小林 欣夫

Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.

BACKGROUND: Patient-reported outcomes of implantable cardioverter defibrillator (ICD), such as those with shock anxiety, have emerged as important endpoints that are related to quality of life (QOL), but they have not been well studied in a sample of the Japanese population. Therefore, we prospectively examined changes in shock anxiety in a large sample of Japanese patients with an ICD. METHODS: We recruited 214 consecutive patients with an ICD who visited the outpatient clinic. At registration and 12 months later, all patients completed the Florida Shock Anxiety Scale (FSAS) questionnaire to allow us to examine changes in shock anxiety over the course of the first year after registration. RESULTS: During the 12-month follow-up period, 10.5% of the patients received ICD shock therapy. Female sex, secondary prevention, and experience of ICD shock therapy were associated with high FSAS scores at registration. The FSAS scores in both patients with appropriate and inappropriate shock were significantly higher at the 12-month follow-up interval than at registration, and there was no significant difference in the extent of changes in FSAS scores (Δ = 5.2 ± 5.1 and Δ = 6.3 ± 9.9, respectively, P = 0.62). CONCLUSIONS: Female sex, secondary prevention, and experience of ICD shock therapy are important risk factors affecting shock anxiety in Japanese patients. Attention should be paid to the after-effects of ICD shock in these patients, regardless of the shock type, with particular attention to women and patients who require secondary prevention.

The PRASFIT-ACS study showed the antiplatelet effect 2–4 h after prasugrel loading. However, there is little information about the antiplatelet effect &lt 2 h after prasugrel loading dose, especially in patients with acute coronary syndrome (ACS). There had not been any comparison between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). Fifty patients with ACS (15 with STEMI and 35 with NSTE-ACS) were enrolled. They received a 20-mg prasugrel loading dose followed by a maintenance dose of 3.75 mg. Platelet reactivity [P2Y12 reaction units (PRU)] was evaluated by the VerifyNow assay at baseline, 30 min, 1, 2, 4, and 6 h, 1 week under prasugrel, and at 1 month after switching to clopidogrel. The primary end point was the change of PRU compared to the baseline. Furthermore, PRU after prasugrel loading between STEMI and NSTE-ACS was compared. A significant reduction in PRU from baseline was observed at ≥2 h after administration of prasugrel. In STEMI patients, a significant reduction in PRU was observed at 4 h after prasugrel loading. STEMI patients had higher PRU compared to NSTE-ACS patients at 2, 4, and 6 h after prasugrel loading. Utilizing &gt 208 PRU as a cutoff value, STEMI patients had a higher prevalence of high on-treatment platelet reactivity at 2–6 h and 1 week after loading. Rapid antiplatelet effect is not achieved by low-dose prasugrel loading in STEMI patients. Platelet inhibition occurs earlier in NSTE-ACS patients, although it takes ≥2 h after loading in the majority of patients.

Treating a patient with heparin-induced thrombocytopenia can be challenging particularly when the patient requires urgent cardiac surgery that uses heparin for anticoagulation. We herein report a case of a 61-year-old man with idiopathic dilated cardiomyopathy associated with heparin-induced thrombocytopenia and who underwent plasma exchange to remove heparin-induced thrombocytopenia antibodies before undergoing left ventricular assist device implantation. The surgery was performed using cardiopulmonary bypass and unfractionated heparin.

Introduction: Cardiac implantable electronic devices (CIEDs) can detect atrial fibrillation (AF) early and accurately. Risk factors for the development of new-onset AF in patients with CIEDs remains uncertain. Methods: Patients with CIEDs who visited Chiba University Hospital between January 2016 and December 2016 were enrolled. We only included patients without single chamber CIEDs or a known history of AF. Results: Of 371 patients with CIEDs, 78 (21.0% median age 61.0 years, 65.5% male) developed new-onset AF. Multivariate analysis demonstrated that independent predictors for the development of new or incident AF were age ≥65 years (odd ratio [OR] 2.76, 95% confidence interval [CI] 1.54–4.96, P = 0.001), diabetes mellitus (OR 2.24, 95% CI 1.20–4.19, P = 0.011), congestive heart failure (OR 1.94, 95% CI 1.06–3.54, P = 0.031), and left atrial volume index &gt 34 ml/m2 (OR 3.51, 95% CI 1.96–6.25, P &lt 0.001). Based on these 4 clinical factors (age ≥ 65, diabetes mellitus, congestive heart failure, left atrial volume index &gt 34 ml/m2) there was a good predictive ability for new AF development (AUC 0.728) and clinically usefulness using decision curve analysis. Conclusions: A substantial number of patients with CIEDs develop new-onset AF. Four clinical factors (age ≥ 65, diabetes mellitus, congestive heart failure, left atrial volume index &gt 34 ml/m2) independently predicted new-onset AF and may provide an approach to clinically useful risk assessment for incident AF.

