Development of pulmonary arterial hypertension following long-term Qing-Dai use for ulcerative colitis.

A 20-year-old woman using Qing-Dai for about 7 years for intractable ulcerative colitis was admitted to the emergency room because of dyspnea and syncope following exertion. The patient was diagnosed with drug-induced pulmonary arterial hypertension (PAH). Discontinuation of Qing-Dai rapidly improved PAH symptoms. The REVEAL 2.0 risk score, which is useful for assessing the severity of PAH and predicting prognosis, improved from high risk (12) to low risk (4) within 10 days. Discontinuing long-term use of Qing-Dai can rapidly improve Qing-Dai-induced PAH. Learning objective: Discontinuing the long-term use of Qing-Dai used for treating ulcerative colitis (UC) can rapidly improve Qing-Dai induced pulmonary arterial hypertension (PAH). REVEAL 2.0 risk score in patients who developed PAH due to Qing-Dai was useful for screening PAH in patients taking Qing-Dai for treatment of UC.

Impact of accelerated washout of Technetium-99m-sestamibi on exercise tolerance in patients with acute coronary syndrome: single-center experience.

Technetium-99m-sestamibi (99mTc-sestamibi) single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with acute coronary syndrome (ACS) could be used to assess area-at-risks, as well as myocardial infarct or saved sizes. In patients with ACS, accelerated washout of 99mTc-sestamibi during early and delayed imaging in the acute phase may suggest mitochondrial dysfunction in the injured but salvaged myocardium. However, the link between 99mTc-sestamibi accelerated washout and exercise tolerance is unknown. The purpose of this study was to investigate a possible association between 99mTc-sestamibi accelerated washout and exercise tolerance in acute ACS patients as they progressed into the chronic phase. One hundred and sixty-five patients with ACS who underwent 99mTc-sestamibi SPECT MPI during the acute phase were recruited. On this basis, we calculated the total perfusion deficits (TPDs) for early (1 h after tracer injection) and delayed (4 h after tracer injection) images using automated quantification software. We then subtracted the early TPDs from the delayed TPDs to calculate the ΔTPD. We conducted a cardiopulmonary exercise test in acute and chronic phases. We divided two groups according to the median ΔTPD (the ΔTPD ≥ 4 group and the ΔTPD < 4 group) and compared anaerobic threshold (AT; ml/kg/min) between the groups. For anaerobic threshold (AT) improvement in data analysis, we employed multivariate logistic regression analysis. A total of 101 ST-segment elevation myocardial infarctions, 36 non-ST-elevation myocardial infarctions, and 28 unstable angina pectoris events were reported as ACS. From acute phase (10.8 ± 4.2 ml/kg/min) to chronic phase (11.9 ± 2.3 ml/kg/min), the AT in the ΔTPD ≥ 4 group was significantly increased (p < 0.0001). This trend was also seen in the ΔTPD < 4 group from acute (11.4 ± 1.8 ml/kg/min) to chronic phase (12.1 ± 2.2 ml/kg/min, p = 0.015). AT was lower in the ΔTPD ≥ 4 group in the acute phase (p = 0.027), but there was no difference in AT between the two groups in the chronic phase (p = 0.60). ΔTPD and the absence of diabetes were both independent predictors of AT improvement in multivariate logistic regression analysis. Receiver-operating characteristic curve analysis determined that ΔTPD = 6 was the best cut-off value, with 60.0% sensitivity and 71.4% specificity, respectively. The accelerated washout of 99mTc-sestamibi in patients with ACS during the acute phase could help to predict improvement in exercise tolerance in the chronic phase.

Impact of neointimal tissue characterization and heterogeneity of bare-metal stents and drug-eluting stents on the time course after stent implantation evaluated by integrated backscatter intravascular ultrasound.

