Nobuo Iguchi

Contact Sensitivity to Polychloroparaxylene‐Coated Cardiac Pacemaker

Poly‐chloroparaxylene (parylene) is widely used as a material for cardiac pacemaker coating. Contact sensitivity to parylene was proven by patch test. Wrapping the pacemaker in a polytetrafluoroethylene sheet prior to implantation prevented further skin reactions.

Delayed enhancement cardiovascular magnetic resonance as a novel technique to predict cardiac events in dilated cardiomyopathy patients

PURPOSE Delayed enhancement cardiovascular magnetic resonance (DE-CMR) can detect cardiac scarring and has the potential to visualize the progression of myocardial remodeling. We determined whether DE-CMR can predict cardiac events in dilated cardiomyopathy patients. MATERIALS AND METHODS Transthoracic echocardiography, coronary arteriography, and DE-CMR studies were performed in 60 consecutive dilated cardiomyopathy (DCM) patients. Percent delayed enhancement (%DE) was determined as the ratio of the area showing delayed enhancement to the total myocardial area in three short-axis views. Patients were classified as advanced group (Group A) when %DE was 10% or higher, and as non-advanced group (Group NA) when %DE was less than 10%. The incidence of cardiac events and the clinical history were compared between Group A and Group NA. RESULTS There were 11 patients in Group A and 49 patients in Group NA. The incidence of cardiac events was significantly higher in Group A (36%; 4/11 patients) than in Group NA (2.0%; 1/49 patients) (log rank, p=0.0001). CONCLUSION DE-CMR is a useful tool to predict cardiac events in DCM patients.

Retinoic acid suppresses endothelin-1 gene expression at the transcription level in endothelial cells

Retinoids have been shown to inhibit cell growth, which can result in an anti-atherosclerotic action in the vasculature. Endothelin-1 (ET-1), a potent vasoconstrictor peptide produced in endothelial cells, plays an important role in inducing proliferation of vascular smooth muscle cells. In this study, we investigated the effect of retinoids on the mRNA expression and transcriptional activity of the ET-1 gene in endothelial cells. All-trans retinoic acid (ATRA) suppressed ET-1 mRNA expression in cultured endothelial cells. Synthetic retinoids, Ch55 and Am580 (retinoic acid receptor (RAR) agonists) markedly enhanced this effect, and an RAR antagonist, LE540, blocked this inhibitory effect on ET-1 gene expression. ATRA did not change ET-1 mRNA half-life. Transfection experiments using 5 kb of the ET-1 promoter-reporter gene construct which contains 5 kb of the preproET-1 promoter revealed that ATRA and Ch55 suppressed ET-1 promoter activity, resulting in down-regulation of ET-1 gene transcription. Taken together, retinoids may be another modulator of endothelial cell function through regulation of vasoactive substances at the transcription level.

Evaluation of automated measurement of left ventricular volume by novel real-time 3-dimensional echocardiographic system: Validation with cardiac magnetic resonance imaging and 2-dimensional echocardiography

BACKGROUND Traditional 3-dimensional echocardiography (3DE) with volumetric scanning technique requires several heart cycles for full-volume acquisition and complicated manual contouring of left ventricular (LV) endocardium. The new real-time 3DE (RT3DE) system allows acquisition of an instantaneous full-volume dataset in a single heart cycle and automated measurement of LV volume by the algorithm software. However, it has not been evaluated adequately whether automated measurement by RT3DE has better agreement with cardiac magnetic resonance imaging (CMR) than 2-dimensional echocardiography (2DE) with CMR. PURPOSE This study aimed to evaluate the accuracy of automated measurement of LV volume using RT3DE compared with 2DE and CMR. METHODS AND RESULTS Forty-four consecutive patients who underwent RT3DE, 2DE, and CMR were evaluated in this study. The feasibility of automated measurement by RT3DE was 93.2% and the mean operation time was 6min. LV volume and ejection fraction (EF) from semi-automated measurement [end-diastolic volume: r=0.96, limits of agreement (LOA) -30.5 to 39.3 ml; end-systolic volume: r=0.97, LOA -22.6 to 32.7 ml; EF: r=0.90, LOA -16.1 to 14.2%, respectively] had better agreement with CMR than those from 2DE (r=0.87, LOA -50.5 to 72.2 ml; r=0.93, LOA -34.1 to 65.2 ml; r=0.89, LOA -20.9 to 10.0%, respectively). CONCLUSION Semi-automated measurement by RT3DE has better agreement with CMR than 2DE in LV volume and EF. In addition, it is simple to operate and acceptable in feasibility for the clinical setting although there may be room for further learning required to incorporate small hypertrophic LV into the automated algorithm software.

