永井 良三

【背景】循環器分野における音声認識技術の有効性の検討やシステムを比較した研究は少ない．【方法】連続293例のホルター心電図（AECG）に対し，音声認識ソフトウェアを用いて判読レポート作成を行った．基本アプリケーションは共通（AmiVoice Ex7）とし，音声入力法として，ハンドマイク（HM）またはヘッドセット（HS）を選択した．音声認識に使用する語彙データベースとして，前者には循環器用語の変換能を強化した電子辞書，後者には一般辞書を用いた．手法ごとにレポート作成の所要時間などを比較した．【結果】HM群（140例）よりもHS群（153例）ではレポート作成時間が短く（615.5秒 vs. 516.0秒，p=0.001），有意所見が増加しても同傾向は維持された．【結語】HSおよび循環器用語の変換に優れた音声認識ソフトウェアを用いたシステムは，AECGレポート作成に際し，作成時間短縮などの時間効率に優れたハンズフリー環境を提供することが示唆された．

71歳，男性．30歳ごろより糖尿病(diabetes mellitus；DM)として加療中であり，感音性難聴の出現時に精査されミトコンドリア遺伝子異常を指摘された．心エコーでは，当初左室肥大を示すのみであったが，2009年ごろより左室駆出分画率(left ventricular ejection fraction；LVEF)低下も出現し，薬物治療が開始された．冠動脈病変はなく，心筋生検はミトコンドリア心筋症に矛盾しない所見であった．うっ血性心不全による入退院を繰り返し，2011年初頭にはβ遮断薬増量のためと考えられる洞機能障害が顕在化した．薬剤抵抗性のNYHA(New York Heart Association)クラスⅢの心不全であり，QRS幅160ms(完全右脚ブロック)，LVEF 27％であったことから心臓再同期療法(cardiac resynchronization therapy；CRT)適応ありと判断した．経静脈的リード留置術後，著明な自覚症状改善に加えて左室腔の縮小，LVEFの改善を認めた．現在までに難聴・糖尿病を呈するミトコンドリア病(maternally inherited deafness and diabetes；MIDD)に対するCRT適用の報告は見当たらず，一連の臨床経過に文献的考察を加えて報告する．

Hypervolemic hyponatremia is often complicated with advanced heart failure together with increased excretion of sodium by diuretics. Tolvaptan, an oral vasopressin-2-receptor antagonist, has been previously reported to improve congestion and correct hyponatremia through increased excretion of free water. However, there is little evidence concerning the administration of tolvaptan in patients with stage D heart failure. We experienced 2 patients with stage D heart failure who received 3.75 mg/day of tolvaptan to correct hyponatremia before ventricular assist device implantation. It may be useful, even for patients with stage D heart failure, to administer a low dose of tolvaptan to treat hyponatremia before ventricular assist device implantation to avoid a drastic alteration in serum sodium concentration perioperatively.

BACKGROUND: Patients with biventricular assist device (BiVAD) placement have a poor prognosis, but preoperative risk factors for the necessity of BiVAD have not been fully elucidated. METHODS AND RESULTS: Data from 79 patients who received left ventricular assist device (LVAD) between November 2002 and December 2011 were retrospectively reviewed. Overall, 9 patients (11.4%) required BiVAD, and the survival rate of BiVAD patients was significantly lower than that of LVAD patients (P<0.001). Multivariate analysis for BiVAD requirement showed left ventricular diastolic diameter (LVDd) ≤62 mm (odds ratio [OR], 10.97; P=0.009) to be significantly associated with BiVAD requirement. Preoperative central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio ≥0.5 (OR, 13.09; P=0.028) was also significantly associated with BiVAD requirement. A new scoring system for predicting BiVAD requirement was created from the combination of CVP/PCWP ratio (≥0.5), body surface area (≤1.4 m(2)), preoperative continuous hemodiafiltration use, B-type natriuretic peptide (≥1,200 pg/ml) and LVDd (≤62 mm), and this had a significantly larger area under the curve (0.909; P=0.003) than right ventricular stroke work index on receiver operating characteristic analysis. A score >20 using the new scoring method indicated significantly high probability of BiVAD requirement (OR, 16.00; P=0.019). CONCLUSIONS: The new scoring method, which includes CVP/PCWP ratio, is a novel risk stratification tool for BiVAD therapy.

We report on a 64-year-old female patient who underwent cardiac surgery for left atrial myxoma, using the superior septal approach with large atrial septal wall resection and patch closure. The superior septal approach is reported to be a relatively safe method for preventing the development of sinus node dysfunction after cardiac surgery. However, this patient developed sinus node dysfunction after surgery and required the implantation of a permanent pacemaker. Moreover, in this case, determining the appropriate positions of the pacemaker leads was difficult because of the presence of a large conduction delay in the interatrium. Selecting the appropriate atrioventricular delay settings was important in order to achieve proper sequential contractions between the left atrium and the left ventricle. © 2012 Japanese Heart Rhythm Society.

Rapid measurement of B-type natriuretic peptide (BNP) plays a practical role in the diagnosis of congestive heart failure. Analytical evaluation of a new small-footprint immunochromatography reader of BNP (Rapidpia®) was performed and compared with the commercially available SHIONOSPOT® Reader as the index. The new BNP assay had a within-run coefficient of variation (CV) of 9.0% and a between-run CV of 2.1%. Correlations between whole blood and plasma samples and those with the index SHIONOSPOT® Reader were y = 0.93x + 0.88, R2 = 0.98 and y = 1.08x - 6.67, R2 = 0.93, respectively. Based on our findings, the two point-of care (POC) assays for BNP, Rapidpia® and SHIONOSPOT® Reader, showed comparable results.

