Search

Aims: As part of the Toon Health Study, which is an ongoing population‐based cohort study, we aimed to develop a prediction model for N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in a general Japanese population. We sought to explore the influence of various demographic and clinical factors on NT‐proBNP levels and assess the model's performance. In addition, our objectives included internal validation and investigation of the diagnostic potential of the observed‐to‐predicted NT‐proBNP ratio (OPR) at baseline for predicting the risk of heart failure with preserved ejection fraction (HFpEF). Methods and results: In this prospective cohort study, participants were recruited from Toon City, Japan, as part of the larger Toon Health Study, focusing on cardiovascular risk factors. We measured the NT‐proBNP levels and used linear regression with penalization (ridge regression) to develop the model. The model incorporated 10 prespecified predictors (age, gender, body mass index, diastolic blood pressure, heart rate, haemoglobin, albumin, total cholesterol, haemoglobin A1c, and estimated glomerular filtration rate) and underwent assessment using R2 and root mean squared error (RMSE). Internal validation was conducted through bootstrapping. In a post hoc analysis, we explored the OPR's diagnostic potential using 5 year follow‐up data (n = 636) to predict the elevation of NT‐proBNP > 125 pg/mL at the 5 year follow‐up as the risk of HFpEF. A total of 2505 participants (age: 60.4 ± 12.9 years, men: 35%) were enrolled in this study. There was a linear relationship between the observed and predicted values of NT‐proBNP in which the logarithm of observed NT‐proBNP was <6, which corresponds to 403 pg/mL in NT‐proBNP. The prediction model demonstrated satisfactory performance (R2: 0.291, RMSE: 0.688), with age identified as a dominant predictor. The stability of the model was underscored by the internal validation. The OPR at baseline predicted NT‐proBNP > 125 pg/mL at the 5 year follow‐up with an area under the curve of 0.793. Conclusions: This study introduces the first prediction model for NT‐proBNP in a general Japanese population. Although the model has acceptable performance, ongoing refinement is essential. Our transparent approach to model development, alongside a web‐based interactive tool, lays the groundwork for further improvements and external validation. The OPR holds potential for predicting the future risk of HFpEF. This research contributes to understanding the nuanced influence of patient backgrounds on levels of NT‐proBNP in asymptomatic individuals within the context of a broader population‐based cohort study. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the utility of the RAND/UCLA appropriateness method (RAM) in validating expert consensus-based multiple-choice questions (MCQs) on electrocardiogram (ECG). Methods: According to the RAM user's manual, nine panelists comprising various experts who routinely handle ECGs were asked to reach a consensus in three phases: a preparatory phase (round 0), an online test phase (round 1), and a face-to-face expert panel meeting (round 2). In round 0, the objectives and future timeline of the study were elucidated to the nine expert panelists with a summary of relevant literature. In round 1, 100 ECG questions prepared by two skilled cardiologists were answered, and the success rate was calculated by dividing the number of correct answers by 9. Furthermore, the questions were stratified into "Appropriate," "Discussion," or "Inappropriate" according to the median score and interquartile range (IQR) of appropriateness rating by nine panelists. In round 2, the validity of the 100 ECG questions was discussed in an expert panel meeting according to the results of round 1 and finally reassessed as "Appropriate," "Candidate," "Revision," and "Defer." Results: In round 1 results, the average success rate of the nine experts was 0.89. Using the median score and IQR, 54 questions were classified as " Discussion." In the expert panel meeting in round 2, 23% of the original 100 questions was ultimately deemed inappropriate, although they had been prepared by two skilled cardiologists. Most of the 46 questions categorized as "Appropriate" using the median score and IQR in round 1 were considered "Appropriate" even after round 2 (44/46, 95.7%). Conclusions: The use of the median score and IQR allowed for a more objective determination of question validity. The RAM may help select appropriate questions, contributing to the preparation of higher-quality tests. [ABSTRACT FROM AUTHOR]

