Identification and Characterization of Synaptic Vesicle Membrane Protein VAT-1 Homolog as a New Catechin-Binding Protein.

(-)-Epigallocatechin-3-gallate (EGCg), a major constituent of green tea extract, is well-known to exhibit many beneficial actions for human health by interacting with numerous proteins. In this study we identified synaptic vesicle membrane protein VAT-1 homolog (VAT1) as a novel EGCg-binding protein in human neuroglioma cell extracts using a magnetic pull-down assay and LC-tandem mass spectrometry. We prepared recombinant human VAT1 and analyzed its direct binding to EGCg and its alkylated derivatives using surface plasmon resonance. For EGCg and the derivative NUP-15, we measured an association constant of 0.02-0.85 ×103 M-1s-1 and a dissociation constant of nearly 8 × 10-4 s-1. The affinity Km(affinity) of their binding to VAT1 was in the 10-20 µM range and comparable with that of other EGCg-binding proteins reported previously. Based on the common structure of the compounds, VAT1 appeared to recognize a catechol or pyrogallol moiety around the B-, C- and G-rings of EGCg. Next, we examined whether VAT1 mediates the effects of EGCg and NUP-15 on expression of neprilysin (NEP). Treatments of mock cells with these compounds upregulated NEP, as observed previously, whereas no effect was observed in the VAT1-overexpressing cells, indicating that VAT1 prevented the effects of EGCg or NUP-15 by binding to and inactivating them in the cells overexpressing VAT1. Further investigation is required to determine the biological significance of the VAT1-EGCg interaction.

Evaluation of novel indices of walking performance taking oxygen desaturation into account during six-minute walk test in cardiovascular disease patients.

In pulmonary disease patients since oxygen desaturation during 6-min walk test (6MWT) affects walk distance (6MWD), some novel indices such as desaturation/distance ratio [DDR, oxygen desaturation area (DAO2)/6MWD] and distance-saturation product [DSP, 6MWD × minimum peripheral oxygen saturation (SpO2)] are evaluated. However, there has been no study examining these indices that consider exercise-induced desaturation (EID) in patients with cardiovascular disease. In 94 cardiovascular disease patients without pulmonary complications, 6MWT and echocardiography were performed at the entry of cardiac rehabilitation. SpO2 was measured during 6MWT using a continuously monitorable pulse oximeter, and DSP and DDR were calculated using minimum SpO2 and DAO2 [sum of (100-SpO2) per second during 6MWT], respectively. EID was defined as SpO2 decrease of ≥ 4% or minimum SpO2 of < 90% during 6MWT. DSP was slightly lower and DDR was markedly higher in patients with EID than in those without. When examining correlations of DSP and DDR with their components, DSP was correlated with 6MWD much closely than minimum SpO2, while DDR was correlated as closely with DAO2 as 6MWD. Furthermore, DAO2, but not minimum SpO2, had a direct correlation with 6MWD. As for associations with cardiac function, DSP was correlated with several cardiac parameters, but DDR was not correlated with any of these parameters. Our findings suggest that oxygen desaturation during 6MWT affects walking distance in cardiovascular disease patients even without pulmonary complications and that DDR is more appropriate than DSP as an index of walking performance that takes EID into consideration, independently of cardiac function.

The E/e' ratio on echocardiography as an independent predictor of the improvement of left ventricular contraction in patients with heart failure with reduced ejection fraction.

OBJECTIVE: Clinical feature of heart failure with improved ejection fraction (HFimpEF) remains to be fully elucidated. The present study investigated the association of clinical and echocardiographic parameters with the subsequent improvement of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). METHODS: From outpatients with a history of hospitalized for heart failure, 128 subjects diagnosed as HFrEF (LVEF <40%) on heart failure hospitalization were enrolled and longitudinally surveyed. During follow-up periods more than 1 year, 58 and 42 patients were identified as HFimpEF (improved LVEF to ≥40% and its increase of ≥10 points) and persistent HFrEF, respectively. RESULTS: There was no difference in age or sex between the two groups with HFimpEF and persistent HFrEF. The rate of ischemic heart disease was lower and that of tachyarrhythmia was higher in the HFimpEF group than in the persistent HFrEF group. At baseline (i.e., on heart failure hospitalization), LVEF did not differ between the two groups, but left ventricular systolic and diastolic diameters were already smaller and the ratio of early diastolic transmitral velocity to early diastolic tissue velocity (E/e') was lower in the HFimpEF group. A multiple logistic regression analysis revealed that lower baseline E/e' was a significant determinant of HFimpEF, independently of confounding factors such as ischemic heart disease, tachyarrhythmia, and baseline left ventricular dimension. CONCLUSION: Our findings indicate that the lower ratio of E/e' in the acute phase of heart failure onset is an independent predictor of the subsequent improvement of LVEF in HFrEF patients.