Malignancy is not uncommon with immunosuppressive therapy, but pancreatic cancer is infrequently complicated in recipients of heart transplantation. Here we report a transplant case diagnosed with pancreatic cancer 4 years and 8 months after the heart transplantation. We changed the immunosuppressive regimen after the malignancy was detected, and administered everolimus along with chemotherapy using S-1, an oral fluoropyrimidine prodrug. The patient lived for 8 months after the diagnosis, and received metallic stenting for the biliary and duodenal obstruction. Also, to the best of our knowledge, this is the first report about chemotherapy and endoscopic intervention for pancreatic cancer in a heart transplantation patient.

Cytomegalovirus (CMV) infection remains a major problem in recipients with heart transplantation (HTx), because it may play a significant role in the development of cardiac allograft vasculopathy, which is one of the major causes of death after HTx. Valganciclovir (VGC) is effective for the treatment of CMV infection, but is often associated with neutropenia, especially when used with mycophenolate mophetil (MMF). We experienced an HTx recipient with positive CMV antigenemia who suffered progressive neutropenia after administration of VGC. We switched MMF to everolimus (EVL) and assay for CMV antigenemia was constantly negative even after discontinuation of VGC. In all other 14 HTx recipients who received EVL for any reason, we found that assay for CMV antigenemia remained negative throughout the period of EVL administration. Considering the prophylactic effect on CMV, EVL can not only be an alternative to rescue from comorbidity, but might also be indicated earlier especially in CMV-seronegative HTx recipients.

The purpose of this study was to investigate the precise pattern of stroke volume (SV) response during exercise in patients with chronic heart failure (CHF) compared with age-matched controls. Fourteen patients with CHF and 7 controls performed symptom-limited bicycle exercise testing with respiratory gas exchange measurement. Patients were classified into group A (n = 7) with peak VO2 ≥ 18.0 mL/kg/minute and group B (n = 7) with peak VO2 < 18.0 mL/kg/ minute. SV and cardiac output (CO) were continuously measured during exercise using a novel thoracic impedance method (Physioflow). CO and SV were lower in the group B patients than those in controls at peak exercise [CO: 11.3 ± 1.0 (SE) versus 15.6 ± 0.9 L/minute, P < 0.05, SV: 89 ± 6 versus 110 ± 6 mL, P < 0.05]. SV reached its peak levels during submaximal exercise and remained close to the peak value until peak exercise in 6 of 7 group B patients (86%). On the other hand, it progressively increased until peak exercise in 6 of 7 controls (86%) and 5 of 7 group A patients (71%). In all subjects, CO at peak exercise was more closely correlated with SV at peak exercise (r = 0.86, P < 0.001) than with peak heart rate (r = 0.69, P < 0.001). CHF patients with impaired exercise capacity had attenuated increment of CO during exercise, and SV reached its peak levels during submaximal exercise.

BACKGROUND: Inflammation plays a key role in neointimal hyperplasia after an arterial injury. Chronic infectious disorders, such as periodontitis, are associated with an increased risk of cardiovascular diseases. However, the effects of a periodontal infection on vascular remodeling have not been examined. We assess the hypothesis that periodontal infection could promote neointimal formation after an arterial injury. METHODS: Mice were implanted with subcutaneous chambers (n = 41). Two weeks after implantation, the femoral arteries were injured, and Porphyromonas gingivalis (n = 21) or phosphate-buffered saline (n = 20) was injected into the chamber. The murine femoral arteries were obtained for the histopathological analysis. The expression level of mRNA in the femoral arteries was analyzed using quantitative reverse transcriptase polymerase chain reaction (n = 19-20). RESULTS: The intima/media thickness ratio in the P. gingivalis infected group was found to be significantly increased in comparison to the non-infected group. The expression of matrix metalloproteinase-2 mRNA was significantly increased in the P. gingivalis infected group compared to the non-infected group. CONCLUSION: These findings demonstrate that P. gingivalis injection can promote neointimal formation after an arterial injury. Periodontitis may be a critical factor in the development of restenosis after arterial intervention.

A 60-year-old man with severe heart failure underwent an orthotopic heart transplant. Maintenance immunosuppression consisted of a calcineurin inhibitor, mycophenolate mofetil (MMF), and a glucocorticoid. Six months after the transplantation, coronary angiography (CAG) and intravascular ultrasound sonography (IVUS) showed rapidly progressive cardiac allograft vasculopathy (CAV) along with acute cellular rejection. Methylprednisone pulse therapy resulted in the resolution of acute rejection. MMF was exchanged for everolimus (EVL) and 6 months after EVL therapy, CAG and IVUS revealed the regression of CAV. EVL can improve established CAV as well as prevent the progression of CAV.

ONO-1301MS is a compound that acts as a prostacyclin agonist with thromboxane A2 synthase inhibitory activity. We investigated the effect of ONO-1301MS on myocardial remodeling in murine cardiac allografts. The hearts of Balb/c mice were transplanted into C3H/He mice (a full allomismatch combination) to assess acute rejection or C57BL/6 hearts into B6.C-H2(‹bm12›) KhEg (a class II mismatch combination) to examine chronic rejection. ONO-1301MS did not prolong full allomismatch cardiac graft survival. Severe myocardial fibrosis with high collagen concentration was observed in untreated class II mismatch allografts on day 60. However, significantly suppressed myocardial fibrosis with less collagen synthesis was observed in the ONO-1301MS-treated group compared to the control group. ONO-1301MS could be an effective strategy to suppress chronic myocardial remodeling in cardiac transplantation.