We evaluated the feasibility of myocardial perfusion ratio to the aorta (MPR) in static computed tomography perfusion (CTP) for detecting myocardial perfusion abnormalities assessed by single-photon emission computed tomography (SPECT). Twenty-five patients with suspected coronary artery disease who underwent dynamic CTP and SPECT were retrospectively evaluated. CTP images scanned at a sub-optimal phase for detecting myocardial perfusion abnormalities were selected from dynamic CTP images and used as static CTP images in the present study. The diagnostic accuracy of MPR derived from static CTP was compared to those of visual assessment and conventional quantitative parameters such as myocardial CT attenuation (HU) and transmural perfusion ratio (TPR). The area under the curve of MPR (0.84; 95% confidence interval [CI], 0.76–0.90) was significantly higher than those of myocardial CT attenuation (0.73; 95% CI, 0.65–0.79) and TPR (0.76; 95% CI, 0.67–0.83) (p < 0.05). Sensitivity and specificity were 67% (95% CI, 54–77%) and 90% (95% CI, 86–92%) for visual assessment, 51% (95% CI, 39–63%) and 86% (95% CI, 82–89%) for myocardial CT attenuation, 63% (95% CI, 51–74%) and 84% (95% CI, 80–88%) for TPR, and 78% (95% CI, 66–86%) and 84% (95% CI, 80–88%) for MPR, respectively. MPR showed higher diagnostic accuracy for detecting myocardial perfusion abnormality compared with myocardial CT attenuation and TPR. [ABSTRACT FROM AUTHOR]

Aims: Cardiac amyloidosis (CA) is an infiltrative myocardial disease that occasionally mimics hypertrophic cardiomyopathy (HCM). The aim of this study is to investigate the discriminatory ability of visual assessment of left atrial (LA) function between CA and HCM on echocardiography. Methods and results: In total, 93 patients with cardiac magnetic resonance imaging (CMR)‐confirmed HCM and 34 with cardiac biopsy‐confirmed CA were retrospectively assessed. LA dilatation was assessed via echocardiography in an apical four‐chamber view. Visual assessment was performed to identify LA dilatation grade (preserved = 1, abnormal = 2, and restricted = 3) based on the extent of outward expansion in the LA reservoir phase. Regarding the reproducibility of visually assessing LA dilatation grade, the kappa values between intra‐ and inter‐observer measurements were 0.82 and 0.70, respectively. Of 127 participants, 57 (45%), 42 (33%), and 28 (22%) presented with LA dilatation Grades 1, 2, and 3, respectively. All 57 patients with preserved LA dilatation (Grade 1) had HCM, and 20 of 28 patients (71%) with restricted LA dilatation (Grade 3) presented with CA. Patients with CA had a higher LA dilatation grade than those with HCM (P < 0.01). LA emptying fraction and reservoir strain were also quantitatively evaluated. The area under the curves of LA dilatation grade (0.88) and LA emptying fraction (0.88) for differentiation of these two diseases were higher than that of LA reservoir strain (0.73) (P < 0.01, respectively). During follow‐up, nine patients with HCM and 16 with CA experienced cardiac event (cardiac death or hospitalization due to heart failure). In Kaplan–Meier analysis including both groups of HCM and CA, the incidence of cardiac events was higher in patients with restricted LA dilatation than in those with preserved or abnormal LA dilatation (log‐rank test, P < 0.01). Conclusions: Restricted LA dilatation is an indicator for the diagnosis of CA. Further, visual assessment of abnormal LA motion may facilitate diagnosis in patients with CA and high‐risk patients with HCM. [ABSTRACT FROM AUTHOR]

Aims: Traditional criteria for heart transplantation by cardiopulmonary exercise testing (CPX) include peak oxygen uptake (VO2) < 14 mL/kg/min. Reaching a sufficient exercise load is challenging for patients with refractory heart failure (HF) because of their exercise intolerance. Recently, a substantial impact of right ventricular (RV) dysfunction was highlighted on urgent heart transplantation and mortality. This study aims to investigate the impact of RV contractile reserve, assessed by low‐load exercise stress echocardiography (ESE), on exercise intolerance defined as peak VO2 < 14 mL/kg/min, in patients with HF. Methods and results: We prospectively examined 67 consecutive patients hospitalized for HF who underwent ESE and CPX under a stabilized HF condition. Although low‐load ESE was defined as 25 W load exercise, an increment in RV systolic (s′) velocity was regarded as the preservation of RV contractile reserve. All patients completed low‐load ESE. During low‐load ESE, the variation in RV s′ velocity significantly correlated with peak VO2 (r = 0.787, P < 0.001). The change in RV s′ velocity during low‐load ESE accurately identified patients with peak VO2 < 14 mL/kg/min (area under the curve, 0.95; sensitivity, 92%; specificity, 85%). The intraclass correlation coefficient for intra‐observer and inter‐observer agreement for the change in RV s′ velocity was 0.96 (95% confidence interval, 0.88–0.99, P < 0.001) and 0.86 (95% confidence interval, 0.64–0.95, P < 0.001), respectively. The RV‐to‐pulmonary circulation (PC) coupling, which was assessed by the slope of the relationship between RV s′ velocity and pulmonary artery systolic pressure at rest and low‐load exercise, was worse in the low‐peak VO2 group (<14 mL/kg/min) than the preserved‐peak VO2 group (≥14 mL/kg/min). Conclusions: The change in RV s′ velocity during low‐load ESE could estimate the exercise capacity in HF patients. The assessments of RV contractile reserve and RV‐to‐PC coupling could be clinically beneficial to distinguish high‐risk HF patients. [ABSTRACT FROM AUTHOR]