Kinetics of atrial and brain natriuretic peptides during hemodialysis are regulated in association with different cardiac functional changes.

The blood levels of atrial and brain natriuretic peptides (ANP and BNP) are both increased markedly in hemodialysis patients, but the kinetics of the two are not always parallel. The present study investigated the association of changes in ANP and BNP levels before and after dialysis with changes in cardiac function in hemodialysis patients. A total of 57 patients (mean age 64 years, 47 males and 10 females) on maintenance hemodialysis with sinus rhythm were enrolled. Blood samples were taken at the beginning and end of dialysis, and plasma levels of ANP and BNP were measured. Changes in cardiac function during dialysis were examined by echocardiography performed just before and after dialysis. Both plasma ANP and BNP concentrations decreased significantly after hemodialysis, but the rate of decrease in BNP [mean ± SD, 555 ± 503 to 519 ± 477 pg/mL (- 6.4%), P = 0.011] was much smaller than that in ANP [233 ± 123 to 132 ± 83 pg/mL (- 43.4%), P < 0.001]. As for the relation to the changes in echocardiographic parameters before and after dialysis, the decrease in inferior vena cava diameter had a close correlation with the decrease in ANP (r = 0.528, P < 0.001), but not BNP. In contrast, the decrease in left ventricular end-diastolic volume index was correlated only with the decrease in BNP (r = 0.297, P = 0.035). The peak velocity ratio of early diastolic to atrial filling decreased with preload reduction by dialysis, and its decrease was more strongly correlated with the decrease in BNP (r = 0.407, P = 0.002) than that in ANP (r = 0.273, P = 0.040). These results demonstrated that in hemodialysis patients, the decrease in plasma ANP by a single dialysis was essentially caused by blood volume reduction, while BNP decrease was mainly induced by the reduction of left ventricular overload. Our findings indicate that the kinetics of both peptides during dialysis are regulated by different cardiac and hemodynamic factors.

Long-term administration of tolvaptan ameliorates annual decline in estimated glomerular filtration rate in outpatients with chronic heart failure.

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, - 8.02 ± 9.35 to - 1.62 ± 5.09 mL/min/1.73m2 /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.

Usefulness of pre- and post-stent optical frequency domain imaging findings in the prediction of periprocedural cardiac troponin elevation in patients with coronary artery disease.

Cholesterol crystals (CCs) are frequently found in high-risk plaques, such as thin-capped fibroatheromas. The purpose of this study was to investigate the associations of CCs, plaque morphologies, and post-stent optical frequency domain imaging (OFDI) findings with periprocedural cardiac troponin (cTn) elevation in patients treated with percutaneous coronary intervention (PCI). This study consists of 119 patients with stable coronary artery disease (CAD) with normal cTn levels who underwent OFDI-guided PCI. Periprocedural cTn elevation was defined as an elevation of cTn ≥ × 5 times the upper reference limit after PCI. Pre- and post-stent OFDI findings, including fibrous cap thickness (FCT), presence of CCs, and parameters for lipid and calcification were analyzed. A total of 37 (31%) patients were classified into the periprocedural cTn elevation group. Compared with lesions without CCs, lesions exhibiting CCs had thinner FCT, larger lipid arc, and longer lipid length, and were more likely to have irregular protrusion and in-stent thrombus (all p < 0.05). For pre-stent OFDI features, FCT < 82 µm [odds ratio (OR) 4.11; p = 0.003] and CCs (OR 3.23; p = 0.017) were associated with periprocedural cTn elevation. For post-stent OFDI features, in-stent dissection (OR 3.08; p = 0.035) and in-stent thrombus (OR 7.98; p = 0.002) were independent predictors of cTn elevation. The combination of CCs and FCT < 82 µm showed increased risk of periprocedural cTn elevation (OR 7.22; p = 0.002). OFDI-guided PCI provides unique insight into the mechanism for periprocedural cTn elevation in CAD patients.