Pathological studies have suggested the different process of in-stent restenosis (ISR) of bare-metal stents (BMS) and drug-eluting stents (DES). Here, we evaluated the components of neointimal tissue using integrated backscatter intravascular ultrasound (IB-IVUS) and focused on the time course after stent implantation and tissue signal distribution. We evaluated 125 lesions of 125 patients who underwent target lesion revascularization for ISR (BMS: n = 73, DES: n = 52). Volume analysis of a 4-mm length centered on a minimum lumen area in every 1-mm cross-sectional area was performed. For IB-IVUS analysis, color-coded maps were constructed from the default setting based on the integrated backscatter (IB) values (middle-IB value, green: fibrous and low-IB value, blue: lipid pool). For the neointimal tissue volume, we evaluated the ratios of the green (%G) and blue (%B) areas. Tissue signal distribution (TD) was also obtained from the default setting based on IB values in each pixel of IB-IVUS imaging. We compared values of neointimal tissues measured by IB-IVUS between the DES and BMS and time course. The observed period was longer after BMS implantation than after DES implantation (BMS: 2545 days, DES: 1233 days, p < 0.001). Overall, %G and %B were similar between the BMS and DES groups (%G: 55% and 51%, respectively, p = 0.10; %B: 36% and 38%, respectively, p = 0.51); however, TD was significantly higher in the DES group than in the BMS group (1091 vs. 1367, p < 0.001). TD in the DES group remained high during the follow-up periods. However, TD in the BMS group was low in the early phase and significantly increased over time (r = 0.56, p < 0.001). When analyzing the ISR within 2 years after stent implantation, the BMS was distinguished with a sensitivity of 66% and a specificity of 90% (cut-off value: TD = 1135, area under the curve 0.83, 95% confidence interval 0.74-0.92). TD could differentiate neointimal tissue after BMS implantation in the early phase. TD can be a useful index in the observation of neoatherosclerosis.

Association of genetic variants with atrial fibrillation.

Recent genome-wide association studies (GWASs) identified various genes and loci that confer susceptibility to coronary artery disease or myocardial infarction among Caucasian populations. As myocardial ischemia is an important risk factor for atrial fibrillation, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to atrial fibrillation through affecting the susceptibility to coronary artery disease. The aim of the present study was to examine the possible association of atrial fibrillation in Japanese individuals with 29 polymorphisms identified as susceptibility loci for coronary artery disease or myocardial infarction in the meta-analyses of GWASs in Caucasian populations. The study subjects comprised 5,470 Japanese individuals (305 subjects with atrial fibrillation and 5,165 controls). Genotypes for 29 polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2 test revealed that rs599839 (G→A) of the proline/serine-rich coiled-coil 1 gene (PSRC1, P=0.0084) and rs11556924 (C→T, Arg363His) of the zinc finger, C3HC-type containing 1 gene (ZC3HC1, P=0.0076) were significantly (P<0.01) associated with atrial fibrillation. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, estimated glomerular filtration rate, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidemia revealed that rs599839 (P=0.0043; odds ratio, 1.56; dominant model) and rs11556924 (P=0.0043; odds ratio, 1.93; dominant model) were significantly associated with atrial fibrillation, with the minor G and T alleles, respectively, representing risk factors for this condition. PSRC1 and ZC3HC1 may thus be susceptibility loci for atrial fibrillation in Japanese individuals.

Impact of gender and healthy aging on pulmonary capillary wedge pressure estimated by the kinetics-tracking index using two-dimensional speckle tracking echocardiography.

Risk stratification in heart failure (HF) among patients and healthy subjects using pulmonary capillary wedge pressure (PCWP) is important for understanding when and why HF develops. The aim of the present study was to evaluate the impact of gender and healthy aging on estimated PCWP using a kinetics-tracking index in patients and in healthy subjects without hypertension. The study population consisted of 198 healthy subjects without cardiovascular or other systemic diseases and who were not taking any medications. Echocardiographic studies were performed using an ACUSON Sequoia 512 ultrasound system. Active left atrial (LA) emptying function (EF) was defined as (pre-atrial contraction LA volume-minimum LA volume)/pre-atrial contraction LA volume × 100%. With an increase in age, the E/A and E/e' ratios (markers of left ventricular (LV) diastolic dysfunction (DD)) showed a similar decrease in males and females. PCWP was maintained at 8.3±1.8 mm Hg in males and 8.2±2.3 mm Hg in females because of compensation by an increase in active LA EF. In contrast, the compensation for LV DD with an increase in active LA EF in females tended to be more gradual (slope=0.11) than in males (slope=0.18, P=0.060 vs. female). The parameters that indicated LV DD deteriorated with advancing age. PCWP might be maintained because of compensation, namely an increase in active LA EF in both males and females. The compensation in female septuagenarians and octogenarians was weaker than in male septuagenarians and octogenarians. This difference in compensation may explain why HF with preserved LV ejection fraction occurs more frequently in females than in males.

