Impact of smoking on coronary microcirculatory resistance in patients with coronary artery disease.

The aim of this study was to investigate the relationship between coronary microvascular function and smoking using the 3 parameters fractional flow reserve (FFR), coronary flow reserve (CFR(thermo)), and index of microcirculatory resistance (IMR) in patients with coronary artery disease (CAD). A total of 97 CAD patients with 148 intermediate stenotic lesions were divided into two groups: current and former smokers (Smokers: n = 54), and those who had never smoked (Non-smokers: n = 43). Coronary physiology measurements were made following coronary angiography at rest and during hyperemia induced with intravenous adenosine triphosphate. If a patient had several intermediate lesions, the lesion producing the largest IMR value and minimum FFR(myo) and CFR(thermo) value was selected. Averaged over all patients, the FFR(myo), CFR(thermo), and IMR values were 0.86 ± 0.10, 2.66 ± 1.50, and 20.8 ± 10.7, respectively. There was no significant correlation between FFR(myo) and IMR. There were no significant differences between smokers and non-smokers in FFR(myo) value (median: 0.85 [IQR: 0.74-0.90] versus 0.87 [IQR: 0.83-0.90], P = 0.15) and CFR(thermo) value (median: 1.90 [IQR: 1.56-3.16] versus 2.10 [IQR: 1.50-2.67] U, P = 0.95). The IMR value was significantly greater in smokers (median: 24.2 [IQR: 16.8-32.5] U versus 18.5 [IQR: 15.4-27.0] U, P = 0.04). In multivariate analysis, smoking was an independent predictor of increased IMR. Smoking appears to have a detrimental effect on coronary microvascular function as measured by IMR.

Progression of hyponatremia is associated with increased cardiac mortality in patients hospitalized for acute decompensated heart failure.

BACKGROUND: Although hyponatremia during hospitalization for acute decompensated heart failure (ADHF) has been reported to correlate with poor prognosis, few studies have examined the effect of progression of hyponatremia on cardiac prognosis in ADHF patients who were normonatremic at admission. METHODS AND RESULTS: Consecutive ADHF patients (n = 662) categorized as New York Heart Association Class III or IV were investigated retrospectively. Of these patients, 634 who survived to discharge were examined and 531 were normonatremic (serum sodium concentration [Na] ≥ 135 and ≤ 145 mmol/L) at admission. The 531 patients were divided into 2 groups: the non-developed group, who remained normonatremic at discharge (n = 455), and the developed group, who had progressed to hyponatremia (Na < 135 mmol/L) at discharge (n = 76). The cardiac event-free rate after 12 months was significantly lower in the developed group than in the non-developed group (22% vs. 71%; P < .0001). Although their baseline levels of brain natriuretic peptide and left ventricular ejection fraction were similar before discharge, the patients in the developed group exhibited higher fractional excretion of sodium and received higher doses of diuretics than did those in the non-developed group. CONCLUSION: Our data suggest that progression to hyponatremia during hospitalization is a robust predictor of poor cardiac prognosis in ADHF patients who were normonatremic at admission.

Improved prognosis of Takayasu arteritis over the past decade--comprehensive analysis of 106 patients.

BACKGROUND: We aimed to describe the recent clinical characteristics of Takayasu arteritis (TA). METHODS AND RESULTS: We enrolled 106 consecutive TA patients and compared the clinical characteristics of patients with TA onset before 1999 and after 2000, patients with onset at age less than 39 years and more than 40 years, patients with monophasic and relapsing-remitting clinical course, and patients with and without human lymphocyte antigen (HLA)-B52 allele. Among the patients with TA onset after 2000, the time from onset to diagnosis had decreased; the frequency of occlusion in aortic arch branches and the complication of moderate or severe aortic regurgitation (AR) had decreased, and the maximum dose of prednisolone and the use of immunosuppressive agents had increased. In patients with onset at age more than 40 years, the complications of coronary artery lesions and hypertension had increased, and the incidence of moderate or severe AR had decreased. In the relapsing-remitting group, the maximum dose of prednisolone and the use of immunosuppressive agents had increased, and the mean dose reduction rate of prednisolone was significantly high. There was no significant difference between patients with and without HLA-B52 allele. CONCLUSIONS: The prognosis of TA patients has improved over the past decade, which may be related to early diagnosis because of the development of noninvasive diagnostic imaging tools and improved medical treatments.

