Jutaro Yamada

Localized elevation of shear stress is related to coronary plaque rupture: a 3-dimensional intravascular ultrasound study with in-vivo color mapping of shear stress distribution.

OBJECTIVES The purpose of the present study was to assess the relationship between shear stress distribution and coronary plaque rupture by means of a new color-mapping program of shear stress with 3-dimensional intravascular ultrasound (IVUS). BACKGROUND Various in-vitro studies have demonstrated that shear stress of the vascular lumen is one of the important determinants of coronary plaque vulnerability. However, the in-vivo relationship between shear stress and plaque rupture is still unclear. METHODS In the present study, 3-dimensional IVUS was used to obtain spatial information on luminal geometry from 20 patients with acute coronary syndrome having a distinct ulcerative lesion. These 3-dimensional contours for each lumen were first reconstructed into mesh polygons, and then analyzed by means of a program for calculating the fluid dynamics. The flow was considered to be a constant laminar one. Then, colorized mappings of the distribution of the streamline, blood pressure, and shear stress were performed. The original luminal contour for each ruptured lesion was obtained by smoothing and extrapolation. RESULTS All patients had a coronary plaque rupture in the proximal or top portion of the plaque hill. In the color mapping, localized elevation of blood pressure and shear stress could be observed on each plaque surface. The shear stress concentration was frequently correlated with the plaque rupture site (kappa = 0.79). CONCLUSIONS Although the absolute value of shear stress is not sufficient to directly provoke mechanical destruction of the fibrous cap, localized high shear stress might be a trigger of fibrous cap rupture.

Comparison of expression of connexin in right atrial myocardium in patients with chronic atrial fibrillation versus those in sinus rhythm

An abnormal distribution of the gap junction occurs in chronic atrial fibrillation (AF). There are conflicting data regarding changes in connexins (Cxs) in experimental models of AF. We examined whether patients with chronic AF have alterations in atrial Cxs. We analyzed the expression of Cx40 and Cx43 in the right atrial myocardium from 10 patients with mitral valvular disease (MVD) who had AF (MVD/AF), 10 patients with MVD who were in normal sinus rhythm (MVD/NSR), and 10 control patients in NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained before surgery, and an electrophysiologic examination was performed during the operation. An immunohistochemical study was performed on atrial tissue. The relative expression level of Cx40 protein was significantly lower in MVD/AF patients (6.5 +/- 4.6) than in either MVD/NSR patients (17.7 +/- 8.9, p <0.05) or controls (24.7 +/- 11.1, p <0.01). The relative expression level of Cx40 messenger ribonucleic acid was also significantly lower in MVD/AF patients (0.23 +/- 0.13) than in MVD/NSR patients (0.47 +/- 0.26, p <0.01) or controls (0.47 +/- 0.17, p <0.01). For Cx43 protein and messenger ribonucleic acid, there was no significant difference in relative expression levels among the 3 groups. Interestingly, the level of serine-phosphorylated Cx40 was approximately 52% greater in MVD/AF patients than in controls. In MVD/AF patients, the immunoreactive signal of Cx40 was significantly lower than in controls. There was no significant difference in the connective tissue-volume fraction among the groups. Thus, downregulation of Cx40 and abnormal phosphorylation of Cx40 may result in abnormal cell-to-cell communication and alteration in the electrophysiologic properties of the atrium, leading to the initiation and/or perpetuation of AF.

Alterations in cardiac sarcoplasmic reticulum Ca2+regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation

OBJECTIVES Our purpose was to determine whether atrial fibrillation (AF) patients have alterations in sarcoplasmic reticulum (SR) Ca2+ regulatory proteins in the atrial myocardium. BACKGROUND Clinically, AF is the most frequently encountered arrhythmia. Recent studies indicate that an inability to maintain intracellular Ca2+ homeostasis with a consequent increase in membrane-triggered activity could be the primary initiating factor in some circumstances, and that cytosolic Ca2+ abnormalities are an important mediator of sustained AF. METHODS We measured the maximum number of [3H]ryanodine binding sites (Bmax) and the expression levels of ryanodine receptor (RyR) mRNA and calcium-adenosine triphosphatase (Ca2+-ATPase) mRNA in atrial myocardial tissue from 13 patients with AF due to mitral valvular disease (MVD) and 9 patients with normal sinus rhythm (NSR). RESULTS In AF patients, 1) Bmax was significantly lower in each atrium (0.21+/-0.03 pmol/mg [right], 0.16+/-0.04 pmol/mg [left]) than in the right atrium (0.26+/-0.08 pmol/mg) of NSR patients; 2) Bmax was significantly lower in the left atrium than in the right atrium; 3) Bmax in the left atrium was significantly lower at higher levels of pulmonary capillary wedge pressure; 4) the expression level of RyR mRNA was significantly lower in both the left (1.24 x 10(-2)+/-1.28 x 10(-2)) and right (1.70 x 10(-2)+/-1.78 x 10(-2)) atrium than in the right atrium of NSR patients (6.11 x 10(-2)+/-2.79 x 10(-2)); and 5) the expression level of Ca2+-ATPase mRNA was significantly lower in both the left (5.67 x 10(-2)+/-4.01 x 10(-2)) and right (7.71 x 10(-2)+/-3.56 x 10(-2)) atrium than in the right atrium (12.60 x 10(-2)+/-3.92 x 10(-2)) of NSR patients. CONCLUSIONS These results provide the first direct evidence of abnormalities in the Ca2+ regulatory proteins of the atrial myocardium in chronic AF patients. Conceivably, such abnormalities may be involved in the initiation and/or perpetuation of AF.

