Yuki Tsuda

Clinical Significance of Natriuretic Peptides and Cyclic GMP in Hemodialysis Patients with Coronary Artery Disease

Background: Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) are suitable markers of ’dry body weight’ (DW) in hemodialysis (HD) patients. However, it is still unknown whether these markers can be applied to patients with renal failure and coronary artery disease (CAD). We examined the reliability of these peptides as volume markers in HD patients with CAD. We also assessed the relationship between natriuretic peptides and indices of left ventricular (LV) function. Methods: Plasma concentrations of ANP, BNP and cGMP were determined before and after HD in patients with CAD (group 1, n = 19, mean age 63 ± 12 years) and were compared with those of patients without cardiac disease (group 2, n = 20, age 61 ± 15 years). Using data obtained by cardiac catheterization, we examined the relationship between natriuretic peptides and indices of LV function in HD patients with CAD. Results: Baseline ANP (244 ± 205 pg/ml), BNP (713 ± 928 pg/ml) and cGMP (29.6 ± 21.6 pmol/ml) were significantly higher in group 1 than in 11 healthy volunteers (18.6 ± 9.9 pg/ml, 7.7 ± 7.6 pg/ml, cGMP 8.9 ± 4.9 pmol/ml, respectively). HD significantly reduced plasma ANP (87 ± 75 pg/ml) and BNP (477 ± 702 pg/ml) although they were still above normal control. HD reduced plasma cGMP (7.2 ± 4.5 pmol/ml) to normal values, suggesting the elimination of cGMP across the dialyzers. Baseline levels of ANP, BNP and cGMP in group 2 were less than those of group 1 but higher than the control. HD reduced natriuretic peptides in group 2 to levels lower than those in post-HD group 1. After HD, there was no significant correlation between reductions in body weight and changes in ANP or BNP. Baseline ANP and BNP levels closely correlated with pulmonary artery pressure, pulmonary artery wedge pressure, left ventricular end-diastolic pressure and left ventricular ejection fraction. A significant correlation was observed between BNP levels and the severity of CAD. Conclusion: ANP, BNP and cGMP seem to be a useful markers for fluid overload but not for DW in HD patients with CAD. Plasma ANP and BNP might be useful markers for left ventricular function.

Involvement of PDGF in pressure-induced mesangial cell proliferation through PKC and tyrosine kinase pathways.

In glomerular hypertension, mesangial cells (MC) are subjected to at least two physical forces: mechanical stretch and high transmural pressure. Increased transmural pressure, as well as mechanical stretch, promotes MC proliferation, which may enhance glomerulosclerosis. The exact mechanism of this effect is not fully understood. We examined the effects of transmural pressure alone on cell proliferation and DNA synthesis and investigated the role of platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), candidates for mediation of glomerular diseases, in the pressure-induced events. Pressure was applied to cultured MC placed in a sealed chamber using compressed helium gas. Application of pressure resulted in a time-dependent ( approximately 2 h) and pressure level-dependent (approximately 80 mmHg) increase in cell number (1.4-fold) and [(3)H]thymidine incorporation (2.7-fold). Pressure-induced DNA synthesis was significantly suppressed by inhibitors of phospholipase C (2-nitro-4-carboxyphenyl-N, N-diphenylcarbamate), protein kinase C [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and chelerythrine], or tyrosine kinases (genistein). Pressure caused a rapid but transient formation of inositol 1,4,5-trisphosphate, which was blocked by the phospholipase C inhibitor. Pressure also promoted a rapid increase in tyrosine kinase activity. Pressure increased mRNA levels of PDGF-B, with a peak at 6 h, but not those of PDGF-A or bFGF. Pressure-induced DNA synthesis was partially inhibited by a neutralizing anti-PDGF antibody but not by an antibody against bFGF or nonimmune IgG. Our results indicated that pressure by itself increases DNA synthesis and proliferation of cultured rat MC possibly through activation of protein kinase C and tyrosine kinases, and PDGF-B could be partially involved in these pathways.

Risk of progression to hypertension in nonhypertensive Japanese workers aged 20-64 years.

Objective: Prehypertension is a known risk factor for hypertension in individuals aged less than 20 or more than 35 years, but no large studies have investigated this risk in individuals aged 20–34 years. This study investigated progression to hypertension in nonhypertensive individuals aged 20–34 years and compared this group with individuals aged 35–64 years. Methods: A total of 12 639 nonhypertensive individuals aged 20–64 years were followed from 1999 to 2008. Hazard ratios for progression to hypertension were calculated for men and women according to three blood pressure (BP) categories (optimal BP: <120/80 mmHg; normal BP: 120–129/80–84 mmHg; high-normal BP: 130–139/85–89 mmHg) and three age groups (20–34, 35–49 and 50–64 years). Results: Progression to hypertension occurred in 4617 individuals (36.5%). The risk of progression to hypertension increased significantly with increasing baseline BP category in men and women in all age groups. The association between baseline BP and progression to hypertension was stronger in the group aged 20–34 years than in the older age groups, especially in men. Conclusion: The results of this study confirm that normal or high-normal BP increases the risk of progression to hypertension in individuals aged 20–34 years. In men, the association between baseline BP and progression to hypertension is stronger in this age group than in older age groups. Health providers should be aware that normal or high-normal BP is a risk factor for progression to hypertension even in individuals aged 20–34 years.