Aims Late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (MRI) in hypertrophic cardiomyopathy (HCM) has been reported to be associated with myocardial fibrosis and cardiac events. In patients with HCM, two-dimensional (2D) strain can identify subclinical global systolic dysfunction despite normal left ventricular (LV) chamber function. Therefore, this study tested the hypothesis that global 2D strain could detect subtle myocardial fibrosis and serve as a novel prognostic parameter in HCM patients. Methods and results Echocardiography and MRI were performed in 48 consecutive patients with HCM and normal chamber function. We measured global longitudinal strain (GLS) in apical two-chamber, four-chamber, and long-axis views using speckle-tracking analysis. The extent of LGE (%LGE = LGE volume/total LV volume) and LV mass index were calculated by MRI using Simpson's rule and custom software. All patients were followed up for major cardiac events. Global longitudinal strain in patients with LGE was significantly lower than that without LGE (−11.8 ± 2.8 vs. −15.0 ± 1.7%, P < 0.001). Multivariate analysis showed that GLS was an independent predictor of %LGE (standard coefficient = 0.627, P < 0.001). During a mean follow-up period of 42 ± 12 months, five patients had cardiac events. When the patients were stratified based on the median level of GLS (−12.9%), all events were observed in the worse GLS group (P = 0.018). Conclusion These results suggest that global 2D strain might provide useful information on myocardial fibrosis and cardiac events in HCM patients with normal chamber function. [ABSTRACT FROM AUTHOR]

BackgroundThe present study examined the inhibitory action of temporary treatment with an angiotensin type 1 (AT1) receptor blocker (ARB) on vascular remodeling using hypertensive mice with overexpression of the human renin (hRN) and angiotensinogen (hANG) genes.MethodshRN/hANG transgenic mice (hRN/hANG-Tg) were treated with an ARB, valsartan, from 4 weeks of age. In some mice, valsartan treatment was stopped at 8 weeks of age (temporary treatment). Inflammatory vascular injury was induced by polyethylene-cuff placement around the femoral artery at the age of 10 weeks.ResultsCompared with wild-type (WT) mice, hRN/hANG-Tg showed higher blood pressure (BP) and enhancement of oxidative stress and medial thickening even before cuff placement. Inflammatory vascular remodeling and oxidative stress after cuff placement were further enhanced in hRN/hANG-Tg. Temporary treatment with valsartan continuously lowered BP even after cessation of administration, and inhibited these changes. In contrast, administration of hydralazine lowered BP to a similar level to that with valsartan, but did not inhibit medial thickening and inflammatory vascular remodeling. In contrast to the valsartan treatment, BP immediately increased to the untreated level after cessation of hydralazine.ConclusionsThese results indicate that temporary ARB treatment leads to prolonged effect of BP lowering and prevents vascular remodeling in hypertensive mice induced by activation of the human renin-angiotensin system. The inhibitory action of valsartan is not due to the BP lowering but is at least in part due to a decrease in oxidative stress and inflammation.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.6 [ABSTRACT FROM AUTHOR]

BackgroundTo explore the metabolic actions of nifedipine on diabetes, we examined glucose intolerance and white adipose tissue changes in type 2 diabetic KK-Ay mice.MethodsMale KK-Ay mice were treated with nifedipine (1.5 mg/kg/day in lab chow) for 5 weeks, which did not affect blood pressure or feeding of KK-Ay mice.ResultsAfter treatment with nifedipine, body weight tended to decrease and the weight of white adipose tissue was reduced. Without food restriction, nifedipine decreased plasma insulin level, while plasma glucose level tended to decrease. In oral glucose tolerance test, nifedipine suppressed the increase in glucose level after a glucose load without affecting plasma insulin concentration. Nifedipine also improved the result of insulin tolerance test. In white adipose tissue, nifedipine increased adipocyte number and the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and adipocyte fatty acid-binding protein related to adipocyte differentiation. In addition, expression of adiponectin, insulin receptor, insulin receptor substrate-1, and glucose transporter type-4 was also increased by nifedipine. Nifedipine also increased the expression of NO synthase in white adipose tissue. Nifedipine did not affect expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in white adipose tissue. Such changes in white adipose tissue were apparent in retroperitoneal adipose tissue. Nifedipine did not change the expression of angiotensin receptors, renin receptor, and angiotensinogen in white adipose tissue. Moreover, nifedipine attenuated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and increased superoxide dismutase (SOD) activity in white adipose tissue.ConclusionThese results suggest that nifedipine can enhance insulin sensitivity and reduce white adipose tissue, possibly related to stimulation of adipocyte differentiation.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.198 [ABSTRACT FROM AUTHOR]