Effect of adiponectin on cardiac allograft vasculopathy.

BACKGROUND: The role of adiponectin (APN), an adipose tissue-specific secretory protein, on chronic rejection after cardiac transplantation in APN-sense transgenic mice (APN-SE) was evaluated. METHODS AND RESULTS: Heterotopic cardiac transplantation in major histocompatibility complex class II-mismatched mice was performed. B6.C-H-2(bm12)KhEg (Bm12) hearts were transplanted into APN-SE, and allografts were harvested at 8 weeks after transplantation. Quantitative polymerase chain reaction (PCR) and immunohistochemical staining showed that the expression of both AdipoR1 and AdipoR2 was induced in APN-SE recipients. Neointimal hyperplasia was significantly decreased in allografts transplanted into APN-SE (luminal occlusion, 8.9 ± 2.2%) compared to those transplanted into controls (49.4 ± 10.5%; P=0.011). APN-SE showed significantly reduced mRNA levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, and monocyte chemoattractant protein-1 (MCP-1) by quantitative PCR. Western blot analysis revealed that the protein levels of IFN-γ and MCP-1 were reduced in APN-SE recipients. Proliferation of smooth muscle cells stimulated with activated T cells was suppressed by APN addition, and this effect was canceled by treatment with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor. CONCLUSIONS: APN plays a critical role in the attenuation of chronic rejection by suppressing inflammatory cytokine and chemokine expression and enhancing APN receptor expression. APN plays a beneficial role in reducing the progression of cardiac allograft vasculopathy through the AMPK pathway.

Comparison of biomarkers for predicting disease severity and long-term respiratory prognosis in patients with acute pulmonary embolism.

Biomarkers are needed for early risk stratification and improved inpatient management to obtain better outcomes in acute pulmonary embolism (PE) patients. The aim of the present study was to evaluate biomarkers of right ventricular dysfunction (RVD) in order to predict a complicated clinical course and long-term respiratory complications in acute PE.We retrospectively enrolled 50 consecutive patients hospitalized for acute PE. Plasma brain natriuretic peptide (BNP), troponin-I, fibrin degradation products, D-dimer, C-reactive protein, and arterial pH were measured to assess their prognostic significance. RVD was evaluated by echocardiography at admission, the clinical course during hospitalization was monitored for the development of complications (death, cardiopulmonary resuscitation, mechanical ventilation or circulatory shock), and the need for home oxygen therapy (HOT) was assessed at/after discharge.Thirty-two patients (64%) had RVD at admission, 6 (12%) developed a complicated clinical course, and 7 (14%) required HOT. Plasma BNP was significantly higher in patients with RVD (median value, 319.3 versus 50.5 pg/mL, P = 0.001). Plasma BNP was also significantly higher (median value, 1307.9 versus 102.6 pg/mL, P = 0.02) and arterial pH significantly lower (acidic) (median value, 7.371 versus 7.438, P = 0.008) in patients who developed a complicated clinical course. In addition, plasma BNP was also significantly higher in patients who required HOT (median value, 505.1 versus 91.1 pg/mL, P = 0.02). Plasma BNP at admission is not only a reliable marker of RVD and predictor of short-term prognosis, but also a predictor of long-term respiratory prognosis in acute PE patients.

Successful off-pump reimplantation of the anomalous right coronary artery from the pulmonary artery: A case report.

Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare occurrence that requires surgical repair, typically via cardiopulmonary bypass (CPB). In this study, we present the case of a patient with ARCAPA with a high risk of cerebral infarction and left main trunk stenosis. However, because of the high risk of cerebral infarction, CPB was no longer an option during surgical intervention. Instead, we performed off-pump reimplantation of the ARCAPA to the ascending aorta and coronary artery bypass grafting of the left coronary artery. The patient had an uneventful postoperative course. Based on the successful outcomes of this case, we suggest off-pump reimplantation of the ARCAPA to the ascending aorta as a useful alternative for patients who are not eligible to undergo CPB during surgical repair. .