BACKGROUND: As we have previously reported, the preoperative profile defined by INTERMACS is a good predictor for the prognosis after left ventricular assist device (LVAD) implantation, but is largely dependent on the physician's decision. Several other risk stratification systems including objective parameters (eg, Leitz-Miller, Columbia, Seattle Heart Failure Model, APACHE II) have been proposed to estimate patient's mortality after LVAD implantation. METHODS AND RESULTS: According to the preoperative data from 59 patients who received LVAD (10 implantable, 49 extracorporeal) since 2002 through 2010, we performed a logistic analysis and constructed a new scoring system (ie, the TODAI VAD score (TVAD score), assigning 8 points to serum albumin <3.2mg/dl (odds ratio [OR] 8.475), 7 points to serum total bilirubin >4.8mg/dl (OR 7.300), 6 points to left ventricular end-diastolic diameter <55mm (OR 5.917), 5 points to central venous pressure >11mmHg (OR 5.128)). The receiver-operating characteristic analysis showed that the area under the curve of our new scoring system (0.864) was significantly larger than any of the abovementioned 5 scoring methods (all P<0.05). With the TVAD score, low (0-8 points), intermediate (9-17 points), and high (18-26 points) risk strata had significantly different 1-year survival rates of 95%, 54%, and 14%, respectively (all P<0.001). CONCLUSIONS: The TVAD score can predict the prognosis after LVAD implantation much better than the previously known methods.

Chronic inflammation plays a fundamental role in coronary heart disease (CHD). Periodontal disease is a common infectious disease and is a potential source of systemic inflammation. However, the effect of periodontal infection on CHD has not yet been proven. The purpose of this study was to determine the effect of periodontopathic bacteria on experimental myocardial infarction (MI). We implanted a chamber into the subcutaneous tissue of each male mouse. Aggregatibacter actinomycetemcomitans (A.a. n = 8), which is a major periodontal pathogen, or PBS (n = 6) was injected into the chamber. Then, MI was induced by permanent ligation of the left anterior descending coronary artery. To exclude the nonspecific effect of the pathogen, we injected A.a. into the mice without MI (n = 4). The plasma level of anti-A.a. antibody was statistically higher in A.a.-infected mice than in vehicle control mice. Seven days after the myocardial ischemia, the A.a.-positive MI hearts showed a larger infarct size and length than the A.a.-negative MI mice. The A.a.-positive MI hearts showed more MOMA-2 positive myocardial infiltrating cells compared to the A.a.-negative MI mice. The injection of A.a. into the mice without MI did not affect their hearts. We concluded that a periodontal pathogen infection might deteriorate ventricular remodeling after MI through inflammatory cell infiltration.

Restenosis after percutaneous coronary intervention (PCI) is still a clinically serious problem. We examined the treatment efficacy of IMD-0354, a novel IKK inhibitor, on arteriopathy. Using C57BL/6J mice, a wire-injury model was prepared and the mice were intraperitoneally injected with IMD-0354 or vehicle twice a day. The vehicle-treated injured arteries showed significantly thickened intima (3.77 ± 0.59, n = 8), however, IMD-0354 suppressed its progression (1.62 ± 0.22, n = 10, P < 0.05) on day 28. While enhanced expression of PCNA and NF-κB was observed in the untreated injured arteries, IMD-0354 significantly suppressed their expressions. Quantitative RT-PCR revealed that the expression of several inflammatory factors was reduced in the arteries from mice which received IMD-0354 treatment compared with the control animals. Thus, this drug may effectively prevent restenosis after coronary intervention and other cardiovascular diseases.

Although a relationship between periodontitis and myocardial hypertrophy has been reported, the precise mechanism has not been clarified. The purpose of this study was to investigate the association between periodontal infection and myocardial hypertrophy. Transverse aortic constriction (TAC) was performed. Mice were injected with Aggregatibacter actinomycetemcomitans (A.a.) (0.1 mL of 10(8) CFU/mL) in the infected group and PBS in the control group. Echocardiography, histopathology, and immunohistochemistry were performed. Echocardiography indicated that left ventricular fractional shortening had decreased in the infected group compared to the control group on day 28. Heart to body weight ratio increased in the infected group compared to the control group. Histopathologically, A.a.-infected mice showed markedly enhanced cardiac hypertrophy, fibrosis and arteriosclerosis 4 weeks after TAC operation. Immunohistochemistry revealed that expression of MMP-2 in the interstitial tissue was enhanced in the infected group. These results suggested that the periodontal pathogen caused a deterioration of pressure overload-induced myocardial hypertrophy through MMP activation.

While diuretic drugs are commonly used in patients with congestive heart failure, the efficacy of their long-term use still remains controversial. Recently, a new class of diuretics, vasopressin receptor 2 antagonists, has been launched, and tolvaptan is one such drug. We describe our initial experience with this novel agent. Tolvaptan is potentially useful for treatment of heart failure patients with fluid overload who are refractory to conventional diuretic therapies.

