 0.30, P= 0.44). In receiver operating characteristic curve analyses,Delta IBS predicted FFR less than or equal to 0.80 (area under the curve= 0.82, P< 0.01, best cutoff value= 6.78), as with MLA (area under the curve= 0.83, P< 0.01, best cutoffvalue=2.38). FFR progressively decreased in association with Delta IBS greater than or equal to 6.78 and MLA less than or equal to 2.38, and was the lowest when these were combined. Conclusion Delta IBS was correlated with FFR in right and left descending coronary arteries. IVUS may assess coronary artery stenosis anatomically and physiologically. (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

Purpose: Right ventricular myocardial (RVM) fibrosis may be a significant indicator of prognosis in pulmonary hypertension (PH). To detect the presence of RVM fibrosis in PH subjects, we employed ECG gated 320-slice CT. Methods: 62 confirmed PH subjects (16 males; 55 +/- 16 years; 45 chronic thromboembolic PH (CTEPH) who underwent conventional non-surgical medical therapy; and 17 pulmonary arterial hypertension (PAH)) underwent ECG-gated 320-slice CT. On CT, RV fibrosis was defined as contrast defect in the early phase and conversely abnormal enhancement in the late phase. Results: RVM fibrosis was observed in 14 subjects (23%) on CT (CTEPH 22%; PAH 29%; P = 0.91). CT attenuation of RVM in the late phasewas significantly greater in subjectswith RVM fibrosis than in thosewithout (P= 0.025). ROC curves of CT attenuation of RVM in the early and late phase, and ratio of CT attenuation of RVM in the early phase/late phase showed AUCs of 0.55, 0.70, and 0.65, respectively. The best cutoff points of 79.5 HU (sensitivity of 50% and specificity of 69% for CT attenuation of RVM in the early phase, P= 0.59), 99.5 HU (sensitivity of 50% and specificity of 88% for CT attenuation of RVM in the late phase, P = 0.025), and 1.416 (sensitivity of 29% and specificity of 94% for ratio of CT attenuation of RVM in the early phase/late phase, P = 0.092) were used to distinguish subjects +/- RVM fibrosis. Conclusion: Quantitative-measurement of CT attenuation of RVMin the late phasemay be able to detect presence of RVM fibrosis in PH subjects. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Purpose: To evaluate the diagnostic accuracy of computed tomography (CT) for the detection of myocardial fibrosis, we compared the frequency of abnormal late enhancement (LE) in left ventricular myocardium(LVM) on CT with that on gadolinium-enhanced cardiac magnetic resonance (CMR) in patients with various myocardial diseases. Methods: Fifty-six patients with suspected various myocardial diseases (19 with hypertrophic cardiomyopathy, 3 with cardiac amyloidosis, 3 with post myocarditis, 2 with dilated cardiomyopathy, 2 with cardiac sarcoidosis, 2 with cardiac tumor, 2 with previous myocardial infarction, 2 with hypertensive heart disease) underwent 1.5-T CMR and cardiac CT within 2 months without clinical accidents. Results: LE on LVM was detected in 31 and 31 patients on CT and CMR, respectively, and in 192 and 197 LVM segments on CT and CMR, respectively, among a total of 952 LVM segments. The sensitivity, specificity, positive and negative predictive values, and consistency for detection of LE on CT in comparison with CMR were 90, 89, 90, 89 and 89%, respectively, on patient-based analysis, and 67, 92, 68, 91 and 87%, respectively, on segment-based analysis. Inter-observer agreement for detection of LE on CT was 0.71 (kappa coefficient), and it was significantly lower than that on CMR (0.82) on segment-based analysis (P < 0.05). Conclusions: Compared with CMR, diagnostic accuracy of CT for the evaluation of LE in LVM in patients with myocardial diseases was relatively higher on patient-based analysis, but was limited on segment-based analysis, and the inter-observer agreement on CT was significantly lower than that on CMR. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Background: Weaimed to optimize the acquisition of the left atrial (LA) and pulmonary vein (PV) ultrasound contours formore accurate integration of intracardiac echocardiography (ICE) and computed tomography (CT) using the CARTO (R) 3 system during atrial fibrillation (AF) ablation. Methods: Eighty-five AF patients underwent integration of ICE and CT using (1) the LA roof and posterior wall contours acquired from the right atrium (RA), (2) all LA/PV contours from the RA (Whole-RA-integration), (3) the LA roof/posterior wall contours from the RA and right ventricular outflow tract (RVOT) (Posterior-RA/RV-integration), and (4) all LA/PV contours from the RA and RVOT (Whole-RA/RV-integration). The integration accuracy was compared using the (1) surface registration error, (2) distances between the three-dimensional CT and eight specific sites on the anterior, posterior, superior, and inferior aspects of the right and left circumferential PV isolation lines, and (3) registration score: a score of 0 or 1 was assigned for whether or not each specific site was visually aligned with the CT, and summed for each method (0 best, 8 worst). Results: Posterior-RA/RV-integration revealed a significantly lower surface registration error (1.30 +/- 0.15 mm) than Whole-RA-and Whole-RA/RV-integration (p < 0.001). The mean distances of the eight specific sites and the registration score for Posterior-RA/RV-integration (median 1.26 mm and 2, respectively) were significantly smaller than those for the other