Prognostic significance of renal dysfunction and its change pattern on outcomes in patients with acute coronary syndrome treated with emergent percutaneous coronary intervention.

Renal dysfunction and its change pattern are associated with short- and long-term mortality. However, it remains to be investigated whether or not worsening renal function (WRF) defined by baseline renal function identified from different time points would provide prognostic implication on outcomes in acute coronary syndrome (ACS) patients. This study consists of 334 ACS patients (mean age 68 ± 11 years, 75% male) treated with emergent percutaneous coronary intervention (PCI). Estimated glomerular filtration rate (eGFR) was evaluated on baseline, during hospitalization, at discharge, and at 3-month follow-up. WRF was defined as a relative decrease of eGFR > 20% at 3 months using baseline eGFR identified from different time points. The primary end point was a composite event of major cardiovascular events (MACE), including all-cause death, ACS, and heart failure hospitalization. The associations of chronic kidney disease (CKD), acute kidney injury (AKI), and WRF with MACE were evaluated. During a mean follow-up of 3.3 ± 1.7 years, a total of 64 MACE were observed. Multivariable analysis revealed that CKD (hazard ratio 2.16; p = 0.018) and AKI (hazard ratio 1.95; p = 0.030) were independent predictors of MACE, but WRF did not remain as an independent predictor of MACE (p = 0.208). The highest risk was observed in AKI patients with CKD when stratified by the presence or absence of CKD and AKI. In ACS patients treated with emergent PCI, this study demonstrated that CKD and AKI were independent predictors of MACE, while there was no independent relationship between WRF and MACE.

Associations of sensitive cardiac troponin-I with left ventricular morphology, function and prognosis in end-stage renal disease patients with preserved ejection fraction.

Sensitive cardiac troponin I (cTnI) predicts all-cause and cardiovascular mortality in various clinical settings. However, its clinical significance in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF) has not been fully elucidated. This study investigated the association of cTnI with LV morphology and function, and its long-term outcome in HD patients with preserved LVEF. This prospective study consists of 96 HD patients with preserved LVEF (69 ± 8 years and 63% male) who underwent two-dimensional echocardiographic examination and biomarker tests including cTnI, brain natriuretic peptide, and high-sensitive C-reactive protein. The primary endpoint was all-cause death and secondary endpoint was cardiovascular death. Factors independently associated with cTnI were systolic blood pressure (ß = - 0.239, p = 0.011), heart rate (ß = 0.216, p = 0.021), LV mass index (ß = 0.231, p = 0.020), and E to e' ratio (ß = 0.237, p = 0.016). During a mean follow-up of 3.6 years, primary and secondary endpoints were observed in 23 (24%) and 18 (19%) patients, respectively. In the multivariate Cox proportional hazard analysis, the upper cTnI tertile has significantly increased risk of all-cause mortality [hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.139-6.386; p = 0.024] and that of cardiovascular death (HR, 4.56; 95% CI 2.021-16.968; p = 0.006) independent of echocardiographic measures and other serum biomarkers. In HD patients with preserved LVEF, serum cTnI levels were significantly associated with diastolic function and risk of mortality independent of echocardiographic variables and other biomarkers.

Incidence and predictors of silent cerebral thromboembolic lesions after catheter ablation for atrial fibrillation in patients treated with direct oral anticoagulants.

There are few reports about the incidence and predictors of silent cerebral thromboembolic lesions (SCLs) after atrial fibrillation (AF) ablation in patients treated with direct oral anticoagulants (DOACs). The purpose of this study is to evaluate the incidence and predictors of SCLs after AF ablation with cerebral magnetic resonance imaging (C-MRI) in patients treated with DOACs. We enrolled 117 consecutive patients who underwent first AF ablation and received DOACs, including apixaban, dabigatran, edoxaban, and rivaroxaban. DOACs were discontinued after administration 24 h before the procedure, and restarted 6 h after the procedure. During the procedure, activated clotting time (ACT) was measured every 15 min, and intravenous heparin infusion was performed to maintain ACT at 300-350 s. All patients underwent C-MRI the day after the procedure. SCLs were detected in 28 patients (24%) after AF ablation. Age, female sex, the presence of persistent AF, left atrial volume, procedure time, radiofrequency energy, electrical cardioversion, and mean ACT showed no correlations with the incidence of SCLs. Multivariate analysis revealed independent predictors of SCLs were CHA2DS2VASc scores ≥3, left atrial appendage (LAA) emptying velocity ≤39 cm/s, and minimum ACT ≤260 s. Patients with both CHA2DS2VASc scores ≥3 and LAA flow velocity ≤39 cm/s had the highest incidence of SCLs 15 of 26 patients (58%). In patients treated with DOACs, CHA2DS2VASc score ≥3, minimum ACT ≤260 s, and LAA emptying velocity ≤39 cm/s were independent risk factors for the SCLs after AF ablation.