Mitral and aortic valve regurgitation is commonly found in osteogenesis imperfecta (OI) patients, however, little is known about the myocardial involvement in this disorder. An 82-year-old man with OI developed heart failure and was admitted to our hospital. Echocardiogram revealed severe mitral regurgitation without left ventricular (LV) dilatation, but with LV wall thickening. Histological analysis exhibited interstitial fibrosis of the myocardium in addition to myxoid changes of the mitral leaflet. These findings suggest that OI patients may develop LV remodeling together with diastolic dysfunction.

BACKGROUND: Cardiac resynchronization therapy/defibrillators (CRTD) and implantable cardioverter defibrillators (ICD) with continuous intrathoracic impedance monitoring might provide an early warning of thoracic fluid retention. In contrast, volume loss events such as dehydration and bleeding are also common events in heart failure patients treated with diuretics and anticoagulants. The correlation between intrathoracic impedance and a volume loss event is not known. METHODS AND RESULTS: This study evaluated the association between intrathoracic impedance and volume loss events in 36 patients with chronic heart failure (New York Heart Association [NYHA] II, III and IV) who had received CRTD/ICD implantation. Elevation of thoracic impedance above the reference line was defined as a positive deviation of thoracic impedance (PDI). This study recorded 249 PDIs including 60 spike PDIs defined as over 5 ohms elevation from the reference line and 17 large PDIs as over 5 ohms elevation and continuing for at least 4 days. Clinically, 96 dehydration events and 2 bleeding events were observed over a 1-year period. The sensitivity and positive predictive value (PPV) for spike PDI was 31.6% and 51.7%, respectively, while those for large PDI were 17.3% and 100%, respectively. CONCLUSIONS: A large PDI reflected dehydration and bleeding events with a high PPV in severe heart failure patients. The large PDI criteria might therefore be useful for predicting volume loss events in chronic heart failure patients.

BACKGROUND: An antianginal K(ATP) channel opener nicorandil has various beneficial effects on cardiovascular systems; however, its effects on pulmonary vasculature under pulmonary arterial hypertension (PAH) have not yet been elucidated. Therefore, we attempted to determine whether nicorandil can attenuate monocrotaline (MCT)-induced PAH in rats. MATERIALS AND METHODS: Sprague-Dawley rats injected intraperitoneally with 60 mg/kg MCT were randomized to receive either vehicle; nicorandil (5.0 mg·kg(-1)·day(-1)) alone; or nicorandil as well as either a K(ATP) channel blocker glibenclamide or a nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME), from immediately or 21 days after MCT injection. Four or five weeks later, right ventricular systolic pressure (RVSP) was measured, and lung tissue was harvested. Also, we evaluated the nicorandil-induced anti-apoptotic effects and activation status of several molecules in cell survival signaling pathway in vitro using human umbilical vein endothelial cells (HUVECs). RESULTS: Four weeks after MCT injection, RVSP was significantly increased in the vehicle-treated group (51.0±4.7 mm Hg), whereas it was attenuated by nicorandil treatment (33.2±3.9 mm Hg; P<0.01). Nicorandil protected pulmonary endothelium from the MCT-induced thromboemboli formation and induction of apoptosis, accompanied with both upregulation of endothelial NOS (eNOS) expression and downregulation of cleaved caspase-3 expression. Late treatment with nicorandil for the established PAH was also effective in suppressing the additional progression of PAH. These beneficial effects of nicorandil were blocked similarly by glibenclamide and l-NAME. Next, HUVECs were incubated in serum-free medium and then exhibited apoptotic morphology, while these changes were significantly attenuated by nicorandil administration. Nicorandil activated the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) pathways in HUVECs, accompanied with the upregulation of both eNOS and Bcl-2 expression. CONCLUSIONS: Nicorandil attenuated MCT-induced vascular endothelial damage and PAH through production of eNOS and anti-apoptotic factors, suggesting that nicorandil might have a promising therapeutic potential for PAH.

The 'evidence' in evidence-based medicine (EBM) is often limited to knowledge obtained from randomized controlled clinical trials (RCT). Most RCTs, however, have strict enrollment criteria which make patient background characteristics and clinical histories significantly different from those encountered in actual practice. Thus it is important to accumulate and analyze data obtained in daily practice to gain insight into a larger clinical picture. Recent developments in information technology and its lowered cost have enabled us to record clinical activity in much greater detail at a lower cost. These factors prompted us to design and develop a coronary angiography and intervention reporting system (CAIRS) to collect data and analyze outcomes of coronary intervention. The resulting advanced CAIRS can record detailed data on coronary angiographic and interventional procedures.To date, data on 10,025 cases of coronary angiography, of which 3,574 were interventional, have been collected over a 5.5 year period. There were 4,343 unique patients, 3,115 (71.7%) of which were male. The overall mean age was 67.0 ± 11.5. The mean age of males was 66.3 ± 11.4 and that of females was 69.0 ± 11.4. About one-third of the patients never underwent a PCI procedure at our institution. For patients that underwent at least one PCI procedure at our institution, the prescription rate of statin increased from 50.8% in 2005 to 80.3% in 2011, while those of nitrate and ticlopidine decreased from 36.7% and 90.8% in 2005 to 21.3% and 0.8% in 2011, respectively. We have also implemented the same system at another institution and compared the data on stent usage between the two institutions, which revealed vastly different stent usage profiles.In conclusion, we have successfully developed and implemented an advanced coronary angiography and intervention reporting system which we call CAIRS. Implementing the same system at multiple institutions and analyzing data collected from several institutions will provide detailed and timely insight into the 'real world' of coronary angiography and interventional procedures and their outcome.