integration approaches (p < 0.001). Conclusions: Image integration with the LA roof and posterior wall contours acquired from the RA and RVOT may provide greater accuracy for catheter navigation with three-dimensional CT during AF ablation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Background: A newtransthoracic echocardiography (TTE) technique allows multi-layer measurement of left ventricular (LV), endocardial, epicardial, and whole layer myocardial strain. We evaluated interobserver and intraobserver TTE reproducibility for 2D LV global longitudinal (GLS) and circumferential strain (GCS) estimates using data from severe aortic stenosis (AS) subjects with preserved LV ejection fraction (EF). Methods: Twenty severe AS subjects (11 male; mean age, 75 +/- 7 years; LV EF >50%) underwent TTE (Vivid E9, GE Healthcare). Quantitative strain measurements of whole, endocardial, and epicardial layers were performed. GLS was defined as all 17 averaged LV segments, according to the American Heart Association classification. GCS was measured at the levels of the mitral valve, papillary muscle, and apex. Results: Interobserver correlation coefficients in whole, endocardial, and epicardial layers for GLS estimates were 0.81, 0.83, and 0.80, respectively, whereas those for GCS estimates were 0.38, 0.56, and 0.19, respectively, for the mitral valve, 0.44, 0.54, and 0.36, respectively, for the papillary muscle, and 0.55, 0.29, and 0.59, respectively, for the apex. Intraobserver correlation coefficients in whole, endocardial, and epicardial layers for GLS estimates were 0.97, 0.97, and 0.94, respectively, whereas those for GCS estimates were 0.86, 0.81, and 0.50, respectively, for the mitral valve, 0.56, 0.72, and 0.28, respectively, for the papillary muscle, and 0.70, 0.69, and 0.62, respectively, for the apex. Conclusion: In severe AS subjectswith preserved LVEF, inter-and intra-observer TTE reproducibility in whole, endocardial, and epicardial layers were more consistent for 2D LV GLS than for 2D LVGCS. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Purpose: To evaluate CT utility for detection of cardiac or lung abnormalities in the diagnosis of organic cardiac disease in subjects with second- or third-degree atrioventricular block (AVB) excepting Wenckebach type. Materials and methods: A total of 50 consecutive patients (25 male; 64 +/- 15 years) with de novo third- or second-degree AVB underwent both TTE and a combination of cardiac and chest 320 slice CT (Aquilion one, Toshiba Medical) and were retrospectively analyzed. The presence of focal left ventricular (LV) wall thinning and thickening was evaluated on both TTE and cardiac CT. We evaluated the presence of significant coronary artery stenosis, focal late enhancement (LE) in LV myocardium, significant-sized (>10 mm) lymph nodes in hialus or mediastinum and/or typical lung nodules for sarcoidosis on CT. Results: Abnormalities for 26%, 30%, and 36% of patients were demonstrated on TTE, cardiac CT, and a combination of cardiac and chest CT, respectively. 12% and 18% patients who did not exhibit cardiac abnormalities on TTE, revealed abnormalities on cardiac CT, or a combination of cardiac and chest CT, respectively. 36% patients had organic cardiac diseases. Sensitivities for detection of organic cardiac disease were significantly greater when cardiac and chest CT were combined than TTE alone (P < 0.01). Conclusions: Approximately one third of patients with third- or second- degree AVB had organic cardiac diseases. For detection of cardiac and chest abnormality and correct diagnosis of organic cardiac disease in patients with third- or second-degree AVB, TTE is not sufficient on its own. CT or a combination of TTE and CT are required. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Purpose: We performed 2D speckle tracking transthoracic-echocardiography (TTE) to compare the ability to predict occurrence of major adverse cardiac events (MACE) between global longitudinal strain (GLS) and circumferential strain (GCS) in left ventricular (LV) myocardium in hypertrophic cardiomyopathy (HCM) patients without obstructed coronary arteries. Methods: We measured 2D LV GLS and GCS retrospectively by TTE within 13 months of performance of cardiac CT in 41 consecutive symptomatic HCM patients (27 males; 60 +/- 13 years) without obstructed coronary arteries on CT. Patients were followed up for a median period of 30 months. Results: MACE occurred in 7 (17%) patients. The Cox proportional hazard model for univariate analysis revealed that 2D LV GLS (hazard ratio (HR) 1.89, P = 0.019) was a significant predictor of MACE but GCS (HR 1.07, P = 0.118) was not. The Cox model for multivariate analysis revealed that 2D LV GLS (hazard ratio 2.144, P = 0.013) was a significant predictor for MACE. In receiver operating characteristic (ROC) curves at a best cut-off of -9.65% (2D LV GLS) and -29.35% (2D LV GCS), the sensitivity and specificity for MACE occurrence were 100% and 64.7% (2D LV GLS) and 100% and 47.1% (2D LV GCS), respectively. Kaplan Meier analysis revealed significant differences in MACE occurrence during the follow-up period between <= - 9.65 and >9.65% of 2D LV GLS (P= 0.004) and <= - 29.35 and > - 29.35% of 2D LV GCS (P = 0.017). Conclusions: Both 2D LV GLS and GCS (2D LV GLS > GCS) on TTE can predict poor prognosis in HCM patients without obstructed coronary arteries. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