Quantitative measures of coronary stenosis severity by 64-Slice CT angiography and relation to physiologic significance of perfusion in nonobese patients: comparison with stress myocardial perfusion imaging.

UNLABELLED: Coronary stenosis severity by 64-slice CT angiography (CTA) is acceptably correlated with intravascular ultrasound. Stress myocardial perfusion imaging using SPECT is an established method for assessment of the functional significance of coronary stenosis. Our aim was to assess a clinical validation of quantitative measurements of coronary stenosis severity by 64-slice CTA and the relation to the physiologic significance of myocardial perfusion. METHODS: One hundred four patients with suspected coronary artery disease underwent 64-slice CTA and stress 201Tl SPECT. The stenosis severities of 105 coronary lesions assessed by CTA with sufficient image quality were compared with the results of stress 201Tl SPECT. The body mass index (BMI) of the patients was 23.8 kg/m2 (range, 21.1-25.6 kg/m2). RESULTS: Reversible defects began to increase progressively when the area of stenosis was at least 60%, and the prevalence of these reversible defects and their severity significantly increased as the degree of stenosis increased. When stenosis severity by CTA is < 60%, ischemia is seldom observed; when stenosis severity is > or =80%, ischemia is common (86%). For intermediate stenosis severity values of 60%-70%, the prevalence of reversible defects was 9 of 27 vessels (33%), and for stenosis severity values of 70%-80%, the prevalence was 20 of 37 vessels (54%). When evaluating the diagnostic accuracy of stenosis severity by CTA to identify patients with ischemia excluding all nonevaluable vessels, applying stenosis thresholds of >70% results in 79% sensitivity, 92% specificity, 66% positive predictive value, and 96% negative predictive value. A lesion minimal luminal cross-sectional area of < 3.7 mm2 was a good accurate cutoff value for significant coronary narrowing using stress SPECT, with a sensitivity of 88% and specificity of 83% by receiver-operating-characteristic analysis. CONCLUSION: Despite an excellent negative predictive value to rule out the presence of ischemia, 64-slice CTA alone is a poor discriminator of the functional significance of myocardial ischemia in a highly selected patient population with a low BMI.

Effects of immunosuppressive and biological agents on refractory Takayasu arteritis patients unresponsive to glucocorticoid treatment.

BACKGROUND: We aimed to investigate the effects of immunosuppressive and biological agents on refractory Takayasu arteritis (TA) patients resistant to or dependent on glucocorticoids. METHODS: Forty-four consecutive TA patients were enrolled, and the clinical characteristics and effectiveness of the immunosuppressive and biological agents in achieving and maintaining remission among glucocorticoid-resistant or glucocorticoid-dependent patients were investigated. RESULTS: Fifteen patients showed favorable response to the initial glucocorticoid treatment, and 29 patients exhibited resistance to initial glucocorticoid treatment or relapsed with tapering glucocorticoid. Of the 29 patients, 5 responded to additional glucocorticoid treatment, and 22 of the remaining 24 glucocorticoid-resistant or glucocorticoid-dependent patients were prescribed immunosuppressive agents. Methotrexate was the most commonly used in these patients as the first-line treatment. In total, 10 patients maintained remission using immunosuppressive agents, with the effectiveness of each agent about 20%. The only significant difference between patients who were and were not able to achieve and maintain remission with immunosuppressive agents was the presence of the HLA-B52 allele (p<0.0001). Biological agents were administered to 6 patients refractory to immunosuppressive agents. All patients were administered tumor necrosis factor (TNF) inhibitors as the first-line treatment, and 3 patients maintained remission. Anti-interleukin-6 receptor antibody was administered to 2 patients who were resistant to the TNF inhibitors, and 1 patient achieved and maintained remission. CONCLUSION: In our cohort, 64% of the glucocorticoid-resistant or glucocorticoid-dependent patients maintained remission through a combined treatment with glucocorticoid, immunosuppressive agents, and/or biological agents. The combined use of immunosuppressive and biological agents appears to be a promising treatment option for achieving and maintaining remission in refractory TA patients.

Vessel Wall Inflammation of Takayasu Arteritis Detected by Contrast-Enhanced Magnetic Resonance Imaging: Association with Disease Distribution and Activity.