Up-regulation of inositol 1,4,5 trisphosphate receptor expression in atrial tissue in patients with chronic atrial fibrillation

BACKGROUND Abnormal intracellular Ca2+ homeostasis occurs in chronic atrial fibrillation(AF). The intracellular Ca2+ concentration is regulated by ryanodine and inositol 1,4,5-trisphosphate (IP3) receptors. Changes occur in ryanodine receptors in atrial tissue from patients in chronic AF. Whether AF patients have alterations in atrial IP3 receptors was investigated. METHODS IP3 receptor expression was analyzed in the right atrial myocardium from 13 mitral valvular disease (MVD) patients with AF (MVD/AF), 5MVD patients with normal sinus rhythm(MVD/NSR), and 8 control patients with NSR(tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on the atrial tissue. RESULTS The relative expression level of IP3 receptor protein was significantly greater in MVD/AF (0.75 +/- 0.26) than in MVD/NSR (0.42 +/- 0.13, p < 0.01), and both were significantly above the control value (0.14 +/- 0.08). The relative expression level of IP3 receptor mRNA was significantly greater in MVD/AF(0.028 +/- 0.008) than in control subjects (0.015 +/- 0.004, p < 0.01), but MVD/AF patients did not differ from MVD/NSR (0.020 +/- 0.006) patients. The relative expression levels of IP3 receptor protein and mRNA were higher in patients with left atrial dimension > or = 40 mm, pulmonary capillary wedge pressure > or = 10 mmHg, and right atrial pressure > or = 5 mmHg. IP3 receptors were overexpressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD. CONCLUSIONS Since chronic mechanical overload of the atrial myocardium increases IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca2+ homeostasis and initiating and/or perpetuating AF.

3D optical coherence tomography: new insights into the process of optimal rewiring of side branches during bifurcational stenting.

AIMS We describe three-dimensional optical coherence tomography (3D-OCT) guided bifurcation stenting and the clinical utility of 3D-OCT. METHODS AND RESULTS Twenty-two consecutive patients who underwent OCT examination to confirm the recrossing position after stent implantation in a bifurcation lesion were enrolled. Frequency domain OCT images were obtained to check the recrossing position and 3D reconstructions were performed off-line. The recrossing position was clearly visualised in 18/22 (81.8%) cases. In 13 cases, serial 3D-OCT could be assessed both before and after final kissing balloon post-dilation (FKBD). We divided these cases into two groups according to the presence of the link between hoops at the carina: free carina type (n=7) and connecting to carina type (n=6). All free carina types complied with the distal rewiring. The percentage of incomplete stent apposition (%ISA) of free carina type at the bifurcation segment after FKBD was significantly smaller than that of the connecting to carina type (0.7±0.9% vs. 12.2±6.5%, p=0.0074). CONCLUSIONS 3D-OCT confirmation of the recrossing into the jailed side branch is feasible during PCI and may help to achieve distal rewiring and favourable stent positioning against the side branch ostium, leading to reduction in ISA and potentially better clinical outcomes.

Urinary 8-hydroxy-2′-deoxyguanosine reflects symptomatic status and severity of systolic dysfunction in patients with chronic heart failure

Oxidative stress is known to play a crucial role in the pathogenesis of heart failure (HF). We investigated whether urinary 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), a product of oxidative DNA damage, is a clinically useful biomarker of the severity of chronic heart failure (CHF) and oxidative stress levels in failing hearts.

Late giant coronary aneurysm associated with a fracture of sirolimus eluting stent: A case report

A 73-year-old female underwent percutaneous coronary intervention (PCI) because of stable angina. An elective PCI for the RCA lesion was first performed with deploying sirolimus eluting stents (SES). Three weeks later, PCI was also provided in the residual LAD lesion. Eight months later, she presented with new angina. CAG revealed an in-stent restenosis in the mid LAD and a large eccentric saccular coronary aneurysm (17 mm x 9 mm) at the proximal RCA. Intravascular ultrasound (IVUS) showed absence of stent struts around the orifice of aneurysm, which suggested a fracture of SES stent. The entry of coronary aneurysm was finally sealed with a polytetrafluoroethylene-covered stent. This report documented a rare case of late giant coronary artery aneurysm associated with a fracture of SES.