Heparin-induced thrombocytopenia associated with polycythemia vera during the treatment of acute coronary syndrome.

Here, we report a case of heparin-induced thrombocytopenia (HIT) associated with polycythemia vera (PV) during the treatment of acute coronary syndrome. An 84-year-old woman with pre-existing PV had an acute myocardial infarction and developed HIT after using heparin. An additional myocardial infarction was caused by HIT, and caused marked damage to her cardiac function. However, she was successfully treated with argatroban infusion and intensive care. In this case, we suspected HIT at an extremely early stage, when the decline in platelet count remained at 16%, which might have prevented further thrombosis. Subsequently, the nadir in the platelet count remained at 32%, which resulted in "intermediate possibility of HIT" according to the 4Ts score; thus, further detailed serological examination may be required for accurate diagnosis of HIT. .

Association of FURIN and ZPR1 polymorphisms with metabolic syndrome.

Although genome-wide association studies (GWASs) have identified various genes and loci in predisposition to metabolic syndrome (MetS) or each component of this condition, the genetic basis of MetS in individuals remains to be identified definitively. The aim of the present study was to examine the possible association of MetS in individuals with 29 polymorphisms that were previously identified as susceptibility loci for coronary artery disease or myocardial infarction by meta-analyses of GWASs. The study population comprised 1,822 subjects with MetS and 1,096 controls. Subjects with MetS had ≥3 of the 5 components of the diagnostic criteria for MetS, whereas control individuals had 0-1 of the 5 components. The genotypes for the 29 polymorphisms were determined by the multiplex bead-based Luminex assay. Comparisons of allele frequencies by the χ2 test revealed that rs17514846 (A→C) of the furin (paired basic amino acid-cleaving enzyme) gene (FURIN; P=0.0006), rs964184 (C→G) of the ZPR1 zinc finger gene (ZPR1; P=0.0078) and rs599839 (G→A) of the proline/serine-rich coiled-coil 1 gene (P=0.0486) were significantly (P<0.05) associated with the prevalence of MetS. Multivariable logistic regression analysis with adjustment for age, gender and smoking status revealed that rs17514846 of FURIN (P=0.0016; odds ratio, 0.76; dominant model) and rs964184 of ZPR1 (P=0.0164; odds ratio, 1.21; dominant model) were significantly associated with MetS. The minor A allele of rs17514846 of FURIN was significantly associated with a decrease in the serum concentration of triglycerides (P=0.0293) and to an increase in the serum concentration of high-density lipoprotein (HDL) cholesterol (P=0.0460). The minor G allele of rs964184 of ZPR1 was significantly associated with increases in the serum concentration of triglycerides (P=6.2×10-9) and fasting plasma glucose level (P=0.0028) and to a decrease in the serum concentration of HDL cholesterol (P=0.0105). FURIN and ZPR1 may thus be susceptibility loci for MetS.

Association of genetic variants with dyslipidemia.