BackgroundPrevious reports indicated that blockade of AT1 receptor stimulation attenuated adipocyte dysfunction. However, the effects of AT2 receptor stimulation on adipose tissue were not yet clear. In the present study, we examined the adipose tissue dysfunction in atherosclerotic apolipoprotein E knockout (ApoEKO) mice with AT2 receptor deficiency.MethodsMale ApoEKO and AT2 receptor/ApoE knockout (AT2/ApoEKO) mice at 6 weeks of age were treated with a normal diet or a high-cholesterol diet (HCD: 1.25% cholesterol). Markers for adipocyte differentiation and inflammation in adipose tissue were assayed with real-time reverse-transcription-PCR and western blot.ResultsCompared with ApoEKO mice, AT2/ApoEKO mice with a normal diet showed only a decrease in expression of adiponectin and CCAAT/enhancer binding protein δ (C/EBPδ) in epididymal adipose tissue without changes in body weight, adipose tissue weight, and adipocyte number even at 6 months of age. After HCD for 4 weeks, the weight of both epididymal and retroperitoneal adipose tissue in AT2/ApoEKO mice was greater than that in ApoEKO mice without a change in body weight. Plasma concentrations of cholesterol and fatty acids were higher in AT2/ApoEKO mice than in ApoEKO mice. In adipose tissue of AT2/ApoEKO mice, the adipocyte number was decreased and the expression of peroxisome proliferator–activated receptor γ (PPARγ), C/EBPα, and aP2 was lower than that in ApoEKO mice, in association with an increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.ConclusionsThese results suggest that AT2 receptor stimulation in adipose tissue is involved in the improvement of adipocyte differentiation and adipose tissue dysfunction in atherosclerotic model.American Journal of Hypertension 2009; doi:10.1038/ajh.2009.85American Journal of Hypertension 2009; 22, 7, 784–791. doi:10.1038/ajh.2009.85 [ABSTRACT FROM AUTHOR]

BackgroundA combination of different types of antihypertensive drugs is widely used for the treatment of hypertension. We examined the inhibitory effects of a combination of an AT1 receptor blocker (ARB), olmesartan, with various calcium channel blockers (CCBs) on inflammatory vascular remodeling.MethodsInflammatory vascular remodeling was induced by polyethylene-cuff placement around the femoral artery of C57BL/6J mice at 10 weeks of age. Olmesartan (0.5 mg/kg/day) was administered intraperitoneally using an osmotic minipump. CCBs (nifedipine 1.0 mg/kg/day, amlodipine 0.1 mg/kg/day, azelnidipine 0.1 mg/kg/day), and hydrochlorothiazide (HCTZ 0.5 mg/kg/day) were administered orally.ResultsIn the injured artery, superoxide anion production and expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p47phox and Rac-1 were markedly increased, together with expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor (TNF)-α. Administration of a single drug alone at each concentration did not significantly inhibit these changes in the injured artery. However, a combination of olmesartan with various CCBs inhibited neointimal formation as well as oxidative stress and inflammatory markers in the injured artery. Moreover, among these CCBs, inhibition of these markers by olmesartan with azelnidipine was stronger than that caused by a combination with other CCBs. On the other hand, a combination of subeffective doses of olmesartan and HCTZ did not significantly affect vascular changes after cuff placement.ConclusionsThese results suggest that the combination of ARB with CCB synergistically inhibits vascular remodeling and that the inhibitory actions of ARB on vascular remodeling may vary depending on the combined CCB.American Journal of Hypertension (2009). doi:10.1038/ajh.2008.344American Journal of Hypertension (2009); 22, 2, 145–150. doi:10.1038/ajh.2008.344 [ABSTRACT FROM AUTHOR]