Clinical Benefit of Sacubitril/Valsartan for Hypertensive Patients in Daily Practice and Predictors of Its Antihypertensive Effect.

Background: The blood pressure (BP)-lowering effect of sacubitril/valsartan (Sac/Val) is greater than that of angiotensin II receptor blockers (ARBs) but in in real-world clinical practice, Sac/Val is used in a variety of patterns other than switching from ARBs. In the present study we investigated the effects of Sac/Val on BP and biochemical parameters when switching from or adding it to various antihypertensive drugs and examined what factors could be predictors of the antihypertensive effect of Sac/Val. Methods and Results: In 108 hypertensive patients treated with antihypertensive agents (including 4 naïve cases), clinic BP and various biochemical parameters were assessed before and after switching to/adding Sac/Val (200 mg/day). Systolic and diastolic BPs significantly decreased after treatment with Sac/Val (P<0.0001, respectively). As for biochemical parameters, alanine aminotransferase, triglycerides, C-reactive protein, and uric acid significantly decreased after administration of Sac/Val, but renal function, B-type natriuretic peptide, and plasma renin activity (PRA) did not change before or after treatment with Sac/Val. Multiple regression analysis revealed that low PRA and high baseline systolic BP were independent determinants of systolic BP reduction after Sac/Val treatment. Conclusions: Sac/Val is beneficial for poorly controlled hypertension in daily clinical practice and low PRA may be a predictor of the antihypertensive effect of switching to/adding Sac/Val.

Predictive value of early-phase heart rate reduction for subsequent recovery of left ventricular systolic function in heart failure with reduced ejection fraction.

INTRODUCTION: Predictors of heart failure with recovered ejection fraction (HFrecEF) remain to be fully elucidated. This study investigated the impact of heart rate and its change on the recovery of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). MATERIAL AND METHODS: From 398 outpatients who had a history of hospitalisation for heart failure, 138 subjects diagnosed as HFrEF (LVEF < 40%) on heart failure hospitalisation were enrolled and longitudinally surveyed. During follow-up periods more than one year, 64 and 46 patients were identified as HFrecEF (improved LVEF to ≥ 40% and its increase of ≥ 10 points) and persistent HFrEF, respectively. RESULTS: In the overall subjects, the reduction of heart rate through the observation periods was closely correlated with the improvement of LVEF (r = -0.508, p < 0.001). Heart rate on hospital admission for heart failure was markedly higher in patients with HFrecEF (112 ± 26 bpm) than in those with persistent HFrEF (90±18 bpm). Whereas heart rate at the first outpatient visit after discharge was already lower in the HFrecEF group (80 ± 13 vs. 85 ± 13 bpm in the persistent HFrEF group). A multivariate logistic regression analysis revealed that the decrease in heart rate from admission to the first visit after discharge was a significant determinant of HFrecEF (p < 0.001), independently of confounding factors such as ischemic heart disease and baseline LVEF and left ventricular dimension. CONCLUSIONS: Our findings suggest that heart rate reduction in the early phase after heart failure onset is a powerful independent predictor of the subsequent recovery of LVEF in HFrEF patients.

Cardiac metastasis of lung cancer presented as mimicking ST-elevation myocardial infarction with reciprocal electrocardiographic changes.