Although genetic variants, which regulate lipid metabolism, have been extensively investigated in Caucasian populations, the genes, which confer susceptibility to dyslipidemia in Japanese individuals, remain to be elucidated. The aim of the present study was to examine a possible association among hypertriglyceridemia, hypo­high density lipoprotein (HDL)­cholesterolemia or hyper­low density lipoprotein (LDL)­cholesterolemia in Japanese individuals with 29 polymorphisms observed to confer susceptibility for coronary heart disease. This was performed through meta­analyses of genome­wide association studies in Caucasian populations. The study population comprised 2,354 individuals with dyslipidemia (hypertriglyceridemia, hypo­HDL­cholesterolemia or hyper­LDL­cholesterolemia) and 3,106 control individuals. To compensate for multiple comparisons of genotypes, a false discovery rate (FDR) of <0.05 was adopted to determine the statistical significance of the associations. Comparisons of allele frequencies using the χ2 test revealed that rs964184 of zinc finger gene (ZPR1; FDR=2.1x10­7), rs4845625 of interleukin 6 receptor (IL6R; FDR=0.032), rs46522 of ubiquitin­conjugating enzyme E2Z gene (UBE2Z; FDR=0.032) and rs17514846 of furin (FDR=0.041) were significantly associated with hypertriglyceridemia. The χ2 test revealed that rs599839 of proline/serine­rich coiled­coil 1 (PSRC1; FDR=0.004) and rs2075650 of translocase of outer mitochondrial membrane 40 homolog (TOMM40; FDR=0.004) were significantly associated with hyper­LDL­cholesterolemia. Multivariate logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 (P=5.1x10­7; odds ratio, 1.37; dominant model), rs4845625 of IL6R (P=0.0019, odds ratio, 1.25; dominant model) and rs46522 of UBE2Z (P=0.0039, odds ratio, 1.19; dominant model) were significantly associated with hypertriglyceridemia, and that rs599839 of PSRC1 (P=0.0004, odds ratio, 0.70; dominant model) and rs2075650 of TOMM40 (P=0.0004, odds ratio, 1.43; dominant model) were significantly associated with hyper­LDL­cholesterolemia. Therefore, ZPR1, IL6R, and UBE2Z may be susceptibility loci for hypertriglyceridemia, whereas PSRC1 and TOMM40 may be such loci for hyper-LDL-cholesterolemia in Japanese individuals.

Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke.

Recent genome-wide association studies (GWASs) and their meta-analyses have identified various genes and loci underlying the predisposition to ischemic stroke or coronary artery disease in Caucasian populations. Given that ischemic stroke and coronary artery disease may have a shared genetic architecture, certain polymorphisms may confer genetic susceptibility to these two diseases. The aim of the present study was to examine the possible association of ischemic stroke with 29 single-nucleotide polymorphisms (SNPs) previously identified by the meta-analyses of GWASs as susceptibility loci for coronary artery disease. The study population comprised 3,187 Japanese individuals, including 894 subjects with ischemic stroke and 2,293 controls. The genotypes for the 29 SNPs of the 28 genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2 test between subjects with ischemic stroke and controls revealed that rs9319428 (G→A) of the fms-related tyrosine kinase 1 gene (P=0.0471), rs2075650 (G→A) of the translocase of outer mitochondrial membrane 40 homolog gene (TOMM40, P=0.0102) and rs273909 (T→C) of the solute carrier family 22, member 4 gene (SLC22A4, P=0.0097) were significantly (P<0.05) associated with the prevalence of ischemic stroke. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, smoking status and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that rs2075650 of TOMM40 (P=0.0443; recessive model; odds ratio=0.50) and rs273909 of SLC22A4 (P=0.0123; dominant model; odds ratio=0.45) were significantly associated with ischemic stroke with the minor G and C allele, respectively, being protective against this condition. TOMM40 and SLC22A4 may thus be susceptibility loci for ischemic stroke in Japanese individuals.

Anti-inflammatory and morphologic effects of pitavastatin on carotid arteries and thoracic aorta evaluated by integrated backscatter trans-esophageal ultrasound and PET/CT: a prospective randomized comparative study with pravastatin (EPICENTRE study).

