Intravascular ultrasound predictors of acute side branch occlusion in coronary artery bifurcation lesions just after single stent crossover.

OBJECTIVES: We aimed to assess the intravascular ultrasound (IVUS) predictors of acute side branch (SB) occlusions just after single stent crossover in percutaneous coronary intervention (PCI) for coronary bifurcation lesions. BACKGROUND: PCI for bifurcation lesions remains technically challenging and has more clinical complications such as SB occlusion than non-bifurcation lesions. Although single stent crossover is the most common approach in treating bifurcation lesions, the predictors of acute SB occlusion are unclear. METHODS: Single stent crossover was performed on 174 patients with a total of 272 bifurcation lesions who were enrolled in this study. Each patient also underwent pre-PCI IVUS in a major vessel (MV). SB was defined as ostium diameter of ≥1.5 mm measured by IVUS, and occluded SB was defined as a thrombolysis in myocardial infarction flow grade of ≤2 just after stent implantation. We defined the SB diameter ratio as ostial SB total diameter (media-to-media) divided by ostial SB luminal diameter (intima-to-intima). RESULTS: There were 52 SBs in the occluded group (19.1%). There were no significant differences in baseline characteristics between the SB occluded and non-SB occluded groups. Logistic-regression analysis revealed that the thickness of MV plaque on the bilateral sides of SB at the junction site and the SB diameter ratio were independent predictors of SB occlusion just after stent implantation. CONCLUSIONS: In the IVUS observation, the MV plaque thickness at the junction site and the SB diameter ratio are predictors of acute SB occlusion just after single stent crossover.

Peripheral blood progenitor cell collection by two programs for autologous and allogeneic transplantation.

BACKGROUND: In the Spectra apheresis instrument (Terumo BCT), both manual (Spectra-MNC) and automated (Spectra-Auto) programs have been widely used to collect peripheral blood progenitor cells (PBPCs). However, direct comparison of these programs remains extremely limited. STUDY DESIGN AND METHODS: We investigated 188 collections and products from autologous (patient) and allogeneic (donor) subjects and analyzed a subset of 89 allogeneic collections and products. Twenty-nine subjects who received apheresis for 2 consecutive days using both programs were also evaluated with a paired crossover comparison. RESULTS: The two programs processed similar volumes, but run time was longer with Spectra-Auto. Yield and efficiency of CD34+ cell collection were similar between these programs in the whole cohort, although white blood cell (WBC) and mononuclear cell (MNC) yields were higher with Spectra-MNC. In the allogeneic cohort, yield and efficiency of WBC collection were greater in Spectra-MNC. However, collected WBCs, MNCs, and CD34+ cells were similar between these programs in paired comparison. Regardless of program, preapheresis peripheral WBC, MNC, and CD34+ cell counts correlated with the number of cells collected. In contrast, preapheresis WBC counts in the whole cohort were negatively correlated with collection efficiencies of CD34+ cells in Spectra-MNC but not Spectra-Auto. The products collected using Spectra-MNC contained more contaminating platelets (PLTs) than Spectra-Auto, with a corresponding reduction in postdonation circulating PLTs. CONCLUSION: Spectra-MNC and Spectra-Auto showed distinct features that should be considered on a case-by-case basis. Similar investigations should be undertaken as new collection platforms are introduced.

Serum tenascin-C level is associated with coronary plaque rupture in patients with acute coronary syndrome.

Tenascin-C, a large oligometric glycoprotein of the extracellular matrix, increases the expression of matrix metalloproteinases that lead to plaque instability and rupture, resulting in acute coronary syndrome (ACS). We hypothesized that a high serum tenascin-C level is associated with plaque rupture in patients with ACS. Fifty-two consecutive ACS patients who underwent emergency percutaneous coronary intervention (PCI) and, as a control, 66 consecutive patients with stable angina pectoris (SAP) were enrolled in this study. Blood samples were obtained from the ascending aorta just prior to the PCI procedures. After coronary guide-wire crossing, intravascular ultrasonography (IVUS) was performed for assessment of plaque characterization. Based on the IVUS findings, ACS patients were assigned to two groups according to whether there was ruptured plaque (ruptured ACS group) or not (nonruptured ACS group). There were 23 patients in the ruptured group and 29 patients in the nonruptured group. Clinical characteristics and IVUS measurements did not differ between the two groups. Tenascin-C levels were significantly higher in the ruptured ACS group than in the SAP group, whereas there was no significant difference between the nonruptured ACS and SAP groups. Importantly, in the ruptured ACS group, tenascin-C levels were significantly higher than in the nonruptured ACS group (71.9 ± 34.9 vs 50.5 ± 20.5 ng/ml, P < 0.005). Our data demonstrate that tenascin-C level is associated with pathologic conditions in ACS, especially the presence of ruptured plaque.