The entirely subcutaneous implantable cardioverter-defibrillator (ICD) system was developed to provide a life-saving defibrillation therapy that does not affect the heart and vasculature. The subcutaneous ICD is preferred over the transvenous ICD for patients with a history of recurrent infection presenting major life-threatening rhythms. In this case report, we describe the first successful intermuscular implantation of a completely subcutaneous ICD in a Japanese patient with pectus excavatum. There were no associated complications with the device implantation or lead positioning. Further, the defibrillation threshold testing did not pose any problem with the abnormal anatomy of the patient.

A 23-year-old female was referred for evaluation of syncope associated with standing for a long time at a morning gathering. She had experienced 2 episodes of syncope and frequent episodes of pre-syncope at morning gathering. Head-up tilt test demonstrated decrease in blood pressure from 104/65 to 55/28 mmHg and heart rate from 69 to 40 bpm associated with pre-syncope 15 min after the table was tilted upright to a 70° angle. Furthermore epinephrine stress test was performed because electrocardiogram showed prolongation of corrected QT interval of 546 msec. With epinephrine infusion, QT interval prolongation of 48 msec that was sensitive and specific marker for LQT1 was observed. Genetic testing identified KCNQ1, A525V mutation that is associated with LQT1. Since starting propranolol, QT interval was shortened from 546 to 492 msec and she has had no symptom. This case emphasizes the importance to exclude possibility of long QT syndrome in patients with neurally mediated syncope. © 2011, Japanese Heart Rhythm Society. All rights reserved.