BACKGROUND: We sought to evaluate the effects of a strong lipophilic statin (pitavastatin) on plaque components and morphology assessed by transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE), as well as plaque inflammation assessed by 18F-fluorodeoxyglucose (FDG) PET/CT in the thoracic aorta and the carotid artery. Furthermore, we compared the effects of pitavastatin with those of mild hydrophilic statin (pravastatin). METHODS: We examined atherosclerotic plaques in the thoracic aorta by TEE and those in the carotid artery by integrated backscatter (IBS)-TTE and PET/CT. We identified the target plaque, where there was macrophage infiltration and inflammation, by strong FDG uptake in the thoracic aorta and carotid arteries and measured maximum standard uptake values (max SUV) by PET/CT. We measured the intima-media thickness (IMT) and the corrected IBS (cIBS) values in the intima-media complex by TEE and TTE at the same site of FDG accumulation by PET/CT. RESULTS: Patients were randomly divided into two treatment groups: a pitavastatin group (PI group: n =10, 68.4 ± 5.1 years) and a pravastatin group (PR group: n =10, 63.9 ± 11.2 years). The same examinations were performed after six months at the same site in each patient. We used calculated target-to-background ratio (TBR) to measure max SUV of plaques and evaluated percent change of TBR. There was no significant difference in low density lipoprotein-cholesterol, TBR, IMT and cIBS values in plaques at baseline between the PI and PR groups. After treatment, there was greater improvement in TBR, cIBS values and IMT in the PI group than the PR group. CONCLUSIONS: The pravastatin treatment was less effective on plaque inflammation than pitavastatin treatment. This trend was the same in the carotid arteries and the thoracic aorta. Pitavastatin not only improved the atherosis as measured by IMT and cIBS values but also attenuated inflammation of plaques as measured by max SUV at the same site. The present study indicated that pitavastatin has stronger effects on the regression and stabilization of plaques in the thoracic aorta and carotid arteries compared with pravastatin.

Association of six genetic variants with myocardial infarction.

Although various genes that confer susceptibility to myocardial infarction (MI) have been identified for Caucasian populations in genome-wide association studies (GWAS), genetic variants related to this condition in Japanese individuals have not been identified definitively. The aim of the present study was to examine an association of MI in Japanese individuals with 29 polymorphisms identified as susceptibility loci for MI or coronary artery disease in Caucasian populations by meta-analyses of GWAS. The study subjects comprised 1,824 subjects with MI and 2,329 controls. Genotypes of the polymorphisms were determined by Luminex bead-based multiplex assay. To compensate for multiple comparisons, we adopted the criterion of a false discovery rate (FDR) of <0.05 for statistical significance for association. Comparisons of allele frequencies by the χ(2) test revealed that rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1, FDR=0.0007), rs4977574 of the CDKN2B antisense RNA 1 gene (CDKN2B-AS1, FDR=0.0038), rs264 of the lipoprotein lipase gene (LPL, FDR=0.0061), rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1, FDR=0.0118), rs9319428 of the fms-related tyrosine kinase 1 gene (FLT1, FDR=0.0118) and rs12413409 of the cyclin and CBS domain divalent metal cation transport mediator 2 gene (CNNM2, FDR=0.0300) were significantly associated with MI. Multivariate logistic regression analysis with adjustment for covariates revealed that rs9369640 (P=0.0005; odds ratio, 0.89), rs4977574 (P=0.0001; odds ratio, 1.50), rs264 (P=0.0405; odds ratio, 0.85), rs599839 (P=0.0003; odds ratio, 0.68), rs9319428 (P=0.0155; odds ratio, 1.20) and rs12413409 (P=0.0076; odds ratio, 0.66) were significantly (P<0.05) associated with MI. PHACTR1, CDKN2B-AS1, LPL, PSRC1, FLT1 and CNNM2 may thus be susceptibility loci for MI in Japanese individuals.

Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus.

Various loci and genes that confer susceptibility to coronary heart disease (CHD) have been identified in Caucasian populations by genome-wide association studies (GWASs). As type 2 diabetes mellitus (DM) is an important risk factor for CHD, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to CHD through affecting the susceptibility to type 2 DM. The purpose of the present study was to examine a possible association of type 2 DM in Japanese individuals with 29 polymorphisms identified as susceptibility loci for CHD by meta-analyses of the GWASs. The study subjects comprised of 3,757 individuals (1,444 subjects with type 2 DM and 2,313 controls). The polymorphism genotypes were determined by the multiplex bead-based Luminex assay, which combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. To compensate for multiple comparisons of genotypes, the criterion of a false discovery rate (FDR) ≤0.05 was adopted for testing the statistical significance of the association. The comparisons of allele frequencies by the χ2 test revealed that the rs964184 (C→G) of the ZPR1 zinc finger gene (ZPR1) was significantly associated (P=0.0017; FDR=0.050) with type 2 DM. Multivariable logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 was significantly associated (P=0.0012; odds ratio, 1.25; dominant model) with type 2 DM with the minor G allele representing a risk factor for this condition. Fasting plasma glucose levels (P=0.0076) and blood glycosylated hemoglobin contents (P=0.0132) significantly differed among ZPR1 genotypes with the G allele associated with increases in these parameters. ZPR1 may thus be a susceptibility locus for type 2 DM in Japanese individuals.