BACKGROUND The roles of the angiotensin (Ang) II type 1 (AT1) receptor in the changes in white adipose tissue were explored in an animal model of atherosclerosis using apolipoprotein E-deficient (ApoEKO) mice. METHODS Apolipoprotein E-deficient (ApoEKO) mice and KK-Ay mice were used. Expression of markers for adipocyte differentiation and inflammation was determined by real-time reverse-transcription polymerase chain reaction. RESULTS Adipose tissue weight and adipocyte size in epididymal white adipose tissue were increased in ApoEKO mice and KK-Ay mice. In the adipose tissue of these models, expression of adiponectin and peroxisome proliferator-activated receptor-γ (PPARγ), which induce adipocyte differentiation, and expression of transcription factors of adipocyte differentiation, such as CCAAT-enhancer-binding protein-α (C/EBPα) and aP2, were decreased. Expression of inflammatory markers and nicotinamide adenine dinucleotide phosphate oxidase subunits was also increased. Deletion of AT1a receptor in ApoEKO mice and administration of an AT1 receptor blocker, valsartan, to KK-Ay mice reduced epididymal adipose tissue weight and adipocyte size significantly. Blockade of the AT1 receptor also reduced the expression of inflammatory chemokines and oxidative stress markers. Moreover, AT1a receptor deletion in ApoEKO mice and AT1 receptor blockade in KK-Ay mice prevented the decrease in expression of adiponectin, PPARγ, C/EBPα, and aP2. Valsartan also increased glucose uptake induced by insulin in adipose tissue of KK-Ay mice. CONCLUSIONS These results suggest that enlargement and weakened differentiation of adipocytes are observed in atherosclerosis and diabetes, and that AT1 receptor blockade prevented adipocyte enlargement and promoted adipocyte differentiation in these models. [ABSTRACT FROM AUTHOR]

Background: The effect of a calcium channel blocker (CCB) on the expression of monocyte chemoattractant protein (MCP)-1 was explored in inflammatory vascular injury, focusing on the role of nuclear factor (NF)-κB. Methods: Vascular injury was induced by cuff placement. Expression of MCP-1 was determined by real-time RT-PCR. NF-κB expression and its activity were detected by Western blot and electrophoretic mobility shift assay. Results: Polyethylene cuff placement around the mouse femoral artery increased MCP-1 expression, together with proliferation of vascular smooth muscle cells and neointimal formation in the injured artery. The content of NF-κB was decreased in the cytosolic fraction but increased in the nuclear fraction prepared from the injured artery. In the nuclear fraction, the binding activity of NF-κB to the promoter region of MCP-1 was markedly increased. On the other hand, IκB content in the cytosolic fraction was decreased in the injured artery after cuff placement, accompanied by an increase in IκB kinase (IKK) phosphorylation. Treatment of mice with a CCB, nifedipine, at a dose of 5 mg/kg/day, significantly decreased vascular smooth muscle cell proliferation and neointimal formation without affecting blood pressure. This dose of nifedipine inhibited the increase in MCP-1 expression in the injured artery. Moreover, nifedipine reduced the nuclear content and DNA-binding activity of NF-κB in the injured artery. In contrast, the decrease in IκB content and the increase in IKK phosphorylation in the cytosolic fraction were attenuated by nifedipine. Conclusions: These results indicate that MCP-1 expression in inflammatory vascular injury is regulated by activation of NF-κB. The results also suggest that nifedipine attenuates MCP-1 expression in the injured artery via inhibition of the nuclear translocation and DNA-binding activity of NF-κB, and thereby improves vascular remodeling. [Copyright &y& Elsevier]

The article presents a case study of a 68-year-old woman suffering from coronary risk factors, hypertension, and others; examined with Coronary CT angiography (CTA) with multidetector computed tomography (MDCT) that revealed lesion in the proximal right coronary artery.

‘Coronary steal’ is frequently observed in the recipient artery supplied from collaterals. Coronary steal during stress may have an adverse effect on myocardial function even in a ‘well-collateralized’ territory. We experienced one case with functional occlusion in which the coronary steal phenomenon was demonstrated non-invasively using transthoracic Doppler echocardiography. The non-invasive assessment of coronary flow measurement might allow us to obtain useful information for understanding the pathophysiology of coronary steal. [ABSTRACT FROM PUBLISHER]

Myocardial bridging (MB) is a congenital anomaly characterized by systolic compression of the tunnelled arterial segment. MB may cause myocardial ischaemia due to abnormal coronary blood flow. We report a case of MB in which transthoracic Doppler echocardiography was used to evaluate the long-term effect of beta-blocker therapy on abnormal coronary blood flow. In this case, beta-blocker therapy with bisoprolol (5.0 mg/day) for 1 month eliminated the patient's symptoms and normalized coronary blood flow through the tunnelled arterial segment. [ABSTRACT FROM AUTHOR]