The efficacy of aliskiren, a direct renin inhibitor, in ventricular remodeling after myocardial infarction (MI) compared with conventional renin-angiotensin system (RAS) inhibitors remains to be defined. This study was performed to examine the protective effects of aliskiren and its addition to valsartan, an angiotensin-II receptor blocker, against ventricular remodeling after MI. MI was induced in 8- to 12-week-old C57BL/6 mice by ligating the left anterior descending artery. At 3 days after MI, mice were divided into five groups and were treated with the following: (1) phosphate-buffered saline (PBS); (2) hydralazine (10 mg kg(-1) day(-1)); (3) valsartan (8 mg kg(-1) day(-1)); (4) aliskiren (25 mg kg(-1) day(-1)); and (5) combined aliskiren (25 mg kg(-1) day(-1)) and valsartan (8 mg kg(-1) day(-1)). With these doses of drugs, blood pressure-lowering effects compared with the PBS group were similar among the treated groups in sham-operated mice. At 28 days after MI, echocardiographic, hemodynamic and histological assessments demonstrated that monotherapy with valsartan or aliskiren alone significantly and similarly ameliorated ventricular remodeling after MI compared with the PBS and the hydralazine groups. Combination therapy of valsartan and aliskiren more greatly improved ventricular remodeling after MI with enhancement of angiogenesis and greater attenuation of tissue oxidative stress and inflammation. Our results indicate that aliskiren can be an alternative to conventional RAS inhibitors in the treatment of post-MI patients. Moreover, the dual therapy of valsartan and aliskiren may be more beneficial than either monotherapy. Further clinical trials will be warranted to sufficiently assess the safety and the efficacy of the use of aliskiren in post-MI patients.

Marfan syndrome (MS) is an inherited connective tissue disorder, and detailed evaluations of multiple organ systems are required for its diagnosis. Genetic testing of the disease-causing fibrillin-1 gene (FBN1) is also important in this diagnostic scheme. The aim of this study was to define the clinical characteristics of Japanese patients with MS and enable the efficient and accurate diagnosis of MS with mutational analysis using a high-throughput microarray-based resequencing system. Fifty-three Japanese probands were recruited, and their clinical characteristics were evaluated using the Ghent criteria. For mutational analysis, an oligonucleotide microarray was designed to interrogate FBN1, and the entire exon and exon-intron boundaries of FBN1 were sequenced. Clinical evaluation revealed more pulmonary phenotypes and fewer skeletal phenotypes in Japanese patients with MS compared to Caucasians. The microarray-based resequencing system detected 35 kinds of mutations, including 23 new mutations. The mutation detection rate for patients who fulfilled the Ghent criteria reached 71%. Of note, splicing mutations accounted for 19% of all mutations, which is more than previously reported. In conclusion, this comprehensive approach successfully detected clinical phenotypes of Japanese patients with MS and demonstrated the usefulness and feasibility of this microarray-based high-throughput resequencing system for mutational analysis of MS.

BACKGROUND: Little is known about associations among echocardiographic variables, frequency of atrial fibrillation (AF), and progression from paroxysmal to persistent AF. OBJECTIVE: The purpose of this study was to investigate echocardiographic predictors of frequency of paroxysmal AF and its progression to persistent AF in hypertensive patients with paroxysmal AF. METHODS: We used data from 286 patients with paroxysmal AF and hypertension in the Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II Study). Echocardiographic evaluation was performed at baseline. Endpoints were (1) percent of AF days measured daily by transtelephonic monitoring over 1 year and (2) development of persistent AF, defined as incidence of AF lasting for longer than 7 days and/or need for electrical cardioversion. Univariate and multivariate linear regression analysis was performed to evaluate the association between echocardiographic variables and percent of AF days. Cox proportional hazards analysis was used to examine the association between echocardiographic variables and development of persistent AF. RESULTS: Among echocardiographic variables, increased left atrial dimension (LAD) was associated with more AF days and development of persistent AF: a 10-mm increase in LAD was associated with a 6.5% increase in AF days (95% confidence interval 2.7%-10.3%) and an 84% increased risk of developing persistent AF (hazard ratio 1.84, 95% confidence interval 1.28-2.67). These associations remained significant after adjustment for age, sex, and other potential confounding factors. CONCLUSION: Increased LAD is associated with more AF days and progression from paroxysmal to persistent AF in patients with paroxysmal AF and hypertension. Increased LAD may be a good echocardiographic predictor of AF frequency and progression.

Osteopontin (OPN) is known to be one of the cytokines that is involved in the vascular inflammation caused by aldosterone (Aldo). Previous reports have shown that Aldo increases OPN transcripts, and the mechanisms for this remain to be clarified. In this study, we investigated how Aldo increases OPN transcripts in the vascular smooth muscle cells of rats. Aldosterone increased OPN transcripts time-dependently as well as dose-dependently. This increase was diminished by eplerenone, a mineralocorticoid receptor (MR) antagonist. Luciferase promoter assays showed that the OPN promoter deleted to the -1599 site retained the same promoting ability as the full-length OPN promoter when stimulated by 10(-7) M Aldo, but the promoter deleted to the -1300 site lost the promoting ability. A glucocorticoid response element (GRE) is located in that deleted region. Luciferase assays of a mutated promoter without the GRE lost the luciferase upregulation, although mutated promoters with the deletion of other consensus sites maintained the promoter activity. The binding of the Aldo-MR complex to the GRE fragment was confirmed by an electrophoretic-mobility shift assay. This is the first report showing that Aldo regulates the transcriptional levels of OPN and inflammatory responses in the vasculature through a specific GRE site in the OPN promoter region.