Association of a transcription factor 21 gene polymorphism with hypertension.

Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously identified by meta-analyses of GWASs as susceptibility loci for CAD. Study subjects comprised of 5,460 individuals (3,348 subjects with hypertension and 2,112 controls). The genotypes of SNPs were determined by the multiplex bead-based Luminex assay. The χ2 test revealed that genotype distributions and allele frequencies for rs12190287 of the transcription factor 21 gene (TCF21) and rs1122608 of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 gene (SMARCA4) were significantly (P<0.05) associated with hypertension. Allele frequencies for rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1) and genotype distributions for rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1) were also significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that rs12190287 of TCF21 (P=0.0014; recessive model; odds ratio, 1.21) was significantly associated with hypertension, and the C allele represented a risk factor for this condition. Similar analyses revealed that rs1122608 of SMARCA4 (P=0.0305; dominant model; odds ratio, 0.86), rs9369640 of PHACTR1 (P=0.0119; dominant model; odds ratio, 0.82) and rs599839 of PSRC1 (P=0.0248; dominant model; odds ratio, 0.84) were also related to hypertension, with the minor T, C and G alleles, respectively, being protective against this condition. Thus, the present results indicate that rs12190287 (G→C) of TCF21 is a susceptibility locus for hypertension.

A novel ultrasound predictor of pulmonary capillary wedge pressure assessed by the combination of left atrial volume and function: A speckle tracking echocardiography study.

BACKGROUND: We hypothesized that a development of a novel index based on the combination of left atrial volume (LAV) and left atrial (LA) function evaluated by the time-LA volume curve using speckle tracking echocardiography (STE) would be accurate and useful to estimate pulmonary capillary wedge pressure (PCWP). Our goal was to develop a novel index of PCWP based on a combination of LAV and LA function using STE. METHODS: A cross-validation study was performed with the patients divided into a training study to define the novel index (n=50) and a testing study to validate the index (n=196). PCWP was measured by right heart catheterization, and phasic LAV and emptying function (EF) were measured by STE. RESULTS: Simple linear regression analysis in the training study revealed that the novel index that best estimated PCWP was the kinetics-tracking index [KT index=log10 (active LAEF/minimum LAV index)]. Multiple regression analysis revealed that the KT index was the most reliable predictor of PCWP. It had the strongest correlation with PCWP (r=-0.86, p<0.001) among all echocardiographic parameters. In the testing study, PCWP estimated by the KT index was also strongly correlated with measured PCWP (r=0.92, p<0.001). These correlations were also strong in the patients with reduced left ventricular ejection fraction (<50%), chronic heart failure, and chronic atrial fibrillation (r=0.92, r=0.91, r=0.79, p<0.001, respectively). CONCLUSIONS: A novel index (KT index) using a combination of LAV and LA function was a powerful and useful predictor of PCWP and may be valuable in routine clinical practice.

Association of a polymorphism of the interleukin 6 receptor gene with chronic kidney disease in Japanese individuals.

AIM: Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified in Caucasian populations by genome-wide association studies (GWASs). The aim of the present study was to examine a possible association of chronic kidney disease (CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta-analyses of GWASs. METHODS: The study population comprised 2247 Japanese individuals, including 1588 subjects with CKD [estimated glomerular filtration rate (eGFR) of <60 mL min(-1) 1.73 m(-2) ] and 659 controls (eGFR of ≥90 mL min(-1) 1.73 m(-2) ). The genotypes for 29 polymorphisms of 28 candidate genes were determined. RESULTS: The χ(2) test revealed that rs4845625 (T→C) of IL6R, rs4773144 (A→G) of COL4A1, rs9319428 (G→A) of FLT1, and rs46522 (T→C) of UBE2Z were significantly (P < 0.05) related to CKD. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidaemia revealed that rs4845625 of IL6R (P = 0.0008; dominant model; odds ratio, 1.49), rs4773144 of COL4A1 (P = 0.0252; dominant model; odds ratio, 1.28), and rs9319428 of FLT1 (P = 0.0260: additive model; odds ratio, 0.77) were significantly associated with CKD. The serum concentration of creatinine was significantly (P = 0.0065) greater and eGFR was significantly (P = 0.0009) lower in individuals with the TC or CC genotype of IL6R than in those with the TT genotype. CONCLUSION: The rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals.