Purpose: Very few studies have investigated the efficacy of ganglionated plexus ablation during the conventional maze procedure. In this study, we sought to evaluate its additive effect in reducing recurrent atrial fibrillation after concomitant maze surgery. Methods: A retrospective study was conducted of 79 patients who underwent Cox maze IV concomitantly with open-heart surgery with (GP group) or without (Maze group) ganglionated plexus mapping. All active ganglionated plexuses were ablated. The two groups were compared and their follow-up data were analyzed. Results: Active ganglionated plexuses were found in 81% of patients who underwent ganglionated plexus mapping. The rates of freedom from atrial fibrillation at 1 year in the GP and Maze groups were 77 and 75%, respectively. The cumulative freedom from atrial fibrillation at follow-up (27.7 ± 17.3 months) was comparable in the two groups (p = 0.427). A multivariate analysis revealed that persistent atrial fibrillation for more than 90 months was an independent predictor of recurrent atrial fibrillation. Conclusion: Ganglionated plexus ablation with Cox maze IV did not reduce the incidence of recurrent atrial fibrillation in comparison to Maze alone.

Forward Projected Model-based Iterative Reconstruction SoluTion (FIRST) is a new reconstruction technique using CT, which provides successful reconstruction of high-quality CT images, especially in low contrast imaging. To evaluate improvements in the diagnostic accuracy of the detection of abnormal late enhancement (LE) in left-ventricular myocardium (LVM) using 320-slice CT with FIRST, we compared this modality with previous CT methods in patients with non-ischemic cardiomyopathy or a cardiac tumor. This was a retrospective study of 88 patients (56 males 57 ± 15 years) suspected of having non-ischemic myocardial disease or a cardiac tumor. The first 52 consecutive patients (Group 1) underwent 16-slice CT at 140 kV tube voltage and an average tube current of 337 ± 20 mA, and 1.5 T MRI. The next 18 patients (Group 2) underwent 1st generation 320-slice CT at 120 kV tube voltage and an average tube current of 255 ± 106 mA, and 1.5T MRI the remaining 18 patients (Group 3) underwent 2nd generation 320-slice CT with FIRST, at 80 kV tube voltage and a tube current of 800 mA, and 1.5T or 3T MRI. On patient-based analysis, no significant differences were observed between the 3 groups. For segment-based analysis, the specificity and overall accuracy were significantly higher (both P &lt 0.05) in Group 3 than in Group 1. Positive predictive value (PPV) was significantly higher in Group 3 than in Groups 1 and 2. The diagnostic accuracy of LE on CT for detecting myocardial fibrosis determined by late gadolinium-enhanced MRI was improved with the use of 2nd generation 320-slice CT with FIRST, in particular regarding specificity, PPV, and overall accuracy. (Int Heart J 2018 59: 542-549)