Background: Three-dimensional quantitative coronary angiography (3D-QCA) reportedly allows more accurate delineation of true vessel geometry when compared with standard two-dimensional (2D) QCA and has been validated by intravascular ultrasound (IVUS). This study sought to compare diagnostic efficiency of 2D- and 3D-QCA, and IVUS in identifying hemodynamically significant coronary stenoses as determined by fractional flow reserve (FFR). Methods: Forty-two lesions in 40 patients were assessed by FFR, IVUS, and 2D- and 3D-QCA. Correlations between FFR values and anatomical parameters obtained by 2D- and 3D-QCA and IVUS were analyzed. The receiver operating characteristic (ROC) curves were used to compare the diagnostic accuracy of the parameters for predicting FFR <= 0.80. Results: Mean FFR value was 0.75 +/- 0.13. FFR <= 0.80 was observed in 28 lesions (67%). Of IVUS measurements, minimum lumen area (MLA) well correlated with FFR values (r = 0.71, p < 0.001). Of 3D- and 2D-QCA measurements, minimum lumen diameter (MLD) correlated best with FFR values (r = 0.79, p < 0.01; r = 0.68,p < 0.01, respectively), followed by MLA (r = 0.76, p < 0.01; r = 0.67, p < 0.01, respectively). The area under the ROC curve for 3D-QCA MLD was greater than those for 2D-QCA MLD (p = 0.03) and 2D-QCA MLA (p = 0.03). On the other hand, the AUC for 3D-QCA MLD, 3D-QCA MLA, and IVUS MLA were not significantly different. Conclusions: 3D-QCA is more useful than 2D-QCA and possibly comparable to IVUS in the assessment of functional stenosis severity. When FFR is not available, 3D-QCA MLA and MLD may assist in the assessment of functional severity of intermediate lesions. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

The aim of this study was to evaluate neointimal coverage in the very early phase after second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Patients who underwent staged percutaneous coronary intervention within 30 days after DES implantation were enrolled. OCT was performed to observe DES previously implanted. The median time interval from implantation to OCT examination was 21.5 days. A total of 10,625 struts of 54 stents (52 everolimus-eluting stents and 2 zotarolimus-eluting stents) in 42 lesions were analyzed. Strut tissue coverage was observed in 71.1 +/- 19.2 % of the struts, malapposed struts in 2.56 +/- 3.37 %, strut tissue coverage at the side branch orifice in 10.6 +/- 17.2 %, and struts with protrusion in 0.95 +/- 3.46 %. Mean tissue thickness on the covered struts was 39.8 +/- 14.2 A mu m. The percentage of stent coverage was significantly lower in the overlapping segments than in the non-overlapping segments (48.4 +/- 17.5 % vs. 74.4 +/- 20.2 %, P < 0.05). Most of the stent struts were covered by tissue within 30 days after second-generation DES implantation. However, the percentage of strut coverage was lower in the overlapping segments than in the non-overlapping segments, suggesting that very early interruption of dual antiplatelet therapy might result in increased risk of stent thrombosis, even in second-generation DES.

BACKGROUND Several studies have reported that central systolic blood pressure (SBP) estimation is affected by calibration methods. However, whether central pulsatile indices, namely pulse pressure (PP) and fractional PP (FPP) (defined as PP/mean arterial pressure (MAP)), also depend on calibration methods remains uninvestigated. This study assessed the accuracy and discriminatory ability of these indices for coronary atherosclerosis using 2 calibration methods. METHODS Post-hoc analysis of a previous cross-sectional study (n = 139) that investigated the association between central pulsatile indices and coronary atherosclerosis. A validated-oscillometric device provided PP and FPP at the brachial artery (bPP and bFPP) and central artery using 2 calibration methods: brachial SBP/diastolic BP (DBP) (cPPsd and cFPPsd) and MAP/DBP (cPPmd and cFPPmd). Accuracy was assessed against invasive measurements (cPPinv and cFPPinv). Multivariate logistic and linear regression analyses were performed to assess the association between pulsatile indices and the presence of coronary artery disease (CAD) and SYNTAX score, respectively. RESULTS cPPmd and cFPPmd were closer to invasive values than cPPsd (cPPsd: 39.6 +/- 12.6; cPPmd: 60.2 +/- 20.1; cPPinv: 71.4 +/- 22.9). cFPP exhibited similar results (cFPPsd: 0.35 +/- 0.09; cFPPmd: 0.55 +/- 0.14; cFPPinv: 0.70 +/- 0.19). In patients = 70 years, only cFPPmd was significantly associated with CAD risk (odds ratio: 1.66 (95% confidence interval: 1.05-2.64)). SYNTAX score was significantly correlated with cPPmd, cFPPmd, and bFPP (standardized beta: cPPmd 0.39, cFPPmd 0.50, bFPP 0.42, all P < 0.01). No significant association was observed in patients aged < 70 years. CONCLUSIONS Central pulsatile indices calibrated with brachial MAP/DBP were more accurate and discriminatory for coronary atherosclerosis than SBP/DBP calibration.