Senescence marker protein-30 (SMP30) deficiency impairs myocardium-induced dilation of coronary arterioles associated with reactive oxygen species.

Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate SMP30's effect on coronary circulation derived from myocytes, we measured the changes in the diameter of isolated coronary arterioles in wild-type (WT) mice exposed to supernatant collected from isolated paced cardiac myocytes from SMP30 KO or WT mice. Pacing increased hydrogen peroxide in myocytes, and hydrogen peroxide was greater in SMP30 KO myocytes compared to WT myocytes. Antimycin enhanced and FCCP (oxidative phosphorylation uncoupler in mitochondria) decreased superoxide production in both groups. Addition of supernatant from stimulated myocytes, either SMP30 KO or WT, caused vasodilation. The degree of the vasodilation response to supernatant was smaller in SMP30 KO mice compared to WT mice. Administration of catalase to arterioles eliminated vasodilation in myocyte supernatant of WT mice and converted vasodilation to vasoconstriction in myocyte supernatant of SMP30 KO mice. This vasoconstriction was eliminated by olmesartan, an angiotensin II receptor antagonist. Thus, SMP30 deficiency combined with oxidant stress increases angiotensin and hydrogen peroxide release from cardiac myocytes. SMP30 plays an important role in the regulation of coronary vascular tone by myocardium.

Adaptive servo ventilation improves cardiac dysfunction and prognosis in chronic heart failure patients with Cheyne-Stokes respiration.

Cheyne-Stokes respiration (CSR) is often observed in patients with chronic heart failure (CHF). Although adaptive servo ventilation (ASV) is effective for CSR, it remains unclear whether ASV improves the cardiac function and prognosis of patients with CHF and CSR.Sixty patients with CHF and CSR (mean left ventricular ejection fraction 38.7%, mean apnea hypopnea index 36.8 times/hour, mean central apnea index 19.1 times/hour) were enrolled in this study. Patients were divided into two groups: 23 patients treated with ASV (ASV group) and 37 patients treated without ASV (Non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels and echocardiography were performed before, 3 and 6 months after treatments in each group. Patients were followed-up for cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, NYHA functional class, BNP levels, cardiac systolic and diastolic function were significantly improved with ASV treatment for 6 months. In contrast, none of these parameters changed in the Non-ASV group. Importantly, Kaplan-Meier analysis clearly demonstrated that the event-free rate was significantly higher in the ASV group than in the Non-ASV group.Adaptive servo ventilation improves cardiac function and prognosis in patients with chronic heart failure and Cheyne-Stokes respiration.

Coronary artery spasm related to thiol oxidation and senescence marker protein-30 in aging.

BACKGROUND: Senescence marker protein-30 (SMP30) decreases with aging, and SMP30 knockout (KO) mice show a short life with increased oxidant stress. AIMS: We assessed the effect of oxidant stress with SMP30 deficiency in coronary artery spasm and clarify its underlying mechanisms. RESULTS: We measured vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) of isolated coronary arteries from SMP30 KO and wild-type (WT) mice. In SMP30 KO mice, ACh-induced vasoconstriction occurred, which was changed to vasodilation by dithiothreitol (DTT), a thiol-reducing agent. However, Nω-nitro-L-arginine-methyl ester, nitric oxide (NO) synthase inhibitor, or tetrahydrobiopterin did not change the ACh response. In isolated coronary arteries of WT mice, ACh-induced vasodilation occurred. Inhibition of glutathione reductase by 1, 3-bis(2-chloroethyl)-1-nitrosourea decreased ACh-induced vasodilation (n=10, p<0.01), which was restored by DTT. To evaluate the thiol oxidation, we measured the fluorescence of monochlorobimane (MCB) in coronary arteries, which covalently labels the total. The fluorescence level to MCB decreased in SMP30 KO mice, but with DTT treatment restored to a level comparable to that of WT mice. The reduced glutathione and total thiol levels were also low in the aorta of SMP30 KO mice compared with those of WT mice. Administration of ACh into the aortic sinus in vivo of SMP30 KO mice induced coronary artery spasm. INNOVATION: The thiol redox state is a key regulator of endothelial NO synthase activity, and thiol oxidation was associated with endothelial dysfunction in the SMP30 deficiency model. CONCLUSION: These results suggest that chronic thiol oxidation by oxidant stress is a trigger of coronary artery spasm, resulting in impaired endothelium-dependent vasodilation.

Age-related oxidant stress with senescence marker protein-30 deficiency plays a pivotal role in coronary artery spasm.