To achieve further risk stratification in hypertrophic cardiomyopathy (HCM) patients, we localized and quantified layer-specific LVM fibrosis on MRI in HCM patients using regional layer-specific peak longitudinal strain (PLS) and peak circumferential strain (PCS) in LV myocardium (LVM) on speckle tracking transthoracic echocardiography (TTE). A total of 18 HCM patients (14 males 58 ± 17 years) underwent 1.5T-MRI and TTE. PLS and PCS in each layer of the LVM (endocardium, epicardium, and whole-layer myocardium) were calculated for 17 AHA-defined lesions. MRI assessment showed that fibrosis was classified as endocardial, epicardial, or whole-layer (= either or both of these). Regional PLS was smaller in fibrotic endocardial lesions than in non-fibrotic endocardial lesions (P = 0.004). To detect LV endocardial lesions with fibrosis, ROC curves of regional PLS revealed an area under the curve (AUC) of 0.609 and a best cut-off point of 13.5%, with sensitivity of 65.3% and specificity of 54.3%. Regional PLS was also smaller in fibrotic epicardial lesions than in non-fibrotic epicardial lesions (P &lt 0.001). To detect LV epicardial lesions with fibrosis, ROC curves of PLS revealed an AUC of 0.684 and a best cut-off point of 9.5%, with sensitivity of 73.5% and specificity of 55.5%. Using whole-layer myocardium analysis, PLS was smaller in fibrotic lesions than in non-fibrotic lesions (P &lt 0.001). To detect whole-layer LV lesions with fibrosis, ROC curves of regional PLS revealed an AUC of 0.674 and a best cut-off point of 12.5%, with sensitivity of 79.0% and specificity of 50.7%. There were no significant differences in PCS of LV myocardium (endocardium, epicardium, and whole-layer) between fibrotic and non-fibrotic lesions. Quantitative regional PLS but not PCS in LV endocardium, epicardium, and whole-layer myocardium provides useful non-invasive information for layer-specific localization of fibrosis in HCM patients.

Aims: Shortening of the atrial-His bundle (AH) interval during the sinus rhythm is occasionally observed after slow pathway ablation for atrioventricular nodal re-entrant tachycardia (AVNRT). In addition, high-rate atrial pacing is useful for avoiding atrioventricular block. We hypothesized that shortening of the AH interval during slow pathway ablation under high-rate atrial pacing would lead to successful ablation of typical AVNRT. Methods and results: This retrospective study included 37 patients in whom successful ablation of typical AVNRT was performed under atrial pacing. The AH interval was measured immediately before the first radiofrequency (RF) application and immediately after the last RF application, prior to the first induction. Twenty-five of 37 patients achieved procedural success at the first induction (i.e. successful group). No patients developed a prolonged AH interval or atrioventricular block. The AH interval was shortened by an average of 14.6 ± 7.7 and 1.8 ± 1.2 ms in the successful and other patient groups, respectively (P < 0.01). An AH interval decrease of > 10 ms was observed in 23 of 27 (85%) patients in the successful group, whereas all other patients had an AH interval decrease of < 5 ms. Conclusion: Shortening of the AH interval during high-rate atrial pacing is a predictor of the successful ablation for typical AVNRT.

We used peak longitudinal strain (PLS) on TTE in HCM patients to differentiate LV myocardium (LVM) into the following 4 groups: group 1—no fibrosis or hypertrophy (≥ 13 mm), group 2—no fibrosis but hypertrophy evident, group 3—fibrosis present but without hypertrophy, and group 4—both fibrosis and hypertrophy. Seventeen HCM patients (13 males, 56 ± 16 years) underwent both 1.5 T CMR and TTE. On TTE, PLS (absolute values) for each LVM segment from 17 AHA-defined lesions was calculated. Of 289 LVM lesions, the numbers in each group, 1–4, were 156, 53, 39, and 41, respectively. PLS for LVM segments in group 1 (13.6 ± 6.4%) were significantly greater than those in group 2 (8.5 ± 4.9%, P &lt 0.001), group 3 (10.4 ± 5.0%, P = 0.006), and group 4 (7.1 ± 4.4%, P &lt 0.001). PLS for LVM segments in group 3 was significantly greater than those in group 4 (P = 0.016). However, significant differences in PLS in LVM between groups 2 and 3, and between 2 and 4 were not observed. Using regional PLS, we demonstrate successful differentiation of LVM in HCM patients for group 1 (LVM with zero fibrosis or hypertrophy) from LVM belonging to groups 2–4 and we also demonstrate successful differentiation of LVM with fibrosis present but without hypertrophy from LVM with both fibrosis and hypertrophy. However, it is not possible to differentiate between LVM with no fibrosis but hypertrophy evident and those with fibrosis present but without hypertrophy and also between LVM with no fibrosis but hypertrophy evident and those with both fibrosis and hypertrophy. Our findings have significant implications for the management of HCM patients.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. Although outpatient coronary angiography has been widely performed in current clinical settings, the feasibility and safety of ACh provocation test in outpatient services are unclear. A total of 323 patients, who electively underwent ACh provocation test in hospitalization and outpatient services, were included. Coronary angiography was performed after insertion of a temporary pacing electrode in the right ventricle. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing accompanied by chest pain and/or ischemic electrocardiographic changes. Cardiac complications defined as composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock, and cardiac tamponade, were evaluated. There were 201 patients (62%) in the hospitalization group and 122 patients (38%) in the outpatient group. The incidence of positive ACh provocation test was similar between the 2 groups (47 vs. 54%, p = 0.21). Coronary angiography in the outpatient group was performed through the radial artery, mostly (98%) with a 4 F sheath. Venous access site was not significantly different between the 2 groups, and the sheath size was 5 F in all cases. There were 2 cases (1.0%) of cardiac complications in the hospitalization group, whereas 1 case (0.8%), which led to unexpected hospitalization, occurred in the outpatient group. In conclusion, intracoronary ACh provocation test for the diagnosis of vasospastic angina in outpatient services was feasible and safe in selected patients.