Background: The subendocardial myocardium normally has higher systolic strain than the subepicardial myocardium and can be damaged first in face of ischemia. We investigated the reproducibility and feasibility of novel three-layer speckle tracking system and compared the diagnostic accuracy with experienced visual interpretation. Methods: An ameroid constrictor was placed around the proximal left circumflex (LCX) coronary artery in 19 pigs. Four weeks later, subtotal stenosis was confirmed in all pigs by coronary angiogram. Two dead pigs and three pigs with pathological infarction were excluded. Transthoracic left ventricle (LV) short-axis echocardiograms were recorded at rest before and 4 weeks after the operation. LV posterior wall motion was scored by two experienced doctors and analyzed by the speckle tracking system (n = 14). Results: Strain variables gave reasonable intra/interobserver reproducibility (mean absolute percentage errors = 13/19, intraclass correlation coefficients = 0.97/0.92). All strain variables and visual wall-motion scores changed significantly during stenosis (P &lt; 0.05). Of all variables, endocardial strains, particularly the circumferential strain demonstrated the highest area under curve (AUC), showing better diagnostic accuracy than experienced visual interpretation (sensitivity 0.93 vs. 0.79, specificity 0.93 vs. 0.73, AUC 0.95 vs. 0.77, P &lt; 0.05). Conclusion: Three-layer speckle tracking is a feasible and reproducible modality. In particular, endocardial speckle tracking provides incremental value in accurately identifying regional ischemia even in the rest echocardiography. (Echocardiography 2011;28:1148-1155)

Nowadays, antiplatelet and anticoagulant drug medications are indicated in patients with a variety of cardiovascular disorders, such as atrial fibrillation, coronary artery disease, and peripheral artery disease. Among cardiology patients, regardless of gastrointestinal (GI) protection, we do not infrequently encounter those patients who have signs and symptoms that are suggestive of GI tract problems. We should bear in mind that such GI signs and symptoms may be attributed to GI cancers, as well as to benign or clinically insignificant lesions. Several clinical studies have shown, albeit controversially that the predictive value of positive fecal occult blood for colorectal malignant neoplasm may not be lower in patients taking antithrombotic medication. In addition, it has been shown that in patients taking antithrombotic drug(s), diagnosed colorectal malignancies are in a relatively earlier phase, suggesting that antithrombotic drugs may facilitate the detection of otherwise unrecognized cancers. The possibility also exists that certain cardiovascular disease may be associated with a higher risk of GI malignant neoplasms. There has been no established evidence concerning whether more aggressive GI tract screening will reduce the probability of cancer death in cardiology patients; nevertheless, GI tract lesions should not be overlooked among cardiology patients, especially when unexplained anemia, gastrointestinal symptoms, or positive fecal occult blood test is present, and GI tract screening should be performed with appropriate timing. (C) 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

症例は39歳女性。他院で乏突起膠星細胞腫瘍に対し開頭摘出術を施行後15日目に急性前壁心筋梗塞を発症し当院へ救急搬送された。緊急冠動脈造影にて左前下行枝(LAD)中間部に99%狭窄を認め、引き続き同病変へ経皮的冠動脈形成術を施行した。血管内エコーにて病変は冠動脈解離を伴っていることが明らかとなり、解離腔のエントリー閉鎖を目的にステントを留置した。しかし、ステント近位部に解離が拡大しLADの完全閉塞に陥ったため、さらなるインターベンションによる解離の拡大を懸念し手技を終了した。1週間後の冠動脈CTでは依然完全閉塞であったが、3ヵ月後には解離腔は狭小化し内腔は開存していた。特発性冠動脈解離は極めてまれな疾患であるが、若年女性の急性冠症候群の原因として念頭に置くべきである。(著者抄録)

BACKGROUND & AIMS: Krüppel-like factor 5 (KLF5) is transcription factor that is expressed by dividing epithelial cells of the intestinal epithelium. KLF5 promotes proliferation in vitro and in vivo and is induced by mitogens and various stress stimuli. To study the role of KLF5 in intestinal epithelial homeostasis, we examined the phenotype of mice with conditional deletion of Klf5 in the gut. METHODS: Mice were generated with intestinal-specific deletion of Klf5 (Vil-Cre;Klf5fl/fl). Morphologic changes in the small intestine and colon were examined by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. RESULTS: Klf5 mutant mice were born at a normal Mendelian ratio but had high mortality compared with controls. Complete deletion of Klf5 from the intestinal mucosa resulted in neonatal lethality that corresponded with an absence of epithelial proliferation. Variegated intestinal-specific deletion of Klf5 in adult mice resulted in morphologic changes that included a regenerative phenotype, impaired barrier function, and inflammation. Adult mutant mice exhibited defects in epithelial differentiation and migration. These changes were associated with reduced expression of Caudal type homeobox (Cdx) 1, Cdx2, and Eph and ephrin signaling proteins. Concomitantly, Wnt signaling to β-catenin was reduced. Proliferation in regenerative crypts was associated with increased expression of the progenitor cell marker Sox9. CONCLUSIONS: Deletion of Klf5 in the gut epithelium of mice demonstrated that KLF5 maintains epithelial proliferation, differentiation, and cell positioning along the crypt radial axis. Morphologic changes that occur with deletion of Klf5 are associated with disruption of canonical Wnt signaling and increased expression of Sox9.