Background: Studies have established the prognostic value of central SBP and pulse pressure (PP). The SphygmoCor XCEL (AtCor Medical, Sydney, Australia) device provides practical central blood pressure (BP) measurement for daily clinical use with its easy-to-use, operator-independent procedure. However, this device has not been validated against invasive measurement. Method: Simultaneous oscillometric and high-fidelity invasive measurements of central SBP and PP were compared for 36 patients who underwent coronary arteriography. Invasive measurement of brachial BP was also performed. Oscillometrically measured brachial SBP and DBP were used for calibration. Results: The differences between the invasive and the oscillometric measurements were -4.6 +/- 9.9mmHg for central SBP and -18.5 +/- 10.6mmHg for central PP (mean +/- SD). We found strong correlation between the invasive and oscillometric measurements (central SBP and central PP, respectively: r = 0.91 and 0.89; slope, 1.28 and 1.38; both P<0.001). Although the large slopes of the regression lines indicated a systemic bias toward lower values when measuring in high pressure ranges, the bias was mainly due to calibration error rather than device-specific error because errors of the central measurements correlated well with those of brachial measurements (SBP and PP, respectively: r = 0.80 and 0.77; both P<0.001). Conclusion: The impaired accuracy of central BP measurement was mainly due to calibration-derived, but not device-dependent, bias. Strong correlation between oscillometric and invasive measurements indicates that SphygmoCor XCEL warrants future investigations to determine the clinical validity of this device.

Intravascular ultrasound (IVUS) is a reliable imaging tool to guide percutaneous coronary intervention. There has been increasing evidence supporting the clinical utility of IVUS-guided drug-eluting stent (DES) implantation, including randomized trials, observational studies, and meta-analyses of both. IVUS provides cross-sectional views of the coronary artery wall, and allows us to assess stenosis severity, identify plaque morphology, optimize stent implantation, and understand mechanism of stent failure. IVUS guidance can increase DES efficacy and decrease clinical events. In this review article, we summarize available evidence on IVUS-guided DES implantation.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral hypoglycemic agents for patients with type 2 diabetes mellitus and have potential antiatherosclerotic properties. Meanwhile, it is unclear how DPP-4 inhibitors have protective effects on atherosclerosis. Our aim was to determine the effects and its mechanisms of DPP-4 inhibitors on cultured endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in hypoxic condition. To evaluate the protective effects of DPP-4 inhibitor on HUVECs, DPP-4 inhibitor was added in the cell culture medium and the cell viability was assessed by TUNEL assay. And we examined the intracellular signaling pathways in relation to the effects of DPP-4 inhibitor. DPP-4 inhibition had beneficial effects by inhibiting the apoptosis under hypoxic conditions in HUVECs. The antiapoptotic effects of DPP-4 inhibitor were abolished by the pretreatment with a CXCR4 antagonist or a Stat3 inhibitor. DPP-4 inhibition has beneficial effects on HUVECs by inhibiting the apoptosis under hypoxic conditions. SDF-1 alpha/CXCR4/Stat3 pathways might be involved in the mechanisms of the cytoprotective effects of DPP-4 inhibitor. These results suggested that DPP-4 inhibitor has a potential for protecting vessels. (C) 2017 The Authors. Production and hosting by Elsevier B. V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

We investigated age-related change in the contribution of stroke volume (SV) to central PP (cPP). Eighty seven adult subjects who were free of vasoactive agents were included. Subjects were divided into three age groups: young (20-39 years, n = 26), middle (40-49 years, n = 29), and old (>= 50 years, n = 32). SV was calculated by Doppler echocardiography. Hemodynamic indices were measured using a brachial cuff-based oscillometric method. The brachial and cPP showed a small decline from the young group to the middle group and a greater rise after 50 years old. SV significantly and positively correlated with brachial (r = 0.53, p < 0.01) and cPP (r = 0.57, p < 0.01) in the young group. In the middle group, the association of SV with brachial pulse pressure was significant (r = 0.38, p = 0.04) and that with cPP was bordering significant (r = 0.34, p = 0.07). No significant association was found between SV and PP in the old group. In conclusion, the contribution of SV to cPP decreases with age. Age-related changes in the determinants of cPP should be considered when investigating the clinical value of cPP.

