Midterm angiographic outcomes with sirolimus- and everolimus-eluting stents for small vessels in diabetic patients: propensity-score-matched comparisons in three different vessel diameters.

We conducted propensity-score-matched comparisons of midterm angiographic follow-up outcomes of sirolimus- versus everolimus-eluting stents (SES, EES) after elective placements for de novo coronary stenosis in small vessels (SV) in patients with diabetes mellitus (DM), because the angiographic efficacy of EES over SES for those cohorts remained unclear. The study was a non-randomized, retrospective, lesion-based, multicenter study, examining lesions followed up angiographically within 550 days, extracted from the unified database of 6 institutes. The endpoint (binary restenosis) was defined as the percentage of subjects having >50% diameter stenosis at follow-up. Propensity-score-matched analyses were conducted in 3 different vessel-size cohorts, defined by a preprocedural reference diameter (RD) <2.10, <2.35, and <2.60 mm, yielding group sizes of n = 107, 183, and 312 baseline-adjusted lesions in each of the 2 stent arms. The frequency of binary restenosis decreased significantly with increasing vessel size, at 16.8, 12.6, and 12.2%, in the SES group. However, it remained almost the same across vessel-size groups in the EES group (8.0, 6.0, and 7.5%). The p values for the significance of the differences in binary restenosis between EES and SES in each vessel size increased with the decrease in vessel size [p = 0.002, 0.040, and 0.063 (the last still nearly significant)]. Thus, in patients with DM, EES showed increasingly superior efficacy over SES for SV stenosis as the vessel size became smaller, i.e., the risk for binary restenosis became greater.

Propensity-Score Matched Comparison of Midterm Angiographic Outcomes of Sirolimus- Versus Everolimus- and Biolimus-Eluting Stents for De Novo Coronary Stenosis.

We conducted propensity-score matched comparisons of midterm angiographic outcomes of sirolimus (SES) versus either everolimus- (EES) or biolimus- (BES) eluting stents after placements for coronary stenosis in a daily practice environment since previous randomized trials did not demonstrate the superiority of EES and BES over SES in terms of midterm angiographic outcomes.The present study was a non-randomized, retrospective, and lesion-based study, recruiting angiographically followed-up lesions within 550 days after successful and elective SES (n = 1793), EES (n = 1303), or BES (n = 324) placement for de novo native coronary stenosis during the period from August 2004 to January 2014 at 6 institutes. The endpoint, as an angiographic surrogate marker of clinical efficacy, was the distribution of in-stent follow-up percent diameter stenosis (%DS) which comprised the percentages of 1) follow-up %DS < 20 and 2) follow-up %DS > 50. Propensityscore matched analyses were conducted to adjust 21 baselines.In 1215 baseline adjusted lesions, the endpoints in the EES group [1) 74.1%, and 2) 4.6%] were significantly different from those in the SES group [57.9%; P < 0.001, 7.2%; P = 0.006, respectively). In 307 baseline adjusted lesions, the endpoints in the BES group [1) 80.5%, 2) 2.0%] were significantly different from those in the SES group [59.3%; P < 0.001, 2) 8.1%; P = 0.001, respectively].The present study is the first to confirm the superiority of midterm angiographic outcomes after the placement of EES and BES over SES for de novo coronary stenosis in a clinical setting.

Effects of Add-on Therapy Consisting of a Selective Mineralocorticoid Receptor Blocker on Arterial Stiffness in Patients with Uncontrolled Hypertension.