Vasodilator responses of coronary conduit and resistance arteries to continuous nitroglycerin infusion in humans: a Doppler guide wire study.

To examine the responses of coronary conduit and resistance arteries to the continuous i.v. administration of nitroglycerin in 15 patients with atypical chest pain, we measured coronary blood flow velocity in the left anterior descending coronary artery using a Doppler guide wire and the lumen diameter and cross-sectional area by quantitative coronary angiography. Systolic flow, diastolic flow, total coronary flow, and coronary vascular resistance were calculated. Stepwise increases in dose of nitroglycerin resulted in significant dose-dependent decrease in mean aortic pressure (p < 0.01) and increase in lumen diameter (p < 0.05). After nitroglycerin administration of 0.5 microg/kg/min, systolic flow decreased significantly by 89.9+/-15.7% (p < 0.01), and diastolic flow increased significantly by 74.2+/-37.1% (p < 0.05). Total coronary flow did not change significantly with the various doses of nitroglycerin. However, coronary vascular resistance decreased significantly at concentrations greater than 0.5 microg/kg/min nitroglycerin. Continuous nitroglycerin infusion did not reduce either diastolic or total coronary blood flow despite a significant reduction in coronary perfusion pressure. These results indicate that subendocardial blood flow might be maintained during continuous i.v. infusion of nitroglycerin within the clinical dose range.

Serial changes in the three-dimensional aspect of the side-branch ostium jailed by a drug-eluting stent assessed by optical coherence tomography

The present study investigated serial changes in the three-dimensional (3D) aspect of the jailed side-branch (SB) ostium. We evaluated 32 patients who underwent examination with optical coherence tomography (OCT) both at baseline and at follow-up. After reconstruction of the 3D images, we classified the configuration of overhanging struts at the SB orifice into three groups according to the 3D aspect of the jailing configuration. The number of compartments divided by the stent strut was counted. The side-branch flow area (SBFA), i.e., the area of the SB ostium except for jailing struts, was measured by cut-plane analysis. Forty-eight SBs of 25 patients were analyzed. Thirteen SBs were classified as the No-jail type (N-type), 19 as the Simple-jail type (S-type; no longitudinal link at the carina), and 16 as the Complex-jail type (C-type; had a link at the carina). In the N-type, the SBFA was significantly increased at follow-up (P = 0.018). In the C-type, the SBFA was significantly decreased at follow-up (P = 0.002). Percent reduction of SBFA in the C-type group was significantly greater than that in the N-type or S-type groups (S-type vs. C-type P = 0.002, N-type vs. C-type P < 0.001). 3D-OCT images showed that some of the compartments were filled with tissue. The number of compartments was significantly decreased at follow-up (P < 0.001). In the C-type group, the SBFA was significantly decreased and small compartments were filled with tissue. These findings suggest that stent jail complexity is associated with the progression of SB ostial stenosis.

Inferior J waves in patients with vasospastic angina might be a risk factor for ventricular fibrillation

BACKGROUND There is little information about the relationship between J waves and the occurrence of ventricular fibrillation (VF) in patients with vasospastic angina (VSA). The present study aimed to assess the incidence of J waves and the occurrence of VF in patients with VSA. METHODS The subjects consisted of 62 patients with VSA diagnosed by acetylcholine provocation tests in our institution from 2002 to 2014. We investigated the VF events, prevalence of J waves, and relationship between the VF events and J waves. RESULTS J waves were observed in 16 patients (26%) and VF events were documented in 11 (18%). The incidence of VF in the patients with J waves was significantly higher than that in those without J waves (38% vs 11%, p=0.026). J waves were observed in the inferior leads in 14 patients, lateral leads in 5, and anterior leads in 3. A univariate analysis indicated that the incidence of VF in the inferior leads of J wave positive patients (46%=6/14) was significantly (p=0.01) higher than that in the inferior leads of J wave negative patients (10%=5/48). The J waves in the anterior and/or lateral leads were not related to the incidence of VF. Notched type and slurred type J waves were not associated with VF. A multivariate analysis revealed that J waves in VSA patients were associated with VF [odds ratio (OR) 6.41, 95% confidence interval (CI) 1.37-29.93, p=0.02] and organic stenosis (OR 6.98, 95% CI 1.39-35.08, p=0.02). Further, J waves in the inferior leads were strongly correlated with VF (OR 11.85, 95% CI 2.05-68.42, p=0.006). CONCLUSIONS The results suggest that the existence of J waves, especially in the inferior leads, might be a risk factor for VF in VSA patients.