AIMS: The assessment of the distribution and activity of vessel wall inflammation is clinically important in patients with Takayasu arteritis. Magnetic resonance imaging (MRI) is a useful tool, but the clinical utility of late gadolinium enhancement (LGE) in Takayasu arteritis has yet to be determined. The aim of the present study was to evaluate the utility of LGE in assessing vessel wall inflammation and disease activity in Takayasu arteritis. METHODS AND RESULTS: We enrolled 49 patients with Takayasu arteritis who had undergone 1.5 T MRI. Patients were divided into Active (n = 19) and Inactive disease (n = 30) groups. The distribution of vessel wall inflammation using angiography and LGE was assessed by qualitative analysis. In 79% and 63% of patients in Active and Inactive groups, respectively, greater distribution of vessel wall inflammation was observed with LGE than with conventional angiography. MRI values of pre- and post-contrast signal-to-noise ratios (SNR), SNR increment (post-SNR minus pre-SNR), pre- and post-contrast contrast-to-noise ratios (CNR), and CNR increment (post-CNR minus pre-CNR) were evaluated at arterial wall sites with the highest signal intensity using quantitative analysis of post-contrast LGE images. No statistically significant differences in MRI parameters were observed between Active and Inactive groups. Contrast-enhanced MRI was unable to accurately detect active disease. CONCLUSION: Contrast-enhanced MRI has utility in detecting the distribution of vessel wall inflammation but has less utility in assessing disease activity in Takayasu arteritis.

Role of FDG PET-CT in Takayasu arteritis: sensitive detection of recurrences.

OBJECTIVES: The aim of this study was to investigate whether the maximum standardized uptake value (max SUV) of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) provides a quantitative indication of disease activity in Takayasu arteritis (TA) cases. BACKGROUND: The clinical value of FDG-PET for assessing TA has been investigated. Clinical evaluation of disease activity is often difficult, because most patients develop recurrent inflammation while receiving corticosteroid treatment. METHODS: Thirty-nine TA patients underwent FDG-PET/CT at Tokyo Medical and Dental University from 2006 to 2010 (35 women and 4 men; median age, 30 years). Disease activity was defined according to National Institutes of Health criteria. Biomarkers including C-reactive protein and erythrocyte sedimentation rate were measured. Forty subjects without vasculitis served as control subjects. RESULTS: The max SUV was significantly higher in active than in inactive cases and control subjects (active [n = 27], median value, 2.7 vs. inactive [n = 12], 1.9; control [n = 40], 1.8; p < 0.001 each). Given a max SUV cutoff of 2.1, sensitivity for active-phase TA was 92.6%, specificity 91.7%, positive predictive value 96.2%, and negative predictive value 84.6%. In receiver-operating characteristic curves comparison, max SUV was superior to C-reactive protein (p < 0.05) and erythrocyte sedimentation rate (p < 0.05). Max SUV was significantly higher in relapsing on treatment cases (n = 17) than in stable on treatment cases (n = 12) (median value, 2.6 vs. 1.9; p < 0.001). CONCLUSIONS: FDG-PET/CT is useful for detection of active inflammation not only in patients with active TA before treatment but also in relapsing patients receiving immunosuppressive agents. The max SUV is useful for assessing subtle activity of TA with high sensitivity.

Adiponectin protects against doxorubicin-induced cardiomyopathy by anti-apoptotic effects through AMPK up-regulation.