62歳女。1年ほど前から労作時息切れを自覚していた。今回、連日眼前暗黒感が生じるようになった。近医にて2:1房室ブロックを診断され、当院紹介となった。モニター心電図において高度房室ブロックを呈していたため、恒久的ペースメーカー埋込み術が施行された。術後経過は良好で退院となったが、再び眼前暗黒感を自覚し、心電図で心室ペーシング不全に伴うR-R間隔延長が認められた。さらに複数回の失神を呈した。テレメトリー記録では頻回の房室ブロックイベントとともに心室ペーシングの増加傾向を認められ、DDDモード作動がほぼ100%となっており、完全房室ブロックへの進展が示唆された。SafeRモードが適さないと判断しSafeRモードを中止した。中止後はめまい症状の頻度は減少したが、その後もめまい、失神症状が持続した。また、心室センシング値・ペーシング閾値の経時的な悪化傾向がみられ、心室リードによる心房波感知イベントも散見された。X線では心室リードの移動は認めないが、微小脱落していると判断して心室リード再貯留術を施行し、DDDモード設定とした。約1年経過して現在までめまい、失神もなく順調である。

A 49-year-old woman suffering from rapidly progressing right-sided heart failure assessed as World Health Organization functional class (WHO-FC) IV is described. After treatment with oxygen and diuretics, she was in WHO-FC III on admission to our hospital, as confirmed by her poor exercise tolerance in cardiopulmonary exercise testing. Upon detailed examination, she was diagnosed as having idiopathic pulmonary arterial hypertension (IPAH). Right heart catheterization (RHC) revealed severe pulmonary hypertension (mPAP = 65 mmHg) with a markedly decreased cardiac index (CI = 1.0 L/minute/m(2)), and an acute vasoreactivity test with nitric oxide inhalation did not show any response. Due to her severe condition, we decided to attempt oral combination therapy consisting of bosentan, tadalafil, and beraprost, prescribed in the same order and titrated up to their maximum respective doses, instead of intravenous (IV) epoprostenol therapy. Her clinical symptoms improved day by day, and the hemodynamic parameters recovered to nearly normal ranges about 6 months after initiation of the combination therapy. Initial/programmed oral combination therapy for severe IPAH patients is not yet fully established, and there is less evidence concerning its efficacy than IV epoprostenol therapy. However, it has tremendous advantages for PAH patients when they respond well. It is very important to further identify what types of PAH patients will respond to this oral combination therapy and should be treated with it as the first-line therapy. (Int Heart J 2011; 52: 323-326)

Renal tubulointerstitial damage is the final common pathway leading from chronic kidney disease to end-stage renal disease. Inflammation is clearly involved in tubulointerstitial injury, but it remains unclear how the inflammatory processes are initiated and regulated. Here, we have shown that in the mouse kidney, the transcription factor Krüppel-like factor-5 (KLF5) is mainly expressed in collecting duct epithelial cells and that Klf5 haploinsufficient mice (Klf5+/- mice) exhibit ameliorated renal injury in the unilateral ureteral obstruction (UUO) model of tubulointerstitial disease. Additionally, Klf5 haploinsufficiency reduced accumulation of CD11b+ F4/80(lo) cells, which expressed proinflammatory cytokines and induced apoptosis among renal epithelial cells, phenotypes indicative of M1-type macrophages. By contrast, it increased accumulation of CD11b+ F4/80(hi) macrophages, which expressed CD206 and CD301 and contributed to fibrosis, in part via TGF-β production--phenotypes indicative of M2-type macrophages. Interestingly, KLF5, in concert with C/EBPα, was found to induce expression of the chemotactic proteins S100A8 and S100A9, which recruited inflammatory monocytes to the kidneys and promoted their activation into M1-type macrophages. Finally, assessing the effects of bone marrow-specific Klf5 haploinsufficiency or collecting duct- or myeloid cell-specific Klf5 deletion confirmed that collecting duct expression of Klf5 is essential for inflammatory responses to UUO. Taken together, our results demonstrate that the renal collecting duct plays a pivotal role in the initiation and progression of tubulointerstitial inflammation.

Background: Although the prevalence of adult congenital heart disease (ACHD) in Japan continues to rise, the number and geographic distribution of facilities potentially serving as regional ACHD centers remains unknown. We examined trends in ACHD care in Japan to identify needs and to determine potential regional responses to this growing patient population. Methods and Results: A descriptive, cross-sectional, nationwide survey was conducted to assess the status and needs of cardiology specialists related to providing ACHD care. Questionnaires were mailed to 138 cardiology departments located in 8 geographical regions throughout Japan; respondents were asked to document the status and future direction of ACHD care for each facility. Of the 109 facilities that responded, approximately one-third currently treat or plan to treat all ACHD patients. Fourteen facilities (12.8%) fulfilled all criteria for becoming regional ACHD centers. Although each regional center was projected to serve a population of 9.1 million, in 2 regions, no centers possessed the necessary care structure. Conclusions: Our findings revealed a shortage of adult cardiologists dedicated to ACHD care. Moreover, basic as well as formal fellowship ACHD training was deemed necessary. In Japan, the number of potential regional ACHD centers has just reached international standards. However, based on the geographic gaps documented here, a strategy other than regional centralization might be required to deliver adequate ACHD care to rural areas. (Circ J 2011; 75: 2220-2227)