OBJECTIVES: We examined the mechanism of coronary artery spasm related to oxidant stress with aging in senescence marker protein-30 (SMP30)-deficient mice because SMP30 decreases with aging and SMP30 knockout (KO) mice show a short life with increased oxidant stress. METHODS: To examine the effect of SMP30 on coronary artery vasomotor tone, we measured the endothelium-dependent [5-hydroxytryptamine (5-HT)] response of isolated, pressurized coronary arteries from SMP30 KO and wild-type (WT) mice (n=10 each). RESULTS: In SMP30 KO mice, 5-HT-induced vasoconstriction occurred, which altered vasodilation with dithiothreitol, a thiol-reducing agent. In WT mice, 5-HT-induced vasodilation occurred. Administration of 5-HT from the aortic sinus induced a coronary artery spasm in SMP30 KO mice, which was prevented by the intravenous administration of Y-27632, rho-kinase inhibitor. The fluorescence level of monochlorobimane in coronary arteries, which covalently labels the reduced total thiols, decreased in SMP30 KO mice, but reverted to a level comparable with that of WT mice on treatment with Y-27632. From these results, SMP30 provides protection against coronary artery spasm. CONCLUSION: Chronic oxidant stress associated with aging plays an important role in coronary artery spasm related to thiol oxidation and rho-kinase signaling.

Deep seating of 5 Fr. guiding catheter across the stenosis with 5 in 7 method was effective for severely calcified lesion.

A 57-year-old male with end stage renal disease underwent coronary angiography (CAG). The CAG revealed two vessel disease with severe calcification. A week after the percutaneous coronary intervention (PCI) to the left anterior descending coronary artery (LAD), we performed PCI to the right coronary artery (RCA). Because of the calcification, no devices could be crossed. We then performed 5 in 7 method using Heartrail ST01, and inserted it across the stenosis, with dilatation balloon at the distal RCA as anchoring. Finally we managed to implant two stents. We report that 5 in 7 method and deep seating of 5 Fr. guiding catheter were effective for the severely calcified lesion.

A reduction of coronary flow reserve is associated with chronic kidney disease and long-term cardio-cerebrovascular events in patients with non-obstructive coronary artery disease and vasospasm.

BACKGROUND: Coronary flow reserve (CFR) provides essential information about the coronary microvasculature. Chronic kidney disease (CKD) is a risk factor for cardio-cerebrovascular diseases. We hypothesized that low CFR is associated with CKD and long-term cardio-cerebrovascular events in the patients without obstructive coronary artery diseases and vasospasm. METHOD AND RESULTS: In this study, 73 patients suspected with coronary artery disease but had no epicardial coronary stenosis and vasospasm were enrolled. There were 13 CKD patients and CFR was measured using the Doppler flow wire methods in the left anterior descending artery. CFR was significantly lower in CKD group than non-CKD group (3.13 ± 0.6 vs. 4.00 ± 1.1, P = 0.007). From multivariate logistic regression analysis, the independent factor associated with the presence of CKD was only CFR (odds ratio 3.85, 95% confidence interval 1.27-11.70, P = 0.017). In the patients with low CFR (≤ 2.8), cardio-cerebrovascular events were more common than those with normal CFR (CFR > 2.8). Besides, in the patients who had both low CFR and CKD, long-term cardio-cerebrovascular events were more likely to occur than those with normal CFR or non-CKD. CONCLUSIONS: Our data suggest that low CFR is associated with CKD and cardio-cerebrovascular events in the patients without coronary stenosis and vasospasm.

Flow-mediated dilatation identifies impaired endothelial function in patients with sleep apnea syndrome.

BACKGROUND: Non-invasive detection of vascular dysfunction in the early stage is clinically important in patients with sleep apnea syndrome (SAS). Flow-mediated dilatation (FMD) is a novel clinical marker of endothelial function. However, it is not clear whether this is useful in the SAS patient. METHODS: Echocardiographic parameters and FMD were measured in 129 patients with SAS. Apnea-hypopnea index (AHI) was defined by polygraphy, and patients were divided into the two Groups: Group A (moderate-severe SAS: AHI≥ 15 times/hr, n=93) and Group B (mild SAS: AHI 5-15 times/hr, n=36). RESULTS: There were no significant differences in echocardiographic parameters between the two groups. However, FMD was significantly lower in Group A than in Group B (3.5±1.6 vs. 7.8±3.1, P< 0.01). CONCLUSIONS: Although cardiac function was not different, vascular dysfunction was evident in patients with moderate-severe SAS. FMD is a useful tool to identify impaired endothelial function non-invasively in patients with SAS.