Background: Cardiovascular surgery is one of the highest risk procedures in the field of surgery. Preoperative assessment of endothelial function has been reported as useful for predicting postoperative adverse events (AEs). The aim of this study was to investigate the relationship between endothelial function assessed by reactive hyperemia index (RHI) and AEs after cardiovascular surgery. Methods and Results: A prospective observational study of 197 patients who underwent cardiovascular surgery was conducted. RHI was measured before the surgery. The primary endpoint was a composite of postoperative death, reoperation, stroke, newly required dialysis, deep sternum infection, and prolonged ventilation within 30 days. The secondary endpoint was new-onset atrial fibrillation (AF) within 30 days. Following cardiovascular surgery, 19 patients (9.6%) had AEs. New-onset AF was documented in 42 (25.9%) of 162 patients without a prior history of AF. In the receiver-operating characteristic curve analysis, RHI significantly predicted AEs (area under the curve [AUC] 0.67, best cutoff value 1.64, P=0.03), whereas RHI did not predict new-onset AF (AUC 0.53, P=0.93). Patients with RHI ≤1.64 had more AEs than those with RHI &gt 1.64 (16.3% vs. 4.5%, P=0.005). Multiple logistic regression analysis showed the number of surgical procedures and RHI ≤1.64 as significant predictors of AEs. Conclusions: Preoperative endothelial dysfunction assessed by RHI was associated with postoperative AEs in patients with cardiovascular surgery.

Augmentation index (AIx) and pulse pressure (PP) amplification can be determined by the SphygmoCor XCEL device in an operator-independent manner. This study aimed to examine its validity against invasive measurements. Simultaneous recordings of central aortic pressure waveforms were performed with oscillometric and high-fidelity invasive methods in 35 patients who underwent coronary arteriography. Brachial blood pressure was also recorded using the two methods. AIx for the aortic pressure waveform was defined as the ratio of augmentation pressure to PP. PP amplification was defined as the ratio of brachial PP to aortic PP. The differences between the invasive and oscillometric measurements were-7.7±12.7% for AIx and 0.17±0.14 for PP amplification (mean±s.d.). Strong correlations between the invasive and oscillometric measurements were found in both indices (AIx: R=0.75 PP amplification: R=0.80 both P&lt 0.001). The Bland-Altman plot showed a proportional bias of PP amplification, but not of AIx (AIx: R=-0.21, P=0.23 PP amplification: R=-0.61 P&lt 0.001). In conclusion, estimated AIx may be reliable considering the high correlation between the invasive and noninvasive values and the lack of proportional bias against invasive assessment. However, a substantial underestimation and a large scatter of estimated AIx were also observed. Further studies using the device to investigate associations with target organ damage or prognoses are needed to clarify its clinical validity.