Contribution of Poststent Irregular Protrusion to Subsequent In-Stent Neoatherosclerosis after the Second-Generation Drug-Eluting Stent Implantation: Optical Coherence Tomography Study

Previous optical coherence tomography (OCT) study reported that irregular protrusion (IP) post drug-eluting stent (DES) implantation was an independent predictor of clinical outcome; however, the relationship between IP and the presence of subsequent in-stent neoatherosclerosis remains unclear. This study aimed to assess the relationship between IP and in-stent neoatheroscrerosis formation using OCT. We evaluated 83 patients (101 lesions) who underwent second-generation DES implantation and 8-month follow-up (8M-FU) using OCT. Lesions were divided into two groups in presence of IP (IP: n = 43, non-IP: n = 58). At prepercutaneous coronary intervention (pre-PCI), lipid-rich plaque, lesions with positive remodeling, and in-stent thrombus formation were more frequent in IP than in non-IP. On multivariate analysis, the thrombus at pre-PCI and the lesions with positive remodeling were independent predictors of IP. At 8M-FU, heterogeneous neointima, microvessel, lipid-laden neointima, and thin-cap fibro-atheroma like neointima were more frequent in IP than in non-IP (respectively, P < 0.05). On multivariate analysis, IP was associated with heterogeneous neointima. Binary restenosis was more frequent and late lumen loss tended to be larger in IP than in non-IP (19% versus 5%, P = 0.04; 1.25 ± 1.24 mm versus 0.91 ± 0.63 mm, P = 0.09); however, the target lesion revascularization rate was similar in both groups at 8M-FU. In conclusion, our study suggested that poststent IP was associated with subsequent neoatherosclerosis formation at 8M-FU after the second-generation DES implantation.

CORONARY ARTERIAL REMODELING AND PERISTENT PLAQUE CHANGE AFTER DRUG-ELUTING STENT IMPLANTATION – COMPARISON BETWEEN ZOTAROLIMUS-ELUTING STENTS AND PACLITAXEL-ELUTING STENTS -

BACKGROUND Out-stent plaque characteristics and eosinophilic inflammatory response, which correlates with positive remodeling after first-generation drug-eluting stent implantation, may be associated with late restenosis and very late stent thrombosis. The differences of out-stent plaque characteristics were compared between paclitaxel-eluting stents (PES) and zotarolimus-eluting stents (ZES), using integrated backscatter-intravascular ultrasound (IB-IVUS). METHODS AND RESULTS Of 78 patients enrolled, 25 receiving PES and 25 receiving ZES had adequate IVUS assessment. Volumetric IVUS analysis was performed after stenting and at 8-month follow-up. Out-stent plaque change in the stented segment was compared on IB-IVUS. The relationship between systemic inflammatory response and out-stent plaque change was evaluated. In PES, vessel volume significantly increased (365-389 mm(3), P<0.0001), whereas it did not change in ZES (315-314 mm(3), P=0.81). In culprit lesions at baseline in PES, fibrous plaque tended to increase (3.1-3.6mm(2), P=0.051) and lipid plaque significantly increased (4.3-5.1mm(2), P=0.02), whereas in ZES the fibrous plaque significantly increased (2.9-4.0mm(2), P<0.0001) but lipid plaque significantly decreased (5.1-3.6mm(2), P<0.0001). Systemic eosinophil increase was significantly correlated with positive remodeling and out-stent lipid plaque increase. CONCLUSIONS Chronic out-stent plaque change in ZES consisted of less positive remodeling and more favorable effects on out-stent plaque characteristics than PES. Systemic eosinophil change might be a marker of out-stent lipid plaque change.

LONG-TERM PROGNOSIS OF PATIENTS WITH IRREGULAR PROTRUSION AFTER SECOND-GENERATION DRUG-ELUTING STENT IMPLANTATION: OPTICAL COHERENCE TOMOGRAPHY STUDY

Previous optical coherence tomography (OCT) study reported that irregular protrusion (IP) post drug-eluting stent (DES) implantation associated with adverse clinical outcome. However, the relationship between IP, neointimal characteristics at follow-up, and future prognosis is still unknown. We

TCT-565 Fate of irregular protrusion after second-generation drug-eluting stent implantation: Serial optical coherence tomography study.