OBJECTIVE: Aldosterone plays an important role in the pathogenesis of atherosclerosis; however, the significance of mineralocorticoid receptor blockade for atherosclerosis has not been fully elucidated. In this study, the effect of add-on eplerenone on the degree of arterial stiffness was examined in patients with uncontrolled hypertension. METHODS: Forty-seven uncontrolled hypertensive patients who had previously been treated with anti-hypertensive drugs were examined retrospectively. Thirty-two patients received add-on therapy consisting of eplerenone (Group E) and 15 patients received add-on therapy with a Calcium channel blocker (CCB) or an increased dose of CCB (Group C) in addition to their baseline medications. Both the systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were significantly decreased at two and 12 months in Group C. In contrast, neither the SBP nor DBP values were significantly changed at two months and eventually decreased at 12 months in Group E. The degree of arterial stiffness, as evaluated according to the cardio-ankle vascular index (CAVI), did not improve at either two or 12 months in Group C, whereas the CAVI values improved as early as at two months and the improvement was sustained at 12 months in Group E. The extent of change in the CAVI was not associated with the level of changes in the SBP or DBP values in Group E. CONCLUSION: Treatment with eplerenone added to the patient's baseline medications improves the degree of arterial stiffness as early as at two months after the beginning of treatment, independent of the blood pressure-lowering actions of these drugs in patients with uncontrolled hypertension.

Fabrication of Ni compound nanocrystal/nanocarbon composites by cooling of chloride-based fluxes.

Unique Ni compound nanocrystals were successfully grown on carbon nanotubes (CNTs) by cooling a mixed chloride flux. Cup-stacked CNTs (CSCNTs) were used as the nanocarbon materials because of their structural features. The grown nanocrystals had a nanosheet structure, which was densely assembled and had a ribbon-like morphology. Therefore, the nanocrystal/CSCNT composites were expected to have a highly active surface area for the catalyst composites. The selected area electron diffraction pattern and the related radial intensity profiles indicated that the grown nanocrystals were Ni(OH)2. When the pristine CSCNTs were used as a starting material, the formation efficiency of the nanocrystal/CSCNT composites decreased because the pristine CSCNTs were not dispersed in the KCl-LiCl flux. Therefore, functionalization of the CSCNTs was carried out with VUV light irradiation. The dispersibility of the VUV light-treated CSCNTs increased in the KCl-LiCl flux in comparison with the pristine CSCNTs because oxygen-containing functional groups, such as -COOH and -CO, were introduced onto the surfaces of the CSCNTs.

Latent genetic backgrounds and molecular pathogenesis in drug-induced long-QT syndrome.

BACKGROUND: Drugs with I(Kr)-blocking action cause secondary long-QT syndrome. Several cases have been associated with mutations of genes coding cardiac ion channels, but their frequency among patients affected by drug-induced long-QT syndrome (dLQTS) and the resultant molecular effects remain unknown. METHODS AND RESULTS: Genetic testing was carried out for long-QT syndrome-related genes in 20 subjects with dLQTS and 176 subjects with congenital long-QT syndrome (cLQTS); electrophysiological characteristics of dLQTS-associated mutations were analyzed using a heterologous expression system with Chinese hamster ovary cells together with a computer simulation model. The positive mutation rate in dLQTS was similar to cLQTS (dLQTS versus cLQTS, 8 of 20 [40%] versus 91 of 176 [52%] subjects, P=0.32). The incidence of mutations was higher in patients with torsades de pointes induced by nonantiarrhythmic drugs than by antiarrhythmic drugs (antiarrhythmic versus others, 3 of 14 [21%] versus 5 of 6 [83%] subjects, P<0.05). When reconstituted in Chinese hamster ovary cells, KCNQ1 and KCNH2 mutant channels showed complex gating defects without dominant negative effects or a relatively mild decreased current density. Drug sensitivity for mutant channels was similar to that of the wild-type channel. With the Luo-Rudy simulation model of action potentials, action potential durations of most mutant channels were between those of wild-type and cLQTS. CONCLUSIONS: dLQTS had a similar positive mutation rate compared with cLQTS, whereas the functional changes of these mutations identified in dLQTS were mild. When I(Kr)-blocking agents produce excessive QT prolongation (dLQTS), the underlying genetic background of the dLQTS subject should also be taken into consideration, as would be the case with cLQTS; dLQTS can be regarded as a latent form of long-QT syndrome.

The insulin sensitizer pioglitazone improves the deterioration of ischemic preconditioning in type 2 diabetes mellitus rats.