Objective: To investigate the relationship between 1-h post-load plasma glucose, measured during an oral glucose tolerance test, and arterial stiffness, determined by brachial–ankle pulse-wave velocity, in normotensive subjects with normal glucose tolerance. Methods: Study subjects were non-industrial workers aged 25–55 years (n = 8381) who underwent a regular health check-up every 5 years. We included only normotensive subjects with normal glucose tolerance based on the American Diabetes Association criteria. Subjects taking medication and having an abnormal ankle–brachial index (⩽1.0 or ⩾1.3) were excluded. The final sample comprised 4970 participants (mean age: 38.8 ± 9.4 years women: n = 2048). Results: 1-h post-load plasma glucose correlated with brachial–ankle pulse-wave velocity in men (β = 0.04, p = 0.01), but not women (β = –0.03, p = 0.13) in multivariate linear regression analysis. We found a significant interaction between 1-h post-load plasma glucose and age in men (p = 0.04) therefore, a subgroup analysis was performed in each 5-year age group. The correlation between 1-h post-load plasma glucose and brachial–ankle pulse-wave velocity was significant in the 55-year-old age group (β = 0.12, p = 0.01) and neared significant in 45-year-old (β = 0.08, p = 0.07) and 50-year-old (β = 0.09, p = 0.07) age groups. Conclusion: Elevated 1-h post-load plasma glucose levels were associated with arterial stiffness in normotensive, middle-aged men with normal glucose tolerance.

Background The aim of this study was to investigate microvascular function in patients with valvular heart disease (VHD), which causes chronic left ventricular volume and/or pressure overload, therefore change in coronary microvascular hemodynamics. Patients and methods We prospectively enrolled 30 patients with VHD considered for surgery (10 aortic stenosis, 12 aortic regurgitation, and eight mitral regurgitation) and 30 controls. Intracoronary physiological assessments were performed in the unobstructed left anterior descending artery using a pressure-temperature sensor guidewire at rest and hyperemia. Results The index of microcirculatory resistance (IMR) was similar between the two groups (16.2 ± 6.5 vs. 16.2± 8.5, P=0.997), whereas coronary flow reserve (CFR) was lower in the VHD group compared with the controls (3.2 ± 1.4 vs. 4.3± 1.7, P=0.005). Resting and hyperemic coronary distal pressure, and hyperemic mean transit time were similar between VHD and controls, whereas resting mean transit time was significantly shorter (0.70±0.29 vs. 0.89± 0.39, P=0.035) and baseline resting microvascular resistance was significantly lower in the VHD group compared with the controls (58.1± 25.4 vs. 78.1± 36.7, P=0.011). Patients with aortic stenosis showed numerically higher IMR values than aortic regurgitation, mitral regurgitation, and controls, although this was not statistically significant (20.4 ± 6.9, P=0.14). CFR was significantly correlated with log highsensitivity cardiac troponin T levels in patients with VHD (r=-0.523, P=0.004). Conclusion CFR was reduced in patients with VHD compared with controls, despite similar microvascular function as assessed by IMR. This appeared to be mainly because of an increased resting coronary flow accompanied by a decreased resting coronary microvascular resistance rather than microvascular disease.

Background: Atrial fibrillation (AF) is the most common arrhythmia in the ageing population in East Asia. Silent cerebral infarction (SCI) is defined as cerebral infarction in the absence of corresponding clinical symptoms, and is a highly prevalent and morbid condition in AF. SCI is increasingly being recognized as a risk factor for future stroke, which can lead to cognitive decline or dementia. The latter is an increasingly common health problem in East Asia. Methods and Results: We conducted a meta-analysis to compare the association of AF and SCI between East Asian and non-Asian patients. AF was associated with SCI in patients with no symptomatic stroke history (relative risk [RR], 2.24 95% CI: 1.26–3.99, I2=83% P=0.006) although the prevalence varied widely between studies (P for heterogeneity&lt 0.001). In non-Asian patients, the prevalence of SCI in AF is higher than that in controls (RR, 1.85 95% CI: 1.65–2.08, I2=17% P&lt 0.001). There was no significant racial difference between Asian and non-Asian studies (P=0.53). Conclusions: In East Asia, AF was significantly associated with SCI and no racial difference was seen between East Asian and non-Asian patients. The present findings offer clinicians new insights into the association between AF and SCI.