AIMS: Adiponectin (APN) has been reported to protect against ischaemia-reperfusion injury and hypertrophy. However, few reports have investigated the cardioprotective effects of APN in doxorubicin (DOX)-induced cardiomyopathy; therefore, we studied the cardioprotective mechanisms of APN in this model. METHODS AND RESULTS: In an in vivo study, we quantified the cardiac pathohistology of C57BL/6 mice [wild-type (WT) mice], APN transgenic mice with high APN concentrations [APN transgenic sense (SE) mice], and those with reduced APN concentrations [APN transgenic antisense (AS) mice] after intraperitoneal injections of DOX (4 mg/kg) weekly for 6 weeks. The survival rate after 14 days was significantly increased in APN-SE mice (WT vs. APN-AS vs. APN-SE: 40 vs. 17 vs. 73%, P < 0.05). We assessed myocardial pathohistological changes and observed that fibrosis and apoptosis were significantly decreased in APN-SE mice compared with those of the other groups. We also assessed DOX-induced apoptotic mechanisms in vitro using cultured cardiomyocytes isolated from neonatal WT mice. The expression of adenosine monophosphate-activated protein kinase (AMPK) and anti-apoptotic factor Bcl-2 increased, but that of pro-apoptotic factor Bax decreased in cardiomyocytes treated with highly concentrated APN. The protective effects of APN were reversed by the addition of an AMPK inhibitor (dorsomorphin) to the culture medium. CONCLUSION: These data suggest that APN improved cardiac function through anti-apoptotic effects by up-regulation of AMPK in DOX-induced cardiomyopathy in mice.

Coronary artery spatial distribution, morphology, and composition of nonculprit coronary plaques by 64-slice computed tomographic angiography in patients with acute myocardial infarction.

Noninvasive identification of nonculprit lesions could improve preventive strategies for acute myocardial infarction (AMI). We assessed the morphology, composition, and spatial distribution of nonculprit coronary plaques in patients with AMI using computed tomographic angiography (CTA). A total of 64 patients with AMI underwent 64-slice CTA within 2 weeks after admission, and 162 symptomatic patients with stable angina pectoris (SAP) underwent CTA and stress myocardial perfusion imaging (MPI). Of these 226 patients, 16 were excluded from the analysis because of image artifacts. The mean number of nonculprit plaques per patient was 5.0 +/- 2.6 in the AMI group (n = 60), 4.2 +/- 2.6 in the SAP group with abnormal MPI findings (n = 67), and 1.1 +/- 1.3 in the SAP group with normal MPI findings (n = 83; p <0.01). Positive remodeling and low-attenuation plaques (<30 Hounsfield units) were more frequently observed in the AMI group (1.9 +/- 1.8) than in the SAP groups (0.6 +/- 0.9 with abnormal MPI findings and 0.2 +/- 0.4 with normal MPI findings; p <0.01). Within the AMI group, positive remodeling and low-attenuation plaques were present significantly more frequently in patients with metabolic syndrome than in those without (2.6 +/- 2.2 vs 1.4 +/- 1.4; p = 0.03) and was significantly more frequently distributed in the proximal segments of the left anterior descending artery (p <0.01). In conclusion, 64-slice CTA could provide promising information for preventive strategies by identifying nonculprit plaque morphology and zones at high risk of future events.

Early validation study of 64-slice multidetector computed tomography for the assessment of myocardial viability and the prediction of left ventricular remodelling after acute myocardial infarction.

AIMS: We aim to validate the ability of multidetector computed tomography (MDCT) for assessing myocardial viability and predicting left ventricular (LV) remodelling after acute myocardial infarction (AMI). METHODS AND RESULTS: In 52 consecutive patients with first AMI, 64-slice MDCT without iodine re-injection was performed immediately following coronary stenting. Electrocardiogram-gated thallium-201 single-photon emission tomography was performed using QGS programs within 5 days and 6 months after onset. Among the 52 patients, 18 patients (Group A) showed transmural contrast-delayed enhancement on MDCT images, 20 patients (Group B) showed subendocardial contrast-delayed enhancement, and 14 patients (Group C) had no contrast-delayed enhancement. In the acute phase, peak creatine kinase-MB [497 (189-744), 182 (90-358), 85 (40-204) IU/mL, respectively, P = 0.0004] was significantly higher in Group A, while the incidence of myocardial blush grade 3 (22, 67, 75%, respectively, P = 0.001) and LV ejection fraction (41 +/- 7, 53 +/- 12, 62 +/- 11%, respectively, P < 0.0001) were significantly lower in Group A. During the 6-month period, LV remodelling (P = 0.001) and the number of rehospitalization for heart failure (P = 0.0017) were more significantly observed in Group A. CONCLUSION: Myocardial contrast-delayed enhancement patterns provide promising information regarding myocardial viability, LV remodelling, and prognosis in AMI.