We investigated the effects of ischemic preconditioning (IP) on reperfusion arrhythmias in type 2 diabetic rats as well as the effects of the insulin sensitizer pioglitazone. Thirty-week-old OLETF rats with or without pioglitazone (10 mg/kgBW, orally) were used as a model for type 2 diabetes. LETO rats served as controls. The incidences and durations of reperfusion ventricular tachyarrhythmias (RVT) were evaluated using a working heart method. After 5 minutes of initial perfusion, the rats were divided into the following groups: 1) control rats without IP (CIP(-)), 2) control rats with IP (CIP(+)), 3) diabetic rats without IP (DIP(-)), 4) diabetic rats with IP (DIP(+)), 5) pioglitazone-treated diabetic rats without IP (TDIP(-)), and 6) pioglitazone-treated diabetic rats with IP (TDIP(+)). Three 2-minute cycles of global diastolic ischemia and 5 minutes of reperfusion before long ischemia were performed as IP. The incidence and duration of RVT in CIP(+) were significantly lower than in CIP(-). There was no significant difference in the duration of RVT between DIP(+) and DIP(-). However, the duration of RVT in TDIP(+) was significantly shorter than TDIP(-). These results suggested that the effects of IP on reperfusion arrhythmias are deteriorated in type 2 diabetic rats. The insulin sensitizer pioglitazone can improve the deterioration of IP against reperfusion arrhythmias in type 2 diabetic rats.

Mitiglinide, a novel oral hypoglycemic agent, preserves the cardioprotective effect of ischemic preconditioning in isolated perfused rat hearts.

Diabetic patients often have manifestation of coronary heart disease. As a consequence, therapeutic strategies for diabetes should pay more attention to hypoglycemic agents which do not have adverse effects on myocardium. Mitiglinide is considered to have little or no impact on the cardioprotective effect of ischemic preconditioning (IP) because of its high selectivity for blocking sulfonylurea receptor1 (SUR1). However, glibenclamide, a nonselective SUR blocker, attenuates this beneficial effect. In the present study, we tested the hypothesis that mitiglinide preserves the protective action of IP evaluated by ischemia/reperfusion ventricular tachyarrhythmia (rVT) in isolated perfused rat hearts. After initial perfusion, the hearts were assigned to one of the following groups: 1) non-IP with control perfusion buffer (non-IP group); 2) IP with control perfusion buffer (IP-C group); 3) IP with perfusion buffer containing glibenclamide (IP-G group); and 4) IP with perfusion buffer containing mitiglinide (IP-M group). The protocol for the non-IP group consisted of 21 minutes of aerobic perfusion before 10 minutes of ischemia. In the other 3 groups (IP groups), there were 3 cycles of 2-minute ischemia followed by 5 minutes of reperfusion before 10 minutes of ischemia. The IP-C group had a significantly shorter rVT duration than the non-IP group (4.4 +/- 1.8 minutes versus 14.3 +/- 2.5 minutes; P < 0.05). rVT duration was the shortest in the IP-M group (3.9 +/- 1.0 minutes), but among the longest in the IP-G group (14.0 +/- 2.6 minutes). In conclusion, mitiglinide preserved the cardioprotective effect of IP, however, glibenclamide abolished this beneficial effect. Therefore, mitiglinide may offer a long-term benefit for myocardial ischemia in diabetic patients.

[Peripartum cardiomyopathy with antiphospholipid antibody: a case report].

A 32-year-old woman tested positive for lupus anticoagulant when she had fever of unknown origin at 18 weeks of pregnancy. Sixteen days after a normal delivery at 35 weeks, she developed dyspnea and was hospitalized with heart failure. Chest radiography showed severe pulmonary edema. Echocardiography showed dilation and diffuse hypokinesis of the left ventricle. The diagnosis was peripartum cardiomyopathy. The patient responded to diuretic and vasodilator therapy. Endomyocardial biopsy revealed mild myocardial degeneration and interstitial fibrosis. Heart failure due to coronary microthrombosis has been indicated in patients with antiphospholipid antibodies, suggesting such a relationship in this case.

Deteriorative effect of smoking on target lesion revascularization after implantation of coronary stents with diameter of 3.0 mm or less.