Patients who have undergone cardiac transplantation are occasionally complicated by the development of a coronary artery fistula. It has been reported that a majority of coronary artery fistulas in a post-heart transplant setting communicate with the right ventricle. Moreover, most had a favorable prognosis and were rarely associated with hemodynamic disorder. In contrast, the present report describes a case with a progressive coronary artery fistula that drained into the pulmonary artery in a Japanese male who underwent size-mismatch orthotopic cardiac transplantation from a white male donor. The fistula gradually enlarged and a left-to-right shunt deteriorated over a 5-year period after transplantation. In this case, because the coronary fistula drained into the pulmonary artery, endomyocardial biopsy was not considered as a possible cause of the fistula. It is conceivable that size-mismatch heart transplantation may be associated with the development of fistula. Copyright © American Society of Artificial Internal Organs.

41歳、男性。生後、修正大血管転位(congenitally corrected transposition of the great arteries;cc-TGA)、心室中隔欠損(ventricular septal defect;VSD)を指摘され、VSD閉鎖術を施行。その後、三尖弁閉鎖不全が悪化し33歳時に三尖弁置換術を施行された。2008年10月突然心肺停止となり、蘇生に成功したが解剖学的右室の著明な収縮低下による心不全管理に難渋した。高度心不全治療を目的に2009年2月当院へ転院となったが、極度の悪液質、開放創(胃瘻)やMRSA保菌もあり、心移植や補助人工心臓は適応外とされた。著明な心室内伝導障害とともに、組織ドプラ法で収縮非同期を認めたため、心臓再同期療法(cardiac resynchronization therapy;CRT)を導入した。植え込みは冠静脈リードの留置も容易で内科的に施行可能であった。CRT治療後、自覚症状およびBNP値が著明に改善し、カテコラミンからも離脱し得た。成人期に達したcc-TGAでは体心室の適応破綻による心不全管理にしばしば難渋するが、同病態に対し、CRTが極めて有効な治療となり得ることを示唆する貴重な症例と考えられたため、報告する。(著者抄録)

Background: Post-ischemic myocardial diastolic stunning persists for a long time after transient ischemia even after systolic function has recovered. We sought to identify coronary artery stenosis in clinical patients using strain imaging diastolic index (SI-DI) at rest. Methods: We retrospectively examined 85 patients with suspected coronary artery disease and preserved ejection fraction (EF; &gt;50%) who underwent both echocardiography and coronary angiography. Speckle tracking strains were measured in 3 apical views and parasternal left ventricular (LV) short-axis views at the papillary muscle level. LV segments with inadequate image quality and deficit segments in the movie were excluded by the blinded observer. After strain analysis, LV segments were classified into no stenosis (&lt;= 50%), mild stenosis (51-75%), and severe stenosis (&gt;75%) groups on the bases of the coronary angiogram. Results: SI-DI decreased significantly in severe stenosis segments (p&lt; 0.05, ANOVA), but none of the peak strains showed significant difference. The area under the curve for predicting severe stenosis in radial, longitudinal, and transverse SI-DI was 0.72, 0.74, and 0.80, respectively. A cut-off value of 49 for transverse SI-DI can predict LV segments with severe stenosis with sensitivity of 0.79 and specificity of 0.73. A screening cut-off value of 63 for transverse SI-DI shows sensitivity of 0.95 and specificity of 0.50. Conclusion: SI-DI at rest is a novel marker in predicting coronary stenosis even in patients with preserved EF. This index can be used to screen patients with suspected coronary artery disease in routine echocardiography and does not require stress provocation. (C) 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Hypertension is a typical modern lifestyle-related disease that is closely associated with the development of cardiovascular disorders. Elevation of angiotensin II (ANG II) is one of several critical factors for hypertension and heart failure; however, the mechanisms underlying the ANG II-mediated pathogenesis are still poorly understood. Here, we show that ANG II-mediated cardiac fibrosis, but not hypertrophy, is regulated by interferon regulatory factor 3 (IRF3), which until now has been exclusively studied in the innate immune system. In a ANG II-infusion mouse model (3.0 mg/kg/d), we compared IRF3-deficient mice (Irf3(-/-)/Bcl2l12(-/-)) with matched wild-type (WT) controls. The development of cardiac fibrosis [3.95 ± 0.62% (WT) vs. 1.41 ± 0.46% (Irf3(-/-)/Bcl2l12(-/-)); P<0.01] and accompanied reduction in left ventricle end-diastolic dimension [2.89 ± 0.10 mm (WT) vs. 3.51 ± 0.15 mm (Irf3(-/-)/Bcl2l12(-/-)); P=0.012] are strongly suppressed in Irf3(-/-)/Bcl2l12(-/-) mice, whereas hypertrophy still develops. Further, we provide evidence for the activation of IRF3 by ANG II signaling in mouse cardiac fibroblasts. Unlike the activation of IRF3 by innate immune receptors, IRF3 activation by ANG II is unique in that it is activated through the canonical ERK signaling pathway. Thus, our present study reveals a hitherto unrecognized function of IRF3 in cardiac remodeling, providing new insight into the progression of hypertension-induced cardiac pathogenesis.