Heparin Regulates Transcription of Endothelin-1 Gene in Endothelial Cells

Heparin, which is widely used as an anticoagulant, has been shown to have antiatherosclerotic and antihypertensive effects in animals and humans. These effects are mediated by the inhibition of endothelin-1 (ET-1) production in endothelial cells. To clarify the mechanism of this inhibition, we investigated the effect of heparin on transcriptional regulation of the ET-1 gene in bovine aortic endothelial cells (BAEC) cultured in fetal calf serum. ET-1 mRNA expression was significantly suppressed by heparin in a dose-dependent manner. Promoter analysis revealed that the minimum ET-1 promoter containing only the GATA and AP-1 sequences as positive cis-acting sites in the ET-1 promoter is sufficient for this suppression. Gel mobility shift assays using oligonucleotides encoding the ET-1 AP-1 and ET-1 GATA sites confirmed that both AP-1 and GATA binding activities in BAEC nuclear extract were markedly inhibited by heparin. Western blot analyses indicated that heparin completely blocked extracellular signal-regulated kinase (ERK) activation, and inhibiting ERK activity resulted in loss of heparin-dependent inhibition of the ET-1 gene. These data indicate that the ET-1 mRNA level is negatively regulated by heparin at the transcription level, through modification of AP-1 and GATA protein binding activities, which direct the ET-1 promoter in BAEC. This effect may be mediated, at least in part, through inhibition of ERK activity.

Late stent malapposition with marked positive vascular remodeling observed only at the site of drug-eluting stents after multivessel coronary stenting

A 74-year-old woman presented with effort-induced chest pain. Diagnostic coronary angiography revealed three-vessel disease. A successful angioplasty was performed with two sirolimus-eluting stents placed in the left anterior descending artery (LAD) and left circumflex artery (LCX). The right coronary artery (RCA) was treated with a bare-metal stent. Follow-up angiography and intravascular ultrasound (IVUS) assessment were performed 8 months later, which showed late stent malapposition (LSM) with marked positive vascular remodeling around the drug-eluting stents (DES) in both LAD and LCX lesions, but there was no evidence of ectatic area around the BMS in the RCA lesion. Compared with the baseline IVUS, a significant increase in external elastic membrane (EEM) cross-sectional area was found. Twenty-seven months later, we performed repeat follow-up angiography. Intravascular ultrasound still showed vessel malapposition. A previous report showed that aneurysmal dilatation of the stented segment with severe localized hypersensitivity reaction could be a potential cause of late thrombosis after DES implantation. If LSM is related to hypersensitivity of the DES, it may have a potential risk of adverse events. Although there is a paucity of data regarding malapposition as the cause of adverse events, careful long-term follow-up of patients with vessel enlargement after DES placement is recommended.

Impact of Acute Kidney Injury on Early to Long-Term Outcomes in Patients Who Underwent Surgery for Type A Acute Aortic Dissection.

Acute kidney injury (AKI) is relatively common after cardiothoracic surgery for type A acute aortic dissection (TA-AAD) and increases mortality. We investigated the incidence and risk factors for AKI in patients with TA-AAD and its impact on their outcomes. The records of 375 consecutive patients who underwent surgical treatment for TA-AAD from October 2007 to March 2013 were analyzed retrospectively. We defined AKI using the Kidney Disease Improving Global Outcomes criteria, which are based on serum creatinine concentration or glomerular filtration rate. We used Kaplan-Meier methods and multivariate Cox proportional hazards regression to assess the impact of AKI on both mortality and major adverse cardiovascular and cerebrovascular events. We also examined the association between risk factors and AKI using logistic regression modeling. Postoperative AKI was observed in 165 patients (44.0%). The overall 30-day and mid- to long-term mortality was 1.6% and 8.8%, respectively. Mortality and major adverse cardiovascular and cerebrovascular events correlated significantly with the severity of AKI, and multivariate analysis showed that AKI stage 3 (the most sever stage) was an independent risk factor for mortality (hazard ratio 6.83, 95% confidence interval 2.52 to 18.52) after adjustment for important confounding factors. Extracorporeal circulation time, body mass index, perioperative peak serum C-reactive protein concentration, renal malperfusion, and perioperative sepsis were found to be risk factors for AKI. In conclusion, AKI was common in patients who underwent surgery for type A acute aortic dissection. The severity of AKI strongly influences patient outcomes, so it should be recognized promptly and treated aggressively when possible.

Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Japanese Hypertrophic Cardiomyopathy Patients.

BACKGROUND In addition to the presence of late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR), the extent of LGE is considered clinically important in hypertrophic cardiomyopathy (HCM). We evaluated the extent of LGE on CMR in a large series of Japanese HCM patients. METHODSANDRESULTS CMR was performed in 317 HCM patients (147 male). The extent of LGE was scored as the sum of LGE-positive segments in a left ventricle (LV) 17-segment model. LGE was present in 246 patients (77.6%). LGE was detected in 3.5±3.1 segments on average. When the patients were divided according to maximum wall thickness (mild, <20 mm; moderate, 20-29 mm; severe, ≥30 mm), median LGE score increased as wall thickness increased (mild, 2 vs. moderate, 4 vs. severe, 5; P=0.000). When the patients were divided according to ejection fraction (EF) (reduced, <50%; low-normal, 50-65%; normal, >65%), median LGE score increased as EF decreased (reduced, 7 vs. low-normal, 4 vs. normal, 2; P=0.000). On multivariate analysis, reduced EF (OR, 0.947, P=0.015), pressure gradient <30 mmHg (OR, 0.359, P=0.000) and increased maximum wall thickness (OR, 1.236, P=0.000) were independent factors associated with extensive LGE. CONCLUSIONS Progression of LGE was related to increased wall thickness, decreased contractility, and reduced intraventricular pressure gradient.

Impact of Frailty Markers for Unplanned Hospital Readmission Following Transcatheter Aortic Valve Implantation

BACKGROUND Various frailty markers have been developed to guide better patient selection for transcatheter aortic valve implantation (TAVI). This study aimed to investigate the frequency and specific causes of unplanned hospital readmission after TAVI, and to investigate which frailty markers better predicted outcomes.Methods and Results:We retrospectively reviewed 155 patients for whom we calculated their Short Physical-Performance Battery (SPPB), Placement of AoRTic TraNscathetER Valve (PARTNER) frailty scale, frailty index, clinical frailty scale, modified Fried scale, and gait speed. The primary endpoint was unplanned readmission following TAVI. The clinical model was established using variables that were identified as independent predictors in multivariate analysis. Incremental values were assessed after adding each frailty marker to the clinical model, and were compared between frailty markers. Although unplanned readmission <30 days was 1.9%, 23% of patients had an unplanned readmission following TAVI mainly because of heart failure and pneumonia within 1 year. Frailty markers other than the modified Fried scale were independently associated with unplanned readmission. The SPPB and the PARTNER frailty scale significantly increased discriminatory performance for predicting unplanned readmission. CONCLUSIONS Unplanned readmissions following TAVI in the present study were fewer than previously reported. There seems to be a difference between frailty markers in their predictive performance. Precise frailty assessment may result in reducing unplanned admissions after TAVI and therefore better quality of life.

Non-invasive diagnosis of coronary artery disease by 123I-BMIPP/201TlCl dual myocardial SPECT in patients with heart failure

BACKGROUND/OBJECTIVES Detecting the presence of coronary artery disease (CAD) is critically important in managing patients with heart failure of uncertain cause. The recently introduced 123I-BMIPP/201TlCl dual myocardial single-photon emission computed tomography (dual SPECT) is potentially a non-invasive diagnostic tool in detecting ischemic heart disease. The aim of our study is to evaluate the efficacy of detecting CAD by dual SPECT in patients with heart failure. METHODS We studied 501 consecutive patients (366 males, mean age 68±12 years) who were admitted because of heart failure between January 2005 and April 2009. In all patients, the dual SPECT was performed in clinically stabilized states, followed by coronary angiography within 1 week. The polar map of the SPECT image was divided into 17 segments, each scored on a scale of 0-4 based on segmental percent uptake. The mismatch score was defined as the difference between 123I-BMIPP defect score and 201TlCI defect score. The uptake of 201TlCl and 123I-BMIPP was analyzed quantitatively using the Heart Score View software. RESULTS The 201TlCI defect score and mismatch score were significantly higher in CAD patients than in non-CAD patients. The receiver operating characteristic (ROC) curve revealed that the mismatch score was a significantly more effective marker in detecting the presence of CAD than 201TlCl defect score (area under the curve: 0.84 versus 0.73, p<0.05). Using the mismatch score, the sensitivity and specificity of dual SPECT in detecting CAD were 84% and 83%, respectively. CONCLUSION Dual SPECT is a useful non-invasive procedure for the detection of CAD in patients with heart failure.