The aim of this study was to investigate the association of aortic pulsatility assessed by a non-invasive brachial cuff-based method with coronary atherosclerosis. In total, 139 patients undergoing coronary angiography were included in this cross-sectional study. Aortic blood pressure (BP) indices were recorded invasively by a fluid-filled catheter and non-invasively by a brachial cuff-based oscillometric device. Fractional pulse pressure (FPP) was defined as pulse pressure (PP)/mean BP and pulsatility index (PI) as PP/diastolic BP. Aortic FPP and PI in coronary artery disease (CAD) patients were significantly higher than in non-CAD patients in both invasive and non-invasive methods. Multivariate logistic regression analysis demonstrated that non-invasively measured aortic FPP and PI were associated with CAD risk in patients aged 70 years [aortic FPP per 0.1 odds ratio (OR)=1.66, 95% confidence interval (CI) 1.05-2.64; aortic PI per 0.1 OR =1.39, 95% CI 1.02-1.88; all p<0.05], but were not associated with CAD risk in patients aged <70 years. In linear regression analysis, non-invasively measured aortic FPP and PI correlated with SYNTAX and Gensini scores only in patients aged 70 years. Aortic FPP and PI measured non-invasively by a brachial cuff-based oscillometric device were associated with coronary atherosclerosis in elderly patients.

Background: Inducing maximal coronary hyperemia is important to measure fractional flow reserve (FFR) accurately. Intravenous adenosine and adenosine 5'-triphosphate (ATP) have been used to achieve maximal hyperemia. However, they may not induce maximal hyperemia in all patients. The present study evaluated the combined effect of intracoronary papaverine and intravenous ATP on FFR measurements. Methods: FFR measurements with administration of intracoronary papaverine (12 mg in the left coronary artery and 8 mg in the right coronary artery), intravenous ATP (140 mu g/kg/min), and combined administration of intracoronary papaverine and intravenous ATP were performed in 51 patients with 57 intermediate lesions. Results: The mean FFR after intravenous ATP was higher compared to intracoronary papaverine and intravenous ATP plus intracoronary papaverine (0.76 +/- 0.13 vs. 0.75 +/- 0.13 vs. 0.75 +/- 0.13, p = 0.01). FFR-positive lesions (FFR <= 0.80) were observed more frequently with intravenous ATP plus intracoronary papaverine compared to intravenous ATP (64.9% vs. 47.4%, p = 0.02). Of 32 and 25 FFR-negative lesions with intravenous ATP and intracoronary papaverine, 11 (34%) and 7 (28%) had positive FFR after administration of intravenous ATP plus intracoronary papaverine. No ventricular tachycardia or ventricular fibrillation was observed after administration of intracoronary papaverine. Conclusions: Maximal hyperemia may not be induced with intravenous ATP in all lesions. When sufficient hyperemia is doubtful during intravenous infusion of ATP, additional intracoronary administration of papaverine may be a possible option. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