Comparison between left atrial features in well-controlled hypertensive patients and normal subjects assessed by three-dimensional speckle tracking echocardiography.

BACKGROUND: Three-dimensional speckle tracking echocardiography (3D-STE) has a major advantage in the improvement of accuracy in the evaluation of cardiac chamber volume without any geometrical assumption. Thus, the aim of this study was to use 3D-STE to elucidate the features of left atrial (LA) volume and function that are altered by hypertension (HTN) by comparing well-controlled HTN patients with normal subjects. METHODS: Conventional echocardiographic parameters and LA phasic volume and function were measured from apical view by 3D-STE in 40 patients with well-controlled HTN [systolic blood pressure (BP) <140 and diastolic BP <90mmHg for more than one year] and 40 normotensive subjects. RESULTS: The passive LA emptying function (EF) in the patients with well-controlled HTN significantly decreased (16±7% vs. 22±8%, p=0.0013) and the active LAEF in patients with well-controlled HTN significantly increased (35±10% vs. 30±9%, p=0.029) compared with the values in normotensive subjects. Multivariate logistic regression analysis revealed that E/e' was an independent determinant of well-controlled HTN. The maximum LA volume index was correlated with elevated E/e' (r=0.30, p=0.0064), whereas the maximum LA volume index was not correlated with LV mass index or systolic BP. This change was independent of age. CONCLUSIONS: These results suggest that LV diastolic dysfunction occurs before structural changes of left atrium and left ventricle even in patients with well-controlled HTN.

Quantitative validation of left atrial structure and function by two-dimensional and three-dimensional speckle tracking echocardiography: a comparative study with three-dimensional computed tomography.

BACKGROUND: The aim of this study was to validate the accuracy of three-dimensional (3D) speckle tracking echocardiography (STE) and two-dimensional (2D)-STE for the assessment of left atrial (LA) volume and function by comparison with 3D-computed tomography (CT) performed on the same day as STE. METHODS: LA phasic volume and emptying function (EF) were measured in 28 patients with paroxysmal atrial fibrillation undergoing catheter ablation (62±11 years old) using both 3D-STE and 2D-STE during sinus rhythm. LA phasic volume and function measured by 3D-STE and 2D-STE were validated using 3D-CT as a gold standard. RESULTS: The intraobserver correlation coefficient and variability in maximum LA volume assessed by 3D-STE were 0.99 and 1.4±6.0%, respectively. The interobserver correlation coefficient and variability in maximum LA volume assessed by 3D-STE were 0.99 and 0.2±4.5%, respectively. There were strong correlations between LA phasic volume measured by 3D-CT and those measured by 3D-STE (r=0.98, p<0.001). There were correlations between LA phasic function measured by 3D-CT and those measured by 3D-STE (r=0.85-0.88, p<0.001). There was a better agreement between 3D-CT and 3D-STE in the assessment of LA phasic volumes and function than between 3D-CT and 2D-STE in apical 2- and 4-chamber view. CONCLUSIONS: 3D-STE allows more accurate measurement of LA volume and function than 2D-STE and has high reproducibility.

Association among blood pressure control in elderly patients with hypertension, left atrial structure and function and new-onset atrial fibrillation: a prospective 2-year study in 234 patients.