We report the case of a patient with metastatic cardiac tumor who presented with chest pain and electrocardiographic changes mimicking acute inferior myocardial infarction. An 84-year-old man who had undergone lung cancer surgery one year earlier was referred to emergency outpatient visit because of chest pain. His 12-lead electrocardiography (ECG) showed ST-segment elevation in the inferior leads with reciprocal ST-segment depression in the precordial and lateral leads, which was initially interpreted as inferior acute myocardial infarction. By emergency coronary angiography, however, there was no significant stenosis or occlusion in the right coronary artery or the left circumflex artery. In echocardiographic examinations after admission, a large mass was found in the area corresponding to the infero-posterior wall of the left ventricle, which had been detected only by positron emission tomography with computed tomography six months earlier. He died one month after admission. Pathological autopsy revealed a tumor of 8 × 5 cm size in the myocardium of the posterior to inferior wall of the left ventricle, and diagnosed as cardiac metastasis from lung cancer. ECG changes with ST-segment elevation, in particular persistent ST-elevation in the absence of Q waves, can be a sign for tumor invasion of the heart. Learning objective: It is necessary to consider the possibility of myocardial metastasis when a patient with malignancy presents with acute myocardial infarction-like electrocardiography findings. Besides, in this case, positron emission tomography with computed tomography (PET-CT) had detected an abnormal accumulation in the left ventricle earlier than when the tumor was pointed out by echocardiography. Multimodality imaging including PET-CT could help physicians to make the early and accurate diagnosis of metastatic cardiac tumor.

Achilles tendon thickness is associated with coronary lesion severity in acute coronary syndrome patients without familial hypercholesterolemia.

BACKGROUND: Thickening of Achilles tendon (≥9 mm on radiography) is one of the diagnostic criteria for familial hypercholesterolemia (FH). Since FH is associated with premature coronary artery disease (CAD) including acute coronary syndrome (ACS), measurement of Achilles tendon thickness (ATT) is important for early diagnosis of FH. However, clinical significance of mild thickening of Achilles tendon in non-FH patients with CAD is unclear. The present study investigated the association of ATT with coronary lesion severity in early-onset ACS without clinically diagnosed FH. METHODS: From outpatients who had a history of ACS under 60 years old, 76 clinically non-FH subjects (71 men and 5 women; mean age at the onset of ACS, 50.5 years) with maximum ATT of <9 mm were enrolled in this study. The severity of coronary lesions was assessed by SYNTAX score derived from coronary angiography at the onset of ACS. RESULTS: ATT levels were not significantly different among patients with ST-elevation myocardial infarction (STEMI, n=47), non-STEMI (n=12), and unstable angina (n=17). Whereas, both average and maximum ATT were significantly larger in patients with multivessel lesions (n=25) than in those with single-vessel disease (n=51). Furthermore, SYNTAX score was positively correlated with average ATT (r=0.368, p=0.0011) and maximum ATT (r=0.388, p=0.0005). As for the relation to clinical parameters, maximum ATT had positive correlations with body mass index and C-reactive protein. A multiple regression analysis revealed that average and maximum ATT were significantly associated with SYNTAX score, independently of various confounding factors. CONCLUSIONS: Our findings demonstrated that ATT, even though its level was <9 mm, was associated with coronary lesion severity in clinically non-FH patients with early-onset ACS. Apart from diagnosing FH, ATT may be a predictor of the progression of CAD.

Renoprotective effect of chronic treatment with sodium-glucose cotransporter 2 inhibitors and its associated factors in Japanese patients with chronic heart failure and diabetes.

Background: Recent clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on renal function in heart failure patients. This study confirmed the renoprotective effect of treatment with SGLT2 inhibitors in Japanese patients with chronic heart failure and diabetes and further investigated what cardiac/hemodynamic and noncardiac factors are involved in its effect. Methods: Eligible 50 outpatients with chronic heart failure and type-2 diabetes mellitus chronically taking SGLT2 inhibitors were enrolled. Annual changing rates of estimated glomerular filtration rate (eGFR) were compered before and after treatment with SGLT2 inhibitors and the associations of the change in eGFR slope after SGLT2 inhibitor administration with changes in various clinical and echocardiographic parameters were evaluated. Results: The mean follow-up periods before and after SGLT2 inhibitor administration were 2.6 and 1.9 years, respectively. Changing rates of eGFR per year were significantly improved after treatment with SGLT2 inhibitors (-5.78 ± 7.67 to -0.43 ± 10.81 mL/min/1.73 m2/year, p = 0.006). The daily doses of loop diuretics were not altered after SGLT2 inhibitor administration. Neither decreased body weight nor increased hematocrit was associated with the change in eGFR slope before and after SGLT2 inhibitor administration. While, the decrease in inferior vena cava diameter and the increase in its respiratory collapsibility were significantly correlated with the improvement of eGFR decline slope after SGLT2 inhibitor administration. Conclusions: Our findings indicated that chronic treatment with SGLT2 inhibitors ameliorated annual decline in eGFR in Japanese patients with chronic heart failure, suggesting the possibility that the improvement of venous congestion was involved in its renoprotective effect.