BackgroundBaseline coronary artery diameter and coronary artery dilation response to nitrate are associated with coronary vasoreactivity.ObjectivesThe present study investigated the predictive value of coronary artery tone for a positive intracoronary acetylcholine (ACh) provocation test.MethodsA total of 197 patients who underwent an ACh provocation test in the right coronary artery were included. A positive ACh provocation test was defined as transient total or subtotal occlusion of a coronary artery with signs/symptoms of myocardial ischemia. The segment, from the ostium to the bifurcation, of the right coronary artery was analyzed quantitatively. Coronary artery dilation response to isosorbide dinitrate (ISDN) was defined as the mean lumen diameter after an intracoronary injection of ISDN divided by the diameter before administration of ACh (i.e. baseline coronary artery diameter).ResultsAfter the administration of ACh, 49 patients (24.9%) had a positive ACh provocation test. Smaller baseline right coronary artery diameter (2.350.45 vs. 2.73 +/- 0.48mm, P<0.001) and greater right coronary artery dilation response to ISDN (1.34 +/- 0.12 vs. 1.15 +/- 0.11, P<0.001) were observed in patients with a positive ACh provocation test. The receiver operating characteristic curve for baseline coronary artery diameter poorly predicted the occurrence of a positive ACh provocation test (area under the curve 0.71). The predictive values of dilation response of the right coronary artery to ISDN for the occurrence of a positive ACh provocation test (area under the curve 0.87) was significantly better compared with that of baseline right coronary artery diameter (P<0.001).ConclusionCoronary artery dilation response to nitrate is a more accurate predictor of a positive intracoronary ACh provocation test compared with baseline coronary artery diameter.

Background: In this study, differences in older patients between drug use as reported in clinical practice and in clinical trials for regulatory approval were examined. Methods: Electronic medical record (EMR) data such as patient background (age, sex), concomitant drugs, data on laboratory tests, and prescribed doses of drugs from outpatients with rheumatoid arthritis, diabetes, high blood pressure, or depression at Chiba University Hospital were obtained for the period from January 2003 to December 2012. These data were compared with data from relevant clinical trials for regulatory approval in order to examine differences in drug use. Results: There were 5134 eligible patients. The prescribed doses of drugs were lower than the standard approved doses for depression and rheumatoid arthritis but were generally within the approved dose range for type 2 diabetes mellitus and hypertension. When comparing the characteristics of older patients taking tacrolimus, 5.6% to 17.0% of those would not be able to participate in clinical trials because of liver or renal abnormality, and the incidence rates of some adverse drug events (ADEs) differed significantly between clinical practice and clinical trials. Conclusions: Appropriate doses of drugs for older patients may differ from approved doses in certain diseases. Complex situations such as a lot of polypharmacy, comorbidity, and functional impairment in older patients in clinical practice make it difficult to evaluate safety based on data from clinical trials. In the future, utilization of a database created from the EMR of older patients should be considered for assessment of drug safety in older patients in clinical practice.

Purpose: We investigated the relationship of left ventricular (LV) diastolic dysfunction and LV mass index (LVMI) against pulmonary hypertension (PH) in systemic autoimmune disease (SAD). Methods: A total of 84 SAD patients (68 females; 53 +/- 17 years; systemic lupus erythematosus, 27%; scleroderma, 17%; vasculitis, 16%; mixed connective tissue disease, 13% and polymyositis/dermatomyositis complex, 10%) without significant pericardial effusion (PE) on TTE (Vivid E9, GE) were analyzed. On TTE, PH was defined as peak tricuspid regurgitation velocity (TRV) of >= 2.9 m/s based upon 2015 ESC guideline. Left atrial volume index (LAVI) and E/E' were measured as indicators of LV diastolic dysfunction. LVMI was also measured. Results: Seven patients (8%) had PH. PH patients had greater LAVI (p < 0.001), E/E' (p = 0.004), LVMI (p= 0.009) than non-PH patients. LAVI (R = 0.458), E/E' (R = 0.337), and LVMI (R = 0.313) significantly and positively correlated with TRV (all p < 0.05). Multiple regression analysis was performed to explore determinants of TRV. Age, female sex, and brain natriuretic peptide (BNP) were included in all the models. Three multiple regression models were generated using 1) LAVI, 2) E/E', and 3) LVMI and included LAVI, E/E', LVMI, and BNP as significant variables influencing TRV. Multi logistic regression analysis for predicting TRV of >= 2.9m/s showed that LAVI, and E/E' were significant predictors (Odds ratio, 1.296, and 1.370, respectively). Conclusion: In SAD patients without PE, LV diastolic dysfunction and increment of LVMI was closely associated with PH based upon TRV. LAVI and E/E' were independent predictors for PH. Measuring LAVI and E/E' may be a key to determine the mechanism of PH in these patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.