Peak longitudinal strain (PLS) of the left ventricular (LV) myocardium by transthoracic echocardiogram (TTE) is useful to detect LV myocardial damage. We hypothesized that myocardial fibrosis (MF) in the LV myocardium may influence PLS. Eighteen hypertrophic cardiomyopathy (HCM) patients (14 males 58 ± 17 years old) underwent 1.5 Tesla cardiac magnetic resonance (CMR) and TTE. Patients with previous myocardial infarction were excluded. We used TTE to assess whole-layer PLS in an American Heart Association-defined 17-segment LV model. Whole-layer PLS was calculated using Echo PAC, version 113 (GE Healthcare). MF was assessed by T1-weighted CMR of the LV endocardial layer, the LV epicardial layer, or both the LV endocardial and epicardial layers for each lesion. Of the 306 segments, MF was detected in the LV endocardial layer only (13 segments), in the LV epicardial layer only (9 segments), or in both LV endocardial and epicardial layers (59 segments). PLS values were significantly lower in segments with MF affecting only the LV endocardial layer (7% ± 4%) (P &lt 0.05) and where MF was observed in both the LV endocardial and epicardial layers (9% ± 5%) (P = 0.001) compared with segments without MF (13% ± 7%). No significant difference in PLS values was detected between the MF segments for the LV epicardial layer only (10% ± 6%) and those without MF (13% ± 7%) (P &gt 0.05). In HCM patients, fibrotic lesions in the LV endocardium have a greater adverse effect on PLS than those in the LV epicardium. Our results are significant for HCM patients with fibrotic lesions within the LV endocardium.

OBJECTIVE: Although severe obstructive sleep apnea (OSA) is an important risk factor for atherosclerosis-related diseases including coronary artery disease (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This study aimed to test our hypothesis that circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the prevalence of CAD in patients with OSA. METHODS: Eighty-two adults diagnosed with OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled. Serum samples were collected from patients with OSA at diagnostic polysomnography and from patients with ACS at disease onset. Serum NBL1-Ab level was measured by amplified luminescence proximity homogeneous assay and its association with clinical variables related to atherosclerosis was evaluated. RESULTS: NBL1-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was markedly higher in patients with severe OSA and OSA patients with a history of CAD. Weak associations were observed between NBL1-Ab level and apnea-hypopnea index, age, mean SpO2 and arousal index, whereas significantly higher NBL1-Ab levels were observed in OSA patients with a history of CAD than in those without a history of CAD. Sensitivity analysis using a logistic regression model also demonstrated that increased NBL1-Ab levels were associated with the previous history of CAD in patients with OSA. CONCLUSIONS: Elevated NBL1-Ab levels may be associated with the prevalence of CAD in patients with OSA, which needs to be confirmed further.

The cutdown technique for the cephalic vein is a common access route for transvenous cardiac device leads (TVLs), and sometimes one cephalic vein can accomodate two TVLs. We examined a novel ligation technique to balance the hemostasis and lead maneuverability for this two-in-one insertion. A total of 22 patients scheduled for cardiac device implantations with two or more leads were enrolled. The ipsilateral cephalic vein was identified for inserting the TVLs with a cutdown. If two TVLs could be introduced into one cephalic vein, hemostasis was established by ligating the venous wall between the TVLs. We measured the amount of hemorrhaging per minute and the operators assessed the lead maneuverability before and after the ligation. We successfully implanted cardiac devices in 15 patients (68%) with this novel method, whereas only one TVL could be introduced via the cephalic vein in 7 patients. As for the successful patients, hemorrhaging from the gap was significantly reduced (5.6 ± 7.3 to 0.41 ± 0.36g/min, p = 0.016) after the novel ligation. The lead maneuverability was well maintained so there was no difficulty placing the leads into the cardiac chambers in all cases. No major complications were observed. In the present study, the novel ligation method provided significant hemostasis as well as a preserved maneuverability. It could be an optional choice for insertion of multiple TVLs.