BACKGROUND: Although smoking cessation is widely encouraged because of the associated risk of cardiovascular events, the impact of smoking on target lesion revascularization (TLR) after percutaneous coronary intervention (PCI) is controversial. Therefore, the present study retrospectively investigated the effect of smoking on TLR after plain-old balloon angioplasty (POBA; n=376) and stenting (STENT; n=434) in patients undergoing secondary coronary angiography at a single center. METHODS AND RESULTS: A smoker was defined as current smoking or quitting within 2 years of the first PCI. In the POBA group, the predictors for TLR, as calculated by multiple logistic regression analysis, were a complex type of lesion (p<0.0001) and the left anterior descending artery (LAD) as affected vessel (p<0.05). In the STENT group, the predictors were the final % diameter of stenosis after stenting, measured by quantitative coronary arteriography (p<0.0005), LAD (p<0.01), and smoking (p=0.049). When the STENT group was divided into 2 groups according to the diameter of the implanted stent, smoking was a predictive factors for TLR in the group that received relatively small stents (diameter < or =3.0 mm) (p<0.02), but not in the group that received larger stents (diameter > or =3.5 mm). CONCLUSION: Smoking has a deteriorative effect on TLR after implantation of relatively small coronary stents with a diameter of 3.0 mm or less.

Usefulness of a 6 fr right judkins catheter for mechanically extracting a massive intracoronary thrombus from an ectasic right coronary artery: a report on two different cases of thrombectomy.

In order to bail out the slow-flow phenomenon (slow flow) created by a massive thrombus in an ectasic right coronary artery, a thrombus was mechanically extracted with a 6 Fr right Judkins (JR) catheter, which proved to be more useful than a usual thrombectomy using a Rescue PT system catheter (Rescue). In case 1, the Rescue was used in combination with thrombolysis but failed to alleviate the slow flow that was implicated in a large infarction. On the other hand, in case 2, aggressive thrombectomy with a 6 Fr JR catheter with an 8 Fr Amplatz guiding catheter successfully extracted the massive intracoronary thrombus, restoring good coronary flow. Therefore, mechanical extraction with a 6 Fr JR catheter is safe and useful in cases of massive thrombus when diffuse coronary artery ectasia complicates an acute myocardial infarction. In addition, this method should be applicable to cases of acute coronary syndrome with massive thrombus.

A case report of late coronary stent thrombosis manifested as acute myocardial infarction 19 months after stenting.

A 63-year-old Japanese man was readmitted to our hospital due to acute broad-anterior myocardial infarction (AMI). The proximal left anterior descending artery (LAD) at the prior stent, which was implanted 19 months earlier and in which no angiographic restenosis was recognized 13 months before the second study, was totally occluded. After crossing a guide wire and balloon angioplasty, angiographic radiolucency was observed at the prior stent, suggesting that AMI was induced by late coronary stent thrombosis. Intravascular ultrasound performed 19 days after the onset of AMI revealed superficial calcification without significant stenosis and an atherosclerotic plaque distal to the stent that was not significantly changed compared to 19 months previously, consistent with the culprit lesion being an intrastent site. AMI may thus be induced by late coronary stent thrombosis during long-term clinical follow-up without clinical symptoms or angiographic restenosis at the second study.

Mitral regurgitation disappearance after cibenzoline treatment in a patient with hypertrophic obstructive cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM), which shows left ventricular outflow pressure gradient (LVPG), is often complicated with mitral regurgitation (MR). We examined a 62-year-old Japanese female with HOCM and MR. Ultrasound echocardiography showed severe MR, asymmetrical septal hypertrophy, systolic anterior movement of the mitral valve anterior leaflet, and left ventricular outflow stenosis. Her LVPG, measured using continuous wave Doppler recording, was 118 mmHg. During heart catheterization, the aortic pressure and left ventricular pressure were simultaneously measured. An intravenous injection of 70 mg cibenzoline decreased the LVPG from 110 mmHg to 16 mmHg. Left ventriculography was performed immediately after the injection and did not show MR. This clearly demonstrates that cibenzoline decreases LVPG in patients with HOCM and also improves the MR that arises from LVPG.