We assessed the hypothesis that blood pressure (BP)-lowering therapy has a beneficial effect on left atrial (LA) structure and function and may decrease the incidence of new-onset atrial fibrillation (AF) in elderly patients with hypertension (HTN). We divided 234 subjects ≥65 years old into four groups based on mean office BP achieved: a normotensive group (n=71), a HTN group with good BP control (n=72), a HTN group with poor BP control (n=41) and a HTN group with moderate BP control (n=50). LA volume, emptying function (EF), strain and strain rate (SR) were measured by speckle tracking echocardiography. LA volume, EF, strain and SR in the HTN group with good BP control were better preserved than those parameters in the HTN group with poor BP control. The incidence of new-onset AF during 2 years was significantly higher in the HTN group with poor BP control (hazard ratio: 7.015; 95% confidence interval: 2.433-20.22; P<0.001). In multivariate Cox regression analysis that included the difference in echocardiographic parameters between baseline and follow-up, both age and being in the HTN group with poor BP control were independent predictors of new-onset AF. In multivariate Cox regression analysis that included only parameters at baseline, ratio of the peak early transmitral flow velocity (E) to the peak early myocardial tissue velocity (E/e') was an independent predictor of new-onset AF. The incidence of new-onset AF depended on the long-term level of BP control rather than short-term changes in LA structure and function. Poor BP control increased the risk of new-onset AF in elderly patients with HTN.

Motion of left atrial appendage as a determinant of thrombus formation in patients with a low CHADS2 score receiving warfarin for persistent nonvalvular atrial fibrillation.

BACKGROUND: The aim of this study was to define the independent determinants of left atrial appendage (LAA) thrombus among various echocardiographic parameters measured by Velocity Vector Imaging (VVI) in patients with nonvalvular atrial fibrillation (AF) receiving warfarin, particularly in patients with a low CHADS2 score. METHODS: LAA emptying fraction (EF) and LAA peak longitudinal strain were measured by VVI using transesophageal echocardiography in 260 consecutive patients with nonvalvular persistent AF receiving warfarin. The patients were divided into two groups according to the presence (n=43) or absence (n=217) of LAA thrombus. Moreover, the patients within each group were further divided into subgroups according to a CHADS2 score ≤1. RESULTS: Multivariate logistic regression analysis showed that LAAEF was an independent determinant of LAA thrombus in the subgroup of 140 with a low CHADS2 score. Receiver operating characteristics curve analysis showed that an LAAEF of 21% was the optimal cutoff value for predicting LAA thrombus. CONCLUSIONS: LAA thrombus formation depended on LAA contractility. AF patients with reduced LAA contractile fraction (LAAEF ≤21%) require strong anticoagulant therapy to avoid thromboembolic events regardless of a low CHADS2 score (≤1).

Evaluation of left atrial degeneration for the prediction of atrial fibrillation: usefulness of integrated backscatter transesophageal echocardiography.

OBJECTIVES: The purpose of this study was to elucidate the usefulness of integrated backscatter (IBS) transesophageal echocardiography (TEE) for the evaluation of atrial degeneration and clarify whether atrial degeneration predicts the occurrence of atrial fibrillation (AF). BACKGROUND: One of the causes of AF is pathological degeneration of the left atrium (LA). However, there is no appropriate method to evaluate degeneration of the LA in the clinical setting. METHODS: The IBS images were acquired with TEE with a 4- to 7-MHz transducer. The IBS values were calculated as the average power of the backscattered signal from regions of interest (ROI). In the pathological study, we measured IBS values of 21 left atrial specimens obtained from 10 autopsied hearts. Relative interstitial area in the ROI was automatically calculated by a personal computer. In the clinical study, we measured IBS values of the entire LA wall at 5-mm intervals (except the posterior wall) in 42 patients (18 non-AF patients, 14 paroxysmal AF patients, and 10 chronic AF patients). Each IBS value was color-coded to construct 3-dimensional maps. RESULTS: There was a weak correlation between the relative interstitial area and IBS values (r = 0.45, p = 0.038). Average corrected IBS values of total voxels in color-coded maps in the AF group (24.4 +/- 6.4 dB) and the paroxysmal AF group (23.9 +/- 9.6 dB) were significantly greater than those in the non-AF group (15.6 +/- 7.4 dB, p = 0.007), whereas there was no significant difference in LA diameter between the paroxysmal AF group (39.4 +/- 6.5 mm) and the non-AF group (36.7 +/- 5.5 mm). CONCLUSIONS: With IBS-TEE, we can identify an increase in atrial degeneration that might predict the occurrence of AF before LA dilation.