Background: Myocardial bridge (MB) has been reported to induce cardiac complications including coronary vasospasm. Although MB has some anatomical and morphological variations, the association of these variations with vasospasmis unclear. The aim of this study was to investigate the relation between morphological severity of MB and vasospasm induced by acetylcholine (ACh) provocation test. Methods: A total of 392 patients without coronary stent in the left anterior descending artery (LAD) undergoing intracoronary ACh provocation test were included. Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. MB was identified on coronary angiography as a milking effect. Total bridged length and maximum percent systolic compression of MB in the LAD were analyzed quantitatively. Results: MBs in the LAD were identified in 140 patients (36%), mostly in the mid segment. Patients with MB in the LAD had greater number of provoked vasospasm in the LAD and positive ACh provocation test compared to those without. The bridged length positively correlated with percent systolic compression of MB (r=0.37, p &lt; 0.001). In the receiver operating characteristic curve analysis, both bridged length and percent systolic compression of MB significantly predicted the provoked LAD spasm (AUC 0.74, p &lt; 0.001, and AUC 0.68, p &lt; 0.001). Multivariate regression analysis demonstrated these factors as independent predictors for provoked LAD spasm. Conclusion: MB, especially morphologically severe MB, may induce greater coronary vasospasm. (C) 2017 Elsevier B.V. All rights reserved.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are hypoglycemic agents. DPP-4 inhibitor has cardioprotective effects after transverse aortic constriction (TAC), but role of DPP-4 on cardiac fibrosis after TAC is not well known. Our aim was to determine the effects of DPP-4 on cardiac fibrosis in murine TAC model. Wildtype mice and DPP-4 knockout mice were subjected to TAC. Wild-type mice were then treated with vehicle or DPP-4 inhibitor. DPP-4 activities in serum and heart tissue were significantly increased at 2 weeks after TAC, but they were significantly decreased by DPP-4 inhibitor treatment. The inhibition of DPP-4 did not affect left ventricular hypertrophy, but improved cardiac function and decreased myocardial and perivascular fibrosis after TAC. The inhibition of DPP-4 decreased the collagen type III/I ratio in myocardium. These results suggest that DPP-4 inhibition ameliorates the progression of heart failure after TAC by changing the quality and quantity of cardiac fibrosis. (c) 2017 The Authors. Production and hosting by Elsevier B.V.

Background: Prevalence of myocardial bridging of the left anterior descending coronary artery (LAD) in patients with takotsubo syndrome (ITS) has been demonstrated. However, the impact of myocardial bridging on in-hospital outcome has not been fully evaluated. Methods: A total of 144 consecutive patients with TTS were enrolled. Coronary angiography and left ventriculography were performed in all patients and absence of obstructive coronary disease explaining the left ventricular contraction abnormality was confirmed. Myocardial bridging was diagnosed when a dynamic compression in systole, so-called "milking effect", was observed in the LAD. We evaluated differences in the clinical characteristics and in-hospital outcome between patients with and without myocardial bridging. Furthermore, multiple logistic regression analysis was performed to predict in hospital death. Results: Myocardial bridging was observed in 33 patients (23%). In-hospital death was more frequent in patients with myocardial bridging (21% vs. 6%, p = 0.02), which was due mainly to a higher non-cardiac death in those patients (15% vs. 5%, p = 0.049). Multiple logistic regression analysis demonstrated myocardial bridging (odds ratio = 12.0, 95% CI = 2.52-78.5, p &lt; 0.01) as one of the independent predictors of in-hospital death. Conclusion: Myocardial bridging is an independent predictor of in-hospital death in patients with TTS. (C) 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

【緒言】完全房室ブロックを呈するリウマチ性心炎は稀であり、限局的な心筋炎所見を呈したリウマチ性心炎は報告がない。心臓MRIにて炎症部位を同定しえた症例を経験したので報告する。【症例】10歳女児。先行する感冒症状に続き失神発作が出現し入院となった。心電図波形は完全房室ブロックであり、心臓超音波検査で心室中隔に局所的な壁運動低下部位を認めた。A群β溶血連鎖球菌抗原迅速キット陽性、ASO296IU/mLであり、完全房室ブロックを併発したリウマチ性心炎と診断した。一時ペーシング、大量ガンマグロブリン静注、ステロイド、ACE阻害剤、およびアンピシリン投与を行った。入院翌日には洞調律となり、同29日目に軽快退院した。同10日目の心臓MRIで心室中隔基部に限局的なT2高信号を示す領域を認めた。発症から8ヵ月後の心臓MRIでは異常所見は消失しており、遅延造影でも同様に異常は見られなかった。【考察】心室中隔基部はHis束の走行部位であり、同部位の限局的な炎症により完全房室ブロック主体のリウマチ性心炎を発症したと考えた。同部位に発生した心臓腫瘍でも同様に完全房室ブロックを起こした症例が報告されており、炎症の部位によってはリウマチ性心炎でも完全房室ブロックの所見を呈することがあると考えられる。リウマチ性心炎の炎症部位の同定には心臓MRIが有用であった。(著者抄録)