Previous optical coherence tomography (OCT) study reported that irregular protrusion (IP), defined as protrusion of material with an irregular surface into lumen between stent struts, and small minimal stent area (MSA) at post drug-eluting stent (DES) implantation were independent predictors of 1-

The Correlation between Post-Procedural Plasma Fractalkine and Lipid Plaque Volume in Target Lesion after Coronary Stent Implantation

Several reports suggest that fractalkine (FKN) and its cognate receptor, CX3CR1, play a role in atherogenesis. Recent data showed that plasma FKN is elevated in patients with unstable angina pectoris and is more elevated with patients with plaque rapture. We assessed the hypothesis that plasma FKN might be elevated after stentimplantation and related to the plaque-characteristics. First of all we tested the time course of plasma FKN level 30-min., 3-hour, 6-hour and 12-hour after coronary stenting. Their levels are elevated at 30 min. after percutaneous coronary intervention (PCI) and maintained the level until 12-hour after PCI. Then we examined the plasma levels of FKN, IL-8 and IL-6 in fifty consecutive patients before and 12-hour after coronary stenting following in integrated backscatterintravascular ultrasound (IB-IVUS) analysis. The plasma IL-8 did not change 12-hour after stenting. Those of FKN and IL-6, however, were significantly elevated 12-hour after stenting (FKN: from 656 ± 122 pg/mL to 811 ± 177 pg/ mL, p<0.0001, IL-6: from 3.15 ± 3.42 pg/mL to 16.0 ± 15.0 pg/mL, p<0.0001). In IB-IVUS analysis the lipid volume and volume fraction were correlated with post-procedural FKN level (R2=0.29, p<0.0001; R2=0.22, p<0.0001), while they were not related with post-procedural IL-6 level. In conclusion, a local release of FKN and IL-6 occurs shortly after PCI, which is possibly related to plaque rapture and/or endothelial traumatism following stent-implantation. We have further shown that local release of FKN is evoked proportionally to the volume of the lipid-rich plaques which are prone to be ruptured. These suggested that anti-FKN treatment could be of benefit to decrease the amount of lipid-rich plaque.

Successful coronary intervention for spontaneous coronary dissection in a patient with fibromuscular dysplasia

Spontaneous coronary artery dissection (SCAD) is a reported rare cause of acute coronary syndrome (ACS) and sudden death among middle-aged women. Some institutes have recently reported fibromuscular dysplasia (FMD) concomitant with SCAD. Therefore, a survey of the presence of comorbid FMD in SCAD patients is important to obtain a definitive diagnosis and for the prediction of possible SCAD recurrence. The optimal treatment of ACS due to SCAD remains undetermined, and technical failures are frequently encountered in primary percutaneous coronary intervention (PCI) owing to the unusual non-atherosclerotic cause of the disease. We report a case of SCAD successfully treated with cutting balloon PCI under intravascular ultrasound guidance without stent implantation, in which FMD was detected in the right external iliac artery through screening by noncoronary angiography, not duplex ultrasound. <Learning objective: SCAD is a rare cause of ACS. Intravascular ultrasound is helpful to avoid the technical failures associated with primary percutaneous coronary intervention in the treatment of ACS due to SCAD. FMD has been recently reported to be concomitant with SCAD. Therefore, this report aimed to survey the presence of comorbid FMD in SCAD patients given its important role in obtaining a definitive diagnosis and predicting the possible recurrence of SCAD.>.

A rare case of myocardial infarction related to diagnostic intravascular ultrasound

A 71-year-old man underwent intracoronary stent implantation for acute inferior myocardial infarction (MI). Immediately after diagnostic intravascular ultrasound (IVUS) at 8 months’ follow-up, an acute occlusion of the sinus node (SN) artery appeared, which developed sinus arrest with junctional escape rhythm. The serum level of high-sensitivity troponin T (TpT) was markedly elevated on the day after the procedure (2.1–32.5 ng/l), which was indicative of MI related to IVUS. Under continuous intravenous infusion of unfractionated heparin, the escape rhythm changed to lower atrial rhythm on the 4th day, and recovered to sinus rhythm on the 14th day. Coronary angiography (CAG) on 15th day showed a recanalization of the SN artery, but optical coherence tomography identified that disrupted plaque and white thrombus still existed in the ostium of the SN artery. The patient was discharged on maintenance anticoagulation therapy. We hypothesized from this case that IVUS-related myocardial injury may exist without clinical problems. Our retrospective investigation showed that the median levels of high-sensitivity TpT in 20 patients who underwent CAG and subsequent diagnostic IVUS significantly increased from 0.6 (interquartile range 0.3–1.1) to 1.6 (0.7–3.6) ng/l (P < 0.05), suggesting that IVUS may induce very low levels of myocardial injury. In conclusion, we experienced a rare case of IVUS-related MI caused by an acute occlusion of the SN artery. This case reaffirms that we should pay more attention to manipulation of IVUS catheters.