Ankle-brachial index, arterial stiffness, and biomarkers in the prediction of mortality and outcomes in patients with end-stage kidney disease.

BACKGROUND: Although ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are significant predictors of major adverse cardiovascular event (MACE), their prognostic value in association with biomarkers has not been fully evaluated in patients with end-stage kidney disease (ESKD). HYPOTHESIS: We hypothesized that ABI/baPWV would provide better prognostic value independent of biomarkers in ESKD patients. METHODS: This study included 104 ESKD patients treated with maintenance hemodialysis who underwent ABI and baPWV examinations and laboratory tests, including brain-natriuretic peptide, high-sensitive cardiac troponin T (hs-cTnT), and high-sensitive C-reactive protein (hs-CRP). MACE was defined as a composite event of all-cause death, acute coronary syndrome, and stroke. RESULTS: During a mean follow-up of 3.6 ± 1.7 years, a total of 51 MACE were observed. The independent factors associated with MACE were age >75 years (adjusted hazard ratio [HR], 2.15; P < .05), abnormal ABI (adjusted HR, 2.01; P < .05), left ventricular ejection fraction (LVEF) <50% (adjusted HR, 3.33; P < .001), the upper tertile of hs-cTnT (adjusted HR, 2.77; P < .05), and hs-CRP (HR, 1.96; P < .05). However, baPWV did not remain as an independent predictor of MACE in the entire cohort and also in patients without abnormal ABI. The combination of predictors improves the predictive value of MACE, providing increased HR with 4.00 for abnormal ABI + hs-CRP, 4.42 for abnormal ABI + hs-cTnT, and 7.04 for abnormal ABI + LVEF <50% (all P < .001). CONCLUSION: Abnormal ABI is a robust predictor of MACE independent of biomarkers and their combination provides better risk stratification compared with a single predictor in ESKD patients.

Effect of azithromycin therapy on coronary circulation in patients with coronary artery disease.

This study examined the effect of azithromycin therapy on the coronary microcirculation using measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography in 35 patients with coronary artery disease. CFVR increased significantly after azithromycin therapy (3.0 +/- 0.7 vs 3.5 +/- 0.7, p <0.001). The changes in CFVR were negatively correlated with changes in high-sensitivity C-reactive protein levels in patients receiving azithromycin.

Cut-off value of coronary flow velocity reserve by transthoracic Doppler echocardiography for diagnosis of significant left anterior descending artery stenosis in patients with coronary risk factors.

The purpose of this study was to evaluate the adequate cut-off value of coronary flow velocity reserve (CFVR) with transthoracic Doppler echocardiography for diagnoses of significant left anterior descending (LAD) artery stenosis in a large study population with various coronary risk factors. CFVR, which has been used for evaluation of significant coronary artery stenosis, can be reduced despite angiographically normal coronary arteries in patients with various coronary risk factors. However, the adequate cut-off value of CFVR for diagnosing significant LAD stenosis has not been fully established in patients with coronary risk factors. We examined 138 consecutive patients who underwent coronary angiography. Clinical histories of coronary risk factors were determined from interviews or medical records. CFVR assessment in the LAD artery by transthoracic Doppler echocardiography was performed in all patients. Of the 138 patients, 30 had significant stenosis, and the remainder had no stenotic lesions in the LAD artery. Receiver-operating characteristic curves for detection of significant LAD stenosis showed that a cut-off value of <2.0 was extremely precise. A cut-off value <2.0 of CFVR had a sensitivity of 90%, a specificity of 93%, a positive predictive value of 77%, and a negative predictive value of 97% for the presence of significant LAD stenosis. A cut-off value <2.0 of CFVR by transthoracic Doppler echocardiography was adequate for the diagnosis of significant LAD stenosis in a population that included patients with coronary risk factors.

Effect of fluvastatin therapy on coronary flow reserve in patients with hypercholesterolemia.

Coronary flow reserve was evaluated using transthoracic Doppler echocardiography before and after 3 months of fluvastatin therapy in patients with hypercholesterolemia. Coronary flow reserve increased significantly after lipid-lowering therapy, and coronary microcirculation was improved in patients with hypercholesterolemia.