The difference in the intraluminal intensity of blood speckle (IBS) on integrated backscatter-intravascular ultrasound (IB-IVUS) across a coronary artery stenosis (i.e., Delta IBS) has previously shown a negative correlation with fractional flow reserve, reflecting an impaired coronary blood flow. Periprocedural myocardial injury (PMI) after coronary stenting has also been associated with coronary circulatory dysfunction. The aim of this study was to investigate the relation between Delta IBS after coronary stenting and PMI. A total of 180 patients who underwent elective coronary stenting under IVUS guidance for a single lesion were included. Intraluminal IBS was measured using IB-IVUS in cross sections at the ostium of the target vessel and at the distal reference of the stent. Delta IBS was calculated as (distal IBS value) (ostium IBS value). PMI was defined as an elevation of troponin I &gt;5 times the 99th percentile upper reference limit (&gt;0.45 ng/ml) within 24 hours after the procedure. The mean Delta IBS after coronary stenting was 6.52 +/- 5.71. There was a significantly greater use of the rotational atherectomy, the number of stents, the total stent length, and RIBS in patients with PMI than those without. In the receiver operating characteristic curve analysis, AIM significantly predicted PMI (area under the curve 0.64, best cut-off value 7.88, p = 0.001). Multiple logistic regression analysis determined that the total stent length, the use of rotational atherectomy, and Delta IBS were independent predictors of PMI. In conclusion, greater Delta IBS assessed by IB-IVUS was significantly associated with PMI after coronary stenting in patients with a stable coronary artery disease. (C) 2017 Elsevier Inc. All rights reserved.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor. Immunocytochemistry of vascular endothelial (VE-) cadherin showed that jagged VE-cadherin staining pattern induced by hypoxia was restored by treatment with Diprotin A. The increased level of cleaved beta-catenin in response to hypoxia was significantly attenuated by Diprotin A, suggesting that DPP-4 inhibition protects endothelial adherens junctions from hypoxia. Subsequently, we found that Diprotin A inhibited hypoxia-induced translocation of NF-kappa B from cytoplasm to nucleus through decreasing TNF-alpha expression level. Furthermore, the tube formation assay showed that Diprotin A significantly restored hypoxia-induced decrease in number of tubes by HUVECs. These results suggest that DPP-4 inhibitior protects HUVECs from hypoxia-induced barrier impairment. (C) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. However, paroxysmal atrial fibrillation (AF) often occurs during intracoronary ACh provocation test, leading to disabling symptoms. The aim of this study was to investigate the incidence and predictors of paroxysmal AF during the test. A total of 377 patients without persistent AF who underwent intracoronary ACh provocation test were included. Paroxysmal AF during ACh provocation test was defined as documented AF on electrocardiogram during the procedure. There were 31 patients (8%) with paroxysmal AF during the test. Of these, 11 (35%) required antiarrhythmic drugs, but none received electrical cardioversion. All of them recovered sinus rhythm within 48 h. At procedure, paroxysmal AF occurred mostly during provocation for the right coronary artery (RCA) rather than for the left coronary artery (LCA) (90 vs. 10%). Multivariate logistic regression analysis demonstrated that a history of paroxysmal AF (OR 4.38 CI 1.42-13.51, p = 0.01) and body mass index (OR 0.88 CI 0.78-0.99, p = 0.03) were independent predictors for occurrence of paroxysmal AF during intracoronary ACh provocation test. In conclusions, paroxysmal AF mostly occurs during ACh provocation test for the RCA, especially in patients with a history of paroxysmal AF and lower body mass index. It may be better to initially administer intracoronary ACh in the LCA when the provocation test is performed.